Molecular Transducers of Physical Activity Consortium (MoTrPAC): Human Studies Design and Protocol.

Physical activity, including structured exercise, is associated with favorable health-related chronic disease outcomes. While there is evidence of various molecular pathways that affect these responses, a comprehensive molecular map of these molecular responses to exercise has not been developed. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) is a multi-center study designed to isolate the effects of structured exercise training on the molecular mechanisms underlying the health benefits of exercise and physical activity. MoTrPAC contains both a pre-clinical and human component. The details of the human studies component of MoTrPAC that include the design and methods are presented here. The human studies contain both an adult and pediatric component. In the adult component, sedentary participants are randomized to 12 weeks of Control, Endurance Exercise Training, or Resistance Exercise Training with outcomes measures completed before and following the 12 weeks. The adult component also includes recruitment of highly active endurance trained or resistance trained participants who only complete measures once. A similar design is used for the pediatric component; however, only endurance exercise is examined. Phenotyping measures include weight, body composition, vital signs, cardiorespiratory fitness, muscular strength, physical activity and diet, and other questionnaires. Participants also complete an acute rest period (adults only) or exercise session (adults, pediatrics) with collection of biospecimens (blood only for pediatrics) to allow for examination of the molecular responses. The design and methods of MoTrPAC may inform other studies. Moreover, MoTrPAC will provide a repository of data that can be used broadly across the scientific community.

Effects of Exercise Training With and Without Ranolazine on Peak Oxygen Consumption, Daily Physical Activity, and Quality of Life in Patients With Chronic Stable Angina Pectoris.

Ranolazine reduces angina frequency and increases exercise capacity. We hypothesized that exercise training with ranolazine would allow subjects to train at greater intensities, resulting in greater improvements in exercise capacity, physical activity, and health-related quality of life (HRQOL). In a pilot study, subjects with chronic stable angina pectoris were randomized to ranolazine (n = 13) or placebo (n = 16). After a 2-week drug titration period, subjects participated in a 12-week exercise program. Peak VO2, physical activity (via accelerometer), and HRQOL were assessed before and after training. After exercise training, peak VO2increased twice as much with ranolazine (2.1 ± 3.4 ml/kg/min) as with placebo (0.9 ± 1.5) (both p <0.05). After exercise training, both groups significantly improved HRQOL score (p <0.05); however, the improvement with ranolazine (19 ± 21) was almost 50% greater than with placebo (13 ± 18). There was a significant decrease in maximal heart rate after training with ranolazine but not with placebo (group difference, p = 0.04). Oxygen pulse (peak VO2/peak HR) increased in both groups after training; but, the increase was 4 times greater with ranolazine - resulting in a significant difference between groups (p = 0.044). In conclusion, patients with angina, the addition of ranolazine to an exercise program may improve aerobic fitness, physical activity, and HRQOL beyond the results of an exercise training program alone. Exercise training with ranolazine led to significantly greater increases in oxygen pulse, which is significantly correlated with stroke volume and is an independent predictor of mortality.

A 35-Year-Old Woman With Shock, Pulseless Electrical Activity Arrest, and Hemodynamic Collapse.

CASE PRESENTATION: A 35-year-old woman presented with 2 days of nausea, abdominal pain, and fatigue. On the day of presentation, her abdominal pain worsened, she developed progressive somnolence, and had several bouts of nonbloody, nonbilious emesis. She denied prior headache, rashes, and toxic or illicit ingestions. The patient had a medical history of diabetes mellitus type 2, hyperlipidemia, and mild cognitive delay (highly functional, maintaining a job, home, and medication responsibilities). She reported taking only simvastatin and short-acting insulin. She had an unknown adverse reaction to metformin. She was a nonsmoker and denied history of drug and alcohol use.

Prevalence and correlates of psychological distress among 13-14 year old adolescent girls in North Karnataka, South India: a cross-sectional study.

BACKGROUND: Mental health disorders among adolescents have emerged as a major public health issue in many low and middle-income countries, including India. There is a paucity of research on the determinants of psychological distress, particularly among the poorest girls in the poorest communities. The purpose of this study was to assess the prevalence and correlates of different indicators of psychological distress among 13-14 year old low caste girls in rural, south India. METHODS: Cross-sectional survey of 1191 low caste girls in two districts in north Karnataka, conducted as part of a cluster randomised-control trial. Bivariate and multivariate logistic regression analysis assessed correlates of different indicators of psychological distress. RESULTS: More than one third of girls (35.1%) reported having no hope for the future. 6.9% reported feeling down, depressed or hopeless in the past 2 weeks. 2.1% reported thinking they would be better off dead or of hurting themselves in some way in the past 2 weeks. 1.6% reported sexual abuse, 8.0% rrecent eve teasing and 6.3% having no parental emotional support. Suicidal ideation was independently associated with sexual abuse (AOR 11.9 (3.0-47.0)) and a lack of parental emotional support (AOR 0.2 (0.1-0.5)). Feeling down, depressed or hopeless was independently associated with recent eve-teasing (AOR 2.9 (1.6-5.4)), a harassing or abusive school environment (AOR 3.9 (1.8-8.2)), being frequently absent (AOR 2.8 (1.5-5.5)) or having dropped out of school (AOR 2.1 (1.0-4.3)), and living in Vijayapura district (AOR 2.5 (1.6-4.1)). Having no hope for the future was independently associated with a range of factors, including recent "eve-teasing" (AOR 1.5 (1.0-2.4)), being engaged (AOR 2.9 (0.9-9.7)), not participating in groups (AOR 0.5 (0.4-0.6)) and a lack of emotional support (AOR 0.6 (0.4-0.7)). CONCLUSIONS: Rather than being a time of optimism, a third of low caste girls in rural north, Karnataka have limited hope for the future, with some contemplating suicide. As well as having important development benefits, interventions that address the upstream structural and gender-norms based determinants of poor mental health, and provide adolescent services for girls who require treatment and support, should have important benefits for girls' psychological wellbeing. TRIAL REGISTRATION: Prospectively registered at ClinicalTrials.GovNCT01996241 . November 27, 2013.

Paradoxical Bronchoconstriction with Short-Acting Beta Agonist.

BACKGROUND Asthma is a common disease in the U.S. POPULATION: Initial therapy in the stepwise approach for asthma management is short-acting ß2-agonist (SABA) therapy as needed for symptom control. However, a significant adverse event that can occur with administration is bronchospasm. Here, we report a case of paradoxical bronchospasm with administration of SABAs during multiple pulmonary function tests (PFTs). CASE REPORT A 25-year-old, non-smoking, African American male with a history of moderate asthma and allergic rhinitis treated with fluticasone/salmeterol diskus, albuterol hydrofluoroalkane (HFA) inhaler, and montelukast presented to our clinic complaining of recurrent episodes of acute shortness of breath immediately following each administration of albuterol for 4 weeks. PFTs were performed with levalbuterol (Xopenex) and albuterol (ProAir), yielding significant decrease in forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC). Nebulized albuterol and ipratropium bromide also improved FEV1 and FVC. He was successfully transitioned to an ipratropium rescue inhaler for asthma exacerbations. CONCLUSIONS Paradoxical bronchoconstriction is the unexpected constriction of smooth muscle walls of the bronchi that occurs in the setting of an expected bronchodilatory response. This phenomenon has been observed with ß2-agonist-containing inhaler formulations and is an under-recognized adverse event. Theories suggest that the formulation excipients can trigger airway hyperresponsiveness in patients with allergically inflamed airways. Removal of excipients or use of anticholinergic inhalers improved respiratory function. Clinicians should be aware of paradoxical bronchospasm as an adverse effect with common inhaler formulations containing ß2-agonists and counsel patients accordingly in the appropriate clinical setting.

Ten weeks of high-intensity interval walk training is associated with reduced disease activity and improved innate immune function in older adults with rheumatoid arthritis: a pilot study.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory disease in which adults have significant joint issues leading to poor health. Poor health is compounded by many factors, including exercise avoidance and increased risk of opportunistic infection. Exercise training can improve the health of patients with RA and potentially improve immune function; however, information on the effects of high-intensity interval training (HIIT) in RA is limited. We sought to determine whether 10 weeks of a walking-based HIIT program would be associated with health improvements as measured by disease activity and aerobic fitness. Further, we assessed whether HIIT was associated with improved immune function, specifically antimicrobial/bacterial functions of neutrophils and monocytes. METHODS: Twelve physically inactive adults aged 64 ± 7 years with either seropositive or radiographically proven (bone erosions) RA completed 10 weeks of high-intensity interval walking. Training consisted of 3 × 30-minute sessions/week of ten ≥ 60-second intervals of high intensity (80-90% VO2reserve) separated by similar bouts of lower-intensity intervals (50-60% VO2reserve). Pre- and postintervention assessments included aerobic and physical function; disease activity as measured by Disease Activity score in 28 joints (DAS28), self-perceived health, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR); plasma interleukin (IL)-1ß, IL-6, chemokine (C-X-C motif) ligand (CXCL)-8, IL-10, and tumor necrosis factor (TNF)-α concentrations; and neutrophil and monocyte phenotypes and functions. RESULTS: Despite minimal body composition change, cardiorespiratory fitness increased by 9% (change in both relative and absolute aerobic capacity; p < 0.001), and resting blood pressure and heart rate were both reduced (both p < 0.05). Postintervention disease activity was reduced by 38% (DAS28; p = 0.001) with significant reductions in ESR and swollen joints as well as improved self-perceived health. Neutrophil migration toward CXCL-8 (p = 0.003), phagocytosis of Escherichia coli (p = 0.03), and ROS production (p < 0.001) all increased following training. The frequency of cluster of differentiation 14-positive (CD14+)/CD16+ monocytes was reduced (p = 0.002), with both nonclassical (CD14dim/CD16bright) and intermediate (CD14bright/CD16positive) monocytes being reduced (both p < 0.05). Following training, the cell surface expression of intermediate monocyte Toll-like receptor 2 (TLR2), TLR4, and HLA-DR was reduced (all p < 0.05), and monocyte phagocytosis of E. coli increased (p = 0.02). No changes were observed for inflammatory markers IL-1ß, IL-6, CXCL-8, IL-10, CRP, or TNF-α. CONCLUSIONS: We report for the first time, to our knowledge, that a high-intensity interval walking protocol in older adults with stable RA is associated with reduced disease activity, improved cardiovascular fitness, and improved innate immune functions, indicative of reduced infection risk and inflammatory potential. Importantly, the exercise program was well tolerated by these patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02528344 . Registered on 19 August 2015.