Contribuições parafiscais e o sistema "S"

Orientador: Betina Treiger GrupenmacherMonografia (graduação) - Universidade Federal do Paraná,Setor de Ciências Jurídicas, Curso de Graduação em DireitoO presente trabalho está dividido em duas partes: na primeira analisa o ambiente histórico de criação e desenvolvimento das entidades que compõem o chamado Sistema "S" e seu ambiente administrativo para, na segunda, analisar os aspectos relacionados ao Direito Tributário relativo a sua principal fonte de financiamento: as Contribuições sociais e de intervenção no domínio econômico. São tratadas questões relacionadas com as especificidades jurídicas relativas aos entes paraestatais chamados de entes de cooperação, que são criados por lei, dotadas de personalidade jurídica privada, sem subordinação ao Poder Executivo Federal,para prestar serviços de interesse público com financiamento disponibilizado por fomento do poder público com a criação de Contribuições Parafiscais de arrecadação compulsória cuja aplicação é diretamente vinculada à finalidade das atividades prestadas pelos entes paraestatais, pressuposto de sua criação. No âmbito tributário, são tratadas questões relacionadas com a definição de tributo, a análise das espécies tributárias, para posterior caracterização das espécies de Contribuições, com ênfase àquelas financiadoras dos entes paraestatais que compões o Sistema "S"

Newborn skin reflection: Proof of concept for a new approach for predicting gestational age at birth. A cross-sectional study

Current methods to assess the gestational age during prenatal care or at birth are a global challenge. Disadvantages, such as low accessibility, high costs, and imprecision of clinical tests and ultrasonography measurements, may compromise health decisions at birth, based on the gestational age. Newborns organs and tissues can indirectly indicate their physical maturity, and we hypothesized that evolutionary changes in their skin, detected using an optoelectronic device meter, may aid in estimating the gestational age. This study analyzed the feasibility of using newborn skin reflectance to estimate the gestational age at birth noninvasively. A cross-sectional study evaluated the skin reflectance of selected infants, preferably premature, at birth. The first-trimester ultrasound was the reference for gestational age. A prototype of a new noninvasive optoelectronic device measured the backscattering of light from the skin, using a light emitting diode at wavelengths of 470 nm, 575 nm, and 630 nm. Univariate and multivariate regression analysis models were employed to predict gestational age, combining skin reflectance with clinical variables for gestational age estimation. The gestational age at birth of 115 newborns from 24.1 to 41.8 weeks of gestation correlated with the light at 630 nm wavelength reflectance 3.3 mm/6.5 mm ratio distant of the sensor, at the forearm and sole . The best-combined variables to predict the gold standard gestational age at birth was the skin reflectance at wavelengths of 630 nm and 470 nm in combination with birth weight, phototherapy, and adjusted to include incubator stay, and sex. The main limitation of the study is that it was very specific to the premature population we studied and needs to be studied in a broader spectrum of newborns

Natural Killer Cell Assessment In Peripheral Circulation And Bronchoalveolar Lavage Fluid Of Patients With Severe Sepsis: A Case Control Study

Sepsis is a complex systemic inflammatory syndrome, the most common cause of which is attributed to systemic underlying bacterial infection. The complete mechanisms of the dynamic pro- and anti-inflammatory processes underlying the pathophysiology of sepsis remain poorly understood. Natural killer (NK) cells play a crucial role in the pathophysiology of sepsis, leading to exaggerated inflammation due their rapid response and production of pro-inflammatory cytokines such as interferon gamma (IFN-gamma). Several studies have already shown that NK cells undergo lymphopenia in the peripheral blood of patients with sepsis. However, our understanding of the mechanisms behind its cellular trafficking and its role in disease development is restricted to studies in animal models. In this study, we aimed to compare the human NK cell subset (CD56(bright or dim)) levels in the peripheral blood and bronchoalveolar lavage (BAL) fluid of sepsis patients. We conducted a case-control study with a sample size consisting of 10 control patients and 23 sepsis patients enrolled at the Hospital Cajuru (Curitiba/PR, Brazil) from 2013 to 2015. Although we were able to confirm previous observations of peripheral blood lymphopenia, no significant differences were detected in NK cell levels in the BAL fluid of these patients. Overall, these findings strengthened the evidence that peripheral blood lymphopenia is likely to be associated with cell death as a consequence of sepsis.183NHMRC Early Career FellowshipNational Breast Cancer Foundation (NBCF) FellowshipCancer Cure Australia Priority-Driven Young Investigator Project Gran

Lip squamous cell carcinoma in a Brazilian population : epidemiological study and clinicopathological associations

Objectives: It was evaluated epidemiological aspects of primary lip squamous cell carcinoma (LSCC) and its associations with clinicopathological factors. Study design: This retrospective, cross-sectional study analysed a sociodemographic, clinical, and morphological data of HNSCC in a Brazilian population (n=30). Data analysis included descriptive statistics and bivariate analyses using the chi-square and Fisher's exact tests to compare the variables. Results: The LSCC represented 10.8% of all oral cavity squamous cell carcinoma. Lip malignant disease was more prevalent in elderly men, with male-to-female ratio of 5:1. Lower lip was more affected. It was observed high rates of chronic solar exposure, and tobacco and alcohol drinking habits. Clinically, early TNM staging, small tumour lesions, and non-metastatic disease were predominant findings. It was identified a high frequency of well differentiated tumor samples. Worse Karnofsky performance status was associated with cervical metastasis. Conclusions: Our findings showed that LSCC patients exhibited similar epidemiological and clinical profiles as noted in other studies. Still, the occurrence of metastatic disease was associated with a worse physical performance status of the LSCC patients during diagnosis. © Medicina Oral S. L

Interferon-gamma and granulocyte/monocyte colony-stimulating factor production by natural killer cells involves different signaling pathways and the adaptor stimulator of interferon genes (STING)

Natural killer (NK) cells are important for innate immunity in particular through the production of IFN-gamma and GM-CSF. Both cytokines are important in restoration of immune function of tolerized leukocytes under inflammatory events. The expression of TLRs in NK cells has been widely studied by analyzing the mRNA of these receptors, rarely seeking their protein expression. We previously showed that murine spleen NK cells express TLR9 intracellularly and respond to CpG oligodeoxynucleotide (CpG-ODN) by producing IFN-gamma and GM-CSF. However, to get such production the presence of accessory cytokines (such as IL-15 and IL-18) was required, whereas CpG-ODN or accessory cytokines alone did not induce IFN-gamma or GM-CSF. We show here that TLR9 overlaps with the Golgi apparatus in NK cells. Furthermore, CpG-ODN stimulation in the presence of accessory cytokines induces the phosphorylation of c-Jun, STAT3, and IkappaBalpha. IFN-gamma and GM-CSF production requires NF-kappaB and STAT3 activation as well as Erk-dependent mechanisms for IFN-gamma and p38 signaling for GM-CSF. Using knock-out-mice, we show that UNC93b1 and IL-12 (produced by NK cells themselves) are also necessary for IFN-gamma and GM-CSF production. IFN-gamma production was found to be MyD88- and TLR9-dependent, whereas GM-CSF was TLR9-independent but dependent on STING (stimulator of interferon genes), a cytosolic adaptor recently described for DNA sensing. Our study thereby allows us to gain insight into the mechanisms of synergy between accessory cytokines and CpG-ODN in NK cells. It also identifies a new and alternative signaling pathway for CpG-ODN in murine NK cells

Loss-of-Function in SMAD4 Might Not Be Critical for Human Natural Killer Cell Responsiveness to TGF-β

We characterized the NK cell phenotype and function in three family members with Hereditary Hemorrhagic Telangiectasia (HHT) due to heterozygous SMAD4 mutations. Loss-of-function mutation in this gene did not induce developmental effects to alter CD56bright or CD56dim NK cell subset proportions in peripheral blood; and did not result in major differences in either their IL-15-induced proliferation, or their cytokine secretion response to TGF-β1. These data suggest that SMAD4 plays a redundant role in downstream TGF-β signaling in NK cells

Que "qualidades" de um produto interferem na percepção de conforto? Conforto percebido de assentos de trabalho

Este artigo descreve uma pesquisa quanto à percepção da qualidade de seis modelos de assentos em situação real de uso no ambiente de trabalho. Foram levantados, na literatura, os atributos que configuram a qualidade de uma cadeira de trabalho. Os quatro atributos identificados (conforto, praticidade, segurança, e adaptabilidade) além do fator "estética" foram discutidos com os usuãrios e, após redefinição dos mesmos, eles foram utilizados para avaliação subjetiva de preferência de 6 assentos de trabalho. Ficou evidente que os atributos não são claros e se confundem na avaliação da percepção do conforto pois, por exemplo, o fa tor estética se mistura com a percepção de "macio" definindo a primeira impressão obtida.This paper describes a research on how people perceive the comfort of six types of seats while using them in a real work situation. The attributes that configure the idea of a seat confort were established according to the reviewed literature. The concept of the four identified attributes (comfort, practicality, safety and adaptability) along with aesthetics were discussed with the research participants. Based on their understanding of each attribute, the six seats were then subjectively evaluated. The results show that the attributes concepts were not very clear being confounded in the process of comfort evaluation. For instance, aesthetics is nested with "softness" seeming to interfere in the subject's first impression of a seat confort

Profiling of lung SARS-CoV-2 and influenza virus infection dissects virus-specific host responses and gene signatures

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which emerged in late 2019 has spread globally, causing a pandemic of respiratory illness designated coronavirus disease 2019 (COVID-19). A better definition of the pulmonary host response to SARS-CoV-2 infection is required to understand viral pathogenesis and to validate putative COVID-19 biomarkers that have been proposed in clinical studies. METHODS: Here, we use targeted transcriptomics of formalin-fixed paraffin-embedded tissue using the NanoString GeoMX platform to generate an in-depth picture of the pulmonary transcriptional landscape of COVID-19, pandemic H1N1 influenza and uninfected control patients. RESULTS: Host transcriptomics showed a significant upregulation of genes associated with inflammation, type I interferon production, coagulation and angiogenesis in the lungs of COVID-19 patients compared to non-infected controls. SARS-CoV-2 was non-uniformly distributed in lungs (emphasising the advantages of spatial transcriptomics) with the areas of high viral load associated with an increased type I interferon response. Once the dominant cell type present in the sample, within patient correlations and patient-patient variation, had been controlled for, only a very limited number of genes were differentially expressed between the lungs of fatal influenza and COVID-19 patients. Strikingly, the interferon-associated gene IFI27, previously identified as a useful blood biomarker to differentiate bacterial and viral lung infections, was significantly upregulated in the lungs of COVID-19 patients compared to patients with influenza. CONCLUSION: Collectively, these data demonstrate that spatial transcriptomics is a powerful tool to identify novel gene signatures within tissues, offering new insights into the pathogenesis of SARS-COV-2 to aid in patient triage and treatment.Arutha Kulasinghe, Chin Wee Tan, Anna Flavia Ribeiro dos Santos Miggiolaro, James Monkman, Habib SadeghiRad, Dharmesh D. Bhuva, Jarbas da Silva Motta Junior, Caroline Busatta Vaz de Paula, Seigo Nagashima, Cristina Pellegrino Baena, Paulo Souza-Fonseca-Guimaraes, Lucia de Noronha, Timothy McCulloch, Gustavo Rodrigues Rossi, Caroline Cooper, Benjamin Tang, Kirsty R. Short, Melissa J. Davis, Fernando Souza-Fonseca-Guimaraes, Gabrielle T. Belz, and Ken O, Byrn

Innate immunodeficiency following genetic ablation of Mcl1 in natural killer cells

The cytokine IL-15 is required for natural killer (NK) cell homeostasis; however, the intrinsic mechanism governing this requirement remains unexplored. Here we identify the absolute requirement for myeloid cell leukaemia sequence-1 (Mcl1) in the sustained survival of NK cells in vivo. Mcl1 is highly expressed in NK cells and regulated by IL-15 in a dose-dependent manner via STAT5 phosphorylation and subsequent binding to the 3'-UTR of Mcl1. Specific deletion of Mcl1 in NK cells results in the absolute loss of NK cells from all tissues owing to a failure to antagonize pro-apoptotic proteins in the outer mitochondrial membrane. This NK lymphopenia results in mice succumbing to multiorgan melanoma metastases, being permissive to allogeneic transplantation and being resistant to toxic shock following polymicrobial sepsis challenge. These results clearly demonstrate a non-redundant pathway linking IL-15 to Mcl1 in the maintenance of NK cells and innate immune responses in vivo