Differentially co-expressed myofibre transcripts associated with abnormal myofibre proportion in chronic obstructive pulmonary disease.

Background: Skeletal muscle dysfunction is a common extrapulmonary manifestation of chronic obstructive pulmonary disease (COPD). Alterations in skeletal muscle myosin heavy chain expression, with reduced type I and increased type II myosin heavy chain expression, are associated with COPD severity when studied in largely male cohorts. The objectives of this study were (1) to define an abnormal myofibre proportion phenotype in both males and females with COPD and (2) to identify transcripts and transcriptional networks associated with abnormal myofibre proportion in COPD.

Bacterial pneumonia-induced shedding of epithelial heparan sulfate inhibits the bactericidal activity of cathelicidin in a murine model.

Bacterial pneumonia is a common clinical syndrome leading to significant morbidity and mortality worldwide. In the current study, we investigate a novel, multidirectional relationship between the pulmonary epithelial glycocalyx and antimicrobial peptides in the setting of methicillin-resistant (MRSA) pneumonia. Using an in vivo pneumonia model, we demonstrate that highly sulfated heparan sulfate (HS) oligosaccharides are shed into the airspaces in response to MRSA pneumonia.

How to use new antibiotics in the therapy of serious multidrug resistant Gram-negative infections?

Purpose Of Review: Multidrug resistant Gram-negative infections are becoming more common and pose a serious threat to both individual patients and the population as a whole. Treatment of these infections can be difficult and result in significant morbidity and mortality. The purpose of this review is to discuss information and strategies for using new antibiotics to combat these infections.

Hospital trajectories and early predictors of clinical outcomes differ between SARS-CoV-2 and influenza pneumonia.

Background: A comparison of pneumonias due to SARS-CoV-2 and influenza, in terms of clinical course and predictors of outcomes, might inform prognosis and resource management. We aimed to compare clinical course and outcome predictors in SARS-CoV-2 and influenza pneumonia using multi-state modelling and supervised machine learning on clinical data among hospitalised patients.

Methods: This multicenter retrospective cohort study of patients hospitalised with SARS-CoV-2 (March-December 2020) or influenza (Jan 2015-March 2020) pneumonia had the composite of hospital mortality and hospice discharge as the primary outcome.

The Predictive Potential of Elevated Serum Inflammatory Markers in Determining the Need for Intubation in CoVID-19 Patients.

Introduction: The predictive potential of demographics, clinical characteristics, and inflammatory markers at admission to determine future intubation needs of hospitalised CoVID-19 patients is unknown. The study aimed to determine the predictive potential of elevated serum inflammatory markers in determining the need for intubation in CoVID-19 Patients.

Methods: In a retrospective cohort study of hospitalised SARS-CoV2 positive patients, single and multivariable regression analyses were used to determine covariate effects on intubation odds, and a minimax concave penalty regularised logistic regression was used to build a predictive model.

Elevated glycohemoglobin is linked to critical illness in CoVID-19: a retrospective analysis.

Background: Several studies have explored hospitalization risk factors with the novel coronavirus disease 2019 (COVID-19) infection. Our goal was to identify clinical characteristics outside of laboratory or radiologic data associated with intubation or death within 7 days of admission.

Methods: The first 436 patients admitted to the University of Colorado Hospital (Denver metropolitan area) with confirmed COVID-19 were included.

Muscle transcriptional networks linked to resistance exercise training hypertrophic response heterogeneity.

The skeletal muscle hypertrophic response to resistance exercise training (RT) is highly variable across individuals. The molecular underpinnings of this heterogeneity are unclear. This study investigated transcriptional networks linked to RT-induced muscle hypertrophy, classified as ) predictive of hypertrophy, ) responsive to RT independent of muscle hypertrophy, or ) plastic with hypertrophy.

Associations of muscle lipid content with physical function and resistance training outcomes in older adults: altered responses with metformin.

Preserving muscle mass and strength is critical for long-term health and longevity. Age-related muscle lipid accumulation has been shown to be detrimental to muscle health. In healthy older individuals, we sought to determine whether muscle lipid content, determined from computed tomography, is associated with self-reported physical function, laboratory-measured performance, and the response to progressive resistance training (PRT), and how metformin may alter these responses (N = 46 placebo, 48 metformin).

Metformin alters skeletal muscle transcriptome adaptations to resistance training in older adults.

Evidence from clinical trials and observational studies suggests that both progressive resistance exercise training (PRT) and metformin delay a variety of age-related morbidities. Previously, we completed a clinical trial testing the effects of 14 weeks of PRT + metformin (metPRT) compared to PRT with placebo (plaPRT) on muscle hypertrophy in older adults. We found that metformin blunted PRT-induced muscle hypertrophic response.

Rehabilitative Impact of Exercise Training on Human Skeletal Muscle Transcriptional Programs in Parkinson's Disease.

Parkinson's disease (PD) is the most common motor neurodegenerative disease, and neuromuscular function deficits associated with PD contribute to disability. Targeting these symptoms, our laboratory has previously evaluated 16-week high-intensity resistance exercise as rehabilitative training (RT) in individuals with PD. We reported significant improvements in muscle mass, neuromuscular function (strength, power, and motor unit activation), indices of neuromuscular junction integrity, total and motor scores on the unified Parkinson's disease rating scale (UPDRS), and total and sub-scores on the 39-item PD Quality of Life Questionnaire (PDQ-39), supporting the use of RT to reverse symptoms.

Preventing SARS-CoV-2 infection by blocking a tissue serine protease.

Currently, there are no proven pharmacologic interventions to reduce the clinical impact and prevent complications of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, the cause of the ongoing Coronavirus Disease of 2019 (COVID-19) pandemic. Selecting specific pharmacological targets for the treatment of viral pathogens has traditionally relied in blockage of specific steps in their replicative lifecycle in human cells. However, an alternative approach is reducing the molecular cleavage of the viral surface spike protein of SARS-CoV-2 to prevent viral entry into epithelial cells.

Skeletal muscle transcriptional networks linked to type I myofiber grouping in Parkinson's disease.

Parkinson's disease (PD) is a common neurodegenerative disorder impacting cognition, movement, and quality of life in >10 million individuals worldwide. We recently characterized and quantified a skeletal muscle pathology in PD represented by exaggerated type I myofiber grouping presumed to result from denervation-reinnervation processes. Our previous findings indicated that impaired neuromuscular junction integrity may be involved in type I grouping, which is associated with excessive motor unit activation during weight-bearing tasks.

Exercise Effects on Mitochondrial Function and Lipid Metabolism during Energy Balance.

Introduction/purpose: Aerobic exercise training (AET) has been shown to improve mitochondrial bioenergetics and upregulate proteins related to lipid metabolism. However, it remains to be determined if these alterations associated with AET persist when measured in energy balance (EB) in the days after the last bout of training. The purpose of the study was to test the hypothesis that improvements in skeletal muscle mitochondrial function induced by AET observed in previous literature would persist when measured after restoring EB conditions 72 h removed from the last exercise bout.

Metformin blunts muscle hypertrophy in response to progressive resistance exercise training in older adults: A randomized, double-blind, placebo-controlled, multicenter trial: The MASTERS trial.

Progressive resistance exercise training (PRT) is the most effective known intervention for combating aging skeletal muscle atrophy. However, the hypertrophic response to PRT is variable, and this may be due to muscle inflammation susceptibility. Metformin reduces inflammation, so we hypothesized that metformin would augment the muscle response to PRT in healthy women and men aged 65 and older.

Relationship between V̇o, cycle economy, and mitochondrial respiration in untrained/trained.

Aerobic capacity is negatively related to locomotion economy. The purpose of this paper is to determine what effect aerobic exercise training has on the relationship between net cycling oxygen uptake (inverse of economy) and aerobic capacity [peak oxygen uptake (V̇o)], as well as what role mitochondrial coupled and uncoupled respiration may play in whole body aerobic capacity and cycling economy. Cycling net oxygen uptake and V̇o were evaluated on 31 premenopausal women before exercise training (baseline) and after 8-16 wk of aerobic training.

A high-protein diet or combination exercise training to improve metabolic health in individuals with long-standing spinal cord injury: a pilot randomized study.

We compared the effects of an 8-week iso-caloric high-protein (HP) diet versus a combined exercise regimen (Comb-Ex) in individuals with long-standing spinal cord injury (SCI). Effects on metabolic profiles, markers of inflammation, and signaling proteins associated with glucose transporter 4 (GLUT-4) translocation in muscles were evaluated. Eleven participants with SCI completed the study (HP diet: n = 5; Comb-Ex: n = 6; 46 ± 8 years; C5-T12 levels; American Spinal Injury Association Impairment Scale A or B).

Paralytic and nonparalytic muscle adaptations to exercise training versus high-protein diet in individuals with long-standing spinal cord injury.

This study compares the effects of an 8-wk isocaloric high-protein (HP) diet versus a combination exercise (Comb-Ex) regimen on paralytic vastus lateralis (VL) and nonparalytic deltoid muscle in individuals with long-standing spinal cord injury (SCI). Fiber-type distribution, cross-sectional area (CSA), levels of translation initiation signaling proteins (Erk-1/2, Akt, p70S6K1, 4EBP1, RPS6, and FAK), and lean thigh mass were analyzed at baseline and after the 8-wk interventions. A total of 11 participants (C5-T12 levels, 21.

Human neuromuscular aging: Sex differences revealed at the myocellular level.

Age-related muscle loss (sarcopenia) is a major clinical problem affecting both men and women - accompanied by muscle weakness, dysfunction, disability, and impaired quality of life. Current definitions of sarcopenia do not fully encompass the age-related changes in skeletal muscle. We therefore examined the influence of aging and sex on elements of skeletal muscle health using a thorough histopathological analysis of myocellular aging and assessments of neuromuscular performance.

Associations of Mitochondrial Fatty Acid Oxidation with Body Fat in Premenopausal Women.

Higher fatty acid (FA) oxidation rates have been reported in obese individuals compared to lean counterparts; however whether this reflects a shift in substrate-specific oxidative capacity at the level of the skeletal muscle mitochondria has not been examined. The purpose of this study was to test the hypothesis that in situ measures of skeletal muscle mitochondria FA oxidation would be positively associated with total body fat. Participants were 38 premenopausal women (BMI = 26.

Effects of acute hyperinsulinemia on skeletal muscle mitochondrial function, reactive oxygen species production, and metabolism in premenopausal women.

Background: Acute metabolic demands that promote excessive and/or prolonged reactive oxygen species production may stimulate changes in mitochondrial oxidative capacity.

Purpose: To assess changes in skeletal muscle HO production, mitochondrial function, and expression of genes at the mRNA and protein levels regulating energy metabolism and mitochondrial dynamics following a hyperinsulinemic-euglycemic clamp in a cohort of 11 healthy premenopausal women.

Methods: Skeletal muscle biopsies of the vastus lateralis were taken at baseline and immediately following the conclusion of a hyperinsulinemic-euglycemic clamp.

Evaluation of Vasopressin for Septic Shock in Patients on Chronic Renin-Angiotensin-Aldosterone System Inhibitors.

Objectives: To compare the hemodynamic response in septic shock patients receiving vasopressin who were on chronic renin-angiotensin-aldosterone system inhibitor therapy with those who were not.

Design: Single-center, retrospective cohort study.

Setting: Medical and surgical ICUs at a 1,100-bed academic medical center.

Randomized, four-arm, dose-response clinical trial to optimize resistance exercise training for older adults with age-related muscle atrophy.

Purpose: The myriad consequences of age-related muscle atrophy include reduced muscular strength, power, and mobility; increased risk of falls, disability, and metabolic disease; and compromised immune function. At its root, aging muscle atrophy results from a loss of myofibers and atrophy of the remaining type II myofibers. The purpose of this trial (NCT02442479) was to titrate the dose of resistance training (RT) in older adults in an effort to maximize muscle regrowth and gains in muscle function.

Atypical Neuroleptic Malignant Syndrome: Diagnosis and Proposal for an Expanded Treatment Algorithm: A Case Report.

Neuroleptic malignant syndrome (NMS) in the absence of an elevated creatine kinase is atypical and more difficult to diagnose. We present a patient with NMS significant risk factors who developed atypical NMS 6 days after a liver transplant. Symptoms of hyperthermia, altered mental status, dyskinesia, and autonomic instability (hypertension and tachycardia) coincided with promethazine administration, with rapid progression to fulminant NMS with lead pipe rigidity after a single injection of intramuscular ziprasidone.