Appetite, gut hormone and energy intake responses to low volume sprint interval and traditional endurance exercise.

Sprint interval exercise improves several health markers but the appetite and energy balance response is unknown. This study compared the effects of sprint interval and endurance exercise on appetite, energy intake and gut hormone responses. Twelve healthy males [mean (SD): age 23 (3) years, body mass index 24.2 (2.9) kg m(-2), maximum oxygen uptake 46.3 (10.2) mL kg(-1) min(-1)] completed three 8 h trials [control (CON), endurance exercise (END), sprint interval exercise (SIE)] separated by 1 week. Trials commenced upon completion of a standardised breakfast. Sixty minutes of cycling at 68.1 (4.3) % of maximum oxygen uptake was performed from 1.75-2.75 h in END. Six 30-s Wingate tests were performed from 2.25-2.75 h in SIE. Appetite ratings, acylated ghrelin and peptide YY (PYY) concentrations were measured throughout each trial. Food intake was monitored from buffet meals at 3.5 and 7 h and an overnight food bag. Appetite (P 0.05). Therefore, relative energy intake (energy intake minus the net energy expenditure of exercise) was lower in END than that in CON (15.7 %; P = 0.006) and SIE (11.5 %; P = 0.082). An acute bout of endurance exercise resulted in lower appetite perceptions in the hours after exercise than sprint interval exercise and induced a greater 24 h energy deficit due to higher energy expenditure during exercise

Smoothing a rugged protein folding landscape by sequence-based redesign

The rugged folding landscapes of functional proteins puts them at risk of misfolding and aggregation. Serine protease inhibitors, or serpins, are paradigms for this delicate balance between function and misfolding. Serpins exist in a metastable state that undergoes a major conformational change in order to inhibit proteases. However, conformational labiality of the native serpin fold renders them susceptible to misfolding, which underlies misfolding diseases such as $\alpha_1$-antitrypsin deficiency. To investigate how serpins balance function and folding, we used consensus design to create $\textit{conserpin}$, a synthetic serpin that folds reversibly, is functional, thermostable, and polymerization resistant. Characterization of its structure, folding and dynamics suggest that consensus design has remodeled the folding landscape to reconcile competing requirements for stability and function. This approach may offer general benefits for engineering functional proteins that have risky folding landscapes, including the removal of aggregation-prone intermediates, and modifying scaffolds for use as protein therapeutics.BTP is a Medical Research Council Career Development Fellow. AAN and JJH are supported by the Wellcome Trust (grant number WT 095195). SM acknowledges fellowship support from the Australian Research Council (FT100100960). NAB is an Australian Research Council Future Fellow (110100223). GIW is an Australian Research Council Discovery Outstanding Researcher Award Fellow (DP140100087). AMB is a National Health and Medical Research Senior Research Fellow (1022688). JCW is an NHMRC Senior Principal Research fellow and also acknowledges the support of an ARC Federation Fellowship. We thank the Australian Synchrotron for beam-time and technical assistance. This work was supported by the Multi-modal Australian ScienceS Imaging and Visualisation Environment (MASSIVE) (www.massive.org.au). We acknowledge the Monash Protein Production Unit and Monash Macromolecular Crystallization Facilit

On the Schoenberg Transformations in Data Analysis: Theory and Illustrations

The class of Schoenberg transformations, embedding Euclidean distances into higher dimensional Euclidean spaces, is presented, and derived from theorems on positive definite and conditionally negative definite matrices. Original results on the arc lengths, angles and curvature of the transformations are proposed, and visualized on artificial data sets by classical multidimensional scaling. A simple distance-based discriminant algorithm illustrates the theory, intimately connected to the Gaussian kernels of Machine Learning

Smoothing a rugged protein folding landscape by sequence-based redesign

The rugged folding landscapes of functional proteins puts them at risk of misfolding and aggregation. Serine protease inhibitors, or serpins, are paradigms for this delicate balance between function and misfolding. Serpins exist in a metastable state that undergoes a major conformational change in order to inhibit proteases. However, conformational labiality of the native serpin fold renders them susceptible to misfolding, which underlies misfolding diseases such as α1-antitrypsin deficiency. To investigate how serpins balance function and folding, we used consensus design to create conserpin, a synthetic serpin that folds reversibly, is functional, thermostable, and polymerization resistant. Characterization of its structure, folding and dynamics suggest that consensus design has remodeled the folding landscape to reconcile competing requirements for stability and function. This approach may offer general benefits for engineering functional proteins that have risky folding landscapes, including the removal of aggregation-prone intermediates, and modifying scaffolds for use as protein therapeutics

Walks4work: Rationale and study design to investigate walking at lunchtime in the workplace setting

Background: Following recruitment of a private sector company, an 8week lunchtime walking intervention was implemented to examine the effect of the intervention on modifiable cardiovascular disease risk factors, and further to see if walking environment had any further effect on the cardiovascular disease risk factors. Methods. For phase 1 of the study participants were divided into three groups, two lunchtime walking intervention groups to walk around either an urban or natural environment twice a week during their lunch break over an 8week period. The third group was a waiting-list control who would be invited to join the walking groups after phase 1. In phase 2 all participants were encouraged to walk during their lunch break on self-selecting routes. Health checks were completed at baseline, end of phase 1 and end of phase 2 in order to measure the impact of the intervention on cardiovascular disease risk. The primary outcome variables of heart rate and heart rate variability were measured to assess autonomic function associated with cardiovascular disease. Secondary outcome variables (Body mass index, blood pressure, fitness, autonomic response to a stressor) related to cardiovascular disease were also measured. The efficacy of the intervention in increasing physical activity was objectively monitored throughout the 8-weeks using an accelerometer device. Discussion. The results of this study will help in developing interventions with low researcher input with high participant output that may be implemented in the workplace. If effective, this study will highlight the contribution that natural environments can make in the reduction of modifiable cardiovascular disease risk factors within the workplace. © 2012 Brown et al.; licensee BioMed Central Ltd

The KiVa antibullying program in primary schools in Chile, with and without the digital game component: study protocol for a randomized controlled trial.

BACKGROUND: Bullying is a major problem worldwide and Chile is no exception. Bullying is defined as a systematic aggressive behavior against a victim who cannot defend him or herself. Victims suffer social isolation and psychological maladjustment, while bullies have a higher risk for conduct problems and substance use disorders. These problems appear to last over time. The KiVa antibullying program has been evaluated in Finland and other European countries, showing preventive effects on victimization and self-reported bullying. The aims of this study are (1) to develop a culturally appropriate version of the KiVa material and (2) to test the effectiveness of the KiVa program, with and without the online game, on reducing experiences of victimization and bullying behavior among vulnerable primary schools in Santiago (Chile), using a cluster randomized controlled trial (RCT) design with three arms: (1) full KiVa program group, (2) partial KiVa (without online game) program group and (3) control group. METHODS AND DESIGN: This is a three-arm, single-blind, cluster randomized controlled trial (RCT) with a target enrolment of 1495 4th and 5th graders attending 13 vulnerable schools per arm. Students in the full and partial KiVa groups will receive universal actions: ten 2-h lessons delivered by trained teachers during 1 year; they will be exposed to posters encouraging them to support victims and behave constructively when witnessing bullying; and a person designated by the school authorities will be present in all school breaks and lunchtimes using a visible KiVa vest to remind everybody that they are in a KiVa school. KiVa schools also will have indicated actions, which consist of a set of discussion groups with the victims and with the bullies, with proper follow-up. Only full KiVa schools will also receive an online game which has the aim to raise awareness of the role of the group in bullying, increase empathy and promote strategies to support victimized peers. Self-reported victimization, bullying others and peer-reported bullying actions, psychological and academic functioning, and sense of school membership will be measured at baseline and 12 months after randomization. DISCUSSION: This is the first cluster RCT of the KiVa antibullying program in Latin America. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT02898324 . Registered on 8 September 2016

Development of a novel small antibody that retains specificity for tumor targeting

<p>Abstract</p> <p>Background</p> <p>For the targeted therapy of solid tumor mediated by monoclonal antibody (mAb), there have different models of rebuilding small antibodies originated from native ones. Almost all natural antibody molecules have the similar structure and conformation, but those rebuilt small antibodies cannot completely keep the original traits of parental antibodies, especially the reduced specificity, which gravely influences the efficacy of small antibodies.</p> <p>Methods</p> <p>In this study, authors developed a novel mimetic in the form of V_HFR1_C-10-V_HCDR1-V_HFR2-V_LCDR3-V_LFR4_N-10for a parental mAb induced with human breast cancer, and the mimetic moiety was conjugated to the C-terminal of toxicin colicin Ia. The novel fusion peptide, named protomimecin (PMN), was administered to MCF-7 breast cancer cells to demonstrate its killing competency <it>in vitro </it>and <it>in vivo</it>.</p> <p>Results</p> <p>Compared with original antibody-colicin Ia (Fab-Ia) and single-chain antibody-colicin Ia (Sc-Ia) fusion proteins, PMN retained the targeting specificity of parental antibody and could specifically kill MCF-7 cells <it>in vitro</it>. By injecting intraperitoneally into BALB/c athymic mice bearing MCF-7 tumors, with reduced affinity, PMN significantly suppressed the growth of tumors compared with control mice treated by toxicin protein, Fab-Ia protein, Sc-Ia protein or by PBS (<it>p </it>< 0.05).</p> <p>Conclusion</p> <p>This novel mimetic antibody retained original specificity of parental antibody, and could effectively guide killer moiety to suppress the growth of breast cancer by targeted cell death.</p

The effectiveness of a preferred intensity exercise programme on the mental health outcomes of young people with depression: a sequential mixed methods evaluation

<p>Abstract</p> <p>Background</p> <p>People with mental illness are more likely to suffer physical health problems than comparable populations who do not have mental illness. There is evidence to suggest that exercise, as well has having obvious physical benefits, also has positive effects on mental health. There is a distinct paucity of research testing its effects on young people seeking help for mental health issues. Additionally, it is generally found that compliance with prescribed exercise programmes is low. As such, encouraging young people to exercise at levels recommended by national guidelines may be unrealistic considering their struggle with mental health difficulties. It is proposed that an exercise intervention tailored to young people's preferred intensity may improve mental health outcomes, overall quality of life, and reduce exercise attrition rates.</p> <p>Methods/Design</p> <p>A sequential mixed methods design will be utilised to assess the effectiveness of an individually tailored exercise programme on the mental health outcomes of young people with depression. The mixed methods design incorporates a Randomised Controlled Trial (RCT), focus groups and interviews and an economic evaluation. <it>Participants: </it>158 young people (14-17 years) recruited from primary care and voluntary services randomly allocated to either the intervention group or control group. <it>Intervention group</it>: Participants will undertake a 12 week exercise programme of 12 × 60 minutes of preferred intensity aerobic exercise receiving motivational coaching and support throughout. Participants will also be invited to attend focus groups and 1-1 interviews following completion of the exercise programme to illicit potential barriers facilitators to participation. <it>Control group</it>: Participants will receive treatment as usual. <it>Primary Outcome measure</it>: Depression using the Children's Depression Inventory 2 (CDI-2). <it>Secondary Outcome measures</it>: Quality of Life (EQ-5D), physical fitness (Borg RPE scale, heart rate), incidents of self-harm, treatment received and compliance with treatment, and the cost effectiveness of the intervention. Outcome measures will be taken at baseline, post intervention and 6 month follow up.</p> <p>Discussion</p> <p>The results of this study will inform policy makers of the effectiveness of preferred intensity exercise on the mental health outcomes of young people with depression, the acceptability of such an intervention to this population and its cost effectiveness.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01474837">NCT01474837</a></p

Acute effects of brisk walking on sugary snack cravings in overweight people, affect and responses to a manipulated stress situation and to a sugary snack cue: a crossover study.

Research has shown that acute exercise reduces urges for chocolate in normal weight people. This study aimed to examine the effects of an acute exercise bout on urges to consume sugary snacks, affect as well as 'psychological and physiological responses' to stress and a 'sugary snack cue', in overweight individuals. Following 3 days of chocolate-abstinence, 47 overweight, sugary snack consumers were assessed, in 2 randomly ordered conditions, in a within-subject design: 15-min brisk walk or passive control. Following each, participants completed 2 tasks: Stroop color-word interference task, and handling sugary snacks. Urges for sugary snacks, affective activation and valence were assessed. ANOVAs revealed significant condition x time interaction effects for: urges to consume sugary snacks, affective valence and activation. Obtained data show that exercise reduces urges for sugary snacks and attenuates urges in response to the stress situation and the cue in overweight people