6 research outputs found

    Alternative splicing of MALT1 controls signaling and activation of CD4+ T cells

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    Avaliação do consumo dietético, desidratação e grau de fadiga em um grupo de ciclistas amadores

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    Introdução e objetivo: O ciclismo é uma modalidade esportiva cada vez mais comum entre os indivíduos. Uma alimentação desiquilibrada, bem como uma ingestão hídrica inadequada podem exercer papel importante na fadiga e no desempenho do atleta. Portanto, este estudo objetivou avaliar o consumo dietético, a desidratação e o grau de fadiga de ciclistas amadores após um treino de 54 km. Materiais e métodos: Trata-se de um estudo transversal, com 12 ciclistas amadores, do sexo masculino e idade entre 27-61 anos, de um grupo de ciclistas de Santa Cruz do Sul-RS, Brasil. Determinou-se o consumo dietético pelo programa DietWin, a partir do registro alimentar de 24h. A desidratação foi determinada pela porcentagem de perda de peso e utilizou-se a escala subjetiva de Borg para avaliar o grau de fadiga. Discussão e Resultados: Dos ciclistas avaliados, 41,7% apresentavam ingestão inadequada de calorias e 50% estavam ingerindo carboidratos insuficientes, assim como 50% deles estavam consumindo gorduras em excesso. Quanto ao consumo de micronutrientes, observou-se uma prevalência de inadequação de 100% para vitamina D. Observou-se baixo consumo e ingestão acima da UL para potássio e o sódio, respectivamente. Com relação a desidratação, os ciclistas apresentaram-se levemente desidratados ou desidratação significante e o treino ciclístico realizado foi considerado razoavelmente fácil (41,7%) ou um pouco difícil (33,3%). Conclusão: Estes dados demostram que ciclistas amadores tendem a realizar uma alimentação desiquilibra, que pode influenciar no seu desempenho. Contudo, mesmo apresentando desidratação leve ou significante, pouco influenciou na percepção subjetiva de fadiga dos mesmos. ABSTRACT Evaluation of dietary intake, dehydration and degree of fatigue in a group of amateur cyclistsIntroduction and Aim: Cycling is a sport modality increasingly common among individuals. Unbalanced diet as well as inadequate water intake can play an important role in athlete fatigue and performance. Therefore, this study aimed to evaluate the dietary intake, dehydration and degree of fatigue of amateur cyclists after a training of 54 km. Materials and Methods: This is a cross-sectional study with 12 male amateur cyclists and 27-61 years old from a group of cyclists from Santa Cruz do Sul-RS, Brazil. Dietary intake was determined by the DietWin program, based on the 24-hour food record. Dehydration was determined by the percentage of weight loss and the subjective Borg scale was used to evaluate the degree of fatigue. Discussion and Results: Of cyclists evaluated, 41.7% presented inadequate calorie intake and 50% were eating insufficient carbohydrates and just as 50% of them were consuming excess fats. Regarding micronutrient intake, a prevalence of inadequacy of 100% for vitamin D was observed. Low intake and intake above UL were observed for potassium and sodium, respectively. Concerning dehydration, cyclists were slightly dehydrated or significant dehydration, and cycling training was considered reasonably easy (41.7%) or slightly difficult (33.3%). Conclusion: These data demonstrate that amateur cyclists tend to perform unbalanced feeding, which may influence their performance. However, even with mild or significant dehydration, it had little influence on the subjective perception of fatigue

    Alternative splicing of MALT1 controls signalling and activation of CD4+ T cells

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    MALT1 channels proximal T-cell receptor (TCR) signalling to downstream signalling pathways. With MALT1A and MALT1B two conserved splice variants exist and we demonstrate here that MALT1 alternative splicing supports optimal T-cell activation. Inclusion of exon7 in MALT1A facilitates the recruitment of TRAF6, which augments MALT1 scaffolding function, but not protease activity. Naive CD4+ T cells express almost exclusively MALT1B and MALT1A expression is induced by TCR stimulation. We identify hnRNP U as a suppressor of exon7 inclusion. Whereas selective depletion of MALT1A impairs T-cell signalling and activation, downregulation of hnRNP U enhances MALT1A expression and T-cell activation. Thus, TCR-induced alternative splicing augments MALT1 scaffolding to enhance downstream signalling and to promote optimal T-cell activation

    Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

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    BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

    Kidney and Cardiovascular Effects of Canagliflozin According to Age and Sex: A Post Hoc Analysis of the CREDENCE Randomized Clinical Trial

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    Rationale & Objective: It is unclear whether the effect of canagliflozin on adverse kidney and cardiovascular events in those with diabetic kid-ney disease varies by age and sex. We assessed the effects of canagliflozin among age group categories and between sexes in the Canagli-flozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study.Study Design: Secondary analysis of a random-ized controlled trial. Setting & Participants: Participants in the CREDENCE trial. Intervention: Participants were randomly assigned to receive canagliflozin 100 mg/d or placebo.Outcomes: Primary composite outcome of kid-ney failure, doubling of serum creatinine con-centration, or death due to kidney or cardiovascular disease. Prespecified secondary and safety outcomes were also analyzed. Out-comes were evaluated by age at baseline (<60, 60-69, and >_70 years) and sex in the intention-to-treat population using Cox regression models.Results: The mean age of the cohort was 63.0 & PLUSMN; 9.2 years, and 34% were female. Older age and female sex were independently associ-ated with a lower risk of the composite of adverse kidney outcomes. There was no evidence that the effect of canagliflozin on the primary outcome (acomposite of kidney failure, a doubling of serum creatinine concentration, or death from kidney or cardiovascular causes) differed between age groups (HRs, 0.67 [95% CI, 0.52-0.87], 0.63 [0.4 8-0.82], and 0.89 [0.61-1.29] for ages <60, 60-69, and >_70 years, respectively; P = 0.3 for interaction) or sexes (HRs, 0.71 [95% CI, 0.5 4-0.95] and 0.69 [0.56-0.8 4] in women and men, respectively; P = 0.8 for interaction). No differences in safety outcomes by age group or sex were observed.Limitations: This was a post hoc analysis with multiple comparisons.Conclusions: Canagliflozin consistently reduced the relative risk of kidney events in people with diabetic kidney disease in both sexes and across age subgroups. As a result of greater background risk, the absolute reduction in adverse kidney outcomes was greater in younger participants.Funding: This post hoc analysis of the CREDENCE trial was not funded. The CREDENCE study was sponsored by Janssen Research and Development and was conducted collaboratively by the sponsor, an academic-led steering committee, and an academic research organization, George Clinical.Trial Registration: The original CREDENCE trial was registered at ClinicalTrials.gov with study number NCT02065791
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