Ethnicity and Response to Drug Therapy

Hypercholesterolemia is a complex disorder presenting in different forms, including the familial form (FH), with varying underlying aetiology, and contributing substantially to coronary artery disease. Particularly, the FH underlies monogenic changes in genes involved in cholesterol synthesis and transport, including the low density lipoprotein receptor, proprotein convertase sublitisin/kexin type 9 and apolipoprotein B. However, hyperlipidemia is largely a complex interaction of changes in multiple genes with environmental factors, such as diet, overweight and obesity that are controllable by adopting healthy eating habits and exercise, which may vary by ethnicity. Diet alone is often not adequate to achieve the desired lipid lowering effect in individuals harbouring very high cholesterol levels, necessitating the use of lipid lowering medication or other forms of therapy. Antilipidemic drugs fall into (a) bile acid sequestrants (b) cholesterol absorption inhibitors, (c) 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, (d) fibric acid derivatives (e) proprotein convertase subtilisin/kexin type 9 inhibitors, (f) miscellaneous agents and (g) drug combinations. Mutations in their various metabolizing enzymes, particularly the cytochrome P450 family, often lead to partially/non-functional, or even rapid metabolizing phenotypes, triggering great variations in the way individuals respond to drug therapy, which in turn depends on ethnicity. This may produce unexpected outcomes such as therapeutic failure, adverse side effects and toxicity in individuals of different ethnic origin. Hence, in-depth information of the impact of ethnicity on these relationships has the huge potential of achieving optimal quality use of drugs as well as improving the efficacy and safety of antilipidemic therapeutic agents

Appraisal survey of the knowledge, attitudes, and behaviors of Jordanian society toward diet and nutrition during COVID-19 era

Introduction: This study aimed to evaluate the knowledge, attitudes, and behavior (KAB) of the Jordanian society toward nutrition and diet during the COVID-19 era. Design and methods: This study is an observational, cross-sectional study using a structured, validated, reproducible, self-administered online Arabic questionnaire. KAB of the study participants was assessed via a web-based, structured, validated, reproducible Arabic questionnaire. The tool for the assessment of the KAB was composed of 33-closed-ended multi-answer questions. Results: A total of 672 people were surveyed, 70.2% were between 18 and 34, and 69.5% were females. Participants have paid little attention to the healthfulness of their diet in the last year. The majority of participant’s attitudes towards using different approaches to manage weight in the next year were: eating smaller portions for weight management, tracking to maximize the amount of time of physical activity, and substituting lower-calorie foods for full-calorie alternatives. Only tenth of participants utilize the time to perform physical activity. The majority made changes to their diet and exercise, and strictly follow commitment in connection with planning for the following year. Conclusions: Educators, legislative, food manufacturers, household heads, and policymakers are called upon to improve Jordanians’ KAB on nutrition and diet. Furthermore, Jordanian nutrition and diet behavior can be invested to improve the dietary interventions designed by nutrition and dietetics professionals

Clinical, genetic, and functional characterization of the glycine receptor β-subunit A455P variant in a family affected by hyperekplexia syndrome

Hyperekplexia is a rare neurological disorder characterized by exaggerated startle response affecting newborns with the hallmark characteristics of hypertonia, apnea, and noise or touch-induced non-epileptic seizures. The genetic causes of the disease can vary and several associated genes and mutations have been reported to affect glycine receptors (GlyRs); however, the mechanistic links between GlyRs and hyperekplexia are not yet understood. Here, we describe a patient with hyperekplexia from a consanguineous family. Extensive genetic screening using exome sequencing coupled with autozygome analysis and iterative filtering supplemented by in silico prediction identified that the patient carries the homozygous missense mutation A455P in GLRB, which encodes the GlyR β-subunit. To unravel the physiological and molecular effects of A455P on GlyRs, we used electrophysiology in a heterologous system as well as immunocytochemistry, confocal microscopy, and cellular biochemistry. We found a reduction in glycine-evoked currents in N2A cells expressing the mutation compared to wild type cells. Western blot analysis also revealed a reduced amount of GlyR β protein both in cell lysates and isolated membrane fractions. In line with the above observations, co-immunoprecipitation assays suggested that the GlyR α1-subunit retained co-assembly with βA455P to form membrane-bound heteromeric receptors. Finally, structural modelling showed that the A455P mutation affected the interaction between the GlyR β-subunit transmembrane domain 4 and the other helices of the subunit. Taken together, our study identifies and validates a novel loss-of-function mutation in GlyRs whose pathogenicity is likely to cause hyperekplexia in affected individuals

Cross-cultural comparison of mental illness stigma and help-seeking attitudes: a multinational population-based study from 16 Arab countries and 10,036 individuals

BackgroundThere is evidence that culture deeply affects beliefs about mental illnesses\u27 causes, treatment, and help-seeking. We aimed to explore and compare knowledge, attitudes toward mental illness and help-seeking, causal attributions, and help-seeking recommendations for mental illnesses across various Arab countries and investigate factors related to attitudes toward help-seeking.MethodsWe carried out a multinational cross-sectional study using online self-administered surveys in the Arabic language from June to November 2021 across 16 Arab countries among participants from the general public.ResultsMore than one in four individuals exhibited stigmatizing attitudes towards mental illness (26.5%), had poor knowledge (31.7%), and hold negative attitudes toward help-seeking (28.0%). ANOVA tests revealed a significant difference between countries regarding attitudes (F = 194.8, p \u3c .001), knowledge (F = 88.7, p \u3c .001), and help-seeking attitudes (F = 32.4, p \u3c .001). Three multivariate regression analysis models were performed for overall sample, as well as Palestinian and Sudanese samples that displayed the lowest and highest ATSPPH-SF scores, respectively. In the overall sample, being female, older, having higher knowledge and more positive attitudes toward mental illness, and endorsing biomedical and psychosocial causations were associated with more favorable help-seeking attitudes; whereas having a family psychiatric history and endorsing religious/supernatural causations were associated with more negative help-seeking attitudes. The same results have been found in the Palestinian sample, while only stigma dimensions helped predict help-seeking attitudes in Sudanese participants.ConclusionInterventions aiming at improving help-seeking attitudes and behaviors and promoting early access to care need to be culturally tailored, and congruent with public beliefs about mental illnesses and their causations

Clinical Characteristics of Non-Intensive Care Unit COVID-19 Patients in Saudi Arabia: A Descriptive Cross-sectional Study

Introduction: The ongoing pandemic of the coronavirus disease 2019 (COVID-19) is a global health concern. It has affected more than 5 million patients worldwide and resulted in an alarming number of deaths globally. While clinical characteristics have been reported elsewhere, data from our region is scarce. We investigated the clinical characteristics of mild to moderate cases of COVID-19 in Saudi Arabia. Methods: This is a descriptive, cross-sectional study. Data of 401 confirmed COVID-19 patients were collected from 22 April 2020 to 21 May 2020 at five tertiary care hospitals in Riyadh, Saudi Arabia. The patients were divided into four groups according to age, Group 1: 0-60 years; and their clinical symptoms were compared. Results: The median (IQR) age in years was 10.5 (1.5-16) in group I, 34 (29-41) in group II, 53 (51-56) in group III, and 66 (61-76) in group IV. Most patients were male (80%, n = 322) and of Arabian or Asian descent. The median length of stay in the hospital was 10 (8-17) days (range 3-42 days). The most common symptoms were cough (53.6%), fever (36.2%), fatigue (26.4%), dyspnea (21.9%), and sore throat (21.9%). Hypertension was the most common underlying comorbidity (14.7%), followed by obesity (11.5%), and diabetes (10%). Hypertensive patients were less likely to present with shortness of breath, cough, sputum, diarrhea, and fever. Conclusion: There was no significant difference in the symptoms among different age groups and comorbidities were mostly seen in the older age group. Interestingly, hypertensive patients were found to have milder symptoms and a shorter length of stay. Further larger collaborative national studies are required to effectively understand clinical characteristics in our part of the world to efficiently manage and control the spread of SARS-CoV-2

Clinical, epidemiological, and laboratory characteristics of mild-to-moderate COVID-19 patients in Saudi Arabia: an observational cohort study

Background Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) emerged from China in December 2019 and has presented as a substantial and serious threat to global health. We aimed to describe the clinical, epidemiological, and laboratory findings of patients in Saudi Arabia infected with SARS-CoV-2 to direct us in helping prevent and treat coronavirus disease 2019 (COVID-19) across Saudi Arabia and around the world. Materials and methods Clinical, epidemiological, laboratory, and radiological characteristics, treatment, and outcomes of pediatric and adult patients in five hospitals in Riyadh, Saudi Arabia, were surveyed in this study. Results 401 patients (mean age 38.16 ± 13.43 years) were identified to be SARS-CoV-2 positive and 80% of cases were male. 160 patients had moderate severity and 241 were mild in severity. The most common signs and symptoms at presentation were cough, fever, fatigue, and shortness of breath. Neutrophil and lymphocyte counts, aspartate aminotransferase, C-reactive protein, and ferritin were higher in the COVID-19 moderate severity patient group. Mild severity patients spent a shorter duration hospitalized and had slightly higher percentages of abnormal CT scans and X-ray imaging. Conclusions This study provides an understanding of the features of non-ICU COVID-19 patients in Saudi Arabia. Further national collaborative studies are needed to streamline screening and treatment procedures for COVID-19

Genetic Insights into the Middle East Respiratory Syndrome Coronavirus Infection among Saudi People

Background: The Middle East respiratory syndrome coronavirus (MERS-CoV) was isolated for the first time in Saudi Arabia from a patient suffering from atypical pneumonia. The Saudi Genome database was built by King Abdulaziz Medical City via the next-generation sequencing of 7000 candidates. Method: A large list of point mutations were reported in the region of the dipeptidyl peptidase 4 (DPP4) gene. The DPP4 amino acid residues correlated to MERS-CoV entry and the site of activity of DPP4 inhibitors was investigated. We retrieved the SNPs (Single-Nucleotide Polymorphism) with a variation frequency of >0.05. Results: SNP 2:162,890,175 and SNP 2:162,891,848 in the intronic region were located within 50 bp of amino acid residues responsible for MERS-CoV entry, amino acids 259–296 and 205–258, respectively. The variation frequency of SNP 2:162,890,175 was 2321 out of 2379 screened individuals. Moreover, mutation of SNP 2:162,891,848, which is located near amino acid residues E205 and E206 (crucial for the activity of DPP4 inhibitors), occurred in 76 out of 2379 screened individuals. Conclusions: Our study shows high variation frequency in the DPP4 region reported in the Saudi Genome database. The identified SNPs are of high significance for MERS-CoV infection in better understanding disease pathogenesis

Sitagliptin Mitigates Diabetic Nephropathy in a Rat Model of Streptozotocin-Induced Type 2 Diabetes: Possible Role of PTP1B/JAK-STAT Pathway

Diabetic nephropathy (DN) is a microvascular complication of diabetes mellitus. This study examined the therapeutic effects of sitagliptin, a dipeptidyl peptidase inhibitor, on DN and explored the underlying mechanism. Male Wistar albino rats (n = 12) were intraperitoneally administered a single dose of streptozotocin (30 mg/kg) to induce diabetes. Streptozotocin-treated and untreated rats (n = 12) were further divided into normal control, normal sitagliptin-treated control, diabetic control, and sitagliptin-treated diabetic groups (n = 6 in each). The normal and diabetic control groups received normal saline, whereas the sitagliptin-treated control and diabetic groups received sitagliptin (100 mg/kg, p.o.). We assessed the serum levels of DN and inflammatory biomarkers. Protein tyrosine phosphatase 1 B (PTP1B), phosphorylated Janus kinase 2 (P-JAK2), and phosphorylated signal transducer activator of transcription (P-STAT3) levels in kidney tissues were assessed using Western blotting, and kidney sections were examined histologically. Sitagliptin reduced DN and inflammatory biomarkers and the expression of PTP1B, p-JAK2, and p-STAT3 (p < 0.001) and improved streptozotocin-induced histological changes in the kidney. These results demonstrate that sitagliptin ameliorates inflammation by inhibiting DPP-4 and consequently modulating the PTP1B-related JAK/STAT axis, leading to the alleviation of DN

A Novel <i>GEMIN4</i> Variant in a Consanguineous Family Leads to Neurodevelopmental Impairment with Severe Microcephaly, Spastic Quadriplegia, Epilepsy, and Cataracts

Pathogenic variants in GEMIN4 contribute to a hereditary disorder characterized by neurodevelopmental features, microcephaly, cataracts, and renal abnormalities (known as NEDMCR). To date, only two homoallelic variations have been linked to the disease. Moreover, clinical features associated with the variants have not been fully elucidated yet. Here, we identified a novel variant in GEMIN4 (NM_015721:exon2:c.440A>G:p.His147Arg) in two siblings from a consanguineous Saudi family by using whole exome sequencing followed by Sanger sequence verification. We comprehensively investigated the patients’ clinical features, including brain imaging and electroencephalogram findings, and compared their phenotypic characteristics with those of previously reported cases. In silico prediction and structural modeling support that the p.His147Arg variant is pathogenic

Arab Women Adherence to the Mediterranean Diet and Insomnia

Background and objective: Sleeping difficulties affect the overall health, nutrition, and wellbeing. The Mediterranean diet has proven effective in improving the quality of life and overall health of people of all ages. Therefore, this study aimed to determine whether adherence to the Mediterranean diet (MD) is linked to reduced insomnia in Arabic-speaking female adults in Jordan. Materials and Methods: A self-administered, cross-sectional survey was used to detect the relationship between MD and sleep quality in Arabic-speaking female adults. Data were collected from 917 Arabic-speaking female participants of 14 Arab nationalities in Jordan between March and May 2021 via social media. All participants answered the whole questionnaire, including questions on sociodemographic aspects, Mediterranean diet adherence, sleeping habits measured with the Athens Insomnia Scale (AIS), and lifestyle components such as smoking and dietary patterns. Results: The mean age of the 917 Arabic-speaking female participants was 36 ± 10 years. Most participants were unemployed (85%) single females (64%) with an undergraduate degree (74%). Most of them (86%) were non-smokers. More than half of the participants were Jordanians (57%). The BMI was normal for 52% of the participants, whereas 26% of them were overweight, and 12% were obese. One-way ANCOVA showed a statistically significant difference between MD adherence score categories and AIS, F (2, 914) = 3.36, p = 0.015. Among the MD adherence score categories, we found that between groups, MD scores above or equal to 10 were associated with a statistically significant difference in AIS. Cohen’s value was calculated for the three MD score categories and indicated a ‘small’ effect size association between all adherence scores of the MD categories and AIS. Conclusions: In conclusion, our findings provide preliminary evidence that participants’ adherence to the MD was significantly associated with better sleep and reduced insomnia symptoms, highlighting the need for further research