CASZ1 upregulates PI3K-AKT-mTOR signaling and promotes T-cell acute lymphoblastic leukemia.

CASZ1 is a conserved transcription factor involved in neural development, blood vessel assembly and heart morphogenesis. CASZ1 has been implicated in cancer, either suppressing or promoting tumor development depending on the tissue. However, the impact of CASZ1 on hematological tumors remains unknown. Here, we show that the T-cell oncogenic transcription factor TAL1 is a direct positive regulator of CASZ1, that T-cell acute lymphoblastic leukemia (T-ALL) samples at diagnosis overexpress CASZ1b isoform, and that CASZ1b expression in patient samples correlates with PI3KAKT- mTOR signaling pathway activation. In agreement, overexpression of CASZ1b in both Ba/F3 and T-ALL cells leads to the activation of PI3K signaling pathway, which is required for CASZ1b-mediated transformation of Ba/F3 cells in vitro and malignant expansion in vivo. We further demonstrate that CASZ1b cooperates with activated NOTCH1 to promote T-ALL development in zebrafish, and that CASZ1b protects human T-ALL cells from serum deprivation and treatment with chemotherapeutic drugs. Taken together, our studies indicate that CASZ1b is a TAL1-regulated gene that promotes T-ALL development and resistance to chemotherapy.

Elaboration and analysis of psychometric properties of a questionnaire to assess pregnant women's knowledge about toxoplasmosis / Elaboração e análise de propriedades psicométricas de um questionário para avaliar o conhecimento de gestantes sobre toxoplasmose

Abstract Objectives: to elaborate and analyze the psychometric properties of a questionnaire to assess among pregnant women's knowledge about toxoplasmosis. Methods: methodological study elaborating an instrument conducted in the north of Minas Gerais in 2019. The steps followed were: 1. Elaboration of the questionnaire items based on medical literature available in indexed databases. 2. Content validation. 3. Apparent validation. 4. Construct validation with hypothesis testing after the application of the questionnaire and comparison of the mean scores using the Mann-Whitney U test. 5. Reliability analysis with internal consistency analysis and test-retest. Results: the final instrument consisted of 26 items. Content validation reached 90% agreement among experts. The hypothesis test found a significant diference among the scores of the groups evaluated (p<0.001). Cronbach's alpha found a value of 0.84 and the test-retest showed an intra-class correlation index of 0.78 (p<0.001). Conclusions: the instrument elaborated proved to be valid and reliable and could be used to assess among pregnant women's knowledge about toxoplasmosis and, therefore, guiding to the educational and preventive measures.

Resumo Objetivos: elaborar e analisar as propriedades psicométricasde um questionáriopara avaliação do conhecimento sobre toxoplasmose entre gestantes. Métodos: estudo metodológico de elaboração de instrumento, realizado no norte de Minas Gerais, em 2019. O estudo seguiu os seguintes passos: 1. Elaboração dos itens a do questionário, com base na literatura médica disponível em bases indexadas. 2. Validação de conteúdo. 3. Validação aparente. 4. Validação de constructo, com teste de hipóteses, após aplicação do questionário e comparação de médias dos escores por meio do teste U de Mann-Whitney. 5. Análise de confabilidade, com análise da consistência interna e teste-reteste. Resultados: o instrumento final foi composto por 26 itens. Na validação de conteúdo alcançou 90% de concordância entre os experts. O teste de hipótese registrou diferença significativa entre os escores dos grupos avaliados (p<0,001). O alfa de Cronbach apresentou valor de 0,84 e o teste-reteste apresentou índice de correlação intra-classe de 0,78 (p<0,001). Conclusão: o instrumento elaborado apresentou-se válido e confável e poderá ser utilizado para avaliação de conhecimento sobre toxoplasmose entre gestantes, norteando medidas educativas e preventivas.

Effects of air pollution exposure on inflammatory and endurance performance in recreationally trained cyclists adapted to traffic-related air pollution.

The aim of the present study was to analyze the effects of traffic-related air pollution (TRAP) on markers of inflammatory, neuroplasticity, and endurance performance-related parameters in recreationally trained cyclists who were adapted to TRAP during a 50-km cycling time trial (50-km cycling TT). Ten male cyclists performed a 50-km cycling TT inside an environmental chamber located in downtown Sao Paulo (Brazil), under TRAP or filtered air conditions. Blood samples were obtained before and after the 50-km cycling TT to measure markers of inflammatory [interleukin-6 (IL-6), C-reactive protein (CRP), interleukin-10 (IL-10), intercellular adhesion molecule-1 (ICAM-1)] and neuroplasticity [brain-derived neurotrophic factor (BDNF)]. Rating of perceived exertion (RPE), heart rate (HR), and power output (PO) were measured throughout the 50-km cycling TT. There were no significant differences between experimental conditions for responses of IL-6, CRP, and IL-10 (P > 0.05). When compared with exercise-induced changes in filtered air condition, TRAP provoked greater exercise-induced increase in BDNF levels (TRAP = 3.3 ± 2.4-fold change; Filtered = 1.3 ± 0.5-fold change; P = 0.04) and lower exercise-induced increase in ICAM-1 (Filtered = 1.1 ± 0.1-fold change; TRAP = 1.0 ± 0.1-fold change; P = 0.01). The endurance performance-related parameters (RPE, HR, PO, and time to complete the 50-km cycling TT) were not different between TRAP and filtered air conditions (P > 0.05). These findings suggest that the potential negative impacts of exposure to pollution on inflammatory, neuroplasticity, and performance-related parameters do not occur in recreationally trained cyclists who are adapted to TRAP.

PTH Spikes During Surgical Treatment for Secondary and Tertiary Hyperparathyroidism: A Prospective Observational Study.

BACKGROUND: The aim of the present study was to determine whether PTH spikes in renal hyperparathyroidism can interfere with the interpretation of intraoperative PTH monitoring and to determine its frequency and characteristics. METHODS: This was a prospective observational study of consecutive patients who underwent surgical treatment in a single tertiary institution. Patients were divided into two groups: spike and no spike. Patients with secondary and tertiary hyperparathyroidism were analyzed separately. Intraoperative PTH monitoring by venous serial samples: two samples were taken before the excision of the parathyroid gland, and two others were taken after resection. RESULTS: PTH spikes occurred in 23.5% (53 of 226), and their occurrence was similar between secondary and tertiary hyperparathyroidism patients (p = 0.074). The relative PTH spike intensity was higher in transplanted patients than in dialysis patients (55 vs. 20%, p = 0.029). A characteristic of the secondary hyperparathyroidism patients was the highest frequency of surgical failure (23 vs. 7.5%, p = 0.016) and the higher occurrence of supernumerary glands in the spike group (23 vs. 10.3%, p = 0.035). Supernumerary parathyroid was associated with surgical failure [19.1 (6.5-55.7) odds ratio [confidence interval], p < 0.001). In the studies evaluating the diagnostic test validity for patients on dialysis and experiencing spikes, the most significant impacts were in the sensitivity, accuracy, and negative predictive value of the method. CONCLUSIONS: PTH spikes occurred in up to 23.5% of renal hyperparathyroidism surgical treatments and can negatively influence the intraoperative parathyroid hormone monitoring. Regarding the phenomenon of PTH spikes, it is prudent to think about the possibility of a hyperplastic supernumerary gland.

MicroRNAs in Obesity-Associated Disorders: The Role of Exercise Training.

Obesity is a worldwide epidemic affecting over 13% of the adult population and is defined by an excess of body fat that predisposes comorbidities. It is considered a multifactorial disease in which environmental and genetic factors interact, and it is a risk marker for cardiovascular disease. Lifestyle modifications remain the mainstay of treatment for obesity based on adequate diet and physical exercise. In addition, obesity is related to cardiovascular and skeletal muscle disorders, such as cardiac hypertrophy, microvascular rarefaction, and skeletal muscle atrophy. The discovery of obesity-involved molecular pathways is an important step to improve both the prevention and management of this disease. MicroRNAs (miRNAs) are a class of gene regulators which bind most commonly, but not exclusively, to the 3'-untranslated regions of messenger RNAs of protein-coding genes and negatively regulate their expression. Considerable effort has been made to identify miRNAs and target genes that predispose to obesity. Besides their intracellular function, recent studies have demonstrated that miRNAs can be exported or released by cells and circulate within the blood in a remarkably stable form. The discovery of circulating miRNAs opens up intriguing possibilities for the use of circulating miRNA patterns as biomarkers for obesity and cardiovascular diseases. The aim of this review is to provide an overview of the recent discoveries of the role played by miRNAs in the obese phenotype and associated comorbidities. Furthermore, we will discuss the role of exercise training on regulating miRNAs, indicating the mechanisms related to these alterations.

Effects of Aerobic Exercise Training on MyomiRs Expression in Cachectic and Non-Cachectic Cancer Mice.

We investigated the effects of AET on myomiRs expression in the skeletal muscle and serum of colon cachectic (CT26) and breast non-cachectic (MMTV-PyMT) cancer mice models. Colon cancer decreased microRNA-486 expression, increasing PTEN in tibialis anterior muscle (TA), decreasing the PI3K/mTOR protein pathway, body and muscle wasting, fibers' cross-sectional area and muscle dysfunction, that were not preserved by AET. In contrast, breast cancer decreased those muscle functions, but were preserved by AET. In circulation, the downregulation of microRNA-486 and -206 in colon cancer, and the downregulation of microRNA-486 and upregulation of microRNA-206 expression in breast cancer might be good cancer serum biomarkers. Since the microRNA-206 is skeletal muscle specific, their expression was increased in the TA, serum and tumor in MMTV, suggesting a communication among these three compartments. The AET prevents these effects on microRNA-206, but not on microRNA-486 in MMTV. In conclusion, cancer induced a downregulation of microRNA-486 expression in TA and serum of CT26 and MMTV mice and these effects were not prevented by AET; however, to MMTV, the trained muscle function was preserved, probably sustained by the downregulation of microRNA-206 expression. Serum microRNA-206 is a potential biomarker for colon (decreased) and breast (increased) cancer to monitor the disease evolution and the effects promoted by the AET.

Traffic-related air pollution and endurance exercise: Characterizing non-targeted serum metabolomics profiling.

Although the exposure to traffic-related air pollution (TRAP) has emerged as one of main problem worldwide to inhabitants' health in urban centers, its impact on metabolic responses during exercise is poorly understood. The aim of study was to characterize the profile of non-target serum metabolomics during prolonged exercise performed under TRAP conditions. Ten healthy men completed two 90 min constant-load cycling trials under conditions of either TRAP or filtered air. Experimental trials were performed in a chamber located on an avenue with a high volume of vehicle traffic. Blood samples were taken at 30 min, 60 min, and 90 min of exercise. Based on Nuclear Magnetic Resonance metabolomics, the non-target analysis was used to assess the metabolic profile. Twelve, 16 and 18 metabolites were identified as discriminants. These were: at 30 min of exercise, the coefficient of determination (R2) 0.98, the predictive relevance, (Q2) 0.12, and the area under the curve (AUC) 0.91. After 60 min of exercise: (R2: 0.99, Q2: 0.09, AUC: 0.94); and at 90 min of exercise (R2: 0.91, Q2: <0.01, AUC: 0.89), respectively. The discriminant metabolites were then considered for the target analysis, which demonstrated that the metabolic pathways of glycine and serine metabolism (p = 0.03) had been altered under TRAP conditions at 30 min of exercise; arginine and proline metabolism (p = 0.04) at 60 min of exercise; and glycolysis (p = 0.05) at 90 min of exercise. The present results suggest that exposure to TRAP during prolonged exercise leads to a significant change in metabolomics, characterized by a transitional pattern and lastly, impairs the glucose metabolism.

Delayed sampling of intraoperative parathormone may be unnecessary during parathyroidectomy in kidney-transplanted and dialysis patients.

INTRODUCTION: Some authors advise in favor of delayed sampling of intraoperative parathormone testing (ioPTH) during parathyroidectomy in dialysis and kidney-transplanted patients. The aim of the present study was to evaluate the intensity and the role of delayed sampling in the interpretation of ioPTH during parathyroidectomy in dialysis patients (2HPT) and successful kidney-transplanted patients (3HPT) compared to those in single parathyroid adenoma patients (1HPT). METHODS: This was a retrospective study of ioPTH profiles in patients with 1HPT, 2HPT, and 3HPT operated on in a single institution. Samples were taken at baseline ioPTH (sampling at the beginning of the operation), ioPTH-10 min (10 minutes after excision of the parathyroid glands), and ioPTH-15 min (15 minutes after excision of the parathyroid glands). The values were compared to baseline. RESULTS: Median percentage values of ioPTH compared to baseline (100%) were as follows: 1HPT, ioPTH-10 min = 20% and ioPTH-15 min = 16%; 2HPT, ioPTH-10 min = 14% and ioPTH-15 min = 12%; 3HPT, ioPTH-10 min = 18% and ioPTH-15 min = 15%. DISCUSSION: The reduction was equally effective at 10 minutes in all groups. In successful cases, ioPTH decreases satisfactorily 10 minutes after parathyroid glands excision in dialysis and transplanted patients, despite significant differences in kidney function. The postponed sampling of ioPTH appears to be unnecessary.

Perfil epidemiológico dos casos notificados de sífilis em gestantes em Minas Gerais, de 2013 a 2017 / Epidemiological profile of notificated cases of syphilis in Minas Gerais, 2013-2017

Introdução: A sífilis durante a gravidez é um grave problema de saúde pública. Em 2016, foram notificados 37.436 casos de sífilis em gestantes e 20.474 casos de sífilis congênita, com 185 óbitos no Brasil. O fator determinante para a diminuição dos casos é o pré-natal de qualidade. Objetivo: Avaliar o perfil dos casos notificados de sífilis em gestante no estado de Minas Gerais, entre 2013 a 2017. Métodos: Trata-se de um estudo transversal descritivo sobre o perfil epidemiológico dos casos notificados de sífilis em gestante em Minas Gerais entre 2013 a 2017. Os dados foram obtidos no Sistema de Informação de Agravos de Notificação, a partir do Departamento de Informática do Sistema Único de Saúde e categorizados quanto ao número de casos, ano de diagnóstico, faixa etária, nível de escolaridade, raça, região e estágio clínico ao diagnóstico. Resultados: Em 2017 foi demonstrado um aumento de 132% dos casos de gestantes com sífilis, em comparação com 2013. Houve predomínio na região central do estado (43,30%). 92,50% se referem a gestantes moradoras da zona urbana. A faixa etária mais acometida foi 20 a 39 anos. A maior parte (46,3%) se declara como parda. E a escolaridade 5ª a 8ª série incompleto do ensino fundamental foi a mais prevalente (16,05%). A classificação clínica mais comum da sífilis materna foi a primária (34,7%). Conclusão: A assistência pré-natal adequada deve ser iniciada precocemente. É necessária a capacitação das equipes das Unidades Básicas para garantirem ações educativas, identificação de situações de risco, diagnóstico e tratamento oportuno.

Introduction: Syphilis during pregnancy is a serious public health problem. In 2016, 37,436 cases of syphilis in pregnant women and 20,474 cases of congenital syphilis were reported, with 185 deaths in Brazil. The determining factor for the decrease in cases is the prenatal quality. Objective: To evaluate the profile of notified cases of syphilis in pregnant women in Minas Gerais, between 2013 to 2017. Methods: This is a cross-sectional descriptive study on the epidemiological profile of notified cases of syphilis in pregnant women in Minas Gerais from 2013 to 2017. Data were obtained from the Notification of Disease Information System, the from the Department of Informatics of the Unified Health System and categorized according to the number of cases, year of diagnosis, age group, level of education, race, region and clinical stage at diagnosis. Results: In 2017 there was a 132% increase in cases of pregnant women with syphilis compared to 2013. There was a predominance in the central region of the state (43.30%). 92.50% refer to pregnant women living in urban areas. The most affected age group was 20 to 39 years. Most (46.3%) declare themselves as brown. And the 5th to 8th grade incomplete elementary schooling was the most prevalent (16.05%). The most common clinical classification of maternal syphilis was primary (34.7%). Conclusion: Appropriate prenatal care should be started as early as possible. The training of Basic Units teams is necessary to ensure educational actions, identification of risk situations, diagnosis and timely treatment.

Formación de Profesores de Lengua Portuguesa en la Perspectiva de la Educación de Sordos / Portuguese Language Teachers' Education on the Perspective of Education of the Deaf

RESUMEN: Las dificultades de las personas sordas en la lengua portuguesa escrita y del docente en su enseñanza, sumadas a la escasez de investigaciones en el área, hacen relevante la revisión de estrategias en el proceso de formación docente. Se trata de una investigación cualitativa y cuantitativa con 16 profesores de los últimos años de Educación Primaria y Secundaria de la lengua portuguesa de la red de escuelas públicas que trabajaron con estudiantes Sordos en algún momento de su experiencia docente. Fueron seleccionados 8 profesores de la Educación Inclusiva y 8 de una escuela Bilingüe para Sordos. Se utilizó el software NVivo10 para el análisis de datos. En la formación inicial, los docentes no tuvieron contacto con la Lengua de Señas ni estrategias metodológicas específicas para la enseñanza de Sordos. En la educación continua, la enseñanza más eficaz fue la de otros profesores con más experiencia. Destaca una dicotomía entre los profesores de las escuelas inclusivas y los de la escuela bilingüe para Sordos, donde los primeros utilizam la Lengua Brasileña de Señales - Libras como una lengua accesoria para la enseñanza del portugués escrito, ya, los docentes de la escuela bilíngue la utilizan como lengua de instrucción con el uso del metalenguaje. En cuanto a las concepciones, los docentes sugirieron algunas prácticas en formación para trabajar con el público Sordo. Por tanto, es fundamental invertir en escuelas inclusivas y bilingües que trabajen con estudiantes Sordos, así como en la formación continua de los docentes, proponiendo grupos de estudio con todo el equipo pedagógico como parte del proceso de formación.

ABSTRACT: The difficulties of the deaf in written Portuguese and of the teacher in teaching, added to the scarcity of research in the area, make the revision of strategies in the process of teacher training relevant. This is a qualitative and quantitative research with 16 teachers from the last years of Elementary and High School of Portuguese language in the public-school network who worked with deaf students at some point in their teaching experience. Eight teachers from Inclusive Education and eight from a Bilingual School for the Deaf were selected. NVivo10 software was used for data analysis. In the initial training, the teachers did not have contact with Sign Language or specific methodological strategies for teaching the Deaf. In continuing education, the most effective teaching was that of other, more experienced teachers. There is a dichotomy between teachers from inclusive schools and those from the bilingual school for the deaf, where the former use the Brazilian Sign Language as an accessory language for the teaching of written Portuguese, whereas teachers in the bilingual school use it as the language of instruction with the use of metalanguage. Regarding the conceptions, the teachers suggested some training practices to work with the Deaf audience. Therefore, it is essential to invest in inclusive and bilingual schools that serve deaf students, as well as in the continued training of teachers, proposing study groups with the entire pedagogical team as part of the training process.

Critical analysis of the intraoperative parathyroid hormone decrease during parathyroidectomy for secondary and tertiary hyperparathyroidism.

BACKGROUND: This study aims to determine whether intraoperative parathyroid hormone monitoring helps to predict early surgical outcomes in patients with renal hyperparathyroidism and evaluate the impact on decision making during surgery. METHODS: A prospective study was conducted. Serial samples of the intraoperative parathyroid hormone were collected; 2 of these were taken before the excision, and 2 were taken after the planned parathyroid resection (10 minutes and 15 minutes). We tested the criterion of an intraoperative parathyroid hormone percentage decay ≥80% of the highest value of the basal samples as a predictor of success. RESULTS: Of the 228 patients, parathyroidectomy achieved success in 92.1%. In patients with secondary hyperparathyroidism, the failure group showed a tendency to stabilize or even increase the intraoperative parathyroid hormone values from the 10-minute measure (577 pg/mL) to the 15-minute measure (535 pg/mL) (P = .903). Conversely, intraoperative parathyroid hormone continued to drop in those with a successful outcome: 245 pg/mL (10 minutes) and 206 pg/mL (15 minutes) (P < .001). The failure group had a significantly lower percentage decay (P < .001) from baseline when compared with the success group. The intraoperative parathyroid hormone influenced the surgical management in up to 7% of the cases. The intraoperative parathyroid hormone dosage method showed an accuracy of 86%, a sensitivity of 88%, and specificity of 67%. CONCLUSION: In patients with renal hyperparathyroidism undergoing parathyroidectomy, the use of intraoperative parathyroid hormone may help to predict an early therapeutic outcome with high sensitivity and accuracy by indicating the operation's success when there is an 80% reduction of baseline intraoperative parathyroid hormone 15 minutes after removal of the enlarged glands, an associated continuous decrease in serum intraoperative parathyroid hormone levels between 10 and 15 minutes, and achievement of plasma target values <500 pg/mL.

Hypoglycemia symptoms and awareness of hypoglycemia in type 1 diabetes mellitus: cross-cultural adaptation and validation of the Portuguese version of three questionnaires and evaluation of its risk factors.

BACKGROUND: To adapt and validate the Clarke and Gold questionnaires and the Edinburgh Hypoglycemia Symptom Scale (EHSS) to Brazilian Portuguese and to determine the prevalence and risk factors associated with impaired awareness of hypoglycemia (IAH) in patients with type 1 diabetes mellitus (T1DM). METHODS: The process of translation, cultural adaptation, and validation of the questionnaires followed the recommendations of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR)-Task Force for Translation and Cultural Adaptation. Patients with T1DM for a minimum of 12 months, aged 18 years or older, and with Brazilian nationality were selected to participate. RESULTS: A total of 123 patients were enrolled. The Clarke and Gold questionnaires as well as the EHSS exhibited adequate internal consistency, test-retest reliability, and convergent validity. The prevalence of IAH was 38.3% with the Clarke questionnaire and 25.2% with the Gold questionnaire. The prevalence increased with longer duration of diabetes, lower HbA1c, and lower eGFR. CONCLUSIONS: The validation and cross-cultural adaptation of the proposed questionnaires to Brazilian Portuguese were adequate. In this sample of T1DM, the prevalence of IAH was high and associated with a longer duration of T1DM, lower HbA1C and lower eGFR.

Severe obstructive sleep apnea is associated with circulating microRNAs related to heart failure, myocardial ischemia, and cancer proliferation.

PURPOSE: Obstructive sleep apnea (OSA) is associated with multiple comorbid conditions including cardiovascular diseases and cancer. There is a growing interest in exploring biomarkers to understand the related mechanisms and improve the risk stratification of OSA. Circulating microRNAs (miRNAs) are single noncoding strands of nearly 22 nucleotides that posttranscriptionally regulate target gene expression. Our aim was to identify miRNA profiles associated with OSA. METHODS: We studied 48 male subjects, mostly Caucasian (63%) and overweight, divided by polysomnography into the no OSA control group (n = 6), mild OSA group (n = 12), moderate OSA group (n = 15), and severe OSA group (n = 15). The study groups were matched for age, body mass index (BMI), and body fat composition. miRNA profiles were measured from peripheral whole blood using two steps: (1) microarray analysis comprising more than 2500 miRNAs in a subsample of 12 subjects (three from each group); and (2) validation phase using real-time quantitative polymerase chain reaction (RTqPCR). RESULTS: The microarray assessment identified 21 differentially expressed miRNAs among the groups. The RT-qPCR assessment showed that miR-1254 and miR-320e presented a gradual increase in expression parallel to OSA severity. Linear regression analysis showed that severe OSA was independently associated with miR-1254 (ß = 68.4; EP = 29.8; p = 0.02) and miR-320e (ß = 76.1; EP = 31.3; p = 0.02). CONCLUSION: Severe OSA is independently associated with miRNAs that are involved in heart failure (miR-1254), myocardial ischemia/reperfusion (miR-320e), and cell proliferation in some cancer types (miR-1254 and miR-320e). Future investigations addressing whether these miRs may provide prognostic information in OSA are needed.

The analysis of green roof's runoff volumes and its water quality in an experimental study in Porto Alegre, Southern Brazil.

The green roofs are structures characterized by the application of vegetation cover in the buildings, using adequate waterproofing and drainage systems. It allows the reduction of surface runoff and delay in peak flow, contributing to the mitigation of flood events in urban areas. Therefore, this study aimed to evaluate the effect of the use of vegetal coverings on the surface runoff, taking into account quantitative and qualitative aspects, using an experimental module installed in the city of Porto Alegre, Brazil. The experimental station consisted of four modules: two horizontal modules with and without vegetation cover and two modules with slopes of 15° with and without vegetation cover. It was evaluated 19 precipitation events, and it was verified the volumes drained in each module after 3, 6 and 12 h from the beginning of precipitation. The water samples were collected in order to analyse the quality of the runoff from the experimental modules. The results have shown that the use of vegetal coverings can provide better distribution of the surface runoff, as well as a decrease of the speed of excess water release with no surface runoff in the first 3 h after the onset of rainfall in the horizontal module. Additionally, it was proved the reduction in drained volumes, with the flat module with vegetation cover being capable of retaining completely precipitations with volumes of approximately 22 mm. The vegetation cover module in roofs was the one that has presented better results regarding the reduction of the flow, presenting an average retention percentage of 91.7% for the first 3 h, indicating that the slope is an important factor. The physical-chemical analysis of the water shows that for all analysed modules, it is possible to use water for non-potable uses, although the water quality of the modules with vegetation cover is lower when compared to the water coming from the module without vegetation cover.

Milk quality in small farms from Southern Region of Brazil / Qualidade do leite em pequenas propriedades da Região Sul do Brasil

ABSTRACT: This study aimed to evaluates some physical chemical aspects of chilled raw milk that meet Brazilian quality standards in smallholder farms from southern Region of Brazil. The fat content, crude protein (CP), total solids (TS), somatic cell count (SCC), and total plate count (TPC) of the chilled raw milk from 78 smallholder farms was analyzed between Oct 2014 and Feb 2017. It was found that 96% of the samples met the Brazilian regulations for fat content, 87% for CP, and 91% for TS. The mean values of TPC and SCC were higher than the maximum limits established by Brazilian regulations. Smallholder farms from Southern Region of Brazil produce milk with an adequate standard for the main chemical indicators. However, there is an important gap in compliance with hygienic-sanitary practices, leading to high levels of chilled raw milk that does not meet the limits of Brazilian regulations.

RESUMO: Objetivou-se avaliar alguns padrões físico-quimicos do leite cru refrigerado em relação ao atendimento aos padrões de qualidade brasileiros em pequenas propriedades da Região Sul do Brasil. O teor de gordura, proteína bruta (PB), sólidos totais (ST), contagem de células somáticas (CCS) e contagem total em placas (CTP) do leite cru refrigerado de 78 pequenas propriedades foram analisadas mensalmente entre outubro de 2014 e fevereiro de 2017. Verificou-se que 96% das amostras atenderam às regulamentações brasileiras para teor de gordura, 87% para PB e 91% para ST. Os valores médios de CTP e CCS foram superiores aos limites máximos estabelecidos pela regulamentação brasileira. Pequenas propriedades da Região Sul do Brasil produzem leite com adequado padrão para os principais indicadores químicos. No entanto, existe uma lacuna importante no cumprimento das práticas higiênico-sanitárias, levando a altos níveis de leite cru refrigerado que não atendem os limites da regulamentação brasileira.

Uso de técnicas de low impact development no controle de impactos hidrológicos / Use of low impact development techniques to control hydrological impacts

RESUMO O crescimento desordenado traz diversas implicações na drenagem das bacias urbanas, principalmente no referente a alterações no escoamento pluvial. A bacia Mãe d'Água em Viamão (RS), no Brasil, retrata esse problema. Assim, levanta-se a seguinte questão: existem soluções de Low Impact Development (LID) compatíveis com a mitigação de impactos hidrológicos em situações de ocupação urbana em consolidação? Para isso, foram realizadas simulações de três cenários de urbanização: o atual, o futuro e o possível. O cenário atual representa o sistema atual; o futuro é representado pela concretização do Plano Diretor de Viamão, com taxa de permeabilidade de 10% nos lotes; e o possível foi apresentado por meio da inserção das medidas de LID (vegetative swales e pavimentos permeáveis) e taxas de permeabilidade de lote do cenário futuro. As simulações foram realizadas no modelo Storm Water Management Model (SWMM) para chuvas de projeto com tempo de retorno de 2, 5, 10 e 20 anos. O cenário que se apresentou mais crítico quanto a problemas de drenagem foi o futuro. No possível, mesmo com medidas mitigadoras, ainda existem volumes extravasados em alguns pontos, porém as LID reduziram o volume escoado na bacia em até 14% para o tempo de retorno de 2 anos. As medidas de LID apresentaram melhor desempenho para chuvas com menores tempos de retorno. A melhor eficiência na redução dos volumes escoados foi através da manutenção de taxas de permeabilidade do solo. Porém, as LID auxiliam na redução do escoamento superficial, sendo uma alternativa viável para áreas que já estão consolidadas.

ABSTRACT The disordered urban growth has several implications for the drainage of urban watersheds, especially regarding changes in runoff. The Mãe d'água watershed in Viamão/RS in Brazil portrays well this problem. Therefore, the following issue arises: are there LID solutions compatible with the mitigation of hydrological impacts in situations of urbanization under consolidation? In this respect, simulations were performed for three different urbanization scenarios, being: the current, the future, and the possible scenarios. The current scenario represents the current system. The future scenario is represented by the implementation of the current Master Plan of Viamão, with permeability rate of 10% in the lots. The possible scenario was presented through the insertion of LID measurements (vegetative swales and permeable pavements) and with the lot permeability rates of the future scenario. The scenario simulations were performed in the SWMM model for design rainfalls with a return period of 2, 5, 10 and 20 years. The most critical scenario regarding drainage problems was the future scenario. In the possible scenario, even with mitigating measures, there are still flood volumes in some points, but the LIDs reduced the volume flowed in the watershed by up to 14% for the RP of 2 years. The LID measurements showed best performance for rainfalls with lower return period. The best efficiency in the reduction of runoff volumes was through the maintenance of soil permeability rates. However, LIDs help to reduce surface runoff, being a viable alternative for areas that are already consolidated.

In vitro evaluation of apical microleakage in retrofillings with different resection angles / Avaliaçâo in vitro da microinfiltraçâo apical de retrobturaçoes com diferentes ángulos de ressecçâo

ABSTRACT Paraendodontic surgery is a procedure that aims to solve problems that could not be solved by, or when it is not possible to perform conventional endodontic treatment. The aim of this experimental study was to compare the apical microleakage of teeth sectioned at 45° or 90° to the long axis of the tooth and root-end filled with mineral trioxide aggregate (MTA) using stereomicroscopy. In this study, 26 maxillary central incisors were used. Cleaning and shaping were performed with use of the Oregon technique and the samples were randomly divided into two groups. In Group A (n=10) apical section was performed at an angle of 90°, making a retrocavity with an ultrasonic tip and retrofilling with MTA. In group B (n=10) the same procedures were performed, but the apical section was at a 45° angle. Then the samples were immersed in a dye (India ink), placed in an oven at 37° for 48 h before applying the clearing technique. Afterwards the teeth were assessed by stereomicroscope at 20x magnification to analyze dye leakage. Data were submitted to the Student's-t test with significance level p<0.05. There was statistically significant difference between groups. Group B showed higher apical microleakage values compared with group A (P=0.004), but both groups showed dye leakage. The results showed that the 90° apical section promoted lower dye microleakage values at the dentin-retrofilling material interface than the 45°-section and could be considered the most effective technique for apical preparation in paraendodontic surgery.

RESUMO A cirurgia paraendodontica é um procedimento que visa resolver problemas que nao poderiam ser resolvidos, ou quando nao é possível realizar o tratamento endodontico convencional. O objetivo deste estudo experimental foi comparar a microinfiltragao apical de dentes seccionados a 45° ou 90° em relagao ao longo eixo do dente e extremidade radicularpreenchida com agregado de trióxido mineral (MTA) utilizando estereomicroscopia. Neste estudo, 26 incisivos centrais superiores foram utilizados. Limpeza e modelagem foram realizadas com o uso da técnica de Oregon e as amostras foram divididas aleatoriamente em dois grupos. No Grupo A (n = 10) foi realizada segao apical em ángulo de 90°, realizando retrocavidade com ponta ultrassonica e retrobturagao com MTA. No grupo B (n = 10), os mesmos procedimentos foram realizados, mas a segao apical estava em um ángulo de 45°. Em seguida, as amostras foram imersas em um corante (nanquim), colocadas em estufa a 37°Cpor 48 h, antes da aplicagao da técnica de clareamento. Posteriormente, os dentes foram avaliados por estereomicroscópio, com aumento de 20x, para análise do vazamento de corante. Os dados foram submetidos ao teste t de Student, com nivel de significáncia p <0,05. Houve diferenga estatisticamente significante entre os grupos. O grupo B apresentou maiores valores de microinfil-tragao apical em comparagao ao grupo A (P = 0,004), mas ambos os grupos apresentaram vazamento de corante. Os resultados mostraram que a segao apical de 90° promoveu menores valores de microinfiltragao de corante na interface do material retrobturador dentinário do que a segao 45° e pode ser considerada a técnica mais efetiva para preparo apical em cirurgia paraendodontica.

Correction to: H3.3 K27M depletion increases differentiation and extends latency of diffuse intrinsic pontine glioma growth in vivo.

The original article can be found online.

H3.3 K27M depletion increases differentiation and extends latency of diffuse intrinsic pontine glioma growth in vivo.

Histone H3 K27M mutation is the defining molecular feature of the devastating pediatric brain tumor, diffuse intrinsic pontine glioma (DIPG). The prevalence of histone H3 K27M mutations indicates a critical role in DIPGs, but the contribution of the mutation to disease pathogenesis remains unclear. We show that knockdown of this mutation in DIPG xenografts restores K27M-dependent loss of H3K27me3 and delays tumor growth. Comparisons of matched DIPG xenografts with and without K27M knockdown allowed identification of mutation-specific effects on the transcriptome and epigenome. The resulting transcriptional changes recapitulate expression signatures from K27M primary DIPG tumors and are strongly enriched for genes associated with nervous system development. Integrated analysis of ChIP-seq and expression data showed that genes upregulated by the mutation are overrepresented in apparently bivalent promoters. Many of these targets are associated with more immature differentiation states. Expression profiles indicate K27M knockdown decreases proliferation and increases differentiation within lineages represented in DIPG. These data suggest that K27M-mediated loss of H3K27me3 directly regulates a subset of genes by releasing poised promoters, and contributes to tumor phenotype and growth by limiting differentiation. The delayed tumor growth associated with knockdown of H3 K27M provides evidence that this highly recurrent mutation is a relevant therapeutic target.

Histone H3.3 K27M Accelerates Spontaneous Brainstem Glioma and Drives Restricted Changes in Bivalent Gene Expression.

Diffuse intrinsic pontine gliomas (DIPGs) are incurable childhood brainstem tumors with frequent histone H3 K27M mutations and recurrent alterations in PDGFRA and TP53. We generated genetically engineered inducible mice and showed that H3.3 K27M enhanced neural stem cell self-renewal while preserving regional identity. Neonatal induction of H3.3 K27M cooperated with activating platelet-derived growth factor receptor α (PDGFRα) mutant and Trp53 loss to accelerate development of diffuse brainstem gliomas that recapitulated human DIPG gene expression signatures and showed global changes in H3K27 posttranslational modifications, but relatively restricted gene expression changes. Genes upregulated in H3.3 K27M tumors were enriched for those associated with neural development where H3K27me3 loss released the poised state of apparently bivalent promoters, whereas downregulated genes were enriched for those encoding homeodomain transcription factors.