Despite the development of new glioma therapies that allow for tumor-targeted in situ delivery of cytotoxic drugs, tumor resistance to apoptosis remains a key impediment to effective treatment. Mounting evidence indicates that microRNAs (miRNA) might play a fundamental role in tumorigenesis, controlling cell proliferation and apoptosis. In gliomas, microRNA-21 (miR-21) levels have been reported to be elevated and their knockdown is associated with increased apoptotic activity. We hypothesized that suppression of miR-21 might sensitize gliomas for cytotoxic tumor therapy. With the use of locked nucleic acid (LNA)-antimiR-21 oligonucleotides, bimodal imaging vectors, and neural precursor cells (NPC) expressing a secretable variant of the cytotoxic agent tumor necrosis factor-related apoptosis inducing ligand (S-TRAIL), we show that the combined suppression of miR-21 and NPC-S-TRAIL leads to a synergistic increase in caspase activity and significantly decreased cell viability in human glioma cells in vitro. This phenomenon persists in vivo, as we observed complete eradication of LNA-antimiR-21-treated gliomas subjected to the presence of NPC-S-TRAIL in the murine brain. Our results reveal the efficacy of miR-21 antagonism in murine glioma models and implicate miR-21 as a target for therapeutic intervention. Furthermore, our findings provide the basis for developing combination therapies using miRNA modulation and cytotoxic tumor therapies.

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Prostate cancer remains a health problem for men. Targeting androgen (AR) and estrogen (ER) receptors improves the outcomes of the disease, and many medicinal plants exert their effects by modulating these pathways. Therefore, a systematic review was conducted to identify medicinal plants and their natural compounds that may modulate the AR and/or ER pathways in cell and animal models. A search was conducted across EMBASE, LILACS, PubMed, Scopus, and Web of Science, with grey literature from Google SCHOLAR and ProQuest. Two authors independently selected eligible studies based on their titles and abstracts, and a third author resolved conflicts. Then, data from the full text of eligible studies were extracted and synthesized.In total, 75 studies were included. Results showed the effects of several different medicinal plants and natural compounds in reduction of AR and/or ER transcription and translation and AR secondary effects: cell growth reduction, induction of apoptosis, and cell cycle arrest. In animal models, tumor size reduction, increase in apoptosis, and downregulation of AR expression in tumors were also observed. No single phytochemical group concentrating molecules with anti-AR and/or ER activity was identified. Nevertheless, several phytochemical compounds showed potential for future clinical studies in the management of the disease.

Objetivo. Atualizar o mapa de evidências sobre os efeitos de intervenções para reabilitação de covid-19 pós-aguda. Métodos. O escopo da busca foi definido conforme a população (pacientes que tiveram covid-19 sintomática e sequelas da doença pós-aguda), o contexto (intervenções para recuperação das sequelas) e o tipo de estudo (revisão sistemática, revisão sistemática rápida, revisão de escopo ou revisão de revisões). Após a busca na PubMed e na Biblioteca Virtual em Saúde, dois autores independentes selecionaram estudos de revisão. A atualização do mapa feita em 27 de julho de 2022 seguiu os mesmos procedimentos descritos anteriormente. Resultados. O mapa inicial de evidências continha 22 estudos (quatro revisões sistemáticas, quatro revisões rápidas, quatro revisões de estudos de caso, uma revisão de escopo e nove protocolos de revisão sistemática). Nesta atualização, outros 10 estudos foram incluídos. Foram identificados quatro grupos de intervenções (multimodal, terapêutica, terapias complementares e farmacológica) e sete grupos de desfechos (condições patológicas, doenças/transtornos respiratórios, dor, indicadores fisiológicos e metabólicos, saúde mental/qualidade de vida, funções sensoriais, mortalidade), totalizando 166 associações entre intervenções e desfechos. As terapias complementares tiveram mais associações com os desfechos (n = 94). Entre os desfechos, destacaram-se os indicadores fisiológicos e metabólicos, as condições patológicas e a saúde mental/qualidade de vida (44, 41 e 35 associações, respectivamente). Conclusões. Na atualização do mapa, analisaram-se 69 associações, com destaque para exercício (isolado, multicomponente ou intervenção multimodal, apresentando 23 efeitos positivos e quatro potencialmente positivos) e intervenções farmacológicas e terapias complementares para funções sensoriais (15 associações). O alto número de protocolos indica que a literatura permanece incipiente.

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14601 Continued efforts to improve local control and to maximize sphincter preservation in patients with rectal carcinoma led to consideration of preoperative chemoradiation. The purpose of this retrospective study is to examine clinical outcomes and find out which prognostic factors are related to survival in patients treated with neoadjuvant chemoradiation in Sparrow Hospital from 1998–2003. Forty two patients with biopsy proven rectal carcinoma without evidence of extra pelvic spread were treated in this fashion. Radiation therapy was administered for a total dose of 5.00 cGy. Chemotherapy used was 5-FU in 37 patients, and in combination with leucovorin in additional 5 patients. Surgical treatments performed were abdominoperineal resection (23 pts), low anterior resection in 13 pts., transanal excisions (2 pts), 2 patients had only exploratory laparotomy and for 2 patients records were not available. Cox proportional hazards regression techniques were used to estimate survival rates. Univariate and multivariate Cox proportional hazards analyses were used to evaluate relationship between risk factors and the survival. The SAS system (V9.1.3, Cary NC) was used for all analyses. Out of 42 patients analyzed 25 were males and 17 females. Mean age was 65 years (range 31 - 85). Median follow-up time was 57 months with a range from 7 to 98 months. After the surgery 4 patients had complete response, 12 were stage I, 10 stage II, 12 patients stage III, one patient had metastatic disease and for 2 patients records were inadequate. Analysis of disease free survival showed actuarial 5-year disease free survival to be 59%. Actuarial 5-year overall survival was 67%. Median overall survival was still not reached, while median disease-free survival is 78 months . Univariate and multivariate analyses showed that only postoperative stage was associated significantly with overall survival. Specifically, there was an increase in the risk of mortality of just over 3-fold for each increment in post-operative stage. In conclusion, in the community settings preoperative chemoradiation seem to provide good overall and disease free survival for patients with rectal cancer. Postoperative stage appears to be the most important prognostic factor for the survival. No significant financial relationships to disclose.

RESUMENRevisamos la disnea, aguda y crónica, ya que es el máscomún de los síntomas de las enfermedades cardiopulmonares y motivo de consulta muy frecuente en los servicios de urgencias. Tenemos en cuenta definición,clasificación,patrones clínicos de presentaciónasí como repercusiónhemodinámica, tratamiento y pronóstico. Se revisan algoritmos de enfoque clínico para un óptimo manejo de los pacientes afectados por las múltiples entidades que pueden producir o deteriorar la clase funcional de la disnea.Palabras clave: disnea, urgencias, patronesclínicos,diagnóstico, tratamiento. ABSTRACTWe reviewdyspnea,acute and chronic, as it is the most commonsymptomsofcardiopulmonarydiseaseandfrequentreason for consultationinthe emergency department. we considerdefinition, classification, clinical patternsofpresentation andhemodynamic consequences, treatment and prognosis.algorithmsare reviewedclinicalapproachfor optimalmanagement of patientsaffected bymultipleentities that mayproduceor degrade thefunctional classof dyspnea.Keywords: dyspnea, emergencies, clinical patterns, diagnosis, treatment. DEFINICIÓNLa disnea se define como la sensación de «falta de aire», de una respiración anormal o incómoda con la percepción de mayor trabajo respiratorio que aparece durante el reposo o con un grado de actividad física inferior a la esperada. No se considera patológica cuando surge con el ejercicio extenuante en individuos sanos con buena condición física ni con el ejercicio moderado en personas sanas no acostumbradas al esfuerzo (1) Es el síntoma cardinal de enfermedades que afectan al sistema cardíaco como respiratorio. Varía en intensidad dependiendo de la sensibilidad del paciente y del grado de afectación del mismo a los esfuerzos (Tabla 1).Se debe tener en cuenta las distintas formas de presentación (Tabla 2). El paciente la describe como: «ten-go fatiga», «no puedo respirar», «no me entra el aire en los pulmones», etc. El médico deberá discernir cuál de las anteriores descripciones, corresponden a una dis-