Hipercolesterolémia Familiar: Em Cada Amostra Sanguínea Uma Oportunidade Diagnóstica

Introdução: A Hipercolesterolémia Familiar (HF) e uma doença hereditária autossómica dominante com uma incidência estimada de 1:500 na sua forma heterozigótica. Caracteriza-se pela existência de níveis de colesterol muito elevados, habitualmente superiores a 300 mg/dl, e que são evidentes desde os primeiros dias de vida. A ausência de um programa de rastreio universal faz do diagnóstico precoce um desafio sobretudo durante a idade pediátrica. O presente trabalho integra-se no Estudo Português de Hipercolesterolémia Familiar e tem como objectivo caracterizar do ponto de vista clinico, laboratorial e genético uma família com HF. Caso clinico: Jovem do sexo masculino de 19 anos seguido em consulta de endocrinologia pediátrica desde os 13 anos por apresentar, em avaliação laboratorial de rotina, colesterol total de 319 mg/ dL. Historia familiar de hipercolesterolemia (colesterol acima de 290 mg/dL) em cinco familiares em primeiro grau, com manifestações clinicas como arco corneano, xantelasmas e ainda morte prematura por enfarte agudo do miocárdio aos 51 anos (avo materna). O estudo genético identificou uma mutação heterozigótica C371X do gene que codifica o receptor LDL (RLDL) no caso index e familiares directos. Trata-se de uma mutação “nonsense” descrita pela primeira vez na população portuguesa e que condiciona uma redução de 50% no número de receptores de LDL (Haploinsuficiência). Conclusão: Nas idades pediátricas, face a ausência de sinais clínicos, a história familiar e o doseamento oportunístico do colesterol sérico, isto e em amostras colhidas por outras razoes, assumem-se como as duas abordagens fundamentais no diagnóstico de HF. As medidas dietéticas e a promoção de estilos de vida saudáveis são as intervenções de primeira linha que devem ser reforçadas perante a confirmação de HF em idade pediátrica. As terapêuticas farmacológicas são ainda tema de discussão na comunidade cientifica, com resultados dispares relativamente a segurança (risco-beneficio) da sua utilização em crianças pre-puberes

Genetic variants of ABC and SLC transporter genes and chronic myeloid leukaemia: impact on susceptibility and prognosis

Solute carrier (SLC) and ATP-binding cassette (ABC) transporters comprise a variety of proteins expressed on cell membranes responsible for intrusion or extrusion of substrates, respectively, including nutrients, xenobiotics, and chemotherapeutic agents. These transporters mediate the cellular disposition of tyrosine kinase inhibitors (TKIs), and their genetic variants could affect its function, potentially predisposing patients to chronic myeloid leukaemia (CML) and modulating treatment response. We explored the impact of genetic variability (single nucleotide variants—SNVs) of drug transporter genes (ABCB1, ABCG2, SLC22A1, and SLC22A5) on CML susceptibility, drug response, and BCR-ABL1 mutation status. We genotyped 10 SNVs by tetra-primers-AMRS-PCR in 198 CML patients and 404 controls, and assessed their role in CML susceptibility and prognosis. We identified five SNVs associated with CML predisposition, with some variants increasing disease risk, including TT genotype ABCB1 (rs1045642), and others showing a protective effect (GG genotype SLC22A5 rs274558). We also observed different haplotypes and genotypic profiles associated with CML predisposition. Relating to drug response impact, we found that CML patients with the CC genotype (rs2231142 ABCG2) had an increased risk of TKI resistance (six-fold). Additionally, CML patients carrying the CG genotype (rs683369 SLC22A1) presented a 4.54-fold higher risk of BCR-ABL1 mutations. Our results suggest that drug transporters’ SNVs might be involved in CML susceptibility and TKI response, and predict the risk of BCR-ABL1 mutations, highlighting the impact that SNVs could have in therapeutic selection.info:eu-repo/semantics/publishedVersio

The Brazilian Registry of Adult Patient Undergoing Cardiovascular Surgery, the BYPASS Project: Results of the First 1,722 Patients

Objective: To report the early results of the BYPASS project - the Brazilian registrY of adult Patient undergoing cArdiovaScular Surgery - a national, observational, prospective, and longitudinal follow-up registry, aiming to chart a profile of patients undergoing cardiovascular surgery in Brazil, assessing the data harvested from the initial 1,722 patients. Methods: Data collection involved institutions throughout the whole country, comprising 17 centers in 4 regions: Southeast (8), Northeast (5), South (3), and Center-West (1). The study population consists of patients over 18 years of age, and the types of operations recorded were: coronary artery bypass graft (CABG), mitral valve, aortic valve (either conventional or transcatheter), surgical correction of atrial fibrillation, cardiac transplantation, mechanical circulatory support and congenital heart diseases in adults. Results: 83.1% of patients came from the public health system (SUS), 9.6% from the supplemental (private insurance) healthcare systemsand 7.3% from private (out-of-pocket) clinic. Male patients comprised 66%, 30% were diabetics, 46% had dyslipidemia, 28% previously sustained a myocardial infarction, and 9.4% underwent prior cardiovascular surgery. Patients underwent coronary artery bypass surgery were 54.1% and 31.5% to valve surgery, either isolated or combined. The overall postoperative mortality up to the 7th postoperative day was 4%for CABG was 2.6%, and for valve operations, 4.4%. Conclusion: This first report outlines the consecution of the Brazilian surgical cardiac database, intended to serve primarily as a tool for providing information for clinical improvement and patient safety and constitute a basis for production of research protocols.Univ Fed Sao Paulo UNIFESP EPM, Hosp Sao Paulo, Sao Paulo, SP, BrazilHosp Caridade Sao Vicente Paulo, Jundiai, SP, BrazilInst Med Integral Prof Fernando Figueira IMIP, Recife, PE, BrazilHosp Base FUNFARME & FAMERP, Sao Jose Do Rio Preto, SP, BrazilIMC, Sao Jose Do Rio Preto, SP, BrazilIrmandade Santa Casa Sao Paulo INCT HPV, Fac Ciencias Med Santa Casa Sao Paulo, Sao Paulo, SP, BrazilFundacao Univ Cardiol, Inst Cardiol Rio Grande do Sul, Porto Alegre, RS, BrazilInst Coracao Natal, Natal, RN, BrazilInst Cardiol Dist Fed, Brasilia, DF, BrazilUniv Fed Maranhao HU UFMA, Univ Hosp, Sao Luis, MA, BrazilHosp Evangelico, Cachoeiro De Itapemirim, ES, BrazilHosp Coracao Sergipe, Aracaju, SE, BrazilHosp Nossa Senhora Salete, Inst Cirurgia Cardiovasc ICCV, Cascavel, PR, BrazilHosp Wilson Rosado, Mossoro, RN, BrazilHosp Bosque Saude, Sao Paulo, SP, BrazilHosp Univ Santa Maria, Santa Maria, RS, BrazilHosp Coracao HCor, Sao Paulo, SP, BrazilHosp Coracao IP HCor, Ins Pesquisa, Sao Paulo, SP, BrazilInst Coracao InCor, Sao Paulo, SP, BrazilUniv Fed Sao Paulo UNIFESP EPM, Hosp Sao Paulo, Sao Paulo, SP, BrazilWeb of Scienc

Diversity and ethics in trauma and acute care surgery teams: results from an international survey

Background Investigating the context of trauma and acute care surgery, the article aims at understanding the factors that can enhance some ethical aspects, namely the importance of patient consent, the perceptiveness of the ethical role of the trauma leader, and the perceived importance of ethics as an educational subject. Methods The article employs an international questionnaire promoted by the World Society of Emergency Surgery. Results Through the analysis of 402 fully filled questionnaires by surgeons from 72 different countries, the three main ethical topics are investigated through the lens of gender, membership of an academic or non-academic institution, an official trauma team, and a diverse group. In general terms, results highlight greater attention paid by surgeons belonging to academic institutions, official trauma teams, and diverse groups. Conclusions Our results underline that some organizational factors (e.g., the fact that the team belongs to a university context or is more diverse) might lead to the development of a higher sensibility on ethical matters. Embracing cultural diversity forces trauma teams to deal with different mindsets. Organizations should, therefore, consider those elements in defining their organizational procedures. Level of evidence Trauma and acute care teams work under tremendous pressure and complex circumstances, with their members needing to make ethical decisions quickly. The international survey allowed to shed light on how team assembly decisions might represent an opportunity to coordinate team member actions and increase performance

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mechanisms of kidney toxicity for chromium- and arsenic-based preservatives: Potential involvement of a pro-oxidative pathway

Metals have been extensively used for the preservation of wood. Among metallic conservatives, mixtures of chromated copper arsenate (CCA) were thoroughly used. However, the release and consequent mobilization of such compounds by biota, may culminate in the exertion of toxic chemical effects. The present study intended to show the toxicological effects caused by arsenic (7.2 mg/kg body weight), chromium (10.2 mg/kg Cr body weight) and the commercial mixture CCA (7.2 mg/kg As body weight and 10.2 mg/kg Cr body weight) in mice, namely the oxidative stress response (catalase - CAT, glutathione peroxidase - GPx, and glutathione-S-transferases - GSTs), in kidney tissues. The determination of the tested parameters was performed after exposure; organisms were exposed, and then sacrificed at two distinct periods, namely 14 and 96 h after the administration of toxicants. Exposure to chromium and arsenic induced significant modifications in the redox state of the test organisms, evidenced by significant alterations in GSTs and GPx activities. No alterations were found concerning the activity of catalase. These findings showed that the chemical mixture used as household product may exert significant toxicological outcomes in exposed animals, such as rodents, conditioning their redox homeostasis and antioxidant response. (C) 2013 Published by Elsevier B.V

Quality assessment and feedback of Smart Device Microphone Spirometry executed by children

Smart device microphone spirometry, based on the audio recording of forced expiratory maneuver (FEM), can be a simple, ubiquitous and easy tool for patients to self-monitor their asthma. Automatic validity assessment is crucial to guarantee that the global effort of the FEM fulfil the admissible minimum or if the maneuver needs to be repeated. In this work an automatic method to classify the sounds from FEM with respect to global effort was developed and evaluated using data from 54 children (5-10 years). The method proposed was able to correctly classify the microphone spirometry with respect to admissible minimum of effort with an accuracy of 86% (specificity 87% and sensitivity 86%). This method can be used to provide immediate feedback of the correct execution of the maneuver, improving the clinical value and utility of this self-monitoring tool.info:eu-repo/semantics/publishedVersio