Swimming training repercussion on metabolic and structural bone development; benefits of the incorporation of whole body vibration or pilometric training; the RENACIMIENTO project

Introduction: Enviromental factors such as exercise participation and nutrition have often been linked to bone improvements. However, not all sports have the same effects, being non-osteogenic sports such as swimming defined as negative or neutral sports to practice regarding bone mass by some authors, similarly exercise-diet interaction in especific groups is still not clear. Objective: To present the methodology of the RENACIMENTO project that aims to evaluate body composition and more specifically bone mass by several techniques in adolescent swimmers and to observe the effects and perdurability of whole body vibration (WBV) and jumping intervention (JIN) on body composition and fitness on this population and explore posible diet interactions. Design: Randomized controlled trial. Methods: 78 swimmers (12-17 y) and 26 sex- and age-matched controls will participate in this study. Dual energy X-ray, peripheral Quantitative Computed Tomography, Quantitative Ultrasound, Bioelectrical Impedance Analysis, and anthropometry measurements will be performed in order to evaluate body composition. Physical activity, nutrition, pubertal development and socio-economical status may act as confounders of body composition and therefore will also be registered. Several fitness factors regarding strength, endurance, performance and others will also be registered to evaluate differences with controls and act as confounders. A 7-month WBV therapy will be performed by 26 swimmers consisting of a training of 15 minutes 3 times per week. An 8 month JIM will also be performed by 26 swimmers 3 times per week. The remaining 26 swimmers will continue their normal swimming training. Four evaluations will be performed, the first one in order to describe differences between swimmers and controls. The second one to describe the effects of the interventions and the third and fourth evaluations to describe the perdurability of the effects of the WBV and JIN. Conclusion: The RENACIMIENTO project will allow to answer several questions regarding body composition, fitness, bone mass and interaction with diet of adolescent swimmers, describe swimming as a positive, negative or neutral sport to practice regarding these parameters and elucidate the effects and perdurability of WBV and JIM on body composition

Validity and reliability of an optoelectronic system to measure movement velocity during bench press and half squat in a Smith machine

The purpose of this study was to determine the validity and reliability of a camera-based optoelectronic system to measure movement velocity during bench press and half squat at different load intensities. A total of 22 active males (age: 28.2 +/- 3.9 years; one-repetition maximum bench press: 77.9 +/- 19.0 kg; one-repetition maximum half squat: 116.6 +/- 22.5 kg) participated in this study. After an initial one-repetition maximum testing session, participants performed five repetitions for each load (40%, 60% and 80% one-repetition maximum) and exercise (bench press and half squat) on a Smith machine in the second testing session. A third testing session was used for the test-retest reliability study. Time, displacement and mean propulsive velocity were simultaneously determined by the reference method (T-Force system) and the Velowin system. In bench press, ordinary least products regression analysis revealed low fixed biases for mean propulsive velocity at 40%, time at 60% and displacement at 80% one-repetition maximum (intercept = 0.065 m s(-1), -28.02 ms and 0.87 cm, respectively). In half squat, low fixed biases were also detected for mean propulsive velocity at 40% and 80% one-repetition maximum (intercept = -0.040 and 0.023 m s(-1), respectively), time at 40% and 60% one-repetition maximum (intercept = -53.05 and -101.85 ms, respectively) and displacement at 60% one-repetition maximum (intercept = -1.95 cm). Proportional bias was only observed for mean propulsive velocity at 80% bench press. In half squat, there was proportional bias for time and mean propulsive velocity at 40% one-repetition maximum, and also for time at 60% one-repetition maximum. The reliability test showed low and comparable fixed and proportional biases between systems across exercises and intensities. Velowin confirmed to be a valid and reliable system to measure movement velocity across a wide range of intensities (40%-80% one-repetition maximum) for two basic strength exercises through a robust statistical approach. Velowin would provide coaches and trainers with a suitable, affordable and easy-to-use equipment capable of measuring movement velocity in various exercises at different load intensities

New Evidence on Regucalcin, Body Composition, and Walking Ability Adaptations to Multicomponent Exercise Training in Functionally Limited and Frail Older Adults

Background: Regucalcin, or senescence marker protein-30 (SMP30), is a Ca2+-binding protein with multiple functions reported in the literature. Physical exercise has been shown to improve aging markers; nevertheless, SMP30 in humans has not been extensively researched. Older adults experience a decline in functional capacity and body composition. The purpose of this study was to examine the effects of a multicomponent training (MCT) program on SMP30 and its regulation of walking ability and body composition in functionally limited, frail, and pre-frail older adults. Methods: A total of 34 older adults (aged 80.3 +/- 6.1 years) were divided into an intervention group (IG = 20) and control group (CG = 14). The IG performed a supervised MCT (strength, endurance, balance, coordination, and flexibility) program for 6 months, 3 days per week, whereas the CG continued their normal lives without any specific physical training. SMP30 was analyzed in plasma after 3 and 6 months of MCT, while some physical fitness variables (Timed Up and Go (TUG) and 6-min walk test (6MWT)) and body composition (fat mass and lean mass) were measured at baseline, as well as after 3 months and 6 months of MCT. Results: No significant changes were observed in SPM30 between the IG (877.5 a.u. to 940.5 a.u., respectively) and CG (790.4 a.u. to 763.8 a.u., respectively). Moreover, no SMP30 differences were found between groups after 3 and 6 months of MCT. The IG improved significantly in the 6MWT after 3 months (472.2 +/- 84.2 m) compared to baseline (411.2 +/- 75.2 m). The IG also significantly enhanced their TUG performance after 3 months (7.6 +/- 1.6 s) and 6 months (7.3 +/- 1.8 s) of training compared to baseline (9.3 +/- 3.2 s) (all, p < 0.001). There were no significant differences in body composition between the IG and CG through the 6 months of MCT. Conclusions: The present study suggests that MCT did not change SMP30 levels from 3 to 6 months, where there were changes in neither walking ability nor body composition; however, MCT was effective in improving 6MWT and TUG performance from baseline to 3 months

Effect of an active video game intervention combined with multicomponent exercise for cardiorespiratory fitness in children with overweight and obesity: randomized controlled trial

Background: Childhood overweight and obesity have become major global health problems and are negatively related with the cardiorespiratory fitness (CRF) level in school children and adolescents. Exercise, specifically multicomponent training, is effective for CRF improvement, but the main challenge is to ensure adherence to exercise in children with overweight and obesity. Therefore, new ways of exercising that are more attractive and motivational for this population are needed and playing or training with active video games (AVGs) has been proposed as an effective alternative because they require full-body movement and therefore increase energy expenditure. Objective: The main aim of this study was to investigate the effects of an AVG intervention combined with multicomponent training on CRF at maximal and submaximal intensities in children with overweight or obesity. Methods: We recruited 28 children (13 girls and 15 boys) aged 9 to 11 years with overweight or obesity from medical centers and divided them into 2 groups, an intervention group (n=20) that participated in a 5-month supervised AVG exercise program combined with multicomponent exercise, and a control group (n=8) that continued daily activities without modification. A maximal stress test to measure CRF using a walking-graded protocol with respiratory gas exchange was performed by the participants. Results: The AVG group showed a significant decrease in heart rate and oxygen uptake for the same intensities in the submaximal stages of the maximal treadmill test, as well as a lower oxygen uptake percentage according to the individual maximal oxygen uptake, whereas the control group did not show overall changes. No change in the peak oxygen uptake (VO2peak) was found. Conclusions: A 5-month AVG intervention combined with multicomponent exercise had positive effects on CRF at submaximal intensity, showing a lower heart rate and oxygen uptake at the same intensities and displaying a lower oxygen uptake percentage according to the individual (VO2peak). Greater benefits were found in children with the highest fat percentage.Trial Registration: ClinicalTrials.gov NCT04418713; https://clinicaltrials.gov/show/NCT0441871

Zero by 2030 and OneHealth: The multidisciplinary challenges of rabies control and elimination

"Rabies, caused by a negative strand RNA-virus belonging to the genus Lyssavirus (family Rhabdoviridae of the order Mononegavirales), remains of global concern [1]. This vaccine-preventable viral zoonotic disease is present in more than 150 countries and territories [2]. Ac- cording to the World Health Organization (WHO), rabies is estimated to cause ~59,000 human deaths annually, with 95% of cases occurring in Africa and Asia [3,4]. However, rabies still occurs in other regions, such as Latin America and the Caribbean [5–8], Central Asia and the Middle East [9,10]. Whilst a number of animals can host the rabies virus, dogs are the main source of human rabies deaths, contributing up to 99% of all rabies transmissions to humans. Dog-mediated rabies has been eliminated from Western Europe, Canada, the United States of America (USA), Japan and some Latin American countries [11]. Nevertheless, the risk of reintroduction and disease among travellers to risk areas is a matter of concern [12–15]. As occurred with many other communicable and non-communicable diseases, the 2020–2022 COVID-19 pandemic negatively impacted the efforts of control and reemergence of rabies in certain countries [7,16,17]. Post-pandemic challenges to enhance con- trol and prevention are multiple and need urgent actions to achieve the goal in eight years by 2030 [16].

PREDICT identifies precipitating events associated with the clinical course of acutely decompensated cirrhosis

Background & Aims: Acute decompensation (AD) of cirrhosis may present without acute-on-chronic liver failure (ACLF) (ADNo ACLF), or with ACLF (AD-ACLF), defined by organ failure(s). Herein, we aimed to analyze and characterize the precipitants leading to both of these AD phenotypes. Methods: The multicenter, prospective, observational PREDICT study (NCT03056612) included 1,273 non-electively hospitalized patients with AD (No ACLF = 1,071; ACLF = 202). Medical history, clinical data and laboratory data were collected at enrolment and during 90-day follow-up, with particular attention given to the following characteristics of precipitants: induction of organ dysfunction or failure, systemic inflammation, chronology, intensity, and relationship to outcome. Results: Among various clinical events, 4 distinct events were precipitants consistently related to AD: proven bacterial infections, severe alcoholic hepatitis, gastrointestinal bleeding with shock and toxic encephalopathy. Among patients with precipitants in the AD-No ACLF cohort and the AD-ACLF cohort (38% and 71%, respectively), almost all (96% and 97%, respectively) showed proven bacterial infection and severe alcoholic hepatitis, either alone or in combination with other events. Survival was similar in patients with proven bacterial infections or severe alcoholic hepatitis in both AD phenotypes. The number of precipitants was associated with significantly increased 90day mortality and was paralleled by increasing levels of surrogates for systemic inflammation. Importantly, adequate first-line antibiotic treatment of proven bacterial infections was associated with a lower ACLF development rate and lower 90-day mortality. Conclusions: This study identified precipitants that are significantly associated with a distinct clinical course and prognosis in patients with AD. Specific preventive and therapeutic strategies targeting these events may improve outcomes in patients with decompensated cirrhosis. Lay summary: Acute decompensation (AD) of cirrhosis is characterized by a rapid deterioration in patient health. Herein, we aimed to analyze the precipitating events that cause AD in patients with cirrhosis. Proven bacterial infections and severe alcoholic hepatitis, either alone or in combination, accounted for almost all (96-97%) cases of AD and acute-on-chronic liver failure. Whilst the type of precipitant was not associated with mortality, the number of precipitant(s) was. This study identified precipitants that are significantly associated with a distinct clinical course and prognosis of patients with AD. Specific preventive and therapeutic strategies targeting these events may improve patient outcomes. (c) 2020 European Association for the Study of the Liver. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

The PREDICT study uncovers three clinical courses of acutely decompensated cirrhosis that have distinct pathophysiology

Acute decompensation (AD) of cirrhosis is defined as the acute development of ascites, gastrointestinal hemorrhage, hepatic encephalopathy, infection or any combination thereof, requiring hospitalization. The presence of organ failure(s) in patients with AD defines acute-on-chronic liver failure (ACLF). The PREDICT study is a European, prospective, observational study, designed to characterize the clinical course of AD and to identify predictors of ACLF. A total of 1,071 patients with AD were enrolled. We collected detailed pre-specified information on the 3-month period prior to enrollment, and clinical and laboratory data at enrollment. Patients were then closely followed up for 3 months. Outcomes (liver transplantation and death) at 1 year were also recorded. Three groups of patients were identified. Pre-ACLF patients (n = 218) developed ACLF and had 3-month and 1-year mortality rates of 53.7% and 67.4%, respectively. Unstable decompensated cirrhosis (UDC) patients (n = 233) required ≥1 readmission but did not develop ACLF and had mortality rates of 21.0% and 35.6%, respectively. Stable decompensated cirrhosis (SDC) patients (n = 620) were not readmitted, did not develop ACLF and had a 1-year mortality rate of only 9.5%. The 3 groups differed significantly regarding the grade and course of systemic inflammation (high-grade at enrollment with aggravation during follow-up in pre-ACLF; low-grade at enrollment with subsequent steady-course in UDC; and low-grade at enrollment with subsequent improvement in SDC) and the prevalence of surrogates of severe portal hypertension throughout the study (high in UDC vs. low in pre-ACLF and SDC). Acute decompensation without ACLF is a heterogeneous condition with 3 different clinical courses and 2 major pathophysiological mechanisms: systemic inflammation and portal hypertension. Predicting the development of ACLF remains a major future challenge. ClinicalTrials.gov number: NCT03056612. Lay summary: Herein, we describe, for the first time, 3 different clinical courses of acute decompensation (AD) of cirrhosis after hospital admission. The first clinical course includes patients who develop acute-on-chronic liver failure (ACLF) and have a high short-term risk of death - termed pre-ACLF. The second clinical course (unstable decompensated cirrhosis) includes patients requiring frequent hospitalizations unrelated to ACLF and is associated with a lower mortality risk than pre-ACLF. Finally, the third clinical course (stable decompensated cirrhosis), includes two-thirds of all patients admitted to hospital with AD - patients in this group rarely require hospital admission and have a much lower 1-year mortality risk

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts