CONTRIBUIÇÕES DE IGNACY SACHS PARA O DESENVOLVIMENTO SUSTENTÁVEL DO OESTE DO PARANÁ

O objetivo desse artigo é o de estudar alguns textos do economista Ignacy Sachs, aonde o autor apresenta suas teorias e práticas sobre o ecodesenvolvimento (desenvolvimento sustentável) e analisar sua contribuição à teoria do desenvolvimento e em particular, analisar como seus pensamentos podem ser utilizados como contribuição ao desenvolvimento da região Oeste do Paraná. Resultado de seus trabalhos e estudos, sua concepção de desenvolvimento alia o crescimento econômico, a preocupação com a preservação ambiental e a ampliação igualitária do bem-estar social. Isso lhe conferiu o título de ecossocioeconomista. Sachs deixa claro que o processo de desenvolvimento pode ocorrer em diferentes escalas, do local ao planetário, assim, é totalmente factível que os conceitos por ele desenvolvidos possam ser aplicados à região Oeste do Paraná. Conceitos como planejamento concertado de governança democrática, como a economia da biomassa, e da inclusão social

A IMPORTÂNCIA DA ASSISTÊNCIA TÉCNICA E EXTENSÃO RURAL PARA AGROINDÚSTRIAS FAMILIARES: O CASO DA AGROINDÚSTRIA DE PANIFICAÇÃO NO OESTE DO PARANÁ

A agricultura familiar é uma categoria da sociedade brasileira com grande importância econômica e social, seja pela sua representação numérica, seja pela função de oferecer alimentos e outros serviços para a população urbana. Manter essas funções depende de políticas de desenvolvimento rural. Uma dessas políticas é a assistência técnica e extensão rural – ATER, que propõe oferecer conhecimentos e tecnologias para serem empregadas nos sistemas de produção e seus negócios, sobretudo aqueles que sejam adequadas às circunstâncias de escassez de capital e às adversidades vividas pelas pequenas propriedades. Esse artigo teve como objetivo estudar a importância da ATER oferecida às agroindústrias familiares do Oeste do Paraná, na percepção dos usuários. Para isso foi utilizado entrevistas semiestruturadas que abordaram o serviço ofertado, a frequência, e os resultados percebidos pelo produtor quanto a rentabilidade, redução de esforço físico e preservação ambiental. Chama a atenção a percepção de que a ATER cumpre sua função estrita e amplia a renda do produtor, porém este espera que além das questões técnicas relativas a produção, a ATER também instrua e auxilie em questões comerciais e de modelo de negócio

Identifying the factors that influence surgeon's compliance with excisional margins of non-melanoma skin cancer

The rising incidence of Non Melanoma Skin Cancers (NMSC) leads to a high number of surgical procedures worldwide. The strict compliance with international guidelines with regard to excisional margins may help decrease the number of re-excision procedures and reduce the risk of NMSC recurrence. The aim of this study was to investigate the prevalence of excisional margins as recommended by the European Academy of Dermatology and Venereology (EADV) and the European Dermatology Forum (EDF) guidelines, and the factors (demographic or clinical) that influence surgeons' compliance with these guidelines.This was a prevalence study looking at surgical excisions of NMSCs performed over a period of 2 years (2011-2012). A sample size of 1669 patients was considered. Definition of excisional margins recommended by the international guidelines (EADV and EDF) were used as point of reference for the analysis. Tumor and histologic specimen size were calculated ex vivo by 5 different pathologists. The size of skin specimens was measured with a major axis and a minor axis. The same was done for the tumor present on the skin specimens. The differences between the major and minor axes of surgical specimen and tumor were calculated. These differences were subsequently divided by two, hypothesizing that the lesion had the same distance from the margins of the surgical specimen. The differences obtained were named "Delta", the formulas applied being the following: Delta major = (major axis specimen-major axis tumor)/2; Delta minor = (minor axis specimen -minor axis tumor)/2.Results show a significant statistical difference, associated with factors such as: Age of the patient, anatomical localization of the tumor, histological diagnosis, and surgeons' experience.The identification of these factors sheds light on clinicians' practice and decision-making regarding excisional margins. Hopefully a higher level of adherence to the guidelines can be achieved in the future

Development of a Single Vector System that Enhances Trans-Splicing of SMN2 Transcripts

RNA modalities are developing as a powerful means to re-direct pathogenic pre-mRNA splicing events. Improving the efficiency of these molecules in vivo is critical as they move towards clinical applications. Spinal muscular atrophy (SMA) is caused by loss of SMN1. A nearly identical copy gene called SMN2 produces low levels of functional protein due to alternative splicing. We previously reported a trans-splicing RNA (tsRNA) that re-directed SMN2 splicing. Now we show that reducing the competition between endogenous splices sites enhanced the efficiency of trans-splicing. A single vector system was developed that expressed the SMN tsRNA and a splice-site blocking antisense (ASO-tsRNA). The ASO-tsRNA vector significantly elevated SMN levels in primary SMA patient fibroblasts, within the central nervous system of SMA mice and increased SMN-dependent in vitro snRNP assembly. These results demonstrate that the ASO-tsRNA strategy provides insight into the trans-splicing mechanism and a means of significantly enhancing trans-splicing activity in vivo

Of Mice and Measures : A Project to Improve How We Advance Duchenne Muscular Dystrophy Therapies to the Clinic.

A new line of dystrophic mdx mice on the DBA/2J (D2) background has emerged as a candidate to study the efficacy of therapeutic approaches for Duchenne muscular dystrophy (DMD). These mice harbor genetic polymorphisms that appear to increase the severity of the dystropathology, with disease modifiers that also occur in DMD patients, making them attractive for efficacy studies and drug development. This workshop aimed at collecting and consolidating available data on the pathological features and the natural history of these new D2/mdx mice, for comparison with classic mdx mice and controls, and to identify gaps in information and their potential value. The overall aim is to establish guidance on how to best use the D2/mdx mouse model in preclinical studies

Antisense correction of SMN2 splicing in the CNS rescues necrosis in a type III SMA mouse model

Increasing survival of motor neuron 2, centromeric (SMN2) exon 7 inclusion to express more full-length SMN protein in motor neurons is a promising approach to treat spinal muscular atrophy (SMA), a genetic neurodegenerative disease. Previously, we identified a potent 2′-O-(2-methoxyethyl) (MOE) phosphorothioate-modified antisense oligonucleotide (ASO) that blocks an SMN2 intronic splicing silencer element and efficiently promotes exon 7 inclusion in transgenic mouse peripheral tissues after systemic administration. Here we address its efficacy in the spinal cord—a prerequisite for disease treatment—and its ability to rescue a mild SMA mouse model that develops tail and ear necrosis, resembling the distal tissue necrosis reported in some SMA infants. Using a micro-osmotic pump, we directly infused the ASO into a lateral cerebral ventricle in adult mice expressing a human SMN2 transgene; the ASO gave a robust and long-lasting increase in SMN2 exon 7 inclusion measured at both the mRNA and protein levels in spinal cord motor neurons. A single embryonic or neonatal intracerebroventricular ASO injection strikingly rescued the tail and ear necrosis in SMA mice. We conclude that this MOE ASO is a promising drug candidate for SMA therapy, and, more generally, that ASOs can be used to efficiently redirect alternative splicing of target genes in the CNS

Intraventricular Brain Injection of Adeno-Associated Virus Type 1 (AAV1) in Neonatal Mice Results in Complementary Patterns of Neuronal Transduction to AAV2 and Total Long-Term Correction of Storage Lesions in the Brains of β-Glucuronidase-Deficient Mice

Inherited metabolic disorders that affect the central nervous system typically result in pathology throughout the brain; thus, gene therapy strategies need to achieve widespread delivery. We previously found that although intraventricular injection of the neonatal mouse brain with adeno-associated virus serotype 2 (AAV2) results in dispersed gene delivery, many brain structures were poorly transduced. This limitation may be overcome by using different AAV serotypes because the capsid proteins use different cellular receptors for entry, which may allow enhanced global targeting of the brain. We tested this with AAV1 and AAV5 vectors. AAV5 showed very limited brain transduction after neonatal injection, even though it has different transduction patterns than AAV2 in adult brain injections. In contrast, AAV1 vectors, which have not been tested in the brain, showed robust widespread transduction. Complementary patterns of transduction between AAV1 and AAV2 were established and maintained in the adult brain after neonatal injection. In the majority of structures, AAV1 transduced many more cells than AAV2. Both vectors transduced mostly neurons, indicating that differential expression of receptors on the surfaces of neurons occurs in the developing brain. The number of cells positive for a vector-encoded secreted enzyme (β-glucuronidase) was notably greater and more widespread in AAV1-injected brains. A comprehensive analysis of AAV1-treated brains from β-glucuronidase-deficient mice (mucopolysaccharidosis type VII) showed complete reversal of pathology in all areas of the brain for at least 1 year, demonstrating that the combination of this serotype and experimental strategy is therapeutically effective for treating global neurometabolic disorders