FoxO3a overexpression prevents both glycogen overload and autophagic buildup in skeletal muscle of Pompe disease

FoxO3a overexpression prevents both glycogen overload and autophagic buildup in skeletal muscle of Pompe disease. 6eme congrès international de Myologi

Satellite cells fail to contribute to muscle repair but are functional in Pompe disease (glycogenosis type II)

Satellite cells fail to contribute to muscle repair but are functional in Pompe disease (glycogenosis type II). 6eme congrés international de Myologi

Cadeia produtiva do gengibre (Zingiber officinale ROSCOE) no estado do Paraná : análise e recomendações para melhoria da qualidade

Orientador : Raquel R.B.NegrelleCo-orientadores: Luiz Doni Filho, Neusa G.A. RuckerTese (doutorado) - Universidade Federal do Paraná. Setor de Ciências Agrárias. Curso de Pós-Graduação em Agronomia - área de concentração Produção Vegetal, Departamento de Fitotecnia e FitossanitarismoInclui bibliografia e glossárioResumo: O presente trabalho teve como objetivo o estudo prospectivo da cadeia produtiva do Zingiber officinale Roscoe no Estado do Paraná, identificando os principais agentes envolvidos e paralelamente proceder análise dos pontos de estrangulamentos, especificamente no que concerne à qualidade microbiológica deste produto em todos os níveis, desde a produção até a fase final da comercialização, visando identificar causas e propor soluções no sentido da melhoria do sistema como um todo. Este estudo foi desenvolvido no período de 2000 a 2002 englobando pesquisa de campo, entrevistas abertas com representantes de estabelecimentos de comercialização, produtores e demais atores da cadeia produtiva, além de análises laboratoriais do produto "in natura" disponível no mercado consumidor da Região Metropolitana de Curitiba - PR. Este documento está organizado em 9 capítulos, que apresentam vastas informações englobando aspectos botânicos, ecológicos, fisico-químicos e farmacológicos do gengibre, e que estão incluídas nos capítulos 1 e 2. O capítulo 3 apresenta características gerais da principal região produtora brasileira, Morretes - PR, englobando localização, aspectos sócio-econômicos, geológicos e geomorfológicos e caracterização climática. O capítulo 4 apresenta o estudo prospectivo da cadeia produtiva do gengibre no Estado do Paraná, que engloba panorama mundial, brasileiro e paranaense do volume de produção agrícola de gengibre. Inclui-se também caracterização da comunidade produtora agrícola do litoral paranaense, além da identificação e caracterização dos outros diferentes níveis da cadeia produtiva do gengibre e a detecção dos principais pontos de estrangulamento nos diferentes níveis desta cadeia produtiva. A caracterização do cultivo e beneficiamento do gengibre no litoral paranaense é apresentada no capítulo 5, evidenciando suas particularidades frente ao descrito na literatura especializada. No capítulo 6 avaliou-se as condições higiênico-sanitárias dos estabelecimentos produtores, do processo de beneficiamento pós-colheita (lavagem, limpeza, secagem e embalagem) e das condições de manipulação do gengibre "in natura" no litoral paranaense. De maneira geral, as condições de higiene e limpeza observadas foram consideradas precárias, determinando alta potencialidade de contaminação do gengibre com agentes que poderiam colocar em risco a saúde do consumidor. No capítulo 7 são apresentados os resultados dos estabelecimentos de comercialização da Região Metropolitana de Curitiba - PR, no que tange à qualidade e adequação às normas vigentes. Dos aspectos observados, as condições dos vestuários e dos equipamentos de proteção individual (manipuladores) foram considerados precários, o que pode potencializar a contaminação do produto e colocar em risco a saúde do consumidor. O capítulo 8 teve como objetivo caracterizar o perfil microbiológico do gengibre "in natura" comercializado na Região Metropolitana de Curitiba - PR, tendo como base a Resolução - CNPPA n. 12 - Brasil, 1978 e a Resolução - RDC n. 12 - Brasil, 2001. Para tanto, foram realizadas a determinação do número mais provável (NMP) de coliformes totais, coliformes a 45° C/g e Escherichia coli, e a presença de Salmonella sp em 25 gramas. Sintetizando, um conjunto de propostas e recomendações aos agentes econômicos que atuam e processam a cadeia produtiva do gengibre no Estado do Paraná, em especial o município de Morretes - PR, é apresentado no capítulo 9Abstract: Prospective studies of the productive chain of the Zingiber officinale Roscoe on Parana State identifying the main agents envolved and parallel procedure analysis of the strangulation points, in order to microbiology qualify this product in whole levels from the production until commercialization last phase, aiming identify causes and propose solutions to the improvement of the system in general. This survey developed from 2000 to 2002 involved field research, interviews with representative of the commercialization establishments, producers and others actors of the productive chain, besides made in laboratories of the quality of crude product available to the consumer market in Curitiba. This paper is organized in nine chapters that present information involving botanical, ecological, physique-chemical and pharmacological aspects of ginger that are included in chapters 1 and 2. The chapter 3 presents the characteristics of the main brazilian productive area, embody localization, social and economic aspects, geologycal, geomorphologycal and climate characterization. The chapter 4 the study of the productive chain of this product in Parana State, which includes the paranaense, the brazilian and the worldwide panoramic view of the production volume and commercialization of the ginger; characterization of the agricultural community; identification and characterization of others different levels of the productive chain and also, the main strangulation points on these different levels of the productive chain. In the chapter 5 the agricultural process of the ginger benefit and cultivation in Morretes Town, Paraná, Brazil was caracterized. In the chapter 6 the hygienic-sanitary conditions of the producers establishments, postharvest benefit system and manipulation conditions of crude ginger in the paranaense coastland, Brazil were evaluated with an aim to subsidy the ofert of the best quality product to consumer market. In general, the cleaning and hygienic conditions were precarious, determining a high potential of ginger contamination with agents that can put in risk the consumers' health. The chapter 7 presents the results of the commercialization establishments in the metropolitan area of Curitiba considering adequation to the current norm. Of the observed items, the manipulation conditions was considered precarious due to the inadequate conditions that contributes to contamination, bringing about serious problems to consumers' health. The chapter 8 aimed the microbiological quality of the ginger market in the metropolitan area of Curitiba based on the Brazilian legislation. The microbiological analysis found total coliforms, 45° C/g coliforms, Escherichia coli most probable number (MPN) and Salmonella sp presence. Synthetizing, a group of considerations and recommendations to economic agents that actuate and carry on the productive chain of the ginger in the Parana State, specially in Morretes Town, is presented in the chapter

Evaluation of the dystrophin carboxy-terminal domain for micro-dystrophin gene therapy in cardiac and skeletal muscles in the DMDmdx rat model

Duchenne muscular dystrophy (DMD) is a muscle wasting disorder caused by mutations in the gene encoding dystrophin. Gene therapy using micro-dystrophin (MD) transgenes and recombinant adeno-associated virus (rAAV) vectors hold great promise. To overcome the limited packaging capacity of rAAV vectors, most MD do not include dystrophin carboxy-terminal (CT) domain. Yet, the CT domain is known to recruit α1- and β1-syntrophins and α-dystrobrevin, a part of the dystrophin-associated protein complex (DAPC), which is a signaling and structural mediator of muscle cells. In this study, we explored the impact of inclusion of the dystrophin CT domain on ΔR4-23/ΔCT MD (MD1), in DMDmdx rats, which allows for relevant evaluations at muscular and cardiac levels. We showed by LC-MS/MS that MD1 expression is sufficient to restore the interactions at a physiological level of most DAPC partners in skeletal and cardiac muscles, and that inclusion of the CT domain increases the recruitment of some DAPC partners at supra-physiological levels. In parallel, we demonstrated that inclusion of the CT domain does not improve MD1 therapeutic efficacy on DMD muscle and cardiac pathologies. Our work highlights new evidences of the therapeutic potential of MD1 and strengthens the relevance of this candidate for gene therapy of DMD

FoxO3a overexpression prevents both glycogen overload and autophagic buildup in skeletal muscle of Pompe disease

FoxO3a overexpression prevents both glycogen overload and autophagic buildup in skeletal muscle of Pompe disease. 6eme congrès international de Myologi

FoxO3a overexpression prevents both glycogen overload and autophagic buildup in skeletal muscle of Pompe disease.

International audienc

Class I/Class II HLA Evolutionary Divergence Ratio Is an Independent Marker Associated With Disease-Free and Overall Survival After Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia

International audienceClass I Human Leukocyte Antigen (HLA) evolutionary divergence (HED) is a metric which reflects immunopeptidome diversity and has been associated with immune checkpoint inhibitor responses in solid tumors. Its impact and interest in allogeneic hematopoietic stem cell transplantation (HCT) have not yet been thoroughly studied. This study analyzed the clinical and immune impact of class I and II HED in 492 acute myeloid leukemia (AML) recipients undergoing HCT. The overall cohort was divided into a training (n=338) and a testing (n=132) set. Univariate cox screening found a positive impact of a high class I HED and a negative impact of a high class II HED on both disease-free (DFS) and overall survival (OS). These results were combined in a unique marker, class I/class II HED ratio, and assessed in the testing cohort. The final multivariate cox model confirmed the positive impact of a high versus low class I/class II HED ratio on both DFS (Hazard Ratio (HR) 0.41 [95% CI 0.2-0.83]; p=0.01) and OS (HR 0.34 [0.19-0.59]; p<0.001), independently of HLA matching and other HCT parameters. No significant association was found between the ratio and graft-versus-host disease (GvHD) nor with neutrophil and platelet recovery. A high class I HED was associated with a tendency for an increase in NK, CD8 T-cell, and B cell recovery at 12 months. These results introduce HED as an original and independent prognosis marker reflecting immunopeptidome diversity and alloreactivity after HCT

Efficacy and Safety of Revaccination against Tetanus, Diphtheria, Haemophilus influenzae Type b and Hepatitis B Virus in a Prospective Cohort of Adult Recipients of Allogeneic Hematopoietic Stem Cell Transplantation

International audienceData on immunogenicity and safety of the recommended revaccination schedule against diphtheria, tetanus, poliomyelitis, pertussis, Haemophilus influenzae type b (Hib), and hepatitis B in adult allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients are limited. This prospective single-center cohort study (April 2014 to March 2018) included adult allo-HSCT recipients referred to a dedicated vaccinology consultation and vaccinated with the pediatric combined diphtheria, tetanus, acellular pertussis, hepatitis B virus, inactivated poliovirus, and Haemophilus influenzae type b (DTaP(±HB)-IPV-Hib) vaccine (3 doses 1 month apart, booster dose 1 year later). The proportion of responders to tetanus, diphtheria, Hib, and hepatitis B vaccine and geometric mean concentrations (GMCs) of antibodies were assessed before and up to 24 months after vaccination. A total of 106 patients were vaccinated at a median (interquartile range) time of 12.4 (10 to 18.4) months post-transplant. At 5.3 (4.8 to 6.6) and 23.1 (21.1 to 25.1) months after vaccine initiation, high and sustained rates of protective antibody titers were achieved for tetanus (97.8% [95% confidence interval (95% CI), 92.4% to 99.7%], n = 91/93 and 100% [95% CI, 92% to 100%], n = 44/44), diphtheria (94.6% [95% CI, 87.9% to 98.2%], n = 88/93 and 90.9% [95% CI, 78.3% to 97.5%], n = 40/44), Hib (96.6% [95% CI, 90.4% to 99.3%], n = 85/88 and 93% [95% CI, 80.9% to 98.5%], n = 40/43), and hepatitis B (83.5% [95% CI, 73.5% to 90.9%], n = 66/79 and 81.1% [95% CI, 64.8% to 92%], n = 30/37). Underlying disease, stem cell source, chronic graft-versus-host-disease, and extracorporeal photopheresis differentially influenced GMCs of tetanus, diphtheria, and hepatitis B antibodies after 3 doses but not in the long term (24 months). Six (5.7%) patients experienced mild side effects. The pediatric DTaP(±HB)-IPV-Hib vaccine was safe and effective in eliciting a sustained protective humoral response in adult allo-HSCT recipients. Hepatitis B revaccination might be optimized by using higher antigen doses

Elderly Patients (Age 70 Years or Older) With Secondary Acute Myeloid Leukemia or Acute Myeloid Leukemia Developed Concurrently to Another Malignant Disease.

INTRODUCTION: Secondary acute myeloid leukemia (sAML) remains a therapeutic challenge. In elderly patients with AML, it is unclear whether sAML displays an inferior outcome compared with de novo AML. PATIENTS AND METHODS: We studied AML with an antecedent of hematologic disease, treatment-related AML, or AML occurring concurrently to another malignancy in a single-center cohort of patients aged 70 and older with AML. The study included 169 patients who were compared with a cohort of patients with de novo AML, without any prior history of malignant disorders, seen during the same period of time. RESULTS: Hematologic antecedents or presence of prior/concurrent solid malignancy did not impact complete remission rates and overall survival. In multivariate analysis, sAML appeared without independent prognostic value in the elderly. CONCLUSION: Our results support that sAML and de novo AML in elderly patients are not prognostically distinct entities. They should therefore not be considered separately when investigating outcomes and new treatment strategies