148 research outputs found

    Introduzione

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    Estabilidade e licença gestante

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    O presente artigo discorre sobre a proteção do trabalho da mulher, especialmente o tratamento dispensado à maternidade. Evidencia a evolução normativa, com base no contexto histórico de inclusão da mulher no mercado de trabalho, levando em consideração os salários mais baixos oferecidos, jornada de trabalho extensa e condições degradantes, considerando também os fatores que deram ensejo ao início da movimentação dos empregados em busca de melhores condições de trabalho. Verifica a diferença entre os institutos estabilidade gestante e licença maternidade, bem como as situações no qual serão aplicados; as alterações legislativas ao longo do período, abolindo normas que caracterizavam discriminação contra a mulher.Evidencia também a responsabilidade objetiva do empregador quanto à comprovação da condição gestacional e o amparo à gestante em todas as situações da relação contratual, antes não protegidas pela lei, baseando-se as alterações na dignidade da pessoa humana e proteção ao nascituro, para lhe conceder melhores condições de vida e subsídios para a sua formação

    Subtelomeric FISH analysis in 76 patients with syndromic developmental delay/intellectual disability

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    <p>Abstract</p> <p>Background</p> <p>Intellectual disability affects approximately 1 to 3% of the general population. The etiology is still poorly understood and it is estimated that one-half of the cases are due to genetic factors. Cryptic subtelomeric aberrations have been found in roughly 5 to 7% of all cases.</p> <p>Methods</p> <p>We performed a subtelomeric FISH analysis on 76 unrelated children with normal standard karyotype ascertained by developmental delay or intellectual disability, associated with congenital malformations, and/or facial dysmorphisms.</p> <p>Results</p> <p>Ten cryptic chromosomal anomalies have been identified in the whole cohort (13,16%), 8 in the group of patients characterized by developmental delay or intellectual disability associated with congenital malformations and facial dysmorphisms, 2 in patients with developmental delay or intellectual disability and facial dysmorphisms only.</p> <p>Conclusion</p> <p>We demonstrate that a careful clinical examination is a very useful tool for pre-selection of patients for genomic analysis, clearly enhancing the chromosomal anomaly detection rate. Clinical features of most of these patients are consistent with the corresponding emerging chromosome phenotypes, pointing out these new clinical syndromes associated with specific genomic imbalances.</p

    Oxygen Sensing in Neurodegenerative Diseases: Current Mechanisms, Implication of Transcriptional Response, and Pharmacological Modulation

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    : Significance: Oxygen (O2) sensing is the fundamental process through which organisms respond to changes in O2 levels. Complex networks exist allowing the maintenance of O2 levels through the perception, capture, binding, transport, and delivery of molecular O2. The brain extreme sensitivity to O2 balance makes the dysregulation of related processes crucial players in the pathogenesis of neurodegenerative diseases (NDs). In this study, we wish to review the most relevant advances in O2 sensing in relation to Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Recent Advances: Over the years, it has been clarified that most NDs share common pathways, a great number of which are in relation to O2 imbalance. These include hypoxia, hyperoxia, reactive oxygen species production, metabolism of metals, protein misfolding, and neuroinflammation. Critical Issues: There is still a gap in knowledge concerning how O2 sensing plays a role in the above indicated neurodegenerations. Specifically, O2 concentrations are perceived in body sites that are not limited to the brain, but primarily reside in other organs. Moreover, the mechanisms of O2 sensing, gene expression, and signal transduction seem to correlate with neurodegeneration, but many aspects are mechanistically still unexplained. Future Directions: Future studies should focus on the precise characterization of O2 level disruption and O2 sensing mechanisms in NDs. Moreover, advances need to be made also concerning the techniques used to assess O2 sensing dysfunctions in these diseases. There is also the need to develop innovative therapies targeting this precise mechanism rather than its secondary effects, as early intervention is necessary. Antioxid. Redox Signal. 38, 160-182

    A Low-Dose CT-Based Radiomic Model to Improve Characterization and Screening Recall Intervals of Indeterminate Prevalent Pulmonary Nodules.

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    Lung cancer (LC) is currently one of the main causes of cancer-related deaths worldwide. Low-dose computed tomography (LDCT) of the chest has been proven effective in secondary prevention (i.e., early detection) of LC by several trials. In this work, we investigated the potential impact of radiomics on indeterminate prevalent pulmonary nodule (PN) characterization and risk stratification in subjects undergoing LDCT-based LC screening. As a proof-of-concept for radiomic analyses, the first aim of our study was to assess whether indeterminate PNs could be automatically classified by an LDCT radiomic classifier as solid or sub-solid (first-level classification), and in particular for sub-solid lesions, as non-solid versus part-solid (second-level classification). The second aim of the study was to assess whether an LCDT radiomic classifier could automatically predict PN risk of malignancy, and thus optimize LDCT recall timing in screening programs. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), accuracy, positive predictive value, negative predictive value, sensitivity, and specificity. The experimental results showed that an LDCT radiomic machine learning classifier can achieve excellent performance for characterization of screen-detected PNs (mean AUC of 0.89 ± 0.02 and 0.80 ± 0.18 on the blinded test dataset for the first-level and second-level classifiers, respectively), providing quantitative information to support clinical management. Our study showed that a radiomic classifier could be used to optimize LDCT recall for indeterminate PNs. According to the performance of such a classifier on the blinded test dataset, within the first 6 months, 46% of the malignant PNs and 38% of the benign ones were identified, improving early detection of LC by doubling the current detection rate of malignant nodules from 23% to 46% at a low cost of false positives. In conclusion, we showed the high potential of LDCT-based radiomics for improving the characterization and optimizing screening recall intervals of indeterminate PNs

    Identification of a novel pathway in sporadic Amyotrophic Lateral Sclerosis mediated by the long non-coding RNA ZEB1-AS1

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    Background: Deregulation of transcription in the pathogenesis of sporadic Amyotrophic Lateral Sclerosis (sALS) is taking central stage with RNA-sequencing analyses from sALS patients tissues highlighting numerous deregulated long non-coding RNAs (lncRNAs). The oncogenic lncRNA ZEB1-AS1 is strongly downregulated in peripheral blood mononuclear cells of sALS patients. In addition, in cancer-derived cell lines, ZEB1-AS1 belongs to a negative feedback loop regulation with hsa-miR-200c, acting as a molecular sponge for this miRNA. The role of the lncRNA ZEB1-AS1 in sALS pathogenesis has not been characterized yet, and its study could help identifying a possible disease-modifying target. Methods: the implication of the ZEB1-AS1/ZEB1/hsa-miR-200c/BMI1 pathway was investigated in multiple patients-derived cellular models (patients-derived peripheral blood mononuclear cells and induced pluripotent stem cells-derived neural stem cells) and in the neuroblastoma cell line SH-SY5Y, where its function was inhibited via RNA interference. Molecular techniques such as Real Time PCR, Western Blot and Immunofluorescence were used to assess the pathway dysregulation. Results: Our results show a dysregulation of a signaling pathway involving ZEB1-AS1/hsa-miR-200c/β-Catenin in peripheral blood mononuclear cells and in induced pluripotent stem cells-derived neural stem cells from sALS patients. These results were validated in vitro on the cell line SH-SY5Y with silenced expression of ZEB1-AS1. Moreover, we found an increase for ZEB1-AS1 during neural differentiation with an aberrant expression of β-Catenin, highlighting also its aggregation and possible impact on neurite length. Conclusions: Our results support and describe the role of ZEB1-AS1 pathway in sALS and specifically in neuronal differentiation, suggesting that an impairment of β-Catenin signaling and an alteration of the neuronal phenotype are taking place

    Crizotinib in Advanced, Chemoresistant Anaplastic Lymphoma Kinase-Positive Lymphoma Patients

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    Anaplastic lymphoma kinase (ALK)-positive lymphomas respond to chemotherapy, but relapses, which bear a poor prognosis, occur. Crizotinib inhibits ALK in vitro and in vivo and was administered as monotherapy to 11 ALK+ lymphoma patients who were resistant/refractory to cytotoxic therapy. The overall response rate was 10 of 11 (90.9%; 95% confidence interval [CI] = 58.7% to 99.8%). Disease status at the latest follow-up is as follows: four patients are in complete response (CR) (months >21, >30, >35, >40) under continuous crizotinib administration; 4 patients had progression of disease (months 1, 2, 2, 2); 1 patient obtained CR on crizotinib, received an allogeneic bone marrow transplant, and is in CR; 2 patients (treated before and/or after allogeneic bone marrow transplant) obtained and are still in CR but they have stopped crizotinib. Overall and progression-free survival rates at 2 years are 72.7% (95% CI = 39.1% to 94.0%) and 63.7% (95% CI = 30.8% to 89.1%), respectively. ALK mutations conferring resistance to crizotinib in vitro could be identified in relapsed patients. Crizotinib exerted a potent antitumor activity with durable responses in advanced, heavily pretreated ALK+ lymphoma patients, with a benign safety profil

    Desafios na gestão do trabalho em saúde: a educação na interface com atenção

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    O objetivo da pesquisa foi de compreender quais so os desafios na gesto dos servios de sade, na interface entre ateno e educao. O estudo est caracterizado como pesquisa qualitativa, descritiva e exploratria, tipo estudo de caso. Os sujeitos da pesquisa foram trabalhadores da equipe multidisciplinar atuantes nas Estratgias da famlia de um municpio da Regio Noroeste do Rio Grande do Sul. Na apreciao dos dados, utilizou-se a anlise de contedo. Os resultados foram agrupados em duas categorias que versas sobre os desafios na ateno em sade e na educao em sade respectivamente. Os desafios da ateno em sade esto relacionados aos fatores como o trabalho na equipe interdisciplinar, a questo de doena dos usurios e da disponibilidade numrica de trabalhadores. Os desafios na educao em sade esto relacionados ao pequeno investimento em sade, tanto para trabalhadores, quanto para os usurios. Conclui-se a gesto na sade complexa e multifacetada e que no cenrio da pesquisa exgua a inter-relao entre fazer gesto, educao e ateno

    Efeito de um programa de fisioterapia funcional em crianças com paralisia cerebral associado a orientações aos cuidadores: estudo preliminar

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    The purpose was to verify the effect of a functional physical therapy program on children with cerebral palsy, associated to guidance to parents and/or caregivers; and to search for correlations between the child's functional abilities and caregivers' assistance, by means of the Pediatric Evaluation Disability Inventory (PEDI). Four hemiplegic, spastic children between 24 and 43 months old, classified at the Gross Motor Function Classification System level I, were submitted to four evaluations, the first prior to program onset, and the others 30, 60, and 90 days after the first one. PEDI parts I (Functional abilities) and II (Caregivers' assistance) were used. Caregivers were provided with written instructions on how to best deliver care at home. The physical therapy program consisted of three weekly 1-hour sessions for three months; two sessions were of physical therapy based on Bobath concept, and one, of daily activities training. The analysis of results showed children obtained a significantly higher score at the last assessment as compared to the first. A high, significant correlation was found between PEDI parts I and II (r=1.0; p=0.083). The functional physical therapy program associated to instructions to caregivers proved thus effective to improve the functional performance of level-I children with spastic hemiplegia.O objetivo foi verificar o efeito de um programa de fisioterapia funcional para crianças com paralisia cerebral, associado a orientações aos pais e/ou cuidadores; e verificar a correlação entre as habilidades funcionais e a assistência do cuidador, utilizando o Inventário de Avaliação Pediátrica de Incapacidade (PEDI). Participaram quatro crianças entre 24 e 43 meses de idade, hemiplégicas, espásticas e nível I no sistema de classificação da função motora ampla (GMFCS). Foram realizadas quatro avaliações - uma antes do início do programa, as demais aos 30, 60 e 90 dias após a primeira -, empregando-se as partes I (Habilidades funcionais) e II (Assistência do cuidador) do PEDI. As crianças foram submetidas a sessões de uma hora de fisioterapia funcional três vezes por semana, durante três meses: duas vezes a sessão era de fisioterapia com base no conceito neuroevolutivo Bobath e uma vez, treino de atividades da vida diária. Também foram dadas orientações por escrito aos pais e/ou cuidadores quanto à assistência à criança, incentivando-os a praticá-la em casa. A análise dos resultados mostrou que, na última avaliação, as crianças obtiveram escores significativamente maiores que na primeira. Foi verificada correlação altamente significativa (r=1,0; p=0,083) entre as partes I e II. O programa de fisioterapia funcional associado às orientações aos pais e/ou cuidadores foi efetivo em melhorar o desempenho funcional de crianças nível I com hemiplegia espástica
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