The purpose of this investigation was to establish a relationship between the number of repetitions an individual can complete at a predetermined load and their percentage of type II muscle fibers in their quadriceps. Subjects included 22 untrained women between the ages of 18 and 35. Day 1 consisted of noninvasive anthropologic testing, 1 repetition maximum (1RM) testing, and recording repetition performance at 70% 1RM. Day 2 consisted of isokinetic dynamometry to determine muscle fiber composition. Results were obtained and analyzed using the Pearson product correlation coefficient (r). The results demonstrated a fair-to-moderate relationship (Pearson r = -0.48, p = 0.02) that individuals with greater percentages of type II muscle fibers performed fewer repetitions at 70% 1RM. The results of this study demonstrate that muscle fiber type composition is an important variable to consider when designing training or rehabilitation programs.

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Introduction: Krabbe disease (KD) is an autosomal recessive disorder caused by mutations in the galactocerebrosidase (GALC) gene resulting in neuro-inflammation and defective myelination in the central and peripheral nervous systems. Most infantile patients present with clinical features before six months of age and die before two years of age. The only treatment available for pre-symptomatic or mildly affected individuals is hematopoietic stem cell transplantation (HSCT). In the animal models, combining bone marrow transplantation (BMT) with gene therapy has shown the best results in disease outcome. In this study, we examine the outcome of gene therapy alone. Methods: Twitcher (twi) mice used in the study, have a W339X mutation in the GALC gene. Genotype identification of the mice was performed shortly after birth or post-natal day 1 (PND1), using polymerase chain reaction on the toe clips followed by restriction enzyme digestion and electrophoresis. Eight or nine-day-old affected mice were used for gene therapy treatment alone or combined with BMT. While iv injection of 4 × 1013 gc/kg of body weight of viral vector was used originally, different viral titers were also used without BMT to evaluate their outcomes. Results: When the standard viral dose was increased four- and ten-fold (4X and 10X) without BMT, the lifespans were increased significantly. Without BMT the affected mice were fertile, had the same weight and appearance as wild type mice and had normal strength and gait. The brains showed no staining for CD68, a marker for activated microglia/macrophages, and less astrogliosis than untreated twi mice. Conclusion: Our results demonstrate that, it may be possible to treat human KD patients with high dose AAVrh10 without blood stem cell transplantation which would eliminate the side effects of HSCT.

A B S T R A C T Our current knowledge of idiopathic pneumonia syndrome (IPS) predates improved specificity in the diagnosis of IPS and advances in hematopoietic cell transplantation (HCT) and critical care practices. In this study, we describe and update the incidence, risk factors, and outcomes of IPS. We performed a retrospective cohort study of all adults who underwent allogeneic HCT at the Fred Hutchinson Cancer Research Center between 2006 and 2013 (n = 1829). IPS was defined using the National Heart, Lung, and Blood Institute consensus definition: multilobar airspace opacities on chest imaging, absence of lower respiratory tract infection, and hypoxemia. We described IPS incidence and mortality within 120 and 365 days after HCT. We examined conditioning intensity (nonmyeloablative versus myeloablative with high-dose total body irradiation [TBI] versus myeloablative with low-dose TBI) as an IPS risk factor in a time-to-event analysis using Cox models, controlled for age at transplant, HLA matching, stem cell source, and pretransplant Lung function Score (a combined measure of impairment in Forced Expiratory Volume in the first second (FEV 1 ) and Diffusion capacity for carbon monoxide (DLCO)). Among 1829 HCT recipients, 67 fulfilled IPS criteria within 120 days (3.7%). Individuals who developed IPS were more likely to be black/non-Hispanic versus other racial groups and have severe pulmonary impairment but were otherwise similar to participants without IPS. In adjusted models, myeloablative conditioning with high-dose TBI was associated with increased risk of IPS (hazard ratio, 2.5; 95% confidence interval, 1.2 to 5.2). Thirty-one patients (46.3%) with IPS died within the first 120 days of HCT and 47 patients (70.1%) died within 365 days of HCT. In contrast, among the 1762 patients who did not acquire IPS in the first 120 days, 204 (11.6%) died within 120 days of HCT and 510 (29.9%) died within 365 days of HCT. Our findings suggest that although the incidence of IPS may be declining, it remains associated with post-transplant mortality. Future study should focus on early detection and identifying pathologic mediators of IPS to facilitate timely, targeted therapies for those most susceptible to lung injury post-HCT.

ObjectivesThe relationship between marijuana use and markers of chronic lung disease in people living with HIV (PLWH) is poorly understood.MethodsWe performed a cross‐sectional analysis of the Examinations of HIV‐Associated Lung Emphysema (EXHALE) study, including 162 HIV‐positive patients and 138 participants without HIV. We modelled marijuana exposure as: (i) current daily or weekly marijuana smoking vs. monthly or less often; or (ii) cumulative marijuana smoking (joint‐years). Linear and logistic regression estimated associations between marijuana exposure and markers of lung disease, adjusted for tobacco smoking and other factors.ResultsIn PLWH, current daily or weekly marijuana use was associated with a larger forced vital capacity (FVC), larger total lung capacity and increased odds of radiographic emphysema compared with marijuana non‐smokers in adjusted models; these associations were not statistically significant in participants without HIV. Marijuana joint‐years were associated with higher forced expiratory volume in 1 s and FVC in PLWH but not with emphysema.ConclusionsIn PLWH, marijuana smoking was associated with higher lung volumes and potentially with radiographic emphysema. No consistently negative associations were observed between marijuana and measures of chronic lung health.

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BackgroundPericardial fat has been implicated in the pathogenesis of obesity-related cardiovascular disease. Proposed mechanisms may be relevant in right heart failure, but relationships between pericardial fat and right ventricular (RV) morphology have not been explored.MethodsThe Multi-Ethnic Study of Atherosclerosis is a prospective cohort that enrolled participants without clinical cardiovascular disease. Pericardial fat was measured using computed tomography and RV parameters using cardiac MRI. Linear regression estimated associations of pericardial fat with RV mass, RV end diastolic volume (RV-EDV), RV end systolic volume (RV-ESV), RV stroke volume (RV-SV), and RV ejection fraction (RV-EF). Limited models adjusted for age, gender, race, height, and study site with and without weight. Fully adjusted models also accounted for socioeconomic parameters and health behaviors. Adjustment for left ventricular morphology, metabolic syndrome, and systemic inflammation was also performed.ResultsThe study sample included 3988 participants with complete assessment of RV morphology, pericardial fat and all covariates. Greater pericardial fat volume was associated with reduced RV mass (-0.3g per 40 cm3 increase in pericardial fat, p<0.001), smaller RV-EDV (-3.7ml per 40 cm3 increase in pericardial fat, p<0.001), smaller RV-ESV (-1.0ml per 40cm3 increase in pericardial fat, p<0.001), and smaller RV-SV (-2.7mL per 40 cm3 increase in pericardial fat, p<0.001) in participants after adjustment for weight. Associations were unchanged when accounting for health behaviors, markers of systemic inflammation, and the metabolic syndrome.ConclusionsGreater pericardial fat was associated with reduced RV mass, smaller RV-EDV, smaller RV-ESV, and smaller RV-SV in participants after adjustment for weight. Relationships between pericardial fat and RV morphology could be relevant to diseases of right heart failure.