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Background: The burden of macro- and microvascular complications in patients with Type 2 diabetes mellitus (T2DM) is substantial in Middle East countries. The current study assessed the healthcare resource utilization (HCRU) and costs related to cardiovascular and renal complications among patients with T2DM., Methodology: This non-interventional, longitudinal, retrospective, cohort study collected secondary data from three insurance claims databases across Kingdom of Saudi Arabia (KSA) of patients diagnosed with T2DM. The study included adult patients aged ≥18 years diagnosed with first cardiovascular disease (CVD) during index time period and at least one T2DM claim anytime during the study time period. The primary analyses were conducted per database, stratified by three cohorts; patients with at least one claim every six months during the 1-year pre-index and 1-year post-index period (cohort 1), patients with at least one claim every six months during the 1-year pre-index, and two years post-index period (cohort 2) and patients with at least one claim every six months during the 1-year pre-index and 3-year post-index period (cohort 3). For each Payer database, demographics, CVD subgroups, HCRU, and costs were analysed. Descriptive statistics were used to analyse the data., Results: The study sample comprised of 72-78% male and 22-28% female T2DM patients with CVD and renal complications. Patients in the age group of 35-65 years or above contributed to the significant disease burden. Nearly 68 to 80% of T2DM patients developed one CVD event, and 19 to 31% of patients developed multiple CVD events during the follow-up period. For most patients with comorbid CVD and renal disease, the average HCRU cost for post‑index periods was higher compared to 1-year pre-index period across the different visit types and activities., Conclusion: The study findings elucidates the need for early initiation of therapies that would reduce the long-term cardiovascular and renal outcomes and the associated costs in patients with T2DM., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Hepatic steatosis (HS) negatively impacts transplant outcomes in living liver donors. To date, liver biopsy is preferred for HS evaluation. This study aims to evaluate the measurement of controlled attenuation parameter (CAP) as a diagnostic tool of HS in living liver donors., Methods: Candidates recruited to this study, conducted from April 2016 to February 2020, were potential donors who had undergone transient elastography using Fibroscan® and CAP measurements at liver segments VI and VII, followed by liver biopsy. The HS grades from liver biopsy were classified as S0 (<5%), S1 (5-33%), S2 (33-66%), and S3 (>66%). For CAP, they were S0 (≤218dB/m), S1 (218-249dB/m)), S2 (250-305dB/m)), and S3 (>305dB/m)). The CAP measurements were compared with the liver biopsy results., Results: Of the 150 potential donors [male, 73.3%; mean age, 30.0±7.0 years; body mass index (BMI), 24.7±3.5kg/m2], 92 (61.3%) had no or mild HS, while 58 (38.7%) and 10% had moderate to severe HS based on CAP and liver biopsy, respectively. Subjects with moderate to severe HS per CAP were mostly males (0.014), and had higher BMI (p = .006), alanine aminotransferase (ALT) (.001), gamma-glutamyl transferase (.026), and high-density lipoprotein (.008). On multivariate analysis, high ALT (OR, 1.051; 95% CI, 1.016-1.087; p = .004) was a predictor of significant HS. The sensitivity, specificity, positive and negative predictive values of CAP to detect significant HS were 93.3%, 67.4, 24.1%, and 98.9%, respectively., Conclusion: The high sensitivity and negative predictive values of CAP make it a good screening test to exclude significant HS in potential living liver donors which, in turn, can help avoid unnecessary liver biopsies., Competing Interests: The authors have declared that no competing interests exist.

In the present study, antibiotic residues were detected in milk samples collected from the dairy herds located in Karnataka, India, by microbiological assay. Subsequently, the detected antibiotics were identified as azithromycin and tetracycline, by high-performance liquid chromatography, further both the antibiotics detected in the cow milk samples were found to be at high concentration (9708.7 and 5460 μg kg-1, respectively). We then investigated the effects of temperature and pH on the stabilities of azithromycin and tetracycline to determine the degradation rate constant k using first-order kinetic equation. Results indicated that significant reduction in stability and antibacterial activity of azithromycin solution when subjected to 70 and 100°C for 24 h. While stability of tetracycline was significantly reduced when subjected to 70 and 100°C for 24 h. However no significant reduction in antibacterial activity of tetracycline was observed at respective temperatures when compared with that of control. In addition, the stabilities of azithromycin and tetracycline were found to be decreased in acidic pH 4-5. The results of the present study revealed the high risk of contamination of milk sample with veterinary antibiotics and also demonstrated the effect of temperature and pH on stability of antibiotics. Therefore the study suggest that the qualitative and quantitative screening of milk for the presence of antibiotics need to be strictly performed to ensure safe drinking milk for consumers., Competing Interests: The authors have declared that no competing interests exist.

Background: Prior acute coronary syndrome (ACS) registries in Saudi Arabia might not have accurately described the true demographics and cardiac care of patients with ACS. We aimed to evaluate the clinical characteristics, management, and outcomes of a representative sample of patients with acute myocardial infarction (AMI) in Saudi Arabia., Methods: We conducted a 1-month snap-shot, prospective, multi-center registry study in 50 hospitals from various health care sectors in Saudi Arabia. We followed patients for 1 month and 1 year after hospital discharge. Patients with AMI included those with or without ST-segment elevation (STEMI or NSTEMI, respectively). This program survey will be repeated every 5 years., Results: Between May 2015 and January 2017, we enrolled 2233 patients with ACS (mean age was 56 [standard deviation = 13] years; 55.6% were Saudi citizens, 85.7% were men, and 65.9% had STEMI). Coronary artery disease risk factors were high; 52.7% had diabetes mellitus and 51.2% had hypertension. Emergency Medical Services (EMS) was utilized in only 5.2% of cases. Revascularization for patients with STEMI included thrombolytic therapy (29%), primary percutaneous coronary intervention (PCI); (42.5%), neither (29%), or a pharmaco-invasive approach (3%). Non-Saudis with STEMI were less likely to undergo primary PCI compared to Saudis (35.8% vs. 48.7%; respectively, p <0.001), and women were less likely than men to achieve a door-to-balloon time of <90 min (42% vs. 65%; respectively, p = 0.003). Around half of the patients with NSTEMI did not undergo a coronary angiogram. All-cause mortality rates were 4%, 5.8%, and 8.1%, in-hospital, at 1 month, and at 1 year, respectively. These rates were significantly higher in women than in men., Conclusions: There is an urgent need for primary prevention programs, improving the EMS infrastructure and utilization, and establishing organized ACS network programs. AMI care needs further improvement, particularly for women and non-Saudis., Competing Interests: Astra Zeneca and Algorithm pharmaceutical companies are the commercial funders of the (STARS-1 Program). This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Androgen receptor (AR) is commonly expressed in both the epithelium of normal mammary glands and in breast cancers. AR expression in breast cancers is independent of estrogen receptor alpha (ERα) status and is frequently associated with overexpression of the ERBB2 oncogene. AR signaling effects on breast cancer progression may depend on ERα and ERBB2 status. Up to 30% of human breast cancers are driven by overactive ERBB2 signaling and it is not clear whether AR expression affects any steps of tumor progression in this cohort of patients. To test this, we generated mammary specific Ar depleted mice (MARKO) by combining the floxed allele of Ar with the MMTV-cre transgene on an MMTV-NeuNT background and compared them to littermate MMTV-NeuNT, Ar(fl)/+ control females. Heterozygous MARKO females displayed reduced levels of AR in mammary glands with mosaic AR expression in ductal epithelium. The loss of AR dramatically accelerated the onset of MMTV-NeuNT tumors in female MARKO mice. In this report we show that accelerated MMTV-NeuNT-dependent tumorigenesis is due specifically to the loss of AR, as hormonal levels, estrogen and progesterone receptors expression, and MMTV-NeuNT expression were similar between MARKO and control groups. MMTV-NeuNT induced tumors in both cohorts displayed distinct loss of AR in addition to ERα, PR, and the pioneer factor FOXA1. Erbb3 mRNA levels were significantly elevated in tumors in comparison to normal mammary glands. Thus the loss of AR in mouse mammary epithelium accelerates malignant transformation rather than the rate of tumorigenesis.

Background: Despite increasing interest in possible differences in virulence and transmissibility between different genotypes of M. tuberculosis, very little is known about how genotypes within a population change over decades, or about relationships to HIV infection., Methods and Principal Findings: In a population-based study in rural Malawi we have examined smears and cultures from tuberculosis patients over a 20-year period using spoligotyping. Isolates were grouped into spoligotype families and lineages following previously published criteria. Time trends, HIV status, drug resistance and outcome were examined by spoligotype family and lineage. In addition, transmissibility was examined among pairs of cases with known epidemiological contact by assessing the proportion of transmissions confirmed for each lineage, on the basis of IS6110 RFLP similarity of the M tuberculosis strains. 760 spoligotypes were obtained from smears from 518 patients from 1986-2002, and 377 spoligotypes from cultures from 347 patients from 2005-2008. There was good consistency in patients with multiple specimens. Among 781 patients with first episode tuberculosis, the majority (76%) had Lineage 4 ("European/American") strains; 9% had Lineage 3 ("East-African/Indian"); 8% Lineage 1 ("Indo-Oceanic"); and 2% Lineage 2 ("East-Asian"); others unclassifiable. Over time the proportion of Lineage 4 decreased from >90% to 60%, with an increase in the other 3 lineages (p<0.001). Lineage 1 strains were more common in those with HIV infection, even after adjusting for age, sex and year. There were no associations with drug resistance or outcome, and no differences by lineage in the proportion of pairs in which transmission was confirmed., Conclusions: This is the first study to describe long term trends in the four M. tuberculosis lineages in a population. Lineage 4 has probably been longstanding in this population, with relatively recent introductions and spread of Lineages1-3, perhaps influenced by the HIV epidemic.