Effect of terbutaline on hyperpnoea-induced bronchoconstriction and urinary club cell protein 16 in athletes

This article is made available through the Brunel Open Access Publishing Fund and is distributed by the Creative Commons CC-BY 3.0 license, under which all are free to reuse or distribute the article under the condition that this original publication must be cited.Repeated injury of the airway epithelium caused by hyperpnoea of poorly conditioned air has been proposed as a key factor in the pathogenesis of exercise-induced bronchoconstriction (EIB) in athletes. In animals, the short-acting β2-agonist terbutaline has been shown to reduce dry airflow-induced bronchoconstriction and the associated shedding of airway epithelial cells. Our aim was to test the efficacy of inhaled terbutaline in attenuating hyperpnoea-induced bronchoconstriction and airway epithelial injury in athletes. Twenty-seven athletes with EIB participated in a randomized, double-blind, placebo-controlled, crossover study. Athletes completed an 8-min eucapnic voluntary hyperpnoea (EVH) test with dry air on two separate days 15 min after inhaling 0.5 mg terbutaline or a matching placebo. Forced expiratory volume in 1 s (FEV1) and urinary concentration of the club cell (Clara cell) protein 16 (CC16, a marker of airway epithelial perturbation) were measured before and up to 60 min after EVH. The maximum fall in FEV1 of 17 ± 8% (SD) on placebo was reduced to 8 ± 5% following terbutaline (P < 0.001). Terbutaline gave bronchoprotection (i.e., post-EVH FEV1 fall <10%) to 22 (81%) athletes. EVH caused an increase in urinary excretion of CC16 in both conditions (P < 0.001), and terbutaline significantly reduced this rise (pre- to postchallenge CC16 increase 416 ± 495 pg/μmol creatinine after placebo vs. 315 ± 523 pg/μmol creatinine after terbutaline, P = 0.016). These results suggest that the inhalation of a single therapeutic dose of terbutaline offers significant protection against hyperpnoea-induced bronchoconstriction and attenuates acute airway epithelial perturbation in athletes.World Anti Doping Agenc

Challenges and opportunities of the COVID-19 pandemic for perinatal mental health care: a mixed-methods study of mental health care staff

The aim of this study was to explore staff perceptions of the impact of the COVID-19 pandemic on mental health service delivery and outcomes for women who were pregnant or in the first year after birth ('perinatal' women). Secondary analysis was undertaken of an online mixed-methods survey open to all mental health care staff in the UK involving 363 staff working with women in the perinatal period. Staff perceived the mental health of perinatal women to be particularly vulnerable to the impact of stressors associated with the pandemic such as social isolation (rated by 79.3% as relevant or extremely relevant; 288/363) and domestic violence and abuse (53.3%; 192/360). As a result of changes to mental health and other health and social care services, staff reported feeling less able to assess women, particularly their relationship with their baby (43.3%; 90/208), and to mobilise safeguarding procedures (29.4%; 62/211). While 42% of staff reported that some women engaged poorly with virtual appointments, they also found flexible remote consulting to be beneficial for some women and helped time management due to reductions in travel time. Delivery of perinatal care needs to be tailored to women's needs; virtual appointments are perceived not to be appropriate for assessments but may be helpful for some women in subsequent interactions. Safeguarding and other risk assessment procedures must remain robust in spite of modifications made to service delivery during pandemics

Influence of southern hemispheric biomass burning on midtropospheric distributions of nonmethane hydrocarbons and selected halocarbons over the remote South Pacific

Aircraft measurements of nonmethane hydrocarbons (NMHCs) and halocarbons were made over the remote South Pacific Ocean during late August-early October 1996 for NASA's Global Tropospheric Experiment (GTE) Pacific Exploratory Mission-Tropics A (PEM-Tropics A). This paper discusses the large-scale spatial distributions of selected trace gases encountered during PEM-Tropics A. The PEM-Tropics A observations are compared to measurements made over the southwestern pacific in early November 1995 as part of Aerosol Characterization Experiment (ACE 1). Continental pollution in the form of layers containing elevated levels of O3 was observed during a majority of PEM-Tropics flights, as well as during several ACE 1 flights. The chemical composition of these air masses indicates that they were not fresh and were derived from nonurban combustion sources. The substantial impact of biomass burning on the vertical structure of the South Pacific troposphere is discussed. Copyright 1999 by the American Geophysical Union

Exercise-induced dehydration alters pulmonary function but does not modify airway responsiveness to dry air in athletes with mild asthma

Background: Local airway water loss is the main physiological trigger for exercise induced bronchoconstriction (EIB). Aim: To investigate the effects of whole-body water loss on airway responsiveness and pulmonary function in athletes with mild asthma and/or EIB. Methods: Ten recreational athletes with a doctor diagnosis of mild asthma and/or EIB completed a randomized, cross-over study. Pulmonary function tests (spirometry, whole body plethysmography and diffusing capacity for carbon monoxide [DLCO]) were conducted before and after three conditions: i) 2 h exercise in the heat with no fluid intake (dehydration); ii) 2 h exercise with ad libitum fluid intake (control); and iii) time-matched rest period (rest). Airway responsiveness was assessed 2 h post-exercise/rest via eucapnic voluntary hyperpnea (EVH) to dry air. Results: Exercise in the heat with no fluid intake induced a state of mild dehydration, with a mean body mass loss of 2.3±0.8% (SD). After EVH, airway narrowing was not different between conditions: median (interquartile range) maximum fall in forced expiratory volume in 1 sec was 13 (7–15)%, 11 (9–24)% and 12 (7–20)% in the dehydration, control and rest conditions, respectively. Dehydration caused a significant reduction in forced vital capacity (300±190 ml, P=0.001) and concomitant increases in residual volume (260±180 ml, P=0.001) and functional residual capacity (260±250 ml, P=0.011), with no change in DLCO. Conclusion: Mild exercise induced dehydration does not exaggerate airway responsiveness to dry air in athletes with mild asthma/EIB, but may affect small airway function.This study was supported by the European Hydration Institute Student Research Grant Scheme

Transglutaminase 2 limits the extravasation and the resultant myocardial fibrosis associated with factor XIII-A deficiency

Background and aims Transglutaminase (TG) 2 and Factor (F) XIII-A have both been implicated in cardiovascular protection and repair. This study was designed to differentiate between two competing hypotheses: that TG2 and FXIII-A mediate these functions in mice by fulfilling separate roles, or that they act redundantly in this respect. Methods Atherosclerosis was assessed in brachiocephalic artery plaques of fat-fed mixed strain apolipoprotein (Apo)e deficient mice that lacked either or both transglutaminases. Cardiac fibrosis was assessed both in the mixed strain mice and also in C57BL/6J Apoe expressing mice lacking either or both transglutaminases. Results No difference was found in the density of buried fibrous caps within brachiocephalic plaques from mice expressing or lacking these transglutaminases. Cardiac fibrosis developed in both Apoe/F13a1 double knockout and F13a1 single knockout mice, but not in Tgm2 knockout mice. However, concomitant Tgm2 knockout markedly increased fibrosis, as apparent in both Apoe/Tgm2/F13a1 knockout and Tgm2/F13a1 knockout mice. Amongst F13a1 knockout and Tgm2/F13a1 knockout mice, the extent of fibrosis correlated with hemosiderin deposition, suggesting that TG2 limits the extravasation of blood in the myocardium, which in turn reduces the pro-fibrotic stimulus. The resulting fibrosis was interstitial in nature and caused only minor changes in cardiac function. Conclusions These studies confirm that FXIII-A and TG2 fulfil different roles in the mouse myocardium. FXIII-A protects against vascular leakage while TG2 contributes to the stability or repair of the vasculature. The protective function of TG2 must be considered when designing clinical anti-fibrotic therapies based upon FXIII-A or TG2 inhibition

Insulin trafficking in a glucose responsive engineered human liver cell line is regulated by the interaction of ATP-sensitive potassium channels and voltage- gated calcium channels

Type I diabetes is caused by the autoimmune destruction of pancreatic beta (â) cells [1]. Current treatment requires multiple daily injections of insulin to control blood glucose levels. Tight glucose control lowers, but does not eliminate, the onset of diabetic complications, which greatly reduce the quality and longevity of life for patients. Transplantation of pancreatic tissue as a treatment is restricted by the scarcity of donors and the requirement for lifelong immunosuppression to preserve the graft, which carries adverse side-effects. This is of particular concern as Type 1 diabetes predominantly affects children. Lack of glucose control could be overcome by genetically engineering "an artificial â-cell" that is capable of synthesising, storing and secreting insulin in response to metabolic signals. The donor cell type must be readily accessible and capable of being engineered to synthesise, process, store and secrete insulin under physiological conditions

Effects of habitat and land use on breeding season density of male Asian Houbara Chlamydotis macqueenii

Landscape-scale habitat and land-use influences on Asian Houbara Chlamydotis macqueenii (IUCN Vulnerable) remain unstudied, while estimating numbers of this cryptic, low-density, over-hunted species is challenging. In spring 2013, male houbara were recorded at 231 point counts, conducted twice, across a gradient of sheep density and shrub assemblages within 14,300 km² of the Kyzylkum Desert, Uzbekistan. Four sets of models related male abundance to: (1) vegetation structure (shrub height and substrate); (2) shrub assemblage; (3) shrub species composition (multidimensional scaling); (4) remote-sensed derived land-cover (GLOBCOVER, 4 variables). Each set also incorporated measures of landscape rugosity and sheep density. For each set, multi-model inference was applied to generalised linear mixed models of visit-specific counts that included important detectability covariates and point ID as a random effect. Vegetation structure received strongest support, followed by shrub species composition and shrub assemblage, with weakest support for the GLOBCOVER model set. Male houbara numbers were greater with lower mean shrub height, more gravel and flatter surfaces, but were unaffected by sheep density. Male density (mean 0.14 km-2, 95% CI, 0.12‒0.15) estimated by distance analysis differed substantially among shrub assemblages, being highest in vegetation dominated by Salsola rigida (0.22 [CI, 0.20‒0.25]), high in areas of S. arbuscula and Astragalus (0.14 [CI, 0.13‒0.16] and 0.15 [CI, 0.14‒0.17] respectively), lower (0.09 [CI, 0.08‒0.10]) in Artemisia and lowest (0.04 [CI, 0.04‒0.05]) in Calligonum. The study area was estimated to hold 1,824 males (CI: 1,645‒2,030). The spatial distribution of relative male houbara abundance, predicted from vegetation structure models, had the strongest correspondence with observed numbers in both model-calibration and the subsequent year’s data. We found no effect of pastoralism on male distribution but potential effects on nesting females are unknown. Density differences among shrub communities suggest extrapolation to estimate country- or range-wide population size must take account of vegetation composition

A telephone survey of cancer awareness among frontline staff: informing training needs

Background: Studies have shown limited awareness about cancer risk factors among hospital-based staff. Less is known about general cancer awareness among community frontline National Health Service and social care staff. Methods: A cross-sectional computer-assisted telephone survey of 4664 frontline community-based health and social care staff in North West England. Results: A total of 671 out of 4664 (14.4%) potentially eligible subjects agreed to take part. Over 92% of staff recognised most warning signs, except an unexplained pain (88.8%, n=596), cough or hoarseness (86.9%, n=583) and a sore that does not heal (77.3%, n=519). The bowel cancer-screening programme was recognised by 61.8% (n=415) of staff. Most staff agreed that smoking and passive smoking ‘increased the chance of getting cancer.’ Fewer agreed about getting sunburnt more than once as a child (78.0%, n=523), being overweight (73.5%, n=493), drinking more than one unit of alcohol per day (50.2%, n=337) or doing less than 30 min of moderate physical exercise five times a week (41.1%, n=276). Conclusion: Cancer awareness is generally good among frontline staff, but important gaps exist, which might be improved by targeted education and training and through developing clearer messages about cancer risk factors