Background: Protein ingestion after a single bout of resistance-type exercise stimulates net muscle protein accretion during acute postexercise recovery. Consequently, it is generally accepted that ...protein supplementation is required to maximize the adaptive response of the skeletal muscle to prolonged resistance-type exercise training. However, there is much discrepancy in the literature regarding the proposed benefits of protein supplementation during prolonged resistance-type exercise training in younger and older populations.Objective: The objective of the study was to define the efficacy of protein supplementation to augment the adaptive response of the skeletal muscle to prolonged resistance-type exercise training in younger and older populations.Design: A systematic review of interventional evidence was performed through the use of a random-effects meta-analysis model. Data from the outcome variables fat-free mass (FFM), fat mass, type I and II muscle fiber cross-sectional area, and 1 repetition maximum (1-RM) leg press strength were collected from randomized controlled trials (RCTs) investigating the effect of dietary protein supplementation during prolonged (>6 wk) resistance-type exercise training.Results: Data were included from 22 RCTs that included 680 subjects. Protein supplementation showed a positive effect for FFM (weighted mean difference: 0.69 kg; 95% CI: 0.47, 0.91 kg; P < 0.00001) and 1-RM leg press strength (weighted mean difference: 13.5 kg; 95% CI: 6.4, 20.7 kg; P < 0.005) compared with a placebo after prolonged resistance-type exercise training in younger and older subjects.Conclusion: Protein supplementation increases muscle mass and strength gains during prolonged resistance-type exercise training in both younger and older subjects.
X-ray absorption studies of the geometric and electronic structure of primarily heterogeneous Co, Ni, and Mn based water oxidation catalysts are reviewed. The X-ray absorption near edge and extended ...X-ray absorption fine structure studies of the metal K-edge, characterize the metal oxidation state, metal-oxygen bond distance, metal-metal distance, and degree of disorder of the catalysts. These properties guide the coordination environment of the transition metal oxide radical that localizes surface holes and is required to oxidize water. The catalysts are investigated both as-prepared, in their native state, and under reaction conditions, while transition metal oxide radicals are generated. The findings of many experiments are summarized in tables. The advantages of future X-ray experiments on water oxidation catalysts, which include the limited data available of the oxygen K-edge, metal L-edge, and resonant inelastic X-ray scattering, are discussed.
X-ray absorption studies of the geometric and electronic structure of primarily heterogeneous Co, Ni, and Mn based water oxidation catalysts are reviewed.
Dietary protein ingestion stimulates muscle protein synthesis by providing amino acids to the muscle. The magnitude and duration of the postprandial increase in muscle protein synthesis rates are ...largely determined by dietary protein digestion and amino acid absorption kinetics.
We assessed the impact of protein type, protein dose, and age on dietary protein digestion and amino acid absorption kinetics in vivo in humans.
We included data from 18 randomized controlled trials with a total of 602 participants age: 53 ± 23 y; BMI (kg/m2): 24.8 ± 3.3 who consumed various quantities of intrinsically ʟ-1-13C-phenylalaninelabeled whey (n = 137),casein (n = 393), or milk (n = 72) protein and received intravenous infusions of ʟ-ring-2H5-phenylalanine, which allowed us to assess protein digestion and phenylalanine absorption kinetics and the postprandial release of dietary protein–derived phenylalanine into the circulation. The effect of aging on these processes was assessed in a subset of 82 young (aged 22 ± 3 y) and 83 older (aged 71 ± 5 y) individuals.
A total of 50% ± 14% of dietary proteinderived phenylalanine appeared in the circulation over a 5-h postprandial period. Casein ingestion resulted in a smaller (45% ± 11%), whey protein ingestion in an intermediate (57% ± 10%), and milk protein ingestion in a greater (65% ± 13%) fraction of dietary proteinderived phenylalanine appearing in the circulation (P < 0.001). The postprandial availability of dietary proteinderived phenylalanine in the circulation increased with the ingestion of greater protein doses (P < 0.05). Protein digestion and phenylalanine absorption kinetics were attenuated in older when compared with young individuals, with 45% ± 10% vs. 51% ± 14% of dietary protein–;derived phenylalanine appearing in the circulation, respectively (P = 0.001).
Protein type, protein dose, and age modulate dietary protein digestion and amino acid absorption kinetics and subsequent postprandial plasma amino acid availability in vivo in humans. These trials were registered at clinicaltrials.gov as NCT00557388, NCT00936039, NCT00991523, NCT01317511, NCT01473576, NCT01576848,NCT01578590, NCT01615276, NCT01680146, NCT01820975, NCT01986842, and NCT02596542, and at http://www.trialregister.nl as NTR3638, NTR3885, NTR4060, NTR4429, and NTR4492.
Purpose
Drug utilization studies have applied different methods to various data types to describe medication use, which hampers comparisons across populations. The aim of this study was to describe ...the time trends in antidepressant prescribing in the last decade and the variation in the prevalence, calculated in a uniform manner, in seven European electronic healthcare databases.
Methods
Annual prevalence per 10,000 person-years (PYs) was calculated for 2001–2009 in databases from Spain, Germany, Denmark, the United Kingdom (UK), and the Netherlands. Prevalence data were stratified according to age, sex, antidepressant type (selective serotonin re-uptake inhibitors SSRIs or tricyclic antidepressants TCAs) and major indications.
Results
The age- and sex-standardized prevalence was lowest in the two Dutch (391 and 429 users per 10,000 PYs) and highest in the two UK (913 and 936 users per 10,000 PYs) populations in 2008. The prevalence in the Danish, German, and Spanish populations was 637, 618, and 644 users per 10,000 PY respectively. Antidepressants were prescribed most often in 20- to 60-year-olds in the two UK populations compared with the others. SSRIs were prescribed more often than TCAs in all except the German population. In the majority of countries we observed an increasing trend of antidepressant prescribing over time. Two different methods identifying recorded indications yielded different ranges of proportions of patients recorded with the specific indication (15–57 % and 39–69 % for depression respectively).
Conclusion
Despite applying uniform methods, variations in the prevalence of antidepressant prescribing were obvious in the different populations. Database characteristics and clinical factors may both explain these variations.
The large-scale genetic profiling of tumours can identify potentially actionable molecular variants for which approved anticancer drugs are available
. However, when patients with such variants are ...treated with drugs outside of their approved label, successes and failures of targeted therapy are not systematically collected or shared. We therefore initiated the Drug Rediscovery protocol, an adaptive, precision-oncology trial that aims to identify signals of activity in cohorts of patients, with defined tumour types and molecular variants, who are being treated with anticancer drugs outside of their approved label. To be eligible for the trial, patients have to have exhausted or declined standard therapies, and have malignancies with potentially actionable variants for which no approved anticancer drugs are available. Here we show an overall rate of clinical benefit-defined as complete or partial response, or as stable disease beyond 16 weeks-of 34% in 215 treated patients, comprising 136 patients who received targeted therapies and 79 patients who received immunotherapy. The overall median duration of clinical benefit was 9 months (95% confidence interval of 8-11 months), including 26 patients who were experiencing ongoing clinical benefit at data cut-off. The potential of the Drug Rediscovery protocol is illustrated by the identification of a successful cohort of patients with microsatellite instable tumours who received nivolumab (clinical benefit rate of 63%), and a cohort of patients with colorectal cancer with relatively low mutational load who experienced only limited clinical benefit from immunotherapy. The Drug Rediscovery protocol facilitates the defined use of approved drugs beyond their labels in rare subgroups of cancer, identifies early signals of activity in these subgroups, accelerates the clinical translation of new insights into the use of anticancer drugs outside of their approved label, and creates a publicly available repository of knowledge for future decision-making.
Disruption of the intestinal microbiota is considered an etiological factor in pediatric functional constipation. Scientifically based selection of potential beneficial probiotic strains in ...functional constipation therapy is not feasible due to insufficient knowledge of microbiota composition in affected subjects. The aim of this study was to describe microbial composition and diversity in children with functional constipation, compared to healthy controls.
Fecal samples from 76 children diagnosed with functional constipation according to the Rome III criteria (median age 8.0 years; range 4.2-17.8) were analyzed by IS-pro, a PCR-based microbiota profiling method. Outcome was compared with intestinal microbiota profiles of 61 healthy children (median 8.6 years; range 4.1-17.9). Microbiota dissimilarity was depicted by principal coordinate analysis (PCoA), diversity was calculated by Shannon diversity index. To determine the most discriminative species, cross validated logistic ridge regression was performed.
Applying total microbiota profiles (all phyla together) or per phylum analysis, no disease-specific separation was observed by PCoA and by calculation of diversity indices. By ridge regression, however, functional constipation and controls could be discriminated with 82% accuracy. Most discriminative species were Bacteroides fragilis, Bacteroides ovatus, Bifidobacterium longum, Parabacteroides species (increased in functional constipation) and Alistipes finegoldii (decreased in functional constipation).
None of the commonly used unsupervised statistical methods allowed for microbiota-based discrimination of children with functional constipation and controls. By ridge regression, however, both groups could be discriminated with 82% accuracy. Optimization of microbiota-based interventions in constipated children warrants further characterization of microbial signatures linked to clinical subgroups of functional constipation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To summarise the current evidence on the effects of physical activity (PA) interventions on cognitive and academic performance in children, and formulate research priorities and recommendations.
...Systematic review (following PRISMA guidelines) with a methodological quality assessment and an international expert panel. We based the evaluation of the consistency of the scientific evidence on the findings reported in studies rated as of high methodological quality.
PubMed, PsycINFO, Cochrane Central, Web of Science, ERIC, and SPORTDiscus.
PA-intervention studies in children with at least one cognitive or academic performance assessment.
Eleven (19%) of 58 included intervention studies received a high-quality rating for methodological quality: four assessed effects of PA interventions on cognitive performance, six assessed effects on academic performance, and one on both. All high-quality studies contrasted the effects of additional/adapted PA activities with regular curriculum activities. For cognitive performance 10 of 21 (48%) constructs analysed showed statistically significant beneficial intervention effects of PA, while for academic performance, 15 of 25 (60%) analyses found a significant beneficial effect of PA. Across all five studies assessing PA effects on mathematics, beneficial effects were reported in six out of seven (86%) outcomes. Experts put forward 46 research questions. The most pressing research priority cluster concerned the causality of the relationship between PA and cognitive/academic performance. The remaining clusters pertained to PA characteristics, moderators and mechanisms governing the 'PA-performance' relationship and miscellaneous topics.
There is currently inconclusive evidence for the beneficial effects of PA interventions on cognitive and overall academic performance in children. We conclude that there is strong evidence for beneficial effects of PA on maths performance.The expert panel confirmed that more 'high-quality' research is warranted. By prioritising the most important research questions and formulating recommendations we aim to guide researchers in generating high-quality evidence. Our recommendations focus on adequate control groups and sample size, the use of valid and reliable measurement instruments for physical activity and cognitive performance, measurement of compliance and data analysis.
CRD42017082505.
Antibody–drug conjugates (ADCs) that are currently on the market or in clinical trials are predominantly based on two drug classes: auristatins and maytansinoids. Both are tubulin binders and block ...the cell in its progression through mitosis. We set out to develop a new class of linker-drugs based on duocarmycins, potent DNA-alkylating agents that are composed of a DNA-alkylating and a DNA-binding moiety and that bind into the minor groove of DNA. Linker-drugs were evaluated as ADCs by conjugation to the anti-HER2 antibody trastuzumab via reduced interchain disulfides. Duocarmycin 3b, bearing an imidazo1,2-apyridine-based DNA-binding unit, was selected as the drug moiety, notably because of its rapid degradation in plasma. The drug was incorporated into the linker-drugs in its inactive prodrug form, seco-duocarmycin 3a. Linker attachment to the hydroxyl group in the DNA-alkylating moiety was favored over linking to the DNA-binding moiety, as the first approach gave more consistent results for in vitro cytotoxicity and generated ADCs with excellent human plasma stability. Linker-drug 2 was eventually selected based on the properties of the corresponding trastuzumab conjugate, SYD983, which had an average drug-to-antibody ratio (DAR) of about 2. SYD983 showed subnanomolar potencies against multiple human cancer cell lines, was highly efficacious in a BT-474 xenograft model, and had a long half-life in cynomolgus monkeys, in line with high stability in monkey and human plasma. Studies comparing ADCs with a different average DAR showed that a higher average DAR leads to increased efficacy but also to somewhat less favorable physicochemical and toxicological properties. Fractionation of SYD983 with hydrophobic interaction chromatography resulted in SYD985, consisting of about 95% DAR2 and DAR4 species in an approximate 2:1 ratio and having an average DAR of about 2.8. SYD985 combines several favorable properties from the unfractionated ADCs with an improved homogeneity. It was selected for further development and recently entered clinical Phase I evaluation.
This large-scale cross-sectional study had the aim to investigate whether adolescent males and females differ in self-perceived self-regulation. The large sample size allowed us to investigate sex ...differences in three age-groups of young (n = 161), middle (n = 133) and late (n = 159) adolescents. Self-regulation was evaluated with a self-report questionnaire, the Amsterdam Executive Functioning Inventory (AEFI). This questionnaire gives a proxi for three executive functions that are important for proper self-regulation: (1) self-control & self-monitoring, (2) attention, and (3) planning & initiative taking. Results revealed clear sex differences in the self-regulation as perceived by mid-adolescents (i.e., 13-16 years). In this age period, females evaluated their attention higher than males, and they reported higher levels of self-control & self-monitoring. Our findings offer important new insights with respect to the decision making, academic achievements and behaviour of 13-16-year olds. Self-regulation is known to have a central role in academic achievement and in behavioural organisation. The sex differences in self-regulation in mid-adolescence may therefore explain part of the difference which males and females in this age-group exhibit in academic achievements and behavioural organisations. The results imply that self-regulation may be a relevant intervention target: rather than focussing on changing behaviour, interventions may focus more on self-insights and thereby changing the adolescent's perceptions about their behaviour. Increased self-insight may have the potency to actually change behaviour, which might be an interesting target for future investigation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Bariatric surgery improves glucose metabolism. Recent data suggest that faecal microbiota transplantation (FMT) using faeces from postbariatric surgery diet-induced obese mice in germ-free mice ...improves glucose metabolism and intestinal homeostasis. We here investigated whether allogenic FMT using faeces from post-Roux-en-Y gastric bypass donors (RYGB-D) compared with using faeces from metabolic syndrome donors (METS-D) has short-term effects on glucose metabolism, intestinal transit time and adipose tissue inflammation in treatment-naïve, obese, insulin-resistant male subjects.
Subjects with metabolic syndrome (n=22) received allogenic FMT either from RYGB-D or METS-D. Hepatic and peripheral insulin sensitivity as well as lipolysis were measured at baseline and 2 weeks after FMT by hyperinsulinaemic euglycaemic stable isotope (
H
-glucose and
H
-glycerol) clamp. Secondary outcome parameters were changes in resting energy expenditure, intestinal transit time, faecal short-chain fatty acids (SCFA) and bile acids, and inflammatory markers in subcutaneous adipose tissue related to intestinal microbiota composition. Faecal SCFA, bile acids, glycaemic control and inflammatory parameters were also evaluated at 8 weeks.
We observed a significant decrease in insulin sensitivity 2 weeks after allogenic METS-D FMT (median rate of glucose disappearance: from 40.6 to 34.0 µmol/kg/min; p<0.01). Moreover, a trend (p=0.052) towards faster intestinal transit time following RYGB-D FMT was seen. Finally, we observed changes in faecal bile acids (increased lithocholic, deoxycholic and (iso)lithocholic acid after METS-D FMT), inflammatory markers (decreased adipose tissue chemokine ligand 2 (CCL2) gene expression and plasma CCL2 after RYGB-D FMT) and changes in several intestinal microbiota taxa.
Allogenic FMT using METS-D decreases insulin sensitivity in metabolic syndrome recipients when compared with using post-RYGB-D. Further research is needed to delineate the role of donor characteristics in FMT efficacy in human insulin-resistant subjects.
NTR4327.
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