Dr. Kent Anger

In 2015, the OHWC team conducted behavioral and organizational change interventions in multiple industries including construction, home care, health care, transportation and in broader cross-sections of the work force, including young workers. They:

• published the results of hypothesis-based research on TWH using strong (randomized trial) research designs.

• developed tools and toolkits to disseminate those results (www.ohsu.edu/ohwc).

• successfully competed for renewed federal funding (2016-2021) of the OHWC.

• Dr. Anger concentrated on implementing TWH interventions in construction and agriculture, especially in vineyards.

Dr. David Hurtado

Peers influence health-related information, attitudes and behaviors at the workplace, and peer-based training has been shown to be effective for personal protective equipment and safety-related procedures. With seed funding from the Oregon Healthy Workforce Center and the Oregon Institute of Occupational Health Sciences, Dr. Hurtado:

• conducted pilot studies in preparation for extramural grants to develop effective peer-based programs that improve occupational health and safety.

• applied Social Network Analysis to detect which workers and social relations are critical to influencing safer workplace norms and practices.

• started a research partnership to identify, train and evaluate the effects of nurses that champion safe patient handling and teamwork at their units at Samaritan Lebanon Community Hospital.

• evaluated the mental health effects of a peer-based program that provides social support and stress management to parole probation officers at the Multnomah County's Department of Community Justice.

Dr. Ryan Olson

With today's modern technologies and growth of knowledge-based work, the boundaries between work and non-work time are blurring. This can create stressful work-family conflict that harms worker health. Related to this problem, Dr. Olson:

• led publication of an intervention aimed to reduce work-family conflict and improve employee health and productivity, with co-author Leslie Hammer, in the flagship paper on sleep outcomes for the Work, Family, and Health Network intervention trial.

• collaborated with Dr. Brad Wipfli to develop the OHSU Enterprise App for iPhone/iPod Touch that was used by supervisors in the program to set goals and self-monitor their supportive supervisory behaviors.

COMPASS Pilot Study Findings

Home care workers who care for society's most vulnerable citizens have limited safety and health support structures, and have elevated injury rates. With Diane Elliot at OHSU and Jennifer Hess from the University of Oregon, Dr. Olson developed and pilot tested the COMmunity of Practice and Safety Support (COMPASS) program for home care workers. COMPASS is a peer-led group program where workers meet regularly for shared learning, goal setting, and social support for solving problems and making changes.

• The results of the COMPASS randomized controlled trial were published. Home care workers participated in the peer-led and supportive group program for one year.

• Post-program results showed that COMPASS participants made large safety improvements, including hazard correction in homes and increased use of ergonomic tools.

• Home care workers also made health changes, such as improved fruit and vegetable consumption and increased good cholesterol.

• Future plans are focused on studying the long-term impact of COMPASS within the Oregon Home Care Commission's training system.

New Funding to Improve Sleep of Truck Driving Teams

Truck drivers experience very challenging sleep conditions due to variable work hours and noise and uncomfortable temperatures when parked at truck stops. However, truck driving teams, where one partner drives while the other sleeps, experience special additional challenges. They perform shift work (driving outside of normal day shift hours) and sleep in a bouncing/jostling vehicle. To address this problem Dr. Ryan Olson and Peter Johnson (University of Washington), proposed a project aimed at reducing driver fatigue and improving sleep and Total Worker Health. Co-investigators also include Steven Shea and Miguel Marino (OHSU Family Medicine).

• This project was funded in 2016 (NIOSH) and will evaluate engineering and behavioral technologies to impact fatigue, sleep and Total Worker Health.

Results of the SHIFT Randomized Trial

Excessive weight gain and ill health are common among truck drivers who, due to their work environment, are often sedentary and have poor diets. To address this, Dr. Ryan Olson developed SHIFT (Safety &Health Involvement For Truckers), a National Heart, Lung and Blood Institute (NHLBI)-funded weight loss and health promotion intervention for truck drivers. The intervention is supported by computer-based training, weekly weight and behavior logging and motivational interviewing.

• With the support of 5 trucking firms, a randomized controlled trial of the program was conducted with drivers recruited from 22 terminals.

• Results published in 2016 showed that SHIFT produced significant and medically meaningful weight loss.

• This degree of weight loss is sufficient to produce an estimated $200 in annual health care savings per person and reduce risk for developing diabetes and high blood pressure.

Oregon Fatality Assessment and Control Evaluation (OR-FACE) Program 

Globally each year about 350,000 workers are killed on the job, with nearly 5,000 deaths occurring in the US.

In 2015, Dr. Ryan Olson and Illa Gilbert-Jones led the successful award of 5 new years of funding (2015- 2020) for the OR-FACE program funded by the National Institute of Occupational Safety &Health. The mission of OR-FACE is to prevent occupational fatalities through surveillance, targeted investigation, assessment, and outreach associated with traumatic work-related deaths in Oregon. OR-FACE is a special workplace safety resource for Oregon, and is one of only seven state-based programs that were funded in this new cycle. The OR-FACE project is a sub-project of the Oregon Occupational Public Health Program, which is a partnership between the Oregon Health Authority (Curtis Cude, Co-Principal Investigator) and our Institute at Oregon Health &Science University (Ryan Olson, Co-Principal Investigator). 

Dr. Leslie Hammer

Safety & Health Improvement Program (SHIP)

SHIP was designed to train supervisors to support balance in employee's work-family demands using a team-based approach. SHIP was tested and shown to be effective in reducing stress and improving safety among City of Portland construction workers. It is now available as a do-it-yourself Toolkit (http://tinyurl.com/ship-prog).

SERVe (the Study of Employment Retention for Veterans)

SERVe, a Department of Defense-funded study, is designed to improve the health and well-being of Oregon veterans, service members and their families, and to increase retention of veterans and service members in the Oregon workforce. Veteran-Supportive Supervisor Training builds on previous validated work, where supervisors in the civilian workforce were trained to better support their employed service members, and involves over 40 organizations in Oregon. Such interventions are particularly critical given the high level of veteran unemployment, and will only strengthen national programs aimed at increasing recruitment and hiring of veterans.

Dr. Diane Rohlman

PUSH (Promoting U through Safety & Health)

This program is aimed at reducing the incidence of workplace injury among young workers using training tools specifically designed to address the needs of this population. In 2015:

• 8 new custom educational videos were produced

• 21 supervisor-led activities for young workers were designed

• development of an expanded online training curriculum was coordinated with a group of national young worker safety experts and stakeholders.

• our PUSH partner, Portland Parks and Recreation Aquatics Department, continues to require the online PUSH training for all new seasonal hires.

The PUSH team also completed a study funded by the Bureau of Labor and Industries Apprenticeship and Training Division and the Oregon Department of Transportation, Office of Civil Rights. The purpose of the study was to identify and characterize factors impacting construction workers' health and safety that reach beyond traditional occupational hazards. The study had two goals:

• conduct an assessment of the health and safety needs of construction apprentices.

• develop and evaluate an online nutrition training program for construction apprentices.

We also worked with Portland Youth Builders (PYB), an alternative education and pre-apprenticeship program that prepares at-risk youth for careers in the building trades. We used the nutrition training developed for registered apprentices to educate over 60 students about the importance of healthy diets on work performance and success in education. 

Dr. Suzanne Mitchell

Dr. Mitchell's lab examines the extent to which different genes are associated with impulsive behavior by comparing impulsivity in drug-naïve selected lines and inbred strains of rodents. Dr. Mitchell also examines whether different levels of impulsivity predict responses the first time rodents are exposed to drugs of abuse, like alcohol, nicotine and methamphetamine. Measures of impulsivity in human subjects are used to examine whether acute exposure to drugs of abuse or withdrawal from use results in impulsive behaviors. She found that:

• individuals with a history of drug and alcohol use are more impulsive than individuals who do not have such a history.
  

• impulsivity can have workplace consequences. 

While Dr. Mitchell's lab continues to publish research focused on impulsive choices, she is also developing a method that will enable investigation of how impulsivity affects the cognitive effort required to obtain a reward;for example, how willing a person is to pay attention before the mind wanders, or, trying to hold information in mind that the subject is required to remember. 

• This research may have workplace relevance in identifying those who might persist to complete tasks despite the odds or identifying when it may not be advisable to do so. 

• Dr. Mitchell received two grants to examine whether her research methods can be used to predict how long smokers interested in quitting can resist their urges to smoke.

Dr. Charles Allen

Examining Circadian-Based Disorders

Dr. Allen showed that non-neuronal support cells in the brain, called astrocytes, communicate with neurons of the brain's circadian clock.

• Astrocytes may offer an additional therapeutic target for the treatment of circadian rhythm disorders.

• Activation of cannabinoid receptors in the suprachiasmatic nucleus phase-advances the circadian clock. The cannabinoid actions are mediated by non- neuronal glial cells.

• This may explain why circadian disruption is observed in chronic marijuana users and provides further evidence for the important role of glial cells in the generation of circadian rhythms.

In an animal model in which the retinal ganglion cell vesicular glutamate transporter protein has been specifically eliminated, Dr. Allen found that:

• glutamate neurotransmission was only partially reduced in that nerve tract (glutamate is an excitatory neurotransmitter).

• vesicular glutamate transporter deletion shortens the postsynaptic current duration and decreases the probability that glutamate will be released at high stimulus frequencies, which in turn can alter the environmental light signals that are responsible for entraining the circadian clock.
  
  

Dr. Steven A. Shea

Steven A. Shea's team conducts research on sleep and the internal body clock (circadian system) and how disturbances of these important functions affect human health. This is a step in efforts to develop strategies to avoid or reduce chronic diseases in populations at risk, such as night shift workers.

Dr. Shea's research is performed in specialized laboratories at the Oregon Clinical &Translational Research Institute (OCTRI) at OHSU that permit precise control of all behaviors and the environment while intensively monitoring physiological function. These studies are performed in constant dim light and with artificial day lengths (participants do not know the actual time of day), allowing separation of circadian system effects from behavioral stresses (such as exercise). This specialized laboratory is one of only a handful of laboratories across the world where such intensive, strictly controlled and prolonged studies can be performed in humans. Example of Dr. Shea's research include:

• study of circadian rhythms in people with obstructive sleep apnea, a condition that is associated with increased risk of cardiovascular disease.

• examination of mechanisms by which the circulatory system is adversely affected by a sedentary lifestyle, and what can be done to avoid such health problems.

• grants from National Space Biomedical Research Association/NASA, the Medical Research Foundation of Oregon and the National Institutes of Health.

In 2015-16, Dr. Shea and colleagues published ten papers with important findings related to the effects of sleep, sleep apnea and the circadian system.

Dr. Doris Kretzschmar

Disturbances of sleep and other circadian rhythms is an early sign of many neurodegenerative diseases, including Alzheimer's disease (AD). Dr. Kretzschmar uses a fruit fly model of AD to study this relationship and discovered that abnormal proteins found in AD alter circadian rhythms. Such alterations, in turn, aggravate the neurodegeneration of AD in the fruit fly model. Dr. Kretzschmar's group is also investigating effects of circadian rhythms on the aging immune system and how this affects development of AD. New discoveries in this area may lead to the development of therapies that reduce or delay the pathology of AD.

Dr. Matt Butler

Shift workers have higher rates of heart disease, diabetes, and cancer that can be traced to disruptions in their internal circadian clock. Dr. Matthew Butler's goal is to understand how our body clocks are synchronized by light and food, and how disruption of the biological clock leads to disease. Dr. Butler:

• has found new measures of sleep apnea, beyond just how many episodes there are, that better predict future heart disease, especially in women.

• established a laboratory in the Institute to focus on the physiology and behavior of mice on simulated shift work schedules. Ongoing studies are focused on how eating patterns synchronize internal clocks, and how shift work experience during pregnancy affects the future metabolic health of the offspring.

• hormones like testosterone and estrogen can affect how fast the biological clock runs, but where the hormones act to do this is not known. To determine how this occurs, Dr. Butler's team implanted tiny pellets of testosterone into the brains of mice where the master circadian clock is found. Testosterone changed clock speed, showing that the brain clock itself is sensitive to hormones. This has implications for why men and women have different sleep schedules and perhaps why women experience more insomnia than men.

• Shift workers experience weight gain that is attributable to changes in the timing of meals and the timing of endogenous biological clocks.

• Dr. Butler's is also interested in how clocks in many different tissues of the body are synchronized to daily cues in the environment like dawn, dusk, and meal patterns. In 2016, Dr. Butler showed that the brain's clock plays an important role in setting the clock in the liver even when meals are at the wrong time. He has also begun a set of experiments to understand how shift work compromises fertility and reproductive success. Ultimately, this work could help mothers who engage in shift work to be healthier.
  
  

Dr. Miranda Lim

Mild traumatic brain injury (mTBI) can lead to long- lasting problems with sleep, mood, and memory. The reasons for this are poorly understood, as objective testing and neuroimaging is often normal. Dr. Miranda Lim:

• developed a rodent model of concussion, which showed persistent disturbances in the sleep encephalogram (EEG).

• studied a population of human subjects with chronic mTBI and found they also had abnormal EEGs while awake, and the degree of abnormality correlated with severity of their post-TBI symptoms.

• showed that mice with mTBI had decreased glutamate, an excitatory neurotransmitter, in wake-promoting neurons in the brain.

• these discoveries may lead to the development of therapies that counter EEG abnormalities and improve wakefulness after TBI.

In 2016, Dr. Lim was awarded grants from the VA Biomedical Laboratory and the VA Rehabilitation Research &Development services, the Brain and Behavior Foundation, the Collins Medical Trust, and the Oregon Medical Research Foundation. Some of the goals of these ongoing projects are to examine brain electrical activity during sleep and its ability to predict traumatic symptoms and functional outcomes at home and at work.

Dr. Mitch Turker

The goal of Dr. Mitch Turker's research is to understand how environmental exposures cause gene expression to change in a stable but abnormal fashion. Such changes can contribute to diseases, such as cancer and neurodegenerative disease. Dr. Turker's work is showing that certain environmental exposures can lead to complex and tissue-specific responses with disease implications.

How Altered Day/Night Sleep Patterns Affect the Body

One environmental exposure the Turker lab is studying is how altered day/night sleep patterns affect the body. He measured the effect on mice of a weekly light/dark phase shift in which the mice lose 6 hours of the night period at each shift (mice are awake at night). In collaboration with Dr. Chuck Allen, they found that 8 weekly shifts significantly disrupted the liver circadian rhythm for at least one full week after the last shift was made. This finding has implications for humans who engage in non-standard work shifts.

Biological Effects of Ionizing Radiation

The Turker lab has studied the biological effects of ionizing radiation. His team found that radiation causes specific genetic mutations that may be useful as biomarkers for detecting the earliest signs of radiation-induced cancers. Dr. Turker also investigated how radiation alters the epigenome, which represents modifications to DNA that control gene expression. In collaboration with other OHSU investigators, Dr. Turker found that radiation can cause epigenome changes that correspond to changes in gene expression, and these changes are tissue-specific —the heart epigenome was found to respond to radiation quite differently than the brain epigenome. Other collaborative work has even shown changes in behavior from radiation exposure.

Dr. Stephen Lloyd

Enhancing DNA Repair in Skin that is Exposed to Sunlight.

Oregon has one of the highest rates of skin cancer in the United States, with malignant melanoma consistently ranking in the top 5 in the country. Although this may appear to be counter-intuitive based on geographical location and frequently overcast skies, these statistics emphasize the need for Oregon workers to take appropriate measures to limit exposures and thus reduce sunlight-induced DNA damage. However, since all skin cancer rates continue to increase annually, our research has focused on increasing the DNA repair capacity of skin. This approach, which was jointly developed in Drs. McCullough and Lloyd laboratories, seeks to activate a new DNA repair system in skin cells, that quickly repairs DNA damage. A DNA repair enzyme was incorporated into a lotion that can be applied to the skin in a manner very similar to sunscreen. In a pre-clinical animal model of human skin, they have shown:

• it is safe even at doses 100-times greater than would be used on skin.

• it rapidly repairs the major form of DNA damage and, in a rodent model, has been shown to dramatically reduce the rate of onset of skin cancers.

• these pre-clinical studies are designed to move toward FDA approval of a product for human use.

Mechanisms to Limit Weight Gain.

The Lloyd lab made significant findings on how to limit weight gain in rodent models, even when animals are fed a very high fat diet. They found that, when DNA repair capacity can be increased in the cellular organelle that produces energy, the mitochondria, the animals became essentially resistant to high fat diet-induced obesity. These findings provide a fundamental understanding of how comparable food intake is differentially processed among individuals.

Genetic Risk of Chemically-induced Cancers.

Additional investigations have focused on the fundamental mechanisms by which chemical contaminants in food lead to liver and lung cancers. These contaminants come from low levels of molds in grains that then become widely distributed throughout the population. Although millions of individuals are potentially exposed, only a subset develop disease –Dr. Lloyd's investigations shed light on the key proteins that limit cancer formation. This work may be applicable to genetic screening, which may provide a mechanism for understanding cancer susceptibility and early detection of disease.

Dr. Amanda McCullough

Genotoxic Consequences of Formaldehyde Exposure

Formaldehyde is a human carcinogen, and there is growing concern over the possible adverse health effects from occupational and environmental human exposures. Although formaldehyde-induced DNA and protein structural changes have been identified, mechanisms that cause genomic instability and cellular tolerance to this damage are not fully characterized. The McCullough lab has previously identified unsuspected key players in the repair of formaldehyde-induced DNA damage.

• In 2016, these findings were extended using a human cell assay of ~400 genes to identify significant interactions among DNA damage response proteins associated with the response to formaldehyde.

Using DNA Repair for More Effective Cancer Treatments

An increased risk for several human cancers, including breast, ovarian, colon, and skin, may arise due to an inability to repair damaged DNA.

• In 2016, the Lloyd &McCullough labs began investigating a treatment strategy that may alleviate some of the toxic effects of chemotherapy and improve patient outcomes.

• Genetic analysis of acute myeloid leukemia subtypes revealed reduced levels of a critical DNA repair gene in patients carrying a specific chromosome defect. The McCullough lab demonstrated that deficiencies in this DNA repair gene can increase cell killing by chemotherapeutic drugs, providing a potential new target for this complex disease.
  

Dr. Doris Kretzschmar

Studying Changes in Neuropathy Target Esterase (NTE)

It has been shown previously by Dr. Kretzschmar and others that organophosphate exposure and genetic changes in a protein called neuropathy target esterase (NTE) result in movement problems and mental retardation accompanied by the degeneration of neurons. This shows that the NTE protein is required for neuron survival, but the molecular mechanisms behind this are unknown. Using a fly model, Dr. Kretzschmar found that:

• changes in NTE produce a cellular stress response called apoptosis that causes cells to die.

• Since drugs that prevent the stress response are available, this discovery could lead to a treatment of NTE-related disorders.

In 2016, Dr. Kretzschmar found that NTE is also required in glia cells, which support and insulate neurons. Loss of NTE in glial cells in the fly brain causes defects in the insulation surrounding neurons and their axons and induces movement problems, even when NTE is present in neurons. Similar results were recently obtained in a rodent model.

• This shows that treatment strategies for NTE-related diseases not only have to be aimed at the survival of neurons but also the survival of glia.
  

Dr. Peter Spencer

Understanding ALS-PDC

Dr. Spencer is interested in the causation and prevention of a prototypical neurodegenerative disease, the amyotrophic lateral sclerosis and parkinsonism-dementia complex (ALS-PDC), that has affected generations of minority (Chamorro) Oregonians and non-Chamorros who have lived on Guam. Dr. Spencer found evidence that Gulf War veterans with ALS may have acquired it from exposure to the Guam environment. The most plausible cause of ALS- PDC is the traditional Chamorro food-use of a highly neurotoxic plant that contains the potent DNA-damaging agent methylazoxymethanol (MAM).

• Since MAM is chemically related to nitrosamines, research to explore possible links between occupational exposure to these substances and ALS/PDC-related neurodegenerative diseases could benefit workers in Oregon and worldwide.

Nodding Syndrome's Link to Measles

Dr. Peter Spencer'steam is investigating the causes, consequences and prevention of Nodding Syndrome, an epidemic neurologic disorder affecting children in East Africa. His team conducted a case-control study that revealed a disease association with measles infection and moldy food at onset of clinical signs.

• Dr. Spencer has proposed that Nodding Syndrome is a post-measles disorder comparable to subacute sclerosing panencephalitis (SSPE). While SSPE is now rare in the U.S. because of widespread measles vaccination, the disease could resurface in communities that have declined to vaccinate for measles.

 

Ryan Olson

Oregon Fatality Assessment and Control Evaluation (OR-FACE) Program

Globally each year about 350,000 workers are killed on the job, with nearly 5,000 deaths occurring in the US. 

In 2015, Dr. Ryan Olson and Illa Gilbert-Jonesled the successful award of 5 new years of funding (2015- 2020) for the OR-FACE program funded by the National Institute of Occupational Safety &Health. The mission of OR-FACE is to prevent occupational fatalities through surveillance, targeted investigation, assessment, and outreach associated with traumatic work-related deaths in Oregon. OR-FACE is a special workplace safety resource for Oregon, and is one of only seven state-based programs that were funded in this new cycle. The OR-FACE project is a sub-project of the Oregon Occupational Public Health Program, which is a partnership between the Oregon Health Authority (Curtis Cude, Co-Principal Investigator) and our Institute at Oregon Health &Science University (Ryan Olson, Co-Principal Investigator).

Dr. Miranda Lim

Lasting Effects of Mild Traumatic Brain Injury (mTBI)

Mild traumatic brain injury (mTBI) can lead to long-lasting problems with motor function, gait and balance. The reasons for this are poorly understood, as objective testing and neuroimaging is often normal. In addition to her studies on mTBI and sleep, Dr. Lim is collaborating with scientists at the University of Oregon to study motor function, gait and balance in Veterans with mTBI.

• Preliminary data indicate that even 1-5 years after injury, gait and balance disturbances persist.

• Moreover, measures of cortical inhibition over the motor cortex are abnormal as assessed by transcranial magnetic stimulation (TMS).

• These data may help lead to a better understanding of the deficits seen after brain injury.

Dede Montgomery, MS, CIH; Fred Berman, DVM, PhD; Anjali Rameshbabu, PhD; Helen Schuckers, MPH

We are proactively engaged in providing timely occupational health and safety information to employees, employers, health and safety professionals, doctors, nurses, and the public. (http://tinyurl.com/Outreach-Education)

The Web

Occhealthsci.org, the Institute's widely respected health & safety resource webpage, links to over 1,200 occupational safety &health resources. In 2016 we began our transition to a new platform that will improve our ability to present information in a format more useful to the devices and computers used today.

Resources

Available to Oregonians: Scientific expertise; webinars; OccHealthSci resource directory, "Oregon & the Workplace" blog; social media; newsletters. Through these means we have provided the following programs and accomplishments (through 2016): 

• Toxicology Information Center has provided individualized no-cost consultation on occupational safety and health on a free-to-Oregon call-in phone line (150-250 calls answered per year for over 15 years).

• Health & Safety Symposia provided in Oregon (2 per year for 22 years).

• 2015 symposia:
• Mindfulness and Total Worker Health
• Temporary and Contingent Worker Safety and Health
• 2016 symposia
• How to Create and Sustain a Culture of Safety ,
• Diversity and Inclusion in the Workplace: Impact on worker health and well-being
• The Oregon Healthy Workforce Center also sponsored the 2016 Occupational Health Psychology (OHP) Summer Institute conference "OHP Innovation and Creative Strategies Leading to Total Worker Health" ( July), and the annual partner's luncheon (November).

• Summer Internships for College Students supported 11 interns in 2015 and 15 interns in 2016 respectively
  
• Exhibits and Presentations at all OR OSHA conferences + regional meetings for over 12 years.
  
• Collaborations with government agencies, universities and associations throughout Oregon and the Northwest.

• Investigation and Outreach on Emerging Issues led to the discovery of a hair smoothing product with undisclosed high levels of formaldehyde that was reformulated for use in the US and banned in some countries due to our initial discovery.
  

Social Media

We use the full range of available web technologies to provide the public with the latest in health and safety information, and continue to improve our ability to engage with Linkedin, Twitter, Facebook, and our blog, Oregon and the Workplace, including live engagement during events. 

Dissemination

Ensuring a healthy worker necessitates a holistic view that is geared toward protecting the worker from workplace hazards as well as enhancing the employee's wellbeing at work and outside of work;this is the "Total Worker Health^®" strategy. Our work is focused on designing, developing, and disseminating effective Total Worker Health^® interventions.

2014 Accomplishments

Total Worker Health

• Established a widely-respected capacity to conduct Intervention Research that interacts with partners at all levels in Oregon. This capacity includes satisfying research requests from state (e.g., Management Labor Advisory Committee/MLAC, Workers' Compensation Division, Oregon OSHA) individual businesses and labor organizations, and high profile federally funded centers/programs (e.g., Oregon Healthy Workforce Center, Let's Get Healthy, Fatality Assessment and Control Evaluation-FACE). Our research capacity encompasses other Oregon partners at OHSU, PSU, UO/LERC, OSU/School of Public Health, Kaiser Center for Health Research, Oregon Health Authority, St. Charles of Bend, and numerous other small colleges/universities through the Institute's summer intern program.

• Providing leadership in the creation of evidence-based "Total Worker Health" interventions that integrate health promotion with injury prevention. Recognizing that a healthy workforce is both safe and productive, Occupational Health Sciences showed national leadership by the creation of the SHIFT intervention for the at-risk population of truck drivers, which is the only published intervention to date (as of 2012) to improve 'Total Worker Health'. SHIFT is a team weight loss competition supported by training and motivational interviewing. Over a 6 month period truck drivers significantly reduced body weight (by a mean of 7.8 pounds) and made medium to large (d = .49 - .88;>.80 is large) reductions in the consumption of sugary drinks and snacks, fast food, dietary fat, as well as hard braking events (recorded by truck engine;associated with fatigue and at-risk driving). The study won the intervention paper competition at Work, Stress, and Health (APA/NIOSH, 2009), and led to an R01 grant from NHLBI ($2.8 M) to conduct a randomized controlled trial of the intervention program.

• Developed the Let's Get Healthy! interactive education and research exhibit in which people learn about research and the quality of their own lifestyle such as diet and exercise in feedback with recommendations. Sought by communities throughout Oregon as a health fair learning experience (43 fairs through 2012), the program has been adopted by St. Charles of Bend for their staff and is being integrated into Oregon school programs (e.g., St. Helens, West Linn, Wilsonville) to help their students, the workforce of the future, meet state health education standards. There have been 10,877 participants (through 2012), the program has loaned kits to 36 organizations, and there are 76 organizations in the queue who have requested a Let's Get Healthy exhibit in the future. The program has been funded by 23 grants, with total funding of $2.2 M. Let's Get Healthy selected by NIH for US Capitol Hill exhibits in 2011 and 2012.

• Invention of cTRAIN computer-based training software that is effective in teaching people with limited education (0 years) to advanced degrees for improving safety knowledge and skills. cTRAIN software is being disseminated along with an editing program so organizations can create their own training in this effective computer- and web-delivered format. Developed a commercial dissemination model to make the software and grant-supported training titles available through a company that now uses revenue (~$400K in awards) to evolve the software in the fast-developing PC and web delivery environments. The software has been a key component (well-reviewed) and funded by 1 OR OSHA grant, 10 multi-year federal grants, 1 Center grant, and 3 contracts to develop training (total awards of ~$6 M). This has led to the development of 20 different training titles completed by over 1200 trainees from uneducated field workers to executive managers in 15 industry sectors, all leading to learning (p<.05) and large effect sizes (d = 0.9 –3.5);significant behavior improvement (e.g., safer pruning, improved floor cleanup to avoid slips;healthy food choices) was also recorded in some studies. Titles have been adopted by the Painter's District Council Training facility in Portland to train all painter apprentices (for ~10 years) and drywall finisher apprentices. 
  

Sleep and Shift Work

• Identified changes in intracellular calcium and action potential firing that contribute to synchronizing the internal circadian clock to the environmental day-night cycle. Circadian and sleep cycle disruption is a major occupational hazard for the 50% of Americans who report daytime sleepiness. Abnormal sleep increases the risks for workplace accidents and chronic diseases such as diabetes, cardiovascular disease and obesity. In order to devise better treatments for circadian-based sleep, and metabolic disorders, current research is focused on characterizing the molecular mechanisms underlying the generation and timing of circadian rhythms.
• Identified genetic mechanisms by which disruption of the internal circadian clock accelerates neurodegeneration and shortens life span (in flies). Internal circadian clocks generate rhythms in physiological and behavioral processes. Disruption of circadian rhythms significantly reduces the lifespan of flies and can accelerate the onset of brain pathologies. Such data may have relevance to the long-term adverse health effects of shift work in humans, as internal circadian rhythmicity becomes disrupted by shift work.
• Identified probable mechanisms underlying the fact that many diseases are worse at different times of day and night (e.g., heart attacks and stroke occur most frequently in the morning, and asthma is generally worst at night). Occupational Health Sciences researchers, along with collaborators at Harvard Medical School in Boston, have performed pioneer studies to examine how daily patterns of disease severity change across the day and night –in relation to the timing of the internal circadian clock and the ongoing stresses and behaviors that recur on a daily basis. Recent findings demonstrate the importance of the internal circadian clock on most aspects of cardiovascular control including blood clotting, blood pressure regulation and heart rate control, pulmonary function, bronchoconstriction in asthma, and even appetite regulation. Furthermore, misalignment of the circadian and behavioral cycles –as occurs with shift work was shown to lead to impairment of glucose regulation, possibly explaining the increased risk of obesity and diabetes in shift workers. The ultimate goal is to understand the biological basis behind these time-variant changes in disease severity in order to provide better therapy (e.g. appropriately timed medication to target specific phases of the body clock or to coincide with specific behaviors that cause vulnerability, such as exercise).  

Exposure: Consequences and Prevention

• Developed patented technologies for repairing sunlight-induced DNA damage for the prevention of skin cancer. This is especially important for outdoor workers in Oregon since the State has one of the highest rates of melanoma skin cancer in the nation (ranking 8th in 2003) and a higher melanoma mortality rate than the national average (ranking 9th in 2004). 
• Developed a comprehensive assessment program to identify and alleviate the toxic effects of cellular exposure to formaldehyde and similar compounds in order to prevent some types of cancers. Since Oregon had the 4th largest industrial release of formaldehyde in the nation in 2002 (latest data available), this is important to many workers and families living near those release points.
• Discovered a direct link between DNA damage associated with oxidative stress and obesity that suggests mechanisms to prevent age and diet-related illness. This discovery is significant since over 28% of Oregonians are obese and this condition leads to numerous health-related problems including diabetes and cardiovascular disease.
• Discovered that ionizing radiation induces complex types of DNA alterations including chromosome breakage and mutations. These observations could impact the incidence of leukemia and lung cancers including the estimated 350 Oregonians that get lung cancer due to radon exposure.
• Developed a new method to identify environmental toxins that can lead to gene silencing, a process in which an actively expressed gene unexpectedly turns off like a light bulb going from the on to the off position. Understanding these silencing events may give insight into mechanisms of cancer induction including breast cancer which affects approximately 5000 Oregonians and their families each year.
• Developed a rapid state-of-the-art drug discovery assay that has been used to screen over 400,000 bioactive molecules for inhibition of DNA replication. This represents the initial step in drug development that may improve therapeutic outcomes in a variety of cancer patients including those with gliomas that are among the most common form of brain cancer and generally regarded as incurable.
• Served on the advisory council for the National Institutes of Environmental Health Sciences through a multi-year commitment to provide leadership on policy decisions that guide national programs. This service provides important opportunities to represent environmental issues that are important for the health of Oregonians.

Injury, Treatment and Recovery

• Identified proteins that coordinate nerve growth and muscle innervation during normal development and following injury.By determining the mechanisms of action of these proteins, we can develop new strategies to speed recovery, or even inhibit damage, from neuromuscular injuries, the major cause of workers' compensation costs in Oregon.
• Discovered that mutations in the protein Neuropathy Target Esterase (NTE) increase the susceptibility to workplace neurotoxicants, including pesticides, by interfering with cell membrane composition and cell signaling leading to neurodegeneration or early aging.
• Discovered a compound that blocks channels in the brain that can provide a novel way to reduce the impact of Alzheimer's Disease. Alzheimer's Disease will affect 125,000 Oregonians by 2025.
• Best practices for pain management in patients with lower back pain. Researchers associated with the Oregon Institute of Occupational Health Sciences have documented the prevalence and comparative effectiveness of high-dose opioid use compared to other techniques used in the management of lower back pain. Lower back pain is one of the greatest expenses to workers compensation claims in Oregon.

Outreach, Education, Dissemination

• Information and outreach serves the our mission by interfacing with our Oregon stakeholders to provide opportunities for education, translation of the Institute's research and individual consultation.
• Resources available to Oregonians: Scientific expertise;webinars;OccHealthSci resource directory, "Oregon &the Workplace" blog;social media;newsletters. Through these means we have provided the following programs and accomplishments (through 2014): 
• Toxicology Information Center has provided individualized no-cost consultation on occupational safety and health on a free-to-Oregon call-in phone line (150-250 calls answered per year for over 15 years).
• Health and Safety Symposia provided in Oregon (2 per year for 22 years).
• Let's Get Healthy! Lending Library wellness training and specific feedback on risks and healthier lifestyles that has been used in 20 Oregon communities is available for broad dissemination in Oregon workplaces.
• Summer Internships for College Students supported 10-15 interns/year for 22 years in the largest OHSU summer internship program and perhaps largest in the state.
• Exhibits and Presentations at all OR OSHA conferences + regional meetings for over 12 years.
• Collaborations with government agencies, universities and associations throughout Oregon and the Northwest.
• Investigation and Outreach on Emerging Issues led to the discovery of a hair smoothing product with undisclosed high levels of formaldehyde that was reformulated for use in the US and banned in some countries due to our initial discovery. 

  

2012-2013 Highlights

Occupational Health Sciences brings federal dollars into the Oregon economy: We receive base operations funding from the Oregon Workers' Compensation System, and we leverage these funds to obtain federal and other research dollars. For every dollar invested by the State's Workers' Benefit Fund in 2012 and 2013, our scientists brought an average $1.70 and $2.40, respectively, of federal grant funding into the Oregon economy. Federal dollars for research in Oregon have a significant positive impact on the state's economy. Expenditures for goods and services, as well as the salaries of scientific and support personnel, produce a multiplier effect on the purchase of goods and services and creation of businesses that support the needs of Oregon's research institutions. Research coming out of the Institute can have a positive impact on the state's economy from new technologies and jobs that spin off from productive research.

Total Worker Health: Improving Workforce Safety, Health, Wellness and Wellbeing 

The Oregon Healthy Workforce Center (OHWC), a National Institute for Occupational Safety and HealthCenter of Excellence in Total Worker Health™, is an affiliation of Oregon Health &Science University's Oregon Institute of Occupational Health Sciences (OHWC home) and Health Promotion and Sports Medicine, Portland State University's Occupational Health Psychology program, the University of Oregon's Labor Education Research Center, Oregon State University's College of Public Health and Human Sciences and the Kaiser Center for Health Research.

OHWC faculty and staff are developing and evaluating Total Worker Health™intervention programs that integrate safety, health, wellness and wellbeing into integrated or associated programs designed to reduce injuries and improve wellness. They accomplish this by increasing healthy eating and exercise and reducing work stress through workplace interventions. The OHWC serves as a resource for western states and supplements the other Centers of Excellence in New England (Connecticut/Massachusetts), at Harvard and Iowa.

The OHWC's theme is intervention effectiveness using team-based and technology-based interventions to promote and protect health, and is designed to be disseminated broadly to the workplace. The OHWC's overarching conceptual model predicts that interventions will lead to changes in knowledge and psychosocial factors that mediate or moderate hazard reductions and behavior change. This will in turn produce hazard reductions, safer work behavior, improved lifestyle choices, and better psychological and physical health. The OHWC is the only Center focusing on intervention effectiveness, successfully conducting randomized trials of innovative interventions and adding value with a cross-study database (Data Repository) of common measures across projects.

The OHWC program consists of the following four research projects, two initially conceptualized as translational projects, educational programs and outreach that are interrelated.

Research Projects

Creating Health and Safety "Communities of Practice" for Home Care workers –Dr. Ryan Olson is using a peer-led scripted curriculum to organize home care workers into neighborhood-based teams that provide education and social support for improving lifestyle (e.g., diet, exercise) and safety behaviors. The program is named COMPASS (COMmunity of Practice And Safety Support). In partnership with the Service Employees International Union Local 503 and the Oregon Home Care Commission, the Olson team developed and pilot-tested COMPASS. Pilot study team meetings were well attended (90% attendance), rated as enjoyable, and produced large knowledge gains. The intervention produced statistically significant improvements in well being, fruit and vegetable consumption, safety compliance scores and counts of specific safety actions in homes, including the adoption of new ergonomic tools (example shown here). During 2013, over 140 participants were enrolled in a randomized trial of COMPASS that includes measurement of health and safety factors at baseline, after 6 months, and after 12 months.

Safety &Health Improvement Program (SHIP) –Dr. Leslie Hammer (PSU) is training supervisors to use a team-based approach to restructure work processes to make them more efficient and support balance in employee's work-family demands, thus reducing stress and improving safety and wellness in City of Portland construction workers. The intervention included a supervisor computer-based training component that focused on supervisor support for work-life and safety;a supervisor behavior tracking component to increase the transfer of the computer-based training to on the job behaviors;and a team-based component that involved facilitated sessions aimed at the reduction of low-value work within the work group to allow more time to encourage supportive behaviors related to safety and health. SHIP was delivered to 10 group supervisors and teams at the Portland Water Bureau and 12 groups at the Portland Bureau of Transportation in 2012. Following the intervention, 388 participants completed assessments of the effectiveness of the intervention at 6 months and 336 participants completed the assessments at 12 months. In addition, 16 groups of controls received SHIP training in 2013. SHIP identified psychosocial risk factors and health and wellness outcomes within this population including the prevalence of injury, unhealthy levels of body fat, and at-risk blood pressure.

Health promotion intervention to reduce health risks among correctional officers (DOC) –Dr. Kerry Kuehl (OHSU) is using a 12-week team-based peer-led approach to improve lifestyle (e.g., diet) choices and safety (e.g., ergonomic issues) in corrections workers. 210 baseline risk assessments on correctional officers from the Oregon State Penitentiary, Oregon State Correctional Institute, Columbia River Correctional Institution and Santiam Correctional Institution were completed in 2012. Post-intervention testing in 2013 demonstrated significantly lower blood pressure, total cholesterol, percent body fat, and improved dietary behaviors among the intervention group as compared to the control group.

Safety and Health Promotion in Young Workers (PUSH) –Dr. Diane Rohlman is using internet-delivered training to foster healthy lifestyle choices and safe work practices in young summer workers in a Parks and Recreation department, and enhancing dissemination by using social media. In 2012, Dr. Rohlman conducted surveys with 210 Portland Parks and Recreation summer youth employees, developed online training for use on social networking sites (Tumblr, Facebook, Pinterest), piloted it with 700 young workers, and recruited 300 young workers into a randomized control trial. In 2013, young workers who received the PUSH training significantly increased knowledge of safety and health immediately following training and at 2 months post-training. Reaction scores from participants who took the PUSH training indicated 59% of young workers "really enjoyed participating in the training" and 60% agreed that the training was "extremely useful for improving [their] health and safety." Additionally, 63% reported changing one or more of their behaviors as a result of participating in the training program, and 67% agreed they would highly recommend the training to their coworkers.

Supervisor training to promote health/safety in construction (Latino+non-Latino) - Dr. Kent Anger is enhancing supervisor team building and training skills, supported by behavior tracking technology, to motivate their employees to adopt healthier lifestyle choices and safer work practices, in Latino and non-Latino supervisors in the construction industry. Funded in 2012, Dr. Anger developed the training and a structured 12-week approach to wellness for employees (pictured). Reactions to the wellness training were positive in 9 International Union of Painters and Allied Trades apprentices and improvements in several wellness measures and team cohesion were seen in the apprentices.

OHWC Pilot Projects funded in 2012 and 2013 

Be Active, Work Safe: A Novel Program for People with a Disability –Drs. Laurel Kincl and Simon Driver (OSU) are working to improve the health and safety of workers with disabilities through the development, testing and dissemination of a web-based intervention that integrates basic occupational health and safety skills into an evidence-based health promotion model. Experts and individuals with a disability evaluated the preliminary testing of content and delivery of the Be Active, Work Safe program. Based on the feedback, changes to the organization (e.g., participant progression through the program), layout (e.g., navigation), and content (e.g., behavior change activities) were made to better meet the needs of individuals with a disability in 2013.

Family-Supportive and Safety-Supportive Supervisor Behavior Training in Corrections Personnel – Dr. Charlotte Fritz is conducting a trial of a family and safety-supportive supervisor behavior training to reduce employee stress and increase employee work-life balance, well being, and safety and health behaviors in corrections personnel. This project was funded in 2013.

OHWC Outreach and Education

Outreach is provided through 1) traditional paper-based newsletters and annual reports that are also electronically available, 2) exhibits at 10-15 practitioner and scientific meetings per year, 3) blog, facebook and twitter postings, 4) CROETweb resource directory (~70,000 hits in 2013), 5) leading sponsorships of wellness conferences leveraging Oregon Institute of Occupational Health Sciences funding, to promote Total Worker Health™. Some of the highlights of our Outreach activities include: 

• Held a Partner's Luncheon in 2012 that drew over 130 registrants from diverse industries, government and labor addressing return on investment of wellness programs. 
• In 2012-13, outreach coordinators Dede Montgomery and Steve Hecker brought major national/international speakers on Total Worker Health™(Ron Goetzel, Larry Chapman, Dov Zohar, Joseph Hurrell, Arla Day, Sandy Hershcovis, Steven Shea, Orfeu Buxton) to the OHWC Partners Luncheon, Occupational Health Psycholoy Summer Institute, and Symposia/webinars. 
• Recruited 8 summer interns at the Oregon Institute of Occupational Health Sciences in first two years –the best applied research poster award was received by OHSU interns in 2012, 2013. 
• In 2013 the OHWC presented a peer-reviewed symposium describing research projects and ongoing data collection at the International Work, Stress, and Health conference in Los Angeles, CA. 
• Presented invited seminars at regional Centers to increase visibility and understanding of Total Worker Health™(University of Washington, Washington State University, WESTon). 
• Presented invited seminars at other NIOSH Centers outside the West (e.g., Mountain and Plains ERC, NIOSH Cincinnati Total Worker Health™Seminar series). 
• Presented at National meetings to increase visibility of Total Worker Health™(e.g., Work, Stress, and Health, American Public Health Association).

Collaborative Activities with Other NIOSH Total Worker Health Projects in 2012-2013

• Established connection with 2 NIOSH Total Worker Health Centers (New England, Iowa) to develop a multi-center total worker health collaboration intervention for emergency services and corrections workers.
• In 2013, a national conference on corrections research needs was planned with other Centers in New England and Washington state.

OHSU Let's Get Healthy! Program

Let's Get Healthy! is a popular education and research exhibit that travels around the state (and nation) to help the public learn about their own health and to collect data that is available for group analysis. Participants receive immediate personalized (multi-lingual) health feedback while their anonymous, linked health information becomes part of a population database available for use in support of school projects, community and workplace wellness policy decisions, and research opportunities. The program accomplishes this by providing an interactive, scientifically-based educational and research experience to schools, communities and workplace partnerships. In 2013, Let's Get Healthy! 

• Held 15 events in Oregon and two in California where 4,718 people partiticipated in the research study, and trained 328 volunteers to assist with the research  study. 
• Conducted 18 events in Oregon through lending library loans, reaching an additional 1395 Oregonians. 
• Held two teacher professional development sessions (56 contact hours each) on 1) epigenetics and 2) data visualization for the classroom. 
• Enrolled an additional 485 people in a longitudinal study of cardiovascular health in women.

Sleep and Shift Work: Impact on Health, Safety, and Productivity

Adequate sleep is not only essential for our safety and productivity but also for our overall well-being and health. It is well known that a tired person is more likely to be involved in an accident, have reduced motivation, poor mood, and strained relationships at home and at work. More recently it has become evident that there are more chronic diseases such as obesity, diabetes, hypertension and stroke among people who sleep less. Unfortunately, sleeping too little is easy and sometimes hard to avoid. Sleep can be disrupted by stresses at home and work, lifestyle choices, by occupational constraints such as shift work, and by sleep disorders themselves –such as sleep apnea and insomnia. 

With night-shift work, we try to fight our natural biological tendencies to remain awake when we are normally expecting to sleep, and to sleep when the body is designed to be most alert. These challenges can be large. But sleep disorders can be treated, sleep habits can improve, and workplace schedules and the internal body clock (the circadian pacemaker) can both be manipulated to improve the health and productivity of shift workers.

At Occupational Health Sciences, we are developing a research program to study all aspects of these large and common sleep problems and to implement solutions, ranging from screening for and treating sleep disorders, educating communities and workforces about 'sleep health', to implementing interventions designed to improve sleep, safety, productivity and overall health in the workplace.

In order to adapt to different shift work schedules, we need to understand how the body clock works, and how to reset the timing of the clocks in the brain and throughout the body so that we function optimally. By studying animals, Dr. Charles Allen and his research team are studying how the internal circadian pacemaker in the brain functions, and the neural mechanisms that govern re-setting this internal body clock. Dr. Doris Kretzschmar's research group uses fruit-flies (Drosophila) to study how circadian rhythms and genes that regulate the circadian system affect healthy aging and neural degeneration, typical of Alzheimer's disease. By performing laboratory studies in humans, Dr. Steven Shea is building on some of this animal research to determine the extent to which similar body-clock and sleep loss issues may help explain the adverse health effects of shift work.

Dr. Matthew Butler is a new faculty member whose research is directed towards understanding the synchronization between environmental cues, the brain's 24-hour clock, and the  clocks in other tissues like the heart and liver.

Dr. Mitchell Turker's research group is examining how sleep loss and circadian rhythms influence the changes in genes caused by the environment (epigenetics).

Other Institute researchers, including Drs. Ryan Olson, Jackie Shannon and Kerry Kuehl (Institute affiliate), are translating these laboratory studies to perform monitoring and interventions onsite in a number of occupations. Specifically, they are examining the impact of work on sleep in nurses, truckers, information technology workers, and correctional officers, and are applying interventions to improve sleep, safety, and health in some of these groups.

 Finally, Occupational Health Sciences' Let's Get Healthy! Program is a popular interactive exhibit used in the workplace, schools and community health fairs to educate people about  many health issues, including sleep health. Let's Get Healthy! is also used for data collection in these groups to help with ongoing research.

Thus, Occupational Health Sciences is developing a research theme related to improving health, safety and productivity among workers by targeting sleep and shift work. This theme  spans basic research in animals, laboratory research in humans, and applied workplace interventions. All of these research endeavors complement each other and improve overall likelihood of success in this area of The Institute's mission.

Exposure: Consequences and Prevention

Many occupational exposures that lead to adverse health effects are preventable or can be minimized. For example, we know that prolonged unprotected exposure to sunlight causes skin cancer, and that chronic exposure to toxic chemicals can adversely affect a variety of organs within the body. To reduce risks associated with such exposures, Institute researchers are using cutting edge science to:

• Characterize the adverse effects of exposure.
• Determine the mechanisms by which these exposures produce adverse effects. 
• Apply that information to develop specific worker training and other innovative strategies to help prevent the exposures in the first place and to reduce the adverse consequences if exposures do occur.

The role of exposure in cancer, aging and other diseases

Throughout life, humans are exposed in both their personal and occupational environments to ultraviolet light irradiation, ionizing radiation and a multitude of chemicals that can lead to debilitating diseases, including cancer. This area of investigation is the subject of two investigators in the Institute, Dr. Amanda McCullough and Dr. Stephen Lloyd. One part of Dr. McCullough's group studies how chemicals such as formaldehyde (which is used extensively in industry in Oregon) cause DNA damage and disease. Her research team has studied how exposure to formaldehyde produces DNA damage that manifests as chromosomal alterations that resemble those seen in certain cancers. Her group is probing the genetic basis by which cells respond to the formation of formaldehyde-induced DNA-protein cross links.

Dr. McCullough's group also leads a highly translational research effort that is designed to prevent skin cancers that arise as a consequence of sunlight exposure. This strategy relies on significantly enhancing the DNA repair capacity of the skin's most susceptible cell population such that these basal keratinocytes can rapidly repair the sunlight-induced damage and maintain a healthy immune environment in the skin. Together with Dr. Lloyd's group, they are hoping to partner with clinicians at OHSU to treat organ transplant patients who are extremely susceptible to this form of cancer.

Dr. Lloyd's research group not only investigates how occupational chemical exposures affect human health, but also how drugs administered as part of therapeutic protocols also cause genetic damage. For example, many of the chemotherapeutic drugs that are used to treat cancers form the same type of DNA damage caused by industrial pollution and occupational toxicants. The Lloyd laboratory has shown these chemicals can cause DNA damage that, if not repaired, can lead to further genetic changes that further promote disease.

Dr. Lloyd's group also has discovered that oxidant stress which results in specific DNA damage can serve as a trigger for alterations in energy metabolism. They have discovered that changes in DNA repair mechanisms can significantly alter how the body processes caloric intake and can shift the metabolism toward a fat storage mechanism. These studies are providing novel insights into understanding the complexities of the ongoing obesity epidemic.

Mutagenesis is the study of how the function of genes can change due to alterations in the DNA sequence. In contrast, epigenetics is the study of how the function of genes can change even without changes in the underlying DNA structure. Environmental exposures can cause both mutational and epigenetic changes. Dr. Mitchell Turker is researching the mechanisms by which such changes in 'gene expression' from these exposures cause disease. The Turker laboratory has:

• Developed new approaches to demonstrate the mutagenic effects of exposure to ionizing radiation, such as from radon exposure or X-rays.
• Developed new assays that foster discovery of new drugs for the treatment of cancer and other diseases.
• Shown that low oxygen conditions and ionizing radiation exposures cause epigenetic changes. 
  

Agriculture contributes hugely to the Oregon economy. Pesticides are commonly applied to prevent crop losses, but exposure to high levels of many of these pesticides can damage the nervous system of humans and other animals –they are 'neurotoxic'. Drs. Diane Rohlman and Kent Anger are measuring the exposures and working to reduce or prevent adverse effects from pesticide exposure. They have demonstrated that:

• Repeated workplace exposure to the commonly used insecticide called chlorpyrifos can affect the nervous system based on tests of memory and attention. Dr. Rohlman's and Anger's research team quantified the relationship between the exposure level and this neurotoxic effect, i.e., the dose-response relationship. Chlorpyrifos now joins only six other   human neurotoxicants whereby chronic or repeated low-level exposures have been shown to cause such neurotoxic effects based on behavioral testing.
• In parallel research, Dr. Doris Kretzschmar's team, using the fruit fly (Drosophila) as a model, discovered that the activity of certain proteins is reduced by exposure to a broad class of organophosphorus chemicals, like the pesticide chlorpyrifos.
  

Dr. Desire Tshala-Katumbay is advancing our understanding of toxicant-induced neurodegeneration through basic and global translational research;his research team has:

• Discovered the specific chemical structures within industrial hydrocarbon chemicals that induce neurotoxicity. These findings will aid the development of test methods for diagnosing and preventing chemically-induced neurological disease.
• Examined the neurotoxic effects of cyanide. Cyanide is a chemical used in many industrial settings, in some warfare settings to which US military could be exposed, and occurs during digestion of some foods, such as the Cassava root. From studies in both Oregon and the Democratic Republic of the Congo in Africa, Dr. Tshala-Katumbay's team has determined the far reaching neurotoxic effects of exposure to dietary-derived cyanide, and they have examined how specific genetic differences between individuals results in different degrees of susceptibility to these neurotoxic effects. These studies will aid in the prevention and treatment of disease from exposure to a variety of industrial and other compounds with cyanide-like activity.
• Exploited the physico-chemical properties of neurotoxicants to develop a peptide-targeting system that is able to deliver small molecules selectively to neurons, thereby circumventing the hurdles posed by the blood brain barrier in the routine exercise of drug administration. The peptides may be injected intramuscularly.

Strategies and Solutions for Vulnerable Workers

Vulnerable workers, including young workers, agriculture workers and solitary workers, have special challenges that may contribute disproportionately to Workers' Compensation costs. Institute scientists are developing unique programs to address the needs of vulnerable workers and prevent adverse consequences. Workplace stressors, physical and emotional, as well as the threat of physical violence, are significant hazards to employee health and safety. These stressors can be particularly hazardous to solitary workers who face workplace hazards alone and without the support of co-workers. Dr. Kent Anger, in collaboration with Dr. Nancy Glass of Johns Hopkins University:

• Developed an intervention program to teach home care workers how to de-escalate potentially violent situations in the workplace. The program is being evaluated to determine the extent to which it can be extended and disseminated widely to workers in other occupations.

Dr. Diane Rohlman is interested in protecting the health and safety of vulnerable workers, including: agricultural workers, who are subjected to a variety of stressors, including physical and chemical hazards, limited access to medical care, and seasonal variations in work-demand that lowers their sense of control in the workplace;young workers, who suffer twice as many non-fatal injuries at work than older workers due in part to their lack of training and assertiveness;and nail salon workers, the vast majority of whom are immigrants, who are exposed daily to a variety of chemical hazards. In 2012, Dr. Rohlman:

• Completed a pilot project examining workplace stress among farmworkers in Oregon.  
• Conducted a survey of young workers to characterize their health promotion and workplace safety activities.
• Developed workplace safety and wellness activities to be used with immigrant and non-immigrant supervisors of construction workers. Methods were tested in electrical and painter apprentice programs.
• Helped coordinate ongoing health and safety activities in collaboration with social service agencies and the Oregon Collaborative for Healthy Nail Salons on behalf of nail salon workers.

Dr. Ryan Olson is developing and testing safety and health interventions for solitary workers in demanding occupations, with the goal of reducing the unique hazards of isolated work, preventing injuries, and promoting health. Employees, such as truck drivers or home health care workers who work alone, are among the most at risk for on the job injuries. 

In 2012-13, Dr. Olson:

• With funding from the National Heart Blood and Lung Institute (NHLBI), partnered with five trucking companies, including companies from Oregon and the Pacific Northwest, to launch the largest randomized controlled trial of a worker health intervention for truck drivers in U.S. history (over 450 drivers from 22 terminals were enrolled). The intervention program, named SHIFT (Safety &Health Involvement For Truckers), is hosted on a mobile-friendly website and involves competition, training, health coaching, and self-monitoring. Results of this trial will improve the overall health, safety, and wellbeing of people, like truckers, who work in environments with significant barriers to healthy eating, exercise, and sleep. 
  
• As a member of the Oregon Healthy Workforce center (OHWC), developed a new team-based total worker health intervention for home care workers that may become a model program for dissemination to other states. 

Injury, Treatment, Recovery and Prevention

Physical injury is the largest contributor to workers' compensation costs in Oregon. In 2009, more than 48,000 Oregonians were injured on the job. Of those injured, 52.6% either lost multiple days from work, were placed on work restriction, or transferred to other duties. Nationally, the total annual cost for musculoskeletal disorders alone has been estimated to exceed 54 billion dollars. To reduce this enormous burden on worker wellness and productivity, Institute scientists are conducting innovative research to better understand: 

• Causes of workplace injury, so the most effective strategies to prevent traumatic injuries can be developed. 
• Effectiveness of treatments, to optimize returning injured workers back to full employment. 
• Recovery from injury, which will enable development of new drugs and therapies to restore function to injured nerves and muscles. 
• Prevention strategies to reduce injury frequency to eliminate as many injuries as possible.

Dr. Ryan Olson heads the Oregon Occupational Fatality Assessment and Control Evaluation (OR-FACE) Program, a National Institute for Occupational Safety and Health sponsored program designed to prevent occupational fatalities through surveillance, targeted investigation, assessment, and outreach associated with traumatic work-related deaths. In 2012-13, Dr. Olson and OR-FACE staff:

• Continued to produce Annual Reports of fatality trends and abstracts, as well as in-depth fatality investigation reports for selected cases. In prior years 2010 and 2011, there were 50 and 59 work-related fatalities in Oregon, representing fatality rates per 100,000 workers of 2.8 and 3.3, respectively.
• Developed and field-tested new evidence-based guides that allow supervisors to present effective safety "tool box talks" to prevent occupational fatalities and reduce the risks that lead to them.
• Published their research, in collaboration with partners at the Oregon Health Authority, on elevated risk of workers over the age of 65 to be killed in transportation-related events. This included analyses of possible contributing factors such as older worker employment in hazardous occupations, as well as factors that could be targeted for intervention, such as the organization of work in small businesses.

Neuromuscular injuries are an overwhelming cause of occupational disability nationally. Dr. Bruce Patton, who is interested in understanding how nerves and muscles develop and grow as well as respond to injury, has revealed previously unknown mechanisms of nerve and muscle cell development that may someday play key roles in establishing new therapies for restoring function in injured workers who would otherwise lose their ability to work. In 2012, Dr. Patton's laboratory has discovered:

• That a cell-adhesion molecule, known as CD44, is required for specific developmental stages of growth and differentiation in nerves and their support cells.
• CD44 is also required for normal growth and regeneration of small peripheral nerve axons.
• These findings are enlightening our understanding of how nerves and muscles might be encouraged, through innovative therapies, to grow and regenerate after injury.

Chronic lower back pain is one of the most frequently encountered ailments of individuals during their working years, and research on the effectiveness of treatment is critical to reducing costs and improving overall worker health and productivity. Dr. Richard Deyo has a long-standing research interest in measuring patient function as it relates to the management of low back pain and has published a variety of influential articles on the effectiveness of various treatment modalities. In 2012, Dr. Deyo:

• Examined the value of routine imaging in low back pain.
• Found that new guidelines for diagnostic imaging could actually improve outcomes, decrease risk, and reduce costs.
• Compared the efficacy of surgical approaches for treating back pain. 
• Discussed complementary and alternative medicines to treat back and neck pain.
• Identified dangers of the growing use of opioids to treat back pain.

    In 2013, Dr. Deyo:

Co-chaired an NIH Task Force on Research Standards for Chronic Low Back pain, with recommendations to be published in 2014.

• Evaluated new technologies for treating spinal stenosis and vertebral fractures.
• Assessed the cost implications of complementary and alternative medicine (CAM) treatments for low back pain (e.g. acupuncture, massage).
• Evaluated the impact of prescribing narcotic painkillers for chronic pain.
• Identified complication rates among older adults having various types of spine surgery.
• Examined the influence of workers compensation coverage policies on rates, complications, and costs of spine surgery.

Outreach and Education

The Oregon Institute of Occupational Health Sciences is proactively engaged in providing timely occupational health and safety information to employees, employers, health and safety professionals, doctors, nurses, and the general public.

The Web: A Powerful Medium for Public Outreach

The Institute uses the full range of available web technologies to provide the public with the latest in health and safety information. 

CROETweb.com, Occupational Health Science's widely respected health and safety resource webpage, contains links to over 1,200 occupational safety and health resources focused on day-to-day workplace issues. 

• 2012 total page views: 80,945
• 2013 page views: 63,000 
• Most widely viewed pages: safety and toolbox talks
  
  
• Our monthly e-newsletter keeps users up-to-date on happenings at the Institute as well as on new web content as it is added.  Issued monthly e-newsletters to approximately 1,000 Oregon stakeholders.

Oregon and the Workplace blog.

• Received 12,157 views in 2012 averaging 33 visitors per day, with each visitor spending an average of 4 minutes per visit. In 2013, just under 32,000 page views were received with viewers reading an average of three blogs per visit. 

Twitter

• The Institute currently has 250 followers on Twitter, including numerous international occupational safety and health organizations. Twitter "re-tweets" extend the Institute's message to thousands of new viewers.

Facebook

• As of 2013, the Institute has 130 "likes".
• Occupational Health Sciences website –where viewers can learn about the Institute, its people,research, and much more.
• Total 2012 page views 32,382, 2013 page views 54,600
• Most viewed pages: 1) summer students;2) faculty pages;3) emerging issues.

Symposia

Occupational Health Sciences provides at least two health and safety symposia per year, one sponsored jointly with the PSU Occupational Health Psychlolgy program. Topics are determined based on feedback from the Oregon occupational health and safety professional community. The Oregon Healthy Workforce Center also sponsors a luncheon that includes talks by authorities in the Health and Safety/Wellness field. The target audience includes health, safety and environmental professionals, although the targeted group varies based on the symposium topic. The Institute presented the following symposia in 2012 &2013:

• Workplace Aggression: Causes, Consequences, and Prevention. Presented by Occupational Health Sciences and PSU Occupational Health Psychology, November 2, 2012. 
• Green Chemistry, Safer Alternatives and Work. Presented by Occupational Health Sciences and Oregon Health Authority, June 15, 2012.
• Oregon Healthy Workforce Center Luncheon: An Authoritative Look at the ROI of Workplace Wellness Programs by Larry Chapman, September 14, 2012.
• The Changing Employment Relationship and Worker Well-Being. Presented by Occupational Health Sciences and PSU Occupational Health Psychology Program, November 15, 2013.
• Sleep and Shift Work: Impact on Health, Safety and Productivity. Presented by Occupational Health Sciences, June 14, 2013.
• Creating Excellence in Worksite Wellness: Taking Your Program to the Next Level. A Short Course at the Oregon Governor's Occupational Safety and Health Conference, March 7, 2013. Co-sponsored by Occupational Health Sciences, the Oregon Healthy Workforce Center, SAIF Corporation and the Portland Business Journal.

  Health and Safety Conferences

The majority of health and safety conferences that the Institute participates in are sponsored by OR-OSHA. Conferences are an important means by which we reach out to working Oregonians: Workers and businesses learn about Occupational Health Sciences and what we have to offer, and Institute personnel learn about the needs and concerns of workers and the industries that employ them. Our scientists are often asked to give health and safety presentations in addition to providing conference exhibits. The Institute also created new stakeholders by attending conferences sponsored by other organizations, including the American Society of Safety Engineers and the American Heart Association Wellness Summit. Overall, conferences represent a tremendous networking opportunity for the Institute's outreach personnel, allowing us to travel to and meet Oregonians in all corners of the state.

Toxicology Information and Occupational Health and Safety Resource Centers

The Toxicology Information Center (TIC), directed by Dr. Fred Berman, and Occupational Health and Safety Resource Center, directed by Dede Montgomery, CIH, provide a vital service to citizens and professionals by responding to their inquiries about workplace safety and hazards of exposure to chemicals and other agents. The goal is to provide up-to-date information in a form that is understandable and useful. Dr. Berman and Ms. Montgomery handle hundreds of consultation requests from occupational safety and health professionals, business owners, government agencies, physicians and nurses, the media, and the general working public. Inquiries cover a variety of issues. Chemical agents of concern include solvents, heavy metals, and pesticides. Physicians often seek information on a variety of potentially occupation-related health complaints. Each request takes from less than an hour up to several days to respond to fully. The TIC is open to calls from 7:30 a.m. to 5:00 p.m., Monday through Friday, and to walk-in visitors from 7:30 a.m. to 3:30 p.m., Monday through Thursday. Patrons have access to a variety of resources, including computers, databases, government reports, textbooks, and journals that are devoted to toxicology-related issues and occupational safety and health. In addition to the TIC, Dr. Berman serves as consultant to the Oregon Department of Agriculture's Pesticide Analytical and Response Center (PARC), which is legislatively mandated to address pesticide-related incidents in Oregon that have suspected health or environmental effects (http://www.oregon.gov/ODA/PEST/parc.shtml). Dr. Berman is also a co-investigator with the National Pesticide Information Center (NPIC), a U.S. Environmental Protection Agency-sponsored project operated cooperatively with Oregon State University. NPIC provides objective, science-based information about pesticides and pesticide-related topics to enable people to make informed decisions about pesticides and their use (http://npic.orst.edu/).

 

2010 CROET Highlights

CROET brings federal dollars into the Oregon economy

CROET receives base operations funding from the Oregon Workers

Workplace studies and applications research

CROET conducts workplace surveys so that prevention and research needs can be identified, and applications research to bring the benefits of science to the workplace floor. It also reaches out to provide education and information to the Oregon workforce and beyond.

Oregon Fatality Assessment and Control Evaluation (OR-FACE) Program

The Oregon Fatality Assessment and Control Evaluation (OR-FACE) program is designed to prevent occupational fatalities through surveillance, targeted investigation, assessment, and outreach that are associated with traumatic work-related deaths in Oregon. Headed by Gary Rischitelli, MD, JD, MPH, FACOEM, OR-FACE is one of only nine state-based FACE programs supported by a cooperative agreement with the National Institute for Occupational Safety and Health (NIOSH). OR-FACE preliminary data for 2010 indicate 44 work-related fatalities in 42 incidents. In 2010, OR-FACE continued to collaborate with the Oregon Young Employee Safety (O[yes]) coalition, attended meetings and events with educators and safety professionals, and gave presentations related to OR-FACE activities and findings. OR-FACE produced its 2007 Annual Report, one investigational report about a temporary mill worker who was killed after he fell down a man lift shaft, and a brochure titled 

Safety and Health Interventions for Lone Workers

Dr. Ryan Olson

Two Vulnerable Populations from Occupational Exposure to Pesticides

Assessment of Health Effects of Children Living in an Agricultural Community

There is increasing concern regarding the use of pesticides in agricultural communities and potential impacts on public health. Organophosphate (OP) pesticides are among those of greatest concern, due to their persistence once in the home and their established neurotoxic effects. Neurobehavioral tests have identified deficits in adult populations exposed to and poisoned by OP pesticides on farms. However, little research has examined OP pesticide exposure in children. While the neurotoxic effects of acute exposure to OP pesticides are well established, chronic low-level exposure are not well studied in adults and very few studies provide evidence of neurobehavioral deficits in farmworker children compared to controls. Children of farmworkers are presumed to be exposed to pesticides throughout development, and this exposure may produce subtle health effects that would not be detected by clinical examinations nor recognized by parents. A study conducted by Dr. Diane Rohlman and funded by the National Institute of Occupational Safety and Health (NIOSH) through the Pacific Northwest Agricultural Safety & Health Center, examines health effects in children living in an agricultural community to determine if they are associated with current home pesticide exposure or an estimate of lifetime exposure. Children

Assessing Vulnerability of the Adolescent Brain to Organophosphorus Pesticides

Organophosphorus (OP) pesticides are used extensively in agriculture throughout the world. There is compelling evidence that repeated (chronic) low-level occupational and environmental pesticide exposures are associated with neurobehavioral performance deficits in adults. Adolescents working in agriculture are exposed to the same risks as adults but it is unknown whether their risk is equivalent to or greater than that of adults. Experimental animal studies indicate that the developing brain is more susceptible to the neurotoxic effects of OPs than the adult brain, and low-level exposures to OP pesticides cause significant neurobehavioral deficits in animal research. Adolescents (ages 15-18) in Egypt are legally hired as seasonal workers to apply pesticides to the cotton crop. This pesticide application is highly regulated and standardized across Egypt, and is limited primarily to OP pesticides (& pyrethrins), generally chlorpyrifos. This provides a unique opportunity to examine the impact of a highly consistent known OP pesticide exposure on the adolescent and their developing nervous system. Recent research in this adolescent Egyptian population found increased reports of symptoms, depressed cholinesterase, and extensive neurobehavioral deficits in adolescents applying chlorpyrifos (vs. controls). While we have preliminary evidence of some of the highest reported exposure concentrations from dermal patch and urinary samples in adult Egyptian applicators, there is no quantitative exposure data available in adolescents. Furthermore, what is not established is if these exposure-related nervous system effects accumulate across time, if the effects increase with repeated exposure, and if they reverse after exposure ends. The goal of this project is to examine the dose-related response of the adolescent nervous system to OP pesticides, to determine if repeated exposures produce a progressive deficit and to determine if this deficit is reversible.

Computer-based Supervisor and Worker Protection Training

Study Provides Training in Most Oregon County Governments

Intimate partner violence (IPV), commonly known as domestic violence, is a problem throughout the world. An estimated 36% to 75% of employed abused woman are monitored, harassed and physically assaulted by their partners or ex-partners while trying to get to work and while at work. Based on interviews of 300 victims and 200 perpetrators of IPV collected in Oregon, we developed interactive training to increase knowledge on how to create supportive and safe workplace for IPV victims, change perceptions and develop an intention to address domestic violence that spills over into the workplace. We conducted a pilot test of that training in a sample of managers and supervisors from a moderately large city and a medium-sized bank in northwestern Oregon, and modified the training based on responses. All participants reacted positively to the training, and there was a significant improvement in knowledge between pre- and post-training test performance (72% versus 96% correct), effect size (d) = 3.56 which is a very large (positive) effect size for workplace training. This work was published in 2010. In order to evaluate the effectiveness of this training and to develop a way to scale the training for delivery more widely, we are providing the training to supervisors and managers in a sample of small businesses throughout Oregon in three formats: Written Brochure, delivery of the training on the internet, and an interactive computer-based presentation. Contemporaneously, we recruited managers and supervisors in 27 (75%) of Oregon

Preventing Violence in Home Care Workers

Workplace violence is well documented in hospitals and clinics. Little is known, however, about homecare workers who deliver medical services in peopleWe held focus groups and individual interviews with 83 Oregon homecare workers (all female), 99 Oregon case managers and other Department of Human Services employees and 11 consumer employers receiving in-home care during 2009-2010. We recruited the homecare workers in urban and rural communities throughout the state of Oregon through advertisements at professional training events and in SEIU Local 503 newsletters; case managers who oversee each through Oregon

Outreach and Education

CROET has been proactively engaged in providing timely occupational health and safety information to employees, employers, health and safety professionals, doctors and nurses.

CROETweb.com

CROETweb.com is an occupational safety and health resource directory that contains links to over 1200 occupational safety and health resources focusing on day-to-day workplace issues. CROETweb serves thousands of users who regularly bookmark this resource, those who subscribe to the monthly electronic newsletter, and those seeking information by search engine (e.g. Google) for occupational health and safety topics on the web. It is widely recognized and respected by industrial health and other safety professionals as well as the general public, based on feedback from user groups. CROETweb was accessed an average 11,000-13,000 times per month for a total of 123,352 hits in 2010.The most popular pages visited for 2010 included Materials for Safety Talks, Hospitality,  Construction and Office ErgonomicsNew topics 2010: Health Promotion & Wellness; Aging Workforce and numerous new subtopicsAs of the end of 2010, CROETweb contains 3855 links and 84 main topic pages.

Toxicology Information Center (TIC)

CROET

CROET

OSHA regulations require employers to maintain Material Safety Data Sheets (MSDS) for the hazardous chemicals used in their workplace. This often proves to be a difficult record-keeping task, and it can be burdensome to ensure that employees have quick access to health and safety information in the workplace when they need it. Since 1998, CROET

Health and Safety Training Symposia

CROET provides two health and safety symposia per year, one sponsored jointly with Portland State University. Topics are determined based on solicited and unsolicited feedback from the Oregon occupational health and safety professional community. The target audience includes health and safety professionals, occupational nurses and physicians, loss control specialists and human resource representatives, although the targeted group varies based on the symposium topic. The purpose of the symposia is to provide timely, up-to-date presentations, forums and discussions on workplace safety and health issues. CROET presented the following symposia series in 2010:Creating a Healthy WorkforcePresented by CROETFriday, June 4, 2010 at NECA/IBEW Training Center in Portland, ORWorkplace Accommodations & Return to WorkPresented by CROET and Portland State UniversityFriday, November 5, 2010University Place, Portland State University, Portland, Oregon

Regional Health and Safety Conferences

OR-OSHA sponsors the majority of health and safety conferences that CROET attends; these conferences are an important means by which CROET reaches out to working Oregonians. Workers and businesses learn about CROET and what it has to offer, and CROET personnel learn about the needs and concerns of workers and the industries that employ them. Moreover, CROET scientists are often asked to give health and safety presentations in addition to providing conference exhibits. Overall, conferences represent a tremendous networking opportunity for CROET outreach personnel. The following are safety and health conferences attended by CROET during 2009-2010:Western Pulp and Paper Workers Safety & Health ConferenceSouthern Oregon Occupational Health and Safety Conference2010 Northwest Occupational Health ConferenceCentral Oregon Occupational Health and Safety ConferenceOregon Small Business FairNorthwest Environmental Health ConferenceWestern Pulp and Paper Workers Safety & Health ConferenceCascade Occupational Safety & Health Conference2010 Women in Trades Career FairBlue Mountain Occupational Health and Safety Conference

OHSU Health Discoveries Program: Let

Let

Injury and Recovery of the Nervous System and Muscles

CROET scientists conduct basic research that examines the causes of injury to nerves and muscles in order to identify protective, preventative, and recovery methodologies for such injuries.

Nerve Support Protein Required for Normal Muscle Function

Damage to nerves and muscles is the primary cause of workplace disability in the United States. In a typical year, five million workers (4%) are injured on the job. Four million (80%) of these involve debilitating pain and/or dysfunction from neuromuscular injuries, including trauma, tears, strains, and musculoskeletal disorders (http://www.bls.gov). Nearly half require a lengthy recuperative period, substantially diminishing productivity and increasing medical costs to employers and employees. Dr. Bruce PattonEach skeletal muscle and nerve is composed of many individual fibers; the surface of each of fiber is covered by a thin, tough sheet of interconnected proteins, called a basal lamina (BL). The BL provides stability to what are some of the largest cells in the body. However, the BL also coordinates growth and functional differentiation during tissue development and after injury. How the BL encodes these activities, and how neuronal and muscle cells respond and interact through the BL, remains poorly understood. The laboratory of Bruce Patton has been testing the real (in vivo) function of BL components in nerve and muscle using genetic engineering methods in mice. Neuromuscular systems of all mammals, including mice and humans, are highly similar in structure, physiology, and response to injury.The primary component of nerve and muscle BLs is laminin-211, a self-polymerizing glycoprotein that provides the main framework of the BL. In humans, dogs, and mice, gene mutations that prevent laminin-211 expression also prevent the formation of the myofiber BL. Because these mutations also cause a severe, degenerative muscle disorder called type IA congenital muscular dystrophy, it has long been assumed that laminin-211 stabilizes the muscle fiber surface membrane during contractions by forming a structurally stable BL along the cell surface. However, in collaborative work with Dr. Rob Burgess (The Jackson Laboratory, Bar Harbor, ME), mutations in the laminin alpha2 protein (a component of laminin-211) were identified that disrupt the ability of laminin-211 to polymerize, but which result in very little dystrophy or muscle membrane damage (Patton et al., 2008, J.Cell Science, 121:1593). The results suggested that laminin-221 may stabilize the muscle surface by alternative mechanisms. To further test this idea, mice were developed which expressed a second polymerizing laminin in the mature muscle fiber BL, namely laminin-511. Laminin-511 is not normally expressed in mature muscles. Mouse muscles that co-expressed laminin-511 along with the normal laminin-211 isoform were normal in structure and function; laminin-511 is therefore not harmful. However, when over-expressed in dystrophic mice that lacked laminin-211, laminin-511 restored the integrity to the muscle fiber BL, but nevertheless did not prevent rapid degeneration of the muscle fibers. Thus, an intact BL does not, by itself, stabilize the myofiber membrane. This result combines with the previous work to strongly indicate laminin-211 supports the myofiber membrane by an alternative mechanism.To develop this idea, the formation of receptor complexes on the muscle fiber surface was compared in normal, laminin-211-deficient, and laminin-511-overexpressing mice. It was discovered that laminin-211 was uniquely active in stabilizing the form and molecular composition of the costameres, which are the main cytoskeletal attachment sites on muscle surfaces. While even non-polymerizing forms of laminin-211 were effective, laminin-511 was not at all effective. Further, it was discovered that during contractions, muscle membranes lacking laminin-211 did not properly fold at costameres, and that a BL of laminin-511 was unable to restore this folding. The results suggest that laminin-211 stabilizes muscles mostly by maintaining tight adhesion between the costamere complex and the intracellular cytoskeleton (which are required to prevent damage to the cell

Chronic Disease and Working Safety

Chronic disease takes a significant toll on our workforce just as it does in the broader community. CROET research seeks to discover causes of chronic diseases that are produced or exacerbated by workplace factors and identifies processes or procedures that can prevent or ameliorate those diseases and improve workplace safety.

Fruit Flies Are Aiding our Understanding of Alzheimer

Alzheimere of the hallmark features of Alzheimerhical concerns, studies in humans have obvious limitations. Therefore, the Kretzschmar lab uses a well-established biological model system, the fruit fly Drosophila, to model this condition. In previous work, the Kretzschmar lab created flies that express APP and produce Ar lab has used this system to identify genetic factors that influence the severity of these effects.In 2010, the Kretzschmar laboratory also used the Drosophila Alzheimer model for drug testing to find treatments that could eventually lead to increased quality of life and productivity of workers in retirement. They have identified a compound that blocks calcium channels as a potential therapeutic agent. This work was conducted in a collaborative project using models from cell culture to transgenic mice funded by the Dean

Sleep Deprivation Costs Oregon Workers and Oregon Businesses - Business Meets

Biology

Collaborating Investigators: Drs. Harvey Mohrenweiser; Jackilen Shannon; Ryan Olson; Diane Rohlman; Charles AllenFifty percent of the workforce arrives at work with some degree of sleep deprivation. Sleep deprivation, a consequence of non-traditional work schedules, biological disorders/sleep apnea and/or lifestyle, negatively impacts a workerSleep is regulated by two mechanisms: the circadian system generates 24-hour rhythms of sleep and homeostatic sleep processes whereby sleep pressure increases during wake and dissipates during sleep. Alterations in the timing of activity and rest disrupt the normal circadian system, with consequences for physiological and neurological function. Overnight operations pose a challenge; it is estimated that performance impairment on the first night of a worker

New Discoveries of Circadian Clock Function Aids Understanding of Sleep-Wake

Cycles

In humans, many physiological processes cycle with a period of twenty-four hours. These circadian rhythms are driven by an internal biological clock so that we are active during the day and sleep at night, which has significant ramifications in our 24-hour society. Approximately 20% of American workers have jobs that require them to work outside of the traditional 8-5 workday. These workers are therefore awake when their internal clock is telling them to sleep. Short-term disruption of the circadian rhythms can lead to higher rates of on-the-job accidents, impairments in cognitive function including poor decision-making, altered hormone activity, and gastrointestinal distress. Long-term disruption of the circadian system contributes to the development of breast and colorectal cancer, cardiovascular disease, mood disorders and a number of metabolic derangements including diabetes.A small brain region structure called the suprachiasmatic nucleus (SCN) contains a molecular time-keeping mechanism that drives biological circadian rhythms. This biological clock sends signals throughout the body that coordinate circadian rhythms in multiple tissues and organs. The long-term goal of our basic research program is to identify the cellular mechanisms underlying the generation and entrainment of circadian rhythms. Successful completion of our work will provide a better understanding of the mechanisms underlying regulation of circadian processes such as sleep. This knowledge can lead to better and more rational treatment of circadian-based sleep and mood disorders.Neuroactive peptides and the intracellular calcium concentration ([Ca2+]i) play important roles in light-induced modulation of gene expression in the SCN neurons that ultimately control behavioral rhythms. Two messenger molecules, vasoactive intestinal peptide (VIP) and arginine vasopressin (AVP), are expressed rhythmically within populations of SCN neurons. Removal of VIP but not AVP completely disrupts the generation of biological timing signals. In 2010, Dr. Allen

Organic Solvents Illuminate our Understanding of Neurological Disorders

Workers exposed to certain organic solvents (such as n-hexane and 1,2-diethylbenzene) can develop nerve and spinal cord damage that leads to a crippling disease known as peripheral neuropathy. While n-hexane neuropathy is all too common today in certain low- and middle-income countries, improved workplace practices have virtually banished the disease from U.S. industry. Now, the neurotoxic metabolites of n-hexane and 1,2-diethylbenzene are used as valuable laboratory tools with which to probe the vulnerabilities of the nervous system. The detoxification products (metabolic byproducts) of such solvents induce abnormal modifications of proteins in the nervous system. Dr. Tshala-Katumbay

Integrity of DNA (DNA damage, genetic alterations and disease)

Human health and risk for disease ultimately depend on the integrity of our DNA, the genetic material that provides the body

Insights Into Mechanisms that Lead to Cancer

The causes and treatment of cancer are important to Oregon workers because some workplace exposures can cause cancer. Moreover, cancer is a disease that will strike a significant number of workers at some point during their career. Work in the Turker laboratory is focused on the underlying causes of cancer at the level of gene and chromosome defects. Each chromosome contains a very large number of specific genes and the correct number of chromosomes is important for a cell to function properly. A hallmark of cancer cells is abnormal numbers of chromosomes because some chromosomes are lost and others are duplicated. These changes lead to cells in which expression of many genes is decreased, increased, or lost entirely. One accomplishment of the Turker laboratory this year was to complete a study that uncovered unexpected levels of chromosome loss in cells obtained from apparently normal (i.e., non-cancerous) kidneys. While this study revealed that chromosome loss per se may be insufficient for cancer to occur, it also revealed that cells vulnerable to become cancerous are unexpectedly common. A second completed study focused on a phenomenon termed 

Enhancing the Effectiveness of Chemotherapeutic Protocols

Cancer is the second leading cause of death in the United States, with over 1,500,000 new cases reported in 2010, a figure that does not include the 1,300,000 new cases of non-melanoma skin cancers diagnosed each year. Lifetime probabilities of having cancer are nearly 50% for men and 35% for women, and this results in greater than 600,000 deaths in the United States each year, nearly 25 percent of all deaths. The nationwide costs for treating and managing these diseases are estimated to be in excess of $264 billion per year. In 2010, more than 21,000 Oregonians were diagnosed with a new cancer and more than 7,500 died as a direct result of these diseases. Many of these cancers are at least partially the result of environmental toxicant exposures, making their prevention and effective treatments a high priority for research in the Lloyd laboratory. A major focus in the laboratory has been to identify more effective cancer treatments that use chemotherapeutic agents.Cancer chemotherapy frequently uses drugs that kill cells by virtue of their ability to chemically fuse together complementary strands of DNA, creating what is referred to as an inter-strand DNA crosslink. The therapeutic efficacy of crosslink-inducing agents resides in their ability to disrupt processes that are essential for cancer cell survival, including DNA replication, RNA transcription, and recombination. For example, the drug Melphalan is used for the treatment of myelomas, Cytoxan for lymphomas, Cisplatin for head and neck, testis and ovarian cancers, and Busulfan for bone marrow cancers. Mitomycin C is used against gastric, pancreatic, and colorectal cancers.The processing and repair of DNA crosslinks in human cells is extremely complex, involving multiple DNA repair and damage tolerance pathways. One such pathway utilizes molecular scissors, called endonucleases, which cut the affected DNA strand on both sides of the crosslink, and translesion synthesis (TLS) polymerases that fill in the gap created by the endonuclease, thereby restoring normal function. The Lloyd laboratory has obtained biochemical data that one translesion synthesis polymerase, known as polymerase kappa (pol ription and homologous recombination can occur. Such an activity would limit the effectiveness of crosslink-inducing chemotherapeutic agents to kill targeted cancer cells. Therefore, there is an urgent need for development of new therapies that do not allow cancer cells to repair crosslinks and avoid being killed by these agents. The Lloyd laboratory has made it a priority to identify small molecule inhibitors targeting pol k as crucial for improving the therapeutic efficacy of chemotherapeutic agents.Specifically, it is hypothesized that pol nducted on 16,000 compounds in collaboration with the NIH Chemical Genomics Center (NCGC) using a fluorescence-based assay. Preliminary candidates were identified and verified using a secondary assay that confirmed the robust nature of high throughput screens to identify potential therapeutic agents. Biological assays were developed to extend these investigations into cell-based studies. The future aims of this investigation are to: 1) conduct high throughput screening of the ~400,000-member Molecular Libraries Small Molecule Repository (MLSMR) collection using the fluorescence-based assay described above; 2) expand the number of related compounds through combinatorial chemistry; and 3) analyze inhibitor effectiveness in biological assays.In addition to pol  either error-free or mutagenic. The latter outcome is most deleterious, since mutagenic repair is likely a primary cause of both secondary cancers and acquired drug-resistance, the two most common complications associated with the clinical use of DNA-crosslinking agents. Thus, it is critically important to identify individual DNA polymerases that might contribute to mutagenic repair of DNA crosslinks. As a result of collaborative efforts between Dr. Lloyd and Dr. Minko, it has been found that human DNA polymerase eta (pol  

Novel Therapeutic Strategy for the Prevention of Skin Cancer

Ultraviolet (UV) light causes DNA damage in skin cells, leading to more than one million cases of non-melanoma skin cancer diagnosed annually in the United States. Human cells possess only one mechanism to repair UV-induced DNA damage, and lack a DNA enzyme that can specifically initiate an alternative DNA repair pathway that is present in other organisms. Certain bacteria and viruses have very efficient systems for the repair of sunlight-induced DNA damage. The McCullough and Lloyd laboratories have identified a DNA repair enzyme from a virus that infects single cell green algae, Chlorella virus PBCV-1, and have engineered this enzyme to contain a nuclear localization sequence (NLS) and a membrane permeabilization peptide (TAT) for enhanced delivery to human skin cells. Drs. Lloyd and McCullough currently have multiple patents either awarded, or in review, for the application of this enzyme and related enzymes in the prevention of skin cancer. Their laboratories have recently demonstrated that this UV-specific DNA repair enzyme can be delivered to human skin cells in culture and to a human skin tissue model via the transmembrane permeabilization peptide, a method which bypasses the more traditional liposomal encapsulation approach of most topical drugs of this nature. The McCullough lab has discovered that, once delivered to the skin cells, the DNA repair enzyme rapidly initiates removal of the DNA damage. The development of this enzyme as a topical therapeutic is being done in collaboration with an Oregon biotechnology research and development company, Restoration Genetics, Inc. (RGI). Drs. Lloyd and McCullough are the founders of RGI and Dr. Lloyd serves as the Chief Scientific Officer and Dr. McCullough as the President of the company. This latest work was published in the Journal of Investigative Dermatology in 2010.

2011 CROET Highlights

CROET brings federal dollars into the Oregon economy

CROET receives base operations funding from the Oregon Workers
the new technologies and jobs that spin off from productive research. In a study conducted by Oregon State University, multiplier effects on the economy from the infusion of federal grant funds were estimated to range from 2 up to 10 dollars per federal dollar received.

 

 

Workplace studies and applications research

 

CROET conducts workplace surveys so that prevention and research needs can be identified, and applications research to bring the benefits of science to the workplace floor. It also reaches out to provide education and information to the Oregon workforce and beyond.

 

 

Oregon Fatality Assessment and Control Evaluation (OR-FACE) Program

 

Dr. Ryan Olson is the director of the Oregon Fatality Assessment and Control Evaluation (OR-FACE) program (funding from NIOSH), and began a 

 

 

Safety Researchers Address Hazards for Oregon Crab Fishermen

 

Ryan Olson, PhD
The (OR-FACE) program at CROET, in partnership with the Field Research Group at the University of Washington, obtained a grant from the Pacific Northwest Agricultural Safety and Health Center (PNASH) to conduct a safety survey and field test a selection of personal flotation devices with Oregon crab fishermen. The U.S. Coast Guard, the Oregon Dungeness Crab Commission, and researchers at the National Institute for Occupational Safety and Health Alaska field station were also included in the project team. The Oregon Dungeness crab fishery represents one of the most dangerous work environments in the US, with most fatalities (79%) resulting from capsized vessels while crossing river bars or working near shore. During the period 2003-2009, 14 deaths were recorded. None of the 14 drowning victims were wearing a personal flotation device at the time of the incident. A study, the Oregon Crab Fishing Safety Assessment, was conducted to (1) administer a survey to commercial Dungeness crab fishermen and solicit their experiences and perspectives on critical safety issues specific to the Oregon crab fishery, and (2) field test the usability and acceptability of current, commercially available Personal Floatation Devices (PFD). The results of the study identified three important areas where additional efforts can be made to prevent drown- ing related fatalities in the Dungeness crab fishery: (1) encourage PFD use among fishermen; (2) increase the frequency of safety training and onboard safety drills; and (3) improve captains

 

 

SHIFT Program for Truck Drivers Funded

 

With new funding from the National Heart, Lung and Blood Institute (NHLBI), the Olson lab kicked off a randomized controlled trial of a weight loss and health promotion program for truck drivers called Safety and Health Involvement for Truckers (SHIFT). This year the SHIFT program was also featured as the cover story in Healthy Trucking Magazine (October 2011). In addition to the SHIFT study, Dr. Olson

 

 

Pesticide Exposure

Assessment of Health Effects of Children Living in an Agricultural Community

Diane Rohlman, PhD
Organophosphorus pesticides (OPs) are used extensively in agriculture throughout the world, including in Oregon. There is increasing concern regarding the use of pesticides in agricultural communities and potential impacts on public health. OPs are among those of greatest concern, due to their persistence once in the home and their established neurotoxic effects. There is compelling evidence that repeated (chronic) low-level occupational and environmental pesticide exposures are associated with neurobehavioral performance deficits in adults. Children of farm workers are presumed to be exposed to pesticides throughout development, and this exposure may produce subtle health effects that would not be detected by clinical examinations nor recognized by parents. A study conducted by Dr. Diane Rohlman and funded by the National Institute of Occupational Safety and Health (NIOSH) through the Pacific Northwest Agricultural Safety & Health Center, examined health effects in children living in an agricultural community. This project established relationships within an agricultural community, built a cohort of 300 agricultural families and controls living in the same community, and assessed the exposure of children and the impact on their development. Mea- sures of dust in the homes where members of this cohort lived revealed a range, from relatively high to very low levels, of several pesticides that would put crawling children at risk of exposure and similarly increase risk for the adults. Training on ways to reduce pesticide exposure at home and work were developed in Spanish and English and presented to several hundred members of the community who attended the county fair.

 

 

Oregon Healthy WorkForce Center

 

W. Kent Anger, PhD
CROET was awarded a grant as a NIOSH Center of Excellence in total worker health, a new term that supports the development of workplace interventions that target, in a single program, improving safety, occupational health and personal wellness. To compete for the grant, CROET partnered with OHSU
The Oregon Healthy WorkForce Center

The 4 projects funded by NIOSH as part of this Center, are:

An added value of the Healthy Workforce Center is the creation of a database of related intervention strategies and common measures housed in a data repository for sharing within and outside the Oregon Center. This will allow the Center to examine how the various interventions achieve their effects on health promotion and health protection. The Center

Critical to the success of our application was CROET

 

 

CROET Scientists Study Training Effectiveness in 27 Oregon Counties

 

Training effectiveness 

is a serious public health problem affecting an estimated one-third of Oregon women between the ages of 20 and 55. And women are not the only victims of DV

In addition to computer-based training, the CROET research team invited victims of domestic violence to have private interviews to describe their abuse experience and to describe how they used the law, for example, for leave. Supervisors and managers were each interviewed to describe their experiences with victims and/or perpetrators of violence and to describe how the law has positively or negatively impacted the workplace. These assessments are revealing how serious a problem DV is in the Oregon workplace. And perhaps most importantly, participants will have been given tools to effectively address DV spillover into the workplace.

 

Highlights - Oregon Crime Victims

The Oregon crime victims

 

 

Outreach and Education

 

CROET has proactively engaged to provide timely occupational health and safety information to employees, employers, health and safety professionals, doctors and nurses.

 

 

CROETweb.com

 

CROETweb.com is an occupational safety and health resource directory that contains links to over 1200 occupational safety and health resources focused on day-to-day workplace issues. CROETweb serves thousands of users who regularly bookmark this resource, those who sub- scribe to the monthly electronic newsletter, and those seeking information by search engine (e.g. Google) for occupational health and safety topics on the web. It is widely recognized and respected by industrial health and other safety professionals as well as the general public, based.on feedback from user groups. CROETweb was redesigned at the end of 2011. CROETweb had 98,000 total page hits and an average of 7,000-9,000 monthly page hits.

General Industry, Hospitality 

 

topic of hair smoothing products containing formaldehyde continued to be a popular internet

resource, receiving approximately 10,800 page views during 2011.

Oregon and the Workplace, to the existing Facebook presence. The Oregon and the

Workplace blog provides information about ongoing CROET activities in brief paragraphs or

bullets with a pictiure depicting the event. It received 4,200 page views from August 

 

 

Health and Safety Training Symposia

 

CROET provides two health and safety symposia per year, one sponsored jointly with Portland State University. Topics are determined based on solicited and unsolicited feedback from the Oregon occupational health and safety professional community. The target audience includes health, safety and environmental professionals, although the targeted group varies based on the symposium topic. The purpose of the symposia is to provide timely, up-to-date presentations, forums and discussions on workplace safety and health issues. CROET presented the following symposia series in 2011:

 

Innovations in Safety Climate

Presented by CROET and Portland State University Friday, October 28, 2011 University Place, PSU, Portland, Oregon

 

Innovative Communications & Messaging

Presented by CROET Friday, June 3, 2011 NECA/IBEW Training Center, Portland, Oregon

 

 

Regional Health and Safety Conferences

 

OR-OSHA sponsors the majority of health and safety conferences that CROET attends; these conferences are an important means by which CROET reaches out to working Oregonians. Workers and businesses learn about CROET and what it has to offer, and CROET personnel learn about the needs and concerns of workers and the industries that employ them. CROET scientists are often asked to give health and safety presentations in addition to providing conference exhibits. Overall, conferences represent a tremendous networking opportunity for CROET outreach personnel. The following page lists safety and health conferences attended by CROET in 2010-2011:

 

 

Toxicology Information Center (TIC)

 

CROET

In addition to the TIC, Dr. Berman serves as consultant to the Oregon Department of Agriculture

 

 

CROET

 

OSHA regulations require employers to maintain Material Safety Data Sheets (MSDS) for the hazardous chemicals used in their workplace. This often proves to be a difficult record-keeping task, and it can be burdensome to ensure that employees have quick access to health and safety information in the workplace when they need it. Since 1998, CROET

 

 

OHSU Let

 

Jackilen Shannon, MPH, RD, PhD, through her work as Director of the Let

In addition to work in the community, Dr. Shannon continues to pursue her work in nutrition and cancer prevention. This past year she completed a clinical trial of fish oil, green tea and early prostate cancer risk and will be wrapping up a trial of broccoli sprout supplementation in women with early stage breast cancer in the coming year. Analyses are ongoing for both of these projects.

 

 

Mechanisms of Disease and Dysfunction

 

Chronic disease takes a significant toll on our workforce just as it does in the broader community. CROET research seeks to discover causes of chronic diseases that are produced or exacerbated by workplace factors and identifies processes or procedures that can prevent or ameliorate those diseases and improve workplace safety.

 

 

Recovery of the nervous system following injury

 

Damage to nerves and muscles is the primary cause of workplace disability in the United States. In a typical year, five million workers (4%) are injured on the job. Four million (80%) of these involve debilitating pain and/or dysfunction from neuromuscular injuries, including trauma, tears, strains, and musculoskeletal disorders (http://www.bls.gov). Nearly half require a lengthy recuperative period, substantially diminishing productivity and increasing medical costs to employers and employees. Dr. Bruce Patton

 

 

Circadian Cycles Research

 

In humans, many physiological processes cycle with a period of twenty-four hours. These circadian rhythms are driven by an internal biological clock, which cause us to be active during the day and sleep at night. Short-term disruption of the circadian rhythms can lead to higher rates of on-the-job accidents, impairments in cognitive function, including poor decision-making, disruptions in hormone activity, and gastrointestinal distress. Long-term disruption of the circadian system contributes to the development of breast and colorectal cancer, cardiovascular disease, mood disorders and a number of metabolic derangements including diabetes. A small brain region structure called the suprachiasmatic nucleus (SCN) contains a molecular time-keeping mechanism that drives biological circadian rhythms. This biological clock sends signals throughout the body that coordinate circadian rhythms in many different tissues and organs. The long-term goal of work in the lab of Dr. Charles Allen is to identify the cellular mechanisms underlying the generation and control of circadian rhythms. Successful completion of his work will provide a better understanding of the mechanisms underlying regulation of circadian processes such as sleep. This knowledge can lead to better and more rational treatment of circadian based sleep and mood disorders and safer shift work schedules. Generation of circadian timing signals in the suprachiasmatic nucleus (SCN) depend on transcriptional repression by the Period (PER) 1 and 2 proteins within single cells and on vasoactive intestinal polypeptide (VIP) signaling between cells. In collaboration with a research team at Washington University in St. Louis led by Dr. Eric Herzog, Dr. Allen

 

 

Loss of Circadian Clock Accelerates Aging

 

Circadian clocks are found in almost any species and affect many cellular and behavioral rhythms. Disruptions in circadian rhythms have been described in neurodegenerative diseases but also in normal aging, however it is unclear whether this is a mere consequence of aging and disease or whether it is actively aggravating these processes or even causing them. To address this question, CROET

 

 

Organic Solvents and Cyanide Metabolites Aid our Understanding of Neurological Disorders

 

Workers exposed to certain organic solvents (such as n-hexane and 1,2-diethylbenzene) or metabolites of cyanogenic compounds can develop nerve and spinal cord damage that lead to a crippling disease known as peripheral neuropathy. While n-hexane neuropathy is all too common today in certain low- and middle-income countries, improved workplace practices have greatly reduced the disease from U.S. industry. The markers and burden of disease associated with workplace exposure to cyanogenic compounds are, however, yet to be elucidated. Now, the neurotoxic metabolites of n-hexane, 1,2-diethylbenzene, or cyanide, are used as valuable laboratory tools with which to probe the vulnerabilities of the nervous system. The detoxification
products (metabolic byproducts) of such solvents, or those of cyanide, induce abnormal modifications of proteins in the nervous system. Dr. Tshala-Katumbay

 

 

DNA Damage, Genetic Alterations and Disease

 

Human health and risk for disease ultimately depend on the integrity of our DNA, the genetic material that provides the body

 

 

CROET Senior Scientist Works at Department of State

 

Dr. Mitchell Turker represented CROET and OHSU at the Department of State from August 2010 to August 2011 as a Jefferson Science Fellow funded by Congress. This program funds a dozen senior scientists each year from around the country to help advise State Department offices on a variety of issues that involve science. Dr. Turker worked in the Office of the Geographer and Global Issues within the Bureau of Intelligence and Research during his fellowship year. His projects included participating in an interagency team preparing the United States position for the World Health Organization

 

 

Clues to Fighting Cancers

 

A long held assumption in cancer research is that mutations cause cancer, and therefore environmental exposures that increase mutations will also increase the risk to develop a cancer. Dr. Turker

 

 

Drug Discovery Program Screens 400,000 Molecules

 

Cancer is the second leading cause of death in the United States, with over 1,500,000 new cases reported in 2010, a figure that does not include the 1,300,000 new cases of non-melanoma skin cancers diagnosed each year. Lifetime probabilities of having cancer are nearly 50% for men and 35% for women, and this results in greater than 600,000 deaths in the United States each year, nearly 25 percent of all deaths. The nationwide costs for treating and managing these diseases are estimated to be in excess of $264 billion per year. In 2010, more than 21,000 Oregonians were diagnosed with a new cancer and more than 7,500 died as a direct result of these diseases. Many of these cancers are at least partially the result of environmental toxicant exposures, (including those found or experienced in the workplace such as polycyclic aromatic hydrocarbons, butadiene, and formaldehyde) making their prevention and effective treatments a high priority for research in the Lloyd laboratory. A major focus in the laboratory has been to identify more effective cancer treatments that use chemotherapeutic agents.

When an individual is diagnosed with a cancer related to exposure, it is the end result of a complex series of events that are related to occupational and environmental exposures to toxic agents combined with the genetic makeup of that individual to either succumb to or fight off the cancer. Once such a diagnosis has been made, treatments often include a combination of surgery, radiation therapy and chemotherapy, all of which are designed to kill (or remove) the cancer cell, but spare as much of the normal healthy tissue as possible. The fundamental concept underlying radiation and chemotherapy is to so severely damage the DNA of the cancer cell that it can no longer replicate (reproduce and grow) and incur so much damage that it dies. However, often cancer cells have adapted special mechanisms that thwart these approaches and one of those mechanisms is to produce large amounts of a substance (enzyme) that ignores the DNA damage and allows the cancer cells to keep growing. This enzyme is called a DNA polymerase. In order to improve cancer therapies, the Lloyd laboratory has initiated a drug discovery program that will identify new drugs to shut off the activity of the DNA polymerases and allow the chemotherapeutic agent to kill the cancer cells. This year they have screened over 400,000 candidate drug molecules for potential therapeutic efficacy, with more than 500 candidate drugs already identified. The immediate goal is to determine which of a small subset of these (~500 drugs) can be further refined and eventually used in human cancer trials.

 

 

Reducing Formaldehyde Damage to DNA

 

Formaldehyde is a reactive chemical that is commonly used in the production of industrial, laboratory, household, and cosmetic products. Inhalation of formaldehyde-containing products is associated with elevated cancer, asthma and nasopharyngeal irritation. Based on the association between formaldehyde exposure and increased incidence of cancers, formaldehyde has been classified as a known human carcinogen. Although it is well established that formaldehyde induces damage to the DNA within cells, little is known about the cellular and genetic changes that can lead to formaldehyde-induced cell death and genetic damage. The McCullough laboratory investigates how cells respond to the deleterious effects of formaldehyde exposure. Recent studies have revealed that there is a specific subset of genes that are critical for repairing formaldehyde- induced DNA damage following an acute high-dose exposure. These studies also demonstrated that cells immediately stop growing prior to cell division. This growth arrest presumably allows cells to repair the DNA damage; however, even in normal repair-proficient cells, formaldehyde exposure can result in cells that contain an abnormal number of chromosomes, a condition frequently found in cancerous cells. Additionally, an elevated number of DNA double-strand breaks, chromosomal breaks, and abnormal chromosome structures were observed in DNA repair-deficient cells following formaldehyde treatment. Collectively, these findings illuminate the role of a specific DNA repair pathway in reducing the sensitivity to formaldehyde-induced DNA damage as shown by the increased genomic (chromosomal) instability and reduced cell viability. These studies have demonstrated a possible mechanism for the causal relationship between formaldehyde exposure and human disease.

 

2008-2009 CROET Highlights

CROET brings federal dollars into the Oregon economy

CROET receives base operations funding from the Oregon Workers Compensation System that, year after year, CROET scientists have successfully leveraged to win federal and other research dollars. For every dollar invested by the States Workers Benefit Fund in the current biennium, CROETs world-class scientists brought an average $1.52 of federal and private grant funding into the Oregon economy (see chart below). Federal dollars for research in Oregon have a significant positive impact on the states economy. Expenditures for goods and services, as well as the salaries of scientific and support personnel, produce a multiplier effect on the purchase of goods and services and creation of businesses that support the needs of Oregons research institutions. Moreover, research coming out of CROET has a greater than average impact on the states economy from the new technologies and jobs that spin off from productive research. In a study conducted by Oregon State University, multiplier effects on the economy from the infusion of federal grant funds were estimated to range from 2 up to 10 dollars per federal dollar received.

Workplace studies and applications research

CROET conducts workplace surveys so that prevention and research needs can be identified, and applications research to bring the benefits of science to the workplace floor. It also reaches out to provide education and information to the Oregon workforce and beyond.

Oregon Fatality Assessment and Control Evaluation (OR-FACE) Program

The Oregon Fatality Assessment and Control Evaluation (OR-FACE) Program is designed to prevent occupational fatalities through surveillance, targeted investigation, assessment, and outreach that are associated with traumatic work-related deaths in Oregon. Headed by Gary Rischitelli MD, JD, MPH, OR-FACE is one of nine state FACE programs funded by the National Institute for Occupational Safety and Health (NIOSH). OR-FACE Preliminary data for 2008 and 2009 indicates 117 work-related fatalities in 108 incidents.During 2008-2009, OR-FACE produced the OR-FACE 2006 Annual Report, six investigational reports on particular incidents, a safety brochure for agriculture in both English and Spanish (Can You Identify Fatal Hazards on Your Farm or Ranch?), a second edition of the safety booklet, Young Workers: Stay Alive on the Job!, and three posters for conference presentations related to young workers, logging, and commercial crab fishing. OR-FACE also collaborated with Oregons Young Worker Health and Safety coalition, attended meetings and events with educators and safety professionals, and gave safety presentations for young audiences.OR-FACE expanded activity in logging safety by completing a pilot study with camera-mounted hardhats, funded by the Pacific Northwest Agriculture Safety and Health Center (Fallers Point of-view Video Observation Study). OR-FACE also completed two logging safety projects funded by Oregon OSHA: one to update the Oregon OSHA Yarding and Loading Handbook, and another to produce an OR-FACE Yarding Logging Safety booklet as a companion volume to the OR-FACE Fallers Logging Safety booklet.In May 2009, OR-FACE hosted the Annual National FACE Program meeting, bringing together federal and state public health workers and academic researchers from across the country. Representatives of the state FACE programs, including Dr. Rischitelli, presented updates on their research activities, discussed regional trends and factors that affect worker fatalities, and shared outreach and education methods.OR-FACE investigational reports and other publications are available on the programs website (http://www.ohsu.edu/xd/research/centers-institutes/croet/outreach/or-face/). Investigation reports from Oregon and other FACE states are also available through the National Institute for Occupational Safety and Health (www.cdc.gov/niosh/face).

Safety and Health Interventions for Lone Workers

Dr. Ryan Olsons research is focused on safety and health interventions for lone workers, and on behavioral self-management methods. The overarching goal of this research is to understand how organizations can best protect and promote health among workers who are physically isolated from their peers. Olsons work is also concerned with understanding workplace and personal factors that help individuals self-regulate and engage in prevention behavior.

Promoting Health and Preventing Injuries Among Truck Drivers

Commercial truck drivers have overweight and obesity rates that are nearly 20% higher than the general population. However, prior efforts to promote weight loss and healthful behaviors with this population had been minimally effective. Dr. Olson led the development and pilot testing of a new health promotion intervention for truck drivers, called SHIFT (Safety & Health Involvement For Truckers). The intervention engages drivers in health promotion with a weight loss and safe driving competition that is supported with computer-based training and motivational interviewing (see www.ohsushift.com for more information). In the pilot test, drivers lost an average of one unit of body mass index and made significant changes to healthful and safe behaviors. The pilot test was completed in 2008 and published in 2009. The study also won 1st place in the Best Practices Intervention Evaluation Competition at Work, Stress, and Health 2009, which is an international conference sponsored by the American Psychological Association (APA) and National Institute for Occupational Safety and Health (NIOSH). Musculoskeletal injuries in commercial truck drivers account for 8% of annual injuries in the US. However, research on drivers exposures to injury hazards during material handling tasks is extremely limited because of the isolated nature of the work. Olson and colleagues used video-based assessment and driver self-assessments to study three drivers over a 6-month period. The resulting analyses identified four environmental predictors of severe back postures among short-haul truck drivers during material handling tasks.

Olson, R., Anger, K., Elliot, D. L., Wipfli, B., & Gray, M. (2009). A new health promotion model for lone workers: Results of the SHIFT pilot study (Safety & Health Involvement for Truckers). Journal of Occupational and Environmental Medicine, 51(11), 1233-1246.

Olson, R., Hahn, D. I., & Buckert, A. (2009). Predictors of severe trunk postures among

short-haul truck drivers during non-driving tasks: An exploratory investigation involving video-assessment and driver behavioural self-monitoring. Ergonomics, 52 (6), 707-722.

Understanding Factors that Promote Prevention Behaviors

One third of all construction fatalities are falls, and 34% of fatal falls are due to a failure to wear personal protective equipment (PPE) that was available at the relevant worksite at the time of the incident. An additional 13% of fatal falls are due to improper use of PPE. One factor that affects the proper use of PPE is whether or not peers are positive social models of the behavior. Prior research had shown that exposure to a single social model wearing PPE had positive effects. However, in the work place an individual is likely to observe the aggregate behavior of their entire work group to decide if wearing PPE is encouraged or discouraged in their work environment. In 2009, Olson and colleagues published the first evidence showing that the aggregate behavior of multiple social models influences PPE use.Behavioral self-monitoring (BSM) methods, where individuals repeatedly observe, evaluate, and record aspects of their own behavior, can produce valuable assessment data about injury hazards and near misses. In 2008, Olson and Winchester published the first quantitative literature review of BSM methods applied in workplace settings.Many jobs require workers to perform sustained visual searching to identify threats or hazards to personal and public safety (e.g., commercial driving, quality control in manufacturing, airport baggage screening). In collaboration with colleagues at Santa Clara University, Olson formalized and produced further evidence for the Vigilance Reinforcement hypothesis, which is the notion that the chance to detect an error or threat actually reinforces vigilant search behaviors.

Olson, R., Grossheusch, A., Wipfli, B., & Schmidt, S. (2009). Observational learning and workplace safety: The effects of viewing the collective behavior of multiple social models on the use of personal protective equipment. Journal of Safety Research, 40 (5), 383-387.

Olson, R. & Winchester, J. (2008). Behavioral self-monitoring of safety and

productivity in the workplace: A methodological primer and quantitative literature review. Journal of Organizational Behavior Management, 28 (1), 9-75

Hogan, L., Bell, M., & Olson, R. (2009). A preliminary investigation of the reinforcement function of signal detections in simulated baggage screening: Further support for the Vigilance Reinforcement Hypothesis. Journal of Organizational Behavior Management, 29 (1), 6-18.

Computer-based Supervisor and Worker Protection Training

CROETs research on computer-based training effectiveness in agriculture has been extended to (1) teach complex capabilities--supervisor skills--to workers with limited education and (2) to identify the need for more frequent repeat training about the Worker Protection Standard than is legally required by the Environmental Protection Agency (EPA). This research was conducted by Drs. Kent Anger and Diane Rohlman of CROET, in collaboration with community partner RN Leda Garside of Tuality Healthcare, Salud! Services, and several Oregon vineyards. The supervisor skills training was developed out of concern that employees with limited education may be excluded from advanced training due to (we believe unfounded) assumptions that the typical agricultural employee might not learn rapidly. The study, published in the Journal of Agricultural Safety and Health, demonstrated that providing computer-based training in supervisor skills to Latino agricultural workers with an average education of 6.4 and 8.2 years (in our intervention and control groups, respectively) did improve performance in a face-to-face workshop designed to teach supervisor skills given on the following two days. The training produced a large positive effect size, much larger than the average effect size reported in workplace training studies. This result suggests that limited educational attainment is not a barrier to learning the complex skills required to supervise employees.Other research, published in the Journal of Agromedicine, examined Worker Protection Standard (WPS) training, which is one of EPAs primary methods for preventing pesticide exposure to agricultural workers. EPA requires retraining of the WPS at 5-year intervals, meaning the knowledge must be retained for that long. Vineyard workers completed a test of their baseline WPS knowledge, computer-based training on WPS, a post-test immediately after training and a re-test 5 months later. There was a relatively high level of baseline knowledge of WPS information, training increased the knowledge and produced a large effect size. Re-test performance at 5 months revealed a return towards but not back to the pre-test levels. Shorter re-training intervals for the WPS were recommended in the publication.The work funded by the National Institute for Occupational Safety and Health (NIOSH) used cTRAIN, developed at CROET, and licensed by OHSU to a company owned by Drs. Anger and Rohlman. OHSU and Drs. Anger and Rohlman have a significant financial interest in Northwest Education Training and Assessment, LLC, a company that may have a commercial interest in the results of this research and technology. This potential conflict has been reviewed and managed by OHSU and the lntegrity Program Oversight Council. Two new research grants employing this computer-based training technology were funded in 2008-2009 (1) to study the effectiveness of training to address the effects of domestic violence in the workplace in Oregon counties and (2) to provide prevention training to home care workers to avoid and prevent violence from their clients or client families.

Research on Pesticides and Terrorism

Organophosphorus (OP) pesticides used in Oregon and worldwide in agriculture are also predicted to be likely terrorism agents that could be used against the US. CROETs Drs. Kent Anger and Pam Lein began studying this chemical in parallel human and animal studies aimed at identifying tests and measures (called biomarkers) that can effectively and quickly determine if humans have been harmed by exposures to these pesticides. The immediate effects of exposure to these OP pesticides at concentrations that cause fatal poisonings (if not treated) are well studied. Drs. Anger and Lein are investigating lower-concentration exposures that may produce silent or unobservable damage--but damage that affects the brain and nervous system. Pesticide exposures in Oregon occur at much lower concentrations than exposures or damage that would be expected following a terrorism event, so the human research led by Dr. Anger is being conducted in Egypts cotton fields during pesticide application, where the highest workplace exposures ever reported are found (demonstrated in an article by the research team in press in NeuroToxicology). Dr. Lein is conducting the animal research under controlled exposures that reproduce the same degree of internal dosing and the same pattern of exposures as the human exposures that were measured in the first year of this research in Egypt. This research is funded by the National Institute of Environmental Health Sciences. Dr. Lein moved to the University of California at Davis after this work was funded and the collaboration continues between her, Dr. Anger of CROET (the two lead investigators on the project), Drs. Rohlman (CROET) and Matt Lattal (OHSU) and investigators at the University of Washington, University of Buffalo and Menoufia University in Egypt. The outcomes of the research will relate to anyone who is exposed to organophosphorus pesticides, whether at the low concentrations experienced on farms or in high concentrations that could be experienced if used as a weapon.

Assessment of Health Effects of Children Living in an Agricultural Community

There is increasing concern regarding the use of pesticides in agricultural communities and potential impacts on public health. Organophosphate (OP) pesticides are among those of greatest concern, due to their persistence once in the home and their established effects on the nervous system. Neurobehavioral tests (e.g. of memory and attention) have identified deficits in adult populations exposed to and poisoned by OP pesticides on farms. However, little research has examined OP pesticide exposure in children. While the neurotoxic effects of acute exposure to OP pesticides are well established, chronic low-level exposures are not well studied in adults and very few studies provide evidence of neurobehavioral deficits in farmworker children compared to controls. Children of farmworkers are presumed to be exposed to pesticides throughout development, and this exposure may produce subtle health effects that would not be detected by clinical examinations nor recognized by parents. A study conducted by Dr. Diane Rohlman and funded by the National Institute of Occupational Safety and Health (NIOSH) through the Pacific Northwest Agricultural Safety & Health Center, examines health effects in children living in an agricultural community to determine if they are associated with current home pesticide exposure or an estimate of lifetime exposure. Childrens exposure to pesticides from the parents work or residence in an agricultural community is measured through questionnaires and dust samples collected from the home. Children will be evaluated a second time, one year later, to obtain longitudinal data that will be used to characterize developmental progress and relate that progress to exposure estimates.

Assessing Vulnerability of the Adolescent Brain to Organophosphorus Pesticides

There is compelling evidence that repeated (chronic) low-level occupational and environmental pesticide exposures are associated with neurobehavioral performance deficits (e.g. in memory and attention) in adults. Adolescents working in agriculture are exposed to the same risks as adults, but it is unknown whether their risk is equivalent to or greater than that of adults. Experimental animal studies indicate that the developing brain is more susceptible to the neurotoxic effects of OPs than the adult brain, and low-level exposures to OP pesticides cause significant neurobehavioral deficits in animal research. Adolescents (ages 15-18) in Egypt are legally hired as seasonal workers to apply pesticides to the cotton crop. The pesticide application to the cotton crop is highly regulated and standardized across Egypt, and is limited primarily to OP pesticides (generally chlorpyrifos) and pyrethrins. This provides a unique opportunity to examine the impact of a highly consistent known OP pesticide exposure on the adolescent and their developing nervous system. Recent research in this adolescent Egyptian population found increasing reports of symptoms, depressed cholinesterase, and extensive neurobehavioral deficits in adolescents applying chlorpyrifos (vs. controls). While we have preliminary evidence of some of the highest reported exposure concentrations from dermal patch and urinary samples in adult Egyptian applicators, there is no quantitative exposure data available in adolescents. Furthermore, what is not established is if these exposure-related nervous system effects accumulate across time, if the effects increase with repeated exposure, and if they reverse after exposure ends. The goal of this project is to examine the dose-related response of the adolescent nervous system to OP pesticides, to determine if repeated exposures produce a progressive deficit and to determine if this deficit is reversible. The Egypt project is funded by NIEHS through the Fogarty International Center. It expands upon some of the work we have done with adolescents in Oregon.

Rohlman DS, Lasarev M, Anger WK, Scherer J, Stupfel J, McCauley L. Neurobehavioral performance of adult and adolescent agricultural workers. Neurotoxicology. 2007 Mar;28(2):374-80. Epub 2006 Dec 4.

Abdel Rasoul GM, Abou Salem ME, Mechael AA, Hendy OM, Rohlman DS, Ismail AA. Effects of occupational pesticide exposure on children applying pesticides. Neurotoxicology. 2008 Sep;29(5):833-8.

Organophosphorus Pesticides May Alter the Incidence of Asthma

Organophosphorus pesticides (OPs) are widely used in agriculture and other pest control environments, including orchards in Oregon. Recent epidemiologic studies have identified OPs as occupational and environmental factors potentially contributing to the increase in asthma prevalence over the last 25 years. In support of this hypothesis, Dr. Pam Leins research group previously demonstrated that real-world concentrations of OPs induce airway hyper-reactivity in guinea pigs. Sensitization to allergens is a significant contributing factor in asthma; therefore, Dr. Lein wanted to determine whether allergen sensitization similarly influences OP-induced airway hyper-reactivity. Non-sensitized and allergen-sensitized guinea pigs were injected subcutaneously with the OP, parathion. Allergen sensitization decreased the threshold dose for parathion-induced airway hyper-reactivity and exacerbated parathion effects on nerve stimulation-induced bronchoconstriction. Pretreatment with antibody to interleukin (IL-5) prevented parathion-induced hyper-reactivity in sensitized, but not in non-sensitized guinea pigs. These results show that antigen sensitization increases vulnerability to parathion-induced airway hyper-reactivity by a mechanism that is dependent on IL-5. Since sensitization to allergens is characteristic of 50% of the general population and 80% of asthmatics (including children), these findings have significant implications for OP risk assessment, intervention, and treatment strategies.

Becky J. Proskocil, Donald A. Bruun, Jesse K. Lorton, Kirsten C. Blensly, David B. Jacoby, Pamela J. Lein,

and Allison D. Fryer. Antigen Sensitization Influences Organophosphorus PesticideInduced Airway Hyperreactivity. Environmental Health Perspectives 116(3), 2008: 381-388

Effects of Developmental Exposure to PCBs Explored

The developmental origins of adult disease hypothesis was originally derived from evidence linking low birth weight to cardiovascular diseases, including stroke. Subsequently, it has been expanded to include developmental exposures to environmental contaminants as risk factors for adult-onset disease. Polychlorinated biphenyls (PCBs) are an important class of environmental contaminant widely used as dielectric fluids in transformers, capacitors, and coolants. Due to PCBs toxicity, the United States Congress banned their production in 1979; however, PCBs continue to present an exposure risk as persistent organic pollutants. Dr. Pam Lein is interested in the hypothesis that developmental exposure to PCBs alters stroke outcome in adults. To test this, pregnant rats were exposed to low levels of the PCB mixture Aroclor 1254 (A1254) in the diet throughout gestation and lactation. Cerebral stroke was induced in the offspring at 68 weeks of age, after which the concentrations of PCB congeners were quantified in brain tissue, and expression of the PBC-inducible metabolic enzymes, Bcl2 and Cyp2C11 were quantified. Interestingly, Dr. Lein found that developmental exposure to A1254 significantly decreased infarct size in females and males, whereas effects of developmental A1254 exposure on Bcl2 and Cyp2C11 expression did not correlate with effects on infarct volume. These data provide proof of principle that developmental exposures to contaminants found in the workplace and larger environment influence the response of the adult brain to ischemic injury and thus represent potentially important determinants of stroke susceptibility.

Suzan Dziennis, Dongren Yang, Jian Cheng, Kim A. Anderson, Nabil J. Alkayed, Patricia D. Hurn,

and Pamela J. Lein. Developmental Exposure to Polychlorinated Biphenyls Influences Stroke Outcome in Adult Rats. VOLUME 116 | NUMBER 4 | April 2008  Environmental Health Perspectives 116(4), 2008: 474-480

Neurodevelopmental disorders are associated with altered patterns of connections between neurons. A critical determinant of neuronal connectivity is the dendritic morphology of individual neurons, which is shaped by experience. The identification of chemical exposures that interfere with dendritic growth and plasticity may, therefore, provide insight into environmental risk factors for neurodevelopmental disorders. Dr. Leins group tested the hypothesis that polychlorinated biphenyls (PCBs), found in electrical transformers, alter dendritic growth and/or plasticity by promoting the activity of ryanodine receptors (RyRs), which are the major cellular mediators of calcium-induced calcium release in animal cells (a mechanism important to dendritic growth and plasticity). The Morris water maze was used to induce experience-dependent neural plasticity in weanling rats exposed to either vehicle or the PCB mixture Aroclor 1254 (A1254) in the maternal diet throughout gestation and lactation. Developmental A1254 exposure promoted dendritic growth in cerebellar and neocortical neurons among untrained animals but attenuated or reversed experience-dependent dendritic growth among maze-trained littermates. These structural changes coincided with subtle deficits in spatial learning and memory, increased [3H]-ryanodine binding sites and RyR expression in the cerebellum of untrained animals, and inhibition of training-induced RyR upregulation. A congener with potent RyR activity, PCB95, but not a congener with negligible RyR activity, PCB66, promoted dendritic growth in primary cortical neuron cultures and this effect was blocked by pharmacologic antagonism of RyR activity. These results show that developmental exposure to PCBs interferes with normal patterns of dendritic growth and plasticity, and these effects may be linked to changes in RyR expression and function. These findings identify PCBs as possible risk factors for neurodevelopmental disorders, especially in children with heritable deficits in calcium signaling.

Dongren Yang, Kyung Ho Kim, Andrew Phimister, Adam D. Bachstetter, Thomas R. Ward, Robert W. Stackman, Ronald F. Mervis, Amy B. Wisniewski, Sabra L. Klein, Prasada Rao S. Kodavanti, Kim A. Anderson, Gary Wayman, Isaac N. Pessah, and Pamela J. Lein. Developmental Exposure to Polychlorinated Biphenyls Interferes with Experience-Dependent Dendritic Plasticity and Ryanodine Receptor Expression in Weanling Rats. Environmental Health Perspectives 117(3), 2009: 426-435

Outreach and Education

CROET has been proactively engaged in providing timely occupational health and safety information to employees, employers, health and safety professionals, doctors and nurses.

CROETweb.com

CROETweb.com is an occupational safety and health resource directory that contains links to over 1200 occupational safety and health resources focusing on day-to-day workplace issues. CROETweb serves thousands of users who regularly bookmark this resource, those who subscribe to the monthly electronic newsletter, and those searching by search engine (e.g. Google) for occupational health and safety topics on the web. It is widely recognized and respected by industrial health and other safety professionals as well as the general public, based on feedback from user groups. CROETweb was accessed an average 12,000-16,000 times per month for a total of 194,676 hits in 2008. This monthly average hit rate has increased almost every year since the inception of CROETweb. The most popular pages visited for 2008-09 included Materials for Safety Talks, Hospitality, Construction and Office ErgonomicsNew topics 2008: Automotive; Indoor Air QualityNew topics 2009: Mass Transit; H1N1/Swine Flu; MRSA; Fishing; Hospitality  Hotel, Restaurant and Kitchen; Landscaping; Logging & Forestry; Acids & Bases; Chromium; Avian Flu; Occupational Asthma; Occupational Reproductive Hazards; Materials for Safety Talks; OSH Professional Development; and Safety, Languageand Culture. Annual page hits  2006: 162,8382007: 166,1342008: 194,6762009: 158,218 More than 1,250 links are posted on CROETweb.com, including Oregon-specific information from OR-OSHA.As of the end of 2009, CROETweb contains 3500 links and 80 main topic pages.

Toxicology Information Center (TIC)

CROETs Toxicology Information Center, directed by Dr. Fred Berman, provides free scientifically accurate information for those with questions or concerns about chemical, biological, physical or other agents encountered in the workplace and elsewhere. In 2008-2009, Dr. Berman handled hundreds of consultation requests from occupational safety and health professionals, business owners, government agencies, physicians and nurses, the media, and the general working public. Inquiries covered a variety of issues, as shown on the chart. Chemical agents of concern included solvents, heavy metals, insecticides, fungicides, and herbicides. Physicians often called seeking information on a variety of potentially occupation-related health complaints. Calls in regard to indoor mold were common as were calls related to acute and chronic medical problems that were attributed to exposure to chemical agents. Each request took from less than an hour up to several days to respond to fully. The TIC is open from 7:30 a.m. to 4:00 p.m., Monday through Thursday. Walk-in visitors have access to a variety of resources, including computers, databases, government reports, textbooks, and journals that are devoted to toxicology-related issues and occupational health.

Chemical Risk Information Service (CRIS)

OSHA regulations require employers to maintain Material Safety Data Sheets (MSDS) for hazardous chemicals used in their workplace. This often proves to be a difficult record-keeping task, and it can be burdensome to ensure that employees have quick access to health and safety information in the workplace when they need it. Since 1998, CROETs Chemical Risk Information Service, directed by Dr. Gregory Higgins, has helped a growing number of local and international industries manage and distribute chemical safety information through its internet-based MSDS management system. CROETs working relationship with the Oregon Poison Center also ensures that employees covered by the program have ready access to medical information in the event of exposure. During 2008-2009, the Chemical Risk Information Service added four new clients, and now provides MSDS management services to 40 municipal, construction, and service companies, most of which are Oregon-based. An enhanced program was developed for our new client Portland METRO, which allows METRO to evaluate and rank the human health, environmental, and physical hazards of the products used in their facilities. We are also developing a website tool for METRO to help ensure green products are chosen for their facilities. Enhancements were made to the website and database during this period. CROET continues to provide expert MSDS management services at a reasonable cost, which is attractive to both small and large organizations.

Health and Safety Training Symposia

CROET provides two health and safety symposia per year, one sponsored jointly with Portland State University. Topics are determined based on solicited and unsolicited feedback from the Oregon occupational health and safety professional community. The target audience includes health and safety professionals, occupational nurses and physicians, loss control specialists and human resource representatives, although the targeted group varies based on the symposium topic. The purpose of the symposia is to provide timely, up-to-date presentations, forums and discussions on workplace safety and health issues. CROET presented the following symposia series in 2008-2009:Managing the Aging Workforce: Implications for Workplace Stress, Health, Safety and PerformancePresented by CROET and Portland State UniversityOctober 30, 2009Oregons Workplace Health and Safety: Looking Forward to 2020Presented by CROET and Oregon OSHASeptember 24, 2009The Bodys Response to Environmental StressMay 29, 2009Work-Family Stress: Implications for Safety and HealthPresented by CROET and Portland State UniversityNovember 7, 2008Driving Safety at WorkHeld at the UA 290 Plumbers Steamfitters Training Center, Tualatin, OR.June 6, 2008

Regional Health and Safety Conferences

OR-OSHA sponsors the majority of health and safety conferences that CROET attends; these conferences are an important means by which CROET reaches out to working Oregonians. Workers and businesses learn about CROET and what it has to offer, and CROET personnel learn about the needs and concerns of workers and the industries that employ them. Moreover, CROET scientists are often asked to give health and safety presentations in addition to providing conference exhibits. Overall, conferences represent a tremendous networking opportunity for CROET outreach personnel. The following are safety and health conferences attended by CROET during 2008-2009:2008 Oregon Employers Traffic Safety Conference 15th Annual Oregon Small Business Fair Blue Mountain Occupational Safety & Health Conference Cascade Occupational Safety & Health Conference Workers Compensation Division 2008 Educational Conference Oregon Tradeswomen, Inc.s 2008 Women in Trades Conference Central Oregon Occupational Safety & Health Conference Southern Oregon Occupational Safety & Health Conference Mid-Oregon Construction Safety Summit Willamette Valley Ag Expo Western Pulp & Paper Workers Safety & Health Conference New Paths - Health and Safety in Western Agriculture Oregon Employers Traffic Safety Conference2009 Oregon Governors Occupational Safety & Health Conference Blue Mountain Occupational Safety & Health Conference Central Oregon Occupational Safety & Health Conference Southern Oregon Occupational Safety & Health Conference NW Environmental Health Conference: Bridging Research, Care and Policy 2009 Women in Trades Career Fair Public Health Week at OMSI - Crack the Case of Good Health Oregon Small Business Fair Oregon Employers Traffic Safety Conference Oregon Workers Compensation Division Educational Conference

OHSU Health Discoveries Program: Lets Get Healthy!

A Research to the Public exhibit titled Lets Get Healthy! has been developed by Jackie Shannon, Ph.D. Originally titled Nutrition World, the exhibit debuted for 2 weeks in 2007 at the Oregon Museum of Science and Industry (OMSI) in Portland, in conjunction with the museums Body Worlds 3 exhibit. In 2008-2009, Lets Get Healthy! was expanded into a popular interactive education and research exhibit that allows community members to learn important information about their body while contributing to science. The exhibit not only educates the public about relationships among diet, weight and chronic disease, but also introduces attendees to biomedical research and invites them to become research participants by providing them an opportunity to obtain tailored feedback on their diet. This included measurements of height, weight, waist circumference and percent body fat, measurements of blood glucose, HDL, LDL and total cholesterol levels. Participants can contribute their health information anonymously to a population database that researchers use to study the relationship between eating habits, body composition and genetics. Now, schools and communities have access to the anonymized data that can be used to encourage healthy living in the community or teach scientific inquiry to students using real data. The program also partners with schools to help teachers meet Oregons state standards in health education. Lets Get Healthy is housed within the Health Discoveries Program, a program designed to support research, data collection and data analysis activities resulting from implementation of the exhibit.In 2008-2009, the Oregon Clinical and Translational Research Institute (OCTRI) and OHSUs Science Education Partnership Award (SEPA) program became engaged in furthering the development and promotion of the exhibit. OCTRI and SEPA were awarded two National Institutes of Health (NIH) administrative supplement grants to take Lets Get Healthy! to rural Oregon communities. The grants have supported a partnership between OCTRI and SEPA at OHSU, OMSI, and the Oregon State University School of Pharmacy. Two new partners were also brought into the project: Oregon Area Health Education Centers (AHECs) and the Oregon Rural Practice-based Research Network (ORPRN). ORPRN and AHEC are helping to bring the Lets Get Healthy! exhibit to the rural communities that they serve, and are facilitating direct community access to the data  in both community venues and medical facilities  thereby serving the interests of the communities, OCTRI and OMSI investigators. This work supports CROETs goal of improving the health of the Oregon workforce.

The Global Health Center (GHC)

The newly formed Global Health Center (GHC), initially housed in the CROET Toxicology Information Center, facilitates OHSU collaboration with the global health community to promote quality and equity in health care at home and abroad. Through the GHC, CROET and OHSU are working with domestic and international communities to develop programs for students, faculty, staff and partners that will promote global health awareness, research, education and advocacy. Dr. Peter Spencer serves as Director of the Global Health Center. Dr. Spencer has long studied the causes and solutions to neglected human diseases in developing countries, and hopes to spawn a new generation of medical and research professionals certified in global health. Built on the principle that there can be an effective two-way exchange on matters such as cultural competency, health education, research opportunities and clinical practice, the long-range goal of the GHC is to maintain a compact, efficient operation on the campus and invest in building healthcare capacity in global communities. In 2008, the GHC was awarded a 3-year Fogarty Framework for Global Health research education award.

Injury and Recovery of the Nervous System and Muscles

CROET scientists conduct basic research that examines the causes of injury to nerves and muscles in order to identify protective, preventative, and recovery methodologies for such injuries.

Nerve Support Protein Plays Unique Role in Neuromuscular Development

Neuromuscular injuries are the largest cause of workplace disability, and Bruce Patton, PhD, is interested in identifying signaling pathways in nerve and muscle cells that control their regeneration. Nerves and muscles have the capacity to regenerate, but typically do so slowly and with errors and internal scarring that result in lingering disability. Nerves include two primary types of cells. Long neuronal axons connect the brain and spine to muscles and other tissues. Schwann cells normally wrap the axons in a supportive sheath (myelin) and support re-growth of injured axons. Results from the Patton lab show how a family of extracellular matrix proteins made by Schwann cells ensure that every axon becomes ensheathed by the proper number and sub-type of Schwann cell. In 2008-2009, these studies were extended to show how one of these proteins, called laminin alpha2, works in part by polymerizing to create a mesh-like scaffold of protein along the surface of the growing nerve fiber, which controls how the Schwann cells proliferate and differentiate as the nerve develops or re-grows. In further work, the lab has discovered that these matrix proteins also play critical roles the growth and maturation of neuronal pathways in the brain. Finally, the lab made an unexpected discovery that defects in maintaining the expression of one of the matrix proteins contributes to chronic kidney disease. These results have implications for treatment strategies for recovery from neurological injuries, as well as diseases such as ALS and multiple sclerosis.

Chronic Disease and Working Safety

Chronic disease takes a significant toll on our workforce just as it does in the broader community. CROET research seeks to discover causes of chronic diseases that are produced or exacerbated by workplace factors and identifies processes or procedures that can prevent or ameliorate those diseases and improve workplace safety.

Can Fruit Flies Get Alzheimers Disease?

Alzheimers Disease is the most common form of dementia, with approximately 26 million people suffering worldwide. It is also expected that with the increase in life span this number will quadruple over the next four decades, and people will continue working later in life than they do today. Starting with memory loss, AD eventually leads to severe mental impairment, and although therapeutic drugs can slow down the progression of cognitive decline, there is currently no cure. One of the hallmark features of Alzheimers Disease is the accumulation of amyloid plaques which consist of small protein segments called amyloid beta (Ab). Ab is cleaved from the larger Amyloid Precursor Protein (APP) by several enzymes, which in addition to Ab results in the production of several other protein fragments. The normal physiological function of APP and its fragments as well as its interaction with other proteins are, however, still not well understood. Due to methodological difficulties and ethical concerns, studies in humans have obvious limitations. Therefore, the Kretzschmar lab uses a well-established biological model system, the fruitfly Drosophila, to model this condition. To study the toxicity of APP, the Kretzchmar lab created flies that express APP and produce Ab. These flies show accumulations of Ab in the brain, neuronal cell death, and behavioral deficits similar to Alzheimer patients. In fact, Dr. Kretzschmar has shown that Drosophila contains its own version of APP and Ab that also cause these defects. Having established that the deleterious effects of APP and Ab are conserved in flies, the Kretzschmar lab is using this system to identify genetic factors that influence the severity of these effects and are performing drug tests to find treatments that could eventually lead to increased quality of life and productivity of workers in retirement.

I. Greeve, D. Kretzschmar, J. Tschpe, A. Beyn, C. Brellinger, M. Schweizer, R. Nitsch and R. Reifegerste. Alzheimers disease-like neuropathology in transgenic Drosophila. Journal of Neuroscience, 24, 3899-3906, 2004.

K. Carmine-Simmen, T. Proctor, J. Tschpe, B. Poeck, T. Triphan, R. Strau and D. Kretzschmar. Neurotoxic effects induced by Ab peptides derived from the Drosophila Amyloid Precursor Protein (APP) suggest a conserved toxic function of APP proteins. Human Molecular Genetics, 33, 274-281, 2009.

L. Wang, H. Ankati, S. Akubathini, M. Balderamos, C. Storey, A. Patel, V. Price, D. Kretzschmar, E. Biehl, and S. DMello. Identification of novel 1, 4- benzoxazine compounds that are protective in tissue culture and in vivo models of neurodegeneration. Journal of Neuroscience Research, epup 2010.

Discoveries of Circadian Clock Function Leads to Enhanced Understanding of Sleep-Wake Cycles

Circadian rhythms are physiological processes that cycle with a period of twenty-four hours. In humans, these rhythms are set so that we are active during the day and sleep at night, which has significant ramifications in our 24 hr. society. Approximately 1 in 5 workers have jobs that require them to work outside of the traditional 8-5 workday. This work schedule requires these workers to be awake when their internal clock is telling them to sleep. Short-term disruption of the circadian system can lead to higher rates of on-the-job accidents, impairments in cognitive function, hormone activity, and gastrointestinal distress. Long-term disruption of the circadian system contributes to the development of breast and colorectal cancer, cardiovascular disease, mood disorders and a number of metabolic derangements. Biological circadian rhythms are controlled by a small brain region structure called the suprachiasmatic nucleus (SCN), which contains a molecular time-keeping mechanism. The signals from this biological clock are sent throughout the body and drive circadian rhythms in multiple tissues and organs. The long-term goal of Dr. Charles Allens basic research program is to identify the cellular mechanisms underlying the generation and entrainment of circadian rhythms. Successful completion of this work will provide a better understanding of the mechanisms underlying regulation of circadian processes such as sleep. This knowledge can lead to better and more rationale treatment of circadian-based sleep and mood disorders.The master circadian pacemaker located in the suprachiasmatic nucleus (SCN) is reset by light intensitydependent signals transmitted via a direct nerve pathway from the eyes retina to the SCN. Short-term plasticity at nerve synapses in this pathway was studied using stimuli that simulated the activity of light sensitive retinal cells. In addition, neuronal communication within the suprachiasmatic nucleus (SCN) network facilitates light-induced phase changes and synchronization of individual nerve oscillators. Using calcium imaging techniques to record changes in the intracellular calcium concentration ([Ca2+]i) in the SCN neural network, Dr. Allens group studied the role of the neurotransmitter GABA in interneuronal communication and modulation of optic nerve stimulations that mimic light input signals. Stimulation of the retinohypothalamic tract (RHT) evoked divergent Ca2+ responses in neurons that varied regionally within the SCN with a pattern related to that evoked by applications of GABA. Application of a GABA receptor antagonist induced changes in baseline [Ca2+]i in a direction opposite to that evoked by GABA, and similarly altered the RHT stimulation-induced Ca2+ response. The GABA induced Ca2+ response varied in time and region within the SCN network. GABA-A and GABA-B receptor agonists and antagonists were used to evaluate components of the GABA-induced changes in [Ca2+]i. These results suggest that physiologic GABA induces opposing effects on [Ca2+]i in the SCN network and may play an important role in neuronal Ca2+ balance, synchronization and modulation of light input signaling.

Organic Solvents Illuminate our Understanding of Neurological Disorders

Workers exposed to certain organic solvents (such as n-hexane and 1,2-diethylbenzene) can develop nerve and spinal cord damage that leads to a crippling disease known as peripheral neuropathy. While n-hexane neuropathy is all too common today in certain low- and middle-income countries, improved workplace practices have virtually banished the disease from U.S. industry. Now, the neurotoxic metabolites of n-hexane and 1,2-diethylbenzene are used here as valuable laboratory tools with which to probe the vulnerabilities of the nervous system. This is important as much for occupational as for general medicine because peripheral neuropathy complicates prevalent metabolic diseases of Americans, notably diabetes. Understanding why nerves degenerate in metabolic syndromes would be a huge stride forward toward prevention and treatment. Previous experimental work on this subject (see CROET Report 2006-7) has provided compelling evidence that nerve proteins are targeted in metabolic and toxic diseases. The CROET team of Staff Scientist Desire Tshala-Katumbay, Emeritus Faculty Mohammad Sabri, and Senior Scientist Peter Spencer has now revealed the identity of some of the targeted proteins. They have identified 34 proteins in the spinal cord proteome that are markedly modified after exposure to the solvent metabolites. Additional work showed a significant alteration in the expression of an enzyme involved in protein folding, the proper activity of which is an absolute requirement for the proper functioning of the nervous system. Modifications were also seen in the further processing of proteins through a system called post-translation modification. While these observations have advanced knowledge of the molecular mechanisms that precede the onset of nerve degeneration, precisely how the cascade of events culminates in breakdown of nerve tissue remains to be shown.

Tshala-Katumbay D, Desjardins P, Sabri M, Butterworth R, Spencer P. New insights into mechanisms of gamma-diketone-induced axonopathy. Neurochem Res. 2009 Nov;34(11):1919-23. Epub 2009 Apr 29.PMID: 19404740

Tshala-Katumbay D, Monterroso V, Kayton R, Lasarev M, Sabri M, Spencer P. Probing mechanisms of axonopathy. Part II: Protein targets of 2,5-hexanedione, the neurotoxic metabolite of the aliphatic solvent n-hexane. Toxicol Sci. 2009 Feb;107(2):482-9. Epub 2008 Nov 25.PMID: 19033394

Tshala-Katumbay D, Monterroso V, Kayton R, Lasarev M, Sabri M, Spencer P. Probing mechanisms of axonopathy. Part I: Protein targets of 1,2-diacetylbenzene, the neurotoxic metabolite of aromatic solvent 1,2-diethylbenzene. Toxicol Sci. 2008 Sep;105(1):134-41. Epub 2008 May 22.PMID: 18502740

Integrity of DNA (DNA damage, genetic alterations and disease)

Human health and risk for disease ultimately depend on the integrity of our DNA, the genetic material that provides the bodys blueprint for manufacturing proteins that carry out the function of cells and organs. Aberrant forms of DNA can produce inherited diseases, and changes in DNA during life are believed to trigger cancer and many other chronic diseases. Such changes can result from exposure to certain chemicals found in the workplace and others in the diet and medications, and to sunlight in outdoor workers. Two broad types of DNA changes are recognized: DNA damage and DNA silencing.

Insights Into Mechanisms That Lead to Cancer

Cancer is a leading cause of death and morbidity in Oregonians, and essentially all human populations. Cancer occurs when a cells genome undergoes subtle or major alterations that cause critical proteins to be made incorrectly or not at all. A cells genome contains DNA, which acts as the blueprint for construction of the cell. The critical proteins altered in cancer cells normally function to control cell growth and to maintain the integrity of the genome. An important question in cancer biology is how cellular DNA is altered leading to development of the cancerous cell. An alteration in DNA, commonly termed a mutation, is a change in the primary sequence of the DNA. Many different types of occupational and environmental exposures cause mutations. These exposures cause cancer because of the link between mutation and cancer.Research in the laboratory of Dr. Mitchell Turker has been directed towards identifying the types of mutations that occur spontaneously or are induced by environmental exposures. Most of this work is done with mouse kidney cells because current methodologies allow mutations to be induced and detected in cultured kidney cells and/or within the intact mouse kidney. One example of a study with cultured kidney cells showed that the types of mutations caused by ultraviolet radiation are different when the cells are first exposed to oxidative stress. Ultraviolet radiation found in sunlight is a major contributor to skin cancer. Another study compared the types of mutations induced by ionizing radiation in cultured kidney cells with mutations induced by radiation exposure in mouse kidneys. This study showed that some types of mutations were induced in both the cultured cells and in the intact kidney, but other types were only observed in the exposed kidney. Moreover, mutant cells from the kidneys exhibited unstable genomes. In total, this study showed mutagenic effects from ionizing radiation exposure, such as from sunlight, and that these effects are best studied in the intact organism.Gene inactivation in cancer cells also occurs via a second pathway termed gene silencing, which involves loss of protein production without a DNA mutation. Gene silencing is analogous to a car motor that has stalled and then shuts down. It may be possible to restart such a gene, but repairs are required. Research in the Turker laboratory established that a stalling of the gene predisposes it to undergo silencing. Additional work demonstrated a way to prevent silencing from occurring. Prevention of gene silencing could lead to approaches to prevent cancer.Skinner AM and Turker MS High Frequency Induction of CC to TT Tandem Mutations in DNA Repair Proficient Mammalian Cells. Photochemistry and Photobiology 84:222-227, 2008.

Oyer JA, Chu A, Brar S, and Turker MS Aberrant Epigenetic Silencing Is Triggered by a Transient Reduction in Gene Expression. PLoS ONE 4: e4832. doi:10.1371/journal.pone.0004832, 2009.

Kronenberg A, Gauny S, Kwoh, E, Connolly L, Dan C, Lasarev M, and Turker MS Comparative Analysis of Cell Killing and Autosomal Mutations in Mouse Kidney Epithelium Exposed to 1 GeV/amu Fe Ions In Vitro and In Situ. Radiation Research 172:550-557, 2009.

Turker MS, Connolly L, Dan C, Lasarev M, Gauny S, Kwoh E, and Kronenberg A, Comparison of Autosomal Mutations in Mouse Kidney Epithelial Cells Exposed to Fe ions In Situ or in Culture. Radiation Research 172:558-566, 2009.

Mechanisms Behind Insulin Secretion Diseases Being Uncovered

ATP-sensitive potassium (KATP) channels are gated by the intracellular nucleotides ATP and ADP, the major energy molecules within cells. As such, they couple cell metabolism to membrane excitability and regulate a variety of physiological processes including insulin secretion, vasodilatation, neurotransmitter release, and cell defenses against cardiac and brain ischemia (stroke). Malfunction of KATP channels due to genetic mutations has been shown to cause congenital hyperinsulinism, diabetes, and delayed cardiomyopathy, all diseases that can affect productivity in the workplace. The primary research focus of Show-Ling Shyng, PhD is to understand the role of KATP channels in health and disease, in particular with regard to the regulation of insulin and glucose homeostasis. A recent highlight of her research is the demonstration that patients diagnosed with congenital hyperinsulinism in childhood as a result of dominant KATP channel mutations are not more susceptible to type II diabetes, contrary to what was proposed previously by others. The large-scale clinical and basic science study, published in the Journal of Clinical Investigation in 2008, was a collaborative effort of researchers from OHSU and the Childrens Hospital of Philadelphia. The work has significant impact on our understanding of the biochemical characteristics of dominant mutant KATP channels associated with congenital hyperinsulinism and the course of disease development. Her ultimate goal is to develop therapeutic strategies to combat diseases caused by KATP channel dysfunction resulting from genetic mutations or environmental/occupational exposures.

Sara E. Pinney, Courtney MacMullen, Susan Becker, Yu-Wen Lin, Cheryl Hanna, Paul Thornton, Arupa Ganguly, Show-Ling Shyng, and Charles A. Stanley. Clinical characteristics and biochemical mechanisms of congenital hyperinsulinism associated with dominant KATP channel mutations. J. Clin. Investigation 118(8): 2877-2886, 2008

Insights Into a Cause of Metabolic Syndrome and Cancer

It is estimated that greater than 45 million Americans suffer from a constellation of at least three out of four of the following diseases: obesity, hypertension, diabetes, and fatty liver disease. Collectively, these are known as the Metabolic Syndrome. The annual health care costs associated with the treatment and ongoing care of these diseases is an enormous health care burden with costs exceeding 100 billion dollars, and seriously increase sick leave and limit workplace productivity.Research in the laboratories of Drs. Stephen Lloyd and Amanda McCullough has been directed toward ascertaining the most fundamental mechanisms that initiate cellular changes that ultimately result in metabolic syndrome and cancer. A unifying hypothesis to explain the origins of all of these diseases is the following: the body naturally produces reactive chemical species that can damage the cells genetic material; these chemical byproducts (reactive oxygen species) not only are generated as part of normal energy production and cellular defense mechanisms, but also are produced from exposure to many environmental toxicants and radiation. These reactive oxygen species damage the cells genetic material (DNA) and if not repaired to its original state, the damage could lead to mutations that would trigger the initiation of metabolic syndrome and/or cancer. Since cells contain DNA in both the nucleus and mitochondria (location of energy production), it is essential to repair damage in both cellular locations.To investigate these hypotheses, the Lloyd and McCullough laboratories have created mice that lack the ability to initiate DNA repair following challenge with reactive oxygen species. Mice that lack one of these repair proteins (NEIL1) are very prone to obesity, fatty liver disease, and insulin resistance (Vartanian et al, 2006). Further, the DNA located within the mitochondria of these mice is severely damaged. In addition to the metabolic syndrome diseases, mice that lack NEIL1 and another repair enzyme (NTH1) were shown to be very prone to spontaneous cancer formation (Chan et al, 2009). Greater than 70% of mice that were deficient in both repair proteins spontaneously developed lung adenomas and carcinomas and nearly 50% also developed liver carcinomas (Chan et al 2009). These data establish for the first time a common link between cellular deficiencies in DNA repair with both cancer and metabolic syndrome.

Vartanian V, Lowell B, Minko IG, Wood TG, Ceci JD, George S, Ballinger SW, Corless CL, McCullough, AK, Lloyd RS. The metabolic syndrome resulting from a knockout of the NEIL1 DNA glycosylase. Proc Natl Acad Sci U S A. 103(6):1864-9, 2006.

Chan, M.K., Ocampo-Hafalla, M.T., Vartanian, V., Juruga, P., Kirkali, G., Koenig, K.L., Brown, S., Lloyd, R.S., Dizdaroglu, M., Teebor, G.W. Targeted deletion of the genes encoding NTH1 and NEIL1 DNA N-glycosylases reveals the existence of novel carcinogenic oxidative damage to DNA. DNA Repair (Amst) 8(7):786-94, 2009.

Cellular Responses to Acute and Chronic Formaldehyde Exposure

The laboratory of Dr. Amanda McCullough is interested in the regulation and roles of DNA repair in cellular responses to occupational and environmental stress and how genetic variation and defects in these systems modify the risk of cancers and other disease states in humans.Formaldehyde exposure occurs both in occupational settings and household environments. Formaldehyde is a respiratory irritant associated with asthma and sick building syndrome, and exposure is associated with the occurrence of nasopharyngeal cancers and DNA damage. In order to identify and characterize the biochemical mechanisms for repair of formaldehyde-induced DNA damage, the McCullough lab is utilizing a yeast model system that allows the entire genome to be screened for genes that confer formaldehyde sensitivity. These studies have identified specific biochemical pathways that protect cells from the cytotoxic effects of acute and chronic formaldehyde exposures; results that will impact the assessment of safe human exposure limits in the workplace and from some consumer products. This work was published in the journal DNA Repair in 2009.

Bendert de Graaf, M.S., Clore, A.J., McCullough, A.K. Cellular Pathways for DNA Repair and Damage Tolerance of Formaldehyde-Induced DNA-Protein Crosslinks. DNA Repair, 2009; 8:1207-14.

DNA Repair-based Therapeutic Strategies for the Prevention of Skin Cancer

Exposure of human skin to ultraviolet light (UV) triggers a progression of events that is initiated by DNA damage and immune suppression and can ultimately result in mutagenesis, actinic keratoses, and skin cancers. The number of affected individuals is rapidly increasing, with over 1 million new skin cancers diagnosed in the United States annually. The carcinogenic effects of UV light, such as from sunlight, are directly mediated by dipyrimidine DNA photoproducts. Human cells have only one mechanism to repair these DNA lesions, while lower organisms possess multiple pathways to repair the deleterious consequences of UV-induced DNA damage. In order to implement proactive strategies to treat and prevent several human diseases that can be directly attributed to inefficient repair of UV-induced DNA lesions, including skin cancer, the McCullough and Lloyd laboratories have discovered and characterized multiple DNA repair enzymes that possess activities that can initiate an additional repair pathway in human cells.

Experimental reduction to practice was demonstrated in 2008-2009 by the following technological breakthroughs: 1) purification and encapsulation of patented enzymes in specific targeting vesicles that are used for topical skin delivery and 2) demonstration of the efficacy of the enzymes to localize to damaged cells and to initiate DNA repair using a fully-differentiated human skin model system and human keratinocyte cell cultures. These findings make it possible to develop topical treatments for UV-induced DNA damage in populations excessively exposed to sunlight, such as outdoor workers.

 

2006-2007 CROET Highlights

What has CROET done for Oregon?

Brought federal dollars into the Oregon economy

CROET receives base operations funding from the Oregon Workers Compensation System that, year after year, CROET scientists have successfully leveraged to win federal and other research dollars. For every dollar invested by the States Workers Benefit Fund, CROETs world-class scientists have brought an averaged $2.40 of federal and private grant funding into the Oregon economy (see chart below). Federal dollars for research in Oregon have a significant positive impact on the states economy. Expenditures for goods and services, as well as the salaries of scientific and support personnel, produce a multiplier effect on the purchase of goods and services and creation of businesses that support the needs of Oregons research institutions. Moreover, research coming out of CROET has a greater than average impact on the states economy from the new technologies and jobs that spin off from productive research, as exemplified later in this report. In a study conducted by Oregon State University, multiplier effects on the economy from the infusion of federal grant funds were estimated to range from 2 up to 10 dollars per federal dollar received.

Conducted workplace studies and applications research

CROET conducts workplace surveys so that prevention and research needs can be identified, and applications research to bring the benefits of science to the workplace floor. It also reaches out to provide education and information to the Oregon workforce and beyond.

Oregon Fatality Assessment and Control Evaluation (OR-FACE) Program

Dr. Gary Rischitelli leads the Oregon Fatality Assessment and Control Evaluation (OR-FACE) program that tracks, investigates, and reports on occupational fatalities in Oregon. In 2006, OR-FACE recorded 79 occupational fatalities in 67 incidents. In 2007, OR-FACE recorded 69 fatalities in 67 incidents. OR-FACE investigates incidents in specific national and local target areas of concern and, between 2006-2007, produced 9 investigation reports with safety recommendations. During 2006-2007, falls became a leading area of concern, and OR-FACE published a hazard alert on falls from elevated work areas, ladders, and suspension from a height. In 2007, OR-FACE published its third annual report summarizing data from 2005 and included an abstract of each incident. The report charted frequencies by age, gender, race/ethnicity, time, month, county, industry, occupation, and event. Principal areas of concern were highlighted in relation to transportation, falls, and contact with objects or equipment. Through its research, OR-FACE has identified several priority areas of concern within specific sectors of the Oregon workforce, including transportation (motor vehicles, trucking), logging, and young workers. Young workers aged 16-24 are involved in 15% of all Oregon fatalities, a finding that inspired establishment of the Oregon Young Worker Health and Safety Coalition, co-sponsored by OR-FACE and the University of Oregons Labor Education & Research Center (LERC). The Coalitions activities include developing occupational safety and health curricula for teens, disseminating educational materials for teachers, conducting teacher education workshops, outreach to employers, and public information campaigns. OR-FACE investigation reports and other publications are available on the programs website (www.ohsu.edu/croet/face). Investigation reports from Oregon and other FACE states are also available through the National Institute for Occupational Safety and Health (www.cdc.gov/niosh/face), which funds the program.

Health Promotion Intervention Model Being Developed for Truck Drivers

Safety and Health Promotion for Truck Drivers (SHIFT), a program developed and headed by Dr. Ryan Olson, is a 6-month safety and health promotion program designed for commercial truck drivers. Commercial truck drivers account for 15% of occupational fatalities, 8% of musculoskeletal injuries, and have a 10-12 year shortened life span. Long and unusual work hours, prolonged sitting, limited food choices, and demanding work put drivers at risk for serious illness and injury - most notably heart disease and back injuries. Drivers who joined the SHIFT program completed training and worked toward goals, including weight loss, diet and safe driving. Drivers competed in teams to achieve the largest improvements in health and safety measures, and were rewarded for both participation and high achievement. To help drivers accomplish their health and safety goals, the program included computer-based training, self-management activities and individualized health coaching. This evidence-based health promotion intervention was funded by a National Occupational Research Agenda (NORA) priority grant from the Northwest Center for Occupational Health & Safety. Please visit www.ohsushift.com to learn more.

Self-Assessment and Self-Management Program Helps Truckers Avoid Musculoskeletal Injury

Behavioral self-monitoring (BSM) methods, where individuals repeatedly observe, evaluate, and record aspects of their own behavior, can produce valuable assessment data about injury hazards and near misses. Dr. Ryan Olson has developed and studied BSM assessment with less-than-truckload (LTL) truck drivers. LTL work involves hauling partially loaded trailers, making multiple daily stops, and performing frequent and demanding material handling work in a variety of customer environments. To address this difficulty, Dr. Olsons research team employed two data collection methods: (1) intensive video monitoring, in which direct observation of work habits and environments were achieved through the use of a customized camera system installed in a working trailer and (2) behavioral self-monitoring, in which individuals repeatedly observed, evaluated, and recorded aspects of their own behavior and environmental conditions. Dr. Olson found that each instance of manual material handling increases the potential for severe (hazardous) body postures by 7%, whereas obtaining customer forklift assistance and preventing manual materials handling by palletizing transported materials decreased this potential by 12% and 20%, respectively. Comparisons between experimenter video observations and driver self-observations showed that drivers are quite accurate at self-assessing hazards that are environmental, frequent, and easy to discriminate, but less so at assessing potentially harmful body postures and rare work-related events or environments. These findings suggest areas in which positive interventions can reduce risk for injury, including organizational management of ground stops (e.g. facilitating the use of forklifts), re-engineering handles and steps that lead into trailers, and having workers self-assess the prevalence of certain work exposures. The results of this project are an important step forward in understanding and preventing musculoskeletal injuries among isolated workers and in advancing our knowledge about the reliability of ergonomic self-assessments.

Study on Vigilance Performance Enhances Error & Threat Detection

Human performance on visual screening tasks is increasingly important to public and workplace safety. These tasks require human operators to detect rare but potentially dangerous signals or threats on some type of visual display. Examples include: aviation security workers searching for unusual passenger behaviors and prohibited items in luggage; radiologists screening for tumors or other abnormalities in sophisticated body images, and manufacturing workers searching for potentially dangerous and costly deviations in high-tech production processes. Dr. Olson collaborated with Lindsey Hogan and Matthew Bell of Santa Clara University (Santa Clara, California) to develop a simulated baggage-screening task that uses x-ray images provided by the Transportation Security Administration to investigate factors that enhance vigilant search behaviors. It is known that observers in visual search tasks miss threats at increasing rates as threats become less frequent (i.e. anomalous objects such as weapons in luggage are relatively rare). The research team tested a Vigilance Reinforcement Hypothesis (VRH), which proposes that signal detection reinforces search behaviors, and predicts more intense searching and better signal detection when signals are abundant. Dr. Olson has completed two laboratory studies that are supportive of this prediction, and has applied to the National Science Foundation (NSF) for funding to support continued work on learning phenomena that could be used to enhance signal detection, such as reinforcing variability in visual search patterns, and using planted signals as an intervention method to sustain vigilant search behaviors.

Computer-based Training Effective for Immigrant Orchard Workers

W. Kent Anger, PhD, CROET Senior Scientist and Associate Director, has been developing and testing the effectiveness of a computer-based training system that is competent across cultures and is now available commercially. It is designed to be effective with the full range of occupational populations, from uneducated (no schooling) immigrant agricultural workers to office workers with graduate educations. Dr. Angers lab is shared with staff scientist Dr. Diane Rohlman, whose independent research focuses on neurotoxic effects in young workers and children of workers exposed to pesticides at work. Latinos dominate the agricultural workforce in Oregon and throughout the US. Many have limited years of education in countries with different systems of education than in the US. Drs. Anger and Rohlman have been investigating whether computer-based instruction (CBI) is suitable for this work group, which generally has an average of 5-6 years of education, though some have not been to school at all. Ladder safety was studied in a Latino orchard workforce that reported little computer experience and reported an average 5.6 years of formal education. The orchard workers rated the training highly and their knowledge of ladder safety improved substantially as measured by standardized tests. More importantly, there was a significant increase in safe work practices immediately after training, at 40 days after training and at 60 days, indicating that the learning was durable over time. This demonstrates that an agricultural workforce can learn job safety from CBI, translate the knowledge to work practice changes, and maintain those changes over time. Dr. Anger published this work in the International Journal of Training and Development.OHSU and Drs. Anger and Rohlman have a significant financial interest in Northwest Education Training and Assessment, LLC, a company that may have a commercial interest in the results of this research and technology. This potential conflict was reviewed, and a management plan, approved by the OHSU Conflict of Interest in Research Committee, was implemented.

Continues to be a trusted information resource for Oregon workers

CROET has been proactively engaged in providing timely occupational health and safety information to employees, employers, health and safety professionals, doctors and nurses.

Toxicology Information Center (TIC)

Directed by Dr. Fred Berman, the TIC provides free scientifically accurate information for those with questions or concerns about chemical, biological, physical or other agents encountered in the workplace and elsewhere. In 2006-2007, Dr. Berman handled hundreds of consultation requests from occupational safety and health professionals, business owners, government agencies, physicians and nurses, the media, and the general working public. Inquiries covered a variety of issues, as shown on the chart. Chemical agents of concern included solvents, heavy metals, insecticides, fungicides, and herbicides. Physicians often called seeking information on a variety of potentially occupation-related health complaints.Calls in regard to indoor mold were common as were calls related to acute and chronic medical problems that were attributed to exposure to chemical agents. Each request took from less than an hour up to several days to respond to fully. The TIC is open from 7:30 a.m. to 4:00 p.m., Monday through Friday. Walk-in visitors have access to a variety of resources, including computers, databases, government reports, textbooks, and journals that are devoted to toxicology-related issues.

CROETweb.com

CROETweb.com is an occupational safety and health resource directory that contains links to over 1200 occupational safety and health resources focusing on day-to-day workplace issues. CROETweb serves thousands of users who regularly bookmark this resource, those who subscribe to the monthly electronic newsletter, and those searching by search engine (e.g. Google) for occupational health and safety topics on the web. It is widely recognized and respected by industrial health and other safety professionals as well as the general public. CROETweb was accessed an average 12,000-16,000 times per month for a total of 166,134 hits in 2007. This monthly average hit rate has increased yearly since the inception of CROETweb. CROETweb added 11 new home page topics, for a total of 83 in 2006Hospitality  Hotel, Restaurant and Kitchen; Landscaping; Logging & Forestry; Acids & Bases; Chromium; Avian Flu; Occupational Asthma; Occupational Reproductive Hazards; Materials for Safety Talks; OSH Professional Development; and Safety, Language and Culture. An additional 13 topics were significantly revamped in 2007Acids and Bases; Asbestos; EMF and Cell Phones; Beryllium; Ergonomics; Office Ergonomics; MSDS Resources; Avian Flu; Healthcare; Solvents; Pesticides; Respirators; Transportation) Annual page hits  2006: 162,8382007: 166,134 More than 1,250 links are posted on CROETweb.com, including Oregon-specific information from OR-OSHA.

Chemical Risk Information Service (CRIS)

OSHA regulations require employers to maintain Material Safety Data Sheets (MSDS) for hazardous chemicals used in their workplace. This often proves to be a difficult record-keeping task, and it can be burdensome to ensure that employees have quick access to health and safety information in the workplace when they need it. Since 1998, CROETs Chemical Risk Information Service, directed by Dr. Gregory Higgins, has helped a growing number of local and international industries manage and distribute chemical safety information through its Internet-based MSDS management system. CROETs working relationship with the Oregon Poison Center also ensures that employees covered by the program have ready access to medical information in the event of exposure. During 2006-2007, the Chemical Risk Information Service added five new clients, and now provides MSDS management services to 40 municipal, construction, and service companies, most of which are Oregon-based. Also during this period, this program began working with SafetyCal, a chemical labeling company located in Eugene, to begin developing a service to link CROETs MSDS program with their labeling service so that clients can have a one-stop location to meet OSHA right-to-know regulations. Enhancements were made to the website and database during this period. CROET continues to provide expert MSDS management services at a reasonable cost, which is attractive to both small and large organizations.

Health and Safety Training Symposia

CROET provides two health and safety symposia per year, one sponsored jointly with Portland State University. Topics are determined based on solicited and unsolicited feedback from the Oregon occupational health and safety professional community. The target audience includes health and safety professionals, occupational nurses and physicians, loss control specialists and human resource representatives, although the targeted group varies based on the symposium topic. The purpose of the symposia is to provide timely, up-to-date presentations, forums and discussions on workplace safety and health issues. CROET presented the following symposia in 2006-2007:Substance Use and Safety in the WorkplaceNovember 2, 2007, Portland State University, Portland, OregonSafety at Work in Informal and Non-Traditional Settings: Protecting Vulnerable WorkersJune 8, 2007 at the NECA/IBEW Electrical Training Center, Portland, OregonWorkplace Violence PreventionDecember 8, 2006 at the Native American Center at Portland State University, Portland, OregonSafety and Health for the Limited English Speaking Workforce: Challenges & SuccessesJune 9, 2006 at the Ambridge Event Center, Portland, Oregon

Regional Health and Safety Conferences

OR-OSHA sponsors the majority of health and safety conferences that CROET attends; these conferences are an important means by which CROET reaches out to working Oregonians. Workers and businesses learn about CROET and what it has to offer, and CROET personnel learn about the needs and concerns of workers and the industries that employ them. Moreover, CROET scientists are often asked to give health and safety presentations in addition to providing conference exhibits. Overall, conferences represent a tremendous networking opportunity for CROET outreach personnel. The following are safety and health conferences attended by CROET during 2006-2007:2006 Oregon Governors Fire Service Summit NIOSH/NORA Town Hall Meeting Agriculture, Forestry and Fishing Bob Bryant Memorial Cascade Occupational Safety & Health Conference Oregon Workers Compensation Educational Conference HealthCare Ergonomics Conference Central Oregon Occupational Safety & Health Conference Southern Oregon Occupational Safety & Health Conference Northwest Occupational Health Conference NexCon 2006 - Next Generation Construction Summit: Defining the New Critical Path Western Pulp & Paper Workers Safety & Health Conference2007 Oregon Governors Occupational Safety & Health Conference Blue Mountain Occupational Safety & Health Conference Central Oregon Occupational Safety & Health Conference Southern Oregon Occupational Safety & Health Conference Northwest Occupational Health Conference

Research to the Public Exhibit

Jackie Shannon, Ph.D. developed and implemented a Research to the Public exhibit as part of the Oregon Museum of Science and Industrys Body Worlds. This interactive exhibit (Nutrition Worlds) provided participants with an opportunity to obtain tailored feedback on their diet, including measurements of height, weight, waist circumference and percent body fat, measurements of blood glucose, HDL, LDL and total cholesterol levels. Participants also had the opportunity to become research subjects, where de-identified data on diet, body composition, cholesterol measures, and salivary samples for DNA extraction and genotyping were obtained. Over 3000 individuals participated in this project and provided data as part of this Research to the Public project. Nutrition Worlds is now being converted into an off the shelf exhibit with the capacity to be used at large health fairs throughout the year. This type of outreach benefits workers and the general public by increasing awareness of factors that contribute to healthy lifestyles and a healthy workforce.

Helped build biotech in Oregon

CROET scientists Stephen Lloyd PhD & Amanda McCullough PhD are interested in DNA mutations and the mechanisms cells use to repair DNA damage induced by environmental stresses, including sunlight. Through basic research into the biomolecular mechanisms of ultraviolet (UV) radiation-induced DNA mutation and repair, they have devised and are now developing a novel strategy for preventing UV-induced skin cancer. Since mammals have only one system for repairing sunlight-induced DNA damage, their strategy is to supply skin cells with a second DNA repair system, which can be applied topically as a lotion to the skin. This involves the use of lipid coatings and protein tags that effectively allows the targeting of the DNA repair system to the cell nucleus, where it can be effective, thereby providing an extra level of protection against UV-induced DNA mutation. The technology has been shown in laboratory experiments to almost completely repair UV-induced DNA damage within 2 hours of application. Drs. McCullough and Lloyd have formed a company, Restoration Genetics, Inc., to develop and commercialize this technology as a therapy for prevention of skin cancer. This technology is explained in more detail in CROET Newsletter Vol. 14, #1, which can be downloaded at: http://www.ohsu.edu/croet/about/pubs.cfm

Became global ambassadors for CROET, OHSU and Oregon workers

The Global Health Center (GHC)

The newly formed Global Health Center (GHC), housed in the CROET Toxicology Information Center, facilitates OHSU collaboration with the global health community to promote quality and equity in health care at home and abroad. Through the GHC, CROET and OHSU are working with domestic and international communities to develop programs for students, faculty, staff and partners that will promote global health awareness, research, education and advocacy. Dr. Peter Spencer, CROET Director and Senior Scientist, serves as Interim Director of the Global Health Center. Dr. Spencer has long studied the causes and solutions to neglected human diseases in developing countries, and hopes to spawn a new generation of medical and research professionals certified in global health. Built on the principle that there can be an effective two-way exchange on matters such as cultural competency, health education, research opportunities and clinical practice, the long-range goal of the GHC is to maintain a compact, efficient operation on the campus and invest in building healthcare capacity in global communities. In 2007, planning began for transdisciplinary global health courses involving faculty, students and staff. This includes a health and hygiene community exchange program, championed by CROETs Valerie Palmer, that brings Portlands refugees from Africa together with students and faculty from OHSU schools of Dentistry, Nursing and Medicine, and other OHSU-based programs of the OSU College of Pharmacy.

Conducted laboratory research aimed at preventing or mitigating the adverse

effects of workplace injuries and exposures

Injury and Recovery of the Nervous System and Muscles

CROET scientists conduct basic research that examines the causes of injury to nerves and muscles in order to identify protective, preventative, and recovery methodologies for such injuries.

New Discoveries on Nervous System Effects of Environmental Pollutants, Statin Drugs, and Pesticides

Biomarkers allow us to determine when chemical exposures reach a toxic level and identify the need for medical intervention. Pamela Lein, PhD has discovered that polychlorinated biphenyls (PCBs), a class of developmental neurotoxicants and environmental pollutant, interfere with neuronal connections in the developing brain by disrupting normal patterns of nerve growth and plasticity (the ability of neurons to change in response to environmental stimulus). This is the first identification of a specific neurodevelopmental event that is altered by exposure to PCBs. Dr. Lein also discovered that exposure to PCBs during development actually alters the susceptibility of the adult brain to damage caused by lack of oxygen that occurs during a stroke. In a related discovery, Dr. Lein found a novel mechanism by which statins, the commonly prescribed lipid-lowering drugs, decrease neuroinflammation  this effect may explain clinical reports and experimental studies identifying a potential therapeutic effect of statins in diverse neuroinflammatory conditions such as migraine headaches, arthritis and asthma. Dr. Lein also discovered that chlorpyrifos, an organophosphate (OP) pesticide still commonly used in the U.S. and throughout the world, interferes with axonal outgrowth in developing neurons via a unique mechanism that involves interference with the morphogenic activity but not the enzymatic activity of acetylcholinesterase (the enzyme responsible for degrading the neurotransmitter, acetylcholine)  this has important ramifications regarding the use of acetylcholinesterase activity as a biomarker of exposure to toxic levels of OPs.

Nerve Support Protein Plays Unique Role in Neuromuscular Development

By understanding basic mechanisms of neuromuscular development and maintenance, we will learn how to repair muscle and nerve connections damaged in workplace accidents. The wiring of the nervous system during development is coordinated by molecular signals exchanged between neurons, glial cells (support cells which ensheath neurons), and target cells that receive innervation. Bruce L. Patton, Ph.D. is studying signals that coordinate these cellular interactions. His interest is focused on the extracellular proteins that mediate direct contact between neurons, glia, and skeletal muscle fibers. The principal component of the extracellular protein matrix that covers a type of glial cell called the Schwann cell and skeletal muscle fibers is a glycoprotein called laminin. The Patton laboratory discovered four novel types of laminin; two are specifically associated with muscle fibers, and are concentrated at sites of synaptic contact, and the other two comprise the primary scaffold of the Schwann cell basal lamina. Pattons lab has used a combination of genetic mutational studies in mice and cell and biochemical studies to show that each laminin subtype plays a unique and primary role during neuromuscular development as well as a continuing role in maintaining the mature tissue. For example: laminin-11 localizes nerve terminal differentiation at embryonic synaptic sites in muscle; laminin-9 organizes the active zones (transmitter release sites) in mature motor nerve terminals; laminins-2 and -8 regulate Schwann cell responses to axonal cues during nerve myelination  they act cooperatively to match the number and type of Schwann cells to the number and type of axons; and laminin-2 stabilizes the muscle membrane during contractions. Current research in the Patton lab is directed at determining precise activities (e.g. differentiation, proliferation, signaling, motility support), and the cellular receptors and pathways that mediate the laminins effects.

Chronic Disease and Working Safety

Chronic disease takes a significant toll on our workforce just as it does in the broader community. CROET research seeks to discover causes of chronic diseases that are produced or exacerbated by workplace factors and identifies processes or procedures that can prevent or ameliorate those diseases and improve workplace safety.

Fruit Flies Enhance Our Understanding of Human Neurodegenerative Diseases

Doris Kretzschmar, PhD is interested in identifying genes and cellular mechanisms that underlie progressive degeneration of the nervous system, such as occurs in Alzheimers disease. She has used specialized mutant and transgenic Drosophila melanogaster (fruit fly) lines to analyze, at the functional and molecular level, a protein called Swiss-Cheese/Neuropathy Target Esterase, which is involved in organophosphate pesticide-induced neuronal degeneration. Dr. Kretzschmar discovered that dysregulation of another cellular protein, known as protein kinase A, when it occurs in the absence of a functional Swiss-Cheese/Neuropathy Target Esterase, leads to neurodegeneration. This finding promises to be of functional significance to our understanding of several important human neurodegenerative diseases. Dr. Kretzschmar is also using her fruit fly model to analyze the physiological and pathological functions of amyloid precursor proteins, which are key factors in the pathology of Alzheimers disease. 

Discoveries of Circadian Clock Function Leads to Enhanced Understanding of Sleep-Wake Cycles

Chuck Allen, PhD is interested in the brains circadian clock, which controls our sleep-wake cycles. Disruption of the circadian clock, such as occurs in workers who work odd shifts, plays an important role in increasing our risk for occupational accidents and chronic diseases. Most organisms, from plants to primates, display circadian rhythms, which are daily oscillations of physiological processes. The master circadian clock driving these circadian rhythms in mammals is located in a nerve group within the brain called the suprachiasmatic nucleus (SCN). Each SCN neuron expresses a molecular clock, which must be synchronized to other SCN neurons by neurotransmitter chemicals. Special classes of retinal cells that measure light intensity maintain the time-dependent coupling between the circadian clock and daily light-dark cycles. The long-term goal of Dr. Allens research is to identify the signaling mechanisms within the SCN and retina that generate and entrain circadian rhythms. In 2006-7, Dr. Allen discovered a variety of cellular mechanisms that control how light-induced signals are processed and passed to areas of the brain that are involved in circadian clock function. A goal of this research is to increase our understanding of circadian clock function so that effective strategies for mitigating the adverse and potentially dangerous effects of shift work and odd work situations can be developed.

Organic Solvents Illuminate our Understanding of Neurological Disorders

Neurotoxic disorders of occupational, therapeutic, or other origin, in which the causative agent is identified, usually present as self-limiting neurodegenerative diseases that impact motor, sensory and other nerve functions. Similarly, some chemical agents, acting alone or aided by a susceptible genetic background, also seem to play a role in the cause of progressive neurodegenerative diseases (e.g., sporadic amyotrophic lateral sclerosis (ALS) and Parkinsons disease). However, the molecular cascade over the long latent period from the beginning of natural disease development to clinical expression is unsolved and a key subject of investigation. Dr. Peter Spencer, Dr. Mohammad Sabri and Dr. Desire Tshala-Katumbay use organic solvents as tools to probe and model, over much shorter time scales, the human neurodegenerative diseases that take such a long time to develop. This requires exploration of the molecular mechanisms underlying the neurotoxic properties of these chemicals, which in turn is helpful in newly identifying hazardous substances in the workplace. New methods to identify and characterize the hazardous properties of chemicals require validation before they can be used to protect public health. One powerful method uses microarrays to capture changes in gene expression of tissues that have been exposed to chemicals and drugs. Microarray technology allows scientists to track the expression of thousands of genes at once. Dr. Spencer and his colleagues joined with six other leading laboratories to determine whether similar results could be obtained when experiments were replicated as closely as possible. The common over-the-counter analgesic acetaminophen was used as the test article because it is well established to produce liver toxicity. The study revealed similarities and some unexplained differences in data generated from different laboratories, but overall new information was captured on the molecular mechanisms of the drugs liver toxicity. The study confirmed the value of microarrays in detecting, characterizing and understanding chemical toxicity. With validation of the method established, these scientists can now utilize microarrays to understand the pathological changes that occur following short- and long-term exposure to organic solvents.

Computational Modeling of Genetic Variation Aids Our Understanding of Occupational Disease

Dr. Harvey Mohrenweiser is interested in reducing morbidity and mortality in individuals with elevated genetic susceptibility to common exposure-related diseases. Obesity, non-traditional work schedules and age are common exposures associated with increased risk of disease, injury and impaired performance. Such exposures have major negative consequences for health care and Worker Compensation costs for Oregon workers and the cost of doing business for Oregon businesses. Genetic variation has a clear role in modifying the susceptibility of individuals to these exposures; however, the problem of identifying the molecular basis for aberrant disease susceptibility is very complex, especially if the deviation from average disease susceptibility and contribution of multiple genes/variants and exposures are all small. Continued development of new experimental designs and approaches to data analysis will be required to address these complex problems, and they must be conquered if the potential for individualization of health care and medicine is to become a reality. Major progress has been made in identifying disease causing genes by studying susceptible families. Through computational and biochemical methods, Dr. Mohrenweiser has predicted that approximately 50% of all gene sequence alterations that have been identified in human genetic variation studies also alter protein function and potentially modify an individuals risk of disease. This begins to explain the role of family history in predicting disease risk. DNA sequence variation with potential to impact gene expression is commonly observed in studies of DNA repair genes and genes with important roles in the response of cells to environmental agents. Dr. Mohrenweiser successfully employed statistical approaches to identify genetic variants that contribute to variation in the capacity of cells to repair damaged DNA. Genetic variation in DNA repair genes with key roles in repair of DNA damage caused by exposure to sunlight was found to explain about 20% of the variation among individuals at risk for melanoma. This is a very early step in efforts to identify people at elevated risk for this disease, as well as other diseases.

Integrity of DNA (DNA damage, genetic alterations and disease)

Human health and risk for disease ultimately depend on the integrity of our DNA, the genetic material that provides the bodys blueprint for manufacturing proteins that carry out the function of cells and organs. Aberrant forms of DNA can produce inherited diseases, and changes in DNA during life are believed to trigger cancer and many other chronic diseases. Such changes can result from exposure to certain chemicals found in the workplace and others in the diet and medications. Two broad types of DNA changes are recognized: DNA damage and DNA silencing.

Genotoxicants Disrupt Neurodevelopment and Induce Neurodegenerative Disease Processes

Glen Kisby, PhD is interested in the role of DNA damage and DNA repair in neurodevelopment and neurodegenerative diseases, and in the influence of environmental factors (e.g., occupation, stress, diet) on brain tissue DNA repair. Synucleinopathies and tauopathies, neurological diseases that result from the pathological accumulation of alpha-synuclein and tau proteins, are important neuropathological hallmarks of neurodegenerative diseases, including Alzheimers disease and the prototypical neurodegenerative disorder, Western Pacific amyotrophic lateral sclerosis/Parkinson-dementia complex (ALS/PDC). The cycad plant has been shown to be a strong causal factor for ALS/PDC. Dr. Kisby has shown that the cycad plant genotoxicant, MAM, disrupts cellular processes that regulate tau and synuclein through a DNA damage mechanism. Further investigation of the relationship between MAM-induced DNA damage and tau protein metabolism during early brain development could provide important clues about how cycads contribute to the neurodegeneration in PDC and related neurological disorders (e.g., Alzheimers and Parkinsons disease). Dr. Kisby has also shown that MAM, as well as the chemotherapeutic agent nitrogen mustard, disrupts early brain development through a DNA damage-mediated mechanism. These findings suggest that the specific combination of DNA lesion and DNA repair capacity within a neuron are key factors that determine whether the immature brain is vulnerable to a particular genotoxicant. Such factors are expected to be particularly important for understanding how environmental genotoxicants or chemotherapeutic agents induce their long-term effects on the developing brain. An understanding of these processes will enable us to avoid workplace/environmental exposures that increase our risk for neurological disease as well as allow us to develop new treatments for such diseases. Following this line of thought, Dr. Kisby has shown that the brain of aging animals on a caloric-restricted diet is more efficient at repairing DNA damage than animals on an unrestricted diet. This finding indicates that dietary changes can have a positive effect on the DNA repair capacity of the brain, particularly among the aging population.

Pesticides May Induce Oxidative Stress and DNA Damage in Agricultural Workers

Multiple studies have reported associations between exposure to agricultural chemicals and various health outcomes including cancer, Parkinsons disease and other neurological diseases. Oxidative stress and DNA damage have been proposed as mechanisms linking pesticide exposure to these adverse health effects. In recent in vivo and in vitro studies, Dr. Kisby has found evidence that organophosphate pesticides induce oxidative stress and DNA damage in agricultural workers. The method of detecting such changes, called biomarkers, increases our understanding of the link between pesticides and a number of health outcomes (e.g., neurological disorders and cancer). This work has been accepted for publication in the journal Toxicology and Applied Pharmacology.

Mechanisms Behind Insulin Secretion Diseases Being Uncovered

ATP-sensitive potassium (KATP) channels are gated by the intracellular nucleotides ATP and ADP, the major energy molecules within cells. As such, they couple cell metabolism to membrane excitability and regulate a variety of physiological processes including insulin secretion, vasodilatation, neurotransmitter release, and cell defenses against cardiac and brain ischemia. Malfunction of KATP channels due to genetic mutations has been shown to cause congenital hyperinsulinism, diabetes, and delayed cardiomyopathy. The primary research focus of Show-Ling Shyng, PhD is to understand the role of KATP channels in health and disease, in particular with regard to the regulation of insulin and glucose homeostasis. Dr. Shyng has discovered new mechanisms by which mutations affect ion channel function to cause insulin secretion diseases. Her ultimate goal is to develop therapeutic strategies to combat diseases caused by KATP channel dysfunction resulting from genetic mutations or environmental/occupational exposures.

Dietary Factors Alter Susceptibility to Cancer

Jackie Shannon, Ph.D., uses epidemiologic methods to investigate the role of bioactive food components and metabolic dysregulation in the early stages of cancer development. She is interested in: 1) the role of dietary compounds, including omega-3 fatty acids and sulforaphane (an anticancer, antidiabetic and antimicrobial compound found in cruciferous vegetables) in the early development and prevention of prostate and breast cancer; 2) genetic susceptibility and dietary interactions in breast and prostate cancer prevention; and 3) metabolic dysregulation (including obesity and lipid metabolism) in cancer prevention. Dr. Shannon published her most recent findings on the relationship between omega-3 fatty acids and breast cancer risk. She is building upon her work by obtaining funding to begin one of OHSUs first chemoprevention trials for women newly diagnosed with ductal carcinoma in situ. Her long-term goal is to enhance the overall health of the workforce through the discovery of factors that reduce the incidence of cancer in our population.

New Gene Silencing System Facilitates Cancer Research

Gene silencing occurs when a gene that should be expressed in a cell turns off unexpectedly. It is a common component of cancer. Aberrant gene silencing plays a causal role in cancer because it leads to inactivation of tumor suppressor genes. The endpoints of silencing are fairly well defined: promoter region DNA methylation and repressive histone modifications. Mitchell Turker, PhD has devised a system to trigger and study gene silencing in mammalian cells. The new system will be useful to determine how workplace and environmental exposures could initiate gene silencing and also to identify diets or drugs that could be designed to prevent gene silencing from occurring.

Mutation Discovery May Lead to New Skin Cancer Prevention Strategies

Dr. Mitchell Turker has identified a combination of cellular exposures that lead to an unusual mutation induced by exposure to ultraviolet radiation (UV). Although rare in most cancers, this mutation (termed the tandem mutation) is found commonly in skin cancers and is due to sun exposure. A combination of UVB, which is the damaging form of ultraviolet light found in sunlight, and oxidative stress was shown to effectively induce the tandem mutation. This observation is aimed at developing strategies to prevent skin cancers, such as those that occur among outdoor workers. Dr. Turker is continuing a long-term project to identify the types of mutations induced by exposure to ionizing radiation. Ionizing radiation is found at low levels in our environment and is used commonly in diagnostic x-rays and in cancer treatment. Knowledge of the types of mutations induced by this form of radiation will be helpful to determine whether a person has been exposed, the consequences of exposure, and to estimate the level of exposure.

New Research Discovers Mechanisms Underlying How Tumor Cells Resist Chemotherapy

Occupational and environmental exposure to chemicals such as butadiene (a major building block in the synthetic rubber and plastics industries) and acrolein (a major contaminant in gasoline and diesel vapors and cigarette smoke) represent a significant health hazard and are classified as human cancer-causing agents. Results from the laboratory group of Stephen Lloyd, PhD demonstrate the mechanisms by which exposure to these chemicals causes modifications in DNA that lead to mutations and transformation of normal cells into cancer cells. These studies were extended to show that these chemicals undergo complex secondary chemical reactions in which the two strands of DNA can be crosslinked to one another, a form of DNA damage that usually leads to cell death. Crosslinking DNA is one of the major mechanisms by which chemotherapeutic agents kill cancer cells. Even though these chemicals can crosslink the DNA strands, further work by the Lloyd group has shown that cells have special enzymes that can copy DNA even if it is crosslinked. This finding has implications for chemotherapeutic treatment of cancers, providing the first evidence for how cells (especially tumor cells) might resist killing by crosslinking agents.

Skin Cancer Prevention Therapeutic Shown to Enhance Repair of Sunlight-Induced DNA Damage in Human Skin

Even though the Pacific Northwest is generally associated with only modest sun exposure, the state ranks in the top 5 nationally for sunlight-induced skin cancers. This is a significant hazard for working Oregonians. Although the reasons underlying the high incidence of skin cancer in Oregonians are complex, it is well established that sun exposure is the primary cause of non-melanoma skin cancers. It is important to take steps to prevent or at least significantly reduce the onset of this disease. Toward this goal, the research laboratories of Drs. Amanda McCullough and Stephen Lloyd have combined research interests and expertise to develop a potential prevention therapy for these skin cancers. Together, they have patented DNA repair enzymes that when delivered to human skin cells, rapidly repair sunlight-induced DNA damage. Their investigations have recently shown that when human skin is grown in the laboratory, repair of sunlight damage rapidly occurs when the DNA repair lotion is applied. These studies are aimed at obtaining FDA safety approval for initial human clinical trials.

Chronic Low-dose Formaldehyde Exposure Results in DNA Damage Processed by the Homologous Recombination Pathway in Yeast

Formaldehyde exposure occurs both in occupational settings and household environments. Formaldehyde is a respiratory irritant associated with asthma and sick building syndrome, and exposure is associated with the occurrence of nasopharyngeal cancers and DNA damage. In order to identify and characterize the biochemical mechanisms for repair of formaldehyde-induced DNA damage, the McCullough lab is utilizing a yeast model system that allows the entire genome to be screened for genes that confer formaldehyde sensitivity. These studies have identified specific biochemical pathways that protect cells from the cytotoxic effects of acute and chronic formaldehyde exposures, results that will impact the assessment of exposure limits considered safe for humans.

 

2004-2005 CROET Highlights

Surveillance, Applications and Outreach

CROET conducts workplace surveillance so that prevention and research needs can be identified, and applications research to bring the benefits of science to the workplace floor. It also reaches out to provide education and information to the Oregon workforce and beyond.

Oregon Fatality Assessment and Control Evaluation (OR-FACE) Program

Dr. Gary Rischitelli leads the Oregon Fatality Assessment and Control Evaluation (OR-FACE) program that tracks, investigates, and reports on occupational fatalities in Oregon. Each incident is investigated, entered in a database, and codes are added for industry, occupation, and event. During 2004 and 2005, OR-FACE recorded 62 and 67 fatalities, respectively. OR-FACE investigates incidents in specific national and local target areas of concern, and each year produces about 12 investigation reports with safety recommendations. During 2004-05, OR-FACE also published two hazard alerts  one on electrocution from high-voltage power lines during highway work and another on the unexpected finding that parked vehicles are a common cause of fatal injury. In 2005, OR-FACE published its first annual report, summarizing data from the programs first full year of operation in 2003. The report charted frequencies by age, gender, race/ethnicity, day, time, month, county, industry, occupation, and event and included an abstract of each incident. Principal areas of concern were highlighted in relation to logging, mobile machinery, and transportation. In the 2004 annual report, an additional area of concern was observed in an elevated fatality rate among workers aged 65 and over, including a high incidence of falls and suicide. OR-FACE investigation reports and other publications are available on the programs website (www.ohsu.edu/croet/face). Investigation reports from Oregon and other FACE states are also available in the electronic library maintained by the National Institute for Occupational Safety and Health (www.cdc.gov/niosh/face), which funds the program. 

Computer-based Training Effective for Shop Floor Workers (food services)

In collaboration with an urban hospital in Portland, Dr. Kent Anger provided interactive computer-based safety training to workers in a food services department that supplies food to hospital patients, visitors, and staff. The food services workers evaluated the training very positively. Based on tests given before and after the training, knowledge improved significantly. Generalization of the knowledge to the workplace was confirmed by increased accuracy in answering on-the-job questions that required application of knowledge to the work setting. Observations were also made of work practices and workplace conditions before and after the training. Problematic kitchen conditions, such as puddles, decreased after-training and after-adjustment for increasing production/workload. Work practice improvement was seen in three-fourths of the workers. These findings demonstrate that the benefits of computer-based safety instruction extend to blue collar workers who do not usually receive computer-based training, which is only rarely studied. It is even more rare for research to study and report changes in reaction (did they like the training?), knowledge, and behavior or work practice change, which adds confidence to the findings. This and other studies demonstrate, in an experimentally rigorous way, that computer-based training can be used with workers on the shop floor, not just in offices where it is most typically used. This work was published in the Journal of Safety Research. 

Evidence of Increased Pesticide Metabolic By-Products in Agricultural Areas

Dr. William Lambert and others at CROET have been investigating the possibility that children of migrant farm workers are at increased risk of exposure to organophosphate (OP) pesticides due to carry-home transport processes and residential location. Although this at-risk status is generally recognized, few available reports describe the extent of this exposure among agricultural communities. It is very difficult to measure the very low levels of pesticide exposures, so Dr. Lambert and others at CROET quantified the metabolic products of organophosphate pesticides in samples of urine from 176 children, 2-6 years of age. The children were from three Oregon communities hosting differing agricultural industries: pears, cherries, and fruit berries. Up to three spot samples of urine were collected from children at the beginning, mid-point, and end of their parents work seasons. The median levels of dimethylthiophosphate (DMTP), the most commonly detected metabolite of OP pesticides, was 2.5 to 4 times higher in urine samples from children in the agricultural communities when compared to a reference group of children who lived in an urban community and whose parents did not work in agriculture. After controlling for confounders, the median level of DMTP in children in the pear community was 1.92 times higher than the level in children of the berry community and 1.75 times higher than the level in children of the cherry community. DMTP levels increased across the work season only within the berry community. Levels decreased in the cherry community and remained constant in the pear community. This variation across time in pesticide levels within the children who were followed demonstrates the need for multiple urine samples to accurately characterize longer term and/or cumulative exposure. This variability could be attributed to the types and amounts of organophosphate pesticides used, the timing of applications and degradation of residues in the environment, work operations and hygiene practices, the proximity of housing to orchards and fields, or the movement of these working families.

Improved Training for Beginning Flight Students

Flight students have the highest risk of landing accidents when flying solo during their first 30 hours of training. Since training innovations may help prevent these potentially fatal crashes, Dr. Ryan Olson investigated the potential benefits of one type of interactive training for new flight students. Personal Computer-Based Aviation Training Devices (PCATDs) are increasingly sophisticated and affordable, but are currently approved only for limited instrument training with experienced students. Dr. Olson hypothesized that PCATDs could be used strategically to prevent landing crashes among novice pilots. In 2005, Dr. Olson published evidence in the Journal of Aviation/Aerospace Education and Research that experimental PCATD training during the first 30 flight hours may improve multiple performance measures. Since no measurable harm was found, early PCATD training should be tested more aggressively as a risk-management intervention. 

CROET Outreach Expansion Continues

CROETweb.com

is the Centers occupational safety and health resource directory that provides information 24 hours a day, seven days a week.

CROETweb topics expanded from 46 different English topics in 2004 to 72 topics  Spanish-language topic pages expanded from 37 in 2004 to 60 topic pages  More than 1,250 links are posted on the CROETweb page

A monthly CROETweb update newsletter is now sent electronically to almost 600 addresses. It hadmore than 19,000 downloads in 2004-2005.Toxicology Information Center (TIC): Directed by Fred Berman, DVM, PhD, the Toxicology Information Center provides current information for thosewith questions about chemical, biological, physical and other agents encountered in the workplace and elsewhere. In 2004-2005, Dr. Berman handled more than 200 requests for such information from physicians and nurses, occupational safety and health professionals, business owners, and the general working public. Inquiries covered a range of issues. Chemical agents of concern included solvents, heavy metals, insecticides, fungicides, and herbicides. Physicians often called seeking information on a variety of potentially occupation-related health complaints. The TIC is open from 7:30 a.m. to 4 p.m., Monday through Friday. Walk-in visitors have access to a variety of resources, including computers, databases, government reports, textbooks, and journals that are devoted to toxicology-related issues. 

Symposia

When Employees Personal Lives Interact with Occupational Safety and Health  The Multidimensional Causes of Accidents and Injuries

Exhibits

Central OR-OSHA; Southern OR-OSHA; Cascade Western Pulp & Paper (OR-OSHA)  Northwest Occupational Health Conferences  Governors Occupational Safety and Health (GOSH) Conference  NexCon Construction Summit  Oregon Governors Fire Service Summit  Healthcare Ergonomics  Oregon Worker Compensation Educational Conference 

Collaboration/Advisory

Developed Outreach Strategic Plan (2004-2006), which was approved by the OHSU PresidentsCROET Advisory Committee

Injury and Recovery of the nervous System and Muscles

CROET scientists conduct basic research that examines the causes of injury to nerves and muscles in order to identify protective, preventive, and recovery methodologies for such injuries.

Organophosphate but not Pyrethroid Pesticides Associated with Airway Muscle Spasm

Over the last 20 years, asthma rates have soared to epidemic levels. According to the United States Center for Disease Control, between 1980 and 1994, the number of people with asthma in the United States increased by 75 percent, and today this disease afflicts more than 15 million people in this country. Very little is known about what causes asthma or how it may be prevented. Recent studies by Dr. Pamela Lein, in collaboration with Dr. Allison Fryer, a professor in the Department of Physiology and Pharmacology at OHSU, suggest that organophosphorous pesticides (OPs) may initiate or aggravate an asthma attack. Using a well-established guinea pig model of asthma, these researchers demonstrated that OPs increase airway hyperreactivity. OPs cause the airway to constrict, which is a hallmark characteristic of asthma. Their studies further suggest that OPs cause increased airway constriction by altering the function of the nerves that control contraction of the muscles lining the airway. OP effects on airway hyperreactivity and nerve function were observed at relatively low doses. These low doses did not inhibit the activity of cholinesterase, which is the enzyme that breaks down acetylcholine, the neurotransmitter released by nerves that cause airway smooth muscle to contract. Interestingly, cholinesterase inhibition is used by a number of state and federal regulatory agencies as a biomarker to indicate whether humans have been exposed to potentially toxic levels of OPs (this is the mechanism by which OPs kill insects). Thus, this research indicates that OPs may trigger airway hyperreactivity in animals and potentially in humans at exposure levels that are generally considered to be safe. Moreover, the most recent data from Dr. Leins studies indicate that guinea pigs that have been sensitized to antigen, which is a type of allergic reaction, are even more sensitive to OPs and exhibit airway hyperreactivity in response to much lower doses than non-sensitized guinea pigs. Since 70 to 80 percent of asthmatic patients also have allergies, these observations suggest that environmental levels of OPs may pose a significant environmental risk factor for asthma in humans. (Fryer, Lein, et al., American Journal of Physiology: Lung, Cellular and Molecular Physiology, 2004; 286: L963-9)

Important Mechanisms of Neuronal Protein Transport Revealed

Nearly every aspect of neuronal function depends on the delivery of proteins from the cell body, where they are made, to their appropriate destinations in axons or dendrites. Nerve cells are especially vulnerable to disruptions of protein transport because they have complicated shapes and because their axons are so long. Exposure to chemicals in the workplace or in the environment can disrupt protein transport, leading to neurological disease. Likewise, many of the neurodegenerative diseases of aging, such as Alzheimers disease, are also associated with alterations in protein transport. Dr. Gary Bankers program is studying the molecular mechanisms that underlie the accuracy and efficiency of protein transport in order to define new molecular targets for therapies to ameliorate or cure diseases that are caused by defects in protein transport. His laboratory initially developed methods to visualize vesicles as they move into axons or dendrites. In 2004, this approach was used to study how proteins that should go to different destinations are directed into the correct vesicle. Dr. Bankers team found that axonal and dendritic proteins contain different localization signals, analogous to address labels, which govern how proteins are packaged into vesicles. Mistakes in these localization signals cause the proteins to be directed to the wrong place. For example, using their assay for imaging vesicles, the Banker team showed that mutations in a dendritic localization signal caused the protein to be packaged in the same carrier as axonal proteins, resulting in its transport to an incorrect destination. Mistakes in protein localization like this can disrupt the electrical and chemical signals that nerve cells use to communicate with each other and with muscles. When they observed the movement of vesicles that contain dendritic proteins, Dr. Banker saw that they move into dendrites, but do not enter axons. To explain this remarkable observation, Dr. Banker hypothesized that the kinesin motors that move vesicles must be smart that they are able to distinguish biochemical differences between axonal and dendritic microtubules and so can move preferentially to dendrites or axons. When the idea was originally proposed several years ago, it was quite speculative. However, in 2005, Dr. Bankers team developed methods to image the movements of the kinesin proteins themselves, when they are not attached to vesicles. This work confirmed the initial prediction that kinesins are smart. Some kinesins moved selectively along axonal microtubules, but avoided dendritic microtubules. The methods Dr. Bankers laboratory has developed to image protein transport also have great promise as assays to identify environmental (occupational) agents or genetic alterations that interfere with protein transport. These methods also could be used to screen for new drugs that might mitigate or correct these kinds of deficits in protein transport. (Silverman, et al., Neuroscience, 2005; 29, 173-180)

Dominant Schwann Cell Role in Nerve Function and Recovery from Injury

All sights, sounds and sensation, as well as all movements of the body, are controlled by electrical impulses traveling along tiny nerve fibers, each about one-tenth the thickness of a human hair. After an injury, whether by insult, accident, or surgery, the fine features of the nerve must be fully regenerated to regain function. The ability of such thin nerve fibers to reliably carry information from one end to the other depends on a thin insulating layer of fat and protein that is rolled around the nerve cell, like gift wrapping paper on a cardboard tube. This material, called myelin, is created at about the time of birth by a special cell called a Schwann cell. Unrolled, the Schwann cell would look a bit like a very thin pancake and would cover more unbrokenarea than almost any cell in the body. How Schwann cells form myelin was described at the level of cell behavior many years ago. But little is known about what tells Schwann cells to form myelin in the manner required for normal function. Dr. Bruce Pattons research on a family of proteins called laminins has led to the discovery that they control Schwann cell proliferation and the decision to form myelin in the manner required for normal function. The laminin proteins form a covering sheet on the outer surface of the myelin, like the cellophane on a new roll of wrapping paper. Mice engineered to be missing the laminins had a normal set of nerves, but none of the nerve fibers were myelinated. The mutant Schwann cells were stuck in an immature state, unable to respond to signals to either proliferate or myelinate nerve fibers. Further studies revealed that laminins serve as a sortof molecular switch, which not only determines the ability of the cells to change after birth, but also ensures that cells proliferate in exactly the proportion needed for the size of the nerve. Dr. Patton is now deciphering molecular networks inside the cells that respond to this laminin switch, in hopes that clinical workers in the future can not only increase functional recovery during nerve regeneration after injury, but possibly reduce the extent of injury in the first place. Dr. Pattons original report can be found at www.jcb.org/cgi/content/abstract/168/4/655.

Chronic Disease and Working Safely

Chronic disease takes a significant toll on our workforce just as it does in the broader community. CROET research seeks to discover causes of chronic diseases that are produced or exacerbated by workplace factors and identifies processes or procedures that can prevent or ameliorate those diseases and improve workplace safety.

Model of Metabolic Syndrome in Obesity

The growing epidemic of human obesity is estimated to affect more than 60 million adult Americans, with secondary consequences including, but not limited to, decreased job performance, increased medical costs, decreased life span, non-alcohol-induced fatty liver disease, increased cardiovascular disease, and an increased incidence of stroke and type 2 diabetes. A majority of the obese population (more than 45 million Americans) has a combination of at least four of these diseases, collectively known as the Metabolic Syndrome. The underlying cause of these diseases is believed to be a combination of genetic susceptibility and chemical stressors, including exposure to pro-oxidant chemicals. Recently, Dr. Stephen Lloyd and his group have created genetically modified mice that are unable to repair certain types of oxidative DNA damage, and discovered that these mice develop symptoms consistent with all the defining hallmarks of the Metabolic Syndrome: severe obesity, disruptions in blood lipids, insulin resistance, and hyperleptinemia. Oxidative damage is believed to underlie some occupational disorders as well as diseases affecting broad segments of our population. The outcome of these investigations will be to provide a working model of the Metabolic Syndrome with which to design and test effective human therapies. By reducing the incidence or severity of disease associated with obesity, a healthier and more productive workforce can be realized.

Neurodegeneration: Drosophila, a Model Test System

Dr. Doris Kretzschmar uses the fruit fly, Drosophila melanogaster, to study basic mechanisms of neurodegeneration that are known to occur in occupational (e.g., chronic solvent exposure) and other diseases, including Alzheimers disease. A key factor in Alzheimers disease is the production, within the central nervous system, of small protein fragments called A, which are the major component of the amyloid plaques found in the brains of Alzheimers patients. A is known to be produced by enzymatic cleavage of a larger protein called Amyloid Precursor Protein; therefore, if a drug can be developed to inhibit the enzymes involved in this processing step, it may be possible to treat Alzheimers disease. However, besides A, three more protein fragments are produced by these enzymatic cleavage events. The Kretzschmar laboratory is using Drosophila as an easily manipulated experimental animal model to study these fragments because they have shown that the pathogenic functions of A, including plaque formation and neuronal cell death, are the same as in human disease. An understanding of the function of the other Amyloid Precursor Protein fragments might aid the design of therapeutic drugs that have fewer adverse side effects than currently used drugs. Moreover, changes in the cleavage pattern as occurs in Alzheimers disease might disrupt functions mediated by these other fragments, an effect that may also contribute to the disease. Although most cases of Alzheimers disease are thought to be sporadic, several environmental and occupational agents have been described as risk factors. The Drosophila model can now be used to study the effects of such factors. By gaining a more complete understanding of the mechanisms of neurodegeneration in the fruit fly, it will be possible to transfer that knowledge from insects to vertebrates, to develop a fuller understanding of processes involved in a variety of human neurodegenerative diseases, including occupational diseases. More information about Dr. Kretzschmars work with fruit flies can be found in the CROET Newsletter, Volume 14, No. 2 (2006), located at www.ohsu.edu/croet/about/pubs.cfm.

Mechanisms Underlying Chronic Health Effects of Organic Solvents are Illuminated

Organic solvents are valuable chemicals with a multitude of uses in a variety of industry sectors. While many are considered safe, a few solvents have the potential to cause neurological disease. Identifying the bad actors, and the reasons for their neurotoxicity, continues to be an important area of investigation in the laboratories of Dr. Peter Spencer and Dr. Mohammad Sabri. Previously reported studies revealed that both straight chain (aliphatic) and ring-structure (aromatic) solvents have neurotoxic potential if their metabolites possess chemical side chains with a particular (gamma-diketone) structure. Advanced methods of protein and gene analysis (toxicogenomics, see below), in combination with mass spectrometry, are being applied to understand why these chemicals are problematic and how they attack the nervous system. Drs. Spencer and Sabri demonstrated that the neurotoxicity of these solvents is directly related to a variety of specific chemical and physical characteristics of proteins, such that proteins in the nervous system are differentially susceptible to damage from the solvent metabolites. They also found that the loss of neuroproteins is accompanied by changes in gene expression that precede the onset of pathological changes in nerve fibers that underlie the appearance of neurological disease. This is hoped to lead to an understanding of how to predict which organic solvents have the potential to cause neurotoxicity and which are safe to use in the workplace.

Publication in Nature Methods Sets Standards for the Practice of Toxicogenomics, a Leading-edge Research Method to Assess Impacts of Stressors on Gene Expression and Its Relationship with Health and Disease

Toxicogenomics is a powerful method to analyze the response of biological systems to changes induced by chemicals, drugs, trauma, and other agents that cause disease and injury. Tens of thousands of genes are simultaneously interrogated to determine whether and how gene expression has been changed from the normal state. The resulting mass of data is interpreted with software that reveals alterations in molecular networks that correlate with abnormal function or a disease state. The reproducibility of this new technique was examined by a CROET investigative team, part of a prestigious Toxicogenomics Research Consortium (TRC) funded by the National Institutes of Environmental Health Sciences (NIEHS). CROET at OHSUcarried out experiments conjointly with TRC members at NIEHS, MIT, Fred Hutchinson Cancer Research Center, University of Washington, Duke University and University of North Carolina. The collaborative research effort revealed critical elements, including the quality and stability of the microarray platform, the precision of the experimental procedures, anchoring gene expression data to established biological landmarks, and the power of innovative biostatistical methods to extract information from the mountain of data that results from toxicogenomics experiments. In sum, these studies show the challenges as well as the strengths of toxicogenomics as a tool to probe and increase understanding of health and disease.(Bammler, et al., Nature Methods, 2005; 2: 351-356).

Reducing the Risk of Prostate Cancer

Prostate cancer is the second leading cause of cancer deaths among U.S. men, and there are currently few options for prevention. Prostate cancer is most likely to be diagnosed in men over the age of 50, and many men are diagnosed with this potentially debilitating disease while still an active part of the workforce. While treatable if caught early, surgery is highly invasive, and five-year survival rates for recurrent disease remain quite low. Dr. Jackilen Shannon has found that men who have been prescribed statins to treat high cholesterol have a 65 percent lower risk of developing prostate cancer than men who have taken no statins at all. When the men were analyzed separately according to the severity of their cancer at diagnosis, theassociation between statin use and prostate cancer prevention was found to be strongest for the more severe cases. One hundred prostate cancer patients were recruited into the study. They had been referred for prostate biopsies at the Portland Veterans Affairs Medical Center (PVAMC) because of elevated prostate-specific antigen (PSA) levels, or abnormal prostate exams. Statin use among these men was recorded and compared to the use of statins among a control group of 202 PVMAC patients whose PSA levels had remained unchanged for a year. Statin use was grouped by duration and intensity of use: those who had used statins for the longest period (more than 2.8 years) and at higher doses (average daily dose of more than40mg/day) reduced their risk the most. (Shannon et al., American Journal of Epidemiology, 2005; 162: 318-325)

Integrity of DNA (DNA damage, genetic alterations, and disease)

Human health and risk for disease ultimately depend on the integrity of our DNA, the genetic material that provides the bodys blueprint for manufacturing proteins that carry out the function of cells and organs. Aberrant forms of DNA can produce inherited diseases, and changes in DNA during life are believed to trigger cancer and many other chronic diseases. Such changes can result from exposure to certain chemicals found in the workplace and others in the diet and medications. Two broad types of DNA changes are recognized: DNA damage and DNA silencing.

Persistence of DNA Damage After a Single Exposure to Ionizing Radiation

DNA damage represents one of the earliest steps in the development of cancer because such damage can lead to mutations in genes that function to prevent cancer. Mutation is defined as changes in DNA structure that alter the ability of a gene to make a protein. Because proteins constitute the basic functional machinery of cells, the resultant change in the amount or activity of a protein (after DNA mutation) can fundamentally alter cellular behavior. Ionizing radiation, such as the common X-ray or ultraviolet radiation from sunlight, causes two types of DNA damage: (1) breaks in the DNA strand and (2) damage to nucleotides, the building blocks of DNA. Cells have a variety of mechanisms to repair DNA damage and hence avoid theinduction of a harmful mutation. Dr. Mitchell Turkers laboratory is asking whether DNA damage caused by exposure to ionizing radiation persists in tissues or whether the damage is fixed by DNA repair mechanisms. Some mouse tissues are exposed to ionizing radiation while others are shielded from exposure. DNA damage is assessed in tissues of the irradiated mice by examining chromosome structure (chromosomes contain the DNA strands) long after treatment. The results demonstrated that specific types of chromosome abnormalities caused by ionizing radiation persist for two years and at levels that were essentially the same as those observed one to four weeks after exposure. Although the ionizing radiation dosages used for this experiment were far higher than those employed in diagnostic procedures, these results support the concept that such procedures should be limited only to those necessary for medical evaluations. While we have learned a great deal about acute exposures, the effects of long-term exposure to low doses of ionizing radiation is still an open question.

Mutations Increase with Age in Mouse Tissues

The greatest risk factor for cancer is age, and cancer is more common in older than in younger persons. This is believed to reflect basic changes in cell structure and function as people get older, but the exact nature of these changes remains to be determined. One type of cellular change that is important in cancer is gene mutation, which occurs when the DNA sequence is altered and expression of genes required to prevent cancer is lost. Dr. Turker examined the frequency of mutations most commonly found in cancer cells of two cell types from mice ranging in age from 6 months to 36 months (laboratory mice rarely live past 40 months of age). The cell types examined were those found in connective tissue and kidney epithelial cells. Most tumors that increase with age arise from epithelial cells. The results of Dr. Turkers experiments demonstrated a steady increase in the frequency of mutations for the kidney cells as a function of age, which was higher at all ages in the female mice. Interestingly, female mice do not live as long as male mice in the strain that was used for this study. For the connective tissue cells, an age-related increase in mutations was only observed for female mice and only in the oldest females. These results demonstrate that mutations with relevance for cancer increase with age mostly in epithelial cell types and suggest that this cell-type-specific increase plays an important role in cancers that arise in older individuals.

Business Spinoffs

The federal government, the State of Oregon, and OHSU encourage the translation of research findings into immediate real-world benefits to society. Often that is in the form of commercial products that generate income for OHSU, part of which returns directly to the laboratory where the idea for the product was generated. This is a natural outgrowth of CROETs legislative mandate since many of its research activities are aimed at solving workplace probems, either through prevention or treatment. Two corporate spinoffs and one for-fee service operating within CROET have achieved significant milestones in 2004-2005. They are described below.

Restoration Genetics, Inc.

The occurrence of skin cancer is rapidly increasing, affecting more than 1 million people in the United States annually. Sunlight exposure produces DNA damage or lesions, and they in turn can produce cancer. Human cells have only one mechanism to repair these DNA lesions, whereas lower organisms possess multiple pathways for protection against the adverse effects of sunlight exposure. In order to implement proactive strategies to prevent skin cancer, Dr. Amanda McCullough and Dr. Stephen Lloyd have discovered, characterized and patented multiple DNA-repair enzymes that possess activities that can initiate a second DNA-repair pathway in human cells. Cell-based studies have demonstrated that repair of sunlightinduced DNA damage can be improved 100 fold over that of non-treated cells. Based on these patented technologies, Drs. McCullough and Lloydco-founded a start-up biotechnology research and development company, Restoration Genetics, Inc., in August 2004. In 2005, the McCullough and Lloyd laboratories were awarded a Springboard Grant from OHSU to facilitate start-up operations for the company. Additionally, a BioScience Innovation Fund Grant from OHSU was awarded to provide funds to demonstrate the feasibility of incorporating these enzymes in an active form in skin-specific vesicles that, upon topical application to skin, will enhance repair of sunlight-induced DNA damage. What this promises is a postsunburn application that can reverse the damage done to the DNA in the skin. These technologies have the potential to repair the most harmful damage caused by sunlight exposure. By restoring the cellular DNA to its original state, mutations that could lead to cancer are prevented and the skins immune responses are restored. It is envisioned that this technology could be used either pre- or post-sunlight exposure, resulting in improved skin health.

Northwest Education Training and Assessment, LLC (NwETA)

Computer-based training is efficient but developed largely by and for well-educated segments of the working population. In 1999-2001, Dr. Kent Anger and Dr. Diane Rohlman developed cTRAIN, a computer-based training software aimed at training populations that had limited or no experience with computers. In 2005, the cTRAIN software was licensed by OHSU to Northwest Education Training and Assessment (www.nweta.com), an OHSU spin-off company formed by Dr. Anger, Dr. Rohlman and other colleagues. The goal of the company is to commercialize cTRAIN and use the proceeds from sales to evolve the software in order to maintain and enhance its utility and competitiveness with other training software. Thesoftware presents training created in Dr. Angers laboratory, but it also has an editing tool in which new content topics can be created. The cTRAIN computer-based training program received seed funding from an OR-OSHA grant to the Painters District Council. Through this grant, Dr. Anger and Mr. Kirkpatrick developed training content on respiratory protection that is still in use at the Painters District Council Training Center today. Federal grants further supported the development of content on slip-and-fall safety in food service operations, ladder safety in agriculture, ergonomic issues in dry wall finishing, hazard communication, Worker Protection Standard for agricultural workers, and a variety of training content programs for vineyards. This led to a small business grant to NwETA from the National Institute of Environmental Health Sciences and a cooperative agreement from the National Institute for Occupational Safety and Health (NIOSH) to develop training content programs for vineyards in collaboration with Leda Garside, RN, BSD, of Tuality Healthcare Salud! Services. NwETAs goal is to bring the efficiencies and advantages of computer-based training to every working person, including those in the workforce with limited or no education.

Chemical Risk Information Service

OSHA regulations require employers to maintain Material Safety Data Sheets (MSDS) for hazardous chemicals used in their workplace. This often proves to be a difficult record-keeping task, and it can be burdensome to ensure that employees have quick access to health and safety information in the workplace when they need it. Since 1998, CROETs Chemical Risk Information Service, directed by Dr. Gregory Higgins, has helped a growing number of local and international industries manage and distribute chemical safety information through its computer-based MSDS management system. CROETs working relationship with the Oregon Poison Center also ensures that employees covered by the program have ready access to medical information in the event of exposure. During 2004-2005, the Chemical Risk Information Service provided MSDS managementservices to more than 35 municipal, construction, and service companies, most of which are Oregon-based. CROET is currently focused on upgrading the database system and improving client websites for MSDS management. All database files and websites were relocated from CROETs local server to OHSUs main server bank, which improved the security and reliability of the service. We also began development of improved search codes for clients to retrieve MSDSs, so that they can begin to search not only by product name, but also by key location parameters at their facilities. This change allows clients to use CROETs system as an inventory control mechanism, as well as a source for MSDSs. CROET continues to provide expert MSDS management service at a reasonable cost which is attractive to both small and large organizations.

 

2003 CROET Highlights

Workplace fatality surveillance in Oregon produces hazard alerts, interactive website

CROET and the Oregon Departments of Human Services and Consumer & Business Services received a cooperative agreement from the National Institute of Occupational Safety and Health (NIOSH) to identify, investigate, and develop prevention strategies for traumatic occupational fatalities in Oregon. Oregon joins 13 other U.S. states in the NIOSH-sponsored Fatality Assessment & Control Evaluation (FACE) program. In the first year of the program (2003), Dr. Gary Rischitelli (Principal Investigator) and Dr. Joan Rothlein have conducted in-depth investigations of over 30 occupational fatalities in Oregon and developed industry-specific recommendations for prevention. For example, one hazard alert focused on electrocutions in Oregon companies using the same equipment (truck-mounted guard rail installer). These hazard alerts and other reports are available at http://www.ohsu.edu/croet/face. This interactive website provides current information on demographic factors in Oregon fatalities.

Computer-based training effective in people with limited formal education

CROETs cTRAIN computer-based training, developed by Dr. Kent Anger, continued to grow in 2003. Content programs on safety in food service and drywall finishing have increased worker knowledge and safe work practices. In addition, the content programs have been well received by workers in those industries. The food services research has been accepted for publication in the Journal of Safety Research. Begun in November, a collaboration between CROET and Medfords Bear Creek Corporation demonstrated that cTRAIN computer-based training can be used to provide critical safety training (ladder safety) to the entire agricultural workforce of orchard workers, including some who had no formal education. Work began on a new grant to use cTRAIN in Oregon vineyards.(http://www.ohsu.edu/croet/faculty/anger/)

CROET website adds second home page to improve access

CROETs website was divided into two separate, but complementary, websites in July. One site (http://www.ohsu.edu/croet/) contains information about CROET faculty and staff projects, while the other is devoted exclusively to CROETs popular and well-regarded occupational safety and health resource directory (http://www.croetweb.com). This change provides easier access to both the resource directory and to CROET research capabilities, outreach, and education. CROETs occupational safety and health resource directory, organized into 46 topic areas, contains links to over 1,000 resources and serves as a major source of safety and health information for working Oregonians and their families. All resources are now stored in a database resulting in new functionality. For example, the website can be sorted for Oregon-specific or Spanish-language materials, and a new search tool allows for specialized searches. Another added functionality of the website is the ability to accept online registrations for CROETs annual health and safety symposia. This resulted in increased efficiency and decreased expenditures for paper and mailing. All of CROETs newsletters dating back to 1999 have been made available online, also reducing mailing costs.

Toxicogenomics, a cutting-edge technology, begins at CROET

Toxicogenomics is a new technology that promises to revolutionize understanding of chemical risk, disease mechanisms, and even treatment options. The heart of the technology is the microarray, a glass plate containing up to 20,000 spots of genetic material obtained from an animal such as the mouse. These spots can be used to interrogate molecules derived from animals that have been exposed to test chemicals. The resulting pattern of microarray response indicates which cellular networks are affected. In 2003, Dr. Peter Spencer and colleagues completed development and initiated research operations of this new laboratory. OHSU and CROET thus became part of NIH National Institutes of Environmental Health Sciences (NIEHS) Toxicogenomics Research Consortium; this consortium includes the Massachusetts Institute of Technology, Fred Hutchinson Cancer Research Center, University of Washington, Duke University, and University of North Carolina. CROET is using the microarray technology to assess the neurotoxicity of organic solvents, including those used as cleaners and degreasers. (http://www.ohsu.edu/croet/research/centers/toxicogenomics/)

New mechanism of organophosphate pesticide damage reveals very low-concentration effects

Nervous system damage follows high-concentration exposures to organophosphate (OP) pesticides such as chlorpyrifos. A metabolite of the pesticide reduces the activity of the enzyme acetylcholinesterase (AChE) which normally acts as a brake on repeated, uncontrolled firing of nerve cells. AChE reduction is therefore widely used as a biomarker or internal measure of exposure to OP pesticides. However, recent animal studies suggest that pesticide concentrations that do not inhibit the AChE may still cause damage to the nervous system in very young or still-developing animals. Learning, memory, and motor behavior are implicated. Assessing risk to children has been complicated by the fact that the mechanisms by which organophosphate pesticides disrupt the developing nervous system are not understood. CROETs Dr. Pamela Lein recently found that chlorpyrifos blocks the effect of AChE in growing nerve cell (axon) processes, and at levels below those required to reduce AchE activity. Since disruption of axon growth has been associated with functional deficits, these findings reveal a mechanism that explains how exposure to very low levels of OP pesticides could cause behavioral problems in children. Since many of the same mechanisms that regulate axon growth in the developing nervous system also influence axon regrowth following injury, Dr. Leins work raises the possibility that exposure to low levels of pesticides may also interfere with nerve regeneration in adults following work-related injuries. Further, these data raise questions of the sensitivity of AChE activity for monitoring damage following exposure to OP pesticides. (http://www.ohsu.edu/croet/faculty/lein/)

One more piece of the sleep-wake jigsaw puzzle

A significant number of Oregonians work nontraditional hours. They are staying awake and working while a part of the brain called the suprachiasmatic nucleus (SCN) is telling them it is time to sleep. Nerve cells in the SCN contain a molecular clock that keeps 24-hour time. Through the work of Dr. Charles Allen, CROET is studying how these nerve cells translate the molecular clock information into an output signal that regulates activities such as sleep and wakefulness. Before now, it was believed that rhythmic neuronsthat cycle on and off during the day and nightcontrolled our circadian rhythm and thus caused us to sleep and wake. However, in 2003, Dr. Allen discovered a group of SCN neurons that are important for driving behavioral and hormonal rhythms, but that are not rhythmic  they do not cycle on and off over time. These findings suggest that the molecular clock that controls sleep and wakefulness is an interaction between rhythmic and non-rhythmic neurons. These observations add another piece of information to complete the puzzle of how the brain generates timing information. A better understanding of the brain timing mechanism will help develop more effective strategies for workers to handle the health and performance challenges arising from rotating or night work schedules. (http://www.ohsu.edu/croet/faculty/allenc/)

Nerve repair: Protein promotes nerve development

Nerves regenerate imperfectly following injury in adults. Nerve formation requires growth of the nerve fiber process (axon), multiplication of attendant Schwann cells to match the length and number of axons, and the formation by Schwann cells of an axon ensheathment that is called myelin. These steps occur on a precise schedule during development and are recapitulated during nerve regeneration after injury. The molecular mechanisms that control the developmental schedule are still largely unknown. Genetic defects in children with a congenital neuropathy have provided a clue. There is a protein missing in these children, called laminin, which normally covers the surface of Schwann cells in the nerve. Working with laboratory mice, Dr. Bruce Pattons research group found that Schwann cells actually make multiple versions or types of laminin. Mice engineered to lack two versions of the laminin protein were completely unable to produce myelin and unable to walk. They tested the feasibility of genetic therapy for these myelin defects by re-engineering the mice to make large amounts of a third version of laminin, which is normally present at very low levels in nerves. The additional protein stimulated myelin formation and enabled the mice to walk. (To see a movie of these mice, visit http://www.ohsu.edu/croet/research/highlights/nerverepair.html.) By increasing the output of this protein in children with neuropathy, or in injured patients, nerve development and regeneration might be improved. Perhaps more importantly, future studies aimed at discovering how the laminins promote myelin formation by Schwann cells may allow the development of drugs that act like laminins, to promote myelination without genetic engineering. (http://www.ohsu.edu/croet/faculty/patton/)

Reducing ultraviolet light exposure to prevent skin cancers

Exposure to solar radiation is the single most significant risk factor associated with the development of skin cancer. More than half of all new cancers are skin cancers, with the total number of new cases exceeding 1 million annually. Occupational exposure to deleterious amounts of natural ultraviolet (UV) sunlight (for example, enough to cause a sunburn) occurs in the farming, maritime, and construction industries, and all of these workers are classified as high-risk groups for skin cancer. This type of skin cancer is named non-melanoma, and it is the most common type of skin cancer. Fortunately, it is usually not malignant or life-threatening. In an effort to prevent or at least delay the onset of non-melanoma skin cancers, research in the laboratories of Dr. Amanda McCullough and Dr. Stephen Lloyd has focused on novel ways to enhance the capacity of skin cells to repair DNA damage caused by sunlight overexposure. If skin can rapidly repair damage from sun overexposure, most skin cancer will not develop. Their research has shown, in a test system consisting of human cells, that the application of a specific type of enzyme repairs the damage caused by UV light by as much as 10 times faster than the skins natural repair enzymes. They have been issued a patent for enzymes that have the potential to reduce or prevent non-melanoma skin cancers and suppression of the bodys immune system, another danger that follows UV overexposure. This technology will allow the development of new DNA repair enzymes that can be introduced into human epidermal (skin) cells through a skin lotion, to rapidly initiate the repair of damage to DNA caused by exposure to UV light. This new DNA repair system is expected to reduce the frequency and rate of onset of non-melanoma skin cancer and prevent or greatly alleviate UV-induced suppression of the immune system. (http://www.ohsu.edu/croet/faculty/mccullough/)

Motor proteins and muscle strength

In order to grow and maintain nerve processes, special molecules called motor proteins transport molecules from the nerve cell bodies, where they are made, out into the axon and dendritic processes, where they do their work. The neuronal transport system is particularly important for motor nerve cells that control muscles, because their axons reach all the way from the the spinal cord out into the arms and legs, where they supply muscles. Loss of motor nerve cells results in profound muscle weakness, as seen in poliomyelitis and Lou Gehrig's disease. Two CROET groups are studying the role of motor proteins in nerve cells. The Banker lab is developing imaging methods to visualize the movement of motor proteins and nutrients in living cells. They have found that some motor proteins are smart they take their cargoes only to a specific location in the cell  unlike their dumb colleagues that cant distinguish between axons and dendrites. Smart motors may be important for ensuring that key cellular molecules always go to the right destination. (http://www.ohsu.edu/croet/faculty/banker/).A second team, led by Dr. Mohammad Sabri, has been investigating how certain solvents used in industry may lead to adverse effects on the nervous system. They discovered that solvent-derived chemicals react with motor and other proteins, causing them to accumulate in swellings that disrupt function and cause muscle weakness. (http://www.ohsu.edu/croet/faculty/sabri/ and http://www.ohsu.edu/croet/faculty/spencer/)

New health effects of pesticidesoxidative stress studied

Most studies involving pesticide exposures compare reported exposure to health effects, such as evidence of damage to the brain and nervous system. However, the amount and frequency of exposure is based on statements by the exposed individuals. Dr. Glen Kisby is studying the biological mechanisms of pesticide exposure to health effects. With former CROET faculty member Dr. Linda McCauley, Dr. Kisby is studying potent organophosphate pesticides (OPs) such as those used in Oregon. OP pesticides have been found to produce oxidative stress. Oxidative stress occurs when oxygen free radicals (oxygen molecules) combine with other molecules in a way that damages those molecules or prevents them from performing their normal function. Dr. Kisby and Dr. McCauley compared pesticide applicators with farmworkers who do not apply pesticides and with people who do not work on farms (controls). The levels of oxidative stress as measured in urine (DNA damage), blood (oxidized lipids), and white blood cells (activity of a DNA repair protein) were much higher in farmworkers and pesticide applicators than in controls. Additional research is under way to confirm and expand these findings in the laboratory and in the field in Oregon. (http://www.ohsu.edu/croet/faculty/kisby/)

2002 CROET Highlights

Nanotechnology: Guidance Proteins Control Growth of Neurons

Drs. Gary Banker and Bruce Patton are exploring the application of nanotechnologythe technology used in the semiconductor industry to make computer chipsto study how growing nerve fibers interact with physical and chemical features in their environment. The goal is to produce interactions between living nerve cells and silicon chips bearing microelectronic circuits, leading to the development of neural prosthetic devices that could restore function of damaged nerves or damaged brain tissue. One of the key challenges in this work is to adapt nanofabrication methods to allow patterning of proteins, including the proteins that guide growing axons, without destroying their biological activity. In 2002, these investigators developed a novel two-step approach that allows formation of accurate patterns while preserving protein function. They have gone on to show that, by preparing patterns combining two different guidance proteins, the growth of axons and dendrites can be controlled independently. This project, which involves collaborations with scientists at Cornell University, is part of one of ten Science and Technology Centers in the country funded by the National Science Foundation to encourage technology transfer and innovative approaches to interdisciplinary activities. (http://www.ohsu.edu/croet/faculty/banker/index.html) (http://www.ohsu.edu/croet/faculty/patton/)

cTRAIN: Ergonomics Training for Drywall Finishers and Food Service Workers

CROETs program to develop effective individual training methods for occupational safety and health continued to grow in 2002. Our computer-based training program, cTRAIN, was developed by Dr. Kent Anger, CROET Associate Director, and Dr. Diane Rohlman in collaboration with Mr. John Kirkpatrick of the Painters District Council. Research continued on the basic principles underlying training, an area almost devoid of research in working adults, demonstrating again the superiority of interactive training(quizzing during training with immediate feedback on answer accuracy). Quiz frequency appeared to be important for some material, with accuracy on the post-test declining in a program with up to 17 screens of information prior to a quiz, but not in programs with more frequent quizzes. Interestingly, open-book quizzes during training produced slightly better recall than closed-book quizzes, when evaluated later by a closed-book test. New programs for drywall finishing (ergonomic and other issues), lab safety, and food handling were developed and began field testing. The food services safety and health content program increased knowledge of fire safety and hazards such as those leading to slips and falls. (http://www.ohsu.edu/croet/faculty/anger/)

Superfund Grant: Findings and Impacts

Now in its third year, CROETs federally funded Superfund Basic Research Center (SBRC) conducts research important to the health of Oregon workers and their environment. Scientists at CROET, Oregon State University, and Battelle Pacific Northwest are working together on a broad range of biomedical and environmental engineering projects. CROET scientists Dr. Mohamed Sabri and Dr. Peter Spencer are studying chemicals that damage the nervous system. Their work has uncovered a potent nerve axon toxin, 1,2-diacetylbenzene (DAB), which is found as a minor component in a number of organic solvent mixtures, including gasoline. 1,2-DAB reacts with proteins to form a blue pigment that can be found in urine, where it may provide a marker of exposure to this and chemically related solvent chemicals with neurotoxic potential. Dr. Jennifer Field, an SBRC scientist based at Oregon State University, is studying ways to enhance microbial transformation (degradation) of trichloroethylene (TCE), a common toxic contaminant at Superfund sites. Natural degradation of TCE in groundwater can be quite inefficient and slow, and toxic metabolic products including vinyl chloride can accumulate if degradation does not proceed to completion. Dr. Field and her colleagues are developing a technology that can speed degradation rates and help prevent accumulation of toxic metabolites. With further refinement, this technology may one day produce an inexpensive, non-toxic chemical additive mixture that will dramatically speed up the rate of groundwater decontamination in comparison to currently existing remediation strategies. (http://www.ohsu.edu/croet/sbrc/)

Toxicology Information Center: TIC Focus Expands

CROETS Toxicology Information Center (TIC) is a special purpose library with holdings relevant to CROETs mission and with access to the worlds electronic resources on the Internet. The TIC, under the directorship of Fred Berman, DVM, PhD, responds to inquiries from professionals and the lay public regarding chemicals encountered inthe workplace, home, or other environments. Examples from the more than 250 phone and Internet queries received last year include: health risks from carbon monoxide, chlorine, freon, trichloroethylene (TCE), benzene, diesel and aviation fuel, and childhood lead exposure. The TIC has also been fielding an increasing number of questions about the broad area of occupational health, beyond its initial scope of toxicology. Just as CROETs research, education, and website have expanded over the years to broad areas of occupational safety and health, the TIC now responds to all occupational health inquiries. The resources of the TIC, including computers, are available to the public Monday through Friday from 8 a.m. until 5 p.m. For more information or to join the CROET mailing list, visit our website or contact CROET by phone at 503-494-4273. (http://www.ohsu.edu/croet/outreach/tic.html)

CROETweb Evolves: Site Redesign, Electronic Newsletter, Movies, Larger Focus Group

CROETweb is a major source of occupational safety and health information for all Oregonians, as well as a repository of information about the Centers many activities. Designed as a directory, the resource area of CROETweb contains links to hundreds of resources for health and safety professionals. Pages are dedicated to all major Oregon industries and occupations, as well as to a variety of safety and health topics that are updated on a regular basis. CROETweb was redesigned in 2002 to improve the navigation and usability of the website. A monthly email newsletter was begun to provide information about whats new on the CROET website, as well as upcoming events. Subscriptions to the newsletter are received daily. Six short movies were created that feature CROET scientists describing their research and how it benefits Oregon. They are available at CROETs home page. Several Oregon safety and health professionals were recruited as new members to CROETs Web Focus Group, which provides feedback about the website and makes content recommendations for the occupation and industry pages. Activity on CROETweb continued to increase. Hits on the site grew to over 190,000 in 2002 (up nearly 80 percent from 2001) with more than 50,000 visitors (up 72 percent from 2001). Oregon safety and health specialists tellus they visit CROETweb frequently. (http://www.croetweb.com)

Education: Responding Across the Full Spectrum of Educational Needs

CROETs education program has a broad scope. The focus of our training programs ranges from occupational safety and health professionals to graduate students and postdoctoral trainees (funded by grants), and from college students in our summer student program to high school students visiting for one or more days in a CROET laboratory. In 2002, we held seminars targeted at the occupational safety and health community: (1) Developing More Effective Training, and (2) Office Workers, the latter as part of our collaboration with Portland State Universitys Occupational Health Psychology Program. CROET also staffed Brain Awareness Week at OMSI, providing neurobehavioral testing for many attendees, from children to post-retirement adults. CROET continued to participate actively in Oregons Saturday Academy program, including mentoring young women as part of the Advocates for Women in Science, Engineering and Mathematics (see award for Dr. Mohammed Sabri in Selected 2002 Accomplishments). (http://www.ohsu.edu/croet/outreach/)

Chemical Risk Information Service: Expanded Services to Oregon Business

CROETs fee-based Chemical Risk Information Service is a 24/7 toxicological risk information program designed to help business and industrial clients comply with the OSHA Hazard Communication Standard. Directed by Greg Higgins, PhD, the program expanded services during 2002 by adding LaserJet printer products to the family of Hewlett Packard (HP) products already drawing on CROETs unique service. Worldwide access is now provided for customers needing MSDSs for HP inkjet and LaserJet printer cartridges and inks. The chemical risk program also began upgrading database management capabilities this year by converting website operations to Microsoft SQL Server. This change is expected to streamline operations, improve customer response time, and provide the infrastructure necessary for continued growth. (http://www.ohsu.edu/croet-cris)

CROET 2001 Highlights

Toxicology Information Center: Responding to Oregonians Questions

CROETS Toxicology Information Center (TIC) is a special purpose library with holdings relevant to the mission of CROET, its scientists and staff, and with access to the worlds electronic resources on the Internet. The TICs printed collection is centered on current publications in industrial, occupational, environmental, and epidemiological research, as well as a core group of basic science journals selected by CROET faculty and staff. Among the TIC resources are special collections of information about occupational and environmental issues assembled from a wide variety of scientific literature, governmental reports, and Internet resources (reviewed). Under the directorship of Fred Berman, DVM, PhD, the TIC is a valuable public information resource, as demonstrated by an ever-increasing number of inquiries from people concerned about the risks of exposure to chemicals encountered in the workplace or home environment. Most inquiries come via telephone, but an increasing number of interested parties are contacting the TIC by email through the CROET website. The TIC is now offering a monthly Internet Sleuthing Workshop. This hands-on Internet information course is available in the TIC the second Friday of each month from 1-3 p.m. The resources of the TIC, including the use of several computers, are available to the public Monday through Friday from 8 a.m. until 5 p.m. (http://www.croetweb.com)

CROETweb: Visitors and Hits Continue to Grow

CROETweb, the Centers website, serves as a major source of occupational safety and health information for all working Oregonians. Designed as a resource directory, the website contains links to hundreds of resources for health and safety professionals. The website has pages dedicated to all major Oregon industries and occupations as well as a variety of safety and health topics. Oregon safety and health specialists visit CROETweb frequently. The most popular occupational safety and health pages in 2001 were semiconductors, restaurant and kitchen safety, artists, back injuries and prevention, and cell phones/EMF safety. New topics/web pages were added in 2001: bioterrorism, ergonomics, evaluating health-related websites, and shiftwork. In September, 2001, Holly Sherburne, MS, joined CROET as the new full-time Web Manager. Ms. Sherburne has a background in toxicology outreach and education, as well as extensive website design and coding experience. In 2001, the home page was revised, reducing loading time by two-thirds, and the update schedule was accelerated. Increasingly, websites from Oregon and around the world link to CROETweb. The number of visitors to the website increased to more than12,000, and hits exceeded 100,000 (up over 15 percent from 2000). (http://www.ohsu.edu/croet or http://www.croetweb.com)

Chemical Risk Information Service: Helping Oregon Business

CROETs Chemical Risk Information Service is a 24/7 toxicological and risk information program designed to help business and industrial clients comply with the OSHA Hazard Communication standard. Directed by Greg Higgins, PhD, with Sundii Moser Gillespie, RN, BA, CSPI, as Program Manager, this program provides client employees and consumers a centralized source for round-the-clock access to Material Safety Data Sheets(MSDSs). Our Worker Right-to-Know Program helps employers give their employees access to MSDSs for the hazardous chemicalspresent in their workplace. We provide toll-free phone access to the program, and MSDSs are available via fax and through our website. Clients also have immediate access to advice from licensed health care professionals via the Oregon Poison Center. Our Product Stewardship program provides a toll-free number for clients to place on their product labels or packing information as a resource for customers who have safety questions concerning the product. This program offers a convenient way for companies to provide their customers with global access toproduct safety information and product MSDSs. Our client list of Oregon businesses served by the Chemical Risk Information Service continues to grow, and during 2001 we added eight new clients from the construction and high-tech industries. (http://www.ohsu.edu/croet-cris/)

Superfund Grant: Supports Worker Safety and Health

CROETs federally funded Superfund Basic Research Center continued its studies of toxic environmental chemicals important to working Oregonians. Scientists at CROET are investigating the neurotoxic effects of aromatic solvents, studying how chlorinated solvents can interact with DNA to cause mutations, and examining how exposure to trace levels of toxic chemicals can affect the early development and maturation of the brain. Collaborating scientists at Battelle are performing cutting-edge computational chemistry studies to characterize the interaction of aromatic solvents with nerve cells and studying how toxic chemicals are absorbed by the body and to what extent they reach particularly vulnerable organs such as the brain. Consortium partners at Oregon State University are pursuing a parallel line of research that investigates how chlorinated solvents behave once they enter the environment and contaminate groundwater. The work conducted by our Superfund Center will lead to a greater understanding of how toxic environmental chemicals can impact nearby residents and workers and will also develop improved cleanup methods. The CROET-led Superfund Center is directed by Peter Spencer, PhD, FRCPath and Greg Higgins, PhD. (http://www.ohsu.edu/croet/sbrc/home_page.html)

Responding to State Requests: Hepatitis C and Public Safety Workers

Last year, CROET researchers prepared a literature review for the Oregon Legislature regarding the risks associated with Hepatitis B and C in police, fire, Emergency Medical Services, and correctional personnel. Because we found important gaps in the scientific literature regarding the prevalence of hepatitis among police, fire, and correctional officers, the Legislature asked CROET researchers to conduct a study to estimate the prevalence of, and risk factors for, Hepatitis C among public safety workers in Oregon. Testing was conducted in Spring, 2001, in Salem, Portland, Corvallis, Keizer, Independence, Monmouth, Dallas, Albany, McMinnville, and Newberg. Of the 719 public safety workers who volunteered to have their blood tested, 710 (98.8 percent) were negative and seven (1.0 percent) were positive. Thus, seroprevalence rates in Oregon are below that reported in the general population and lower than, or similar to, those published for other public safety officer populations. These data suggest that the occupational contribution to risk for hepatitis is small and that, in the absence of data demonstrating a significant association with occupational risk factors, non-occupational risk factors probably predominate. Nonetheless, employers and employees should continue to seek to reduce opportunities for exposure to blood and body fluids through the implementation of exposure control methods.(http://www.ohsu.edu/croet/faculty/rischitelli/index.html)

Collaborative Training Information Repository: A Practical Demonstration

CROETs Dr. Mitchell Altschuler worked closely with Portlands Painters District Council and their associated contractors to design a secure web-based database containing records of member training, medical evaluations, and respirator fit testing. The database, named the Collaborative Training Information Repository (cTIR), can be updated by the District Council and accessed by signatory contractors to confirm and document employee training. Updates trigger automatic recalculation of items such as current-year training hours, important for propercalculation of pay rates. Prior to the cTIR, contractors telephoned the District Council data specialist who reviewed records for the worker and mailed documentation to the contractor, adding personnel costs to the District Council and delays for the contractor. The cTIR Internet system allows the contractor to verify training records 24/7,and it eliminates the need for redundant training that was often repeated when records could not be obtained and time was of the essence. Both the District Council and construction contractors have praised the system. The design elements of this demonstration program are available and can be modified for any occupational specific issue. A generic demonstration is available on CROETweb for review, in 2002. (http://www.ohsu.edu/croet/faculty/anger/index.html)

Partnerships in Surveillance and Prevention: New Workers Compensation Data

CROET scientists are engaged in a collaborative project with the Oregon Department of Health and Human Services and workerscompensation insurers in the state, which will demonstrate the value of working with insurers to recognize injury trends and opportunities for prevention strategies. Currently, Oregon data on work-related injuries and illnesses are only reported for those injuries/illnesses that are serious enough to cause more than three days of work loss (defined as time-loss injuries). Private and public workers compensation (WC) insurers, however, maintain databases of all injuries, both time-loss and those in which employees return to work within three days (defined as medical-only cases). This project is testing the feasibility of merging WC claims data from multiple insurers into a common database that will provide information on differences in the disabling time-loss and medical-only claims among different insurers according to type of injury/illness, age and gender of claimants, type of industry and occupation. Comparisons will be made in the profile of occupational injury and illness available in state WC databases and the profile available in data from insurers. This project will demonstrate the utility of complete insurer databases in monitoring clusters of illness and injury, trends and patterns of claims, and identifying new intervention opportunities as they emerge. (http://www.ohsu.edu/croet/faculty/mccauley/index.html)

cTRAIN: Computerized Training Program Expands

CROETs interactive training program to develop effective individual training methods for occupational safety and health continued to grow in 2001 with initiation of two new federal grants to CROET and an OR OSHA grant to the Painters and Drywall Finishers. cTRAIN was developed by CROET Associate Director Dr. Kent Anger in collaboration with Mr. John Kirkpatrick of the Painters District Council. In 2001, the basic principles underlying cTRAIN were examined to determine how frequently quizzes and feedback are needed for maximum recall and learner acceptance. A collaboration with Monrovia, a wholesale plant nursery in Dayton, Oregon, led to the development of new system training instructions (how to use cTRAIN) presented in Spanish that were effective for Latino migrant workers with limited education. Collaborations to create new content in cTRAIN were also developed with the Oregon Association of Nurserymen, a labor and industry consortium involving drywall finishers, and OHSU offices responsible for food handling and lab safety. (http://www.ohsu.edu/croet/faculty/anger/index.html)

What Muscles Tell Their Nerves: New Signal for Proper Synapse Function Found

Recovery from traumatic injury requires accurate, functional reconnection of nerves with their targets. Nerves do form synapses on appropriate targets during embryonic development, and these synapses contain microdomains called active zones, where the chemical neurotransmitter is secreted. At the neuromuscular junction, the large synapse between motor neuron and muscle fiber, multiple active zones are positioned very precisely across the synapse from the folds in the postsynaptic surface of the muscle cell. This arrangement has been preserved over several hundred million years of vertebrate evolution, showing the importance of carefully controlling the site of neurosecretion. Mice were genetically engineered to lack a muscle protein, causing their motor nerves to locate active zones randomly in the nerve terminal. The discovery that this protein is a key factor in guiding nerves to reconnect with the proper muscle area will guide efforts to improve recovery from neuromuscular injury. (http://www.ohsu.edu/croet/faculty/patton/index.html)

Risk Assessment for Multnomah County Divers: Addressing Local Concerns

On December 1, 2000, the Portland Harbor was listed as an EPA Superfund site because Willamette River sediments are contaminated with metals, pesticides, polychlorinated biphenyls, and petroleum products. Several months later, CROET researcher Joan Rothlein, PhD, was asked by the Multnomah County Sheriffs Office to assist with an evaluation of potential occupational exposures to contaminants in the Portland Harbor among members of the department who dive and patrol in the Portland Harbor as part of their search and rescue activities. With the cooperation of Oregon Department of Environmental Quality(DEQ), EPA, and ATSDR, Dr. Rothlein and other CROET scientists are addressing the health and safety concerns of members of the Sheriffs Office by: (1) Identifying microbial and chemical hazards in the water and sediment in the Portland Harbor and other dive locations from federal reports; (2) Evaluating personal protective equipment options; (3) Calculating possible human health risk using reported contaminant levels and information on the location and duration of each dive extracted from individual dive logs. (http://www.ohsu.edu/croet/faculty/rothlein/index.html)

 

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27. McFerrin J, Patton BL, Sunderhaus ER, Kretzschmar D. NTE/PNPLA6 is expressed in mature Schwann cells and is required for glial ensheathment of Remak fibers. GLIA 2017 May;65(5): 804-816.
28. McHill AW, Klerman EB, Slater B, Kangarloo T, Mankowski P, Shaw ND. The relationship between estrogen and the decline in delta power during adolescence. Sleep 2017;40(3): 1-8.
29. McHill AW, Phillips AJK, Czeisler CA, Keating L, Yee K, Barger LK, Garaulet M, Scheer FAJL, Klerman EB. Later circadian timing of food intake is associated with increased body fat. Am J. Clin. Nutr. Nov 2017;106(5): 1213-1219.
30. McHill AW, Wright Jr KP. Role of sleep and circadian disruption on energy expenditure and in metabolic predisposition to human obesity and metabolic disease. Obesity Reviews 2017;Suppl 1:15-24.
31. Minko IG, Rizzo CJ, Lloyd RS. Mutagenic potential of nitrogen mustard-induced formamidopyrimidine DNA adduct: Contribution of the non-canonical α-anomer. Journal of Biological Chemistry. 2017 Jan 1;292(46):18790-18799.
32. Mitchell S.H. (2017) Devaluation of Outcomes Due to Their Cost: Extending Discounting Models Beyond Delay. In: Stevens J. (eds) Impulsivity. Nebraska Symposium on Motivation, vol 64. Springer, Cham.
33. Mitchell SH. Quantifying impatience using models of delay discounting in substance use disorders. Am. J. Drug and Alcohol Abuse 2017;43(3): 234-236.
34. Modarres MH, Kuzma NN, Kretzmer T, Pack AI, Lim MM. EEG slow waves in traumatic brain injury: Convergent findings in mouse and man. Neurobiol. of Sleep and Circ. Rhythms Jan 2017;2: 59-70.
35. Moen P, Kelly EL, Lee S, Oakes MJ, Fan W, Bray J, Almeida D, Hammer L, Moldavan MG, Cravetchi O, Allen CN. GABA transporters regulate tonic and synaptic GABAA receptor-mediated currents in the Suprachiasmatic Nucleus Neurons. J Neurophysiol. 2017 Aug 30: jn. 00194.2017. doi:10.1152/jn.00194.2017. [Epub ahead of print]
36. Newman M, Kretzschmar D, Kahn I, Chen M, Verdile G, Lardelli M. Animal Models of Alzheimer's Disease. Animal Models for the Study of Human Disease: Second Edition. Elsevier Inc., 2017: 1031-1085.
37. Korabik K, Van Rhijn TR, Lero DS, Ayman R and Hammer LB. Gender, polychronicity and work-family conflict: Is multitasking beneficial? Community, Work and Family. 2017;20: 307-326.
38. Qu, W., Zheng, W., Spencer P., Zheng, J., Yang, L., Yan, L., Ma, W., Zhou, Y, Zheng, Y., Wang. Y. Public health concerns arising from interventions designed to circumvent polluted surface drinking water. The Lancet 2017;390: S87.
39. Reis, J., Handschumacher, P., Palmer, V.S., Spencer, P.S. Climatic factors under the tropics. In Preux P-M., Dumas, M. eds., Neuroepidemiology in Tropical Health., San Diego, Academic Medicine, 2017, pp. 26-39.
40. Rineer JR, Truxillo DM, Bodner TE, Hammer LB, Kraner MA. The moderating effect of perceived organizational support on the relationships between organizational justice and objective measures of cardiovascular health. European Journal of Work and Organizational Psychology. 2017 Jan;26(3): 1-12.
41. Ritchie HK, Burke TM, Dear TB, Mchill AW, Axelsson J, Wright KP Jr. Impact of sleep inertia on visual selective attention for rare targets and the influence of chronotype. J. Sleep Res. Oct 2017;26(5): 551–558.
42. Roya Ayman, Leslie B. Hammer, Nahren Ishaya. The work-family interface in the United States. The Work-Family Interface in Global Context. Taylor and Francis, 2017. p. 103-117.
43. Sandsmark DK, Elliott JE, Lim MM. Sleep-wake disturbances after traumatic brain injury: Synthesis of human and animal studies. Sleep May 2017;40(5): https://doi.org/10.1093/sleep/zsx044.
44. Sha Y, Minko IG, Malik CK, Rizzo CJ, Lloyd RS. Error-prone replication bypass of the imidazole ring-opened formamidopyrimidine deoxyguanosine adduct. Environmental and Molecular Mutagenesis. 2017 May 1;58(4): 182-189.
45. Spencer PS, Mazumder R, Palmer VS. Response to R. Colebunders: Helminth infections in Nodding Syndrome. J. Neurol. Sci. Jan 2017;372: 441.
46. Spencer PS, Palmer VS. The enigma of litchi toxicity: an emerging health concern in southern Asia. The Lancet Global Health Jan 2017;5(4): e383-e384.
47. Spencer PS, Schmutzhard E, Winkler AS. Nodding Syndrome in the spotlight –Placing recent findings in perspective. Trends in Parasitology July 2017;33(7): 490-492.
48. Spencer, P.S. and Palmer, V.S. Food plant chemicals linked with neurological and neurodegenerative disease. In: Aschner M., Costa, LG., eds., Environmental Factors in Neurodegenerative Diseases, Chapter 9, Elsevier, New York, Advances in Neurotoxicology, vol. 1, 2017;pp 247-78.
49. Spencer, P.S. and Reis, J. International Conference Tackles Air Pollution, Emerging Medical Issues. World Neurology January 31, 2017.
50. Spencer, P.S., and Palmer, V.S. The enigma of litchi toxicity: an emerging health concern in southern Asia. The Lancet, January 30, 2017. Invited Commentary on paper by Shrivastava, A., et al. Lancet Global Health, published on line Jan. 30, 2017.
51. Stothard ER, McHill AW, Depner CM, Birks BR, Moehlman TM, Ritchie HK, Guzzetti JR, Chinoy ED, LeBourgeois MK, Axelsson J, Wright KP Jr. Circadian Entrainment to the Natural Light-Dark Cycle across Seasons and the Weekend. Current Biol. Feb 2017;27(4): 508-513.
52. Swanson C, Shea SA, Wolfe P, Markwardt S, Cain SW, Munch M, Czeisler CA, Orwoll ES, Buxton OM. 24-hour profile of serum sclerostin and its association with bone biomarkers in men. Osteoporos Int. 2017 Nov;28(11): 3205-3213.
53. Swanson CM, Shea SA, Wolfe P, Cain SW, Munch M, Vujovic N, Czeisler CA, Buxton OM, Orwoll ES. Bone Turnover Markers After Sleep Restriction and Circadian Disruption: A Mechanism for Sleep-Related Bone Loss in Humans. J Clin Endocrinol Metab. 2017 Oct 1;102(10): 3722-3730.
54. Turker MS, Grygoryev D, Lasarev M, Ohlrich A, Rwatambuga FA, Johnson S, Dan C, Eckelmann B, Hryciw G, Mao JH, Snijders AM, Gauny S, Kronenberg A. Simulated space radiation-induced mutants in the mouse kidney display widespread genomic change. PLoS One. 2017 Jul 6;12(7): e0180412.
55. Vartanian V, Minko IG, Chawanthayatham S, Egner PA, Lin YC, Earley LF, Makar R, Eng JR, Camp MT, Li L, Stone MP, Lasarev MR, Groopman JD, Croy RG, Essigmann JM, McCullough AK, Lloyd RS. NEIL1 protects against aflatoxin-induced hepatocellular carcinoma in mice. PNAS Apr 18 2017;114(16): 4207-4212.
56. Vartanian V, Tumova J, Dobrzyn P, Dobrzyn A, Nakabeppu Y, Lloyd RS, Sampath H. 8-oxoguanine DNA glycosylase (OGG1) deficiency elicits coordinated changes in lipid and mitochondrial metabolism in muscle. PLoS ONE. 2017 Jul 1;12(7). e0181687. Available from, DOI: 10.1371/journal.pone.0181687
57. Weymann KB, Lim MM. Sleep disturbances in TBI and PTSD and potential risk of neurodegeneration. Current Sleep Medicine Reports 2017;3(3): 179-192.
58. Wiedmeier JE, Ohlrich A, Chu A, Rountree MR, Turker MS. Induction of the long noncoding RNA NBR2 from the bidirectional BRCA1 promoter under hypoxic conditions. Mutat Res. 2017 Feb;796: 13-19.
59. Yragui NL, Demsky CA, Hammer LB, Van Dyck S and Neradilek MB. Linking workplace aggression to employee work and well-being: The moderating role of family-supportive supervisory behaviors (FSSB). Journal of Business and Psychology. 2017;32: 179–196. doi:10.1007/s10869-016-9443-z

1. Berman, A, Thosar, S, Shea, SA. Are we underestimating the lifelong benefits of therapy for obstructive sleep apnea? Nature and Science of Sleep. 2016 8:87-88.
   
2. Chang HC, Sun T, Sultana N, Lim MM, Khan TH, Ismail AF. Conductive PEDOT:PSS coated polylactide (PLA) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) electrospun membranes: Fabrication and characterization. Mater Sci Eng C Mater Biol Appl. 2016 Apr 1;61:396-410. doi: 10.1016/j.msec.2015.12.074. Epub 2015 Dec 31
3. Chang, A-M, Bjonnes, AC., Aeschbach, Daniel, Buxton, OM., Gooley, JJ., Anderson, C, Van Reena, E, Cain, SW, Czeisler, Cain, Duffya JF, Lockley, SW, Shea, SA, Scheer, FAJL , and Saxena, R. Circadian gene variants influence sleep and the sleep electroencephalogram inhumans. Chronobiology International, 2016, 1-13
   
4. DePasquale, N., Davis, K.D., Zarit, S.H., K., Moen, P., Hammer, L.B., &Almeida,D.M.  (2016). Combining formal and informal caregiving roles: The psychosocial implications of double-and triple-duty care.  Journals of Gerontology, Series B: Psychological Sciences and Social Sciences, 71(2), 201-211. doi:10.1093/geronb/gbu139.
5. Deyo RA. Can Parsimonious Practice Please Patients and Practitioners? The Case of Spine Imaging. J Gen Intern Med. 2016 Feb;31(2):140-1. doi: 10.1007/s11606-015-3523-z.
6. Enthoven WT, Roelofs PD, Deyo RA, van Tulder MW, Koes BW. Non-steroidal anti-inflammatory drugs for chronic low back pain. Cochrane Database Syst Rev. 2016 Feb 10;2:CD012087. doi: 10.1002/14651858.CD012087. Review.
7. Grygoryev, Dmytro, Gauny, Stacy, Lasarev, Michael, Ohlrich, Anna, Kronenberg, Amy. Charged Particle mutagenesis at low dose and fluence in mouse splenic T cells. Mutat Res. 2016 Mar 29. pii: S0027-5107(16)30030-6
8. Johnson EA, Zubair MM, Armsby LR, Burch GH, Good MK, Lasarev MR, Hohimer AR, Muralidaran A, Langley SM. Surgical Quality Predicts Length of Stay in Patients with Congenital Heart Disease. Pediatr Cardiol. 2016 Jan 7. [Epub ahead of print]
9. Imprey, Soren, Pelz, Carl, Tafessu, Amanuel, Marzulla, Tessa, Turker, Mitchell S., Raber, Jacob. BMC Genomics, 2016 17-273-282.
   
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11. Lam, DJ, Shea, SL. A growth spurt in pediatric sleep research, Nature and Science of Sleep, 2016 8:133-135.
    
12. Lane JM, Chang AM, Bjonnes AC, Aeschbach D, Anderson C, Cade BE, Cain SW, Czeisler CA, Gharib SA, Gooley JJ, Gottlieb DJ, Grant SF, Klerman EB, Lauderdale DS, Lockley SW, Munch M, Patel S, Punjabi NM, Rajaratnam SM, Rueger M, St Hilaire MA, Santhi N, Scheuermaier K, Van Reen E, Zee PC, Shea SA, Duffy JF, Buxton OM, Redline S, Scheer FA, Saxena R. Impact of common diabetes risk variant in MTNR1B on sleep, circadian and melatonin physiology. Diabetes. 2016 Feb 11. pii: db150999. [Epub ahead of print]
13. Lim MM, Ju YE. A reply to "To travel or not to travel: The modern day struggle of the academic researcher". Ann Neurol. 2016 Feb;79(2):333. doi: 10.1002/ana.24589. Epub 2016 Jan 18. No abstract available. 
14. Marshall LM, Litwack-Harrison S, Cawthon PM, Kado DM, Deyo RA, Makris UE, Carlson HL, Nevitt MC;Study of Osteoporotic Fractures (SOF) Research Group. A Prospective Study of Back Pain and Risk of Falls Among Older Community-dwelling Women. J Gerontol A Biol Sci Med Sci. 2016 Jan 12. pii: glv225. [Epub ahead of print]
15. Marriott, Lisa, Charbonneau, Allison, Moss, Berk, Shannon, Jackilen, Thornburg, Kent, Turker, Mitchell. Epigenetics: A new science for middle school - and why you should teach it. Science Scope Feb 2016:6-11.
    
16. Olson R, Thompson SV, Wipfli B, Hanson G, Elliot DL, Anger WK, Bodner T, Hammer LB, Hohn E, Perrin NA. Sleep, Dietary, and Exercise Behavioral Clusters Among Truck Drivers With Obesity: Implications for Interventions. J Occup Environ Med. 2016 Mar;58(3):314-321.
17. Olson, R, Varga, A, Cannon, A, Jones, J, Gilbert-Jones, I, Zoller, E (2016). Toolbox talks to prevent construction fatalities: Empirical development and Evaluation. Science Safety 86:122-131.
    
18. Parish M, Rohlman DS, Elliot DL, Lasarev M. Factors associated with occupational injuries in seasonal young workers. Occup Med (Lond). 2016 Mar;66(2):164-7. doi: 10.1093/occmed/kqv183. Epub 2015 Nov 8.
19. Penney LS, Ritenbaugh C, Elder C, Schneider J, Deyo RA, DeBar LL. Primary care physicians, acupuncture and chiropractic clinicians, and chronic pain patients: a qualitative analysis of communication and care coordination patterns. BMC Complement Altern Med. 2016 Jan 25;16(1):30. doi: 10.1186/s12906-016-1005-4.
20. Rajhbeharrysingh U, El Youssef J, Leon E, Lasarev MR, Klein R, Vanek C, Mattar S, Berber E, Siperstein A, Shindo M, Milas M. Expanding the net: The re-evaluation of the multidimensional nomogram calculating the upper limit of normal PTH (maxPTH) in the setting of secondary hyperparathyroidism and the development of the MultIdimensional Predictive hyperparaTHyroid model (Mi-PTH). Surgery. 2016 Jan;159(1):226-39. doi: 10.1016/j.surg.2015.09.006. Epub 2015 Oct 31.

1. Anger WK, Elliot DL, Bodner T, Olson R, Rohlman DS, Truxillo DM, Kuehl KS, Hammer LB, Montgomery D. Effectiveness of total worker health interventions. J Occup Health Psychol. 2015 Apr;20(2):226-47. doi: 10.1037/a0038340. Epub 2014 Dec 22.
2. Arble DM, Bass J, Behn CD, Butler MP, Challet E, et al. Impact of Sleep and Circadian Disruption on Energy Balance and Diabetes: A Summary of Workshop Discussions. Sleep. 2015;38(12): 1849-60.
3. Bakhtiani PA, El Youssef J, Duell AK, Branigan DL, Jacobs PG, Lasarev MR, Castle JR, Ward WK. Factors affecting the success of glucagon delivered during an automated closed-loop system in type 1 diabetes. J Diabetes Complications. 2015 Jan-Feb;29(1):93-8. doi: 10.1016/j.jdiacomp.2014.09.001. Epub 2014 Sep 16.
4. Barbosa C, Bray JW, Dowd WN, Mills MJ, Moen P, Wipfli B, Olson R, Kelly EL. Return on Investment of a Work-Family Intervention: Evidence From the Work, Family, and Health Network. J Occup Environ Med. 2015 Sep;57(9): 943-51.
5. Berkman  LB, Liu SY, Hammer LB, Moen P, Klein LC, Kelly E, Fay M, Davis K, Durham M, Karuntzos G, Buxton OM. Work/family demands, cardiometabolic risk and sleep duration in extended care employees. Journal of Occupational Health Psychology 2015;20: 420-433. doi: 10.1037/a0039143
6. Brinjikni W, Luetmer PH, Comstock B, Bresnahan BW, Chen LE, Deyo RA, Halabi S, Turner JA, Avins AL, James K, Wald JT, Kallmes DF, Jarvik JG. Systematic literature review of imaging features of spinal degeneration in asymptomatic populations. Am J Neuroradiol 2015;36: 811-816
7. Butler MP, Smales C, Wu H, Hussain MV, Mohamed YA, et al. The Circadian System Contributes to Apnea Lengthening across the Night in Obstructive Sleep Apnea. Sleep. 2015;38(11): 1793-801.
8. Chang HC, Sun T, Sultana N, Lim MM, Khan TH, Ismail AF. Conductive PEDOT:PSS coated polylactide (PLA) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) electrospun membranes: Fabrication and characterization. Mater Sci Eng C Mater Biol Appl. 2016 Apr 1;61:396-410. doi: 10.1016/j.msec.2015.12.074. Epub 2015 Dec 31
9. Chiarotto A, Deyo RA, Terwee CB, Boers M, Buchbinder R, Corbin TP, Costa LO, Foster NE, Grotle M, Koes BW, Kovacs FM, Lin CW, Maher CG, Pearson AM, Peul WC, Schoene ML, Turk DC, van Tulder MW, Ostelo RW. Core outcome domains for clinical trials in non-specific low back pain. Eur Spine J. 2015 Jun;24(6): 1127-42. doi: 10.1007/s00586-015-3892-3. Epub 2015 Apr 5. Erratum in: Eur Spine J. 2015 Sep;24(9): 2097.
10. Chou R, Turner JA, Devine EB, Hansen RN, Sullivan SD, Blazina I, Dana T, Bougatsos C, Deyo RA. The effectiveness and risks of long-term opioid therapy for chronic pain: a systematic review for a National Institutes of Health Pathways to Prevention Workshop. Ann Intern Med. 2015 Feb 17;162(4):276-86. doi: 10.7326/M14-2559.
11. Davis KD, Lawson K, Almeida DM, Kelly E, King RB, Hammer LB, Casper L,Okechukwu C, Hanson G and McHale SM (2015). Parents' daily time with their children: A workplace intervention. Pediatrics, 135(5): 875-882. doi: 10.1542/peds.2014-2057
12. Okechukwu C, Hanson G and McHale SM (2015). Parents' daily time with their children: A workplace intervention. Pediatrics, 135(5): 875-882. doi: 10.1542/peds.2014-2057
13. DePasquale N,Davis KD, Zarit SH, Moen P, Hammer LB and Almeida DM (2016). Combining formal and informal caregiving roles: The psychosocial implications of double-and triple-duty care.  Journals of Gerontology, Series B: Psychological Sciences and Social Sciences, 71(2): 201-211. doi:10.1093/geronb/gbu139.
14. DePasquale N, Polenick C, Davis KD, Moen P, Hammer LB and Almeida DM (2015). The psychosocial implications of managing work and family caregiving roles: Gender differences among IT professionals. Journal of Family Issues, 1-25. doi: 10.1177/0192513X15584680
15. Deyo RA, Ramsey K, Buckley DI, Michaels L, Kobus A, Eckstrom E, Forro V, Morris C. Performance of a Patient Reported Outcomes Measurement Information System (PROMIS) Short Form in Older Adults with Chronic Musculoskeletal Pain. Pain Med. 2015 Dec 24. pii: pnv046. [Epub ahead of print]
16. Deyo RA, Dworkin SF, Amtmann D, Andersson G, Borenstein D, Carragee E, Carrino J, Chou R, Cook K, DeLitto A, Goertz C, Khalsa P, Loeser J, Mackey S, Panagis J, Rainville J, Tosteson T, Turk D, Von Korff M, Weiner DK. Report of the NIH Task Force on Research Standards for Chronic Low Back Pain. Int J Ther Massage Bodywork. 2015 Sep 1;8(3): 16-33. eCollection 2015 Sep.
17. Deyo RA, Bryan M, Comstock BA, Turner JA, Heagerty P, Friedly J, Avins AL, Nedeljkovic SS, Nerenz DR, Jarvik JG. Trajectories of symptoms and function in older adults with low back disorders. Spine. 2015 Sep 1;40(17): 1352-62. doi: 10.1097/BRS.0000000000000975.
18. Deyo RA. Biopsychosocial care for chronic back pain. BMJ. 2015 Feb 18;350:h538. doi: 10.1136/bmj.h538.
19. Deyo RA, Dworkin SF, Amtmann D, Andersson G, Borenstein D, Carragee E, Carrino J, Chou R, Cook K, Delitto A, Goertz C, Khalsa P, Loeser J, Mackey S, Panagis J, Rainville J, Tosteson T, Turk D, Von Korff M, Weiner DK. Report of the NIH Task Force on research standards for chronic low back pain. Phys Ther. 2015 Feb;95(2): e1-e18. doi: 10.2522/ptj.2015.95.2.e1.
20. Deyo RA. Fusion surgery for lumbar degenerative disc disease: still more questions than answers. Spine J. 2015 Feb 1;15(2): 272-4. doi: 10.1016/j.spinee.2014.11.004.
21. Deyo RA, Von Korff M, Duhrkoop D. Opioids for low back pain. BMJ. 2015 Jan 5;350: g6380. doi: 10.1136/bmj.g6380.
22. Deyo RA, Irvine JM, Hallvik SE, Hildebran C, Baran T, Millet LM, Marino M. Leading a Horse to Water: Facilitating registration and use of a prescription drug monitoring program. Clin. J Pain 2015;31: 782-787
23. Donley N, Jaruga P, Coskun E, Dizdaroglu M, McCullough AK, Lloyd RS. Small Molecule Inhibitors of 8-Oxoguanine DNA Glycosylase-1 (OGG1). ACS Chem Biol. 2015;10(10): 2334-43. doi: 10.1021/acschembio.5b00452. Epub 2015 Aug 7.
24. Elder C, DeBar L, Ritenbaugh C, Vollmer W, Deyo RA, Dickerson J, Kindler L. Acupuncture and chiropractic care: utilization and electronic medical record capture. Am J Manag Care. 2015;21(7): e414-21.
25. Elkind JA, Lim MM, Johnson BN, Palmer CP, Putnam BJ, Kirschen MP, Cohen AS. Efficacy, dosage, and duration of action of branched chain amino Acid therapy for traumatic brain injury. Front Neurol. 2015;6: 73. doi: 10.3389/fneur.2015.00073. eCollection 2015.
26. Furlan AD, Malmivaara A, Chou R, Maher CG, Deyo RA, Schoene M, Bronfort G, van Tulder MW. 2015 updated method guideline for systematic reviews in the Cochrane back and neck group. Spine 2015;40(21): 1660-1673
27. Gray NE, Sampath H, Zweig JA, Quinn JF, Soumyanath A. Centella asiatica Attenuates Amyloid-β-Induced Oxidative Stress and Mitochondrial Dysfunction. J Alzheimers Dis. 2015;45(3): 933-46. doi: 10.3233/JAD-142217.
28. Hammer L, Truxillo D, Bodner T, Rineer J, Pytlovany A and Richman A. Effects of a workplace intervention targeting psychosocial risk factors on safety and health outcomes: Psychosocial factors and workers health and safety. BioMed Research International, vol. 2015, Article ID 836967, 12 pages, 2015. doi:10.1155/2015/836967.
29. Hinson HE, Puybasset L, Weiss N, Perlbarg V, Benali H, Galanaud D, Lasarev M, Stevens RD. Neuroanatomical basis of paroxysmal sympathetic hyperactivity: a diffusion tensor imaging analysis. Neuro Imaging for Coma Emergence, Recovery (NICER) Consortium. Brain Inj. 2015;29(4): 455-61. doi: 10.3109/02699052.2014.995229. Epub 2015 Jan 7.
30. Hurtado DA, Nelson CC, Hashimoto D, Sorensen G. Supervisors' support for nurses' meal breaks and mental health. Workplace Health Saf. 2015;63(3): 107-15. doi: 10.1177/2165079915571354.
31. Hryciw G, Grygoryev D, Lasarev M, Ohlrich A, Dan C, Madhira R, Eckelmann B, Gauny S, Kronenberg A, Turker MS. Accelerated (48)Ti Ions Induce Autosomal Mutations in Mouse Kidney Epithelium at Low Dose and Fluence. Radiation Res. 2015;184(4): 367-77. doi: 10.1667/RR14130.1. Epub 2015 Sep 23.
32. Jarjisian SG, Butler MP, Paul MJ, Place NJ, Prendergast BJ, et al. Dorsomedial hypothalamic lesions counteract decreases in locomotor activity in male Syrian hamsters transferred from long to short day lengths. Journal of biological rhythms. 2015;30(1): 42-52. NIHMSID: NIHMS674095
33. Jarvik JG, Comstock BA, James KT, Avins AL, Bresnahan BW, Deyo RA, Luetmer PH, Friedly JL, Meier EN, Cherkin DC, Gold LS, Rundell SD, Halabi SS, Kallmes DF, Tan KW, Turner JA, Kessler LG, Lavallee DC, Stephens KA, Heagerty PJ. Lumbar Imaging With Reporting Of Epidemiology (LIRE)-Protocol for a pragmatic cluster randomized trial. Contemp Clin Trials. 2015;45(Pt B): 157-63. doi: 10.1016/j.cct.2015.10.003. Epub 2015 Oct 19.
34. Jarvik JG, Gold LS, Comstock BA, Heagerty PJ, Rundell SD, Turner JA, Avins AL, Bauer Z, Bresnahan BW, Friedly JL, James K, Kessler L, Nedeljkovic SS, Nerenz DR, Shi X, Sullivan SD, Chan L, Schwalb JM, Deyo RA. Association of early imaging for back pain with clinical outcomes in older adults. JAMA. 2015;313(11): 1143-53. doi: 10.1001/jama.2015.1871. Erratum in: JAMA. 2015;313(17): 1758.
35. Kmoch S, Majewski J, Ramamurthy V, Cao S, Fahiminiya S, Ren H, MacDonald IM, Lopez I, Sun V, Keser V, Khan A, Stránecký V, Hartmannová H, Přistoupilová A, Hodaňová K, Piherová L, Kuchař L, Baxová A, Chen R, Barsottini OG, Pyle A, Griffin H, Splitt M, Sallum J, Tolmie JL, Sampson JR, Chinnery P;Care4Rare Canada, Banin E, Sharon D, Dutta S, Grebler R, Helfrich-Foerster C, Pedroso JL, Kretzschmar D, Cayouette M, Koenekoop RK. Mutations in PNPLA6 are linked to photoreceptor degeneration and various forms of childhood blindness. Nature communications. 2015;6: 5614.
36. Kumari A, Owen N, Juarez E, McCullough AK. BLM protein mitigates formaldehyde-induced genomic instability. DNA Repair (Amst). 2015;28: 73-82. doi: 10.1016/j.dnarep.2015.02.010. Epub 2015 Feb 19.
37. Kumari A, Choudhary S, Arora S, Sharma V. Stability of aspartame and neotame in pasteurized and in-bottle sterilized flavoured milk. Food Chem. 2016;196: 533-8. doi: 10.1016/j.foodchem.2015.09.082. Epub 2015 Sep 26.
38. Lam DD, de Souza FS, Nasif S, Yamashita M, López-Leal R, Otero-Corchon V, Meece K, Sampath H, Mercer AJ, Wardlaw SL, Rubinstein M, Low MJ. Partially redundant enhancers cooperatively maintain Mammalian pomc expression above a critical functional threshold. PLoS Genet. 2015;11(2): e1004935. doi: 10.1371/journal.pgen.1004935. eCollection 2015 Feb. Erratum in: PLoS Genet. 2015 Apr;11(4): e1005133.
39. Lam J, Fox K, Fan W, Moen P, Kelly EL, Hammer L, Kossek E. Manager Characteristics and Employee Job Insecurity around a Merger Announcement: The Role of Status and Crossover. The Sociological Quarterly. 2015;56(3): 558-580.
40. Lim MM, Szymusiak R. Neurobiology of Arousal and Sleep: Updates and Insights into Neurological Disorders. Current Sleep Medicine Reports 2015;1(2): 91-100. PMID pending.
41. Lim MM, Baumann CR. Sleep-wake disorders in patients with traumatic brain injury. UpToDate online 2015.
42. Mann B, Kumari A, Kumar R, Sharma R, Prajapati K, Mahboob S, Athira S. Antioxidant activity of whey protein hydrolysates in milk beverage system. J Food Sci Technol. 2015;52(6): 3235-41. doi: 10.1007/s13197-014-1361-3. Epub 2014 Apr 29.
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2. Bolkan BJ, Triphan T, Kretzschmar D. β-secretase cleavage of the fly amyloid precursor protein is required for glial survival. J Neurosci. 2012 Nov 14; 32(46): 16181-92. 
3. Bowman GL, Silbert LC, Howieson D, Dodge HH, Traber MG, Frei B, Kaye JA, Shannon J, Quinn JF. Nutrient biomarker patterns, cognitive function, and MRI measures of brain aging. Neurology. 2012 Jan 24; 78(4): 241-9.
4. Buxton OM, Cain SW, O’Connor SP, Porter JH, Duffy JF, Wang W, Czeisler CA, Shea SA. Adverse metabolic consequences in humans of prolonged sleep restriction combined with circadian disruption. Sci Transl Med. 2012 Apr 11; 4(129): 129ra43.
5. Carney PA, Hamada JL, Rdesinski R, Sprager L, Nichols KR, Liu BY, Pelayo J, Sanchez MA, Shannon J. Impact of a community gardening project on vegetable intake, food security and family relationships: a community-based participatory research study. J Community Health. 2012 Aug; 37(4): 874-81. 
6. Chan JM, Harrison SL, Bauer SR, Daniels NA, Wilt TJ, Shannon J, Bauer DC. Statin use and risk of prostate cancer in the prospective Osteoporotic Fractures in Men (MrOS) Study. Cancer Epidemiol Biomarkers Prev. 2012 Aug 9.
7. Chary P, Beard WA, Wilson SH, Lloyd RS. DNA polymerase β gap-filling translesion DNA synthesis. Chem Res Toxicol. 2012 Dec 17; 25(12): 2744-54.
8. Chen J, Anger WK, Boyes WK, Fox DA, Kim E, Li A, Lorens J, Luchinni R, Zheng W (Editors) Neurotoxicity and Neurodegeneration: Local Effect and Global Impact. NeuroToxicology. 2012, 33: 621-946.
9. Christov PP, Yamanaka K, Choi JY, Takata K, Wood RD, Guengerich FP, Lloyd RS, Rizzo CJ. Replication of the 2,6-diamino-4-hydroxy-N(5)-(methyl)-formamidopyrimidine (MeFapy-dGuo) adduct by eukaryotic DNA polymerases. Chem Res Toxicol. 2012 Aug 20; 25(8): 1652-61.
10. Cook M, Mani P, Wentzell JS, Kretzschmar D. Increased RhoA prenylation in the loechrig (loe) mutant leads to progressive neurodegeneration. PLoS One. 2012; 7(9): e44440.
11. Dodson ML, Walker RC, Lloyd RS. Carbinolamine formation and dehydration in a DNA repair enzyme active site. PLoS One. 2012; 7(2): e31377.
12. Dutta S, McFerrin J, Patton BL, Kretzschmar D. Prechordate conservation of glia-type specific expression and function of Neuropathy Target Esterase. Mol Biol Cell. 2012: 23(suppl): 2840.
13. Eastwood E, Allen CN, Raber J. Effects of neonatal methamphetamine and thioperamide exposure on spatial memory retention and circadian activity later in life. Behav Brain Res. 2012 Apr 21; 230(1): 229-36. 
14. Fox DA, Lucchini R, Aschner M, Chen J, Anger WK, Kim EA, Boyes WK, Llorens J. Local effects and global impact in neurotoxicity and neurodegeneration: the Xi’an International Neurotoxicology Conference. Neurotoxicology. 2012 Aug; 33(4): 629-30.
15. Frankenfeld CL, Lampe JW, Shannon J, Gao DL, Li W, Ray RM, Chen C, King IB, Thomas DB. Fruit and vegetable intakes in relation to plasma nutrient concentrations in women in Shanghai, China. Public Health Nutr. 2012 Jan; 15(1): 167-75. 
16. Hu K, Meijer JH, Shea SA,VanderLeest HT, Pittman-Polletta B, Houben T, van Oosterhout F, Deboer T, Scheer FA. Fractal patterns of neural activity exist within the suprachiasmatic nucleus and require extrinsic network interactions. PLoS One. 2012; 7(11): e48927. 
17. Ismail AA, Bodner TE, Rohlman DS. Neurobehavioral performance among agricultural workers and pesticide applicators: a meta-analytic study. Occup Environ Med. 2012 Jul; 69(7): 457-64.
18. Jeyaraj D, Scheer FA, Ripperger JA, Haldar SM, Lu Y, Prosdocimo DA, Eapen SJ, Eapen BL, Cui Y, Mahabeleshwar GH, Lee HG, Smith MA, Casadesus G, Mintz EM, Sun H, Wang Y, Ramsey KM, Bass J, Shea SA, Albrecht U, Jain MK. Klf15 orchestrates circadian nitrogen homeostasis. Cell Metab. 2012; 15: 311-23
19. Jeyaraj D, Haldar SM, Wan X, McCauley MD, Ripperger JA, Hu K, Lu Y, Eapen BL, Sharma N, Ficker E, Cutler MJ, Gulick J, Sanbe A, Robbins J, Demolombe S, Kondratov RV, Shea SA, Albrecht U, Wehrens XH, Rosenbaum DS, Jain MK. Circadian rhythms govern cardiac repolarization and arrhythmogenesis. Nature. 2012; 483: 96-9 Kassa R, Monterroso V, Wentzell J, Ramos AL, Couchi E, Lecomte MC, Iordanov M, Kretzschmar D, Nicolas G, Tshala-Katumbay D. Proximal giant neurofilamentous axonopathy in mice genetically engineered to resist calpain and caspase cleavage of α-II spectrin. J Mol Neurosci. 2012 Jul; 47(3): 631-8. 
20. Klug AR, Harbut MB, Lloyd RS, Minko IG. Replication bypass of N2-deoxyguanosine interstrand cross-links by human DNA polymerases η and ι. Chem Res Toxicol. 2012; 25 (3): 755-762. 
21. Krishnan N, Rakshit K, Chow ES, Wentzell JS, Kretzschmar D, Giebultowicz JM. Loss of circadian clock accelerates aging in neurodegeneration-prone mutants. Neurobiol Dis. 2012 Mar; 45(3):1129-35. 
22. Kumari A, Lim YX, Newell AH, Olson SB, McCullough AK. Formaldehyde-induced genome instability is suppressed by an XPF-dependent pathway. DNA Repair (Amst). 2012 Mar 1; 11(3): 236-46.
23. Lein PJ, Bonner MR, Farahat FM, Olson JR, Rohlman DS, Fenske RA, Lattal KM, Lasarev MR, Galvin K, Farahat TM, Anger WK. Experimental strategy for translational studies of organophosphorus pesticide neurotoxicity based on real-world occupational exposures to chlorpyrifos. Neurotoxicology. 2012 Aug; 33(4): 660-8.
24. Li AA, Levine TE, Burns CJ, Anger WK. Integration of epidemiology and animal neurotoxicity data for risk assessment. Neurotoxicology. 2012 Aug; 33(4): 823-32.  London L,
25. Beseler C, Bouchard MF, Bellinger DC, Colosio C, Grandjean P, Harari R, Kootbodien T, Kromhout H, Little F, Meijster T, Moretto A, Rohlman DS, Stallones L. Neurobehavioral and neurodevelopmental effects of pesticide exposures. Neurotoxicology. 2012 Aug; 33(4): 887-96.
26. Luyster FS, Strollo PJ Jr, Zee PC, Walsh JK; Boards of Directors of the American Academy of Sleep Medicine and the Sleep Research Society. Sleep: a health imperative. Sleep. 2012 Jun 1; 35(6): 727-34. 
27. Marriott LK, Cameron WE, Purnell JQ, Cetola S, Ito MK, Williams CD, Newcomb KC, Randall JA, Messenger WB, Lipus AC, Shannon J. Let’s Get Healthy! Health awareness through public participation in an education and research exhibit. Prog Community Health Partnersh. 2012 Fall; 6(3): 331-7
28. Marriott LK, Nelson DA, Allen S, Calhoun K, Eldredge CE, Kimminau KS, Lucero RJ, Pineda-Reyes F, Rumala BB, Varanasi AP, Wasser JS, Shannon J. Using health information technology to engage communities in health, education, and research. Sci Transl Med. 2012; 4: 119.
29. Messenger W, Nielson CM, Li H, Beer T, Barrett-Connor E, Stone K, Shannon J. Serum and dietary vitamin D and cardiovascular disease risk in elderly men: a prospective cohort study. Nutr Metab Cardiovasc Dis. 2012 Oct; 22(10): 856-63. Miller S, McFerrin J, Banine F, Su W, Sherman LS and Patton BL. CD44 required for neuregulin-dependent axonal sorting and nonmyelinating Schwann cell differentiation. Mol Biol Cell. 2012; 23 (suppl): 2901.
30. Olson R, Wipfli B and Garcia LR. Ergonomics: Practical guidance for assessing truck drivers. Professional Safety. 2012 Apr: 38-43 Poeck B, Strauss R, Kretzschmar D. Analysis of amyloid precursor protein function in Drosophila melanogaster. Exp Brain Res. 2012 Apr; 217(3-4): 413-21. 
31. Rohlman DS, Nuwayhid I, Ismail A, Saddik B. Using epidemiology and neurotoxicology to reduce risks to young workers. Neurotoxicology. 2012 Aug; 33(4): 817-22.
32. Sampath H, McCullough AK, Lloyd RS. Regulation of DNA glycosylases and their role in limiting disease. Free Radic Res. 2012 Apr; 46(4): 460-78.
33. Sampath H, Vartanian V, Rollins MR, Sakumi K, Nakabeppu Y, Lloyd RS. 8-Oxoguanine DNA glycosylase (OGG1) deficiency increases susceptibility to obesity and metabolic dysfunction. PLoS One. 2012; 7(12): e51697. 
34. Scheer FA, Morris CJ, Garcia JI, Smales C, Kelly EE, Marks J, Malhotra A, Shea SA. Repeated melatonin supplementation improves sleep in hypertensive patients treated with beta-blockers: a randomized controlled trial. Sleep. 2012 Oct 1; 35(10): 1395-402. 
35. Shea SA. Obesity and pharmacologic control of the body clock. N Engl J Med. 2012 Jul 12; 367(2): 175-8.
36. Spencer PS and Palmer VS. Interrelationships of undernutrition and neurotoxicity: food for thought and research attention. Neurotoxicology 22: 605-16, 2012. 
37. Spencer PS, Fry, RC and Kisby, GE. Unraveling 50-year-old clues linking neurodegeneration and cancer to cycad toxins: Are microRNAs common mediators? Frontiers in Genetics 2012; 3: 192.
38. Spencer PS, Fry RC, Palmer VS and Kisby GE. Western Pacific ALS-PDC: a prototypical neurodegenerative disorder linked to DNA damage and aberrant proteogenesis? Frontiers in Neurology 2012; 3: 180. 
39. Wentzell JS, Bolkan BJ, Carmine-Simmen K, Swanson TL, Musashe DT, Kretzschmar D. Amyloid precursor proteins are protective in Drosophila models of progressive neurodegeneration. Neurobiol Dis. 2012 Apr; 46(1): 78-87.
40. Wipfli B, Olson R, Wright RR, Garrigues L, Lees J. Characterizing hazards and injuries among home care workers. Home Healthcare Nurse June/July 2012; 30(7): 387-393. 
41. Yamanaka K, Dorjsuren D, Eoff RL, Egli M, Maloney DJ, Jadhav A, Simeonov A, Lloyd RS. A comprehensive strategy to discover inhibitors of the translesion synthesis DNA polymerase κ. PLoS One. 2012; 7(10): e45032.