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INTRODUCTION: Few studies have considered the impact of COVID-19 on the mental health of healthcare workers (HCWs) in the Kingdom of Saudi Arabia (KSA). We estimated the prevalence and severity of psychological distress and characterized predisposing risk factors among HCWs in KSA during the COVID-19 pandemic. METHODS: We conducted a cross-sectional online survey of 1,985 HCWs from 6 hospitals across the country designated with caring for COVID-19 patients between April 16 and June 21, 2020. Our data analysis was performed using logistic regressions. Ordered logistic regressions were also performed using forward stepwise model selection to explore the effects of risk factors on psychological distress. RESULTS: The prevalence of psychological distress reported by HCWs in KSA was high, ranging from mild-moderate to severe in severity. Younger HCWs, women, those in contact with COVID-19 patients, and those who either had loved ones affected or who were themselves affected by COVID-19 were the most at-risk of psychological distress. Risk factors such as insomnia, loneliness, fear of transmission, and separation from loved ones most significantly predicted elevated levels of distress among HCWs. CONCLUSIONS: Increasing psychological distress was commonly reported by HCWs during the early months of COVID-19 pandemic in KSA. Public health policy makers and mental health professionals must give special attention to risk factors that predispose HCWs in KSA to psychological distress.

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Dronedarone biodistribution in hyperlipidemia and dronedarone metabolism in hyperlipidemia or obesity were assessed. Male Sprague-Dawley rats were given either normal standard chow with water or various high-fat or high-carbohydrate diets for 14 weeks. There was also a nonobese hyperlipidemic group given poloxamer 407 intraperitoneally. Liver and intestinal microsomes were prepared and the metabolic conversion of dronedarone to desbutyldronedarone was followed. A biodistribution study of dronedarone given orally was conducted in hyperlipidemic and control normolipidemic rats. The metabolism of dronedarone to desbutyldronedarone in control rats was consistent with substrate inhibition. However in the treatment groups, the formation of desbutyldronedarone did not follow substrate inhibition; hyperlipidemia and high-calorie diets created remarkable changes in dronedarone metabolic profiles and reduction in formation velocities. Tissue concentrations of dronedarone were much higher than in plasma. Furthermore, in hyperlipidemia, plasma and lung dronedarone concentrations were significantly higher compared to normolipidemia.

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BACKGROUND: Metformin toxicity is well known to cause lactic acidosis. Multiple cases of hypoglycemia due to isolated metformin overdose have been reported. Increased glucose consumption secondary to anaerobic metabolism has been reported as a possible explanation. CASE PRESENTATION: A 23-year-old Arabic woman took 30 g of metformin. In the emergency department, 4 hours after of the event, she was fatigued but vitally stable. During her hospitalization, she had severe lactic acidosis, hypotension corrected with fluid boluses and vasopressors, and multiple episodes of hypoglycemia (6.3 mg/dL, 38 mg/dL, and 42 mg/dL), requiring multiple 50% dextrose-water boluses. The three hypoglycemic episodes occurred coincident with severe lactic acidosis. She improved after 24 hours of continuous renal replacement therapy. CONCLUSIONS: Hypoglycemia can be induced by metformin toxicity in the absence of co-ingestants. A possible explanation of metformin-induced hypoglycemia is increased glucose consumption due to anaerobic metabolism, decreased oral intake, decreased liver glucose production, and decreased glucose absorption.

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The metabolism and biodistribution of the antiarrhythmic drug amiodarone (AM) was assessed in male Sprague-Dawley rats given either normal chow or high-fat and high-fructose diets for 14 weeks. After the feeding period, microsomes were prepared from liver and intestine, and the metabolism of AM to desethylamiodarone was determined. Intrinsic clearance (CL) was reduced by hepatic microsomes isolated from rats given high-calorie diets. In intestinal microsomes, there was no change or a small increase in metabolic rate in obese rats. A biodistribution study was also undertaken in a group of control and high-fat + high fructose-fed rats. Excess calories led to a significant increase in plasma AM compared to normal chow-fed control animals. A population pharmacokinetic analysis of AM confirmed that its oral CL was reduced. In plasma, there was a decrease in the metabolite to drug ratio. Some tissue:plasma ratios of AM in high calorie-fed rats were aligned with a decrease in plasma unbound fraction. It is concluded that the findings reinforced those of a recent report where we found decreases in expressions of enzymes involved in AM dealkylation, in showing greater exposure and lower oral CL, and generally decreases in liver microsomal metabolism of AM after high-calorie diets.

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Structural changes affecting cardiomyocyte function may contribute to the pathophysiological remodeling underlying cardiac function impairment. Recent reports have shown that endogenous nitric oxide (NO) plays an important role in this process. In order to examine the role of NO in cardiomyocyte remodeling, male rats were acclimated to room temperature (22 ± 1 °C) or cold (4 ± 1 °C) and treated with 2.25% l-arginine·HCl or 0.01% l-NAME (Nω-nitro-l-arginine methyl ester)·HCl for 45 days. Untreated groups served as controls. Right heart ventricles were routinely prepared for light microscopic examination. Stereological estimations of volume densities of cardiomyocytes, surrounding blood vessels and connective tissue, as well as the morphometric measurements of cardiomyocyte diameters were performed. Tissue sections were also analyzed for structural alterations. We observed that both l-arginine and l-NAME supplementation induced cardiomyocyte hypertrophy, regardless of ambient temperature. However, cardiomyocyte hypertrophy was associated with fibrosis and extra collagen deposition only in the l-NAME treated group. Taken together, our results suggest that NO has a modulatory role in right heart ventricle remodeling by coordinating hypertrophy of cardiomyocytes and fibrous tissue preventing cardiac fibrosis.

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OBJECTIVES: To determine the knowledge, attitude, and practice regarding evidence-based medicine (EBM) among hospital physicians in Qassim region of Saudi Arabia. METHODS: It is a cross-sectional study. A self-administered questionnaire survey was done among 288 physicians working in secondary and tertiary care centers. The study was conducted between June and September 2015. RESULTS: The overall response rate for the survey was 72%. Majority of the respondents had a positive attitude toward EBM and welcomed the concept. A total of 83% respondents stated that they used EBM in their daily practice and 93.5% agreed that practicing EBM improves patient care. There was a moderate level of awareness regarding extracting information from journals and clinical evidence databases. Although the respondents were aware and demonstrated familiarity with the process of knowledge extraction procedures to determine the best care, as many as 40% did not use them. The respondents had a poor overall understanding of the technical terms used in EBM. Among the respondents, 38.5% thought that the best way to move from opinion-based medicine to EBM was through learning the skills of EBM. The factors that positively affected physician awareness included: Academic qualification and professional title. Knowledge and attitude were affected by qualification, professional title and specialty. CONCLUSION: The attitude of most physician practitioners in this study is favorable toward EBM, but this was not correlated with knowledge and awareness. The inclusion of physician training courses in EBM concepts, technical terms and applied practice is highly recommended.

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Obesity is caused by a number of factors including heredity, lack of exercise, and poor diet. Diets rich in fats and carbohydrates are the common culprits leading to obesity. Here we studied the effects of these components on proteins involved in drug disposition. Male rats were given a normal diet (lean controls) or one rich in fats, carbohydrates (as high-fructose corn syrup equivalent) or in combination. After 14 weeks, plasma biochemistry, liver and kidney mRNA and protein for selected cytochrome P450 (CYP) and transporters were determined. Significant increases in body and perinephric fat weight were noted in each of the high-calorie diet-fed groups, with increases being higher in those given high-fat diets. Increases in the protein of CYP3A1/2 and CYP2C11 were seen in liver in high-fat-fed rats. No changes were seen for CYP1A1 at the level of mRNA or protein. For transporters, decreases in expressions of Oct1/2 and Mate1 were seen, with no change in Mdr1. The results showed similarity to earlier assessments of genetically prone rats and suggested that diet-induced obesity has the potential to lead to decreases in the clearance of drugs acting as substrates for CYP 3A, 2C11, and organic cation transport.

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A distribuiçao dos genótipos cagA, vacA e iceA foi avaliada, por meio de reaçao de polimerizaçao em cadeia, para detecçao dos diferentes alelos dos genes, em amostras de Helicobacter pylori isoladas de crianças e adultos com gastrite, úlcera péptica duodenal ou adenocarcinoma gástrico, encaminhadas para esclarecimento diagnóstico. Foi, também, investigada a associaçao entre diferentes genótipos e a distribuiçao dos mesmos de acordo com faixa etária e sexo. Observou-se predomínio de pacientes com monoinfecçao pela bactéria. A prevalência de infecçao mista variou conforme o marcador genético analisado, mas foi inferior às taxas relatadas, por outros autores, para pacientes tanto de países desenvolvidos como de países em desenvolvimento. Foi observada principalmente em crianças, o que pode estar relacionado às precárias condiçoes de higiene e saneamento da populaçao carente no Brasil. Predominância dos genótipos cagA positivo, s11m1 e iceA2 foi observada. Apenas a variante s1b foi detectada em amostras da bactéria isoladas de pacientes com monoinfecçao, refletindo, provavelmente, relaçoes históricas da populaçao brasileira com colonizadores portugueses. O genótipo cagA positivo mostrou-se fortemente associado com os alelos s1 e m1 do vacA, como observado em diferentes regioes do mundo ocidental. Os genótipos cagA positivo, s11m1 e iceA2 estavam associados com úlcera duodenal e carcinoma gástrico. Nao foi observada associaçao entre tamanho do amplicon de iceA2 e doença apresentada pelo paciente. A genotipagem de amostras da bactéria, no que se refere ao cagA e vacA, parece ser clinicamente relevante, inclusive no nosso meio, para predizer a evoluçao da infecçao. Entretanto, iceA2 nao deve ser considerado marcador molecular de patogenicidade, uma vez que os resultados obtidos em diferentes regioes do mundo sao contraditórios. A freqüência de amostras cagA positivas, bem como daquelas com genótipo s1/m1 e iceA2 aumentou com a idade, sugerindo que faixa etária pode ser importante na determinaçao da susceptibilidade à colonizaçao por amostras de...(au)

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