The Radiotherapy: Basic Concepts And Recent Techniques Advances For Thoracic Malignancies.

Radiation therapy (RT) is a clinical modality treatment that uses ionizing radiation in the approach of malignant tumors, (and occasionally benign diseases). Since its inception, the goal of RT has been to cure cancer without excessive side effects. The most important factors affecting the results of RT are the tumor histology, its location and regional extent, the anatomic area of involvement and the geometric accuracy with which a calculated radiation dose is delivered. Radiotherapy is one of the basic treatment modalities in thoracic malignancies and is used across all histology types and stages. Technical developments of radiotherapy have further strengthened and redefined its place in the management of lung cancer. High precision intensity-modulated radiation therapy, volumetric modulated arc therapy, and stereotactic body radiation therapy (SBRT), coupled with management of tumor motion and on-board imaging, increased efficacy and markedly decreased treatment-related toxicity. With this brief review, the authors pretend to present basic concepts and recent techniques advances in the use of radiation therapy for thoracic malignancies.

Influence of alcohol and tobacco consumption on maternal and perinatal outcomes of puerperal women attended at the Brazilian National Health System / Influência do consumo de álcool e tabaco em desfechos maternos e perinatais de puérperas atendidas no Sistema Único de Saúde

Abstract Objectives: to evaluate the association between alcohol and tobacco consumption during pregnancy with maternal and child health conditions. Methods: cross-sectional study with a probabilistic sample of pregnant women living in Santa Catarina who conducted prenatal care and childbirth in the public national health service in 2019. A face-to-face survey questionnaire was applied to 3,580 pregnant women including maternal health issues during pregnancy and perinatal health of the newborn. Crude logistic regression analyzes were performed and adjusted for socio-demographic and maternal health conditions. Results: the prevalence of alcohol and tobacco consumption during pregnancy was 7.2% and 9.3%, respectively. Alcohol consumption during pregnancy increased the chance of maternal anemia by 45% (CI95%=1.09-1.91), increased the chance of gestational diabetes by 73% (CI95%=1.14-2.63) and reduced the chance of hypertension (OR=0.59; CI95%=0.37-0.94). Tobacco consumption doubled the chance of low birth weight (OR=2.16; CI95%=1.33-3.51). Conclusion: the consumption of alcoholic beverages during pregnancy increased the chance of maternal health complications, such as anemia and gestational diabetes, while tobacco increased the chance of low birth weight.

Resumo Objetivos: avaliar a associação entre o consumo de álcool e de tabaco durante a gravidez com condições de saúde maternas e da criança. Métodos: estudo transversal com amostra probabilística de gestantes residentes em Santa Catarina que realizaram o pré-natal e o parto na rede pública do estado em 2019. Foi aplicado questionário face-a-face com 3.580 gestantes incluindo questões de saúde maternas durante a gestação e saúde perinatal do recém-nascido. Foram realizadas análises de regressão logística brutas e ajustadas para condições sócio-demográficas e de saúde maternas. Resultados: as prevalências de consumo de bebidas alcoólicas e de tabaco durante a gestação foram de 7,2% e 9,3%, respectivamente. O consumo de álcool durante a gestação aumentou em 45% a chance de anemia materna (IC95%=1,09-1,91) e em 73% a de diabetes gestacional (IC95%=1,14-2,63) e reduziu a chance de hipertensão (OR=0,59; IC95%=0,37-0,94). O consumo de tabaco dobrou a chance de baixo peso gestacional ao nascer (OR=2,16; IC95%=1,33-3,51). Conclusão: o consumo de bebidas alcoólicas durante a gestação aumentou a chance de intercorrências de saúde maternas, como anemia e diabetes gestacional, enquanto o tabaco aumentou a chance de baixo peso ao nascer.

Origem social e percurso: mérito e contingência entre egressos de um curso superior / Social origin and career: merit and contingency among graduates / Origen social y trayectorias mérito y contingencia entre los graduados

A problemática das desigualdades educacionais evidencia a influência da origem social sobre aspectos que envolvem o acesso e a permanência dos estudantes no ensino superior e ao longo da trajetória profissional. Este artigo tem como objetivo analisar em que medida o Curso de Administração Pública (CSAP) da Fundação João Pinheiro (FJP) é atravessado pela reprodução da estrutura de classes, seja da perspectiva dos ingressantes, seja da perspectiva dos egressos, à luz do referencial teórico de Bourdieu e Lahire. Realizou-se uma análise quanti e qualitativa dos dados dos alunos egressos do Curso de Administração Pública da Fundação João Pinheiro. A abordagem quantitativa nos forneceu um perfil do grupo estudado, a partir da análise de variáveis relacionadas à origem de classe. Entrevistas foram utilizadas para entender os percursos específicos dos sujeitos entrevistados. Corroborando o que apontam estudos da sociologia da educação, verificou-se estatisticamente que a origem social impacta sobre as chances de acesso ao curso. Por outro lado, dentre os indivíduos oriundos das camadas populares, há aqueles que vencem a barreira do ingresso e constroem trajetórias de sucesso acadêmico e profissional. Assim, por meio de análise qualitativa, procurou-se vislumbrar os fatores que possibilitaram o acesso ao CSAP e a permanência na carreira. Percebeu-se a importância da socialização secundária, da bolsa de estudos assegurada pelo curso, da garantia do ingresso no serviço público prevista com a conclusão da graduação e da persistência.

The problem of educational inequalities evidences the influence of social origin on aspects that involve the access and permanence of students in higher education and along the professional trajectory. This article aims to analyze the extent to which the Public Administration Course (CSAP) of the João Pinheiro Foundation (FJP) is affected by the reproduction of class structure, either from the perspective of the students or from the perspective of the graduates, in the light of the theoretical framework of Bourdieu and Lahire. A quantitative and qualitative analysis of the students and graduates of the Public Administration Course of the João Pinheiro Foundation was carried out. The quantitative approach provided a profile of the group studied, from the analysis of variables related to the origin of the class. Interviews were used to understand the specific paths of the subjects interviewed. Corroborating with studies of the sociology of education, it verified statistically that the social origin affects the chances of access to the course. On the other hand, among individuals from the popular classes, there are those who overcome the entrance barrier and build trajectories of academic and professional success. Thus, through a qualitative analysis, it sought to glimpse the factors that made it possible, as far as this group is concerned, access to the CSAP and the permanence in the career. The importance of the secondary socialization, the scholarship assured by the course, the guarantee of the entrance in the public service provided with the graduation and the persistence was confirmed, corroborating the theory.

La problemática de las desigualdades educativas evidencia la influencia del origen social sobre aspectos que involucran el acceso y la permanencia de los estudiantes en la enseñanza superior y al largo de la trayectoria profesional. Este artículo tiene como objetivo analizar en qué medida el Curso de Administración Pública (CSAP) de la Fundación João Pinheiro (FJP) es atravesado por la reproducción de la estructura de clases, sea desde la perspectiva de los ingresantes, sea desde la perspectiva de los egresados, a la luz del referencial teórico de Bourdieu y Lahire. Se realizó un análisis cuantitativo y cualitativo de los alumnos y egresados ​​del Curso de Administración Pública de la Fundación João Pinheiro. El enfoque cuantitativo proporcionó un perfil del grupo estudiado, a partir del análisis de variables relacionadas con el origen de clase. Entrevistas se utilizaron para entender los itinerarios específicos de los sujetos entrevistados. Corroborando con lo que apuntan estudios de la sociología de la educación, se verificó estadísticamente que el origen social impacta sobre las posibilidades de acceso al curso. Por otro lado, entre los individuos oriundos de las clases populares, hay aquellos que vencen la barrera del ingreso y construyen trayectorias de éxito académico y profesional. Así, por medio de análisis cualitativo, se procuró vislumbrar los factores que posibilitar, en lo que se refiere a ese grupo, el acceso al CSAP y la permanencia en la carrera. Se percibió la importancia de la socialización secundaria, de la beca de estudios asegurada por el curso, de la garantía del ingreso en el servicio público prevista con la conclusión de la graduación y de la persistencia.

Development and Characterization of PLGA Nanoparticles Containing 17-DMAG, an Hsp90 Inhibitor.

Leishmaniasis is a spectrum of neglected tropical diseases and its cutaneous form (CL) is characterized by papillary or ulcerated skin lesions that negatively impact patients' quality of life. Current CL treatments suffer limitations, such as severe side effects and high cost, making the search for new therapeutic alternatives an imperative. In this context, heat shock protein 90 (Hsp90) could present a novel therapeutic target, as evidence suggests that Hsp90 inhibitors, such as 17-Dimethylaminoethylamino-17-Demethoxygeldanamycin (17-DMAG), may represent promising chemotherapeutic agents against CL. As innovative input for formulation development of 17-DMAG, nano-based drug delivery systems could provide controlled release, targeting properties, and reduced drug toxicity. In this work, a double emulsion method was used to develop poly (lactic-co-glycolic acid) (PLGA) nanoparticles containing 17-DMAG. The nanoparticle was developed using two distinct protocols: Protocol 1 (P1) and Protocol 2 (P2), which differed concerning the organic solvent (acetone or dichloromethane, respectively) and procedure used to form double-emulsions (Ultra-Turrax® homogenization or sonication, respectively). The nanoparticles produced by P2 were comparatively smaller (305.5 vs. 489.0 nm) and more homogeneous polydispersion index (PdI) (0.129 vs. 0.33) than the ones made by P1. Afterward, the P2 was optimized and the best composition consisted of 2 mg of 17-DMAG, 100 mg of PLGA, 5% of polyethylene glycol (PEG 8000), 1.5 mL of the internal aqueous phase, 1% of polyvinyl alcohol (PVA), and 4 mL of the organic phase. Optimized P2 nanoparticles had a particle size of 297.2 nm (288.6-304.1) and encapsulation efficacy of 19.35% (15.42-42.18) by the supernatant method and 31.60% (19.9-48.79) by the filter/column method. Release kinetics performed at 37°C indicated that ~16% of the encapsulated 17-DMAG was released about to 72 h. In a separate set of experiments, a cell uptake assay employing confocal fluorescence microscopy revealed the internalization by macrophages of P2-optimized rhodamine B labeled nanoparticles at 30 min, 1, 2, 4, 6, 24, 48, and 72 h. Collectively, our results indicate the superior performance of P2 concerning the parameters used to assess nanoparticle development. Therefore, these findings warrant further research to evaluate optimized 17-DMAG-loaded nanoparticles (NP2-17-DMAG) for toxicity and antileishmanial effects in vitro and in vivo.

Câncer de mama: Reprogramação do metabolismo tumoral / Breast Cancer: tumoral metabolism reprogramming

O câncer de mama é a neoplasia de maior incidência em mulheres de todo o mundo, cuja mortalidade se deve principalmente ao desenvolvimento de metástases (condição patológica em que as células tumorais conseguem atravessar a matriz extracelular e se estabelecer em outros tecidos). Devido à importância epidemiológica dessa doença, estudos têm sido realizados em busca de uma melhor compreensão dos processos que atuam na carcinogênese e/ou tumorigênese e que, consequentemente, levam ao desenvolvimento de novas formas de diagnóstico e tratamento que sejam cada vez mais efetivos. Para manter a alta taxa de proliferação e desenvolver um perfil agressivo, características que são observadas em células tumorais, diversas alterações no metabolismo celular se tornam necessárias. O metabolismo tumoral começou a ser descrito por Otto Warburg em 1920, onde afirma que células cancerosas metabolizam glicose de forma diferente das células normais através da glicólise aeróbica. Dados recentes mostram que as alterações também ocorrem no metabolismo lipídico, apontando para uma reprogramação celular. A possibilidade de novos alvos farmacológicos inseriu o metabolismo como alvo das pesquisas recentes. Entretanto, e apesar do avanço, 90 anos depois da descoberta feita por Warburg, os estudos ainda não conseguiram esclarecer por completo como o metabolismo tumoral funciona, demonstrando assim a necessidade de mais pesquisas. Tendo em vista este cenário, essa revisão tem como objetivo documentar e discutir os principais resultados obtidos até o momento, como apontar e sugerir áreas de investigação. (AU)

Breast cancer is the most prevalent neoplasm in women worldwide, whose mortality is mainly due to the development of metastasis (pathological condition in which cancer cells can cross the extracellular matrix and settle in other tissues). Due to the epidemiological importance of this disease, studies have been carried out in order to better understand the processes involved in carcinogenesis and/or tumorigenesis and, consequently, allow the development of new forms of diagnosis and treatment that are increasingly effective. To maintain the high proliferation rate and develop an aggressive profile, features that are observed in tumor cells, several changes in cellular metabolism become necessary. Tumor metabolism began to be described by Otto Warburg in 1920, where he states that cancer cells metabolize glucose differently from normal cells through aerobic glycolysis. Recent data show that changes also occur in lipid metabolism, pointing to cellular reprogramming. The possibility of new pharmacological targets, inserted the metabolism as a target of recent research. However, despite the breakthrough, 90 years after Warburg discovery, studies have not yet been able to fully clarify how tumor metabolism works, demonstrating the need for more research. In view of this scenario, this review aims to document the main results obtained so far and to discuss those aspects that are not yet well understood. (AU)

Evaluation of Outpatient Parenteral Antimicrobial Therapy at a Veterans Affairs Hospital.

We reviewed outpatient parenteral antimicrobial therapy at a Veterans Affairs Medical Center to identify opportunities for antimicrobial stewardship intervention. A definite or possible modification would have been recommended in 60% of courses. Forty-one percent of outpatient parenteral antimicrobial therapy courses were potentially avoidable, including 22% involving infectious diseases consultation.

Chronic treatment with 17-DMAG improves balance and coordination in a new mouse model of Machado-Joseph disease.

Machado-Joseph disease (MJD) or spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disease currently with no treatment. We describe a novel mouse model of MJD which expresses mutant human ataxin-3 at near endogenous levels and manifests MJD-like motor symptoms that appear gradually and progress over time. CMVMJD135 mice show ataxin-3 intranuclear inclusions in the CNS and neurodegenerative changes in key disease regions, such as the pontine and dentate nuclei. Hsp90 inhibition has shown promising outcomes in some neurodegenerative diseases, but nothing is known about its effects in MJD. Chronic treatment of CMVMJD mice with Hsp90 inhibitor 17-DMAG resulted in a delay in the progression of their motor coordination deficits and, at 22 and 24 weeks of age, was able to rescue the uncoordination phenotype to wild-type levels; in parallel, a reduction in neuropathology was observed in treated animals. We observed limited induction of heat-shock proteins with treatment, but found evidence that 17-DMAG may be acting through autophagy, as LC3-II (both at mRNA and protein levels) and beclin-1 were induced in the brain of treated animals. This resulted in decreased levels of the mutant ataxin-3 and reduced intranuclear aggregation of this protein. Our data validate this novel mouse model as a relevant tool for the study of MJD pathogenesis and for pre-clinical studies, and show that Hsp90 inhibition is a promising therapeutic strategy for MJD.