Previous Catheter Ablation Predicts In-Hospital Restoration of Sinus Rhythm in Patients Presenting with Recent-Onset Atrial Fibrillation-The Retrospective HAMBURG-AF Study.

Background and Objectives: Atrial fibrillation (AF) is the most common arrythmia of the human heart. Patients mostly present highly symptomatic with dyspnea and tachycardia and have a disproportionate risk of developing heart failure or stroke events. We aimed to evaluate the determinants of early conversion into sinus rhythm during initial stay at the emergency department of a large tertiary care center. Materials and Methods: A total of 1384 subjects with recent-onset AF were recruited between October 2014 and April 2017. Patients with longstanding AF were excluded, resulting in a total of 935 patients for the present analysis. Results: In multivariate adjusted logistic regression analyses, previous catheter ablation therapy was a strong predictor of conversion in sinus rhythm during the stay in the emergency department, with an odds ratio (OR) of 3.87 (95% CI 2.40, 6.54; p < 0.001). In contrast, existing antiarrhythmic medication showed no association with facilitated conversion [OR 0.89 (95%CI 0.65, 1.20); p = 0.44]. Likewise, conventional cardiovascular risk factors (hypertension, dyslipidemia, diabetes) were also not associated with conversion during hospital stay. Conclusion: This is the first report on the relevance of previous ablation therapy for early restoration of sinus rhythm in recent-onset AF. Although catheter ablation is associated with relevant risk of late recurrence of atrial fibrillation, it seems to have a large benefit for patients with recent-onset AF.

Activating mutations in CTNNB1 in aldosterone producing adenomas.

Primary aldosteronism (PA) is the most common cause of secondary hypertension with a prevalence of 5-10% in unreferred hypertensive patients. Aldosterone producing adenomas (APAs) constitute a large proportion of PA cases and represent a surgically correctable form of the disease. The WNT signaling pathway is activated in APAs. In other tumors, a frequent cause of aberrant WNT signaling is mutation in the CTNNB1 gene coding for ß-catenin. Our objective was to screen for CTNNB1 mutations in a well-characterized cohort of 198 APAs. Somatic CTNNB1 mutations were detected in 5.1% of the tumors, occurring mutually exclusive from mutations in KCNJ5, ATP1A1, ATP2B3 and CACNA1D. All of the observed mutations altered serine/threonine residues in the GSK3ß binding domain in exon 3. The mutations were associated with stabilized ß-catenin and increased AXIN2 expression, suggesting activation of WNT signaling. By CYP11B2 mRNA expression, CYP11B2 protein expression, and direct measurement of aldosterone in tumor tissue, we confirmed the ability for aldosterone production. This report provides compelling evidence that aberrant WNT signaling caused by mutations in CTNNB1 occur in APAs. This also suggests that other mechanisms that constitutively activate the WNT pathway may be important in APA formation.

Novel somatic mutations and distinct molecular signature in aldosterone-producing adenomas.

Aldosterone-producing adenomas (APAs) are found in 1.5-3.0% of hypertensive patients in primary care and can be cured by surgery. Elucidation of genetic events may improve our understanding of these tumors and ultimately improve patient care. Approximately 40% of APAs harbor a missense mutation in the KCNJ5 gene. More recently, somatic mutations in CACNA1D, ATP1A1 and ATP2B3, also important for membrane potential/intracellular Ca(2) (+) regulation, were observed in APAs. In this study, we analyzed 165 APAs for mutations in selected regions of these genes. We then correlated mutational findings with clinical and molecular phenotype using transcriptome analysis, immunohistochemistry and semiquantitative PCR. Somatic mutations in CACNA1D in 3.0% (one novel mutation), ATP1A1 in 6.1% (six novel mutations) and ATP2B3 in 3.0% (two novel mutations) were detected. All observed mutations were located in previously described hotspot regions. Patients with tumors harboring mutations in CACNA1D, ATP1A1 and ATP2B3 were operated at an older age, were more often male and had tumors that were smaller than those in patients with KCNJ5 mutated tumors. Microarray transcriptome analysis segregated KCNJ5 mutated tumors from ATP1A1/ATP2B3 mutated tumors and those without mutation. We observed significant transcription upregulation of CYP11B2, as well as the previously described glomerulosa-specific gene NPNT, in ATP1A1/ATP2B3 mutated tumors compared to KCNJ5 mutated tumors. In summary, we describe novel somatic mutations in proteins regulating the membrane potential/intracellular Ca(2) (+) levels, and also a distinct mRNA and clinical signature, dependent on genetic alteration.

[Transcultural adaptation of the HIV/AIDS-Target Quality of Life for HIV/AIDS for the evaluation of patients' quality of life]. / Adaptação transcultural do questionário HIV/AIDS-Target Quality of Life para avaliação da qualidade de vida em pacientes com HIV/aids.

The objectives of this study were to carry out cross-cultural adaptation of the HIV/AIDS-Target Quality of Life Instrument for Portuguese and to observe its psychometric properties. Translations, translations synthesis, back translation, analysis by a committee of specialists, pre-final version test, studies of validity and reliability of the final version were carried out. Psychometric properties were evaluated by the administration of the Brazilian version in 50 consecutive HIV positive patients, from the DST/HIV/AIDS municipal ambulatory of São Miguel do Oeste, Santa Catarina State. The internal consistency was observed by a-Cronbach. The reliability was estimated using the intraclass correlation coefficient and Bland-Altmann diagram. The validity was observed comparing the scores of the questionnaire with the WHOQOL-HIV-Brief through the Spearman rank correlation coefficient. The results pointed out to a-Cronbach of 0.893. The correlations obtained were 0.934 for inter-interviewer and 0.977 for intra-interviewer. The correlation with WHOQOL-HIV-Bref was 0.824. It was concluded that the cross-cultural adaptation process was successful and the adapted questionnaire demonstrated good psychometric properties.

Enriquecimento ambiental como princípio ético nas pesquisas com animais / Environmental enrichment as an ethical principle in animal research / El enriquecimiento ambiental como un principio ético en la investigación con animales

Animais utilizados em experimentos dispõem de reduzidos meios de bem-estar, estando vulneráveis a dor e sofrimento. Considerando que a técnica de enriquecimento ambiental aumenta a qualidade de vida de animais cativos, objetivou-se avaliar sua aplicação científica no âmbito da promoção de bem-estar por meio do reconhecimento da vulnerabilidade de modelos biológicos. Para tanto, conduziram-se análises documentais e ensaios experimentais, atestando que apesar de a técnica de enriquecimento ambiental ter sido aplicada principalmente em estudos de neurociência, endossando sua viabilidade, e da melhora no aprendizado, a justificativa para sua utilização tem se limitado ao bom desenvolvimento da pesquisa, e não em reconhecimento da vulnerabilidade e necessidade de bem-estar e qualidade de vida do animal. Em contraponto, foi proposta a aplicação do enriquecimento ambiental em animais de laboratório, num âmbito de contratualismo científico e responsabilidade do pesquisador, como norma a ser adotada para benefício mútuo do desenvolvimento científico e qualidade de vida animal.

Animals used in experiments have reduced levels of welfare and are thus vulnerable to pain and suffering. Considering that environmental enrichment increases the quality of life of captive animals, we aimed to assess its scientific application regarding the promotion of animal welfare by recognizing the vulnerability of biological models. Documentary analysis and experimental tests were conducted, stating that despite this technique having been applied mainly in neuroscience studies, endorsing their feasibility and the improvement in learning, the rationale for its use has been limited to the successful development of research, that is, not in recognition of animals' vulnerability, their need for welfare and quality of life. In contrast, we proposed the application of environmental enrichment for laboratory animals, within a framework of scientific contractualism and the researcher's responsibility, as a standard to be adopted for the mutual benefit of scientific development and the quality of animal life.

Los animales utilizados en experimentos disponen de un bienestar reducido y están expuestos al dolor y al sufrimiento. Considerando que la técnica de enriquecimiento ambiental aumenta la calidad de vida de los animales en cautiverio, el objetivo de este estudio fue evaluar su aplicación científica en el ámbito de la promoción del bienestar mediante el reconocimiento de la vulnerabilidad de los modelos biológicos. Para ello, se realizaron análisis documentales y ensayos experimentales, señalando que a pesar de que la técnica de EA se ha aplicado principalmente en estudios de neurociencia, respaldando su viabilidad y la mejora en el aprendizaje, la justificación para su utilización se ha limitado al desarrollo exitoso de la investigación, es decir, no hay un reconocimiento de la vulnerabilidad y de la necesidad de bienestar y de calidad de vida del animal. Por el contrario, se propone la aplicación de enriquecimiento ambiental en animales de laboratorio, en un marco de contractualismo científico y de responsabilidad del investigador, como un estándar a ser adoptado para el beneficio mutuo del desarrollo científico y de la calidad de vida de los animales.

Adaptação transcultural do questionário HIV/AIDS-Target Quality of Life para avaliação da qualidade de vida em pacientes com HIV/aids / Transcultural adaptation of the HIV/AIDS-Target Quality of Life for HIV/AIDS for the evaluation of patients' quality of life

O objetivo desse estudo foi realizar a adaptação transcultural do questionário HIV/AIDS-Target Quality of Life Instrument para o português e avaliar suas propriedades psicométricas. Foram realizadas traduções, síntese das traduções, retrotradução, análise por comitê de especialistas, teste da versão pré-final, estudos de validade e confiabilidade. As propriedades psicométricas foram avaliadas pela administração da versão brasileira em cinquenta pacientes consecutivos soropositivos atendidos no Ambulatório de DST/HIV/aids de São Miguel do Oeste (SC). Observou-se a consistência interna através do a-Cronbach. A confiabilidade foi estimada pelo coeficiente de correlação intraclasses e diagrama de Bland-Altmann. A validade foi observada comparando os escores do instrumento com o WHOQOL-HIV-Bref por meio do coeficiente de correlação por postos de Spearman. Os resultados apontaram para um a-Cronbach de 0,893. A correlação inter-entrevistador foi de 0,934 e intra-entrevistador de 0,977. A correlação com WHOQOL-HIV-Bref foi de 0,824. Pôde-se concluir que o processo de adaptação transcultural obteve sucesso e o instrumento adaptado demonstrou boas propriedades psicométricas.

The objectives of this study were to carry out cross-cultural adaptation of the HIV/AIDS-Target Quality of Life Instrument for Portuguese and to observe its psychometric properties. Translations, translations synthesis, back translation, analysis by a committee of specialists, pre-final version test, studies of validity and reliability of the final version were carried out. Psychometric properties were evaluated by the administration of the Brazilian version in 50 consecutive HIV positive patients, from the DST/HIV/AIDS municipal ambulatory of São Miguel do Oeste, Santa Catarina State. The internal consistency was observed by a-Cronbach. The reliability was estimated using the intraclass correlation coefficient and Bland-Altmann diagram. The validity was observed comparing the scores of the questionnaire with the WHOQOL-HIV-Brief through the Spearman rank correlation coefficient. The results pointed out to a-Cronbach of 0.893. The correlations obtained were 0.934 for inter-interviewer and 0.977 for intra-interviewer. The correlation with WHOQOL-HIV-Bref was 0.824. It was concluded that the cross-cultural adaptation process was successful and the adapted questionnaire demonstrated good psychometric properties.