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Abstract Classification of pathogenic E. coli has been focused either in mammalian host or infection site, which offers limited resolution. This review presents a comprehensive framework for classifying all E. coli branches within a single, unifying figure. This approach integrates established methods based on virulence factors, serotypes and clinical syndromes, offering a more nuanced and informative perspective on E. coli pathogenicity. The presence of the LEE island in pathogenic E. coli is a key genetic marker differentiating EHEC from STEC strains. The coexistence of stx and eae genes within the bacterial genome is a primary characteristic used to distinguish STEC from other pathogenic E. coli strains. The presence of the inv plasmid, Afa/Dr adhesins, CFA-CS-LT-ST and EAST1 are key distinguishing features for identifying pathogenic E. coli strains belonging to EIEC, DAEC, ETEC and EAEC pathotypes respectively. Food microbiological criteria differentiate pathogenic E. coli in food matrices. ‘Zero-tolerance’ applies to most ready-to-eat (RTE) foods due to high illness risk. Non-RTE foods' roles may allow limited E. coli presence, which expose consumers to potential risk; particularly from the concerning Shiga toxin-producing E. coli (STEC) strains, which can lead to life-threatening complications in humans, including haemolytic uremic syndrome (HUS) and even death in susceptible individuals. These findings suggest that decision-makers should consider incorporating the separate detection of STEC serotypes into food microbiological criteria, in addition to existing enumeration methods. Contamination of STEC is mainly linked to food consumption, therefore, outbreaks of E. coli STEC has been reviewed here and showed a link also to water as a potential contamination route. Since their discovery in 1982, over 39,787 STEC cases associated with 1,343 outbreaks have been documented. The majority of these outbreaks occurred in the Americas, followed by Europe, Asia and Africa. The most common serotypes identified among the outbreaks were O157, the ‘Big Six’ (O26, O45, O103, O111, O121, and O145), and other serotypes such as O55, O80, O101, O104, O116, O165, O174 and O183. This review provides valuable insights into the most prevalent serotypes implicated in STEC outbreaks and identifies gaps in microbiological criteria, particularly for E. coli non-O157 and non-Big Six serotypes.

BACKGROUND: Non-communicable diseases (NCDs) are a major public health challenge globally, including in Saudi Arabia. However, measuring the true extent of NCD prevalence has been hampered by a paucity of nationally representative epidemiological studies. OBJECTIVES: Assess the prevalence of selected NCDs, using population-based electronic health records and applying novel analytical methods to identify cases of NCDs. DESIGN: Retrospective SETTINGS: A large healthcare network in Saudi Arabia. PATIENTS AND METHODS: We included all beneficiaries aged 16 years or older (n=650 835[a]) and used the International Classification of Disease (ICD-10) codes, laboratory results, and associated medications to identify individuals with diabetes, obesity, hypertension, dyslipidemia, mental disorders, and injuries. For diabetes and hypertension, we used natural language processing (NLP) on clinical notes in the electronic health records. The prevalence of multimorbidity across age groups was also tabulated, and logistic regression was used to examine its association with glycemic control. MAIN OUTCOME MEASURES: The primary outcomes measured were the prevalence of diabetes, hypertension, and multimorbidity, and their association with glycemic control. SAMPLE SIZE: 650 835 individuals aged 16 years or older. RESULTS: The study population was relatively young, with 41.2% aged between 26 and 45 years, and around two-thirds were married. The prevalence of diabetes and hypertension was 18.5% (95% CI: 18.5-18.7) and 13.0% (95% CI: 12.9-13.1), respectively. Approximately 26.7% (95% CI: 26.7-26.8) of the population had multimorbidity, with levels increasing to 62.9% for those aged 65 or older. Multimorbidity was associated with a four-fold increase in the likelihood of poor glycemic control. NLP analysis suggested that the prevalence of diabetes or hypertension may be underestimated by no more than 1.5%. CONCLUSIONS: The study suggests a higher prevalence of NCDs than earlier national estimates. Electronic health records with regular analysis provide an opportunity to estimate changes in the prevalence of NCDs in Saudi Arabia. Health policies and interventions are needed to address the high levels of multimorbidity, which adversely impact glycemic control. LIMITATIONS: Retrospective design and reliance on electronic health records, which may not capture all cases of NCDs.

Abstract Ephedra alata Decne is a medicinal plant widely used in traditional medicine for the management of bronchial asthma and cancer. Phytochemical analysis and biological activities, including antioxidant and anticancer effects, were investigated in the current work as new findings for the plant E. alata, a species growing wildly in the marsh and saline environments of the central area of Saudi Arabia. The Ultra Pressure Liquid Chromatography coupled with Electron spray ionization-Quadropole-Time of flight (UPLC-ESI-Q-TOF) system was used for the phytochemical analysis of the plant constituents. In addition, Polyphenolic profiling including the total phenolic (TPC) and flavonoid (TFC) contents of the plant extracts were measured. Phenolic acids were found at the highest relative percentages among all the identified compounds and were measured at 66.07 mg GAE (Gallic acid equivalent). The UPLC analysis of the E. alata extract indicated the presence of chlorogenic acid, syringic acid, caffeic acid, vanillic acid, rosmarinic acid, umbelliferone, isorhoifolin, and apigenin at the highest relative percentages. Mineral analysis indicated that the microelement content of E. alata was relatively low, except for magnesium (Mg). In vitro antioxidant assays revealed the ability of the plant to scavenge DPPH free radicals, reduced molybdenum ions, and ferrous at levels of 14.63, 19.97, and 27.78 mg Trolox equivalents, respectively. The extract induced transition metal chelation at 31.36 mg EDTA equivalents. The extract induced cytotoxic effects against MDA-231 and A549 cell lines at IC50 levels of 25.31 and 39.81 µg/mL, respectively. The plant extract inhibited the colonization and migration of cancer cells as part of its potential anticancer effects. In addition, major E. alata constituents like isorhoifolin, chlorogenic acid, apigenin, and rosmarinic acid exhibited the lowest binding energy to the CAIX enzyme at − 8.41, − 6.64, − 6.32, and − 6.26 kcal/mol, respectively, compared to the binding energy (− 7.72 kcal/mol) of the co-crystallized ligand (Y0R). The docking results further supported the selection of the CAIX enzyme as a standard predictive therapeutic target, since it exhibited significant binding interactions with the major constituents of the plant.

Charu Sharma,1 Abubaker Suliman,2 Sania Mazin AL Hamad,3 Javed Yasin,1 Mohamed Abuzakouk,4 Juma AlKaabi,1 Elhadi Husein Aburawi3 1Department of Internal Medicine, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, 15551, United Arab Emirates; 2Institute of Public Health, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, 15551, United Arab Emirates; 3Department of Pediatrics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, 15551, United Arab Emirates; 4Department of Immunology & Allergy, Cleveland Clinic, Abu Dhabi, United Arab EmiratesCorrespondence: Elhadi Husein Aburawi, Department of Pediatrics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, 15551, United Arab Emirates, Email e.aburawi@uaeu.ac.aeObjective: The United Arab Emirates (UAE), with its characteristic local population, geography, and history, presents several risk factors for cardiovascular diseases (CVDs) in obese individuals. Obesity and its associated complications, including diabetes, atherogenic dyslipidemia, and CVDs leading to significant health risks. In the present study, “Youths” defined as young people between 18 and 22 years. We assessed dyslipidemia, inflammation, and oxidative stress biomarker levels and their association with endothelial dysfunction (ED) in both overweight/obese and normal weight youths of UAE.Methods: There were 160 youths with overweight/obese (BMI ≥ 25 kg/m2) patients and healthy age- and sex-matched normal weight (BMI ≤ 24.9 kg/m2) as controls participated in this study. The anthropometric data and blood samples were collected to assess the biomarkers for dyslipidemia, inflammation, oxidative stress, ED from all the youths.Results: The overall mean age and male-to-female ratio were 20± 1.5years and 1.0:1.2, respectively. There was statistically significant difference in HDL-C (p< 0.001), triglycerides (TG) (p< 0.001), ApoA (p=0.002), ApoB/ApoA ratio (p=0.009) between the overweight/obese and normal weight youths. Among, inflammatory markers: hs-CRP, IL-6, TNF-α also showed significant p< 0.001 and oxidative stress markers: DNA/RNA Damage, catalase and nitric oxide (NO) showed significant p< 0.001 between groups. Spearman correlation of ED markers with lipid profile markers showed Vitamin C levels positively correlated with HDL-C (p< 0.001) and negatively correlated with glucose (p< 0.001). ICAM-1showed significant negative correlation with HDL-C (p< 0.01) and ApoA (p< 0.001) but positive correlation with TG (p< 0.01) and HbA1c (p< 0.001) among groups. Spearman correlation of ED markers with inflammatory/oxidative stress biomarkers showed Vitamin C levels negatively correlated with ferritin (p < 0.001), NO (p < 0.001), GGT (p < 0.001), and ALT (p < 0.001) levels. The ICAM-1showed significant positive correlation with hs-CRP (p < 0.01), IL-6 (p < 0.001), TNF-α (p < 0.01), GGT (p < 0.05), and ALT (p < 0.05) in both groups.Conclusion: This study revealed a strong link between the biomarkers of dyslipidemia, inflammation, and oxidative stress with ED in overweight/obese patients. This study might be used to predict future cardiovascular events in this population.Keywords: dyslipidemia, inflammation, oxidative stress, endothelial dysfunction, obesity, youth

Background: The actual burden of the Omicron variants remains unclear. Therefore, this study aims to analyze the epidemiological and clinical features of Omicron-infected patients and investigate factors influencing hospital admission. Methods: This retrospective single-center study included individuals with positive SARS-CoV-2 infection, specifically the Omicron variants (XBB, EG or JN), identified through real-time reverse-transcriptase polymerase chain reaction assays from January 2022 to December 2023. Results: A total of 305 Omicron-infected patients were included; (53.11 %) were females and (46.89 %) were males, with a median age of 39 years [interquartile range (IQR): 30, 53]. Underlying diseases, including endocrine/metabolic disorders (22.30 %), hypertension (12.79 %), chronic respiratory disease (10.49 %), and malignancy (9.18 %) were prevalent, while (40.98 %) were medically free. The XBB variant was predominant (73.11 %), followed by JN (20.33 %), and EG variant (6.56 %). The seasonality analysis demonstrates XBB variants' domination in 2022, with a surge to 40 cases in December. The trend continued in 2023, peaking at 76 XBB cases in March. May 2023 reported 38 XBB cases and the emergence of 17 EG instances. Notably, in December, only one XBB case was reported, and 62 instances emerged with the JN variant. Overall, 233 out of 305 cases were reported during flu season (September to March) (76.39 %). Moreover, hospitalization occurred in (16.39 %), with a (1.31 %) mortality rate (all deaths in the JN variant). Multivariable analysis confirmed renal disease, chronic respiratory disease, endocrine/metabolism issues, and polymicrobial infection as positive predictors of hospitalization (p

Ammar Abdulrahman Jairoun,1,2 Sabaa Saleh Al-Hemyari,1,3 Moyad Shahwan,4,5 Sumaya Abdulrahman Jairoun,6 Nasser M Alorfi,7 Sa’ed H Zyoud,8,9 Abdulhaq A Suliman,5,10 Manar Khalil Shahwan,4,5 Ghala Alnuaimi,4 Monzer Shahwan,11 Tariq Al-Qirim,12 Faris El-Dahiyat13,14 1Discipline of Clinical Pharmacy, School of Pharmaceutical Sciences, Universiti Sains Malaysia (USM), Pulau Pinang, 11500, Malaysia; 2Health and Safety Department, Dubai Municipality, Dubai, United Arab Emirates; 3Pharmacy Department, Emirates Health Services, Dubai, United Arab Emirates; 4College of Pharmacy and Health Sciences, Ajman University, Ajman, 346, United Arab Emirates; 5Centre of Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates; 6Department of Clinical Pharmacy & Pharmacotherapeutics, Dubai Pharmacy College for Girls, Al Mizhar Dubai, United Arab Emirates; 7Pharmacology and Toxicology Department, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia; 8Department of Clinical and Community Pharmacy, College of Medicine and Health Sciences, An-Najah National University, Nablus, 44839, Palestine; 9Clinical Research Centre, An-Najah National University Hospital, Nablus, 44839, Palestine; 10College of Dentistry, Ajman University, Ajman, United Arab Emirates; 11Diabetes Clinic, AL-Swity Center for Dermatology and Chronic Diseases, Ramallah, 972, Palestine; 12Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman, 11733, Jordan; 13Clinical Pharmacy Program, College of Pharmacy, Al Ain University, Al Ain, 64141, United Arab Emirates; 14AAU Health and Biomedical Research Center, Al Ain University, Abu Dhabi, 112612, United Arab EmiratesCorrespondence: Moyad Shahwan; Ammar Abdulrahman Jairoun, Tel +971558099957, Email m.shahwan@ajman.ac.ae; dr_ammar_91_@hotmail.comBackground: Providing accurate and sufficient information is a crucial requirement for delivering effective diabetes care, making it essential for community pharmacists to possess adequate knowledge of diabetes mellitus (DM) and its management.Objective: To investigate community pharmacists’ level of expertise and engagement in providing counseling and health promotion services for individuals with DM in the United Arab Emirates (UAE).Methods: A cross-sectional study design was used. The community Pharmacies were chosen via random sampling and researchers then conducted face-to-face interviews with them using the structured questionnaire. The questionnaire included demographic data, 14 questions on the knowledge and 9 questions about the practice concerning pharmaceutical care for Diabetes Mellitus.Results: The average age ± SD was 31 ± 6.3. Of the total 516 community pharmacists recruited in the study, 37.2% (n=192) were male and 62.8% (n=324) were female. The average knowledge score about DM prevention and management was 9.7 with a 95% confidence interval (CI) [9.5, 9.9] and the average practice score about DM prevention and management was 7.1 with a 95% confidence interval (CI) [6.9, 7.2]. Better knowledge scores were observed in chief pharmacists (OR 1.29; 95% CI 1.08– 1.56), pharmacists with 6– 10 Years of experience (OR 6.92; 95% CI 3.43– 8.86), pharmacist with > 10 years of experience (OR 1.99; 95% CI 1.67– 2.36), when the number of patients the pharmacist serve is 5– 10 (OR 1.27; 95% CI 1.06– 1.53) and being trained on DM prevention and management (OR 2.18; 95% CI 1.92– 2.47). Similarly, better practice scores were observed in older participants (OR1.02; 95% CI 1.001– 1.03), chain pharmacies (OR 1.42; 95% CI 1.20– 1.68), chief pharmacists (OR 1.56; 95% CI 1.18– 2.06), when the number of patients the pharmacists serve was 5– 10 (OR 12.26; 95% CI 7.26– 16.19), when the number of patients the pharmacists serve was 11– 20 (OR 4.23; 95% CI 3.54– 5.06) and being trained on DM prevention and management (OR 1.33; 95% CI 1.11– 1.59). The most commonly reported barriers to providing counseling and health promotion services for diabetes mellitus (DM) in community pharmacies include a lack of coordination with other healthcare professionals (77%) and insufficient knowledge or clinical skills (68.7%).Conclusion: Our study revealed that community pharmacy staff members displayed a noteworthy level of involvement in providing pharmaceutical care services for patients with diabetes mellitus. Based on these findings, it is recommended to enhance pharmacy education by incorporating more advanced, evidence-based training and curricula focusing on disease management and appropriate therapies, particularly for diabetes.Keywords: diabetes mellitus, knowledge, practice, pharmaceutical care, type 2 diabetes mellitus, diabetes care and community pharmacies

Malware attacks have escalated significantly with an increase in the number of internet users and connected devices. With the increasingly different types of malware released by hackers, designing new and competitive techniques to detect advanced malware is essential. In the proposed research, we have developed a multi-level feature extraction technique using deep learning architectures and a classification model to classify malware families. The essential features from the malware images are extracted using the Gated Recurrent Unit in the first step, which are further fed to a Convolutional Neural Network model for extracting the final feature vector. The multi-level feature selection is followed by classification into various malware families using Cost-sensitive Boot Strapped Weighted Random Forest (CSBW-RF). The proposed approach gave promising results of 99.58 % accuracy in distinguishing the 25 different malware families on the Mallmg dataset. This hybrid model gave significantly better performance scores for classifying visually similar malware families. The generalizability of the proposed model is benchmarked with the popular Microsoft Big 2015 dataset and has achieved comparatively higher performance scores than many existing models. This benchmarking demonstrates the robustness and scalability of our approach. The use of cost-sensitive learning and bootstrapping techniques also contributed to the model’s ability to generalize well to new and unseen data. These enhancements ensure that our model can be effectively applied in diverse real-world scenarios, maintaining high performance across different environments and malware types. This research can contribute to detecting malware attacks and can be integrated in threat monitoring systems. The successful application of this hybrid model indicates its potential for deployment in real-world cybersecurity environments, providing a strong defense against evolving malware threats.

Objectives: This study investigates the association between specific SNPs in the Toll-like receptor 3 (TLR3) gene and susceptibility to Acute Lymphoblastic Leukemia (ALL) in the Saudi population, aiming to clarify genetic influences on ALL risk. Methods: We evaluated four SNPs of TLR3 (rs3775296 C/A, rs5743312 C/T, rs3775291 C/T, and rs3775290 C/T) for their association with ALL. The allelic and genotypic frequencies of these SNPs were compared between 150 patients and 115 control subjects in this case-control study. All participants were genotyped using TaqMan PCR techniques. Additionally, mRNA expression levels were assessed in patients with ALL and matched healthy individuals using Real-Time Quantitative Reverse Transcription PCR (qRT-PCR). Results: Significant differences in genotype frequencies were observed for the TLR3 SNPs rs5743312 C/T and rs3775290 C/T between the ALL patients and control subjects. No significant differences were detected for rs3775296 C/A and rs3775291 C/T. Notably, the rs5743312 SNP was associated with an increased risk of ALL, while rs3775290 was associated with a decreased risk in the Saudi population. Conclusions: Our study demonstrates significant associations of the TLR3 SNPs rs5743312 C/T and rs3775290 C/T with ALL in the Saudi population. These polymorphisms could be pivotal in developing genetic screening tools and enhancing risk prediction strategies for ALL.

The impulsive fractional differential equation of the Sobolev type, including deviating arguments, is the subject of the study. The analytic semigroup and fixed point approaches serve the purpose of determining the existence of the approximations. The fractional power of a closed linear operator concept is used to show how the approximation converges. To arrive at a unique approach, an approximation strategy is used. Our main conclusions are defined using an example.

Liver transplant (LT) candidates undergo transthoracic echocardiography (TTE) before surgery to assess cardiac function and evaluate the echocardiographic probability of pulmonary hypertension (PHT). The improvement of pulmonary artery systolic pressure (PAPS) after transplant is associated with higher survival rates in patients with mild or moderate PHT. Although studies analyze the outcomes of LT in patients treated for PHT, the prognostic value of PAPS in patients without PHT in the follow-up is unknown. The aim of our study is to evaluate pre- and post-LT cardiac function, right ventricular function, pulmonary artery pressure, and their association with long-term mortality. 102 patients who underwent LT between 2011 and 2018 were compared for echocardiographic and hemodynamic parameters pre- and post-LT. After LT, systolic blood pressure, heart rate (HR), and PASP significantly increased, while tricuspid annular plane systolic excursion/PAPS decreased. Moreover, the higher difference in HR and PASP between pre- and post-LT was highlighted in those patients who died during the follow-up period after LT. Among all the parameters tested, in the multi-variable Cox regression for mortality, left ventricular ejection fraction and PASP difference were predictors of mortality. This study highlights the importance of TTE in LT screening as a tool to stratify patients at higher risk of death due to advanced cirrhotic cardiomyopathy and the importance of the change of echocardiographic parameters, in particular right and left ventricular hemodynamics, during the follow-up period. These parameters could be used to guide a more aggressive therapy.

Background A retrospective chart audit was performed to review biliary stent utilisation from January 2020 to January 2021. Non-guideline-based stent insertion was identified in 16% of patients with common bile duct (CBD) stones presenting for endoscopic retrograde cholangiopancreatography (ERCP). To improve this knowledge-practice gap, a quality improvement (QI) intervention was devised and trialled.Aim To synchronise clinical indications for biliary stent insertion in patients with CBD stones in accordance with published guidelines.Methods Using a QI pre–post study design, chart audits were completed and shared with the ERCP team (n=6). Indication for biliary stent insertion was compared to published guidelines assessed by two reviewers independently (kappa statistic calculated). The QI intervention included an education session and quarterly practice audits. An interrupted time series with segmented regression was completed.Results A total of 661 patients (337 F), mean age 59±19 years (range 12–98 years), underwent 885 ERCPs during this postintervention period. Of 661 patients, 384 (58%) were referred for CBD stones. A total of 192 biliary stents (105 plastic, 85 metal) were placed during the first ERCP (192/661, 29%), as compared with the preintervention year (223/598, 37%, p=0.2). Furthermore, 13/192 stents (7%) were placed not in accordance with published guidelines (kappa=0.53), compared with 63/223 (28%) in the preintervention year (p

Abstract Background The burden of respiratory syncytial virus (RSV) in high-risk pediatric patients remains unclear. Therefore, this study aims to characterize pediatric RSV cases from January 2019 to December 2022 and assess the impact of the COVID-19 pandemic on RSV burden and RSV-related outcomes. In addition, examining factors influencing RSV-related hospitalization. Methods This is a retrospective study that included pediatric patients (aged 14 and below) who presented at King Faisal Specialist Hospital and Research Centre (KFSHRC) in Riyadh, Saudi Arabia with RSV infection identified using real-time reverse-transcriptase polymerase chain reaction assays. Statistical analyses were performed using STATA. Results A total of 885 RSV cases were reported; (56.05%) were males and (43.95%) were females with a median age of 24 months [interquartile range (IQR): 11–60]. 534 (60.34%) required hospitalization. As for RSV seasonality, there was a significant increase in RSV prevalence following the COVID-19 pandemic, escalating from 205 cases in 2019 to 425 cases in 2022. The increase in 2022 was evident in January and persisted from September to December, reaching its peak during the months of October (20.70% − 88 cases) and November (32.00% − 136 cases). About (27.12%) of RSV infected children were medically free patients. Symptomatic patients exhibited various clinical manifestations, with ventilation necessary in (13.11%) of cases. Further analysis revealed significant changes in RSV-related outcomes post-COVID-19, including a decrease in hospitalization rates, an increase in medically free patients, and a lower need for ventilation (p

Background: Children with medical complexity (CMC) account for a substantial proportion of healthcare spending, and one-third of their expenditures are due to readmissions. However, knowledge regarding the healthcare-resource utilization and characteristics of CMC in Saudi Arabia is limited. Objectives: To describe hospitalization patterns and characteristics of Saudi CMC with an unplanned 30-day readmission. Methodology: This retrospective study included Saudi CMC (aged 0–14 years) who had an unplanned 30-day readmission at six tertiary centers in Riyadh, Jeddah, Dammam, Alahsa, and Almadina between January 2016 and December 2020. Hospital-based inclusion criteria focused on CMC with multiple complex chronic conditions (CCCs) and technology assistance (TA) device use. CMC were compared across demographics, clinical characteristics, and hospital-resource utilization. Results: A total of 9139 pediatric patients had unplanned 30-day readmission during the study period, of which 680 (7.4%) met the inclusion criteria. Genetic conditions were the most predominant primary pathology (66.3%), with one-third of cases (33.7%) involving the neuromuscular system. During the index admission, pneumonia was the most common diagnosis (33.1%). Approximately 35.1% of the readmissions were after 2 weeks. Pneumonia accounted for 32.5% of the readmissions. After readmission, 16.9% of patients were diagnosed with another CCC or received a new TA device, and the in-hospital mortality rate was 6.6%. Conclusion: The rate of unplanned 30-day readmissions in children with medical complexity in Saudi Arabia is 7.4%, which is lower than those reported from developed countries. Saudi children with CCCs and TA devices were readmitted approximately within similar post-discharge time and showed distinct hospitalization patterns associated with specific diagnoses. To effectively reduce the risk of 30-day readmissions, targeted measures must be introduced both during the hospitalization period and after discharge.

Salinity is one of the most important abiotic stresses that significantly decreases the productivity of agricultural crops. Melatonin (MT) acts as an antioxidant and plays a vital role in overcoming oxidative damage. However, previous literature has not provided a clear understanding of the impact of MT on lettuce plants under salinity stress. So, we investigated the effect of exogenous MT at 0 μM, 50 μM, 100 μM and 150 μM on lettuce plants grown under salinity stress (0 mM NaCl, 50 mM NaCl and 100 mM NaCl) with respect to vegetative growth, photosynthetic pigments, relative water content (RWC), electrolyte leakage (EL), malondialdehyde (MDA), H2O2, O2•- and antioxidants enzymes. Results showed that NaCl stress significantly decreased vegetative growth, RWC and photosynthetic pigments and in contrast enhanced dry matter, EL, MDA, H2O2, O2•-, Na+, Cl-, peroxidase (POD), superoxide dismutase (SOD) and glutathione reductase (GR) of lettuce plants compared to non-salinized control. The results demonstrated that under salinity conditions, foliar applications of MT significantly alleviated the harmful effects of salinity and increased number of leaves, leaf area, fresh weight, chlorophyll (a), chlorophyll (b), total chlorophyll, carotenoids and RWC in comparison to untreated plants (control). Meanwhile, dry matter, MDA, H2O2, O2•-, Na+, Cl-, POD, SOD and GR were significantly decreased compared to untreated lettuce plants. In this respect, spraying MT at 150 μM ranked the first, then 100 μM, compared to the lower concentration (50 μM). In conclusion, MT application can be used to alleviate harmful effects of salinity stress.

Abstract Background In Saudi Arabia (SA), there has been an alarming increase in the prevalence of chronic kidney diseases (CKD) over the last three decades. Despite being one of the largest countries in the Middle East, renal conditions remain understudied, and there is limited data on their epidemiology and outcomes in SA. Objectives To document the experience of establishing a local renal registry assessing the epidemiology of CKD and identifying potential areas for improving the quality and delivery of care for CKD patients. Methods This is a multi-center retrospective registry. Potential participants were identified through the ICD-10 codes from five hospitals serving the National Guard affiliates in SA. Patients aged ≥ 18 years treated in any National Guard hospital since 2010 for glomerulonephritis, CKD, or received hemodialysis, peritoneal dialysis, or renal transplant were enrolled. Once enrolled in the registry, patients were followed to the last visit date. RedCap was used to create and host the online registry platform. Results A total of 2,912 patients were included, and more than half were younger than 60 years old. Two-thirds of the patients were overweight (25%) or obese (37%). Glomerulonephritis was diagnosed in 10% of the patients, and dialysis-dependent and kidney transplant patients accounted for 31.4% and 24.4%, respectively. Hypertension and diabetes mellitus were detected among 52% and 43% of the participants, respectively. Hemodialysis was the most prevalent dialysis method, with patients spending 3.6 ± 0.4 h per session to receive this treatment. One in every five participants had a kidney biopsy taken (21%). Several barriers and facilitators of the success of this registry were identified. Conclusions The KIND registry provides much-needed information about CKD in Saudi Arabia and serves as a model for future projects investigating the natural history and progression of the spectrum of renal diseases. Logistic and financial challenges to the sustainability of registries are identified and discussed.

Charu Sharma,1 Abubaker Suliman,2 Sania Mazin AL Hamad,3 Javed Yasin,1 Mohamed Abuzakouk,4 Juma AlKaabi,1 Elhadi Husein Aburawi3 1Department of Internal Medicine, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, 15551, United Arab Emirates; 2Institute of Public Health, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, 15551, United Arab Emirates; 3Department of Pediatrics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, 15551, United Arab Emirates; 4Department of Immunology & Allergy, Cleveland Clinic, Abu Dhabi, United Arab EmiratesCorrespondence: Elhadi Husein Aburawi, Department of Pediatrics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, 15551, United Arab Emirates, Email e.aburawi@uaeu.ac.ae

Successful disaster risk reduction (DRR) and preparedness require the active participation of all genders and age groups. However, gender roles and relations are often overlooked in disaster management. This study explores the critical role of women in enhancing gender-responsive resilience within DRR in Oman. It highlights existing gender disparities in DRR strategies and emphasizes the need for inclusive policies that leverage women's knowledge, leadership, and adaptive capacities. By examining Oman's experience with natural disasters (cyclones) and COVID-19, the research underscores the importance of integrating gender perspectives in DRR for more effective outcomes. Utilizing a quantitative survey and statistical analysis, the study investigates variables shaping women's participation in DRR, including knowledge, communication, experience, social protection, and voluntarism. Findings demonstrate the crucial role of women in enhancing disaster resilience and their potential in mitigating disaster risks effectively. Policy recommendations advocate for empowering women and promoting their active participation in DRR to strengthen community resilience and contribute to broader socio-economic development goals in Oman. This study calls on policymakers, practitioners, and stakeholders to support the pivotal role of women in building resilient societies and to adopt a more equitable approach to disaster management.

Phytoconstituents are being emphasized as chemotherapeutic agents, as well as probable anticancer agents. The purpose of the present research was to assess the antioxidant, anti-inflammatory, and anticancer properties of crude ethanolic extracts and bioactive fractions of Adiantum venustum D. Don collected from three sites in Himachal Pradesh, India. The bioactive phytoconstituents were examined qualitatively and quantitatively in crude ethanolic extracts and fractions of all sites, and biological activities were analyzed. The potential presence of terpenoids, saponins, tannins, phenols, and flavonoids was examined, and it came to light that BF-II [n-butanol fraction of Site-II (2000 m altitude)] had a significantly higher phytochemical concentration. Additionally, the crude ethanolic extracts and fractions were examined for antioxidant and anti-inflammatory properties, and BF-II was found to have potential antioxidant and anti-inflammatory activity, as verified by the IC50 values (lowest half inhibitory concentration) in the DPPH (57.86 ± 0.72 μg/mL), reducing power assay (45.20 ± 0.72 μg/mL), FRAP (73.12 ± 0.23 μM Fe equivalent), BSA (56.76 ± 0.25 μg/mL), and EAA (EAA59.84 ± 0.13 μg/mL). Following that, the anticancer potential was investigated further using the MTT assay on the HeLa cell line, MTT assay revealed that BF-II possesses significantly higher anticancer potential. Furthermore, the dominant crude ethanolic extract and fraction were further investigated using gas chromatography-mass spectroscopy, and high-performance thin layer chromatography techniques from the selected plant. Overall, the study suggests that the n-butanol fraction of A. venustum possesses significantly higher therapeutic value but is still not explored to the extent of its potential.

In this work, we synthesized a series of six unsymmetrical benzimidazolium salts 2 and their pyridine-enhanced precatalyst preparation stabilization and initiation (PEPPSI)-themed palladium N-heterocyclic carbene complexes [PdCl2(NHC)(Py)]. All the products were isolated in satisfactory yields (75-85%). The synthesis of these novel palladium PEPPSI complexes involved in reacting NHC precursors with PdCl2 in pyridine at 60°C in the presence of excess K2CO3. The structures of all compounds have been characterized by 1H NMR, 13C NMR, HRMS and IR spectroscopy, as well as elemental analysis techniques, which support the proposed structures. The catalytic activity of the six complexes was assessed in the Suzuki-Miyaura cross-coupling of phenylboronic acid and aryl halides. The reactions required only a low catalyst loading (0.1 mol%) and were carried out under mild aerobic conditions in a green, water-based solvent mixture.

While Saudi coffee (SC) holds deep cultural and historical significance within the Kingdom, rising global exposure and modern coffee shops are driving domestic consumers toward other coffee (OC) varieties. In this context, this study has two objectives: First, to segment the coffee market and analyze how consumer characteristics vary among its components, and second, to estimate the coffee expenditure function. The study data were collected through our custom online survey. We employed a multinomial probit model to estimate choices within the identified market segments of individuals consuming: (1) SC, (2) OC varieties, such as American or Turkish coffee and (3) Both Saudi and OC types. Additionally, we applied an ordered probit model to estimate coffee-related expenditure. The results offer valuable insights for marketing and policy considerations relevant to the concurrent government’s efforts as consumers are increasing their consumption of OC types.

ABSTRACTBackground Immune checkpoints are receptors on the surface of T cells that function crucially in suppressing the immune response, and they are implicated in autoimmunity and cancer diseases.Aim The present study aimed to investigate the relationship between functional single nucleotide polymorphisms (SNPs) of two immune checkpoint molecules, CTLA-4 and TIM-3, and acute myeloid leukemia (AML) in a Saudi population.Methods Two SNPs in CTLA-4 (rs231775, A > G) and TIM-3 (rs10515746, A > C) were genotyped in 229 subjects, including 98 patients and 131 healthy controls, from the Saudi population using TaqMan assay methods. Differential expression of these two genes was performed using in silico analysis.Results An association was found between polymorphisms in TIM-3 (OR: 6.01; 95% CI: 3.99–9.05, P

Colorectal cancer (CRC) is the most common cause of cancer-related mortality globally. It ranks as the most common cancer among men and the third most prevalent among women in Saudi Arabia, especially in the eastern region. The immune system's response to cancer is significantly influenced by natural killer cells through their killer-cell immunoglobulin-like receptors (KIRs) interaction with human leukocyte antigen (HLA) molecules. Our research aimed to target a homogeneous ethnic group in the eastern region of Saudi Arabia, analyzing the distribution of 16 KIR genes and HLA-C1/C2 allotypes in 50 CRC patients and 63 healthy controls using the sequence-specific PCR amplification method. Findings revealed significantly lower frequencies of the 2DL2 and 3DL1 genes in CRC patients compared to controls (OR = 2.21; P = 0.04) and (OR = 7.46; P = 0.00009), respectively. Additionally, a higher prevalence of HLA-C2 was noted in CRC patients (84 %) versus controls (66.7 %) (OR = 2.26; P = 0.04). Conversely, the HLA-C1C2 combination showed a protective effect against CRC (OR = 0.38; P = 0.04). Our combinatorial analysis further identified specific gene combinations correlating with CRC risk or protection. Notably, the absence of KIR2DL2 combined with the presence of KIR2DS2 emerged as a significant risk factor, while various combinations involving KIR2DL2 and/or KIR2DS1 with HLA-C ligands were associated with either increased susceptibility or protection. The study underscores the protective role of KIR2DL2 against CRC in Saudi Arabia's eastern region and suggests that the absence of KIR2DL2, especially when KIR2DS2 is present, might increase CRC risk. This research contributes to understanding genetic influences on CRC susceptibility, emphasizing the potential of KIR and HLA interactions as biomarkers for CRC risk assessment.

Examining the results of existence and Ulam stability in a fractional dynamic system, including a neutral integro-differential equation that incorporates periodic boundary conditions on time scales and the Caputo fractional nabla derivative, is the main objective of the study. Standard fixed-point techniques are applied to obtain the results. Additionally, controllability and Ulam stability results are included. The application of the theoretical results is illustrated with a suitable example.

تهدف هذه الدراسة إلى مواكبة التطوير للبرامج الجامعية على مستوى العالم، من خلال تطوير برنامج بكالوريوس اللغة العربية وآدابها في قسم اللغة العربية في كلية الآداب والعلوم الاجتماعية في جامعة السلطان قابوس، بما يتواكب مع حركة العصر، وطموح القسم والكلية والجامعة في تحديث طريقة التعليم والتعلّم لمقررات البرنامج. وتفيد الدراسة من المنهج الوصفي المرتكز على المدخل المسحي، فقد تمَّ الرجوع للعديد من الأدبيات ذات الصلة باستعمال تقنيات الذكاء الاصطناعي في منظومة التعليم والتعلم؛ للوصول إلى مجموعة من المجالات التي يمكن استخدامها في عملية تقييم مدى فاعلية هذه التقنيات في تعزيز مهارات اللغة العربية من وجهة نظر الطلبة، فقد تمَّ تطوير استبانة تشمل مجموعة من الأبعاد لجمع بيانات أولية من مجتمع الدراسة، وقُسِّمت الاستبانة إلى ثلاثة أقسام: الأول يكشف عن مدى إلمام الطلبة بالذكاء الاصطناعي، والثاني يبيِّن المجالات التي يصلح فيها استعماله من وجهة نظر الطلبة، والثالث يحتوي على فقرات يمكن قياسها لتوضيح مدى نجاح الذكاء الاصطناعي في تعزيز مهارات الخريج في قسم اللغة العربية وآدابها. وسعت الدراسة إلى تحقيق مجموعة من الأهداف هي: تحسين جودة تعليم اللغة العربية وآدابها على المستوى الجامعي، وتنمية المهارات المرتبطة باللغة، من مثل: النطق بأسلوب صحيح والمحادثة الفصيحة، والكتابة بشكل سليم، وتحليل النصوص الأدبية بدقة. لتنتهي الدراسة إلى نتيجة تؤكِّد تزايد أهمية تقنية الذكاء الاصطناعي في مجال التعلّم والتعليم، ولا سيَّما فيما يتعلَّق باللغة العربية.

Background: Metoclopramide and domperidone are prokinetic agents commonly used to treat gastrointestinal dysmotility disorders. This study aimed to evaluate the safety and associated side effects of prolonged-use metoclopramide and domperidone as treatment for chronic gastrointestinal dysmotility disorders in patients with systemic sclerosis (SSc). Methods: A quantitative observational survey was conducted by interview questionnaire in rheumatology outpatients at a tertiary teaching hospital in Riyadh, Saudi Arabia. The study included all patients aged 25–80 years diagnosed with SSc. All patients were on metoclopramide or domperidone for the treatment of chronic gastrointestinal dysmotility symptoms over at least 12 weeks. Results: Eighteen eligible patients were included. Most study participants were diagnosed with SSc complicated by interstitial lung disease (n = 13; 72.2 %). The most frequently reported side effect that occurred while taking prokinetic drugs was shortness of breath (n = 12; 66.7 %). None of the participants reported experiencing depression, galactorrhea, or syncope. CNS side effects were reported in 5.6 %. There were no differences in side effects based on the type and dosage of prokinetic drug used. Conclusions: Use of metoclopramide and domperidone for the treatment of chronic gastrointestinal dysmotility in SSc patients for 12 weeks or longer was not associated with any troublesome side effects. Further studies with more participants are needed to confirm our findings.

BACKGROUND: Noncommunicable diseases (NCDs) are a leading threat to population health in Saudi Arabia. Addressing NCDs is a priority for health-care transformation, and understanding the current disease prevalence is crucial. The prevalence in other settings is unknown because studies have relied on data from households or public health-care institutions. This study aims to investigate the prevalence and predictors of diabetes in the privately insured population. MATERIALS AND METHODS: This retrospective study explored the prevalence and predictors of diabetes in beneficiaries aged 15 years or older who sought medical care in 2022. Data were sourced from the National Platform for Health and Insurance Exchange Services, a unified health insurance claim platform. We used the International Classification of Disease-10 to capture the condition. To identify predictors of diabetes, we employed a backward selection approach for logistic regression. RESULTS: Over 3.3 million beneficiaries sought medical care during the study. The population was relatively young aged 26–39 years, (47.5%) and two-thirds of males. The prevalence of diabetes was 11.0% and varied across regions, with the highest in Bahah (18.4%) and the lowest in Jizan (9.5%). Age, gender, nationality, insurance company size, body mass index, region, hypertension, and coronary heart disease were significant predictors of diabetes. Hypertensive patients were over five times more likely to have diabetes than those without hypertension (odds ratio OR = 5.08; 95% confidence interval CI = 5.02–5.24). Saudis were 30% more likely to have diabetes than other nationalities (OR = 1.3; 95% CI = 1.28–1.31). CONCLUSION: We found a higher prevalence of diabetes in privately insured beneficiaries than the recent national estimate. This necessitates population health management strategies at all levels (primary, secondary, and tertiary) to mitigate the burden of diabetes in privately insured individuals. This study provides valuable baseline data for the prevalence of diabetes in this population and emphasizes the urgent need for targeted interventions, especially in regions with a higher prevalence.

Abstract Background The plant kingdom has long been considered a valuable source for therapeutic agents, however, some plant species still untapped and need to be phytochemically and biologically explored. Although several Atriplex species have been investigated in depth, A. leucoclada, a halophytic plant native to Saudi Arabian desert, remains to be explored for its phytochemical content and biological potentials. Herein, the current study investigated the metabolic content and the anti-inflammatory potential of A. leucoclada. Methods Powdered aerial parts of the plant were defatted with n-hexane then the defatted powder was extracted with 80% methanol. n-Hexane extract (ATH) was analyzed using GC–MS, while the defatted extract (ATD) was subjected to different chromatographic methods to isolate the major phytoconstituents. The structures of the purified compounds were elucidated using different spectroscopic methods including advanced NMR techniques. Anti-inflammatory activity of both extracts against COX-1 and COX-2 enzymes were examined in vitro. Molecular docking of the identified compounds into the active sites of COX-1 and COX-2 enzymes was conducted using pdb entries 6Y3C and 5IKV, respectively. Results Phytochemical investigation of ATD extract led to purification and identification of nine compounds. Interestingly, all the compounds, except for 20-hydroxy ecdysone (1), are reported for the first time from A. leucoclada, also luteolin (6) and pallidol (8) are isolated for the first time from genus Atriplex. Inhibitory activity of ATD and ATH extracts against COX-1 and COX-2 enzymes revealed concentration dependent activity of both fractions with IC50 41.22, 14.40 μg/ml for ATD and 16.74 and 5.96 μg/ml for ATH against COX-1 and COX-2, respectively. Both extracts displayed selectivity indices of 2.86 and 2.80, respectively as compared to 2.56 for Ibuprofen indicating a promising selectivity towards COX-2. Molecular docking study supported in vitro testing results, where purified metabolites showed binding affinity scores ranged from -9 to -6.4 and -8.5 to -6.6 kcal/mol for COX-1 and 2, respectively, in addition the binding energies of GC–MS detected compounds ranged from -8.9 to -5.5 and -8.3 to -5.1 kcal/mol for COX-1 and 2, respectively as compared to Ibuprofen (-6.9 and -7.5 kcal/mol, respectively), indicating high binding affinities of most of the compounds. Analysis of the binding orientations revealed variable binding patterns depending on the nature of the compounds. Our study suggested A. leucoclada as a generous source for anti-inflammatory agents.

Abstract Objective There is growing evidence supporting the presence of oral manifestations associated with COVID-19. The study investigates the knowledge of dental undergraduates and recently graduated dentists concerning oral presentations related to COVID-19. Methods A cross-sectional descriptive study in Saudi Arabia comprised 305 individuals, including undergraduate dental students, interns, and freshly graduated dentists. Data were collected using a questionnaire disseminated to approximately 500 subjects via WhatsApp groups and other applications. The questionnaire was tested in a pilot study for validity, edited, and validated by 2 supervisors at the College of Dentistry, Qassim University, Buraydah, Saudi Arabia. The questionnaire consisted of questions regarding sociodemographic attributes, the level of expertise of dental practitioners, and their knowledge and perspectives regarding COVID-19 and the implementation of oral lesions interrelated to it. The data was subjected to analysis through the utilization of descriptive statistics and chi-square tests, employing the statistical software SPSS (version 24). Results About 43.9% of subjects stated that COVID-19 causes oral symptoms. Respondents most frequently reported COVID-19-related dry mouth. Oral ulcers, Candida infection, Hyperpigmentation, tongue coating, atrophy, Petechiae, Herpes, white lesions, Gingivitis, and Periodontitis are further symptoms. COVID-19’s oral manifestation was unknown to 41.0% of subjects, and 37.7% of respondents lacked knowledge regarding the most impacted locations of oral manifestations. Oral signs and COVID-19 symptoms are debated and significantly associated with higher educational levels. Conclusion The dental students and freshly graduated dentists in this study have proper knowledge of COVID-19 and its symptoms. Also, most dental students and newly graduated dentists recognize the potential correlation between COVID-19 and oral manifestations with an average to excellent knowledge of the types and sites commonly affected. The level of awareness was associated with higher educational levels.

ABSTRACTThere is a significant load of degenerative and chronic illnesses, especially cancer, which is one of the main reasons for morbidity and death globally. Polyphenolic phytochemicals found in many plant diets have been shown in epidemiologic and preclinical studies to have chemopreventive activities against numerous cancer types. As a result, there is growing interest in possible cancer chemopreventive medicines derived from natural compounds, such as polyphenols, which may provide a novel, cost-effective way to reduce the global cancer burden. Various epidemiologic researchers have found a link between a soy-rich diet and tumor avoidance, which has been linked to the existence of genistein, a phenolic component found in soy-based diets. Genistein controlled strong anti-inflammatory actions through the blocking of different signaling pathways such as (PGs) Prostaglandins, pro-inflammatory (ROS) reactive oxygen species and cytokines, (iNOS) inducible nitric oxide synthase and (NF-κB) nuclear factor kappa-B. Furthermore, therapeutic effects of genistein have been conveyed in various pathological situations through modifying intracellular paths such as Akt, mTOR, PI3K, PPARγ, NF-κB, Nrf2 and AMPK. Genistein works as a chemotherapeutic drug against several cancers, primarily through modifying the cell cycle, apoptosis, and angiogenesis, as well as limiting metastasis. Genistein also exhibits a synergistic attitude with renowned anticancer medicines including adriamycin, tamoxifen and docetaxel indicating a possible role in grouping treatment. The study presents the recent data available on genistein’s beneficial effects against various forms of cancers.

Background: During the COVID-19 pandemic, countries around the world implemented various interventions to manage the spread of respiratory illnesses, including influenza. However, there is a lack of studies that have assessed the influence of COVID-19 on influenza prevalence in Saudi Arabia. In this study, we aimed to evaluate the prevalence of positive influenza cases before and during the COVID-19 pandemic in relation to the mitigation measures and policy initiatives in Saudi Arabia. Methods: A multicenter, time-series cross-sectional study was conducted to evaluate influenza prevalence before and during the COVID-19 pandemic between 01/01/2017 and 31/12/2021. This study included all patients who were screened for influenza infection at healthcare facilities across Saudi Arabia using polymerase chain reaction (PCR). The primary outcome was to determine the prevalence of influenza infections before and during the COVID-19 pandemic, while the secondary outcome was to describe the demographic data and comorbidities of the included patients in both periods. Results: During the study period, 5238 cases were identified based on a positive PCR result for influenza virus. The yearly number of influenza cases in the pre-COVID-19 period was 1123 (2.03 %), 1075 (1.63 %), and 1883 (2.20 %) cases in 2017, 2018, and 2019, respectively. On the other hand, the number of cases during the COVID-19 pandemic was 417 (0.63 %) and 740 (1.27 %) in 2020 and 2021, respectively, with a comparable number of performed tests. Patients infected with the influenza virus between 2020 and 2021 were older than patients who were infected before the COVID-19 pandemic. Conclusion: The study found a lower number of influenza cases during the COVID-19 pandemic, with no clear peak during November and December 2020 and 2021.

ABSTRACTCurcumin is a phenolic pigment, naturally present in Curcuma longa species. It is a yellow active ingredient and shows a pivotal role in the modulation of biological processes resulting in the prevention of cancer particularly due to its radical scavenging activities. In gastrointestinal cancer cells, curcumin has been shown to induce cell death through apoptosis and to cause cell cycle arrest, down-regulating glycolytic enzyme expressions alongside inhibition of the matrix metalloproteinase-2 (MMP-2) promoter activity and SDF-1α-induced cell invasion. It also activates the expression of cleaved caspase-3, reduces cell viability, regulates the ratio of Bcl-2/Bax, decreases the number of cells in the proliferative G0/G1 phase and increases the number of cells in the S phase. Additionally, curcumin prevents DNA from replication during the S phase. This review discusses the chemo-preventive role of curcumin and its mechanisms against human gastrointestinal cancers to understand its activity and potential utilization as a therapeutic moiety.

Background and Objectives: Colorectal cancer (CRC) remains a major global health issue. Although chemotherapy is the first-line treatment, its effectiveness is limited due to drug resistance developed in CRC. To overcome resistance and improve the prognosis of CRC patients, investigating new therapeutic approaches is necessary. Materials and Methods: Using human colorectal adenocarcinoma (HT29) and metastatic CRC (SW620) cell lines, the potential anticancer properties of a newly synthesized compound 1-(Isobutyl)-3-(4-methylbenzyl) benzimidazolium chloride (IMBZC) were evaluated by performing MTT cytotoxicity, cell migration, and colony formation assays, as well as by monitoring apoptosis-related protein and gene expression using Western blot and reverse transcription–quantitative polymerase chain reaction technologies. Results: Tested at various concentrations, the half-maximal inhibitory concentrations (IC50) of IMBZC on HT29 and SW620 cell growth were determined to be 22.13 µM (6.97 μg/mL) and 15.53 µM (4.89 μg/mL), respectively. IMBZC did not alter the cell growth of normal HEK293 cell lines. In addition, IMBZC inhibited cell migration and significantly decreased colony formation, suggesting its promising role in suppressing cancer metastasis. Mechanistic analyses revealed that IMBZC treatment increased the expression of pro-apoptotic proteins p53 and Bax, while decreasing the expression of anti-apoptotic proteins Bcl-2 and Bcl-xL, thus indicating the induction of apoptosis in IMBZC-treated CRC cells, compared to untreated cells. Additionally, the addition of IMBZC to conventional chemotherapeutic drugs (i.e., 5-fluorouracil, irinotecan, and oxaliplatin) resulted in an increase in the cytotoxic potential of the drugs. Conclusions: This study suggests that IMBZC has substantial anticancer effects against CRC cells through its ability to induce apoptosis, inhibit cancer cell migration and colony formation, and enhance the cytotoxic effects of conventional chemotherapeutic drugs. These findings indicate that IMBZC could be a promising chemotherapeutic drug for the treatment of CRC. Further research should be conducted using in vivo models to confirm the anti-CRC activities of IMBZC.

Fentanyl is a synthetic μ-opioid receptor agonist approved to treat severe to moderate pain with faster onset of action and about 100 times more potent than morphine. Over last two decades, abuse of fentanyl and its derivatives has an increased trend, globally. Currently, the United States (US) faces the most serious situation related to fentanyl overdose, commonly referred to as the opioid epidemic. Nowadays, fentanyl is considered as the number one cause of death for adults aged 18–45 in the US. Synthesis and derivatization of fentanyl is inexpensive to manufacture and easily achievable. Indeed, more than 1400 fentanyl derivatives have been described in the scientific literature and patents. In addition, accessibility and efficacy of fentanyl and its derivatives can play a potential role in misuse of these compounds as a chemical weapon. In this review, the properties, general pharmacology, and overdose death cases associated with fentanyl and selected derivatives are presented. Moreover, current opioid epidemic in the US, Moscow theatre hostage crisis, and potential misuse of fentanyl and its derivatives as a chemical weapon are disclosed.

In an era of cost pressure, substituting generic drugs represents one of the main cost-containment strategies of healthcare systems. Despite the obvious financial benefits, in a minority of cases, substitution may require caution or even be contraindicated. In most jurisdictions, to obtain approval, the bioequivalence of generic products with the brand-name equivalent needs to be shown via bioavailability studies in healthy subjects. Rare diseases, defined as medical conditions with a low prevalence, are a group of heterogenous diseases that are typically severe, disabling, progressive, degenerative, and life-threatening or chronically debilitating, and disproportionally affect the very young and elderly. Despite these unique features of rare diseases, generic bioequivalence studies are typically carried out with single doses and exclude children or the elderly. Furthermore, the excipients and manufacturing processes for generic/biosimilar products can differ from the brand products which may affect the shelf-life of the product, its appearance, smell, taste, bioavailability, safety and potency. This may result in approval of generics/biosimilars which are not bioequivalent/comparable in their target population or that meet bioequivalence but not therapeutic equivalence criteria. Another concern relates to the interchangeability of generics and biosimilars which cannot be guaranteed due to the phenomenon of biocreep. This review summarizes potential concerns with generic substitution of orphan drugs and discusses potentially problematic cases including narrow therapeutic index drugs or critical conditions where therapeutic failure could lead to serious complications or even death. Finally, we put forward the need for refining regulatory frameworks, with emphasis on Saudi Arabia, for generic substitution and recent efforts toward this direction.

Individuals who are diagnosed with chronic kidney disease, particularly those receiving maintenance hemodialysis treatment, face a greater likelihood of suffering from severe symptoms and fatality due to COVID-19. This study aimed to explore the optimal vaccination approach for these individuals. The study used data analysis tasks such as data preprocessing, cleaning, and exploration, and machine learning models including linear regression, random forest, XGBoost, gradient boosting, AdaBoost, decision trees, Lasso, and ridge regression were used to construct the predictive model. The study found that the Lasso model performed the best overall in predicting anti-S IgG antibodies levels in response to COVID-19 vaccines for people with kidney failure with MAE of 8.81, RMSE of 19.59, and R2 value of 0.93. The adjusted R2 value for the Lasso model was also 0.93, indicating that the model's ability to explain the variance in the data was not affected by the number of predictors in the model. The Random Forest model best predicted the duration of immunogenicity, with R2 and adjusted R2 values of 0.71 and 0.69, respectively. The ensemble model that includes all eight models, i.e., Ridge, Lasso, Linear Regression, Random Forest, AdaBoost, Gradient Boosting, XGBoost, and Decision Tree, has the best performance with the lowest MAE, the lowest RMSE, the highest R2, and the highest adjusted R2 values of 3.91, 5.00, 0.73, and 0.72, respectively. However, further research is required to validate these models and extend their application to different populations and vaccine types, as well as considering other factors that may affect immune response to COVID-19 vaccines. These findings can be helpful in improving vaccination strategies and promoting public health.

Aluminum can potentially cause toxicity in pediatrics and neonates receiving parenteral nutrition. Some PN solutions and ingredients in Saudi Arabia do not comply with US FDA regulations regarding aluminum exposure. This study aims to determine the aluminum concentration in samples of PN solutions and ingredients used to feed infants in Saudi Arabia. The aluminum in the samples was determined using inductively coupled plasma mass spectrometry. The concentration of metal contaminants in each sample was determined in triplicate. The aluminum content of 38 samples was investigated, 15 of which originated from components included in the prepared PN solutions. Among the 15 samples, the least measurable aluminum content was detected in potassium chloride solutions (0.81 mcg/L). In contrast, the greatest amount of aluminum was detected in potassium phosphate and calcium gluconate (141,64 mcg/L and 462.7 mcg/L), respectively. The results showed that the final PN solution (PNS) product contained more aluminum levels than the content ingredients; in addition, the study found a statistically significant relationship among 18 pediatric patients at KFMC who had intestinal failure and needed long-term parenteral nutrition. Specifically, their high aluminum levels, exceeding the normal range of 0.6 ng/ml, indicate that the current use of PN solutions will likely cause toxicity due to aluminum contamination in additives. Hence, reducing aluminum in PN solutions is imperative to ensure patient safety.

Background Decisions on the management of interstitial lung diseases (ILD) and prognostication require an accurate diagnosis. It has been proposed that multidisciplinary team (MDT) meetings for ILD (ILD-MDT) improve these decisions in challenging cases of ILD. However, most studies in this field have been based on the decisions of individual clinicians and there are few reports on the outcomes of the ILD-MDT approach. We therefore describe the experience of the ILD-MDT meetings at our institution.

ABSTRACTQuercetin, a flavonoid, is a dietary component that has attracted the attention of dietitians and medicinal chemists due to its anticancer potential. It is an antioxidant that has a significant role in reducing different human cancers such as breast, pancreatic, prostate, colon, blood, and oral. Being as an additional anti-cancer agent, it can stop cancer cell invasion and metastasis, induce apoptosis and autophagy, decrease cancer cell growth and proliferation. Multiple mechanisms, including suppression of pathways involved in cell survival, angiogenesis, and inflammation, are thought to be responsible for these anticancer effects. Quercetin has anti-inflammatory properties in both in vitro and in vivo tests, which is important as chronic inflammation is a major contributor to cancer. Preventing the synthesis of cytokines and chemokines that encourage inflammation can support to lessen inflammation and stop the spread of cancer. In cancer cells, quercetin can cause programmed cell death, which can stop the cells from rapidly multiplying and replicating. It provides protection against degradation of DNA induced by radiation and other carcinogens. The PI3K/Akt/mTOR pathway, the NF-κB system, and the Wnt/β-catenin pathway is few of the signaling pathways that quercetin modulates. It can activate the process of autophagy, which breaks the growth and range of cancer by having cells terminate and recover damaged or unwanted cellular mechanisms. The best treatment plans for various cancer kinds will need to be determined through additional research, which will also help confirm its safety and effectiveness in humans.

ABSTRACTHoney, propolis, and passionflower contain a flavone known as chrysin. Researchers are studying chrysin to prove its potential to stop cancer cells growth. Chrysin cancer therapeutic potential is of great interest and numerous studies have been done to illustrate this potential. It is associated protein pathways effectively suppress tumor growth within the body. It is shown to have the ability to kill breast, prostate, lung, liver, and stomach cancerous cells. It can block Phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) and Mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling in different animals against various cancers. Chrysin has the potential to kill breast cancer cells in a laboratory setting by inhibiting their cell division. Chrysin strongly suppresses Matrix metalloproteinase-9 (MMP-9), Urokinase plasminogen activator (uPA) and Vascular endothelial growth factor (VEGF), i.e. factors that can cause cancer. Chrysin has the ability to suppress the androgen receptor (AR), a protein necessary for prostate cancer development and metastasis. It starts the caspase cascade and blocks protein synthesis to kill lung cancer cells. Unnecessary apoptosis can be prevented by stopping certain protein pathways. Chrysin significantly decreased lung cancer metastasis in various animal-modeled studies. Chrysin induces apoptosis and stops colon cancer cells in the G2/M cell cycle phase. Chrysin suppresses colon cancer-promoting cyclin B1 and cyclin-dependent kinase 2. Chrysin suppressed cyclin B1 and CDK2 production in order to stop cancerous growth. Chrysin prevents tumor growth and cancer spread by blocking blood vessel expansion. Chrysin’s solubility, accessibility and bioavailability may limit its medical use. Chrysin targets numerous cancer-related communication pathways present in cells. Chrysin may reduce the chances of the onset of cancer, it can also serve as an alternative treatment as a whole to prevent and treat various cancers, but more clinical trials and research studies are needed to fully unlock its potential.

ABSTRACTApigenin (4,’5,7-trihydroxyflavone) is one of the most studied flavonoids with low toxicity and abundantly present phenolic compound in the plant kingdom. The main sources of apigenin are fruits, vegetables, nuts, herbs, honey, and plant-based drinks like tea. Numerous plants produce apigenin as a secondary metabolite and its intake is strongly related to its anti-inflammatory propensities. The purpose of present review was to wade through the literature on the anti-inflammatory mechanisms of this metabolite in various diseases and summarize the key objectives as they appear. Existing literature reported that apigenin is a promising candidate in managing a panoply of inflammatory-related diseases including cancer, diabetes, obesity, depression, insomnia, infection, and respiratory, cardiovascular, hepatoprotective, neurodegenerative, and skin diseases. Studies showed that apigenin significantly decreases the secretion of various proinflammatory cytokines specifically tumor necrosis factor (TNF)-α, IL-1β, IL-6, and IL-10. Moreover, apigenin effectively blocks the nitric oxide-mediated cyclooxygenase-2 expression and monocyte attachment and Prostaglandin by lowering iNOS and COX-2 in both microglial and macrophage mouse cells. Apigenin can slow the course of nonalcoholic fatty liver disease (NAFLD) in vivo by reducing high fat diet (HFD)-induced deposition of lipids and oxidative stress. It also controlled redox imbalances, suppress neuronal death and showed memory enhancement/learning skills and a reduction of fibrillar amyloid deposits with lowered insoluble Aβ concentrations in vivo. Taken together, it can be argued that apigenin can wane inflammation and thus offers a promising future in slowing down the development of chronic diseases and associated complications.

ABSTRACTAsiatic acid (AA) is a natural aglycone of pentacyclic triterpenoids and is abundantly present in many edible and medicinal plants, including Centella Asiatica, which is a reputed herb for wound healing and neuropsychiatric disorders in many traditional medicine formulations. Asiatic acid has various pharmacological functions such as antioxidant and anti-inflammatory and controls apoptosis, which in numerous diseases credits to its medicinal impact. In preclinical trials, asiatic acid demonstrated potent antihypertensive, neuroprotective, cardioprotective, antidiabetic, antimicrobial, and antitumor behaviors. It has been shown to influence multiple enzymes, receptors, growth factors, transcription factors, apoptotic proteins, and cell signaling cascades in several in vitro and in vivo experiments. This review aims to reflect the current therapeutic potential reports and the underlying pharmacological and molecular mechanisms of asiatic acid. In various diseases, studies display Asiatic acid’s polypharmacological properties, therapeutic ability, and molecular pathways. With the available research data, asiatic acid appears to be a significant multi-targeted, natural-origin polypharmacological agent for further pharmaceutical production and clinical use. Provided advantageous pharmacokinetics, protection, and effectiveness, along with commonly used modern drugs. Asiatic acid may be a potential agent or adjuvant, with a pharmacological justification for its usage in therapeutics.

ABSTRACTKaempferol, found in various plants and foods, has gained attention as a useful flavonoid owing to its potential biological properties, including anticancer characteristics. Recent research studies suggest that kaempferol is effective in the inhibition and treatments of several forms of cancer, e.g. lung, ovarian, breast and lung cancer. One probable mechanism of action of kaempferol is its anti-inflammatory and antioxidant potentials, which may help to prevent DNA damage and inhibit the proliferation of cancerous cells. Besides triggering apoptosis in cancerous cells, Kaempferol may also inhibit the growth and relocation of cancerous cells. Moreover, kaempferol has a very wide range of bioactivities, involving anti-inflammatory and antioxidant effects. This includes understanding the optimal dosing and timing of kaempferol treatment, as well as the potential interactions with other medications and the long-term safety of kaempferol use. Overall, the available evidence and studies suggest that kaempferol may provide a potential natural agent for the prevention and treatments of cancers. Despite the promising findings in preclinical and clinical research, further research is needed to confirm its efficacy and understand the mechanisms of action, and to fully explore the potential of kaempferol in different cancers.

ABSTRACTPolymethoxyflavones (PMFs) are dietary bioactive phytochemicals, naturally present in all forms of citrus or plants. For this updated review, the specialized databases of PubMed and Web of Science were researched using keywords such as “polymethoxy flavones,” “pharmacology,” “molecular mechanisms,” “signaling pathways,” and “therapeutic applications.” The most prominent citrus PMFs with proven pharmacological effects are tangeretin, nobiletin, 5′-demethylnobiletin, tetramethyl-o-scutellarein, pentamethoxyflavone, tetramethyl-o-isoscutellarein, and sinensetine. The results of in vivo and in vitro preclinical studies of PMFs have highlighted molecular mechanisms and signaling pathways for anti-inflammatory, anti-cancer, chemopreventive, antidiabetic, anti-obesity, hepatoprotective and neuroprotective effects in neurodegenerative diseases. The results of the studies support the traditional effects of PMFs and therefore it is necessary that these natural compounds be further investigated in clinical trials. PMFs should be designed and formulated in nanoformulations that increase their bioavailability and transport them precisely to the target in order to increase their therapeutic effects.

ABSTRACTBerberine is a metabolite of many medicinal plants. Chemically, berberine belongs to the isoquinoline alkaloids family. The roots of plants grown at lower elevations have a higher concentration of berberine as compared to plants grown at higher elevations. Berberine is a natural substance, which is now among the patent pharmaceuticals for reducing chronic disorders and malignancies. Berberine is also classified as a nutraceutical. Nutraceuticals have been associated with various health benefits via modifying microRNA (miR) expression systems, apoptosis, gene activity, chemical signals/pathways and activation of transcription factors thus aiding in the prevention from various ailments. The pharmacokinetic studies revealed that berberine is poorly absorbed via intestinal walls therefore, its concentration level is extremely low in body fluid. However, the quantity of berberine and its active derivatives in organs is higher as compared to blood as it stably present in tissues. Berberine has an effective role in the body as an anticancer, antidiabetic, antiobesity, antioxidant, antiinflammatory, neuroprotective, hepatoprotective, antiaging and cardioprotective agent. In this review, the therapeutic potentials of berberine are discussed to understand its nutraceutical importance.

ABSTRACTGlobalization witnessed changing trends in consumer markets. However, their long-term impacts include lifestyle and dietary changes. Although research in the pharmaceutical and chemical sciences led to the discovery and development of drugs saving millions of lives, their persistent use led to safety and toxicological issues. The plants previously used in Chinese and Ayurveda medicines received attention of the researchers to validate their traditional therapeutic applications. As a result, the reliance of communities on complementary and alternative medicines started to recover in the last few decades. The myrobalan (Terminalia chebula) is one such example that was renowned as the king of medicinal plants in Ayurveda due to its wide range of utilization in herbal decoctions to treat various health disparities. The current review showed phytochemical profile, that includes phenolic acids, casuarinin, chebulagic acid, chebulinic acid, rutin, and corilagin. Phytochemistry is linked with its medicinal applications and several research studies validated its antioxidant, antimicrobial, anti-inflammatory, hypoglycemic, and digestive tonic. The facts presented in the current article are derived from cell culture, animal, and human studies. Moreover, conceptualized framework regarding the effectiveness against cardiovascular disorders, immune dysfunction, cancer insurgence, and neurological disorders is in the limelight of the article. In last, a comprehensive discussion regarding its potential inclusion in the modern-day functional food market and presents its future applications.

Abstract The Coronavirus disease 2019 (COVID-19) pandemic has emerged as a significant global health concern, impacting millions of individuals worldwide. However, there remains a notable gap in the literature regarding pediatric studies, specifically focusing on children with rheumatic diseases and the potential risk factors associated with COVID-19 contraction in this specific patient population. Patients with rheumatic diseases are often undergoing immunemodulator/immunosuppressant therapies, which can further complicate their immune system response to infections. This is a retrospective cohort study conducted at King Abdullah Specialized Children’s Hospital (KASCH), the largest tertiary care children’s hospital in Saudi Arabia. The aim was to investigate the rate, clinical manifestations, risk factors, and outcomes of COVID-19 infection in pediatric patients with rheumatic diseases. All rheumatology patients (

Abstract This paper attempts to prove the Lipschitz continuity of the resolvent operator associated with a $$(P,\eta )$$ ( P , η ) -accretive mapping and compute an estimate of its Lipschitz constant. This is done under some new appropriate conditions that are imposed on the parameter and mappings involved in it; with the goal of approximating a common element of the solution set of a system of generalized variational-like inclusions and the fixed point set of a total asymptotically nonexpansive mapping in the framework of real Banach spaces. A new iterative algorithm based on the resolvent operator technique is proposed. Under suitable conditions, we prove the strong convergence of the sequence generated by our proposed iterative algorithm to a common element of the two sets mentioned above. The final section is dedicated to investigating and analyzing the notion of a generalized H(., .)-accretive mapping introduced and studied by Kazmi et al. (Appl Math Comput 217:9679–9688, 2011). In this section, we provide some comments based on the relevant results presented in their work.

The purpose of this paper is to identify the opportunities and barriers to the implementation of VBHC in SMEs in Qatar. A semi-structured survey was developed to investigate the perspectives of healthcare providers, from SMEs of public and private sectors, on the opportunities and barriers to the adoption of VBHC in Qatar. The respondents include government officials, CEOs, middle managers, first-line managers, and physicians. Twenty-four out of forty respondents responded. The collected data was aggregated and analyzed. Interestingly, the aggregated information is similar in content to some other countries. Examples of main opportunities include ease of implementation, focus being on outcomes that matter to patients and fosterage of integration and collaboration between public and private sectors. The key barriers/challenges include need for standardized communications and technological infrastructure, and conflicting interests of public and private sectors. The concept of VBHC was first introduced in the United States of America (USA) in 2006 to drive the move from fee-for-service (FFS) approach to fee-for-value (FFV) model. Nonetheless, the debate on the effectiveness of this transformation continues. Although the current emphasis on VBHC may offer new opportunities, barriers are also anticipated. Furthermore, the published evidence on this phenomenon is still limited.

A new form of basis functions structures has been constructed. These basis functions constitute a mix of Chebyshev polynomials and Legendre polynomials. The main purpose of these structures is to present several forms of differentiation matrices. These matrices were built from the perspective of pseudospectral approximation. Also, an investigation of the error analysis for the proposed expansion has been done. Then, we showed the presented matrices' efficiency and accuracy with several test functions. Consequently, the correctness of our matrices is demonstrated by solving ordinary differential equations and some initial boundary value problems. Finally, some comparisons between the presented approximations, exact solutions, and other methods ensured the efficiency and accuracy of the proposed matrices.

Pembrolizumab is one of the approved treatments for many types of cancer including clear cell renal cell carcinoma (ccRCC). It has improved the prognosis of renal cell carcinoma, yet has many possible immune-related side effects. We discuss a rare case of rhabdomyolysis in an ccRCC patient treated with pembrolizumab. The case was complicated with acute kidney injury and severe hypothyroidism, which can be attributed to pembrolizumab.