The awareness of renal stones amongst Syrian refugees in northern Jordan.

Kidney Stone Disease (KSD) is a globally prevalent condition that can be effectively addressed through proper education. This study investigated the awareness of kidney stones among refugees residing in northern Jordan. A questionnaire was administered to 487 refugees of diverse ages and socioeconomic backgrounds. Notably, 97.3% of the respondents had not attended university, and 30.8% held unskilled jobs. Upon familiarizing themselves with the signs and symptoms of kidney stones, 16.22% of men and 12.32% of women reported experiencing such symptoms. This revealed a significant association, suggesting that men might be more susceptible to developing kidney stones than women due to a lack of medical follow-up and examination for men in the camp. However, 38.77% of individuals were uncertain whether they had kidney stones. Furthermore, 38.96% of refugees were unsure about which healthcare professional to consult when experiencing kidney stone symptoms. This report highlights a serious issue with refugees' knowledge of the symptoms, causes, and treatments for kidney stones. The results indicate that Syrian refugees face challenges in acquiring adequate disease awareness, potentially related to issues of migration and war, including low levels of education, limited income, living in camps, and difficulties accessing treatments when needed. Implementing additional policies is necessary to address these challenges among Syrian refugees; however, further studies are needed to validate these findings.

The Validation and Determination of Empagliflozin Concentration in the Presence of Grapefruit Juice Using HPLC for Pharmacokinetic Applications.

Type 2 diabetes mellitus is a multifactorial disorder whose primary manifestation usually initiates with elevated blood sugar levels. Several antidiabetic agents are used to manage type 2 diabetes mellitus, of which empagliflozin is an oral sodium-glucose co-transporter (SGLT-2) inhibitor in the kidney. This research aims to develop and validate a simple analytical method for determining empagliflozin levels in biological fluid and to further evaluate grapefruit juice's impact on empagliflozin pharmacokinetics in rats. High-Performance Liquid Chromatography (HPLC) was used to establish a simple, rapid, and accurate method for determining empagliflozin levels in rat plasma, in the presence of grapefruit juice. Four groups of rats (n = 10 rats in each) were used in the preclinical study. Group A (healthy rats) received empagliflozin alone; Group B (healthy rats) received empagliflozin with grapefruit; Group C (diabetic rats) received empagliflozin with grapefruit; and Group D (healthy, negative control) received no medication. The rats (n = 10) were given grapefruit juice instead of water for seven days before receiving the empagliflozin dose (0.16 mg/kg). Some pharmacokinetic parameters for each group were determined. The maximum plasma concentration (Cmax) and area under the curve (AUC) of empagliflozin in Group A without grapefruit intake were 730 ng/mL and 9264.6 ng × h/mL, respectively, with Tmax (2 h). In Group B, Cmax was 1907 ng/mL and AUC was 10,290.75 ng × h/mL in the presence of grapefruit, with Tmax (1 h); whereas, in Group C, the Cmax was 2936 ng/mL and AUC was 18657 ng × h/mL, with Tmax (2 h). In conclusion, our results showed that the co-administration of grapefruit with empagliflozin should be cautiously monitored and avoided, in which grapefruit elevates the plasma level of empagliflozin. This may be attributed to the inhibition of the uridine enzyme in the grapefruit by hesperidin, naringin, and flavonoid.

SNP rs11185644 in RXRA gene and SNP rs2235544 in DIO1 gene predict dosage requirements in a cross-sectional sample of hypothyroid patients.

BACKGROUND AND PURPOSE: Primary hypothyroidism due to abnormality in the thyroid gland is the most common endocrine disease The recommended starting dose of levothyroxine replacement therapy is 1.6 µg/kg. This dose however is not optimal for every patient and dose adjustments are frequently done. Genetic polymorphisms in the absorption and metabolism pathway of levothyroxine are likely to influence its dose requirements. This study aimed to study the influence of genetic polymorphisms on levothyroxine replacement requirements. METHODS: This was a cross-sectional study. Participants were recruited through a private nutrition clinic and through announcements distributed in the University of Petra in Amman, Jordan between September 2020 and February 2021. Hypothyroid patients had already been on stable doses of levothyroxine for the previous 3 months. A questionnaire was distributed to collect demographic and clinical information and a blood sample was taken for DNA extraction and clinical biochemistry analysis. rs11249460, rs2235544, rs225014, rs225015, rs3806596, rs11185644, rs4588, rs602662 were analyzed using Applied Biosystems TaqMan™ SNP Genotyping Assays on Rotor-Gene® Q and rs3064744 by direct sequencing. SPSS and Excel were used to perform analysis. RESULTS: 76 patients were studied. The equation we calculated to find predicted daily dose of levothyroxine (mcg/kg) is 3.22+ (0.348 for CT genotype of rs11185644, 0 for other genotypes) + 0.027*disease duration (years) - 0.014*age (years) - 0.434*T3 (pmol/L) levels+ (0.296 for CC genotype of rs2235544, 0 for other genotypes). CONCLUSION: SNP rs11185644 in RXRA gene and SNP rs2235544 in DIO1 affect dose requirement in hypothyroid patients and if confirmed in larger trials they can be used to individualize thyroxine starting doses.

The Role of Pharmacists and Community Pharmacies in the Screening, Knowledge, and Awareness of Diabetes Mellitus Type 2 in Jordanian People Visiting Community Pharmacies.

BACKGROUND: According to the International Diabetes Federation (IDF), diabetes is increasing exponentially worldwide and will become more prevalent than ever in the Middle East by 2045, with a 110% increase. This study aims to clarify the role of pharmacists and community pharmacies in the screening, knowledge, and awareness of Type 2 diabetes among Jordanian people who visit community pharmacies in Amman, Jordan. METHODS: Study design: This was a cross-sectional prospective study that was conducted from September to December 2021 in Amman, Jordan. Data were collected using a standardized questionnaire that was composed of multiple parts. The first part collected information on demographics, residence, educational level, and insurance status; the second part was composed of 14 knowledge assessing questions; the last part was composed of the American Diabetes Association (ADA) diabetes risk score card test. Additionally, after confirming that each participant had returned their completed sheets, participants who scored greater than 5 had their blood sugar levels checked using a finger-prick blood test. The questionnaire was administered in person by a trained researcher. Using Slovin's formula, a 95% confidence interval (CI), and a 0.05 margin of error, the sample size was determined to be 267 participants. The study included 305 participants. Descriptive and regression analyses were performed by using the Statistical Package for Social Science (SPSS) with a significance level of p < 0.05. RESULTS: A significant relationship was found between specialty (medical education) and the knowledge of risk factors for Type 2 diabetes mellitus (T2DM), (p < 0.012). In terms of knowledge, from a total of 13 correct knowledge points (13 marks for correct answers out of 14), some subjects scored slightly higher than others (n = 175; 57.4% of participants scored above 7, nearly over half of the correct answers, compared to n = 130; 42.6% scoring below 7). We found 132 individuals (44%) with risk scores of five or above (high risk for developing T2DM according to ADA). Smokers comprised n = 138, 45%, and nonsmokers comprised n = 148, 48%. Although 50.5% of the participants (n = 154) held a bachelor's, master's, or doctorate degree, these degrees did not improve the participants' overall general knowledge levels. The association was tested using chi-squared analysis, but no significance was found. CONCLUSIONS: Random visitors to Jordanian community pharmacies are expected to benefit from awareness and educational campaigns. These test results revealed a lack of knowledge, indicating the need for education to dispel myths and highlight the serious risks associated with T2DM. The study discovered that participants' understanding of diabetes disease prevention through lifestyle and dietary changes was inadequate. A specialist-led educational program may increase knowledge among visitors who participate. In order to prevent the spread of diabetes, more campaigns and health-promoting and prevention educational activities are required.

Transcriptional profiling of drug-induced liver injury biomarkers: association of hepatic Srebf1/Pparα signaling and crosstalk of thrombin, alcohol dehydrogenase, MDR and DNA damage regulators.

Cell stress transcribing genes provide a diverse platform of molecular mediators that vary in response to toxicity. Common drug-induced liver injury (DILI) biomarkers are usually expressed in mild toxicity and limited to confirming it rather than categorizing its intensity. Thus, new parametric biomarkers are needed to be explored. Classifying the toxicological response based on the dose-level and severity of stimuli will aid in the evaluation and approach against drug exposure. The present research explored the involvement of gene expression of potential biomarkers as a severity-specific hallmark in different acetaminophen (APAP)-induced hepatotoxicity levels in C57BL/6 mice. The differentially expressed genes were annotated and analyzed using bioinformatics tools to predict canonical pathways altered by DILI. The results revealed alteration in genes encoding for antioxidant enhancement; Slc7a11, bile efflux; MDR4, fatty acid metabolism and transcriptional factors namely Srebf1 and Pparα. Potential APAP toxicity biomarkers included Adh1 and thrombin, and other DNA damage and stress chaperones which were changed at least fourfold between control and the three tested severity models. The current investigation demonstrates a dose-mediated association of several hallmark genes in APAP-induced liver damage and addressed the involvement of uncommonly studied molecular responses. Such biomarkers can be further developed into predictive models, translated for risk assessment against drug exposure and guide in building theragnostic targets.

Pathway Analysis of Patients with Severe Acute Respiratory Syndrome.

BACKGROUND: Coronaviruses are emerging threats for human health, as demonstrated by the ongoing coronavirus disease 2019 (COVID-19) pandemic that is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is closely related to SARS-CoV-1, which was the cause of the 2002-2004 SARS outbreak, but SARS-CoV-1 has been the subject of a relatively limited number of studies. Understanding the potential pathways and molecular targets of SARS-CoV-1 will contribute to current drug repurposing strategies by helping to predict potential drug-disease associations. METHODS: A microarray dataset, GSE1739, of 10 SARS patients and 4 healthy controls was downloaded from NCBI's GEO repository, and differential expression was identified using NCBI's GEO2R software. Pathway and enrichment analysis of the differentially expressed genes was carried out using Ingenuity Pathway Analysis and Gene Set Enrichment Analysis, respectively. RESULTS: Our findings show that the drugs dexamethasone, filgrastim, interferon alfacon-1, and levodopa were among the most significant upstream regulators of differential gene expression in SARS patients, while neutrophil degranulation was the most significantly enriched pathway. CONCLUSION: An enhanced understanding of the pathways and molecular targets of SARS-CoV-1 in humans will contribute to current and future drug repurposing strategies, which are an essential tool to combat rapidly emerging health threats.

Pathway analysis of smoking-induced changes in buccal mucosal gene expression.

Background: Cigarette smoking is the leading preventable cause of death worldwide, and it is the most common cause of oral cancers. This study aims to provide a deeper understanding of the molecular pathways in the oral cavity that are altered by exposure to cigarette smoke. Methods: The gene expression dataset (accession number GSE8987, GPL96) of buccal mucosa samples from smokers (n = 5) and never smokers (n = 5) was downloaded from The National Center for Biotechnology Information's (NCBI) Gene Expression Omnibus (GEO) repository. Differential expression was ascertained via NCBI's GEO2R software, and Ingenuity Pathway Analysis (IPA) software was used to perform a pathway analysis. Results: A total of 459 genes were found to be significantly differentially expressed in smoker buccal mucosa (p < 0.05). A total of 261 genes were over-expressed while 198 genes were under-expressed. The top canonical pathways predicted by IPA were nitric oxide and reactive oxygen production at macrophages, macrophages/fibroblasts and endothelial cells in rheumatoid arthritis, and thyroid cancer pathways. The IPA upstream analysis predicted that the TP53, APP, SMAD3, and TNF proteins as well as dexamethasone drug would be top transcriptional regulators. Conclusions: IPA highlighted critical pathways of carcinogenesis, mainly nitric oxide and reactive oxygen production at macrophages, and confirmed widespread injury in the buccal mucosa due to exposure to cigarette smoke. Our findings suggest that cigarette smoking significantly impacts gene pathways in the buccal mucosa and may highlight potential targets for treating the effects of cigarette smoking. Supplementary Information: The online version contains supplementary material available at 10.1186/s43042-022-00268-y.

A Single Nucleotide Polymorphism (rs4236480) in TRPV5 Calcium Channel Gene Is Associated with Stone Multiplicity in Calcium Nephrolithiasis Patients.

Nephrolithiasis is characterized by calcification of stones in the kidneys from an unknown cause. Animal models demonstrated the functional roles of the transient receptor potential vanilloid member 5 (TRPV5) gene in calcium renal reabsorption and hypercalciuria. Therefore, TRPV5 was suggested to be involved in calcium homeostasis. However, whether genetic polymorphisms of TRPV5 are associated with kidney stone multiplicity or recurrence is unclear. In this study, 365 Taiwanese kidney-stone patients were recruited. Both biochemical data and DNA samples were collected. Genotyping was performed by a TaqMan allelic discrimination assay. We found that a TRPV5 polymorphism (rs4236480) was observed to be associated with stone multiplicity of calcium nephrolithiasis, as the risk of stone multiplicity was higher in patients with the TT+CT genotype than in patients with the CC genotype (p = 0.0271). In summary, despite the complexity of nephrolithiasis and the potential association of numerous calcium homeostatic absorption/reabsorption factors, TRPV5 plays an important role in the pathogenesis of calcium nephrolithiasis.

miRTarBase update 2014: an information resource for experimentally validated miRNA-target interactions.

MicroRNAs (miRNAs) are small non-coding RNA molecules capable of negatively regulating gene expression to control many cellular mechanisms. The miRTarBase database (http://mirtarbase.mbc.nctu.edu.tw/) provides the most current and comprehensive information of experimentally validated miRNA-target interactions. The database was launched in 2010 with data sources for >100 published studies in the identification of miRNA targets, molecular networks of miRNA targets and systems biology, and the current release (2013, version 4) includes significant expansions and enhancements over the initial release (2010, version 1). This article reports the current status of and recent improvements to the database, including (i) a 14-fold increase to miRNA-target interaction entries, (ii) a miRNA-target network, (iii) expression profile of miRNA and its target gene, (iv) miRNA target-associated diseases and (v) additional utilities including an upgrade reminder and an error reporting/user feedback system.