Germ fate determinants protect germ precursor cell division by reducing septin and anillin levels at the cell division plane.

Animal cell cytokinesis, or the physical division of one cell into two, is thought to be driven by constriction of an actomyosin contractile ring at the division plane. The mechanisms underlying cell type-specific differences in cytokinesis remain unknown. Germ cells are totipotent cells that pass genetic information to the next generation. Previously, using formincyk-1(ts) mutant Caenorhabditis elegans 4-cell embryos, we found that the P2 germ precursor cell is protected from cytokinesis failure and can divide with greatly reduced F-actin levels at the cell division plane. Here, we identified two canonical germ fate determinants required for P2-specific cytokinetic protection: PIE-1 and POS-1. Neither has been implicated previously in cytokinesis. These germ fate determinants protect P2 cytokinesis by reducing the accumulation of septinUNC-59 and anillinANI-1 at the division plane, which here act as negative regulators of cytokinesis. These findings may provide insight into the regulation of cytokinesis in other cell types, especially in stem cells with high potency.

The plasmidome associated with Gram-negative bloodstream infections: A large-scale observational study using complete plasmid assemblies.

Plasmids carry genes conferring antimicrobial resistance and other clinically important traits, and contribute to the rapid dissemination of such genes. Previous studies using complete plasmid assemblies, which are essential for reliable inference, have been small and/or limited to plasmids carrying antimicrobial resistance genes (ARGs). In this study, we sequenced 1,880 complete plasmids from 738 isolates from bloodstream infections in Oxfordshire, UK. The bacteria had been originally isolated in 2009 (194 isolates) and 2018 (368 isolates), plus a stratified selection from intervening years (176 isolates). We demonstrate that plasmids are largely, but not entirely, constrained to a single host species, although there is substantial overlap between species of plasmid gene-repertoire. Most ARGs are carried by a relatively small number of plasmid groups with biological features that are predictable. Plasmids carrying ARGs (including those encoding carbapenemases) share a putative 'backbone' of core genes with those carrying no such genes. These findings suggest that future surveillance should, in addition to tracking plasmids currently associated with clinically important genes, focus on identifying and monitoring the dissemination of high-risk plasmid groups with the potential to rapidly acquire and disseminate these genes.

Discordance between different bioinformatic methods for identifying resistance genes from short-read genomic data, with a focus on Escherichia coli.

Several bioinformatics genotyping algorithms are now commonly used to characterize antimicrobial resistance (AMR) gene profiles in whole-genome sequencing (WGS) data, with a view to understanding AMR epidemiology and developing resistance prediction workflows using WGS in clinical settings. Accurately evaluating AMR in Enterobacterales, particularly Escherichia coli, is of major importance, because this is a common pathogen. However, robust comparisons of different genotyping approaches on relevant simulated and large real-life WGS datasets are lacking. Here, we used both simulated datasets and a large set of real E. coli WGS data (n=1818 isolates) to systematically investigate genotyping methods in greater detail. Simulated constructs and real sequences were processed using four different bioinformatic programs (ABRicate, ARIBA, KmerResistance and SRST2, run with the ResFinder database) and their outputs compared. For simulation tests where 3079 AMR gene variants were inserted into random sequence constructs, KmerResistance was correct for 3076 (99.9 %) simulations, ABRicate for 3054 (99.2 %), ARIBA for 2783 (90.4 %) and SRST2 for 2108 (68.5 %). For simulation tests where two closely related gene variants were inserted into random sequence constructs, KmerResistance identified the correct alleles in 35 338/46 318 (76.3 %) simulations, ABRicate identified them in 11 842/46 318 (25.6 %) simulations, ARIBA identified them in 1679/46 318 (3.6 %) simulations and SRST2 identified them in 2000/46 318 (4.3 %) simulations. In real data, across all methods, 1392/1818 (76 %) isolates had discrepant allele calls for at least 1 gene. In addition to highlighting areas for improvement in challenging scenarios, (e.g. identification of AMR genes at <10× coverage, identifying multiple closely related AMR genes present in the same sample), our evaluations identified some more systematic errors that could be readily soluble, such as repeated misclassification (i.e. naming) of genes as shorter variants of the same gene present within the reference resistance gene database. Such naming errors accounted for at least 2530/4321 (59 %) of the discrepancies seen in real data. Moreover, many of the remaining discrepancies were likely 'artefactual', with reporting of cut-off differences accounting for at least 1430/4321 (33 %) discrepants. Whilst we found that comparing outputs generated by running multiple algorithms on the same dataset could identify and resolve these algorithmic artefacts, the results of our evaluations emphasize the need for developing new and more robust genotyping algorithms to further improve accuracy and performance.

Germ fate determinants protect germ precursor cell division by restricting septin and anillin levels at the division plane.

Animal cell cytokinesis, or the physical division of one cell into two, is thought to be driven by constriction of an actomyosin contractile ring at the division plane. The mechanisms underlying cell type-specific differences in cytokinesis remain unknown. Germ cells are totipotent cells that pass genetic information to the next generation. Previously, using formin cyk-1 (ts) mutant C. elegans embryos, we found that the P2 germ precursor cell is protected from cytokinesis failure and can divide without detectable F-actin at the division plane. Here, we identified two canonical germ fate determinants required for P2-specific cytokinetic protection: PIE-1 and POS-1. Neither has been implicated previously in cytokinesis. These germ fate determinants protect P2 cytokinesis by reducing the accumulation of septin UNC-59 and anillin ANI-1 at the division plane, which here act as negative regulators of cytokinesis. These findings may provide insight into cytokinetic regulation in other cell types, especially in stem cells with high potency.

Diet suppresses glioblastoma initiation in mice by maintaining quiescence of mutation-bearing neural stem cells.

Glioblastoma is thought to originate from neural stem cells (NSCs) of the subventricular zone that acquire genetic alterations. In the adult brain, NSCs are largely quiescent, suggesting that deregulation of quiescence maintenance may be a prerequisite for tumor initiation. Although inactivation of the tumor suppressor p53 is a frequent event in gliomagenesis, whether or how it affects quiescent NSCs (qNSCs) remains unclear. Here, we show that p53 maintains quiescence by inducing fatty-acid oxidation (FAO) and that acute p53 deletion in qNSCs results in their premature activation to a proliferative state. Mechanistically, this occurs through direct transcriptional induction of PPARGC1a, which in turn activates PPARα to upregulate FAO genes. Dietary supplementation with fish oil containing omega-3 fatty acids, natural PPARα ligands, fully restores quiescence of p53-deficient NSCs and delays tumor initiation in a glioblastoma mouse model. Thus, diet can silence glioblastoma driver mutations, with important implications for cancer prevention.

Effect of resistance training on local muscle endurance in middle-aged and older adults: A systematic review with meta-analysis and meta-regression.

BACKGROUND: Local muscle endurance (LME) is a significant indicator of muscle health and function in middle-aged and older adults. However, resistance training (RT) practices which optimise performance in this population are currently unclear. This study examined: 1) the effect of RT on LME; and 2) the impact of acute resistance exercise program variables on LME in middle-aged and older adults. METHODS: Five electronic databases were searched using terms related to RT, LME, and older adults. Random effects (Hedges' g) meta-analyses were undertaken to estimate the effect of RT on upper and lower body LME assessed via maximal repetitions during an isotonic test. The impact of resistance exercise program variables on LME effects was explored using meta-regression analyses. RESULTS: Fifteen studies met the inclusion criteria for this review. Upon sensitivity analysis, one study was removed. Large effects favoured RT for LME of the upper body (g = 1.10, p < 0.001) and lower body (g = 1.18, p < 0.001). Large effects on LME from RT were found irrespective of training intensity or other resistance exercise program variables. Moderate heterogeneity and publication bias were found in most analyses. DISCUSSION: RT is an effective means for improving LME in middle-aged and older adults. Optimal training characteristics have not been defined by this review, as improvement in LME was unrelated to RT volume or loading intensity. Caution is warranted when interpreting the findings due to heterogeneity and bias present in existing literature. Additional studies are needed with direct comparisons of various training techniques.

Effect of High-Volume Cluster Sets vs. Lower-Volume Traditional Sets on Accuracy of Estimated Repetitions to Failure.

ABSTRACT: Davies, TB, Li, J, and Hackett, DA. Effect of high-volume cluster sets vs. lower-volume traditional sets on accuracy of estimated repetitions to failure. J Strength Cond Res 37(6): 1191-1198, 2023-This study investigated the effects of resistance training using cluster (CLUS) vs. traditional (TRAD) set structures on the accuracy of estimated repetitions to failure (ERF). Nineteen healthy male resistance trainers (age 21.0 ± 4.4 years) were randomized into 1 of the 2 bench press training routines performed for 6 weeks. Cluster ( n = 10) performed 6 sets of 5 repetitions at 85% of 1 repetition maximum (1RM) with 30-second interrepetition rest and 3 minutes of interset rest. Traditional ( n = 9) performed 3 sets of 5 repetitions at 85% 1RM with 5 minutes of interset rest. Maximum repetitions at 85% 1RM was performed before and after intervention to assess error in ERF and mean concentric velocity (MCV). The ERF, rating of perceived exertion, and maintenance of MCV were assessed throughout the intervention. Rating of perceived exertion was lower for sets 1-3 in CLUS compared with TRAD from weeks 1 to 4 (effect size [ES] = 0.8-2.4, p ≤ 0.04). The ERF was greater for sets 1-3 in CLUS than in TRAD during all intervention weeks (ES = 1.0-5.1, p ≤ 0.04). Maintenance of MCV was greater in CLUS compared with TRAD for all sets at week 1 (ES = 0.76, p = 0.002) and sets 4-6 at week 6 (ES = 0.77, p = 0.006). After the intervention, error in ERF did not change, and no differences were found between the groups. Findings indicate that accuracy of ERF does not improve after resistance training using set structures that induce different transient fatigue-related effects when using high loads in experienced resistance trainers.

Self-Reported Training and Supplementation Practices Between Performance-Enhancing Drug-User Bodybuilders Compared with Natural Bodybuilders.

ABSTRACT: Li, J, Davies, TB, and Hackett, DA. Self-reported training and supplementation practices between performance-enhancing drug-user bodybuilders compared with natural bodybuilders. J Strength Cond Res 37(5): 1079-1088, 2023-This study aimed to examine whether the training and supplementation practices differ between performance-enhancing drug (PED)-using bodybuilders (BB) and natural BB. One hundred eighty-seven competitive male bodybuilders with a median age of 27.0 years completed an online survey. Of this sample, 40 respondents reported using PED (PED-user) and 147 respondents reported to be natural. Compared with natural BB, PED-user BB reported greater off-season body weight ( p < 0.001) and weight loss before a competition ( p < 0.001). In the off-season, PED-user BB performed a greater number of exercises per muscle group ( p < 0.001), number of repetition maximum (RM) per set ( p < 0.01), and less recovery between the sets ( p < 0.01). During the precompetition phase, the natural BB increased their number of RM; however, the PED-user BB still reported using a greater number of RM per set ( p = 0.02), exercises per muscle group ( p < 0.001), and less recovery time between the sets ( p < 0.01). Both the PED-user BB and natural BB reported greater aerobic exercise frequency ( p < 0.001) and session duration ( p < 0.001), although PED-user BB performed a greater number of aerobic exercise sessions ( p = 0.04) and at a higher intensity ( p < 0.01). Advanced training techniques, including negatives, partial repetitions, preexhaustion sets, and timed repetitions, were more popular among PED-user BB ( p < 0.05). Creatine monohydrate usage was more popular among natural BB ( p < 0.001), whereas branched-chain and essential amino acids were more popular among PED-user BB ( p ≤ 0.001). Findings suggest that PED-user BB perform more metabolically demanding resistance training sessions, more strenuous aerobic training during the precompetition phase, and may have different supplementation preferences compared with natural BB.

Effect of Set-Structure on Upper-Body Muscular Hypertrophy and Performance in Recreationally-Trained Male and Female.

ABSTRACT: Davies, TB, Halaki, M, Orr, R, Mitchell, L, Helms, ER, Clarke, J, and Hackett, DA. Effect of set structure on upper-body muscular hypertrophy and performance in recreationally trained men and women. J Strength Cond Res 36(8): 2176-2185, 2022-This study explored the effect of volume-equated traditional-set and cluster-set structures on muscular hypertrophy and performance after high-load resistance training manipulating the bench press exercise. Twenty-one recreationally trained subjects (12 men and 9 women) performed a 3-week familiarization phase and were then randomized into one of two 8-week upper-body and lower-body split programs occurring over 3 and then progressing to 4 sessions per week. Subjects performed 4 sets of 5 repetitions at 85% one repetition maximum (1RM) using a traditional-set structure (TRAD, n = 10), which involved 5 minutes of interset rest only, or a cluster-set structure, which included 30-second inter-repetition rest and 3 minutes of interset rest (CLUS, n = 11). A 1RM bench press, repetitions to failure at 70% 1RM, regional muscle thickness, and dual-energy x-ray absorptiometry were used to estimate changes in muscular strength, local muscular endurance, regional muscular hypertrophy, and body composition, respectively. Velocity loss was assessed using a linear position transducer at the intervention midpoint. TRAD demonstrated a significantly greater velocity loss magnitude (g = 1.50) and muscle thickness of the proximal pectoralis major (g = -0.34) compared with CLUS. There were no significant differences between groups for the remaining outcomes, although a small effect size favoring TRAD was observed for the middle region of the pectoralis major (g = -0.25). It seems that the greater velocity losses during sets observed in traditional-set compared with cluster-set structures may promote superior muscular hypertrophy within specific regions of the pectoralis major in recreationally trained subjects.

Effect of high-volume cluster sets versus lower-volume traditional sets on muscular performance.

BACKGROUND: Similar muscle performance adaptations have been shown following volume-equated resistance training using cluster (CLUS) versus traditional (TRAD) set structures. This study aimed to examine the effects of higher-volume CLUS compared to lower-volume TRAD set structures on muscle performance. METHODS: Twenty resistance-trained males (age 20.9±4.3 years) were randomized into one of two bench press training routines performed for 6 weeks. Subjects in CLUS (N.=10), performed six sets of five repetitions at 85% one-repetition maximum (1RM) with 30 seconds inter-repetition rest and three minutes of inter-set rest. In contrast, subjects in TRAD (N.=10) performed three sets of five repetitions at 85% 1RM with five minutes of inter-set rest. Muscular strength (1RM), concentric velocity, power, local muscular endurance and maintenance of muscle performance (in training sessions) were assessed. RESULTS: For 1RM there was a significant time effect (P<0.001) with moderate effect sizes (ES) within each group (CLUS: ES=0.48; TRAD: ES=0.67). A trend towards significant time effect was found for concentric velocity (P=0.05; CLUS: ES=-0.36; TRAD ES=-0.96). There were no other significant time or group effects nor group × time interactions. Greater maintenance of concentric velocity and power (sets 1-3) was found for CLUS compared to TRAD at week one (P<0.05) but not at week 6. CONCLUSIONS: High load resistance training in the bench press exercise, utilizing intra-set rest periods to increase the training volume, does not yield any muscular performance benefits compared to traditional set structures.

Long-Term Adaptations in the Squat, Bench Press, and Deadlift: Assessing Strength Gain in Powerlifting Athletes.

PURPOSE: Understanding strength changes with resistance training is important in human performance. It also enables better understanding into the expected magnitude of strength increase and factors that influence this change over time. METHODS: Squat, bench press, and deadlift scores were collated from 407 powerlifting meets (n = 1896 unique competitors: ~625 females, ~1270 males) between 2003 and 2018. Absolute (in kilograms) and relative starting strength (in kilograms per body weight) for each lift type was expressed for both sexes. Maximum and overall strength gain per day and per year (in kilograms) was calculated by comparing first and final, or maximum scores for each lift, respectively, and considered based on strength quartile classification. Paired and independent t-tests compared strength changes from baseline and between sexes. One-way ANOVAs compared strength changes between quartiles. Pearson correlations assessed relationships between strength changes over time, and baseline strength, number of competitions, and total days competing. RESULTS: Maximum strength adaptations were greater for squat (20.2-25.4 kg·yr-1) and deadlift (18.1-21.1 kg·yr-1) compared with bench press (10.5-12.8 kg·yr-1, P ≤ 0.001). However, the change in absolute (all lifts: P = 0.247-0.379) and relative strength (all lifts: P = 0.641-0.821) did not differ between sexes. For females, maximum strength gain per day did not differ by quartile (all lifts: P = 0.091-0.746), nor did overall strength gain per day (P = 0.151-0.575). Conversely, males in the fourth quartile generally displayed lower maximum and overall strength gain per day. CONCLUSIONS: These findings show differences in strength gain between upper- and lower-body lifts, but not sex differences in the change in strength. In line with previous research, the strongest males likely gain strength more slowly than weaker counterparts. Professionals should consider this information in the training, assessment, and long-term benchmarking of athletes whose sports require a focus on muscular strength.

Impact of antibiotic use on patient-level risk of death in 36 million hospital admissions in England.

OBJECTIVES: Initiatives to curb hospital antibiotic use might be associated with harm from under-treatment. We examined the extent to which variation in hospital antibiotic prescribing is associated with mortality risk in acute/general medicine inpatients. METHODS: This ecological analysis examined Hospital Episode Statistics from 36,124,372 acute/general medicine admissions (≥16y) to 135 acute hospitals in England, 01/April/2010-31/March/2017. Random-effects meta-regression was used to investigate whether heterogeneity in adjusted 30-day mortality was associated with hospital-level antibiotic use, measured in defined-daily-doses (DDD)/1,000 bed-days. Models also considered DDDs/1,000 admissions and DDDs for narrow-spectrum/broad-spectrum antibiotics, parenteral/oral, and local interpretations of World Health Organization Access, Watch, and Reserve antibiotics. RESULTS: Hospital-level antibiotic DDDs/1,000 bed-days varied 15-fold with comparable variation in broad-spectrum, parenteral, and Reserve antibiotic use. After extensive adjusting for hospital case-mix, the probability of 30-day mortality changed -0.010% (95% CI: -0.064,+0.044) for each increase of 500 hospital-level antibiotic DDDs/1,000 bed-days. Analyses of other metrics of antibiotic use showed no consistent association with mortality risk. CONCLUSIONS: We found no evidence that wide variation in hospital antibiotic use is associated with adjusted mortality risk in acute/general medicine inpatients. Using low-prescribing hospitals as benchmarks could help drive safe and substantial reductions in antibiotic consumption of up-to one-third in this population.

Effect of 10 sets versus 5 sets of resistance training on muscular endurance.

BACKGROUND: A paucity of research exists examining whether resistance training with a greater number of sets per exercise enhances the development of muscular endurance. The aim of this study was to investigate the effects of ten sets versus five sets of resistance training on muscle endurance. METHODS: Fifteen healthy males (age 23.7±4.6 y) with at least 1 year resistance training experience were randomly assigned to 6 weeks of 10 sets (10-SET) or 5 sets (5-SET) of 10 repetitions at 60-80% one-repetition maximum (1RM) for specific compound resistance exercises with rest intervals between sets of 60-90 s and 60 s between exercises, performed 3 times per week. Relative muscle endurance was assessed via maximal repetitions using 70% 1RM for the bench press, lat pulldown and leg press. RESULTS: There was a significant increase in the number of repetitions to failure in the muscle endurance test for the leg press in 10-SET (40.9%, P=0.04) and 5-SET (27.9%; P=0.03), although no statistical differences between groups in the post-intervention results. Both groups increased volume-load in the muscle endurance test for the bench press (≥14.3%, P<0.05) and leg press (≥36.7%, P<0.05), but there were no statistical differences between groups in the post-intervention results. CONCLUSIONS: Findings suggest that performing 10 sets compared to 5 sets of resistance training does not enhance the development of relative muscle endurance. The volume-load accrued within an individual set rather than across sets may be of greater importance when targeting muscular endurance.

Ten-year longitudinal molecular epidemiology study of Escherichia coli and Klebsiella species bloodstream infections in Oxfordshire, UK.

BACKGROUND: The incidence of Gram-negative bloodstream infections (BSIs), predominantly caused by Escherichia coli and Klebsiella species, continues to increase; however, the causes of this are unclear and effective interventions are therefore hard to design. METHODS: In this study, we sequenced 3468 unselected isolates over a decade in Oxfordshire (UK) and linked this data to routinely collected electronic healthcare records and mandatory surveillance reports. We annotated genomes for clinically relevant genes, contrasting the distribution of these within and between species, and compared incidence trends over time using stacked negative binomial regression. RESULTS: We demonstrate that the observed increases in E. coli incidence were not driven by the success of one or more sequence types (STs); instead, four STs continue to dominate a stable population structure, with no evidence of adaptation to hospital/community settings. Conversely in Klebsiella spp., most infections are caused by sporadic STs with the exception of a local drug-resistant outbreak strain (ST490). Virulence elements are highly structured by ST in E. coli but not Klebsiella spp. where they occur in a diverse spectrum of STs and equally across healthcare and community settings. Most clinically hypervirulent (i.e. community-onset) Klebsiella BSIs have no known acquired virulence loci. Finally, we demonstrate a diverse but largely genus-restricted mobilome with close associations between antimicrobial resistance (AMR) genes and insertion sequences but not typically specific plasmid replicon types, consistent with the dissemination of AMR genes being highly contingent on smaller mobile genetic elements (MGEs). CONCLUSIONS: Our large genomic study highlights distinct differences in the molecular epidemiology of E. coli and Klebsiella BSIs and suggests that no single specific pathogen genetic factors (e.g. AMR/virulence genes/sequence type) are likely contributing to the increasing incidence of BSI overall, that association with AMR genes in E. coli is a contributor to the increasing number of E. coli BSIs, and that more attention should be given to AMR gene associations with non-plasmid MGEs to try and understand horizontal gene transfer networks.

Investigation and management of papillary thyroid microcarcinoma - a Scottish regional case series and literature review.

BACKGROUND AND AIMS: Papillary thyroid microcarcinoma is defined as papillary thyroid cancer with a diameter of ≤1 cm. Despite its prevalence, there is wide variation in practice in the investigation and management of patients with papillary thyroid microcarcinoma throughout the UK and internationally. The primary aim of this paper is to describe the experience of investigation and management in a Scottish health board over the past 10 years. METHODS AND RESULTS: Retrospective analysis of thyroidectomy and hemithyroidectomy resection samples from March 2009 to March 2020. 532 specimens were reviewed and 20 patients with PTMC were identified. 12 patients had an incidental finding of PTMC. Median U score- 3, Median Thy score- 2.5 for dominant or radiologically suspicious nodules. 8 specimens demonstrated aggressive histopathological features. 1 patient with positive nodal disease in the neck and 0 patients with positive nodal disease in the thorax on CT Neck and Chest. CONCLUSION: Here we report the first UK Cohort describing the radiological investigation and management of papillary thyroid microcarcinoma. The results of our study are in accordance with a recent meta-analysis which found 4% nodal disease and 0.025% distant metastasis at time of presentation in patients with PTMC.

Appendiceal adenocarcinoma with breast metastases.

Malignant lesions of the vermiform appendix make up a rare subset of colorectal cancer. While colorectal cancer frequently metastasises to the liver, lung, regional lymph nodes and peritoneum, metastasis to the breast is extremely rare. Here, we describe the case of an 84-year-old woman who had the incidental finding of appendiceal adenocarcinoma following emergency laparoscopic appendectomy. She declined further operative or adjuvant treatment for her disease. She represented 1 year later with metastatic appendiceal adenocarcinoma disease to her left breast. A simple mastectomy for symptomatic treatment was performed. In this report, we describe the first case of appendiceal adenocarcinoma metastases to the breast. Due to its rarity, there is a paucity of evidence related to the management of this condition. The limited evidence is reviewed and discussed.

Effect of Set-Structure on Upper-Body Muscular Hypertrophy and Performance in Recreationally-Trained Male and Female.

ABSTRACT: Davies, TB, Halaki, M, Orr, R, Mitchell, L, Helms, ER, Clarke, J, and Hackett, DA. Effect of set structure on upper-body muscular hypertrophy and performance in recreationally trained men and women. J Strength Cond Res XX(X): 000-000, 2021-This study explored the effect of volume-equated traditional-set and cluster-set structures on muscular hypertrophy and performance after high-load resistance training manipulating the bench press exercise. Twenty-one recreationally trained subjects (12 men and 9 women) performed a 3-week familiarization phase and were then randomized into one of two 8-week upper-body and lower-body split programs occurring over 3 and then progressing to 4 sessions per week. Subjects performed 4 sets of 5 repetitions at 85% one repetition maximum (1RM) using a traditional-set structure (TRAD, n = 10), which involved 5 minutes of interset rest only, or a cluster-set structure, which included 30-second inter-repetition rest and 3 minutes of interset rest (CLUS, n = 11). A 1RM bench press, repetitions to failure at 70% 1RM, regional muscle thickness, and dual-energy x-ray absorptiometry were used to estimate changes in muscular strength, local muscular endurance, regional muscular hypertrophy, and body composition, respectively. Velocity loss was assessed using a linear position transducer at the intervention midpoint. TRAD demonstrated a significantly greater velocity loss magnitude (g = 1.50) and muscle thickness of the proximal pectoralis major (g = -0.34) compared with CLUS. There were no significant differences between groups for the remaining outcomes, although a small effect size favoring TRAD was observed for the middle region of the pectoralis major (g = -0.25). It seems that the greater velocity losses during sets observed in traditional-set compared with cluster-set structures may promote superior muscular hypertrophy within specific regions of the pectoralis major in recreationally trained subjects.

"Just not knowing" can make life sweeter (and saltier): Reward uncertainty alters the sensory experience and consumption of palatable food and drinks.

Reward uncertainty can prompt exploration and learning, strengthening approach and consummatory behaviors. For humans, these phenomena are exploited in marketing promotions and gambling products, sometimes spurring hedonic consumption. Here, in four experiments, we sought to identify whether reward uncertainty-as a state of "not knowing" that exists between an action and a positively valanced outcome-enhances the in-the-moment consumption and experience of other palatable food and drink rewards. In Experiment 1, we demonstrate that reward uncertainty can increase consumption of commercial alcoholic drinks and energy-dense savory snacks. In Experiment 2, we show that reward uncertainty is unlikely to promote consumption through gross increases in impulsivity (expressed as higher discounting rates) or risk tolerance (expressed as lower probability discounting rates). In Experiment 3, we find that reward uncertainty intensifies the taste of, and hedonic responses to, sucrose solutions in a concentration-dependent manner among individuals with heightened preferences for sweet tastes. Finally, in Experiment 4, we replicate and extend these findings by showing that reward uncertainty intensifies the taste of palatable foods and drinks in ways that are independent of individuals' discounting rates, motor control, reflection impulsivity, and momentary happiness but are strongly moderated by recent depressive symptoms. These data suggest a working hypothesis that (incidental) reward uncertainty, as a state of not knowing, operates as a mood-dependent "taste intensifier" of palatable food and drink rewards, possibly sustaining reward seeking and consumption. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The impact of frailty on epistaxis admission, a retrospective cohort study.

OBJECTIVES: Epistaxis is frequently managed with intra-nasal packing devices, traditionally requiring patient admission. Current COVID-19 guidelines encourage ambulatory care where possible in this patient cohort. This paper aims to establish the impact of the Clinical Frailty Scale, anticoagulant/antiplatelet therapeutics and season variation on pre-pandemic admissions to help identify patients suitable for ambulatory epistaxis management. DESIGN: Retrospective cohort study SETTING: Scottish Regional Health Board PARTICIPANTS: Adult patients attending secondary care with epistaxis between March 2019 and March 2020. MAIN OUTCOME MEASURES: Likelihood of epistaxis hospital admission based on Clinical Frailty Scale. RESULTS: 299 epistaxis presentations were identified, of which 122 (40.8%) required admission. Clinical Frailty Scale of ≥4 had an increased likelihood of admission (OR 3.15 (95% CI:1.94-5.16), P < .05). In the majority of presentations (66.2%), patients were taking either an antiplatelet or anticoagulant. Of these presentations, the use of an anticoagulant (OR: 2.00 (95% CI: 1.20-3.33), P < .05 and dual antiplatelet (OR: 2.82 (95% CI: 1.02-7.86), P < .05) demonstrated increased likelihood of admission. CONCLUSIONS: We have shown that frailty increases the risk of admission in adult patients presenting with epistaxis. Clinical Frailty Scale (CFS) could be utilised in risk stratification to identify suitable patients for outpatient management. Patients with CFS ≤ 3 could be considered for outpatient management of their epistaxis. It is likely that patients with CFS ≥4 on anticoagulant or dual antiplatelet will require admission.