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Usman Rashid Malik,1– 3 Jie Chang,1– 3 Furqan Hashmi,4 Naveel Atif,1– 3 Hareem Basir,5 Khezar Hayat,1– 3,6 Faiz Ullah Khan,1– 3 John Alimamy Kabba,1– 3 Krizzia Lambojon,1– 3 Yu Fang1– 3 1Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmacy, Xi’an Jiaotong University, Xi’an, 710061, People’s Republic of China; 2Center for Drug Safety and Policy Research, Xi’an Jiaotong University, Xi’an, 710061, People’s Republic of China; 3Research Institute for Drug Safety and Monitoring, Institute of Pharmaceutical Science and Technology, China’s Western Technology Innovation Harbour, Xi’an, 710000, People’s Republic of China; 4University College of Pharmacy, University of the Punjab, Lahore, 54000, Pakistan; 5Royal Albert Edward Infirmary, Wigan, WN1 2NN, UK; 6Institute of Pharmaceutical Sciences, University of Veterinary and Animal Sciences, Lahore, 54000, PakistanCorrespondence: Yu FangDepartment of Pharmacy Administration and Clinical Pharmacy, School of Pharmacy, Xi’an Jiaotong University, Xi’an, 710061, People’s Republic of ChinaTel +86-29-8265-5132Fax +86-29-8265-5424Email yufang@mail.xjtu.edu.cnIntroduction: The excessive consumption of antibiotics is a significant contributor to antimicrobial resistance, especially in children. Children are often advised antibiotics for viral infections. In developing countries, drugstores are a prime source of easy access to nonprescription antibiotics. Moreover, in Pakistan, their irrational use is an “everyday routine”. The study, therefore, aimed to evaluate the dispensing of nonprescription antibiotics to children.Methods: Using pediatric acute diarrhea and acute upper respiratory infection as disease scenarios, a simulated client, cross-sectional study was conducted in Lahore, Pakistan, to explore the antibiotics’ ease of availability at both categories of drugstores (pharmacies and medical stores) from November 1st, 2019 to January 31st, 2020. Chi-square (χ2) test was used to compare the differences in practices of different categorical variables. Multivariable logistic regression was applied to analyze the association of various factors with antibiotics dispensing.Results: Antibiotics were dispensed without prescription in 456 (59%) of 773 simulated visits out of which 425 (93.2%) were dispensed on the advice of the drugstore staff. A qualified pharmacist was available in only 164 (21.2%) cases. Of the 386 visits for acute diarrhea and 387 for acute upper respiratory infection, nonprescription antibiotic dispensing occurred in 259 (67.1%) and 197 (50.9%) visits, respectively. There were considerable differences (p-value < 0.05) in the practices and antibiotics dispensing between each disease scenario presented. Moreover, antibiotics were less commonly dispensed at pharmacist-supervised drugstores compared to unsupervised ones.Conclusion: Overall, inappropriate dispensing practices were prevalent to a large extent at the drugstores, and antibiotics were effortlessly obtainable without prescription. The quality of the services provided, especially by the non-pharmacist staff, was also not satisfactory. Therefore, the Drug Regulating Authority of Pakistan must enforce strict implementation of drug laws at the drugstores without delay, especially in major cities to help curb the felonious use of antibiotics.Keywords: antibiotics, nonprescription, drugstores, community pharmacies, simulated client, Pakistan

Abstract Background Patients with autosomal dominant polycystic kidney disease (ADPKD) have an increased risk of cardiovascular morbidity and mortality. Impaired left ventricular (LV) global longitudinal strain (GLS) can be a sign of subclinical cardiac dysfunction even in patients with otherwise preserved ejection fraction (EF). Transmitral early filling velocity to early diastolic strain rate (E/SRe) is a novel measure of LV filling pressure, which is often affected early in cardiac disease. Methods A total of 110 ADPKD patients not on dialysis were included in this prospective study. All patients underwent an extensive echocardiographic examination including two-dimensional speckle tracking. GLS and strain rates were measured. The distribution of GLS and E/SRe was determined and patient characteristics were compared by median levels of GLS (− 17.8%) and E/SRe (91.4 cm). Twenty healthy participants were included as control group. Results There was a significantly worse GLS in the ADPKD patients (mean: − 17.8 ± 2.5%) compared to the healthy controls (mean: − 21.9 ± 1.9%), p

Background. In end-stage liver disease, alterations in iron metabolism can lead to iron overload and development of iron overload cardiomyopathy. In liver transplant candidates, evaluation for cardiac iron overload and dysfunction can help to identify candidates at increased risk for peritransplant morbidity and mortality, though recommendations for pretransplant evaluation of cardiac iron overload are not standardized. Cardiac Magnetic Resonance Imaging T2* (CMRI-T2*) is a validated method to quantify cardiac iron deposition, with normal T2* value of 20 ms or greater. In this study, we sought to identify the incidence and predictors of iron overload by CMRI-T2* and to evaluate the impact of cardiac and iron overload on morbidity and mortality after liver transplantation. Methods. In this retrospective single-center cohort study, all liver transplant candidates who underwent a pretransplant CMRI-T2* between January 1, 2008, and June 30, 2016, were included to analyze the association between clinical characteristics and low T2* using logistic regression. Results. One hundred seventy-nine liver transplant candidates who received CMRI-T2* were included. Median age was 57 years, 73.2% were male, and 47.6% were white. 49.7% had hepatitis C and 2.8% had hemochromatosis. Median Model for End-Stage Liver Disease score was 25. 65.2% were Child-Pugh C. In multivariable logistic regression, T2* less than 20 ms (n = 35) was associated with Model for End-Stage Liver Disease score of 25 or greater (odds ratio [OR], 3.65; P = 0.007), Child-Pugh C (OR, 3.42; P = 0.03), and echocardiographic systolic ejection fraction less than 65% (OR, 2.24; P = 0.01). Posttransplant heart failure occurred exclusively in recipients with T2* less than 15 ms. Survival was worse in T2* 10 to 14.9 versus T2* of 20 ms or greater (hazard ratio, 3.85; P = 0.003), but not for 15 to 19.9 versus T2* of 20 ms or greater. Conclusions. Severity of liver disease and systolic dysfunction is associated with T2* less than 20 ms, though there was no difference in posttransplant outcomes between T2* 15 to 19.9 and T2* 20 ms or greater, suggesting that individuals with T2* of 15 ms or greater may be suitable transplant candidates. CMRI-T2* is an additional diagnostic tool in evaluating transplant candidates at high risk for posttransplant cardiac complications.

Aim. To determine absorbed radiation dose (ARD) in radiosensitive organs during prospective and full phase dose modulation using ECG-gated MDCTA scanner under 64- and 320-row detector modes. Methods. Female phantom was used to measure organ radiation dose. Five DP-3 radiation detectors were used to measure ARD to lungs, breast, and thyroid using the Aquilion ONE scanner in 64- and 320-row modes using both prospective and dose modulation in full phase acquisition. Five measurements were made using three tube voltages: 100, 120, and 135 kVp at 400 mA at heart rate (HR) of 60 and 75 bpm for each protocol. Mean acquisition was recorded in milligrays (mGy). Results. Mean ARD was less for 320-row versus 64-row mode for each imaging protocol. Prospective EKG-gated imaging protocol resulted in a statistically lower ARD using 320-row versus 64-row modes for midbreast (6.728 versus 19.687 mGy, P

Pathway-based association methods have been proposed to be an effective approach in identifying disease genes, when single-marker association tests do not have sufficient power. The analysis of quantitative traits may be benefited from these approaches, by sampling from two extreme tails of the distribution. Here we tested a pathway association approach on a small genome-wide association study (GWAS) on 653 subjects with extremely high high-density lipoprotein cholesterol (HDL-C) levels and 784 subjects with low HDL-C levels. We identified 102 genes in the sterol transport and metabolism pathways that collectively associate with HDL-C levels, and replicated these association signals in an independent GWAS. Interestingly, the pathways include 18 genes implicated in previous GWAS on lipid traits, suggesting that genuine HDL-C genes are highly enriched in these pathways. Additionally, multiple biologically relevant loci in the pathways were not detected by previous GWAS, including genes implicated in previous candidate gene association studies (such as LEPR, APOA2, HDLBP, SOAT2), genes that cause Mendelian forms of lipid disorders (such as DHCR24), and genes expressing dyslipidemia phenotypes in knockout mice (such as SOAT1, PON1). Our study suggests that sampling from two extreme tails of a quantitative trait and examining genetic pathways may yield biological insights from smaller samples than are generally required using single-marker analysis in large-scale GWAS. Our results also implicates that functionally related genes work together to regulate complex quantitative traits, and that future large-scale studies may benefit from pathway-association approaches to identify novel pathways regulating HDL-C levels.

Coronary heart disease (CHD) is the leading cause of mortality in African Americans. To identify common genetic polymorphisms associated with CHD and its risk factors (LDL- and HDL-cholesterol (LDL-C and HDL-C), hypertension, smoking, and type-2 diabetes) in individuals of African ancestry, we performed a genome-wide association study (GWAS) in 8,090 African Americans from five population-based cohorts. We replicated 17 loci previously associated with CHD or its risk factors in Caucasians. For five of these regions (CHD: CDKN2A/CDKN2B; HDL-C: FADS1-3, PLTP, LPL, and ABCA1), we could leverage the distinct linkage disequilibrium (LD) patterns in African Americans to identify DNA polymorphisms more strongly associated with the phenotypes than the previously reported index SNPs found in Caucasian populations. We also developed a new approach for association testing in admixed populations that uses allelic and local ancestry variation. Using this method, we discovered several loci that would have been missed using the basic allelic and global ancestry information only. Our conclusions suggest that no major loci uniquely explain the high prevalence of CHD in African Americans. Our project has developed resources and methods that address both admixture- and SNP-association to maximize power for genetic discovery in even larger African-American consortia.

ObjectiveHigher serum leptin levels have been associated with a modestly higher incidence of cardiovascular disease in studies involving mostly Caucasian men. We aimed to assess the hypothesis that higher baseline levels of serum leptin are associated with higher risk of future cardiovascular disease in a diverse cohort.MethodsThe Multi-Ethnic Study of Atherosclerosis (MESA) is a modern, community-based, ethnically-diverse, and sex-balanced prospective cohort study of US adults free from cardiovascular disease. Serum leptin was measured in an ancillary study in 2002-2005. This analysis included 1905 MESA participants with baseline leptin and incident cardiovascular event data. Leptin levels were modeled as a log-transformed continuous variable and multivariable-adjusted Cox regression was performed for the primary outcome of hard cardiovascular disease, including coronary heart disease and stroke.ResultsThe median follow-up was 7.6 years (25th-75th 7.1-8.3) with 7051 and 6738 person-years of follow-up in women and men. A hard cardiovascular disease event occurred in 47 women and 63 men. The age- and ethnicity-adjusted hazard ratio estimates for a 1 standard deviation increase in ln(leptin) were 1.16 in women (95% CI 0.78-1.73, p = 0.46) and 0.91 (95% CI 0.69-1.20, p = 0.51) in men. Pooling sexes, and adjusting for sex in addition to age and ethnicity, estimates were 0.98 (95% CI 0.78-1.23, p = 0.89). With additional adjustment for cardiovascular risk factors, the results remained nonsignificant: 0.87 (95% CI 0.68-1.11, p = 0.26).ConclusionIn conclusion, in a modern, US prospective cohort study of multi-ethnic women and men of multi-ethnic backgrounds, leptin levels are not associated with incident cardiovascular events.

This study uses physical and geochemical characteristics of crude oil samples representing the Cretaceous and Palaeogene reservoir sequence of the Melut Basin, southern Sudan to gain information about source rock properties, including organic matter characters, depositional environment and thermal maturity. The overall results show that the Melut Basin's oils have API values between 14.6° and 33.3° and indicate that most of oils are not biodegraded; except one heavy oil sample with low API gravity of 14.6°, which is likely biodegraded. The studied oils were generated from clay‐rich source rocks, containing a blend of organic matter derived primarily from a mixed organic matter of aquatic and terrestrial origin and deposited in a lacustrine setting under suboxic to relatively oxic conditions as demonstrated by their biomarker and carbon isotopic compositions (δ13C). The biomarker maturity indicators show that most of the Melut Basin's oils were generated in the main stage of oil generation, exhibiting a range of peak‐mature to late‐mature. The biomarker environmental indicators reveal that the shale source rocks of the Al‐Gayger and Galhak formations contributed to these oil samples. [ABSTRACT FROM AUTHOR]

Mixed ionic-electronic conductors (MIECs) play a crucial role in the landscape of energy conversion and storage technologies, with a pronounced focus on electrode materials’ application in solid oxide fuel cells (SOFCs) and proton-conducting ceramic fuel cells (PCFCs). In parallel, the emergence of semiconductor ionic materials (SIMs) has introduced a new paradigm in the field of functional materials, particularly for both electrode and electrolyte development for low-temperature, 300–550 ​°C, SOFCs, and PCFCs. This review article critically delves into the intricate mechanisms underpinning the synergistic relationship between MIECs and SIMs, with a particular emphasis on elucidating the fundamental working principles of semiconductor ionic membrane fuel cells (SIMFCs). By exploring critical facets such as ion-coupled electron transfer/transport, junction effect, energy bands alignment, and theoretical computations, it casts an illuminating spotlight on the transformative potential of MIECs, also involving triple charge conducting oxides (TCOs) in the context of SIMs and advanced fuel cells (FCs). The insights and findings articulated herein contribute substantially to the advancement of SIMs and SIMFCs by tailoring MIECs (TCOs) as promising avenues toward the emergence of high-performance SIMFCs. This scientific quest not only addresses the insistent challenges surrounding efficient charge transfer, ionic transport and power output but also unlocks the profound potential for the widespread commercialization of FC technology.