Effects of exercise intensity and nutrition advice on myocardial function in obese children and adolescents: a multicentre randomised controlled trial study protocol.

INTRODUCTION: The prevalence of paediatric obesity is increasing, and with it, lifestyle-related diseases in children and adolescents. High-intensity interval training (HIIT) has recently been explored as an alternate to traditional moderate-intensity continuous training (MICT) in adults with chronic disease and has been shown to induce a rapid reversal of subclinical disease markers in obese children and adolescents. The primary aim of this study is to compare the effects of HIIT with MICT on myocardial function in obese children and adolescents. METHODS AND ANALYSIS: Multicentre randomised controlled trial of 100 obese children and adolescents in the cities of Trondheim (Norway) and Brisbane (Australia). The trial will examine the efficacy of HIIT to improve cardiometabolic outcomes in obese children and adolescents. Participants will be randomised to (1) HIIT and nutrition advice, (2) MICT and nutrition advice or (3) nutrition advice. Participants will partake in supervised exercise training and/or nutrition sessions for 3 months. Measurements for study end points will occur at baseline, 3 months (postintervention) and 12 months (follow-up). The primary end point is myocardial function (peak systolic tissue velocity). Secondary end points include vascular function (flow-mediated dilation assessment), quantity of visceral and subcutaneous adipose tissue, myocardial structure and function, body composition, cardiorespiratory fitness, autonomic function, blood biochemistry, physical activity and nutrition. Lean, healthy children and adolescents will complete measurements for all study end points at one time point for comparative cross-sectional analyses. ETHICS AND DISSEMINATION: This randomised controlled trial will generate substantial information regarding the effects of exercise intensity on paediatric obesity, specifically the cardiometabolic health of this at-risk population. It is expected that communication of results will allow for the development of more effective evidence-based exercise prescription guidelines in this population while investigating the benefits of HIIT on subclinical markers of disease. TRIAL REGISTRATION NUMBER: NCT01991106

Laparoscopic adjustable gastric band in an obese unrelated living donor prior to kidney transplantation: a case report

Introduction. Obese living donors who undergo donor nephrectomy have higher rates of intra-operative and post-operative complications. Many centres exclude obese donors from living donor transplant programs. Diet, exercise and medication are often ineffective weight loss interventions for donors, hence bariatric surgery should be considered. Case presentation. We report the case of a 53-year-old Caucasian woman who underwent laparoscopically adjustable gastric banding. The procedure enabled her to lose sufficient weight to gain eligibility for kidney donation. After losing weight, she had an uncomplicated laparoscopic donor nephrectomy surgery, and the recipient underwent successful kidney transplantation. Conclusion. Laparoscopically adjustable gastric banding should be considered for obese potential living kidney donors whenever transplantation units restrict access to donor nephrectomy based on the increased surgical risk for donors

Examining links between anxiety, reinvestment and walking when talking by older adults during adaptive gait

Falls by older adults often result in reduced quality of life and debilitating fear of further falls. Stopping walking when talking (SWWT) is a significant predictor of future falls by older adults and is thought to reflect age-related increases in attentional demands of walking. We examine whether SWWT is associated with use of explicit movement cues during locomotion, and evaluate if conscious control (i.e., movement specific reinvestment) is causally linked to falls-related anxiety during a complex walking task. We observed whether twenty-four older adults stopped walking when talking when asked a question during an adaptive gait task. After certain trials, participants completed a visual-spatial recall task regarding walkway features, or answered questions about their movements during the walk. In a subsequent experimental condition, participants completed the walking task under conditions of raised postural threat. Compared to a control group, participants who SWWT reported higher scores for aspects of reinvestment relating to conscious motor processing but not movement self-consciousness. The higher scores for conscious motor processing were preserved when scores representing cognitive function were included as a covariate. There were no group differences in measures of general cognitive function, visual spatial working memory or balance confidence. However, the SWWT group reported higher scores on a test of external awareness when walking, indicating allocation of attention away from task-relevant environmental features. Under conditions of increased threat, participants self-reported significantly greater state anxiety and reinvestment and displayed more accurate responses about their movements during the task. SWWT is not associated solely with age-related cognitive decline or generic increases in age-related attentional demands of walking. SWWT may be caused by competition for phonological resources of working memory associated with consciously processing motor actions and appears to be causally linked with fall-related anxiety and increased vigilance.This research was supported by The Royal Society (IE131576) and British Academy (SG132820)

Identification of the Regulatory Logic Controlling Salmonella Pathoadaptation by the SsrA-SsrB Two-Component System

Sequence data from the past decade has laid bare the significance of horizontal gene transfer in creating genetic diversity in the bacterial world. Regulatory evolution, in which non-coding DNA is mutated to create new regulatory nodes, also contributes to this diversity to allow niche adaptation and the evolution of pathogenesis. To survive in the host environment, Salmonella enterica uses a type III secretion system and effector proteins, which are activated by the SsrA-SsrB two-component system in response to the host environment. To better understand the phenomenon of regulatory evolution in S. enterica, we defined the SsrB regulon and asked how this transcription factor interacts with the cis-regulatory region of target genes. Using ChIP-on-chip, cDNA hybridization, and comparative genomics analyses, we describe the SsrB-dependent regulon of ancestral and horizontally acquired genes. Further, we used a genetic screen and computational analyses integrating experimental data from S. enterica and sequence data from an orthologous regulatory system in the insect endosymbiont, Sodalis glossinidius, to identify the conserved yet flexible palindrome sequence that defines DNA recognition by SsrB. Mutational analysis of a representative promoter validated this palindrome as the minimal architecture needed for regulatory input by SsrB. These data provide a high-resolution map of a regulatory network and the underlying logic enabling pathogen adaptation to a host

A semiparametric modeling framework for potential biomarker discovery and the development of metabonomic profiles

<p>Abstract</p> <p>Background</p> <p>The discovery of biomarkers is an important step towards the development of criteria for early diagnosis of disease status. Recently electrospray ionization (ESI) and matrix assisted laser desorption (MALDI) time-of-flight (TOF) mass spectrometry have been used to identify biomarkers both in proteomics and metabonomics studies. Data sets generated from such studies are generally very large in size and thus require the use of sophisticated statistical techniques to glean useful information. Most recent attempts to process these types of data model each compound's intensity either discretely by positional (mass to charge ratio) clustering or through each compounds' own intensity distribution. Traditionally data processing steps such as noise removal, background elimination and m/z alignment, are generally carried out separately resulting in unsatisfactory propagation of signals in the final model.</p> <p>Results</p> <p>In the present study a novel semi-parametric approach has been developed to distinguish urinary metabolic profiles in a group of traumatic patients from those of a control group consisting of normal individuals. Data sets obtained from the replicates of a single subject were used to develop a functional profile through Dirichlet mixture of beta distribution. This functional profile is flexible enough to accommodate variability of the instrument and the inherent variability of each individual, thus simultaneously addressing different sources of systematic error. To address instrument variability, all data sets were analyzed in replicate, an important issue ignored by most studies in the past. Different model comparisons were performed to select the best model for each subject. The m/z values in the window of the irregular pattern are then further recommended for possible biomarker discovery.</p> <p>Conclusion</p> <p>To the best of our knowledge this is the very first attempt to model the physical process behind the time-of flight mass spectrometry. Most of the state of the art techniques does not take these physical principles in consideration while modeling such data. The proposed modeling process will apply as long as the basic physical principle presented in this paper is valid. Notably we have confined our present work mostly within the modeling aspect. Nevertheless clinical validation of our recommended list of potential biomarkers will be required. Hence, we have termed our modeling approach as a "framework" for further work.</p

Improved precision on the experimental E0 decay branching ratio of the Hoyle state

Stellar carbon synthesis occurs exclusively via the $3\alpha$ process, in which three $\alpha$ particles fuse to form $^{12}$C in the excited Hoyle state, followed by electromagnetic decay to the ground state. The Hoyle state is above the $\alpha$ threshold, and the rate of stellar carbon production depends on the radiative width of this state. The radiative width cannot be measured directly, and must instead be deduced by combining three separately measured quantities. One of these quantities is the $E0$ decay branching ratio of the Hoyle state, and the current $10$\% uncertainty on the radiative width stems mainly from the uncertainty on this ratio. The $E0$ branching ratio was deduced from a series of pair conversion measurements of the $E0$ and $E2$ transitions depopulating the $0^+_2$ Hoyle state and $2^+_1$ state in $^{12}$C, respectively. The excited states were populated by the $^{12}$C$(p,p^\prime)$ reaction at 10.5 MeV beam energy, and the pairs were detected with the electron-positron pair spectrometer, Super-e, at the Australian National University. The deduced branching ratio required knowledge of the proton population of the two states, as well as the alignment of the $2^+_1$ state in the reaction. For this purpose, proton scattering and $\gamma$-ray angular distribution experiments were also performed. An $E0$ branching ratio of $\Gamma^{E0}_{\pi}/\Gamma=8.2(5)\times10^{-6}$ was deduced in the current work, and an adopted value of $\Gamma^{E0}_{\pi}/\Gamma=7.6(4)\times10^{-6}$ is recommended based on a weighted average of previous literature values and the new result. The new recommended value for the $E0$ branching ratio is about 14% larger than the previous adopted value of $\Gamma^{E0}_{\pi}/\Gamma=6.7(6)\times10^{-6}$, while the uncertainty has been reduced from 9% to 5%.Comment: Accepted for publication as a Regular Article in Phys. Rev. C on July 29 202

Embedding physical activity in the heart of the NHS: the need for a whole-system approach

Solutions to the global challenge of physical inactivity have tended to focus on interventions at an individual level, when evidence shows that wider factors, including the social and physical environment, play a major part in influencing health-related behaviour. A multidisciplinary perspective is needed to rewrite the research agenda on physical activity if population-level public health benefits are to be demonstrated. This article explores the questions that this raises regarding the particular role that the UK National Health Service (NHS) plays in the system. The National Centre for Sport and Exercise Medicine in Sheffield is put forward as a case study to discuss some of the ways in which health systems can work in collaboration with other partners to develop environments and systems that promote active lives for patients and staff

A Novel Secretion Pathway of Salmonella enterica Acts as an Antivirulence Modulator during Salmonellosis

Salmonella spp. are Gram-negative enteropathogenic bacteria that infect a variety of vertebrate hosts. Like any other living organism, protein secretion is a fundamental process essential for various aspects of Salmonella biology. Herein we report the identification and characterization of a horizontally acquired, autonomous and previously unreported secretion pathway. In Salmonella enterica serovar Typhimurium, this novel secretion pathway is encoded by STM1669 and STM1668, designated zirT and zirS, respectively. We show that ZirT is localized to the bacterial outer membrane, expected to adopt a compact β-barrel conformation, and functions as a translocator for ZirS. ZirS is an exoprotein, which is secreted into the extracellular environment in a ZirT-dependent manner. The ZirTS secretion pathway was found to share several important features with two-partner secretion (TPS) systems and members of the intimin/invasin family of adhesions. We show that zirTS expression is affected by zinc; and that in vivo, induction of zirT occurs distinctively in Salmonella colonizing the small intestine, but not in systemic sites. Additionally, strong expression of zirT takes place in Salmonella shed in fecal pellets during acute and persistent infections of mice. Inactivation of ZirTS results in a hypervirulence phenotype of Salmonella during oral infection of mice. Cumulatively, these results indicate that the ZirTS pathway plays a unique role as an antivirulence modulator during systemic disease and is involved in fine-tuning a host–pathogen balance during salmonellosis