Long-term effects of myo-inositol on traumatic brain injury: Epigenomic and transcriptomic studies.

Background and purpose: Traumatic brain injury (TBI) and its consequences remain great challenges for neurology. Consequences of TBI are associated with various alterations in the brain but little is known about long-term changes of epigenetic DNA methylation patterns. Moreover, nothing is known about potential treatments that can alter these epigenetic changes in beneficial ways. Therefore, we have examined myo-inositol (MI), which has positive effects on several pathological conditions. Methods: TBI was induced in mice by controlled cortical impact (CCI). One group of CCI animals received saline injections for two months (TBI+SAL), another CCI group received MI treatment (TBI+MI) for the same period and one group served as a sham-operated control. Mice were sacrificed 4 months after CCI and changes in DNA methylome and transcriptomes were examined. Results: For the first time we: (i) provide comprehensive map of long-term DNA methylation changes after CCI in the hippocampus; (ii) identify differences by methylation sites between the groups; (iii) characterize transcriptome changes; (iv) provide association between DNA methylation sites and gene expression. MI treatment is linked with upregulation of genes covering 33 biological processes, involved in immune response and inflammation. In support of these findings, we have shown that expression of BATF2, a transcription factor involved in immune-regulatory networks, is upregulated in the hippocampus of the TBI+MI group where the BATF2 gene is demethylated. Conclusion: TBI is followed by long-term epigenetic and transcriptomic changes in hippocampus. MI treatment has a significant effect on these processes by modulation of immune response and biological pathways of inflammation.

The association of forced expiratory volume in one second with occupational exposures in a longitudinal study of adults in a rural community in Iowa.

PURPOSE: The Keokuk County Rural Health Study (KCRHS) is a longitudinal population-based study conducted in rural Iowa. A prior analysis of enrollment data identified an association of airflow obstruction with occupational exposures only among cigarette smokers. The current study used spirometry data from all three rounds to investigate whether level of forced expiratory volume in one second (FEV1) and longitudinal change in FEV1 were associated with occupational vapor-gas, dust, and fumes (VGDF) exposures, and whether these associations were modified by smoking. METHODS: This study sample comprised 1071 adult KCRHS participants with longitudinal data. A job-exposure matrix (JEM) was applied to participants' lifetime work histories to assign exposures to occupational VGDF. Mixed regression models of pre-bronchodilator FEV1 (millimeters, ml) were fit to test for associations with occupational exposures while adjusting for potential confounders. RESULTS: Mineral dust had the most consistent association with change in FEV1, including ever/never ( - 6.3 ml/year) and nearly every level of duration, intensity, and cumulative exposure. Because 92% of participants with mineral dust also had organic dust exposure, the results for mineral dust may be due to a combination of the two. An association of FEV1 level with fumes was observed for high intensity ( - 91.4 ml) among all participants, and limited to cigarette smokers with results of - 104.6 ml ever/never exposed, - 170.3 ml high duration, and - 172.4 ml high cumulative. CONCLUSION: The current findings suggest that mineral dust, possibly in combination with organic dust, and fumes exposure, especially among cigarette smokers, were risk factors for adverse FEV1 results.

Characterization of Arsenic and Atrazine Contaminations in Drinking Water in Iowa: A Public Health Concern.

Arsenic and atrazine are two water contaminants of high public health concern in Iowa. The occurrence of arsenic and atrazine in drinking water from Iowa's private wells and public water systems was investigated over several decades. In this study, the percentages of detection and violation of regulations were compared over region, season, and water source, and factors affecting the detection and concentration of arsenic and atrazine were analyzed using a mixed-effects model. Atrazine contamination in drinking water was found to vary by region, depending on agricultural usage patterns and hydrogeological features. The annual median atrazine levels of all public water systems were below the drinking water standard of 3 ppb in 2001-2014. Around 40% of public water systems contained arsenic at levels > 1 ppb in 2014, with 13.8% containing arsenic at levels of 5-10 ppb and 2.6% exceeding 10 ppb. This unexpected result highlights the ongoing public health threat posed by arsenic in drinking water in Iowa, emphasizing the need for continued monitoring and mitigation efforts to reduce exposure and associated health risks. Additionally, an atrazine metabolite, desethylatrazine, should be monitored to obtain a complete account of atrazine exposure and possible health effects.

Burden of Disease and Unmet Needs in Atopic Dermatitis: Results From a Patient Survey.

Background: Atopic dermatitis (AD) affects 2%-10% of adults worldwide. Occurrence and severity of symptoms and treatment success vary among patients. Objective: To determine disease severity, burden, and treatment use and satisfaction in adults with AD. Methods: An international internet-based survey was conducted (October 5-November 1, 2021) in participants with AD from Canada, France, Germany, Italy, Japan, Spain, the United Kingdom, and the United States. Results: Of 2005 AD patients surveyed, 92% had body surface area (BSA) involvement <10%. Itch was the most bothersome symptom; 48.5% of participants reported severe itch in the past week (Itch Numerical Rating Scale [NRS] 7-10; 45.9% for BSA <10%, 75.0% for BSA ≥10%). Most participants reported moderate or severe sleep disturbance in the past week (Sleep NRS 4-10; 67.1% for BSA <10%, 92.3% for BSA ≥10%). Itch was the top reason for participants' most recent health care provider visit; reducing itching was their top treatment goal. Topical therapies, which were most commonly used, resulted in low treatment satisfaction. Conclusions: Itch was the most bothersome AD symptom. Although clinical development has focused on improving skin lesions, improving itch is patients' top treatment goal. This survey highlights the need for systemic antipruritic therapies that could reduce itch in nonlesional and lesional skin.

Phenotypic predictors of suicide subtypes from pre-to postdeployment in active duty military personnel.

Military service members are at increased risk for suicide, but there are few strategies for detecting those who are at highest risk after a deployment. Using all available data collected from 4119 Military service members before and after their deployment to Iraq for Operation Iraqi Freedom, we tested whether predeployment characteristics clustered together to predict postdeployment suicidal risk. Latent class analysis showed that three classes best characterized the sample at predeployment. Class 1 had significantly higher scores on PTSD severity pre- and postdeployment than Classes 2 and 3 (Ps < .001). At postdeployment, Class 1 also had a greater proportion of endorsement of lifetime and past year suicidal ideation than Classes 2 and 3 (Ps < .05) and a greater proportion of lifetime suicide attempts than Class 3 (P < .001). Class 1 also had a greater proportion of endorsement of past-30-days intention to act on suicidal thoughts than Classes 2 and 3 (Ps < .05) and past-30-days specific plan for suicide than Classes 2 and 3 (Ps < .05). The study showed that based only on predeployment data, it is possible to determine which service members might be at highest risk for suicidal ideation and behavior at postdeployment.

Prevalence of Fibromyalgia Syndrome in Active-Duty Military Personnel.

OBJECTIVE: Previous research with civilian populations has found strong associations between fibromyalgia (FM) and posttraumatic stress disorder (PTSD). We undertook this study to investigate the prevalence of FM in military service members with and without PTSD. METHODS: Participants were active duty military personnel recruited into either an epidemiologic cohort study of service members before a military deployment or 1 of 3 PTSD treatment trials. Instruments used to document FM and PTSD included the PTSD Checklist-Stressor-Specific Version, the PTSD Symptom Scale-Interview, and the 2012 American College of Rheumatology FM questionnaire. RESULTS: Across the 4 studies, 4,376 subjects completed surveys. The prevalence of FM was 2.9% in the predeployment cohort, and the prevalence was significantly higher in individuals with PTSD (10.8%) compared with those without PTSD (0.8%). In the treatment trials, all of the participants met criteria for PTSD before starting treatment, and the prevalence of FM was 39.7%. CONCLUSION: The prevalence of FM in active duty service members preparing to deploy is similar to that reported for the general population of the US but is higher than expected for a predominantly male cohort. Furthermore, the prevalence of FM was significantly higher in service members with comorbid PTSD and was highest among those seeking treatment for PTSD. Further investigation is needed to determine the factors linking PTSD and FM.

Oculomotor, vestibular, reaction time, and cognitive tests as objective measures of neural deficits in patients post COVID-19 infection.

Objective: An alarming proportion (>30%) of patients affected by SARS-CoV-2 (COVID-19) continue to experience neurological symptoms, including headache, dizziness, smell and/or taste abnormalities, and impaired consciousness (brain fog), after recovery from the acute infection. These symptoms are self-reported and vary from patient to patient, making it difficult to accurately diagnose and initiate a proper treatment course. Objective measures to identify and quantify neural deficits underlying the symptom profiles are lacking. This study tested the hypothesis that oculomotor, vestibular, reaction time, and cognitive (OVRT-C) testing using eye-tracking can objectively identify and measure functional neural deficits post COVID-19 infection. Methods: Subjects diagnosed with COVID-19 (n = 77) were tested post-infection with a battery of 20 OVRT-C tests delivered on a portable eye-tracking device (Neurolign Dx100). Data from 14 tests were compared to previously collected normative data from subjects with similar demographics. Post-COVID subjects were also administered the Neurobehavioral Symptom Inventory (NSI) for symptom evaluation. Results: A significant percentage of post COVID-19 patients (up to 86%) scored outside the norms in 12 out of 14 tests, with smooth pursuit and optokinetic responses being most severely affected. A multivariate model constructed using stepwise logistic regression identified 6 metrics as significant indicators of post-COVID patients. The area under the receiver operating characteristic curve (AUC) was 0.89, the estimated specificity was 98% (with cutoff value of 0.5) and the sensitivity was 88%. There were moderate but significant correlations between NSI domain key variables and OVRT-C tests. Conclusions: This study demonstrates the feasibility of OVRT-C testing to provide objective measures of neural deficits in people recovering from COVID-19 infection. Such testing may serve as an efficient tool for identifying hidden neurological deficits post COVID-19, screening patients at risk of developing long COVID, and may help guide rehabilitation and treatment strategies.

The association of chronic bronchitis and airflow obstruction with lifetime and current farm activities in a sample of rural adults in Iowa.

OBJECTIVE: Farmers have an increased risk for chronic bronchitis and airflow obstruction. The objective of this study was to investigate the association of these health outcomes with farm activities. METHODS: We evaluated the Keokuk County Rural Health Study (KCRHS) enrollment data for farm activities and the two health outcomes chronic bronchitis based on self-reported symptoms and airflow obstruction based on spirometry. We used logistic regression to model the health outcomes, yielding an odds ratio (OR) and 95% confidence interval (95% CI) for farm activities while adjusting for potential confounders and other risk factors. RESULTS: Of the 1234 farmers, 104 (8.4%) had chronic bronchitis, 75 (6.1%) fulfilled the criteria for airflow obstruction, and the two outcomes overlapped by 18 participants. Chronic bronchitis without airflow obstruction (n = 86) had a statistically significant association with crop storage insecticides (OR 3.1, 95% CI 1.6, 6.1) and a low number of years (≤ 3) worked with turkeys (OR 3.3, 95% CI 1.2, 9.4). The latter result should be interpreted with caution because it is based on a small number of cases (n = 5). Airflow obstruction with or without chronic bronchitis (n = 75) was significantly associated with ever working in a hog or chicken confinement setting (OR 2.2, 95% CI 1.0, 4.5). CONCLUSIONS: These results suggest that work with crop storage insecticides or turkeys may increase the risk for chronic bronchitis and work in hog or chicken confinement may increase the risk for airflow obstruction.

STRONG STAR and the Consortium to Alleviate PTSD: Shaping the future of combat PTSD and related conditions in military and veteran populations.

The STRONG STAR Consortium (South Texas Research Organizational Network Guiding Studies on Trauma and Resilience) and the Consortium to Alleviate PTSD are interdisciplinary and multi-institutional research consortia focused on the detection, diagnosis, prevention, and treatment of combat-related posttraumatic stress disorder (PTSD) and comorbid conditions in military personnel and veterans. This manuscript outlines the consortia's state-of-the-science collaborative research model and how this can be used as a roadmap for future trauma-related research. STRONG STAR was initially funded for 5 years in 2008 by the U.S. Department of Defense's (DoD) Psychological Health and Traumatic Brain Injury Research Program. Since the initial funding of STRONG STAR, almost 50 additional peer-reviewed STRONG STAR-affiliated projects have been funded through the DoD, the U.S. Department of Veterans Affairs (VA), the National Institutes of Health, and private organizations. In 2013, STRONG STAR investigators partnered with the VA's National Center for PTSD and were selected for joint DoD/VA funding to establish the Consortium to Alleviate PTSD. STRONG STAR and the Consortium to Alleviate PTSD have assembled a critical mass of investigators and institutions with the synergy required to make major scientific and public health advances in the prevention and treatment of combat PTSD and related conditions. This manuscript provides an overview of the establishment of these two research consortia, including their history, vision, mission, goals, and accomplishments. Comprehensive tables provide descriptions of over 70 projects supported by the consortia. Examples are provided of collaborations among over 50 worldwide academic research institutions and over 150 investigators.

Identifying suicidal subtypes and dynamic indicators of increasing and decreasing suicide risk in active duty military personnel: Study protocol.

OBJECTIVES: Several recent studies have demonstrated that posttraumatic stress disorder (PTSD) and insomnia treatments are associated with significant reductions in suicidal ideation (SI) among service members. However, few investigations have evaluated the manner in which suicide risk changes over time among military personnel receiving PTSD or insomnia treatments. This paper describes the study protocol for a project with these aims: (1) explore potential genetic, clinical, and demographic subtypes of suicide risk in a large cohort of deployed service members; (2) explore subtype change in SI as a result of evidence-based psychotherapies for PTSD and insomnia; (3) evaluate the speed of change in suicide risk; and (4) identify predictors of higher- and lower-risk for suicide. METHODS: Active duty military personnel were recruited for four clinical trials (three for PTSD treatment and one for insomnia treatment) and a large prospective epidemiological study of deployed service members, all conducted through the South Texas Research Organizational Network Guiding Studies on Trauma and Resilience (STRONG STAR Consortium). Participants completed similar measures of demographic and clinical characteristics and subsets provided blood samples for genetic testing. The primary measures that we will analyze are the Beck Scale for Suicide Ideation, Beck Depression Inventory, and the PTSD Checklist for DSM-IV. DISCUSSION: Results from this study will offer new insights into the presence of discrete subtypes of suicide risk among active duty personnel, changes in risk over time among those subtypes, and predictors of subtypes. Findings will inform treatment development for military service members at risk for suicide.

Gender differences in respiratory health outcomes among farming cohorts around the globe: findings from the AGRICOH consortium.

Purpose: Respiratory hazards of farming have been identified for centuries, with little focus on gender differences. We used data from the AGRICOH consortium, a collective of prospective cohorts of agricultural workers, to assess respiratory disease prevalence among adults in 18 cohorts representing over 200,000 farmers, farm workers, and their spouses from six continents.Methods: Cohorts collected data between 1992 and 2016 and ranged in size from 200 to >128,000 individuals; 44% of participants were female. Farming practices varied from subsistence farming to large-scale industrial agriculture. All cohorts provided respiratory outcome information for their cohort based on their study definitions. The majority of outcomes were based on self-report using standard respiratory questionnaires; the greatest variability in assessment methods was associated with chronic obstructive pulmonary disease (COPD).Results: For all three respiratory symptoms (cough, phlegm, and wheeze), the median prevalence in men was higher than in women, with the greatest difference for phlegm (17% vs. 10%). For asthma, women had a higher prevalence (7.8% vs 6.5%), with the difference associated with allergic asthma. The relative proportion of allergic asthma varied among cohorts. In two of eight cohorts for women and two of seven cohorts for men, allergic asthma was more common than non-allergic asthma.Conclusions: These findings indicate that respiratory outcomes are common among farmers around the world despite differences in agricultural production. As women in the general population are at higher risk of asthma, exploring gender differences in occupational studies is critical for a deeper understanding of respiratory disease among agricultural workers.

Health Indicators of a Cohort of Midwest Farmers: Health Outcomes of Participants in the Certified Safe Farm Program.

Occupational illness, injury, and fatality rates for those working in production agriculture are higher than in any other industry. A potential risk factor contributing to occupational injuries across all industries is acute or chronic co-morbidity (e.g., obesity, high blood pressure, high cholesterol), and related health issues that increase the risk for an occupational injury or illness. These chronic health conditions have been associated not only with increased risk for injuries, but also higher health-care costs, and greater absenteeism. Certified Safe Farm (CSF) is a comprehensive intervention program aimed to reduce occupational health and safety hazards and to promote general health among farmers. Prior publications have described CSF program efforts to reduce hazardous exposures, disabling injuries, organic dust toxic syndrome, occupational health-care costs, and to increase positive occupational health behaviors. This paper reports on the general health indicators of a cohort of 438 Iowa farm owner/operators enrolled in the CSF program. Overall, this study found that the farming population in Iowa has higher body mass index (BMI), but lower total cholesterol, low-density lipoprotein (LDL), and lower prevalence of hypertension compared to the general population. There was evidence that the combination of high blood pressure, cholesterol, and BMI were related to increased injury rates. Poor self-reported health status was also related to increased injuries but was not related to clinical health indicators. The CSF intervention led to improvements on health outcomes, particularly among those in the 35 to 49 age group. Little research has focused on the individual's general health status as a predictor of risk of occupational injury. This study suggests the need for additional research and interventions integrating occupational safety and health prevention along with health promotion.

Toxicokinetics of Chiral PCB 136 and Its Hydroxylated Metabolites in Mice with a Liver-Specific Deletion of Cytochrome P450 Reductase.

Exposure to polychlorinated biphenyls (PCBs) has been implicated in adverse human health effects, including developmental neurotoxicity. Several neurotoxic PCBs are chiral and undergo atropisomeric enrichment in vivo due to atropselective metabolism by cytochrome P450 enzymes. Here we study how the liver-specific deletion of the cytochrome P450 reductase ( cpr) gene alters the toxicokinetics of 2,2',3,3',6,6'-hexachlorobiphenyl (PCB 136) in mice. Male and female mice with a liver-specific deletion of cpr (KO) and congenic wild-type (WT) mice were exposed to a single oral dose of racemic PCB 136 (6.63 mg/kg). Levels and chiral signatures of PCB 136 and its hydroxylated metabolites were determined 1-48 h after PCB exposure in whole blood. Blood levels of PCB 136 were typically higher in M-WT compared to F-WT mice. At the later time points, F-KO mice had significantly higher PCB 136 levels than F-WT mice. 2,2',3',4,6,6'-Hexachlorobiphenyl-3-ol (3-150), 2,2',3,3',6,6'-hexachlorobiphenyl-4-ol (4-136), 2,2',3,3',6,6'-hexachlorobiphenyl-5-ol (5-136), and 4,5-dihydroxy-2,2',3,3',6,6'-hexachlorobiphenyl (4,5-136) were detected in blood, with 5-136 and 4-136 being major metabolites. At later time points, the sum of HO-PCB (∑HO-PCB) levels exceeded PCB 136 levels in the blood; however, higher ∑HO-PCB than PCB 136 levels were observed later in KO than WT mice. PCB 136 and its major metabolites displayed atropisomeric enrichment in a manner that depended on the time point, sex, and genotype. Toxicokinetic analysis revealed sex and genotype-dependent differences in toxicokinetic parameters for PCB 136 atropisomers and its metabolites. The results suggest that mice with a liver-specific deletion of the cpr gene can potentially be used to assess how an altered metabolism of neurotoxic PCB congeners affects neurotoxic outcomes following exposure of the offspring to PCBs via the maternal diet.

Trust in the Work Environment and Cardiovascular Disease Risk: Findings from the Gallup-Sharecare Well-Being Index.

This study examined associations between trust, an important aspect of workplace social capital, with seven cardiovascular disease (CVD) risk factors (American Heart Association Life's Simple 7 (LS7)): smoking, obesity, low physical activity, poor diet, diabetes, high cholesterol, and high blood pressure. Data are from the U.S. Gallup-Sharecare Well-Being Index (2010⁻2012), a nationally representative telephone survey of U.S. workers (n = 412,884). The independent variable was the response to a work environment (WE) question as to whether their supervisor always creates an open and trusting environment. Regression models were adjusted for demographic characteristics with each of the LS7 CVD risk factors as dependent variables. Twenty-one percent of workers reported that their supervisor did not create an open and trusting environment. Trust was associated with increased adjusted odds of having many of the LS7 CVD risk factors. Among those workers whose supervisor created a mistrustful environment, the odds ratios were greatest (>20%) for having four or more of the LS7 CVD risk factors.

Seizures, Antiepileptic Drugs, and CKD.

There are 2 major categories of patients with seizures and chronic kidney disease (CKD): patients who develop acute symptomatic seizures in the setting of CKD and patients with epilepsy who at some point develop CKD. The incidence of uremic seizures with kidney failure is ∼10%. These seizures are often nonconvulsive and may mimic uremic encephalopathy. Recognition and management of such situations may be challenging for treating physicians who are non-neurologists. Furthermore, practitioners caring for patients with seizures with or without an established diagnosis of epilepsy in the setting of CKD frequently encounter challenges in the selection, loading, titration, and maintenance of antiepileptic drugs (AEDs) due to potentially altered pharmacokinetics of the AEDs. We review the pathophysiology of uremia, uremic seizures, and other neurologic complications of kidney failure; management approaches to the treatment of such complications; the relevant mechanisms of action and pharmacokinetics of AEDs with their use in CKD; and in particular, the management of AEDs in patients requiring hemodialysis therapy.

Oculomotor, Vestibular, and Reaction Time Effects of Sports-Related Concussion: Video-Oculography in Assessing Sports-Related Concussion.

OBJECTIVE: The purpose of the study was to test the ability of oculomotor, vestibular, and reaction time (OVRT) metrics to serve as a concussion assessment or diagnostic tool for general clinical use. SETTING AND PARTICIPANTS: Patients with concussion were high school-aged athletes clinically diagnosed in a hospital setting with a sports-related concussion (n = 50). Control subjects were previously recruited male and female high school student athletes from 3 local high schools (n = 170). DESIGN: Video-oculography was used to acquire eye movement metrics during OVRT tasks, combined with other measures. Measures were compared between groups, and a subset was incorporated into linear regression models that could serve as indicators of concussion. MEASURES: The OVRT test battery included multiple metrics of saccades, smooth pursuit tracking, nystagmoid movements, vestibular function, and reaction time latencies. RESULTS: Some OVRT metrics were significantly different between groups. Linear regression models distinguished control subjects from concussion subjects with high accuracy. Metrics included changes in smooth pursuit tracking, increased reaction time and reduced saccade velocity in a complex motor task, and decreased optokinetic nystagmus (OKN) gain. In addition, optokinetic gain was reduced and more variable in subjects assessed 22 or more days after injury. CONCLUSION: These results indicate that OVRT tests can be used as a reliable adjunctive tool in the assessment of concussion and that OKN results appear to be associated with a prolonged expression of concussion symptoms.

Research Methodologies for Total Worker Health®: Proceedings From a Workshop.

OBJECTIVE: There is growing interest in the NIOSH Total Worker Health program, specifically in the process of designing and implementing safer, health-promoting work and workplaces. A Total Worker Health (TWH) Research Methodology Workshop was convened to discuss research methods and future needs. METHODS: Twenty-six experts in occupational safety and health and related fields reviewed and discussed current methodological and measurement issues and those showing promise. RESULTS: TWH intervention studies face the same challenges as other workplace intervention studies and some unique ones. Examples are provided of different approaches and their applications to TWH intervention studies, and desired developments in the TWH literature. CONCLUSIONS: This report discusses and outlines principles important to building the TWH intervention research base. Rigorous, valid methodologic, and measurement approaches are needed for TWH intervention as well as for basic/etiologic, translational, and surveillance research.