Cardiopulmonary Exercise Testing Provides Additional Prognostic Information in Cystic Fibrosis

RATIONALE: The prognostic value of cardiopulmonary exercise testing (CPET) for survival in cystic fibrosis (CF) in the context of current clinical management, when controlling for other known prognostic factors, is unclear. OBJECTIVES: To determine the prognostic value of CPET-derived measures beyond peak oxygen uptake (V.o2peak) following rigorous adjustment for other predictors. METHODS: Data from 10 CF centers in Australia, Europe, and North America were collected retrospectively. A total of 510 patients completed a cycle CPET between January 2000 and December 2007, of which 433 fulfilled the criteria for a maximal effort. Time to death/lung transplantation was analyzed using Cox proportional hazards regression. In addition, phenotyping using hierarchical Ward clustering was performed to characterize high-risk subgroups. MEASUREMENTS AND MAIN RESULTS: Cox regression showed, even after adjustment for sex, FEV1% predicted, body mass index (z-score), age at CPET, Pseudomonas aeruginosa status, and CF-related diabetes as covariates in the model, that V.o2peak in % predicted (hazard ratio [HR], 0.964; 95% confidence interval [CI], 0.944–0.986), peak work rate (% predicted; HR, 0.969; 95% CI, 0.951–0.988), ventilatory equivalent for oxygen (HR, 1.085; 95% CI, 1.041–1.132), and carbon dioxide (HR, 1.060; 95% CI, 1.007–1.115) (all P < 0.05) were significant predictors of death or lung transplantation at 10-year follow-up. Phenotyping revealed that CPET-derived measures were important for clustering. We identified a high-risk cluster characterized by poor lung function, nutritional status, and exercise capacity. CONCLUSIONS: CPET provides additional prognostic information to established predictors of death/lung transplantation in CF. High-risk patients may especially benefit from regular monitoring of exercise capacity and exercise counseling

Dopamine Transporter and Reward Anticipation in a Dimensional Perspective : A Multimodal Brain Imaging Study

We would like to thank Christine Baron, Vincent Brulon, Stéphane LeHelleix, Stéphane Demphel, Claude Comtat, Frédéric Dollé, Philippe Gervais, and Renaud Maroy from the Service Hospitalier Frédéric Joliot for their efficient technical support and 11C radioligand preparation. They thank Marie Prat, Audrey Pepin, and Audrey Mabondo for their help in PET processing and Pr. Maria-Joao Santiago-Ribeiro and Dr Renaud de Beaurepaire for their involvement in the recruitment of participants.Peer reviewedPostprin

Responsiveness of pituitary to galanin throughout the reproductive cycle of male European sea bass (Dicentrarchus labrax)

The neuropeptide galanin (Gal) is a putative factor regulating puberty onset and reproduction through its actions on the pituitary. The present study investigated the pituitary responsiveness to galanin and the patterns of galanin receptors (Galrs) expression throughout the reproductive cycle of two years old male European sea bass (Dicentrarchus labrax), an important aquaculture species. Quantitative analysis of pituitary and hypothalamus transcript expression of four galr subtypes revealed differential regulation according to the testicular developmental stage, with an overall decrease in expression from the immature stage to the mid-recrudescence stage. Incubation of pituitary cells with mammalian 1-29 Gal peptide induced significant changes in cAMP concentration, with sensitivities that varied according to the testicular development stages. Furthermore 1-29 Gal was able to stimulate both follicle stimulating hormone (Fsh) and luteinizing hormone (Lh) release from pituitary cell suspensions. The magnitude of the effects and effective concentrations varied according to reproductive stage, with generalized induction of Fsh and Lh release in animals sampled in January (full spermiation). The differential expression of galrs in pituitary and hypothalamus across the reproductive season, together with the differential effects of Gal on gonadotropins release in vitro strongly suggests the involvement of the galaninergic system in the regulation the hypothalamus-pituitary-gonad axis of male sea bass. This is to our knowledge the first clear evidence for the involvement of galanin in the regulation of reproduction in non-mammalian vertebrates. (C) 2017 Elsevier Inc. All rights reserved.European Union Seventh Framework Programme [262336]Spanish Ministry of Science and Innovation (MICINN)Spanish Ministry of the Economy and Competitiveness (MINECO) [AGL2009-11086]Spanish Ministry of the Economy and CompetitivenessRegional Government of Valencia [PROME-TEOH/2014/051]info:eu-repo/semantics/acceptedVersio

Effects of a partially supervised conditioning programme in cystic fibrosis: an international multi-centre randomised controlled trial (ACTIVATE-CF): study protocol

Physical activity (PA) and exercise have become an accepted and valued component of cystic fibrosis (CF) care. Regular PA and exercise can positively impact pulmonary function, improve physical fitness, and enhance health-related quality of life (HRQoL). However, motivating people to be more active is challenging. Supervised exercise programs are expensive and labour intensive, and adherence falls off significantly once supervision ends. Unsupervised or partially supervised programs are less costly and more flexible, but compliance can be more problematic. The primary objective of this study is to evaluate the effects of a partially supervised exercise intervention along with regular motivation on forced expiratory volume in 1 s (FEV1) at 6 months in a large international group of CF patients. Secondary endpoints include patient reported HRQoL, as well as levels of anxiety and depression, and control of blood sugar.; It is planned that a total of 292 patients with CF 12 years and older with a FEV1 ≥ 35% predicted shall be randomised. Following baseline assessments (2 visits) patients are randomised into an intervention and a control group. Thereafter, they will be seen every 3 months for assessments in their centre for one year (4 follow-up visits). Along with individual counselling to increase vigorous PA by at least 3 h per week on each clinic visit, the intervention group documents daily PA and inactivity time and receives a step counter to record their progress within a web-based diary. They also receive monthly phone calls from the study staff during the first 6 months of the study. After 6 months, they continue with the step counter and web-based programme for a further 6 months. The control group receives standard care and keeps their PA level constant during the study period. Thereafter, they receive the intervention as well.; This is the first large, international multi-centre study to investigate the effects of a PA intervention in CF with motivational feedback on several health outcomes using modern technology. Should this relatively simple programme prove successful, it will be made available on a wider scale internationally.; ClinicalTrials.gov Identifier: NCT01744561 ; Registration date: December 6, 2012

Bioenergetics Failure and Oxidative Stress in Brain Stem Mediates Cardiovascular Collapse Associated with Fatal Methamphetamine Intoxication

Background: Whereas sudden death, most often associated with cardiovascular collapse, occurs in abusers of the psychostimulant methamphetamine (METH), the underlying mechanism is much less understood. The demonstration that successful resuscitation of an arrested heart depends on maintained functionality of the rostral ventrolateral medulla (RVLM), which is responsible for the maintenance of stable blood pressure, suggests that failure of brain stem cardiovascular regulation, rather than the heart, holds the key to cardiovascular collapse. We tested the hypothesis that cessation of brain stem cardiovascular regulation because of a loss of functionality in RVLM mediated by bioenergetics failure and oxidative stress underlies the cardiovascular collapse elicited by lethal doses of METH. Methodology/Principal Findings: Survival rate, cardiovascular responses and biochemical or morphological changes in RVLM induced by intravenous administration of METH in Sprague-Dawley rats were investigated. High doses of METH induced significant mortality within 20 min that paralleled concomitant the collapse of arterial pressure or heart rate and loss of functionality in RVLM. There were concurrent increases in the concentration of METH in serum and ventrolateral medulla, along with tissue anoxia, cessation of microvascular perfusion and necrotic cell death in RVLM. Furthermore, mitochondrial respiratory chain enzyme activity or electron transport capacity and ATP production in RVLM were reduced, and mitochondria-derived superoxide anion level was augmented. All those detrimental physiological and biochemica

Gambling Problems among Community Cocaine Users

Cocaine use is highly prevalent and a major public health problem. While some studies have reported frequent comorbidity problems among cocaine users, few studies have included evaluation of gambling problems. This study aimed to estimate the prevalence of gambling problems and compare those who were at-risk gamblers with non-problem gamblers in terms of mental health problems, substance use problems, and some risk factors (i.e. family antecedents, erroneous perceptions and coping strategies) among individuals who smoke or inject cocaine. METHOD: A total of 424 smoked or injected cocaine users recruited through community-based programs in Montreal, Quebec completed the questionnaire, including the Canadian Pathological Gambling Index, the Composite International Diagnostic Interview (CIDI), the CAGE, and the Severity Dependence Scale (SDS). RESULTS: Of the sample, 18.4 % were considered at-risk gamblers, of whom 7.8 % had problems gambling and 10.6 % were moderate-risk gamblers. The at-risk group was more likely to have experienced a recent phobic disorder and alcohol problems than the non-problem group. A multivariate analysis showed that, compared to those who were non-problem gamblers, the at-risk ones were more likely to have lost a large sum of money when they first started gambling, believed that their luck would turn, and gambled in reaction to painful life events. These results indicate the need to include routines for screening to identify gambling problem among cocaine user

Bronchopulmonary dysplasia: clinical aspects and preventive and therapeutic strategies

Abstract Background Bronchopulmonary dysplasia (BPD) is the result of a complex process in which several prenatal and/or postnatal factors interfere with lower respiratory tract development, leading to a severe, lifelong disease. In this review, what is presently known regarding BPD pathogenesis, its impact on long-term pulmonary morbidity and mortality and the available preventive and therapeutic strategies are discussed. Main body Bronchopulmonary dysplasia is associated with persistent lung impairment later in life, significantly impacting health services because subjects with BPD have, in most cases, frequent respiratory diseases and reductions in quality of life and life expectancy. Prematurity per se is associated with an increased risk of long-term lung problems. However, in children with BPD, impairment of pulmonary structures and function is even greater, although the characterization of long-term outcomes of BPD is difficult because the adults presently available to study have received outdated treatment. Prenatal and postnatal preventive measures are extremely important to reduce the risk of BPD. Conclusion Bronchopulmonary dysplasia is a respiratory condition that presently occurs in preterm neonates and can lead to chronic respiratory problems. Although knowledge about BPD pathogenesis has significantly increased in recent years, not all of the mechanisms that lead to lung damage are completely understood, which explains why therapeutic approaches that are theoretically effective have been only partly satisfactory or useless and, in some cases, potentially negative. However, prevention of prematurity, systematic use of nonaggressive ventilator measures, avoiding supraphysiologic oxygen exposure and administration of surfactant, caffeine and vitamin A can significantly reduce the risk of BPD development. Cell therapy is the most fascinating new measure to address the lung damage due to BPD. It is desirable that ongoing studies yield positive results to definitively solve a major clinical, social and economic problem