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. In a randomized, double‐blind trial, participants received 1,700 mg/day metformin (N = 46) or placebo (N = 48) throughout the study, and all subjects performed 14 weeks of supervised PRT. Although responses to PRT varied, placebo gained more lean body mass (p = .003) and thigh muscle mass (p < .001) than metformin. CT scan showed that increases in thigh muscle area (p = .005) and density (p = .020) were greater in placebo versus metformin. There was a trend for blunted strength gains in metformin that did not reach statistical significance. Analyses of vastus lateralis muscle biopsies showed that metformin did not affect fiber hypertrophy, or increases in satellite cell or macrophage abundance with PRT. However, placebo had decreased type I fiber percentage while metformin did not (p = .007). Metformin led to an increase in AMPK signaling, and a trend for blunted increases in mTORC1 signaling in response to PRT. These results underscore the benefits of PRT in older adults, but metformin negatively impacts the hypertrophic response to resistance training in healthy older individuals. ClinicalTrials.gov Identifier: NCT02308228.

Objective The purpose of this study was to evaluate changes in the synovial fluid proteome following acute anterior cruciate ligament (ACL) injury. Design This study represents a secondary analysis of synovial fluid samples collected from the placebo group of a previous randomized trial. Arthrocentesis was performed twice on 6 patients with an isolated acute ACL tear at a mean of 6 and 14 days postinjury. Synovial fluid was analyzed by a highly multiplexed assay of 1129 proteins (SOMAscan version 3, SomaLogic, Inc., Boulder, CO). Pathway analysis using DAVID was performed; genes included met 3 criteria: significant change between the 2 study time points using a paired t test, significant change between the 2 study time points using a Mann-Whitney nonparametric test, and significant Benjamini post hoc analysis. Results Fifteen analytes demonstrated significant increases between time points. Five of the 15 have been previously associated with the onset and/or severity of rheumatoid arthritis, including apoliopoprotein E and isoform E3, vascular cell adhesion protein 1, interleukin-34, and cell surface glycoprotein CD200 receptor 1. Chondrodegenerative enzymes and products of cartilage degeneration all increased over time following injury: MMP-1 ( P = 0.08, standardized response mean [SRM] = 1.00), MMP-3 ( P = 0.05, SRM = 0.90), ADAM12 ( P = 0.03, SRM = 1.31), aggrecan ( P = 0.08, SRM = 1.13), and CTX-II ( P = 0.07, SRM = 0.56). Notable pathways that were differentially expressed following injury were the cytokine-cytokine receptor interaction and osteoclast differentiation pathways. Conclusions The proteomic results and pathway analysis demonstrated a pattern of cartilage degeneration, not only consistent with previous findings but also changes consistent with an inflammatory arthritogenic process post-ACL injury.

Exposure to Early Life Stress (ELS) is associated with behavioral-related alterations, increases in body mass index and higher systolic blood pressure in humans. Postnatal maternal separation and early weaning (MSEW) is a mouse model of neglect characterized by a long-term dysregulation of the neuroendocrine system. Objectives Given the contribution of adrenal-derived hormones to the development of obesity, we hypothesized that exposure to MSEW could contribute to worsen the cardiometabolic function in response to chronic high fat diet (HF) feeding by promoting adipose tissue expansion and insulin resistance. Subjects MSEW was performed in C57BL/6 mice from postnatal days 2–16 and weaned at postnatal day 17. Undisturbed litters weaned at postnatal day 21 served as the control (C) group. At the weaning day, mice were placed on a low fat diet (LF) or HF for 16 weeks. Results When fed a LF, male and female mice exposed to MSEW display similar body weight but increased fat mass compared to controls. However, when fed a HF, only female MSEW mice display increased body weight, fat mass and adipocyte hypertrophy compared with controls. Also, female MSEW mice display evidence of an early onset of cardiometabolic risk factors, including hyperinsulinemia, glucose intolerance and hypercholesterolemia. Yet, both male and female MSEW mice fed a HF show increased blood pressure compared with controls. Conclusions This study shows that MSEW promotes a sex-specific dysregulation of the adipose tissue expansion and glucose homeostasis that precedes the development of obesity-induced hypertension.

Background Students with disabilities receive school-based physical therapy services under the Individuals with Disabilities Education Improvement Act of 2004. Little research exists regarding therapy services in schools. Objective This study explored the school-based services that students received and the activities and interventions that physical therapists implemented, and determined if services differed based on the student's functional gross motor ability and age. Design This was a prospective observational cohort study using a practice-based evidence design. Methods Data were collected by 109 physical therapists for 296 students, aged 5 to 12 years, receiving school-based physical therapy. Physical therapists completed the School-Physical Therapy Interventions for Pediatrics data form for 20 weeks during 1 school year. This evaluation included the type of service delivery, the amount of time spent on each student (consultation/documentation), minutes spent in activities, the specific interventions implemented, and the student's level of participation. The Gross Motor Function Classification System (GMFCS) was used to describe the students' functional ability. Results Physical therapists provided an average of 26.7 min/wk (standard deviation [SD] = 15.1) of direct services and 13.1 min/wk (SD = 7.7) of services on behalf of the student. Primary activities were physical education/recreation (7.7 min/wk, SD = 8.2), mobility (6.7 min/wk, SD = 7.9), and sitting/standing/transitions (6.3 min/wk, SD = 8.1). Primary interventions were neuromuscular (32.5 counts per student, SD = 15.9), mobility (15.3 counts per student, SD = 14.65), and musculoskeletal (14.4 counts per student, SD = 10.3). Differences existed based on GMFCS but not student age. Limitations Physical therapists reported School-Physical Therapy Interventions for Pediatrics data weekly, not necessarily after each therapy session. The GMFCS was used as a proxy of students’ functional gross motor ability. Conclusions Our description of services is provided to encourage physical therapists to reflect on the services they provide and to foster future examinations of service effectiveness.

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