In-silico and in-vitro functional validation of imidazole derivatives as potential sirtuin inhibitor.

Introduction: Epigenetic enzymes can interact with a wide range of genes that actively participate in the progression or repression of a diseased condition, as they are involved in maintaining cellular homeostasis. Sirtuins are a family of Class III epigenetic modifying enzymes that regulate cellular processes by removing acetyl groups from proteins. They rely on NAD+ as a coenzyme in contrast to classical histone deacetylases (HDACs) (Class I, II, and IV) that depend on Zn+ for their activation, linking their function to cellular energy levels. There are seven mammalian sirtuin isoforms (Sirt1-7), each located in different subcellular compartments. Sirtuins have emerged as a promising target, given that inhibitors of natural and synthetic sources are highly warranted. Imidazole derivatives are often investigated as sirtuin regulators due to their ability to interact with the binding site and modulate their activity. Imidazole bestows many possible substitutions on its ring and neighboring atoms to design and synthesize derivatives with specific target selectivity and improved pharmacokinetic properties, optimizing drug development. Materials and methods: Ligand preparation, protein preparation, molecular docking, molecular dynamics, density function theory (DFT) analysis, and absorption, distribution, metabolism, and excretion (ADME) analysis were performed to understand the interacting potential and effective stability of the ligand with the protein. RT-PCR and Western blot analyses were performed to understand the impact of ligands on the gene and protein expression of Class III HDAC enzymes. Results and discussion: We evaluated the sirtuin inhibition activity of our in-house compound comprised of imidazole derivatives by docking the molecules with the protein data bank. ADME properties of all the compounds used in the study were evaluated, and it was found that all fall within the favorable range of being a potential drug. The molecule with the highest docking score was analyzed using DFT, and the specific compound was used to treat the non-small cell lung cancer (NSCLC) cell lines A549 and NCI-H460. The gene and protein expression data support the in-silico finding that the compound Ethyl 2-[5-(4-chlorophenyl)-2-methyl-1-H-Imidazole-4-yl) acetate has an inhibitory effect on nuclear sirtuins. In conclusion, targeting sirtuins is an emerging strategy to combat carcinogenesis. In this study, we establish that Ethyl 2-[5-(4-chlorophenyl)-2-methyl-1-H-Imidazole-4-yl) acetate possesses a strong inhibitory effect on nuclear sirtuins in NSCLC cell lines.

Epidemiology, Risk Factors for Gastric Cancer and Surveillance of Premalignant Gastric Lesions: A Prospective Cohort Study of Central Saudi Arabia.

(1) Background: Saudi Arabia (SA) is a country with a low incidence of gastric cancer (GC). In this study, we sought to assess the epidemiology of GC, its clinicopathological profiles, and its association with risk factors as well as to identify premalignant gastric lesions (PGL) and examine neoplastic progression. (2) Methods: This five-year prospective study screened for GC and PGL in asymptomatic Saudi patients, aged 45-75 years (n = 35,640) and living in Al Kharj, Riyadh province in central SA. Those who were positive in a high-sensitivity guaiac fecal occult blood test (HSgFOBT+) and had negative results in colonoscopy offered to undergo upper GI endoscopy (n = 1242). Factors associated with GC were examined. (3) Results: The five-year participation rate was 87% (1080/1242). The incidence rate of GC was 26.9 new cases per 100,000 population per year (9.6 new cases per year/total population at risk-35,640), and it was 8.9 cases per 1000 persons per year among the 1080 subjects with HSgFOBT+ and negative colonoscopy results. The five-year mortality rate was 67% among patients with GC (n = 48), 3.0% among participants in the gastric screening program (n = 1080) and 0.09% among the original population participating in the colorectal screening program (n = 35,640). Intestinal-type adenocarcinoma was the most frequent type (77%), with the tumor most commonly located in the antrum (41%). Overall, 334 participants had PGL, and seven of them (2.1%) showed neoplastic progression to GC during the follow-up. Factors associated with GC were age, Helicobacter pylori (HP) infection, obesity (body mass index BMI > 30), smoking, a diet of salty preserved foods, low income and a family history of GC. (4) Conclusions: The incidence of GC is low in central SA, but screening for PGL and GC among patients with HSgFOBT+ and negative colonoscopy may prevent or result in the early treatment of GC. HP eradication, normal body weight, not smoking and adhering to a healthy diet can reduce the risk of GC. The resulting data provide important input for the improvement of national guidelines.

Predictors of Cardiovascular Morbidity Among Adult Hypertensive Patients: A Cross-Sectional Study from the Kingdom of Saudi Arabia.

Background: Hypertension is a public health issue affecting over a billion people globally. 15% of the adults in the Kingdom of Saudi Arabia (KSA) are thought to have hypertension. A large proportion of them remain undiagnosed or are sub-optimally treated. Those with inadequately treated hypertension have a high risk of life-threatening cardiovascular complications such as ischemic heart disease, left ventricular hypertrophy and heart failure. This study was undertaken to elucidate the cardiovascular morbidity seen in a sample of adult hypertensive patients in Saudi Arabia and identify key demographic and clinical factors associated with cardiovascular morbidity. Methods: A multicentric cross-sectional study was conducted from November 2019 to November 2021 at three hospitals in Al-Kharj KSA. Totally, 105 adult patients with a documented history of primary hypertension for at least 5 years irrespective of treatment status presenting themselves to the study sites were included. Patients with secondary hypertension, and those without confirmed cause and duration of hypertension were excluded. Logistic regression analysis was performed to determine the factors associated with cardiovascular morbidity. Results: The study included 105 participants aged 47.75±13.46 years. 50 (47.6%) were males and 62 (59%) were not Saudis. Left Ventricular Hypertrophy, 64 (61%), diastolic dysfunction, 44 (41.9%), and retinopathy, 33 (31.4%) were the most frequently observed morbidities. Participants aged over 45, those with diabetes, or those with dyslipidemia were more likely to have cardiovascular morbidities (adjusted odds ratio (AOR)): 4.01 (1.29-12.46), p = 0.016, AOR: 6.4 (1.62-25.28), p = 0.008, and AOR: 6.71 (1.46-30.83), p = 0.014, respectively. Conclusion: Older age, the presence of comorbid diabetes mellitus, and dyslipidemia are associated with a higher likelihood of cardiovascular morbidity in hypertensive patients of Saudi Arabia.

Undergraduate health sciences students' response regarding COVID-19 pandemic in Saudi Arabia: an observational study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic represents a major health problem, and its influences may persist with emerging viral variants. The current work was to evaluate the knowledge, attitude, and learning satisfaction of health sciences students (HSS) regarding the COVID-19 pandemic. METHODS: A questionnaire-based cross-sectional study was conducted from 20 February 2021 to 20 March 2021. Participants were undergraduate HSS at Prince Sattam bin Abdulaziz University in Al Kharj, Saudi Arabia. The questionnaire has been generated and distributed via online form. The questionnaire used was based on previous studies and included demographic information and knowledge, attitudes, perception, and learning satisfaction related to the COVID-19 pandemic. RESULTS: Out of the 400 questionnaires distributed to eligible students, the current study included a total of 330 HSS (82.5% response rate) from colleges of medicine (25.5%), dentistry (11.8%), pharmacy (33.6%), and Applied Medical Sciences (29.1%) of participants. The mean scores of knowledge, attitude, and learning satisfaction attained by students were 5.63 ± 0.65 out of 6, 4.22 ± 1.01 out of 5, and 11.28 ± 2.9 out of 19, respectively. Results show an association between the knowledge score of students and their age-group and specialty-college. Students with chronic diseases reported lower attitude scores and rate of COVID-19 vaccine-willingness. Younger HSS had a higher learning satisfaction score than the older participants. CONCLUSION: Overall, participants show high knowledge level and positive attitude toward COVID-19 but fair learning satisfaction during the pandemic. Further studies are needed to improve the learning satisfaction and attitude of HSS in the future.

A 5-year evaluation of early-and late-onset sporadic colorectal cancer screening in central Saudi Arabia.

Background: The Al-Kharj colorectal cancer (CRC) screening program was implemented for five years (2017-2022) in a central urban area of Riyadh Province, Saudi Arabia, to assess the participation and impact of the program in average-risk individuals. Methods: The high sensitivity-guaiac based-fecal occult blood test (HSgFOBT) was used as a first-line investigation to identify asymptomatic patients, aged 45-75 years, requiring CRC screening using colonoscopy. The program was run in three tertiary hospitals in the area. Results: The five-year participation rate was 73% (35,640/48,897). The average age was 53 years (range 45-75), 49% were female (17,464/35,640), all were asymptomatic, and 77% had adequate bowel preparation. The HSgFOBT (+) rate was 6.3% (n = 2245), and 76% (n = 1701) of these underwent colonoscopy. The prevalence of findings were as follows: CRC, 4.8% (81/1701); advanced adenoma, 9.5% (162/1701); adenoma, 15.9% (270/1701); non-adenomatous polyps, 7.9% (135/1701); and no polyps or tumors, 25.4% (432/1701). Among participants aged 45-50 years, early onset-CRC had female predominance, while those ≥50 years with late onset-CRC were predominantly male. CRC was more prevalent in the left colon (P < 0.005). Conclusions: Approximately one-third of the participants diagnosed with CRC had early-onset CRC. Screening participation was desirable for the defined target population. Public education is necessary along with expanded colonoscopy resources to continue further citizen participation.

Ameliorative inhibition of sirtuin 6 by imidazole derivative triggers oxidative stress-mediated apoptosis associated with Nrf2/Keap1 signaling in non-small cell lung cancer cell lines.

Background: Redox homeostasis is the vital regulatory system with respect to antioxidative response and detoxification. The imbalance of redox homeostasis causes oxidative stress. Nuclear factor-erythroid 2 p45-related factor 2 (Nrf2, also called Nfe2l2)/Kelchlike ECH-associated protein 1 (Keap1) signaling is the major regulator of redox homeostasis. Nrf2/Keap1 signaling is reported to be involved in cancer cell growth and survival. A high level of Nrf2 in cancers is associated with poor prognosis, resistance to therapeutics, and rapid proliferation, framing Nrf2 as an interesting target in cancer biology. Sirtuins (SIRT1-7) are class III histone deacetylases with NAD + dependent deacetylase activity that have a remarkable impact on antioxidant and redox signaling (ARS) linked with Nrf2 deacetylation thereby increasing its transcription by epigenetic modifications which has been identified as a crucial event in cancer progression under the influence of oxidative stress in various transformed cells. SIRT6 plays an important role in the cytoprotective effect of multiple diseases, including cancer. This study aimed to inhibit SIRT6 using an imidazole derivative, Ethyl 2-[5-(4-chlorophenyl)-2-methyl-1-H-Imidazole-4-yl] acetate, to assess its impact on Nrf2/Keap1 signaling in A549 and NCI-H460 cell lines. Method: Half maximal inhibitory concentration (IC50) of Ethyl 2-[5-(4-chlorophenyl)-2-methyl-1-H-Imidazole-4-yl] acetate was fixed by cell viability assay. The changes in the gene expression of important regulators involved in this study were examined using quantitative real-time PCR (qRT-PCR) and protein expression changes were confirmed by Western blotting. The changes in the antioxidant molecules are determined by biochemical assays. Further, morphological studies were performed to observe the generation of reactive oxygen species, mitochondrial damage, and apoptosis. Results: We inhibited SIRT6 using Ethyl 2-[5-(4-chlorophenyl)-2-methyl-1-H-Imidazole-4-yl] acetate and demonstrated that SIRT6 inhibition impacts the modulation of antioxidant and redox signaling. The level of antioxidant enzymes and percentage of reactive oxygen species scavenging activity were depleted. The morphological studies showed ROS generation, mitochondrial damage, nuclear damage, and apoptosis. The molecular examination of apoptotic factors confirmed apoptotic cell death. Further, molecular studies confirmed the changes in Nrf2 and Keap1 expression during SIRT6 inhibition. Conclusion: The overall study suggests that SIRT6 inhibition by imidazole derivative disrupts Nrf2/Keap1 signaling leading to oxidative stress and apoptosis induction.

Postpartum Depression Prevalence and Associated Factors: An Observational Study in Saudi Arabia.

Background and Objectives: Postpartum depression (PPD) is a psychological disorder in women who recently gave birth. It can present as mild to severe depression. Multiple studies across the globe have used the Edinburgh Postnatal Depression Scale to reveal the factors that affect the prevalence of PPD. Results from various published studies showed a high prevalence of PPD in Saudi Arabia. The objective of this study is to investigate the major factors that increase PPD and other associated factors. Materials and Methods: An observational cross-sectional study was carried out at primary healthcare centres and military hospitals in Al Kharj. The study measured the rate of PPD among Saudi women during the postpartum period. We studied 279 women aged 19-45 (mean age 31.91, SD ± 6.45) in their postpartum period and followed up to 2 months after delivery. Results: The prevalence of PPD in our cohort was 32.8%. Multivariate logistic regression analysis showed that previous depression diagnosis (p = 0.001), lower education status (p = 0.029), unemployment (p = 0.014), and delivery disposition of C-section (p = 0.002) remained associated with an increased risk of developing PPD. Conclusions: The increasing number of Saudi women with PPD demonstrates that it is a highly prevalent condition. PPD affects not only the health of the mother but also that of her baby and other family members. Our results showed that the history of diagnosed depression, lower education status, unemployment, and delivery disposition of C-sections were independent predictors of PPD development. Raising awareness and controlling the vulnerable factors could decrease the high risk of its effects.

Validity and reliability of the Arabic version of the revised illness perception questionnaire for patients with hypertension.

Background: Hypertension is one of the leading causes of morbidity and mortality in Saudi Arabia affecting 31.4% of the population. The Illness Perception Questionnaire-Revised (IPQ-R) is a validated and reliable tool for assessing the perception of hypertension among patients. This cross-sectional study aimed to translate the Revised Illness Perception Questionnaire (IPQ-R) into Arabic and validate it among Arabic patients with hypertension from the outpatient departments of the Prince Sattam University Hospital and King Khalid Hospital (KKH) in Al-Kharj City in the Kingdom of Saudi Arabia. Methods: A bilingual panel of doctors and medical translators was assembled to translate the IPQ-R into Arabic. The questionnaire was administered to 100 adult Arabic speaking patients with clinically diagnosed primary hypertension. Patients with secondary hypertension or complications of hypertension were excluded from the study. Results: Fifty-seven patients (57%) were male and sixty-five (65%) were older than 40 years. Headache was the most common symptom of hypertension reported by 65% of the participants. The internal consistency of the questionnaire excluding the domain of 'Disease Identity' was 0.76 indicating satisfactory consistency. There were weak to moderate positive linear correlations (r = 0.003-0.561) between the domains of IPQ-R suggesting a reasonable discriminant validity among the domains. Conclusion: The Arabic version of the IPQ-R for hypertensive patients is a consistent, valid, and reliable tool to be used by researchers or clinicians for assessing knowledge, beliefs, and attitudes of Arabic speaking patients with hypertension living in Saudi Arabia.

A network-based pharmacological investigation to identify the mechanistic regulatory pathway of andrographolide against colorectal cancer.

Traditional cancer treatments have posed numerous obstacles, including toxicity, multiple drug resistance, and financial cost. On the contrary, bioactive phytochemicals used in complementary alternative medicine have recently increased attention due to their potential to modulate a wide range of molecular mechanisms with a less toxic effect. Therefore, we investigated the potential regulatory mechanisms of andrographolide to treat colorectal cancer (CRC) using a network pharmacology approach. Target genes of andrographolide were retrieved from public databases (PharmMapper, Swiss target prediction, Targetnet, STITCH, and SuperPred), while targets related to CRC were retrieved from disease databases (Genecards and DisGeNet) and expression datasets (GSE32323 and GSE8671) were retrieved from gene expression omnibus (GEO). Protein-protein interaction networks (PPI) were generated using STRING and Cytoscape, and hub genes were identified by topology analysis and MCODE. Annotation of target proteins was performed using Gene Ontology (GO) database DAVID and signaling pathway enrichment analysis using the Kyoto Encyclopedia and Genome Database (KEGG). Survival and molecular docking analysis for the hub genes revealed three genes (PDGFRA, PTGS2, and MMP9) were involved in the overall survival of CRC patients, and the top three genes with the lowest binding energy include PDGFRA, MET, and MAPK1. MET gene upregulation and PDGFRA and PTGS2 gene downregulation are associated with the survival of CRC patients, as revealed by box plots and correlation analysis. In conclusion, this study has provided the first scientific evidence to support the use of andrographolide to inhibit cellular proliferation, migration, and growth, and induce apoptosis by targeting the hub genes (PDGFRA, PTGS2, MMP9, MAPK1, and MET) involved in CRC migration and invasion.

Incidental detection of paranasal sinuses abnormalities on CT imaging of the head in Saudi adult population.

The paranasal sinuses are hollowed, air-filled cavities surrounding the nasal cavity. Many pathological processes affect the sinuses, but inflammatory conditions are the commonest, even in asymptomatic patients who undergo head imaging for other indications showing one or more abnormalities of the sinuses. Our research aims to determine the prevalence of incidental paranasal sinuses abnormalities seen among patients who undergo head CT scanning. In addition, it provides baseline information for further investigations required. The study was designed to evaluate all patients who underwent head CT scanning for any reason unrelated to paranasal sinuses abnormalities. 1849 cases were selected and retrospectively analyzed from the elective and emergency CT in the last nine months, from August 2020 to April 2021. In order to meet the inclusion criteria, indications for imaging must not be sinus-related. The study was conducted on 1849 cases who had undergone head CT scans for pathology, 1204 (65%) were male and 645 (35%) were female. Abnormalities of the sinuses were found in about 617 (33%) of all patients, with a higher rate in males (22.23%) than females (11.14%). In addition, these abnormalities were found in younger patients at a higher rate than in middle and old ages 19.74%, 7.19%, and 6.44%, respectively. Our findings revealed that the prevalence of paranasal sinuses abnormalities in asymptomatic Saudi patients was high (33%). Most of the affected sinuses were the maxillary. The male patients were more affected than females in all findings.

Psychological Wellbeing of Diabetic Individuals, Prediabetics, and Non-diabetics: A Population-Based Study in Saudi Arabia.

Background: The increased burden of diabetes affects the quality of life, including psychosocial problems. The study aims to compare the psychological well-being of individuals who are prediabetic, diabetic, or non-diabetic. Methods: A cross-sectional exploratory study was conducted from January to June 2016 (n = 1,019) in Al Kharj, Saudi Arabia. After consent and questionnaires were filled out, trained staff took blood samples followed by anthropometry. Chi-squared tests, one-way ANOVA, and multiple linear regression analyses were conducted to examine the association between diabetes classes defined by HbA1c cut-off levels set by the American Diabetes Association (three categories), individual items, and total score in general health questionnaire (GHQ). An ROC curve was plotted for the total GHQ-12 score against HbA1c. Findings: The mean GHQ score for psychological distress was significantly higher (F = 6.569, P = 0.038) in the diabetics (mean = 14.7) and the prediabetics (12.4) than in the non-diabetics (10.71). Four out of six positive GHQ items and three out of six negative GHQ items significantly differed among the three classes of diabetes. The adjusted multivariate analysis revealed that people with diabetes were most likely to report psychological distress compared to non-diabetics (unstandardized beta = 2.414; P = 0.037). The AUC examining the relationship between HBA1c and GHQ scores showed a moderate but statistically insignificant sensitivity/specificity of 0.643 (P = 0.23). Conclusion: This study demonstrates that psychological wellbeing is substantially poorer among diabetic or prediabetic individuals than non-diabetic individuals. Future longitudinal studies are required to examine a plausible causal relationship between diabetes/prediabetes and psychological distress.

Combined' Neck/Back Pain and Psychological Distress/Morbidity Among the Saudi Population: A Cross-Sectional Study.

Background: Psychological distress/morbidity is amongst the primary reason for the cause of pain at multiple sites, its progression, and recovery. Though still not very clear if physical pain in the neck or the back may predict psychological morbidities or not. Thus, we investigated the association between combined neck or back pain and psychological distress/morbidity. Methods: A cross-sectional study was conducted in Al-Kharj, Saudi Arabia, including 1,003 individuals. The questionnaire comprised of General Health Questionnaire-12 (GHQ-12) and some questions about neck and back pain. Data analysis was done using statistical software SPSS version 26.0. Results: The results of the multivariate analysis revealed a significant positive association between neck/back pain status and total GHQ score (unstandardized Beta = 2.442, P ≤ 0.0001). Having neck/back pain had almost a 2.5 times greater risk of psychological distress/morbidity. Further, females were more likely to have a higher risk of psychological distress/morbidity (unstandardized Beta = 1.334, P = 0.007) than males while adjusting for sociodemographic and clinical characteristics. Conclusion: The combination of neck and back pain was significantly associated with the Saudi population's psychological problems. Therefore, the Saudi government needs to devise high-risk strategies and allocate adequate resources to the cause so that at-risk people can be shielded from the adverse complications arising from this condition in the long run.

EGFR-Based Targeted Therapy for Colorectal Cancer-Promises and Challenges.

Colorectal carcinoma (CRC) is the most lethal and common form of cancer in the world. It was responsible for almost 881,000 cancer deaths in 2018. Approximately 25% of cases are diagnosed at advanced stages with metastasis-this poses challenges for effective surgical control and future tumor-related mortality. There are numerous diagnostic methods that can be used to reduce the risk of colorectal carcinoma. Among these, targeted nanotherapy aims to eliminate the tumor and any metastasis. Active targeting can increase the effectiveness and quantity of drugs delivered to the target site. Antibodies that target overexpressed receptors on cell surfaces and indicators are coupled with drug-loaded carriers. The major target receptors of chemotherapeutic drugs delivery include VEGFR, EGFR, FGFR, HER2, and TGF. On account of its major and diverse roles in cancer, it is important to target EGFR in particular for better tumor selection, as EGFR is overexpressed in 25 to 82% of colorectal carcinoma cases. The EGFR monoclonal immunoglobulins cetuximab/panitumumab can thus be used to treat colorectal cancer. This review examines carriers that contain cetuximab-conjugated therapeutic drugs as well as their efficacy in anticancer activities.

The association of metabolic risk factors with ischemic heart disease and heart failure in Saudi Arabia - A cross sectional study.

Background: Cardiovascular diseases (CVDs) are the leading non-communicable cause of morbidity and mortality worldwide. This study aimed at determining the association of metabolic risk factors with ischemic heart disease (IHD) and heart failure (HF). Methods: A cross-sectional study including 104 participants was conducted in three major hospitals between October 2020 and October 2021. All adult patients of either gender, over the age of 35, attending the CVD screening program at the family medicine clinics of the hospitals were included in the study. The physician collected demographic details, history of CVD, diabetes or hypertension, and current medication. Each patient's body mass index (BMI) was calculated, electrocardiogram (ECG) and blood tests were done. Univariate and multivariate logistic regressions were checked. Results: The mean age of the participants was 47.6 (SD = 13.5) years. Diabetes and hypertension had increased odds of IHD by 129 (CI = 6.20 - 2698.42, P = 0.002) and 195 (CI = 13.87 - 2743.11, P < 0.001) times, respectively. Diabetes mellitus (Chi2 = 11.93, P < 0.001) and hypertension (Chi2 = 14.74, P < 0.001) had significant association with HF. Dyslipidemia was significantly associated with IHD (OR = 12.41, CI = 1.15 - 134.12, P = 0.038) and high-grade HF (OR = 14.91 CI = 3.61 - 61.40, P < 0.001). Conclusion: Age, dyslipidemia, diabetes, hypertension, and left ventricular hypertrophy have significant association with IHD or HF among the study population.

Physicians' Perception About Use of Vitamin B12 in the Treatment or Prevention of Diabetic Neuropathy: A Cross-sectional Survey in Saudi Arabia.

BACKGROUND: Diabetic neuropathy is a condition that is prevalent among type 2 diabetic patients. Some physicians prescribe vitamin B12 or vitamin B complex supplements to improve symptoms, but studies have shown that there is little to no evidence of vitamin B12 being an effective treatment for diabetic neuropathy. Thus, this study aims to investigate local physicians' knowledge and tendency to prescribe vitamin B12 or vitamin B complex for the treatment or prevention of diabetic peripheral neuropathy. METHODS: It was a cross-sectional study, conducted between May and November of 2019, in several primary healthcare centers in different cities of Saudi Arabia. A total of 412 physicians with a minimum of three years of experience answered a three-part questionnaire on their demographic information, prescribing behavior, and knowledge of the relationship between vitamin B12 or vitamin B complex and diabetic neuropathy. RESULTS: The study found that only 42% of the physicians believed that vitamin B12 supplementation did not prevent diabetic neuropathy, while only 52.7% found it to be an ineffective treatment for this condition. Moreover, 58.7% stated that they had certainly prescribed vitamin B12 or multivitamins as a form of treatment or prevention of diabetic neuropathy. 47.8% of the patients requested a vitamin B12 prescription 1-6 times from their physicians, while 31.6% of them requested it ≥ 7 times, with 42.5% of physicians agreeing that their prescriptions of vitamin B12 had been a result of patient demand more than clinical justification. Likewise, 43% of respondents were aware that vitamin B12 levels should be tested annually. Furthermore, a higher proportion of consultants chose not to prescribe vitamin B12 to prevent or treat diabetic neuropathy than any other rank. CONCLUSION: The findings of this study indicate a tendency of unnecessarily prescribing vitamin B12 supplementation for the prevention or treatment of diabetic neuropathy as well as a lack of knowledge on the matter among doctors in primary care hospitals in Saudi Arabia. The study has also shown that there are patients who often request this prescription, adding pressure on their physicians to comply. Future studies should investigate most of the hospitals in Saudi cities and include less experienced residents and medical students.

In silico identification of potential inhibitors against main protease of SARS-CoV-2 6LU7 from Andrographis panniculata via molecular docking, binding energy calculations and molecular dynamics simulation studies.

BACKGROUND: The ongoing global outbreak of new corona virus (SARS-CoV-2) has been recognized as global public health concern since it causes high morbidity and mortality every day. Due to the rapid spreading and re-emerging, we need to find a potent drug against SARS-CoV-2. Synthetic drugs, such as hydroxychloroquine, remdisivir have paid more attention and the effects of these drugs are still under investigation, due to their severe side effects. Therefore, the aim of the present study was performed to identify the potential inhibitor against main protease SARS-CoV-2 6LU7. OBJECTIVE: In this study, RO5, ADME properties, molecular dynamic simulations and free binding energy prediction were mainly investigated. RESULTS: The molecular docking study findings revealed that andrographolide had higher binding affinity among the selected natural diterpenoids compared to co-crystal native ligand inhibitor N3. The persistent inhibition of Ki for diterpenoids was analogous. Furthermore, the simulations of molecular dynamics and free binding energy findings have shown that andrographolide possesses a large amount of dynamic properties such as stability, flexibility and binding energy. CONCLUSION: In conclusion, findings of the current study suggest that selected diterpenoids were predicted to be the significant phytonutrient-based inhibitor against SARS-CoV-2 6LU7 (Mpro). However, preclinical and clinical trials are needed for the further scientific validation before use.

Association between stuttering and psychosocial complications in Saudi Arabian individuals: A pilot study.

Background: Stuttering is a multifaceted speech disorder that affects the interpersonal communication. It has a significant psychosocial impact on individuals who stutter and on their families. Stuttering is associated with substantial psychosocial morbidity, including social or generalized anxiety, stigmatization or discrimination, impaired self-image, and poor quality of life. Psychosocial morbidity, such as the one reported among stuttering individuals, may provoke suicidal ideation that varies with gender, age, geographic region, and psychosocial reality. The present research aimed to determine the association between stuttering and psychosocial complications in Saudi Arabian individuals. Materials and Methods: This study targeted a total of 107 male patients with stuttering. Only 59 of them fulfilled both inclusion and exclusion criteria. The researchers formulated a valid questionnaire to obtain quantifiable data for analysis. The questionnaire consisted of 76 questions spanning various domains. Following the data collection, a quantitative analysis was carried out. Results: A total of 79.5% of the participants were adolescents or young adults between the ages of 16 and 26. Among them, 17.8% had a later onset of stuttering. The age of onset tended to be higher than 5 years, with over 80% of respondents reporting an age of onset in the last 5 years of their age. Among the participants, 57.6% reported a positive family history of stuttering. Conclusions: The present study reports that patients who stutter (PWS) are at a higher risk of developing negative thoughts leading to suicidal attempts due to social anxiety and depression. Therefore, future studies should be designed to establish the relationship between stuttering and suicidal thoughts in order to establish policies that may improve the quality of life of those who stutter.

Prevalence and correlates of diastolic dysfunction in patients with hypertension: a cross-sectional study from in The Kingdom of Saudi Arabia.

INTRODUCTION: diastolic dysfunction refers to impaired ventricular relaxation or filling regardless of ejection fraction and symptoms. It accounts for 8% and 25% in the hospitalized and general population, respectively. The present study was conducted to determine the prevalence and correlates of diastolic dysfunction in hypertensive patients living in Saudi Arabia. METHODS: a multicentric, cross-sectional study was conducted from February 2019 to February 2020 at King Khalid Hospital and Prince Sultan Center for Health Services, Prince Sattam Bin Abdulaziz University hospital in Al Kharj, and Al Kharj Military Industries Corporation hospital, KSA. All patients with hypertension who underwent an echocardiography were included in the study. Logistic regression analysis was performed to determine factors associated with left ventricular diastolic dysfunction (LVDD). RESULTS: the study included a total of 104 participants, where 51.9% were females and the mean age of the patients was 48.01±12.81 years. Most patients had an abnormal echocardiography finding (64.4%, n = 67). The most common abnormalities were left ventricular (LV) hypertrophy (44.2%, n = 46), and diastolic dysfunction, (35.6%, n = 37). The study revealed that age (aOR: 6.1, 95% CI 1.17-31.3; p = 0.032) and dyslipidemia (aOR: 3.45, 95% CI 1.16-10.24; p = 0.026) have significant association with LVDD in the patients with hypertension. CONCLUSION: in conclusion, diastolic dysfunction is prevalent among older hypertensive patients and those with dyslipidaemia. Age and dyslipidaemia were non-modifiable and modifiable factors associated with LVDD in hypertensive patients, respectively.

Association between prehypertension and psychological distress among adults in Saudi Arabia: A population-based survey.

BACKGROUND: Prehypertension is a precursor to hypertension status. Psychological distress has been identified earlier among hypertensives; however, there is little evidence for the presumptive relationship between prehypertension and psychological distress. OBJECTIVE: The study aimed to assess the psychological wellbeing of the Al-Kharj, Saudi Arabia population, using the General Health Questionnaire (GHQ-12) and correlating it with prehypertensive patients in the same population. METHODS: A cross-sectional analysis of the population of Al-Kharj, Saudi Arabia, was carried out between January and June of 2016. With an 85 percent response rate, a total of 1016 participants participated in the study. A multiple linear regression analysis was performed to assess the relationship between prehypertension and psychological distress. RESULTS: The findings of the adjusted analysis demonstrated that, on average prehypertensive patients were more distressed psychologically than non-hypertensive patients (unstandardized Beta regression coefficient = 3.600; P-value 0.025). Similarly, on average women were found to be more psychologically distressed than men (unstandardized Beta = 1.511, P-value 0.002). Civil workers and unemployed individuals were more psychologically distressed than employed individuals (unstandardized Beta = 1.326, P-value 0.041) while adjusting for the sociodemographic and other variables such as BMI, diabetes status, cholesterol, and smoking status. CONCLUSION: The current study shows that as compared to normotensive patients, self-rated mental wellbeing and psychological wellbeing are all considerably poorer among prehypertensive patients. To prevent individuals from having negative psychological outcomes and their long-term complications, the Government of Saudi Arabia needs to concentrate on prehypertensive, female, and unemployed individuals. Well-designed longitudinal studies, primarily in Saudi Arabia, are needed in the future to research the cause and impact of poor mental health and prehypertension.

Clinical, epidemiological, and management aspects of burn injuries in Saudi Arabia - A cross-sectional study.

BACKGROUND: Burns are a deleterious, but largely preventable health problem foisting physical, economic, social, emotional, and relational issues worldwide. METHODS: A cross-sectional study was conducted at the King Khalid Hospital and Prince Sultan Center for Health Services, and Prince Sattam Bin Abdulaziz University hospital in Al Kharj in the Kingdom of Saudi Arabia. The study included patients who presented themselves to the emergency department of the targeted hospitals with at least one documented burn injury between October 2018 and October 2019. The patients were followed from presentation to discharge. The etiology, location, severity, and options of treatment offered to them were recorded. The SPSS version 22.0 was used to analyze the data. Descriptive statistics were used to summarize the data as means, frequencies, and standard deviations. Categorical variables were compared using the Pearson's chi-square test. RESULTS: 180 patients with burn injuries were included in the study. The majority were adolescents and adults under the age of 40 (n = 171). The prevalence of first-degree burns was 12.8%, that of second-degree burns was 71.1%, and that of third-degree burns was 16.1%. The most common cause, area, and type of treatment were hot water injuries (36.1%), upper limbs (62.2%), and skin debridement respectively. CONCLUSION: Adolescents and young adults are the most frequently affected by burns while skin debridement was the most common treatment offered to the patients. In this context emergency hospital staff was required to be adequately equipped and trained.