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

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

New Noncovalent Inhibitors of Penicillin-Binding Proteins from Penicillin-Resistant Bacteria

BACKGROUND: Penicillin-binding proteins (PBPs) are well known and validated targets for antibacterial therapy. The most important clinically used inhibitors of PBPs beta-lactams inhibit transpeptidase activity of PBPs by forming a covalent penicilloyl-enzyme complex that blocks the normal transpeptidation reaction; this finally results in bacterial death. In some resistant bacteria the resistance is acquired by active-site distortion of PBPs, which lowers their acylation efficiency for beta-lactams. To address this problem we focused our attention to discovery of novel noncovalent inhibitors of PBPs. METHODOLOGY/PRINCIPAL FINDINGS: Our in-house bank of compounds was screened for inhibition of three PBPs from resistant bacteria: PBP2a from Methicillin-resistant Staphylococcus aureus (MRSA), PBP2x from Streptococcus pneumoniae strain 5204, and PBP5fm from Enterococcus faecium strain D63r. Initial hit inhibitor obtained by screening was then used as a starting point for computational similarity searching for structurally related compounds and several new noncovalent inhibitors were discovered. Two compounds had promising inhibitory activities of both PBP2a and PBP2x 5204, and good in-vitro antibacterial activities against a panel of Gram-positive bacterial strains. CONCLUSIONS: We found new noncovalent inhibitors of PBPs which represent important starting points for development of more potent inhibitors of PBPs that can target penicillin-resistant bacteria.Eur-Intafa

The VICI-trial: high frequency oscillation versus conventional mechanical ventilation in newborns with congenital diaphragmatic hernia: an international multicentre randomized controlled trial

Background: Congenital diaphragmatic hernia (CDH) is a severe congenital anomaly of the diaphragm resulting in pulmonary hypoplasia and pulmonary hypertension. It is associated with a high risk of mortality and pulmonary morbidity. Previous retrospective studies have reported high frequency oscillatory ventilation (HFO) to reduce pulmonary morbidity in infants with CDH, while others indicated HFO to be associated with worse outcome. We therefore aimed to develop a randomized controlled trial to compare initial ventilatory treatment with high-frequency oscillation and conventional ventilation in infants with CDH.Methods/design: This trial is designed as a multicentre trial in which 400 infants (200 in each arm) will be included. Primary outcome measures are BPD, described as oxygen dependency by day 28 according to the definition of Jobe and Bancalari, and/or mortality by day 28. All liveborn infants with CDH born at a gestational age of over 34 weeks and no other severe congenital anomalies are eligible for inclusion. Parental informed consent is asked antenatally and the allocated ventilation mode starts within two hours after birth. Laboratory samples of blood, urine and tracheal aspirate are taken at the first day of life, day 3, day 7, day 14 and day 28 to evaluate laboratory markers for ventilator-induced lung injury and pulmonary hypertension.Discussion: To date, randomized clinical trials are lacking in the field of CDH. The VICI-trial, as the first randomized clinical trial in the field of CDH, may provide further insight in ventilation strategies in CDH patient. This may hopefully prevent mortality and morbidity.Trial registration: Netherlands Trial Register (NTR): NTR1310

Circulating microparticles: square the circle

Background: The present review summarizes current knowledge about microparticles (MPs) and provides a systematic overview of last 20 years of research on circulating MPs, with particular focus on their clinical relevance. Results: MPs are a heterogeneous population of cell-derived vesicles, with sizes ranging between 50 and 1000 nm. MPs are capable of transferring peptides, proteins, lipid components, microRNA, mRNA, and DNA from one cell to another without direct cell-to-cell contact. Growing evidence suggests that MPs present in peripheral blood and body fluids contribute to the development and progression of cancer, and are of pathophysiological relevance for autoimmune, inflammatory, infectious, cardiovascular, hematological, and other diseases. MPs have large diagnostic potential as biomarkers; however, due to current technological limitations in purification of MPs and an absence of standardized methods of MP detection, challenges remain in validating the potential of MPs as a non-invasive and early diagnostic platform. Conclusions: Improvements in the effective deciphering of MP molecular signatures will be critical not only for diagnostics, but also for the evaluation of treatment regimens and predicting disease outcomes

Uncommon nucleotide excision repair phenotypes revealed by targeted high-throughput sequencing

BACKGROUND: Deficient nucleotide excision repair (NER) activity causes a variety of autosomal recessive diseases including xeroderma pigmentosum (XP) a disorder which pre-disposes to skin cancer, and the severe multisystem condition known as Cockayne syndrome (CS). In view of the clinical overlap between NER-related disorders, as well as the existence of multiple phenotypes and the numerous genes involved, we developed a new diagnostic approach based on the enrichment of 16 NER-related genes by multiplex amplification coupled with next-generation sequencing (NGS). METHODS: Our test cohort consisted of 11 DNA samples, all with known mutations and/or non pathogenic SNPs in two of the tested genes. We then used the same technique to analyse samples from a prospective cohort of 40 patients. Multiplex amplification and sequencing were performed using AmpliSeq protocol on the Ion Torrent PGM (Life Technologies). RESULTS: We identified causative mutations in 17 out of the 40 patients (43 %). Four patients showed biallelic mutations in the ERCC6(CSB) gene, five in the ERCC8(CSA) gene: most of them had classical CS features but some had very mild and incomplete phenotypes. A small cohort of 4 unrelated classic XP patients from the Basque country (Northern Spain) revealed a common splicing mutation in POLH (XP-variant), demonstrating a new founder effect in this population. Interestingly, our results also found ERCC2(XPD), ERCC3(XPB) or ERCC5(XPG) mutations in two cases of UV-sensitive syndrome and in two cases with mixed XP/CS phenotypes. CONCLUSIONS: Our study confirms that NGS is an efficient technique for the analysis of NER-related disorders on a molecular level. It is particularly useful for phenotypes with combined features or unusually mild symptoms. Targeted NGS used in conjunction with DNA repair functional tests and precise clinical evaluation permits rapid and cost-effective diagnosis in patients with NER-defects

Abundance and scarcity: classical theories of money, bank balance sheets and business models, and the British restriction of 1797‐1818.

The thesis looks through the lens of bank balance sheet accounting to investigate the structural change in the British banking system between 1780 and 1832, and how classical quantity theorists of money attempted to respond to the ensuing financialisation of the wartime economy with its growing reliance on credit funded with paper-based instruments (the ‘Vansittart system’ of war finance). The thesis combines contributions to three separate fields to construct a holistic historical example of the challenges faced by monetary economists when ‘modelling’ financial innovation, credit growth, ‘fringe’ banking, and agent incentives – at a time of radical experimentation: the suspension of the 80-year-old gold standard (“the Restriction”). First, critical text analysis of the history of economics argues that the 1809-10 debate between Ricardo and Bosanquet at the peak of the credit boom, bifurcated classical theory into two timeless competing policy paradigms advocating the ‘Scarcity’ or ‘Abundance’ of money relative to exchange transactions. The competing hypotheses regarding the role of money and credit are identified and the rest of the thesis examines the archival evidence for each. Second, the core of the thesis contributes to the historical literature on banking in relation to money by reconstructing a taxonomy of bank business models, their relationships with the London inter-bank settlement system, and their responses to the Restriction - drawing on some 17,000 mostly new data points collected from the financial records of London and Country banks. The final section contributes to the economic history of money by constructing aggregated views of total bank liabilities from the firm-level data, scaled to recently available British GDP estimates. These are examined to establish (with hindsight) the relative merits and lacuna of the competing theoretical hypotheses postulated by political economists. It was the period of deleveraging after 1810 that revealed the lacuna of both paradigms