Human skeletal muscle has large capacity to increase carnosine content in response to beta-alanine supplementation: a systematic review with Bayesian individual and aggregate data E-Max model and meta-analysis.

Beta-alanine (BA) supplementation increases muscle carnosine content (MCarn) and is ergogenic in many situations. Currently, many questions on the nature of the Mcarn response to supplementation are open, and the responses to these have considerable potential to enhance the efficacy and applications of this supplementation strategy. The objective of this study was to conduct a Bayesian analysis of available data on the Mcarn response to BA supplementation. A systematic review (with meta-analysis) of individual and published aggregate data was conducted, using a dose response (Emax) model. The protocol was designed according to PRISMA guidelines. A three-step screening strategy was undertaken in order to identify studies that measured the Mcarn response to BA supplementation. In addition, the research analysed individual data from five separate studies, conducted in the authors' laboratory. Data were extracted from all controlled and uncontrolled supplementation studies conducted on healthy humans. Meta-regression was used to consider the influence of potential moderators on the primary outcome, including dose, sex, age, baseline Mcarn and analysis method used. The Emax model indicated that human skeletal muscle has a large capacity for non-linear Mcarn accumulation and that commonly-used BA supplementation protocols may not come close to saturating muscle carnosine content. Neither baseline values nor sex appear to influence subsequent response to supplementation. Analysis of individual data indicated that Mcarn is relatively stable in the absence of intervention, and effectually all participants respond to BA supplementation (99.3% response [95%CrI: 96.2 –100])

UM RELATO DA DOCÊNCIA

O presente artigo apresenta reflexões sobre a realidade do trabalho docente a partir de questões atuais vivenciadas por professores. Desta maneira, o objetivo é apresentar e refletir aspectos acerca de uma experiência formativa de pesquisa e prática pedagógica de estágio remoto emergencial enquanto processo de formação inicial de licenciandos. O artigo fundamenta-se nos pressupostos qualitativos de pesquisa em educação. Desta forma, foram abordados, por meio de um relato de experiência, tecido nas atividades de estágio supervisionado, alguns dos desafios enfrentados dentro da sala de aula e do cotidiano do trabalho docente, apontando como a sociedade contribui para a desvalorização da profissão. Há nesse sentido, uma via de mão dupla acerca das expectativas em relação à docência: de um lado, o professor que deve oferecer aulas de qualidade e priorizar uma séria formação para uma melhor atuação que preze pelo respeito à diversidade e à subjetividade; e do outro, se espera o reconhecimento social e valorização profissional, além de autonomia para melhor realizar suas atividades e ter seus direitos garantidos

Structure-Activity relationship of novel second-generation synthetic cathinones: Mechanism of action, locomotion, reward, and immediate-early genes

Several new synthetic cathinones, which mimic the effect of classical psychostimulants such as cocaine or MDMA, have appeared in the global illicit drug market in the last decades. In fact, the illicit drug market is continually evolving by constantly adding small modifications to the common chemical structure of synthetic cathinones. Thus, the aim of this study was to investigate the in vitro and in vivo structure-activity relationship of six novel synthetic cathinones currently popular as recreational drugs, Pentedrone, Pentylone, N-ethyl-pentedrone (NEPD), N-ethyl-pentylone (NEP), 4-methyl-pentedrone (4-MPD) and 4-methyl-ethylaminopentedrone (4-MeAP), which structurally differ in the absence or presence of different aromatic substituents and in their amino terminal group. Human embryonic kidney cells (HEK293) expressing the human isoforms of SERT and DAT were used for the uptake inhibition and release assays. Moreover, Swiss-CD-1 mice were used to investigate their psychostimulant effect, rewarding properties (3, 10 and 30 mg/kg, i.p.) and the induction of immediate-early genes (IEGs) such as arc and c-fos in dorsal (DS) and ventral striatum (VS) as well as bdnf in medial prefrontal cortex (mPFC). Our results demonstrated that all tested synthetic cathinones are potent dopamine (DA) uptake inhibitors, especially the N-ethyl analogues, while the ring-substituted cathinones tested showed higher potency as SERT inhibitors than their no ring-substituted analogues. Moreover, unlike NEP, all tested compounds showed 'hybrid' properties, acting as DAT blockers but SERT substrates. Regarding the locomotion, NEP and NEPD were more efficacious (10 mg/kg) than their N-methyl analogues, which correlates with their higher potency inhibiting DAT and an overexpression of arc levels in DS and VS. Furthermore, all compounds tested induced an increase in c-fos expression in DS, except for 4-MPD, the least effective compound at inducing hyperlocomotion. Moreover, NEP induced an up-regulation of bdnf in mPFC that correlates whit its 5-HTergic properties. Finally, the present study demonstrated for the first time that pentylone, NEP, 4-MPD and 4-MeAP induce reward in mice. Altogether, this study provides valuable information about the mechanism of action, psychostimulant and rewarding properties as well as changes in the expression of IEGs related to addiction induced by novel second-generation synthetic cathinones

Many Labs 5:Testing pre-data collection peer review as an intervention to increase replicability

Replication studies in psychological science sometimes fail to reproduce prior findings. If these studies use methods that are unfaithful to the original study or ineffective in eliciting the phenomenon of interest, then a failure to replicate may be a failure of the protocol rather than a challenge to the original finding. Formal pre-data-collection peer review by experts may address shortcomings and increase replicability rates. We selected 10 replication studies from the Reproducibility Project: Psychology (RP:P; Open Science Collaboration, 2015) for which the original authors had expressed concerns about the replication designs before data collection; only one of these studies had yielded a statistically significant effect (p < .05). Commenters suggested that lack of adherence to expert review and low-powered tests were the reasons that most of these RP:P studies failed to replicate the original effects. We revised the replication protocols and received formal peer review prior to conducting new replication studies. We administered the RP:P and revised protocols in multiple laboratories (median number of laboratories per original study = 6.5, range = 3?9; median total sample = 1,279.5, range = 276?3,512) for high-powered tests of each original finding with both protocols. Overall, following the preregistered analysis plan, we found that the revised protocols produced effect sizes similar to those of the RP:P protocols (?r = .002 or .014, depending on analytic approach). The median effect size for the revised protocols (r = .05) was similar to that of the RP:P protocols (r = .04) and the original RP:P replications (r = .11), and smaller than that of the original studies (r = .37). Analysis of the cumulative evidence across the original studies and the corresponding three replication attempts provided very precise estimates of the 10 tested effects and indicated that their effect sizes (median r = .07, range = .00?.15) were 78% smaller, on average, than the original effect sizes (median r = .37, range = .19?.50)