A quantitative feedback intervention to reduce binge drinking in young adults.

OBJECTIVE: Existing binge drinking reduction interventions such as brief intervention and personalized normative feedback have shown modest impact. The purpose of this study was to evaluate the feasibility (recruitment and retention rates), acceptability, and preliminary efficacy testing of a short-term "know your numbers (KYN)" intervention on motivating young adults to reduce their engagement in binge drinking. METHOD: Young adults (N=94, mean age 21 years) with a history of binge drinking received a 4-week KYN intervention that included information about their U.S. Alcohol Use Disorders Test (USAUDIT) scores and the alcohol biomarker phosphatidylethanol (PEth) level in relationship to different risk levels of alcohol use. At baseline and 4-weeks, measures included USAUDIT scores, PEth levels, motivation (Alcohol Contemplation Ladder) and other drinking measures. Focus groups were conducted at 4-weeks for feedback on the KYN approach. RESULTS: The recruitment rate was 82.26% (retention rate 76.9%). At 4-weeks there was a 62% increase in contemplation scores (indicating higher motivation), a decrease in USADUIT scores with an increase in the percent of participants classified as low-risk drinkers. No differences were found between baseline and 4-week PEth levels or number of binge episodes. Focus group results revealed satisfaction with the KYN approach but the need to understand how PEth levels and USAUDIT scores corresponded to health consequences and alcohol use levels. CONCLUSIONS: Results from this pilot study support the acceptability and potential use of a KYN approach in helping young adults understand their drinking levels.

The six-minute step test can predict COPD exacerbations: a 36-month follow-up study.

The six-minute step test (6MST) has been shown to be effective in assessing exercise capacity in individuals with COPD regardless of severity and, despite its easy execution, accessibility and validity, information on the prognostic power of this test remains uncertain. The aim of this study is to investigate whether the 6MST can predict the occurrence of exacerbations in patients with COPD. This is a prospective cohort study with a 36-month follow-up in patients with COPD. All patients completed a clinical assessment, followed by pulmonary function testing and a 6MST. The 6MST was performed on a 20 cm high step; heart rate, blood pressure, oxygen saturation, BORG dyspnea and fatigue were collected. Sixty-four patients were included in the study, the majority being elderly men. Performance on the 6MST demonstrated lower performance compared to normative values proposed in the literature, indicating a reduced functional capacity. Kaplan Meier analysis revealed that ≤ 59 steps climbed during the 6MST was a strong predictor of COPD exacerbation over a 36-month follow-up. We have identified a minimal threshold number of steps (≤ 59) obtained through the 6MST may be able predict the risk of exacerbations in patients with COPD.

Mentoring strategies to support diversity in research-focused junior faculty: A scoping review.

Objective: The purpose of this scoping review is two-fold: to assess the literature that quantitatively measures outcomes of mentorship programs designed to support research-focused junior faculty and to identify mentoring strategies that promote diversity within academic medicine mentoring programs. Methods: Studies were identified by searching Medline using MESH terms for mentoring and academic medicine. Eligibility criteria included studies focused on junior faculty in research-focused positions, receiving mentorship, in an academic medical center in the USA, with outcomes collected to measure career success (career trajectory, career satisfaction, quality of life, research productivity, leadership positions). Data were abstracted using a standardized data collection form, and best practices were summarized. Results: Search terms resulted in 1,842 articles for title and abstract review, with 27 manuscripts meeting inclusion criteria. Two studies focused specifically on women, and four studies focused on junior faculty from racial/ethnic backgrounds underrepresented in medicine. From the initial search, few studies were designed to specifically increase diversity or capture outcomes relevant to promotion within academic medicine. Of those which did, most studies captured the impact on research productivity and career satisfaction. Traditional one-on-one mentorship, structured peer mentorship facilitated by a senior mentor, and peer mentorship in combination with one-on-one mentorship were found to be effective strategies to facilitate research productivity. Conclusion: Efforts are needed at the mentee, mentor, and institutional level to provide mentorship to diverse junior faculty on research competencies and career trajectory, create a sense of belonging, and connect junior faculty with institutional resources to support career success.

Feasibility, impact, and priority of key strategies to enhance diverse and inclusive training programs in clinical and translational research: A mixed methods study.

Background: Enhancing diversity in the scientific workforce is a long-standing issue. This study uses mixed methods to understand the feasibility, impact, and priority of six key strategies to promote diverse and inclusive training and contextualize the six key strategies across Clinical and Translational Science Awards (CTSAs) Program Institutions. Methods: Four breakout sessions were held at the NCATS 2020 CTSA Program annual meeting focused on diversity, equity, and inclusion (DEI) efforts. This paper focuses on the breakout session for Enhancing DEI in Translational Science Training Programs. Data were analyzed using a mixed methods convergent approach. The quantitative strand includes the online polling results. The qualitative strand includes the breakout session and the chat box in response to the training presentation. Results: Across feasibility, impact, and priority questions, prioritizing representation ranked number 1. Building partnerships ranked number 2 in feasibility and priority, while making it personal ranked number 2 for impact. Across each strategy, rankings supported the qualitative data findings in feasibility through shared experiences, impact in the ability to increase DEI, and priority rankings in comparison to the other strategies. No divergence was found across quantitative and qualitative data findings. Conclusion: Findings provide robust support for prioritizing representation as a number one strategy to focus on in training programs. Specifically, this strategy can be operationalized through integration of community representation, diversity advocates, and adopting a holistic approach to recruiting a diverse cadre of scholars into translational science training programs at the national level across CTSAs.

Advancing diversity, equity, and inclusion within clinical and translational science training programs: A qualitative content analysis of the training breakout session at the national CTSA program meeting.

Background: Diversity, equity, and inclusion (DEI) in clinical and translational science (CTS) are paramount to driving innovation and increasing health equity. One important area for improving diversity is among trainees in CTS programs. This paper reports on findings from a special session at the November 2020 Clinical and Translational Science Award (CTSA) national program meeting that focused on advancing diversity and inclusion within CTS training programs. Methods: Using qualitative content analysis, we identified approaches brought forth to increase DEI in KL2 career development and other training programs aimed at early-stage CTS investigators, beyond the six strategies put forth to guide the breakout session (prioritizing representation, building partnerships, making it personal, designing program structure, improving through feedback, and winning endorsement). We used an inductive qualitative content analysis approach to identify themes from a transcript of the panel of KL2 program leaders centered on DEI in training programs. Results: We identified four themes for advancing DEI within CTS training programs: 1) institutional buy-in; 2) proactive recruitment efforts; 3) an equitable application process; and 4) high-quality, diverse mentorship. Conclusion: Implementing these strategies in CTS and other training programs will be an important step for advancing DEI. However, processes need to be established to evaluate the implementation and effectiveness of these strategies through continuous quality improvement, a key component of the CTSA program. Training programs within the CTSA are well-positioned to be leaders in this critical effort to increase the diversity of the scientific workforce.

The effects of COVID-19 on respiratory muscle performance: making the case for respiratory muscle testing and training.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection results in multiorgan damage primarily mediated by viral infiltration via angiotensin-converting enzyme-2 receptors on the surface of cells. A primary symptom for many patients is exertional dyspnoea which may persist even beyond recovery from the viral infection. Respiratory muscle (RM) performance was hypothesised as a contributing factor to the severity of coronavirus disease 2019 (COVID-19) symptoms, such as dyspnoea, and outcomes. This was attributed to similarities between patient populations at elevated risk for severe COVID-19 symptoms and those with a greater likelihood of baseline RM weakness and the effects of prolonged mechanical ventilation. More recent evidence suggests that SARS-CoV-2 infection itself may cause damage to the RM, and many patients who have recovered report persistent dyspnoea despite having mild cases, normal lung function or undamaged lung parenchyma. These more recent findings suggest that the role of RM in the persistent dyspnoea due to COVID-19 may be more substantial than originally hypothesised. Therefore, screening for RM weakness and providing interventions to improve RM performance appears to be important for patients with COVID-19. This article will review the impact of SARS-CoV-2 infection on RM performance and provide clinical recommendations for screening RM performance and treatment interventions.

Hemispheric lateralization, endothelial function, and arterial compliance in chronic post-stroke individuals: A cross-sectional exploratory study.

Purpose/Aim: Cardiovascular function is controlled and regulated by a functional brain-heart axis. Although the exact mechanism is not fully understood, several studies suggest a hemispheric asymmetry in the neural control of cardiovascular function. Thus, the purpose of this study was to examine whether endothelial function and arterial compliance differ between individuals with left- and right-sided strokes.Materials and Methods: This was a cross-sectional exploratory study. Thirty individuals more than 6 months after stroke participated in the study. The endothelial function was assessed by ultrasound-measured flow-mediated dilation of the nonparetic arm brachial artery (baFMD). The arterial stiffness was assessed by measuring carotid-femoral pulse wave velocity (cfPWV) and central aortic pulse wave analysis [augmentation index (AIx), augmentation index normalized to a heart rate of 75 bpm (AIx@75) and reflection magnitude (RM)] using applanation tonometry. Results: Participants with right-sided stroke had worse endothelial function than those with left-sided stroke. This difference (baFMD = 2.51%) was significant (p = 0.037), and it represented a medium effect size (r = 0.38). Likewise, they had higher arterial stiffness than those with left-sided stroke. This difference (AIx = 10%; RM = 7%) was significant (p = 0.011; p = 0.012), and it represented a medium effect size (r = 0.48; r = 0.47).Conclusions: Our findings suggest that individuals with right-sided stroke have reduced endothelial function and arterial compliance compared to those with left-sided stroke. These data may indicate that those with right-sided strokes are more susceptible to cardiovascular events.

DNA Hypomethylation as a Potential Link between Excessive Alcohol Intake and Cardiometabolic Dysfunction in Morbidly Obese Adults.

A large percentage of obese patients in the United States suffer a comorbid substance use disorder, mainly alcohol use. Alcohol consumption interferes with the absorption of dietary methyl donors such as folate required for the one-carbon metabolism pathway and subsequently for DNA methylation. In this study, we assessed the association between alcohol consumption and DNA methylation in obese subjects. We obtained visceral adipose tissue (VAT) biopsies from bariatric patients. DNA methylation of 94 genes implicated in inflammation and immunity were analyzed in VAT in relation to alcohol consumption data obtained via questionnaires. Vasoreactivity was measured in the brachial artery and the VAT-isolated arterioles. Pro-inflammatory genes were significantly hypomethylated in the heavy drinking category correlating with higher levels of circulating inflammatory cytokines. Alcohol consumption correlated positively with body mass index (BMI), fat percentage, insulin resistance, impaired lipid profile, and systemic inflammation and negatively with plasma folate and vitamin B12, inflammatory gene DNA methylation, and vasoreactivity. In conclusion, these data suggest that alcohol intake is associated with lower DNA methylation and higher inflammation and cardiometabolic risk in obese individuals.

Alcohol Consumption: A New Risk Factor for Arterial Stiffness?

The relationship between alcohol consumption and cardiovascular disease risk is complex. Low-to-moderate daily alcohol consumption (1-2 drinks/day) is associated with reduced risk, whereas greater amounts of alcohol consumption and a "binge" pattern of drinking are associated with increased cardiovascular risk and mortality. Arterial stiffness may help explain the complex relationship. This integrated review summarizes data from studies examining the associations between alcohol consumption and pulse wave velocity, a gold standard measure of arterial stiffness. We also briefly review the concept and methodology of pulse wave velocity measurement as well as the mechanisms of alcohol-induced arterial stiffening. Findings among the different studies reviewed were inconsistent with methodological challenges related to alcohol use assessment. While making specific conclusions regarding this relationship is tenuous; the data suggest that excessive alcohol consumption or a binge drinking pattern is associated with increased arterial stiffness.

Effects of Exercise Mode on Improving Cardiovascular Function and Cardiorespiratory Fitness After Bariatric Surgery: A Narrative Review.

ABSTRACT: Obesity affects 600 million people globally and increases the risk of developing cardiovascular disease, stroke, diabetes, and cancer. Bariatric surgery is an increasingly popular therapeutic intervention for morbid obesity to induce rapid weight loss and reduce obesity-related comorbidities. However, some bariatric surgery patients, after what is considered a successful surgical procedure, continue to manifest obesity-related health issues, including weight gain, reduced physical function, persistent elevations in blood pressure, and reduced cardiorespiratory fitness. Cardiorespiratory fitness is a strong predictor of mortality and several health outcomes and could be improved by an appropriate exercise prescription after bariatric surgery. This review provides a broad overview of exercise training for patients after bariatric surgery and discusses cardiorespiratory fitness and other potential physiological adaptations in response to exercise training.

The physiological benefits of sitting less and moving more: Opportunities for future research.

Sedentary behavior (SB) and physical activity (PA) are important risk factors of cardiovascular disease morbidity and mortality. In addition to increasing the amount of moderate-to-vigorous PA (MVPA), the current PA guidelines recommend that adults should reduce SB, or any waking activity performed while sitting, reclining, or lying, with low energy expenditure. While mounting evidence has emphasized the benefits of increasing MVPA, little has focused on the effect of SB on health. Therefore, this review discusses the pathophysiological effects of SB and the potential physiological benefits of reducing/breaking up SB at the levels below the current guidelines for PA. Such knowledge is important, given that the majority of the United States population performs insufficient or no MVPA and is at high risk of being negatively impacted by SB. Interventions targeting sedentary time, such as breaking up SB by standing and moving, may be safe, feasible, and applicable to execute daily for a wide range of the population. This review also discusses the importance of monitoring SB in the era of the coronavirus disease 2019 (COVID-19) pandemic and the clinical implications of sitting less and moving more.

DNA methylation profile of genes involved in inflammation and autoimmunity correlates with vascular function in morbidly obese adults.

Obesity is a major risk factor for cardiovascular disease. Blood-detected epigenetic profiles may serve as non-invasive clinically relevant biomarkers. Therefore, we investigated DNA methylation of genes involved in inflammation in peripheral blood of obese subjects and lean controls and their correlation with cardiometabolic measurements. We obtained blood and adipose tissue (AT) samples from bariatric patients (n = 24) and control adults (n = 24). AT-isolated arterioles were tested for flow-induced dilation (FID) and production of nitric oxide (NO) and reactive oxygen species (ROS). Brachial artery flow-mediated dilation (FMD) was measured via doppler ultrasound. Promoter methylation of 94 genes involved in inflammation and autoimmunity were analysed in whole-blood DNA in relation to vascular function and cardiometabolic risk factors. 77 genes had ahigher methylated fraction in the controls compare obese subjects and 28 proinflammatory genes were significantly hypomethylated in the obese individuals; on top of these genes are CXCL1, CXCL12, CXCL6, IGF2BP2, HDAC4, IL12A, and IL17RA. Fifteen of these genes had significantly higher mRNA in obese subjects compared to controls; on top of these genes are CXCL6, TLR5, IL6ST, EGR1, IL15RA, and HDAC4. Methylation % inversely correlated with BMI, total fat %, visceral fat%, blood pressure, fasting plasma insulin, serum IL6 and C-reactive protein, arteriolar ROS, and alcohol consumption and positive correlations with lean %, HDL, plasma folate and vitamin B12, arteriolar FID and NO production, and brachial FMD. Our results suggest that vascular dysfunction in obese adults may be attributed to asystemic hypomethylation and over expression of the immune-related genes.

Longitudinal physical performance and blood pressure changes in older women: Findings form the women's health initiative.

BACKGROUND: This study evaluated the association between changes in physical performance and blood pressure (BP) (e.g., systolic [SBP], diastolic [DBP], pulse pressure) in older women. METHODS: 5627 women (mean age 69.8 ± 3.7 y) with grip strength, chair stand, gait speed performance and clinic-measured BP at baseline and at least one follow-up (years 1, 3 or 6) were included. Generalized estimating equation analysis of multivariable models with standardized point estimates described the longitudinal association between physical performance and BP changes in the overall cohort, and in models stratified by baseline cardiovascular disease (CVD), time-varying antihypertensive medication use (none, ≥1) and enrollment age (65-69 y; 70-79 y). RESULTS: Overall, each z-score unit increment in grip strength was associated with 0.59 mmHg (95% CI 0.10, 1.08) higher SBP, and 0.39 mmHg (95% CI 0.11, 0.67) higher DBP. In stratified models, a standardized increment in grip strength was associated with higher SBP in women without CVD (0.81; 95% CI 0.23-1.39), among antihypertensive medication users (0.93; 95% CI 0.44, 1.41) and non-users (0.37; 95% CI 0.03, 0.71), and in those aged 65-69 y (0.64; 95% CI 0.04, 1.24). Similarly, a standardized increment in any of the three performance measures was associated with modestly higher DBP in antihypertensive medication users, and those aged 70-79 y. Associations between any performance measure and pulse pressure change were not significant. CONCLUSION: These results suggest a positive, and statistically significant relationship between physical performance and BP that appears to be influenced by CVD history, antihypertensive medication use, and age.

Differential effects of obesity on visceral versus subcutaneous adipose arteries: role of shear-activated Kir2.1 and alterations to the glycocalyx.

Obesity imposes well-established deficits to endothelial function. We recently showed that obesity-induced endothelial dysfunction was mediated by disruption of the glycocalyx and a loss of Kir channel flow sensitivity. However, obesity-induced endothelial dysfunction is not observed in all vascular beds: visceral adipose arteries (VAAs), but not subcutaneous adipose arteries (SAAs), exhibit endothelial dysfunction. To determine whether differences in SAA versus VAA endothelial function observed in obesity are attributed to differential impairment of Kir channels and alterations to the glycocalyx, mice were fed a normal rodent diet, or a high-fat Western diet to induce obesity. Flow-induced vasodilation (FIV) was measured ex vivo. Functional downregulation of endothelial Kir2.1 was accomplished by transducing adipose arteries from mice and obese humans with adenovirus containing a dominant-negative Kir2.1 construct. Kir function was tested in freshly isolated endothelial cells seeded in a flow chamber for electrophysiological recordings under fluid shear. Atomic force microscopy was used to assess biophysical properties of the glycocalyx. Endothelial dysfunction was observed in VAAs of obese mice and humans. Downregulating Kir2.1 blunted FIV in SAAs, but had no effect on VAAs, from obese mice and humans. Obesity abolished Kir shear sensitivity in VAA endothelial cells and significantly altered the VAA glycocalyx. In contrast, Kir shear sensitivity was observed in SAA endothelial cells from obese mice and effects on SAA glycocalyx were less pronounced. We reveal distinct differences in Kir function and alterations to the glycocalyx that we propose contribute to the dichotomy in SAA versus VAA endothelial function with obesity.NEW & NOTEWORTHY We identified a role for endothelial Kir2.1 in the differences observed in VAA versus SAA endothelial function with obesity. The endothelial glycocalyx, a regulator of Kir activation by shear, is unequally perturbed in VAAs as compared with SAAs, which we propose results in a near complete loss of VAA endothelial Kir shear sensitivity and endothelial dysfunction. We propose that these differences underly the preserved endothelial function of SAA in obese mice and humans.

Precision Medicine and Physical Therapy: A Healthy Living Medicine Approach for the Next Century.

There is a reciprocal relationship between common health conditions encountered in physical therapist practice, disability, and healthy living factors, such as physical inactivity, blood pressure, sleep quality, diet, and obesity. This relationship is apparent across all practice settings. Physical therapists are well positioned in the health care system to mitigate chronic disease by routinely screening and addressing healthy living factors to improve overall health and lower the risk for chronic disease (healthy living medicine). However, there are several challenges to the successful implementation of this framework in physical therapist practice. This Perspective will elucidate this relationship between healthy living behaviors and physical therapist practice, review the current state of practice regarding screening and intervention of 5 key healthy living behaviors, and outline future steps the profession can take toward implementing precision medicine using a healthy living medicine approach.

Cholesterol-Induced Suppression of Endothelial Kir Channels Is a Driver of Impairment of Arteriolar Flow-Induced Vasodilation in Humans.

Dyslipidemia-induced endothelial dysfunction is an important factor in the progression of cardiovascular disease; however, the underlying mechanisms are unclear. Our recent studies demonstrated that flow-induced vasodilation (FIV) is regulated by inwardly rectifying K+ channels (Kir2.1) in resistance arteries. Furthermore, we showed that hypercholesterolemia inhibits Kir2.1-dependent vasodilation. In this study, we introduced 2 new mouse models: (1) endothelial-specific deletion of Kir2.1 to demonstrate the role of endothelial Kir2.1 in FIV and (2) cholesterol-insensitive Kir2.1 mutant to determine the Kir2.1 regulation in FIV under hypercholesterolemia. FIV was significantly reduced in endothelial-specific Kir2.1 knock-out mouse mesenteric arteries compared with control groups. In cholesterol-insensitive Kir2.1 mutant mice, Kir2.1 currents were not affected by cyclodextrin and FIV was restored in cells and arteries, respectively, with a hypercholesterolemic background. To extend our observations to humans, 16 healthy subjects were recruited with LDL (low-density lipoprotein)-cholesterol ranging from 51 to 153 mg/dL and FIV was assessed in resistance arteries isolated from gluteal adipose. Resistance arteries from participants with >100 mg/dL LDL (high-LDL) exhibited reduced FIV as compared with those participants with <100 mg/dL LDL (low-LDL). A significant negative correlation was observed between LDL cholesterol and FIV in high-LDL. Expressing dominant-negative Kir2.1 in endothelium blunted FIV in arteries from low-LDL but had no further effect on FIV in arteries from high-LDL. The Kir2.1-dependent vasodilation more negatively correlated to LDL cholesterol in high-LDL. Overexpressing wild-type Kir2.1 in endothelium fully recovered FIV in arteries from participants with high-LDL. Our data suggest that cholesterol-induced suppression of Kir2.1 is a major mechanism underlying endothelial dysfunction in hypercholesterolemia.

The Influence of Sedentary Behavior on the Relationship Between Cognitive Function and Vascular Function in Older Adults with and without Chronic Kidney Disease.

Cognitive impairment and vascular dysfunction are common in older adults with and without chronic kidney disease (CKD). Older adults with and without CKD are also sedentary - a behavior associated with cognitive and vascular function. The objective of this study was to explore whether sedentary behavior influenced the relationship between cognitive and vascular function in older adults with preclinical cognitive impairment with and without CKD. In our study, 48 older adults underwent assessment of cognition, vascular compliance, and sedentary behavior, and relationships were explored with regression moderation analysis. Sedentary time and breaks did not moderate the relationship between vascular and cognitive function. Although significant moderation was not found, cognition, vascular function, and sedentary behavior are important to assess when evaluating older adults with and without CKD.