PEGylation Strategy for Improving the Pharmacokinetic and Antitumoral Activity of the IL-2 No-alpha Mutein.

BACKGROUND: In a previous work, an IL-2Rßγ biased mutant derived from human IL-2 and called IL-2noα, was designed and developed. Greater antitumor effects and lower toxicity were observed compared to native IL-2. Nevertheless, mutein has some disadvantages, such as a very short half-life of about 9-12 min, propensity for aggregation, and solubility problems. OBJECTIVE: In this study, PEGylation was employed to improve the pharmacokinetic and antitumoral properties of the novel protein. METHODS: Pegylated IL-2noα was characterized by polyacrylamide gel electrophoresis, size exclusion chromatography, in vitro cell proliferation and in vivo cell expansion bioassays, and pharmacokinetic and antitumor studies. RESULTS: IL-2noα-conjugates with polyethylene glycol (PEG) of 1.2 kDa, 20 kDa, and 40 kDa were obtained by classical acylation. No significant changes in the secondary and tertiary structures of the modified protein were detected. A decrease in biological activity in vitro and a significant improvement in half-life were observed, especially for IL-2noα-PEG20K. PEGylation of IL-2noα with PEG20K did not affect the capacity of the mutant to induce preferential expansion of T effector cells over Treg cells. This pegylated IL-2noα exhibited a higher antimetastatic effect compared to unmodified IL-2noα in the B16F0 experimental metastases model, even when administered at lower doses and less frequently. CONCLUSION: PEG20K was selected as the best modification strategy, to improve the blood circulation time of the IL-2noα with a superior antimetastatic effect achieved with lower doses.

Forecasting Brassica napus production under climate change with a mechanistic species distribution model.

Brassica napus, a versatile crop with significant socioeconomic importance, serves as a valuable source of nutrition for humans and animals while also being utilized in biodiesel production. The expansion potential of B. napus is profoundly influenced by climatic variations, yet there remains a scarcity of studies investigating the correlation between climatic factors and its distribution. This research employs CLIMEX to identify the current and future ecological niches of B. napus under the RCP 8.5 emission scenario, utilizing the Access 1.0 and CNRM-CM5 models for the time frame of 2040-2059. Additionally, a sensitivity analysis of parameters was conducted to determine the primary climatic factors affecting B. napus distribution and model responsiveness. The simulated outcomes demonstrate a satisfactory alignment with the known current distribution of B. napus, with 98% of occurrence records classified as having medium to high climatic suitability. However, the species displays high sensitivity to thermal parameters, thereby suggesting that temperature increases could trigger shifts in suitable and unsuitable areas for B. napus, impacting regions such as Canada, China, Brazil, and the United States.

Comparative Effectiveness of COVID-19 Vaccines in Preventing Infections and Disease Progression from SARS-CoV-2 Omicron BA.5 and BA.2, Portugal.

We estimated comparative primary and booster vaccine effectiveness (VE) of SARS-CoV-2 Omicron BA.5 and BA.2 lineages against infection and disease progression. During April-June 2022, we implemented a case-case and cohort study and classified lineages using whole-genome sequencing or spike gene target failure. For the case-case study, we estimated the adjusted odds ratios (aORs) of vaccination using a logistic regression. For the cohort study, we estimated VE against disease progression using a penalized logistic regression. We observed no reduced VE for primary (aOR 1.07 [95% CI 0.93-1.23]) or booster (aOR 0.96 [95% CI 0.84-1.09]) vaccination against BA.5 infection. Among BA.5 case-patients, booster VE against progression to hospitalization was lower than that among BA.2 case-patients (VE 77% [95% CI 49%-90%] vs. VE 93% [95% CI 86%-97%]). Although booster vaccination is less effective against BA.5 than against BA.2, it offers substantial protection against progression from BA.5 infection to severe disease.

The impact of anemia on treatment management and clinical outcomes of women hospitalized for uterine leiomyomas.

OBJECTIVES: Uterine leiomyomas are the most common benign gynecological tumors. Symptomatic leiomyomas represent a major cause of hospitalization, particularly those associated with abnormal uterine bleeding (AUB) and anemia. The aim of this study was to identify predictors of anemia in women hospitalized due to uterine leiomyomas and evaluate its impact on treatment management and clinical outcomes. MATERIAL AND METHODS: Population-based retrospective study of women hospitalized for uterine fibroids in public hospitals in mainland Portugal between 2010 and 2015. Data were extracted from the national database of the Central Administration of the Portuguese Health System. Comparative and multivariable logistic regression analysis was performed to assess outcomes. RESULTS: A total of 36 295 patients were hospitalized due to uterine leiomyomas during this period. Of those, 11.5% presented with anemia. Age, obesity, intramural type of leiomyoma and AUB are independent predictors of anemia (p < 0.001, AUC 0.7056). Anemia was associated with a high risk of inpatient hospitalization (OR: 5.161, 95% CI: 4.376-6.085), urgent admission (OR: 1.953, 95% CI: 1.797-2.121), radical surgical approach (OR: 2.559, 95% CI: 2.298-2.849), laparoscopic hysterectomy (OR: 1.575, 95% CI: 1.393-1.780) and intra- and post-operative complications (OR: 5.285, 95% CI: 4.332-6.448). It was also associated with longer hospital stays (p < 0.001). These outcomes were more pronounced in acute anemic patients. CONCLUSIONS: Anemia has a significant impact on treatment approaches and clinical outcomes of women hospitalized for uterine leiomyomas. Age, obesity, intramural leiomyomas and AUB are some predictors of anemia that could represent a risk-stratification opportunity, allowing for its prompt identification and correction, therefore improving patient care.

Formação do psicólogo para atuação comunitária no contexto das drogas: uma análise das matrizes curriculares / Training in community psychology action in the context of drugs: an analysis of curricular matrices

A psicologia comunitária enfatiza a prevenção e promoção da saúde. Neste contexto, questões relacionadas ao consumo de drogas emergem enquanto demanda de trabalho. Diante disso, este estudo teve como objetivo analisar a formação em psicologia com relação à atuação no contexto comunitário frente às demandas relacionadas ao uso de drogas, a partir da análise das matrizes curriculares. Para tanto, realizou-se uma análise das matrizes curriculares dos cursos de psicologia do Sul do país. Dos 102 cursos analisados, 21 oferecem disciplinas sobre drogas e 73 sobre comunidade. Em 12 instituições, foi identificada a presença de ambas as disciplinas. Tais resultados indicam que, embora a formação em psicologia tenha avançado quanto à psicologia comunitária, o tema “drogas” ainda é pouco explorado, o que dificulta ações pautadas num aporte teórico-metodológico que convirjam com evidências científicas relacionadas ao tema. É imprescindível uma formação que prepare o profissional para atuar de forma ética e comprometida com demandas relacionadas à questão do consumo de drogas presentes na comunidade.(AU)

Community psychology emphasizes prevention and health promotion. In this context, issues related to drug use emerge as a demand for work. Therefore, this study aimed to discuss the training of the psychologist as an ethical commitment to act in the community context regarding the demands related to drug use. For that, an analysis of the curricular matrices of the psychology courses of the country ́s South was carried out. Of the 102 courses analyzed, 21 offer courses on drugs and 73 courses on community. In 12 institutions, the presence of both disciplines was identified. Although the formation of the Psychologist has advanced in relation to community psychology, the theme "drugs" is still little explored, which hampers actions based on a theoretical and methodological contribution that converge with scientific evidence related to the theme. It is essential a training that prepares the professional to act with ethics and committed to the demands of the community.(AU)

Vulnerabilidade, família e o uso de drogas: uma revisão integrativa de literatura / Vulnerability, family and drug use: an integrating literature review / Vulnerabilidad, familia y el uso de drogas: una revisión integral de literatura

Os problemas relacionados ao uso de álcool e outras drogas é uma realidade na sociedade atual e revela a existência de diferentes fatores relacionados. Entre eles, destaca-se a condição de vulnerabilidade como importante elemento contribuinte para o uso abusivo, bem como a família, sendo entendida como fator de risco e/ou proteção e como sistema diretamente afetado pelo problema. Diante disso, este estudo teve como objetivo realizar uma revisão integrativa de literatura sobre a relação entre vulnerabilidade, drogas e contexto familiar. Para tanto, foi realizada uma busca por artigos nas bases de dados Scielo e BVS utilizando os descritores "vulnerabilidade AND drogas AND família" que rastreou um total de 105 artigos. Após a aplicação dos critérios de inclusão, restaram 22 artigos. Desses, sete envolveram adolescentes escolares, cinco pessoas em situação de rua e cinco familiares de usuários, quatro foram realizados com os próprios usuários de drogas e um com profissionais da saúde. Os resultados das análises dos estudos sugerem que a relação entre uso de drogas, família e condição de vulnerabilidade é intrínseca, sendo difícil analisá-los isoladamente. A compreensão do problema das drogas requer uma visão ampliada e sistêmica de todos os fatores envolvidos neste complexo processo para ser possível o planejamento e a qualificação das políticas públicas.

The problems related to the use of alcohol and other drugs are a reality in today's society and reveal the existence of different related factors. Among them, the condition of vulnerability stands out as an important contributing element to abusive use, as well as family context, being understood as a risk and/or protective factor and as a system directly affected by the problem. Therefore, this study aimed to carry out an integrative literature review on the relationship between vulnerability, drugs and family. For this, a search for articles in the Scielo and VHL databases was carried out combining the descriptors "AND drugs AND family vulnerability", which tracked a total of 105 articles. After using the inclusion criteria, there were 22 articles remaining to be analyzed. From the 22 studies, seven involved school adolescents, five with street people, five with family members, four with drug users and one with health professionals. Results have shown that the relationship between drug use, family and vulnerability is intrinsic, making it difficult to analyze them in isolation. Understanding the drug problem requires an expanded and systemic view of all factors involved in this complex process in order to plan and qualify public policies.

Los problemas relacionados con el uso de alcohol y otras drogas es una realidad en la sociedad actual y revela la existencia de diferentes factores constitutivos y activos para determinar el fenómeno. Entre éstos, la condición de vulnerabilidad se destaca como un contribuyente importante al uso abusivo, así como a la familia, que se entiende como un factor de riesgo y / o protección y como un sistema directamente afectado por el problema. Por lo tanto, este estudio tuvo como objetivo realizar una revisión bibliográfica integradora sobre la relación entre vulnerabilidad, drogas y contexto familiar. Para este fin, se realizó una búsqueda de artículos en las bases de datos Scielo y BVS apoyada en la combinación de los descriptores "vulnerabilidad Y drogas Y familia" que rastrearon un total de 105 artículos. Después de aplicar los criterios de inclusión, quedaron 22 artículos, que fueron analizados en su totalidad. De éstos, siete se llevaron a cabo con adolescentes escolares, cinco con personas sin hogar, cinco con familiares de usuarios, cuatro con consumidores de drogas y uno con profesionales de la salud. Los resultados del análisis de los estudios sugieren que la relación entre el consumo de drogas, la familia y la condición de vulnerabilidad es intrínseca, lo que dificulta su análisis de forma aislada. Comprender el problema de las drogas requiere una visión ampliada y sistémica de todos los factores involucrados en este complejo proceso, para que sea posible planificar y calificar las políticas públicas.

National trends and determinants of hospitalization for uterine leiomyomas - Portuguese public database analysis from 2000 to 2015.

OBJECTIVE: To determine the trends of hospitalization (inpatients and outpatients) for uterine leiomyomas in Portugal, over a period of fifteen years. STUDY DESIGN: We perform a population- and register-based retrospective study of women who were hospitalized with a primary diagnosis of uterine fibroid in public hospitals in continental Portugal, in the period between January 1, 2000 and December 31, 2015. Patient data regarding hospital codes, admission and discharge dates, patient age, diagnosis, procedures and complications were extracted from the national database of Administração Central do Sistema de Saúde (ACSS). All calculations were performed with the STATA software, version 13.1. Categorical data were analysed by the χ2 test and the means of continuous variables were analysed with Student's t-test. Statistical significance was set at p < 0.05. RESULTS: Between 2000 and 2015, 102 476 patients were admitted to public hospitals in Portugal due to uterine leiomyomas. The majority were admitted to hospital for surgery: 73.6 % for hysterectomy and 13.0 % for myomectomy. During this period, the definitive treatment (hysterectomy) decreased from 83.2% to 63.0% (p < 0.001), with a change towards more conservative treatments such as myomectomies (6.4% to 22.6%, p < 0.001). Additionally, in women submitted to hysterectomy, laparoscopic and vaginal routes increased (1.1%-11.5%, p < 0.001 and 2.1%-4.0%, p < 0.001; respectively). Globally, there was a 14.3 % reduction in hospitalizations due to uterine fibroids and an increase in the outpatient rate (from 3.1% to 22.1%). The mean number of hospitalization days for inpatients also decreased (from 6.3 ± 4.1-4.0 ± 3.0, p < 0.001). Regarding urgently hospitalized women, 11.8 % required a blood transfusion. In women submitted to surgical procedures, 0.5 % had an intraoperative complication and 2.3 % a post-operative complication, directly related to the surgical procedure. CONCLUSION: There was a reduction in hospitalizations due to uterine fibroids and a change towards more conservative treatments.

Ecotoxicological effects of lanthanum in Mytilus galloprovincialis: Biochemical and histopathological impacts.

Inappropriate processing and disposal of electronic waste contributes to the contamination of aquatic systems by various types of pollutants such as the rare-earth elements (REE) in which lanthanum (La) is included. Knowledge on the toxicity of these elements in marine organisms is still scarce when compared to other metals such as mercury (Hg) and arsenic (As). Therefore, this study aims to assess the toxicity of La on the mussel Mytilus galloprovincialis, considered a good bioindicator of aquatic pollution, through the analysis of metabolic, oxidative stress, neurotoxicity and histopathological markers. Organisms were exposed to different concentrations of La for a period of 28 days (0, 0.1, 1, 10 mg/L) under controlled temperature (18 °C ± 1.0) and salinity (30 ± 1) conditions. La concentrations in mussels increased in higher exposure concentrations. La exposure demonstrated a biochemical response in mussels, evidenced by lowered metabolism and accumulation of energy reserves, activation of the antioxidant defences SOD and GPx as well as the biotransformation enzymes GSTs, especially at intermediate concentrations. Despite oxidative stress being shown by a decrease in GSH/GSSG, oxidative damage was avoided as evidenced by lower LPO and PC levels. Inhibition of the enzyme AChE demonstrated the neurotoxicity of La in this species. Histopathological indices were significantly different from the control group, indicating impacts in gonads, gills and digestive glands of mussels due to La. These results show that La can be considered a risk for marine organisms and thus its discharge into the environment should be monitored.

Prevenção e promoção da saúde: revisão integrativa de pesquisas sobre drogas / Prevention and health promotion: an integrative review of drugs research

Os modelos de saúde que orientam o entendimento do processo saúde e doença sustentam as diferentes noções de prevenção e promoção da saúde. O objetivo deste artigo foi investigar o panorama da produção científica por meio de uma revisão integrativa sobre prevenção e promoção da saúde em estudos sobre drogas no Brasil. Foram utilizados os descritores “prevenção”, “promoção” e “drogas” na Biblioteca Virtual em Saúde – Brasil. Oito artigos corresponderam aos critérios de inclusão para este estudo e foram analisados na íntegra. Os estudos foram predominantemente quantitativos e tiveram como participantes adolescentes. Os conceitos de prevenção e promoção não foram discutidos explicitamente em nenhum artigo, requerendo a análise destes a partir dos resultados apresentados e da perspectiva teórico-metodológica norteadora dos estudos.

Health care models that guide the understanding of health and disease process support different notions of prevention and health promotion. The aim of this paper was to investigate the landscape of scientific production through an integrative review of prevention and health promotion in studies of drugs in Brazil. The descriptors “prevention”, “promotion” and “drug” were used in the Virtual Health Library – Brazil. Eight articles matched the inclusion criteria for this study and were examined in details. The studies were predominantly quantitative and had as participants adolescents. The concepts of prevention and promotion were not explicitly discussed in any article, requiring the analysis of these from the results presented and the theoretical and methodological perspective guiding the studies.

Expectativas sobre vias de parto entre acadêmicas de psicologia / Expectations regarding the types of delivery among psychology students

Introdução: vários fatores interferem de maneira significativa na escolha da via de parto. No início da gravidez a maioria das mulheres indica preferência pelo parto normal, entretanto, a maior parte termina por fazer a cesárea. No Brasil, 55% dos partos realizados são cesáreas e há um predomínio deste tipo de parto, especialmente no sistema privado de saúde. Objetivo: compreender as expectativas de acadêmicas de Psicologia que nunca passaram pela experiência de parto, sobre as vias de parto. Metodologia: foi utilizado como instrumento de coleta de dados um questionário semiestruturado de autoaplicação individual com questões abertas referentes a expectativas em relação ao parto. A pesquisa configura-se como um estudo qualitativo e para análise de dados foi utilizada a análise de conteúdo. Resultados: participaram da pesquisa 109 mulheres, com média de idade de 22,7 anos, desvio padrão de 4,6, que nunca passaram pela experiência de parto. Estas mulheres demonstraram esperar, principalmente, uma assistência médica de qualidade, desejavam o parto normal por este possibilitar uma recuperação melhor e mais rápida, afirmaram sentirem medo que haja complicações e sofrimento no parto e tinham medo da dor. Conclusão: é necessário fornecer à mulher mais informações, apoio e suporte no momento da escolha da via de parto.

Introduction: various factors significantly interfere in the type of delivery choice. At the start of a pregnancy, the majority of women indicate a preference for a normal delivery, however, a greater part end up having a caesarean delivery. In Brazil, 55% of deliveries performed are Caesarean, and there is a predominance of this type of delivery especially in the private health care system. Objective: to understand the expectations of Psychology students who have never gone through the experience of delivery regarding the types of delivery. Methodology: a self-administrated semi-structured questionnaire with open questions regarding expectations relating to delivery was utilized as a data collection instrument. The research was configured as a qualitative study, and for the data analysis, content analysis was utilized. Results: the participants were 109 women, averaging 22.7 years old with a standard error of 4.6, who never passed through the childbirth experience. These women hoped, principally, for quality medical assistance, and wished for this to enable a better and faster recovery from normal delivery. They stated that they feared that there would be complications and pain during the delivery, and that they were afraid of the pain. Conclusion: it´s necessary to provide more information and support to the woman when choosing the type of delivery.

Rede social significativa de usuários de um CAPSad: perspectivas para o cuidado / Significant social network of users of a CAPsad: perspectives for care

Os Centros de Atenção Psicossocial Álcool e Drogas (CAPSad) são destinados ao cuidado de usuários com problemas relacionados ao uso álcool e outras drogas. O trabalho desenvolvido pressupõe a participação das redes sociais do usuário. Diante disso, este estudo teve como objetivo caracterizar a estrutura, os vínculos e funções das redes sociais significativas de usuários de um CAPSad do sul do país que têm problemas relacionados ao uso do álcool. Participaram do estudo oito usuários. Para coleta de dados foi utilizado entrevista semiestruturada e a construção do mapa de rede. Os resultados demonstraram que as redes sociais significativas dos usuários eram constituídas predominantemente por familiares, profissionais e colegas do CAPSad. As principais funções desempenhadas pelos membros da rede foi o apoio emocional, guia cognitivo e conselhos e companhia social. Ressalta-se a importância do fortalecimento da rede social significativa dos usuários para que o processo do cuidado seja potencializado.(AU)

Problems related to alcohol use are regarded as one of the today's major public health problems. In Brazil, the Psychosocial Attention Centres alcohol and drugs (CAPSad) represent the main device for users with problems related to the use of alcohol and other drugs. The work developed by CAPSad presume the participation of the family and the community, since ties and social relations are a major factor in the care process. Therefore, the present study aimed to characterize the structure, the links and their functions, of the significant social networks of CAPSad users in southern part of Brazil who have problems related to alcohol use. Eight users, as instruments were collected using semi-structured interviews along with the construction of users' network map. The data were subjected to content analysis. The results showed that the users' significant social network consisted mainly of family members, professionals and colleagues in CAPSad. The main functions performed by members of the network were emotional support, cognitive guide and advice and social company. It is important to stress the importance of strengthening the social network of users so that the care process is enhanced.(AU)

Família, redes sociais e o uso de drogas: tensionamento entre o risco e a proteção / Family, social networks and drug use: tensioning between risk and protection / Familia, redes sociales y uso de drogas: tensionamento entre el riesgo y la protección

Este estudo teve como objetivo realizar uma revisão sistemática de artigos nacionais e internacionais, publicados entre os anos de 2004 e 2015, sobre a relação entre família, redes sociais e uso de drogas. Foram acessadas quatro bases de dados: Biblioteca Virtual em Saúde (BVS), PubMed, Scielo e PscInfo, tendo como descritores as expressões "social AND networks"; "family" e "drugs". De um total de 234 artigos encontrados, 17 abordavam diretamente os temas deste estudo e constituem o corpus de análise. Os resultados sugerem que: a) a rede social tende a ser restrita entre os usuários de drogas, b) na rede social há membros que também fazem uso de drogas, e c) que as redes constituídas por membros familiares tendem a ser protetoras para evitar o uso/abuso de drogas. Destaca-se que o contexto social e/ou comunitário interfere decididamente na composição e funções da rede social constituída em torno de usuários de drogas, seja como fator potencialmente de risco, seja de proteção.

This study aimed to carry out a systematic review of national and international articles published between the years 2004 and 2015 on the relationship between family, social networks and drug use. Four databases were accessed: Virtual Health Library (VHL), PubMed, Scielo and PscInfo, with the descriptors "social AND networks"; "Family" and "drugs." Of a total of 234 articles found, 17 directly addressed the themes of this study and constitute the corpus of analysis. Results suggest that: a) the social network tends to be restricted among drug users, b) in the social network there are members who also use drugs, and c) networks made up of family members tend to be protective to avoid the use /drugs abuse. It is highlighted that social and / or community context decisively influences the composition and functions of the social network constituted around drug users, as a potential risk or protection factor.

Este estudio tuvo como objetivo realizar una revisión sistemática de artículos nacionales e internacionales publicados entre los años 2004 y 2015 sobre la relación entre familia, redes sociales y consumo de drogas. Se accedieron a cuatro bases de datos: Biblioteca Virtual en Salud (BVS), PubMed, Scielo y PscInfo, con los descriptores "redes sociales AND"; "Familia" y "drogas". De un total de 234 artículos encontrados, 17 abordaron directamente los temas de este estudio y constituyeron el corpus de análisis. Los resultados sugieren que: a) la red social tiende a ser restringida entre los usuarios de drogas, b) en la red social hay miembros que también consumen drogas, y c) las redes formadas por miembros de la familia tienden a ser protectoras para evitar el uso / abuso. Se destaca que el contexto social y / o comunitario influye de manera decisiva en la composición y funciones de la red social constituida en torno a los consumidores de drogas, como un factor potencial de riesgo o protección.

Hysterectomies in Portugal (2000-2014): What has changed?

OBJECTIVE: To describe conditions regarding hysterectomies during the past 15 years in Portugal. STUDY DESIGN: Nationwide retrospective study of women who underwent hysterectomy in Portuguese public hospitals in the period between 2000 and 2014. Patient data regarding hospital codes, geography, patient age, indications, operative techniques, associated procedures, complications, admission dates, discharge dates and 30-day postoperative readmissions were extracted from the national database with information regarding all public hospitals in Portugal. For calculation of hysterectomy rates, the total number of women was found using the Statistics Portugal website. Data were analysed using STATA version 13.1. RESULTS: A total of 166 177 hysterectomies were performed between 2000 and 2014 in public hospitals in Portugal. The overall rate of hysterectomy decreased 19.3% (from 212/100 000 to 171/100 000 women per year). The average age of women at time of hysterectomy increased from 51.6±11.4 to 55.2±12.3years (p<0.001). There was an increase in laparoscopic [1.2%-9.5%, p<0.001] and vaginal route [13.3%-21.2%, p<0.001], with a consequent decrease in laparotomic route [85.5%-69.1%, p<0.001]. There was a change in the pattern of indications for hysterectomy; however, uterine fibroids remain the major indication for hysterectomy [45.3%-37.6%, p<0.001]. In women with hysterectomy for benign pathology, the rate of bilateral adnexectomy decreased from 71.0% to 51.9% (p<0.001) and the rate of bilateral salpingectomy increased from 1.0% to 15.1% (p<0.001). The mean number of hospitalization days decreased from 7.1±6.1 (in 2000-2004) to 5.4±5.0 (in 2010-2014) (p<0.001). Globally, the rate of complications increased from 3.3% in 2000-2004 to 3.6% in 2010-2014 (p<0.01). CONCLUSION: In Portugal, the rate of hysterectomies decreased in the last 15 years with an increase in age at the time of the procedure and a change towards less invasive routes. Uterine fibroids remain the major indication for hysterectomy. Additionally, we noted a significant shift towards more concomitant bilateral salpingectomy (and less bilateral adnexectomy) during hysterectomy for benign indications, according to the evidence suggesting the fallopian tube as the origin of ovarian cancer.

Nodular glomerulosclerosis in a non-diabetic hypertensive, dyslipidemic, smoker patient: a case report.

INTRODUCTION: This is a case report of a patient with idiopathic nodular glomerulosclerosis whose pathogenesis and morphology are similar to diabetic nephropathy. CASE PRESENTATION: A 64-year-old Brazilian man, leukoderma, dyslipidemic, obese with chronic obstructive pulmonary disease secondary to tobacco smoking, known to be hypertensive for five years and he had no history of diabetes. He was admitted with sudden anasarca, rapid loss of renal function and needed to start hemodialysis immediately. Renal biopsy was performed, and the sections were examined by light microscopy, immunofluorescence and electron microscopy. Morphological and ultrastructural findings showed that the profile of the disease studied herein strongly resembles diabetic nephropathy. However, the absence of diabetes mellitus, the presence of arteriolar hyalinosis in renal arterioles, tobacco smoking, and other clinical factors observed can play a significant role in nodular formation. CONCLUSION: The clinical features of the patient, and most importantly, the fact that he is a smoker, favor the diagnosis of "nodular glomerulosclerosis associated with smoking", a nomenclature proposed by some authors as an alternative to the term idiopathic nodular glomerulosclerosis. This clinical case report highlights idiopathic nodular glomerulosclerosis as a rare disease of little known etiopathogenesis; thus, further studies are necessary in order to elucidate the causes of this disease.

Nodular glomerulosclerosis in a non-diabetic hypertensive, dyslipidemic, smoker patient: a case report / Glomeruloesclerose nodular em paciente fumante não diabético, hipertenso e dislipidêmico: relato de caso

Abstract Introduction: This is a case report of a patient with idiopathic nodular glomerulosclerosis whose pathogenesis and morphology are similar to diabetic nephropathy. Case presentation: A 64-year-old Brazilian man, leukoderma, dyslipidemic, obese with chronic obstructive pulmonary disease secondary to tobacco smoking, known to be hypertensive for five years and he had no history of diabetes. He was admitted with sudden anasarca, rapid loss of renal function and needed to start hemodialysis immediately. Renal biopsy was performed, and the sections were examined by light microscopy, immunofluorescence and electron microscopy. Morphological and ultrastructural findings showed that the profile of the disease studied herein strongly resembles diabetic nephropathy. However, the absence of diabetes mellitus, the presence of arteriolar hyalinosis in renal arterioles, tobacco smoking, and other clinical factors observed can play a significant role in nodular formation. Conclusion: The clinical features of the patient, and most importantly, the fact that he is a smoker, favor the diagnosis of "nodular glomerulosclerosis associated with smoking", a nomenclature proposed by some authors as an alternative to the term idiopathic nodular glomerulosclerosis. This clinical case report highlights idiopathic nodular glomerulosclerosis as a rare disease of little known etiopathogenesis; thus, further studies are necessary in order to elucidate the causes of this disease.

Resumo Introdução: Este é um relato de caso de um paciente com glomeruloesclerose nodular idiopática, cuja patogênese e morfologia são semelhantes à nefropatia diabética. Apresentação do caso: Homem, 64 anos de idade, leucodermo, com dislipidemia, obesidade, doença pulmonar obstrutiva crônica secundária ao tabagismo, hipertenso há cinco anos e sem história de diabetes mellitus. Ele foi internado com anasarca súbita, perda rápida da função renal com necessidade de hemodiálise imediata. A biópsia renal foi realizada, e as seções foram examinadas por microscopia luz, imunofluorescência e microscopia eletrônica. Achados morfológicos e ultraestruturais mostraram que o perfil da doença estudado fortemente se assemelha à nefropatia diabética. No entanto, a ausência de diabetes mellitus, a presença de hialinose arteriolar em arteríolas renais, o fumo do tabaco, e outros fatores clínicos observados podem desempenhar um papel significativo na formação nodular. Conclusão: As características clínicas do paciente e, o mais importante, o fato de que ele é fumante favorecem o diagnóstico de "glomeruloesclerose nodular associada ao tabagismo", uma nomenclatura proposta por alguns autores como uma alternativa para o termo glomeruloesclerose nodular idiopática. Este relato de caso clínico realça glomeruloesclerose nodular idiopática como uma doença rara, de etiopatogenia pouco conhecida. Desse modo, mais estudos são necessários para elucidar as causas desta doença.

miR-155 in the progression of lung fibrosis in systemic sclerosis.

BACKGROUND: MicroRNA (miRNA) control key elements of mRNA stability and likely contribute to the dysregulated lung gene expression observed in systemic sclerosis associated interstitial lung disease (SSc-ILD). We analyzed the miRNA gene expression of tissue and cells from patients with SSc-ILD. A chronic lung fibrotic murine model was used. METHODS: RNA was isolated from lung tissue of 12 patients with SSc-ILD and 5 controls. High-resolution computed tomography (HRCT) was performed at baseline and 2-3 years after treatment. Lung fibroblasts and peripheral blood mononuclear cells (PBMC) were isolated from healthy controls and patients with SSc-ILD. miRNA and mRNA were analyzed by microarray, quantitative polymerase chain reaction, and/or Nanostring; pathway analysis was performed by DNA Intelligent Analysis (DIANA)-miRPath v2.0 software. Wild-type and miR-155 deficient (miR-155ko) mice were exposed to bleomycin. RESULTS: Lung miRNA microarray data distinguished patients with SSc-ILD from healthy controls with 185 miRNA differentially expressed (q < 0.25). DIANA-miRPath revealed 57 Kyoto Encyclopedia of Genes and Genomes pathways related to the most dysregulated miRNA. miR-155 and miR-143 were strongly correlated with progression of the HRCT score. Lung fibroblasts only mildly expressed miR-155/miR-21 after several stimuli. miR-155 PBMC expression strongly correlated with lung function tests in SSc-ILD. miR-155ko mice developed milder lung fibrosis, survived longer, and weaker lung induction of several genes after bleomycin exposure compared to wild-type mice. CONCLUSIONS: miRNA are dysregulated in the lungs and PBMC of patients with SSc-ILD. Based on mRNA-miRNA interaction analysis and pathway tools, miRNA may play a role in the progression of the disease. Our findings suggest that targeting miR-155 might provide a novel therapeutic strategy for SSc-ILD.

Arterite de Takayasu: diagnóstico, evolução e tratamento de paciente com ulceração em couro cabeludo. Relato de caso / Takayasu's arteritis: diagnosis, evolution and treatment of patient with scalp ulceration. Case report

A arterite de Takayasu é uma vasculite autoimune rara, que afeta predominantemente a aorta e seus ramos principais, produzindo variados sinais e sintomas, como febre, mialgia, hipertensão, úlceras e isquemia. É mais comum na Ásia e menos frequente nos países ocidentais, acometendo mulheres em idade reprodutiva. As manifestações cutâneas podem estar presentes. Os critérios diagnósticos do American College of Rheumatology incluem idade <40 anos, diminuição dos pulsos braquiais, claudicação de extremidades, diferença de 10mmHg na pressão arterial sistólica de membros superiores, sopros em suclávia e aorta, e alterações angiográficas de aorta e seus arcos principais. Os melhores resultados terapêuticos baseiam-se na corticoterapia associada à imunossupressores como metotrexato. O uso de imunobiológicos é incipiente e carece de estudos para comprovar sua eficácia. A paciente em questão apresentava-se com quadro atípico, manifestando ulceração em couro cabeludo, decorrente de estenose em ramos superficiais da carótida externa. Evoluiu com trombose venosa cerebral e osteomielite, sendo submetida à oxigenoterapia hiperbárica e imunossupressão com 160mg de prednisona.Velocidade de hemossedimentação e proteína C-reativa estavam elevados, mas seu valor isolado carece de especificidade, embora sejam critérios de atividade da doença. A terapêutica com prednisona, metotrexato e anticoagulação com varfarina foi eficiente, pois reduziu a área da lesão em couro cabeludo e minimizou o quadro sistêmico, propiciando melhor qualidade de vida para a paciente.

Takayasu's arteritis is a rare autoimmune vasculitis, which primarily affects the aorta and its main branches, producing varied symptoms and signs, such as fever, myalgia, hypertension, ulcers, and ischemia. It is more common in Asia and less frequente in western countries, affecting women of childbearing age.Cutaneous manifestations may be present. The diagnostic criteria of the American College of Rheumatology include age <40 years,reduction of brachial pulses, extremity claudication, difference of 10 mmHg in systolic blood pressure of upper limbs, murmurs in subclavian artery and aorta, and angiographic changes of the aorta and its main arches. The best therapeutic results are based on corticosteroid therapy associated with immunosuppressants such as methotrexate. The use of immunobiologicals is incipiente and requires studies to prove its effectiveness. The patient presented with an atypical clinical picture, showing ulceration on the scalp as a result of stenosis in superficial branches of the external carotid. She progressed with cerebral venous thrombosis and osteomyelitis, undergoing hyperbaric oxygen therapy and immunosuppression with 160mg of prednisone. Erythrocyte sedimentationrate and C-Reactive Protein were high, but their individual value lacks specificity, although they are criteria for disease activity. Therapy with prednisone, methotrexate, and anticoagulation with warfarin were efficient, because they reduced the area of the lesion on the scalp, and minimized the systemic picture, providing better quality of life for the patient.

Galectin-9 as an important marker in the differential diagnosis between oral squamous cell carcinoma, oral leukoplakia and oral lichen planus.

OBJECTIVES: To evaluate the expression of Galectins (Gal) 1, 3 and 9, Metalloproteinase 3 (MMP-3) and mast cell density in oral lesions of patients with potentially malignant disorders (PMD) and oral squamous cell carcinomas (OSCC) by comparison with the controls. STUDY DESIGN: We selected 40 cases of PMD, 40 OSCC and 13 with normal histopathological profile. Immunohistochemistry was performed for Gal-1, Gal-3, Gal-9 and MMP-3. RESULTS: Gal-9 was significantly higher in patients with OSCC than in others groups (p < 0.001). Gal-1 expression was significantly lower in patients with leukoplakia than those with OSCC and controls (p = 0.0001). Gal-3 was significantly lower in patients with OSCC than those with leukoplakia (p = 0.03). MMP-3 was lower in patients with leukoplakia in comparison with the lichen planus group (p = 0.013). CONCLUSION: The increased expression of Gal-9 may be helpful to differentiate of OSCC from other oral cavity lesions.

Lowered national cesarean section rates after a concerted action.

OBJECTIVE: To evaluate national cesarean section (CS) rates and other obstetric indicators after a concerted action to reduce CS rates was undertaken in Portugal from 2010 onwards. This action was based on the transmission of information and training of healthcare professionals, together with the inclusion of CS rates as a criterion for hospital funding. DESIGN: Retrospective observational population-based study. SETTING: Portugal. POPULATION: Births occurring in Portugal between 2000 and 2014. METHODS: Governmental sources were used to obtain data on national CS, perinatal and maternal mortality rates. Rates of instrumental vaginal delivery, vaginal birth after cesarean (VBAC), hypoxia-related complications and perineal lacerations were retrieved for state-owned hospitals. MAIN OUTCOME MEASURES: CS, perinatal and maternal mortality, instrumental vaginal delivery, VBAC, hypoxia-related complications and perineal lacerations. RESULTS: After a continuous rise between 2000 and 2009, national CS rates declined significantly over the following 5 years (36.6% vs. 33.1%, time trend p ≤ 0.001). Perinatal mortality maintained a downward trend during this period, while maternal mortality remained unchanged. Rates of instrumental vaginal delivery, VBAC and perineal lacerations increased, while the incidence of hypoxia-related complications decreased. CONCLUSIONS: A concerted action based on the transmission of information and training of healthcare professionals, together with the inclusion of CS rates as a criterion for hospital funding, was followed by a significant reduction in national CS rates, as well as an improvement in most related obstetric indicators. There may be an association between the reported intervention and the observed changes.

Association of Interferon- and transforming growth factor ß-regulated genes and macrophage activation with systemic sclerosis-related progressive lung fibrosis.

OBJECTIVE: Systemic sclerosis (SSc)-related interstitial lung disease (ILD) is one of the leading causes of mortality. We undertook this study to analyze the gene expression of lung tissue in a prospective cohort of patients with SSc-related ILD and to compare it with that in control lungs and with 2 prospective clinical parameters in order to understand the molecular pathways implicated in progressive lung disease. METHODS: Lung tissue was obtained by open lung biopsy in 28 consecutive patients with SSc-related ILD and in 4 controls. High-resolution computed tomography (HRCT) and pulmonary function testing (PFT) were performed at baseline and 2-3 years after treatment based on lung histologic classification. Microarray analysis was performed, and the results were correlated with changes in the HRCT score (FibMax) and PFT values. Quantitative polymerase chain reaction (qPCR) and immunohistochemistry were used to confirm differential levels of messenger RNA and protein. RESULTS: Lung microarray data distinguished patients with SSc-related ILD from healthy controls. In the lungs of patients with SSc-related ILD who had nonspecific interstitial pneumonia (NSIP), expressed genes included macrophage markers, chemokines, collagen, and transforming growth factor ß (TGFß)- and interferon (IFN)-regulated genes. Expression of these genes correlated with progressive lung fibrosis defined by the change in FibMax. Immunohistochemistry confirmed increased markers of collagen (COL1A1), IFN (OAS1 and IFI44), and macrophages (CCL18 and CD163), and the positive correlation with the change in FibMax was confirmed by qPCR in a larger group of SSc patients with NSIP. Several genes correlated with both the change in FibMax (r > 0.4) and the change in % predicted forced vital capacity (r < -0.1), including IFN and macrophage markers, chemokines, and heat-shock proteins. CONCLUSION: These results highlight major pathogenic pathways relevant to progressive pulmonary fibrosis in SSc-related ILD: macrophage emigration and activation, and up-regulated expression of TGFß- and IFN-regulated genes.