Littman, D

The inheritance of gene expression patterns is dependent on epigenetic regulation, but the establishment and maintenance of epigenetic landscapes during T cell differentiation are incompletely understood. Here we show that two stage-specific Cd4 cis-elements, the previously characterized enhancer E4p and a novel enhancer E4m, coordinately promote Cd4 transcription in mature thymic MHC-II-specific T cells, in part through the canonical Wnt pathway. Specifically, E4p licenses E4m to orchestrate DNA demethylation by TET1 and TET3, which in turn poises the Cd4 locus for transcription in peripheral T cells...

OBJECTIVES: Regular vigorous physical activity (PA) and high levels of physical fitness (PF) confer health benefits. Conversely, sedentary time is a risk factor for chronic illness, independent of PA. We evaluated associations between self-reported PA, sedentary time, and objective PF measures in military Service members. DESIGN: Cross-sectional study including 10,105 Air Force Millennium Cohort participants with a valid physical fitness assessment (PFA). METHODS: Linear regression assessed associations between self-report PA, screen time, and usual activity and abdominal circumference (AC) and VO2 max; logistic regression was used for PFA failure...

OBJECTIVES: Posttraumatic stress disorder (PTSD) and unhealthy alcohol use are commonly associated conditions. It is unknown whether specific symptoms of PTSD are associated with subsequent initiation of unhealthy alcohol use. METHODS: Data from the first 3 enrollment panels (n = 151,567) of the longitudinal Millennium Cohort Study of military personnel were analyzed (2001-2012). Complementary log-log models were fit to estimate whether specific PTSD symptoms and symptom clusters were associated with subsequent initiation of 2 domains of unhealthy alcohol use: risky and problem drinking (experience of 1 or more alcohol-related consequences)...

OBJECTIVES: The aim of this study was to determine whether specific individual posttraumatic stress disorder (PTSD) symptoms or symptom clusters predict cigarette smoking initiation. METHODS: Longitudinal data from the Millennium Cohort Study were used to estimate the relative risk for smoking initiation associated with PTSD symptoms among 2 groups: (1) all individuals who initially indicated they were nonsmokers (n = 44,968, main sample) and (2) a subset of the main sample who screened positive for PTSD (n = 1622)...

Myeloid dendritic cells (DCs) have the innate capacity to sense pathogens and orchestrate immune responses. However, DCs do not mount efficient immune responses to HIV-1, primarily due to restriction of virus reverse transcription, which prevents accumulation of viral cDNA and limits its detection through the cGAS-STING pathway. By allowing reverse transcription to proceed, we find that DCs detect HIV-1 in distinct phases, before and after virus integration. Blocking integration suppresses, but does not abolish, activation of the transcription factor IRF3, downstream interferon (IFN) responses, and DC maturation...

INTRODUCTION: The associations between stressful military experiences and tobacco use and alcohol misuse among Service members are well documented. However, little is known about whether stressful military experiences are associated with tobacco use and alcohol misuse among military spouses. METHODS: Using 9872 Service member-spouse dyads enrolled in the Millennium Cohort Family Study, we employed logistic regression to estimate the odds of self-reported cigarette smoking, risky drinking, and problem drinking among spouses by Service member deployment status, communication regarding deployment, and stress associated with military-related experiences, while adjusting for demographic, mental health, military experiences, and Service member military characteristics...

In the first known longitudinal study of the topic, we examined whether experiencing sexual assault or sexual harassment while in the military was associated with increased risk for subsequent unhealthy alcohol use and smoking among U.S. service members in the Millennium Cohort Study (2001-2012). Adjusted complementary log-log models were fit to estimate the relative risk of (a) smoking relapse among former smokers (men: n = 4,610; women: n = 1,453); (b) initiation of unhealthy alcohol use (problem drinking and/or drinking over recommended limits) among those with no known history of unhealthy alcohol use (men: n = 8,459; women: n = 4,816); and (c) relapse among those previously reporting unhealthy alcohol use (men: n = 3,487; women: n = 1,318)...

Purpose: To evaluate the impact of image magnification correction on superficial retinal vessel density (SRVD) and foveal avascular zone area (FAZA) measurements using optical coherence tomography angiography (OCTA). Methods: Participants with healthy retinas were recruited for ocular biometry, refraction, and RTVue XR Avanti OCTA imaging with the 3 × 3-mm protocol. The foveal and parafoveal SRVD and FAZA were quantified with custom software before and after correction for magnification error using the Littman and the modified Bennett formulae...

The adaptive immune system is dependent on functionally distinct lineages of T cell antigen receptor αβ-expressing T cells that differentiate from a common progenitor in the thymus. CD4(+)CD8(+) progenitor thymocytes undergo selection following interaction with MHC class I and class II molecules bearing peptide self-antigens, giving rise to CD8(+) cytotoxic and CD4(+) helper or regulatory T cell lineages, respectively. The strict correspondence of CD4 and CD8 expression with distinct cellular phenotypes has made their genes useful surrogates for investigating molecular mechanisms of lineage commitment...

BACKGROUND: Regular physical activity (PA) is essential for aging well with a disability, preventing the onset or worsening of chronic conditions, functional loss, and maintaining or improving quality of life, yet PA levels are low in those with disabilities, including those with a lower extremity amputation (LEA). OBJECTIVE: To determine methods for promoting PA in this population, our objective was to better understand the barriers and facilitators to PA that persons with LEA face...

This article summarizes outcomes of the behavioral interventions work group for the Veterans Health Administration (VHA) State of the Art Conference (SOTA) for Weight Management. Sixteen VHA and non-VHA subject matter experts, representing clinical care delivery, research, and policy arenas, participated. The work group reviewed current evidence of efficacy, effectiveness, and implementation of behavioral interventions for weight management, participated in phone- and online-based consensus processes, generated key questions to address gaps, and attended an in-person conference in March 2016...

PURPOSE: Obesity disproportionately burdens individuals with serious mental illness (SMI), especially women. This observational study investigated whether there were sex differences in weight loss and program participation among veterans with SMI enrolled in the Veterans Health Administration's (VHA) MOVE! weight management program. PROCEDURES: Participants were identified from a national cohort of 148,254 veterans enrolled in MOVE! during fiscal years 2008 through 2012 who attended two or more sessions within 12 months of enrollment...

Veterans who use Veterans Health Affairs (VHA) have the option of enrolling in and obtaining care from other non-VA sources. Dual system use may improve care by increasing options or it may result in poorer outcomes because of fragmented care. Our objective was to assess whether dual system use of VHA and Medicare for wound care was associated with chronic wound healing. We conducted a retrospective cohort study of 227 Medicare-enrolled VHA users in the Pacific Northwest who had an incident, chronic lower limb wound between October 1, 2006 and September 30, 2007 identified through VHA chart review...

BACKGROUND: Three-quarters of Iraq and Afghanistan veterans enrolled in Veterans Health Administration (VHA) care are overweight or obese. The VHA MOVE!® weight management program can mitigate the risks of obesity-related morbidity. However, many Iraq and Afghanistan veterans experience barriers to VHA services, which may affect participation, especially among those with posttraumatic stress disorder (PTSD) and/or depression. Little is known about MOVE! engagement among recent veterans...

OBJECTIVE: To characterize weight change after amputation by identifying typical weight trajectories in men with incident lower-limb amputation (LLA) and describing characteristics associated with each trajectory. DESIGN: Retrospective cohort study and analyzed using group-based trajectory modeling. SETTING: Administrative data. PARTICIPANTS: Veterans who were men (N=759), living in the Northwest United States, and who had an incident toe, foot, or leg amputation between 1997 and 2008 and at least 18 months of amputation-free survival thereafter...

During development, progenitor cells with binary potential give rise to daughter cells that have distinct functions. Heritable epigenetic mechanisms then lock in gene-expression programs that define lineage identity. Regulation of the gene encoding the T cell-specific coreceptor CD4 in helper and cytotoxic T cells exemplifies this process, with enhancer- and silencer-regulated establishment of epigenetic memory for stable gene expression and repression, respectively. Using a genetic screen, we identified the DNA-methylation machinery as essential for maintaining silencing of Cd4 in the cytotoxic lineage...

PURPOSE: Veterans in rural areas generally have lower health care utilization than veterans in urban areas, but the impact of this difference on health outcomes has received little study. Chronic wounds provide a model for studying access to complex chronic care since they often are related to underlying health conditions and require lengthy treatment. Our goals were to describe chronic wound care utilization among rural and urban veterans and to determine the association between rural residence and wound healing...

16S ribosomal RNA (rRNA) gene and other environmental sequencing techniques provide snapshots of microbial communities, revealing phylogeny and the abundances of microbial populations across diverse ecosystems. While changes in microbial community structure are demonstrably associated with certain environmental conditions (from metabolic and immunological health in mammals to ecological stability in soils and oceans), identification of underlying mechanisms requires new statistical tools, as these datasets present several technical challenges...

OBJECTIVES: We examined whether military service, including deployment and combat experience, were related to smoking initiation and relapse. METHODS: We included older (panel 1) and younger (panel 2) participants in the Millennium Cohort Study. Never smokers were followed for 3 to 6 years for smoking initiation, and former smokers were followed for relapse. Complementary log-log regression models estimated the relative risk (RR) of initiation and relapse by military exposure while adjusting for demographic, health, and lifestyle factors...

BACKGROUND: Obesity is thought to be highly prevalent in persons with lower extremity amputations (LEAs) and can impair physical and social functioning. OBJECTIVE: The aim of this study was to determine the prevalence of weight loss intention, weight loss strategies, dietary patterns, and barriers to making dietary changes, and their associations with body mass index (BMI, kg/m(2)), amputation characteristics, health status, and socioeconomic factors. METHODS: We conducted a cross-sectional study (n = 150) using data from a self-administered questionnaire...