Appetite and gut hormone responses to moderate-intensity continuous exercise versus high-intensity interval exercise, in normoxic and hypoxic conditions.

This study investigated the effects of continuous moderate-intensity exercise (MIE) and high-intensity interval exercise (HIIE) in combination with short exposure to hypoxia on appetite and plasma concentrations of acylated ghrelin, peptide YY (PYY), and glucagon-like peptide-1 (GLP-1). Twelve healthy males completed four, 2.6 h trials in a random order: 1) MIE-normoxia, 2) MIE-hypoxia, 3) HIIE-normoxia, and 4) HIIE-hypoxia. Exercise took place in an environmental chamber. During MIE, participants ran for 50 min at 70% of altitude-specific maximal oxygen uptake ( 2max) and during HIIE performed 6 x 3 min running at 90% 2max interspersed with 6 x 3 min active recovery at 50% 2max with a 7 min warm-up and cool-down at 70% 2max (50 min total). In hypoxic trials, exercise was performed at a simulated altitude of 2,980 m (14.5% O2). Exercise was completed after a standardised breakfast. A second meal standardised to 30% of participants’ daily energy requirements was provided 45 min after exercise. Appetite was suppressed more in hypoxia than normoxia during exercise, post-exercise, and for the full 2.6 h trial period (linear mixed modelling, p 0.05). These findings demonstrate that short exposure to hypoxia causes suppressions in appetite and plasma acylated ghrelin concentrations. Furthermore, appetite responses to exercise do not appear to be influenced by exercise modality

Comparative effectiveness of ZUMA-5 (axi-cel) vs SCHOLAR-5 external control in relapsed/refractory follicular lymphoma

Follicular lymphomaLimfoma fol·licularLinfoma folicularIn the pivotal ZUMA-5 trial, axicabtagene ciloleucel (axi-cel; an autologous anti-CD19 chimeric antigen receptor T-cell therapy) demonstrated high rates of durable response in relapsed/refractory (r/r) follicular lymphoma (FL) patients. Here, outcomes from ZUMA-5 are compared with the international SCHOLAR-5 cohort, which applied key ZUMA-5 trial eligibility criteria simulating randomized controlled trial conditions. SCHOLAR-5 data were extracted from institutions in 5 countries, and from 1 historical clinical trial, for r/r FL patients who initiated a third or higher line of therapy after July 2014. Patient characteristics were balanced through propensity scoring on prespecified prognostic factors using standardized mortality ratio (SMR) weighting. Time-to-event outcomes were evaluated using weighted Kaplan-Meier analysis. Overall response rate (ORR) and complete response (CR) rate were compared using weighted odds ratios. The 143 ScHOLAR-5 patients reduced to an effective sample of 85 patients after SMR weighting vs 86 patients in ZUMA-5. Median follow-up time was 25.4 and 23.3 months for SCHOLAR-5 and ZUMA-5. Median overall survival (OS) and progression-free survival (PFS) in SCHOLAR-5 were 59.8 months and 12.7 months and not reached in ZUMA-5. Hazard ratios for OS and PFS were 0.42 (95% confidence interval [CI], 0.21-0.83) and 0.30 (95% CI, 0.18-0.49). The ORR and CR rate were 49.9% and 29.9% in SCHOLAR-5 and 94.2% and 79.1% in ZUMA-5, for odds ratios of 16.2 (95% CI, 5.6-46.9) and 8.9 (95% CI, 4.3-18.3). Compared with available therapies, axi-cel demonstrated an improvement in meaningful clinical endpoints, suggesting axi-cel addresses an important unmet need for r/r FL patients. This trial was registered at www.clinicaltrials.gov as #NCT03105336.Was provided by Kite Pharma, a Gilead company, for this study

Children and young people’s experiences of completing mental health and wellbeing measures for research: learning from two school-based pilot projects

BACKGROUND: In recent years there has been growing interest in child and adolescent mental health and wellbeing, alongside increasing emphasis on schools as a crucial site for research and intervention. This has coincided with an increased use of self-report mental health and wellbeing measures in research with this population, including in school-based research projects. We set out to explore the way that children and young people perceive and experience completing mental health and wellbeing measures, with a specific focus on completion in a school context, in order to inform future measure and research design. METHODS: We conducted semi-structured interviews and focus groups with 133 participants aged 8–16 years following their completion of mental health and wellbeing measures as part of school-based research programmes, using thematic analysis to identify patterns of experience. FINDINGS: We identified six themes: Reflecting on emotions during completion; the importance of anonymity; understanding what is going to happen; ease of responding to items; level of demand; and interacting with the measure format. CONCLUSIONS: Our findings offer greater insight into children and young people’s perceptions and experiences in reporting on their mental health and wellbeing. Such understanding can be used to support more ethical and robust data collection procedures in child and adolescent mental health research, both for data quality and ethical purposes. We offer several practical recommendations for researchers, including facilitating this in a school context

Children and young people’s experiences of completing mental health and wellbeing measures for research: learning from two school‑based pilot projects

Background: In recent years there has been growing interest in child and adolescent mental health and wellbeing, alongside increasing emphasis on schools as a crucial site for research and intervention. This has coincided with an increased use of self-report mental health and wellbeing measures in research with this population, including in school-based research projects. We set out to explore the way that children and young people perceive and experience completing mental health and wellbeing measures, with a specific focus on completion in a school context, in order to inform future measure and research design. Methods: We conducted semi-structured interviews and focus groups with 133 participants aged 8–16 years following their completion of mental health and wellbeing measures as part of school-based research programmes, using thematic analysis to identify patterns of experience. Findings: We identified six themes: Reflecting on emotions during completion; the importance of anonymity; understanding what is going to happen; ease of responding to items; level of demand; and interacting with the measure format. Conclusions: Our findings offer greater insight into children and young people’s perceptions and experiences in reporting on their mental health and wellbeing. Such understanding can be used to support more ethical and robust data collection procedures in child and adolescent mental health research, both for data quality and ethical purposes. We offer several practical recommendations for researchers, including facilitating this in a school context

Interactions among mitochondrial proteins altered in glioblastoma

Mitochondrial dysfunction is putatively central to glioblastoma (GBM) pathophysiology but there has been no systematic analysis in GBM of the proteins which are integral to mitochondrial function. Alterations in proteins in mitochondrial enriched fractions from patients with GBM were defined with label-free liquid chromatography mass spectrometry. 256 mitochondrially-associated proteins were identified in mitochondrial enriched fractions and 117 of these mitochondrial proteins were markedly (fold-change ≥2) and significantly altered in GBM (p ≤ 0.05). Proteins associated with oxidative damage (including catalase, superoxide dismutase 2, peroxiredoxin 1 and peroxiredoxin 4) were increased in GBM. Protein–protein interaction analysis highlighted a reduction in multiple proteins coupled to energy metabolism (in particular respiratory chain proteins, including 23 complex-I proteins). Qualitative ultrastructural analysis in GBM with electron microscopy showed a notably higher prevalence of mitochondria with cristolysis in GBM. This study highlights the complex mitochondrial proteomic adjustments which occur in GBM pathophysiology

School-based intervention study examining approaches for well-being and mental health literacy of pupils in Year 9 in England: study protocol for a multischool, parallel group cluster randomised controlled trial (AWARE)

Introduction The prevalence of emotional difficulties in young people is increasing. This upward trend is largely accounted for by escalating symptoms of anxiety and depression. As part of a public health response, there is increasing emphasis on universal prevention programmes delivered in school settings. This protocol describes a three-arm, parallel group cluster randomised controlled trial, investigating the effectiveness and cost-effectiveness of two interventions, alongside a process and implementation evaluation, to improve mental health and well-being of Year 9 pupils in English secondary schools. Method A three-arm, parallel group cluster randomised controlled trial comparing two different interventions, the Youth Aware of Mental Health (YAM) or the Mental Health and High School Curriculum Guide (The Guide), to Usual Provision. Overall, 144 secondary schools in England will be recruited, involving 8600 Year 9 pupils. The primary outcome for YAM is depressive symptoms, and for The Guide it is intended help-seeking. These will be measured at baseline, 3–6 months and 9–12 months after the intervention commenced. Secondary outcomes measured concurrently include changes to: positive well-being, behavioural difficulties, support from school staff, stigma-related knowledge, attitudes and behaviours, and mental health first aid. An economic evaluation will assess the cost-effectiveness of the interventions, and a process and implementation evaluation (including a qualitative research component) will explore several aspects of implementation (fidelity, quality, dosage, reach, participant responsiveness, adaptations), social validity (acceptability, feasibility, utility), and their moderating effects on the outcomes of interest, and perceived impact. Ethics and dissemination This trial has been approved by the University College London Research Ethics Committee. Findings will be published in a report to the Department for Education, in peer-reviewed journals and at conferences

Substrate oxidation and the influence of breakfast in normobaric hypoxia and normoxia

Purpose: Reported substrate oxidation responses in hypoxia are divergent, and may be due to differences in methodological design, such as pre-exercise nutritional status and exercise intensity. This study investigated the effect of breakfast consumption versus omission on substrate oxidation at varying exercise intensities in normobaric hypoxia compared with normoxia. Methods: Twelve participants rested and exercised once after breakfast consumption and once after omission in normobaric hypoxia (4300 m: FiO2 ~11.7%) and normoxia. Exercise consisted of walking for 20-minutes at 40%, 50% and 60% of altitude-specific V̇O2max at 10-15% gradient with a 10 kg backpack. Indirect calorimetry was used to calculate carbohydrate and fat oxidation. Results: The relative contribution of carbohydrate oxidation to energy expenditure was significantly reduced in hypoxia compared with normoxia during exercise after breakfast omission at 40% (22.4 ± 17.5% vs. 38.5±15.5%, p = 0.03) and 60% V̇O2max (35.4±12.4 vs. 50.1±17.6%, p = 0.03), with a trend observed at 50% V̇O2max (23.6±17.9% vs. 38.1± 17.0%, p = 0.07). The relative contribution of carbohydrate oxidation to energy expenditure was not significantly different in hypoxia compared with normoxia during exercise after breakfast consumption at 40% (42.4±15.7% vs. 48.5±13.3%, p = 0.99), 50% (43.1±11.7% vs. 47.1±14.0%, p = 0.99) and 60% V̇O2max (54.6±17.8% vs. 55.1±15.0%, p = 0.99). Conclusions: Relative carbohydrate oxidation was significantly reduced in hypoxia compared with normoxia during exercise after breakfast omission but not during exercise after breakfast consumption. This response remained consistent with increasing exercise intensities. These findings may explain some of the disparity in the literatur

The effects of environmental hypoxia on substrate utilisation during exercise : A meta-analysis

Background: A better understanding of hypoxia-induced changes in substrate utilisation can facilitate the development of nutritional strategies for mountaineers, military personnel and athletes during exposure to altitude. However, reported metabolic responses are currently divergent. As such, this systematic review and meta-analysis aims to determine the changes in substrate utilisation during exercise in hypoxia compared with normoxia and identify study characteristics responsible for the heterogeneity in findings. Methods: A total of six databases (PubMed, the Cochrane Library, MEDLINE, SPORTDiscus, PsychINFO, and CINAHL via EBSCOhost) were searched for published original studies, conference proceedings, abstracts, dissertations and theses. Studies were included if they evaluated respiratory exchange ratio (RER) and/or carbohydrate or fat oxidation during steady state exercise matched for relative intensities in normoxia and hypoxia (normobaric or hypobaric). A random-effects meta-analysis was performed on outcome variables. Meta-regression analysis was performed to investigate potential sources of heterogeneity. Results: In total, 18 studies were included in the meta-analysis. There was no significant change in RER during exercise matched for relative exercise intensities in hypoxia, compared with normoxia (mean difference: 0.01, 95% CI: -0.02 to 0.05; n = 31, p = 0.45). Meta-regression analysis suggests that consumption of a pre-exercise meal (p < 0.01) and a higher exercise intensity (p = 0.04) when exposed to hypoxia may increase carbohydrate oxidation compared with normoxia. Conclusions: Exposure to hypoxia did not induce a consistent change in the relative contribution of carbohydrate or fat to the total energy yield during exercise matched for relative intensities, compared with normoxia. The direction of these responses appears to be mediated by the consumption of a pre-exercise meal and exercise intensity. Key words: Altitude, exercise, substrate, carbohydrate, fat, oxidation, systematic revie

The effect of high altitude on central blood pressure and arterial stiffness

Central arterial systolic blood pressure (SBP) and arterial stiffness are known to be better predictors of adverse cardiovascular outcomes than brachial SBP. The effect of progressive high altitude (HA) on these parameters has not been examined. Ninety healthy adults were included. Central BP and the augmentation index (AI) were measured at the level of the brachial artery (Uscom BP + device) at < 200 m and at 3619, 4600 and 5140 m. The average age of the subjects (70% men) were 32.2±8.7 years. Compared with central arterial pressures, brachial SBP (+8.1±6.4 mm Hg; P < 0.0001) and pulse pressure (+10.9±6.6 mm Hg; P < 0.0001) were significantly higher and brachial diastolic BP was lower (-2.8±1.6 mm Hg; P < 0.0001). Compared with < 200 m, HA led to a significant increase in brachial and central SBP. Central SBP correlated with AI (r=0.50; 95% confidence interval (CI): 0.41-0.58; P < 0.0001) and age (r=0.32; 95% CI: 21-0.41; P < 0.001). AI positively correlated with age (r=0.39; P < 0.001) and inversely with subject height (r=-0.22; P < 0.0001), weight (r=-0.19; P=0.006) and heart rate (r=-0.49; P < 0.0001). There was no relationship between acute mountain sickness scores (Lake Louis Scoring System (LLS)) and AI or central BP. The independent predictors of central SBP were male sex (coefficient, t=4.7; P < 0.0001), age (t=3.6; P=0.004) and AI (t=7.5; P < 0.0001; overall r 2 =0.40; P < 0.0001). Subject height (t=2.4; P=0.02), age (7.4; P < 0.0001) and heart rate (t=11.4; P < 0.0001) were the only independent predictors of AI (overall r 2 =0.43; P < 0.0001). Central BP and AI significantly increase at HA. This rise was influenced by subject-related factors and heart rate but not independently by altitude, LLS or SpO 2