Impact of Timing of Lung resection on Survival for Clinical Stage I and II Lung Cancer

Background: Lung cancer has the highest mortality among the leading cancers in the U.S. Surgical resection is considered as the most effective treatment for lung cancer in early stages, providing greater long-term survival. Clinical guidelines on delays in resection of early-stage lung cancer do not exist. This work aims to assess whether increasing time between diagnosis/first doctor visit and surgery for early stage non-small cell lung cancer (NSCLC) is associated with poorer survival. Methods: We identified a retrospective cohort of incident lung cancer cases who had surgical treatment for lung cancer at our institution between January 2009 and December 2017, and no prior radiation or chemotherapy. We assessed overall survival (OS) and predictors included a) time from first contact to surgery; and b) time from diagnosis to surgery. The association between time from diagnosis and time from first contact to surgery, and survival for patients with early stage NSCLC was assessed using multivariable Cox proportional hazard. We investigated four cut-off points: surgery within 15 days, 30 days, 60 days and 90 days. We controlled for sociodemographic characteristics as well as clinical outcomes. Results: Our cohort comprised 491 patients. The age average was 66.9 years, 61% female, 94.7% white, and 9% never smoked. Clinical Stage 1A and 1B corresponded to 86.5% of patients while in pathological stage it was 76%. The 5-year overall survival was 56.0%. Surgery occurred a median 40 days after the diagnosis and 43 days after the first visit and within 35 days if the first appointment was with a thoracic surgeon. The threshold time associated with statistically significant worse survival was 60 days after diagnosis. Surgery was performed more than 60 days of diagnosis in 115 (25.7%) patients, their OS was significantly worse than patients who had surgery earlier (HR=1.7 [95% CI: 1.1-2.6]). Conclusions: Greater intervals between diagnosis of early-stage NSCLC and surgery are associated with worse survival. Efforts to minimize delays, particularly factors that prolong the period from diagnosis to first contact with a lung cancer provider may improve survival

Dmdmdx/Largemyd: a new mouse model of neuromuscular diseases useful for studying physiopathological mechanisms and testing therapies

Although muscular dystrophies are among the most common human genetic disorders, there are few treatment options available. Animal models have become increasingly important for testing new therapies prior to entering human clinical trials. The Dmdmdx mouse is the most widely used animal model for Duchenne muscular dystrophy (DMD), presenting the same molecular and protein defect as seen in humans with the disease. However, this mouse is not useful for clinical trials because of its very mild phenotype. The mouse model for congenital myodystrophy type 1D, Largemyd, harbors a mutation in the glycosyltransferase Large gene and displays a severe phenotype. To help elucidate the role of the proteins dystrophin and LARGE in the organization of the dystrophin-glycoprotein complex in muscle sarcolemma, we generated double-mutant mice for the dystrophin and LARGE proteins. The new Dmdmdx/Largemyd mouse model is viable and shows a severe phenotype that is associated with the lack of dystrophin in muscle. We tested the usefulness of our new mouse model for cell therapy by systemically injecting them with normal murine mesenchymal adipose stem cells (mASCs). We verified that the mASCs were hosted in the dystrophic muscle. The new mouse model has proven to be very useful for the study of several other therapies, because injected cells can be screened both through DNA and protein analysis. Study of its substantial muscle weakness will also be very informative in the evaluation of functional benefits of these therapies.FAPESP - CEPIDInstituto Nacional de Ciência e Tecnologia em Células-Tronco e Terapia Celular (INCTC) - CNPqFINEPABDIMCAPES / COFECU

Globalização económica e fragmentação geopolítica : a caminho de um mundo de equilíbrios instáveis e temporários?

Este texto explora a ideia de que a evolução mundial nos próximos anos vai ser marcada pela interacção complexa entre, por um lado as tensões associadas à Globalização da Economia Mundial, e por outro as Incertezas em torno da Fragmentação Geopolítica Mundial. Começa por identificar os grandes processos envolvidos na primeira "força motriz" - uma ampliação e "regionalização" da Economia Mundial; uma dinâmica de Globalização económica; uma competição acesa entre "Modelos de Capitalísmo"; uma mutação tecnológica abrangente, que modifica as estruturas económicas e a posição relativa das economias; e por último uma regulação económica global que procura responder à acumulação de tensões geradas pela interacção dos processos anteriores. Seguidamente identifica alguns processos chave que organizam a segunda" força motriz", como sejam o avanço da democratização, decorrendo em paralelo com a sobreposição de crises profundas em diversos Estados; um processo de fragmentação e "regionalização" em termos geopolíticos e de segurança; uma alteração na relação de forças entre potências, que está ainda numa fase inconclusiva; uma mutação tecnológica militar que pode influenciar decisivamente essa alteração; e a manifestação de dificuldades na regulação estratégica e geopolítica mundial, pela interacção dos processos anteriores e no contexto da ultrapassagem dos mecanismos de regulação típicos da guerra fria. Por último o texto ilustra algumas das interacções que se podem estabelecer entre as dinâmicas das duas "forças motrizes" sem explorar em profundidade o tema

Cooperation between Apoptotic and Viable Metacyclics Enhances the Pathogenesis of Leishmaniasis

Mimicking mammalian apoptotic cells by exposing phosphatidylserine (PS) is a strategy used by virus and parasitic protozoa to escape host protective inflammatory responses. With Leishmania amazonensis (La), apoptotic mimicry is a prerogative of the intramacrophagic amastigote form of the parasite and is modulated by the host. Now we show that differently from what happens with amastigotes, promastigotes exposing PS are non-viable, non-infective cells, undergoing apoptotic death. As part of the normal metacyclogenic process occurring in axenic cultures and in the gut of sand fly vectors, a sub-population of metacyclic promastigotes exposes PS. Apoptotic death of the purified PS-positive (PSPOS) sub-population was confirmed by TUNEL staining and DNA laddering. Transmission electron microscopy revealed morphological alterations in PSPOS metacyclics such as DNA condensation, cytoplasm degradation and mitochondrion and kinetoplast destruction, both in in vitro cultures and in sand fly guts. TUNELPOS promastigotes were detected only in the anterior midgut to foregut boundary of infected sand flies. Interestingly, caspase inhibitors modulated parasite death and PS exposure, when added to parasite cultures in a specific time window. Efficient in vitro macrophage infections and in vivo lesions only occur when PSPOS and PS-negative (PSNEG) parasites were simultaneously added to the cell culture or inoculated in the mammalian host. The viable PSNEG promastigote was the infective form, as shown by following the fate of fluorescently labeled parasites, while the PSPOS apoptotic sub-population inhibited host macrophage inflammatory response. PS exposure and macrophage inhibition by a subpopulation of promastigotes is a different mechanism than the one previously described with amastigotes, where the entire population exposes PS. Both mechanisms co-exist and play a role in the transmission and development of the disease in case of infection by La. Since both processes confer selective advantages to the infective microorganism they justify the occurrence of apoptotic features in a unicellular pathogen

Nutritional value and inclusion levels of residual annatto seed meal in diets for Japanese quails

Background:Residual annatto seed meal (RASM) is a byproduct after extraction of bixin in the cosmetic industry and may be used in animal diets. Objective: Two experiments were carried out to determine the nutritive value and effect of RASM inclusion levels in the diets of Japanese quails. Methods: For the digestibility experiment, 160 Japanese quails were distributed in a randomized study with two treatments and 10 replicates with eight birds each. The treatments consisted of a reference diet and a test diet containing 75% of the reference diet and 25% of RASM. For the performance assay, 192 Japanese quails were used in a randomized study with six treatments and four replicates with eight birds each. Treatments consisted of a control corn-based diet (Contr1) and another diet based on sorghum + canthaxanthin (Contr2), and four diets based on sorghum with increasing inclusion levels of RASM (0, 3, 6, and 9%). Results: Digestibility of dry matter and crude protein, metabolization coefficient of gross energy, and retention of calcium and phosphorus were 41.05, 43.12, 47.97, 25.49, and 30.35%, respectively. RASM inclusion did not influence bird productivity; however, feed conversion worsened in treatments with 0–6% RASM inclusion relative to that in Contr1. Yolk color increased due to RASM treatment. Conclusion: RASM may be included in sorghum-based diets for quails at 9%, with improvement in yolk color and no negative effects on productivity and egg quality.Antecedentes: O farelo residual da semente de urucum (RASM) é um subproduto da extração da bixina pela indústria cosmética e pode ser usado na alimentação animal. Objetivo: Dois experimentos foram conduzidos para determinar o valor nutritivo e os efeitos de inclusão do FRSU em dietas para codornas Japonesas. Métodos: Para o experimento de digestibilidade, 160 codornas Japonesas foram distribuídas em um estudo casualizado com dois tratamentos e 10 repetições com oito aves cada. Os tratamentos consistiram em uma dieta referência e uma dieta teste, a qual era composta por 75% da dieta referência e 25% de RASM. Para o ensaio de desempenho, 192 codornas Japonesas foram usadas em estudo ao acaso com seis tratamentos e quatro repetições com oito aves cada. Os tratamentos consistiram em uma dieta controle a base de milho (Contr1) e outra à base de sorgo com cantaxantina (Contr2) e quatro dietas a base de sorgo com níveis de inclusão de RASM (0, 3, 6 e 9%). Resultados: Os coeficientes de digestiblidade de matéria seca e proteína bruta, coeficiente de metabolização da energia bruta e retenção de cálcio e fósforo foram 41,05; 43,12; 47,97; 25,49 e 30,35%, respectivamente. A inclusão do FRSU não influenciou a produtividade das aves; entretanto, a conversão alimentar piorou devido aos tratamentos com 0-6% FRSU comparado com o tratamento Contr1. A cor da gema aumentou devido ao FRSU. Conclusão: RASM pode ser incluido em dietas baseadas em sorgo para codornas em 9%, devido a mehoria na cor da gema e nenhum efeito negativo no desempenho produtivo e qualidade de ovo.Antecedentes: La harina de la semilla de achiote (RASM) es un subproducto de la extracción de bixina por la industria cosmética y puede ser usada en alimentación animal. Objetivo: Se realizaron dos experimentos para determinar el valor nutritivo y los efectos de la inclusión de RASM en dietas para codorniz. Métodos: Para el experimento de digestibilidad, 160 codornices japonesas fueron distribuidas en un estudio al azar con dos tratamientos y 10 repeticiones con ocho aves cada uno. Los tratamientos consistieron en una dieta referencia y una dieta de prueba, la cual estuvo compuesta por 75% de la dieta referencia y 25% de RASM. Para el ensayo de desempeño, 192 codornices japonesas fueron usadas en un estudio al azar con seis tratamientos y cuatro repeticiones con ocho aves cada uno. Los tratamientos consistieron en una dieta control a base de maíz (Contr1) y otra a base de sorgo + cantaxantina (Contr2) y cuatro dietas a base de sorgo con niveles de inclusión de RASM (0, 3, 6 y 9%). Resultados: Los coeficientes de digestibilidad de materia seca y proteína bruta, el coeficiente de metabolización de la energía bruta y la retención de calcio y fósforo fueron 41,05; 43,12; 47,97; 25,49 y 30,35%, respectivamente. La inclusión de RASM no influyó la productividad de las aves; entretanto la conversión alimenticia empeoró debido a los tratamientos con 0-6% RASM comparado con el tratamiento Contr1. El color de la yema aumentó debido a la RASM. Conclusión: RASM puede ser incluido en dietas a base de sorgo para codornices en un 9%, debido a la mejora en el color de la yema, además de no tener ningún efecto negativo en el desempeño productivo y calidad del huevo