gebhart/patrepeval huggingface dataset:
40 horas na ESF? (2011)

Recentemente um tema interessante alvoroçou os ânimos na lista de discussão virtual (sbmfc@googlegroups.com) da So­ciedade Brasileira de Medicina de Família e Comunidade (SB­MFC): a insatisfação com a carga horária de quarenta horas semanais na Estratégia de Saúde da Família (ESF). A polêmica é compreensível: a ESF é hoje o principal mercado de trabalho do Médico de Família e Comunidade (MFC). Além disso, é um modelo de atenção primária que valoriza nossa especiali­dade, e que inclusive contou com nossa participação em sua concepção. Se não é ideal, a ESF é o mais próximo do que os MFC’s creem ser adequado às necessidades da população brasileira, ao menos se comparada com as iniciativas que até hoje existiram em atenção primária no país. Os MFC’s nutrem um carinho pela ESF, muito porque ela parece estar realmente melhorando o cuidado das pessoas no Sistema Único de Saúde. Mas alguns profissionais começam a questionar alguns aspec­tos do modelo, e a dedicação de quarenta horas semanais que a Estratégia exige parece ser o primeiro ponto de discórdia. Antes de colocar algumas impressões pessoais a convite da SBMFC, selecionei alguns trechos do embate virtual vi­venciado nas últimas semanas, os adaptando pelos limites de tamanho de meu texto. Os trechos ilustram a pluralidade de ideias. Mas, como irei defender logo adiante, elas não são divergentes. Vejamos os argumentos de alguns colegas que se posicionam a favor da flexibilização: “Provavelmente quem trabalhou razoável tempo no interior na APS, ou na periferia pobre e violenta da metrópole, reconhece que trabalhar 8 horas por dia na Saúde da Família é exces­sivo, cansativo, tedioso. A gente chega acabado em casa se pega uns casos “daqueles”, em meio a um dia cheio. Se a gente começa (quando eu começava) às 8h clinicando (comumente apressado, tentando viabilizar acesso e, por isso, considerando a pressão da demanda espontânea) até de tarde sem enrolar, dedicando-se aos pacientes com energia, lá pelas 15:30h - 16h já se está muito cansado, às 17 já está sem paciência para ouvir, ficando seco e retrancado... já fica querendo “chutar” os pacientes”
Serum C-reactive protein level in postsplenectomized thalassemic patients. (2000)

C-reactive protein is an established marker for the detection of acute and chronic inflammatory processes. The most potent stimulator for the hepatic synthesis of this protein is interleukin 6. Previous studies have shown that inflammatory cells and inflammatory cytokines, such as interleukin 6, interferon gamma, etc were elevated in postsplenectomized thalassemic patients. The aim of this study was to determine serum C-reactive protein concentration in postsplenectomized beta thalassemic patients (beta thal/HbE postsplenec), and to compare them with those in nonsplenectomized beta thalassemic patients (beta thal/HbE), postsplenectomized non thalassemic patients (postsplenec), reactive thrombocytosis (RT), chronic myeloproliferative disorders (MPD) and normal adult volunteers. Serum C-reactive protein concentration as determined by an automatic Behring Nephelometer was carried out in 28 beta thal/HbE postsplenec, 22 beta thal/HbE, 12 postsplenec, 23 RT, 21 MPD, and 26 healthy adult volunteers. The values of CRP in beta thal/HbE postsplenec were significantly higher when compared with beta thal/HbE, and normal volunteers (4.1 +/- 0.7 vs 1.6 +/- 0.4 mg/L P = 0.006, and 4.1 +/- 0.7 vs 0.45 +/- 0.09 mg/L, P < 0.001). CRP levels in beta thal/HbE postsplenec were also higher than the postsplenec group (4.1 +/- 0.7 vs 0.19 +/- 0.7 mg/L P = 0.095). On the contrary, they were significantly lower than those in RT (4.1 +/- 0.7 vs 55.4 +/- 14.8 mg/L, P = 0.002). However, when compared to those with MPD, the values were not statistically different (4.1 +/- 0.7 vs 17.1 +/- 12.3 mg/L, P = 0.871). Interestingly, there was a trend towards increasing C-reactive protein levels in beta thal/HbE postsplenec patients with higher platelet count, although no correlation was observed. Besides the inflammatory process, platelet and/or factor(s) that control(s) thrombopoiesis seem(s) to play a role in the high serum C-reactive protein levels in the studied population.
HIV-1 Vaccination Administered Intramuscularly Can Induce Both Systemic and Mucosal T Cell Immunity in HIV-1-Uninfected Individuals (2003)

A vaccine regimen that can rapidly control HIV-1 replication at the site of exposure following sexual contact is likely to be the most effective in preventing HIV-1 infection. As part of a larger, phase II clinical trial, we evaluated the ability of a recombinant canarypox HIV-1 vaccine to induce CTL that can be detected in both the systemic and mucosal compartments following i.m. immunization in 12 low- and high-risk HIV-1 seronegative volunteers. In the 7 volunteers receiving four immunizations with live recombinant canarypox ALVAC-HIV vaccine with or without rgp120/SF-2, HIV-1-specific CTL were detected in the blood of 5 (71%) and in the rectum of 4 (57%). CTL responses were observed in both risk strata. In contrast, 5 volunteers receiving placebo had undetectable responses in both compartments. Vaccine-induced, HIV-1-specific effector activities included IFN-gamma secretion and class I MHC-restricted CD8(+) CTL. Rectal and systemic CD8(+) CTL clones established in 1 vaccine recipient revealed similar Env-specific responses and MHC restriction. These findings indicate that parenteral vaccination can induce HIV-1-specific CTL that localize to sites of HIV-1 acquisition, where their presence may be critical in the control of initial viral replication and eventual dissemination. Determination of the optimal strategy to induce mucosal T cells requires future clinical studies.
CD39 and CD161 Modulate Th17 Responses in Crohn's Disease (2014)

CD39 (ENTPD1) is expressed by subsets of pathogenic human CD4(+) T cells, such as Th17 cells. These Th17 cells are considered important in intestinal inflammation, such as seen in Crohn's disease (CD). Recently, CD161 (NKR-P1A) was shown to be a phenotypic marker of human Th17 cells. In this study, we report that coexpression of CD161 and CD39 not only identifies these cells but also promotes Th17 generation. We note that human CD4(+)CD39(+)CD161(+) T cells can be induced under stimulatory conditions that promote Th17 in vitro. Furthermore, CD4(+)CD39(+)CD161(+) cells purified from blood and intestinal tissues, from both healthy controls and patients with CD, are of the Th17 phenotype and exhibit proinflammatory functions. CD39 is coexpressed with CD161, and this association augments acid sphingomyelinase (ASM) activity upon stimulation of CD4(+) T cells. These pathways regulate mammalian target of rapamycin and STAT3 signaling to drive the Th17 phenotype. Inhibition of ASM activity by pharmacological blockers or knockdown of ASM abrogates STAT3 signaling, thereby limiting IL-17 production in CD4(+) T cells obtained from both controls and patients with active CD. Increased levels of CD39(+)CD161(+) CD4(+) T cells in blood or lamina propria are noted in patients with CD, and levels directly correlate with clinical disease activity. Hence, coexpression of CD39 and CD161 by CD4(+) T cells might serve as a biomarker to monitor Th17 responsiveness. Collectively, CD39 and CD161 modulate human Th17 responses in CD through alterations in purinergic nucleotide-mediated responses and ASM catalytic bioactivity, respectively.
Current thoughts on the phosphatidylinositol transfer protein family (2002)

Monomeric transport of lipids is carried out by a class of proteins that can shield a lipid from the aqueous environment by binding the lipid in a hydrophobic cavity. One such group of proteins is the phosphatidylinositol transfer proteins (PITP) that can bind phosphatidylinositol and phosphatidylcholine and transfer them from one membrane compartment to another. PITPs are found in both unicellular and multicellular organisms but not bacteria. In mice and humans, the PITP domain responsible for lipid transfer is found in five proteins, which can be classified into two classes based on sequence. Class I PITPs comprises two family members, alpha and beta, small 35 kDa proteins with a single PITP domain which are ubiquitously expressed. Class IIA PITPs (RdgBalphaI and II) are larger proteins possessing additional domains that target the protein to membranes and are only able to bind lipids but not mediate transfer. Finally, Class IIB PITP (RdgBbeta) is similar to Class I in size (38 kDa) and is also ubiquitously expressed. Class III PITPs, exemplified by the Sec14p family, are found in yeast and plants but are unrelated in sequence and structure to Class I and Class II PITPs. In this review we discuss whether PITP proteins are passive transporters or are regulated proteins that are able to couple their transport and binding properties to specific biological functions including inositol lipid signalling and membrane turnover.
Epitope mapping of a chimeric CD137 mAb: a necessary step for assessing the biologic relevance of non‐human primate models (2009)

Antibody based manipulation of the CD137 (4-1BB) co-signaling pathway is an attractive option for the treatment of cancer and autoimmune disease. We developed a chimeric anti-human CD137 monoclonal antibody (GG) and characterized its function. As a component of planned preclinical studies, we evaluated the binding of GG to activated peripheral blood mononuclear cells (PBMCs) from cynomolgus macaque and baboon against human. Interestingly, GG only recognized human CD137, while a commercial anti-CD137 mAb (4B4-1), recognized activated PBMCs from both human and non-human primates (NHP). Subsequent analysis revealed that the amino acid sequence of CD137 is largely conserved between primate species ( approximately 95% identical), with the extracellular domain differing by only 9-10 amino acids. Based on these data, we generated mutant constructs in the extracellular domain, replacing NHP with human CD137 sequences, and identified 3 amino acids critical for GG binding. These residues are likely part of a conformational epitope, as a peptide spanning this region is unable to block mAb binding. These data demonstrate that subtle sequence variations of defined co-stimulatory molecules amongst primate species can be employed as a strategy for mapping residues necessary for antibody binding to conformational epitopes.
GRP78, but Not Protein-disulfide Isomerase, Partially Reverses Hyperglycemia-induced Inhibition of Insulin Synthesis and Secretion in Pancreatic β-Cells (2008)

Chronic hyperglycemia contributes to pancreatic beta-cell dysfunction during the development of type 2 diabetes. Treatment of pancreatic beta-cells with prolonged high glucose concentrations has been shown to reduce insulin promoter activity and insulin gene expression. Here, we examined the effect of high glucose on endoplasmic reticulum (ER) stress pathway activation and insulin production in INS-1 832/13 pancreatic beta-cells. Treatment of cells with 25 mm glucose for 24-48 h decreased insulin mRNA and protein levels and reduced the proinsulin translation rate, which was accompanied by enhanced unfolded protein response pathway activation (XBP-1 mRNA splicing and increased phospho-eIF2alpha, CHOP, and active ATF6 levels). Overexpressing the ER chaperone GRP78 partially rescued high glucose-induced suppression of proinsulin levels and improved glucose-stimulated insulin secretion with no effect on insulin 2 mRNA levels. Under these conditions, there was little effect of GRP78 overexpression on ER stress markers. Knockdown of GRP78 expression under basal glucose conditions reduced cellular insulin levels and glucose-stimulated insulin secretion. Thus, GRP78 is essential for insulin biosynthesis, and enhancing chaperone capacity can improve beta-cell function in the presence of prolonged hyperglycemia. In contrast, overexpression of the ER chaperone and oxidoreductase protein-disulfide isomerase (PDI) reduced glucose-stimulated insulin secretion and induced ER stress resulting from the accumulation of proinsulin in the ER. These results suggest a role for both GRP78 and PDI in insulin biosynthesis, although an excess of PDI disrupts normal proinsulin processing.
A Unified Model of Fire Suppression by (1992)

Based on the fire point equation developed by Rasbash, a unified model of fire suppres sion is developed. The model includes both solid and gas phase effects including sur face cooling, gas phase dilution, chemical inhibition of flame reactions, and endothermic agent decomposition. The unified model is compared with available experimental data. The need for further experimental work is clearly indicated.The model can be used to evaluate the suppressibility of various materials and as aid to agent selection for a given material. In addition, the model can be used in the develop ment and evaluation of new suppression agents developed to replace existing environ mentally objectionable agents.
Role of Resident Peritoneal Macrophages and Mast Cells in Chemokine Production and Neutrophil Migration in Acute Inflammation: Evidence for an Inhibitory Loop Involving Endogenous IL-10 (1999)

The roles played by resident macrophages (Mphi) and mast cells (MCs) in polymorphonuclear leukocyte (PMN) accumulation and chemokine production within the mouse peritoneal cavity in response to administration of zymosan (0.2 and 1 mg), LPS (1 mg/kg), and thioglycolate (0.5 ml of a 3% suspension) were investigated. A marked reduction (>95%) in intact MC numbers was obtained by pretreatment with the MC activator compound 48/80, whereas resident Mphi were greatly diminished (>85%) by a 3-day treatment with liposomes encapsulating the cytotoxic drug dichloromethylene-bisphosphonate. No modulation of thioglycolate-induced inflammation was seen with either pretreatment. Removal of either MCs or Mphi attenuated LPS-induced PMN extravasation without affecting the levels of the chemokines murine monocyte chemoattractant protein-1 and KC measured in the lavage fluids. In contrast, MC depletion inhibited PMN accumulation and murine monocyte chemoattractant protein-1 and KC production in the zymosan peritonitis model. Removal of Mphi augmented the accumulation of PMN elicited by the latter stimulus. This was due to an inhibitory action of Mphi-derived IL-10 because there was 1) a time-dependent release of IL-10 in the zymosan exudates; 2) a reduction in IL-10 levels following Mphi, but not MC, depletion; and 3) an increased PMN influx and chemokine production in IL-10 knockout mice. In conclusion, we propose a stimulus-dependent role of resident MCs in chemokine production and the existence of a regulatory loop between endogenous IL-10 and the chemokine-mediated cellular component of acute inflammation.
Interleukin-13 and interleukin-4 are coexpressed in atopic asthma. (1996)

Interleukin-4 (IL-4) is an important cytokine in the allergic inflammation associated with atopic asthma. Interleukin-13 shares many of the biological effects of IL-4, and the evidence suggests that the expression of these two cytokine genes may be coregulated. We have investigated the expression of IL-13 and IL-4 mRNA in the bronchial mucosa of nine stable atopic asthmatics and 10 normal controls, characterized the major cellular source of IL-13 mRNA, and examined the colocalization of IL-13 and IL-4 mRNA. Endobronchial biopsies were obtained and examined for IL-13 and IL-4 mRNA using radiolabeled in situ hybridization. The number of positive cells per millimeter of basement membrane for both IL-13 and IL-4 mRNA was increased significantly in the bronchial mucosa of atopic asthmatics compared to normal controls (p < .001). In the atopic asthmatics, the expression of IL-13 was significantly greater than that for IL-4 (p < .01). In these subjects, 90% of the IL-13 mRNA-positive cells were CD3-positive T cells. Furthermore, although 100% of IL-4-positive cells also expressed IL-13 mRNA, only 60% of IL-13-positive cells also expressed IL-4. These results demonstrate that, in mild atopic asthma, IL-13 and IL-4 are coexpressed and that the upregulation of IL-13 expression is greater than that of IL-4. Our data support the role of IL-13 in the allergic inflammation present in atopic asthma.
Adverse Events After Outpatient Colonoscopy in the Medicare Population (2009)

Risks for adverse events after outpatient colonoscopy among elderly Medicare beneficiaries were low; however, they increased with age with specific comorbid conditions and depending on whether polypectomy was done. These data may inform decisions on whether to perform colonoscopy in persons of advanced age or those with comorbid conditions.
Complementary functions of the antiapoptotic protein A1 and serine/threonine kinase pim-1 in the BCR/ABL-mediated leukemogenesis (2002)

BCR/ABL oncogenic tyrosine kinase activates STAT5, which plays an important role in leukemogenesis. The downstream effectors of the BCR/ABL-->STAT5 pathway remain poorly defined. We show here that expression of the antiapoptotic protein A1, a member of the Bcl-2 family, and the serine/threonine kinase pim-1 are enhanced by BCR/ABL. This up-regulation requires activation of STAT5 by the signaling from SH3+SH2 domains of BCR/ABL. Enhanced expression of A1 and pim-1 played a key role in the BCR/ABL-mediated cell protection from apoptosis. In addition, pim-1 promoted proliferation of the BCR/ABL-transformed cells. Both A1 and pim-1 were required to induce interleukin 3-independent cell growth, inhibit activation of caspase 3, and stimulate cell cycle progression. Moreover, simultaneous up-regulation of both A1 and pim-1 was essential for in vitro transformation and in vivo leukemogenesis mediated by BCR/ABL. These data indicate that induction of A1 and pim-1 expression may play a critical role in the BCR/ABL-dependent transformation.
Laminar Arrangement of Ventricular Myocytes Influences Electrical Behavior of the Heart (2007)

The response of the heart to electrical shock, electrical propagation in sinus rhythm, and the spatiotemporal dynamics of ventricular fibrillation all depend critically on the electrical anisotropy of cardiac tissue. A long-held view of cardiac electrical anisotropy is that electrical conductivity is greatest along the myocyte axis allowing most rapid propagation of electrical activation in this direction, and that conductivity is isotropic transverse to the myocyte axis supporting a slower uniform spread of activation in this plane. In this context, knowledge of conductivity in two directions, parallel and transverse to the myofiber axis, is sufficient to characterize the electrical action of the heart. Here we present new experimental data that challenge this view. We have used a novel combination of intramural electrical mapping, and experiment-specific computer modeling, to demonstrate that left ventricular myocardium has unique bulk conductivities associated with three microstructurally-defined axes. We show that voltage fields induced by intramural current injection are influenced by not only myofiber direction, but also the transmural arrangement of muscle layers or myolaminae. Computer models of these experiments, in which measured 3D tissue structure was reconstructed in-silico, best matched recorded voltages with conductivities in the myofiber direction, and parallel and normal to myolaminae, set in the ratio 4:2:1, respectively. These findings redefine cardiac tissue as an electrically orthotropic substrate and enhance our understanding of how external shocks may act to successfully reset the fibrillating heart into a uniform electrical state. More generally, the mechanisms governing the destabilization of coordinated electrical propagation into ventricular arrhythmia need to be evaluated in the light of this discovery.
Distribution of haplotypes derived from three common variants of the NR4A2 gene in Japanese patients with schizophrenia (2002)

Dysregulation in dopaminergic neurotransmission might play a role in the pathogenesis of schizophrenia, and therefore genetic components of the dopamine (DA) pathway may confer risk. The NR4A2 (Nurr1) gene is essential for the development and maintenance of mesencephalic DA-synthesizing neurons. Moreover, Nurr1 forms a heterodimer with the retinoid X receptor and disturbances in the retinoid-signaling cascade may be involved in susceptibility to schizophrenia. To investigate the potential genetic contribution of NR4A2, we performed a case-control association study using three common variants in the gene [-2922(C)2-3, IVS6 + 17 approximately +18insG, EX8 + 657(CA)9-10] that were in strong linkage disequilibrium with each other. We did not detect a significant allelic or genotypic association. Haplotypes derived from all three polymorphisms generated similar results. These data do not support the notion that the NR4A2 gene plays a major role in risk for schizophrenia among Japanese individuals.
The production of iron carbide (1997)

From 1994 until the present, Nucor Corporation's iron carbide plant in Trinidad, West Indies, has gad to avercome many obstacles in order to achieve its designed production capacity. This article discusses the resolution of equipment/design and quality problems, which helped the plant achieve production capacity.
Niacin for dyslipidemia: Considerations in product selection (2003)

The efficacy and safety profiles of various forms of niacin for treating dyslipidemia are described. Niacin is well recognized for treating dyslipidemia in adults and has been shown to be effective in reducing coronary events. It has a broad range of effects on serum lipids and lipoproteins, including lowering total cholesterol, low-density-lipoprotein (LDL) cholesterol, and triglycerides. Niacin is the most effective lipid-modifying drug for raising high-density-lipoprotein (HDL) cholesterol levels and has been shown to lower Lp(a) lipoprotein. Niacin reduces triglycerides and very-low-density-lipoprotein and LDL cholesterol synthesis, primarily by decreasing fatty acid mobilization from adipose tissue. Niacin appears to raise HDL cholesterol by reducing hepatic apolipoprotein A-l clearance and enhancing reverse cholesterol transport. Niacin is metabolized through a conjugation or nicotinamide pathway. Standard immediate-release niacin is metabolized primarily through the conjugation pathway, which results in a high frequency of flushing. Long-acting niacin is metabolized through the nicotinamide pathway, which results in less flushing but increases the risk of hepatotoxicity. Extended-release niacin has a more balanced metabolism and causes fewer of both types of adverse effects. Improved serum lipid levels during niacin therapy have been associated with clinical and angiographic evidence of reduced coronary artery disease, especially when combined with statins. Niacin is particularly useful for managing high triglyceride and low HDL cholesterol levels as well as the lipid abnormalities associated with metabolic syndrome, including those commonly encountered in patients with diabetes. Several niacin products are available with significant differences in their safety and efficacy profiles. Health care providers must consider the differences between agents when recommending niacin for dyslipidemia treatment.