Cardiac pathology in mucopolysaccharidosis I mice: Losartan modifies ERK1/2 activation during cardiac remodeling.

Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disorder caused by mutations in the IDUA gene, that codifies the alpha-L-iduronidase enzyme, which deficiency leads to storage of glycosaminoglycans, with multiple clinical manifestations. One of the leading causes of death in MPS I patients are cardiac complications such as cardiac valve thickening, conduction abnormalities, myocardial dysfunction, and cardiac hypertrophy. The mechanism leading to cardiac dysfunction in MPS I is not entirely understood. In a previous study, we have demonstrated that losartan and propranolol improved the cardiac function in MPS I mice. Thus, we aimed to investigate whether the pathways influenced by these drugs may modulate the cardiac remodeling process in MPS I mice. According to our previous observation, losartan and propranolol restore the heart function, without altering valve thickness. MPS I mice presented reduced activation of AKT and ERK1/2, increased activity of cathepsins, but no alteration in metalloproteinase activity was observed. Animals treated with losartan showed a reduction in cathepsin activity and restored ERK1/2 activation. While both losartan and propranolol improved heart function, no mechanistic evidence was found for propranolol so far. Our results suggest that losartan or propranolol could be used to ameliorate the cardiac disease in MPS I and could be considered as adjuvant treatment candidates for therapy optimization.

Cardiac hypertrophy in mice submitted to a swimming protocol: influence of training volume and intensity on myocardial renin-angiotensin system.

Exercise promotes physiological cardiac hypertrophy and activates the renin-angiotensin system (RAS), which plays an important role in cardiac physiology, both through the classical axis [angiotensin II type 1 receptor (AT1R) activated by angiotensin II (ANG II)] and the alternative axis [proto-oncogene Mas receptor (MASR) activated by angiotensin-(1-7)]. However, very intense exercise could have deleterious effects on the cardiovascular system. We aimed to analyze the cardiac hypertrophy phenotype and the classical and alternative RAS axes in the myocardium of mice submitted to swimming exercises of varying volume and intensity for the development of cardiac hypertrophy. Male Balb/c mice were divided into three groups, sedentary, swimming twice a day without overload (T2), and swimming three times a day with a 2% body weight overload (T3), totaling 6 wk of training. Both training groups developed similar cardiac hypertrophy, but only T3 mice improved their oxidative capacity. We observed that T2 had increased levels of MASR, which was followed by the activation of its main downstream protein AKT; meanwhile, AT1R and its main downstream protein ERK remained unchanged. Furthermore, no change was observed regarding the levels of angiotensin peptides, in either group. In addition, we observed no change in the ratio of expression of the myosin heavy chain ß-isoform to that of the α-isoform. Fibrosis was not observed in any of the groups. In conclusion, our results suggest that increasing exercise volume and intensity did not induce a pathological hypertrophy phenotype, but instead improved the oxidative capacity, and this process might have the participation of the RAS alternative axis.

Study of anesthetics for euthanasia in rats and mice: A systematic review and meta-analysis on the impact upon biological outcomes (SAFE-RM).

AIM: To summarize the knowledge on the effect of anesthetics employed right before euthanasia on biological outcomes. DATA SOURCE: A systematic review of the literature to find studies with isoflurane, ketamine, halothane, pentobarbital, or thiopental just before euthanasia of laboratory rats or mice. STUDY SELECTION: Controlled studies with quantitative data available. DATA EXTRACTION: The search, data extraction, and risk of bias (RoB) were performed independently by two reviewers using a structured form. For each outcome, an effect size (ES) was calculated relative to the control group. Meta-analysis was performed using robust variance meta-regression for hierarchical data structures, with adjustment for small samples. DATA SYNTHESIS: We included 20 studies with 407 biological outcomes (110 unique). RoB analysis indicated that 87.5% of the domains evaluated showed unclear risk, 2% high risk, and 10.5% low risk. The effect size for all anesthetics considered together was 0.99 (CI95% = 0.75-1.23; p < 0.0001). Sub-analyses indicate high effect sizes for pentobarbital (1.14; CI95% = 0.75-1.52; p < 0.0001), and isoflurane (1.01; CI95% = 0.58-1.44; p = 0.0005) but not for ketamine (1.49; CI95% = -7.95-10.9; p = 0.295). CONCLUSION: We showed that anesthetics interfere differently with the majority of the outcomes assessed. However, our data did not support the use of one anesthetic over others or even the killing without anesthetics. We conclude that outcomes cannot be compared among studies without considering the killing method. This protocol was registered at Prospero (CRD42019119520). FUNDING: There was no direct funding for this research.

Exercise training modalities for heart transplant recipients: a systematic review and network meta-analysis protocol.

INTRODUCTION: Heart transplantation is the gold standard treatment for selected patients with end-stage heart failure. Although this procedure can improve quality and prolong life expectancy, several of these patients persist with decreased exercise tolerance. Evidence suggests that exercise training can bring multifactorial benefits to heart transplant (HTx) recipients. However, it is unclear that exercise modality should be preferred. Therefore, the aim of this systematic review and network meta-analysis is to compare the efficacy and safety of different training modalities in HTx recipients. METHODS AND ANALYSIS: We will perform a comprehensive literature search in PubMed/MEDLINE, Embase, The Cochrane Library, CINAHL, Scopus, SportDISCUS, Web of Science Core Collection and PEDro from inception until November 2020. Two registries (ClinicalTrials.gov and REBEC) will also be searched for potential results in unpublished studies. There will be no restriction on language, date of publication, publication status or sample size. We will include randomised controlled trials enrolling adult HTx recipients with the presence of at least one exercise training group, which might be compared with another training modality and/or a non-exercise control group for a minimum of 4 weeks of intervention. The primary outcomes will be peak oxygen consumption and occurrence of adverse events. As secondary outcomes, the interaction between pulmonary ventilation, pulmonary perfusion and cardiac output, oxygen uptake efficiency slope, heart rate response, oxygen pulse, peak blood pressure and peak subjective perception of effort. In addition, we will evaluate the 6 min walking distance, health-related quality of life, endothelial function, muscle strength, body fat percentage and lean mass. Risk of bias will be assessed using the Cochrane RoB V.2.0 tool, and we plan to use the Confidence in Network Meta-Analysis tool to assess confidence in the results. All materials (raw data, processed data, statistical code and outputs) will be shared in a public repository. ETHICS AND DISSEMINATION: Given the nature of this study, no ethical approval will be required. We believe that the findings of this study may show which is the most efficacious and safe physical training modality for HTx recipients. The completed systematic review and network meta-analysis will be submitted to a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42020191192.

Incidence of injuries in soccer players - mappingfoot: a prospective cohort study / Incidencia de lesiones en jugadores de fútbol - mappingfoot: un estudio de cohorte prospectivo / Incidência de lesões em jogadores de futebol - mappingfoot: um estudo de coorte prospectivo

ABSTRACT Introduction: Although the positive effects of physical activity on global health are well documented, sports practice is associated with a greater risk of injury; in professional soccer in particular, the risk is substantial. Objective: The primary objective of this study was to investigate the incidence of injuries among male athletes competing in the regional soccer championship. The secondary objective was to determine the prevalence of injuries. Methods: In this prospective cohort study, level of evidence II, the incidence and prevalence of injuries were assessed using an adapted version of the UEFA Champions League Study questionnaire. Results: This study included 310 male athletes from ten teams, aged 26.53±4.75 years, height 180.93±6.49 cm, and weight 79.32±8.29 kg, with a 4-month follow-up. Ninety-two injuries were recorded, representing a prevalence of 29.68% injuries. The body part most frequently injured was the lower limbs (86.9%). The main types of injuries were muscle tear/strain (37.0%), sprain/ligament (19.6%), and other injuries (14.1%). The injuries were mainly caused during run/sprint (33.7%), kick (12.0%) and jumping/landing (6.5%). The incidences of injuries were 15.88±8.57, 2.04±1.09, and 3.65±1.50 injuries/1000h of exposure during matches, training, and matches/training, respectively. Time-loss over the season was between 1 and 50 days, and the severity of the injuries was as follows: light (25%), minor (22.8%), moderate (43.5%) and severe (8.7%). Conclusion: This study suggests that there is a higher incidence of injuries during matches compared to training, among male regional soccer championship players. The lower limbs are the body part most affected, with a higher prevalence of rupture/strain in the thigh region, during running/sprinting. Level of evidence II; Prospective Cohort Study .

RESUMEN Introducción: Aunque los efectos positivos de la actividad física en la salud global estén bien documentados, la práctica deportiva está asociada a un riesgo mayor de lesiones; especialmente en el fútbol profesional, el riesgo es sustancial. Objetivo: El objetivo primario de este estudio fue investigar la incidencia de lesiones en atletas del sexo masculino que compiten en campeonatos regionales de fútbol. El resultado secundario fue determinar la prevalencia de lesiones. Métodos: En este estudio de cohorte prospectivo, nivel de evidencia II, la incidencia y la prevalencia de lesiones fueron evaluadas usando una versión adaptada del cuestionario de estudio de la Liga de Campeones de la UEFA. Resultados: Este estudio incluyó a 310 atletas del sexo masculino de 10 equipos, edad 26,53 ± 4,75 años, estatura 180,93 ± 6,49 cm y peso 79,32 ± 8,29 kg, durante 4 meses de acompañamiento. Se registraron 92 lesiones, lo que representa una prevalencia de 29,68%. La parte del cuerpo que tuvo lesiones más frecuentes fueron los miembros inferiores (86,9%). Los principales tipos de lesión fueron rotura/distensión muscular (37,0%), esguince/ligamento (19,6%) y otras lesiones (14,1%). Las lesiones fueron causadas principalmente durante carrera/sprint (33,7%), puntapié (12,0%) y salto/aterrizaje (6,5%). La incidencia de lesiones fue de 15,88 ± 8,57, 2,04 ± 1,09 y 3,65 ± 1,50 lesiones/1000 horas de exposición durante partidos, entrenamientos y partidos/entrenamientos, respectivamente. El tiempo de alejamiento en la temporada varió de 1 a 50 días, y la gravedad de las lesiones fue la siguiente: leve (25%), menor (22,8%), moderada (43,5%) y grave (8,7%). Conclusión: El presente estudio sugiere que existe mayor incidencia de lesiones durante los partidos en comparación con los entrenamientos entre jugadores del sexo masculino en campeonatos regionales de fútbol. Los miembros inferiores son la región más acometida, con mayor prevalencia de rotura/distensión en la región del muslo durante la carrera/sprint. Nivel de evidencia II, Estudio de cohorte prospectivo .

RESUMO Introdução: Embora os efeitos positivos da atividade física na saúde global sejam bem documentados, a prática esportiva está associada a um risco maior de lesões; especialmente no futebol profissional, o risco é substancial. Objetivo: O objetivo primário deste estudo foi investigar a incidência de lesões em atletas do sexo masculino que competem em campeonatos regionais de futebol. O objetivo secundário foi determinar a prevalência de lesões. Métodos: Neste estudo de coorte prospectivo, nível de evidência II, a incidência e a prevalência de lesões foram avaliados usando uma versão adaptada do questionário de estudo da Liga dos Campeões da UEFA. Resultados: Este estudo incluiu 310 atletas do sexo masculino de 10 equipes, com idade 26,53 ± 4,75 anos, estatura 180,93 ± 6,49 cm e peso 79,32 ± 8,29 kg, durante 4 meses de acompanhamento. Foram registradas 92 lesões, o que representa uma prevalência de 29,68%. A parte do corpo que teve lesões mais frequentes foram os membros inferiores (86,9%). Os principais tipos de lesão foram ruptura/distensão muscular (37,0%), entorse/ligamento (19,6%) e outras lesões (14,1%). As lesões foram causadas principalmente durante corrida/sprint (33,7%), chute (12,0%) e salto/aterrissagem (6,5%). A incidência de lesões foi de 15,88 ± 8,57, 2,04 ± 1,09 e 3,65 ± 1,50 lesões/1.000 horas de exposição durante jogos, treinamento e jogos/treinamento, respectivamente. O tempo de afastamento na temporada variou de 1 a 50 dias e a gravidade das lesões foi a seguinte: leve (25%), menor (22,8%), moderada (43,5%) e grave (8,7%). Conclusão: O presente estudo sugere que existe maior incidência de lesões durante os jogos em comparação com os treinos entre jogadores do sexo masculino em campeonatos regionais de futebol. Os membros inferiores são a região mais acometida, com maior prevalência de ruptura/distensão na região da coxa durante a corrida/sprint. Nível de evidência II; Estudo de coorte prospectivo .