Computational Approaches to Evaluate the Acetylcholinesterase Binding Interaction with Taxifolin for the Management of Alzheimer's Disease.

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are enzymes that break down and reduce the level of the neurotransmitter acetylcholine (ACh). This can cause a variety of cognitive and neurological problems, including Alzheimer's disease. Taxifolin is a natural phytochemical generally found in yew tree bark and has significant pharmacological properties, such as being anti-cancer, anti-inflammatory, and antioxidant. The binding affinity and inhibitory potency of taxifolin to these enzymes were evaluated through molecular docking and molecular dynamics simulations followed by the MMPBSA approach, and the results were significant. Taxifolin's affinity for binding to the AChE-taxifolin complex was -8.85 kcal/mol, with an inhibition constant of 326.70 nM. It was observed to interact through hydrogen bonds. In contrast, the BChE-taxifolin complex binding energy was observed to be -7.42 kcal/mol, and it was significantly nearly equal to the standard inhibitor donepezil. The molecular dynamics and simulation signified the observed interactions of taxifolin with the studied enzymes. The MMPBSA total free energy of binding for AChE-taxifolin was -24.34 kcal/mol, while BChE-taxifolin was -16.14 kcal/mol. The present research suggests that taxifolin has a strong ability to bind and inhibit AChE and BChE and could be used to manage neuron-associated problems; however, further research is required to explore taxifolin's neurological therapeutic potential using animal models of Alzheimer's disease.

Molecular docking analysis of PPARγ antagonists for obesity associated diabetes management.

Obesity is a major metabolic disorder in developed countries, with an increasing number of people affected globally. PPARγ is primarily expressed in adipose tissue with a lesser extent in other tissues. PPARγ is an important mediator in several metabolic processes such as insulin sensitivity and adipogenesis. Because of its critical role in these processes, PPARγ is regarded as a critical target for therapeutic intervention in obesity treatment. A library of 2,320 bioactive compounds was screened insilico to identify compounds that strongly interact with the PPARγ protein. The compounds Z1982689600, Z2235802137, Z2235801970, and Z2037275165, demonstrated notable binding affinity values towards the PPARγ protein with values of -12.1, -11.7, -11.4, and -11.4 kcal/mol, respectively, which were higher than the binding affinity value observed for the control compound (-10.5 kcal/mol). These compounds bind tightly to PPARγ and have several amino acid residue interactions in common with the control compound. In addition, these compounds meet the ADMET criteria. These compounds could aid in the development of PPARγ antagonists for the management of obesity associated diabetes. However, additional research is needed to optimize their efficacy in wet laboratory conditions.

Prevalence of Irritable Bowel Syndrome in Saudi Arabia: A Systematic Review and Meta-Analysis.

Irritable bowel syndrome (IBS) is a commonly found global functional pathology with no detectable structural changes. It affects the quality of life and often coexists with psychiatric and somatic issues. We reviewed all articles published between 1990 and April 2023. The databases used for the data search were Google Scholar, Web of Science, Cochrane Library, and PubMed/MEDLINE. Ovid search engine was also used to broaden the search strategy. Predefined keywords, including "Irritable bowel syndrome" (MeSH) OR "IBS" (all fields), along with "Saudi Arabia" and "Middle East," were used to avoid data loss and ambiguity. Any cross-sectional study that reported the prevalence of IBS in any gender, age, and group of the Saudi population was included. Data extraction was independently performed in duplicate to mitigate bias and data loss. Statistical analysis of proportion was conducted by using Miller (Freeman-Tukey double arcsine - exact inverse). Out of 350 records identified, only 38 studies were included in the quantitative synthesis. The total number of study participants was 26,567, on the basis of the predefined inclusion criteria of the study. StatsDirect software was used for the statistical analysis of the study parameters. Based on all 38 identified studies, the calculated pooled prevalence was 20.7% (95% confidence interval (CI) = 17.8% to 23.7% by applying random effects (DerSimonian-Laird method). IBS was identified in 21% (95% CI = 16.7% to 25.7%) of the general population, 22% (95% CI = 17.6% to 26.7%) of students, and 18.3% (95% CI = 13.3% to 23.9%) of healthcare workers. The pooled prevalence of IBS among the Saudi population was 20.7%. The pathophysiology of IBS is complexed and significantly affected by genetics, diet, cultural characteristics, age, anxiety, depression, stress, and sleep disorders. This study fills a gap in understanding IBS prevalence in Saudi Arabia, contributing valuable data to this region.

Assessing the Knowledge and Practices of Burn First Aid in Al-Baha Region, Saudi Arabia.

Background Burns are a prevalent type of injury that can result in substantial morbidity and mortality. Burn first aid knowledge is essential for reducing its complications and improving outcomes. However, evidence of the amount of burn first aid knowledge among the general population in many nations is sparse. Methodology A cross-sectional survey was conducted among 346 persons over the age of 18 from the Al-Baha region of Saudi Arabia. The participants' knowledge of first aid for burns, including the appropriate steps to take in the event of a burn, the types of burns, and the proper application of burn dressings was assessed using a structured questionnaire. Results The majority of participants (73.6%) had inadequate knowledge of first aid for burns, while only 26.4% had adequate knowledge. The most common misconception among participants was the use of toothpaste, honey, or ice for burn treatment, which is not recommended. Additionally, hot water was the main cause of burning in this study. Conclusions This study underscores the necessity for targeted education and awareness-raising activities to improve the general population's knowledge and habits about first aid for burns. Such programs can be tailored to clarify myths and misunderstandings regarding burn treatment and encourage evidence-based strategies for preventing and treating burns.

The Prevalence of Irritable Bowel Syndrome and Its Co-existence With Migraine in Medical and Non-medical Students at Al-Baha University, Saudi Arabia.

BACKGROUND: It was hypothesized that the prevalence of irritable bowel syndrome (IBS) and migraine and their co-existence are higher among medical students. In this study, we aim to establish the prevalence of IBS and migraine in the medical and non-medical students at Al-Baha University, Saudi Arabia, and to observe the association and relationship between IBS and migraine using the Rome IV diagnostic criteria for IBS and the International Classification of Headache Disorders (ICHD)-3 criteria for migraine. METHODOLOGY: This cross-sectional study was done on the Saudi Arabian campus of Al-Baha University between July 2022 and July 2023. Al-Baha city-dwelling male and female college students aged 18 to 29 comprised the study population. A self-administered electronic questionnaire was sent online to determine the prevalence of IBS and migraine, in addition to associated risk factors. The questionnaire consisted of three sections: demographic and lifestyle data, the Rome IV criteria for diagnosing and subclassifying IBS, and the ICHD-3 criteria for diagnosing migraine. RESULTS: The study was conducted among 452 participants with a mean age of 21.64 years. The majority of participants were not from medical schools. The majority of medical and non-medical participants were male, at 66.6% and 63.1%, respectively. In our study, 36.9% of the individuals reported having a first-degree relative diagnosed with IBS, whereas 2.7% reported having IBS themselves. Regarding migraine, 17.9% of respondents claimed to have a first-degree relative with migraine, while 6.9% of respondents themselves reported experiencing migraine. Regarding IBS prevalence, there was no significant difference between participants from non-MBBS colleges and MBBS colleges. Similarly, there was no significant difference in migraine prevalence between these two groups (92.0% vs. 95.4%, p=0.185). CONCLUSION: The current study contributes significantly to our understanding of the prevalence of IBS and migraines among medical students, as well as these individuals' demographic characteristics, familial histories, and aggravating variables.

Anti-Fibrotic Efficacy of Apigenin in a Mice Model of Carbon Tetrachloride-Induced Hepatic Fibrosis by Modulation of Oxidative Stress, Inflammation, and Fibrogenesis: A Preclinical Study.

BACKGROUND: Hepatic fibrosis is a major health problem all over the world, and there is no effective treatment to cure it. Hence, the current study sought to assess the anti-fibrotic efficacy of apigenin against CCl4-induced hepatic fibrosis in mice. METHODS: Forty-eight mice were put into six groups. G1: Normal Control, G2: CCl4 Control, G3: Silymarin (100 mg/kg), G4 and G5: Apigenin (2 &20 mg/Kg), G6: Apigenin alone (20 mg/Kg). Groups 2, 3, 4, and 5 were given CCl4 (0.5 mL/kg. i.p.) twice/week for six weeks. The level of AST, ALT, TC, TG, and TB in serum and IL-1ß, IL-6, and TNF-α in tissue homogenates were assessed. Histological studies by H&E staining and Immunostaining of liver tissues were also performed. RESULTS: The CCl4-challenged group showed increased serum AST (4-fold), ALT (6-fold), and TB (5-fold). Both silymarin and apigenin treatments significantly improved these hepatic biomarkers. The CCl4-challenged group showed reduced levels of CAT (89%), GSH (53%), and increased MDA (3-fold). Both silymarin and apigenin treatments significantly altered these oxidative markers in tissue homogenates. The CCl4-treated group showed a two-fold increase in IL-1ß, IL-6, and TNF-α levels. Silymarin and apigenin treatment considerably decreased the IL-1ß, IL-6, and TNF-α levels. Apigenin treatment inhibited angiogenic activity, as evidenced by a decrease in VEGF (vascular endothelial growth factor) expression in liver tissues, and a decline in vascular endothelial cell antigen expression (CD34). CONCLUSIONS: Finally, these data collectively imply that apigenin may have antifibrotic properties, which may be explained by its anti-inflammatory, antioxidant, and antiangiogenic activities.

Assessment of the Current Knowledge and Practice of General Practitioners Towards Laryngopharyngeal Reflux in Saudi Arabia.

Background General practitioners (GPs) have a significant role in the diagnosis of patients with laryngopharyngeal reflux (LPR). Some published data revealed a lack of knowledge among GPs about the disease, consequently, this lack of knowledge impacted their performance. This survey aims to assess the current knowledge and practice of general practitioners regarding laryngopharyngeal reflux in Saudi Arabia. Methodology This survey study was conducted to assess the current knowledge and practice of general practitioners regarding laryngopharyngeal reflux in Saudi Arabia using an online questionnaire. The questionnaire was distributed and collected from the five regions in Saudi Arabia, which are The Central Region (Riyadh, Qassim), Eastern Region (Dammam, Al-Kharj, Al-Ahasa), Western Region (Makkah, Madinah, Jeddah), Southern Region (Asir, Najran, Jizan), and Northern Region (Tabuk, Jouf, Hail). Results In the current study, we collected data from 387 general practitioners, 61.8% of whom were aged between 21-30 years old, and 57.4% of the participants were males. Moreover, 40.6% of the participants thought that both LPR and gastroesophageal reflux disease (GERD) share pathophysiology, however, they are two different diseases considering their clinical presentation. Moreover, it was found that heartburn was the most known symptom of LPR among the participants (Mean score 2.14 (SD=1.31), where a lower score indicated more relation). Considering the treatment of LPR, 40.6% and 40.3% of the participants reported using proton pump inhibitors once or twice daily respectively. In contrast, antihistamine/H2 blockers, alginate, and magaldrate were used to a lesser extent as reported by 27.1%, 21.7%, and 12.1%. Conclusion The current study showed limited knowledge among general practitioners considering LPR with a higher rate of referring patients to other departments depending on symptoms which may increase the pressure on other departments of mild cases.

Chemistry and Pharmacological Actions of Delphinidin, a Dietary Purple Pigment in Anthocyanidin and Anthocyanin Forms.

Anthocyanins are naturally occurring water-soluble flavonoids abundantly present in fruits and vegetables. They are polymethoxyderivatives of 2-phenyl-benzopyrylium or flavylium salts. Delphinidin (Dp) is a purple-colored plant pigment, which occurs in a variety of berries, eggplant, roselle, and wine. It is found in a variety of glycosidic forms ranging from glucoside to arabinoside. Dp is highly active in its aglycone form, but the presence of a sugar moiety is vital for its bioavailability. Several animal and human clinical studies have shown that it exerts beneficial effects on gut microbiota. Dp exhibits a variety of useful biological activities by distinct and complex mechanisms. This manuscript highlights the basic characteristics, chemistry, biosynthesis, stability profiling, chemical synthesis, physicochemical parameters along with various analytical methods developed for extraction, isolation and characterization, diverse biological activities and granted patents to this lead anthocyanin molecule, Dp. This review aims to open pathways for further exploration and research investigation on the true potential of the naturally occurring purple pigment (Dp) in its anthocyanidin and anthocyanin forms beyond nutrition.

Incidence and nature of adverse drug events in paediatric intensive care units: A prospective multicentre study.

AIMS: The aim of this study was to assess the incidence, nature, preventability and severity of adverse drug events (ADEs) across three paediatric intensive care units (PICUs) in England. METHODS: A prospective observational cohort study was conducted across three PICUs over a three-month period during 2019. Included patients were aged ≤18 years and stayed in PICU for a minimum of 24 hours. Identification of suspected ADEs was performed by trained PICU pharmacists. A multidisciplinary expert panel assessed causality, preventability and severity of events. RESULTS: A total of 302 patients were included and 62 ADEs were confirmed (definite/probable causality). One in six patients experienced one or more ADEs. The estimated incidence of ADEs were 20.5 per 100 patients (95% CI 15.3-27.5) and 16.7 per 1000 patient-days (95% CI 9.3-29.9). The majority of ADEs were judged preventable by the expert panel (36/62, 58.1%). ADEs were commonly involved with medicines prescribing (29/62, 46.8%) and caused temporary patient harm (42/62, 67.7%). Medications for the central nervous system (14/62, 22.6%), infections (13/62, 20.9%) and cardiovascular system (12/62, 19.4%) were commonly implicated with ADEs. Multivariable analysis revealed that patients who stayed in PICU for ≥7 days (OR 6.29, 95% CI 2.42-16.32) were more likely to experience an ADE compared to patients with a stay of 1-6 days. CONCLUSION: ADEs are common in English PICUs and most of them may be preventable. There is a strong association between ADE occurrence and duration of PICU stay, which represents a target for remedial interventions. Exploring contributory factors of preventable ADEs is now necessary to inform preventive policies.

A Mixed-Methods Analysis of Medication Safety Incidents Reported in Neonatal and Children's Intensive Care.

BACKGROUND: Critically ill neonates and paediatric patients may be at a greater risk of medication-related safety incidents than those in other clinical areas. OBJECTIVE: This study aimed to examine the nature of, and contributory factors associated with, medication-related safety incidents reported in neonatal and paediatric intensive care units (ICUs). METHODS: We carried out a mixed-methods analysis of anonymised medication safety incidents reported to the National Reporting and Learning System that involved children (aged ≤ 18 years) admitted to ICUs across England and Wales over a 9-year period (2010-2018). Data were analysed descriptively, and free-text descriptions of harmful incidents were examined to explore potential contributory factors associated with incidents. RESULTS: In total, 25,567 eligible medication-related incident reports were examined. Incidents commonly occurred during the medicines administration (n = 13,668 [53.5%]) and prescribing stages (n = 7412 [29%]). The most commonly implicated error types were drug omission (n = 4812 [18.8%]) and dosing errors (n = 4475 [17.5%]). Neonates were commonly involved in reported incidents (n = 12,235 [47.9%]). Anti-infectives (n = 6483 [25.4%]) were the medications most commonly associated with incidents and commonly involved neonates. Incidents that were reported to have caused patient harm accounted for 12.2% (n = 3129) and commonly involved neonates (n = 1570/3129 [50.2%]). Common contributing factors to harmful incidents included staff-related factors (68.7%), such as failure to follow protocols or errors in documentation, which were often associated with working conditions, inadequate guidelines, and design of systems and protocols. CONCLUSIONS: Neonates were commonly involved in medication-related incidents reported in children's intensive care settings. Improvements in staffing and workload, design of systems and processes, and the use of anti-infective medications may reduce this risk.

Prevalence and Nature of Medication Errors and Preventable Adverse Drug Events in Paediatric and Neonatal Intensive Care Settings: A Systematic Review.

INTRODUCTION: Children admitted to paediatric and neonatal intensive care units may be at high risk from medication errors and preventable adverse drug events. OBJECTIVE: The objective of this systematic review was to review empirical studies examining the prevalence and nature of medication errors and preventable adverse drug events in paediatric and neonatal intensive care units. DATA SOURCES: Seven electronic databases were searched between January 2000 and March 2019. STUDY SELECTION: Quantitative studies that examined medication errors/preventable adverse drug events using direct observation, medication chart review, or a mixture of methods in children ≤ 18 years of age admitted to paediatric or neonatal intensive care units were included. DATA EXTRACTION: Data on study design, detection method used, rates and types of medication errors/preventable adverse drug events, and medication classes involved were extracted. RESULTS: Thirty-five unique studies were identified for inclusion. In paediatric intensive care units, the median rate of medication errors was 14.6 per 100 medication orders (interquartile range 5.7-48.8%, n = 3) and between 6.4 and 9.1 per 1000 patient-days (n = 2). In neonatal intensive care units, medication error rates ranged from 4 to 35.1 per 1000 patient-days (n = 2) and from 5.5 to 77.9 per 100 medication orders (n = 2). In both settings, prescribing and medication administration errors were found to be the most common medication errors, with dosing errors the most frequently reported error subtype. Preventable adverse drug event rates were reported in three paediatric intensive care unit studies as 2.3 per 100 patients (n = 1) and 21-29 per 1000 patient-days (n = 2). In neonatal intensive care units, preventable adverse drug event rates from three studies were 0.86 per 1000 doses (n = 1) and 0.47-14.38 per 1000 patient-days (n = 2). Anti-infective agents were commonly involved with medication errors/preventable adverse drug events in both settings. CONCLUSIONS: Medication errors occur frequently in critically ill children admitted to paediatric and neonatal intensive care units and may lead to patient harm. Important targets such as dosing errors and anti-infective medications were identified to guide the development of remedial interventions.