COVID-19 Vaccination Attitudes and Intentions Among U.S. Soldiers: Results from the U.S. Army Behavioral Health Advisory Team (BHAT).

INTRODUCTION: The objective of this study is to characterize the associations between demographic, attitudinal, and leadership factors with COVID-19 vaccination rates, vaccination intentions among those not vaccinated, and attitudes about vaccination safety, effectiveness, and importance. METHODS: A serial cross-sectional anonymous online survey was administered to soldiers at two large U.S. Army Divisions located in the Southwestern region of the U.S. at two different time points (April-May 2021 [Time 1; T1] N = 24,629; July-August 2021 [Time 2; T2] N = 21,116). Binary logistic regressions were used to assess demographic and attitudinal predictors of vaccination receipt and vaccination intent. Multinomial logistic regressions were used to assess demographic and leadership predictors of endorsement of three vaccination attitudes concerning effectiveness, safety, and importance. RESULTS: Approximately 43% of soldiers reported that they received a COVID-19 vaccine at T1, increasing to 67% at T2. Soldiers who agreed with three separate statements on vaccination effectiveness, safety, or importance were more likely to indicate that they intended to get the vaccination at both time points. Soldiers who reported that their immediate supervisor encouraged soldiers to get a COVID-19 vaccine were more likely to indicate that the vaccination was effective, safe, or important at both time points. DISCUSSION: Negative attitudes about COVID-19 vaccines were prevalent and correlated with less intention to get a vaccination. However, prioritizing leadership engagement around the importance of vaccinations may be a simple but widely effective intervention point to increase future vaccine uptake following the development of novel vaccines to future COVID-19 variants.

The role of premeditation in suicide: Identifying factors associated with increased planning among suicide decedents.

INTRODUCTION: Suicide premeditation is a critical factor to consider when assessing suicide risk. Understanding which individuals are more or less likely to plan their suicidal behavior can shed light on how suicidal thoughts turn into actions. METHOD: The present study used psychological autopsy data to identify factors associated with level of premeditation among 131 adults who died by suicide. RESULTS: Logistic regression analyses indicated that suicide decedents with higher premeditation scores had higher odds of being diagnosed with a depressive disorder and choosing a violent suicide method, specifically a firearm. Individuals with lower premeditation scores had higher odds of being diagnosed with a polysubstance use disorder. CONCLUSION: Suicide decedents exhibiting greater premeditation before their deaths were different in several ways from suicide decedents exhibiting less premeditation. A better understanding of suicide premeditation can ultimately aid in the development of improved risk assessments and targeted safety interventions for those struggling with suicidal thoughts.

Can I count on you? Social support, depression and suicide risk.

OBJECTIVES: Interpersonal factors play an important role in the etiology and treatment of depression. Social support derives from compassionate words and helpful actions provided by family, friends or a significant other. The present study was designed to examine various sources of social support as they relate to the severity of depressive symptoms, hopelessness and suicide risk in adult psychiatric outpatients. METHOD: Participants were recruited through mental health clinics at a veteran's affairs medical centre. A total of 96 depressed patients were assessed using a diagnostic interview and self-report measures of depression severity, hopelessness and social support. Among these depressed adults, 45.8% had attempted suicide at least once. Social support variables were compared between suicide attempters and non-attempters to better understand the relationship between social support and suicidal behaviour. RESULTS: Depression severity and hopelessness were both significantly associated with lower levels of social support in multiple areas. Individuals with a history of suicide attempt reported lower levels of available support as compared to those who have never attempted suicide. CONCLUSION: Deficient social relationships increase the risk of suicide in depressed patients, exceeding the impact of depression alone on suicide risk. The lack of social support may play a vital role in feelings of hopelessness and isolation that contribute to a suicidal crisis. Psychosocial treatment should be considered to reduce the risk of suicide and severity of depression by strengthening social support and bolstering interpersonal relationships.

Impact of the COVID-19 pandemic on army families: Household finances, familial experiences, and soldiers' behavioral health.

The Coronavirus Disease 2019 (COVID-19) pandemic has significantly impacted employment and finances, childcare, and behavioral health across the United States. The Behavioral Health Advisory Team assessed the pandemic's impact on the behavioral health of U.S. Army soldiers and their families. Over 20,000 soldiers at three large installation groups headquartered in the northwestern continental U.S., Republic of Korea, and Germany participated in the cross-sectional survey. Multivariable logistic regression models indicated that key demographics (gender, rank), severity of household financial impact, changes in work situation due to childcare issues, and family members' difficulty coping (both self and spouse/partner and/or child) were independently and consistently associated with greater odds of screening positive for probable clinical depression and generalized anxiety, respectively. These findings highlight how Army families were impacted similarly by the pandemic as their civilian counterparts. Army leadership may action these findings with targeted support for soldiers and their families to ensure they are utilizing supportive services available to them, and that military services continually evolve to meet soldier and family needs during times of crisis and beyond.

Randomized Controlled Trial of a Dichoptic Digital Therapeutic for Amblyopia.

PURPOSE: Digital therapeutics are a new class of interventions that are software driven and are intended to treat various conditions. We developed and evaluated a dichoptic digital therapeutic for amblyopia, a neurodevelopmental disorder for which current treatments may be limited by poor adherence and residual vision deficits. DESIGN: Randomized controlled trial. PARTICIPANTS: One hundred five children 4 to 7 years of age with amblyopia were enrolled at 21 academic and community sites in the United States. Participants were randomized 1:1 to the treatment or comparison group, stratified by site. METHODS: We conducted a phase 3 randomized controlled trial to evaluate the safety and efficacy of a dichoptic digital therapeutic for amblyopia. Participants in the treatment group used the therapeutic at home for 1 hour per day, 6 days per week and wore glasses full-time. Participants in the comparison group continued wearing glasses full-time alone. MAIN OUTCOME MEASURES: The primary efficacy outcome was change in amblyopic eye visual acuity (VA) from baseline at 12 weeks, and VA was measured by masked examiners. Safety was evaluated using the frequency and severity of study-related adverse events. Primary analyses were conducted using the intention-to-treat population. RESULTS: Between January 16, 2019, and January 15, 2020, 105 participants were enrolled; 51 were randomized to the treatment group and 54 were randomized to the comparison group. At 12 weeks, amblyopic eye VA improved by 1.8 lines (95% confidence interval [CI], 1.4-2.3 lines; n = 45) in the treatment group and by 0.8 lines (95% CI, 0.4-1.3 lines; n = 45) in the comparison group. At the planned interim analysis (adjusted α = 0.0193), the difference between groups was significant (1.0 lines; P = 0.0011; 96.14% CI, 0.33-1.63 lines) and the study was stopped early for success, according to the protocol. No serious adverse events were reported. CONCLUSIONS: Our findings support the value of the therapeutic in clinical practice as an effective treatment. Future studies should evaluate the therapeutic compared with other methods and in additional patient populations.

US soldiers and the role of leadership: COVID-19, mental health, and adherence to public health guidelines.

BACKGROUND: Previous studies have documented the impact of domain-specific leadership behaviors on targeted health outcomes in employees. The goal of the present study was to determine the association between specific leadership behaviors addressing COVID-19 and US soldiers' mental health and adherence to COVID-19 public health guidelines. METHODS: An electronic, anonymous survey was administered to US Army soldiers across three major commands (N = 7,829) from December 2020 to January 2021. The primary predictor of interest was soldiers' ratings of their immediate supervisors' behaviors related to COVID-19. The outcomes were soldiers' mental health (i.e., depression and generalized anxiety) and adherence to COVID-19 public health guidelines. Covariates were rank, gender, ratings of immediate supervisors' general leadership, level of COVID-19 concerns, and COVID-19 status (e.g., tested positive, became seriously ill). Logistic regressions were used to model the unique association of COVID-19 leadership behaviors with outcomes after adjusting for covariates. RESULTS: High levels of COVID-19 leadership behaviors were associated with lesser likelihood of soldiers' screening positive for depression (AOR = 0.46; 95% CI [0.39, 0.54]) and anxiety (AOR = 0.54; 95% CI [0.45, 0.64]), and greater likelihood of frequent adherence to preventive health guidelines (AORs = 1.58; 95% CI [1.39, 1.80] to 2.50; 95% CI [2.01, 3.11]). CONCLUSION: Higher levels of COVID-19 leadership behaviors may support soldiers' mental health and encourage their adherence to COVID-19 public health guidelines. Given the link between these leader behaviors and soldier adaptation to the pandemic over and above general leadership, training for supervisors should focus on targeting specific health-promoting behaviors. Results can inform leader training for the military and other high-risk occupations.

The path not taken: Distinguishing individuals who die by suicide from those who die by natural causes despite a shared history of suicide attempt.

OBJECTIVES: This study aimed to identify variables that distinguish suicide risk among individuals with previous suicide attempts. METHOD: Using psychological autopsy procedures, we evaluated 86 decedents who had at least one lifetime suicide attempt before eventual death by suicide (n = 65) or natural causes (n = 21). RESULTS: The Suicide Death group was more likely to be male, to have alcohol in the toxicology report at time of death, and to have a depression diagnosis, while the Natural Cause Death group was more likely to have personality disorder traits, a polysubstance use disorder, higher reported health stress, and an antidepressant in the toxicology report at time of death. Hopelessness and ambivalence were found to distinguish between groups during the 6 months before death. CONCLUSIONS: These findings suggest important differences between individuals with a shared history of a suicide attempt who die by suicide versus natural causes.

Combining epigenetic and immune therapy to overcome cancer resistance.

Cancer undergoes "immune editing" to evade destruction by cells of the host immune system including natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). Current adoptive cellular immune therapies include CAR T cells and dendritic cell vaccines, strategies that have yet to show success for a wide range of tumors. Cancer resistance to immune therapy is driven by extrinsic factors and tumor cell intrinsic factors that contribute to immune evasion. These extrinsic factors include immunosuppressive cell populations such as regulatory T cells (Tregs), tumor-associated macrophages (TAMS), and myeloid-derived suppressor cells (MDSCs). These cells produce and secrete immunosuppressive factors and express inhibitory ligands that interact with receptors on T cells including PD-1 and CTLA-4. Immune checkpoint blockade (ICB) therapies such as anti-PD-1 and anti-CTLA-4 have shown success by increasing immune activation to eradicate cancer, though both primary and acquired resistance remain a problem. Tumor cell intrinsic factors driving primary and acquired resistance to these immune therapies include genetic and epigenetic mechanisms. Epigenetic therapies for cancer including DNA methyltransferase inhibitors (DNMTi), histone deacetylase inhibitors (HDACi), and histone methyltransferase inhibitors (HMTi) can stimulate anti-tumor immunity in both tumor cells and host immune cells. Here we discuss in detail tumor mechanisms of immune evasion and how common epigenetic therapies for cancer may be used to reverse immune evasion. Lastly, we summarize current clinical trials combining epigenetic therapies with immune therapies to reverse cancer immune resistance mechanisms.

Frailty Worsens Antidepressant Treatment Outcomes in Late Life Depression.

OBJECTIVE: To investigate the relationship between frailty and treatment response to antidepressant medications in adults with late life depression (LLD). METHODS: Data were evaluated from 100 individuals over age 60 years (34 men, 66 women) with a depressive diagnosis, who were assessed for frailty at baseline (characteristics include gait speed, grip strength, activity levels, fatigue, and weight loss) and enrolled in an 8-week trial of antidepressant medication followed by 10 months of open-treatment. RESULTS: Frail individuals (n = 49 with ≥3 deficits in frailty characteristics) did not differ at baseline from the non/intermediate frail (n = 51 with 0-2 deficits) on demographic, medical comorbidity, cognitive, or depression variables. On average, frail individuals experienced 2.82 fewer Hamilton Rating Scale for Depression (HRSD) points of improvement (t = 2.12, df 89, p = 0.037) than the non/intermediate frail over acute treatment, with this difference persisting over 10 months of open-treatment. Weak grip strength and low physical activity levels were each associated with decreased HRSD improvement, and lower response and remission rates over the course of the study. Despite their poorer outcomes, frail individuals received more antidepressant medication trials than the non/intermediate frail. CONCLUSION: Adults with LLD and frailty have an attenuated response to antidepressant medication and a greater degree of disability compared to non/intermediate frail individuals. This disability and attenuated response remain even after receiving a greater number of antidepressant medication trials. Future research must focus on understanding the specific pathophysiology associated with the frail-depressed phenotype to permit the design and implementation of precision medicine interventions for this high-risk population.

Frailty and Its Correlates in Adults With Late Life Depression.

OBJECTIVE: To investigate the rates of frailty and frailty characteristics and examine the clinical and neuropsychological correlates of frailty in adults with late life depression (LLD). METHODS: Data were used from the evaluation of 134 individuals over the age of 60 years (45 men, 89 women) with a depressive diagnosis who enrolled in studies for the treatment of their depression. Depression, neuropsychological functioning, white matter hyperintensity (WMH) burden via magnetic resonance imaging, and characteristics of frailty were assessed. RESULTS: Fried frailty burden (≥3 characteristics) was present in 25% of the sample, with this rate increasing to 45.5% when using clinically meaningful cut-scores for gait speed (<1 m/s) and physical activity levels (<1000 kcal/week). Moreover, 62% of the sample exhibited gait slowing (<1 m/s) or weakness (grip strength), with 29% demonstrating both. Greater frailty burden was associated with greater Hamilton Depression Rating Scale severity in covariate adjusted linear regression models (t127 = 2.41, p = 0.02). Greater frailty burden was not associated with neuropsychological dysfunction, nor was it associated with greater WMH burden. CONCLUSION: Findings from this study show that frailty, specifically physical frailty deficits in mobility and strength, is highly comorbid in adults with LLD, associated with greater depressive symptom severity, and does not appear to be associated with the vascular depression subtype of LLD. Future research should investigate the relationship between frailty and antidepressant treatment response as well as test whether there are age-related biological processes that result in the manifestation of the frail-depressed subtype of LLD.

Declining Skeletal Muscle Mitochondrial Function Associated With Increased Risk of Depression in Later Life.

OBJECTIVE: Late-life depression (LLD) is a chronic and heterogeneous disorder. Recent studies have implicated non-normative age-related processes in its pathogenesis. This investigation examined both cross-sectional and longitudinal associations between skeletal muscle mitochondrial function and LLD. METHODS: Data from 603 men and women from the Baltimore Longitudinal Study on Aging were analyzed, of whom 167 provided data from a follow-up visit. Muscle bioenergetics was measured by postexercise recovery rate of phosphocreatine (PCr) using phosphorus magnetic resonance spectroscopy. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) Scale. RESULTS: There was no cross-sectional association between baseline depression status and either the PCr recovery rate constant (kPCr; t = -0.553, df = 542; p = 0.580) or mitochondrial capacity largely independent of exercise intensity (adenosine triphosphate maximum [ATPmax]; t = 0.804, df = 553; p = 0.422). Covariate-adjusted Firth logistic regression models however showed that greater decreases in skeletal muscle mitochondrial function from baseline to follow-up were associated with higher odds of clinically significant depressive symptoms (CES-D ≥16) at follow-up (ΔATPmax: odds ratio = 2.63, χ2 = 5.62, df =1; p = 0.018; ΔkPCr: odds ratio = 2.32, χ2 = 5.79, df =1; p = 0.016). CONCLUSION: Findings suggest that declining skeletal muscle mitochondrial function in older adults is associated with clinically significant depressive symptoms at follow-up, thereby providing preliminary support for the hypothesis that mitochondrial dysfunction may be a potential key pathophysiological mechanism in adults with LLD.

[Performance of medical schools in Mexico: results from the Examen Nacional para Aspirantes a Residencias Médicas]. / Desempeño de las escuelas de medicina en México: resultados del Examen Nacional para Aspirantes a Residencias Médicas.

OBJECTIVE: To assess the performance of medical schools (FEM) by analyzing the results of their applicants in the Examen Nacional para Aspirantes a Residencias Médicas (ENARM). MATERIALS AND METHODS: Five performance criteria, two official and three created on purpose, were calculated from the ENARM-2016 and -2017 official databases to assess FEM performance. RESULTS: In 2016 and 2017, applicants registered from 112 and 115 FEM, respectively. Depending on the performance criteria, the FEM in the first place obtained 5 to 20 points more than the one placed second, and 23 to 98 points more than the FEM in the last place. Approximately 25% applicants were classified as "knowledge-deficient," and about 80% of these originated from less than one third of the FEM. CONCLUSIONS: The ENARM results provide information on the performance of the FEM. Approximately one of every four applicants obtained scores lower than the approval threshold of any specialty.

OBJECTIVE: Evaluar el desempeño de las facultades y escuelas de medicina (FEM) utilizando como subrogado los resultados del Examen Nacional para Aspirantes a Residencias Médicas (ENARM). MATERIALS AND METHODS: Se analizaron las bases de datos oficiales del ENARM 2016 y 2017, empleando cinco criterios de desempeño (CD) por cada FEM: dos oficiales y tres creados exprofeso. RESULTS: En 2016 y 2017 se registraron sustentantes de 112 y 115 FEM, respectivamente. Dependiendo del CD, la FEM que quedó clasificada en el primer lugar obtuvo entre 5 y 20 puntos más que la del segundo lugar, y entre 23 y 98 puntos más que la FEM ubicada en el último lugar. Aproximadamente 25% de los sustentantes fueron calificados como "deficientes en conocimientos" y aproximadamente 80% de éstos provenían de menos de un tercio de las FEM. CONCLUSIONS: El ENARM arroja información sobre el desempeño de las FEM. Aproximadamente uno de cada cuatro sustentantes obtuvo puntajes menores al aprobatorio en cualquier especialidad.

Marching on the Road to Quality: Army Public Health Experience Adopting NACCHO's Roadmap to a Culture of Quality Framework.

The US Army Public Health Center (APHC) adopted the National Association of County and City Health Officials' (NACCHO) Roadmap to a Culture of Quality (CoQ) Improvement framework to define its current culture and adapted the NACCHO's Organizational CoQ Self-Assessment Tool for applicability to a federal agency and workforce. More than 500 Civilian and Military personnel completed the self-assessment in October 2017. The results indicated that the APHC was categorized in the third of six total phases of the NACCHO's Roadmap to a CoQ (Phase 3: Informal or Ad Hoc QI Activities), which generated 13 transitional strategies to advance the APHC toward a CoQ. The APHC demonstrated that a federal public health organization can use and apply results from currently available self-assessment tools and frameworks related to a CoQ. By doing so, the APHC is optimizing its ability to ensure America's Soldiers and the Army Family receive essential and effective public health services.

Are there sensitive periods when child maltreatment substantially elevates suicide risk? Results from a nationally representative sample of adolescents.

BACKGROUND: Although child maltreatment is a well documented risk factor for suicidal behavior, little is known about whether the timing of child maltreatment differentially associates with risk of suicidal ideation, suicide plans, or suicide attempts. The goal of this study was to examine whether a first exposure to physical or sexual abuse during specific developmental periods significantly elevated risk for suicidal behavior in adolescents. METHODS: Data came from the National Comorbidity Survey Adolescent Supplement, a population-based sample of US adolescents aged 13-18 years old (n = 9,272). Using discrete time survival analysis, we assessed the association between timing of first abuse (early childhood: ages 0-5; middle childhood: ages 6-10; adolescence: ages 11-18) and suicidal ideation, plans, and attempts. RESULTS: Exposure to either physical or sexual abuse increased the odds of reporting suicidal ideation (odds ratio [OR] = 5.06 and OR = 3.56, respectively), plans (OR = 3.63 and OR = 3.58, respectively), and attempts (OR = 5.80 and OR = 4.21, respectively), even after controlling for sociodemographic covariates and psychiatric disorders. However, the timing of physical and sexual abuse exposure was unassociated with suicidal behavior (all p values >.05). CONCLUSIONS: Exposure to child maltreatment is strongly associated with risk for adolescent suicidal behaviors, though this association did not vary based on the developmental timing of first exposure. These findings suggest that prevention efforts should be implemented throughout early development and target all children, regardless of when they were first exposed.

Ubiquitin interacts with the Tollip C2 and CUE domains and inhibits binding of Tollip to phosphoinositides.

A large number of cellular signaling processes are directed through internalization, via endocytosis, of polyubiquitinated cargo proteins. Tollip is an adaptor protein that facilitates endosomal cargo sorting for lysosomal degradation. Tollip preferentially binds phosphatidylinositol 3-phosphate (PtdIns(3)P) via its C2 domain, an association that may be required for endosomal membrane targeting. Here, we show that Tollip binds ubiquitin through its C2 and CUE domains and that its association with the C2 domain inhibits PtdIns(3)P binding. NMR analysis demonstrates that the C2 and CUE domains bind to overlapping sites on ubiquitin, suggesting that two ubiquitin molecules associate with Tollip simultaneously. Hydrodynamic studies reveal that ubiquitin forms heterodimers with the CUE domain, indicating that the association disrupts the dimeric state of the CUE domain. We propose that, in the absence of polyubiquitinated cargo, the dual binding of ubiquitin partitions Tollip into membrane-bound and membrane-free states, a function that contributes to the engagement of Tollip in both membrane trafficking and cytosolic pathways.

COVID-19 Concerns, Information Needs, and Adverse Mental Health Outcomes among U.S. Soldiers.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic disrupted U.S. Military operations and potentially compounded the risk for adverse mental health outcomes by layering unique occupational stress on top of general restrictions, fears, and concerns. The objective of the current study was to characterize the prevalence of COVID-19 concerns and information needs, demographic disparities in these outcomes, and the degree to which COVID-19 concerns and information needs were associated with heightened risk for adverse mental health outcomes among U.S. Army soldiers. MATERIALS AND METHODS: Command-directed anonymous surveys were administered electronically to U.S. soldiers assigned to one of three regional commands in the Northwest United States, Europe, and Asia-Pacific Region. Surveys were administered in May to June 2020 to complete (time 1: n = 21,294) and again in December 2020 to January 2021 (time 2: n = 10,861). Only active duty or active reservists/national guard were eligible to participate. Members from other branches of service were also not eligible. RESULTS: Highly prevalent COVID-19 concerns included the inability to spend time with friends/family, social activities, and changing rules, regulations, and guidance related to COVID-19. Some information needs were endorsed by one quarter or more soldiers at both time points, including stress management/coping, travel, how to protect oneself, and maintaining mission readiness. COVID-19 concerns and information needs were most prevalent among non-White soldiers. Concerns and information needs did not decline overall between the assessments. Finally, COVID-19 concerns were associated with greater risk of multiple adverse mental health outcomes at both time points. CONCLUSIONS: COVID-19 concerns and information needs were prevalent and showed little evidence of decrement over the course of the first 6 months of the pandemic. COVID-19 concerns were consistently associated with adverse mental health outcomes. These data highlight two targets and potential demographic subgroups such that local leadership and Army medicine and public health enterprises can be better prepared to monitor and address to maintain force health and readiness in the face of possible future biomedical threats.

Mental Health Outcomes Among American Indian and Alaska Native U.S. Army Soldiers: A Serial Cross-Sectional Analysis.

INTRODUCTION: American Indian and Alaska Native (AI/AN) individuals in the USA experience higher rates of mental illness and preventable death than the general population. Published research demonstrates that AI/AN veterans experience similar disparities to other minorities compared to non-minority veterans; few studies, however, have assessed mental health outcomes in AI/AN active duty military members. The objective of this study was to determine differences in depression, anxiety, hazardous alcohol consumption, and suicidal ideation among AI/AN soldiers compared to soldiers of other races during the Coronavirus Disease 2019 (COVID-19) pandemic. MATERIALS AND METHODS: We conducted repeated cross-sectional electronic surveys to assess the mental health of active duty and activated reserve U.S. Army soldiers within three commands in the Northwestern Continental United States , Republic of Korea, and Germany during May-June 2020 (T1) and December 2020-January 2021 (T2). The primary exposure of interest in the present analysis was race and ethnicity, and the primary outcomes were probable depression with functional impairment (subsequently "depression"), probable anxiety with functional impairment (subsequently "anxiety"), hazardous alcohol use, and suicidal ideation. Multivariable logistic regression models were used to determine the association between demographics and COVID-19 concerns on mental health outcomes for each time point. RESULTS: A total of 21,293 participants responded to the survey at T1 (participation rate = 28.0%), and 10,861 participants responded to the survey at T2 (participation rate = 14.7%). In the multivariable model, AI/AN participants had 1.36 higher adjusted odds of suicidal ideation (95% CI: 1.02-1.82) at T1 and 1.50 greater adjusted odds of suicidal ideation at T2 (95% CI: 1.00-2.24), when compared to non-Hispanic White participants. During T1, there was no significant difference detected between AI/AN and non-Hispanic White participants for anxiety (adjusted odds ratio: 1.21; 95% CI: 0.91-1.60) (Table IV). However, AI/AN participants had 1.82 greater adjusted odds of anxiety when compared to non-Hispanic White participants at T2 (adjusted odds ratio: 1.82; 95% CI: 1.29-2.57). There were no significant differences detected between AI/AN participants and non-Hispanic White participants in multivariable models for either depression or hazardous alcohol use at both time points. CONCLUSIONS: Although we hypothesized that all adverse mental health outcomes would be higher for AI/AN service members at both time points, there were no significant differences at each of the time points analyzed for most of the outcomes analyzed. However, differences in suicidal ideation were found at both time points. Analyses and proposed interventions should account for diversity and heterogeneity of AI/AN populations.

Age Dependent Changes in Corneal Epithelial Cell Signaling.

The cornea is exposed daily to a number of mechanical stresses including shear stress from tear film and blinking. Over time, these stressors can lead to changes in the extracellular matrix that alter corneal stiffness, cell-substrate structures, and the integrity of cell-cell junctions. We hypothesized that changes in tissue stiffness of the cornea with age may alter calcium signaling between cells after injury, and the downstream effects of this signaling on cellular motility and wound healing. Nanoindentation studies revealed that there were significant differences in the stiffness of the corneal epithelium and stroma between corneas of 9- and 27-week mice. These changes corresponded to differences in the timeline of wound healing and in cell signaling. Corneas from 9-week mice were fully healed within 24 h. However, the wounds on corneas from 27-week mice remained incompletely healed. Furthermore, in the 27-week cohort there was no detectable calcium signaling at the wound in either apical or basal corneal epithelial cells. This is in contrast to the young cohort, where there was elevated basal cell activity relative to background levels. Cell culture experiments were performed to assess the roles of P2Y2, P2X7, and pannexin-1 in cellular motility during wound healing. Inhibition of P2Y2, P2X7, or pannexin-1 all significantly reduce wound closure. However, the inhibitors all have different effects on the trajectories of individual migrating cells. Together, these findings suggest that there are several significant differences in the stiffness and signaling that underlie the decreased wound healing efficacy of the cornea in older mice.

The Role of Program Evaluation in Keeping Army Health "Army Strong": Translating Lessons Learned Into Best Practices.

Service Members and military beneficiaries face complex and ill-structured challenges, including suicide, sexual violence, increasing health care costs, and the evolving coronavirus pandemic. Military and other government practitioners must identify effective programs, policies, and initiatives to preserve the health and ensure the readiness of our Force. Both research and program evaluation are critical to identify interventions best positioned to prevent disease, protect the public's health, and promote health and well-being within our ranks to retain a medically ready force and reduce the global burden of disease. While military and medical leaders are typically well versed in research and understand the role of research in evidence-informed decisions, they may be less aware of program evaluation. Program evaluation is the systematic application of scientific methods to assess the design, implementation, improvement, or outcomes of a program, policy, or initiative. Although program evaluators commonly utilize scientific or research methods to answer evaluation questions, evaluation ultimately differs from research in its intent. Several recently published federal and Department of Defense policies specifically reference program evaluation, emphasizing its importance to the military and government as a whole. The Army is uniquely positioned to conduct medical and public health evaluation activities and there are several Army organizations and entities that routinely perform this work. For example, the United States Army Public Health Center (APHC) is among recognized military experts in public health assessment and program evaluation. Given the breadth of our work, the APHC understands the challenges to conducting evaluation studies in the Army and we have thoughtfully examined the conditions common to successful evaluation studies. In this commentary, we share our lessons learned to assist military colleagues, potential partners, and others in successfully evaluating the programs, policies, and initiatives necessary to keep our Service Members and beneficiaries healthy and ready. There are several challenges to executing evaluation studies in the Army that may be relevant across all Services. These include but are not limited to frequent Army leadership transitions, urgency to report study results, lack of program documentation and adequate planning for evaluation, expectation management to ensure stakeholders are well-informed about the evaluation process, and a disorganized data landscape. These challenges may hinder the successful execution of evaluation studies, or prevent them from being attempted in the first place, depriving Army leaders of quality, actionable information to make evidence-informed decisions. Despite the aforementioned challenges, we have identified a number of best practices to overcome these challenges and conduct successful evaluation studies. These facilitators of successful evaluations can be summarized as: collaboration with engaged stakeholders who understand the value of evaluation, evaluation studies aligned with larger strategic priorities, agile methodology, thoughtful evaluation planning, and effective communication with stakeholders. We wholeheartedly recommend and encourage program evaluation at every opportunity, and we anticipate the call for evaluation and evidence-informed decisions to continually increase. Our hope is that others - to include partners and stakeholders within and external to the military - will be able to leverage and apply this information, especially the identified best practices, in their evaluation efforts to ensure success.

Live-Cell Imaging of Intact Ex Vivo Globes Using a Novel 3D Printed Holder.

Corneal epithelial wound healing is a migratory process initiated by the activation of purinergic receptors expressed on epithelial cells. This activation results in calcium mobilization events that propagate from cell to cell, which are essential for initiating cellular motility into the wound bed, promoting efficient wound healing. The Trinkaus-Randall lab has developed a methodology for imaging the corneal wound healing response in ex vivo murine globes in real time. This approach involves enucleating an intact globe from a mouse that has been euthanized per established protocols and immediately incubating the globe with a calcium indicator dye. A counterstain that stains other features of the cell can be applied at this stage to assist with imaging and show cellular landmarks. The protocol worked well with several different live cell dyes used for counterstaining, including SiR actin to stain actin and deep red plasma membrane stain to stain the cell membrane. To examine the response to a wound, the corneal epithelium is injured using a 25 G needle, and the globes are placed in a 3D printed holder. The dimensions of the 3D printed holder are calibrated to ensure immobilization of the globe throughout the duration of the experiment and can be modified to accommodate eyes of different sizes. Live cell imaging of the wound response is performed continuously at various depths throughout the tissue over time using confocal microscopy. This protocol allows us to generate high-resolution, publication-quality images using a 20x air objective on a confocal microscope. Other objectives can also be used for this protocol. It represents a significant improvement in the quality of live cell imaging in ex vivo murine globes and permits the identification of nerves and epithelium.