The Role of MET Inhibitor Therapies in the Treatment of Advanced Non-Small Cell Lung Cancer

Introduction: Non-small cell lung cancer (NSCLC) is the second most common cancer globally. The mesenchymal-epithelial transition (MET) proto-oncogene can be targeted in NSCLC patients.Methods: We performed a literature search on PubMed in December 2019 for studies on MET inhibitors and NSCLC. Phase II and III clinical trials published in English between 2014 and 2019 were selected.Results: Data on MET inhibitors (tivantinib, cabozantinib, and crizotinib) and anti-MET antibodies (emibetuzumab and onartuzumab) are reported in the text.Conclusion: Emibetuzumab could be used for NSCLC cases with highMETexpression. Further, studies on onartuzumab failed to prove its efficacy, while the results of tivantinib trials were clinically but not statistically significant. Additionally, cabozantinib was effective, but adverse reactions were common, and crizotinib was generally well-tolerated

Parasites and allergy: observations from Brazil.

Brazil is a middle-income country undergoing the epidemiological transition. Effects of changes in daily life habits, and access to clean water, sanitation and urban services on a growing urban population have contributed to a double burden of both infectious and non-communicable chronic diseases. Studies have indicated that parasite infections may modulate the human immune system and influence the development of allergic conditions such as asthma. However, there is no consensus in the published literature on the effects of parasitic infections on allergy, perhaps as a consequence of factors determining the epidemiology of these infections that vary between populations such as age of first infection, duration and chronicity of infections, parasite burden and species, and host genetic susceptibility. In this review, we discuss the observations from Brazil concerning the relationship between parasite infections and allergy. This article is protected by copyright. All rights reserved

Data on prevalence and risk factors associated with Toxocara spp infection, atopy and asthma development in Northeast Brazilian school children.

In the present article, we provide shortly, data on risk factors for acquiring Toxocara spp. infection and investigate possible associations between this infection with atopy and asthma in school children of a small town and its semi-rural areas of Northeast Brazil. The data set are composed by demographic, social and home environment variables. The detection of anti-Toxocara spp. IgG and specific IgE to aeroallergens was determined by ELISA and ImmunocAP/Phadiatrope systems, respectively. The data presented in this article are related to the article entitled "Risk factors for Toxocara spp. seroprevalence and its association with atopy and asthma phenotypes in school-age children in a small town and semi-rural areas of Northeast Brazil" (M.B. Silva, A.L. Amor, L.N. Santos, A.A. Galvão, A.V. Oviedo Vera, E.S. Silva et al., 2016) [1]

A prospective seroepidemiological study of toxocariasis during early childhood in coastal Ecuador: potential for congenital transmission and risk factors for infection.

BACKGROUND: Although Toxocara spp. infection has a worldwide distribution, to our knowledge, no data from birth cohorts have been reported in published studies on the potential for congenital transmission and determinants of infection in early childhood. METHODS: We followed 290 mother-infant pairs from birth to 5 years of age through periodic collection of data and samples at birth, 7 and 13 months and 2, 3 and 5 years of age. Data on potential risk factors and confounders were collected by maternal questionnaire. Blood for plasma was collected from the mother at time of birth and periodically from the child for detection of anti-Toxocara spp. immunoglobulin G (IgG) antibodies using a Toxocara canis larval excretory-secretory antigen-based enzyme-linked immunosorbent assay. Stool samples were collected from the mother around the time of birth and periodically from the child for microscopic detection of soil-transmitted helminths (STH). Associations between potential risk factors and Toxocara spp. seroprevalence and seroconversion were estimated using multivariable logistic regression and generalized estimating equations. RESULTS: Toxocara spp. seroprevalence was 80.7% in mothers and in children was 0%, 9.3%, 48.4%, 64.9%, and 80.9% at 7 months, 13 months, 2, 3 and 5 years, respectively. Risk factors significantly associated with increases in seroprevalence over the first 5 years of life in multivariable analyses were age [Odds ratio (OR) 2.06, 95% confidence interval (CI) 1.39-2.27, P < 0001], male sex (female vs. male: OR 0.66, 95% CI 0.48-0.89, P = 0.006), maternal ethnicity (non-Afro vs. Afro-Ecuadorian: OR 0.65, 95% CI 0.47-0.91, P = 0.011), lower maternal educational and socioeconomic level, and childhood STH (OR 2.29, 95% CI 1.51-3.47, P < 0.001). Seroconversion rates for infection were greatest at 2 years of age (3.8%/month). Factors associated significantly with seroconversion at 2, 3 or 5 years were childhood STH infection, male sex, and more frequent domestic cat exposure. CONCLUSIONS: Our data, from an area of high Toxocara spp. endemicity, indicate no congenital transmission but high rates of seroconversion after 13 months of age reaching maternal levels of seroprevalence by 5 years of age. Factors associated with seroprevalence and seroconversion included STH infections, domestic cats, maternal ethnicity, male sex, STH infections, and markers of greater poverty

Analysis of spectral indexes for heart rate variability in middle-aged men and postmenopausal women

OBJECTIVE: To analyze and compare heart rate variability (HRV) in middle-aged men and women under resting conditions. METHOD: Ten men (54 &plusmn; 3.2 years) and fourteen postmenopausal women (56 &plusmn; 2.6 years) who were not using hormonal therapy were studied. Heart rates (HR) and R-R intervals (iR-R) on a beat-to-beat basis were obtained from electrocardiograms over an eight-minute period under resting conditions, in the supine and sitting positions. The HRV was analyzed in the frequency domain by means of fast Fourier transforms and the low (LF) and high (HF) frequency bands were obtained and presented as normalized units (LFnu and HFnu) and the LF/HF ratio. Wilcoxon and Mann-Whitney non-parametric statistical tests were used, with the significance level set at 5%. RESULTS: Comparing between the groups, the women presented significantly higher HFnu and lower LFnu and LF/HF ratios than did the men (p0.05) were found in the HRV indexes between the supine and sitting positions for either study group. CONCLUSION: Our results show greater vagal modulation and lower sympathetic activity in autonomic heart rate control among women than among men of similar age. This suggests that the gender-related autonomic differences are not solely dependent on estrogen levels, since the women studied were already postmenopausal. Other factors may be contributing towards these differences.OBJETIVO: Analisar e comparar a variabilidade da freqüência cardíaca (VFC), em repouso, de homens e mulheres de meia-idade. MÉTODOS: Foram estudados 10 homens (54 &plusmn; 3,2 anos) e 14 mulheres na pós-menopausa (56 &plusmn; 2,6 anos) que não faziam uso de terapia hormonal. A freqüência cardíaca (FC) e os intervalos R-R foram obtidos a partir do eletrocardiograma, batimento a batimento, durante 8 minutos em repouso, nas posições supina e sentada. A VFC foi analisada no domínio da freqüência, usando a transformada rápida de Fourier, por meio da qual foram obtidas as bandas de baixa (BF) e alta freqüência (AF), as quais foram expressas em unidades normalizadas (AFun) e (BFun) e na razão BF/AF. Foram utilizados os testes estatísticos não-paramétricos de Mann-Whitney e de Wilcoxon, com nível de significância de alfa= 5%. RESULTADOS: Na comparação intergrupo, as mulheres apresentaram maiores valores da banda AFun e menores valores da banda BFun e da razão BF/AF em relação aos homens, diferenças essas significativas (p<0,05). Na comparação intragrupo, não foram observadas diferenças significativas nos índices de VFC entre as posições supina e sentada para os 2 grupos estudados. CONCLUSÃO: Nossos resultados mostram uma maior modulação vagal e menor simpática no controle autonômico da FC para as mulheres em comparação aos homens de mesma idade, o que sugere que as diferenças autonômicas relacionadas ao gênero não se devem unicamente aos níveis hormonais de estrogênio, uma vez que as mulheres estudadas já se encontravam na fase pós-menopausa. Outros fatores podem estar contribuindo para essas diferenças.401406Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Nanostructured 3D Constructs Based on Chitosan and Chondroitin Sulphate Multilayers for Cartilage Tissue Engineering

Nanostructured three-dimensional constructs combining layer-by-layer technology (LbL) and template leaching were processed and evaluated as possible support structures for cartilage tissue engineering. Multilayered constructs were formed by depositing the polyelectrolytes chitosan (CHT) and chondroitin sulphate (CS) on either bidimensional glass surfaces or 3D packet of paraffin spheres. 2D CHT/CS multi-layered constructs proved to support the attachment and proliferation of bovine chondrocytes (BCH). The technology was transposed to 3D level and CHT/CS multi-layered hierarchical scaffolds were retrieved after paraffin leaching. The obtained nanostructured 3D constructs had a high porosity and water uptake capacity of about 300%. Dynamical mechanical analysis (DMA) showed the viscoelastic nature of the scaffolds. Cellular tests were performed with the culture of BCH and multipotent bone marrow derived stromal cells (hMSCs) up to 21 days in chondrogenic differentiation media. Together with scanning electronic microscopy analysis, viability tests and DNA quantification, our results clearly showed that cells attached, proliferated and were metabolically active over the entire scaffold. Cartilaginous extracellular matrix (ECM) formation was further assessed and results showed that GAG secretion occurred indicating the maintenance of the chondrogenic phenotype and the chondrogenic differentiation of hMSCs

Jogo educativo sobre drogas para cegos: construção e avaliação

Estudo realizado com o objetivo de construir e avaliar um jogo educativo sobre drogas psicoativas acessível a pessoas cegas, desenvolvido em três etapas: construção do jogo educativo, avaliação por três especialistas em educação especial e doze cegos. Foi construído um jogo de tabuleiro denominado Drogas: jogando limpo . Na Versão Alfa os especialistas fizeram sugestões em relação às e instruções e ao tabuleiro: textura das casas, peças do jogo e escrita em Braille. Na Versão Beta, procedeu-se à avaliação pelos cegos, os quais sugeriram alterações na textura das casas e colocação de velcro para fixação do pino no tabuleiro. Passou-se, então, à Versão Gama, jogada pelas últimas três duplas de cegos e considerada adequada. Na avaliação dos juízes, o jogo revelou-se adequado, pois permite o acesso à informação sobre drogas psicoativas de maneira lúdica

Contribution of microscopy for understanding the mechanism of action against trypanosomatids

Transmission electron microscopy (TEM) has proved to be a useful tool to study the ultrastructural alterations and the target organelles of new antitrypanosomatid drugs. Thus, it has been observed that sesquiterpene lactones induce diverse ultrastructural alterations in both T. cruzi and Leishmania spp., such as cytoplasmic vacuolization, appearance of multilamellar structures, condensation of nuclear DNA, and, in some cases, an important accumulation of lipid vacuoles. This accumulation could be related to apoptotic events. Some of the sesquiterpene lactones (e.g., psilostachyin) have also been demonstrated to cause an intense mitochondrial swelling accompanied by a visible kinetoplast deformation as well as the appearance of multivesicular bodies. This mitochondrial swelling could be related to the generation of oxidative stress and associated to alterations in the ergosterol metabolism. The appearance of multilamellar structures and multiple kinetoplasts and flagella induced by the sesquiterpene lactone psilostachyin C indicates that this compound would act at the parasite cell cycle level, in an intermediate stage between kinetoplast segregation and nuclear division. In turn, the diterpene lactone icetexane has proved to induce the external membrane budding on T. cruzi together with an apparent disorganization of the pericellar cytoskeleton. Thus, ultrastructural TEM studies allow elucidating the possible mechanisms and the subsequent identification of molecular targets for the action of natural compounds on trypanosomatids.Fil: Lozano, Esteban Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Spina Zapata, Renata María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Barrera, Patricia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Tonn, Carlos Eugenio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; ArgentinaFil: Sosa Escudero, Miguel Angel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentin

First two unrelated cases of isolated sedoheptulokinase deficiency: A benign disorder?

We present the first two reported unrelated patients with an isolated sedoheptulokinase (SHPK) deficiency. The first patient presented with neonatal cholestasis, hypoglycemia, and anemia, while the second patient presented with congenital arthrogryposis multiplex, multiple contractures, and dysmorphisms. Both patients had elevated excretion of erythritol and sedoheptulose, and each had a homozygous nonsense mutation in SHPK. SHPK is an enzyme that phosphorylates sedoheptulose to sedoheptulose-7-phosphate, which is an important intermediate of the pentose phosphate pathway. It is questionable whether SHPK deficiency is a causal factor for the clinical phenotypes of our patients. This study illustrates the necessity of extensive functional and clinical workup for interpreting a novel variant, including nonsense variants