Miracle-dz/UniFAR-FTUs huggingface dataset:
Perceived predictors of quality of life in patients with end-stage renal disease on dialysis

Background Reduced quality of life (QOL) is associated with shorter survival, and is more marked in patients with end-stage renal disease (ESRD). Predictors of health, which include policymaking, social factors, health services, individual behaviour, biology and genetics, have an impact on the QOL of patients with ESRD. Patients with ESRD in South Africa are cared for in public and private hospitals, with public health institutions characterised by several challenges. Objective To explore and analyse the perceived predictors of QOL in patients with ESRD in the three district hospitals that provide renal services in KwaZulu-Natal. Methods An exploratory, descriptive qualitative research approach based on grounded theory research design was used and three focus group discussions (FGDs) were conducted. The researcher recruited 18 participants, 6 in each focus group. Three phases of data analysis were followed: open coding, axial coding, and selective coding. Results Predictors of QOL that emerged were the geographic location of the patients, accessibility of haemodialysis centres, patients’ adaptation and acceptance of the condition, self-management, support by family members and caregivers and availability of adequately trained nurses. Conclusion Predictors of QOL in patients with ESRD are associated with an increased risk of morbidity and mortality resulting from dialysis. The broad range of dimensions of life is negatively affected and requires intervention by the renal team and policymakers to improve the QOL of patients.
Serotype Distribution and Antimicrobial Resistance of Salmonella Isolates in Korea between 2016 and 2017

Salmonella is one of the major causes of food-borne infections. We investigated the serotype distribution and antimicrobial resistance of Salmonella isolates collected in Korea between January 2016 and December 2017. In total, 669 Salmonella isolates were collected from clinical specimens at 19 university hospitals. Serotyping was performed according to the Kauffmann–White scheme, and antimicrobial susceptibility was tested using Sensititre EUVSEC plates or disk diffusion. Among the strains, C (39.8%) and B (36.6%) were the most prevalent serogroups. In total, 51 serotypes were identified, and common serotypes were S. enterica serovar I 4,[5],12:i:- (16.7%), S. Enteritidis (16.1%), S. Bareilly (14.6%), S. Typhimurium (9.9%), and S. Infantis (6.9%). The resistance rates to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole were 32.6%, 12.1%, and 8.4%, respectively. The resistance rates to cefotaxime and ciprofloxacin were 8.1% and 3.0%, respectively, while 5.4% were multidrug-resistant. S. enterica serovar I 4,[5],12:i:- and S. Enteritidis were highly prevalent, and there was an increase in rare serotypes. Multidrug resistance and ciprofloxacin resistance were highly prevalent. Periodic investigations of Salmonella serotypes and antimicrobial resistance are needed.
New evidence for managing Gram-negative bloodstream infections

Purpose of review Gram-negative bloodstream infections (GNBSI) are common and carry considerable mortality. Treatment is complicated by increasing antimicrobial resistance, posing a challenge for timely appropriate antibiotics and limiting the choices of effective definitive therapy. The present review aims to summarize recent studies addressing the management of GNBSI. Recent findings New rapid diagnostic tests (RDT) for pathogen identification and antibiotic susceptibility are associated with improved antimicrobial stewardship and reduced length of stay. No mortality benefit or patient-related outcomes are reported. Data regarding the use of new beta-lactam beta-lactamase inhibitors (BLBLIs) for treating multidrug resistance Gram-negative bacteria is supportive, though questions regarding combinations, optimal dosing, mode of administration, and resistance emergence remain to be clarified. Current data regarding cefiderocol necessitates further studies in order to support its use in GNBSI. Shortened (≤7 days) duration of therapy and early oral step down for GNBSI are supported by the literature. The role of repeated blood cultures should be further defined. Summary RDTs should be implemented to improve antibiotic stewardship. Clinical implications on patient-related outcomes should be evaluated. New BLBLIs show promise in the treatment of GNBSI. Additional data are needed regarding the use of cefiderocol. Antibiotic therapy should be shortened and early oral step down should be considered.
Identification and Evaluation of Methodologies to Assess the Quality of Mobile Health Apps in High-, Low-, and Middle-Income Countries: Rapid Review

Background In recent years, there has been rapid growth in the availability and use of mobile health (mHealth) apps around the world. A consensus regarding an accepted standard to assess the quality of such apps has yet to be reached. A factor that exacerbates the challenge of mHealth app quality assessment is variations in the interpretation of quality and its subdimensions. Consequently, it has become increasingly difficult for health care professionals worldwide to distinguish apps of high quality from those of lower quality. This exposes both patients and health care professionals to unnecessary risks. Despite progress, limited understanding of the contributions of researchers in low- and middle-income countries (LMICs) exists on this topic. Furthermore, the applicability of quality assessment methodologies in LMIC settings remains relatively unexplored. Objective This rapid review aims to identify current methodologies in the literature to assess the quality of mHealth apps, understand what aspects of quality these methodologies address, determine what input has been made by authors from LMICs, and examine the applicability of such methodologies in LMICs. Methods This review was registered with PROSPERO (International Prospective Register of Systematic Reviews). A search of PubMed, EMBASE, Web of Science, and Scopus was performed for papers related to mHealth app quality assessment methodologies, which were published in English between 2005 and 2020. By taking a rapid review approach, a thematic and descriptive analysis of the papers was performed. Results Electronic database searches identified 841 papers. After the screening process, 52 papers remained for inclusion. Of the 52 papers, 5 (10%) proposed novel methodologies that could be used to evaluate mHealth apps of diverse medical areas of interest, 8 (15%) proposed methodologies that could be used to assess apps concerned with a specific medical focus, and 39 (75%) used methodologies developed by other published authors to evaluate the quality of various groups of mHealth apps. The authors in 6% (3/52) of papers were solely affiliated to institutes in LMICs. A further 15% (8/52) of papers had at least one coauthor affiliated to an institute in an LMIC. Conclusions Quality assessment of mHealth apps is complex in nature and at times subjective. Despite growing research on this topic, to date, an all-encompassing appropriate means for evaluating the quality of mHealth apps does not exist. There has been engagement with authors affiliated to institutes across LMICs; however, limited consideration of current generic methodologies for application in LMIC settings has been identified. Trial Registration PROSPERO CRD42020205149; https://www.crd. york.ac. uk/prospero/display_record. php? RecordID=205149
Minimum information to report about a flow cytometry experiment on extracellular vesicles: Communication from the ISTH SSC subcommittee on vascular biology

The Extracellular Vesicle Flow Cytometry Working Group (http://www.evflowcytometry.org) is formed by members of the International Society for Extracellular Vesicles (ISEV), the International Society for Advancement of Cytometry (ISAC), and the International Society on Thrombosis and Haemostasis (ISTH). This working group of flow cytometry experts develops guidelines for best practices regarding flow cytometry detection of extracellular vesicles. To improve rigor and standardization, this working group published a framework outlining the minimal information to report about a flow cytometry experiment on extracellular vesicles (MIFlowCyt‐EV) in the Journal of Extracellular Vesicles, the ISEV journal, in 2020. In parallel, an article explaining MIFlowCyt‐EV was published in Cytometry Part A, one of the ISAC journals, and now will be introduced to the ISTH as an SSC Communication in the Journal of Thrombosis and Haemostasis. The goal of this SSC Communication is to explain why flow cytometry is becoming the instrument of choice to characterize single extracellular vesicles, the obstacles that have been identified and (mostly) overcome by developing procedures to calibrate flow cytometers, and the relevance of reporting minimal information to improve reliability and reproducibility of experiments in which flow cytometers are used for characterization of extracellular vesicles.
Rapid cloud removal of dimethyl sulfide oxidation products limits SO2 and cloud condensation nuclei production in the marine atmosphere

Significance Ocean emissions of dimethyl sulfide (DMS) are a major precursor for the production and growth of aerosol particles, which can act as seeds for the formation of cloud droplets in the marine atmosphere with the subsequent impacts on Earth’s climate. Global aircraft observations indicate that DMS is efficiently oxidized to hydroperoxymethyl thioformate (HPMTF), a previously unrecognized molecule, which necessitates revisiting DMS oxidation chemistry in the marine atmosphere. We show through ambient observations and global modeling that a dominant loss pathway for HPMTF is uptake into cloud droplets. This loss process short circuits gas-phase oxidation and significantly alters the dynamics of aerosol production and growth in the marine atmosphere. Oceans emit large quantities of dimethyl sulfide (DMS) to the marine atmosphere. The oxidation of DMS leads to the formation and growth of cloud condensation nuclei (CCN) with consequent effects on Earth’s radiation balance and climate. The quantitative assessment of the impact of DMS emissions on CCN concentrations necessitates a detailed description of the oxidation of DMS in the presence of existing aerosol particles and clouds. In the unpolluted marine atmosphere, DMS is efficiently oxidized to hydroperoxymethyl thioformate (HPMTF), a stable intermediate in the chemical trajectory toward sulfur dioxide (SO2) and ultimately sulfate aerosol. Using direct airborne flux measurements, we demonstrate that the irreversible loss of HPMTF to clouds in the marine boundary layer determines the HPMTF lifetime (τHPMTF < 2 h) and terminates DMS oxidation to SO2. When accounting for HPMTF cloud loss in a global chemical transport model, we show that SO2 production from DMS is reduced by 35% globally and near-surface (0 to 3 km) SO2 concentrations over the ocean are lowered by 24%. This large, previously unconsidered loss process for volatile sulfur accelerates the timescale for the conversion of DMS to sulfate while limiting new particle formation in the marine atmosphere and changing the dynamics of aerosol growth. This loss process potentially reduces the spatial scale over which DMS emissions contribute to aerosol production and growth and weakens the link between DMS emission and marine CCN production with subsequent implications for cloud formation, radiative forcing, and climate.
Periodic Comparability Verification and Within-Laboratory Harmonization of Clinical Chemistry Laboratory Results at a Large Healthcare Center With Multiple Instruments

Background Results from laboratories using multiple instruments should be standardized or harmonized and comparability-verified for consistent quality control. We developed a simple frequent comparability verification methodology applicable to large healthcare centers using multiple clinical chemistry instruments from different manufacturers. Methods Comparability of five clinical chemistry instruments (Beckman Coulter AU5800, Abbott Architect Ci16000, two Siemens Vista 1500, and Ortho Vitros 5600) was evaluated from 2015 to 2019 for 12 clinical chemistry measurements. Pooled residual patient samples were used for weekly verifications. Results from any instrument exceeding the allowable verification range versus the results from the comparative instrument (AU5800) were reported to clinicians after being multiplied by conversion factors that were determined via a linear regression equation obtained from simplified comparison. Results Over the five-year study period, 432 weekly inter-instrument comparability verification results were obtained. Approximately 58% of results were converted due to non-comparable verification. Expected average absolute percent bias and percentage of non-comparable results for non-converted and converted results after conversion action were much lower than those for data measured before conversion action. The inter-instrument CV for both non-converted and converted results after conversion action was much lower than that for measured data before conversion action for all analytes. Conclusions We maintained within-laboratory comparability of clinical chemistry tests from multiple instruments for five years using frequent low-labor periodic comparability verification methods from pooled residual sera. This methodology is applicable to large testing facilities using multiple instruments.
Maternal melatonin: Effective intervention against developmental programming of cardiovascular dysfunction in adult offspring of complicated pregnancy

Adopting an integrative approach, by combining studies of cardiovascular function with those at cellular and molecular levels, this study investigated whether maternal treatment with melatonin protects against programmed cardiovascular dysfunction in the offspring using an established rodent model of hypoxic pregnancy. Wistar rats were divided into normoxic (N) or hypoxic (H, 10% O2) pregnancy ± melatonin (M) treatment (5 μg·ml−1.day−1) in the maternal drinking water. Hypoxia ± melatonin treatment was from day 15–20 of gestation (term is ca. 22 days). To control for possible effects of maternal hypoxia‐induced reductions in maternal food intake, additional dams underwent pregnancy under normoxic conditions but were pair‐fed (PF) to the daily amount consumed by hypoxic dams from day 15 of gestation. In one cohort of animals from each experimental group (N, NM, H, HM, PF, PFM), measurements were made at the end of gestation. In another, following delivery of the offspring, investigations were made at adulthood. In both fetal and adult offspring, fixed aorta and hearts were studied stereologically and frozen hearts were processed for molecular studies. In adult offspring, mesenteric vessels were isolated and vascular reactivity determined by in‐vitro wire myography. Melatonin treatment during normoxic, hypoxic or pair‐fed pregnancy elevated circulating plasma melatonin in the pregnant dam and fetus. Relative to normoxic pregnancy, hypoxic pregnancy increased fetal haematocrit, promoted asymmetric fetal growth restriction and resulted in accelerated postnatal catch‐up growth. Whilst fetal offspring of hypoxic pregnancy showed aortic wall thickening, adult offspring of hypoxic pregnancy showed dilated cardiomyopathy. Similarly, whilst cardiac protein expression of eNOS was downregulated in the fetal heart, eNOS protein expression was elevated in the heart of adult offspring of hypoxic pregnancy. Adult offspring of hypoxic pregnancy further showed enhanced mesenteric vasoconstrictor reactivity to phenylephrine and the thromboxane mimetic U46619. The effects of hypoxic pregnancy on cardiovascular remodelling and function in the fetal and adult offspring were independent of hypoxia‐induced reductions in maternal food intake. Conversely, the effects of hypoxic pregnancy on fetal and postanal growth were similar in pair‐fed pregnancies. Whilst maternal treatment of normoxic or pair‐fed pregnancies with melatonin on the offspring cardiovascular system was unremarkable, treatment of hypoxic pregnancies with melatonin in doses lower than those recommended for overcoming jet lag in humans enhanced fetal cardiac eNOS expression and prevented all alterations in cardiovascular structure and function in fetal and adult offspring. Therefore, the data support that melatonin is a potential therapeutic target for clinical intervention against developmental origins of cardiovascular dysfunction in pregnancy complicated by chronic fetal hypoxia.
Interferon-γ Impairs Human Coronary Artery Endothelial Glucose Metabolism by Tryptophan Catabolism and Activates Fatty Acid Oxidation

Supplemental Digital Content is available in the text. Background: Endothelial cells depend on glycolysis for much of their energy production. Impaired endothelial glycolysis has been associated with various vascular pathobiologies, including impaired angiogenesis and atherogenesis. IFN-γ (interferon-γ)–producing CD4+ and CD8+ T lymphocytes have been identified as the predominant pathological cell subsets in human atherosclerotic plaques. Although the immunologic consequences of these cells have been extensively evaluated, their IFN-γ–mediated metabolic effects on endothelial cells remain unknown. The purpose of this study was to determine the metabolic consequences of the T-lymphocyte cytokine, IFN-γ, on human coronary artery endothelial cells. Methods: The metabolic effects of IFN-γ on primary human coronary artery endothelial cells were assessed by unbiased transcriptomic and metabolomic analyses combined with real-time extracellular flux analyses and molecular mechanistic studies. Cellular phenotypic correlations were made by measuring altered endothelial intracellular cGMP content, wound-healing capacity, and adhesion molecule expression. Results: IFN-γ exposure inhibited basal glycolysis of quiescent primary human coronary artery endothelial cells by 20% through the global transcriptional suppression of glycolytic enzymes resulting from decreased basal HIF1α (hypoxia-inducible factor 1α) nuclear availability in normoxia. The decrease in HIF1α activity was a consequence of IFN-γ–induced tryptophan catabolism resulting in ARNT (aryl hydrocarbon receptor nuclear translocator)/HIF1β sequestration by the kynurenine-activated AHR (aryl hydrocarbon receptor). In addition, IFN-γ resulted in a 23% depletion of intracellular nicotinamide adenine dinucleotide in human coronary artery endothelial cells. This altered glucose metabolism was met with concomitant activation of fatty acid oxidation, which augmented its contribution to intracellular ATP balance by >20%. These metabolic derangements were associated with adverse endothelial phenotypic changes, including decreased basal intracellular cGMP, impaired endothelial migration, and a switch to a proinflammatory state. Conclusions: IFN-γ impairs endothelial glucose metabolism by altered tryptophan catabolism destabilizing HIF1, depletes nicotinamide adenine dinucleotide, and results in a metabolic shift toward increased fatty acid oxidation. This work suggests a novel mechanistic basis for pathological T lymphocyte–endothelial interactions in atherosclerosis mediated by IFN-γ, linking endothelial glucose, tryptophan, and fatty acid metabolism with the nicotinamide adenine dinucleotide balance and ATP generation and their adverse endothelial functional consequences.
Interaction of Native Cyclodextrins and Their Hydroxypropylated Derivatives with Carbamazepine in Aqueous Solution. Evaluation of Inclusion Complexes and Aggregates Formation

A detailed comprehensive study on how the formation of soluble and insoluble carbamazepine/cyclodextrins (CBZ/CD) complexes (with consequent changes in the solid-phase composition) depends on the CD structure is not yet available. Moreover, the study of possible influence of this drug on the tendency of CDs and their complexes to self-aggregate is still lacking. Phase-solubility studies demonstrated that CDs and CBZ form a range of soluble (AL-type: αCD, βCD, and hydroxypropylated CDs) and insoluble (BS-type: γCD) complexes depending on CD used. HPβCD proved to be the best CD solubilizer for CBZ forming the most stable complex with highest apparent solubility, whereas γCD was shown to be the best native CD. For the native CDs, CBZ solubilization increases with increasing CD cavity diameter (αCD ≪ βCD < γCD). Solid phases collected from phase-solubility studies were characterized by Fourier-transformed infrared spectroscopy, differential scanning calorimetry, and X-ray powder diffraction to elucidate their composition and crystalline structure. They provided similar conclusions being overall supportive of phase-solubility, osmolality, and permeation studies results. Solid CBZ was the only detected component for AL-type profiles over the CD concentration range studied, whereas precipitation of poorly soluble CBZ/γCD complexes (BS-type) was observed (i.e., at and beyond plateau region). Osmometry and permeation studies were applied to evaluate the effect of CBZ on the aggregate formation and also to elucidate their influence on CD complex solubility and permeation profile. Permeation method was shown to be the most effective method to detect and evaluate aggregate formation in aqueous γCD and HPβCD solutions containing CBZ. CBZ did not affect the HPβCD tendency to self-aggregate but CBZ did modify the aggregation behavior of γCD decreasing the apparent critical aggregation concentration value from 4.2% (w/v) (in pure aqueous γCD solution) to 2.5% (w/v) (when CBZ was present).
Acute Kidney Injury Associated with Area under the Curve versus Trough Monitoring of Vancomycin in Obese Patients

Vancomycin is a first-line agent used in the treatment of methicillin-resistant Staphylococcus aureus; however, vancomycin is associated with acute kidney injury (AKI). Previous literature demonstrates decreased incidence of AKI using 24-h area under the concentration-time curve (AUC24) monitoring, but its safety is unknown in obese populations. ABSTRACT Vancomycin is a first-line agent used in the treatment of methicillin-resistant Staphylococcus aureus; however, vancomycin is associated with acute kidney injury (AKI). Previous literature demonstrates decreased incidence of AKI using 24-h area under the concentration-time curve (AUC24) monitoring, but its safety is unknown in obese populations. Patients ≥18 years, with body mass indices (BMI) ≥30 kg/m2, admitted between August 2015 and July 2017 or October 2017 and September 2019, who received vancomycin for ≥72 h and had level(s) drawn within 96 h of initiation were included. The primary outcome was incidence of AKI. Secondary outcomes included inpatient mortality rate, median inpatient length of stay, median vancomycin trough concentration, and median vancomycin AUC24. AKI was identified using the highest serum creatinine value compared with the value immediately prior to vancomycin initiation based on Kidney Disease Improving Global Outcomes (KDIGO) criteria. Overall, 1,024 patients met inclusion criteria, with 142 out of 626 patients in the trough group and 65 out of 398 patients in the AUC24 group meeting criteria for AKI (22.7% versus 16.3%, P = 0.008). Logistic regression of the data to account for confounding factors maintained significance for the reduction in incidence of AKI with AUC24 monitoring compared to trough monitoring (P = 0.010). Monitoring of vancomycin with AUC24 was associated with a decreased risk of AKI when compared with trough monitoring in obese patients.