A matter of food and substrain: obesogenic diets induce differential severity of cardiac remodeling in C57Bl/6J and C57Bl/6N substrains.

The prevalence of metabolic syndrome in cardiac diseases such as heart failure with preserved ejection fraction (HFpEF) prompts the scientific community to investigate its adverse effects on cardiac function and remodeling. However, the selection of a preclinical model of obesity-induced cardiac remodeling has proven more challenging with inconsistencies often found in very similar mouse models. Here, we investigated the implication of genetic background as well as diet composition to identify a suitable model of diet-induced cardiac alterations. C57Bl/6J and C57Bl/6N male mice were subjected to distinct obesogenic diets consisting of high-fat and moderate-sucrose content (HF-S) or High-Sucrose and moderate-lipid content (F-HS) versus matching control diets. 5-month dietary intervention with obesogenic diets induced weight gain, adipocyte hypertrophy and increased visceral and subcutaneous fat mass in both substrains. Obese mice showed similar impairment of glucose disposition and insulin tolerance, both strains developing insulin resistance within two months. However, echocardiographic follow-up and histological analysis confirmed that HF-S diet increases cardiac hypertrophy, interstitial fibrosis as well as left atrial area in the C57Bl/6J strain only. On the contrary C57Bl/6N exhibit cardiac eccentric remodeling under control diets, possibly owing to a genetic mutation in the myosin light-chain-kinase 3 (Mylk3) gene, specific to this substrain, which was not further enhanced under obesogenic diets. Altogether, the present results highlight the importance of carefully selecting the suitable mouse strain and diets to model diet-induced cardiac remodeling. In this regard, C57Bl/6J mice develop significant cardiac remodeling in response to HF-S, and seem a suitable model for cardiometabolic disease.

Exploring the impact of violence in video games.

Playing a violent game for a few weeks did not alter neural and behavioral responses to the pain of others in inexperienced male gamers.

Comparing Sequence-Based and Literature-Based Pathogenicity Scoring Methods for Human Variants.

Assessing the pathogenicity of genetic variants is a critical aspect of genomic medicine and precision healthcare. Over the last decades, the identification of genetic variants and their characterization has become simpler (advent of high-throughput sequencing technologies, analysis, and visualization support tools, etc.). However, the quality of assessments to distinguish benign from pathogenic variants is critical to inform clinical decision-making and improve patient outcomes. In this article, we investigate the relationships using correlation tests between the characterization of genetic variants in the literature and their pathogenicity scores computed by two state-of-the-art assessment tools (SIFT and PolyPhen-2).

Pain reflects the informational value of nociceptive inputs.

ABSTRACT: Pain perception and its modulation are fundamental to human learning and adaptive behavior. This study investigated the hypothesis that pain perception is tied to pain's learning function. Thirty-one participants performed a threat conditioning task where certain cues were associated with a possibility of receiving a painful electric shock. The cues that signaled potential pain or safety were regularly changed, requiring participants to continually establish new associations. Using computational models, we quantified participants' pain expectations and prediction errors throughout the task and assessed their relationship with pain perception and electrophysiological responses. Our findings suggest that subjective pain perception increases with prediction error, that is, when pain was unexpected. Prediction errors were also related to physiological nociceptive responses, including the amplitude of nociceptive flexion reflex and electroencephalography markers of cortical nociceptive processing (N1-P2-evoked potential and gamma-band power). In addition, higher pain expectations were related to increased late event-related potential responses and alpha/beta decreases in amplitude during cue presentation. These results further strengthen the idea of a crucial link between pain and learning and suggest that understanding the influence of learning mechanisms in pain modulation could help us understand when and why pain perception is modulated in health and disease.

Relative dose intensity of first-line triplet chemotherapy in metastatic colorectal cancer.

PURPOSE: Relative dose intensity (RDI) is a measurement of chemotherapy (CT) dose defined as the actual dose received divided by the standard calculated dose during a set period. The study objective was to assess the impact of a RDI ≥ 80% on response and survival of patients treated in first line CT by FOLFOXIRI or FOLFIRINOX ± Bevacizumab (BV) for an unresectable metastatic colorectal cancer (mCRC). MATERIALS AND METHODS: It was a retrospective, non-interventional, multicenter study calculating RDI from the first cycles of CT to the first CT-scan evaluation (CT-scan1). Objective response and disease control rates (ORR and DCR), progression-free survival (PFS) and overall survival (OS) were compared between patients with RDI ≥ 80% and <80% and results were adjusted for age, gender, ECOG, tumor location, number of metastatic sites, RAS and BRAF status, the CT regimen, the use of BV, the delay from C1 to CT scan1. RESULTS: Among 152 screened patients, 100 met inclusion criteria, with a mean (± standard deviation) age at 59.0 (± 10.7) years. The ECOG performance status was 0-1 in 96 (96%) patients; metastases were synchronous in 95 (95%), RAS and BRAF were mutated in 60 (60%) and 22 (22%), respectively. ORR was observed in 51 (51%) at CT-scan1 with median PFS and OS of 10.5 and 21.9 months, respectively. A RDI ≥ 80% was observed in 44 (44%) patients without impact on ORR (ORa: 1.04, 95% CI: 0.37 to 2.89, p = 0.94) but was significantly associated to improved PFS and OS with HRa 0.50 (95%CI: 0.29 to 0.87, p = 0.013) and 0.52 (95% CI: 0.29 to 0.91, p = 0.023), respectively. CONCLUSION: Our results suggest a low level of FOLFOXIRI or FOLFIRINOX +/- BV exposure in first-line mCRC is associated with a significant trend on PFS and OS.

A anamnese nas epilepsias / Clinical examination in epilepsy

Para evitar grandes desníveis na informaçäo obtida através da anamnese de pacientes epilépticos no ambulatório de Neurologia de um Hospital Universitário, elaborou-se um roteiro para atendimento. Adicionalmente elaborou-se questionário que pode ser utilizado para guia no atendimento e, pelos familiares dos pacientes acometidos por epilepsias graves da infância, para descriçäo mais adequada das crises epilépticas. Questionário e roteiros säo expostos. Um exemplo da utilidade do primeiro é mostrado através das descriçöes de crises efetuadas pela genitora de uma paciente

Reflexöes sobre a formaçäo do pesquisador nas áreas médicas no Brasil ou a propósito de "A anamnese nas epilepsias" e "Protocolo de estudos em epilepsia: um modelo simples e eficiente" / Reflections on the training of researches in the medical area in Brasil, or about \"Anamnesis in epilepsy\" and \"Study protocols in epilepsy: a simple and efficient model\"

Nos trabalhos científicos publicados no país nem sempre se identificam cuidados com a ortografia, obediência as regras gramaticais vigentes e utilizaçäo das palavras de maneira a ser preservado o seu conteúdo simbólico. Hipóteses näo testadas, sao, por vezes, tomadas a priori como base para estudos em serie, cujos resultados podem ser completamente diferentes do que seriam, caso as mesmas tivessem sido testadas previamente. A análise crítica de trabalhos científicos pode pecar por comparaçäo de dados, ou instrumentais de colheita de dados, diferentes quanto ao seu objetivo e possibilidades informativas. O trabalho recentemente publicado por Bittencourt & Silvado é prodigo em exemplos no referente aos tres topicos analisados. Alguns desses exemplos foram destacados a guisa de ilustraçäo e com finalidade de demonstrar que as questöes aqui levantadas estao longe de serem abstratas. Na condiçäo de hipotese para justificar os problemas mencionados, invoca-se a possibilidade de que as escolas médicas näo estejam dando suficiente atençäo as questöes referidas. Cursos de pos-graduaçäo näo sao frequentados por todos os que pretendam se dedicar a pesquisa médica no país e podem näo incluir disciplinas dedicadas aos temas em discussao. Por essas razöes, sugerimos que sejam incluidas nos curriculos das escolas médicas disciplinas dedicadas a metodologia da pesquisa, análise crítica de trabalhos científicos e ao treinamento no que se refere a redaçäo de trabalhos científicos. Tal atitude poderia ser estimulante no sentido de que mais profissionais se dedicassem a pesquisa médica ou pudessem transmitir, dentro de parametros aceitaveis, as suas experiencias

Epilepsia na síndome do anel do cromossomo 14 / Epilepsy in ring chromosome 14 syndrome

Os autores relatam o caso de paciente, com anel do cromossomo 14. Com base neste e na revisäo de 28 casos publicados, determinam a freqüência dos sinais e sintomas clínicos, salientam a incidência constante e precoce de crises epilépticas e descrevem suas características. Enumeraram as malformaçöes congênitas associadas e chamam a atençäo para sua importância na indicaçäo do cariótipo e conseqüente detecçäo de novos casos