Pharmacokinetics/pharmacodynamics of glucocorticoids: modeling the glucocorticoid receptor dynamics and dose/response of commonly prescribed glucocorticoids.

Background And Purpose: The main features of the dynamics of the glucocorticoid receptor (GR) have been known for 50 years: 1) in the absence of glucocorticoid (G), the receptor is localized entirely in the cytoplasm; 2) upon G binding, GR is converted into a tightly bound G form and is rapidly imported into the nucleus where it can bind DNA and modulate transcription; 3) nuclear export of GR is very slow; and 4) the nuclear form of GR can recycle through an unbound form, back to the bound transcription modulating form without leaving the nucleus.

Experimental Approach: A kinetic model that captures these features is presented, a set of model parameters for dexamethasone is derived, and the clinical implication for the commonly used glucocorticoids is discussed.

Key Results: At the high concentrations normally used to describe G pharmacodynamics, the model reduces to the standard Michaelis-Menten equation with a that is a function of 4 model parameters.

Alcohol Alters Skeletal Muscle Bioenergetic Function: A Scoping Review.

Bioenergetic pathways uniquely support sarcomere function which, in turn, helps to maintain functional skeletal muscle (SKM) mass. Emerging evidence supports alcohol (EtOH)-induced bioenergetic impairments in SKM and muscle precursor cells. We performed a scoping review to synthesize existing evidence regarding the effects of EtOH on SKM bioenergetics.

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.

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.

Development of a Pharmacokinetic Model That Accounts for the Plasma Concentrations of Conjugated and Unconjugated Bilirubin Observed in a Variety of Disease States.

Introduction: For a large variety of liver pathologies, the plasma unconjugated (UB) and conjugated (CB) bilirubin concentrations appear to be coupled. For example, in alcoholic cirrhosis, UB and CB are roughly the same over a large range of total bilirubin, requiring an initial massive increase (about 40-fold) in plasma CB to reach the level of UB and then similar increases in UB and CB as the disease progresses. This coupling has been either unrecognized or ignored and this paper is the first attempt to try to explain it quantitatively in terms of known hepatic cell metabolic and membrane transport properties.

Sexually Transmitted Infection Risks and Symptoms Heightened Among Female Sex Workers who Started Selling Sex Before the Age of 18 in Five Cities in Cameroon.

Many adolescents under 18 years old who sell sex are at elevated risk for sexually transmitted infection (STI) acquisition, which may persist into adulthood. There has been limited study of the burden of the risks and vulnerabilities among women who started selling sex as adolescents across Sub-Saharan Africa. In this study, a Adult female sex workers (FSW) recruited through respondent-driven sampling in five cities in Cameroon from December 2015 to October 2016 completed a questionnaire and human immunodeficiency virus (HIV) and syphilis testing.

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.

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.

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.

The profile of orthopaedic sports medicine publishing in South Africa.

Background: The South African Journal of Sports Medicine (SAJSM) and the South African Orthopaedic Journal (SAOJ) are two open access, peer-reviewed journals which provide ongoing education to the sports medicine community.

Objectives: The purpose of this review was to appraise articles with a sports orthopaedic focus published in SAJSM and SAOJ. A secondary aim was to evaluate trends regarding the focus of the articles, levels of evidence, authors' affiliations, and country of origin.

Development and application of a simple pharmacokinetic model that quantitatively describes the distribution and elimination of the commonly measured proteins.

Increased plasma concentrations of a variety of cellular enzymes (alanine transaminase, aspartate aminotransferase, alkaline phosphatase, amylase, etc.) are commonly used as routine screening tests for a range of conditions. An increased concentration usually is assumed to result from an increased rate of delivery to the plasma.

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.

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.

Offshore detention: cross-sectional analysis of the health of children and young people seeking asylum in Australia.

Objective: To describe the health and well-being of children and young people (CYP) seeking asylum subjected to Australia's immigration policy of indefinite mandatory detention on Nauru.

Design: Cross-sectional analysis of a cohort of CYP seeking asylum.

Setting: Australian paediatric clinicians from 10 health services completed detailed health assessments around the time of transfer from Nauru, mostly to Australia.

Progressive resistance training in young people with Prader-Willi syndrome: protocol for a randomised trial (PRESTO).

Introduction: Preliminary evidence suggests that progressive resistance training may be beneficial for people with Prader-Willi Syndrome (PWS), a rare genetic condition that results in muscle weakness and low muscle tone.To establish whether community-based progressive resistance training is effective in improving the muscle strength of people with PWS; to determine cost-effectiveness; and, to complete a process evaluation assessing intervention fidelity, exploring mechanisms of impact, understanding participant experiences and identifying contextual factors affecting implementation.

Methods And Analysis: A multisite, randomised controlled trial will be completed.

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.

Constructing Health State Descriptions for Low-Risk Thyroid Cancer: Stakeholder Engagement and Formative Qualitative Research.

Overview: This paper describes stakeholder involvement and formative qualitative research in the creation of health state descriptions (HSDs) or vignettes for low-risk thyroid cancer. The aim of this project was to engage stakeholders in the contribution of a novel set of HSDs, an important first step in the process of assessing value in thyroid cancer health states.

Methods: We draw upon formative, descriptive qualitative methods, following a multi-stage framework of data collection.

Modeling the potential impact of pre-exposure prophylaxis for HIV among men who have sex with men in Cameroon.

Background: Men who have sex with men (MSM) are consistently burdened by HIV at higher levels than other adults. While HIV prevention programs for MSM are growing in coverage and quality, HIV incidence remains high. In response, pre-exposure prophylaxis (PrEP) was introduced in 2019 to support HIV risk reduction among MSM in Cameroon.

Cost-Effectiveness of Care Coordination for Children With Chronic Noncomplex Medical Conditions: Results From a Multicenter Randomized Clinical Trial.

Objectives: To assess the cost-effectiveness of care coordination, compared with standard care, for children with chronic noncomplex medical conditions.

Methods: A total of 81 children aged between 2 and 15 years newly diagnosed with a noncomplex chronic condition were randomized to either care coordination or standard care as part of a multicenter randomized controlled trial. Families receiving care coordination were provided access to an Allied Health Liaison Officer, who facilitated family-centered healthcare access across hospital, education, primary care, and community sectors.

A Phase I Study of Apolizumab, an Anti-HLA-DR ß-chain Monoclonal Antibody, in Patients With Solid Tumor Malignancies.

Background: Human leukocyte antigen (HLA)-DR, a member of the major histocompatibility complex class II antigen family, is a target for antibody-based therapeutics. Apolizumab (Hu1D10, Remitogen), a humanized IgG1 monoclonal anti-HLA-DR ß-chain antibody targets the antigen, 1D10, expressed on a wide variety of hematologic and solid tumor malignancies. In this Phase 1 trial, the maximum tolerated dose and dose-limiting toxicity of weekly apolizumab in patients with advanced solid tumor malignancies were determined.