Effect of the secretome of mesenchymal stem cells overexpressing BMP-9 on osteoblast differentiation and bone repair.

The secretome present in the conditioned medium (CM) of mesenchymal stem cells (MSCs) is a promising tool to be used in therapies to promote bone regeneration. Considering the high osteogenic potential of the bone morphogenetic protein 9 (BMP-9), we hypothesized that the secretome of MSCs overexpressing BMP-9 (MSCsBMP-9 ) enhances the osteoblast differentiation of MSCs and the bone formation in calvarial defects. CM of either MSCsBMP-9 (CM-MSCsBMP-9 ) or MSCs without BMP-9 overexpression (CM-MSCsVPR ) were obtained at different periods. As the CM-MSCsBMP-9 generated after 1 h presented the highest BMP-9 concentration, CM-MSCsBMP-9 and CM-MSCsVPR were collected at this time point and used to culture MSCs and to be injected into mouse calvarial defects. The CM-MSCsBMP-9 enhanced the osteoblast differentiation of MSC by upregulating RUNX2, alkaline phosphatase (ALP) and osteopontin protein expression, and ALP activity, compared with CM-MSCsVPR . The CM-MSCsBMP-9 also enhanced the bone repair of mouse calvarial defects, increasing bone volume, bone volume/total volume, bone surface, and trabecular number compared with untreated defects and defects treated with CM-MSCsVPR or even with MSCsBMP-9 themselves. In conclusion, the potential of the MSCBMP-9 -secretome to induce osteoblast differentiation and bone formation shed lights on novel cell-free-based therapies to promote bone regeneration of challenging defects.

Influence of Arm Fat on the Indirect Measurement of Blood Pressure: A Statistical and Machine Learning Approach. / Influência da Gordura do Braço sobre Medida Indireta da Pressão Sanguínea: Uma Abordagem Estatística e de Machine Learning.

BACKGROUND: The indirect measurement of blood pressure (BP) is known to be influenced by many factors such as the technique, observer, and equipment; however, the influence of arm composition has not been investigated yet. OBJECTIVE: To identify the influence of arm fat on the indirect measurement of blood pressure using statistical inference and machine learning models. METHODS: Cross-sectional study, with 489 healthy young adults aged from 18 to 29 years old. Measurements of arm length (AL), arm circumference (AC) and arm fat index (AFI) were taken. BP was measured in both arms simultaneously. Data were processed using Python 3.0 and its specific packages for descriptive analysis, regression and cluster analysis. Significance levels: 5% for all calculations. RESULTS: BP and anthropometric measurements were different between the hemi-bodies. In the right arm, systolic blood pressure (SBP), AL and AFI were higher, while AC was similar compared with the left arm. AL and AC showed positive correlation with SBP. According to the regression model, for a fixed value of AC and AL, SBP readings could be reduced by a mean of 1.80 mmHg in the right arm, and 1.62 mmHg in the left arm for every 10% increase in AFI. Clustering analysis corroborated the regression results. CONCLUSION: There was a significant influence of AFI on BP readings. SBP had a positive correlation with AL and AC, and a negative correlation with AFI, suggesting the need for further investigations on the relationship between BP and percentages of arm muscle and fat.

FUNDAMENTO: A mensuração indireta da pressão sanguínea (PS) é sabidamente influenciada por diversos fatores como técnica, observador e equipamento, mas a influência da composição do braço ainda não foi investigada. OBJETIVO: Identificar a influência da gordura do braço sobre a medida indireta da pressão sanguínea, utilizando modelos de inferência estatística e machine learning. MÉTODOS: Estudo transversal, com 489 adultos jovens saudáveis de 18 a 29 anos de idade. Foram medidos comprimento (COB), circunferência do braço (CB) e índice de gordura do braço (IGB). A PS foi mensurada em ambos os braços, simultaneamente. Os dados foram processados utilizando-se Python 3.0 e pacotes específicos para análise descritiva, regressão e clusterização. Um nível de significância de 5% foi adotado para todos os cálculos. RESULTADOS: A PS e as medidas antropométricas foram diferentes entre os hemicorpos. A pressão sanguínea sistólica (PAS), COB, e IGB foram maiores no braço direito (BD), enquanto CB foi similar em comparação ao braço esquerdo. COB e CB apresentaram correlação positiva com a PAS. Conforme o modelo de regressão, para determinado valor de CB e COB, a leitura da PAS poderá ter uma redução média de 1,80 mmHg no BD, e 1,62 mmHg no braço esquerdo, a cada 10% de aumento na IGB. A clusterização corroborou os resultados da regressão. CONCLUSÃO: Foi encontrada uma influência significativa do IGB sobre a leitura da PS. A PAS teve correlação positiva com COB e CB, e correlação negativa com IGB, o que sugere a necessidade de mais investigações sobre a relação da PS com as frações de gordura e músculo do braço.

Effects of Modulation of the Hedgehog and Notch Signaling Pathways on Osteoblast Differentiation Induced by Titanium with Nanotopography.

BACKGROUND: The events of bone formation and osteoblast/titanium (Ti) interactions may be affected by Hedgehog and Notch signalling pathways. Herein, we investigated the effects of modulation of these signalling pathways on osteoblast differentiation caused by the nanostructured Ti (Ti-Nano) generated by H2SO4/H2O2. METHODS: Osteoblasts from newborn rat calvariae were cultured on Ti-Control and Ti-Nano in the presence of the Hedgehog agonist purmorphamine or antagonist cyclopamine and of the Notch antagonist N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) or agonist bexarotene. Osteoblast differentiation was evaluated by alkaline phosphatase activity and mineralization, and the expression of Hedgehog and Notch receptors was also evaluated. RESULTS: In general, purmorphamine and DAPT increased while cyclopamine and bexarotene decreased osteoblast differentiation and regulated the receptor expression on both Ti surfaces, with more prominent effects on Ti-Nano. The purmorphamine and DAPT combination exhibited synergistic effects on osteoblast differentiation that was more intense on Ti-Nano. CONCLUSION: Our results indicated that the Hedgehog and Notch signalling pathways drive osteoblast/Ti interactions more intensely on nanotopography. We also demonstrated that combining Hedgehog activation with Notch inhibition exhibits synergistic effects on osteoblast differentiation, especially on Ti-Nano. The uncovering of these cellular mechanisms contributes to create strategies to control the process of osseointegration based on the development of nanostructured surfaces.

Influência da Gordura do Braço sobre Medida Indireta da Pressão Sanguínea: Uma Abordagem Estatística e de Machine Learning / Influence of Arm Fat on the Indirect Measurement of Blood Pressure: A Statistical and Machine Learning Approach

Resumo Fundamento A mensuração indireta da pressão sanguínea (PS) é sabidamente influenciada por diversos fatores como técnica, observador e equipamento, mas a influência da composição do braço ainda não foi investigada. Objetivo Identificar a influência da gordura do braço sobre a medida indireta da pressão sanguínea, utilizando modelos de inferência estatística e machine learning. Métodos Estudo transversal, com 489 adultos jovens saudáveis de 18 a 29 anos de idade. Foram medidos comprimento (COB), circunferência do braço (CB) e índice de gordura do braço (IGB). A PS foi mensurada em ambos os braços, simultaneamente. Os dados foram processados utilizando-se Python 3.0 e pacotes específicos para análise descritiva, regressão e clusterização. Um nível de significância de 5% foi adotado para todos os cálculos. Resultados A PS e as medidas antropométricas foram diferentes entre os hemicorpos. A pressão sanguínea sistólica (PAS), COB, e IGB foram maiores no braço direito (BD), enquanto CB foi similar em comparação ao braço esquerdo. COB e CB apresentaram correlação positiva com a PAS. Conforme o modelo de regressão, para determinado valor de CB e COB, a leitura da PAS poderá ter uma redução média de 1,80 mmHg no BD, e 1,62 mmHg no braço esquerdo, a cada 10% de aumento na IGB. A clusterização corroborou os resultados da regressão. Conclusão Foi encontrada uma influência significativa do IGB sobre a leitura da PS. A PAS teve correlação positiva com COB e CB, e correlação negativa com IGB, o que sugere a necessidade de mais investigações sobre a relação da PS com as frações de gordura e músculo do braço.

Abstract Background The indirect measurement of blood pressure (BP) is known to be influenced by many factors such as the technique, observer, and equipment; however, the influence of arm composition has not been investigated yet. Objective To identify the influence of arm fat on the indirect measurement of blood pressure using statistical inference and machine learning models. Methods Cross-sectional study, with 489 healthy young adults aged from 18 to 29 years old. Measurements of arm length (AL), arm circumference (AC) and arm fat index (AFI) were taken. BP was measured in both arms simultaneously. Data were processed using Python 3.0 and its specific packages for descriptive analysis, regression and cluster analysis. Significance levels: 5% for all calculations. Results BP and anthropometric measurements were different between the hemi-bodies. In the right arm, systolic blood pressure (SBP), AL and AFI were higher, while AC was similar compared with the left arm. AL and AC showed positive correlation with SBP. According to the regression model, for a fixed value of AC and AL, SBP readings could be reduced by a mean of 1.80 mmHg in the right arm, and 1.62 mmHg in the left arm for every 10% increase in AFI. Clustering analysis corroborated the regression results. Conclusion There was a significant influence of AFI on BP readings. SBP had a positive correlation with AL and AC, and a negative correlation with AFI, suggesting the need for further investigations on the relationship between BP and percentages of arm muscle and fat.

Suicide Attempt by Glass Shard Ingestion: A Case Report.

A 42-year-old man with schizophrenia and human immunodeficiency syndrome swallowed several glass shards in an attempted suicide. Two days later, he was admitted to the ER of the Florianópolis Hospital with a complaint of upper abdominal pain. The patient showed normal vital signs on physical examination; there was tenderness of palpation of the epigastrium. The investigation on admission included hemogram, CXR, abdominal X-ray, and upper GI scope. Radiographs showed several radiopaque image fragments in the stomach, as well as in the small and large intestines. Hemogram showed normal results. Upper gastrointestinal endoscopy found no signs of esophagogastroduodenal perforation; several glass shards were removed from the patient's stomach. The patient remained in the ward for four days and underwent continuous vital signs monitoring, serial physical examinations, hematimetric control, and daily imaging tests. He showed normal vital signs and progressive improvement of abdominal pain during hospitalization, although hematochezia episodes took place during defecation. The patient no longer complained of abdominal pain on the fifth hospitalization day; the complete removal of the glass fragments was confirmed through imaging examinations, and the patient was transferred to a specialized hospital in order to better treat his psychiatric condition.

Relationship between the toxicity of raw Annona muricata leaves extract and 7, 12-dimethylbenzathracene (DMBA) with histopathological changes in wistar rats / Relación entre la toxicidad del extracto de hojas crudas de Annona muricata y el 7, 12-dimetilbenz antraceno (DMBA) con cambios histopatológicos en ratas Wistar

Abstract Aims: To identify the histopathological alterations in organs of Wistar rats to evaluate toxic effects of use of Annonamuricata Raw Leaf Extract (AMRLE) alone or in association with DMBA. Settings and Design: Sixty female Wistar rats were used, separated into groups and treated with a single dose of 65 mg/kg of DMBA and/or with 50; 100 and 200 mg/kg of AMRLE. Hematoxylin-Eosin (HE) and 1% methylene blue stains were used in the histopathological analysis and quantification of Aberrant Crypts (ACs) and Aberrant Crypt Focus (ACF). Fischer and Kruskal Wallis tests were used in the statistical analysis. Results: The administration of 65 mg/kg of DMBA and/or 50, 100 and 200 mg/kg of AMRLE did not influence weight development. Some histopathological alterations (hepatic steatosis; inflammatory foci in the liver, kidney and lung; pulmonary lymphoid hyperplasia, ectasia and hyperplasia in mammary gland epithelium) and the development of ACs and ACF in the intestinal colon were observed in all groups, except in the group negative control, with no statistical difference between analysed groups. Conclusions: Histopathological alterations and the formation of ACs and ACF did not show a statistically significant difference between the groups analysed. However, although AMRLE has antioxidant effects due to the presence of phenolic components, there was still the formation of some pathological processes that may be related to the isolated toxic action of DMBA and/or associated with other components of AMRLE, since these changes were not seen in the negative control group.

Resumen Objetivos: Identificar las alteraciones histopatológicas en órganos de ratas Wistar para evaluar los efectos tóxicos del uso del Extracto de Hoja Cruda de Annona muricata (AMRLE) solo o en asociación con DMBA. Configuración y diseño: Se utilizaron sesenta ratas hembras Wistar, se separaron en grupos y se trataron con una dosis única de 65 mg/kg de DMBA y/o con 50, 100 y 200 mg/kg de AMRLE. Se utilizaron tinciones de hematoxilina-eosina (HE) y azul de metileno al 1% en el análisis histopatológico y la cuantificación de criptas aberrantes (CA) y focus de criptas aberrantes (FCA). En el análisis estadístico se utilizaron las pruebas de Fischer y Kruskal Wallis. Resultados: La administración de 65 mg/kg de DMBA y/o 50, 100 y 200 mg/kg de AMRLE no influyó en el desarrollo del peso. Se observaron algunas alteraciones histopatológicas (esteatosis hepática; focus inflamatórios en el hígado, riñón y pulmón; hiperplasia, ectasia en epitelio de la glándula mamaria e hiperplasia linfoide pulmonar) y el desarrollo de CA y FCA en el colon intestinal en todos los grupos, excepto en el grupo control negativo, sin diferencias estadísticas entre los grupos analizados. Conclusiones: Las alteraciones histopatológicas y la formación de CA y FCA no mostraron diferencias estadísticamente significativas entre los grupos analizados. Sin embargo, aunque AMRLE tiene efectos antioxidantes debido a la presencia de componentes fenólicos, aún existe la formación de algunos procesos patológicos que pueden estar relacionados con la acción tóxica aislada del DMBA y/o asociados con otros componentes de AMRLE, ya que estos cambios no fueron observados en el grupo control negativo.

Da violência epistemológica a epistemologias próprias: experiências de narrativas com mulheres cis periféricas, mulheres trans e travestis / From epistemological violence to own epistemologies: narrative experiences with peripheral cis women, trans women and transvestite

RESUMO Este artigo apresenta compreensão de problemáticas enfrentadas por mulheres cis periféricas, mulheres trans e travestis na construção de epistemologias próprias no campo das ciências. Para tal, baseia-se no campo construído por três teses de doutorado, cujos autores são os mesmos deste artigo. As teses, embora não tenham como foco principal e central o mesmo do presente artigo, evidenciam, a partir do campo construído, que pouco conhecimento a respeito das populações trans, travesti e periférica é produzido por seus integrantes. Identifica-se, a partir da releitura do material produzido pelos pesquisadores, a existência de trincheiras, que se interpõem no caminho percorrido por mulheres trans, travestis e mulheres cis periféricas para produzir conhecimento. São elas: a própria sobrevivência, a permanência no ensino e a validação do conhecimento produzido por corpos e existências não hegemônicas. Discute-se, por fim, que há um descompasso entre as políticas de educação vigentes e as experiências vividas, indicando uma fissura em práticas de saúde e no cuidado integral dessa população. A isso, somam-se violências e iniquidades em saúde que acabam interferindo na comunicação e na potência do saber popular como estratégia de resistência e saber científico, contrapondo-se ao saber acadêmico hegemônico.

ABSTRACT This article presents an understanding of the problems faced by peripheral cis women, trans women, and transvestites in the construction of their own epistemologies in the field of sciences. For that, it is based on the field built by three doctoral theses, whose authors are the same as in this article. The theses, although they do not have the main focus of the present article, show, from the field constructed, that little knowledge about the trans, transvestite, and peripheral populations is produced by their members. From the re-reading of the material produced by the researchers, the existence of trenches is identified, which stand in the path taken by trans women, transvestites, and peripheral cis women to produce knowledge. The trenches are: survival, permanence at university, and the validation of knowledge produced by bodies and non-hegemonic existences. Finally, it discusses the existing mismatch between the current education policies and the experiences, indicating a fissure in health practices and in the comprehensive care of this population. In addition, we see violence and inequities in health that end up interfering in the communication and power of popular knowledge as a strategy of resistance and scientific knowledge, in contrast to hegemonic academic knowledge.

Brief Report: Young Age and Sex Work Are Associated With HIV Seroconversion Among Transgender Women in São Paulo, Brazil.

BACKGROUND: Transgender women worldwide have the highest prevalence of HIV and the lowest access to prevention among groups at risk of HIV. However, few longitudinal studies have directly measured HIV incidence and identified predictors of HIV acquisition among transgender women. SETTING: São Paulo, Latin America's largest city. METHODS: We conducted a longitudinal study among transgender women in São Paulo. Participants were recruited by a long-chain peer referral process from May 2017 to July 2019. Those aged 18 years and older and who were HIV-negative at baseline were retested every 6 months up to 18 months. HIV incidence was calculated by dividing the number of seroconversions by the person-years (PYs) of follow-up; 95% confidence intervals (CIs) were constructed assuming a Poisson distribution. Conditional maximum likelihood ratios assessed differences in HIV incidence by risk factors. RESULTS: A racially/ethnically diverse sample of 545 HIV-negative transgender women was enrolled. In 485.5 PYs of follow-up, 13 seroconversions were observed, yielding an incidence of 2.68 per 100 PYs (95% CI: 1.43 to 4.58). HIV incidence was significantly higher among transgender women aged 18-24 years (rate ratio 3.85, 95% CI: 1.24 to 12.93) and among those who engaged in sex work in the preceding month (rate ratio 5.90, 95% CI: 1.71 to 26.62). CONCLUSIONS: HIV transmission continues at a high rate among transgender women in Brazil. Factors such as young age, lower level of education, and limited employment opportunities may lead to dependence on sex work that in turn increases HIV risk. Transgender-friendly prevention services, particularly programs delivering pre-exposure prophylaxis, are urgently needed.

The expression patterns and prognostic significance of pleckstrin homology-like domain family A (PHLDA) in lung cancer and malignant mesothelioma.

BACKGROUND: Pleckstrin homology domain family A (PHLDA) genes play important roles in cancer cellular processes, including inhibiting Akt activation, repressing growth factor signaling, inhibiting the negative feedback of EGFR/ErbB2 signaling cells, and inducing apoptosis. However, the prognostic significance of PHLDA in non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MM) remains unclear. The present study investigates the associations between PHLDA expression patterns and their prognostic value in lung adenocarcinoma (LUAD) and MM. METHODS: We analyzed PHLDA family members at the genomic level in silico to explore their mRNA expression pattern and predictive significance in LUAD and MM. We then created a PHLDA-drug interaction network and a protein-protein interaction (PPI) network using different databases. Finally, we immunohistochemically assessed the protein expression of each PHLDA family member on tissue microarrays (TMAs) in both LUAD and MM cohorts with long-term follow-up. RESULTS: While PHLDA1 mRNA expression in both LUAD and MM was lower than that of normal tissue, PHLDA2 mRNA was significantly overexpressed in LUAD, and PHLDA3 mRNA was overexpressed in MM. In NSCLC, both low PHLDA1 mRNA expression and high PHLDA3 mRNA expression correlated with worse overall survival (OS) (P<0.01), whereas high PHLDA2 mRNA expression was associated with better OS (P<0.01). In MM, patients presenting high PHLDA1 and PHLDA2 mRNA expression had poor OS (P=0.01 and P<0.01, respectively). In addition, the PHLDA-drug interaction network indicated that several common drugs could potentially modulate PHLDA expression, and the PPI network suggested that PHLDA1 interacts with Notch family members, whereas PHLDA3 interacts with TP53. Our results also showed that the expression of PHLDA2 and PHLDA3 was significantly higher in LUAD and MM than that of PHLDA1 (P<0.05) and was associated with the risk of death. While patients with PHLDA2 >85.09 cells/mm2 had a low risk of death (P=0.01) and a median survival time of 48 months, those with PHLDA3 <70.38 cells/mm2 had a high risk of death (P=0.03) and a median survival time of 34 months. CONCLUSIONS: We shed light on the role of the PHLDA family as promising predictive biomarkers and potential therapeutic targets in LUAD and MM.

Young age and sex work are associated with HIV seroconversion among transgender women in São Paulo, Brazil

Background: Transgender women worldwide have among the highest prevalence of HIV and the lowest access to prevention among groups at risk. However, few longitudinal studies have directly measured HIV incidence and identified predictors of HIV acquisition among transgender women. Setting: São Paulo, Latin America's largest city. Methods: We conducted a longitudinal study among transgender women in São Paulo. Participants were recruited by a long-chain peer referral process from May 2017 to July 2019. Those age 18 years and older and HIV-negative at baseline were retested every 6 months up to 18 months. HIV incidence was calculated by dividing the number of seroconversions by the person-years (py) of follow-up; 95% confidence intervals (CI) were constructed assuming a Poisson distribution. Conditional maximum likelihood ratios assessed differences in HIV incidence by risk factors. Results: A racial/ethnically diverse sample of 545 transgender women were enrolled. In 485.5 py of follow-up, 13 seroconversions were observed yielding an incidence of 2.68 per 100 py (95% CI 1.43­4.58). HIV incidence was significantly higher among transgender women age 18 to 24 years (rate ratio 3.85, 95% CI 1.24­12.93) and among those who engaged in sex work in the preceding month (rate ratio 5.90, 95% CI 1.71­26.62). Conclusion: HIV transmission continues at a high rate among transgender women in Brazil. Factors such as young age, lower level of education, and limited employment opportunities may lead to dependence upon sex work which in turn increase HIV risk. Transgender-friendly prevention services, particularly programs delivering pre-exposure prophylaxis (PrEP) are urgently needed.

Perfil Anatomopatológico e Imuno-histoquímico de Gliomas de Pacientes da Região de Maringá-PR / Anatomopathological and Immunohistochemical Profile of Gliomas of Patients in the Region of Maringá-PR / Perfil Anatomopatológico e Inmunohistoquímico de Gliomas en Pacientes la Región de Maringá-PR

Introdução: Os gliomas representam 80% dos tumores do sistema nervoso central. A Organização Mundial da Saúde (OMS) adicionou, em 2016, critérios moleculares na classificação dos gliomas. A fisiopatologia e os fatores de risco desses tumores ainda não são totalmente conhecidos. Objetivo: Realizar uma análise retrospectiva dos laudos anatomopatológicos e imuno-histoquímicos de gliomas. Método: Estudo transversal, retrospectivo e descritivo, a partir de exames anatomopatológicos e imuno-histoquímicos realizados entre janeiro de 2014 e dezembro de 2018 em um laboratório de anatomia patológica na cidade de Maringá-PR. Dos 234 laudos relacionados com o termo glioma, 204 foram selecionados para este estudo. Resultados: Foram encontrados tumores astrocitários, ependimários e oligodendrogliais, sendo que os astrocitomas corresponderam à maioria (86,8% dos casos encontrados). A média de idade ao diagnóstico foi de 51,8 anos e houve maior prevalência desses tumores no sexo masculino. Também foram analisadas mutações detectáveis por imuno-histoquímica como p53 (mutada em 66,7% dos testados), isocitrato desidrogenase (IDH) (28,6% mutados), X-linked alpha-thalassemia mental retardation (ATRX) (21,0%) e marcadores diagnósticos como o epithelial membrane antigen (EMA) positivo em todos os ependimomas analisados. Conclusão: É inegável a necessidade de novas pesquisas sobre os gliomas tanto no campo epidemiológico, tendo em vista a nova classificação, quanto no escopo fisiopatológico e clínico, com o objetivo de melhorar o entendimento sobre a patologia e o tratamento dos pacientes

Introduction: Gliomas represent 80% of the central nervous system tumors. World Health Organization (WHO) has added, in 2016, molecular features to the classification of gliomas. The pathophysiology and risk factors of these tumors are not yet fully understood. Objective: Perform a retrospective analysis of immunohistochemical and anatomopathological reports of gliomas. Method: Cross-sectional, retrospective and descriptive study carried out from anatomopathological and immunohistochemical exams made between January 2014 and December 2018 in a pathological anatomy laboratory in the city of Maringá-PR. Of the 234 reports related to the term glioma, 204 were selected for this study. Results: Astrocytic, ependymal and oligodendroglial tumors were found, with astrocytomas accounting for the majority (86.8% of the cases found). Mean age at diagnosis was 51.8 years and the prevalence was higher in men. Furthermore, immunohistochemically detectable mutations were analyzed, such as p53 (mutated in 66.7% of those tested), isocitrate dehydrogenase (IDH) (28.6% mutated), X-linked alpha-thalassemia mental retardation (ATRX) (21.0%) and diagnostic markers such as positive epithelial membrane antigen (EMA) in all analyzed ependymomas. Conclusion: The necessity of further researches on gliomas is undeniable , both epidemiologically considering the new classification and within the clinical and pathophysiological scope in order to improve the understanding of the pathology and the treatment for the patients

Introducción: Los gliomas representan 80% de los tumores del sistema nervioso central. La Organización Mundial de la Salud (OMS) agregó, en 2016, criterios moleculares sobre como clasificar los gliomas. La fisiopatología y los factores de riesgo de estos tumores aún no se comprenden completamente. Objetivo: Realizar un análisis retrospectivo de informes inmunohistoquímicos y anatomopatológicos de gliomas. Método: Estudio transversal, retrospectivo y descriptivo con base em pruebas anatomopatológicas e inmunohistoquímicas realizadas entre enero de 2014 y diciembre de 2018 en un laboratorio de anatomía patológica de la ciudad de Maringá-PR. De los 234 informes relacionados con el término glioma, se seleccionaron 204 para este estudio. Resultados: Se encontraron tumores astrocíticos, ependimarios y oligodendrogliales, siendo los astrocitomas la mayoría (86,8% de los casos encontrados). La edad media al diagnóstico fue de 51,8 años y hubo una mayor prevalencia de estos tumores en el sexo masculino. También se analizaron mutaciones detectables inmunohistoquímicamente, como p53 (mutado en 66,7% de los analizados), isocitrato desidrogenase(IDH) (28,6% mutado), X-linked alpha-thalassemia mental retardation (ATRX) (21,0%) y marcadores de diagnóstico como epithelial membrane antigen (EMA) positivo en todos los ependimomas analizados. Conclusión: Es innegable la necesidad de profundizaren las investigaciones sobre los gliomas, tanto en el campo epidemiológico, ante la nueva clasificación, como en el ámbito fisiopatológico y clínico, con el objetivo de mejorar el conocimiento sobre la patología y el tratamiento de los pacientes

Different histological patterns of type-V collagen levels confer a matrices-privileged tissue microenvironment for invasion in malignant tumors with prognostic value.

Previous studies have reported a close relationship between type V collagen (Col V) and tumor invasion and motility in both breast cancer (BC) and lung cancer (LC). The present work aims to determine whether the extracellular-matrix (ECM)-defined microenvironment influences patient clinical outcome and investigate to which extent histological patterns of Col V expression in malignant cells have a prognostic effect in patients. To that end, we examined the expression of Col V in the tissues of 174 primary tumors (MM, N = 82; LC, N = 41; and BC, N = 46) by immunohistochemistry. We found: (1) diffuse strong green birefringence in membrane and cytoplasm individualizing malignant cells in MM; (2) a focal and weak birefringence mainly in cytoplasmic membrane involving groups of malignant cells in LC and BC; (3) higher average H-score of Col V in MM than in LC and BC samples; (4) a direct correlation between Col V histologic pattern and TNM stage IV, status and median overall survival; (5) patients with LC in TNM stage I, and Col V ≤ 41.7 IOD/mm2 had a low risk of death and a median survival time more than 20 months; (6) patients with MM in TNM stage IV and Col V > 41.7 IOD/mm2 presented a high risk of death and a median survival time of just 20 months. These findings suggest that high levels of Col V individualizing malignant cells, as observed in MM, and low levels grouping malignant cells, as observed in LC and BC, confers different immune-privileged tissue microenvironment for tumor invasion with impact on prognosis of the patients.

Evaluation of Antineoplasic Activity of Zingiber Officinale Essential Oil in the Colorectal Region of Wistar Rats.

INTRODUCTION: Aberrant Crypt (AC) and Aberrant Crypt Focus (ACF) are considered pre-neoplasic lesions, ranging from hyperplasia to different degrees of dysplasia in the colon. This work aimed to evaluate and quantify the chemopreventive activity of Zingiber officinale essential oil in the colorectal region of Wistar rats. MATERIALS AND METHODS: We extracted the essential oil from ginger rhizomes and carried out ACF induction, in rats, with 1.2 Dimethylhydrazine (DMH) at a 20 mg/kg dose. The experimental groups were GI (negative control); GII (positive induction control); GIII (DMH + essential oil); GIV (DMH +5-Florouracil) and GV (essential oil). The histological techniques used were methylene blue, hematoxylin-eosin (HE) dyeing, and immunohistochemistry (IHQ). RESULTS: The major essential oil compounds were citral (17.25%), δ-citral (10.25%), camphene (9.55%), α-zingiberene (7.57%), nerol (6.37%) and plelandrene (6.83%). For the presence of AC or ACF, we did not observe them in GI and GV, while in GII and GIII, they were observed, in high values, in both regions, but only in the distal region, there was a significant difference between them. For GIV, for both regions, there were significant lower numbers of AC when compared to GIII. As observed, with HE, there were hyperplastic and dysplastic ACF in the proximal and distal portions of the colon. For IHQ analyses, there were positively PCNA antibody marked cells in all experimental groups. Yet, there was no significant correlation of mitotic index among them. Moreover, the results of GIII compared to GIV were very similar. CONCLUSION: In this sense, the Zingiber officinale essential oil has good antioxidant potential because it presents a mixture of monoterpene and sesquiterpene compounds. Thus, it is able to develop a chemoprotective effect, as it presented similar results to the standard drug, showing cell proliferation control.

The recurrence of the melanotic neuroectodermal tumour of infancy: an unusual presentation of a rare tumour.

The melanotic neuroectodermal tumour of infancy (MNTI), also known as melanotic progonoma, is a rare neoplasm derived from neural crest cells. Although it is fundamentally benign, the tumour may present a locally aggressive behaviour, characterised by a rapid progression and a destructive invasion of adjacent structures, hence causing deformities. Unfortunately, perhaps due to the low incidence of this type of tumour, the published cases in the literature do not characterise the factors that imply the malignant or recurrent behaviour of the disease, nor the therapy to conduct these cases. Here, we report a rare case of a recurrent benign MNTI, approached unusually with a favourable outcome.

Indoleamine 2,3-dioxygenase in melanoma progression and BRAF inhibitor resistance.

Indoleamine 2,3-dioxygenase (IDO) is associated with the progression of many types of tumors, including melanoma. However, there is limited information about IDO modulation on tumor cell itself and the effect of BRAF inhibitor (BRAFi) treatment and resistance. Herein, IDO expression was analyzed in different stages of melanoma development and progression linked to BRAFi resistance. IDO expression was increased in primary and metastatic melanomas from patients' biopsies, especially in the immune cells infiltrate. Using a bioinformatics approach, we also identified an increase in the IDO mRNA in the vertical growth and metastatic phases of melanoma. Using in silico analyses, we found that IDO mRNA was increased in BRAFi resistance. In an in vitro model, IDO expression and activity induced by interferon-gamma (IFNγ) in sensitive melanoma cells was decreased by BRAFi treatment. However, cells that became resistant to BRAFi presented random IDO expression levels. Also, we identified that treatment with the IDO inhibitor, 1-methyltryptophan (1-MT), was able to reduce clonogenicity for parental and BRAFi-resistant cells. In conclusion, our results support the hypothesis that the decreased IDO expression in tumor cells is one of the many additional outcomes contributing to the therapeutic effects of BRAFi. Still, the IDO production changeability by the BRAFi-resistant cells reiterates the complexity of the response arising from resistance, making it not possible, at this stage, to associate IDO expression in tumor cells with resistance. On the other hand, the maintenance of 1-MT off-target effect endorses its use as an adjuvant treatment of melanoma that has become BRAFi-resistant.

Brazilian dentists' perception of dentin hypersensitivity management.

The aim of this study was to investigate how Brazilian dentists perceive and manage dentin hypersensitivity (DH) in their clinical routine. A 13-item questionnaire-based survey was developed and sent electronically to a convenience sample of dentists. The questionnaire assessed the personal and dental practice characteristics of the sample, the occurrence of DH in their daily clinical practice, and management strategies. The data were analyzed descriptively and together with the chi-square test (a = 0.05). A total of 353 responses were obtained from September 2017 to March 2018. Of all the respondents, 62% were females, 49.9% reported fewer than five years of dental practice, and 70.5% were self-identified as private practitioners. Most of the dentists reported an estimated frequency (30-60%) of patients with DH in their practice. The most frequently cited (91.79%) trigger of DH was air blast and/or scratching with a probe. The first-choice strategy to manage DH was a dentin desensitizer (48.16%). The number of years in clinical practice did not influence DH relapse frequency (p = 0.76) significantly, or consider DH treatment as a problem (p = 0.22). The present findings indicate that, regardless of clinical experience, dentists in Brazil still consider DH management a challenge in their daily dental practice. In addition, the results suggest that guidelines should be developed to disseminate the available knowledge regarding this condition in ways that may influence decision-making processes among practitioners.

Paraoxonase 1 serum activity in women: the effects of menopause, the C(-107)T polymorphism and food intake

ABSTRACT Objective The aims of this study were to investigate changes in serum paraoxonase 1 (PON1) activity in women at the pre and postmenopausal stages and its association with the PON1 C(-107)T polymorphism and food intake profile. Subjects and methods A cross-sectional study with female patients aged between 35 and 59 years old was conducted. Women were divided into two groups: premenopausal (n = 40) and postmenopausal (n = 36). Women enrolled in the study had serum PON1, total cholesterol, HDL, LDL, glucose and HbA1c, as well as the BMI measured. Additionally, women were genotyped for the PON1 T(-107)C polymorphism and the food intake profile was obtained through interview. Results Glucose (p = 0.03), HbA1c (p = 0.002) and total cholesterol (p = 0.002)concentrations were higher in post than premenopausal women, however PON1 activity was not different (p > 0.05). Carriers of the C allele had higher PON1 activity (CC: 88.9 ± 6.5 U/mL and CT: 79.9 ± 4.7 U/mL) than women of the TT genotype (66.6 ± 5.9 U/mL) (p < 0.05). However, the model predicting PON1 activity was slightly better when genotype, total fat and cholesterol content in the diet were all included. Conclusion In sum, we observed that the PON1 C(-107)T genotype was the major regulator of PON1 activity, and menopause had no effect on PON1 activity. The lipid and glycemic profile were altered in postmenopausal women.

Paraoxonase 1 serum activity in women: the effects of menopause, the C(-107)T polymorphism and food intake.

OBJECTIVE: The aims of this study were to investigate changes in serum paraoxonase 1 (PON1) activity in women at the pre and postmenopausal stages and its association with the PON1 C(-107)T polymorphism and food intake profile. SUBJECTS AND METHODS: A cross-sectional study with female patients aged between 35 and 59 years old was conducted. Women were divided into two groups: premenopausal (n = 40) and postmenopausal (n = 36). Women enrolled in the study had serum PON1, total cholesterol, HDL, LDL, glucose and HbA1c, as well as the BMI measured. Additionally, women were genotyped for the PON1 T(-107)C polymorphism and the food intake profile was obtained through interview. RESULTS: Glucose (p = 0.03), HbA1c (p = 0.002) and total cholesterol (p = 0.002)concentrations were higher in post than premenopausal women, however PON1 activity was not different (p > 0.05). Carriers of the C allele had higher PON1 activity (CC: 88.9 ± 6.5 U/mL and CT: 79.9 ± 4.7 U/mL) than women of the TT genotype (66.6 ± 5.9 U/mL) (p < 0.05). However, the model predicting PON1 activity was slightly better when genotype, total fat and cholesterol content in the diet were all included. CONCLUSION: In sum, we observed that the PON1 C(-107)T genotype was the major regulator of PON1 activity, and menopause had no effect on PON1 activity. The lipid and glycemic profile were altered in postmenopausal women.

Home-based physiotherapy programmes for individuals with neurological diseases: systematic review / Programas de fisioterapia Home-based para indivíduos com doenças neurológicas: revisão sistemática / Programas de fisioterapia Home-based para individuos con enfermedades neurológicas: revisión sistemática

Abstract Introduction: Home-based programmes have received increasing attention in rehabilitation, providing an opportunity to continue aspects of therapy, benefiting the retention of established intervention effects. Objective: To describe the available home-based physiotherapy programmes in neurorehabilitation for people with neurological diseases. Method: MEDLINE, EMBASE, Cochrane Library, OTseeker and PEDro were searched, no restrictions regarding the date of publication or language restrictions for randomized controlled clinical trial. The quality of the selected studies using the PEDro scale and the Cochrane Collaboration's tool for assessing the risk of bias. Results: Fifteen articles met the eligibility criteria and quality assessment and were selected for the present systematic review. The findings supports the positive impact of home-based intervention, finding evidence in the changes in activity level, improvement in the control and muscle strength, balance and walking in patients with neurological conditions who perform rehabilitation program at home, with a good adherence of participants in total. Conclusion: Models of rehabilitative such as home-based programmes can be an alternative efficient method to deliver rehabilitation, showing to be beneficial in improving different aspects of activities, and participation.

Resumo Introdução: Programas home-based têm recebido atenção crescente na reabilitação, proporcionando uma oportunidade para continuar os aspectos da terapia, beneficiando a retenção de efeitos de intervenção estabelecidos. Objetivo: Descrever os programas de fisioterapia home-based disponíveis na neurorreabilitação para pessoas com doenças neurológicas. Método: MEDLINE, EMBASE, Biblioteca Cochrane, OTseeker e PEDro foram pesquisados, sem restrições quanto à data de publicação ou restrições de idioma para ensaios clínicos randomizados controlados. A qualidade dos estudos selecionados usando a escala PEDro e a ferramenta Cochrane Collaboration para avaliar o risco de viés. Resultados: Quinze artigos preencheram os critérios de elegibilidade e avaliação de qualidade e foram selecionados para a presente revisão sistemática. Evidências foram encontradas sobre mudanças no nível de atividade, melhora no controle e força muscular, equilíbrio e deambulação em pacientes com condições neurológicas que realizam um programa de reabilitação home-based, com boa adesão dos participantes no total. Conclusão: Os modelos de reabilitação, como os programas home-based, podem ser um método eficiente alternativo para promover a reabilitação, mostrando-se benéficos na melhoria dos diferentes aspectos das atividades e na participação.

Resumen Introducción: Los programas home-based han recibido una atención creciente en la rehabilitación, proporcionando una oportunidad para continuar los aspectos de la terapia, beneficiando la retención de efectos de intervención establecidos. Objetivo: Describir los programas de fisioterapia Home-Based disponibles en la neurorreabilitación para personas con enfermedades neurológicas. Método: MEDLINE, EMBASE, Biblioteca Cochrane, OTseeker y PEDro fueron investigados, sin restricciones en cuanto a la fecha de publicación o restricciones de idioma para ensayos clínicos randomizados controlados. La calidad de los estudios seleccionados mediante la escala PEDRO y la herramienta Cochrane Collaboration para evaluar el riesgo de sesgo. Resultados: Quince artículos cumplieron los criterios de elegibilidad y evaluación de calidad y fueron seleccionados para la presente revisión sistemática. Se encontraron evidencias sobre cambios en el nivel de actividad, mejora en el control y fuerza muscular, equilibrio y deambulación en pacientes con condiciones neurológicas que realizan un programa de rehabilitación Home-Based, con buena adhesión de los participantes en el total. Conclusión: Los modelos de rehabilitación, como los programas Home-Based, pueden ser un método eficiente alternativo para promover la rehabilitación, mostrándose beneficiosos en la mejora de los diferentes aspectos de las actividades y en la participación.

Relationship between noncarious cervical lesions, cervical dentin hypersensitivity, gingival recession, and associated risk factors: A cross-sectional study.

OBJECTIVES: The aim of this study was to evaluate the risk factors associated with noncarious cervical lesions (NCCLs), cervical dentin hypersensitivity (CDH), and gingival recession (GR), besides the relationship among these conditions in a specific Brazilian sample population. METHODS: 185 patients who attended the "Ambulatory Program for Rehabilitation of Patients with Noncarious Cervical Lesions and Cervical Dentin Hypersensitivity" were evaluated, and 5180 teeth were analyzed. The subjects filled out a form and a calibrated examiner performed the clinical exams to determine the presence of NCCLs, CDH, and GR. NCCLs were classified according to their morphology and depth, CDH levels were evaluated according to air stimuli response, and GRs were categorized according to Miller's classification. The association of the risk factors with NCCLs, CDH, and GR was determined with the Mann-Whitney U test and multiple linear regression. For the correlations, the Spearman test was used with a 95%-confidence level. RESULTS: The NCCLs, CDH, and GR distributions within the study were 88.1%, 89.1%, and 59.4%, respectively. Maxillary premolars were the most affected by all three conditions. A positive correlation was found between age, NCCLs, and GR; between NCCLs and CDH; CDH and GR; GR and NCCLs. Age, gender, oral hygiene, gastroesophageal diseases, and occlusal trauma were significantly associated with the presence of all three conditions. CONCLUSIONS: The NCCLs and GR distributions increased with age; NCCLs, CDH, and GR had positive correlation; the lesions' depth and morphology contributed to high levels of sensitivity and severity of recessions; age, gender, gastric disease, and occlusal trauma were relevant factors for the occurrence of NCCLs, CDH, and GR. CLINICAL SIGNIFICANCE: The increasing distribution of NCCLs, CDH, and GR is closely associated with people's lifestyles. Thus, it is important for the clinicians to recognize the etiological factors and their most relevant associations to prevent and control such alterations, in order to improve the population's quality of life.