REFLEXÕES ACERCA DE INICIATIVAS AGROECOLÓGICAS NO LITORAL NORTE DO RS

As iniciativas agroecológicas representam uma proposta alternativa para um modelo de desenvolvimento rural sustentável. O objetivo deste estudo foi conhecer e analisar as iniciativas agroecológicas no município de Caraá, Litoral Norte do estado do Rio Grande do Sul. Para atender ao objetivo, foram realizadas quatro entrevistas a representantes de instituições municipais e nove entrevistas à representantes de iniciativas agroecológicas. Os resultados do estudo, permitem inferir que, as iniciativas possuem menos de cinco anos de experiência, com importante participação feminina no trabalho e na gestão, presença de público neo-rural e ampla diversidade de atividades remuneradas, mostrando a pluriatividade destes estabelecimentos. Conclui-se, portanto que estas iniciativas são importantes e exercem influência na economia local, na qualidade de vida e na permanência da população no meio rural

Childhood trauma and resilience : vulnerabilities to develop crack/cocaine dependence

Background: Crack cocaine dependence is a health problem of epidemic proportions and there is lack of evidence concerning vulnerability factors that could lead to crack cocaine use. The aim of this study is to investigate characteristics of resilience in a group of crack cocaine users and its association with childhood trauma and PTSD. Method: This is a case-control study in which we evaluated 218 crack cocaine inpatients users and 215 healthy controls, recruited from the capital city of the southern State of Brazil. Childhood Trauma was evaluated with the Childhood Trauma Questionnaire; resilience was evaluated with the Resilience Scale; and post-traumatic stress disorder (PTSD) was evaluated with the Mini-International Neuropsychiatric Interview. Results: Childhood trauma was significantly higher among crack cocaine users in all trauma domains (p<0.001), except for sexual abuse. Most resilience scores was lower among crack cocaine users (p<0.01). Having higher scores of childhood trauma and lower scores of resilience increase the odds to become a crack cocaine user (p<0.001), despite the diagnosis of PTSD. Discussion: Childhood trauma appears to be a risk factor to become a crack cocaine user while resilience features may be a protection factor. To understand factors of vulnerabilities in this population is important for the development of more efficacious treatment and preventive strategies

Effects of the glucagon-like peptide-1 receptor agonist liraglutide in juvenile transgenic pigs modeling a pre-diabetic condition

Background: The glucagon-like peptide-1 receptor (GLP1R) agonist liraglutide improves glycemic control and reduces body weight of adult type 2 diabetic patients. However, efficacy and safety of liraglutide in adolescents has not been systematically investigated. Furthermore, possible pro-proliferative effects of GLP1R agonists on the endocrine and exocrine pancreas need to be further evaluated. We studied effects of liraglutide in adolescent pigs expressing a dominant-negative glucose-dependent insulinotropic polypeptide receptor (GIPRdn) in the beta-cells, leading to a pre-diabetic condition including disturbed glucose tolerance, reduced insulin secretion and progressive reduction of functional beta-cell mass. Methods: Two-month-old GIPRdn transgenic pigs were treated daily with liraglutide (0.6-1.2 mg per day) or placebo for 90 days. Glucose homeostasis was evaluated prior to and at the end of the treatment period by performing mixed meal and intravenous glucose tolerance tests (MMGTT and IVGTT). Finally animals were subjected to necropsy and quantitative-stereological analyses were performed for evaluation of alpha-and beta-cell mass, beta-cell proliferation as well as acinus-cell proliferation. Results: MMGTT at the end of the study revealed 23% smaller area under the curve (AUC) for glucose, a 36% smaller AUC insulin, and improved insulin sensitivity, while IVGTT showed a 15% smaller AUC glucose but unchanged AUC insulin in liraglutide-vs. placebo-treated animals. Liraglutide led to marked reductions in body weight gain (-31%) and food intake (-30%) compared to placebo treatment, associated with reduced phosphorylation of insulin receptor beta (INSRB)/insulin-like growth factor-1 receptor beta (IGF1RB) and protein kinase B (AKT) in skeletal muscle. Absolute alpha-and beta-cell mass was reduced in liraglutide-treated animals, but alpha-and beta-cell mass-to-body weight ratios were unchanged. Liraglutide neither stimulated beta-cell proliferation in the endocrine pancreas nor acinus-cell proliferation in the exocrine pancreas, excluding both beneficial and detrimental effects on the pig pancreas. Conclusions: Although plasma liraglutide levels of adolescent transgenic pigs treated in our study were higher compared to human trials, pro-proliferative effects on the endocrine or exocrine pancreas or other liraglutide-related side-effects were not observed

PERFIL DE IDOSOS INSTITUCIONALIZADOS PARTICIPANTES DE PROJETO DE EXTENSÃO E BENEFÍCIOS AOS ENVOLVIDOS

Este estudo teve por objetivo descrever o perfil dos idosos envolvidos no projeto de Extensão “Ações Interdisciplinares voltadas aos Idosos Institucionalizados e Cuidadores” bem como as atividades realizadas, destacando os benefícios para a formação acadêmica e qualidade de vida dos idosos. Trata-se de um estudo com abordagem quali-quantitativa, por meio do levantamento de dados das fichas de avaliação/evolução da Fisioterapia e prontuários dos idosos, além da descrição das atividades desenvolvidas, no período entre setembro de 2016 a outubro de 2017, em uma ILPI localizada no noroeste do estado do Rio Grande do Sul. Os idosos foram divididos em dois grupos: dependentes e independentes. Em idosos dependentes (acamados) o objetivo das intervenções foi diminuir atrofias musculares, rigidez muscular e imobilidade no leito. Com os idosos independentes ou parcialmente dependentes foram realizados atendimentos em grupo. As atividades tinham o objetivo de manutenção e ganho de amplitude de movimento e mobilidade articular, melhora da deambulação, equilíbrio, motricidade, estímulo da memória e coordenação motora. Houve predomínio do sexo feminino e as patologias mais recorrentes foram hipertensão arterial sistêmica, depressão e problemas cardiovasculares. As ações realizadas a partir do projeto de extensão proporcionaram aos idosos diferentes atividades que promoveram a saúde, a qualidade de vida e mudanças no estilo de vida, além de aproximar os acadêmicos da realidade social, viabilizando o acesso à comunidade, a socialização e trocas de experiências

Separate and combined effects of genetic variants and pre-treatment whole blood gene expression on response to exposure-based cognitive behavioural therapy for anxiety disorders

Objectives: Exposure-based cognitive behavioural therapy (eCBT) is an effective treatment for anxiety disorders. Response varies between individuals. Gene expression integrates genetic and environmental influences. We analysed the effect of gene expression and genetic markers separately and together on treatment response. Methods: Adult participants (n ≤ 181) diagnosed with panic disorder or a specific phobia underwent eCBT as part of standard care. Percentage decrease in the Clinical Global Impression severity rating was assessed across treatment, and between baseline and a 6-month follow-up. Associations with treatment response were assessed using expression data from 3,233 probes, and expression profiles clustered in a data- and literature-driven manner. A total of 3,343,497 genetic variants were used to predict treatment response alone and combined in polygenic risk scores. Genotype and expression data were combined in expression quantitative trait loci (eQTL) analyses. Results: Expression levels were not associated with either treatment phenotype in any analysis. A total of 1,492 eQTLs were identified with q < 0.05, but interactions between genetic variants and treatment response did not affect expression levels significantly. Genetic variants did not significantly predict treatment response alone or in polygenic risk scores. Conclusions: We assessed gene expression alone and alongside genetic variants. No associations with treatment outcome were identified. Future studies require larger sample sizes to discover associations

Efficient production of multi-modified pigs for xenotransplantation by ‘combineering’, gene stacking and gene editing

Xenotransplantation from pigs could alleviate the shortage of human tissues and organs for transplantation. Means have been identified to overcome hyperacute rejection and acute vascular rejection mechanisms mounted by the recipient. The challenge is to combine multiple genetic modifications to enable normal animal breeding and meet the demand for transplants. We used two methods to colocate xenoprotective transgenes at one locus, sequential targeted transgene placement - ‘gene stacking’, and cointegration of multiple engineered large vectors - ‘combineering’, to generate pigs carrying modifications considered necessary to inhibit short to mid-term xenograft rejection. Pigs were generated by serial nuclear transfer and analysed at intermediate stages. Human complement inhibitors CD46, CD55 and CD59 were abundantly expressed in all tissues examined, human HO1 and human A20 were widely expressed. ZFN or CRISPR/Cas9 mediated homozygous GGTA1 and CMAH knockout abolished α-Gal and Neu5Gc epitopes. Cells from multi-transgenic piglets showed complete protection against human complement-mediated lysis, even before GGTA1 knockout. Blockade of endothelial activation reduced TNFα-induced E-selectin expression, IFNγ-induced MHC class-II upregulation and TNFα/cycloheximide caspase induction. Microbial analysis found no PERV-C, PCMV or 13 other infectious agents. These animals are a major advance towards clinical porcine xenotransplantation and demonstrate that livestock engineering has come of age

Factors influencing the efficiency of generating genetically engineered pigs by nuclear transfer: multi-factorial analysis of a large data set

Background: Somatic cell nuclear transfer (SCNT) using genetically engineered donor cells is currently the most widely used strategy to generate tailored pig models for biomedical research. Although this approach facilitates a similar spectrum of genetic modifications as in rodent models, the outcome in terms of live cloned piglets is quite variable. In this study, we aimed at a comprehensive analysis of environmental and experimental factors that are substantially influencing the efficiency of generating genetically engineered pigs. Based on a considerably large data set from 274 SCNT experiments (in total 18,649 reconstructed embryos transferred into 193 recipients), performed over a period of three years, we assessed the relative contribution of season, type of genetic modification, donor cell source, number of cloning rounds, and pre-selection of cloned embryos for early development to the cloning efficiency. Results: 109 (56%) recipients became pregnant and 85 (78%) of them gave birth to offspring. Out of 318 cloned piglets, 243 (76%) were alive, but only 97 (40%) were clinically healthy and showed normal development. The proportion of stillborn piglets was 24% (75/318), and another 31% (100/318) of the cloned piglets died soon after birth. The overall cloning efficiency, defined as the number of offspring born per SCNT embryos transferred, including only recipients that delivered, was 3.95%. SCNT experiments performed during winter using fetal fibroblasts or kidney cells after additive gene transfer resulted in the highest number of live and healthy offspring, while two or more rounds of cloning and nuclear transfer experiments performed during summer decreased the number of healthy offspring. Conclusion: Although the effects of individual factors may be different between various laboratories, our results and analysis strategy will help to identify and optimize the factors, which are most critical to cloning success in programs aiming at the generation of genetically engineered pig models

Functionalizing avß3- or a5ß1-selective integrin antagonists for surface coating: A new tool to discriminate integrin subtypes in vitro

Thumbnail image of graphical abstract Stuck with the right choice: avß3- or a5ß1-selective integrin ligands were functionalized for surface coating without losing activity and selectivity. The coating of nanostructured gold surfaces with these compounds stimulated subtype-selective cell adhesion of genetically modified avß3- or a5ß1-expressing fibroblasts in vitro.Postprint (published version