Maternally inherited cardiomyopathy: clinical and molecula characterization of a large kindred harboring the A4300G point mutation in mtDNA

OBJECTIVES: The purpose of this study was to describe the clinical and molecular features of a large family with maternally inherited cardiomyopathy (MICM). BACKGROUND: Recently, several mitochondrial deoxyribonucleic acid (mtDNA) point mutations have been associated with MICM. However, the distinctive clinical and morphologic features of MICM are not fully appreciated. This is partially due to the small size of the reported pedigrees, often lacking detailed clinical and laboratory information. METHODS: Clinical and genetic analysis of the family was carried out. RESULTS: Echocardiography showed mostly symmetrical hypertrophic cardiomyopathy in 10 family members. The illness had an unfavorable course. Progressive heart failure occurred in three subjects, who eventually died; one individual underwent heart transplantation. Electrocardiographic or echocardiographic signs of cardiac hypertrophy in the absence of significant clinical complaints were observed in five subjects. Neurologic examination was normal. The mutation was detected in blood from all available subjects. Abundance of mutated molecules ranged between 13% and 100% of total mtDNA genomes. The severity of the disease could not be foreseen by the proportion of mutation in blood. CONCLUSIONS: This report contributes a better description of the clinical aspects of MICM and provides important clues to distinguish it from hypertrophic cardiomyopathy. We suggest that mtDNA mutations, particularly in the transfer ribonucleic acid for isoleucin, should be systematically searched in patients with MICM. The identification of an underlying maternally inherited mitochondrial DNA defect in familial cases of cardiomyopathy may considerably influence the management and genetic counseling of affected patients

Learning impact of education during pulmonary rehabilitation program. An observational short-term cohort study

Background: Among the several components integrating a pulmonary rehabilitation (PR) course, education may contribute to the individual\u2019s recognition of symptoms and worsening of the disease. However, the specific gain of education is far to be clearly documented to the health care providers. Aim of our preliminary study was to assess the learning impact of educational sessions (ES) in Chronic Obstructive Pulmonary Disease (COPD) patients referred to standard PR.Methods: Six ES on 3 areas (Symptoms-Therapies, Aids, Mood) were applied during PR at our clinic. The learning effect was prospectively evaluated by a specific questionnaire (ESQ) in 285 COPD patients (age 69\ub18 years, FEV1 53\ub114 % pred), then grouped into those who have completed ES (Completers group, n=226) or who did not (mean 2\ub11 ES) (Control group, n=59). Total and partial ESQ scores, and PR outcomes (6-minute walking test-6MWD, effort-dyspnoea at Medical Research Council scale-MRC, and health-related quality of life scale-SGRQ) were assessed in a pre (T0) to post (Tend) design.Results: Similar improvement in PR outcomes was recorded in both groups at Tend, whereas ESQ total and partial scores significantly increased in Completers only (p<0.001). ESQ-Aids score improved to a greater extent in Completers than in Control (+0.60\ub11.03 vs +0.27\ub11.27 point respectively, p=0.036). A higher proportion of Completers improved above the median change of both ESQ total and aids scores (p<0.05).Conclusion: Attending educational sessions produces a specific short-term learning effect during rehabilitation of COPD patients

BRAF exon 15 mutations in papillary carcinoma and adjacent thyroid parenchyma: A search for the early molecular events associated with tumor development

BRAF exon 15 mutations are the most common molecular alterations found in papillary thyroid carcinoma (PTC). To date, there is no information regarding BRAF alterations in the thyroid parenchyma surrounding the tumor. To explore the early events associated with the development of PTC, we used massively parallel sequencing to investigate BRAF exon 15 in 30 PTCs and in 100 samples from the thyroid parenchyma surrounding the tumor. BRAF p.V600E was identified in 19/30 PTCs (63.3%). BRAF p.V600E mutations were identified in the tissue adjacent the PTC only in samples containing psammoma bodies. The other samples were either BRAF wild type (WT) or carried BRAF non p.V600E mutations. Specifically, BRAF p.G593D,-p.A598T,-p.V600M,-p.R603Q,-p.S607F, and-p.S607P were identified in 4 of 36 (11.1%) samples with follicular cell atypia, in 2 of 16 (12.5%) with follicular cell hyperplasia, and in 1 of 33 (3.0%) histologically normal samples\u2014only in tissue surrounding BRAF p.V600E mutated PTCs. These mutations are predicted to affect protein function in silico but, in vitro, have kinase activity and BRAF phosphorylation levels similar to BRAF WT. No BRAF exon 15 mutations were identified in samples adjacent to PTCs that were BRAF WT. A mutagenic process affecting BRAF exon 15 occurs in a subset of thyroid glands that develop BRAF p.V600E mutated PTCs

Association of a PIT1 gene polymorphism with growth hormone mRNA levels in pig pituitary glands.

Fourty-six non-castrated, halothane-free, male Landrace pigs were genotyped by PCR-RFLP for the Rsa I polymorphism in the PIT1 gene and classified into AA and AB genotypes. Total RNA was extracted from the pituitaries and the relative quantities of growth hormone (GH) mRNA were determined by semi-quantitative RT-PCR. Pigs with the AB genotype had higher levels of GH mRNA than those with the AA genotype (p = 0.034; Kruskal-Wallis test). This result suggests that the Rsa I polymorphism may be involved in Pit-1 protein expression or function, which in turn may influence GH transcription and expression. Thus, the Rsa I PIT1 gene polymorphism in this pig line may be used as a molecular marker to identify higher GH expression and possibly select for carcass and performance traits affected by GH

REFORMA DA COFINS: UM ESTUDO COMPARATIVO DA ARRECADAÇÃO PROJETADA PELA TRIBUTAÇÃO CUMULATIVA E O IMPACTO DA NÃO-CUMULATIVIDADE SOBRE AS EMPRESAS DE TRANSPORTES DE CARGAS

This study examines whether the changes in the method of calculating the COFINS levy decreased the tax costs for trucking companies in metropolitan region of Vitória, Espírito Santo state. We used regression analysis to infer the amount of projected tax revenue and compare it with the real revenue published by the federal government at 2004 prices. We find that the projected and observed amounts were similar, at 1% significance. We observed, through field research, that the studied companies paid more, not less, COFINS under the new method. However, we also found that for the government, the new COFINS calculation method caused neither an increase nor decrease in the amount of revenue raised from this levy because of the introduction of the non-cumulative calculation method. We suppose that this balance may have been influenced by the exclusion of various companies, sectors and activities from the non-cumulative calculation regime, despite the increased tax burden on the companies studied. Therefore, we suggest investigation of the influence of other factors on the revenues generated under the new COFINS calculation method.El trabajo pretende verificar si la reforma en la metodología de cálculo de la COFINS (Contribución para la Financiación de la Seguridad Social de Brasil) exoneró los gastos tributarios de las empresas de transporte de cargas establecidas en la región metropolitana de Vitória, estado de Espírito Santo. Se utiliza el análisis de regresión como modelo estadístico para inferir el valor de la recaudación y para comparar los resultados encontrados a la recaudación real, a precios de 2004, divulgada por el gobierno federal. Se verificó que los valores previstos y los valores reales son similares, y las diferencias entre los dos están dentro del intervalo de confianza a un nivel de significación del 1%. Se observó, por medio de la investigación de campo, que las empresas estudiadas tuvieron un incremento en los gastos tributarios de la COFINS. Se constató que, para el gobierno, la nueva COFINS no parece interferir en la recaudación total de ese tributo, visto que no se verificó su incremento ni disminución después de la introducción de la no acumulación. Se supone que el equilibrio encontrado puede haber sido influenciado por la exclusión de varias empresas, de sectores y de actividades de la no acumulación, frente al incremento de la carga tributaria impuesta a las empresas. Así, se sugiere la investigación de la influencia de ese y de otros factores en la recaudación de la nueva COFINS en futuros trabajos.O trabalho objetiva verificar se a reforma na metodologia de cálculo da COFINS desonerou os custos tributários das empresas de transporte de cargas estabelecidas na região metropolitana de Vitória, estado do Espírito Santo. Utiliza-se a análise de regressão como modelo estatístico para inferir o valor da arrecadação e para comparar os resultados encontrados à arrecadação real, a preços de 2004, divulgada pelo governo federal. Verificou-se que os valores previstos e os valores reais são similares, e as diferenças entre os mesmos encontram-se dentro do intervalo de confiança a um nível de significância de 1%. Observou-se, por meio da pesquisa de campo, que as empresas estudadas sofreram aumento nos custos tributários da COFINS. Constatou-se que, para o governo, a nova COFINS parece não interferir na arrecadação total desse tributo, uma vez que não foi verificado aumento nem diminuição da mesma após a introdução da não-cumulatividade. Supõe-se que o equilíbrio encontrado pode ter sido influenciado pela exclusão de várias empresas, de setores e de atividades da não-cumulatividade, frente ao aumento da carga tributária imposta às empresas. Assim, sugere-se a investigação da influência desse e de outros fatores na arrecadação da nova COFINS, em futuros trabalhos

Análise de agrupamento e componentes principais na avaliação de sistemas integrados de produção agropecuária no nordeste paraense.

Edição especial dos anais do Encontro Mineiro de Estatística, 12., 2013, Uberlândia. Resumo

Large Cell Neuroendocrine Carcinoma of the Lung: Current Understanding and Challenges

Large cell neuroendocrine carcinoma of the lung (LCNEC) is a rare and highly aggres-sive type of lung cancer, with a complex biology that shares similarities with both small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC). The prognosis of LCNEC is poor, with a median overall survival of 8–12 months. The diagnosis of LCNEC requires the identification of neuroendocrine morphology and the expression of at least one of the neuroendocrine markers (chromogranin A, synaptophysin or CD56). In the last few years, the introduction of next-generation sequencing allowed the identification of molecular subtypes of LCNEC, with prognostic and potential therapeutic implications: one subtype is similar to SCLC (SCLC-like), while the other is similar to NSCLC (NSCLC-like). Because of LCNEC rarity, most evidence comes from small retrospective studies and treatment strategies that are extrapolated from those adopted in patients with SCLC and NSCLC. Nevertheless, limited but promising data about targeted therapies and immune checkpoint inhibitors in patients with LCNEC are emerging. LCNEC clinical management is still controversial and standardized treatment strategies are currently lacking. The aim of this manuscript is to review clinical and molecular data about LCNEC to better understand the optimal management and the potential prognostic and therapeutic implications of molecular subtypes