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Pandemic preparedness is a key function of any health care facility. Activities pertaining to pandemic preparedness should be developed and maintained within a broader emergency management plan. The use of a Hospital Incident Command System can centralize coordination of the response and facilitate internal and external communication. This review addresses several components of pandemic preparedness, including incident management, health care personnel safety, strategies to support ongoing clinical activities, and organizational communication during a pandemic. Preparations addressing potential ethical challenges and the psychological impact associated with pandemic response are also reviewed.

We examined partner-seeking and sexual behaviors among a representative sample of U.S. adults (N = 1,161) during the first year of the COVID-19 pandemic. Approximately 10% of survey respondents sought a new partner, with age and sexual identity being associated with partner seeking behavior. Approximately 7% of respondents had sex with a new partner, which marks a decrease as compared to a pre-pandemic estimate from 2015 - 2016 in which 16% of U.S. adults reported having sex with a new partner during the past year. Among respondents who had in-person sex with a new partner during the first year of the pandemic, public health guidelines for in-person sexual activity were infrequently followed.

For locally advanced esophageal squamous cell carcinoma (ESCC), chemoradiation (ChemoRT) followed by surgery offers the best chance of cure, with a 35–50% pathologic complete response (pCR) rate. Given the morbidity of esophagectomy and the possibility of pCR with ChemoRT, a ‘watch and wait’ strategy has been proposed, particularly for squamous cell carcinoma. The ability to accurately predict which patients will have pCR from ChemoRT is critical in treatment decision making. This study assessed positron emission tomography (PET) in predicting pCR after neoadjuvant ChemoRT for ESCC. ESCC patients treated with ChemoRT followed by surgery were identified. Maximum standard uptake value (SUV), metabolic tumor volume, total lesion glycolysis, and first-order textual features of standard deviation, kurtosis and skewness were measured from PET. Univariable and multivariable generalized linear method analyses were performed. A metabolic complete response (mCR) was defined as a post-therapy PET scan with maximum SUV < 4.0. Twenty-seven patients underwent ChemoRT followed by surgery, with overall pCR seen in 11 (41%) patients and radiographic mCR seen in 12 (44%) patients. Final pathology for these 12 patients revealed pCR (ypT0N0M0) in 5 (42%) patients and persistent disease in 7 (58%) patients. Univariate analysis did not reveal PET parameters predictive of pCR. Treatment of ESCC with ChemoRT often results in a robust clinical response. Among patients with an mCR after ChemoRT, disease persistence was found in 58%. The inability of PET to predict pCR is important in the context of a ‘watch and wait’ strategy for ESCC treated with ChemoRT.

Behavioral responses such as social distancing are important in the fight to contain COVID‐19 transmission, yet motivating such responses is an overwhelming, resource‐intensive task. Using multi‐wave data from 23,735 US adults collected in May/September 2020, and January 2021, this study examines how financial preparedness in the form of savings influences the relationship predicted by the Health Belief Model between the degree of concern for COVID‐19 and engagement in social distancing. Findings indicate that general concern for COVID‐19 is related to the decision to engage in social distancing for individuals who have less saved. Curiously, higher levels of financial preparedness are associated with a lower likelihood of social distancing at least among people who had been laid off during the pandemic. The findings suggest a tradeoff between protecting one's standard of living and their health. Government and public health agencies should consider financial preparedness in the design of public health communications. [ABSTRACT FROM AUTHOR] Copyright of Journal of Consumer Affairs is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

High-intensity interval training (HIIT) promotes positive cardiometabolic and body composition changes. Essential amino acids (EAA) may support changes associated with HIIT, but evaluation of potential synergistic effects is lacking. The purpose of this study was to compare independent and combined effects of HIIT and EAA on total body composition and metabolism in men and women considered overweight/obese; an exploratory aim was to evaluate the modulatory effects of sex. Sixty-six healthy adults (50% female; Age: 36.7 ± 6.0 years; BMI: 32.0 ± 4.2 kg/m2) completed 8 weeks of: (1) HIIT, 2 days/weeks; (2) EAA supplementation, 3.6 g twice daily; (3) HIIT + EAA; or (4) control. Body composition, resting metabolic rate (RMR), substrate metabolism (respiratory exchange ratio; RER), and cardiorespiratory fitness were measured at baseline, 4 weeks, and 8 weeks; cardiometabolic blood markers were measured at baseline and 8 weeks. Differences between groups were assessed by linear mixed models covaried for baseline values, followed by 95% confidence intervals (CI) on adjusted mean change scores. There were no significant changes in body composition (p > 0.05) for any group. Changes in RER, but not RMR, occurred with HIIT (mean change; [95% CI]: − 0.04; [− 0.07, − 0.02]) and EAA (− 0.03; [− 0.06, − 0.01]) after 8 weeks. Cardiorespiratory fitness increased following 8 weeks of HIIT (+ 5.1 ml/kg/min [3.3,6.8]) and HIIT + EAA (+ 4.1 ml/kg/min [1.0,6.4]). Changes with HIIT + EAA were not significantly different from HIIT. There were no changes in cardiometabolic markers (p > 0.05) and no sex interaction (p > 0.05). HIIT is efficacious for promoting positive changes in cardiorespiratory fitness and resting substrate metabolism in adults considered overweight/obese. Addition of EAA did not significantly enhance HIIT-induced adaptations. ClinicalTrials.gov ID#NCT04080102.

Introduction: With the unprecedented expansion of women's roles in the U.S. military during recent (post-9/11) conflicts in Iraq and Afghanistan, the number of women seeking healthcare through the Veterans Health Administration (VHA) has increased substantially. Women Veterans often present as medically complex due to multiple medical, mental health, and psychosocial comorbidities, and consequently may be underserved. Thus, we conducted the nationwide Women Veterans Cohort Study (WVCS) to examine post-9/11 Veterans' unique healthcare needs and to identify potential disparities in health outcomes and care. Methods: We present baseline data from a comprehensive questionnaire battery that was administered from 2016 to 2019 to a national sample of post-9/11 men and women Veterans who enrolled in Veterans Affairs care (WVCS2). Data were analyzed for descriptives and to compare characteristics by gender, including demographics; health risk factors and symptoms of cardiovascular disease, chronic pain, and mental health; healthcare utilization, access, and insurance. Results: WVCS2 included 1,141 Veterans (51% women). Women were younger, more diverse, and with higher educational attainment than men. Women also endorsed lower traditional cardiovascular risk factors and comorbidities (e.g., weight, hypertension) and greater nontraditional cardiovascular risk factors (e.g., trauma, psychological symptoms). More women reported single-site pain (e.g., neck, stomach, pelvic) and multisite pain, but did not differ from men in posttraumatic stress disorder (PTSD) symptoms or treatment for PTSD. Women seek care at VHA medical centers more frequently, often combined with outside health services, but do not significantly differ from men in their insurance coverage. Conclusion: Overall, this investigation indicates substantial variation in risk factors, health outcomes, and healthcare utilization among post-9/11 men and women Veterans. Further research is needed to determine best practices for managing women Veterans in the VHA healthcare system.

Rationale CC16 (club cell secretory protein) is a pneumoprotein produced predominantly by pulmonary club cells. Circulating CC16 is associated with protection from the inception and progression of ...

BACKGROUND: Associations between online sex seeking and increased risk for sexually transmitted infections (STIs) and human immunodeficiency virus (HIV) among men who have sex with men (MSM) typically rely on convenience samples. We examined Internet and mobile app use for finding sex partners among a nationally representative sample of MSM. METHODS: We analyzed 2011 to 2017 data from the National Survey of Family Growth, a nationally representative sample of the civilian, non-institutionalized US population (15–44 years). The analytic sample was comprised of men who reported 1 or more same-sex partners in the past year. We also assessed associations between online sex-seeking and STI risk, sexual health care behaviors, and condom use. RESULTS: Of 13,320 male respondents, 442 (3.0%) reported sex with a man in the past year, of whom 215 (46.3%) had met a partner online. Between MSM who met partners online and those who did not, we found no differences by age, education, race/ethnicity or socioeconomic status. Men who have sex with men with online partners were more likely to identify as gay (68.4% vs 49.5%, P = 0.0124). They also reported more sex partners overall (M = 3.04 vs 1.60, P < 0.0001), and multiple insertive (46.3% vs 8.5%, P < 0.0001) and receptive (33.2% vs 15.4%, P = 0.0055) anal sex partners, in the past year. They were also more likely to receive sexual risk assessments (56.0% vs 40.4%, P = 0.0129), STI testing (57.4% vs 35.3%, P = 0.0002), and STI treatment (17.8% vs 8.7%, P = 0.0152) in the past year. We found no differences in condom use. CONCLUSIONS: Men who have sex with men who report using online sources to find sex partners are more likely than other MSM to report behaviors that increase risk for STI/HIV but are also more likely to engage in behaviors that may mitigate further transmission, such as STI testing.

Bone nonunions arising from large bone defects and composite injuries remain compelling challenges for orthopedic surgeons. Biological changes associated with nonunions, such as systemic immune dysregulation, can contribute to an adverse healing environment. Bone morphogenetic protein 2 (BMP-2), an osteoinductive and potentially immunomodulatory growth factor, is a promising strategy; however, burst release from the clinical standard collagen sponge delivery vehicle can result in adverse side effects such as heterotopic ossification (HO) and irregular bone structure, especially when using supraphysiological BMP-2 doses for complex injuries at high risk for nonunion. To address this challenge, biomaterials that strongly bind BMP-2, such as heparin methacrylamide microparticles (HMPs), may be used to limit exposure and spatially constrain proteins within the injury site. Here, we investigate moderately high dose BMP-2 delivered in HMPs within an injectable hydrogel system in two challenging nonunion models exhibiting characteristics of systemic immune dysregulation. The HMP delivery system increased total bone volume and decreased peak HO compared to collagen sponge delivery of the same BMP-2 dose. Multivariate analyses of systemic immune markers showed the collagen sponge group correlated with markers that are hallmarks of systemic immune dysregulation, including immunosuppressive myeloid-derived suppressor cells, whereas the HMP groups were associated with immune effector cells, including T cells, and cytokines linked to robust bone regeneration. Overall, our results demonstrate that HMP delivery of moderately high doses of BMP-2 promotes repair of complex bone nonunion injuries and that local delivery strategies for potent growth factors like BMP-2 may positively affect the systemic immune response to traumatic injury.

Developing working knowledge of integrated care models can guide pharmacists in operationalizing comprehensive medication management (CMM) alongside behavioral health services for holistic primary care integration. Over the last decade forces from both within and outside the pharmacy profession have culminated in trends toward an oversupply of pharmacists in the United States. In response, advocates of the profession have called for the materialization of long-awaited advancements in innovative, team-based, medication management roles. Although pharmacists are uniquely qualified to provide CMM services, the widespread integration to primary care teams has lagged behind that of other professions, such as behavioral health. Through the application of evidence-based integrated care models, behavioral health clinicians have become regular and routine contributors to primary care teams. To thrive in primary care roles, pharmacists must be able to navigate established teams practicing within existing integrated care models. Understanding how primary care physicians interact with other specialties, such as behavioral health, and the implications this has for pharmacy will play a role in meaningful adaptation of CMM services.

Preventing unintended pregnancy and sexually transmitted diseases (STDs), including human immunodeficiency virus (HIV) infection, among adolescents is a public health priority. This report presents prevalence estimates for condom and contraceptive use among sexually active U.S. high school students from the 2019 Youth Risk Behavior Survey. Behaviors examined included any condom use, primary contraceptive method use, and condom use with a more effective contraceptive method, all reported at last sexual intercourse. Analyses were limited to sexually active students (i.e., those who had sexual intercourse with one or more persons during the 3 months before the survey). Except for any condom use, students reporting only same-sex sexual contact were excluded from analyses. Weighted prevalence estimates were calculated, and bivariate differences in prevalence were examined by demographic characteristics (sex, race/ethnicity, and grade) and other sexual risk behaviors (age of sexual initiation, previous 3-month and lifetime number of sex partners, and substance use before last sexual intercourse). Nationwide, 27.4% of high school students reported being sexually active (n = 3,226). Among sexually active students who reported having had sexual contact with someone of the opposite sex (n = 2,698), most students (89.7%) had used a condom or a primary contraceptive method at last sexual intercourse. Prevalence of any condom use at last sexual intercourse was 54.3%, and condoms were the most prevalent primary contraceptive method (43.9% versus 23.3% for birth control pills; 4.8% for intrauterine device [IUD] or implant; and 3.3% for shot, patch, or ring). Approximately 9% had used condoms with an IUD, implant, shot, patch, ring, or birth control pills. Using no pregnancy prevention method was more common among non-Hispanic black (23.2%) and Hispanic (12.8%) students compared with non-Hispanic white students (6.8%); compared with Hispanic students, using no pregnancy prevention method was more common among non-Hispanic black students. Prevalence of condom use was consistently lower among students with other sexual risk behaviors. Results underscore the need for public health professionals to provide quality sexual and reproductive health education and clinical services for preventing unintended pregnancy and STDs/HIV and decreasing disparities among sexually active youths.

The bacterial pathogen Staphylococcus aureus is capable of infecting a broad spectrum of host tissues, in part due to flexibility of metabolic programs. S. aureus, like all organisms, requires essential biosynthetic intermediates to synthesize macromolecules. We therefore sought to determine the metabolic pathways contributing to synthesis of essential precursors during invasive S. aureus infection. We focused specifically on staphylococcal infection of bone, one of the most common sites of invasive S. aureus infection and a unique environment characterized by dynamic substrate accessibility, infection-induced hypoxia, and a metabolic profile skewed toward aerobic glycolysis. Using a murine model of osteomyelitis, we examined survival of S. aureus mutants deficient in central metabolic pathways, including glycolysis, gluconeogenesis, the tricarboxylic acid (TCA) cycle, and amino acid synthesis/catabolism. Despite the high glycolytic demand of skeletal cells, we discovered that S. aureus requires glycolysis for survival in bone. Furthermore, the TCA cycle is dispensable for survival during osteomyelitis, and S. aureus instead has a critical need for anaplerosis. Bacterial synthesis of aspartate in particular is absolutely essential for staphylococcal survival in bone, despite the presence of an aspartate transporter, which we identified as GltT and confirmed biochemically. This dependence on endogenous aspartate synthesis derives from the presence of excess glutamate in infected tissue, which inhibits aspartate acquisition by S. aureus Together, these data elucidate the metabolic pathways required for staphylococcal infection within bone and demonstrate that the host nutrient milieu can determine essentiality of bacterial nutrient biosynthesis pathways despite the presence of dedicated transporters.

Initial microbial colonization and later succession in the gut of human infants are linked to health and disease later in life. The timing of the appearance of the first gut microbiome, and the consequences for the early life metabolome, are just starting to be defined. Here, we evaluated the gut microbiome, proteome and metabolome in 88 African-American newborns using faecal samples collected in the first few days of life. Gut bacteria became detectable using molecular methods by 16 h after birth. Detailed analysis of the three most common species, Escherichia coli, Enterococcus faecalis and Bacteroides vulgatus, did not suggest a genomic signature for neonatal gut colonization. The appearance of bacteria was associated with reduced abundance of approximately 50 human proteins, decreased levels of free amino acids and an increase in products of bacterial fermentation, including acetate and succinate. Using flux balance modelling and in vitro experiments, we provide evidence that fermentation of amino acids provides a mechanism for the initial growth of E. coli, the most common early colonizer, under anaerobic conditions. These results provide a deep characterization of the first microbes in the human gut and show how the biochemical environment is altered by their appearance. Using a multi-omics approach to analyse meconium and stool samples from babies during the first few days of life, the authors show that the gut is detectably colonized within 16 h of birth, with Escherichia coli dominating, and that this correlates with proteome and metabolome changes including the fermentation of amino acids.

Objective OEF/OIF/OND Veterans have an elevated risk for developing cardiovascular disease (CVD), but research suggests that engagement in CVD preventive behaviors is low even among at-risk individuals. It is critical to understand barriers to prevention engagement among Veterans to inform the development of tailored interventions addressing barriers and reducing CVD incidence. Method The Women Veterans Cohort Study survey of OEF/OIF/OND Veterans (586 women and 555 men) assessed patient, interpersonal, and systems level barriers to CVD risk prevention. Prevalence of barriers was determined, and chi-squares were conducted to examine sex differences. Multivariate logistic regressions were conducted to determine if sex differences remained when adjusting for demographic factors (age, marital status, education, employment status). Results Despite a low response rate (11.5%), endorsement of barriers was high for both women and men, with most (56.8%) not perceiving themselves to be at CVD risk. More men preferred making no lifestyle change (40.9% vs. 29.1%). More women endorsed lack of confidence (42.4% vs. 36.1%), stress (36.9% vs. 27.8%) and depression (36.9% vs. 27.8%), and inadequate social support (26% vs. 20.9%), along with the belief that their clinician does not perceive them as at risk (57.8% vs. 32%) and has not explained CVD preventive behaviors (19% vs. 12.3%). Multivariate analyses reduced statistical significance of sex differences. Conclusions Given the low response rate, testing of efforts-for example, implementation science methods-to assess CVD risk reduction barriers in this population are needed, a task for which the Veterans Health Administration is well suited. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Yersinia pestis, the cause of plague, could be weaponized. Unfortunately, development of new vaccines is limited by lack of correlates of protection. We used pre- and post-vaccination sera and peripheral blood mononuclear cells from a flagellin adjuvanted F1/V vaccine trial to evaluate for protective markers. Here, we report for the first time in humans that inverse caspase-3 levels, which are measures of protective antibody, significantly increased by 29% and 75% on days 14 and 28 post-second vaccination, respectively. In addition, there were significant increases in T-cell responses on day 28 post-second vaccination. The strongest positive and negative correlations between protective antibody levels and gene expression signatures were identified for IFNG and ENSG00000225107 genes, respectively. Flagellin/F1/V subunit vaccine induced macrophage-protective antibody and significant CD4+ T-cell responses. Several genes associated with these responses were identified that could serve as potential correlates of protection.

BACKGROUND: Recent increases in high-risk substance use (HRSU; i.e., injection drug use, heroin, methamphetamine, crack/cocaine) have coincided with rising primary and secondary (P&S) syphilis rates. To further understand these trends, we examined sexual risk behaviors among women, men who have sex with women only (MSW), and men who have sex with men (MSM) who were diagnosed with P&S syphilis in 2018 and reported HRSU. METHODS: Data on HRSU and sexual risk behaviors among persons with P&S syphilis were drawn from syphilis case reports in 2018 from the National Notifiable Diseases Surveillance System. Persons with P&S syphilis were asked about sexual risk behaviors in the past 12 months including exchange sex for drugs/money, sex while intoxicated and/or high on drugs, sex with a person who injects drugs (PWID), sex with an anonymous partner, and number of sex partners. We describe percentages and adjusted prevalence ratios (aPRs) for women, MSW, and MSM reporting these behaviors by age, race/Hispanic ethnicity, type of drug used, and incarceration history (both in the past 12 months). RESULTS: Among 19,634 persons diagnosed with P&S syphilis in 2018 with information on HRSU, 29.3% of women, 22.7% of MSW, and 12.4% of MSM reported HRSU. Among those reporting HRSU, percentages reporting exchange sex ranged from 17% to 35% (highest for women), whereas reports of anonymous sex ranged from 44% to 71% (highest for MSM). In this population, sexual risk behaviors were more commonly reported among those with a recent incarceration history than those without such history. Among those reporting injection drug use or heroin use, percentages reporting sex with a PWID ranged from 51% to 77%. In adjusted models, HRSU was significantly associated with one or more sexual risk behaviors for women (aPR, 2.63 [95% confidence interval {CI}, 2.39–2.90]; MSW: aPR, 1.38 [95% CI, 1.31–1.46]; and MSM: aPR, 1.30 [95% CI, 1.26–1.34]). CONCLUSIONS: Collaborative partnerships across the US public health system could help address barriers to timely clinical care among persons diagnosed with P&S syphilis who report HRSU.

Human epidemiological studies implicate exposure to infection during gestation in the etiology of neurodevelopmental disorders. Animal models of maternal immune activation (MIA) have identified the maternal immune response as the critical link between maternal infection and aberrant offspring brain and behavior development. Here we evaluate neurodevelopment of male rhesus monkeys (Macaca mulatta) born to MIA-treated dams (n= 14) injected with a modified form of the viral mimic polyinosinic:polycytidylic acid at the end of the first trimester. Control dams received saline injections at the same gestational time points (n= 10) or were untreated (n= 4). MIA-treated dams exhibited a strong immune response as indexed by transient increases in sickness behavior, temperature, and inflammatory cytokines. Although offspring born to control or MIA-treated dams did not differ on measures of physical growth and early developmental milestones, the MIA-treated animals exhibited subtle changes in cognitive development and deviated from species-typical brain growth trajectories. Longitudinal MRI revealed significant gray matter volume reductions in the prefrontal and frontal cortices of MIA-treated offspring at 6 months that persisted through the final time point at 45 months along with smaller frontal white matter volumes in MIA-treated animals at 36 and 45 months. These findings provide the first evidence of early postnatal changes in brain development in MIA-exposed nonhuman primates and establish a translationally relevant model system to explore the neurodevelopmental trajectory of risk associated with prenatal immune challenge from birth through late adolescence.SIGNIFICANCE STATEMENTWomen exposed to infection during pregnancy have an increased risk of giving birth to a child who will later be diagnosed with a neurodevelopmental disorder. Preclinical maternal immune activation (MIA) models have demonstrated that the effects of maternal infection on fetal brain development are mediated by maternal immune response. Since the majority of MIA models are conducted in rodents, the nonhuman primate provides a unique system to evaluate the MIA hypothesis in a species closely related to humans. Here we report the first longitudinal study conducted in a nonhuman primate MIA model. MIA-exposed offspring demonstrate subtle changes in cognitive development paired with marked reductions in frontal gray and white matter, further supporting the association between prenatal immune challenge and alterations in offspring neurodevelopment.

Community testing programs focused on the unvaccinated population are being enacted in populations with mixed vaccination status to mitigate SARS-CoV-2 spread. Presumably, these policies assume that the unvaccinated are driving transmission, though it is not well understood how viral spread occurs in mixed-status populations. Here, we analyze a model of transmission in which a variable fraction of the population is vaccinated, with unvaccinated individuals proactively screened for infection. By exploring a range of transmission rates, vaccine effectiveness (VE) scenarios, and rates of prior infection, this analysis reveals principles of viral spread in communities of mixed vaccination status, with implications for screening policies. As vaccination rates increase, the proportion of transmission driven by the unvaccinated population decreases, such that most community spread is driven by breakthrough infections once vaccine coverage exceeds 55% (omicron) or 80% (delta), with additional variation dependent on waning or boosted VE. More broadly, the potential impacts of unvaccinated-only screening fall into three distinct parameter regions: (I) “flattening the curve” with little impact on cumulative infections, (II) effectively suppressing transmission, and (III) negligible impact because herd immunity is reached without screening. By evaluating a wide range of scenarios, this work finds broadly that effective mitigation of SARS-CoV-2 transmission by unvaccinated-only screening is highly dependent on vaccination rate, population-level immunity, screening compliance, and vaccine effectiveness against the current variant.

Cabre, HE, Greenwalt, CE, Gould, LM, Hirsch, KR, Blue, MNM, and Smith-Ryan, AE. Exploring the "Athlete's Paradox": Division I cross-country runners demonstrate similar muscle characteristics to recreationally trained young adults. J Strength Cond Res XX(X): 000-000, 2021-Endurance training can influence body composition and muscle characteristics. Endurance athletes have demonstrated elevated intramuscular fat (IMF), yet individuals with greater body fat also demonstrate elevated IMF. The purpose of this study was to examine differences in muscle characteristics (echo intensity [EI] and muscle cross-sectional area [mCSA]) and body composition between Division I collegiate athletes and college-age adults matched for percent fat (%fat). Thirty cross-country athletes (XC) and 30 normal-weight (NW) recreationally active college students (male athletes: n = 30; female athletes: n = 30; mean ± SD: age: 19.2 ± 1.1 years; body mass: 61.7 ± 8.7 kg; %fat: 18.0 ± 5.2%) underwent a panoramic ultrasound scan of the vastus lateralis to evaluate EI and mCSA. A full-body dual-energy x-ray absorptiometry scan was used to assess fat mass (FM), lean mass (LM), and %fat. Independent t-tests were used to evaluate mCSA, EI, and body composition. Significance level was set at ≤ 0.05. There were no significant differences between the XC and NW cohorts in mCSA (mean difference [MD; XC - NW], -1.30 ± -0.40 cm3; p = 0.340) or EI (MD: 3.97 ± 2.66 a.u.; p = 0.478). Body composition was not different between the groups: FM (MD: -0.14 ± -0.54 kg; p = 0.848), LM (-3.07 ± 1.25 kg; p = 0.268), or bone mineral content (-0.21 ± 0.03 kg; p = 0.120). There were also no significant differences for any outcome variables when stratified by male athletes (p = 0.097-0.468) or female athletes (p = 0.055-0.700). These results suggest that XC athletes may have similar muscle characteristics to NW individuals when matched for %fat. Understanding and tracking muscle characteristics in XC athletes may be important for performance, injury prevention, and the transition to retirement.

Maternal obesity during pregnancy is associated with neurodevelopmental disorder (NDD) risk. We utilized integrative multi-omics to examine maternal obesity effects on offspring neurodevelopment in rhesus macaques by comparison to lean controls and two interventions. Differentially methylated regions (DMRs) from longitudinal maternal blood-derived cell-free fetal DNA (cffDNA) significantly overlapped with DMRs from infant brain. The DMRs were enriched for neurodevelopmental functions, methylation-sensitive developmental transcription factor motifs, and human NDD DMRs identified from brain and placenta. Brain and cffDNA methylation levels from a large region overlapping mir-663 correlated with maternal obesity, metabolic and immune markers, and infant behavior. A DUX4 hippocampal co-methylation network correlated with maternal obesity, infant behavior, infant hippocampal lipidomic and metabolomic profiles, and maternal blood measurements of DUX4 cffDNA methylation, cytokines, and metabolites. Ultimately, maternal obesity altered infant brain and behavior, and these differences were detectable in pregnancy through integrative analyses of cffDNA methylation with immune and metabolic biomarkers.

Understanding the effects of acute feeding on body composition and metabolic measures is essential to the translational component and practical application of measurement and clinical use. To investigate the influence of acute feeding on the validity of dual-energy X-ray absorptiometry (DXA), a four-compartment model (4C) and indirect calorimetry metabolic outcomes, thirty-nine healthy young adults (n 19 females; age: 21·8 (sd 3·1) years, weight; 71·5 (sd 10·0) kg) participated in a randomised cross-over study. Subjects were provided one of four randomised meals on separate occasions (high carbohydrate, high protein, ad libitum or fasted baseline) prior to body composition and metabolic assessments. Regardless of macronutrient content, acute feeding increased DXA percent body fat (%fat) for the total sample and females (average constant error (CE):–0·30 %; total error (TE): 2·34 %), although not significant (P = 0·062); the error in males was minimal (CE: 0·11 %; TE: 0·86 %). DXA fat mass (CE: 0·26 kg; TE: 0·75 kg) and lean mass (LM) (CE: 0·83 kg; TE: 1·23 kg) were not altered beyond measurement error for the total sample. 4C %fat was significantly impacted from all acute feedings (avg CE: 0·46 %; TE: 3·7 %). 4C fat mass (CE: 0·71 kg; TE: 3·38 kg) and fat-free mass (CE: 0·55 kg; TE: 3·05 kg) exceeded measurement error for the total sample. RMR was increased for each feeding condition (TE: 1666·9 kJ/d; 398 kcal/d). Standard pre-testing fasting guidelines may be important when evaluating DXA and 4C %fat, whereas additional DXA variables (fat mass and LM) may not be significantly impacted by an acute meal. Measuring body composition via DXA under less stringent pre-testing guidelines may be valid and increase feasibility of testing in clinical settings.

Bevacizumab (known by the tradename Avastin) is an antibody that binds VEGF and blocks its binding to VEGF receptors on endothelial cells, and is used to treat cancers and other diseases associated with excessive vascular growth. Our previous findings showed enhanced VEGF binding to Avastin in the presence of heparin, indicating that colocalizing heparin with Avastin could enhance VEGF inhibitory activity. Thus, the aim of the present study was to determine if conjugating Avastin and heparin to one another would lead to enhanced anti-VEGF activity. Avastin was conjugated to either biotin or streptavidin, and biotin–heparin was used to bring the two molecules into close proximity via biotin–streptavidin binding. Radioligand binding assays with 125 I-VEGF and cell migration assays using human umbilical vein endothelial cells were used to evaluate the impact of heparin on Avastin binding and activity. We found that bringing Avastin and heparin together, either on a surface or through streptavidin conjugation of Avastin, led to increased VEGF binding compared to that with each molecule alone. The heparin-mediated increase in VEGF binding was also noted at acidic pH where Avastin showed decreased VEGF binding. Conditions where Avastin and heparin showed enhanced VEGF binding also showed reduced VEGF-induced migration of human umbilical vein endothelial cells. These findings suggest design principles for a modified Avastin-based inhibitor of angiogenesis.

Current seasonal and pre-pandemic influenza vaccines induce short-lived predominantly strain-specific and limited heterosubtypic responses. To better understand how vaccine adjuvants AS03 and MF59 may provide improved antibody responses to vaccination, we interrogated serum from subjects who received 2 doses of inactivated monovalent influenza A/Indonesia/05/2005 vaccine with or without AS03 or MF59 using hemagglutinin (HA) microarrays. The arrays were designed to reflect both full length and globular head HA proteins derived from 17 influenza A subtypes (H1 to H16 and H18) and influenza B strains. We observed significantly increased strain-specific and broad homo- and hetero-subtypic antibody responses with both AS03 and MF59 adjuvanted vaccination with AS03 achieving a higher titer and breadth of IgG responses relative to MF59. Adjuvanted vaccine was also associated with the elicitation of stalk directed antibody. Finally, we established good correlation of the array antibody responses to H5 antigens with standard hemagglutination inhibition and microneutralization titers.

Background Nearly 6% of American men report having had sex with another male since puberty. However, as men age, their sexual repertoires likely change. Recent sexual behaviors may be more important with respect to risk for bacterial STDs. We investigated recent sexual behaviors and STD/HIV testing among US men who report having had sex with both men and women in their lifetime (MSMW). Methods MSMW aged 15–44 years who participated in the National Survey of Family Growth during 2011–2019 were included. MSMW were further classified based on gender of recent (past 12 months) sex partners: (1) both men and women, (2) only men and (3) only women. Weighted percentages and corresponding 95% confidence intervals (CI) of behaviors were estimated. Results Among all MSMW (n=801), 23% (95% CI: 20–27) reported recent sex with both men and women, 21% (95% CI: 17–24) with only men and 56% (95% CI: 51–61) with only women. Among MSMW who recently had sex with both men and women, half (52%, 95% CI: 41–62) identified as bisexual and almost half (46%, 95% CI: 36–56) had 4+ sex partners in the past year, higher than MSMW who recently had sex with only men (29%, 95% CI: 20–38) or only women (6%, 95% CI: 4–9). Compared to MSMW who recently had sex with both men and women, MSMW who recently had sex with men only were more likely to have had a recent HIV test (57%, 95% CI: 49–68 versus 30%, 95% CI: 21–39) and a recent STD test (55%, 95% CI: 46–64 versus 45%, 95% CI: 35–55). Conclusion MSMW are a heterogeneous group with respect to recent sexual behaviors and may have different sexual health needs. The collection of sexual history at clinical visits is critical to ensuring culturally competent sexual health care for this population.

Background As part of an ongoing sexual network study, we assessed the impact of COVID-19 on sexual behavior of men who have sex with men (MSM). Methods The Columbus, Ohio arm of the multi-site Network Epidemiology of Syphilis Transmission (NEST) study is following 241 MSM over two years. Participants attend quarterly visits with behavioral surveys and HIV/STI testing. In April 2020, we implemented an additional survey to measure the impact of COVID-19 on sexual behavior. Our analysis compared participants’ reported sexual behavior during two periods: April-July 2020 (T1) and August-December 2020 (T2). Results Of the 200 participants who completed at least one COVID-19 survey in either time period, 10 (5%) self-reported a previous COVID-19 diagnosis. We compared behaviors reported by 174 respondents who submitted surveys in both time periods. During T1, about half (46%) said they felt more anxious about sex since COVID-19; anxiety was similar during T2 (43%). Many reported engaging in online sexual activities, though we saw no meaningful differences by time period for starting or increasing chatting on hookup apps (T1=30%, T2=30%), sexting (T1=30%, T2=25%), or video chat sex (T1=16%, T2=14%). Watching pornography was reported more often in T1 than T2 (53% vs. 42%). Nearly a third of respondents (30%) in T1 reported that they were not having sex; this decreased to 17% in T2. Compared to pre-pandemic behavior, in T1 a majority of participants (74%) said they were less likely to have sex with a new partner, compared to 61% during T2. Conclusion During COVID-19, nearly half of MSM reported feeling more anxious about sex, and many turned to online activities in lieu of in-person sex. However, when comparing the early months of the pandemic to later months of 2020, more participants are resuming in-person sex, and willingness to have sex with new partners also rose.

Ischemic heart disease is the single most common cause of death worldwide with an annual death rate of over 9 million people. Genome-wide association studies have uncovered over 200 genetic loci underlying the disease, providing a deeper understanding of the causal mechanisms leading to it. However, in order to understand ischemic heart disease at the cellular and molecular level, it is necessary to identify the cell-type-specific circuits enabling dissection of driver variants, genes, and signaling pathways in normal and diseased tissues. Here, we provide the first detailed single-cell dissection of the cell types and disease-associated gene expression changes in the living human heart, using cardiac biopsies collected during open-heart surgery from control, ischemic heart disease, and ischemic and non-ischemic heart failure patients. We identify 84 cell types/states, grouped in 12 major cell types. We define markers for each cell type, providing the first extensive reference set for the live human heart. These major cell types include cardiovascular cells (cardiomyocytes, endothelial cells, fibroblasts), rarer cell types (B lymphocytes, neurons, Schwann cells), and rich populations of previously understudied layer-specific epicardial and endocardial cells. In addition, we reveal substantial differences in disease-associated gene expression at the cell subtype level, revealing t arterial pericytes as having a central role in the pathogenesis of ischemic heart disease and heart failure. Our results demonstrate the importance of high-resolution cellular subtype mapping in gaining mechanistic insight into human cardiovascular disease.

OBJECTIVES: Recent evidence is pointing toward the effect of nutrients on neurotransmission. Therefore, dietary patterns may impact the stress response as well as mental wellbeing. This study aims to investigate the relationship between dietary patterns and perceived stress as a way to shed light on the impact of diet quality on psychological stress. METHODS: An anonymous questionnaire combining three validated scales was distributed through several social media platforms. The questionnaire included the Food-Mood Questionnaire, the Perceived Stress Scale, and the Kessler-6 scale as well as questions assessing frequency of consumption of various tyrosine-rich foods. Inclusion criteria included adults 18 years old or older. Results were analyzed using Spearman's Rho correlation and principal component analysis using SPSS Version 24.0. RESULTS: Our results indicated that several components of the Mediterranean diet such as whole grains (P

Background The potential long-term effects of childhood fluoxetine therapy on brain serotonin systems were studied using a nonhuman primate model, the rhesus monkey. Methods Juvenile male rhesus (1–4 years of age, corresponding to 4–11 years of age in children) were treated orally with fluoxetine (2 mg/kg) or vehicle daily for 2 years and removed from treatment during the third year. Each treatment group was assigned an equal number of subjects with low and high transcription polymorphisms of MAOA. One year after discontinuation of treatment, positron emission tomography scans were conducted (n = 8 treated monkeys, n = 8 control monkeys) using [11C]DASB to quantify serotonin transporter in 16 cortical and subcortical regions. Results Fluoxetine-treated monkeys with MAOA low transcription polymorphism had significantly lower [11C]DASB binding potentials than control monkeys. This finding was seen throughout the brain but was strongest in prefrontal and cingulate cortices. The MAOA × fluoxetine interaction was enhanced by binding potentials that were nonsignificantly higher in monkeys with high transcription polymorphism. Conclusions Juvenile fluoxetine treatment has residual posttreatment effects on brain serotonin transporter that depend on MAOA genotype. MAOA genotype may be important to consider when treating children with fluoxetine.

Background and Purpose— In older populations, transient ischemic attack (TIA) and ischemic stroke have been linked to psychological factors, including posttraumatic stress disorder (PTSD). Whether PTSD also increases risk for early incident stroke in young adults is unknown. Methods— We prospectively assessed the incidence of TIA and ischemic stroke in a cohort of 987 855 young and middle-aged Veterans (mean age of 30.29±9.19 years; 87.8% men, 64.4% white) who first accessed care through the Veterans Health Administration from October 2001 to November 2014 and were free of TIA and ischemic stroke at baseline. For each outcome, time-varying multivariate Cox models were constructed to examine the effect of PTSD on incident stroke. We also assessed for effect modification by sex. Additional sensitivity analyses controlled for healthcare utilization. Results— Over a 13-year period, TIA and ischemic stroke were diagnosed in 766 and 1877 patients, respectively. PTSD was diagnosed in 28.6% of the sample during follow-up. In unadjusted analyses, PTSD was significantly associated with new-onset TIA (hazard ratio [HR], 2.02; 95% CI, 1.62–2.52) and ischemic stroke (HR, 1.62; 95% CI, 1.47–1.79). In fully adjusted models, the association between PTSD and incident TIA (HR, 1.61; 95% CI, 1.27–2.04) and ischemic stroke (HR, 1.36; 95% CI, 1.22–1.52) remained significant. The effect of PTSD on ischemic stroke risk was stronger in men than in women (HR, 0.63; 95% CI, 0.47–0.86; P =0.003), but no effect of sex was found for TIA. Conclusions— PTSD is associated with a significant increase in risk of early incident TIA and ischemic stroke independent of established stroke risk factors, coexisting psychiatric disorders, and healthcare utilization. Sex moderated the relationship for adults with ischemic stroke but not TIA. These findings suggest that psychological factors, including PTSD, may be important targets for future age-specific prevention strategies for young adults.