Effectiveness of Using Exercise App in Improving Exercise Adherence and Aerobic Endurance of Football Players

Introduction. The use of mobile apps known as mHealth is starting to shape the delivery of physical therapy care not only in patients but also to the healthy population. Using an exercise app is a potential strategy to promote physical activity among individuals. Thus, this pilot study examined the utility of the Nike® Training Club app in increasing exercise adherence and enhancing aerobic endurance. Methods. The study utilized one-way repeated measures over time quasi-experimental design. It used purposive sampling to select 10 college football players aged 18-25 years old. After downloading the app, the participants were required to perform a workout plan composed of 15–45 minutes workouts through circuit interval training. The 20-day workout plan was done for 6 weeks (3-4 workouts per week). Aerobic endurance was measured at baseline and every after 2 weeks of intervention using Cooper’s 12-minute run test. Results. An extremely high adherence rate (85%, SD = 2.11) to exercise was exhibited by the participants based on recorded logs in the app. Also, the participants agreed that the app was easy to use (x̅ = 3.9, SD = .18) due to its user-friendly interface, uncomplicated design, and comprehensive features. Results also showed an improvement in their aerobic endurance at the end of the 6-week training with a change of 3.8 ml/kg/min, however, ANOVA showed no statistically significant difference in VO2 max from baseline to post-tests [F (3, 10) = 2.18, p = .11]. Discussion. A high adherence to exercise may be achieved when exercise is facilitated using the app. The app has potential to provide information that could lead to improvements in aerobic endurance and can be a useful tool in maintaining an active lifestyle among the well population

Biallelic JAK1 mutations in immunodeficient patient with mycobacterial infection

Mutations in genes encoding components of the immune system cause primary immunodeficiencies. Here, we study a patient with recurrent atypical mycobacterial infection and early-onset metastatic bladder carcinoma. Exome sequencing identified two homozygous missense germline mutations, P733L and P832S, in the JAK1 protein that mediates signalling from multiple cytokine receptors. Cells from this patient exhibit reduced JAK1 and STAT phosphorylation following cytokine stimulations, reduced induction of expression of interferon-regulated genes and dysregulated cytokine production; which are indicative of signalling defects in multiple immune response pathways including Interferon-γ production. Reconstitution experiments in the JAK1-deficient cells demonstrate that the impaired JAK1 function is mainly attributable to the effect of the P733L mutation. Further analyses of the mutant protein reveal a phosphorylation-independent role of JAK1 in signal transduction. These findings clarify JAK1 signalling mechanisms and demonstrate a critical function of JAK1 in protection against mycobacterial infection and possibly the immunological surveillance of cancer.Wellcome Trust (095198/Z/10/Z and 090233/Z/09/Z); Higher Education Funding Council for England; Great Ormond Street Hospital Children’s Charity; National Institute for Health Research (NIHR); Great Ormond Street Hospital Biomedical Research Centre; NIHR Cambridge Biomedical Research Centre; Alfonso Martin Escudero Foundatio

Natural Killer Cells from Patients with Recombinase-Activating Gene and Non-Homologous End Joining Gene Defects Comprise a Higher Frequency of CD56bright NKG2A+++ Cells, and Yet Display Increased Degranulation and Higher Perforin Content.

Mutations of the recombinase Activating Genes 1 and 2 (RAG1, RAG2) in humans are associated with a broad range of phenotypes. For patients with severe clinical presentation, hematopoietic stem cell transplantation (HSCT) represents the only curative treatment, however high rates of graft failure and incomplete immune reconstitution have been observed, especially after unconditioned haploidentical transplantation. Studies in mice have shown that Rag-/- NK cells have a mature phenotype, reduced fitness and increased cytotoxicity. We aimed to analyze NK cell phenotype and function in patients with mutations in RAG and in non-homologous end joining (NHEJ) genes. Here we provide evidence that NK cells from these patients have an immature phenotype, with significant expansion of CD56bright CD16-/int CD57- cells, yet increased degranulation and high perforin content. Correlation was observed between in vitro recombinase activity of the mutant proteins, NK cell abnormalities, and in vivo clinical phenotype. Addition of serotherapy in the conditioning regimen, with the aim of depleting the autologous NK cell compartment, may be important to facilitate engraftment and immune reconstitution in patients with RAG and NHEJ defects treated by HSCT

Wiskott-Aldrich syndrome protein regulates autophagy and inflammasome activity in innate immune cells.

Dysregulation of autophagy and inflammasome activity contributes to the development of auto-inflammatory diseases. Emerging evidence highlights the importance of the actin cytoskeleton in modulating inflammatory responses. Here we show that deficiency of Wiskott-Aldrich syndrome protein (WASp), which signals to the actin cytoskeleton, modulates autophagy and inflammasome function. In a model of sterile inflammation utilizing TLR4 ligation followed by ATP or nigericin treatment, inflammasome activation is enhanced in monocytes from WAS patients and in WAS-knockout mouse dendritic cells. In ex vivo models of enteropathogenic Escherichia coli and Shigella flexneri infection, WASp deficiency causes defective bacterial clearance, excessive inflammasome activation and host cell death that are associated with dysregulated septin cage-like formation, impaired autophagic p62/LC3 recruitment and defective formation of canonical autophagosomes. Taken together, we propose that dysregulation of autophagy and inflammasome activities contribute to the autoinflammatory manifestations of WAS, thereby identifying potential targets for therapeutic intervention

The severity of pandemic H1N1 influenza in the United States, from April to July 2009: A Bayesian analysis

Background: Accurate measures of the severity of pandemic (H1N1) 2009 influenza (pH1N1) are needed to assess the likely impact of an anticipated resurgence in the autumn in the Northern Hemisphere. Severity has been difficult to measure because jurisdictions with large numbers of deaths and other severe outcomes have had too many cases to assess the total number with confidence. Also, detection of severe cases may be more likely, resulting in overestimation of the severity of an average case. We sought to estimate the probabilities that symptomatic infection would lead to hospitalization, ICU admission, and death by combining data from multiple sources. Methods and Findings: We used complementary data from two US cities: Milwaukee attempted to identify cases of medically attended infection whether or not they required hospitalization, while New York City focused on the identification of hospitalizations, intensive care admission or mechanical ventilation (hereafter, ICU), and deaths. New York data were used to estimate numerators for ICU and death, and two sources of data - medically attended cases in Milwaukee or self-reported influenza-like illness (ILI) in New York - were used to estimate ratios of symptomatic cases to hospitalizations. Combining these data with estimates of the fraction detected for each level of severity, we estimated the proportion of symptomatic patients who died (symptomatic case-fatality ratio, sCFR), required ICU (sCIR), and required hospitalization (sCHR), overall and by age category. Evidence, prior information, and associated uncertainty were analyzed in a Bayesian evidence synthesis framework. Using medically attended cases and estimates of the proportion of symptomatic cases medically attended, we estimated an sCFR of 0.048% (95% credible interval [CI] 0.026%-0.096%), sCIR of 0.239% (0.134%-0.458%), and sCHR of 1.44% (0.83%-2.64%). Using self-reported ILI, we obtained estimates approximately 7-96lower. sCFR and sCIR appear to be highest in persons aged 18 y and older, and lowest in children aged 5-17 y. sCHR appears to be lowest in persons aged 5-17; our data were too sparse to allow us to determine the group in which it was the highest. Conclusions: These estimates suggest that an autumn-winter pandemic wave of pH1N1 with comparable severity per case could lead to a number of deaths in the range from considerably below that associated with seasonal influenza to slightly higher, but with the greatest impact in children aged 0-4 and adults 18-64. These estimates of impact depend on assumptions about total incidence of infection and would be larger if incidence of symptomatic infection were higher or shifted toward adults, if viral virulence increased, or if suboptimal treatment resulted from stress on the health care system; numbers would decrease if the total proportion of the population symptomatically infected were lower than assumed.published_or_final_versio

Lung oxidative stress as related to exercise and altitude. Lipid peroxidation evidence in exhaled breath condensate: A possible predictor of acute mountain sickness

Lung oxidative stress (OS) was explored in resting and in exercising subjects exposed to moderate and high altitude. Exhaled breath condensate (EBC) was collected under field conditions in male high-competition mountain bikers performing a maximal cycloergometric exercise at 670 m and at 2,160 m, as well as, in male soldiers climbing up to 6,125 m in Northern Chile. Malondialdehyde concentration [MDA] was measured by high-performance liquid chromatography in EBC and in serum samples. Hydrogen peroxide concentration [H2O2] was analysed in EBC according to the spectrophotometric FOX2 assay. [MDA] in EBC of bikers did not change while exercising at 670 m, but increased from 30.0 ± 8.0 to 50.0 ± 11.0 nmol l-1 (P < 0.05) at 2,160 m. Concomitantly, [MDA] in serum and [H2O2] in EBC remained constant. On the other hand, in mountaineering soldiers, [H2O2] in EBC under resting conditions increased from 0.30 ± 0.12 μmol l-1 at 670 m to 1.14 ± 0.29 μmol l-1 immediately on return from the mountain

Predictive Properties of the Asthma Control Test and Its Component Questions for Severe Asthma Exacerbations

BACKGROUND: Current US guidelines recommend the Asthma Control Test (ACT) for assessing disease control and selecting treatment. OBJECTIVE: The goal of this study was to prospectively assess the ACT and its component questions for their utility in predicting the risk of severe asthma exacerbations. METHODS: Individuals were participants in the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-Ethnicity, and those included in the current analysis had the following characteristics: age 18 years or more, physician-diagnosed asthma, and longitudinal care received at a large health system in southeastern Michigan. Study participants underwent a baseline evaluation, which included answering the ACT. A severe asthma exacerbation was defined as one requiring oral steroids, an emergency department visit, or inpatient admission. Receiver-operator characteristic curves were used to measure and compare the predictive utility of the ACT and its component questions for severe asthma exacerbations. RESULTS: Of 1180 participants, 354 (30.0%) experienced a severe asthma exacerbation within 6 months of their baseline evaluation. When compared with the individual questions that composed the ACT, the composite score was significantly better at predicting severe exacerbations with 1 exception; the composite ACT score and the question assessing rescue medication use were not significantly different (P = .580). Pharmacy-based records of metered-dose inhaler short-acting beta-agonist use and asthma severity were also not significantly different from the composite ACT score. CONCLUSIONS: Our study demonstrates that although the ACT is modestly predictive for exacerbations, the composite score may not be superior to assessing rescue medication use alone for predicting the risk of severe asthma exacerbations

Predictive Properties of the Asthma Control Test and Its Component Questions for Severe Asthma Exacerbations

BACKGROUND: Current US guidelines recommend the Asthma Control Test (ACT) for assessing disease control and selecting treatment. OBJECTIVE: The goal of this study was to prospectively assess the ACT and its component questions for their utility in predicting the risk of severe asthma exacerbations. METHODS: Individuals were participants in the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-Ethnicity, and those included in the current analysis had the following characteristics: age 18 years or more, physician-diagnosed asthma, and longitudinal care received at a large health system in southeastern Michigan. Study participants underwent a baseline evaluation, which included answering the ACT. A severe asthma exacerbation was defined as one requiring oral steroids, an emergency department visit, or inpatient admission. Receiver-operator characteristic curves were used to measure and compare the predictive utility of the ACT and its component questions for severe asthma exacerbations. RESULTS: Of 1180 participants, 354 (30.0%) experienced a severe asthma exacerbation within 6 months of their baseline evaluation. When compared with the individual questions that composed the ACT, the composite score was significantly better at predicting severe exacerbations with 1 exception; the composite ACT score and the question assessing rescue medication use were not significantly different (P = .580). Pharmacy-based records of metered-dose inhaler short-acting beta-agonist use and asthma severity were also not significantly different from the composite ACT score. CONCLUSIONS: Our study demonstrates that although the ACT is modestly predictive for exacerbations, the composite score may not be superior to assessing rescue medication use alone for predicting the risk of severe asthma exacerbations

Loss of Janus Associated Kinase1 alters urothelial cell functionand facilitates the development of bladder cancer

Inherited Primary Immunodeficiency (PID) disorders are associated with increased risk ofmalignancy that may relate to impaired antitumor immune responses or a direct role for PIDgermline mutations in tumorigenesis. We recently identified germline loss of function mutations inJanus Associated Kinase 1 (JAK1) causing primary immunodeficiency characterised by infectionsand associated with early onset, fatal high-grade bladder carcinoma. Somatic mutations in JAK1,required for immune cell signalling in response to interferon gamma (IFNγ), have been associatedwith several non-hematopoietic and hematopoietic cancer cell types but pathogenic mechanismsremain largely unexplored. Here we demonstrate that JAK1 is required for the intrinsic IFNγresponse of urothelial cells impacting immunogenicity and cell survival. Specifically, JAK1-deficient urothelial cells showed reduced surface expression of major histocompatibility complexclass II (MHC II), intercellular adhesion molecule-1 (ICAM-1) and programmed death-ligand-1(PD-L1) after IFNγ stimulation and were resistant to IFNγ-induced apoptosis and lymphocytemediatedkilling. In addition, we identify a previously unknown role for IFNγ signalling inmodulating urothelial differentiation. Together, our findings support a role for urothelial cell JAK1in immune surveillance and development of bladder cancer. Our results have implications forpatients with rare JAK1 PID and, more broadly, inform development of biomarker and targetedtherapies for urothelial carcinoma