Pharmacophore-Based Virtual Screening, Quantum Mechanics Calculations, and Molecular Dynamics Simulation Approaches Identified Potential Natural Antiviral Drug Candidates against MERS-CoV S1-NTD.

Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly infectious zoonotic virus first reported into the human population in September 2012 on the Arabian Peninsula. The virus causes severe and often lethal respiratory illness in humans with an unusually high fatality rate. The N-terminal domain (NTD) of receptor-binding S1 subunit of coronavirus spike (S) proteins can recognize a variety of host protein and mediates entry into human host cells. Blocking the entry by targeting the S1-NTD of the virus can facilitate the development of effective antiviral drug candidates against the pathogen. Therefore, the study has been designed to identify effective antiviral drug candidates against the MERS-CoV by targeting S1-NTD. Initially, a structure-based pharmacophore model (SBPM) to the active site (AS) cavity of the S1-NTD has been generated, followed by pharmacophore-based virtual screening of 11,295 natural compounds. Hits generated through the pharmacophore-based virtual screening have re-ranked by molecular docking and further evaluated through the ADMET properties. The compounds with the best ADME and toxicity properties have been retrieved, and a quantum mechanical (QM) based density-functional theory (DFT) has been performed to optimize the geometry of the selected compounds. Three optimized natural compounds, namely Taiwanhomoflavone B (Amb23604132), 2,3-Dihydrohinokiflavone (Amb23604659), and Sophoricoside (Amb1153724), have exhibited substantial docking energy >-9.00 kcal/mol, where analysis of frontier molecular orbital (FMO) theory found the low chemical reactivity correspondence to the bioactivity of the compounds. Molecular dynamics (MD) simulation confirmed the stability of the selected natural compound to the binding site of the protein. Additionally, molecular mechanics generalized born surface area (MM/GBSA) predicted the good value of binding free energies (ΔG bind) of the compounds to the desired protein. Convincingly, all the results support the potentiality of the selected compounds as natural antiviral candidates against the MERS-CoV S1-NTD.

Clinical and Immunological Characterization of Combined Immunodeficiency Due to TFRC Mutation in Eight Patients.

PURPOSE: Combined immunodeficiency (CID), due to mutations in TFRC gene that encodes the transferrin receptors (TfR1), is a rare monogenic disorder. In this study, we further characterize the clinical and immunological phenotypes in a cohort of eight patients. METHODS: A retrospective review of clinical and immunological features of patients diagnosed with a TFRC gene mutation between 2015 and 2019 in three tertiary centers. RESULTS: Eight patients from six unrelated families were enrolled. The patients had a median age of 7 years (4-32 years). All patients presented with recurrent sinopulmonary infections, chronic diarrhea, and failure to thrive in early life. Less common features were skin abscesses, conjunctivitis, global developmental delay, optic nerve atrophy, vitiligo, multinodular goiter, and hemophagocytic lymphohistiocytosis-like symptoms. All patients had intermittent neutropenia and 87% of the patients had recurrent thrombocytopenia. Anemia was found in 62%. All patients had hypogammaglobinemia and one had a persistent high IgM level. All patients had impaired function of T cells. The same homozygous missense mutation c.58T>C:p.Y20H, in the TFRC gene, was detected in all patients. Stem cell transplantation from matched donors was successful in two patients. Five patients did not receive stem cell transplantation, and they are on prophylactic treatment. One patient died due to severe sepsis and neurological complications. CONCLUSION: This report provides a large cohort with a long follow up of patients with this disease. Our cohort showed variable disease severity.

The Health Benefits of Probiotic Lactiplantibacillus plantarum: A Systematic Review and Meta-Analysis.

To ensure effective administration of probiotics in clinical practice, it is crucial to comprehend the specific strains and their association with human health. Therefore, we conducted a systematic review and meta-analysis to evaluate the scientific evidence on the impact of Lactiplantibacillus plantarum probiotic consumption on human health. Out of 11,831 records, 135 studies were assessed qualitatively, and 18 studies were included in the meta-analysis. This systematic review demonstrated that probiotic supplementation with L. plantarum, either alone or in combination, can significantly improve outcomes for patients with specific medical conditions. Meta-analysis revealed notable benefits in periodontal health, evidenced by reduced pocket depth and bleeding on probing (p < 0.001); in gastroenterological health, marked by significant reductions in abdominal pain (p < 0.001); and in infectious disease, through a reduction in C-reactive protein levels (p < 0.001). Cardiovascular benefits included lowered total cholesterol and low-density lipoprotein cholesterol in the L. plantarum intervention group (p < 0.05). Our study's clinical significance highlights the importance of considering probiotic strain and their application to specific diseases when planning future studies and clinical interventions, emphasizing the need for further research in this area.

Preparation and Optimization of Itraconazole Transferosomes-Loaded HPMC Hydrogel for Enhancing Its Antifungal Activity: 23 Full Factorial Design.

Itraconazole (ITZ) is a triazole antifungal agent characterized by broad-spectrum activity against fungal infections. The main drawback of ITZ, when applied topically, is the low skin permeability due to the stratum corneum, the outermost layer of the skin, which represents the main barrier for drug penetration. Therefore, this study aimed to prepare itraconazole as transferosomes (ITZ-TFS) to overcome the barrier function of the skin. ITZ-TFSs were prepared by thin lipid film hydration technique using different surfactants, sodium lauryl sulfate (SLS) and sodium deoxycholate (SDC). The prepared ITZ-TFS were evaluated for entrapment efficiency (EE) %, particle size, polydispersity index (PDI), zeta potential, and in vitro drug release to obtain an optimized formula. The surface morphology of the optimized formula of ITZ-TFS was determined by transmission electron microscope (TEM). The optimized formulation was prepared in the form of gel using hydroxyl propyl methyl cellulose (HPMC) gel base. The prepared ITZ-TFS gel was evaluated for homogeneity, drug content, spreadability, pH, and in vitro antifungal activity in comparison with the free ITZ gel. The prepared ITZ-TFS formulations exhibited high EE% ranging from 89.02 ± 1.65% to 98.17 ± 1.28% with particle size ranging from 132.6 ± 2.15 nm to 384.1 ± 3.46. The PDI for all ITZ-TFSs was less than 0.5 and had a negative zeta potential. The TEM image for the optimized formulation (ITZ-TFS4) showed spherical vesicles with a smooth surface. The prepared gels had good spreadability, pH, and acceptable drug content. ITZ-TFS gel showed higher antifungal activity than free ITZ gel as determined by zone of inhibition. ITZ was successfully prepared in form of TFSs with higher antifungal activity than the free drug.

Awareness of Keratoconus and Its Association With Eye Rubbing Among the Population in Aseer Province.

BACKGROUND: Keratoconus (KC), is a non-inflammatory, bilateral, asymmetrical, progressive disease characterized by ectasia, thinning, increasing corneal curvature, and loss of visual acuity. In Saudi Arabia, it was discovered that KC has been the main reason for corneal transplantation in the past 20 years. Eye rubbing is considered one of the most significant risk factors for KC based on available data. PARTICIPANTS AND METHODS: A cross-sectional study was conducted among adults in Aseer province, Saudi Arabia in 2023. Data were collected through a pre-designed online questionnaire consisting of 17 questions divided into three sections. The questionnaire was preceded by informed consent and insured to maintain the confidentiality of the data. RESULTS: A total of 498 respondents were included in this study. The majority of the study's participants were in the 18 to 25 age group and females made up the majority. The majority of participants had a university education. 41.6% of individuals reported experiencing an allergic disorder, 59.0% reported having knowledge about KC, and the overall participants' awareness regarding KC was poor at 85.74%, with the highest percentage of good awareness (22.2%) detected among the 18-25 age group. CONCLUSION: The study revealed a concerning lack of awareness about KC among the population in Aseer Province, Saudi Arabia. Additionally, a significant percentage of participants engaged in eye rubbing, a behavior associated with increased risk for KC. There is a need for increased awareness about KC and the importance of avoiding eye rubbing.

Knowledge, Attitude, and Practice of Parents Regarding Children's Eye Care in Al-Qunfudah Governorate, Saudi Arabia.

BACKGROUND: Visual impairment and blindness have a long-term impact on children. Common causes include refractive error, amblyopia, and cataracts, all of which are preventable. OBJECTIVES: This study aims to evaluate the knowledge, attitude, and practice of parents regarding children's eye care in Al-Qunfudah governorate, Saudi Arabia. METHODS: A cross-sectional study was carried out on a convenience sample of 403 parents residing in the governorate of Al-Qunfudah. Data were gathered using a validated, self-administered online questionnaire that required participants' consent and ensured data confidentiality. IBM SPSS Statistics for Windows, Version 26.0 (Released 2019; IBM Corp., Armonk, New York, United States) was used to do the statistical analysis of the data. RESULTS: This study included 403 participants; 41.2% of them were 36-45 years old, 75.9% were female, and 88.8% were married. Most of the participants had had their children undergo eye examinations (65%). A positive attitude about child eye care among the participants was observed in 48.9% of them, while the level of knowledge about eye care and its regular examinations was poor in 60% of the study sample. A significant positive correlation was detected between participants' attitudes and knowledge scores about the eye care of their children (r = 0.238, p-value = <0.001). Older adults (P = 0.004), those with employment (P = 0.004), and those with a history of children suffering from eye problems (P = 0.018) are associated with a positive attitude, while better knowledge is associated with the parent's age (P = 0.007) and higher education level (P = 0.047). CONCLUSION: The knowledge and attitude of the parents regarding their children's eye care were suboptimal, and the main reason for conducting eye examinations on their children was the presence of active eye disease and a symptomatic child. Positive attitudes were more prevalent among those aged 36-45 years, employed, and with a higher number of children with eye problems. Those in the age group of 36-45 who had a bachelor's degree were associated with greater knowledge. There is an urgent need to educate parents about routine and recommended eye screening. Family physicians should conduct opportunistic eye screenings for children who attend primary healthcare facilities and provide parents with educational materials about common eye disorders and children's eye care.

Poly(2-Hydroxyethyl Methacrylate) Hydrogel-Based Microneedles for Metformin Release.

The release of metformin, a drug used in the treatment of cancer and diabetes, from poly(2-hydroxyethyl methacrylate), pHEMA, hydrogel-based microneedle patches is demonstrated in vitro. Tuning the composition of the pHEMA hydrogels enables preparation of robust microneedle patches with mechanical properties such that they would penetrate skin (insertion force of a single microneedle to be ≈40 N). Swelling experiments conducted at 20, 35, and 60 °C show temperature-dependent degrees of swelling and diffusion kinetics. Drug release from the pHEMA hydrogel-based microneedles is fitted to various models (e.g., zero order, first order, second order). Such pHEMA microneedles have potential application for transdermal delivery of metformin for the treatment of aging, cancer, diabetes, etc.

Lessons Learned From COVID-19 Lockdown: An ASPED/MENA Study on Lifestyle Changes and Quality of Life During Ramadan Fasting in Children and Adolescents Living With Type 1 Diabetes.

Background: Lockdown was a unique experience that affected many aspects of life, particularly during the challenge of Ramadan fasting (RF). Studying this can increase understanding of the effects of lifestyle changes on quality of life (QoL) for children with type 1 diabetes (T1D) during RF. Methods: A cross-sectional study that assessed the effect of lockdown on lifestyle and QoL on fasting children living with T1D during Ramadan in the Middle East and North Africa region (2020-2021). We compared the child (self) and parent (proxy) reports using PEDQoL v3.0 disease specific questionnaire during lockdown and non-lockdown periods, and assessed correlations with lifestyle changes using regression and gap analyses. Results: A total of 998 reports from 499 children with T1D aged 8 to 18 years (study = 276, control = 223), and their parents during RF in lockdown and non-lockdown periods. Fathers were more involved in their children's care during lockdown (P = .019). Patients had better compliance with treatment (P = .002), a reversed sleep pattern (P = .033), increased food intake (P ⩽ .001), and less exercise (P < .001). Children and parents perceived better QoL during lockdown (P ⩽.001) with no differences between their reports in "Diabetes Symptoms", "Treatment Adherence," and "Communication" domains. Self and proxy reports were different in all domains during non-lockdown (P = <.001-.009). In gap analysis, although not statistically significant, the gap was approximated between children's and parents' perceptions in all domains during lockdown. Conclusion: COVID-19 lockdown had a positive impact on QoL of children living with T1D during RF, possibly due to lifestyle changes and superior psychosocial family dynamics.

The Effect of the COVID-19 Vaccine on the Menstrual Cycle Among Reproductive-Aged Females in Saudi Arabia.

BACKGROUND: A global concern about a possible association between COVID-19 vaccines and menstrual disturbance has been raised. Moreover, women who have experienced menstrual changes are worried about the length of the side effects and are hesitant to receive booster doses. Therefore, the aim of this study is to evaluate the impact of the COVID-19 vaccine on all features of the menstrual cycle, including cycle length, amount of bleeding, and pain. METHODOLOGY: We retrospectively analyzed menstrual cycles following at least two doses of COVID-19 vaccines; the cycle changes within the individual pre-vaccination and post-vaccination were compared. All reproductive-aged females from 18 to 45 years who fit the inclusion criteria were included in the study and categorized into five sub-categories based on age to investigate whether certain age groups were most affected. The data were collected through a well-structured self-administered questionnaire. Participants obtained their vaccination information (date, type of vaccine) from Tawakkalna, the official COVID-19 application in the Kingdom of Saudi Arabia. IBM Corp. Released 2019. IBM SPSS Statistics for Windows, Version 26.0. Armonk, NY: IBM Corp was performed in data entry and statistical analysis. Variables were described as frequency and percentage, as all were categorical. To investigate the association between menstrual changes and its possible associated factors, we used the Chi-square test, and the statistical significance was determined at p<0.05. RESULTS: The online questionnaire received responses from a total of 1092 reproductive females. However, out of which, 419 were not fitting into the inclusion criteria. Thus, a total of 673 females were included in the final report. Overall, the changes in the menstrual cycles after both COVID-19 vaccine doses were observed among 46.7%, mainly more menstrual pain in 22.9% following the first dose compared with 21.4% after the second. Menstrual changes were observed among almost two-thirds of women in the age groups 18-22 years (65.2%) and 38-45 years (65.4%) compared with only 43.5% of those in the age group 23-27 years, p<0.001. The Moderna vaccine was associated with the highest rate of menstrual changes (65.4%), whereas Oxford-AstraZeneca was associated with the lowest rate (44.9%), p=0.040. The duration of changes in the cycles after the COVID-19 vaccine (one dose or both) was less than one month among 42.5% of females, whereas it was three months or more among 27.1%. CONCLUSION: The COVID-19 vaccination is associated with a minor and transient change in the menstrual cycle, resulting mainly more menstrual pain and increased bleeding.

Prevalence of impaired awareness of hypoglycemia and its risk factors among patients with type 1 diabetes in Saudi Arabia.

BACKGROUND AND AIMS: To determine the prevalence of impaired awareness of hypoglycemia (IHA) and self-identification of symptoms in patients with type 1 diabetes (T1D). METHODS: A cross-sectional study was conducted on 242 patients with T1D at the Diabetes Treatment Center, Prince Sultan Military Medical City (PSMMC), Riyadh, Saudi Arabia from May 2021 to September 2021. In addition to the demographic data, patients' HbA1c level was also collected. Awareness and symptoms of hypoglycemia were assessed using two validated questionnaire-based methods, namely the Gold and Edinburgh methods. RESULTS: The prevalence of IAH among patients with T1D was 62.8% and the presence of IAH was significantly associated with the duration of T1D (p = 0.019). Compared to males, females had significantly higher (p < 0.05) levels of warmth, pounding heart, and inability to concentrate. Compared to unmarried, married patients had significantly higher levels of (p < 0.05) drowsiness, dizziness, and blurred vision. Similarly, compared to school educated, college-educated showed a higher hunger level (p < 0.05). Patients with HbA1c ≥ 7% possess a significantly higher level of drowsiness, dizziness, and hunger. Dizziness, warmth, difficulty speaking, pounding heart, and blurred vision were significantly higher among patients with diabetes duration ≥10 yrs. Nausea was significantly higher among smokers than non-smokers (p < 0.05). CONCLUSION: The prevalence of IAH is high among patients with T1D in Saudi Arabia. Focused and evidence-based interventions are essential to minimize the hypoglycemia risk among patients with T1D.

Correlation of Bariatric Surgery Effect on Lipid Profile Among Obese Patients.

Background A considerable subpopulation of patients with morbid obesity present with dyslipidemia. It is characterized by elevated total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and low high-density lipoprotein (HDL) concentrations. Sleeve gastrectomy (SG) is considered a method of treating morbid obesity and associated dyslipidemia. Objective To assess the effect of bariatric and metabolic surgery on lipid profile of morbidly obese patients. Methods We used a retrospective approach analyzing the lipid profiles of patients who underwent SG between January 2018 and July 2020. Patients were enrolled according to age (>17 years), pre-operative body mass index (BMI; >30 kg/m2), undergoing SG, and having complete follow-up records of lipid profiles. Baseline and post-operative lipid profiles, their variation, and the percentage of variation were compared. Results We analyzed data of 163 patients who underwent SG. The mean age was 36.75 ± 10.75 years, the mean BMI was 45.66 ±8.46, and the mean pre-operative TC, LDL, HDL, and TG were 4.67 ± 1.02, 2.55 ± 1.1, 1.14 ± 0.32, and 1.5 ± 1.11, respectively. There was a significant change in the mean level of TG as it was significantly higher pre-operatively compared to its mean level post-operatively. Furthermore, a significant change was observed in HDL. There was a non-significant change in levels of TC and LDL post-operatively. Conclusion SG showed to significantly reduce TG and elevate HDL in morbidly obese patients. On the contrary, TC and LDL were non-significantly affected. Further studies with longer follow-up are warranted to provide more reliable evidence.

Assessment of Behavioural Disorders in Children with Functional Constipation.

BACKGROUND: Functional constipation (FC) is a common health problem in paediatrics that causes significant physical and emotional distress to patients and their families. AIM: In the current work, we assessed the presence of behavioural problems in children with functional constipation and their pattern and relation to various demographic and disease-associated factors. METHODS: A cross-sectional case-control study was conducted, including 55 consecutive children aged 4-16 years diagnosed with functional constipation and 55 healthy age and sex-matched controls. Psychological assessment was done using the Pediatric Symptom Checklist - 17 (PSC-17). RESULTS: Twenty-six (47.3%) patients with FC had positive total PSC-17 scores while none of the controls had positive scores (p-value < 0.001). Positive internalising and externalising behaviours scores and attention problems were found in 36 (65.5%), 15 (27.3%) and 12 (21.8%) of the patients respectively in contrary to controls where only 6 (10.9%) had positive scores in internalising behaviour, and non-showed externalising behaviour and 4 (7.3%) were inattentive. Older age, longer duration of illness, residency in rural areas and presence of encopresis were found to have a significant association with the presence of such problems. CONCLUSION: Children with FC have more behavioural disorders compared to healthy controls. Integration of psychosocial aspects and their management is recommended during dealing with patients with FC.