TrkB-Targeted Therapy for Mucoepidermoid Carcinoma.

The brain-derived neurotrophic factor (BDNF)/tyrosine receptor kinase B (TrkB) pathway was previously associated with key oncogenic outcomes in a number of adenocarcinomas. The aim of our study was to determine the role of this pathway in mucoepidermoid carcinoma (MEC). Three MEC cell lines (UM-HMC-2, H253 and H292) were exposed to Cisplatin, the TrkB inhibitor, ANA-12 and a combination of these drugs. Ultrastructural changes were assessed through transmission electron microscopy; scratch and Transwell assays were used to assess migration and invasion; and a clonogenic assay and spheroid-forming assay allowed assessment of survival and percentage of cancer stem cells (CSC). Changes in cell ultrastructure demonstrated Cisplatin cytotoxicity, while the effects of ANA-12 were less pronounced. Both drugs, used individually and in combination, delayed MEC cell migration, invasion and survival. ANA-12 significantly reduced the number of CSC, but the Cisplatin effect was greater, almost eliminating this cell population in all MEC cell lines. Interestingly, the spheroid forming capacity recovered, following the combination therapy, as compared to Cisplatin alone. Our studies allowed us to conclude that the TrkB inhibition, efficiently impaired MEC cell migration, invasion and survival in vitro, however, the decrease in CSC number, following the combined treatment of ANA-12 and Cisplatin, was less than that seen with Cisplatin alone; this represents a limiting factor.

Screening for vulnerable older people: Is the Probability of Repeated Admission scale an accurate tool?

AIM: To evaluate the Probability of Repeated Admission (Pra) scale performance in predicting healthcare utilization and death in a community sample of Rio de Janeiro city, Brazil. METHODS: This was a prospective longitudinal study. The sample was composed of community-dwelling older people who participated in the research network Frailty in Brazilian Older People Study, Rio de Janeiro section. It analyzed data from the baseline and the follow up. At the baseline, 764 older adults were stratified by the Pra, and, 3 years later, data on health services utilization and survival status were collected. The Pra accuracy, obtained by the area under the curve, the sensitivity and the specificity to predict hospitalization in 3 years; visits to the emergency department; and death were determined. Cox regression estimated the survival curves, according to the risk strata. RESULTS: The accuracy, the sensitivity and the specificity of Pra were 62% (95% CI 57-68%), 8.8% and 95.4% for hospitalization in 3 years; 59% (95% CI 53-64%), 8.3% and 94.8% for emergency room visits; 66% (95% CI 59-74%) and 68% (95% CI 63-73%), 15.0% and 96.0% for death. Survival curves showed that high-risk individuals were more likely to die compared with the low-risk individuals, adjusted to covariables (P < 0.001). CONCLUSIONS: The Pra presented low accuracy, low sensitivity and high specificity for all outcomes observed, indicating a poor performance to screen vulnerable older adults in Brazil. Therefore, this tool should not be used alone, as a case-finding instrument. Geriatr Gerontol Int 2020; 20: 360-365.

Matrix stiffness mechanically conditions EMT and migratory behavior of oral squamous cell carcinoma.

Tumors are composed of heterogeneous phenotypes, each having different sensitivities to the microenvironment. One microenvironment characteristic - matrix stiffness - helps to regulate malignant transformation and invasion in mammary tumors, but its influence on oral squamous cell carcinoma (OSCC) is unclear. We observed that, on stiff matrices, a highly invasive OSCC cell line (SCC25) comprising a low E-cad to N-cad ratio (InvH/E:NL; SCC25) had increased migration velocity and decreased adhesion strength compared to a less invasive OSCC cell line (Cal27) with high E-cad to N-cad ratio (InvL/E:NH; Cal27). However, InvL/E:NH cells acquire a mesenchymal signature and begin to migrate faster when exposed to prolonged time on a stiff niche, suggesting that cells can be mechanically conditioned. Owing to increased focal adhesion assembly, InvL/E:NH cells migrated faster, which could be reduced when increasing integrin affinity with high divalent cation concentrations. Mirroring these data in human patients, we observed that collagen organization, an indicator of matrix stiffness, was increased with advanced disease and correlated with early recurrence. Consistent with epithelial tumors, our data suggest that OSCC cells are mechanically sensitive and that their contribution to tumor progression is mediated in part by this sensitivity.This article has an associated First Person interview with the first author of the paper.

Analysis of different anthropometric indicators in the detection of high blood pressure in school adolescents: a cross-sectional study with 8295 adolescents.

BACKGROUND: High blood pressure is strongly associated with obesity in different populations. However, it is unclear whether different anthropometric indicators of obesity can satisfactorily predict high blood pressure in the school setting. OBJECTIVES: This study evaluated the sensitivity and specificity of body mass index, waist circumference, and waist to height ratio in the detection of high blood pressure in adolescents. METHODS: The sample consisted of 8295 adolescents aged 10-17 years. Weight was measured using a digital scale, height with a stadiometer, and waist circumference using a tape measure. Blood pressure was measured by an automatic blood pressure measuring device. ROC curves were used for the analysis of sensitivity and specificity of the three anthropometric indices in identifying high blood pressure. Binary Logistic Regression was used to assess the association of body mass index, waist circumference, and waist to height ratio with high blood pressure. RESULTS: Low values of sensitivity were observed for body mass index (0.35), waist circumference (0.37), and waist to height ratio (0.31) and high values of specificity for body mass index (0.86), waist circumference (0.82), and waist to height ratio (0.83) in the detection of high blood pressure. An association was observed between adolescents classified with high body mass index (OR=3.57 [95% CI=3.10-4.10]), waist cirumference (OR=3.24 [95% CI=2.83-3.72]), and waist to height ratio (OR=2.94 [95% CI=2.54-3.40]) with high blood pressure. CONCLUSIONS: Body mass index, waist circumference, and waist to height ratio presented low sensitivity to identify adolescents with high blood pressure. However, adolescents classified with high body mass index, waist circumference, and waist to height ratio demonstrated a high association of presenting high blood pressure.

Implementation of the "Saúde na Boa" intervention: process evaluation and characteristics of participants and dropouts / Implementação da intervenção "Saúde na Boa": avaliação de processo e características dos estudantes permanecentes e não permanecentes

School-based interventions have been evaluated to examine its implementation quality and to identify the characteristics of successful participants. The objective was to analyze the process evaluation of the "Saúde na Boa" intervention and to test differences between successful participants and dropouts. Twenty schools were randomly selected to receive the intervention (n= 10) or the control (n= 10), in Recife-PE and Florianopolis-SC. The process evaluation was performed in the intervention schools using a checklist of items from five domains (knowledge, visibility, environment, Physical Education classes and extracurricular activities). The operational intervention quality was classified using the median score from each domain (median from 0.0 to 1.0= low, from 1.1 to 2.0= moderate, and from 2.1 to 3.0= high). Student characteristics were assessed at baseline (March 2006) and were compared between the participants who successfully completed the intervention (n= 989) and the dropouts (n= 1,166). We verified moderate to high operational quality of the intervention for knowledge (median= 2.0), fruit distribution and bike rack installation (median= 1.5), acquisition of materials (median= 3.0) and distribution of journals (median= 2.0). Students who dropped out were significantly more frequent in male (47.8% vs. 40.3%), in workers students (49.2% vs. 44.2%), those who smoked (21.8% vs. 13.6%) and consumed alcoholic beverages (57.4% vs. 49.5%), and slept ≥8 h/day (19.5% vs. 27.3%), than participants who did not drop out. Therefore, the "Saúde na Boa" intervention was of moderate operational quality. Participants and dropout students differed according to their gender, work status and use of licit drugs.

Intervenções no ambiente escolar têm sido avaliadas para analisar a qualidade da implementação de suas ações e o perfil dos participantes envolvidos. O objetivo deste estudo foi analisar os resultados da avaliação de processo da intervenção "Saúde na Boa"; e testar diferenças entre estudantes permanecentes e não permanecentes até o final da intervenção. Das vinte escolas selecionadas, dez foram sorteadas para a condição "intervenção" e dez compuseram o grupo "controle", em Recife/PE, e Florianópolis/SC. A avaliação de processo foi realizada nestas escolas, considerando cinco eixos (conhecimento, visibilidade, ambiente, aulas de Educação Física e atividades extraclasse), classificando-se a qualidade operacional da intervenção conforme a mediana do escore em cada um destes fatores (Mediana= 0,0 a 1,0: baixa; 1,1 a 2,0: moderada; 2,1 a 3,0: elevada). As características dos estudantes na linha de base (março de 2006) foram comparadas entre os permanecentes (n= 989) e não permanecentes (n= 1166). Verificou-se qualidade operacional moderada à elevada da intervenção para os itens conhecimento da intervenção (Mediana= 2,0), distribuição de frutas e instalação de bicicletários (Mediana= 1,5), aquisição de materiais (Mediana= 3,0) e distribuição de boletins (Mediana= 2,0). O grupo de não permanecentes apresentou significativamente maior frequência de rapazes (47,8% vs. 40,3%), de jovens que trabalhavam (49,2% vs. 44,2), que consumiam cigarros (21,8% vs. 13,6%) e bebidas alcoólicas (57,4% vs. 49,5%), e dormiam ≥8 h/dia (19,5% vs. 27,3%) do que os permanecentes. Portanto, a intervenção apresentou qualidade operacional moderada, e o perfil do abandono diferiu com relação ao sexo, ocupação e consumo de drogas lícitas.

The use of regional citrate anticoagulation for continuous venovenous hemodiafiltration in acute kidney injury.

OBJECTIVE: Continuous renal replacement therapy is commonly used in the treatment of acute kidney injury. Although the optimal anticoagulation system is not well defined, citrate has emerged as the most promising method. We evaluated the data of 143 patients with acute kidney injury subjected to citrate-based continuous venovenous hemodiafiltration. DESIGN: Retrospective cohort study. SETTING: Intensive care unit of tertiary care private hospital. PATIENTS: Patients with acute kidney injury treated from February 2004 to July 2006. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The main cause of acute kidney injury was sepsis (58%). The mean dialysis dose was 36.6 mL/kg/hr allowing for excellent metabolic control (last tests: creatinine, 1.1 mg/dL; urea, 46 mg/dL). No significant bleeding, severe electrolyte, or calcium disorders were observed. Of the 418 filters used, almost 28,000 hrs of treatment, hemofilter patency was 68% at 72 hrs. Hospital mortality was 59%, and 22% of survivors were dialysis-dependent at the time of discharge. Within our sample, we identified 21 patients with liver failure (mean prothrombin time index, 21% vs. 67%, p < 0.001). This group presented with a lesser median systemic ionized calcium level (1.06 vs. 1.12 mmol/L, p < 0.001) and similar mean total calcium level (8.5 vs. 8.6 mg/dL, not significant), compared with patients without liver failure. These subjects also showed acidemia (median pH, 7.31 vs. 7.40, p < 0.001); however, they exhibited higher levels of lactate (median 29 vs. 16 mg/dL, p < 0.001), chloride (mean 109 vs. 107 mEq/L, p = 0.045) and had a trend to higher mortality rate (76% vs. 56%). CONCLUSIONS: Besides a trend toward higher mortality rate observed in the group with liver failure, we found that citrate-based continuous venovenous hemodiafiltration allowed an effective dialysis dose and reasonable filter patency.

[Vaginal ulcers in Behçet disease]. / Ulceras vaginales en enfermedad de Behçet.

Incidence of Behçet disease in USA is 0.12 in 100,000; but in Mexico there are just two isolated cases. This paper reports a case of a 30 year-old female, who, when 26, had vaginal ulcers. She received antimicrobial therapy during four years. In March 2007 she came to author's hospital with a cervical vaginitis diagnose study, and presenting thorax with venous collateral circulation secondary to superior and inferior cava vein thrombosis. Colposcopy and vaginal wall biopsy were practiced and found chronic ulcer with vascular damage; oral ulcers were found too, and Pathergy test was positive. Currently there is no ocular damage. Patient received azathioprine therapy without improvement, later she received anticoagulant therapy with corticoids and has good evolution.

Tratamento MARS (Molecular Adsorbent Recirculating System) em pacientes com cirrose biliar primária: relato da primeira expectativa ambulatorial no Brasil / The MARS (Molecular Adsorbent Recirculating System): patient with primary biliary cirrhosis: first experience report in Brazil

O tratamento MARS (Molecular Adsorbent Recirculating System) permite a remoção de toxinas hepáticas ligadas à albumina. Dentre estas substâncias estão os ácidos biliares, que têm importante papel no prurido nas síndromes colestáticas. Relato do Caso: Descrição da primeira experiência brasileira ambulatorial de diálise MARS em paciente de 39 anos, sexo feminino, com diagnóstico de cirrose biliar primária e prurido recorrente após transplante de fígado e refratário às medidas clínicas, havendo também importante comprometimento na qualidade de vida. Após a realização de 2 sessões consecutivas do tratamento MARS, houve controle do prurido por pelo menos 7 meses. Procedimento bem tolerado e sem intercorrências Conclusão: O tratamento MARS é uma opção para pacientes com prurido intratável secundário a síndromes colestáticas e está associado à reduzida taxa de complicações

Perfil epidemiológico da infecção pelo HIV-1 em gestantes do estado de Mato Grosso do Sul - Brasil / Epidemiological profile of HIV-1 infection in pregnant women of state of Mato Grosso do Sul - Brazil

Introdução: a infeccao HIV-1 em gestantes muitas vezes é subdiagnosticada, devido à caracteristica assintomática ou sub-clínica inicial durante a gestação. O conhecimento da realidade local, bem como do perfil epidemiológico da infecção HIV-1 durante o período gestacional é importaute em pupulações brasileiras. Objetivo: avaliar a freqüência, o perfil epidemiológico e a associação da infecção HIV-I com a idade materna em gestantes submetidas à triagem pré-natal de um estado da região Centro-Oeste brasileira. Métodos: estudo prospectivo de 71 gestantes com diagnóstico de infecção pelo vírus HIV-1 de 32.512 gestantes submetidas à triagem pré-natal no período de novembro de 2002 a outubro de 2003. Esta triagem inclui uma investigação sorológica de 10 infecções através da técnica de papel-filtro, utilizando a metodologia ELISA, sendo a infecção pelo vírus HIV-1 triada pelo método ELISA e confirmada por Western-Blot. A mensuração das variáveis foi expressa pelas médias, ao passo que a associação entre algumas variáveis foi avaliada pelo teste do x² em tabelas de contingência de dupla entrada. Resultados: dentre as 32.512 gestantes triadas, foi encontrada uma freqüência de 0,2 por cento (71) para infecção pelo vírus HIV-I, sendo que a maioria das pacientes desconhecia ser portadora do vírus HIV- I previamente ao pré-natal. A média de idade ao diagnóstico foi de 24,4±5,3 anos, sendo que as gestantes provenientes do interior do Estado representaram 62 po cento da amostra. Não houve asso-ciação estatística significante entre a freqüência dos casos e faixa etária das gestantes. Quanto à paridade, a maioria das gestantes se encontrava na terceira gestação, sendo o segundo trimestre o período gestacional mais prevalente da realização do diagnóstico. 0 tipo de parto predominante foi cesárea a termo, havendo um aborto e um óbito fetal. Conclusão: a freqüência da infecção HIV- I em gestantcs de estado da região Centro-Oeste brasileira ficou abaixo da encontrada em outros estudos nacionais e próxima da observada em estudos internacionais. Não há na literatura mundial ampla triagem pré-natal comparativamente ao presente trahalho. A importância da triagem sorológica do vírus HIV-1 durante o pré-natal o mais precocemente possível deve ser enfatizada, uma vez que no presente estudo, a maioria absoluta das gestantes descobriu-se portadora do vírus HIV pela primeira vez durante o período gestacional...

Cultural meanings of tuberculosis in Aceh Province, Sumatra.

This paper shows how disease transmission and particularly what biomedicine calls tuberculosis are interpreted in the non-Western context of Aceh Province, Sumatra, Indonesia. It tries also to focus on factors influencing perceptions and health-seeking behaviors. Results show that what biomedicine calls TB is represented by a semantic network of illnesses. Parts of this network are clearly identified as transmissible while others are related to specific phenomena affecting the individual, such as terbuk (poisoning) or trouk (fatigue produced by hard work), and are not considered contagious. Forms of transmission are interpreted mostly through empirical and analogic categories. TB is attributed to four different aspects: (a) biomedical categories such as germ theory; (b) socio-economic conditions; (c) transgression of social rules; and (d) poisoning and the influences of supernatural powers. Health-seeking behaviors are related to the perceived causes of the disease, economic factors, and the accessibility of health services.

On changes in pancreas cytomorphometry, serum insulin and metabolic adjustments induced by long term orchidectomy and substitutive therapy with testosterone in dogs

Se usaron perros callejeros, machos, en ayunas, no anestesiados, bajo alguno de los siguientes tratamientos alternativos: 1) nada; 2) orquidectomía con 4 meses de antelación; 3) orquidectomía con 10 meses de antelación; 4) orquidectomía como (3) seguida de tratamiento i.m. con propileneglicol, 0.05 ml/kg peso corporal/día, 15 días (controles de vehículo), y 5) orquidectomía como (3) seguida de tratamiento i.m. con hemisuccinato de testosterona en propileneglicol, 0.75 mg en 0.05 ml/kg, peso corporal día, 15 días. Cortes de páncreas de cada grupo de estos animales (en ayunas, bajo anestesia con pentobarbital sódico) fueron teñidos por la técnica de la inmunoperoxidasa. Se midió el tamño de los islotes pancreáticos. Se estimó su contenido de insulina por la absorbancia media en un citoespectrofotómetro computarizado. Se midieron la insulina sérica inmunorreactiva (IRI sérica), la glucemia (G) y el nivel de ácidos grasos libres (AGL) séricos de estos animales basalmente y durante pruebas de glucosa e insulina, por radioinmunoensayo, con un autoanalizador Technicon y por el método de Itaya y Ui, respectivamente. La evolución del hipogonadismo masculino (4 a 10 meses) condujo a los siguientes cambios, sin afectarse las demás variables estudiadas: 1) disminución progresiva de la tolerancia a la glucosa y del espacio de glucosa, 2) aumento pasajero en la respuesta insulinémica a la hiperglucemia, 3) disminución progresiva de la hipoglucemia insulínica, 4) disminución progresiva del pico... (AU)

On changes in pancreas cytomorphometry, serum insulin and metabolic adjustments induced by long term orchidectomy and substitutive therapy with testosterone in dogs

Se usaron perros callejeros, machos, en ayunas, no anestesiados, bajo alguno de los siguientes tratamientos alternativos: 1) nada; 2) orquidectomía con 4 meses de antelación; 3) orquidectomía con 10 meses de antelación; 4) orquidectomía como (3) seguida de tratamiento i.m. con propileneglicol, 0.05 ml/kg peso corporal/día, 15 días (controles de vehículo), y 5) orquidectomía como (3) seguida de tratamiento i.m. con hemisuccinato de testosterona en propileneglicol, 0.75 mg en 0.05 ml/kg, peso corporal día, 15 días. Cortes de páncreas de cada grupo de estos animales (en ayunas, bajo anestesia con pentobarbital sódico) fueron teñidos por la técnica de la inmunoperoxidasa. Se midió el tamño de los islotes pancreáticos. Se estimó su contenido de insulina por la absorbancia media en un citoespectrofotómetro computarizado. Se midieron la insulina sérica inmunorreactiva (IRI sérica), la glucemia (G) y el nivel de ácidos grasos libres (AGL) séricos de estos animales basalmente y durante pruebas de glucosa e insulina, por radioinmunoensayo, con un autoanalizador Technicon y por el método de Itaya y Ui, respectivamente. La evolución del hipogonadismo masculino (4 a 10 meses) condujo a los siguientes cambios, sin afectarse las demás variables estudiadas: 1) disminución progresiva de la tolerancia a la glucosa y del espacio de glucosa, 2) aumento pasajero en la respuesta insulinémica a la hiperglucemia, 3) disminución progresiva de la hipoglucemia insulínica, 4) disminución progresiva del pico...

Metabolic and pancreatic chances caused in male dogs by testosterone chronic administration

Se estudiaron la citología pancreática y las respuestas glucémica, insulinémica y de ácidos grasos libres séricos que se observan en perros durante la hiperglucemia inducida por la glucosa y en el curso de una hipoglucemia insulínica. Los perros estaban en una de las 3 condiciones siguientes: 1) no tratados, 2) bajo tratamiento con propilenoglicol (controles de vehículo) y 3) bajo tratamiento con propionato de testosterona en su vehículo. Dosis de testosterona: 0.75 mg/Kg peso corporal/día, una vez por día. Ambos tratamientos, intramusculares, duraron 2 semanas. En los páncreas de perros no tratados, los islotes presentaban bordes irregulares con saliencias agudas, y las células B se podían apreciar claramente, con su elevado contenido de gránulos de insulina. Las imágenes negativas de los núcleos de las células B se presentaron en la parte central de dichas. En los páncreas de perros tratados con testosterona, los citoplasmas amarillentos de las células B parecían vacíos, conteniendo sólo unos pocos gránulos beta (pequeña cantidad de insulina almacenada). Parecía que las células B presentaban una gran cantidad de vacuolas. El perfil glucémico en las pruebas de glucosa e insulina, el espacio de glucosa y el tiempo de media vida de la insulina en ciruclación en los perros bajo tratamiento con testosterona en su vehículo fueron simulares a los observados en perros tratados con propilenoglicol sólo, cuando se los estudió de igual modo. Aunque la testosterona no tuvo influencia alguna sobre la secreción de insulina, el espacio de insulina y la velocidad de desaparición de la insulina de la circulación, ella hace que la respuesta hipoglucemiante de la insulina exógena sea apenas mayor que lo normal, aumenta el nivel basal de ácidos grasos libres séricos, acelera la disminución de dichos ácidos durante la prueba de glucosa y favorece su aumento durante el período de recuperación de la hiperglucemia y su rebote durante la hipoglucemia insulínica. Todas estas acciones están relacionadas con la testosterona misma, más allá de las ocasionadas por el vehículo solo

Metabolic and pancreatic chances caused in male dogs by testosterone chronic administration

Se estudiaron la citología pancreática y las respuestas glucémica, insulinémica y de ácidos grasos libres séricos que se observan en perros durante la hiperglucemia inducida por la glucosa y en el curso de una hipoglucemia insulínica. Los perros estaban en una de las 3 condiciones siguientes: 1) no tratados, 2) bajo tratamiento con propilenoglicol (controles de vehículo) y 3) bajo tratamiento con propionato de testosterona en su vehículo. Dosis de testosterona: 0.75 mg/Kg peso corporal/día, una vez por día. Ambos tratamientos, intramusculares, duraron 2 semanas. En los páncreas de perros no tratados, los islotes presentaban bordes irregulares con saliencias agudas, y las células B se podían apreciar claramente, con su elevado contenido de gránulos de insulina. Las imágenes negativas de los núcleos de las células B se presentaron en la parte central de dichas. En los páncreas de perros tratados con testosterona, los citoplasmas amarillentos de las células B parecían vacíos, conteniendo sólo unos pocos gránulos beta (pequeña cantidad de insulina almacenada). Parecía que las células B presentaban una gran cantidad de vacuolas. El perfil glucémico en las pruebas de glucosa e insulina, el espacio de glucosa y el tiempo de media vida de la insulina en ciruclación en los perros bajo tratamiento con testosterona en su vehículo fueron simulares a los observados en perros tratados con propilenoglicol sólo, cuando se los estudió de igual modo. Aunque la testosterona no tuvo influencia alguna sobre la secreción de insulina, el espacio de insulina y la velocidad de desaparición de la insulina de la circulación, ella hace que la respuesta hipoglucemiante de la insulina exógena sea apenas mayor que lo normal, aumenta el nivel basal de ácidos grasos libres séricos, acelera la disminución de dichos ácidos durante la prueba de glucosa y favorece su aumento durante el período de recuperación de la hiperglucemia y su rebote durante la hipoglucemia insulínica. Todas estas acciones están relacionadas con la testosterona misma, más allá de las ocasionadas por el vehículo solo (AU)