Miracle-dz/UniFAR-FTUs huggingface dataset:
Good, better or best: A study of standards of prevention and care in HIV prevention trials

This article examines the relationship between bioethics and the therapeutic standards in HIV prevention research in the developing world, focusing on the closure of the pre-exposure prophylaxis (PrEP) trials in the early 2000s. I situate the PrEP trials in the historical context of the vertical transmission debates of the 1990s, where there was protracted debate over the use of placebos despite the existence of a proven intervention. I then discuss the dramatic improvement in the clinical management of HIV and the treatment access movement, and consider how these contexts have influenced research practice. I argue that as HIV prevention trials oblige researchers to observe the rate at which vulnerable people under their care acquire HIV, there is an obligation to provide antiretroviral treatment to seroconverters and other health care benefits that fall within the scope of researchers’ entrustment, both to avoid exploitation and to enact reciprocal justice. I argue against propositions that the obligations to provide specific benefits are vague, fall only upon researchers and sponsors, and create injustices by privileging the few over the many. Finally, I contend that the realisation of a broader standard of care in HIV prevention research broadens the role of research from being a simple tool to produce knowledge to a complex intervention that can play a part in the reduction of health disparities.
Collaborative progress test (cPT) in three medical schools in Indonesia: The validity, reliability and its use as a curriculum evaluation tool

Abstract Background: Three medical schools in Indonesia have been collaborating in evaluating the learning process in the current curriculum by administering a collaborative progress test (cPT). The 120 multiple choice questions for cPT was developed by the three schools. This study aimed to assess the validity and reliability of the cPT as a part of curriculum evaluation. Method: The cPT was administered to year 1–5 students. A stratified random sampling based on the student Grade Point Average (GPA) was performed. The construct validity was established by assessing the accordant increase of mean score of cPT to the student year level. Finally, the reliability of the cPT was calculated using Cronbach Alpha coefficient. Result and discussion: A total of 223, 219 and 161 year 1 to 5 students completed the cPT in FM UI, FM UNAND, and FM UNS, respectively. The content and construct validity of the cPT were evident. There was an increase of the mean score from year 1 to 5, either in the pooled data (one way ANOVA F 174.7(4), p < 0.001) and in each school (one way ANOVA FMUI F 102.5 (4) p < 0.001, FM UNAND F 83.0 (4) p < 0.001, FM UNS 28.28(4) p < 0.001). The internal consistency of the cPT was very good in the three institutions. Conclusion: The cPT was proven to be a valid and reliable test to measure the increase of knowledge of medical students and was also useful to provide feedback for curriculum evaluation in the three medical schools. Further improvement is required in assuring the test blueprint and the content of the test items.
Perception, attitude and involvement of men in maternal health care in a Nigerian community

This study aimed to examine men’s perception, attitude and involvement in maternal care. A cross-sectional descriptive survey was carried out in Atelewo community in Osogbo, Osun State, Nigeria using multi-stage sampling technique to select 400 respondents. Participants were adult men of reproductive age. Data were collected using semi-structured questionnaire. In the study, there was no intervention component; and main outcome measures were perception of men about maternal health, attitude of men to maternal health and involvement of men in maternal care. Results revealed majority of the respondents 225 (62.2%) were within the age group 20 to 39 years with a mean age of 36.3 years ±10.86. Most of them were skilled workers 144 (39.8%) and many 147 (40.6%) had post primary school education. One hundred and eighty-six (51.5%) of the respondents had poor knowledge while 205 (56.5%) had a good attitude towards maternal health care. Concerning the involvement of the men in maternal health care of their wives, about a quarter 62 (29.1%), 87 (24.0%), 98 (27.1%) ever followed their wives to family planning clinic, ante-natal clinic and the delivery room respectively. Thus, the level of awareness of men about maternal heath was high, but their involvement in giving care was poor and only about half of them had good attitude towards maternal health care. Education and awareness programs should therefore be carried out by governmental agencies, non-governmental organizations and other voluntary groups to address involvement of men in maternal health care. Key words: Perception, attitude, involvement, maternal health, reproductive health, men, women.
Force-Regulated In Situ TCR–Peptide-Bound MHC Class II Kinetics Determine Functions of CD4+ T Cells

We have recently shown that two-dimensional (2D) and force-regulated kinetics of TCR–peptide-bound MHC class I (pMHC-I) interactions predict responses of CD8+ T cells. To test whether these findings are applicable to CD4+ T cells, we analyzed the in situ 3.L2 TCR–pMHC-II interactions for a well-characterized panel of altered peptide ligands on the T cell surface using the adhesion frequency assay with a micropipette and the thermal fluctuation and force-clamp assays with a biomembrane force probe. We found that the 2D effective TCR–pMHC-II affinity and off-rate correlate with, but better predict the T cell response than, the corresponding measurements with the surface plasmon resonance in three dimensions. The 2D affinity of the CD4 for MHC-II was very low, approaching the detection limit, making it one to two orders of magnitude lower than the affinity of CD8 for MHC-I. In addition, the signal-dependent cooperation between TCR and coreceptor for pMHC binding previously observed for CD8 was not observed for CD4. Interestingly, force elicited TCR–pMHC-II catch-slip bonds for agonists but slip-only bonds for antagonists, thereby amplifying the power of discrimination between altered peptide ligands. These results show that the force-regulated 2D binding kinetics of the 3.L2 TCR for pMHC-II determine functions of CD4+ T cells.
Involvement of NK Cells and NKp30 Pathway in Antisynthetase Syndrome

Antisynthetase syndrome (aSS) is characterized by the association of interstitial lung disease and myositis with anti–tRNA synthetase autoantibodies. Immune mechanisms leading to aSS could be initiated in the lungs, but the role of NK cells has not yet been studied. Both extensive NK cell phenotype and functions were compared between 33 patients and 26 controls. Direct and redirected polyfunctionality assays (degranulation and intracellular production of TNF-α and IFN-γ) were performed spontaneously or after IL-12 plus IL-18 stimulation in the presence of K562 or P815 target cells, respectively. NK cells from inactive patients showed normal phenotype, whereas active aSS revealed a differentiated NK cell profile, as indicated by increased CD57 and Ig-like transcript 2 and an inability to produce IFN-γ (p = 0.002) compared with controls. Importantly, active aSS was more specifically associated with a significant NKp30 decrease (p = 0.009), although levels of mRNA and intracellular protein were similar in aSS and healthy controls. This NKp30 decrease was strongly correlated with reduced NK cell polyfunctionality in both direct and redirected killing assays with anti-NKp30 Abs (p = 0.009 and p = 0.03, respectively), confirming its important impact in aSS. Histological studies revealed massive infiltrations of NK cells inside the lungs of aSS patients (148 versus 11/mm2). Taken together, these data suggest that NK cells and NKp30 could play a role in aSS pathogenesis.
Categorical Analysis of Human T Cell Heterogeneity with One-Dimensional Soli-Expression by Nonlinear Stochastic Embedding

Rapid progress in single-cell analysis methods allow for exploration of cellular diversity at unprecedented depth and throughput. Visualizing and understanding these large, high-dimensional datasets poses a major analytical challenge. Mass cytometry allows for simultaneous measurement of >40 different proteins, permitting in-depth analysis of multiple aspects of cellular diversity. In this article, we present one-dimensional soli-expression by nonlinear stochastic embedding (One-SENSE), a dimensionality reduction method based on the t-distributed stochastic neighbor embedding (t-SNE) algorithm, for categorical analysis of mass cytometry data. With One-SENSE, measured parameters are grouped into predefined categories, and cells are projected onto a space composed of one dimension for each category. In contrast with higher-dimensional t-SNE, each dimension (plot axis) in One-SENSE has biological meaning that can be easily annotated with binned heat plots. We applied One-SENSE to probe relationships between categories of human T cell phenotypes and observed previously unappreciated cellular populations within an orchestrated view of immune cell diversity. The presentation of high-dimensional cytometric data using One-SENSE showed a significant improvement in distinguished T cell diversity compared with the original t-SNE algorithm and could be useful for any high-dimensional dataset.
Integration Deficits of IT Controlling – Historical Background , Analysis of Integration Potentials and Method Integration

The paper is based on the thesis that IT controlling suffers from two integration deficits. On the one hand, this is a lack of synchronization between research on IT controlling methods and developments in practice; on the other hand, a lack of integration of IT controlling methods with methods of business and information systems engineering (BISE). Historical developments in IT controlling practice and research are explored to reason about potentials for further integration.
Erythrocyte omega-3 and omega-6 fatty acids profile in Sudanese women with pre-eclampsia

A case-control study was conducted in Khartoum hospital, Sudan to compare omega-3 and omega-6 fatty acids profile in three phospholipid fractions (phosphatidylethanolamine, phosphatidylcholine and sphingomyelin) using gas chromatography in erythrocytes from 65 pre-eclamptic women and well-matched 60 healthy control pregnant women, both in the third trimester of pregnancy. While levels of arachidonic acid (omega-6 fatty acid) was significantly higher in women with pre-eclampsia in the sphingomyelin fraction only, the levels of eicosapentaenoic and docosahexaenoic acid (omega-3 fatty acid) in the three phospholipids fractions were significantly higher in women with pre-eclampsia than in the control group. Both omega-3 and omega-6 fatty acids profiles were not significantly different between patients with mild (diastolic blood pressure (DBP) <110 mmHg) and severe (DBP ≥110 mmHg) pre-eclampsia.
Allergy-Protective Arabinogalactan Modulates Human Dendritic Cells via C-Type Lectins and Inhibition of NF-κB

Arabinogalactan (AG) isolated from dust of a traditional farm prevents disease in murine models of allergy. However, it is unclear whether this polysaccharide has immune regulatory properties in humans. The aim of this study was to test the influence of AG on the immune-stimulating properties of human dendritic cells (DCs). Moreover, we sought to identify the receptor to which AG binds. AG was produced from plant callus tissue under sterile conditions to avoid the influence of pathogen-associated molecular patterns in subsequent experiments. The influence of AG on the human immune system was investigated by analyzing its impact on monocyte-derived DCs. To analyze whether the T cell stimulatory capacity of AG-stimulated DCs is altered, an MLR with naive Th cells was performed. We revealed that AG reduced T cell proliferation in a human MLR. In the search for a molecular mechanism, we found that AG binds to the immune modulatory receptors DC-specific ICAM-3–grabbing non integrin (DC-SIGN) and macrophage mannose receptor 1 (MMR-1). Stimulation of these receptors with AG simultaneously with TLR4 stimulation with LPS increased the expression of the E3 ubiquitin-protein ligase tripartite motif–containing protein 21 and decreased the phosphorylation of NF-κB p65 in DCs. This led to a reduced activation profile with reduced costimulatory molecules and proinflammatory cytokine production. Blocking of MMR-1 or DC-SIGN with neutralizing Abs partially inhibits this effect. We conclude that AG dampens the activation of human DCs by LPS via binding to DC-SIGN and MMR-1, leading to attenuated TLR signaling. This results in a reduced T cell activation capacity of DCs.
Multiple Inflammatory Cytokines Converge To Regulate CD8+ T Cell Expansion and Function during Tuberculosis

The differentiation of effector CD8+ T cells is a dynamically regulated process that varies during different infections and is influenced by the inflammatory milieu of the host. In this study, we define three signals regulating CD8+ T cell responses during tuberculosis by focusing on cytokines known to affect disease outcome: IL-12, type I IFN, and IL-27. Using mixed bone marrow chimeras, we compared wild-type and cytokine receptor knockout CD8+ T cells within the same mouse following aerosol infection with Mycobacterium tuberculosis. Four weeks postinfection, IL-12, type 1 IFN, and IL-27 were all required for efficient CD8+ T cell expansion in the lungs. We next determined if these cytokines directly promote CD8+ T cell priming or are required only for expansion in the lungs. Using retrogenic CD8+ T cells specific for the M. tuberculosis Ag TB10.4 (EsxH), we observed that IL-12 is the dominant cytokine driving both CD8+ T cell priming in the lymph node and expansion in the lungs; however, type I IFN and IL-27 have nonredundant roles supporting pulmonary CD8+ T cell expansion. Thus, IL-12 is a major signal promoting priming in the lymph node, but a multitude of inflammatory signals converge in the lung to promote continued expansion. Furthermore, these cytokines regulate the differentiation and function of CD8+ T cells during tuberculosis. These data demonstrate distinct and overlapping roles for each of the cytokines examined and underscore the complexity of CD8+ T cell regulation during tuberculosis.
Dietary Habits and Nutrition Knowledge of Children Using Community Food Service Centers according to Family Type

The objective of this study was to assess dietary habits and nutrition knowledge of elementary school students who use community food-service centers according to family type. The subjects were comprised of 147 individuals in lowincome households, aged from 7 to 12 years, and who consumed free meals at community welfare centers or at local children’s centers in Seoul and Kyunggi-do, Korea. Dietary habits and dietary intake were obtained using 24-hr recall. Children in low-income single parent families skipped breakfast more frequently than children in low-income married parent families. No difference in nutrition intake or dietary habits was observed between children in low-income single parent families and children in low-income married parent families. More interest and financial support of the govern ment are required to develop nutrition education and food assistance programs for children in low-income single parent families. (Korean J Nutr 2011; 44(3): 255 ~ 263)
Basal serum cortisol as a predictor for adrenal reserve in children with adrenal insufficiency

Background: Secondary adrenocortical insufficiency occurs in children who have been suffering from pathological conditions in the hypothalamo-pituitary region such as infection, irradiation, and after tumor removal. The basal serum cortisol level as a predictor of secondary adrenocortical insufficiency has been studied mostly in adult and rarely in children. The aim of this study is to evaluate the basal morning cortisol level as a predictor of secondary adrenocortical insufficiency. Material and method: Forty-nine children, aged 2-15 years, were recruited for this study. Forty-six had tumors in the suprasellar region, two had suprasellar arachnoid cysts, and one had a history of high dose cranial irradiation. In addition, 52 idiopathic short children with proven normal hypothalamo-pituitary function were a control group. Serum basal morning cortisol level (7.30-9.00 am) was measured, and then the insulin tolerance test (ITT) was performed as a gold standard in all children. Results: A basal morning cortisol level of less than 4 μg/dL suggested the diagnosis of secondary adrenocortical insufficiency with specificity of 100% and positive predictive value (PPV) of 100%. In addition, basal cortisol level of more than 18 μg/dL could exclude the secondary adrenocorticol insufficiency with specificity of 100% and PPV of 100%. The more additional pituitary hormone deficiency was, the less was serum basal cortisol level, which represented the potential severity of pituitary gland insult. Conclusion: Measurement of morning basal cortisol level finding less than 4 and more than 18 μg/dL can predict the outcome of hypothalamo-pituitary reserve function with 100% PPV in order to avoid a complicated and risky ITT in children with pathology around suprasellar region.
Imatinib Triggers Phagolysosome Acidification and Antimicrobial Activity against Mycobacterium bovis Bacille Calmette–Guérin in Glucocorticoid-Treated Human Macrophages

Glucocorticoids are extensively used to treat inflammatory diseases; however, their chronic intake increases the risk for mycobacterial infections. Meanwhile, the effects of glucocorticoids on innate host responses are incompletely understood. In this study, we investigated the direct effects of glucocorticoids on antimycobacterial host defense in primary human macrophages. We found that glucocorticoids triggered the expression of cathelicidin, an antimicrobial critical for antimycobacterial responses, independent of the intracellular vitamin D metabolism. Despite upregulating cathelicidin, glucocorticoids failed to promote macrophage antimycobacterial activity. Gene expression profiles of human macrophages treated with glucocorticoids and/or IFN-γ, which promotes induction of cathelicidin, as well as antimycobacterial activity, were investigated. Using weighted gene coexpression network analysis, we identified a module of highly connected genes that was strongly inversely correlated with glucocorticoid treatment and associated with IFN-γ stimulation. This module was linked to the biological functions autophagy, phagosome maturation, and lytic vacuole/lysosome, and contained the vacuolar H+-ATPase subunit a3, alias TCIRG1, a known antimycobacterial host defense gene, as a top hub gene. We next found that glucocorticoids, in contrast with IFN-γ, failed to trigger expression and phagolysosome recruitment of TCIRG1, as well as to promote lysosome acidification. Finally, we demonstrated that the tyrosine kinase inhibitor imatinib induces lysosome acidification and antimicrobial activity in glucocorticoid-treated macrophages without reversing the anti-inflammatory effects of glucocorticoids. Taken together, we provide evidence that the induction of cathelicidin by glucocorticoids is not sufficient for macrophage antimicrobial activity, and identify the vacuolar H+-ATPase as a potential target for host-directed therapy in the context of glucocorticoid therapy.
Fatores de risco e medidas profiláticas nas pneumonias adquiridas na comunidade

This article reviews the effects of aging, tobacco-smoking, chronic bronchitis and emphysema, heart failure, oropharyngeal colonization, aspiration (micro and macro), alcoholism, hepatic cirrhosis, nutritional deficiency, immunosuppression, and environmental factors on the risk of community-acquired pneumonia and its severity. In the second part, the authors review the prophylactic action of anti-influenza and anti-pneumococcus vaccines as well as the role of prevention and treatment of antiviral agents in community-acquired pneumonia.
Complement Destabilizes Cardiomyocyte Function In Vivo after Polymicrobial Sepsis and In Vitro

There is accumulating evidence during sepsis that cardiomyocyte (CM) homeostasis is compromised, resulting in cardiac dysfunction. An important role for complement in these outcomes is now demonstrated. Addition of C5a to electrically paced CMs caused prolonged elevations of intracellular Ca2+ concentrations during diastole, together with the appearance of spontaneous Ca2+ transients. In polymicrobial sepsis in mice, we found that three key homeostasis-regulating proteins in CMs were reduced: Na+/K+-ATPase, which is vital for effective action potentials in CMs, and two intracellular Ca2+ concentration regulatory proteins, that is, sarcoplasmic/endoplasmic reticulum calcium ATPase 2 and the Na+/Ca2+ exchanger. Sepsis caused reduced mRNA levels and reductions in protein concentrations in CMs for all three proteins. The absence of either C5a receptor mitigated sepsis-induced reductions in the three regulatory proteins. Absence of either C5a receptor (C5aR1 or C5aR2) diminished development of defective systolic and diastolic echocardiographic/Doppler parameters developing in the heart (cardiac output, left ventricular stroke volume, isovolumic relaxation, E′ septal annulus, E/E′ septal annulus, left ventricular diastolic volume). We also found in CMs from septic mice the presence of defective current densities for Ik1, l-type calcium channel, and Na+/Ca2+ exchanger. These defects were accentuated in the copresence of C5a. These data suggest complement-related mechanisms responsible for development of cardiac dysfunction during sepsis.
Are attendings different?. Intensivists explain their handoff ideals, perceptions, and practices.

PURPOSE What is known about physician handoffs is almost entirely limited to resident practice, but attending physicians ultimately determine care plans and goals of care. This study sought to understand what is unique about attending intensivist handoffs, to identify perceptions of the ideal content and format of intensive care unit (ICU) attending handoffs, and to understand how ideal and reported practices are aligned in the delivery of care. METHODS Intensivists in active practice in U.S. adult academic ICUs were purposively sampled and interviewed over 9 months in 2011 to 2012. MEASUREMENTS AND MAIN RESULTS Thirty attendings from 15 institutions in nine U.S. states were interviewed. Subjects' specialties included anesthesiology, emergency medicine, internal medicine, and surgery. The "perfect handoff" was described as succinct, included verbal plus written communication, and took place in person. Respondents believed that the attending handoff should be less detailed than resident handoffs. Most attendings participated in handoffs at the end of each ICU rotation (n = 26). Standardized handoff practice was rare (n = 1). Media used for handoffs included combinations of telephone conversations (n = 25), in-person communications (n = 11), e-mail (n = 9), or text message (n = 2). Handoff duration varied from 10 to 120 minutes for 5 to 42 patients. Five of 30 respondents had undergone formal training in how to conduct handoffs. CONCLUSIONS A national sample of academic intensivists identified common ideal attributes of attending handoffs, yet their reported handoff practices varied widely. Ideal handoff practices may form the basis of future interventions to improve communication between intensivists.