APTIDÃO URBANA AOS INSTRUMENTOS DO ESTATUTO DA CIDADE: PERSPECTIVAS METODOLÓGICAS

A Lei Federal 10.257/01, conhecida como Estatuto da Cidade, cuja função principal é regulamentar os artigos 182 e 183 da Constituição Federal de 1988, instituiu a obrigatoriedade da elaboração de planos diretores para municípios com mais de 20.000 habitantes e municípios com situações específicas como os que integram as regiões metropolitanas ou aqueles de interesse turístico. Simultaneamente, o Estatuto da Cidade legitimou instrumentos criados a partir da década de 1950 em várias cidades brasileiras, quando a questão urbana passou a ser vista como um problema social a ser equacionado no âmbito municipal, direcionado e gerenciado pelos planos diretores, monitorado por novos instrumentos complementares aos pré-existentes. No entanto, a implementação desses instrumentos integrados às leis dos planos diretores municipais, passa pelo gargalo da seleção da maior aptidão de cada setor urbano, ou outra unidade territorial da cidade, para a implantação de cada instrumento ou de um conjunto de instrumentos. Nesse contexto, o presente artigo visa colaborar, discutindo o estabelecimento de indicadores que, relacionados a cada instrumento, possam identificar tais aptidões, através de análises simplificadas das características das cidades. É importante destacar que essa metodologia está voltada principalmente a cidades de porte médio, que se posicionam aquém das metrópoles, quanto a demandas de estudos mais apurados, face às características das variáveis que se sobrepõem em sua estrutura urbana. Outro aspecto importante que vale salientar é que a aplicação dos instrumentos baseados nos indicadores não garante por si só os resultados pretendidos, dependendo de outras variáveis de cunho político e da visão dos atores sociais. São alternativas a serem submetidas ao processo decisório

Age- and stress-associated C. elegans granulins impair lysosomal function and induce a compensatory HLH-30/TFEB transcriptional response.

The progressive failure of protein homeostasis is a hallmark of aging and a common feature in neurodegenerative disease. As the enzymes executing the final stages of autophagy, lysosomal proteases are key contributors to the maintenance of protein homeostasis with age. We previously reported that expression of granulin peptides, the cleavage products of the neurodegenerative disease protein progranulin, enhance the accumulation and toxicity of TAR DNA binding protein 43 (TDP-43) in Caenorhabditis elegans (C. elegans). In this study we show that C. elegans granulins are produced in an age- and stress-dependent manner. Granulins localize to the endolysosomal compartment where they impair lysosomal protease expression and activity. Consequently, protein homeostasis is disrupted, promoting the nuclear translocation of the lysosomal transcription factor HLH-30/TFEB, and prompting cells to activate a compensatory transcriptional program. The three C. elegans granulin peptides exhibited distinct but overlapping functional effects in our assays, which may be due to amino acid composition that results in distinct electrostatic and hydrophobicity profiles. Our results support a model in which granulin production modulates a critical transition between the normal, physiological regulation of protease activity and the impairment of lysosomal function that can occur with age and disease

PPARα-targeted mitochondrial bioenergetics mediate repair of intestinal barriers at the host-microbe intersection during SIV infection.

Chronic gut inflammatory diseases are associated with disruption of intestinal epithelial barriers and impaired mucosal immunity. HIV-1 (HIV) causes depletion of mucosal CD4+ T cells early in infection and disruption of gut epithelium, resulting in chronic inflammation and immunodeficiency. Although antiretroviral therapy (ART) is effective in suppressing viral replication, it is incapable of restoring the "leaky gut," which poses an impediment for HIV cure efforts. Strategies are needed for rapid repair of the epithelium to protect intestinal microenvironments and immunity in inflamed gut. Using an in vivo nonhuman primate intestinal loop model of HIV/AIDS, we identified the pathogenic mechanism underlying sustained disruption of gut epithelium and explored rapid repair of gut epithelium at the intersection of microbial metabolism. Molecular, immunological, and metabolomic analyses revealed marked loss of peroxisomal proliferator-activated receptor-α (PPARα) signaling, predominant impairment of mitochondrial function, and epithelial disruption both in vivo and in vitro. To elucidate pathways regulating intestinal epithelial integrity, we introduced probiotic Lactobacillus plantarum into Simian immunodeficiency virus (SIV)-inflamed intestinal lumen. Rapid recovery of the epithelium occurred within 5 h of L. plantarum administration, independent of mucosal CD4+ T cell recovery, and in the absence of ART. This intestinal barrier repair was driven by L. plantarum-induced PPARα activation and restoration of mitochondrial structure and fatty acid β-oxidation. Our data highlight the critical role of PPARα at the intersection between microbial metabolism and epithelial repair in virally inflamed gut and as a potential mitochondrial target for restoring gut barriers in other infectious or gut inflammatory diseases

Avaliação do tratamento da hérnia perineal bilateral no cão por acesso dorsal ao ânus

Observing the evolution and complications in the treatment of bilateral perineal hernias by dorsal access to the anus was the objective of this study. Fourteen dogs of various breeds were operated with an inverted "U" shaped incision, which extended from the lateral portion of the tuberosity Isquiatica on the left, bending into the direction of the midline, dorsally to anus and heading out symmetrically to the tip of the tuberosity Isquiatica contralateral. After reduction of the hernia, the right and left muscles of the pelvic diaphragm were sutured by the technique of raising the internal obturator muscle. The complications observed in the postoperative period were fecal incontinence, contamination of the wound, dehiscence of suture points of the skin, urinary incontinence and recurrence in a dog with 19 days after surgery. The access used was feasible and all dogs undergoing surgical technical proposal showed no recurrence in a period of five to ten months of postoperative assessment.O objetivo do presente estudo foi avaliar a evolução e as complicações pós-operatórias do tratamento de hérnias perineais bilaterais, por acesso dorsal ao ânus, em 14 cães com idade entre seis e 12 anos. Realizou-se incisão em forma de 'U' invertido, a qual se estendeu desde a porção lateral da tuberosidade isquiática do lado esquerdo, curvando-se em direção à linha mediana, dois centímetros dorsalmente ao ânus e dirigindo-se simetricamente para a extremidade da tuberosidade isquiática contralateral. Após redução da hérnia, os músculos do diafragma pélvico direito e esquerdo foram suturados pela técnica de elevação do músculo obturador interno. As complicações observadas no período pós-operatório foram incontinência fecal, contaminação da ferida, deiscência de pontos da sutura cutânea, incontinência urinária e recidiva em um cão 19 dias após procedimento cirúrgico. O acesso utilizado foi exequível e todos os cães submetidos à técnica operatória proposta não apresentaram recidivas em um período entre cinco e dez meses de avaliação pós-operatório

Electro-acupuncture and Chinese herbs for treatment of cervical intervertebral disk disease in a dog

A non-ambulatory dog with tetraparesis following a pain episode that had evolved over 2 months was submitted for medical treatment and diagnosed with intervertebral disk disease at C3-C4 and dorsal extradural compression at C1-C2 and C3-C4 using myelography and computed tomography. The dog experienced ambulation recovery after 15 days of treatment with only electroacupuncture and Chinese herbal medicine, with marked improvement occurring after only 10 treatments. Six months of follow-up demonstrated that the dog was stable and had no recurrence of symptoms. Therefore, it was concluded that the combination of electroacupuncture and Chinese herbal medicine was responsible for motor rehabilitation

Tomografia computadorizada do tórax de cadelas portadoras de neoplasias malignas: II - Avaliação dos campos pulmonares

Seen the importancy of the malignant mammary gland tumors in the veterinary medicine clinic, the new perspectives of the diagnostic imaging in order to evaluate pacients that have this neoplasia, and the few information of this subject in the literature this research proposed to compare contrast computed tomographic and survey radiographic techniques in the lung's evaluation of female dogs with malignant mammary gland tumors. This research was performed at the Diagnostic Imaging Service of the Veterinary School Hospital of the Faculdade de Medicina Veterinária e Zootecnia at the University of São Paulo in twenty, from different breed and age, bitches with malignant mammary gland tumors that were examined at the Obstetric and Ginecology and Small Animal Surgery Services of the same hospital. The tomographic exam showed up as an important complement of the radiographic exam in searching for mammary gland tumor metastasis, concerning the evaluation of the pulmonary intersticium.Visto a importância das neoplasias mamárias na clínica médico-veterinária e as novas perspectivas do diagnóstico por imagem, o presente trabalho visou comparar o exame tomográfico contrastado com o exame radiográfico simples dos campos pulmonares de cadelas portadoras de tumores mamários malignos. Para tanto, foram realizados exames de tomografia computadorizada contrastada da cavidade torácica de vinte fêmeas da espécie canina, de diferentes raças e idades, portadoras de neoplasias mamárias malignas encaminhadas ao Serviço de Diagnóstico por Imagem do Hospital Veterinário da Faculdade de Medicina Veterinária e Zootecnia da Universidade de São Paulo pelos Serviços de Obstetrícia e Ginecologia e de Cirurgia de Pequenos Animais da mesma instituição. Concluiu-se que, o exame tomográfico se mostrou um importante complemento do exame radiográfico na pesquisa de metástases de neoplasias mamárias em cadelas no que se refere à avaliação do interstício pulmonar

A Multiclass Radiomics Method-Based WHO Severity Scale for Improving COVID-19 Patient Assessment and Disease Characterization From CT Scans.

OBJECTIVES The aim of this study was to evaluate the severity of COVID-19 patients' disease by comparing a multiclass lung lesion model to a single-class lung lesion model and radiologists' assessments in chest computed tomography scans. MATERIALS AND METHODS The proposed method, AssessNet-19, was developed in 2 stages in this retrospective study. Four COVID-19-induced tissue lesions were manually segmented to train a 2D-U-Net network for a multiclass segmentation task followed by extensive extraction of radiomic features from the lung lesions. LASSO regression was used to reduce the feature set, and the XGBoost algorithm was trained to classify disease severity based on the World Health Organization Clinical Progression Scale. The model was evaluated using 2 multicenter cohorts: a development cohort of 145 COVID-19-positive patients from 3 centers to train and test the severity prediction model using manually segmented lung lesions. In addition, an evaluation set of 90 COVID-19-positive patients was collected from 2 centers to evaluate AssessNet-19 in a fully automated fashion. RESULTS AssessNet-19 achieved an F1-score of 0.76 ± 0.02 for severity classification in the evaluation set, which was superior to the 3 expert thoracic radiologists (F1 = 0.63 ± 0.02) and the single-class lesion segmentation model (F1 = 0.64 ± 0.02). In addition, AssessNet-19 automated multiclass lesion segmentation obtained a mean Dice score of 0.70 for ground-glass opacity, 0.68 for consolidation, 0.65 for pleural effusion, and 0.30 for band-like structures compared with ground truth. Moreover, it achieved a high agreement with radiologists for quantifying disease extent with Cohen κ of 0.94, 0.92, and 0.95. CONCLUSIONS A novel artificial intelligence multiclass radiomics model including 4 lung lesions to assess disease severity based on the World Health Organization Clinical Progression Scale more accurately determines the severity of COVID-19 patients than a single-class model and radiologists' assessment

Topografia do cone medular do quati (Nasua nasua Linnaeus, 1766)

A anestesia epidural é uma das técnicas anestésicas regionais mais utilizadas e com boa margem de segurança, sendo aplicada a mais de 80 anos através de inúmeras metodologias ensaiadas com o objetivo de anestesiar nervos espinhais da região lombar e sacral. Para tanto, faz-se necessário o conhecimento não só dos procedimentos anestésicos como também dos conhecimentos anatômicos da espécie a ser manipulada. Assim, este trabalho teve por objetivo determinar a topografia do cone medular do quati, subsidiando a realização de técnicas anestésicas nesta espécie de carnívoro silvestre. Foram utilizados três animais adultos, machos, provenientes do Criatório Científico – CECRIMPAS, da Faculdade de Medicina Veterinária do Centro Universitário da Fundação de Ensino Octávio Bastos – UNIFEOB. Os animais foram fixados e dissecados em toda sua extensão medular. O cone medular tem sua base entre a 5ª e 6ª vértebras lombares e ápice na 3ª vértebra sacral, com comprimento total variando entre 5,2cm e 5,8cm. Assim, concluímos que o local mais adequado para a realização de anestesia epidural no quati é na região sacrocaudal

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery