Dual mechanism of brain injury and novel treatment strategy in maple syrup urine disease

Maple syrup urine disease (MSUD) is an inherited disorder of branched-chain amino acid metabolism presenting with lifethreatening cerebral oedema and dysmyelination in affected individuals. Treatment requires life-long dietary restriction and monitoring of branched-chain amino acids to avoid brain injury. Despite careful management, children commonly suffer metabolic decompensation in the context of catabolic stress associated with non-specific illness. The mechanisms underlying this decompensation and brain injury are poorly understood. Using recently developed mouse models of classic and intermediate maple syrup urine disease, we assessed biochemical, behavioural and neuropathological changes that occurred during encephalopathy in these mice. Here, we show that rapid brain leucine accumulation displaces other essential amino acids resulting in neurotransmitter depletion and disruption of normal brain growth and development. A novel approach of administering norleucine to heterozygous mothers of classic maple syrup urine disease pups reduced branched-chain amino acid accumulation in milk as well as blood and brain of these pups to enhance survival. Similarly, norleucine substantially delayed encephalopathy in intermediate maple syrup urine disease mice placed on a high protein diet that mimics the catabolic stress shown to cause encephalopathy in human maple syrup urine disease. Current findings suggest two converging mechanisms of brain injury in maple syrup urine disease including: (i) neurotransmitter deficiencies and growth restriction associated with branchedchain amino acid accumulation and (ii) energy deprivation through Krebs cycle disruption associated with branched-chain ketoacid accumulation. Both classic and intermediate models appear to be useful to study the mechanism of brain injury and potential treatment strategies for maple syrup urine disease. Norleucine should be further tested as a potential treatment to prevent encephalopathy in children with maple syrup urine disease during catabolic stress

Delayed meal timing after exercise is associated with reduced appetite and energy intake in adolescents with obesity

Background While the beneficial effects of exercise on appetite might depend on its timing during the day or relative to a meal, this remains poorly explored in youth. Objectives To examine the importance of meal timing (+30 vs +90 minutes) after performing exercise on energy intake, appetite and food reward in adolescents with obesity. Methods Eighteen adolescents with obesity randomly completed three conditions: (a) lunch (12:00 pm) set 30 minutes after a rest session (11:00 am); (b) lunch (12:00 pm) set 30 minutes after an exercise session (11:00 am)(MEAL‐30); (c) lunch (01:00 pm) set 90 minutes after an exercise session (11:00 am)(MEAL‐90). Lunch and dinner ad libitum energy intake was assessed, food reward (LFPQ) assessed before and after lunch, and before dinner, appetite sensations were assessed at regular intervals. Results Energy intake was lower at MEAL‐90 than MEAL‐30 and CON at lunch (P < .05 and P < .01, respectively) and lunch + dinner combined (P < .001). A decrease in intake (g) of protein, fat and carbohydrate was observed. Post‐exercise hunger was lower on MEAL‐90 compared with CON. No condition effects were found at lunch for food reward. Conclusions Delaying the timing of the meal after exercise might help affect energy balance by decreasing ad libitum energy intake without increasing hunger and by improving satiety in adolescents with obesity

Walk well:a randomised controlled trial of a walking intervention for adults with intellectual disabilities: study protocol

Background - Walking interventions have been shown to have a positive impact on physical activity (PA) levels, health and wellbeing for adult and older adult populations. There has been very little work carried out to explore the effectiveness of walking interventions for adults with intellectual disabilities. This paper will provide details of the Walk Well intervention, designed for adults with intellectual disabilities, and a randomised controlled trial (RCT) to test its effectiveness. Methods/design - This study will adopt a RCT design, with participants allocated to the walking intervention group or a waiting list control group. The intervention consists of three PA consultations (baseline, six weeks and 12 weeks) and an individualised 12 week walking programme. A range of measures will be completed by participants at baseline, post intervention (three months from baseline) and at follow up (three months post intervention and six months from baseline). All outcome measures will be collected by a researcher who will be blinded to the study groups. The primary outcome will be steps walked per day, measured using accelerometers. Secondary outcome measures will include time spent in PA per day (across various intensity levels), time spent in sedentary behaviour per day, quality of life, self-efficacy and anthropometric measures to monitor weight change. Discussion - Since there are currently no published RCTs of walking interventions for adults with intellectual disabilities, this RCT will examine if a walking intervention can successfully increase PA, health and wellbeing of adults with intellectual disabilities

Does exercising before or after a meal affect energy balance in adolescents with obesity?

Background and aim Exercise timing has been suggested to affect appetite and energy intake (EI). The aim of this study was to examine the impact of exercising immediately before or after a meal on EI, appetite sensations and food reward (FR) in adolescents with obesity. Methods and results Seventeen adolescents with obesity completed 3 experimental sessions (randomized controlled trial): rest + lunch (CON); exercise + lunch (EX-MEAL); lunch + exercise (MEAL-EX). The exercise consisted of cycling 30 min at 65%V̇O2peak. Outcomes included ad libitum EI (weighed lunch and dinner), FR (Leeds Food Preference Questionnaire at pre- and post-combination of exercise/rest and lunch, and pre-dinner) and appetite sensations (visual analogue scales). EI was not different between conditions. Compared with CON, relative EI at lunch was lower in EX-MEAL and MEAL-EX (p ≤ 0.05) and daily only in MEAL-EX (p < 0.01). Postprandial fullness was higher in EX-MEAL compared to CON. Compared with CON, both EX-MEAL and MEAL-EX attenuated the increase in wanting for sweet food and reduced explicit liking for fat. Conclusions These preliminary results suggest that exercising immediately before or after a meal produce few differences in appetite and have small beneficial effects on overall energy balance in adolescents with obesity, as well as on FR. Clinical trials NCT03967782

Theorizing construction industry practice within a disaster risk reduction setting: is it a panacea or an illusion?

Construction industry practice is strongly influenced by the culture surrounding its operations and, with the prevailing emphasis on achieving efficiency, there is a strong focus on outcome metrics such as profitability and employee productivity. With the recent increases in natural hazard events worldwide, and the likelihood that this will worsen still further with anticipated climate changes, the industry is increasingly contributing to building resilience within disaster-affected communities. Existing industry expertise, its educational approaches and the related theoretical frameworks, however, all require adjustment if these changing needs are to be fully addressed. Most importantly, an agenda shift is required from the philosophical side and a more pragmatic approach is needed if community resilience goals and objectives are to be met, rather than the narrower focus of the current metrics-driven management system. A synthesis of the current literature is therefore presented, along with relevant case histories illustrating how such an agenda shift within a disaster management context may influence the development of appropriate theory, as well as impacting upon grass-roots educational requirements. The research concludes by discussing how the ‘mainstreaming’ of disaster management within construction industry practice could drive forward developments in theorizing expertise and educational provisions across the constituent discipline

Study protocol: a pragmatic randomised controlled trial of a 12-week physical activity and nutritional education program for overweight Aboriginal and Torres Strait Islander women

<p>Abstract</p> <p>Background</p> <p>Aboriginal and Torres Strait Islander women have a higher prevalence and incidence of obesity and type 2 diabetes than non-Indigenous Australian women. Physical inactivity is a key modifiable risk factor for obesity and evidence shows that even modest reductions in waist circumference (WC) have significant health benefits. Trialing physical activity programs in difficult-to-reach high risk groups, especially urban Indigenous Australians poses distinct implementation challenges.</p> <p>Methods/Design</p> <p>The trial objective is to evaluate the effectiveness of a structured 12-week physical activity group program with nutritional advice. The design is a pragmatic randomised controlled trial. This study protocol describes the implementation and evaluation of the program. Participants are randomised into either an intervention or waitlisted group. The waitlisted group have a 12 month waiting period before commencing the 12-week program. Participant data is collected at baseline, 12, 24 and 52 weeks. Participants are Aboriginal and Torres Strait Islander women, aged 18-64 years with a waist circumference greater than 80 centimetres residing in Adelaide. The primary outcome measure is WC change immediately post program from baseline. Secondary outcomes include short term and long term changes in WC, weight, blood pressure, fasting blood glucose, insulin, insulin resistance (calculated HOMA), haemoglobin A1C (HbA1C), triglycerides and C-reactive protein (CRP). Behavioural and psychosocial surveys are administered to assess physical activity, dietary intake and the participant's motivation, self-efficacy and perceived social support for physical activity. Qualitative interviews focusing on participants' motivation, enablers and barriers to healthy eating and physical activity will be undertaken. Implementation fidelity and participation are also assessed.</p> <p>Discussion</p> <p>The Aboriginal and Torres Strait Islander Women's Fitness Program (WFP) is designed to provide a rigorous physiological and client-based evaluation of a structured 12-week program aimed to increase metabolic fitness and reduce WC in this high risk population. Evaluation results aim to provide the support necessary to design programs that are accessible, affordable and effective at reducing WC, while also improving the metabolic profile of overweight Aboriginal and Torres Strait Islander women.</p> <p>Trial registration</p> <p>Australian New Zealand Clinical Trials Registry <a href="http://www.anzctr.org.au/ACTRN12610000224022.aspx">ACTRN12610000224022</a></p

Design and evaluation protocol of "FATaintPHAT", a computer-tailored intervention to prevent excessive weight gain in adolescents

<p>Abstract</p> <p>Background</p> <p>Computer tailoring may be a promising technique for prevention of overweight in adolescents. However, very few well-developed, evidence-based computer-tailored interventions are available for this target group. We developed and evaluated a computer-tailored intervention for adolescents targeting energy balance-related behaviours: i.e. consumption of snacks, sugar-sweetened beverages, fruit, vegetables, and fibre, physical activity, and sedentary behaviours. This paper describes the planned development of a school-based computer-tailored intervention aimed at improving energy balance-related behaviours in order to prevent excessive weight gain in adolescents, and the protocol for evaluating this intervention.</p> <p>Methods/design</p> <p>Intervention development: Informed by the Precaution Adoption Process Model and the Theory of Planned Behaviour, the computer-tailored intervention provided feedback on personal behaviour and suggestions on how to modify it. The intervention (VETisnietVET translated as 'FATaintPHAT') has been developed for use in the first year of secondary school during eight lessons.</p> <p>Evaluation design: The intervention will be evaluated in a cluster-randomised trial including 20 schools with a 4-months and a 2-years follow-up. Outcome measures are BMI, waist circumference, energy balance-related behaviours, and potential determinants of these behaviours. Process measures are appreciation of and satisfaction with the program, exposure to the program's content, and implementation facilitators and barriers measured among students and teachers.</p> <p>Discussion</p> <p>This project resulted in a theory and evidence-based intervention that can be implemented in a school setting. A large-scale randomised controlled trial with a short and long-term follow-up will provide sound statements about the effectiveness of this computer-tailored intervention in adolescents.</p> <p>Trial Registration</p> <p>ISRCTN15743786</p

The effect of two different health messages on physical activity levels and health in sedentary overweight, middle-aged women

Background: Most public health guidelines recommend that adults need to participate in 30 minutes of moderate intensity physical activity on most days of the week to maintain good health. Achieving the recommended 30 minutes of exercise a day can be difficult in middle aged, overweight women. This 12 week study evaluated whether a 10,000 steps per day message was more effective than a 30 minutes a day message in increasing physical activity in low active, overweight women. Methods: Thirty participants were randomized into 2 groups: Group 1 was asked to undertake 30 minutes of walking/day, whereas Group 2 was asked to accumulate 10,000 steps/day using their pedometers. Results: Results showed that there were no changes in anthropometric and blood pressure measures between or within groups. However, the 10,000 step and the 30 minutes groups’ daily average number of steps/day were significantly higher than baseline at week 6 (p = 0.038 and p = 0.039 respectively) and at week 12 (p = 0.028 and p = 0.038 respectively). At week 12, the 10,000 steps group were taking an average of 4616 steps per day more (43% increase) than at baseline and the 30 minutes group were taking an average of 2761 steps per day more (35% increase) than at baseline. There was a significant difference in the number of steps with the 10,000 steps group versus 30 minutes group at 12 weeks (p = 0.045).Conclusions: This study found that low active, overweight women undertook significantly more physical activity when they had a daily 10,000 step goal using a pedometer, than when they were asked to achieve 30 minutes of walking/day. Therefore we suggest that a public health recommendation of “10,000 steps/day”, rather than the “30 min/day” could be applied to promote increased physical activity in sedentary middle aged women

Safe To Walk? Neighborhood Safety and Physical Activity Among Public Housing Residents

Garry Bennett and colleagues measured exercise levels and obtained opinions on neighborhood safety. They concluded that residing in a neighborhood perceived to be unsafe at night is a barrier to regular physical activity