Testing the intrinsic mechanisms driving the dynamics of Ross River Virus across Australia.

The mechanisms driving dynamics of many epidemiologically important mosquito-borne pathogens are complex, involving combinations of vector and host factors (e.g., species composition and life-history traits), and factors associated with transmission and reporting. Understanding which intrinsic mechanisms contribute most to observed disease dynamics is important, yet often poorly understood. Ross River virus (RRV) is Australia's most important mosquito-borne disease, with variable transmission dynamics across geographic regions. We used deterministic ordinary differential equation models to test mechanisms driving RRV dynamics across major epidemic centers in Brisbane, Darwin, Mandurah, Mildura, Gippsland, Renmark, Murray Bridge, and Coorong. We considered models with up to two vector species (Aedes vigilax, Culex annulirostris, Aedes camptorhynchus, Culex globocoxitus), two reservoir hosts (macropods, possums), seasonal transmission effects, and transmission parameters. We fit models against long-term RRV surveillance data (1991-2017) and used Akaike Information Criterion to select important mechanisms. The combination of two vector species, two reservoir hosts, and seasonal transmission effects explained RRV dynamics best across sites. Estimated vector-human transmission rate (average ß = 8.04x10-4per vector per day) was similar despite different dynamics. Models estimate 43% underreporting of RRV infections. Findings enhance understanding of RRV transmission mechanisms, provide disease parameter estimates which can be used to guide future research into public health improvements and offer a basis to evaluate mitigation practices.

Structures of fungal and plant acetohydroxyacid synthases.

Acetohydroxyacid synthase (AHAS), also known as acetolactate synthase, is a flavin adenine dinucleotide-, thiamine diphosphate- and magnesium-dependent enzyme that catalyses the first step in the biosynthesis of branched-chain amino acids1. It is the target for more than 50 commercial herbicides2. AHAS requires both catalytic and regulatory subunits for maximal activity and functionality. Here we describe structures of the hexadecameric AHAS complexes of Saccharomyces cerevisiae and dodecameric AHAS complexes of Arabidopsis thaliana. We found that the regulatory subunits of these AHAS complexes form a core to which the catalytic subunit dimers are attached, adopting the shape of a Maltese cross. The structures show how the catalytic and regulatory subunits communicate with each other to provide a pathway for activation and for feedback inhibition by branched-chain amino acids. We also show that the AHAS complex of Mycobacterium tuberculosis adopts a similar structure, thus demonstrating that the overall AHAS architecture is conserved across kingdoms.

Biventricular responses to exercise and their relation to cardiorespiratory fitness in pediatric pulmonary hypertension.

Despite exercise intolerance being predictive of outcomes in pulmonary arterial hypertension (PAH), its underlying cardiac mechanisms are not well described. The aim of the study was to explore the biventricular response to exercise and its associations with cardiorespiratory fitness in children with PAH. Participants underwent incremental cardiopulmonary exercise testing and simultaneous exercise echocardiography on a recumbent cycle ergometer. Linear mixed models were used to assess cardiac function variance and associations between cardiac and metabolic parameters during exercise. Eleven participants were included with a mean age of 13.4 ± 2.9 yr old. Right ventricle (RV) systolic pressure (RVsp) increased from a mean of 59 ± 25 mmHg at rest to 130 ± 40 mmHg at peak exercise (P < 0.001), whereas RV fractional area change (RV-FAC) and RV-free wall longitudinal strain (RVFW-Sl) worsened (35.2 vs. 27%, P = 0.09 and -16.6 vs. -14.6%, P = 0.1, respectively). At low- and moderate-intensity exercise, RVsp was positively associated with stroke volume and O2 pulse (P < 0.1). At high-intensity exercise, RV-FAC, RVFW-Sl, and left ventricular longitudinal strain were positively associated with oxygen uptake and O2 pulse (P < 0.1), whereas stroke volume decreased toward peak (P = 0.04). In children with PAH, the increase of pulmonary pressure alone does not limit peak exercise, but rather the concomitant reduced RV functional reserve, resulting in RV to pulmonary artery (RV-PA) uncoupling, worsening of interventricular interaction and LV dysfunction. A better mechanistic understanding of PAH exercise physiopathology can inform stress testing and cardiac rehabilitation in this population.NEW & NOTEWORTHY In children with pulmonary arterial hypertension, there is a marked increase in pulmonary artery pressure during physical activity, but this is not the underlying mechanism that limits exercise. Instead, right ventricle-to-pulmonary artery uncoupling occurs at the transition from moderate to high-intensity exercise and correlates with lower peak oxygen uptake. This highlights the more complex underlying pathological responses and the need for multiparametric assessment of cardiac function reserve in these patients when feasible.

9-Azahomocubane.

Homocubane, a highly strained cage hydrocarbon, contains two very different positions for the introduction of a nitrogen atom into the skeleton, e. g., a position 1 exchange results in a tertiary amine whereas position 9 yields a secondary amine. Herein reported is the synthesis of 9-azahomocubane along with associated structural characterization, physical property analysis and chemical reactivity. Not only is 9-azahomocubane readily synthesized, and found to be stable as predicted, the basicity of the secondary amine was observed to be significantly lower than the structurally related azabicyclo[2.2.1]heptane, although similar to 1-azahomocubane.

seco-1-Azacubane-2-carboxylic Acid: Derivative Scope and Comparative Biological Evaluation.

The unusual and sterically constrained amino acid, seco-1-azacubane-2-carboxylic acid, was incorporated into a range of bioactive chemical templates, including enalaprilat, perindoprilat, endomorphin-2 and isoniazid, and subjected to biological testing. The endomorphin-2 derivative displayed increased activity at the δ opioid receptor, but a loss in activity was observed in the other cases, although human normal cell line evaluation suggests limited cytotoxic effects.

Macrocyclic Copper(II) Complexes as Catalysts for Electrochemically Mediated Atom Transfer.

Copper-catalyzed electrochemical atom transfer radical addition (eATRA) is a new method for the creation of new C-C bonds under mild conditions. In this work, we have explored the reactivity of an analogous series of N4 macrocyclic CuII complexes as eATRA precatalysts, which are primed by reduction to their monovalent oxidation state. These complexes were fully characterized structurally, spectroscopically, and electrochemically. A spectrum of radical activation reactivity was found across the series [CuI(Me4cyclen)(NCMe)]+ (Me4cyclen = 1,4,7,10-tetramethyl-1,4,7,10-tetraazacyclododecane), [CuI(Me4cyclam)(NCMe)]+ (Me4cyclam = 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane), and [CuI(Me2py2clen)(NCMe)]+ (Me2py2clen = 3,7-dimethyl-3,7-diaza-1,5(2,6)-dipyridinacyclo-octaphane). The rate of radical production by [Cu(Me2py2clen)(NCMe)]+ was modest, but rapid radical capture to form the organocopper complex [CuI(Me2py2clen)(CH2CN)] led to a dramatic acceleration in catalysis, greater than seen in any comparable Cu complex, but this led to rapid radical self-termination instead of radical addition.

Numerical computation of temperature on steel and an insulator with simulation compared to experimental data.

In this report, we are computing the temperature from the heat equation for a disk of a given thickness. A laser beam of Gaussian profile is assumed at the surface of a circular sample. Prediction of temperature for a laser pulse with a Gaussian profile is shown for a circular symmetry. Temperature distributions are performed analytically and numerically for a power with a Gaussian profile at different depths from the surface. In the previous computation the laser beam was assumed to be small compared to the disk's radius. The calculations performed are useful to predict the proper spacing between marks during a laser procedure. Computations of the temperature for a beam spot size much larger than the sample dimensions are also shown for a modulated laser beam. The computation of temperature for the modulated laser beam is also compared to experimental data points obtained on bone.

Process evaluation of school-based high-intensity interval training interventions for children and adolescents: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Several systematic reviews have been published to investigate the effectiveness of high-intensity interval training (HIIT) in schools. However, there has been limited attention given to understanding the functioning of the intervention processes, which is of paramount importance for interpreting and translating the intervention effectiveness. The aim of this systematic review is to determine the extent to which process evaluation is measured in school-based HIIT interventions and to explore the effects of process evaluation and intervention characteristics on cardiorespiratory fitness (CRF), body composition, muscular strength, and blood pressure. METHODS: A comprehensive search was conducted in SPORT Discus (EBSCOhost), Web of Science, Scopus, Medline (Ovid) and Cochrane Central Register of Controlled Trials. The extent to which process evaluation is measured was narratively reported, alongside with the guidance of process evaluation of complex interventions by UK Medical Research Council. Meta-analyses and meta-regressions were conducted to determine the effects of process evaluation and intervention characteristics to the intervention outcomes. RESULTS: The literature search identified 77 studies reporting on 45 school-based HIIT interventions. In total, five interventions reported process evaluation in a section or in a separate study, and only one intervention adopted a process evaluation framework. On average, 6 out of 12 process evaluation measures were reported in all interventions. Subgroup analyses did not indicate any beneficial treatment effects for studies with process evaluation group, whereas all pooled data and studies without process evaluation group showed significant improvement for CRF and body composition. CONCLUSION: Process evaluation is frequently omitted in the literature of school-based HIIT in children and adolescents. Although reporting of process evaluation measures may not directly associate with better intervention outcomes, it allows accurate interpretation of intervention outcomes, thereby enhancing the generalisability and dissemination of the interventions.

Stakeholder perspectives on the barriers and facilitators of engagement in healthy lifestyle behaviours in underrepresented adolescents: a focus group study from the European SEEDS project.

BACKGROUND: Obesity in adolescence has increased in the last decades. Adolescents fail to meet the recommended guidelines for physical activity (PA) and healthy diet. Adolescents with a low socioeconomic status (SES) particularly seem to have fewer healthy lifestyle behaviours. The European Science Engagement to Empower aDolescentS (SEEDS) project used an extreme citizen science approach to develop and implement healthy lifestyle behaviour interventions in high schools. As part of this project, key stakeholders were invited to reflect on the intentions of adolescents to engage in healthy lifestyle behaviours. The aim of this study was to gain stakeholder insights into the barriers and facilitators to healthy lifestyle behaviours of adolescents from low SES areas and on the possible role of these stakeholders in facilitating healthy lifestyle behaviours. METHODS: Six semi-structured focus groups were conducted in four European countries with 28 stakeholders from different settings (schools, community, and government), like teachers, policy advisors and youth workers. The theoretical framework of focus groups was based on the Theory of Planned Behaviour. The main questions of the focus groups were centred on PA and healthy diet. The focus groups were qualitatively analysed in NVivo using thematic analysis to identify topics and themes. RESULTS: According to stakeholders, adolescents have sufficient understanding of the importance of PA and a healthy diet, but nevertheless engage in unhealthy behaviour. Parents were mentioned as important facilitators for engaging adolescents in healthy lifestyle behaviours. Stakeholders listed lack of knowledge, time, and financial resources as barriers for adolescents from low SES families to engage in healthy lifestyle behaviours. The school environment was listed as an important facilitator of adolescents' healthy lifestyle changes, but stakeholders acknowledged that current school days, curriculum and buildings are not designed to promote healthy lifestyle behaviours. External support and collaboration with community and governmental stakeholders was seen as potentially beneficial to improve healthy lifestyle behaviours. CONCLUSIONS: This study shows the variety of barriers adolescents from low SES areas face, and the need for a broader collaboration between key stakeholders to facilitate healthy lifestyle behaviours. Schools are regarded specifically as important facilitators. Currently, the school environment entails various barriers. However, when addressing those, schools can increase opportunities for healthy lifestyle behaviours of adolescents from low SES areas. TRIAL REGISTRATION: This study is registered in ClinicalTrials.gov on 12/08/2021: NCT05002049.

Problems most concerning to parents of children with ADHD and emotional dysregulation in a randomized controlled trial of multinutrients: MADDY secondary analysis.

OBJECTIVE: With dual focus on structured, objective quantification of parent observations of child's behavior and identifying behaviors most amenable to change, this report examines Parent Target Problems (PTP) as a secondary outcome in a randomized clinical trial (RCT) of children with attention-deficit/ hyperactivity disorder (ADHD) in which one primary outcome, Clinical Global Impression-Improvement, showed a significant advantage of multinutrients over placebo and the other, Likert-type parent ratings, showed significant improvement in both groups, without significant difference between them. METHOD: In a multisite 8-week RCT of broad-spectrum micronutrients ("multinutrients"), parents of children ages 6-12 (N = 126, 73% male, 88% white) with ADHD and emotional dysregulation nominated their child's most concerning problem(s) at baseline and quantified them by frequency, duration, impairment, and consequences. At subsequent visits, parents re-quantified the problem(s). Blinded child psychiatrists independently reviewed the PTPs and rated change at two timepoints compared to baseline. PTPs were grouped into 9 categories. Mean ratings were compared between active and placebo groups and explored by category. RESULTS: By week 8, a significant separation favored multinutrients: 38% of the multinutrient group were "definitely improved" or better, compared to 25% of the placebo group, and ratings of "no change" or "worse" occurred in 35% with placebo versus 23% with multinutrients (p = 0.04). Inattention (72.2%) and emotional dysregulation (69.1%) were the most frequently reported PTP categories. Inattention and internalizing symptoms improved more with multinutrients than placebo (p = 0.01, d = 0.55; p = 0.03, d = 0.80, respectively). The multinutrient advantage was not significant for 7 other symptoms, including hyperactivity/impulsivity, aggression, autistic symptoms, or emotional dysregulation/irritable oppositionality. CONCLUSIONS: This secondary analysis found that the multinutrients, compared to placebo, were associated with improvements in parental concerns overall, and in two domains specifically: inattention and internalizing symptoms (anxiety/depression), but not in seven domains: hyperactivity/impulsivity, aggression, autistic symptoms or physiological symptoms, peer relationships or emotional dysregulation/irritable oppositionality.

The Influence of Acute Hypoxia on Oxygen Uptake and Muscle Oxygenation Kinetics During Cycling Exercise in Prepubertal Boys.

PURPOSE: To examine the effect of normobaric hypoxia on pulmonary oxygen uptake (V˙O2) and muscle oxygenation kinetics during incremental and moderate-intensity exercise in children. METHODS: Eight prepubertal boys (9-11 y) performed incremental cycle tests to exhaustion in both normoxia and hypoxia (fraction of inspired O2 of 15%) followed by repeat 6-minute transitions of moderate-intensity exercise in each condition over subsequent visits. RESULTS: Maximal oxygen uptake (V˙O2max) was reduced in hypoxia compared with normoxia (1.69 [0.20] vs 1.87 [0.26] L·min-1, P = .028), although the gas exchange threshold was not altered in absolute terms (P = .33) or relative to V˙O2max (P = .78). During moderate-intensity exercise, the phase II V˙O2 time constant (τ) was increased in hypoxia (18 [9] vs 24 [8] s, P = .025), with deoxyhemoglobin τ unchanged (17 [8] vs 16 [6], P ≥ .28). CONCLUSIONS: In prepubertal boys, hypoxia reduced V˙O2max and slowed V˙O2 phase II kinetics during moderate-intensity exercise, despite unchanged deoxyhemoglobin kinetics. These data suggest an oxygen delivery dependence of V˙O2max and moderate-intensity V˙O2 kinetics under conditions of reduced oxygen availability in prepubertal boys.

Validation and Calibration for Embedding Rating of Perceived Exertion Into High-Intensity Interval Exercise in Adolescents: A Lab-Based Study.

PURPOSE: Rating of perceived exertion (RPE) is a convenient and cost-effective tool that can be used to monitor high-intensity interval exercise (HIIE). However, no methodological study has demonstrated the validity of RPE in this context. Therefore, the aim of this study was to validate and calibrate RPE for monitoring HIIE in adolescents. METHODS: RPE, heart rate (HR), and oxygen uptake (V˙O2) data were retrospectively extracted from 3 lab-based crossover studies, with a pooled sample size of 45 adolescents, performing either cycling-based or running-based HIIE sessions. Within-participant correlations were calculated for RPE-HR and RPE-V˙O2, and receiver operator characteristic curve analysis was used to establish RPE cut points. RESULTS: The results showed that RPE-HR demonstrated acceptable criterion validity (r = .53-.74, P < .01), while RPE-V˙O2 had poor validity (r = .40-.48, P < .01), except for HIIE at 100% peak power (r = .59, P < .01). RPE cut points of 4 and 5 were established in corresponding to HR/V˙O2 based thresholds. CONCLUSION: RPE has some utility in evaluating intensity during lab-based running or cycling HIIE in adolescents. Future studies should expand the validation and calibration of RPE for prescribing and monitoring HIIE in children and adolescents in field-based contexts.

Parental recommendations and exercise attitudes in congenital hearts.

BACKGROUND: Children and young people with CHD benefit from regular physical activity. Parents are reported as facilitators and barriers to their children's physical activity. The aim of this study was to explore parental factors, child factors, and their clinical experience on physical activity participation in young people with CHD. METHODS: An online questionnaire was co-developed with parents (n = 3) who have children with CHD. The survey was then distributed in the United Kingdom by social media and CHD networks, between October 2021 and February 2022. Data were analysed using mixed methods. RESULTS: Eighty-three parents/guardians responded (94% mothers). Young people with CHD were 7.3 ± 5.0 years old (range 0-20 years; 53% female) and 84% performed activity. Parental participation in activity (X2(1) = 6.9, P < 0.05) and perceiving activity as important for their child were positively associated with activity (Fisher's Exact, P < 0.05). Some parents (∼15%) were unsure of the safety of activity, and most (∼70%) were unsure where to access further information about activity. Fifty-two parents (72%) had never received activity advice in clinic, and of the 20 who received advice, 10 said it was inconsistent. Qualitative analysis produced the theme "Knowledge is power and comfort." Parents described not knowing what activity was appropriate or the impact of it on their child. CONCLUSION: Parental participation and attitudes towards activity potentially influence their child's activity. A large proportion of young people performed activity despite a lack and inconsistency of activity advice offered by CHD clinics. Young people with CHD would benefit from activity advice with their families in clinics.

Web-based physical activity promotion in young people with CF: a randomised controlled trial.

BACKGROUND: Physical activity levels are known to decline following hospitalisation for people with cystic fibrosis (pwCF). However, optimal physical activity promotion strategies are unclear. This study investigated the effect of a web-based application (ActivOnline) in promoting physical activity in young pwCF. METHODS: Multicentre randomised controlled trial with assessor blinding and qualitative evaluation. People with CF (12-35 years) admitted to hospital for a respiratory cause were eligible and randomised to the 12-week ActivOnline intervention (AO) or usual care (UC). The primary outcome was change in device-based time spent in moderate-to-vigorous physical activity (MVPA) from baseline to post-intervention. Follow-up was at 6 months from hospital discharge when qualitative evaluation was undertaken. RESULTS: 107 participants were randomised to AO (n=52) or UC (n=55). Sixty-three participants (59%) contributed to the intention-to-treat analysis. Mean (SD) age was 21 (6) years (n=46, <18 years). At baseline, physical activity levels were high in both groups (AO 102 (52) vs UC 127 (73) min/day). There was no statistically significant difference in MVPA between groups at either timepoint (post-intervention mean difference (95% CI) -14 mins (-45 to 16)). Uptake of the intervention was low with only 40% (n=21) of participants accessing the web application. CONCLUSION: A web-based application, including individualised goal setting, real-time feedback and motivation for behavioural change, was no better than usual care at promoting physical activity in young pwCF following hospital discharge. High levels of baseline physical activity levels in both groups, and limited engagement with the intervention, suggest alternative strategies may be necessary to identify and support young pwCF who would benefit from enhanced physical activity. TRIAL REGISTRATION NUMBER: ACTRN12617001009303, 13 July 13 2017.

Clinical and Genomic Characterization of Interval Colorectal Cancer in 3 Prospective Cohorts.

BACKGROUND & AIMS: Interval colorectal cancers (CRCs), cancers diagnosed after a screening/surveillance examination in which no cancer is detected, and before the date of next recommended examination, reflect an unprecedented challenge in CRC detection and prevention. To better understand this poorly characterized CRC variant, we examined the clinical and mutational characteristics of interval CRCs in comparison with screen detected CRCs. METHODS: We included 1175 CRCs documented in the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial and 3661 CRCs in the Nurses' Health Study (NHS) and Health Professionals Follow-up Study (HPFS). Multivariable Cox models were performed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of death risk. Whole exome sequencing was conducted in 147 PLCO cases and 796 NHS/HPFS cases. RESULTS: A total of 619 deaths (312 CRC-specific) and 2404 deaths (1904 CRC-specific) were confirmed during follow-up of PLCO and NHS/HPFS, respectively. Compared with screen detected CRCs, interval CRCs had a multivariate-adjusted HR (95% CI) of 1.47 (1.21-1.78) for CRC-specific mortality and 1.27 (1.09-1.47) for overall mortality (meta-analysis combining all 3 cohorts). However, we did not observe significant differences in mutational features between interval and screen detected CRCs (false discovery rate adjusted P > .05). CONCLUSION: Interval CRCs had a significantly increased risk of death compared with screen detected CRCs that were not explained by established clinical prognostic factors, including stage at diagnosis. The survival disadvantage of interval CRCs did not appear to be explained by differences in the genomic landscape of tumors characterized by whole exome sequencing.

Aspirin and antiplatelet treatments in cancer.

Platelets have been hypothesized to promote certain neoplastic malignancies; however, antiplatelet drugs are still not part of routine pharmacological cancer prevention and treatment protocols. Paracrine interactions between platelets and cancer cells have been implicated in potentiating the dissemination, survival within the circulation, and extravasation of cancer cells at distant sites of metastasis. Signals from platelets have also been suggested to confer epigenetic alterations, including upregulating oncoproteins in circulating tumor cells, and secretion of potent growth factors may play roles in promoting mitogenesis, angiogenesis, and metastatic outgrowth. Thrombocytosis remains a marker of poor prognosis in patients with solid tumors. Experimental data suggest that lowering of platelet count may reduce tumor growth and metastasis. On the basis of the mechanisms by which platelets could contribute to cancer growth and metastasis, it is conceivable that drugs reducing platelet count or platelet activation might attenuate cancer progression and improve outcomes. We will review select pharmacological approaches that inhibit platelets and may affect cancer development and propagation. We begin by presenting an overview of clinical cancer prevention and outcome studies with low-dose aspirin. We then review current nonclinical development of drugs targeted to platelet binding, activation, and count as potential mitigating agents in cancer.

The effect of various breath-hold techniques on the cardiorespiratory response to facial immersion in humans.

NEW FINDINGS: What is the central question of this study? What is the effect of three repeated breath-hold techniques routinely used by freedivers, thought to manipulate arterial partial pressures of O2 and CO2 , on the cardiorespiratory and haematological response to breath-holding during facial immersion? What is the main finding and its importance? All three techniques increased breath-hold by a similar duration, probably owing to the similar marked increase in end-tidal O2 and decrease in end-tidal CO2 observed in all three trials before facial immersion. These were the only cardiorespiratory changes that were consistently manipulated before the maximal breath-hold. This would suggest that pronounced bradycardia and vasoconstriction of selective vascular beds are probably not obligatory for prolonging breath-hold duration. ABSTRACT: Repeated maximal breath-holds have been demonstrated to induce bradycardia, increase haematocrit and haemoglobin and prolong subsequent breath-hold duration by 20%. Freedivers use non-maximal breath-hold techniques (BHTs) to improve breath-hold duration. The aim of this study was to investigate the cardiorespiratory and haematological responses to various BHTs. Ten healthy men (34.5 ± 1.9 years) attended five randomized experimental trials and performed a 40 min period of quiet rest or one of three BHTs followed by a maximal breath-hold challenge during facial immersion in water at 30 or 10°C. Cardiovascular and respiratory parameters were measured continuously using finger plethysmography and breath-by-breath gas analysis, respectively, and venous blood samples were collected throughout. Facial immersion in cold water caused marked bradycardia (74.1 vs. 50.2 beats/min after 40 s) but did not increase breath-hold duration compared with warm water control conditions. Facial immersion breath-hold duration was 30.8-43.3% greater than the control duration when preceded by BHTs that involved repeated breath-holds of constant duration (P = 0.021), increasing duration (P < 0.001) or increasing frequency (P < 0.001), with no difference observed between BHTs. The increased duration of apnoea across all three BHT protocols was associated with a 6.8% increase in end-tidal O2 and a 13.1% decrease in end-tidal CO2 immediately before facial immersion. There were no differences in blood pressure, cardiac output, heart rate, haematocrit or haemoglobin between each BHT and control conditions (P > 0.05). In conclusion, the duration of apnoea can be extended by manipulating blood gases through repeated prior breath-holds, but changes in cardiac output and red blood cell mass do not appear essential.

The effect of 4 weeks of high-intensity interval training and 2 weeks of detraining on cardiovascular disease risk factors in male adolescents.

NEW FINDINGS: What is the central question of this study? What is the effect of 4 weeks of high-intensity interval training (HIIT) and 2 weeks of detraining on vascular function and traditional cardiovascular disease (CVD) risk factors in male adolescents? What is the main finding and its importance? Four weeks of HIIT improved macrovascular function in adolescents. However, this training period did not measurably change microvascular function, body composition or blood biomarkers. Following 2 weeks of detraining, the improvement in flow-mediated dilatation (FMD) was lost. This highlights the importance of the continuation of regular exercise for the primary prevention of CVD. ABSTRACT: High-intensity interval training (HIIT) represents an effective method to improve cardiometabolic health in adolescents. This study aimed to investigate the effect of 4 weeks of HIIT followed by 2 weeks of detraining on vascular function and traditional cardiovascular disease (CVD) risk factors in adolescent boys. Nineteen male adolescents (13.3 ± 0.5 years) were randomly allocated to either a training (TRAIN, n = 10) or control (CON, n = 9) group. Participants in TRAIN completed 4 weeks of HIIT running with three sessions per week. Macro- (flow-mediated dilatation, FMD) and microvascular (peak reactive hyperaemia, PRH) function, body composition (fat mass, fat free mass, body fat percentage) and blood biomarkers (glucose, insulin, total cholesterol, high- and low-density lipoprotein, triacylglycerol) were assessed pre-, 48 h post- and 2 weeks post-training for TRAIN and at equivalent time points for CON. Following training, FMD was significantly greater in TRAIN compared to CON (9.88 ± 2.40% and 8.64 ± 2.70%, respectively; P = 0.036) but this difference was lost 2 weeks after training cessation (8.22 ± 2.47% and 8.61 ± 1.99%, respectively; P = 0.062). No differences were detected between groups for PRH (P = 0.821), body composition (all P > 0.14) or blood biomarkers (all P > 0.18). In conclusion, 4 weeks of HIIT improved macrovascular function; however, this training period did not measurably change microvascular function, body composition or blood biomarkers. The reversal of the FMD improvement 2 weeks post-training highlights the importance of the continuation of regular exercise for the primary prevention of CVD.

seco-1-Azacubane-2-carboxylic acid-Amide Bond Comparison to Proline.

seco-1-Azacubane-2-carboxylic acid, an unusual and sterically constrained amino acid, was found to undergo amide bond formation at both the N- and C-termini using proline based bioactive molecule templates as a concept platform.

Kinetico-Mechanistic Studies on a Reactive Organocopper(II) Complex: Cu-C Bond Homolysis versus Heterolysis.

Organocopper(II) reagents are an unexplored frontier of copper catalysis. Despite being proposed as reactive intermediates, an understanding of the stability and reactivity of the CuII-C bond has remained elusive. Two main pathways can be considered for the cleavage mode of a CuII-C bond: homolysis and heterolysis. We recently showed how organocopper(II) reagents can react with alkenes via radical addition, a homolytic pathway. In this work, the decomposition of the complex [CuIILR]+ [L = tris(2- dimethylaminoethyl)amine, Me6tren, R = NCCH2-] in the absence and presence of an initiator (RX, X = Cl, Br) was evaluated. When no initiator was present, first-order CuII-C bond homolysis occurred producing [CuIL]+ and succinonitrile, via radical termination. When an excess of the initiator was present, a subsequent formation of [CuIILX]+ via a second-order reaction was found, which results from the reaction of [CuIL]+ with RX following homolysis. However, when Brønsted acids (R'-OH: R' = H, Me, Ph, PhCO) were present, heterolytic cleavage of the CuII-C bond produced [CuIIL(OR')]+ and MeCN. Kinetic studies were undertaken to obtain the thermal (ΔH⧧, ΔS⧧) and pressure (ΔV⧧) activation parameters and deuterium kinetic isotopic effects, which provided an understanding of the strength of the CuII-C bond and the nature of the transition state for the reactions involved. These results reveal possible reaction pathways for organocopper(II) complexes relevant to their applications as catalysts in C-C bond forming reactions.