The volume fraction of the extracellular matrix (ECM) within the layer of airway smooth muscle (ASM) is increased in subjects with fixed airflow obstruction. We postulated that changes in ECM within the ASM layer will impact force transmission during induced contraction and / or in response to externally applied stresses like a deep inspiration (DI). Subjects were patients undergoing lung resection surgery who were categorized as unobstructed (n=12) or obstructed 'fixed' (n=6), based on pre-operative spirometry. The response to a DI, assessed by the ratio of isovolumic flows from maximal and partial inspirations (M/P ratio), was also measured pre-operatively. M/P ratio was reduced in the obstructed group (p=0.02).Post-operatively, bronchial segments were obtained from resected tissue and luminal narrowing to acetylcholine and bronchodilation to simulated DI were assessed in vitro. Airway wall dimensions and the volume fraction of ECM within the ASM were quantified. Maximal airway narrowing to acetylcholine (p=0.01) and the volume fraction of ECM within the ASM layer (p=0.02) were increased in the obstructed group, without a change in ASM thickness. While bronchodilation to simulated DI in vitro was not different between obstructed and unobstructed groups, it was correlated with increased M/P ratio (bronchodilation / less bronchoconstriction) in vivo (p=0.03). The volume fraction of ECM was inversely related to FEV1%predicted (p=0.04) and M/P ratio (p=0.01). Results show that in subjects with fixed airflow obstruction the mechanical behaviour of the airway wall is altered, and there is a contemporaneous shift in the structural composition of the ASM layer.AIM This study aimed to investigate and compare the magnitude of exercise-induced hypoalgesia (EIH) with low intensity blood flow restriction (BFR) resistance exercise (RE) at varying pressures to other intensities of resistance exercise and examine endogenous mechanisms of pain reduction. METHODOLOGY Twelve individuals performed four experimental trials involving unilateral leg press exercise in a randomised crossover design low load RE at 30% of one repetition maximum (1RM), high load RE (70% 1RM) and BFR-RE (30% 1RM) at a low and high pressure. BFR pressure was prescribed relative to limb occlusion pressure at 40% and 80% for the low- and high-pressure trials. Pressure pain thresholds (PPT) were assessed before, 5-min and 24-h following exercise in exercising and non-exercising muscles. Venous blood samples were collected at the same timepoints to determine plasma concentrations of beta-endorphin and 2-arachidonoylglycerol. RESULTS High pressure BFR-RE increased PPTs in the exercising limb to a greater extent than all other trials. Comparable systemic EIH effects were observed with HLRE and both BFR-RE trials. PPTs in the exercising limb remained elevated above baseline at 24-h post-exercise following both BFR-RE trials. Post-exercise plasma beta-endorphin concentration was elevated during the BFR-RE trials. No changes to 2-arachidonoylglycerol concentration were observed. CONCLUSION High pressure BFR-RE causes a greater EIH response in the exercising limb that persists for up to 24-h following exercise. The reduction in pain sensitivity with BFR-RE is partly driven by endogenous opioid production of beta-endorphin. BFR-RE should be introduced as a possible pain-modulation tool in individuals with acute and chronic pain.Oxidative stress may be involved in disease pathology and dependent on both modifiable and non-modifiable factors. This study aimed to assess exercise-induced changes in markers of oxidative stress among older, sedentary adults, and to determine the effects of metabolic syndrome (MetS) status, aerobic capacity, age, sex and weight on these biomarkers. 206 participants (mean ± SE; 66.8 ± 6.4 years, 104 women) of the Brain in Motion study underwent a 6-month aerobic exercise intervention. At three time points, venous blood samples were collected and analyzed for markers of oxidative stress (advanced oxidation protein products [AOPP], malondialdehyde [MDA], 3-nitrotyrosine [3-NT]) and antioxidant status (catalase, uric acid [UA], superoxide dismutase [SOD], and ferric-reducing antioxidant power [FRAP]). AOPP levels significantly decreased after six months of aerobic exercise (p=0.003). This decrease was not modified by MetS status (p=0.183). Subjects with MetS possessed significantly higher levels of AOPP (p less then 0.001), MDA (p=0.004) and FRAP (p=0.049) across the intervention (month 0 to 6). Men possessed significantly higher levels of FRAP (p less then 0.001), catalase (p=0.023) and UA (p=0.037) across the intervention (month 0 to 6). Sex-MetS status interaction analyses revealed that the effect of MetS is highly sex-dependent. These findings are multifaceted because the effect of MetS status seems distinctly different between sexes, pointing to the importance of acknowledging modifiable and non-modifiable factor differences in individuals who possess conditions where oxidative stress may be part of the etiology.The development of tissue-specific inducible transgenic mice has provided a powerful tool to study gene function and cell biology in almost any tissue of interest at any given time within the animal's life. The purpose of this review is to describe how to use two different inducible transgenic systems, the Cre-loxP system and the Tet-ON/OFF system, that can be used to study skeletal muscle physiology Myofiber- and satellite cell-specific Cre-loxP transgenic mice are described and how these mice can be used to knockout a gene of interest or to deplete satellite cells in adult skeletal muscle, respectively. A myofiber-specific Tet-ON system is described and how such mice can be used to over-express a gene of interest or to label myonuclei. How to effectively breed and genotype the transgenic mice are also described in detail. The hope is this review will provide the basic information necessary to facilitate the incorporation of tissue-specific inducible transgenic mice into a skeletal muscle research program.Cold environmental temperatures during exercise and recovery alter the acute response to cellular signaling and training adaptations. Approximately three weeks is required for cold temperature acclimation to occur. PURPOSE To determine the impact of cold environmental temperature on training adaptations, fitness measurements, and aerobic performance. IRAK4-IN-4 nmr METHODS Two groups of twelve untrained male subjects completed 1-hour of cycling in sixteen temperature acclimation sessions in either a 7°C or 20°C environmental temperature. Fitness assessments before and after acclimation occurred in standard room temperature. Muscle biopsies were taken from the vastus lateralis before training and after training to assess molecular markers related to mitochondrial development. RESULTS PGC-1α mRNA was higher in 7°C than 20°C in response to acute exercise before training (p=0.012) but not after training (p=0.813). PGC-1α mRNA was lower after training (p0.05). Cycling power increased during the daily training (p less then 0.001) but was not different between temperatures (p=0.