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Otávio T Nóbrega,1 Alessandra M Campos-Staffico,2 Elayne Kelen Oliveira,3 Daniel B Munhoz,3 Filipe A Moura,3 Luis Sérgio F Carvalho,4 Alexandre Anderson SM Soares,1,5 Ciro M Gomes,1,6 Audrey C Tonet-Furioso,7 Andrei C Sposito1,3 On behalf of Brasilia Heart Study and the Brasilia Heart Study Group1Programa de Pós-Graduação em Ciências Médicas, Faculdade de Medicina, Universidade de Brasília (UnB), Brasília, DF, Brazil; 2Departamento de Farmácia, Faculdade de Ciências da Saúde, Universidade de Brasília (UnB), Brasília, DF, Brazil; 3Departamento de Cardiologia, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (Unicamp), Campinas, SP, Brazil; 4Centro de Inovação, Ensino e Pesquisa, Instituto de Gestão Estratégica em Saúde do Distrito Federal, Brasília, DF, Brazil; 5Serviço de Cardiologia, Instituto Biocárdios, Brasília, DF, Brazil; 6Laboratório de Dermatomicologia, Faculdade de Medicina, Universidade de Brasília (UnB), Brasília, DF, Brazil; 7Programa de Pós-Graduação em Gerontologia, Universidade Católica de Brasília (UCB-DF), Taguatinga, DF, BrazilCorrespondence: Andrei C SpositoLaboratório de Biologia Vascular e Aterosclerose (AteroLab), Departamento de Cardiologia, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (Unicamp), 126 Rua Tessália Vieira de Camargo, Campinas, 13083-887, SP, BrazilTel +55 19 3521 9590Fax +55 19 3289 4107Email andreisposito@gmail.comBackground: Glycemic disorders are strong predictors of mortality in ST-elevation myocardial infarction (STEMI) patients, and disruption in nitric oxide (NO) production is associated with insulin-resistant states. We evaluated whether a defective allele of the neuronal nitric oxide synthase (nNOS) gene (NOS1) might influence insulin response and blood-glucose balance during the acute phase of STEMI and if post-infarction total plasma-NO levels and vasodilation scores varied across nNOS genotypes.Methods: Consecutive patients with STEMI (n=354) underwent clinical evaluations and genotyping for the promoter variation rs41279104. In-hospital clinical and blood evaluations were performed at admission and five days after STEMI, with glycemic, insulinemic, and disposition indices assessed at the same times. Flow-mediated dilation (FMD) was assessed by reactive hyperemia on the 30th day.Results: Homozygotes for the defective allele (A) showed lower glycemia and insulin sensitivity on day 1 while showing the highest β-cell function and no changes in the circulating NO pool, which is compatible with hyperresponsive β cells counteracting the inherent glucose-resistant state of AA patients. At day 5, glycemic scores had shifted to indicate greater insulin sensitivity among A homozygotes, paralleled by a significant yet poor increase in NO bioavailability compared to that among G carriers. All in all, defective homozygotes showed greater insulin resistance at admission that had reversed by 5 days after STEMI. Even so, A carriers developed lower FMD scores compared to G homozygotes after the acute phase.Conclusion: A defective nNOS allele (and due decline in NO production) seemed to elicit a hyperinsulinemia response to compensate for an insulin-resistant state during the acute phase of STEMI and to be associated with poor endothelial function after the acute phase.Keywords: nitric oxide, insulin, blood glucose, vasodilation, polymorphism, myocardial infarction

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is linked to high mortality, primarily through an intense inflammatory response. Diacerein has emerged as a potential therapy for COVID-19 due to its potential impact in decreasing the inflammasome activation and coronavirus replication. This study aims to explore diacerein's influence in inhibiting both viral replication and the inflammatory response after SARS-CoV-2 infection., Methods: Human peripheral blood mononuclear cells (PBMCs) were obtained from healthy volunteers and infected in vitro with SARS-CoV-2. Additionally, we carried out a pilot randomized, double-blind, placebo-controlled study with 14 participants allocated to diacerein (n = 7) or placebo (n = 7) therapies every 12 h for 10 days. The primary endpoint was change in plasma markers of inflammasome activation (NLRP3, caspase-1, and gasdermin-D)., Results: In vitro protocols have shown that rhein, diacerein's primary metabolite, decreased IL-1β secretion caused by SARS-CoV-2 infection in human PBMCs ( p < 0.05), and suppressed viral replication when administered either before or after the virus incubation ( p < 0.05). This later effect was, at least partially, attributed to its inhibitory effect on 3-chymotrypsin-like protease (SARS-CoV-2 3CL pro ) and papain-like protease in the SARS-CoV-2 (SARS-CoV-2 PL pro ) virus and in the phosphorylation of proteins related cytoskeleton network ( p < 0.05). Diacerein-treated COVID-19 patients presented a smaller area under the curve for NLRP3, caspase-1 and GSDM-D measured on days 2, 5, and 10 after hospitalization compared to those receiving a placebo ( p < 0.05)., Conclusion: The indicated mechanisms of action of diacerein/rhein can reduce viral replication and mitigate the inflammatory response related to SARS-CoV-2. These findings are preliminary and require confirmation in clinical trials., Competing Interests: DB discloses the following relationships - Advisory Board: Angiowave, Bayer, Boehringer Ingelheim, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Stasys; Board of Directors: American Heart Association New York City, Angiowave (stock options), Bristol Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock); Consultant: Broadview Ventures, GlaxoSmithKline, Hims, SFJ, Youngene; Data Monitoring Committees: Acesion Pharma, Assistance Publique-Hô pitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic, Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical; for ALLAY-HF, funded by Alleviant Medical), Novartis, Population Health Research Institute; Rutgers University (for the NIH-funded MINT Trial); Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol-Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), CSL Behring (AHA lecture), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and United States national co-leader, funded by Bayer), WebMD (CME steering committees), (steering committee); Other: Clinical Cardiology (Deputy Editor); Patent: Sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women' s Hospital who assigned to Lexicon; neither I nor Brigham and Women' s Hospital receive any income from this patent); Research Funding: Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, 89Bio; Royalties: Elsevier (Editor, Braunwald’s Heart Disease); Site Co-Investigator: Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, Vascular Solutions; Trustee: American College of Cardiology; Unfunded Research: FlowCo. AS discloses the following relationships - Research Funding: Amgen, AstraZeneca, National Council for Scientific and Technological Development (CNPq) and Fundaç and#227; o de Apoio and#224; Pesquisa do Estado de Sã o Paulo (FAPESP). Dr. Pedro Gonç alves de Oliveira is responsible for R&D activities at TRB Pharma Indú stria Quí mica e Farmace utica Ltda, SP, Brazil. TRB Pharma is the owner of the product ARTRODAR® a diacerein-based product for osteoarthritis treatment. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Carmo, Castillo, Bonilha, Gomes, Barreto, Moura, Davanzo, de Brito Monteiro, Muraro, Fabiano de Souza, Morari, Galdino, Brunetti, Reis-de-Oliveira, Carregari, Nadruz, Martins-de-Souza, Farias, Velloso, Proenca-Modena, Mori, Loh, Bhatt, Yellon, Davidson, De Oliveira, Moraes-Vieira and Sposito.)

Aims: To develop a clinical risk model to identify individuals at higher risk of developing new-onset diabetes and who might benefit more from weight loss pharmacotherapy., Materials and Methods: A total of 21 143 patients without type 2 diabetes at baseline from two TIMI clinical trials of stable cardiovascular patients were divided into a derivation (~2/3) and validation (~1/3) cohort. The primary outcome was new-onset diabetes. Twenty-seven candidate risk variables were considered, and variable selection was performed using multivariable Cox regression. The final model was evaluated for discrimination and calibration, and for its ability to identify patients who experienced a larger benefit from the weight loss medication lorcaserin in terms of risk of new-onset diabetes., Results: During a median (interquartile range) follow-up of 2.3 (1.8-2.7) years, new-onset diabetes occurred in 1013 patients (7.7%). The final model included five independent predictors (glycated haemoglobin, fasting glucose, age, body mass index, and triglycerides/high-density lipoprotein). The clinical risk model showed good discrimination (Harrell's C-indices 0.802, 95% confidence interval [CI] 0.788-0.817 and 0.807, 95% CI 0.788-0.826) in the derivation and validation cohorts. The calibration plot demonstrated adequate calibration (2.5-year area under the curve was 81.2 [79.1-83.5]). While hazard ratios for new-onset diabetes with a weight-loss therapy were comparable across risk groups (annual risks of <1%, 1%-5%, and >5%), there was a sixfold gradient in absolute risk reduction from lowest to highest risk group (p = 0.027)., Conclusions: The developed clinical risk model effectively predicts new-onset diabetes, with potential implications for personalized patient care and therapeutic decision making., (© 2024 John Wiley & Sons Ltd.)

The incorporation of triaxial accelerometers into Global Positioning Systems (GPS) has significantly advanced our understanding of accelerations in sports. However, inter-positional differences are unknown. This study aimed to explore the variability of acceleration and deceleration (Acc) distribution curves according to players' positions during soccer matches. Thirty-seven male players from a national-level Portuguese club were monitored using 10 Hz GPS with an embedded accelerometer during the 2021/2022 season. Resultant Acc was obtained from the x (lateral), y (frontal/back), and z (vertical) axes and expressed in gravitational units (g). Statistical Parametric Mapping was employed to compare playing positions: central defenders (CD), fullbacks (FB), central midfielders (CM), wide midfielders (WM), and strikers (ST). All positions exhibited a decreasing Acc distribution curve, very similar in shape, with a high frequency of events in the lower ranges (i.e., 0 to 1 g) and a lower frequency of events in the higher values (2 to 10 g). Post hoc comparisons revealed significant differences between all positions, except between FB and WM. Out of 1000 points in the curve, CD had 540, 535, 414, and 264 different points compared to FB, CM, WM, and ST, respectively. These findings indicate that players in different positions face distinct demands during matches, emphasizing the need for position-specific Acc analysis and training programming. By analyzing Acc as a continuous variable, this study highlights the importance of individualized monitoring to ensure the comprehensive and precise tracking of all player activities, without overlooking or omitting critical information.

Introduction: This study aimed to verify whether implicit and explicit informational constraints generate differences in tactical performance and behavior in U-20 national-level soccer players., Methods: Thirty-two under-20 male athletes from two clubs participated. Four 4-a-side small-sided games (SSG) protocols were used: R1 - explicit rule for high-press marking, R2 - implicit rule for high-press marking, R3 - game with both previous rules simultaneous and FR - free game, without additional rules. SSGs comprised 4 vs. 4+ goalkeepers games on a 42 m × 29 m field. Position data from 10 Hz Global Positioning System (GPS) devices were used to evaluate individual and collective tactical behavior (spatial occupation metrics) and performance (interpersonal coordination). MANOVA was used for normally distributed variables, and Friedman's with Dunn or Bonferroni post hoc was used for variables without normal distribution. For SEI, an ANOVA was used with Bonferroni post hoc ., Results: The R1 protocol showed higher SEI, length, width, and LpWratio than the FR protocol ( p  = 0.009). There was an effect of the different protocols in SEI values ( p  < 0.001). Under the explicit rule, players also showed the highest in-phase interpersonal coordination values ( p  < 0.001)., Discussion: Providing players with explicit tactical instructions improves tactical performance acutely for high-pressing defensive actions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Abreu, Aburachid, Lima, Moura, Bedo, Ribas and Praça.)

Football teams' tactical organization on the pitch is usually represented by the surface area. Considering the different shapes adopted by the teams during the match, the role of the tactical variability for success is lacking. The aim of this study was to explore and to evaluate the association between recurrent states of tactical organization and technical performance during football matches. A total of 28 teams of Brazilian First Division Championships were analysed. Teams' surface area shapes were represented by the maximum value of the Multiscale Fractal Dimension in each timestamp, producing a time series. Recurrences of states of tactical organization were determined via recurrence plots and recurrence quantitative analysis during attacking and defending phases, and considering the whole match. The outcomes were correlated with nine traditional technical performance indicators. The main results showed that structural recurrence or variability on tactical organization is associated with performance success during the defending and attacking actions. Recurrence plot and measures based on the recurrence density proved to be valuable tools to represent teams' dynamics., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Moura et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The development and course of inflammatory bowel disease (IBD) are significantly influenced by inflammation and oxidative stress. Antioxidant therapy is a promising therapeutic option to enhance the clinical results of these individuals in this particular scenario. The purpose of this study is to assess the impact of curcumin, with or without piperine, on cytokines, fecal calprotectin (CalF), and oxidative stress enzymatic and non-enzymatic indicators in patients with IBD., Methods: Patients with Crohn's disease (CD) or ulcerative colitis (UC) who were at least 18 years old and had intact liver and kidney function participated in this randomized, double-blind trial (trial registration: ensaiosclinicos.gov.br as RBR-89q4ydz). For 12 weeks, participants were randomly assigned to one of three groups: placebo, curcumin (1000 mg/day), or curcumin plus piperine (1000 mg + 10 mg/day). In order to examine oxidative stress indicators, CalF, and pro-inflammatory cytokines, blood and fecal samples were obtained, both prior to and following the intervention time., Results: After adjusting for age, sex, and type of IBD, the curcumin plus piperine group had substantially higher serum levels of superoxide dismutase (SOD) than the placebo group (4346.9 ± 879.0 vs. 3614.5 ± 731.5; p = 0.041). There were no discernible variations between the groups in CalF, inflammatory markers, or other indicators of oxidative stress., Conclusions: In patients with inflammatory bowel disease (IBD), our study indicates that a 12-week curcumin plus piperine treatment effectively increases enzymatic antioxidant defense, especially SOD. These results demonstrate the potential therapeutic benefits of managing redox imbalance in individuals with IBD.

The present study aimed to assess the use of technical-tactical variables and machine learning (ML) classifiers in the automatic classification of the passing difficulty (DP) level in soccer matches and to illustrate the use of the model with the best performance to distinguish the best passing players. We compared eight ML classifiers according to their accuracy performance in classifying passing events using 35 technical-tactical variables based on spatiotemporal data. The Support Vector Machine (SVM) algorithm achieved a balanced accuracy of 0.70 ± 0.04%, considering a multi-class classification. Next, we illustrate the use of the best-performing classifier in the assessment of players. In our study, 2,522 pass actions were classified by the SVM algorithm as low (53.9%), medium (23.6%), and high difficulty passes (22.5%). Furthermore, we used successful rates in low-DP, medium-DP, and high-DP as inputs for principal component analysis (PCA). The first principal component (PC1) showed a higher correlation with high-DP (0.80), followed by medium-DP (0.73), and low-DP accuracy (0.24). The PC1 scores were used to rank the best passing players. This information can be a very rich performance indication by ranking the best passing players and teams and can be applied in offensive sequences analysis and talent identification., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Merlin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Reducing the levels of triglycerides and triglyceride-rich lipoproteins remains an unmet clinical need. Olezarsen is an antisense oligonucleotide targeting messenger RNA for apolipoprotein C-III (APOC3), a genetically validated target for triglyceride lowering., Methods: In this phase 2b, randomized, controlled trial, we assigned adults either with moderate hypertriglyceridemia (triglyceride level, 150 to 499 mg per deciliter) and elevated cardiovascular risk or with severe hypertriglyceridemia (triglyceride level, ≥500 mg per deciliter) in a 1:1 ratio to either a 50-mg or 80-mg cohort. Patients were then assigned in a 3:1 ratio to receive monthly subcutaneous olezarsen or matching placebo within each cohort. The primary outcome was the percent change in the triglyceride level from baseline to 6 months, reported as the difference between each olezarsen group and placebo. Key secondary outcomes were changes in levels of APOC3, apolipoprotein B, non-high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol., Results: A total of 154 patients underwent randomization at 24 sites in North America. The median age of the patients was 62 years, and the median triglyceride level was 241.5 mg per deciliter. The 50-mg and 80-mg doses of olezarsen reduced triglyceride levels by 49.3 percentage points and 53.1 percentage points, respectively, as compared with placebo (P<0.001 for both comparisons). As compared with placebo, each dose of olezarsen also significantly reduced the levels of APOC3, apolipoprotein B, and non-HDL cholesterol, with no significant change in the LDL cholesterol level. The risks of adverse events and serious adverse events were similar in the three groups. Clinically meaningful hepatic, renal, or platelet abnormalities were uncommon, with similar risks in the three groups., Conclusions: In patients with predominantly moderate hypertriglyceridemia at elevated cardiovascular risk, olezarsen significantly reduced levels of triglycerides, apolipoprotein B, and non-HDL cholesterol, with no major safety concerns identified. (Funded by Ionis Pharmaceuticals; Bridge-TIMI 73a ClinicalTrials.gov number, NCT05355402.)., (Copyright © 2024 Massachusetts Medical Society.)

While chemotherapy treatment can be lifesaving, it also has adverse effects that negatively impact the quality of life. To investigate the effects of doxorubicin chemotherapy on body weight loss, strength and muscle mass loss, and physical function impairments, all key markers of cachexia, sarcopenia, and frailty. Seventeen C57/BL/6 mice were allocated into groups. 1) Control (n = 7): mice were exposed to intraperitoneal (i.p.) injections of saline solution. 2) Dox (n = 10): mice were exposed to doxorubicin chemotherapy cycles (total dose of 18 mg/kg divided over 15 days). The body weight loss and decreased food intake were monitored to assess cachexia. To assess sarcopenia, we measured muscle strength loss using a traction method and evaluated muscle atrophy through histology of the gastrocnemius muscle. To evaluate physical function impairments and assess frailty, we employed the open field test to measure exploratory capacity. Doxorubicin administration led to the development of cachexia, as evidenced by a significant body weight loss (13%) and a substantial decrease in food intake (34%) over a 15-day period. Furthermore, 90% of the mice treated with doxorubicin exhibited sarcopenia, characterized by a 20% reduction in traction strength (p<0,05), a 10% decrease in muscle mass, and a 33% reduction in locomotor activity. Importantly, all mice subjected to doxorubicin treatment were considered frail based on the evaluation of their overall condition and functional impairments. The proposed model holds significant characteristics of human chemotherapy treatment and can be useful to understand the intricate relationship between chemotherapy, cachexia, sarcopenia, and frailty., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Cella et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes 1,2 and molecular mechanisms that are often specific to cell type 3,4 . Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P < 5 × 10 -8 ) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores 5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care., (© 2024. The Author(s).)

Background: Body mass index (BMI) is a controversial marker of cardiovascular prognosis, especially in women. Coronary microvascular dysfunction (CMD) is prevalent in obese patients and a better discriminator of risk than BMI, but its association with body composition is unknown., Objectives: The authors used a deep learning model for body composition analysis to investigate the relationship between CMD, skeletal muscle (SM), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT), and their contribution to adverse outcomes in patients referred for evaluation of coronary artery disease., Methods: Consecutive patients (n = 400) with normal perfusion and preserved left ventricular ejection fraction on cardiac stress positron emission tomography were followed (median, 6.0 years) for major adverse events, including death and hospitalization for myocardial infarction or heart failure. Coronary flow reserve (CFR) was quantified as stress/rest myocardial blood flow from positron emission tomography. SM, SAT, and VAT cross-sectional areas were extracted from abdominal computed tomography at the third lumbar vertebra using a validated automated algorithm., Results: Median age was 63, 71% were female, 50% non-White, and 50% obese. Compared with the nonobese, patients with obesity (BMI: 30.0-68.4 kg/m 2 ) had higher SAT, VAT, and SM, and lower CFR (all P < 0.001). In adjusted analyses, decreased SM but not increased SAT or VAT was significantly associated with CMD (CFR <2; OR: 1.38; 95% CI: 1.08-1.75 per -10 cm 2 /m 2 SM index; P < 0.01). Both lower CFR and SM, but not higher SAT or VAT, were independently associated with adverse events (HR: 1.83; 95% CI: 1.25-2.68 per -1 U CFR and HR: 1.53; 95% CI: 1.20-1.96 per -10 cm 2 /m 2 SM index, respectively; P < 0.002 for both), especially heart failure hospitalization (HR: 2.36; 95% CI: 1.31-4.24 per -1 U CFR and HR: 1.87; 95% CI: 1.30-2.69 per -10 cm 2 /m 2 SM index; P < 0.004 for both). There was a significant interaction between CFR and SM (adjusted P = 0.026), such that patients with CMD and sarcopenia demonstrated the highest rate of adverse events, especially among young, female, and obese patients (all P < 0.005)., Conclusions: In a predominantly female cohort of patients without flow-limiting coronary artery disease, deficient muscularity, not excess adiposity, was independently associated with CMD and future adverse outcomes, especially heart failure. In patients with suspected ischemia and no obstructive coronary artery disease, characterization of lean body mass and coronary microvascular function may help to distinguish obese phenotypes at risk for cardiovascular events., Competing Interests: Funding Support and Author Disclosures This research was supported by a Lemann Cardiovascular Research Fellowship (Dr Souza); the National Institutes of Health (NIH) (U01CA320272, U01CA200468, and U10CA180821), the Lustgarten Foundation Dedicated Lab at Dana-Farber Cancer Institute, the Lustgarten Foundation and Stand Up To Cancer Pancreatic Cancer Collaborative, and the Hale Family Center for Pancreatic Cancer Research at Dana-Farber (Dr Rosenthal); a joint KL2/Catalyst Medical Research Investigator Training (CMeRIT) award from Harvard Catalyst and the Boston Claude D. Pepper Older Americans Independence Center (5P30AG031679-10) (Dr Divakaran); NIH K23HL151909 (Dr Osborne); and the Gilead Sciences Research Scholars Program in Cardiovascular Disease and NIH K23HL135438 (Dr Taqueti). Dr Blankenstein has received research support from Amgen Inc and Novartis Inc. Dr Osborne has received consulting fees from WCG Intrinsic Imaging for unrelated work. Dr Dorbala has received research grants from Pfizer, Attralus, and GE Healthcare; and consulting fees from Janssen, Pfizer, and GE Healthcare. Dr Di Carli has received research grants from Gilead Sciences and Spectrum Dynamics, and consulting fees from Bayer and Janssen. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Turning while walking is a complex component of locomotor capacity, which can be challenging in the daily lives of people with Parkinson's disease. The aim of the study was to compare biomechanical strategies during turning of gait in individuals with Parkinson's disease and its different clinical subtypes., Methods: A cross-sectional study, comprising of 43 individuals with idiopathic Parkinson's disease, divided in subgroups: akineto-rigid, dominant tremor and mixed. Motor impairment was assessed using the Unified Parkinson's Disease Rating Scale. The gait biomechanical parameters (number of steps, step length, cadence, amplitude, velocity and radius of the turn) were analyzed during turning in a kinematics laboratory. In the statistical analysis, a comparison was made between subgroups, and correlations between biomechanical parameters., Findings: There was no statistically significant difference between the subgroups. In the correlation analysis, notable correlations were found between the anticipatory step length and the following variables: number of steps (r = -0.418), step length while turning (r = 0.805), step length after turning (r = 0.644), average velocity (r = 0.830), average velocity while turning (r = 0.755), and maximum velocity (rho = 0.835)., Interpretation: The difficulties primarily occur during the anticipatory phase of the turn, which affects the entire task. The greater the length of the anticipatory step, the greater the length of the step taken to turn as well as the step taken after turning. And the greater the velocity, the greater the step length, and to fewer steps taken to perform the task., Competing Interests: Declaration of competing interest The authors declare that there are no potential conflicts of interest., (Copyright © 2023. Published by Elsevier Ltd.)

Knee osteoarthritis (OA) is a public health problem affecting millions of people worldwide. The intensity of the tibiofemoral contact forces is related to cartilage degeneration, and so is the importance of quantifying joint loads during daily activities. Although simulation with musculoskeletal models has been used to calculate joint loads, it demands high-cost equipment and a very time-consuming process. This study aimed to evaluate consolidated machine learning algorithms to predict tibiofemoral forces during gait analysis of healthy individuals and knee OA patients. Also, we evaluated three different datasets to train each model, considering different combinations of primary kinematic and kinetic data, and post-processing data. We evaluated 14 patients with severe unilateral knee OA and 14 healthy individuals during 3-5 gait trials. Data were split into 70% and 30% of the samples as training and test data. Test data was independently evaluated considering a mixture of pathological and healthy individuals, and only OA and Control patients. The main results showed that accurate predictions of the tibiofemoral contact forces were achieved using machine learning methods and that the predictions were sensitive to changes in the input data as training. The present study provided insights into the most promising regressions methods to predict knee contact forces representing an important starting point for the broader application of biomechanical analysis in clinical environments., (© 2024. The Author(s).)

Background: The aim of this study was to develop a low-cost and personalized method for external breast prosthesis production., Methods: The projected light method was used for the acquisition of the 3D geometry of the left breast of a healthy 29-year-old woman, 69 kg and 1.69 m. The 3D modeling software Blender was used to make the prosthesis model and mold with adjustments to the model's mesh, such as smoothing, assigning thickness, and creating the walls of the prosthesis mold. Two counter-molds were created. The pieces were manufactured on the 3D printer Stella Lite 3 using polylactic acid filament. Finally, the silicone was pigmented, and the mold was filled., Findings: Prototype 1 of the prosthesis was produced using a mold without a counter-mold, which resulted in a prosthesis of 495 g, considered heavy compared to traditional prostheses for the same breast size. To solve this issue, a counter-mold with pins was used to produce prototype 2 with a mass of 393 g, 20.6% lighter than prototype 1. Prototype 3 was made with a central-volume counter-mold and presented a mass of 355 g, a reduction of 28.3% compared to prototype 1. The definitive breast prosthesis was made with the pin counter-mold with a different silicone. It has nipple and areola pigmentation and a mass of 294 g, 25.2% lighter than prototype 2., Interpretation: The results suggest that the projected light method and additive manufacturing are potential tools for developing external breast prostheses, which may improve the health conditions and quality of life of mastectomized women., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The choice of musculoskeletal (MSK) model is crucial for performing MSK estimations to evaluate muscle demands and joint forces. This study compared two previously published generic MSK models and a modified model to estimate tibiofemoral reaction forces (TFRF) during gait, sit-to-stand, and stand-to-sit. The estimated tibiofemoral reaction forces were compared with an in vivo dataset from six patients using an instrumented knee prosthesis. A correlation and root mean square error (RMSE) in the time-series analysis and relative peak error (RPE) were evaluated. The results showed that the three MSK models were similar in estimating the vertical forces, with a large correlation, and RPE was found around 20 % during gait. The RMSE and the RPE indicated that the modified model had lower total and lateral compartment forces errors for sit-to-stand and stand-to-sit, showing the best performance. The shear forces for all tasks and models showed significant errors. Future MSK studies should consider these findings when researching functional tasks. The modified model was found to be more effective in estimating the vertical tibiofemoral joint reaction forces in tasks that impose greater demands on muscle forces and require high knee and hip flexion., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2023 IPEM. Published by Elsevier Ltd. All rights reserved.)

Background: The escalating prevalence of type 2 diabetes (T2DM) poses an unparalleled economic catastrophe to developing countries. Cardiovascular diseases remain the primary source of costs among individuals with T2DM, incurring expenses for medications, hospitalizations, and surgical interventions. Compelling evidence suggests that the risk of cardiovascular outcomes can be reduced by three classes of glucose-lowering therapies (GLT), including SGLT2i, GLP-1A, and pioglitazone. However, an evidence-based and cost-effective protocol is still unavailable for many countries. The objective of the current study is to compare the effectiveness and cost-effectiveness of GLT in individuals with T2DM in Brazil., Methods: We employed Bayesian Networks to calculate the incremental cost-effectiveness ratios (ICER), expressed in international dollars (Int$) per disease-adjusted life years [DALYs] averted. To determine the effectiveness of GLT, we conducted a systematic review with network meta-analysis (NMA) to provide insights for our model. Additionally, we obtained cardiovascular outcome incidence data from two real-world cohorts comprising 851 and 1337 patients in primary and secondary prevention, respectively. Our cost analysis took into account the perspective of the Brazilian public health system, and all values were converted to Int$., Results: In the NMA, SGLT2i [HR: 0.81 (95% CI 0.69-0.96)], GLP-1A [HR: 0.79 (95% CI 0.67-0.94)], and pioglitazone [HR: 0.73 (95% CI 0.59-0.91)] demonstrated reduced relative risks of non-fatal cardiovascular events. In the context of primary prevention, pioglitazone yielded 0.2339 DALYs averted, with an ICER of Int$7,082 (95% CI 4,521-10,770) per DALY averted when compared to standard care. SGLT2i and GLP-1A also increased effectiveness, resulting in 0.261 and 0.259 DALYs averted, respectively, but with higher ICERs of Int$12,061 (95% CI: 7,227-18,121) and Int$29,119 (95% CI: 23,811-35,367) per DALY averted. In the secondary prevention scenario, all three classes of treatments were deemed cost-effective at a maximum willingness-to-pay threshold of Int$26,700. Notably, pioglitazone consistently exhibited the highest probability of being cost-effective in both scenarios., Conclusions: In Brazil, pioglitazone presented a higher probability of being cost-effective both in primary and secondary prevention, followed by SGLT2i and GLP-1A. Our findings support the use of cost-effectiveness models to build optimized and hierarchical therapeutic strategy in the management of T2DM., Trial Registration: CRD42020194415., (© 2023. Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist approved for type 2 diabetes. We performed a meta-analysis to assess tirzepatide's weight reduction efficacy and safety., Methods: We searched PubMed, Embase, and Cochrane for randomized controlled trials published from inception to July 2022, comparing tirzepatide with placebo for the co-primary endpoints of absolute and percent change in weight. Mean difference (MD) and odds ratio (OR) were calculated for continuous and binary outcomes, respectively. Review Manager 5.4.1 and RStudio were used for the statistical analysis, and RoB-2 (Cochrane) to assess the risk of bias., Results: Of 397 search results, 6 studies (4036 participants) ranging from 12 to 72 weeks were included. Pooled analysis showed that tirzepatide 5 mg, 10 mg, and 15 mg were more effective than placebo, with MD in body weight of -7.7 kg (95% CI -11.0, -4.4; p < 0.001), -11.6 kg (95% CI -18.8, -4.3; p = 0.002), and -11.8 kg (95% CI -17.4, -6.2; p < 0.001), respectively, and MD in percent change in weight of -8.1% (95% CI -11.0, -5.2; p < 0.001), -11.9% (95% CI -18.1, -5.6; p < 0.001), and -12.4% (95% CI -17.2, -7.5; p < 0.001), respectively. Tirzepatide also reduced BMI and waist circumference. Adverse events were more common with tirzepatide with respect to nausea (OR 4.2; 95% CI 2.4, 7.5; p < 0.001), vomiting (OR 7.0; 95% CI 4.3, 11.4; p < 0.001), and diarrhea (OR 2.8; 95% CI 1.6, 4.9; p < 0.001) (15 mg dose), when compared with placebo., Conclusions: The results support that tirzepatide leads to substantial weight reduction and constitutes a valuable therapeutic option for weight management, despite an increase in gastrointestinal symptoms., Protocol Registration: CRD42022348576., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: To develop a risk assessment tool to identify patients with type 2 diabetes (T2D) at higher risk for kidney disease progression and who might benefit more from sodium-glucose cotransporter 2 (SGLT2) inhibition., Research Design and Methods: A total of 41,204 patients with T2D from four Thrombolysis In Myocardial Infarction (TIMI) clinical trials were divided into derivation (70%) and validation cohorts (30%). Candidate predictors of kidney disease progression (composite of sustained ≥40% decline in estimated glomerular filtration rate [eGFR], end-stage kidney disease, or kidney death) were selected with multivariable Cox regression. Efficacy of dapagliflozin was assessed by risk categories (low: <0.5%; intermediate: 0.5 to <2%; high: ≥2%) in Dapagliflozin Effect on Cardiovascular Events (DECLARE)-TIMI 58., Results: There were 695 events over a median follow-up of 2.4 years. The final model comprised eight independent predictors of kidney disease progression: atherosclerotic cardiovascular disease, heart failure, systolic blood pressure, T2D duration, glycated hemoglobin, eGFR, urine albumin-to-creatinine ratio, and hemoglobin. The c-indices were 0.798 (95% CI, 0.774-0.821) and 0.798 (95% CI, 0.765-0.831) in the derivation and validation cohort, respectively. The calibration plot slope (deciles of predicted vs. observed risk) was 0.98 (95% CI, 0.93-1.04) in the validation cohort. Whereas relative risk reductions with dapagliflozin did not differ across risk categories, there was greater absolute risk reduction in patients with higher baseline risk, with a 3.5% absolute risk reduction in kidney disease progression at 4 years in the highest risk group (≥1%/year). Results were similar with the 2022 Chronic Kidney Disease Prognosis Consortium risk prediction model., Conclusions: Risk models for kidney disease progression can be applied in patients with T2D to stratify risk and identify those who experience a greater magnitude of benefit from SGLT2 inhibition., (© 2023 by the American Diabetes Association.)

The objective of this study is to assess the effectiveness of treatment for inflammatory bowel diseases in modulating oxidative stress biomarkers and cytokine levels. A systematic review of clinical trials was conducted, searching electronic databases including PubMed, Science Direct, and Scopus. After excluding articles that did not meet the inclusion criteria, 19 studies were included in the systematic review and 8 in the meta-analysis (6 for antioxidant capacity, 6 for superoxide dismutase (SOD), and 5 for lipid peroxidation analyzed through malondialdehyde (MDA) levels). SOD was significantly modulated (RR = 0.3764, 95% CI [0.0262 to 0.7267], p = 0.035) but not antioxidant capacity (RR = 0.3424, 95% CI [0.0334 to 0.7183], p = 0.0742) or MDA (RR = -0.8534, 95% CI [-1.9333 to 0.2265], p = 0.1214). Nonetheless, studies investigating oxidative stress biomarkers and cytokines in the context of alternative therapies for IBD treatment are still scarce. This review highlights the potential of antioxidant supplementation in IBD management and underscores the need for further investigations into its effects on oxidative stress biomarkers and cytokines to improve therapeutic approaches for IBD patients.

Ulcerative colitis (UC) is a chronic and recurrent inflammatory bowel disease (IBD) characterized by continuous inflammation in the colonic mucosa. Extraintestinal manifestations (EIM) occur due to the disruption of the intestinal barrier and increased permeability caused by redox imbalance, dysbiosis, and inflammation originating from the intestine and contribute to morbidity and mortality. The aim of this study is to investigate the effects of oral N -acetylcysteine (NAC) on colonic, hepatic, and renal tissues in mice with colitis induced by dextran sulfate sodium (DSS). Male Swiss mice received NAC (150 mg/kg/day) in the drinking water for 30 days before and during (DSS 5% v/v; for 7 days) colitis induction. On the 38 th day, colon, liver, and kidney were collected and adequately prepared for the analysis of oxidative stress (superoxide dismutase (SOD), catalase (CAT), glutathione reduced (GSH), glutathione oxidized (GSSG), malondialdehyde (MDA), and hydrogen peroxide (H 2 O 2 )) and inflammatory biomarkers (myeloperoxidase (MPO) -, tumor necrosis factor alpha - (TNF- α , and interleukin-10 (IL-10)). In colon, NAC protected the histological architecture. However, NAC did not level up SOD, in contrast, it increased MDA and pro-inflammatory effect (increased of TNF- α and decreased of IL-10). In liver, colitis caused both oxidative (MDA, SOD, and GSH) and inflammatory damage (IL-10). NAC was able only to increase GSH and GSH/GSSG ratio. Kidney was not affected by colitis; however, NAC despite increasing CAT, GSH, and GSH/GSSG ratio promoted lipid peroxidation (increased MDA) and pro-inflammatory action (decreased IL-10). Despite some beneficial antioxidant effects of NAC, the negative outcomes concerning irreversible oxidative and inflammatory damage in the colon, liver, and kidney confirm the nonsafety of the prophylactic use of this antioxidant in models of induced colitis, suggesting that additional studies are needed, and its use in humans not yet recommended for the therapeutic routine of this disease., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Amylly Sanuelly da Paz Martins et al.)

This study verified the relationship between body size and skeletal age (SA) with the behavior of blood markers of muscle damage and delayed onset muscle soreness (DOMS) after a soccer match in the U-13 and U-15 categories. The sample consisted of 28 soccer players in the U-13 and 16 in the U-15 categories. Creatine kinase (CK), lactate dehydrogenase (LDH), and DOMS were evaluated up to 72 h after the match. Muscle damage was elevated at 0 h in U-13, and from 0 h to 24 h in U-15. DOMS increased from 0 h to 72 h in U-13 and from 0 h to 48 h in U-15. Significant associations of SA and fat-free mass (FFM) with muscle damage markers and DOMS were observed only in U-13, specifically at time 0 h, when SA explained 56% of CK and 48% of DOMS and FFM explained 48% of DOMS. We concluded that in the U-13 category, higher SA is significantly associated with muscle damage markers, and increase in FFM is associated with muscle damage markers and DOMS. Furthermore, U-13 players need 24 h to recover pre-match muscle damage markers and more than 72 h to recover DOMS. In contrast, the U-15 category needs 48 h to recover muscle damage markers and 72 h to recover DOMS., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Risk of atherothrombotic events is not uniform in patients with type 2 diabetes mellitus (T2DM). Tailored risk assessment may help guide selection of pharmacotherapies for cardiovascular primary and secondary prevention., Objectives: The purpose of this study was to develop a risk model for atherothrombosis in patients with T2DM., Methods: We developed and validated a risk model for myocardial infarction (MI) or ischemic stroke (IS) in a pooled cohort of 42,181 patients with T2DM from 4 TIMI (Thrombolysis In Myocardial Infarction) clinical trial cohorts. Candidate variables were assessed with multivariable Cox regression, and independent variables (P < 0.05) were retained in the final model. Discrimination and calibration were assessed. Treatment interactions with dapagliflozin (sodium-glucose cotransporter-2 inhibitor) and evolocumab (proprotein convertase subtilisin/kexin type 9 inhibitor) were explored in the DECLARE-TIMI 58 (Dapagliflozin Effect on CardiovascuLAR Events-Thrombolysis In Myocardial Infarction 58) and FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) trials, respectively., Results: Sixteen variables were independent predictors of MI or IS. The model identified a >8-fold gradient of MI or IS rates between the top vs bottom risk quintiles in the validation cohort (3-year Kaplan-Meier rate: 14.9% vs 1.4%; P < 0.0001). C-indexes were 0.704 and 0.706 in the derivation and validation cohorts, respectively. The model was well-calibrated in both primary and secondary prevention. Absolute reduction in the rates of MI or IS tended to be greater in patients with higher baseline predicted risk for both dapagliflozin (absolute risk reduction: 2.1% vs 0.2%) and evolocumab (absolute risk reduction: 3.2% vs 1.0%)., Conclusions: We developed and validated a risk score for atherothrombotic events, leveraging 16 routinely assessed clinical variables in patients with T2DM. The score has the potential to improve risk assessment and inform clinical decision-making., Competing Interests: Funding Support and Author Disclosures The SAVOR-TIMI 53 and DECLARE-TIMI 58 trials were supported by institutional research grants to Brigham and Women’s Hospital from AstraZeneca. The FOURIER trial was supported by an institutional research grant to Brigham and Women’s Hospital from Amgen. The CAMELLIA-TIMI 61 trial was supported by an institutional research grant to Brigham and Women’s Hospital from Eisai. Drs Berg, Moura, Scirica, Wiviott, Feinberg, Morrow, and Sabatine were supported for the present analysis by the American Heart Association Cardiometabolic Health and Type 2 Diabetes Mellitus Strategically Focused Research Network (20SFRN35120087). Drs Berg, Moura, Bellavia, Scirica, Wiviott, Bohula, Giugliano, Park, Braunwald, Morrow, and Sabatine are members of the TIMI Study Group, which has received institutional research grant support through Brigham and Women’s Hospital from Abbott, Abiomed, Amgen, Anthos Therapeutics, ARCA Biopharma, Inc, AstraZeneca, Bayer HealthCare Pharmaceuticals, Daiichi-Sankyo, Eisai, Intarcia, Ionis Pharmaceuticals, Janssen Research and Development, MedImmune, Merck, Novartis, Pfizer, Quark Pharmaceuticals, Regeneron Pharmaceuticals, Roche, Siemens Healthcare Diagnostics, Softcell Medical Limited, The Medicines Company, and Zora Biosciences. Dr Berg has received research grant support to his institution from AstraZeneca and Pfizer; has received consulting fees from AstraZeneca, Mobility Bio, Inc, and Youngene Therapeutics; has received honoraria from the Medical Education Speakers Network (MESN) and USV Private Limited; and participates on clinical endpoint committees for studies sponsored by Kowa Pharmaceuticals. Dr Scirica has received institutional research grants to Brigham and Women’s Hospital from Better Therapeutics, Merck, Novo Nordisk, and Pfizer; has received consulting fees from Allergan, Boehringer Ingelheim, Better Therapeutics, Elsevier Practice Update Cardiology, Esperion, Hanmi, Lexicon, and Novo Nordisk; and has equity in Health [at] Scale and Doximity. Dr Wiviott has received grants from Amgen, AstraZeneca, Daiichi-Sankyo, Eisai, Janssen, Merck, and Pfizer; has received consulting fees from AstraZeneca, Boston Clinical Research Institute, Icon Clinical, and Novo Nordisk; and his spouse is a former employee of Merck and is a current employee of Flagship Labs 86. Dr Bhatt has served on the Advisory Board of AngioWave, Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, and Stasys; has served on the Board of Directors of AngioWave (stock options), Boston VA Research Institute, Bristol Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock), Society of Cardiovascular Patient Care, and TobeSoft; is Inaugural Chair of the American Heart Association Quality Oversight Committee; has served as a consultant for Broadview Ventures; has served on Data Monitoring Committees for Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi-Sankyo; for the ABILITY-DM trial, funded by Concept Medical), Novartis, Population Health Research Institute, and Rutgers University (for the National Institutes of Health-funded MINT Trial); has received honoraria from the American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor-in-Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor-in-Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national coleader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees), and Wiley (steering committee); has served as Deputy Editor of Clinical Cardiology; is Chair of the NCDR-ACTION Registry Steering Committee and VA CART Research and Publications Committee; has a patent for Sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women's Hospital who assigned to Lexicon; neither I nor Brigham and Women's Hospital receive any income from this patent); has received research funding from Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, and 89Bio; has received royalties from Elsevier (Editor, Braunwald’s Heart Disease); is site co-investigator for Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, and Vascular Solutions; is a Trustee of the American College of Cardiology; and has performed unfunded research for FlowCo and Takeda. Dr Raz has received personal fees from AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Concenter BioPharma and Silkim, Eli Lilly, Merck Sharp and Dohme, Novo Nordisk, Orgenesis, Pfizer, Sanofi, SmartZyme Innovation, Panaxia, FuturRx, InsuLine Medical, Medial EarlySign, CameraEyes, Exscopia, Dermal Biomics, Johnson and Johnson, Novartis, Teva, GlucoMe, and DarioHealth. Dr Bohula has received personal fees from Servier, Kowa, Medscape, Novo Nordisk, Amgen, PriMed, and Merck. Dr Giugliano has received research support from Amgen, Anthos Therapeutics, and Daiichi-Sankyo; has received honoraria for lectures/CME programs for Amgen, Centrix, Daiichi-Sankyo, Dr Reddy’s Laboratories, Medical Education Resources, Medscape, Menarini, Merck, Pfizer, SAJA Pharmaceuticals, Servier, Shanghai Medical Telescope, and Voxmedia; and has received consultant fees from Amarin, Amgen, Boston Scientific, CryoLife, CSL Behring, CVS Caremark, Daiichi-Sankyo, Esperion, Gilead, Hengrui, Inari, Janssen, Novartis, Pfizer, PhaseBio Pharmaceuticals, St. Lukes, and Samsung. Dr Braunwald has received research grants through his institution from AstraZeneca, Daiichi-Sankyo, Merck, and Novartis; and has received consultancy fees from Amgen, Bristol Myers Squibb, Boehringer Ingelheim/Lilly, Cardurion, and Verve. Dr Morrow has received grants to the Brigham and Women’s Hospital from Abbott Laboratories, Amgen, Anthos Therapeutics, AstraZeneca, Eisai, The Medicines Company, Merck, Novartis, Pfizer, Roche Diagnostics, and Siemens; and has received consultant fees from InCardia, Inflammatix, Merck and Co, Novartis, and Roche Diagnostics. Dr Sabatine has received research grant support through Brigham and Women’s Hospital from Abbott, Amgen, Anthos Therapeutics, AstraZeneca, Daiichi-Sankyo, Eisai, Intarcia, Ionis, Merck, Novartis, and Pfizer; and has served as a consultant for Althera, Amgen, Anthos Therapeutics, AstraZeneca, Beren Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Fibrogen, Intarcia, Merck, Moderna, Novo Nordisk, and Silence Therapeutics., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Prior research has suggested relevance to anthropometric variance of youth athletes at various stages of their maturation, and prior studies of youth players' soccer skills have failed to consider their interdependent interactions during play. Accordingly, to address both of these separate research omissions, we aimed in this study to analyze the relationships between young (U-13 and U-15 groups) soccer players' bone age and body size indicators and centrality measures of their pass interactions during small sided games. We included young 81 athletes ( M age = 14.4, SD = 1.1 years) from whom we took anthropometric measurements of body mass, height, and trunk-cephalic height and obtained their bone age using the Tanner-Whitehouse 3 classification method. We also filmed small-sided games in the goal keeper/three player (GK3-3GK) format to analyze the centrality of their passing actions on the following measures: degree of centrality, closeness of centrality, degree of prestige, and proximity of prestige. There were no group differences in the prominence of passing actions across these three measures (t mean = -3.13; p > .05). Canonical correlations of these relationships were significant only in the U-13 group, in which centrality in passing actions was related to body size ( r = 0.71; R 2 = 0.21; ʌ = 0.28; p = .03). U-13 players who were physically larger and who presented higher bone age showed centralized main passing actions.

The purpose of this study was to characterise the interpersonal coordination between opponent players during offensive sequences in official matches and to verify if offensive sequences ended in shots to goal present different coordination patterns when compared than those that ended in defensive tackles. A total of 580 offensive sequences occurred during matches resulting in shots to goal ( n  = 172) or defensive tackles ( n  = 408) were analysed. The bidimensional coordinates and technical actions of male professional football players ( n  = 1160) were obtained using a video-based tracking system. Dyads were defined using a network analysis and composed of the nearest opponent. Interpersonal coordination of the dyads was analysed using the vector coding and the frequency for each coordination pattern was computed. In-phase was predominant for all displacement directions and offensive sequences outcomes, and antiphase was the least frequent. For lateral displacements, offensive sequences ending in shot to goal presented lower frequency for in-phase and higher frequency for offensive player phase than ended in defensive tackle. This information about the relationship of opponent players dyads during decisive moments of the matches provides fundamentals for future research and assists coaches to understand the different behaviours in successful and unsuccessful attacks.

This study aimed to observe the relationships between the maturity status on the network-based centrality measures of young athletes in small-sided soccer games (SSG). The study included 81 male players (14.4 ± 1.1 years). Measurements included height, sitting height, body mass, and bone age (TW3 method). The applied protocols were the following: Countermovement Jump (CMJ), Yo-Yo Intermittent Recovery Test Level 1 (YYIRT1), Repeated Sprints Ability (RSA), observational analysis of techniques, and interactions performed by players in SSG. The relationship between the set of evaluated variables within each maturity status was obtained from the correlational analysis of networks (P < 0.05). The maturity status explained a significant portion of the variance in body mass (η 2  = 0.37), height (η 2  = 0.30), sitting height (η 2  = 0.30), and performance on the YYIRT1 (η 2  = 0.08), CMJ (η 2  = 0.14), and RSA (η 2  = 0.13). No effect of maturity status on network-based centrality measures of young athletes was identified (P > 0.05). For the late maturity group, there was a correlation between the degree of centrality and physical growth indicators (r mean  = 0.88). For players with maturation "on time", physical growth indicators relate to the degree of prestige (r mean  = 0.36). It is concluded that body size and bone age impact how late and on-time maturity groups interact within the match., (© 2023. The Author(s).)

Application methods of transcranial direct current stimulation (tDCS) in Parkinson's disease (PD) are quite divergent making it difficult to define the clinical effectiveness of the tDCS on PD. Thus, the aim of this study was to verify the acute effects of tDCS when applied to different targets (Cz or C3-Cz-C4) combined to physical therapy to improve balance and gait in individuals with PD. A randomized controlled trial was conducted, with 50 individuals who were separated into four groups: 1) Real tDCS (Cz) + physical therapy, 2) Real tDCS (C3-Cz-C4) + physical therapy, 3) Sham tDCS + physical therapy and 4) Educational lecture + physical therapy. The current intensity was 2 mA, applied for 20 min. For the instrumental assessment of balance and gait, the 3D motion analysis system was used. For the biomechanical analysis of gait, three different conditions were performed: normal gait, dual task gait and obstacle gait. For balance analysis, the following positions were utilized: Romberg with eyes opened, Romberg with eyes closed, Tandem with eyes opened and Tandem with eyes closed. All evaluations were performed pre-intervention, post-intervention (immediately at the end of the intervention) and were followed-up on (24 h after the end of the intervention). No statistically significant differences were found for all gait and balance outcomes when considering the interaction between time (pre, post and follow-up assessments) versus group (Education, Sham, Cz and C3-Cz-C4). In conclusion, it was found that one session of tDCS, stimulating Cz or C3-Cz-C4 combined with physical therapy, was not effective in improving the balance and gait in people with PD as compared to sham tDCS or educational lecture plus physiotherapy., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Limited data are available regarding the differences between immunological, biochemical, and cellular contents of human colostrum following maternal infection during pregnancy with coronavirus 2 disease (COVID-19)., Objective: To investigate whether maternal COVID-19 infection may affect immunological, biochemical, and cellular contents of human colostrum., Methods: Using a case-control study design, we collected colostrum from 14 lactating women with a previous diagnosis of COVID-19 during pregnancy and 12 without a clear diagnosis during September 2020 to May 2021. Colostrum samples were analysed for some enzymes and non-enzymatic oxidative stress markers (SOD, CAT, GPx, MDA, GSH, GSSG, H 2 O 2 , MPO) and for IL-1β, IL-6, tumour necrosis factor (TNF)-α, protein induced by interferon gamma (IP)-10, IL-8, IFN-λ1, IL12p70, IFN-α2, IFN-λ2/3, granulocyte macrophage colony stimulating factor (GM-CSF), IFN-β, IL-10 and IFN-γ, along with IgA and IgG for the SARS-CoV-2 S protein. We perform immunophenotyping to assess the frequency of different cell types in the colostrum., Results: Colostrum from the COVID-19 symptomatic group in pregnancy contained reduced levels of H 2 O 2 , IFN-α2, and GM-CSF. This group had higher levels of GSH, and both NK cell subtypes CD3 - CD56 bright CD16 - CD27 + IFN-γ + and CD3 - CD56 dim CD16 + CD27 - were also increased., Conclusion: The present results reinforce the protective role of colostrum even in the case of mild SARS-Cov-2 infection, in addition to demonstrating how adaptive the composition of colostrum is after infections. It also supports the recommendation to encourage lactating women to continue breastfeeding after COVID-19 illness., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Graciliano, Tenório, Fragoso, Moura, Botelho, Tanabe, Borbely, Borbely, Oliveira and Goulart.)

Background: Total knee arthroplasty is the most common treatment for severe knee osteoarthritis. Coordination and variability analyses are effective measures of the injury stage or rehabilitation process. This study compared the inter-joint coordination before and after arthroplasty, compared to controls., Methods: Twenty-seven patients were evaluated before and 12 months after surgery, compared to 27 controls. Coordination and variability in the sagittal plane between the hip-knee and knee-ankle were calculated using vector coding and circular statistics. Coordination was categorized as in-phase, anti-phase, or distal or proximal joint-phase. The gait cycle was divided into sub-phases for the coordination, variability, and range of motion results., Findings: Coordination and range of motion differed significantly between the patient groups and controls, while small differences between pre- and post-operative groups were also detected. The hip-knee showed a reduced in-phase frequency in the patient group compared to control during stance, particularly mid-stance: pre-operative 24.3% ± 33.9, post-operative 29.5 ± 29.7, and controls 70.7 ± 17.0. This difference was compensated for by increasing proximal-phase (hip) frequency in the patient groups. For knee-ankle coordination, the patient groups showed higher distal-phase (ankle) frequency during the early and mid-stance. Coordination variability was higher post-operatively during swing and terminal swing phases, compared to controls., Interpretation: The results indicated reduced degrees of freedom for the knee during stance phase with a reduced capacity to move the knee and hip in opposing directions before and one year after surgery. The patient group after the surgery increased knee range of motion and coordination compared to pre-operative during swing phase., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

In 2019, a new rule was applied in soccer. It allows the goalkeeper to have only one foot or part of it on the goal line when the kicker hits the ball, unlike the previous rule that determined the goalkeeper should have both feet on the line. The purpose of the present study was to analyze how the change in the rule and the lower limbs laterality influences on the diving save kinematic performance in penalties. Six goalkeepers, two professionals and four amateurs, performed a total of 20 dives in the laboratory and had their force and impulse exerted by the lower limb and displacement/velocity data from the center of body mass collected through force plates and kinematic analysis. The side preference was collected through an inventory. The results showed that goalkeepers dive further (p < 0.001) and faster (p < 0.001) when diving according to the new rule. Dives for the non-dominant side presented higher values than the trials for the dominant side in mediolateral (p = 0.02) and resultant (p = 0.03) displacements. Concluding, the goalkeepers performed better with the new rule in the analyzed variables and the lower limb preference has influenced only the mediolateral and resultant displacement., (© 2022. The Author(s).)

Introduction: Usually, the players' or teams' efficiency to perform passes is measured in terms of accuracy. The degree of difficulty of this action has been overlooked in the literature., Objectives: The present study aimed to classify the degree of passing difficulty in soccer matches and to identify and to discuss the variables that most explain the passing difficulty using spatiotemporal data., Results: The data used corresponds to 2,856 passes and 32 independent variables. The Fisher Discriminant Analysis presented 72.0% of the original grouped cases classified correctly. The passes analyzed were classified as low (56.5%), medium (22.6%), and high difficulty (20.9%), and we identified 16 variables that best explain the degree of passing difficulty related to the passing receiver, ball trajectory, pitch position and passing player., Conclusions: The merit and ability of the player to perform passes with high difficulty should be valued and can be used to rank the best players and teams.In addition, the highlighted variables should be looked carefully by coaches when analyzing profiles, strengths and weaknesses of players and teams, and talent identification context., Practical Implications: The values found for each variable can be used as a reference for planning training, such as small side games, and in future research.

Background: Colorectal cancer (CRC) is the third most incident cancer in the world and the second leading cause of cancer death. Significant decreases in incidence and mortality can be achieved by reducing risk factors and adhering to healthy lifestyle recommendations, as well as screening for the disease., Objective: To evaluate the clinical nutritional profile of individuals at medium risk screened for CRC residing in the city of Piranhas/Alagoas., Methods: Cross-sectional study conducted from September to October 2020, with individuals at medium risk for CRC, of both sexes and aged between 50 and 70 years old. Participants were screened for CRC with fecal immunochemical testing (FIT) and colonoscopy. Personal, socioeconomic, clinical, lifestyle and nutritional assessment data were collected. The latter was performed using anthropometric data (weight, height, arm circumference and triceps skinfold thickness), body composition (bioimpedance) and physical examination. Descriptive analysis of data frequencies and dichotomization according to the presence or absence of overweight was performed, followed by comparison of means and medians and frequencies by chi-square or Fisher's exact test., Results: In total, 82 people agreed to undergo the clinical nutritional assessment, most of them female (56.1%; n=46), adults (56.1%; n=46), with a mean age of 59.02 years (±6.30 SD). Pre-cancerous lesions were identified in 54.5% (n=42) of those screened, 52.4% (n=43) were smokers or former smokers, and 65.9% (n=54) did not practice scheduled physical activity. Nutritional assessment showed that 64.6% (n=53) were overweight according to body mass index. On the other hand, the muscle mass, % arm muscle circumference adequacy and body muscle mass (kg) markers showed that 32.9% (n=27) and 47.6% (n=39) of the subjects were muscle depleted, respectively. Above all, overweight participants had, in parallel, lower muscle mass (P<0.05), suggesting sarcopenic obesity in this population., Conclusion: Obesity is one of the main risk factors for CRC; when concomitant with sarcopenia, it favors worse health outcomes. In this context, evidence shows the need to assess muscle composition in people with obesity, especially through other methods of assessing body composition. Our results add to the evidence on the importance of the population being guided about screening and adherence to healthy lifestyle recommendations, especially strategies aimed at weight control and the practice of physical activity.

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve endothelial dysfunction and reduce cardiovascular events in individuals with type 2 diabetes (T2D). Proprotein convertase subtilisin/kexin 9 (PCSK9i) inhibitors reduce cardiovascular events in high-risk patients. Whether the addition of PCSK9i to SGLT2i treatment adds benefits is not known., Objectives: To assess the PCSK9-i effect on the endothelial function of T2D individuals under treatment with SGLT2-i., Methods: Individuals with T2D were randomized in a 1:1 ratio to a 16-week treatment with either empagliflozin (E) or empagliflozin plus evolocumab (EE). The primary endpoint was post-treatment change from baseline in flow-mediated dilation (FMD) at 1-min. Secondary outcomes included changes in plasma levels of nitric oxide metabolites and isoprostane., Results: A total of 110 patients were enrolled, the mean age was 58 years, and 71% were men. The median post-treatment change in FMD at 1-min was 2.7% (interquartile range [IQR]: 0.9%) and 0.4% (IQR: 0.9%) in the EE and E groups, respectively (p < 0.001). There was a greater increase in plasma levels of nitrate [5.9 (16.5) vs. 2.6 (11.8); p = 0.001] and nitrite [0.14 (0.72) vs. 0.02 (0.74); p = 0.025] in the EE group than in the E group, respectively. Isoprostane reduction was more pronounced in the EE group when compared to the E group [-1.7 (5.9) vs. -1.1 (5.3); p < 0.001)., Conclusions: In individuals with T2D, the addition of evolocumab on top of empagliflozin improves endothelial function., (© 2022. The Author(s).)

Purpose: Although the role of signal transducers and activators of transcription (STAT3) in cachexia due to the association of circulating IL-6 and muscle wasting has been extensively demonstrated, the effect of resistance training on STAT3 in mediating muscle atrophy in tumor-bearing mice is unknown. The aim of this study is to investigate the effects of resistance exercise training on inflammatory cytokines and oxidative-mediated STAT3 activation and muscle loss prevention in tumor-bearing mice., Methods: Male Swiss mice were inoculated with Ehrlich tumor cells and exposed or not exposed to resistance exercise protocol of ladder climbing. Skeletal muscle STAT3 protein content was measured, compared between groups, and tested for possible association with plasma interleukins and local oxidative stress markers. Components of the ubiquitin-proteasome and autophagy pathways were assessed by real-time PCR or immunoblotting., Results: Resistance training prevented STAT3 excessive activation in skeletal muscle mediated by the overabundance of plasma IL-6 and muscle oxidative stress. These mechanisms contributed to preventing the increased key genes and proteins of ubiquitin-proteasome and autophagy pathways in tumor-bearing mice, such as Atrogin-1, LC3B-II, and Beclin-1. Beyond preventing muscle atrophy, RT also prevented strength loss and impaired locomotor capacity, hallmarks of sarcopenia., Conclusion: Our results suggest that STAT3 inhibition is central in resistance exercise protective effects against cancer-induced muscle atrophy and strength loss., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Testa, Cella, Marinello, Frajacomo, Padilha, Perandini, Moura, Duarte, Cecchini, Guarnier and Deminice.)

Aims: This study aimed to investigate if titanium dioxide (TiO 2 ) joint administration is a useful pre-clinical model to study sarcopenia-related chronic arthritis, and if exercise is a useful therapeutic approach against the pathogenesis of TiO 2 -induced arthritis and sarcopenia in mice., Main Methods: Two experiments were conducted. Firstly, 36 female Swiss mice were randomly divided into a control group (n = 12) and two groups who received intra-articular TiO 2 injections of 0.3-mg (n = 12) and 3-mg (n = 12), respectively. Mice were euthanized 4 and 8 weeks after TiO 2 injections. Based on data of the first experiment, mice were exposed to four groups: control (C, n = 10), exercised (Ex, n = 10), injected with 3-mg of TiO 2 (TiO 2 , n = 10), and injected with 3-mg of TiO 2 and exercised (TiO 2  + Ex, n = 10) for a total of 8-weeks., Key Findings: Eight-week of 3 mg of TiO 2 joint administration promoted characteristics of chronic inflammation such as elevated histopathological score, inflammation, edema and pain. Hallmarks of sarcopenia were also observed such as muscle atrophy and loss of strength. Furthermore, voluntary exercise running reduced TiO 2 -induced chronic inflammation and pain, attenuating chronic arthritis-related muscle atrophy, strength loss and impairment of locomotion capacity. In addition, exercise was also able to prevent TiO 2 -induced collagen degradation, an important marker of functional and structural integrity loss of cartilage and chronic arthritis disease progression., Significance: TiO 2 joint administration mimed titanium prosthesis release-induced joint chronic arthritis and sarcopenia-related chronic arthritis, disturbances that were attenuated by voluntary exercise., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: This study compared the physical, physiological, and spatiotemporal responses of soccer athletes in small-sided games (SSG) in two experimental conditions: progression to the target rule (PG), in which they should take the ball to the opponent's endline to score points, and SSG with regular rules (RG), in which they should score goals to win the game., Methods: Twenty U-20 athletes played both SSG formats. The SSG were played as four 4-minute bouts with four minutes of passive recovery in two consecutive days. Heart rate, physical (distances and accelerations), and positional data (length, width, and spatial exploration) were collected by a 10 hz GPS device and compared between the protocols using a MANOVA with Bonferroni's correction for multiple comparisons., Results: Results showed that the RG condition demanded more spatial exploration eliciting greater occupation of the pitch width. There were higher mean and maximum heart rates and greater low-to-moderate distances and accelerations in the RG, while the PG rule increased the distances covered at the highest speed and acceleration zones., Conclusions: The progression to the target rule should be adopted to emphasize players' ability to use the width during the offensive phase. Additionally, the PG rule should also be used to emphasize the development of speed and acceleration skills.

Kicking powerfully and accurately is essential in soccer, and players who kick proficiently with both feet are highly sought after. Assessing performance in youth players is often confounded by more physically developed players outperforming their smaller peers. To alleviate such bias, we present a testing protocol and normative data developed with an elite Brazilian soccer academy that controls for players' age and size to assess kick performance with both feet. We measured kick speed and kick accuracy of 178 players and recorded their age (10-20 years), height, and mass. Combining age, height, and mass into an age and size index (ASI), we developed equations describing the relationship between ASI and performance. To determine the underlying predictors of performance, we also measured sprint ability and soccer-specific motor control of each foot with ball dribbling tasks. Kicking speed with the dominant foot was predicted by ASI, sprint speed, and motor control of the nondominant foot, while kicking speed with the nondominant foot was predicted by ASI and motor control of the nondominant foot. Kick accuracy with each foot was predicted by ASI and motor control of the corresponding foot. To improve kicking performance, we suggest training programs focus on motor control.

This study aimed to investigate the concordance of different nutritional assessment methods and the prevalence of inadequate nutritional status in newly diagnosed Colorectal cancer (CRC) patients. Cross sectional study was conducted in a public hospital in Alagoas, Brazil. Clinical, nutritional (patient-generated subjective global assessment [PG-SGA], body mass index [BMI], arm circumference [AC], triceps skinfold [TSF], arm muscle circumference [AMC]) and functional (handgrip strength [HGS]) data were collected from July 2017-January 2019. Of the 31 CRC patients with a mean age of 58.97 ± 14.96 years, 48.4% were elderly and 51.6% were female. TSF adequacy (80.8%) and PG-SGA (80.0%) revealed the highest prevalence of malnutrition. BMI identified the same prevalence of malnutrition and excess weight (30.0%). The concordance between PG-SGA and BMI (kappa = 0.086; p  = 0.426) was slight, with fair HGS (kappa = 0.268; p  = 0.124). PG-SGA and AC (kappa = 0.015; p  = 0.99), TSF (kappa = 0.195; p  = 0.558) and AMC adequacy (kappa = 0.142; p  = 0.380) were poor. PG-SGA can diagnose malnutrition, even in those who are eutrophic/overweight, by other methods. Various methods do not show concordance with PG-SGA, confirming the need for both objective and subjective methods for better diagnosis of CRC patients.

Background: Foot type classification is well recognized in clinical practice and orthopedic literature, a universally accepted classification or standardized measures to determine foot types are lacking. The objective of this study was to identify which non-radiographic assessment methods are considered valid and/or reliable for the classification of foot types., Method: A systematic database search was performed. Only cross-sectional studies that performed reliability and/or validity analysis of non-radiographic methods were included. To evaluate the risk of bias, the Critical Appraisal Tool (CAT) was used to evaluate the measurement properties of objective clinical methods., Results: Twenty-six studies were included. The results of reliability and validity, in general, demonstrated high scores, but, inconsistencies were related to the variability of the measurements, heterogeneity of the methods used to determine reliability and validity, and lack of parameters for classifying foot types, which resulted in few elements to determine which method of foot type evaluation is valid and reliable., Conclusion: Given the Intraclass Correlation Coefficient and CAT results and the presence of normative values, the static measurements of the "Arch Height Index", "Foot Posture Index", and "Staheli Arch Index" can be suggested to classify foot types., (Copyright © 2021 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.)

Objective: To compare redox imbalance and inflammation biomarkers in umbilical cords from pregnancies with and without preeclampsia (PE) and to analyse their relationships with perinatal outcomes., Methods: A controlled cross-sectional study was conducted in Maceió, Alagoas, Brazil, that involved pregnant women with PE and a group of women without the disease, through the application of a standardized questionnaire. After delivery, umbilical cord samples were collected to measure antioxidant defense, products from oxidative damage, and inflammation biomarkers such as myeloperoxidase (MPO), interleukin- (IL-) 6, IL-8, IL-10, and tumor necrosis factor-alpha (TNF- α ). Statistical analyses were performed using Stata version 13.0 software and IBM Statistical Package for the Social Sciences (SPSS) 20.0, adopting a 95% confidence level ( α = 0.05), with the chi-square test, the Wilcoxon-Mann-Whitney test, and the multinomial and Poisson regression tests., Results: One hundred PE pregnant women and 50 women without the disease were studied. The umbilical cords from PE pregnancies showed higher levels of reduced glutathione (GSH) ( p ≤ 0.001), glutathione peroxidase (GPx) ( p = 0.016), and malondialdehyde (MDA) ( p = 0.028) and lower levels of IL-6 ( p = 0.030) and TNF- α ( p ≤ 0.001) than the other group, with some associations among these biomarkers with perinatal outcomes., Conclusion: The higher levels of GSH and GPx, in addition to the lower levels of IL-6 and TNF- α , found in the PE umbilical cord, may result from adaptive mechanisms to maintain the oxidative and inflammatory balance; however, despite these changes, the damage to the cell membranes was not minimized, as the MDA level was higher in women with PE than in women without the disease. This implies that a redox imbalance is present, confirming that other physiological and adaptive mechanisms are being activated to preserve foetal health. Therefore, the present work unveils an important role of the umbilical cord in controlling redox imbalance and inflammation in PE pregnancies. Our results reinforce the necessity for continuous research on GSH as a protective compound for the perinatal outcome, especially in PE women., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2021 Marilene Brandão Tenório Fragoso et al.)

We investigated the effects of caffeine mouth rinse on endurance performance, muscle recruitment (i.e., electromyographic activity of the vastus lateralis and rectus femoris), rating of perceived effort and heart rate. Twelve physically-active healthy men cycled at 80% of their respiratory compensation point until task failure. The participants rinsed their mouths for 10 seconds with placebo (PLA, 25 mL of a solution composed of non-caloric mint essence) or caffeine (CAF, 25 mL of 1.2% of anhydrous caffeine concentration with non-caloric mint essence) every 15 minutes of exercise. Time until exhaustion increased 17% (effect size = 0.70) in CAF compared to PLA (p = 0.04). The wavebands of low-frequency electromyographic activity (EMG) of the vastus lateralis and rectus femoris was lower in CAF group than PLA at 50% of the time until exhaustion (p = 0.04). The global EMG signal was lower in CAF group than PLA at 100% of the time until exhaustion (p = 0.001). The rating of perceived effort pooled was higher in CAF mouth rinse (p = 0.001) than PLA group. No effect was found on the heart rate between the groups (p > 0.05). Caffeine mouth rinse increases endurance performance, rating of perceived effort and decreases muscle activity during a moderate-intensity exercise., (Copyright © Biology of Sport 2021.)

Dominant regions are defined as regions of the pitch where a player can reach before any other and are commonly determined without considering the free-spaces in the pitch. We presented an approach to football players' dominant regions analysis, based on movement models created from players' positions, displacement, velocity, and acceleration vectors. 109 Brazilian male professional football players were analysed during official matches, computing over 15 million positional data obtained by video-based tracking system. Movement models were created based on players' instantaneous vectorial kinematics variables, then probabilities models and dominant regions were determined. Accuracy in determining dominant regions by the proposed model was tested for different time-lag windows. We calculated the areas of dominant, free-spaces, and Voronoi regions. Mean correct predictions of dominant region were 96.56%, 88.64%, and 72.31% for one, two, and three seconds, respectively. Dominant regions areas were lower than the ones computed by Voronoi, with median values of 73 and 171 m 2 , respectively. A median value of 5537 m 2 was presented for free-space regions, representing a large part of the pitch. The proposed movement model proved to be more realistic, representing the match dynamics and can be a useful method to evaluate the players' tactical behaviours during matches., (© 2021. The Author(s).)

The aim of this study was to evaluate different shape descriptors applied to images of polygons that represent the organization of football teams on the pitch. The effectiveness of different shape descriptors (area/perimeter, fractal area, circularity, maximum fractal, rectangularity, multiscale fractal curve-MFC), and the concatenation of all shape descriptors (except MFC), denominated Alldescriptors (AllD)) was evaluated and applied to polygons corresponding to the shapes represented by the convex hull obtained from players' 2D coordinates. A content-based image retrieval system (CBIR) was applied for 25 users (mean age of 31.9 ± 8.4 years) to evaluate the relevant images. Measures of effectiveness were used to evaluate the shape descriptors (P@n and R@n). The MFD (P@5, 0.46±0.37 and P@10, 0.40±0.31, p < 0.001; R@5, 0.14±0.13 and R@10, 0.24±0.19, p < 0.001) and AllD (P@5 = 0.43±0.36 and P@10 = 0.39±0.32, p < 0.001; R@5 = 0.13±0.11 and R@10 = 0.24±0.20, p < 0.001) descriptors presented higher values of effectiveness. As a practical demonstration, the best evaluated shape descriptor (MFC) was applied for tactical analysis of an official match. K-means clustering technique was applied, and different shapes of organization could be identified throughout the match. The MFC was the most effective shape descriptor in relation to all others, making it possible to apply this descriptor in the analysis of professional football matches., Competing Interests: The authors have declared that no competing interests exist.