Adverse Skeletal Muscle Adaptations in Individuals Born Preterm-A Comprehensive Review.

Infants born preterm face an increased risk of deleterious effects on lung and brain health that can significantly alter long-term function and quality of life and even lead to death. Moreover, preterm birth is also associated with a heightened risk of diabetes and obesity later in life, leading to an increased risk of all-cause mortality in young adults born prematurely. While these preterm-birth-related conditions have been well characterized, less is known about the long-term effects of preterm birth on skeletal muscle health and, specifically, an individual's skeletal muscle hypertrophic potential later in life. In this review, we discuss how a confluence of potentially interrelated and self-perpetuating elements associated with preterm birth might converge on anabolic and catabolic pathways to ultimately blunt skeletal muscle hypertrophy, identifying critical areas for future research.

Alcohol Impairs Bioenergetics and Differentiation Capacity of Myoblasts from Simian Immunodeficiency Virus-Infected Female Macaques.

Alcohol misuse and HIV independently induce myopathy. We previously showed that chronic binge alcohol (CBA) administration, with or without simian immunodeficiency virus (SIV), decreases differentiation capacity of male rhesus macaque myoblasts. We hypothesized that short-term alcohol and CBA/SIV would synergistically decrease differentiation capacity and impair bioenergetic parameters in female macaque myoblasts. Myoblasts from naïve (CBA-/SIV-), vehicle [VEH]/SIV, and CBA/SIV (N = 4-6/group) groups were proliferated (3 days) and differentiated (5 days) with 0 or 50 mM ethanol (short-term). CBA/SIV decreased differentiation and increased non-mitochondrial oxygen consumption rate (OCR) versus naïve and/or VEH/SIV. Short-term alcohol decreased differentiation; increased maximal and non-mitochondrial OCR, mitochondrial reactive oxygen species (ROS) production, and aldolase activity; and decreased glycolytic measures, ATP production, mitochondrial membrane potential (ΔΨm), and pyruvate kinase activity. Mitochondrial ROS production was closely associated with mitochondrial network volume, and differentiation indices were closely associated with key bioenergetic health and function parameters. Results indicate that short-term alcohol and CBA non-synergistically decrease myoblast differentiation capacity. Short-term alcohol impaired myoblast glycolytic function, driving the bioenergetic deficit. Results suggest potentially differing mechanisms underlying decreased differentiation capacity with short-term alcohol and CBA, highlighting the need to elucidate the impact of different alcohol use patterns on myopathy.

Critical Emergency Department Interventions and Clinical Deterioration in Children With Nonsevere Traumatic Intracranial Hemorrhage.

OBJECTIVE: Substantial practice variation exists in the management of children with nonsevere traumatic intracranial hemorrhage (tICH). A comprehensive understanding of rates and timing of clinically important tICH, including critical interventions and deterioration, along with associated clinical and neuroradiographic characteristics, will inform accurate risk stratification. METHODS: We conducted a single-center retrospective cohort study of children aged younger than 18 years evaluated in the emergency department (ED) from May 1, 2014 to February 28, 2020 with tICH and initial Glasgow Coma Scale (GCS) score of higher than 8. We determined rates of clinically important tICH after injury and within 96 hours of ED arrival, defined as immediate ED interventions (intubation, hyperosmotic agents, or neurosurgery within 4 hours of arrival) or clinically important deterioration (signs/symptoms with change in management). Associations between outcome and clinical and neuroradiographic characteristics were calculated using individual logistic regression models. RESULTS: Our sample included 135 children. Clinically important tICH was observed in 13.3% (n = 18); 9 (6.7%) underwent immediate ED interventions and 9 (6.7%) developed deterioration. Most (93.3%, n = 127) presented with an initial GCS ≥ 14, including all children who later deteriorated. Initial GCS (P = 0.001) and nonaccidental trauma (P = 0.024) mechanism were associated with the outcome. None of the 71 (52.6%) children with initial GCS ≥ 14, isolated, nonepidural hemorrhage after accidental injury developed clinically important tICH. CONCLUSIONS: Clinically important tICH occurred in 13% of children with nonsevere tICH, and 7% of children who did not undergo immediate ED interventions later deteriorated, all of whom had an initial GCS ≥ 14. However, a subgroup of children was identified as low risk based on clinical and neuroradiographic characteristics.

An aerobic exercise intervention to improve metabolic health among people living with HIV with at-risk alcohol use: the ALIVE-Ex research study protocol.

BACKGROUND: Effective antiretroviral therapy (ART) in people living with HIV (PLWH) has improved life expectancy and increased risk of age-associated cardiometabolic comorbidities. At-risk alcohol use is more frequent among PLWH and increases the risk of health challenges. PLWH with at-risk alcohol use are more likely to meet criteria for prediabetes/diabetes and this is associated with impaired whole-body glucose-insulin dynamics. METHODS: The Alcohol & Metabolic Comorbidities in PLWH: Evidence Driven Interventions Study (ALIVE-Ex Study, NCT03299205) is a longitudinal, prospective, interventional study to determine the effects of an aerobic exercise protocol on improving dysglycemia among PLWH with at-risk alcohol use. The intervention is a moderate intensity aerobic exercise protocol implemented 3 days per week for 10 weeks at the Louisiana State University Health Sciences Center-New Orleans. Participants who have a fasting blood glucose level between 94 and 125 mg/dl will be enrolled in the study. Oral glucose tolerance tests, fitness assessments, and skeletal muscle biopsies will be performed pre- and post-exercise intervention. The primary outcome is to determine whether the exercise protocol improves measures of whole-body glucose-insulin dynamics, cardiorespiratory fitness, and skeletal muscle metabolic and bioenergetic function. Secondary outcomes are to determine whether the exercise intervention improves cognitive function and overall quality of life. Results generated will demonstrate the effect of exercise on glycemic measures in PLWH with subclinical dysglycemia and at-risk alcohol use. CONCLUSIONS: The proposed intervention will also have the potential to be scalable to promote lifestyle changes among PLWH, particularly in underserved communities.

Verbal Encouragement Improves Game Intensity, Technical Aspects, and Psychological Responses During Soccer-Specific Training.

BACKGROUND: Soccer match outcomes rely on technical accuracy, intensity of play, and athlete motivation, and these parameters can be developed during sport-specific practice such as during small-sided games (SSGs). Verbal encouragement as a coaching technique improves exercise intensity and athlete enjoyment (indicative of motivation), but the impact on technical performance alongside these critical parameters remains unknown. PURPOSE: To examine the effects of verbal encouragement on technical performance, exercise intensity, and enjoyment during SSGs. METHODS: Sixteen male youth soccer players (mean [SD]; age: 17.2 [0.4] y; height: 176.3 [7.0] cm; body mass: 68.0 [4.1] kg; body fat: 11.9% [2.2%]) completed 4 sessions of 4-per-side SSG without a goalkeeper. Two sessions were conducted as SSGs with verbal encouragement and 2 without verbal encouragement. Each SSG lasted 25 minutes (4 × 4-min work, 3-min passive recovery between bouts) on a 25 × 35-m pitch. Heart rate (HR) was continuously recorded, and rating of perceived exertion was collected after each SSG. Video analysis was used to quantify technical actions during SSG. Enjoyment was assessed after each SSG using the Physical Activity Enjoyment Scale. RESULTS: Paired t tests revealed that SSGs with verbal encouragement induced higher HR (% maximum HR and mean HR), rating of perceived exertion, and Physical Activity Enjoyment Scale score than SSGs without verbal encouragement (all P < .001, all d ≥ 0.92, large). Compared with SSGs without verbal encouragement, SSGs with verbal encouragement resulted in an increased percentage of successful passes (P < .001, d = 0.73, medium) and number of interceptions (P < .001, d = 0.89, large) and fewer lost balls (P < .001, d = 0.68, medium). CONCLUSIONS: Coaches should use verbal encouragement during SSGs to improve physical effort, technical performance, and psychological status in soccer players.

Monitoring mood state to improve performance in soccer players: A brief review.

Introduction: Psychological aspects of sport are key in maintaining athlete motivation and make a difference in competitive outcomes. Adjustments to training may be necessary according to athletes' emotional state. Therefore, it is important to assess and quantify mood states throughout the season in team sports, including among soccer players. The Profile of Mood States (POMS) is a widely used questionnaire that assesses emotional states characterized by positive or negative feelings and can be administered repeatedly to assess changes in mood state. This review aims to assess and summarize the current literature on mood state variation in soccer players with a specific focus on training loads, training modalities, and competitive performance. Methods: A literature search was systematically conducted and resulted in 156 records. After removing duplicates, items with irrelevant titles and abstracts were screened out, and full texts were then screened for relevance and compared with inclusion and exclusion criteria. The remaining 37 articles were included in the final qualitative synthesis. Results: POMS scores were related to variability in training load, intensity of the training period, modality of training exercises, competitive performance and time of day in soccer players. Common recommendations include monitoring the mood state of soccer players during training sessions, matches, and throughout training periods to detect early signs of psychological disturbance and aid in optimizing high-level training performance. Conclusion: The POMS allows for monitoring of players' psychological state, providing coaches with data to aid in adjusting acute program variables according to players' psychological states and improve performance. Results offer practical support for the use of a simple POMS measurement as part of an overall program to monitor the players' psychological states. Results also highlight how training choices (i.e., load and exercise modality) and competitive performance are related to mood states (i.e., tension, anger, confusion, depression, fatigue, and vigor).

Differential expression of adipocyte and myotube extracellular vesicle miRNA cargo in chronic binge alcohol-administered SIV-infected male macaques.

Our studies in chronic binge alcohol (CBA) -treated simian immunodeficiency virus (SIV)-infected macaques and in people living with HIV (PLWH) show significant alterations in metabolic homeostasis. CBA promotes a profibrotic phenotype in adipose tissue and skeletal muscle (SKM) and decreases adipose-derived stem cell and myoblast differentiation, making adipose and SKM potential drivers in metabolic dysregulation. Furthermore, we have shown that the differential expression of microRNAs (miRs) in SKM contributes to impaired myoblast differentiation potential. Beyond modulation of intracellular responses, miRs can be transported in extracellular vesicles (EVs) to mediate numerous cellular responses through intercellular and interorgan communication. This study tested the hypothesis that CBA alters concentration and miR cargo of EVs derived from adipocytes and myotubes isolated from SIV-infected male macaques. Fourteen male rhesus macaques received either CBA (2.5 g/kg/day) or sucrose (VEH) for 14.5 months. Three months following the initiation of CBA/VEH, all animals were infected with SIVmac251 and 2.5 months later were initiated on antiretroviral therapy. SKM and adipose tissue samples were collected at the study endpoint (blood alcohol concentration = 0 mM). EVs were isolated by ultracentrifugation of myotube and adipocyte cell culture supernatant. Nanoparticle tracking revealed no differences in concentration or size of particles between VEH and CBA groups. Adipocyte-derived EVs from CBA animals showed decreased miR-let-7a expression (p = 0.03). Myotube-derived EVs from CBA animals had decreased miR-16 (p = 0.04) and increased miR-133a and miR-133b (both p = 0.04) expression. These results indicate that CBA administration differentially regulates EV miR content but does not alter the number of EVs from adipocytes or myotubes. Future studies are warranted to determine the functional relevance of CBA-altered EV miR cargo and their role in intercellular and interorgan communication and metabolic dysregulation.

Effect of Intensified Training Camp on Psychometric Status, Mood State, and Hematological Markers in Youth Soccer Players.

During training camps, training load is purposefully intensified. Intensified training loads (TL) are associated with psychological variations, increased fatigue, insufficient recovery, decreased muscular performance, and biological changes in adult athletes, but whether these changes occur during training camps in youth athletes has not been established. The aim of this study was to assess changes in psychometric status, vertical jump performance (i.e., height), and hematological markers before and after an intensive training camp in youth soccer players. In this case, 15male youth soccer players (mean ± SD: age: 14.8 ± 0.4 years; height: 172.0 ± 6.9 cm, body mass: 60.8 ± 7.9 kg; training experience: 5.2 ± 0.7 years) completed a 2-week training program consisting of 1 week of moderate TL (MT) and 1 week of intensive training camp (TC). Rate of perceived exertion (RPE), TL, monotony, strain, and psychometric status (total quality of recovery (TQR) and well-being indices (sleep, stress, fatigue, and muscle soreness) were monitored before each first daily training session across two weeks. The profile of mood states (POMS), countermovement jump (CMJ) height, and blood markers (complete blood count, urea, and creatinine) were assessed before and after TC. TL (d = 5.39, large), monotony (d = 3.03, large), strain (d = 4.38, large), and well-being index (d = 7.5, large) scores increased and TQR (d = 4.6, large) decreased during TC. The TC increased tension, fatigue, and total mood disturbance and decreased vigor (all p <0.01). CMJ performance p < 0.01, d = 0.52, moderate), creatinine (p < 0.01, d = 1.29, large), and leukocyte concentration (p < 0.01, d = 1.4, large) and granulocyte concentration (p < 0.01, d = 1.93, large) increased after TC. Percentage of lymphocytes (p < 0.05, d = 1.17, large) and monocytes (p < 0.01, d = 1.05, large) decreased while the percentage of granulocytes (p < 0.05, d = 0.86, large) increased significantly. Well-being, quality of recovery, mood, granulocyte concentration, and creatinine were all altered during the week-long intensified training camp. These results may provide coaches with valuable information about psychometric status and physiological fatigue and recovery of youth soccer players to better prescribe and adjust training loads during intensive training periods.

Alcohol use, physical activity, and muscle strength moderate the relationship between body composition and frailty risk among people living with HIV.

BACKGROUND: Antiretroviral therapy has improved life expectancy among people living with HIV (PLWH). Despite increased longevity, PLWH are at increased risk of age-related comorbidities, including frailty. We examined the relationship between body composition and frailty among PLWH, and moderation of this relationship by substance use, physical activity (PA), and physical function. METHODS: Participants (n = 341; 71% male, 48 ± 10 years, body mass index (BMI) = 27.3 ± 7.0 kg/m2 ) enrolled in the New Orleans Alcohol Use in HIV (NOAH) study underwent measures of body composition, muscle strength, and gait speed. Whole blood phosphatidylethanol (PEth) was measured, and substance use and PA were self-reported. Frailty risk measures included the 58-Item Deficit Index (DI58) and the Veterans Aging Cohort Study (VACS) Index 1.0, where higher scores indicate greater frailty risk. RESULTS: Multivariable linear regression adjusted for age, sex, and race showed that higher fat-free mass index (FFMI), body fat (%), waist-to-hip ratio, and body mass index (BMI) ≥ 25.0 kg/m2 vs. < 25.0 kg/m2 were significantly (p < 0.05) associated with decreased frailty risk measured by the VACS Index, whereas adjusted analyses showed no association between body composition variables and the DI58 score. Recent alcohol use, muscle strength, and PA, but not lifetime alcohol use or gait speed, significantly moderated associations between body composition variables and frailty risk with medium-to-large effect sizes. Subgroup analyses revealed a negative relationship between DI58 and FFMI among people with PEth > 8 ng/ml and negative relationships of VACS Index with FFMI and WHR in people with lower muscle strength. Overweight or obese BMI categories were positively associated with DI58 in people with lower muscle strength or higher PA level but negatively associated in those with higher muscle strength. CONCLUSIONS: Our findings indicate that body composition has significant modulatory effects on frailty risk in PLWH, where obesity increases the risk of frailty and greater muscle mass may be protective, even in individuals who use alcohol. These results highlight the importance of considering body composition, physical activity, and physical function in assessing frailty risk in PLWH, particularly among individuals who use alcohol. Moreover, they support the implementation of physical activity interventions to ameliorate the risk of frailty in aging PLWH.

A Practical Approach to Assessing Physical Freshness: Utility of a Simple Perceived Physical Freshness Status Scale.

Background: Monitoring physical freshness is essential in assessing athletes' conditions during training periods, training sessions, or competitions. To date, no single physical freshness scale has been successfully validated against training load variables and widely used scales measuring different facets of physical freshness. Objective: In this study, we develop and test the practical utility of a perceived physical freshness (RPF) scale to monitor the condition of the athletes and to prevent excessive fatigue and insufficient recovery during training sessions or competitions. Methods: Sixteen professional male soccer players (mean ± SD age 26 ± 4 years) were enrolled. Training load (TL), monotony, strain, rate of perceived exertion (RPE), well-being indices (sleep, stress, fatigue, and muscle soreness), total quality recovery (TQR) and RPF were determined each day for two weeks of training, including a week intensified training (IW) and a week taper (TW). The validity of the RPF scale was assessed by measuring the level of agreement of a player's perceived physical freshness relative to their TL variables, recovery state and well-being indices during each training phase (IW and TW) and during the overall training period (TP). Results: RPF increased during the TW compared to IW (ES = 2.31, p < 0.001, large). For the TP, IW and TW, weekly RPF was related to weekly TL (r = −0.81, r = −0.80, r = −0.69, respectively), well-being (r = −0.91, r = −0.82, r = −0.84, respectively) and TQR (r = 0.76, r = 0.91, r = 0.52, respectively), all p < 0.01. For the TP, IW and TW, daily RPF was related to TL (r = −0.75, r = −0.66, r = −0.70, respectively), well-being (r = −0.84, r = −0.81, r = −0.78, respectively) and TQR (r = 0.82, r = 0.81, r = 0.75, respectively), all p < 0.01. Conclusions: RPF was effective for evaluating the professional soccer players' physical freshness and may be a strategy for coaches to monitor the physical, psycho-physiological, and psychometric state of the players before training session or matches.

Sex-specific mitochondrial dynamics and mitophagy response to muscle damage.

Muscle damage imposes stress on mitochondria resulting in mitochondrial fusion, fission, and mitophagy. Testosterone is a regulator of these processes. However, no study has examined the effect of sex-specific resistance exercise (RE)-induced hormonal response on mitochondrial dynamics and mitophagy after muscle damage in untrained men and women. Untrained men and women performed two sessions of 80 unilateral maximal eccentric knee extensions (ECC) followed by upper-body RE (ECC+RE) aimed to induce hormonal changes and maintain a similar lower body demands between conditions or 20 min seated rest (ECC+REST). Vastus lateralis samples were analyzed for gene and protein expression of OPA1, MFN1, DRP1, PINK1, and Parkin at baseline (BL), 12 and 24 h. Testosterone area under the curve was greater for ECC+RE than ECC+REST in men and was greater in men than women for both conditions. A significant time × sex × condition effect was found for Parkin protein expression. At 12 and 24 h, Parkin was lower for ECC + REST than ECC + RE for men; whereas, Parkin was increased at 24 h for women regardless of condition. A significant time effect was found for OPA1 protein expression increasing at 12 and 24 h. A significant time × sex × condition effects were found for MFN1, DRP1, and PINK1 gene expression with increases at 12 h in men for ECC + RE. A significant time × sex effect was found for OPA1 gene expression with a decrease at 12 h in men, and 12 h expression in men was lower than women. RE-induced hormonal changes promoted expression of fission, fusion, and mitophagy markers in men. With muscle damage, regardless of condition, expression of inner mitochondrial membrane fusion markers are promoted in both sexes; whereas, those for mitophagy were promoted in women but reduced in men.

Alcohol Impairs Immunometabolism and Promotes Naïve T Cell Differentiation to Pro-Inflammatory Th1 CD4+ T Cells.

CD4+ T cell differentiation to pro-inflammatory and immunosuppressive subsets depends on immunometabolism. Pro-inflammatory CD4+ subsets rely on glycolysis, while immunosuppressive Treg cells require functional mitochondria for their differentiation and function. Previous pre-clinical studies have shown that ethanol (EtOH) administration increases pro-inflammatory CD4+ T cell subsets; whether this shift in immunophenotype is linked to alterations in CD4+ T cell metabolism had not been previously examined. The objective of this study was to determine whether ethanol alters CD4+ immunometabolism, and whether this affects CD4+ T cell differentiation. Naïve human CD4+ T cells were plated on anti-CD3 coated plates with soluble anti-CD28, and differentiated with IL-12 in the presence of ethanol (0 and 50 mM) for 3 days. Both Tbet-expressing (Th1) and FOXP3-expressing (Treg) CD4+ T cells increased after differentiation. Ethanol dysregulated CD4+ T cell differentiation by increasing Th1 and decreasing Treg CD4+ T cell subsets. Ethanol increased glycolysis and impaired oxidative phosphorylation in differentiated CD4+ T cells. Moreover, the glycolytic inhibitor 2-deoxyglucose (2-DG) prevented the ethanol-mediated increase in Tbet-expressing CD4+ T cells but did not attenuate the decrease in FOXP3 expression in differentiated CD4+ T cells. Ethanol increased Treg mitochondrial volume and altered expression of genes implicated in mitophagy and autophagosome formation (PINK1 and ATG7). These results suggest that ethanol impairs CD4+ T cell immunometabolism and disrupts mitochondrial repair processes as it promotes CD4+ T cell differentiation to a pro-inflammatory phenotype.

Reducing Pediatric Emergency Department Prescription Errors.

BACKGROUND: Prescription errors are a significant cause of iatrogenic harm in the health care system. Pediatric emergency department (ED) patients are particularly vulnerable to error. We sought to decrease prescription errors in an academic pediatric ED by 20% over a 24-month period by implementing identified national best practice guidelines. METHODS: From 2017 to 2019, a multidisciplinary, fellow-driven quality improvement (QI) project was conducted using the Model for Improvement. Four key drivers were identified including simplifying the electronic order entry into prescription folders, improving knowledge of dosing by indication, increasing error feedback to prescribers, and creating awareness of common prescription pitfalls. Four interventions were subsequently implemented. Outcome measures included prescription errors per 1000 prescriptions written for all medications and top 10 error-prone antibiotics. Process measures included provider awareness and use of prescription folders; the balancing measure was provider satisfaction. Differences in outcome measures were assessed by statistical process control methodology. Process and balancing measures were analyzed using 1-way analysis of variance and χ2 testing. RESULTS: Before our interventions, 8.6 errors per 1000 prescriptions written were identified, with 62% of errors from the top 10 most error-prone antibiotics. After interventions, error rate per 1000 prescriptions decreased from 8.6 to 4.5 overall and from 20.1 to 8.8 for top 10 error-prone antibiotics. Provider awareness of prescription folders was significantly increased. CONCLUSION: QI efforts to implement previously defined best practices, including simplifying and standardizing computerized provider order entry (CPOE), significantly reduced prescription errors. Synergistic effect of educational and technological efforts likely contributed to the measured improvement.

Training, psychometric status, biological markers and neuromuscular fatigue in soccer.

The study examined the relationship between psychometric status, neuromuscular, and biochemical markers of fatigue in response to an intensified training (IT) period in soccer. Fifteen professional soccer players volunteered to participate in the study (mean ± SD: age: 25 ± 1 years; body height: 179 ± 7 cm, body mass: 73.7 ± 16.2 kg, experience: 13.2 ± 3 years). Training load, monotony, strain, Hooper index and total quality recovery (TQR) were determined for each training session during a 2-week of IT. Counter-movement jump (CMJ) and biochemical responses [testosterone, cortisol, testosterone-to-cortisol ratio (T/C ratio), creatine kinase, and C-reactive protein] were collected before and after IT. Results showed that IT induced significant increases in cortisol, creatine kinase and C-reactive protein and significant decreases in T/C ratio and CMJ performance from before to after IT (p < 0.01, p < 0.001, p < 0.001, p < 0.01, p < 0.05, respectively). However, testosterone did not differ from before to after IT (p > 0.05). Training loads were positively correlated with Hooper index (p < 0.05) and negatively correlated with total quality recovery (p < 0.05). Hooper index was positively correlated with cortisol (p < 0.05), T/C ratio (p < 0.01), and creatine kinase (p < 0.01), and negatively correlated with CMJ (p < 0.05). Furthermore, TQR was negatively correlated with T/C ratio (p < 0.01), creatine kinase (p < 0.001), and C-reactive protein (p < 0.05), and positively correlated with CMJ (p < 0.01). Neuromuscular fatigue, muscle damage, and change in the anabolic/catabolic state induced by the IT were related to well-being and perceived recovery state among professional soccer players.

A review of alcohol-pathogen interactions: New insights into combined disease pathomechanisms.

Progression of chronic infections to end-stage diseases and poor treatment results are frequently associated with alcohol abuse. Alcohol metabolism suppresses innate and adaptive immunity leading to increased viral load and its spread. In case of hepatotropic infections, viruses accelerate alcohol-induced hepatitis and liver fibrosis, thereby promoting end-stage outcomes, including cirrhosis and hepatocellular carcinoma (HCC). In this review, we concentrate on several unexplored aspects of these phenomena, which illustrate the combined effects of viral/bacterial infections and alcohol in disease development. We review alcohol-induced alterations implicated in immunometabolism as a central mechanism impacting metabolic homeostasis and viral pathogenesis in Simian immunodeficiency virus/human immunodeficiency virus infection. Furthermore, in hepatocytes, both HIV infection and alcohol activate oxidative stress to cause lysosomal dysfunction and leakage and apoptotic cell death, thereby increasing hepatotoxicity. In addition, we discuss the mechanisms of hepatocellular carcinoma and tumor signaling in hepatitis C virus infection. Finally, we analyze studies that review and describe the immune derangements in hepatotropic viral infections focusing on the development of novel targets and strategies to restore effective immunocompetency in alcohol-associated liver disease. In conclusion, alcohol exacerbates the pathogenesis of viral infections, contributing to a chronic course and poor outcomes, but the mechanisms behind these events are virus specific and depend on virus-alcohol interactions, which differ among the various infections.

Effect of Previous-Day Alcohol Ingestion on Muscle Function and Performance of Severe-Intensity Exercise.

PURPOSE: Many athletes report consuming alcohol the day before their event, which might negatively affect their performance. However, the effects of previous-day alcohol ingestion on performance are equivocal, in part, due to no standardization of alcohol dose in previous studies. The purpose of this study was to examine the impact of a standardized previous-day alcohol dose and its corresponding impact on morning-after muscular strength, muscular power, and muscular fatigue in a short-duration test and on performance of severe-intensity exercise. METHODS: On 2 occasions, 12 recreationally active individuals reported to the Applied Physiology Laboratory in the evening and ingested a beverage containing either 1.09 g ethanol·kg-1 fat-free body mass (ALC condition) or water (PLA condition). The following morning, they completed a hangover symptom questionnaire, vertical jumps, isometric midthigh pulls, biceps curls, and a constant-power cycle ergometer test to exhaustion. The responses from ALC and PLA were compared using paired-means t tests. RESULTS: Time to exhaustion in the cycle ergometer tests was less (P = .03) in the ALC condition (181 [39] s vs 203 [34] s; -11%, Cohen d = 0.61). There was no difference in performance in vertical jump test, isometric midthigh pulls, and biceps curls tests between the ALC and PLA conditions. CONCLUSIONS: Previous-day alcohol consumption significantly reduces morning-after performance of severe-intensity exercise. Practitioners should educate their athletes, especially those whose events rely on anaerobic capacity and/or a rapid response of the aerobic pathways, of the adverse effect of previous-day alcohol consumption on performance.

Unique circulating microRNA associations with dysglycemia in people living with HIV and alcohol use.

People living with HIV (PLWH) have increased prevalence of comorbid conditions including insulin resistance and at-risk alcohol use. Circulating microRNAs (miRs) may serve as minimally invasive indicators of pathophysiological states. We aimed to identify whether alcohol modulates circulating miR associations with measures of glucose/insulin dynamics in PLWH. PLWH (n = 96; 69.8% males) enrolled in the Alcohol & Metabolic Comorbidities in PLWH: Evidence-Driven Interventions (ALIVE-Ex) study were stratified into negative phosphatidylethanol (PEth < 8 ng/mL, n = 42) and positive PEth (PEth ≥ 8 ng/mL, n = 54) groups. An oral glucose tolerance test (OGTT) was administered, and total RNA was isolated from fasting plasma to determine absolute miR expression. Circulating miRs were selected based on their role in skeletal muscle (miR-133a and miR-206), pancreatic ß-cell (miR-375), liver (miR-20a), and adipose tissue (miR-let-7b, miR-146a, and miR-221) function. Correlation and multiple regression analyses between miR expression and adiponectin, 2 h glucose, insulin, and C-peptide values were performed adjusting for body mass index (BMI) category, age, sex, and viral load. miR-133a was negatively associated with adiponectin (P = 0.002) in the negative PEth group, and miR-20a was positively associated with 2 h glucose (P = 0.013) in the positive PEth group. Regression analyses combining miRs demonstrated that miR-133a (P < 0.001) and miR-221 (P = 0.010) together predicted adiponectin in the negative PEth group. miR-20a (P < 0.001) and miR-375 (P = 0.002) together predicted 2 h glucose in the positive PEth group. Our results indicate that associations between miRs and measures of glucose/insulin dynamics differed between PEth groups, suggesting that the pathophysiological mechanisms contributing to altered glucose homeostasis in PLWH are potentially modulated by alcohol use.

Alcohol, Resistance Exercise, and mTOR Pathway Signaling: An Evidence-Based Narrative Review.

Skeletal muscle mass is determined by the balance between muscle protein synthesis (MPS) and degradation. Several intracellular signaling pathways control this balance, including mammalian/mechanistic target of rapamycin (mTOR) complex 1 (C1). Activation of this pathway in skeletal muscle is controlled, in part, by nutrition (e.g., amino acids and alcohol) and exercise (e.g., resistance exercise (RE)). Acute and chronic alcohol use can result in myopathy, and evidence points to altered mTORC1 signaling as a contributing factor. Moreover, individuals who regularly perform RE or vigorous aerobic exercise are more likely to use alcohol frequently and in larger quantities. Therefore, alcohol may antagonize beneficial exercise-induced increases in mTORC1 pathway signaling. The purpose of this review is to synthesize up-to-date evidence regarding mTORC1 pathway signaling and the independent and combined effects of acute alcohol and RE on activation of the mTORC1 pathway. Overall, acute alcohol impairs and RE activates mTORC1 pathway signaling; however, effects vary by model, sex, feeding, training status, quantity, etc., such that anabolic stimuli may partially rescue the alcohol-mediated pathway inhibition. Likewise, the impact of alcohol on RE-induced mTORC1 pathway signaling appears dependent on several factors including nutrition and sex, although many questions remain unanswered. Accordingly, we identify gaps in the literature that remain to be elucidated to fully understand the independent and combined impacts of alcohol and RE on mTORC1 pathway signaling.

Differential Autophagy Response in Men and Women After Muscle Damage.

Following muscle damage, autophagy is crucial for muscle regeneration. Hormones (e.g., testosterone, cortisol) regulate this process and sex differences in autophagic flux exist in the basal state. However, to date, no study has examined the effect of a transient hormonal response following eccentric exercise-induced muscle damage (EE) between untrained young men and women. Untrained men (n = 8, 22 ± 3 years) and women (n = 8, 19 ± 1 year) completed two sessions of 80 unilateral maximal eccentric knee extensions followed by either upper body resistance exercise (RE; designed to induce a hormonal response; EE + RE) or a time-matched rest period (20 min; EE + REST). Vastus lateralis biopsy samples were collected before (BL), and 12 h, and 24 h after RE/REST. Gene and protein expression levels of selective markers for autophagic initiation signaling, phagophore initiation, and elongation/sequestration were determined. Basal markers of autophagy were not different between sexes. For EE + RE, although initiation signaling (FOXO3) and autophagy-promoting (BECN1) genes were greater (p < 0.0001; 12.4-fold, p = 0.0010; 10.5-fold, respectively) for women than men, autophagic flux (LC3-II/LC3-I protein ratio) did not change for women and was lower (p < 0.0001 3.0-fold) than men. Furthermore, regardless of hormonal changes, LC3-I and LC3-II protein content decreased (p = 0.0090; 0.547-fold, p = 0.0410; 0.307-fold, respectively) for men suggesting increased LC3-I lipidation and autophagosome degradation whereas LC3-I protein content increased (p = 0.0360; 1.485-fold) for women suggesting decreased LC3-I lipidation. Collectively, our findings demonstrated basal autophagy was not different between men and women, did not change after EE alone, and was promoted with the acute hormonal increase after RE only in men but not in women. Thus, the autophagy response to moderate muscle damage is promoted by RE-induced hormonal changes in men only.

Skeletal muscle bioenergetic health and function in people living with HIV: association with glucose tolerance and alcohol use.

At-risk alcohol use is prevalent and increases dysglycemia among people living with human immunodeficiency virus (PLWH). Skeletal muscle (SKM) bioenergetic dysregulation is implicated in dysglycemia and type 2 diabetes. The objective of this study was to determine the relationship between at-risk alcohol, glucose tolerance, and SKM bioenergetic function in PLWH. Thirty-five PLWH (11 females, 24 males, age: 53 ± 9 yr, body mass index: 29.0 ± 6.6 kg/m2) with elevated fasting glucose enrolled in the ALIVE-Ex study provided medical history and alcohol use information [Alcohol Use Disorders Identification Test (AUDIT)], then underwent an oral glucose tolerance test (OGTT) and SKM biopsy. Bioenergetic health and function and mitochondrial volume were measured in isolated myoblasts. Mitochondrial gene expression was measured in SKM. Linear regression adjusting for age, sex, and smoking was performed to examine the relationship between glucose tolerance (2-h glucose post-OGTT), AUDIT, and their interaction with each outcome measure. Negative indicators of bioenergetic health were significantly (P < 0.05) greater with higher 2-h glucose (proton leak) and AUDIT (proton leak, nonmitochondrial oxygen consumption, and bioenergetic health index). Mitochondrial volume was increased with the interaction of higher 2-h glucose and AUDIT. Mitochondrial gene expression decreased with higher 2-h glucose (TFAM, PGC1B, PPARG, MFN1), AUDIT (MFN1, DRP1, MFF), and their interaction (PPARG, PPARD, MFF). Decreased expression of mitochondrial genes were coupled with increased mitochondrial volume and decreased bioenergetic health in SKM of PLWH with higher AUDIT and 2-h glucose. We hypothesize these mechanisms reflect poorer mitochondrial health and may precede overt SKM bioenergetic dysregulation observed in type 2 diabetes.