Comparison of Four Purification Methods on Serum Extracellular Vesicle Recovery, Size Distribution, and Proteomics.

In recent decades, the role played by extracellular vesicles in physiological and pathological processes has attracted attention. Extracellular vesicles are released by different types of cells and carry molecules that could become biomarkers for the diagnosis of diseases. Extracellular vesicles are also moldable tools for the controlled release of bioactive substances in clinical and therapeutic applications. However, one of the significant challenges when studying these exciting and versatile vesicles is the purification process, which presents significant difficulties in terms of lack of purity, yield, and reproducibility, reflected in unreliable data. Therefore, our objective in the present study was to compare the proteomic profile of serum-derived EVs purified using ExoQuick™ (Systems Biosciences), Total Isolation Kit (Life Technologies), Ultracentrifugation, and Ultrafiltration. Each technique utilized for purification has shown different concentrations and populations of purified particles. The results showed marked differences in distribution, size, and protein content, demonstrating the need to develop reproducible and reliable protocols to isolate extracellular vesicles for their clinical application.

¿Qué saben de pubertad, relaciones de pareja y reproducción, un grupo de jóvenes chilenos con Síndrome de Down? / What do a Group of Young Chilean with Down Syndrome Know about Puberty, Relationshipsand Reproduction?

Introducción: vivir la sexualidad y afectividad de forma plena es fundamental en todo ser humano; sin embargo, las personas con síndrome de Down (SD) tienen escasas instancias de educación sexual y pocos espacios de socialización para experimentarla. Objetivos: describir el conocimiento que tienen jóvenes con SD sobre temáticas básicas de pubertad, relaciones de pareja y reproducción. Metodología: estudio cualitativo, descriptivo, exploratorio, en dos grupos focales de jóvenes con SD, entre 13 y 18 años, separados por género. La información fue grabada, transcrita y codificada según categorías emergentes. Resultados: sobre la palabra “sexualidad”, las mujeresdeclararon no haberla escuchado y los hombres hicieron referencia a “sexo”, “relaciones de pareja”, “amor” y “familia”. Para “cambios puberales”, ambos grupos señalaron los cambios más visibles, pero nada respecto a reproducción. Solo un participante entendía el concepto de “relación sexual”. Las mujeres consideraron el “inicio de la vida humana” como un evento de generación espontánea y los hombres plantearon una teoría fantasiosa. La familia fue la principal fuente de información. Discusión: los participantes mostraron un manejo deficiente e infantilizado de la información. Son urgentes la investigación y el desarrollo de programas de Educación Sexual y así dignificar la sexualidad y afectividad de personas con SD, desde un enfoque de derechos. (AU)

Introduction: living sexuality and affectivity fully is fundamental in every human being, however, people with Down syndrome (DS) have few instances of sex-ual education and few spaces for socialization to experience it. Objectives: describe the knowledge that young people with DS have on basic issues of puberty, relationships and reproduction. Methodology: qualitative, descriptive, exploratory study in two focus groups of young people with DS, between 13 and 18 years old, separated by gender. The information was recorded, coded according to categories. Results: regarding the word “sexuality”, the women declared that they had not heard it and the men referred to “sex”, “couple relationships”, “love” and “family”. For “pubertal changes”, both groups reported the most visible changes, but nothing regarding reproduction. Only one participant understood the concept of “sexual relationship”. Women considered the “beginning of human life” as a spontaneous generation event and the men came up with a fanciful theory. The family was the main source of information. Discussion: par-ticipants showed deficient and infantilized handling of information. Research and devel-opment of Sex Education programs are urgent to dignify the sexuality and affectivity of people with DS, from a rights’ perspective. (AU)

Rotatividade da equipe de enfermagem em hospital privado / Turnover of nursing staff in private hospital

Os recursos humanos de enfermagem têm assumido relevância no cenário de saúde, tanto em termos quantitativos como qualitativos e têm sido associados positivamente a uma assistência qualificada e segura. A rotatividade da equipe de enfermagem representa um desafio para os gestores das instituições de saúde, frente ao impacto gerado tanto na assistência como nos custos. Este estudo teve por objetivo analisar a rotatividade dos trabalhadores de enfermagem em uma instituição hospitalar. Estudo descritivo, retrospectivo, quantitativo, realizado em um hospital de atendimento para alta complexidade do interior do Estado de São Paulo, pertencente a uma operadora de medicina de grupo e acreditado em nível de excelência pela Organização Nacional de Acreditação (ONA). A população foi constituída por todos os trabalhadores de enfermagem (enfermeiro, técnico e auxiliar de enfermagem) que no período de 1° janeiro de 2013 a 31 dezembro de 2017 apresentaram vínculo formal de emprego nas unidades selecionadas para a investigação e que neste período desligaram-se da instituição por diferentes razões. Os dados foram coletados de relatórios fornecidos pelo Centro de Recursos Humanos da instituição, constituindo-se em variáveis de interesse a idade, o sexo, a categoria profissional, a data de admissão e de desligamento e a unidade de trabalho. As medidas de rotatividade utilizadas foram as taxas de admissão e desligamento e a mediana de tempo de serviço dos demitentes. No período do estudo, 499 trabalhadores de enfermagem desligaram-se, sendo 141 (28,3%) enfermeiros, 82 (16,4%) técnicos de enfermagem e 276 (55,3%) auxiliares de enfermagem. O ano de 2013 foi o que apresentou o maior percentual (22,4%). Em relação ao sexo, para o conjunto das três categorias de trabalhadores, houve predomínio das mulheres (73,4%). A idade média do grupo foi de 32,7 anos e a mediana de 31 anos. Dentre os enfermeiros demitentes, 64 (45,4%) deixaram a instituição no primeiro ano trabalhado. Entre o período da admissão até 5 anos na instituição, essa quantidade chegou a 124 (88%) profissionais. Na categoria dos técnicos de enfermagem, 28 (34%) saíram no primeiro ano e 57 (69,5%) em até 5 anos. Em relação aos auxiliares de enfermagem, 92 (33,3%) profissionais permaneceram menos de um ano e 225 (81,5%) até 5 anos. Na média dos anos, a taxa de admissão (TA) (19,6%) superou a taxa de desligamento (TD) (18,7%). Os enfermeiros demitentes permaneceram em atividade nesse hospital no mínimo 16 e no máximo, 23 meses; os técnicos de enfermagem, no mínimo 17 e no máximo 28 meses; e os auxiliares de enfermagem, no mínimo 16 e no máximo 23 meses. As unidades de internações médicas, seguidas pelas cirúrgicas foram os locais de onde saíram a maior parte dos enfermeiros e auxiliares de enfermagem e o Centro de Terapia Intensiva, a área que mais perdeu técnicos de enfermagem. A permanência dos trabalhadores nas instituições pode ter relação direta com a qualidade dos ambientes de prática, satisfação e bem-estar. A análise da rotatividade fornece subsídios aos gerentes de enfermagem, com possibilidade de intervenções de curto prazo para solução de não conformidades identificadas nas instituições de saúde

Nursing staff have assumed relevance in the health scenario, both in quantitative and qualitative terms and have been positively associated with the results that are desired related to qualified and safe care. The nursing personnel turnover represents a major challenge for managers of health institutions, given the impact on both care and costs. This study aimed to analyze the nursing personnel turnover in a hospital institution. This is a descriptive, retrospective and quantitative study, carried out in a hospital of high complexity, located in the interior of the state of São Paulo, which belongs to a group medicine operator and is accredited as excellence level by the National Accreditation Organization (ONA). The population consisted of all nursing staff (nurse, technician and nursing assistant) who had formal employment in the units selected for the research and that from January 1, 2013 to December 31, 2017 left the institution for different reasons. Data were collected from reports provided by the Human Resources Center of the institution, constituting variables of interest the age, gender, professional category, date of admission and dismissal and unit of work. The turnover measures used were admission and dismissal rates and median of length of service of the resigning professionals. In the period of study, 499 nursing workers resigned, being 141 (28.3%) nurses, 82 (16.4%) nursing technicians and 276 (55.3%) nursing assistants. 2013 was the year that showed the highest percentage (22.4%). Regarding gender, for all three categories of workers, there was a predominance of women (73.4%). The average age of the group was 32.7 years and a median of 31 years. Among the resigning nurses, 64 (45.4%) left the institution in the first year worked. From the admission up to 5 years in the institution, this value reached 124 (88%) professionals. In the category of nursing technicians, 28 (34%) left work in the first year and 57 (69.5%) within 5 years. Regarding nursing assistants, 92 (33.3%) professionals remained less than one year and 225 (81.5%) within 5 years. In the average of the years, the admission rate (AR) (19.6%) was higher than the dismissal rate (DR) (18.7%). The resigning nurses remained active at this hospital for a minimum of 16 months and a maximum of 23 months; the nursing technicians, for a minimum of 17 months and maximum of 28 months; and the nursing assistants, for a minimum of 16 months and maximum of 23 months. The medical inpatient units, followed by the surgical units were the places from which most nurses and nursing assistants left; and in the Center for Intensive Therapy, most were nursing technicians. The permanence of workers in institutions can be directly related to the quality of the practice environments, satisfaction and well-being. The turnover analysis provides support to nursing managers, with the possibility of short-term interventions to solve nonconformities identified in health institutions

Lysosomal Acid Lipase Deficiency Leading to Liver Cirrhosis: a Case Report of a Rare Variant Mutation.

Lysosomal acid lipase deficiency is a poorly diagnosed genetic disorder, leading to accumulation of cholesterol esters and triglycerides in the liver, with progression to chronic liver disease, dyslipidemia, and cardiovascular complications. Lack of awareness on diagnosis of this condition may hamper specific treatment, which consists on enzymatic replacement. It may prevent the progression of liver disease and its complications. We describe the case of a 53-year-old Brazilian man who was referred to our center due to the diagnosis of liver cirrhosis of unknown etiology. He was asymptomatic and had normal body mass index. He had dyslipidemia, and family history of myocardial infarction and stroke. Abdominal imaging tests showed liver cirrhosis features and the presence of intrahepatic calcifications. Initial investigation of the etiology of the liver disease was not elucidated, but liver biopsy showed microgoticular steatosis and cholesterol esters deposits in Kuppfer cells. The dosage of serum lysosomal acid lipase was undetectable and we found the presence of a rare homozygous mutation in the gene associated with the lysosomal acid lipase deficiency, (allele c.386A > G homozygous p.H129R).

Desenvolvimento infantil: manual para a Atenção Básica em Saúde / Child development: guide to Primary Health Care

Essa cartilha foi desenvolvida por uma equipe multidisciplinar com o objetivo de ser um guia para os profissionais que diariamente atendem crianças e pais em suas unidades e podem se deparar com dúvidas sobre seus desenvolvimentos. As informações estão compiladas e para um maior aprofundamento deixamos as referências utilizadas.

Hand-foot syndrome due to hepatitis C therapy.

INTRODUCTION: Direct-acting antivirals are new drugs for chronic hepatitis C treatment. They are usually safe and well tolerated, but can sometimes cause serious adverse effects and there is no consensus on how to treat or prevent them. We described a case of hand-foot syndrome due to hepatitis C virus interferon-free therapy. METHODS: We report the case of a 49-year-old man with compensated liver cirrhosis due to chronic hepatitis C genotype 1, treatment-naïve, who started viral treatment with sofosbuvir, simeprevir and ribavirin for 12 weeks. RESULTS: At the sixth week of treatment he had anemia, requiring a lower dose of ribavirin. At the tenth week, he had erythematous, pruritic, scaly and flaky lesions on hands and feet, which showed a partial response to oral antihistamines and topical corticosteroids. It was not necessary to discontinue antiviral treatment, but in the first week after the end of treatment, there was worsening of injuries, including signs of secondary infection, that required hospitalization, antibiotics and oral corticosteroid, with progressive improvement. Biopsy of the lesions was consistent with pharmacodermia. The patient had sustained a virological response, despite the side effect. He had a history of pharmacodermia one year ago attributed to the use of topiramate, responsive to oral corticosteroid. CONCLUSION: Interferon-free therapies can rarely lead to severe adverse reactions, such as skin lesions. Patients receiving ribavirin combinations and those who had a history of pharmacodermia or skin disease may be more susceptible. There is no consensus on how to prevent skin reactions in these patients.

Serum sodium, model for end-stage liver disease, and a recent invasive procedure are risk factors for severe acute-on-chronic liver failure and death in cirrhotic patients hospitalized with bacterial infection.

INTRODUCTION: Bacterial infection is present in up to 30% of hospitalized cirrhotic patients. It can lead, even after its resolution, to organ dysfunction and even acute-on-chronic liver failure (ACLF). It is the precipitating factor of ACLF in one third of the cases and is the main cause of mortality in patients with liver cirrhosis. OBJECTIVES: The aim of this study was to evaluate the prevalence and identify early risk factors for severe ACLF and death in hospitalized patients with liver cirrhosis with bacterial infection. PATIENTS AND METHODS: This was a prospective observational study. Hospitalized patients with liver cirrhosis and bacterial infection were included. Clinical and laboratory data and their evolution to organ dysfunction and death were assessed. A statistical analysis were carried out to identify predictors of severe ACLF and in-hospital mortality. RESULTS: This study included 88 patients. ACLF was observed in 62 (70%) patients, with 48 (55%) grade 2 or higher. Of the 27 deaths (31% of all patients), 26 had severe ACLF (54% mortality) (P<0.0001). The independent risk factors for ACLF of at least 2 and death were baseline serum sodium [odds ratio (OR): 0.874; P=0.01, and OR: 0.9, P=0.04], initial MELD (OR: 1.255, P=0.0001, and OR: 1.162, P=0.005), and a recent invasive procedure (OR: 3.169, P=0.01, and OR: 6.648, P=0.003). CONCLUSION: Lower serum sodium values, higher MELD scores at diagnosis of infection, and a recent history of invasive procedures were independent risk factors for severe ACLF and death in patients with cirrhosis and bacterial infection.

Hand-foot syndrome due to hepatitis C therapy

SUMMARY INTRODUCTION Direct-acting antivirals are new drugs for chronic hepatitis C treatment. They are usually safe and well tolerated, but can sometimes cause serious adverse effects and there is no consensus on how to treat or prevent them. We described a case of hand-foot syndrome due to hepatitis C virus interferon-free therapy. METHODS We report the case of a 49-year-old man with compensated liver cirrhosis due to chronic hepatitis C genotype 1, treatment-naïve, who started viral treatment with sofosbuvir, simeprevir and ribavirin for 12 weeks. RESULTS At the sixth week of treatment he had anemia, requiring a lower dose of ribavirin. At the tenth week, he had erythematous, pruritic, scaly and flaky lesions on hands and feet, which showed a partial response to oral antihistamines and topical corticosteroids. It was not necessary to discontinue antiviral treatment, but in the first week after the end of treatment, there was worsening of injuries, including signs of secondary infection, that required hospitalization, antibiotics and oral corticosteroid, with progressive improvement. Biopsy of the lesions was consistent with pharmacodermia. The patient had sustained a virological response, despite the side effect. He had a history of pharmacodermia one year ago attributed to the use of topiramate, responsive to oral corticosteroid. CONCLUSION Interferon-free therapies can rarely lead to severe adverse reactions, such as skin lesions. Patients receiving ribavirin combinations and those who had a history of pharmacodermia or skin disease may be more susceptible. There is no consensus on how to prevent skin reactions in these patients.

RESUMO INTRODUÇÃO Antivirais de ação direta são as novas drogas utilizadas no tratamento da hepatite C crônica. São geralmente seguros, com boa tolerância, mas eventualmente podem causar efeitos adversos graves, e não há consenso sobre como tratá-los ou preveni-los. Descrevemos um caso de síndrome mão-pé secundária à terapia livre de interferon para hepatite C crônica. Materiais e métodos Relatamos o caso de um paciente de 49 anos com cirrose hepática compensada secundária à hepatite C crônica, genótipo 1, virgem de tratamento, que iniciou terapia com sofosbuvir, simeprevir e ribavirina por 12 semanas. Resultados Na sexta semana de tratamento, apresentou anemia, sendo necessária redução de dose da ribavirina. Na 20a semana, apresentou lesões eritematosas e descamativas, com prurido em mãos e pés, que teve resposta parcial ao uso de anti-histamínico oral e corticoide tópico. Não foi necessário descontinuar os antivirais, mas na primeira semana após o término do tratamento, houve piora das lesões, com sinais de infecção secundária, sendo necessárias hospitalização e terapia com antibiótico e corticoide oral, com melhora progressiva. Biópsias das lesões foram compatíveis com farmacodermia. O paciente teve resposta virológica sustentada, apesar dos efeitos adversos. Tinha história de farmacodermia há um ano, atribuída ao uso de topiramato, responsiva a corticoterapia oral. Conclusão Os tratamentos livres de interferon raramente causam eventos adversos graves, como lesões cutâneas. Pacientes em uso de ribavirina e com história de farmacodermia ou doença cutânea prévia podem ser mais susceptíveis. Não existe consenso sobre como prevenir reações cutâneas nesses pacientes.

Localized gastrointestinal amyloidosis presenting with protein-losing enteropathy and massive hemorrhage

Amyloidosis of the gastrointestinal tract is usually a systemic disease. Localized gastrointestinal amyloidosis without evidence of extraintestinal involvement or an associated plasma cell dyscrasia is uncommon and does not usually cause death. We report a case of a patient with localized gastrointestinal amyloidosis who presented with protein-losing enteropathy and a fatal upper gastrointestinal bleed (AU)

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Localized gastrointestinal amyloidosis presenting with protein-losing enteropathy and massive hemorrhage.

Amyloidosis of the gastrointestinal tract is usually a systemic disease. Localized gastrointestinal amyloidosis without evidence of extraintestinal involvement or an associated plasma cell dyscrasia is uncommon and does not usually cause death. We report a case of a patient with localized gastrointestinal amyloidosis who presented with protein-losing enteropathy and a fatal upper gastrointestinal bleed.

Herbal Medicine in Mexico: A Cause of Hepatotoxicity. A Critical Review.

In Mexico, herbal products are commonly used as therapeutic tools. The analysis of several publications reveals that there are dozens of different herbs and herbal products used for different reasons, some of which have been implicated in causing toxic liver disease. However, methodological aspects limit the attribution of causality, and the precise incidence and clinical manifestations of herb-induced liver injury have not been well characterized. This review outlines the history of traditional herbal medicine in Mexico, critically summarizes the mechanisms and adverse effects of commonly used herbal plants, and examines the regulatory issues regarding the legal use of these products.

Avaliação da Função Renal e Alterações Morfológicas em Ratos Tratados com Dipirona em Diferentes Doses / Evaluation of Renal Function and Morphological Changes in rats Treated with Dipyrone in Different Dosing

A dipirona é um fármaco muito utilizado para o tratamento da febre e da dor, entretanto, seus efeitos em doses altas podem levar a danosirreversíveis e até letais. Na presente investigação foram utilizados 32 ratos albinos machos da linhagem Wistar. Um grupo (1) recebeu uma dose única, 5.000 mg/Kg de dipirona por gavagem e o outro grupo (2) administração uma vez ao dia, por quatro dias consecutivos, de 600mg/Kg de dipirona. Ao final de quatro dias, para o grupo 2 e após 3 horas de ingestão do medicamento para o grupo 1, os animais foram eutanasiados em câmara de CO2, conforme a aprovação do Comitê de Ética Animal do Centro Universitário Barão de Mauá (CEPAn). Foram avaliados os parâmetros ureia e creatinina e a histopatologia renal. Os resultados dos escores hemorragia glomerular, congestão renal e processo inflamatório foram estatisticamente significativos nos três parâmetros analisados para dose única; congestão renal e processo inflamatório para dose múltipla. O marcador de função renal, ureia apresentou diferença estatística significativa com a dose única. Os resultados do modelo experimental atestam que a metodologia aplicada foi capaz de demonstrar as alterações histopatológicas do grupo tratado com dipirona dose única assim como alterações na dosagem de ureia e a preservação das características normais do grupo controle. O mesmo não ocorreu com o grupo tratado com doses múltiplas.

Dipyrone is a drug widely used for the treatment of fever and pain, but their effects at high doses can lead to irreversible and even lethal damages.In the present study it was used 32 male albino rats of Wistar strain. First group received a single dose 5.000 mg/kg by gavage dipyrone and the second given once daily for four consecutive days of 600 mg/kg Dipyrone. At the end of four days, for group 2 and 3 hours after ingestion of the drug for group 1, the animals were euthanized in a CO2 chamber, as the approval of the Baron of Maua University Center (Cepan) Animal Ethics Committee. The urea and creatinine parameters and renal histopathology were evaluated. The results of the scores glomerular bleeding, renal congestion and inflammation were statistically significant in all parameters analyzed for single dose; renal congestion and inflammation to multiple dose. The marker of renal function, urea statistically significant difference with the single dose. The results of the experimental model show that the methodology was able to demonstrate the histopathological changes in the group treated with single dose dipyrone as well as changes in the levels of urea and the preservation of the normal characteristics of the control group. This did not occur with the group treated with multiple doses.