Military Exposures Predict Mental Health Symptoms in Explosives Personnel but Not Always as Expected.

OBJECTIVE: The aim of this study was to determine the unique and combined associations of various military stress exposures with positive and negative mental health symptoms in active duty service members. MATERIALS AND METHODS: We investigated 87 male U.S. Navy Explosive Ordnance Disposal (EOD) technicians (age M ± SE, range 33.7 ± 0.6, 22-47 years). Those who endorsed a positive traumatic brain injury diagnosis were excluded to eliminate the confounding effects on mental health symptoms. Using a survey platform on a computer tablet, EOD technicians self-reported combat exposure, deployment frequency (total number of deployments), blast exposure (vehicle crash/blast or 50-m blast involvement), depression, anxiety, posttraumatic stress, perceived stress, and life satisfaction during an in-person laboratory session. RESULTS: When controlling for other military stressors, EOD technicians with previous involvement in a vehicle crash/blast endorsed worse mental health than their nonexposed counterparts. The interactions of vehicle crash/blast with deployment frequency and combat exposure had moderate effect sizes, and combat and deployment exposures demonstrated protective, rather than catalytic, effects on negative mental health scores. CONCLUSIONS: Military stressors may adversely influence self-reported symptoms of negative mental health, but deployment experience and combat exposure may confer stress inoculation.

Greater Fitness Is Associated With Improved Functional Movement Characteristics in Explosive Ordnance Disposal Technicians.

ABSTRACT: Hernández, LM, Coffin, SD, and Taylor, MK. Greater fitness is associated with improved functional movement characteristics in explosive ordnance disposal technicians. J Strength Cond Res 36(6): 1731-1737, 2022-Low fitness and poor functional movement (FM) have been linked to higher musculoskeletal injury risk. The FM Screen (FMS) and Y-Balance Test (YBT) are useful indicators of potential injury risk in military personnel. U.S. Navy Explosive Ordnance Disposal (EOD) technicians are the premier combat force for countering explosive hazards and must operate in austere environments. To safeguard health and mission success, it is critical to assess factors related to injury risk in this specialized military population. This study evaluated the relationship between fitness and FM characteristics in 64 male EOD technicians (mean age ± SD = 34.2 ± 7.0 years). Body fat percentage (BF%), maximum volume of oxygen uptake (V̇o2max), muscular strength, and FM (i.e., FMS, YBT) were assessed. Body fat percentage and V̇o2max were associated with FMS and YBT scores (all p < 0.05). A nonlinear model further revealed that the group with the lowest V̇o2max values had the bottommost FMS and YBT scores (all p < 0.01), but FM scores did not differ among those with a higher V̇o2max, implying a "threshold" effect. No correlations were observed with muscular strength. By characterizing the unique and shared contributions of BF% and V̇o2max, and exploring the nonlinear relationship between V̇o2max and FM, this study expands on accruing data that indicate individuals who are more physically fit have better FM and lower injury risk. Although muscular strength is a critical element of overall fitness, body composition and cardiorespiratory fitness may more strongly influence FM and injury risk.

Combat and blast exposure blunt sympathetic response to acute exercise stress in specialised military men.

Electrodermal activity (EDA)-a measure of electrical skin conductance reflecting (exclusive) sympathetic control of the eccrine sweat gland-holds promise as an indicator of central sympathetic activation. The aim of this study was to determine whether combat and blast exposure modulate the EDA response to acute exercise stress in specialised military men. Fifty-one men (age M = 36.1, SD = 6.5) participated in this study as part of the Explosive Ordnance Disposal Operational Health Surveillance System. The EDA complex (i.e., tonic + phasic conductance) was continuously measured throughout a maximal effort, graded exercise test. As expected, exercise stress resulted in measurable, stepwise increases in EDA before tapering at higher exercise intensities. Individuals with more substantial combat exposure and those with blast exposure demonstrated blunted EDA patterns in comparison to their low/nonexposed counterparts. This blunted pattern might imply sub-optimal sympathetic nervous system function in the exposed cohorts and enhances our knowledge of factors influencing resilience in these men.

Toward a "Dashboard" Indicator of Retention in U.S. Navy Personnel.

INTRODUCTION: Retention is a top priority for the U.S. Navy. However, our understanding of factors influencing retention of Navy personnel is limited. Current research implies that poor mental health, low appraisals of unit cohesion, low leadership satisfaction, and low social support may adversely affect retention. There is a need to understand how these and other factors influence retention in U.S. Navy personnel. We evaluated a broad range of factors influencing job satisfaction and career intentions (proxies of retention) in a large sample of Navy service members. MATERIALS AND METHODS: Seven hundred and ninety-eight U.S. Navy men and women participated in this study as part of the Naval Unit Behavioral Health Needs Survey (NHRC.2014.0006). Independent variables included personal and unit morale, unit cohesion, affective organizational commitment, social support, behavioral health, sleep, leadership satisfaction, and perceived stress. Dependent variables include job satisfaction and career intentions. Separate multivariate regression models examined the unique and combined associations of independent and demographic variables with each dependent variable, respectively. RESULTS: Regression models accounted for 48% of variance in job satisfaction and 55% of variance in career intentions, respectively. The most robust predictors of job satisfaction were affective organizational commitment (i.e., one's emotional attachment to, identification with, and involvement in an organization), depressive symptoms, unit cohesion, and perceived stress; primary predictors of career intentions included affective organizational commitment, years of military service, marital status, and race/ethnicity. CONCLUSION: In this study, we identified diverse predictors of job satisfaction and career intentions of Navy men and women, with overall models accounting for substantial variance in both outcomes. This study informs evidence-based policies, programs, practices, and processes designed to influence job satisfaction, career intentions, and retention in U.S. Navy service members. These study findings also inform the development of a dashboard indicator of retention of U.S. Navy men and women.

Post-awakening Cortisol in Explosive Ordnance Disposal Technicians: A Replication Study in a Novel Population.

INTRODUCTION: Amassing evidence suggests that post-awakening salivary cortisol rhythms (changes in cortisol throughout the day) may indicate health status. We previously established summary parameters for salivary cortisol in U.S. Navy Sea, Air, and Land and reported excellent parameter stability across 2 days of repeated sampling. To confirm the generalizability of our original findings to other military populations, we replicated the procedures of our prior report in another specialized military group. The purpose of this study was to (1) establish summary parameters of daily salivary cortisol rhythms, (2) evaluate summary parameter stability, and (3) assess the impact of sampling compliance in U.S. Navy Explosive Ordnance Disposal (EOD) technicians. MATERIALS AND METHODS: Seventy active duty, male Explosive Ordnance Disposal technicians (mean ± SD age; 34.9 ± 6.5 years) self-collected saliva samples in a nondeployed setting on two consecutive weekdays at WAKE, WAKE + 30 min, WAKE + 60 min, 4 p.m., and 9 p.m. For salivary cortisol, we computed summary parameters, i.e., measures of magnitude and measures of pattern, and then evaluated their stabilities via correlational analyses and Cronbach's alpha (α). Compliance was objectively and subjectively evaluated using actigraphy and self-reported data, respectively. This research was conducted under a Naval Health Research Center Institutional Review Board approved study (NHRC.2015.0013). RESULTS: Average salivary cortisol concentrations increased at WAKE + 30 (mean ± SE reactivity; 48.9 + 6.8%) from WAKE, followed by a swift recovery at WAKE + 60. Approximately 10.9% of the group were classified as negative-responders (i.e., < 0% change from WAKE to WAKE + 30). The measures of magnitude demonstrated fair stability across two days (r value range: 0.37-0.45, ps < 0.01; α range: 0.54-0.62). Fifty-five percent of the sample was classified as compliant (defined as <15 min deviation from target sampling times) across both days. Compliance decreased to 31% when compliance criteria were refined to <5 min deviation; however, controlling for compliance did not overwhelmingly influence the more stable summary parameters of magnitude. CONCLUSIONS: These findings demonstrate a thorough replication, with some additional refinement, of our prior study, implying generalizability across diverse military populations. Study limitations include unsupervised saliva collection in a free-living setting, which is counterbalanced by ecological validity. The noninvasive salivary sampling protocol used in this study yields stable estimations of daily cortisol rhythms in specialized military men and is recommended as an operational health surveillance tool by which to monitor chronically stressed military members.

Trauma Exposure and Functional Movement Characteristics of Male Tactical Athletes.

CONTEXT: Tactical athletes commonly experience high levels of physical stress, which may increase their risk of musculoskeletal injury. It is critical to understand psychological predictors of functional movement (FM), which may help prevent musculoskeletal injury in this population. OBJECTIVE: To determine the associations of combat and trauma exposure with FM characteristics of male tactical athletes. Secondary objectives were to explore confounding influences of age and physical injury history as well as the mediating role of bodily pain. DESIGN: Cross-sectional study. SETTING: Research laboratory. PATIENTS OR OTHER PARTICIPANTS: Eighty-two healthy, male, active-duty US Navy Explosive Ordnance Disposal personnel (age = 34.0 ± 6.7 years). MAIN OUTCOME MEASURE(S): Participants completed measures of combat exposure, trauma exposure, physical injury history, and bodily pain. We assessed FM characteristics (ie, Functional Movement Screen [FMS], Y-Balance Test), from which we derived a composite functional status (CFS) measure. Hypotheses were tested using correlational and multiple regression (causal-steps) models. RESULTS: In unadjusted models, trauma exposure was inversely associated with the FMS (P = .005) and CFS (P = .009) scores. In adjusted models, these relationships were robust to the confounding influences of age and physical injury history. Trauma exposure and bodily pain were substantive, independent predictors of FMS and CFS in causal-steps models (all P values < .05), implying additive rather than mediated effects (R2adj = 0.18-0.20). Combat exposure did not predict FM characteristics. CONCLUSIONS: To our knowledge, this is the first evidence of the influence of trauma exposure on the FM characteristics of male tactical athletes, independent of age, physical injury, and bodily pain. This program of research may help to advance the prevention and treatment of musculoskeletal injuries in the tactical environment.

Blast exposure interacts with genetic variant 5HTTLPR to predict posttraumatic stress symptoms in military explosives personnel.

The first of its kind, this study determined whether blast exposure interacts with genetic variant 5HTTLPR to predict posttraumatic stress (PTS) symptoms in 78 military explosives operators. In all models, blast-exposed 5HTTLPR S carriers registered definitively higher PTS symptoms in comparison to non-exposed S carriers, as well as exposed and non-exposed LL carriers (all p < 0.01). All findings were robust to confounding influences of age and traumatic brain injury diagnosis. Not only is blast exposure prevalent in EOD personnel, but it also interacts with genetic predisposition to predict trauma symptoms in this unique, at-risk military population.

Genetic, Physiologic, and Behavioral Predictors of Cardiorespiratory Fitness in Specialized Military Men.

INTRODUCTION: Cardiorespiratory fitness (CRF) is a crucial performance requirement of specialized military occupations. Age and physical activity are established predictors of CRF, but it is not clear how these predictors combine with each other and/or with genetic predisposition. The goal of this study was to derive inclusive explanatory models of CRF in US Navy Explosive Ordnance Disposal (EOD) operators, synthesizing conventional (e.g., age, body composition, and physical activity) and novel influences (e.g., genetic variance). MATERIALS AND METHODS: In this cross-sectional study, 40 male, active duty EOD operators completed a graded exercise test to assess maximal oxygen consumption and ventilatory threshold (VT) using the Bruce protocol. Aerobic performance was further quantified via time of test termination and time at which VT was achieved. Body composition was determined via dual x-ray absorptiometry, and physical activity was assessed by self-report. Genetic variants underlying human stress systems (5HTTLPR, BclI, -2 C/G, and COMT) were assayed. Descriptive analyses were conducted to summarize subject characteristics. Hypotheses were tested with linear regression models. Specifically, separate univariate regression models first determined associations between each of the independent and dependent variables. This protocol was approved by the Naval Health Research Center Institutional Review Board (NHRC.2015.0013). RESULTS: In univariate regression models, age, body composition, physical activity, and 5HTTLPR consistently predicted CRF and/or aerobic performance (R2 range 0.07-0.55). Multivariate regression models routinely outperformed the univariate models, explaining 36-62% of variance. CONCLUSION: This study signifies a shift toward inclusive explanatory models of CRF and aerobic performance, accounting for combined roles of genetic, physiologic, and behavioral influences. Although we were able to quantify combined effects, we were unable to evaluate interaction effects (e.g., gene-gene, gene-behavior) due to limited statistical power. Other limitations are that this specialized military population may not readily generalize to broader populations, and the current sample was all male. Considering these limitations, we aim to replicate this study in various populations, both male and female. Despite its limitations, this study reflects a shift toward more comprehensive predictive models of CRF, explaining the unique and shared contributions of genetic predisposition, physiology, and behavior. These findings have implications for assessment, selection, and training of specialized military members, and may also impact mission success and survivability. Future studies are needed to better characterize additive, interactive, and mediated effects.

Psychological Strategies During Military Training Are Linked to Resilience in US Navy Explosive Ordnance Disposal Operators.

PURPOSE: We describe the psychological strategies (PS) used by a specialized military population, US Navy explosive ordnance disposal (EOD), during training and military operations. We also aim to establish the relationship between PS and resilience. METHODS: The Test of Performance Strategies was adapted to the military environment and subsequently was administered to 58 EOD Operators in conjunction with the 10-item Connor- Davidson Resilience Scale. Differences between high- and low-resilience Operators for PS were evaluated with discriminant models. RESULTS: The PS of EOD Operators were comparable to those of Olympic athletes described in our prior study. The most frequently used strategies during training and military operations were goal setting and emotional control. Discriminant analysis indicated an overall difference between high- and low-resilience Operators with respect to the six training subscales (ρ < .05), with goal setting, emotional control, and attentional control contributing most to the discriminant function. CONCLUSION: EOD Operators' use of PS was comparable to that of elite athletes. We provide evidence that more-resilient EOD Operators differ from their less resilient counterparts in the strategies they use. These findings have implications for mental preparation strategies used during military training and operations.

Functional Characterization of Abicipar-Pegol, an Anti-VEGF DARPin Therapeutic That Potently Inhibits Angiogenesis and Vascular Permeability.

Purpose: DARPin molecules are a novel class of small proteins that contain engineered ankyrin repeat domain(s) and bind to target proteins with high specificity and affinity. Abicipar-pegol (abicipar), a DARPin molecule targeting vascular endothelial growth factor-A (VEGF-A), is currently under evaluation in patients with age-related macular degeneration. The pharmacodynamic properties of abicipar were characterized using in vivo and in vitro assays. Methods: The binding affinity of abicipar was assessed using a kinetic exclusion assay (KinExA). In vitro assays evaluated abicipar effects on VEGF-A165-induced calcium mobilization and tube formation in human umbilical vein endothelial cells. Abicipar was tested in vivo in a mouse model of corneal neovascularization and a rabbit model of chronic retinal neovascularization. The efficacies of abicipar and ranibizumab were compared in a rabbit model of VEGF-A165-induced retinal vasculopathy. Results: Abicipar has a high affinity for the soluble isoforms of VEGF-A; binding affinities for human VEGF-A165 are approximately 100-fold greater than those of ranibizumab and bevacizumab and are similar for rat VEGF-A164 but approximately 20-fold lower for rabbit VEGF-A165. Abicipar was effective in cell-based and in vivo models of angiogenesis and vascular leak, blocking neovascularization in a mouse model of corneal neovascularization and vascular permeability in a rabbit model of chronic neovascularization. In a rabbit model of VEGF-A165-induced vasculopathy, the duration of effect of abicipar was longer than ranibizumab when the two compounds were administered at molar-equivalent doses. Conclusions: These data support the testing of abicipar as a treatment for retinal diseases characterized by neovascularization and vascular leak.

Morning Cortisol Is Associated With Stress and Sleep in Elite Military Men: A Brief Report.

INTRODUCTION: Accumulating evidence suggests that trends in salivary cortisol after awakening may be reliable biological predictors of morbidity and mortality. In a sample of elite military men, our lab recently established summary parameters of morning cortisol as well as their stability across 2 d of repeated sampling. MATERIALS AND METHODS: In this follow-on study, we evaluated summary parameters and their relationships to theoretically relevant demographic (i.e., age, body mass index) and biobehavioral correlates (i.e., blood pressure [BP], sleep parameters, fatigue, and perceived stress). Fifty-eight male active duty U.S. Navy SEALs self-collected salivary samples on 2 consecutive, midweek workdays upon waking (WAKE), WAKE+30 min, WAKE+60 min, 4 p.m., and 9 p.m. in a nondeployed, free-living setting. Resting BP was measured manually, and sleep-wake periods were objectively derived using actigraphy. Daily fatigue and perceived stress were measured by self-report. Summary parameters of morning cortisol magnitude (i.e., peak value [Peak], area under the curve in terms of ground [AUCG], and average of morning samples [AVE]) were assessed with respect to each demographic and biobehavioral item via correlational analyses. A subgroup of 29 participants was selected for compliance with salivary sampling in the morning across 2 d. RESULTS: Perceived stress was positively associated with Peak (r[27] = 0.437, p < 0.05), AUCG (r[25] = 0.500, p < 0.01), and AVE (r[25] = 0.506, p < 0.01). Total sleep time was also positively associated with Peak (r[26] = 0.378, p < 0.05). There were borderline associations between some summary parameters and diastolic BP, percent sleep, and wake after sleep onset. Age, systolic BP, body mass index, time in bed, sleep efficiency, and fatigue did not associate with morning cortisol. CONCLUSIONS: Preliminary evidence of morning cortisol summary parameters as biobehavioral indicators was established, and these parameters appeared to associate with stress and sleep in elite military men.

The "yin and yang" of the adrenal and gonadal systems in elite military men.

We recently established daily, free-living profiles of the adrenal hormone cortisol, the (primarily adrenal) anabolic precursor dehydroepiandrosterone (DHEA) and the (primarily gonadal) anabolic hormone testosterone in elite military men. A prevailing view is that adrenal and gonadal systems reciprocally modulate each other; however, recent paradigm shifts prompted the characterization of these systems as parallel, cooperative processes (i.e. the "positive coupling" hypothesis). In this study, we tested the positive coupling hypothesis in 57 elite military men by evaluating associations between adrenal and gonadal biomarkers across the day. Salivary DHEA was moderately and positively coupled with salivary cortisol, as was salivary testosterone. Anabolic processes (i.e. salivary DHEA and testosterone) were also positively and reliably coupled across the day. In multivariate models, salivary DHEA and cortisol combined to account for substantial variance in salivary testosterone concentrations across the day, but this was driven almost exclusively by DHEA. This may reflect choreographed adrenal release of DHEA with testicular and/or adrenal release of testosterone, systemic conversion of DHEA to testosterone, or both. DHEA and testosterone modestly and less robustly predicted cortisol concentrations; this was confined to the morning, and testosterone was the primary predictor. Altogether, top-down co-activation of adrenal and gonadal hormone secretion may complement bottom-up counter-regulatory functions to foster anabolic balance and neuronal survival; hence, the "yin and yang" of adrenal and gonadal systems. This may be an adaptive process that is amplified by stress, competition, and/or dominance hierarchy.

Anabolic hormone profiles in elite military men: Robust associations with age, stress, and fatigue.

We recently established stable daily profiles of the anabolic hormones dehydroepiandrosterone (DHEA) and testosterone in 57 elite military men. In this follow-on study, we explored associations of salivary anabolic hormone profiles with demographic (i.e., age, body mass index [BMI]) and biobehavioral health indices (i.e., blood pressure, sleep, perceived stress, fatigue) via correlational models. Next, nuanced patterns were constructed using quartile splits followed by one-way analysis of variance and post hoc subgroup comparisons. Both DHEA (r range: -0.33 to -0.49) and testosterone (r range: -0.19 to -0.41) were inversely associated with age. Quartile comparisons revealed that age-related declines in DHEA were linear, curvilinear, or sigmoidal, depending on the summary parameter of interest. Anabolic hormone profiles did not associate with BMI, blood pressure, or sleep efficiency. Robust linear associations were observed between testosterone and perceived stress (r range: -0.29 to -0.36); concentration-dependent patterns were less discernible. Lower DHEA (r range: -0.22 to -0.30) and testosterone (r range: -0.22 to -0.36) concentrations associated with higher fatigue. Subsequent quartile comparisons suggested a concentration-dependent threshold with respect to evening testosterone. Specifically, those individuals within the lowest quartile (≤68.4pg/mL) endorsed the highest fatigue of the four groups (p=0.01), while the remaining three groups did not differ from each other. This study not only showed that anabolic hormone profiles have distinctive age trajectories, but are also valuable predictors of stress and fatigue in elite military men. This highlights the importance of routine monitoring of anabolic hormone profiles to sustain and optimize health and readiness in chronically stressed populations.

A genetic risk factor for major depression and suicidal ideation is mitigated by physical activity.

We evaluated associations of five candidate polymorphisms (Bcl1 [rs41423247], -2C/G [rs2070951], COMT [rs737865], Val66Met [rs6265], and 5HTTLPR [biallelic and triallelic [5HTTLPR/rs25531]) with probable MDD and suicidal ideation (SI), the effects of physical activity on these endpoints, and whether physical activity attenuates genetic risk in military members (N=736). C carriers who were also less physically active were 3.3 times as likely to meet criteria for probable MDD and 9.6 times as likely to endorse SI as compared to physically active GG carriers. An adequate dose of physical activity diminishes risk of MDD and SI imposed by a genetic predisposition.

Cortisol Awakening Response in Elite Military Men: Summary Parameters, Stability Measurement, and Effect of Compliance.

The cortisol awakening response (CAR) holds promise as a clinically important marker of health status. However, CAR research is routinely challenged by its innate complexity, sensitivity to confounds, and methodological inconsistencies. In this unprecedented characterization of CAR in elite military men (N = 58), we established summary parameters, evaluated sampling stability across two consecutive days, and explored the effect of subject compliance. Average salivary cortisol concentrations increased nearly 60% within 30 minutes of waking, followed by a swift recovery to waking values at 60 minutes. Approximately one in six were classified as negative responders (i.e., <0% change from waking to 30-minute postawakening). Three summary parameters of magnitude, as well as three summary parameters of pattern, were computed. Consistent with our hypothesis, summary parameters of magnitude displayed superior stability compared with summary parameters of pattern in the total sample. As expected, compliance with target sampling times was relatively good; average deviations of self-reported morning sampling times in relation to actigraph-derived wake times across both days were within ±5 minutes, and nearly two-thirds of the sample was classified as CAR compliant across both days. Although compliance had equivocal effects on some measures of magnitude, it substantially improved the stability of summary parameters of pattern. The first of its kind, this study established the foundation for a program of CAR research in a profoundly resilient yet chronically stressed population. Building from this, our forthcoming research will evaluate demographic, biobehavioral, and clinical determinants of CAR in this unique population.

Anabolic hormone profiles in elite military men.

We recently characterized the awakening responses and daily profiles of the catabolic stress hormone cortisol in elite military men. Anabolic hormones follow a similar daily pattern and may counteract the catabolic effects of cortisol. This companion report is the first to characterize daily profiles of anabolic hormones dehydroepiandrosterone (DHEA) and testosterone in this population. Overall, the men in this study displayed anabolic hormone profiles comparable to that of healthy, athletic populations. Consistent with the cortisol findings in our prior report, summary parameters of magnitude (hormone output) within the first hour after awakening displayed superior stability versus summary parameters of pattern for both DHEA (r range: 0.77-0.82) and testosterone (r range: 0.62-0.69). Summary parameters of evening function were stable for the two hormones (both p<0.001), while the absolute decrease in testosterone across the day was a stable proxy of diurnal function (p<0.001). Removal of noncompliant subjects did not appreciably affect concentration estimates for either hormone at any time point, nor did it alter the repeatability of any summary parameter. The first of its kind, this report enables accurate estimations of anabolic balance and resultant effects upon health and human performance in this highly resilient yet chronically stressed population.

Genetic and environmental modulation of neurotrophic and anabolic stress response: Counterbalancing forces.

The serotonin transporter genetic variant 5HTTLPR influences activation and feedback control of the hypothalamic-pituitary-adrenal axis, and has been shown to influence the effect of stressful life events on behavioral health. We recently reported that 5HTTLPR modulates cortisol response in healthy military men exposed to intense stress. Less is known of its combined effects with environmental factors in this context, or of its effect on neuroprotective stress responses. In this follow-up study, we examined the unique and combined effects of 5HTTLPR and prior trauma exposure on neuroprotective (salivary nerve growth factor [sNGF]), anabolic (dehydroepiandrosterone sulfate [DHEAS] and testosterone), and catabolic (cortisol) stress responses. Ninety-three healthy, active-duty military men were studied before, during, and 24h after a stressful 12-day survival course. Distinct and interactive effects of 5HTTLPR long allele carriage [L] versus homozygous short allele carriage [SS]) and prior trauma exposure (low versus high) were evaluated, after which a priori group comparisons were performed between hypothesized high resilience (L/low) and low resilience (SS/high) groups. For sNGF, L/low produced the greatest sNGF throughout stress exposure while SS/high demonstrated the smallest; L/high and SS/low bisected these two extremes and were nearly identical to each other (i.e., SS/high < SS/low = L/high < L/low). Thus, 5HTTLPR and prior trauma exposure demonstrated counterbalancing (additive) forces. Similar patterns were found for DHEAS. To our knowledge, this study is the first to report counterbalancing genetic and environmental effects on novel biomarkers related to resilience in humans exposed to real-world stress. These findings have profound implications for health, performance and training in high-stress occupational settings.

Influence of resistance training combined with daily consumption of an egg-based or bagel-based breakfast on risk factors for chronic diseases in healthy untrained individuals.

OBJECTIVE: Egg consumption is often discouraged due to cholesterol content; however, recent studies have not demonstrated a clear adverse influence of eggs on blood lipids. Furthermore, exercise training promotes improved lipids and blood pressure. The purpose of the study was to examine the effect of eating an isoenergetic (400 kcal) egg-based (including two eggs per day) versus bagel-based breakfasts, daily, combined with resistance training three times per week, prior to breakfast, on plasma lipids, glucose, insulin, insulin sensitivity and blood pressure in untrained individuals. METHODS: Twenty-five healthy adult men and women (18-35 years of age) participated in the twelve week study following random assignment to study groups. Lipids and blood pressure were examined at baseline and after 6 and 12 weeks. RESULTS: Plasma triglycerides (TG) decreased significantly in the egg- based breakfast (EBB) group from baseline to six weeks (p = 0.011) and from six to twelve weeks (p = 0.045). A significant (p = 0.033) decrease in insulin sensitivity was observed in the bagel-based breakfast (BBB) group from zero to six weeks. No significant effects on systolic blood pressure, diastolic blood pressure, total cholesterol, high density lipoprotein- cholesterol or low density lipoprotein cholesterol were detected. CONCLUSION: Overall, daily breakfasts including two eggs for twelve weeks did not adversely affect lipids during a resistance training program and promoted improvements in plasma TG.

Effects of dark chocolate on azoxymethane-induced colonic aberrant crypt foci.

Epidemiologic evidence supports that diets rich in polyphenols promote health and may delay the onset of colon cancer. Cocoa and chocolate products have some of the highest polyphenolic concentrations compared to other polyphenolic food sources. This study tested the hypothesis that a diet including dark chocolate can protect against colon cancer by inhibiting aberrant crypt foci (ACF) formation, downregulating gene expression of inflammatory mediators, and favorably altering cell kinetics. We also investigated whether bloomed dark chocolate retains the antioxidant capacity and protects against colon cancer. Forty-eight rats received either a diet containing control (no chocolate), regular dark chocolate, or bloomed dark chocolate and were injected subcutaneously with saline or azoxymethane. Relative to control, both regular and bloomed dark chocolate diets lowered the total number of ACF (P = 0.022). Chocolate diet-fed animals downregulated transcription levels of COX-2 (P = 0.035) and RelA (P = 0.045). Both chocolate diets lowered the proliferation index (P = 0.001). These results suggest that a diet including dark chocolate can reduce cell proliferation and some gene expression involving inflammation, which may explain the lower number of early preneoplastic lesions. These results provide new insight on polyphenol-rich chocolate foods and colon cancer prevention.

Identification of a novel selective H1-antihistamine with optimized pharmacokinetic properties for clinical evaluation in the treatment of insomnia.

Analogs of the known H(1)-antihistamine R-dimethindene with suitable selectivity for key GPCRs, P450 enzymes and hERG channel were assessed for metabolism profile and in vivo properties. Several analogs were determined to exhibit diverse metabolism. One of these compounds, 10a, showed equivalent efficacy in a rat EEG/EMG model to a previously identified clinical candidate and a potentially superior pharmacokinetic profile as determined from a human microdose study.