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Atrial fibrillation (AF), the most common arrhythmia, has been associated with different electrophysiological, molecular, and structural alterations in atrial cardiomyocytes. Therefore, more studies are required to elucidate the genetic and molecular basis of AF. Various genome-wide association studies (GWAS) have strongly associated different single nucleotide polymorphisms (SNPs) with AF. One of these GWAS identified the rs13376333 risk SNP as the most significant one from the 1q21 chromosomal region. The rs13376333 risk SNP is intronic to the KCNN3 gene that encodes for small conductance calcium-activated potassium channels type 3 (SK3). However, the functional electrophysiological effects of this variant are not known. SK channels represent a unique family of K+ channels, primarily regulated by cytosolic Ca2+ concentration, and different studies support their critical role in the regulation of atrial excitability and consequently in the development of arrhythmias like AF. Since different studies have shown that both upregulation and downregulation of SK3 channels can lead to arrhythmias by different mechanisms, an important goal is to elucidate whether the rs13376333 risk SNP is a gain-of-function (GoF) or a loss-of-function (LoF) variant. A better understanding of the functional consequences associated with these SNPs could influence clinical practice guidelines by improving genotype-based risk stratification and personalized treatment. Although research using native human atrial cardiomyocytes and animal models has provided useful insights, each model has its limitations. Therefore, there is a critical need to develop a human-derived model that represents human physiology more accurately than existing animal models. In this context, research with human induced pluripotent stem cells (hiPSC) and subsequent generation of cardiomyocytes derived from hiPSC (hiPSC-CMs) has revealed the underlying causes of various cardiovascular diseases and identified treatment opportunities that were not possible using in vitro or in vivo studies with animal models. Thus, the ability to generate atrial cardiomyocytes and atrial tissue derived from hiPSCs from human/patients with specific genetic diseases, incorporating novel genetic editing tools to generate isogenic controls and organelle-specific reporters, and 3D bioprinting of atrial tissue could be essential to study AF pathophysiological mechanisms. In this review, we will first give an overview of SK-channel function, its role in atrial fibrillation and outline pathophysiological mechanisms of KCNN3 risk SNPs. We will then highlight the advantages of using the hiPSC-CM model to investigate SNPs associated with AF, while addressing limitations and best practices for rigorous hiPSC studies.

Abstract Objectives: to evaluate the association of episiotomy with pelvic floor function and the occurrence of urinary and fecal incontinence in primiparous adolescents. Methods: a cross-sectional study was conducted with primiparous adolescents aged ten to 19 years, seven and 48 months before data collection. Participants completed a form containing their personal data and the International Consultation on Urinary Incontinence (UI) Short Form, Incontinence Severity Index and the Jorge & Wexner Incontinence Scale. Results: the mean values were statistically significant for the variables analyzed. Lower mean values were obtained for strength, endurance and number of sustained and rapid contractions in the group exposed to episiotomy, compared to the control group. Episiotomy increased the odds of: UI (OR= 15.2; CI95%= 8.1-28.4), UI-related changes in quality of life (OR= 15.9; CI95%= 8.5-30.0), fecal incontinence (OR= 18.5; CI95%= 6.4-5.7) and constipation (OR= 10.8; CI95%= 4.8-24.2) in primiparous adolescents, compared to the control group. Conclusions: episiotomy can negatively influence pelvic floor function and urinary and fecal retention. Professionals working in maternal health care should be aware of and reflect on obstetric practices during childbirth in adolescents.

Objective: To analyze the Benefit of Modulated Masking (BMM) on hearing in young, adult and elderly normal-hearing individuals. Methods: The sample included 60 normal-hearing individuals aged 18–75 years who underwent behavioral assessment (sentence recognition test in the presence of steady and modulated noise) and electrophysiological assessment (cortical Auditory Evoked Potential) to investigate BMM. The results were analyzed comparatively using the paired t-test and ANOVA for repeated measures, followed by the Bonferroni post-hoc test (p-value

Zooplankton such as copepods and krill are currently used to produce marine oil supplements, with the aim of helping consumers achieve the recommended intake of n-3 long chain polyunsaturated fatty acids (n-3 LC-PUFAs). Oils from lower trophic levels differ from fish oil in the distribution of lipids into different classes, and this can influence the bioaccessibility of fatty acids, i.e., the percentage of fatty acids that are released into the intestine in a form that can be absorbed by enterocytes. We evaluated fatty acid release after in vitro digestion in four commercial marine oil supplements containing fish, krill and Calanus finmarchicus oils using two different analytical approaches, TLC-FID and 1H-NMR spectroscopy. The results clearly indicated that the release of free fatty acids (FFAs) after simulated digestion mainly depends on the oil source and is mainly related to the partitioning of lipids into different classes. In fact, the lowest FFA release was detected in Calanus oils, which contain high amounts of wax esters. The different release of FFAs, which appeared secondarily related to encapsulation, can modulate the absorption and blood concentration of the administered n-3 LC-PUFAs and therefore their efficacy. This may partly explain the inconsistencies in intervention studies using marine oil supplements.

O trabalho maneja o conceito de campo de controle do crime de David Garland, ao mesmo tempo que discute suas limitações e potencialidades, a partir das teorizações da criminologia do sul. A perspectiva epistemológica critica o manejo de estudos criminológicos advindos do norte global, que têm a pretensão de explicações universalistas e generalizantes, e propõe que as peculiaridades locais políticas, históricas, econômicas e culturais sejam consideradas. Seguindo essa perspectiva, aponta o texto que o ponto de partida da análise das questões criminais é essencial, porém a sociologia brasileira há muito já aponta caminhos no mesmo sentido, de modo que o racismo é uma estrutura reatualizada no sistema de justiça criminal que impede se falar de mudança no sentido do punitivismo, indicando permanências.

Quem são as pessoas presas em flagrante por tráfico de drogas no Recife durante a pandemia? As gratificações pagas aos policiais em razão do Programa Pacto pela Vida demonstram algum impacto nas prisões neste período? O estudo mapeia prisões em flagrante por tráfico de entorpecentes em Recife (Pernambuco) entre 17 de março de 2020 e 17 de março de 2021, apresentando dados quantitativos referentes ao perfil dos sujeitos presos e as condições de realização do flagrante. De um lado, dispensando maiores esforços teóricos em torno de uma já solidificada discussão criminológica acerca da seletividade que opera no sistema punitivo, evidencia-se continuidades, em que o jovem preto ou pardo, de baixa escolaridade e frequentador das áreas periféricas da cidade é o alvo preferencial da polícia militar; de outro, discute-se o incremento das práticas autoritárias apresentadas, analiticamente, em três blocos: a perversidade do sistema de justiça criminal para quem não teve o direito de lutar para viver, as ilegalidades relativas ao flagrante e a monetarização da violência policial. A partir da lente teórica da criminologia atuarial, somada ao cruzamento dos dados, compreende-se a política de segurança por uma perspectiva eficientista e identifica-se a potencialização de violações a direitos fundamentais, dado o cenário de emergência sanitária.

Atrial fibrillation (AF), the most common arrhythmia, has been associated with different electrophysiological, molecular, and structural alterations in atrial cardiomyocytes. Therefore, more studies are required to elucidate the genetic and molecular basis of AF. Various genome-wide association studies (GWAS) have strongly associated different single nucleotide polymorphisms (SNPs) with AF. One of these GWAS identified the rs13376333 risk SNP as the most significant one from the 1q21 chromosomal region. The rs13376333 risk SNP is intronic to the KCNN3 gene that encodes for small conductance calcium-activated potassium channels type 3 (SK3). However, the functional electrophysiological effects of this variant are not known. SK channels represent a unique family of K+ channels, primarily regulated by cytosolic Ca2+ concentration, and different studies support their critical role in the regulation of atrial excitability and consequently in the development of arrhythmias like AF. Since different studies have shown that both upregulation and downregulation of SK3 channels can lead to arrhythmias by different mechanisms, an important goal is to elucidate whether the rs13376333 risk SNP is a gain-of-function (GoF) or a loss-of-function (LoF) variant. A better understanding of the functional consequences associated with these SNPs could influence clinical practice guidelines by improving genotype-based risk stratification and personalized treatment. Although research using native human atrial cardiomyocytes and animal models has provided useful insights, each model has its limitations. Therefore, there is a critical need to develop a human-derived model that represents human physiology more accurately than existing animal models. In this context, research with human induced pluripotent stem cells (hiPSC) and subsequent generation of cardiomyocytes derived from hiPSC (hiPSC-CMs) has revealed the underlying causes of various cardiovascular diseases and identified treatment opportunities that were not possible using in vitro or in vivo studies with animal models. Thus, the ability to generate atrial cardiomyocytes and atrial tissue derived from hiPSCs from human/patients with specific genetic diseases, incorporating novel genetic editing tools to generate isogenic controls and organelle-specific reporters, and 3D bioprinting of atrial tissue could be essential to study AF pathophysiological mechanisms. In this review, we will first give an overview of SK-channel function, its role in atrial fibrillation and outline pathophysiological mechanisms of KCNN3 risk SNPs. We will then highlight the advantages of using the hiPSC-CM model to investigate SNPs associated with AF, while addressing limitations and best practices for rigorous hiPSC studies.

Despite recent advances in prevention, detection and treatment, oral squamous cell carcinoma (OSCC) remains a global health concern, strongly associated with environmental and lifestyle risk factors and infection with oncogenic viruses. Merkel Cell Polyomavirus (MCPyV), well known to be the causative agent of Merkel Cell Carcinoma (MCC) has been found in OSCC, suggesting its potential role as a co-factor in the development of oral cavity cancers. To improve our understanding about MCPyV in oral cavities, the detection and analysis of MCPyV DNA, transcripts and miRNA were performed on OSCCs and oral potentially malignant disorders (OPMDs). In addition, the cellular miR-375, known to be deregulated in tumors, was examined. MCPyV DNA was found in 3 out of 11 OSCC and 4 out of 12 OPMD samples, with a viral mean value of 1.49 × 102 copies/mL. Viral integration was not observed and LTAg and VP1 transcripts were detected. Viral miRNAs were not detected whereas the cellular miR-375 was found over expressed in all MCPyV positive oral specimens. Our results reported evidence of MCPyV replication in both OSCC and OPMD suggesting the oral cavity as a site of replicative MCPyV infection, therefore underscoring an active role of this virus in the occurrence of oral lesions.