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1.
Mil Med ; 189(3-4): e878-e887, 2024 Feb 27.
Article En | MEDLINE | ID: mdl-37715687

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.


COVID-19 , Military Personnel , Humans , United States/epidemiology , COVID-19/epidemiology , Outcome Assessment, Health Care , Europe
2.
Transpl Infect Dis ; 25(6): e14122, 2023 Dec.
Article En | MEDLINE | ID: mdl-37707287

BACKGROUND: Understanding immunogenicity and alloimmune risk following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in kidney transplant recipients is imperative to understanding the correlates of protection and to inform clinical guidelines. METHODS: We studied 50 kidney transplant recipients following SARS-CoV-2 vaccination and quantified their anti-spike protein antibody, donor-derived cell-free DNA (dd-cfDNA), gene expression profiling (GEP), and alloantibody formation. RESULTS: Participants were stratified using nucleocapsid testing as either SARS-CoV-2-naïve or experienced prior to vaccination. One of 34 (3%) SARS-CoV-2 naïve participants developed anti-spike protein antibodies. In contrast, the odds ratio for the association of a prior history of SARS-CoV-2 infection with vaccine response was 18.3 (95% confidence interval 3.2, 105.0, p < 0.01). Pre- and post-vaccination levels did not change for median dd-cfDNA (0.23% vs. 0.21% respectively, p = 0.13), GEP scores (9.85 vs. 10.4 respectively, p = 0.45), calculated panel reactive antibody, de-novo donor specific antibody status, or estimated glomerular filtration rate. CONCLUSIONS: SARS-CoV-2 vaccines do not appear to trigger alloimmunity in kidney transplant recipients. The degree of vaccine immunogenicity was associated most strongly with a prior history of SARS-CoV-2 infection.


COVID-19 , Cell-Free Nucleic Acids , Kidney Transplantation , Humans , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Immunity , SARS-CoV-2 , Transplant Recipients , Vaccination
3.
Cardiovasc Diabetol ; 22(1): 243, 2023 09 07.
Article En | MEDLINE | ID: mdl-37679748

BACKGROUND: Endogenous estrogen is cardio-protective in healthy premenopausal women. Despite this favorable action of estrogen, animal models depict a detrimental effect of estradiol on vascular function in the presence of diabetes. The present study sought to determine the role of endogenous estradiol on endothelial function in women with type 1 diabetes. METHOD: 32 women with type 1 diabetes (HbA1c = 8.6 ± 1.7%) and 25 apparently healthy women (HbA1c = 5.2 ± 0.3%) participated. Flow-mediated dilation (FMD), a bioassay of nitric-oxide bioavailability and endothelial function was performed during menses (M) and the late follicular (LF) phase of the menstrual cycle to represent low and high concentrations of estrogen, respectively. In addition, a venous blood sample was collected at each visit to determine circulating concentrations of estradiol, thiobarbituric acid reactive substances (TBARS), and nitrate/nitrite (NOx), biomarkers of oxidative stress and nitric oxide, respectively. Data were collected in (1) 9 additional women with type 1 diabetes using oral hormonal birth control (HBC) (HbA1c = 8.3 ± 2.1%) during the placebo pill week and second active pill week, and (2) a subgroup of 9 demographically matched women with type 1 diabetes not using HBC (HbA1c = 8.9 ± 2.1%). RESULTS: Overall, estradiol was significantly increased during the LF phase compared to M in both type 1 diabetes (Δestradiol = 75 ± 86 pg/mL) and controls (Δestradiol = 71 ± 76 pg/mL); however, an increase in TBARS was only observed in patients with type 1 diabetes (ΔTBARS = 3 ± 13 µM) compared to controls (ΔTBARS = 0 ± 4 µM). FMD was similar (p = 0.406) between groups at M. In addition, FMD increased significantly from M to the LF phase in controls (p = 0.024), whereas a decrease was observed in type 1 diabetes. FMD was greater (p = 0.015) in patients using HBC compared to those not on HBC, independent of menstrual cycle phase. CONCLUSION: Endogenous estradiol increases oxidative stress and contributes to endothelial dysfunction in women with diabetes. Additionally, HBC use appears to be beneficial to endothelial function in type 1 diabetes.


Diabetes Mellitus, Type 1 , Vascular Diseases , Female , Animals , Diabetes Mellitus, Type 1/diagnosis , Diabetes Mellitus, Type 1/drug therapy , Estradiol , Thiobarbituric Acid Reactive Substances , Estrogens
4.
Mil Psychol ; 35(5): 420-430, 2023.
Article En | MEDLINE | ID: mdl-37615551

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.


COVID-19 , Military Personnel , Humans , COVID-19/epidemiology , Cross-Sectional Studies , Family Characteristics , Military Personnel/psychology , Pandemics , United States/epidemiology
5.
Biophys J ; 122(19): 3843-3859, 2023 Oct 03.
Article En | MEDLINE | ID: mdl-37571824

Cephalic furrow formation (CFF) is a major morphogenetic movement during gastrulation in Drosophila melanogaster embryos that gives rise to a deep, transitory epithelial invagination. Recent studies have identified the individual cell shape changes that drive the initiation and progression phases of CFF; however, the underlying mechanics are not yet well understood. During the progression phase, the furrow deepens as columnar cells from both the anterior and posterior directions fold inwards rotating by 90°. To analyze the mechanics of this process, we have developed an advanced two-dimensional lateral vertex model that includes multinode representation of cellular membranes and allows us to capture the membrane curvature associated with pressure variation. Our investigations reveal some key potential mechanical features of CFF, as follows. When cells begin to roll over the cephalic furrow cleft, they become wedge shaped as their apical cortices and overlying membranes expand, lateral cortices and overlying membranes release tension, internal pressures drop, and basal cortices and membranes contract. Then, cells reverse this process by shortening apical cortices and membranes, increasing lateral tension, and causing internal pressures to rise. Since the basal membranes expand, the cells recover their rotated columnar shape once in the furrow. Interestingly, our findings indicate that the basal membranes may be passively reactive throughout the progression phase. We also find that the smooth rolling of cells over the cephalic furrow cleft necessitates that internalized cells provide a solid base through high levels of membrane tension and internal pressure, which allows the transmission of tensile force that pulls new cells into the furrow. These results lead us to suggest that CFF helps to establish a baseline tension across the apical surface of the embryo to facilitate cellular coordination of other morphogenetic movements via mechanical stress feedback mechanisms.

6.
Psychiatry ; 86(2): 124-136, 2023.
Article En | MEDLINE | ID: mdl-37010387

OBJECTIVE: The purpose was to examine five types of adversity and their associations with separating from military service among a nationally representative sample of U.S. National Guard and Reserve (NGR) service members. METHODS: Multivariate logistic regression analyses were conducted to examine the association between separating from the service and adversities, and demographic differences in adversities experienced among those who had separated from the service and those who stayed in the service. RESULTS: Those who left the military were more likely to report financial (OR = 1.65, 95% CI = 1.01-2.70) and healthcare access problems (OR = 2.21, 95% CI = 1.10-4.46). Among those who left the military, female service members were more likely to experience interpersonal adversity (OR = 4.28, 95% CI = 1.15-15.87), and Army and Marine service members were more likely to experience job-employment adversity (OR = 4.92, 95% CI = 1.50-16.12) and financial adversity (OR = 6.46, 95% CI = 1.22-34.33). CONCLUSION: Separating service members experience financial adversity and challenges with healthcare access. Interpersonal difficulties are particularly experienced by female service members, and job/employment difficulties experienced by Army and Marine veterans. Continued efforts are needed to facilitate service delivery for NGR separating service members who need them.


Military Personnel , Suicide , Veterans , Humans , Female , United States
7.
Sci Total Environ ; 867: 161209, 2023 Apr 01.
Article En | MEDLINE | ID: mdl-36581264

Global changes, including climate and land use changes, can result in significant impact to water resources. Planning for these changes requires making projections, even in the face of considerable uncertainties, to make informed management and policy decisions. A number of climate change scenarios and projections at global and regional levels are available that can be used to predict the likely range of outcomes. However, there is a need to translate these projections into potential implications for hydrology and water quality. Since there are dozens of hydrologic models, there is a need to evaluate them critically and to develop guidance regarding selecting the appropriate model for a given objective. We conducted a review of 21 different models commonly used for modeling hydrology (8), water quality (6) or both (7) at the watershed scale. Six of the models are strictly water quality models that depend on a separate model or observed data for hydrology. Seven additional models are useful for estimating hydrology and water quality simultaneously. The models were then evaluated based on ten different criteria, including functionality, scope, ability to model extreme events, data requirements, availability, and technical support, among others. The models were ranked Low, Medium or High in each of the criteria. The results indicate that three hydrologic models, MIKE-SHE, HEC-HMS, and MODHMS, as well as two full hydrology and water quality models, SWAT and WARMF, stand out in terms of functionality, availability, applicability to a wide range of watersheds and scales, ease of implementation, and availability of support. Modelers should carefully select the best model for their application, in part guided by the criteria discussed herein.

8.
Front Surg ; 9: 1015367, 2022.
Article En | MEDLINE | ID: mdl-36277285

Background: Advances in machine learning and robotics have allowed the development of increasingly autonomous robotic systems which are able to make decisions and learn from experience. This distribution of decision-making away from human supervision poses a legal challenge for determining liability. Methods: The iRobotSurgeon survey aimed to explore public opinion towards the issue of liability with robotic surgical systems. The survey included five hypothetical scenarios where a patient comes to harm and the respondent needs to determine who they believe is most responsible: the surgeon, the robot manufacturer, the hospital, or another party. Results: A total of 2,191 completed surveys were gathered evaluating 10,955 individual scenario responses from 78 countries spanning 6 continents. The survey demonstrated a pattern in which participants were sensitive to shifts from fully surgeon-controlled scenarios to scenarios in which robotic systems played a larger role in decision-making such that surgeons were blamed less. However, there was a limit to this shift with human surgeons still being ascribed blame in scenarios of autonomous robotic systems where humans had no role in decision-making. Importantly, there was no clear consensus among respondents where to allocate blame in the case of harm occurring from a fully autonomous system. Conclusions: The iRobotSurgeon Survey demonstrated a dilemma among respondents on who to blame when harm is caused by a fully autonomous surgical robotic system. Importantly, it also showed that the surgeon is ascribed blame even when they have had no role in decision-making which adds weight to concerns that human operators could act as "moral crumple zones" and bear the brunt of legal responsibility when a complex autonomous system causes harm.

9.
Function (Oxf) ; 3(4): zqac029, 2022.
Article En | MEDLINE | ID: mdl-35774591

Adverse childhood experiences (ACEs) are traumatic events during the first years of life that are associated with a higher risk of developing cardiovascular disease (CVD) during adulthood. The medial prefrontal cortex (mPFC) is a core region in the brain that modulates emotions and is directly involved in the cardiovascular response to stress by increasing vascular resistance. In the present study we examined the relationship between ACEs, mPFC and peripheral vascular function. Forty-five, adults (33±5 yrs.) participated in the present study to evaluate cerebral hemodynamics and peripheral vascular function. The impact of adverse experiences was evaluated through the ACE questionnaire. Among those that experienced ACEs (ACE group, n = 22), there was a significantly (P < 0.001) reduced activation of the mPFC as well as greater peripheral vascular resistance observed in the small (P ≤ 0.035), conduit (P ≤ 0.042) and large (P ≤ 0.001) blood vessels, when compared to those that did not report ACEs (Control group, n = 23). In addition, relationships between the number of ACEs and mPFC activation (rs = -0.428; P = 0.003) and peripheral vascular function (rs ≤ -0.373; P ≤ 0.009) were observed. Findings from the present study support that adults who experienced ACEs exhibit a reduced activation of the mPFC along with systemic vascular dysfunction. In addition, individuals exposed to more childhood traumatic events exhibited a progressively greater inactivation of the mPFC and an increased peripheral vasoconstriction in a dose-dependent manner. These findings provide novel insights into the potential role that the brain and the peripheral vasculature may have in connecting adverse childhood events to the increased risk of CVD.


Adverse Childhood Experiences , Cardiovascular Diseases , Adult , Humans , Cardiovascular Diseases/epidemiology , Surveys and Questionnaires , Hemodynamics
10.
BMC Public Health ; 22(1): 943, 2022 05 11.
Article En | MEDLINE | ID: mdl-35546398

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.


COVID-19 , Military Personnel , Humans , Leadership , Mental Health , Military Personnel/psychology , Public Health
11.
Nat Commun ; 13(1): 2610, 2022 May 11.
Article En | MEDLINE | ID: mdl-35545622

High-power continuous-wave (CW) lasers are used in a variety of areas including industry, medicine, communications, and defense. Yet, conventional optics, which are based on multi-layer coatings, are damaged when illuminated by high-power CW laser light, primarily due to thermal loading. This hampers the effectiveness, restricts the scope and utility, and raises the cost and complexity of high-power CW laser applications. Here we demonstrate monolithic and highly reflective mirrors that operate under high-power CW laser irradiation without damage. In contrast to conventional mirrors, ours are realized by etching nanostructures into the surface of single-crystal diamond, a material with exceptional optical and thermal properties. We measure reflectivities of greater than 98% and demonstrate damage-free operation using 10 kW of CW laser light at 1070 nm, focused to a spot of 750 µm diameter. In contrast, we observe damage to a conventional dielectric mirror when illuminated by the same beam. Our results initiate a new category of optics that operate under extreme conditions, which has potential to improve or create new applications of high-power lasers.

12.
Physiol Rep ; 10(10): e15335, 2022 05.
Article En | MEDLINE | ID: mdl-35593213

Upregulation of endothelin-1 (ET-1) is the hallmark of various cardiovascular diseases (CVD). The purpose of the present study was to assess the ET-1 response to an acute bout of whole-body vibration (WBV) in humans and to determine the role of adiposity. Twenty-two participants volunteered for the study; they were grouped into overweight/obese [(OW/OB): n = 11, Age: 33 ± 4 years, Body mass index (BMI): 35 ± 10 kg/m2 ] or normal weight [(NW): n = 11, Age: 28 ± 7 years, BMI: 21 ± 2 kg/m2 ]. Participants engaged in 10 cycles of WBV exercise (1 cycle = 1 min WBV followed by 30 s of rest). Blood samples were analyzed for ET-1 pre-WBV (PRE), immediately post (POST), 1 h (1H), 3 h (3H), and 24 h (24H) post-WBV. There was a significant time main effect of WBV on circulating ET-1 (F = 12.5, p < 0.001); however, the ET-1 response was similar (F = 0.180, p = 0.677) between groups. Specifically, compared to PRE, a significant increase in ET-1 was observed at 1H (p = 0.017) and 3H (p = 0.025). In addition, concentrations of ET-1 were significantly lower at 24H compared to PRE (p = 0.019), 1H (p < 0.001), and 3H (p < 0.001). Maximal oxygen uptake during WBV was similar between the two groups. Acute WBV resulted in an initial rise in ET-1, followed by a significantly lower ET-1 at 24H in both groups. Findings support the utility of routine WBV exercise to elicit a decrease in ET-1 and improve CVD risk, similar to what has been reported with traditional modes of exercise.


Cardiovascular Diseases , Vibration , Adult , Endothelin-1 , Exercise/physiology , Humans , Obesity/therapy , Young Adult
13.
Am J Physiol Endocrinol Metab ; 322(6): E508-E516, 2022 06 01.
Article En | MEDLINE | ID: mdl-35373585

Increased adiposity is associated with dysregulation of the endothelin system, both of which increase the risk of cardiovascular disease (CVD). Preclinical data indicate that endothelin dysregulation also reduces resting energy expenditure (REE). The objective was to test the hypothesis that endothelin receptor antagonism will increase REE in people with obesity compared with healthy weight individuals. Using a double blind, placebo-controlled, crossover design, 32 participants [healthy weight (HW): n = 16, BMI: 21.3 ± 2.8 kg/m2, age: 26 ± 7 yr and overweight/obese (OB): n = 16, BMI: 33.5 ± 9.5 kg/m2, age: 31 ± 6 yr] were randomized to receive either 125 mg of bosentan (ETA/B antagonism) or placebo twice per day for 3 days. Breath-by-breath gas exchange data were collected and REE was assessed by indirect calorimetry. Venous blood samples were analyzed for concentrations of endothelin-1 (ET-1). Treatment with bosentan increased plasma ET-1 in both OB and HW groups. Within the OB group, the changes in absolute REE (PLA: -77.6 ± 127.6 vs. BOS: 72.2 ± 146.6 kcal/day; P = 0.046). The change in REE was not different following either treatment in the HW group. Overall, absolute plasma concentrations of ET-1 following treatment with bosentan were significantly associated with kcal/day of fat (r = 0.488, P = 0.005), percentage of fat utilization (r = 0.415, P = 0.020), and inversely associated with the percentage of carbohydrates (r = -0.419, P = 0.019), and respiratory exchange ratio (r = -0.407, P = 0.023). Taken together, these results suggest that modulation of the endothelin system may represent a novel therapeutic approach to increase both resting metabolism and caloric expenditure, and reduce CVD risk in people with increased adiposity.NEW & NOTEWORTHY Findings from our current translational investigation demonstrate that dual endothelin A/B receptor antagonism increases total REE in overweight/obese individuals. These results suggest that modulation of the endothelin system may represent a novel therapeutic target to increase both resting metabolism and caloric expenditure, enhance weight loss, and reduce CVD risk in seemingly healthy individuals with elevated adiposity.


Adiposity , Cardiovascular Diseases , Adult , Basal Metabolism , Bosentan , Calorimetry, Indirect , Endothelins/metabolism , Energy Metabolism , Humans , Obesity/metabolism , Overweight/metabolism , Receptors, Endothelin/metabolism , Young Adult
14.
Physiol Rep ; 10(5): e15208, 2022 03.
Article En | MEDLINE | ID: mdl-35238491

Whole-body vibration (WBV) is an exercise mimetic that elicits beneficial metabolic effects. This study aims to investigate the effects of WBV amplitude on metabolic, inflammatory, and muscle oxygenation responses. Forty women and men were assigned to a high (HI; n = 20, Age: 31 ± 6 y) or a low-amplitude group (LO; n = 20, Age: 33 ± 6 y). Participants engaged in 10 cycles of WBV [1 cycle =1 min of vibration followed by 30 s of rest], while gastrocnemius muscle oxygen consumption (mVO2 ) was assessed using near-infrared spectroscopy (NIRS). Blood samples were collected PRE, POST, 1H, 3Hs, and 24H post-WBV and analyzed for insulin, glucose, and IL-6. In the LO group, Homeostatic Model Assessment for Insulin Resistant (HOMA-IR) at 3 h (0.7 ± 0.2) was significantly lower compared to PRE (1.1 ± 0.2; p = 0.018), POST (1.3 ± 0.3; p = 0.045), 1H (1.3 ± 0.3; p = 0.010), and 24H (1.4 ± 0.2; p < 0.001). In addition, at 24H, HOMA-IR was significantly lower in the LO when compared to the HI group (LO: 1.4 ± 0.2 vs. HI: 2.2 ± 0.4; p = 0.030). mVO2 was higher (p = 0.003) in the LO (0.93 ± 0.29 ml/min/100 ml) when compared to the HI group (0.63 ± 0.28 ml/min/100 ml). IL-6 at 3H (LO: 13.2 ± 2.7 vs. HI: 19.6 ± 4.0 pg·ml-1 ; p = 0.045) and 24H (LO: 4.2 ± 1.1 vs. HI: 12.5 ± 3.1 pg·ml-1 ; p = 0.016) was greater in the HI compared to the LO group. These findings indicate that low-amplitude WBV provides greater metabolic benefits compared to high-amplitude WBV.


Interleukin-6 , Vibration , Adult , Female , Glucose/metabolism , Humans , Inflammation/metabolism , Insulin/metabolism , Interleukin-6/metabolism , Male , Muscle, Skeletal/metabolism
15.
J Appl Physiol (1985) ; 132(1): 73-83, 2022 01 01.
Article En | MEDLINE | ID: mdl-34762528

Obesity is associated with dysregulation of the endothelin system. In individuals with obesity, an exaggerated pressor response to acute stress is accompanied by increased circulating endothelin-1 (ET-1). The impact of combined endothelin A/B receptor (ETA/B) antagonism on the stress-induced pressor response in overweight/obese (OB) individuals is unknown. The objective of this study is to test the hypothesis that treatment with an ETA/B antagonist (bosentan) would reduce the stress-induced pressor response and arterial stiffness in overweight/obese compared with normal weight (NW) individuals. Forty participants [normal weight (NW): n = 20, body mass index (BMI): 21.7 ± 2.4 kg/m2 and overweight/obese (OB): n = 20, BMI: 33.8 ± 8.2 kg/m2] were randomized to placebo or 125 mg of bosentan twice a day (250 mg total) for 3 days. Hemodynamics were assessed before, during, and after a cold pressor test (CPT). Endothelin-1 was assessed at baseline and immediately after CPT. Following a washout period, the same protocol was repeated with the opposite treatment. The change from baseline in mean arterial pressure (MAP) during CPT following bosentan was significantly lower (P = 0.039) in the OB group than in the NW group (OB: 28 ± 12 vs. NW: 34 ± 15 mmHg). These results suggest that ETA/B antagonism favorably blunts the pressor response to acute stress in overweight/obese individuals.NEW & NOTEWORTHY Findings from our current translational investigation demonstrate that dual endothelin A/B receptor antagonism blunts the pressor response to acute stress in overweight/obese individuals. These results suggest that modulation of the endothelin system may represent a novel therapeutic target to reduce cardiovascular disease (CVD) risk by blunting the stress response in overweight/obese individuals.


Obesity , Overweight , Blood Pressure , Endothelin B Receptor Antagonists , Endothelin Receptor Antagonists/pharmacology , Endothelin-1 , Endothelins , Female , Humans , Male , Obesity/drug therapy , Receptor, Endothelin A
16.
Psychol Med ; 52(13): 2492-2499, 2022 10.
Article En | MEDLINE | ID: mdl-33261701

BACKGROUND: For decades confirmatory factor analysis (CFA) has been the preeminent method to study the underlying structure of posttraumatic stress disorder (PTSD); however, methodological limitations of CFA have led to the emergence of other analytic approaches. In particular, network analysis has become a gold standard to investigate the structure and relationships between PTSD symptoms. A key methodological limitation, however, which has significant clinical implications, is the lack of data on the potential impact of item order effects on the conclusions reached through network analyses. METHODS: The current study, involving a large sample (N = 5055) of active duty army soldiers following deployment to Iraq, assessed the vulnerability of network analyses and prevalence rate to item order effects. This was done by comparing symptom networks of the DSM-IV PTSD checklist items to these same items distributed in random order. Half of the participants rated their symptoms on traditionally ordered items and half the participants rated the same items, but in random order and interspersed between items from other validated scales. Differences in prevalence rate and network composition were examined. RESULTS: The prevalence rate differed between the ordered and random item samples. Network analyses using the ordered survey closely replicated the conclusions reached in the existing network analyses literature. However, in the random item survey, network composition differed considerably. CONCLUSION: Order effects appear to have a significant impact on conclusions reached from PTSD network analysis. Prevalence rates were also impacted by order effects. These findings have important diagnostic and clinical treatment implications.


Military Personnel , Stress Disorders, Post-Traumatic , Humans , Stress Disorders, Post-Traumatic/epidemiology , Concept Formation , Diagnostic and Statistical Manual of Mental Disorders , Factor Analysis, Statistical
17.
Sci Rep ; 11(1): 24122, 2021 12 16.
Article En | MEDLINE | ID: mdl-34916543

Smoking increases systemic inflammation and circulating endothelin-1 (ET-1), both of which contribute to an elevated risk of cardiovascular disease (CVD). The present study sought to test the hypothesis that a 12-week smoking cessation intervention would contribute to a long-term reduction in circulating ET-1, tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6). 30 individuals participated in a 12-week evidence-based smoking cessation program at Augusta University. Serum cotinine, plasma inflammatory cytokines, and plasma ET-1 were determined at baseline, immediately after the 12-week cessation program (end of treatment, EOT), and 12-months (12M) following the cessation program. Serum cotinine was significantly reduced (p < 0.001) at EOT and 12M following the smoking cessation program. Compared to BL (7.0 ± 1.6 pg/mL), TNF-α was significantly reduced at EOT (6.3 ± 1.5 pg/mL, p = 0.001) and 12M (5.2 ± 2.7 pg/mL, p < 0.001). ET-1 was significantly lower at EOT (1.9 ± 0.6 pg/mL, p = 0.013) and at 12M (2.0 ± 0.8 pg/mL, p = 0.091) following smoking cessation compared with BL (2.3 ± 0.6 pg/mL). BL concentrations of cotinine were significantly associated with basal ET-1 (r = 0.449, p = 0.013) and the change in cotinine at 12M following smoking cessation was significantly associated with the change in plasma ET-1 at 12M (r = 0.457, p = 0.011). Findings from the present pilot investigation demonstrate that a 12-week smoking cessation program reduces circulating concentrations of ET-1 and TNF-α for at least a year. The reduction in serum cotinine was associated with the decrease in circulating ET-1. The attenuation in ET-1 and inflammation may in part, contribute to the lower risk of CVD that is observed with smoking cessation.


Endothelin-1/blood , Inflammation Mediators/blood , Inflammation/etiology , Inflammation/prevention & control , Smoking Cessation , Smoking/adverse effects , Adult , Cotinine/blood , Female , Heart Disease Risk Factors , Humans , Interleukin-6/blood , Male , Middle Aged , Pilot Projects , Risk , Tumor Necrosis Factor-alpha/blood , Young Adult
18.
J Dev Biol ; 9(4)2021 Oct 16.
Article En | MEDLINE | ID: mdl-34698210

In order to determine the frequency of SARS-CoV-2 placental and fetal involvements, we analyzed placentas of 197 women positive for infection at delivery and fetal tissues in cases of pregnancy loss in women positive by SARS-CoV-2 PCR (N = 2) and COVID-19 serology (N = 4), using in situ hybridization (ISH), immunohistochemistry (IHC) and, in selected cases, RT-PCR of tissue homogenates. The virus was identified in situ, accompanied by intervillositis, in 2 of 197 placentas (1.02%). In three more cases, SARS-CoV-2 was detected by tissue PCR without in situ localization and placental inflammation. There were no maternal mortality or association of placental infection with the clinical severity of COVID-19. All tested neonates born to SARS-CoV-2-positive women (N = 172) were negative for the virus. There were three pregnancy losses among 197 infected women and in two cases available fetal tissues were negative for SARS-CoV-2. In one of four fetal autopsies performed in women with positive COVID-19 serology, the mother-to-child transmission (MTCT) could be inferred based on positive SARS-CoV-2 nucleocapsid IHC in fetal pulmonary endothelium. Placental involvement by SARS-CoV-2 is rare, but may be underestimated due to its transient nature. MTCT is even rarer, supporting the protective role of placenta in SARS-CoV-2 infection.

19.
PLoS Comput Biol ; 17(7): e1009173, 2021 07.
Article En | MEDLINE | ID: mdl-34228708

Formation of the ventral furrow in the Drosophila embryo relies on the apical constriction of cells in the ventral region to produce bending forces that drive tissue invagination. In our recent paper we observed that apical constrictions during the initial phase of ventral furrow formation produce elongated patterns of cellular constriction chains prior to invagination and argued that these are indicative of tensile stress feedback. Here, we quantitatively analyze the constriction patterns preceding ventral furrow formation and find that they are consistent with the predictions of our active-granular-fluid model of a monolayer of mechanically coupled stress-sensitive constricting particles. Our model shows that tensile feedback causes constriction chains to develop along underlying precursor tensile stress chains that gradually strengthen with subsequent cellular constrictions. As seen in both our model and available optogenetic experiments, this mechanism allows constriction chains to penetrate or circumvent zones of reduced cell contractility, thus increasing the robustness of ventral furrow formation to spatial variation of cell contractility by rescuing cellular constrictions in the disrupted regions.


Drosophila/embryology , Embryo, Nonmammalian/physiology , Feedback, Physiological/physiology , Gastrulation/physiology , Animals , Biomechanical Phenomena/physiology , Computational Biology , Models, Biological
20.
Integr Environ Assess Manag ; 17(6): 1255-1262, 2021 Nov.
Article En | MEDLINE | ID: mdl-33760353

In 2016, the US Environmental Protection Agency (USEPA) issued revised aquatic life water quality criteria for selenium (Se). The criteria ("elements") consisted of threshold concentrations applicable to fish tissue (three tissue types, though the egg and ovary tissue takes precedence over the whole-body and muscle tissue thresholds), and water column. The agency rationalized that measured concentrations of Se in fish tissue were more predictive of potential adverse reproductive effects than those measured in external media. The agency provided two mechanisms for derivation of site-specific Se water criteria: a bioaccumulation factor (BAF) approach, and a partitioning-based bioaccumulation model approach. The use of either approach assumes that fish tissue concentrations exceed one or more of the tissue criteria. We compared the two approaches using fish tissue samples from various species in the Ohio River to evaluate resulting similarities and differences in the calculated Se water quality criteria. Fish (five species) were collected near two coal-fired power plants at sites unaffected by Se from wastewater discharges. Using results for all species and all sites combined, the resulting site-specific Se criteria for the BAF and partitioning-based model approach (median values) were 2.0 and 1.5 µg/L, respectively. Considering all species, resulting criteria differed little between the two power plant locations. Resulting criteria for both methods were strongly influenced by a small (less than detection) background Se water concentration. At least for the upper Ohio River, the BAF approach (requiring less input data) seems adequate for derivation of site-specific Se water criteria. In the current study, however, none of the tissue samples exceeded USEPA's tissue criteria. Thus, the decision to derive site-specific Se water quality criteria should be evaluated on a case-by-case basis, because the process may result in either a more stringent or less stringent value, wholly dependent on local factors. Integr Environ Assess Manag 2021;17:1255-1262. © 2021 SETAC.


Selenium , Water Pollutants, Chemical , Animals , Environmental Monitoring , Female , Fishes , Rivers , Selenium/analysis , Water Pollutants, Chemical/analysis , Water Pollutants, Chemical/toxicity , Water Quality
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