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Background: Acne vulgaris is a self-limiting condition that may affect the patients quality of life. The most efficacious treatment of choice for acne is isotretinoin. However, adverse effects and relapse of acne after completing an isotretinoin course pose major hurdles for treatment compliance and adherence. Method: The authors conducted a cross-sectional study using a self-administered questionnaire. The prevalence and risk factors associated with the relapse of acne following isotretinoin use among Saudi patients were assessed. In addition, the reasons for discontinuing treatment, extent of awareness about isotretinoin use-associated teratogenicity, side effects such as liver enzymes impairments, dry mouth, skin, eyes, and the number of people using isotretinoin without a prescription were determined. Results: Four hundred and twenty seven acne vulgaris patients (mean age: 25.0 years, female: 83%) were included in this study. Of the 57% subjects who used isotretinoin, 45.12% patients showed relapse. The daily dose of oral isotretinoin of 20 and 40 mg/day was taken by 80% in both group of patients, and the mean duration of isotretinoin use was 7.15(±4.5) months. Those patients who were taking higher doses of oral isotretinoin reported having more relapses.Although a majority of patients received the medication through prescription, unfortunately, they were not aware of relapse and side effects. Conclusion: Almost half of the patients showed relapse of acne after using isotretinoin. A lack of understanding regarding relapse and side effects indicates a need to improve public and professional awareness of isotretinoin. Keywords: Acne vulgaris, Isotretinoin, Prevalence, Risk factors, Saudi Arabia

Mashooq Ahmad Bhat,1 Mohamed A Al-Omar,1 Azmat Ali Khan,1 Amer M Alanazi,1 Ahmed M Naglah2,31Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 2Department of Pharmaceutical Chemistry, Drug Exploration and Development Chair (DEDC), College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 3Peptide Chemistry Department, Chemical Industries Research Division, National Research, Centre, Cairo, EgyptPurpose: To evaluate the antihepatotoxic activity of dihydropyrimidinone derivative linked with 1,4-benzodioxane.Methods: A series of novel dihydropyrimidinone derivatives linked with 1,4-benzodioxane moiety were synthesized in good yield. Modern spectroscopic techniques and elemental analysis were used for the identification of the synthesized compounds. The hepatoprotective properties of compound 2, 4-(4-nitrophenyl)-5-(2,3-dihydro-1,4-benzodioxin-6-ylcarbonyl)-3,4-dihydropyrimidin-2(1H)-one, was evaluated in a carbon tetrachloride (CCl4)-induced hepatotoxicity rat model.Results: Administration of compound 2 prior to CCl4 exposure produced a dose-dependent decrease in the levels of elevated biochemical parameters compared with the standard drug silymarin. CCl4 induced oxidative stress, increased lipid profile, and decreased high-density lipoprotein (HDL) levels. Compound 2 (20 mg/kg) significantly reduced the lipid profile and significantly improved HDL levels in a dose-dependent manner. CCl4 treatment increased malondialdehyde (MDA) level and decreased nonprotein thiol (NP-SH) and total protein (TP) in liver tissues. Pretreatment of rats with compound 2 (20 mg/kg) decreased MDA level and increased NP-SH and TP in liver tissues. Histopathological examination of liver tissues also confirmed the hepatoprotective activity of compound 2.Conclusion: These results demonstrate the antihepatotoxic activity of compound 2 in CCl4-induced hepatotoxicity model.Keywords: antihepatotoxic activity, dihydropyrimidinone, 14-benzodioxane, carbon tetrachloride, silymarin

Photophysical studies of 4-Dicyanomethylene-2,6-Dimethyl-4H-Pyran (DDP) dye with globular proteins, Human Serum Albumin (HSA) and Bovine Serum Albumin (BSA) were carried out in aqueous solution. An isosbestic point resulted on the addition of serum albumins, which signifies a complex or an equilibrium state of DDP dye with albumin. Addition of BSA to DDP dye results in a fluorescence enhancement accompanied with a significant hypsochromic shift, whereas with that of HSA, a fluorescence quenching with a considerable blue shift resulted. Excited state studies of DDP dye with serum albumins portray that the role of binding sites of dye with albumins vary considerably and the nature of interaction is presumably attributed to combined hydrogen-bonding and hydrophobic interactions. Molecular docking studies of DDP dye with albumins and two other derivatives 4-(Dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran (DCM) dye and 4-(Dicyanomethylene)-2-methyl-6-(4-t-buyl)-4H-pyran (DCT) dyes with BSA and HSA elucidates that the hydrogen-bonding interaction accompanied with several hydrophobic, pi–pi an pi–alkyl interactions coexist between dye and albumins. The binding energy, intermolecular energy and stability of the DDP, DCM and DCT dyes through docking techniques with albumins authenticate that the dye predominantly acts as hydrogen-bonding acceptor site and the protein molecule as the donor. DDP dye prefers to exist in four different binding sites of HSA, whereas, in the case of BSA, the most preferred site is found to be hydrophobic domain (site I). Interestingly, the most preferred site of DCT dye is III A subdomain of HSA, whereas DCM dye is oriented towards I B subdomain. DDP and DCT are smaller in size and reside in the domain preferred for smaller ligands (II A and IIIA) as resulted in several drugs-HSA interaction whereas DCM dye which is categorized as medium to larger ligand based on the extended structure resides in the most favoured site IB. Fluorescence techniques in combination with molecular docking methods elucidate binding characteristics and the domain in which the dye resides in a micro heterogeneous environment is established in this study.

High performance liquid chromatography (HPLC) and second-order derivative spectrophotometry have been used for simultaneous determination of pravastatin (PS) and fenofibrate (FF) in pharmaceutical formulations. HPLC separation was performed on a phenyl HYPERSIL C18 column (125 mm × 4.6 mm i.d., 5 μm particle diameter) in the isocratic mode using a mobile phase acetonitrile/0.1 % diethyl amine (50:50, V/V, pH 4.5) pumped at a flow rate of 1.0 mL min-1. Measurement was made at 240 nm. Both drugs were well resolved on the stationary phase, with retention times of 2.15 and 5.79 min for PS and FF, respectively. Calibration curves were linear (R = 0.999 for PS and 0.996 for FF) in the concentration range of 5-50 and 20-200 µg mL-1 for PS and FF, respectively. Pravastatin and fenofibrate were quantitated in combined preparations also using the second-order derivative response at 237.6 and 295.1 nm for PS and FF, respectively. Calibration curves were linear, with the correlation coefficient R = 0.999 for pravastatin and fenofibrate, in the concentration range of 5-20 and 3-20 µg mL-1 for PS and FF, respectively. Both methods were fully validated and compared, the results confirmed that they were highly suitable for their intended purpose.

A simple, sensitive and accurate HPLC method with high throughput has been developed and validated for the simultaneous determination of irbesartan (IRB) and hydrochlorothiazide (HCT) in combined pharmaceutical dosage forms. The proposed method employed, for the first time, a monolithic column in the analysis. Optimal chromatographic separation of the analytes was achieved on Chromolith® Performance RP-18e column using a mobile phase consisting of phosphate buffer (pH 4)/acetonitrile (50:50, V/V) pumped isocratically at a flow rate of 1.0 mL min-1. The eluted analytes were monitored with a UV detector set at 270 nm. Under the optimum chromatographic conditions, linear relationship with a good correlation coefficient (R ≥ 0.9997) was found between the peak area and the corresponding concentrations of both IRB and HCT in the ranges of 10-200 and 1-20 ng mL-1. The limits of detection were 2.34 and 0.03 ng mL-1 for IRB and HCT, respectively. The intra- and inter-assay precisions were satisfactory as the RSD values did not exceed 3 %. The accuracy of the proposed method was > 97 %. The proposed method had high throughput as the analysis involved a simple procedure and a very short run- -time of < 3 min. The results demonstrated that the method is applicable in the quality control of combined pharmaceutical tablets containing IRB and HCT

In the twenty-first century, we are experiencing persistent waves of diverse pathogen variations, contributing significantly to global illness and death rates. Within this varied spectrum of illnesses, malaria and oxidative damage emerge as prominent obstacles that have persistently affected human health. The motivation for exploring the antioxidant potential of transition metal (II) complexes with tridentate Schiff base ligands is driven by the need for effective treatments against malaria and oxidative stress-related conditions. Both malaria and oxidative damage are significant global health concerns. Transition metal complexes can potentially offer enhanced anti-malarial and antioxidant activities, providing a dual benefit. To explore the aforementioned facts and examine the therapeutic potential, the previously synthesized pyrrolopyrimidinehydrazide-3-chlorobenzaldehyde, such as HPPHmCB ligand(1)andtheirMn(II),Fe(II),Co(II),Ni(II), Pd(II),Cu(II),Zn(II),Cd(II),Hg(II)complexes(2-10) of benzaldehydes and pyrrolopyrimidinehydrazide were proposed for in vitro anti-malarial and antioxidant investigation. These compounds were assessed for their anti-malarial efficacy against Plasmodium falciparum using a micro assay protocol, with IC 50 values indicating the concentration required to inhibit parasite maturation by 50%. The Hg(II) complex displays pronounced antimalarial activity with an IC 50 value of 1.98 ± 0.08 µM, closely aligning with the efficacy of quinine, whereas Zn(II), Cu(II), Pd(II) complexes demonstrates most significant anti-malarial activity, with IC 50 values close to the reference compound quinine. The antioxidant activity of the compounds was evaluated using the DPPH assay, with several metal complexes such as Cu(II)and Zn(II) showing strong potential in neutralizing oxidative stress. Furthermore, molecular docking simulations were conducted to explore the binding interactions of the compounds with PfNDH2, providing insights into their pharmacological potential. The study also examined the electronic properties, solubility, and potential hepatotoxicity of the compounds. The findings suggest that the metal complexes could be promising candidates for further development as anti-malarial agents, offering enhanced potency compared to the base compound., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: The aim of this study was to assess the stress level and depression among orthopaedic surgeons in Saudi Arabia. In addition, to evaluate orthopedic training programs related factors that might have a critical role in the development of depression among orthopaedic surgeons., Methods: The study adopted a cross-sectional study design. Two validated questionnaires were utilized, the Patient Health Questionnaire 9 (PHQ-9) and the Perceived Stress Scale (PSS-10) for assessing depressive symptoms and stress levels. Data was collected by sending the survey to the Saudi Commission for Health Specialties so they could be distributed throughout all registered orthopaedic surgeons., Results: The study sample consisted of 325 participants. The results revealed that the severity of depression varied across the different groups. As per the PHQ-9 criteria, 74 (22.8%) were initially diagnosed with major depression. Among assistant consultants, 39.5% reported severe depression, while 34.9% reported mild depression. Consultants predominantly reported moderate perceived stress (82.9%) with a notable proportion experiencing high perceived stress (12.4%). Assistant consultants showed a balanced distribution, with 93.0% reporting moderate perceived stress and 4.7% reporting high perceived stress. Demographic variables gender, relationship status and having children revealed statistically significant relationship with PHQ-9 scores (p-value < 0.05) but not with PSS-10 scores., Conclusion: The study highlights pressing need to address mental health concerns within orthopaedic surgeons. To address these challenges, healthcare institutions should implement comprehensive mental health support programs offering resources for stress management, counseling services, and peer support groups., (© 2024. The Author(s).)

NUDIX hydrolase 5 (NUDT5) is an enzyme involved in the hydrolysis of nucleoside diphosphates linked to other moieties, such as ADP-ribose. This cofactor is vital in redox reactions and is essential for the activity of sirtuins and poly(ADP-ribose) polymerases, which are involved in DNA repair and genomic stability. It has been shown that NUDT5 activity can also influence NAD+ homeostasis, thereby affecting cancer cell metabolism and survival. In this regard, the discovery of NUDT5 inhibitors has emerged as a potential therapeutic approach in cancer treatment. In this study, we conducted a high-throughput virtual screening of marine bacterial compounds against the NUDT5 enzyme and four molecules were selected based on their docking scores. These compounds established strong interactions within the NUDT5 active site, with molecular analysis highlighting the key role of Trp 28A and Trp 46B residues. Molecular dynamics simulations over 200 ns indicated a stable behavior, in association with root mean square deviation values always below 3 Å, suggesting conformational stability. Free energy landscape analysis further supported their potential as NUDT5 inhibitors, offering avenues for novel therapeutic strategies against NUDT5-associated breast cancer., (© 2024. The Author(s).)

Newcastle disease virus (NDV) is a highly infectious viral disease that impacts birds globally, especially domestic poultry. NDV is a type of avian paramyxovirus which poses a major threat to the poultry industry due to its ability to inflict significant economic damage. The membrane protein, Hemagglutinin-Neuraminidase (HN) of NDV is an attractive therapeutic candidate. It contributes to pathogenicity through various functions, such as promoting fusion and preventing viral self-agglutination, which allows for viral spread. In this study, we used pharmacophore modeling to identify natural molecules that can inhibit the HN protein of NDV. Physicochemical characteristics and phylogenetic analysis were determined to elucidate structural information and phylogeny of target protein across different species as well as members of the virus family. For structural analysis, the missing residues of HN target protein were filled and the structure was evaluated by PROCHECK and VERIFY 3D. Moreover, shape and feature-based pharmacophore model was employed to screen natural compounds' library through numerous scoring schemes. Top 48 hits with 0.8860 pharmacophore fit score were subjected towards structure-based molecular docking. Top 9 compounds were observed witihin the range of -8.9 to -7.5 kcal/mol binding score. Five best-fitting compounds in complex with HN receptor were subjected to predict biological activity and further analysis. Top two hits were selected for MD simulations to validate binding modes and structural stability. Finally, upon scrutinization, A1 (ZINC05223166) emerges as potential HN inhibitor to treat NDV, necessitating further validation via clinical trials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: To assess whether a health education video increased prosthodontic treatment demand for replacing missing teeth compared to a traditional health education (IEC) leaflet among patients visiting a university dental care center in Saudi Arabia., Materials and Methods: A nonrandomized educational intervention was conducted among patients with missing teeth. A total of 350 participants were divided equally into two health-education intervention groups: leaflet group and video group. Two major variants were ascertained: demand for prosthodontic dental care and awareness (knowledge) about the importance of replacing missing teeth. These two variants were studied for the difference in the scores between base line and at the end of the program (after 3 months). Bivariate analysis was done with chi-square test, McNemar chi-square test, and Wilcoxon matched-pairs tests, and finally binary logistic regression analysis was done., Results: The final analysis included 324 participants. There was improvement in both knowledge and demand for prosthodontic care in both the groups after health education, but a statistically significant improvement in demand for dental care was observed in the video group compared to the leaflet group (42.9% vs 63.2%). Logistic regression analysis identified that missing teeth in the anterior region and being in the video group were two significant factors associated with increased demand for care., Conclusions: The health education video method was found to be a more effective method compared to leaflets in improving knowledge and demand for replacing missing teeth.

Bee products, abundant in bioactive ingredients, have been utilized in both traditional and contemporary medicine. Their antioxidant, antimicrobial, and anti-inflammatory properties make them valuable for food, preservation, and cosmetics applications. Honeybees are a vast reservoir of potentially beneficial products such as honey, bee pollen, bee bread, beeswax, bee venom, and royal jelly. These products are rich in metabolites vital to human health, including proteins, amino acids, peptides, enzymes, sugars, vitamins, polyphenols, flavonoids, and minerals. The advancement of nanotechnology has led to a continuous search for new natural sources that can facilitate the easy, low-cost, and eco-friendly synthesis of nanomaterials. Nanoparticles (NPs) are actively synthesized using honeybee products, which serve dual purposes in preventive and interceptive treatment strategies due to their richness in essential metabolites. This review aims to highlight the potential role of bee products in this line and their applications as catalysts and food preservatives and to point out their anticancer, antibacterial, antifungal, and antioxidant underlying impacts. The research used several online databases, namely Google Scholar, Science Direct, and Sci Finder. The overall findings suggest that these bee-derived substances exhibit remarkable properties, making them promising candidates for the economical and eco-friendly production of NPs.

Emergency and trauma surgeries present unique challenges for anesthesiologists due to the acuity of patient conditions and the need for rapid intervention. This review aims to provide insights into the optimal management of anesthesia in emergency and trauma surgery settings. We searched the National Institute of Health PubMed, Scopus, MEDLINE, and Web of Science databases between 2014 and 2024 to synthesize current evidence and best practices for anesthesia management during emergency and trauma surgeries. This literature review examines the evolving role of anesthesia in emergency and trauma surgeries, focusing on key considerations such as patient management, hemodynamic stability, and the choice of anesthetic agents. The review discusses recent advancements in anesthesia techniques, including the use of regional anesthesia and multimodal analgesia, to optimize patient outcomes while minimizing complications. Additionally, it discusses the importance of interdisciplinary collaboration among anesthesiologists, surgeons, and other healthcare professionals in delivering timely and effective care to critically injured patients., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Alnsour et al.)

Genomic instability is one of the main drivers of tumorigenesis and the development of hematological malignancies. Cancer cells can remedy chemotherapeutic-induced DNA damage by upregulating DNA-repair genes and ultimately inducing therapy resistance. Nevertheless, the association between the DNA-repair genes, drug resistance, and disease relapse has not been well characterized in acute lymphoblastic leukemia (ALL). This study aimed to explore the role of the DNA-repair machinery and the molecular mechanisms by which it is regulated in early- and late-relapsing pediatric ALL patients. We performed secondary data analysis on the Therapeutically Applicable Research to Generate Effective Treatments (TARGET)-ALL expansion phase II trial of 198 relapsed pediatric precursor B-cell ALL. Comprehensive genetic and epigenetic investigations of 147 DNA-repair genes were conducted in the study. Gene expression was assessed using Microarray and RNA-sequencing platforms. Genomic alternations, methylation status, and miRNA transcriptome were investigated for the candidate DNA-repair genes. We identified three DNA-repair genes, ALKBH3 , NHEJ1 , and PARP1 , that were upregulated in early relapsers compared to late relapsers ( p < 0.05). Such upregulation at diagnosis was significantly associated with disease-free survival and overall survival in precursor-B-ALL ( p < 0.05). Moreover, PARP1 upregulation accompanied a significant downregulation of its targeting miRNA, miR-1301-3 p ( p = 0.0152), which was strongly linked with poorer disease-free and overall survivals. Upregulation of DNA-repair genes, PARP1 in particular, increases the likelihood of early relapse of precursor-B-ALL in children. The observation that PARP1 was upregulated in early relapsers relative to late relapsers might serve as a valid rationale for proposing alternative treatment approaches, such as using PARP inhibitors with chemotherapy.

The current study aimed to evaluate the physicochemical properties of Fernandoa adenophylla. Powder studies were carried out to estimate the quantitative physicochemical characteristics of the crude drug, including moisture content, ash content, and extractive values. Using a Soxhlet apparatus and different analytical grade solvents, 3 sample extracts of a crude drug were made. To evaluate the potentially toxic nature, an acute oral toxicity study was performed as per OECD guideline no. 423. Sample extracts were tested and analyzed by ANOVA for pharmacological potential (analgesic, antipyretic, and antidiabetic) using Wister-Albino rats. Where physicochemical analysis indicated purity, quality, and presence of organic/inorganic materials in crude drug extracts, no sign of mortality was found up to 2000 mg/kg of body weight of Fernandoa adenophyllas extracts. Analgesic activity was observed in all sample extracts, whereas only chloroform and ethanolic extracts expressed antipyretic and antidiabetic potential. Ethanolic extract was found to be most potent in pharmacological potential as 200 mg/kg extract dose exhibited %age pain inhibition of 55.12 % and reduced body temperature from 39.78±0.03 °C to 37.22±0.02 °C in hyperthermic rats. A decrease in blood glucose levels up to 57.88 % was observed on the 21 st day of the treatment with 500 mg/kg ethanolic extract., (© 2024 The Authors. Chemistry & Biodiversity published by Wiley-VHCA AG.)

Assessment of the antimicrobial, micro tensile bond strength (μTBS), and degree of conversion (DC) of fifth-generation adhesive modified using photoactivated 0.5% rose bengal (RB) and photoactivated RB-doped titanium dioxide nanoparticles (TiO 2 NPs) in different concentrations (2% and 5%) as compared with the unmodified adhesive bonded to the carious affected dentin (CAD). Forty mandibular molars with caries progression up to the middle third of the dentin, as per the International Caries Detection and Assessment System (ICDAS) score of 4 and 5 were included. Specimens were divided into four groups based on etch and rinse adhesive (ERA) modification group 1: unmodified ERA, group 2: photoactivated 0.5% RB photosensitizer (PS) modified ERA, group 3: photoactivated RB-doped 2 wt% TiO 2 NPs adhesive, group 4: photoactivated RB-doped 5 wt% TiO 2 NPs adhesive. Followed by adhesive and composite restoration on the CAD surface. All the specimens were thermocycled and an assessment of μTBS and failure pattern analysis was performed. The antibacterial potency of RB and RB-doped TiO 2 NPs (2% and 5%) followed by their activation using visible light against Streptococcus mutans (S.mutans) were tested. The survival rate of S.mutans was assessed using the Kruskal-Wallis test. The analysis of μTBS involved the use of ANOVA, followed by a post-hoc Tukey honestly significant difference (HSD) multiple comparisons test. Group 1 (Unmodified ERA) (0.52 ± 0.31 CFU/mL) treated samples unveiled the highest means of bacterial survival and lowest μTBS (11.32 ± 0.63 MPa). Nevertheless, group 4: photoactivated RB-doped 5 wt% TiO2NPs adhesive displayed the lowest outcomes of S.mutans survival (0.11 ± 0.02 CFU/mL) and highest bond strength (18.76 ± 1.45 MPa). The photoactivated RB-doped 2 wt% TiO 2 NPs in adhesive demonstrated promising enhancements in both μTBS and antibacterial efficacy against S.mutans. However, it is noteworthy that this modification led to a decrease in the DC of the adhesive. RESEARCH HIGHLIGHTS: Unmodified ERA-treated samples unveiled the highest bacterial survival and the lowest μTBS. Photoactivated RB-doped 5 wt% TiO 2 NPs adhesive displayed the lowest S.mutans survival rate and highest bond strength. DC decreased with an increase in concentration of TiO 2 ., (© 2024 Wiley Periodicals LLC.)

Introduction Delirium is an acute and fluctuating decline in attention and cognition caused by reversible neural disruption. Post-operative delirium (POD) may happen 10 minutes after anesthesia administration up to discharge. POD has been associated with increased days of mechanical ventilation, increased patients' functional decline, prolonged intensive care unit (ICU) stay, and prolonged hospital length of stay, which can lead to nosocomial complications, further investigations, and increased treatment costs. In this study, we aim to determine the prevalence of POD and identify demographic or surgical variables associated with POD. Materials and methods This retrospective cross-sectional study was conducted at the National Guard Health Affairs Hospital (NGHA), a teaching tertiary care center in Riyadh, Kingdom of Saudi Arabia. The study included all patients older than 65 who developed POD from January 2017 to January 2023 and a control group of the same time window. The data were analyzed using custom Python code. Results The study included 108 patients, 72 of whom were male patients. General anesthesia was most used compared to other anesthesia techniques (79.630%). Patients with hypertension (HTN) and diabetes mellitus (DM) each account for 75 cases. Elective surgeries account for 86.111% of cases. Our analysis showed a significant association between POD and advanced age, male gender, DM, HTN, congestive heart failure (CHF), and chronic kidney disease (CKD).  Conclusion With our study, we hope to aid the process of better understanding POD to help healthcare providers identify high-risk patients, implement preventative measures, and enhance patient safety and satisfaction., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Almashari et al.)

Background: Chronic myeloid leukemia is a hematological malignancy characterized by the abnormal proliferation of leukemic cells. Despite significant progress with tyrosine kinase inhibitors, such as Dasatinib, resistance remains a challenge. The aim of the present study was to investigate the potential of Selinexor, an Exportin-1 inhibitor, to improve TKI effectiveness on CML., Methods: Human CML cell lines (LAMA84 and K562) were treated with Selinexor, Dasatinib, or their combination. Apoptosis, mitochondrial membrane potential, and mitochondrial mass were assessed using flow cytometry. Real-time RT-PCR was used to evaluate the expression of genes related to mitochondrial function. Western blot and confocal microscopy examined PINK and heme oxygenase-1 (HO-1) protein levels., Results: Selinexor induced apoptosis and mitochondrial depolarization in CML cell lines, reducing cell viability. The Dasatinib/Selinexor combination further enhanced cytotoxicity, modified mitochondrial fitness, and downregulated HO-1 nuclear translocation, which has been associated with drug resistance in different models., Conclusions: In conclusion, this study suggests that Dasatinib/Selinexor could be a promising therapeutic strategy for CML, providing new insights for new targeted therapies.

The Coronavirus Disease 2019, commonly referred to as COVID-19, is responsible for one of the deadliest pandemics in human history. The direct, indirect and lasting repercussions of the COVID-19 pandemic on individuals and public health, as well as health systems can still be observed, even today. In the midst of the initial chaos, the role of tobacco as a prognostic factor for unfavourable COVID-19 outcomes was largely neglected. As of 2023, numerous studies have confirmed that use of tobacco, a leading risk factor for cardiovascular and other diseases, is strongly associated with increased risks of severe COVID-19 complications (e.g., hospitalisation, ICU admission, need for mechanical ventilation, long COVID, etc.) and deaths from COVID-19. In addition, evidence suggests that COVID-19 directly affects multiple organs beyond the respiratory system, disproportionately impacting individuals with comorbidities. Notably, people living with cardiovascular disease are more prone to experiencing worse outcomes, as COVID-19 often inherently manifests as thrombotic cardiovascular complications. As such, the triad of tobacco, COVID-19 and cardiovascular disease constitutes a dangerous cocktail. The lockdowns and social distancing measures imposed by governments have also had adverse effects on our lifestyles (e.g., shifts in diets, physical activity, tobacco consumption patterns, etc.) and mental well-being, all of which affect cardiovascular health. In particular, vulnerable populations are especially susceptible to tobacco use, cardiovascular disease and the psychological fallout from the pandemic. Therefore, national pandemic responses need to consider health equity as well as the social determinants of health. The pandemic has also had catastrophic impacts on many health systems, bringing some to the brink of collapse. As a result, many health services, such as services for cardiovascular disease or tobacco cessation, were severely disrupted due to fears of transmission and redirection of resources for COVID-19 care. Unfortunately, the return to pre-pandemic levels of cardiovascular disease care activity has stagnated. Nevertheless, digital solutions, such as telemedicine and apps, have flourished, and may help reduce the gaps. Advancing tobacco control was especially challenging due to interference from the tobacco industry. The industry exploited lingering uncertainties to propagate misleading information on tobacco and COVID-19 in order to promote its products. Regrettably, the links between tobacco use and risk of SARS-CoV-2 infection remain inconclusive. However, a robust body of evidence has, since then, demonstrated that tobacco use is associated with more severe COVID-19 illness and complications. Additionally, the tobacco industry also repeatedly attempted to forge partnerships with governments under the guise of corporate social responsibility. The implementation of the WHO Framework Convention on Tobacco Control could address many of the aforementioned challenges and alleviate the burden of tobacco, COVID-19, and cardiovascular disease. In particular, the implementation of Article 5.3 could protect public health policies from the vested interests of the industry. The world can learn from the COVID-19 pandemic to better prepare for future health emergencies of international concern. In light of the impact of tobacco on the COVID-19 pandemic, it is imperative that tobacco control remains a central component in pandemic preparedness and response plans., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

Objective: The present study evaluated the oral tissue expression of micro-RNA (miRNAs) linked to the potential malignant evolution of oral lichen planus (OLP). Furthermore, the correlation between OLP severity and miRNAs expression was assessed, and possible predictors of miRNAs in OLP patients were identified., Methods: The present study enrolled 41 patients with OLP (median age 58 years) and 42 healthy controls (median age 59 years). In each patient, miRNA levels (miR-7a-3p,-7a2-3p,-7a-5p,-21-3p,-21-5p,-100-3p,-100-5p,-125b-2-3p,-125b-5p,-200b-3p,-200b-5p) were assessed and analyzed through reverse transcription polymerase chain reaction. Clinical parameters and the eventual presence of OLP symptoms, signs, and disease severity scores in each patient were reported using an anamnestic questionnaire., Results: In comparison with healthy controls, OLP patients showed significantly higher miR-7a-3p,-7a-2-3p,-21-3p, miR-21-5p and miR-100-5p levels (p < 0.05) and significantly lower miR-125b-2-3p,-125b-5p,-200b-3p, and -200b-5p levels (p < 0.05). Furthermore, OLP symptoms and signs and disease severity scores were significantly correlated and were also predictors of all analyzed miRNAs (p < 0.05)., Conclusions: In comparison with healthy subjects, OLP patients exhibited unbalanced oral miRNAs expression linked to the risk of potential malignant evolution of OLP. Furthermore, some miRNAs were correlated with OLP extent and were significant predictors of OLP symptoms, signs, and disease severity scores., (© 2023 The Authors. Oral Diseases published by Wiley Periodicals LLC.)

Background: Cardiorespiratory function is one of the key health indicators that promote good health. Knowing the correlation between body mass index (BMI) and cardiorespiratory functioning might assist in the creation of evidence-based therapies that focus on addressing difficulties associated with obesity., Objective: To assess the correlation between BMI and cardiorespiratory functions among medical students at Northern Border University., Materials and Methods: A cross-sectional study was conducted among medical students at Northern Border University, Saudi Arabia. The blood pressure (BP), respiratory rate (RR), heart rate (HR), mean arterial pressure (MAP), pulse pressure (PP), and BMI of the students were measured., Results: The mean age of the students was 17.1 ± 1.9 years. Nearly 40% of students were overweight or obese. Our study revealed a significant positive correlation between BMI and BP, RR, tidal volume (TV), and MAP., Conclusions:  The correlation analysis of our study revealed a significant positive correlation of BMI with BP, RR, TV, and MAP., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Local Committee of Bioethics at Northern Border University (HAP-09-A-043) issued approval 95/23/H. We obtained ethical approval from the Local Committee of Bioethics at Northern Border University (HAP-09-A-043) with decision number 95/23/H, dated: 12-10-2023. There is no risk to participants because the study is questionnaire-based, and students have complete control over whether to participate or not. Data privacy and confidentiality were assured. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Abd El Mawgod et al.)

Down Syndrome (DS) is a common genetic disorder characterized by an extra copy of chromosome 21, leading to dysregulation of various metabolic pathways. Oxidative stress in DS is associated with neurodevelopmental defects, neuronal dysfunction, and a dementia onset resembling Alzheimer's disease. Additionally, chronic oxidative stress contributes to cardiovascular diseases and certain cancers prevalent in DS individuals. This study investigates the impact of ageing on oxidative stress and liver fibrosis using a DS murine model (Ts2Cje mice). Our results show that DS mice show increased liver oxidative stress and impaired antioxidant defenses, as evidenced by reduced glutathione levels and increased lipid peroxidation. Therefore, DS liver exhibits an altered inflammatory response and mitochondrial fitness as we showed by assaying the expression of HMOX1, CLPP, and the heat shock proteins Hsp90 and Hsp60. DS liver also displays dysregulated lipid metabolism, indicated by altered expression of PPARα, PPARγ, FATP5, and CTP2. Consistently, these changes might contribute to non-alcoholic fatty liver disease development, a condition characterized by liver fat accumulation. Consistently, histological analysis of DS liver reveals increased fibrosis and steatosis, as showed by Col1a1 increased expression, indicative of potential progression to liver cirrhosis. Therefore, our findings suggest an increased risk of liver pathologies in DS individuals, particularly when combined with the higher prevalence of obesity and metabolic dysfunctions in DS patients. These results shed a light on the liver's role in DS-associated pathologies and suggest potential therapeutic strategies targeting oxidative stress and lipid metabolism to prevent or mitigate liver-related complications in DS individuals.

Background: Nonalcoholic fatty liver disease (NAFLD) is a prevalent condition characterized by hepatic fat accumulation, often progressing to severe liver injury, for which approved treatments are currently lacking. This study explores the potential therapeutic impact of alpha-lipoic acid (ALA), a natural compound crucial in lipid metabolism, on NAFLD using an in vitro model., Methods: HepG2 cells were treated with a palmitic acid:oleic acid (PA:OA) mixture, representing a cellular model of steatosis. Subsequent treatment with ALA at concentrations of 1 µM and 5 µM aimed to evaluate its effects on lipid content and metabolism. Real-time polymerase chain reaction (PCR), BODIPY staining, cytofluorimetric analysis, and lipidomics were used to assess gene expression, lipid droplet accumulation, and fatty acid profiles., Results: Our results showed that ALA significantly reduced lipid droplets in PA:OA-treated HepG2 cells, with a concentration-dependent effect. Analysis of fatty acid profiles demonstrated a decrease in palmitic acid levels with ALA treatment, while oleic acid reduction was observed only at the higher concentration. Moreover, ALA modulated the expression of genes involved in cholesterol biosynthesis and low-density lipoprotein (LDL) metabolism, indicating a potential role in lipid homeostasis. Further insights into molecular mechanisms revealed that ALA modulated peroxisome proliferator activated receptors (PPARs), specifically PPAR-alpha and PPAR-gamma, involved in fatty acid metabolism and insulin sensitivity. Finally, ALA counteracted the overexpression of thermogenic genes induced by exogenous fatty acids, suggesting a regulatory role in energy dissipation pathways., Conclusion: In conclusion, this study highlights ALA as a therapeutic agent in mitigating lipid accumulation and dysregulation in NAFLD., Competing Interests: Given their role as Guest Editor, GLV had no involvement in the peer-review of this article and have no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Margaret O. James. The authors declare no other conflict of interest., (© 2024 The Author(s). Published by IMR Press.)

Background: Septic shock is associated with systemic inflammatory response, hemodynamic instability, impaired sympathetic control, and the development of multiorgan dysfunction that requires vasopressor or inotropic support. The regulation of immune function in sepsis is complex and varies over time. However, activating Beta-2 receptors and blocking Beta-1 receptors reduces the proinflammatory response by influencing cytokine production. Evidence that supports the concomitant use of ultra short beta-blockers with inotropes and vasopressors in patients with septic shock is still limited. This study aimed to evaluate the use of ultra short beta-blockers and its impact on the ICU related outcomes such as mortality, length of stay, heart rate control, shock resolution, and vasopressors/inotropes requirements., Methods: A systematic review and meta-analysis of randomized controlled trials including critically ill patients with septic shock who received inotropes and vasopressors. Patients who received either epinephrine or norepinephrine without beta-blockers "control group" were compared to patients who received ultra short beta-blockers concomitantly with either epinephrine or norepinephrine "Intervention group". MEDLINE and Embase databases were utilized to systematically search for studies investigating the use of ultra short beta-blockers in critically ill patients on either epinephrine or norepinephrine from inception to October 10, 2023. The primary outcome was the 28-day mortality. While, length of stay, heart rate control, and inotropes/ vasopressors requirements were considered secondary outcomes., Results: Among 47 potentially relevant studies, nine were included in the analysis. The 28-day mortality risk was lower in patients with septic shock who used ultra short beta-blockers concomitantly with either epinephrine or norepinephrine compared with the control group (RR (95%CI): 0.69 (0.53, 0.89),  I 2=26%;  P =0.24). In addition, heart rate was statistically significantly lower with a standardized mean difference (SMD) of -22.39 (95% CI: -24.71, -20.06) among the beta-blockers group than the control group. The SMD for hospital length of stay and the inotropes requirement were not statistically different between the two groups (SMD (95%CI): -0.57 (-2.77, 1.64), and SMD (95%CI): 0.08 (-0.02, 0.19), respectively)., Conclusion: The use of ultra short beta-blockers concomitantly with either epinephrine or norepinephrine in critically ill patients with septic shock was associated with better heart rate control and survival benefits without increment in the inotropes and vasopressors requirement., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

KRAS G12D are the most prevalent oncogenic mutations and a promising target for solid tumor therapies. However, its inhibition exhibits tremendous challenge due to the necessity of high binding affinity to obviate the need for covalent binders. Here we report the evidence of a novel class of Imidazo[1,2-a]pyridine derivative as potentially significant novel inhibitors of KRAS G12D , discovered through extensive ligand-based screening against 2-[(2R)-piperidin-2-yl]-1H-indole, an important scaffold for KRAS G12D inhibition via switch-I/II (S-I/II) pocket. The proposed compounds exhibited similar binding affinities and overlapped pose configurations to 2-[(2R)-piperidin-2-yl]-1H-indole, serving as a reliable starting point for drug discovery. Comparative free energy profiles demonstrated that C4 [2-methyl-3-((5-phenyl-1H-1,2,4-triazol-3-yl)methyl)imidazo[1,2-a]pyridine] effectively shifted the protein to a stable low-energy conformation via a prominent transition state. The conformational changes across the transition revealed the conformational shift of switch-I and II to a previously known off-like conformation of inactive KRAS G12D with rmsd of 0.91 Å. These conformations were even more prominent than the privileged scaffold 2-[(2R)-piperidin-2-yl]-1H-indole. The representative structure overlay of C4 and another X-ray crystallography solved BI-2852 bound inactive KRAS G12D revealed that Switch-I and II exhibited off-like conformations. The cumulative variance across the first eigenvalue that accounted for 57 % of the collective variance validated this on-to-off transition. In addition, the relative interaction of C4 binding showed consistent patterns with BI-2852. Taken together, our results support the inhibitory activity of [2-methyl-3-((5-phenyl-1H-1,2,4-triazol-3-yl)methyl)imidazo[1,2-a]pyridine] by shifting active KRAS G12D to an inactive conformation., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background Autism spectrum disorder (ASD) is a psychopathologic disorder caused by several factors. The early signs include poor interaction and communication, delayed milestones, and repeated behavior patterns. This study aimed to assess the relationship between screen time and ASD severity and investigate the types of electronic devices associated with ASD in children aged four to six years in Arar City, Kingdom of Saudi Arabia (KSA). Methodology A cross-sectional study was conducted in primary healthcare centers (PHCs) in Arar City, KSA. The study enrolled all parents with children aged four to six years attending the PHCs in Arar City, KSA. Results The total sample size was 199 participants. Regarding the relationship between screen time exposure and ASD, there were variable screen time exposure durations, with 22.6% of children exposed for less than an hour, 30.7% for one to two hours, and 46.7% for more than two hours. Moreover, the type of electronic devices to which children were exposed varied, with smartphones being the most prevalent (68.3%). In terms of the age of children since exposure to electronic devices, the data indicated that 30.2% were exposed before the age of two, 35.2% between two and three years, and 34.7% after three years of age. Regarding the relationship with sociodemographic characteristics, there was a statistically significant relationship with the mother's age at birth (p = 0.050), mother's education level (p = 0.009), father's education level (p = 0.049), whether the child was suffering from any chronic or neurological disease (p = 0.008), age since the child was exposed to electronic devices (p = 0.049), and screen time exposure duration (p = 0.040). Conclusions The study highlights the significant association between screen time exposure and the development of ASD in children. Public awareness of this associated risk among caregivers is recommended to follow the protective guidelines. Further research and interventions are needed to better understand and address the impact of screen media use on children's neurodevelopment and overall well-being., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Local Bioethics Committee, Northern Border University issued approval 107/23/H. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Alenazi et al.)

Organoclays have been proposed as efficient removal agents for colored wastewater treatment. In this study, organo-acid-activated clays were investigated for their ability to remove eosin Y dye molecules. Firstly, the clay was acid activated using sulfuric solution at 90 °C for overnight. Secondly, the resulting materials were treated by hexadecyltetramethylammonium bromide solutions to obtain organo-acid-activated clays. Several techniques were used, such as X-ray diffraction, carbon hydrogen nitrogen analysis, silicon-29 and carbon-13 solid-state nuclear magnetic resonance, and nitrogen adsorption isotherms. The cation exchange capacity values were reduced and the specific surface area values increased from 80.1 m2/g to 183.2 m2/g during the acid activation process. The resulting organo-acid-activated clays had a similar expansion of interlayer spacing of 3.90 nm with less intercalated hexadecyltetramethylammonium surfactants, ranging from 0.80 mmol/g to 1.22 mmol/g; 13C solid NMR indicated that the intercalated surfactants exhibited different degree of conformation. Many factors, including the solid dose, solution pH, amount of intercalated surfactants, and starting eosin-Y concentrations, were studied in relation to the removal capabilities of organo acid-activated clays. Based on the Langmuir model, the removal capacity of the organo acid-activated clays ranged from a minimum of 43.5 mg/g to a maximum of 79.3 mg/g, dependent on the surfactant quantities and acid activation degree. , and the pH. The removal percentage of eosin-Y was increased from 50.5 % to 80.8 % by treating the organo acid-activated clay with HCl solution before the removal procedure. Regeneration and reuse of two selected organo acid-activated clays were carried out for seven successive cycles, and a reduction in the initial efficiency was in the range of 26.4 %-30.1 %. However, for organoclay (without acid activation), approximately 52.1 % efficiency was maintained. Using the Langmuir model and mass balance equations, a single-stage adsorber design was suggested for different dye volumes at a constant starting concentration., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objective: Evaluation of contemporary disinfection techniques, Moringa Oleifera (M.Oleifera), Phycocyanin activated by photodynamic therapy (PDT), and Chitosan, on S.mutans survival rate and bond integrity of composite to carious-affected dentin (CAD)., Methods: The in vitro study was conducted at King Saud University and concluded within three months. Sixty mandibular teeth with cavities extending to the middle third of the dentin were sterilized. S.mutans was inoculated onto the CAD surface of twenty samples. The samples were randomly divided into four groups (n: 15) based on various disinfection regimes. Group-1 received 2% CHX, Group-2 Phycocyanin activated by photodynamic therapy (PDT), Group-3 Chitosan, and Group-4 M.oleifera. S.mutans survival rate was calculated. Ten CAD samples from each group were restored using composite. The bond integrity of samples was assessed using a Universal testing machine (UTM) and failure mode using a stereomicroscope. Analysis of variance (ANOVA) and Tukey's Post Hoc test were used to calculate statistical significance (p=0.05)., Results: Group-2 samples subjected to Phycocyanin activated using PDT, displayed minimal survival rate (0.24 ± 0.05 CFU/ml) of S.mutans.Group-1 samples treated with CHX exhibited the highest count of S.mutans (0.69 ± 0.12 CFU/ml). The most robust bond was observed in Group-3 (Chitosan) samples (19.33 ± 0.47 MPa). In contrast, SBS values were lowest in Group-1 (CHX) treated study samples (13.17 ± 1.88 MPa)., Conclusion: Chitosan, Phycocyanin activated by PDT, and Moringa Oleifera extract exhibit potential as viable substitutes for chlorhexidine (CHX) in clinical settings, presenting the possibility of better eradication of S.mutans and greater adhesive strength to CAD., Competing Interests: Conflict of interest Statement: None., (Copyright: © Pakistan Journal of Medical Sciences.)

In the current work, favipiravir (an antiviral drug) loaded pH-responsive polymeric hydrogels were developed by the free redical polymerization technique. Box-Behnken design method via Design Expert version 11 was employed to furnish the composition of all hydrogel formulations. Here, polyethylene glycol (PEG) has been utilized as a polymer, acrylic acid (AA) as a monomer, and potassium persulfate (KPS) and methylene-bisacrylamide (MBA) as initiator and cross-linker, respectively. All networks were evaluated for in-vitro drug release (%), sol-gel fraction (%), swelling studies (%), porosity (%), percentage entrapment efficiency, and chemical compatibilities. According to findings, the swelling was pH sensitive and was shown to be greatest at a pH of 6.8 (2500%). The optimum gel fraction offered was 97.8%. A sufficient porosity allows the hydrogel to load a substantial amount of favipiravir despite its hydrophobic behavior. Hydrogels exhibited maximum entrapment efficiency of favipiravir upto 98%. The in-vitro release studies of drug-formulated hydrogel revealed that the drug release from hydrogel was between 85 to 110% within 24 h. Drug-release kinetic results showed that the Korsmeyer Peppas model was followed by most of the developed formulations based on the R 2 value. In conclusion, the hydrogel-based technology proved to be an excellent option for creating the sustained-release dosage form of the antiviral drug favipiravir., (© 2024. The Author(s).)

To date, little is known concerning the circulating levels of biochemically relevant metabolites (antioxidants, oxidative/nitrosative stress biomarkers, purines, and pyrimidines) in patients with primary myelofibrosis (PMF), a rare form of myeloproliferative tumor causing a dramatic decrease in erythropoiesis and angiogenesis. In this study, using a targeted metabolomic approach, serum samples of 22 PMF patients and of 22 control healthy donors were analyzed to quantify the circulating concentrations of hypoxanthine, xanthine, uric acid (as representative purines), uracil, β-pseudouridine, uridine (as representative pyrimidines), reduced glutathione (GSH), ascorbic acid (as two of the main water-soluble antioxidants), malondialdehyde, nitrite, nitrate (as oxidative/nitrosative stress biomarkers) and creatinine, using well-established HPLC method for their determination. Results showed that PMF patients have dramatic depletions of both ascorbic acid and GSH (37.3- and 3.81-times lower circulating concentrations, respectively, than those recorded in healthy controls, p < 0.0001), accompanied by significant increases in malondialdehyde (MDA) and nitrite + nitrate (4.73- and 1.66-times higher circulating concentrations, respectively, than those recorded in healthy controls, p < 0.0001). Additionally, PMF patients have remarkable alterations of circulating purines, pyrimidines, and creatinine, suggesting potential mitochondrial dysfunctions causing energy metabolism imbalance and consequent increases in these cell energy-related compounds. Overall, these results, besides evidencing previously unknown serum metabolic alterations in PMF patients, suggest that the determination of serum levels of the aforementioned compounds may be useful to evaluate PMF patients on hospital admission for adjunctive therapies aimed at recovering their correct antioxidant status, as well as to monitor patients' status and potential pharmacological treatments.

Polyelectrolyte complexes (PECs) formed by the interaction between oppositely charged polymers have emerged as promising carriers for accomplishing colon-specific release. In this study, we have explored the potential of polyelectrolyte complexes between a succinate derivative of Leucaena leucocephala galactomannan and cationic guar gum for colon delivery of synbiotic. The PECs were prepared using a polyelectrolyte complexation method and characterized. The PECs exhibited excellent stability, with high encapsulation efficiency for both probiotics (95.53 %) and prebiotics (83.33 %). In vitro studies demonstrated enhanced survivability and proliferation of the encapsulated probiotics in the presence of prebiotics (93.29 %). The SEM images revealed a smooth and firm structure with reduced number of pores when both prebiotic and probiotic were encapsulated together. The treatment with synbiotic PECs in acetic acid induced IBD rats significantly relieves colitis symptoms as was evident from colon/body ratio, DAI score and histopathology studies. An increase in the protein and reduced glutathione levels and reduction in superoxide dismutase activity was observed in colitic rats that received synbiotic treatment as compared to colitic rats. Overall, this study highlights the potential of Leucaena leucocephala succinate-cationic guar gum PECs as a promising system for colon-specific synbiotic delivery, with implications for improved gut health and the treatment of various gastrointestinal disorders., Competing Interests: We hereby declare that there is no conflict of interest with this manuscript entitled“Leucaena leucocephala Succinate based Polyelectrolyte complexes for Colon Delivery of Synbiotic in Management of Inflammatory Bowel Disease.” The authors have approved the order of authors listed in the manuscript., (© 2024 The Authors.)

Background: The importance of children's eye health cannot be overstated as it has significant implications for personal life, education, career, health, financial status, and overall satisfaction. This study aims to assess the awareness of parents regarding pediatric eye diseases to identify potential gaps in knowledge. By understanding parental awareness, we can develop targeted educational initiatives to promote early detection, timely intervention, and overall improved eye health in children. This research seeks to contribute valuable insights for enhancing preventive measures and fostering healthier eyesight in younger generations., Methodology:  A descriptive cross-sectional study was conducted in the Hail and Al-Qassim regions, of Saudi Arabia. Parents with children aged less than 15 years were included. Targeted parents were selected consecutively using an online questionnaire for data collection. Data included parents' data, children's eye diseases, and parents' knowledge, practice, and attitude toward pediatric eye diseases.  Results: A total of 618 eligible parents were included, 429 (69.4%) from Al-Qassim and 189 (30.6%) from Hail. Parents' ages ranged from 20 to 59 years with a mean age of 35.4 ± 11.5 years. A total of 510 (82.5%) respondents were females. A total of 442 (71.5%) of the study parents had poor knowledge about their pediatric eye problems, 154 (24.9%) had a good knowledge level, and only 22 (3.6%) had excellent knowledge. As for their practice, 458 (74.1%) of the parents arranged for their children to undergo an eye or visual test; 254 (55.5%) did so when the child was six to ten years of age., Conclusion:  The current study showed poor awareness levels about pediatric eye diseases among parents, mainly regarding cataracts and glaucoma. On the other hand, parents demonstrated a high level of engagement in visually assessing their children. The primary hindrance to conducting assessments was the absence of symptoms and signs or active complaints, leading to a lack of proactive seeking of visual evaluations., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Alshammari et al.)

Muscle damage resulting from physical activities such as exercise triggers an immune response crucial for tissue repair and recovery. This study investigates the immune cell profiles in muscle biopsies of individuals engaged in resistance exercise (RE) and explores the impact of age and sex on the immune response following exercise-induced muscle damage. Microarray datasets from muscle biopsies of young and old subjects were analyzed, focusing on the gene expression patterns associated with immune cell activation. Genes were compared with immune cell signatures to reveal the cellular landscape during exercise. Results show that the most significant modulated gene after RE was Folliculin Interacting Protein 2 (FNIP2) a crucial regulator in cellular homeostasis. Moreover, the transcriptome was stratified based on the expression of FNIP2 and the 203 genes common to the groups obtained based on sex and age. Gene ontology analysis highlighted the FLCN-FNIP1-FNIP2 complex, which exerts as a negative feedback loop to Pi3k-Akt-mTORC1 pathway. Furthermore, we highlighted that the young females exhibit a distinct innate immune cell activation signature compared to males after a RE session. Specifically, young females demonstrate a notable overlap with dendritic cells (DCs), M1 macrophages, M2 macrophages, and neutrophils, while young males overlap with M1 macrophages, M2 macrophages, and motor neurons. Interestingly, in elderly subjects, both sexes display M1 macrophage activation signatures. Comparison of young and elderly signatures reveals an increased M1 macrophage percentage in young subjects. Additionally, common genes were identified in both sexes across different age groups, elucidating biological functions related to cell remodeling and immune activation. This study underscores the intricate interplay between sex, age, and the immune response in muscle tissue following RE, offering potential directions for future research. Nevertheless, there is a need for further studies to delve deeper and confirm the dynamics of immune cells in response to exercise-induced muscle damage., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The purpose of this study was to produce hyaluronic acid customized nanoparticles with chitosan for the delivery of chebulinic acid (CLA) to enhance its anticancer potential against breast cancer. A significant portion of CLA was encapsulated (89.72 ± 4.38 %) and loaded (43.15 ± 5.61 %) within hybrid nanoparticles. The colloidal hybrid nanoparticles demonstrated a polydispersity index (PDI) of about 0.379 ± 0.112, with zeta capacitance of 32.69 ± 5.12 (mV), and an average size of 115 ± 8 (nm). It was found that CLA-CT-HA-NPs had stronger anticancer effects on MCF-7 cells (IC 50  = 8.18 ± 3.02 μM) than pure CLA (IC 50  = 17.15 ± 5.11 μM). The initial cytotoxicity findings were supported by additional investigations based on comet assay and flow cytometry analysis. Tumor remission and survival were evaluated in five separate groups of mice. When juxtaposed with pure CLA (3.17 ± 0.419 %), CLA-CT-HA-NPs improved survival rates and reduced tumor burden by 3.76 ± 0.811(%). Furthermore, in-silico molecular docking investigations revealed that various biodegradable polymers had several levels of compatibility with CLA. The outcomes of this study might potentially served as an effective strategy for delivering drugs in the context of breast cancer therapy., Competing Interests: Declaration of competing interest The authors state that there are no competing interests involved., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Tobacco smoking is one of the most significant health-related problems worldwide. However, the prevalence and sociodemographic determinants of tobacco and nicotine use among students on healthcare courses in Saudi Arabia are limited., Methods: This cross-sectional study used a questionnaire that was distributed via SurveyMonkey between November 2022 and June 2023 to all student universities offering healthcare courses. Data are presented as frequency and percentages. The associated sociodemographic factors with current tobacco and nicotine use were subjected to logistic regression., Results: Overall, 5,012, of whom 3,872 (77.25%) were males, responded to the online survey. The prevalence of current tobacco and nicotine use was 3,553 (71%). The majority of users used electronic nicotine delivery systems (1,622: 32.36%). The current use of cigarettes (AOR: 1.75 (1.42 to 2.15)), e-cigarettes (AOR: 1.17 (1.01 to 1.37)), and smokeless tobacco substances (AOR: 1.35 (1.02 to 1.90)) were more pronounced among males compared to female students. However, the current use of a hookah was less among males (AOR: 0.74 (95% CI: 61 to 0.91)). Smoking cigarettes was practiced less among students living in other regions compared to the Central Region. However, smokeless tobacco substances seem to be more prevalent in the Western, Southern, and Northern Regions, (AOR: 1.57 (95% CI: 1.09 to 2.26)), (AOR: 1.43 (95% CI: 1.04 to 1.95)), and (AOR: 1.57 (95% CI: 1.09 to 2.26)), respectively., Conclusion: Smoking is prevalent among students in the healthcare disciplines, with electronic nicotine delivery systems being the most used product. Several sociodemographic factors were associated with higher tobacco or nicotine use., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Aldhahir, Siraj, Alqarni, Alqahtani, Alyami, Majrshi, Alwafi, Alqahtani, Monshi, Al-Zalabani and Alanazi.)

In contemporary wastewater treatment industry, advanced oxidation techniques, membrane filtration, ion exchange, and reverse osmosis are used to treat chemically loaded wastewater. All these methods required highly toxic oxidizing chemicals, high capital investment in membrane/filter materials, and the installation of sophisticated equipment. Wastewater treatment through an adsorption process using biomass-based adsorbent is economical, user-friendly, and sustainable. Neem tree waste has been explored as an adsorbent for wastewater treatment. The chemical components in the neem biomass include carbohydrates, fat, fiber, cellulose, hemicellulose, and lignin, which support the functionalization of neem biomass. Moreover, adsorbent preparation from renewable resources is not only cost-effective and environmentally friendly but also helps in waste management for sustainable growth. Contemporary researchers explored the pre- and post-surface-modified neem biomass adsorbents in scavenging the pollutants from contaminated water. This review extensively explores the activation process of neem biomass, physical and chemical methods of surface modification mechanism, and the factors affecting surface modification. The pollutant removal through pre and post-surface-modified neem biomass adsorbents was also summarized. Furthermore, it also provides a comprehensive summary of the factors that affect the adsorption performance of the neem biomass-derived adsorbents against dyes, metal ions, and other emerging pollutants. Understanding the surface-modification mechanisms and the adsorption efficiency factor of adsorbents will help in harnessing their potential for more efficiently combatting environmental pollution and making strides toward a greener and more sustainable future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Despite the success of antibiotics in medicine, the treatment of bacterial infection is still challenging due to emerging resistance and suitable drug delivery system, therefore, innovative approaches focused on nanoparticles based antimicrobial drug delivery systems are highly desired. This research aimed to synthesize Cymbopogon citratus ( C. citratus ) aqueous extract-mediated copper oxide (CuO-Nps) conjugated with levofloxacin (LFX). The synthesized CuO NPs-LFX nano conjugate was confirmed by analysis using scanning electron microscopy (SEM), thermal gravimetric analysis (TGA), and infrared and ultraviolet/visible spectroscopy. Antibacterial activities were assessed in vitro through the agar well diffusion method against six bacterial strains of clinical relevance. CuO NPs confirmed by UV-Vis analysis absorption peak observed at 380 nm. TGA analysis showed 8.98% weight loss between the 400-800 ° C temperature range. The functional group's presence was confirmed by FTIR analysis. Spherical shape nanoparticles with an average particle size of 55 nm were recorded by FESEM. Results from agar well diffusion assay showed that CuO NPs-LFX prohibited the development of both gram-positive and gram-negative bacteria at all established concentrations, and the antibacterial propensity was more pronounced as compared to bare CuO NPs, Levofloxacin and C. citratus aqueous extract alone. The results showed that gram-negative bacteria are more susceptible to CuO NPs-LFX nano conjugate and at 10 μgmL -1 concentration, form a 10.1 mm zone of inhibition (ZOI), whereas gram-positive bacteria on the same concentration form 9.5 mm ZOI. LFX-loaded CuO NPs antibacterial activity was observed higher than plant extract, bare CuO NPs, and standard drug (Levofloxacin). This study provides a novel approach for the fabrication of biogenic CuO NPs with antibacterial drug levofloxacin and their usage as nano antibiotic carriers against pathogenic bacteria, especially antibiotic-resistant microbes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objective: This study aims to determine the efficacy of the Acacia arabica (Lam.) Willd. and Cinnamomum camphora (L.) J. Presl. vaginal suppository in addressing heavy menstrual bleeding (HMB) and their impact on participants' health-related quality of life (HRQoL) analyzed using machine learning algorithms. Method: A total of 62 participants were enrolled in a double-dummy, single-center study. They were randomly assigned to either the suppository group (SG), receiving a formulation prepared with Acacia arabica gum ( Gond Babul ) and camphor from Cinnamomum camphora ( Kafoor ) through two vaginal suppositories (each weighing 3,500 mg) for 7 days at bedtime along with oral placebo capsules, or the tranexamic group (TG), receiving oral tranexamic acid (500 mg) twice a day for 5 days and two placebo vaginal suppositories during menstruation at bedtime for three consecutive menstrual cycles. The primary outcome was the pictorial blood loss assessment chart (PBLAC) for HMB, and secondary outcomes included hemoglobin level and SF-36 HRQoL questionnaire scores. Additionally, machine learning algorithms such as k-nearest neighbor (KNN), AdaBoost (AB), naive Bayes (NB), and random forest (RF) classifiers were employed for analysis. Results: In the SG and TG, the mean PBLAC score decreased from 635.322 ± 504.23 to 67.70 ± 22.37 and 512.93 ± 283.57 to 97.96 ± 39.25, respectively, at post-intervention (TF3), demonstrating a statistically significant difference ( p < 0.001). A higher percentage of participants in the SG achieved normal menstrual blood loss compared to the TG (93.5% vs 74.2%). The SG showed a considerable improvement in total SF-36 scores (73.56%) compared to the TG (65.65%), with a statistically significant difference ( p < 0.001). Additionally, no serious adverse events were reported in either group. Notably, machine learning algorithms, particularly AB and KNN, demonstrated the highest accuracy within cross-validation models for both primary and secondary outcomes. Conclusion: The A. arabica and C. camphora vaginal suppository is effective, cost-effective, and safe in controlling HMB. This botanical vaginal suppository provides a novel and innovative alternative to traditional interventions, demonstrating promise as an effective management approach for HMB., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Fazmiya, Sultana, Heyat, Parveen, Rahman, Akhtar, Khan, Alanazi, Ahmed, Díez, Ballester and Saripalli.)

The COVID-19 pandemic caused unprecedented damage to humanity, and while vaccines have been developed, they are not fully effective against the SARS-CoV-2 virus. Limited targeted drugs, such as Remdesivir and Paxlovid, are available against the virus. Hence, there is an urgent need to explore and develop new drugs to combat COVID-19. This study focuses on exploring microbial natural products from soil-isolated bacteria Streptomyces sp. strain 196 and RI.24 as a potential source of new targeted drugs against SARS-CoV-2. Molecular docking studies were performed on holoRdRp and nsp13, two key factors responsible for virus replication factor. Our in silico studies, K-252-C aglycone indolocarbazole alkaloid (K252C) and daunorubicin were found to have better binding affinities than the respective control drugs, with K252C exhibiting binding energy of - 9.1 kcal/mol with holoRdRp and - 9.2 kcal/mol with nsp13, and daunorubicin showing binding energy at - 8.1 kcal/mol with holoRdRp and - 9.3 kcal/mol with nsp13. ADMET analysis, MD simulation, and MM/GBSA studies indicated that K252C and daunorubicin have the potential to be developed as targeted drugs against SARS-CoV-2. The study concludes that K252C and daunorubicin are potential lead compounds that might suppress the inhibition of SARS-CoV-2 replication among the tested microbial compounds and could be developed as targeted drugs against COVID-19. In the future, further in vitro studies are required to validate these findings., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This study developed a new dual delivery system of naringenin (NRG), a polyphenol, and doxofylline (DOX), a xanthine derivative, as an inhaled microsphere system. In this system, NRG has been first loaded into glyceryl tristearate-based solid lipid nanoparticles (NRG SLN), which were further loaded with DOX into swellable chitosan-tripolyphosphate-based microspheres (NRG SLN DOX sMS). The system was characterized based on particle size, PDI, zeta potential, surface morphology (SEM, AFM, and TEM), solid-state and chemical properties (XRD, IR, and NMR), aerodynamic parameters, drug loading, entrapment efficiency and in vitro drug release study. The optimized NRG SLN DOX sMS exhibited particle size, zeta potential, and PDI of 2.1 µm, 31.2 mV, and 0.310, respectively; a drug entrapment efficiency > 79 %; a drug loading efficiency > 13 %; cumulative drug releases of about 78 % for DOX and 72 % for NRG after 6 and 12 h, respectively; good swelling and desirable aerodynamic properties. In addition, in vivo studies conducted in mice, a murine model of asthma showed significant reductions in serum bicarbonate and eosinophil counts and improvement in respiratory flow rate, tidal volume, and bronchial wall lining compared with the asthmatic control group. Overall, this novel inhalable dual-delivery system may represent a good alternative for the effective treatment of asthma., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier B.V.)

Background: Non-alcoholic fatty liver disease (NAFLD) is a liver disorder characterized by the ac-cumulation of fat in hepatocytes without alcohol consumption. Mitochondrial dysfunction and endoplasmic reticulum (ER) stress play significant roles in NAFLD pathogenesis. The unfolded protein response in mitochondria (UPRmt) is an adaptive mechanism that aims to restore mitochondrial protein homeostasis and mitigate cellular stress. This study aimed to investigate the effects of ( +)-Lipoic acid (ALA) on UPRmt, inflammation, and oxidative stress in an in vitro model of NAFLD using HepG2 cells treated with palmitic acid and oleic acid to induce steatosis., Results: Treatment with palmitic and oleic acids increased UPRmt-related proteins HSP90 and HSP60 (heat shock protein), and decreased CLPP (caseinolytic protease P), indicating ER stress activation. ALA treatment at 1 μM and 5 μM restored UPRmt-related protein levels. PA:OA (palmitic acid:oleic acid)-induced ER stress markers IRE1α (Inositol requiring enzyme-1), CHOP (C/EBP Homologous Protein), BIP (Binding Immunoglobulin Protein), and BAX (Bcl-2-associated X protein) were significantly reduced by ALA treatment. ALA also enhanced ER-mediated protein glycosylation and reduced oxidative stress, as evidenced by decreased GPX1 (Glutathione peroxidase 1), GSTP1 (glutathione S-transferase pi 1), and GSR (glutathione-disulfide reductase) expression and increased GSH (Glutathione) levels, and improved cellular senescence as shown by the markers β-galactosidase, γH2Ax and Klotho-beta., Conclusions: In conclusion, ALA ameliorated ER stress, oxidative stress, and inflammation in HepG2 cells treated with palmitic and oleic acids, potentially offering therapeutic benefits for NAFLD providing a possible biochemical mechanism underlying ALA beneficial effects., (© 2024. The Author(s).)

Mitochondrial dysfunction is the leading cause of neurodegenerative disorders like Alzheimer's disease and Parkinson's disease. Mitochondria is a highly dynamic organelle continuously undergoing the process of fission and fusion for even distribution of components and maintaining proper shape, number, and bioenergetic functionality. A set of genes governs the process of fission and fusion. OPA1, Mfn1 , and Mfn2 govern fusion, while Drp1 , Fis1 , MIEF1 , and MIEF2 genes control fission. Determination of specific molecular patterns of transcripts of these genes revealed the impact of compositional constraints on selecting optimal codons. AGA and CCA codons were over-represented, and CCC, GTC, TTC, GGG, ACG were under-represented in the fusion gene set. In contrast, CTG was over-represented, and GCG, CCG, and TCG were under-represented in the fission gene set. Hydropathicity analysis revealed non-polar protein products of both fission and fusion gene set transcripts. AGA codon repeats are an integral part of translational regulation machinery and present a distinct pattern of over-representation and under-representation in different transcripts within the gene sets, suggestive of selective translational force precisely controlling the occurrence of the codon. Out of six synonymous codons, five synonymous codons encoding for leucine were used differently in both gene sets. Hence, forces regulating the occurrence of AGA and five synonymous leucine-encoding codons suggest translational selection. A correlation of mutational bias with gene expression and codon bias and GRAVY and AROMA signifies the selection pressure in both gene sets, while the correlation of compositional bias with gene expression, codon bias, protein properties, and minimum free energy signifies the presence of compositional constraints. More than 25% of codons of both gene sets showed a significant difference in codon usage. The overall analysis shed light on molecular features of gene sets involved in fission and fusion., Competing Interests: There are no conflicts of interest.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

In this study, we demonstrate the green synthesis of bimetallic silver-copper nanoparticles (Ag-Cu NPs) using Aerva lanata plant extract. These NPs possess diverse biological properties, including in vitro antioxidant, antibiofilm, and cytotoxic activities. The synthesis involves the reduction of silver nitrate and copper oxide salts mediated by the plant extract, resulting in the formation of crystalline Ag-Cu NPs with a face-centered cubic structure. Characterization techniques confirm the presence of functional groups from the plant extract, acting as stabilizing and reducing agents. The synthesized NPs exhibit uniform-sized spherical morphology ranging from 7 to 12 nm. They demonstrate significant antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa, inhibiting extracellular polysaccharide secretion in a dose-dependent manner. The Ag-Cu NPs also exhibit potent cytotoxic activity against cancerous HeLa cell lines, with an inhibitory concentration (IC 50 ) of 17.63 µg mL -1 . Additionally, they demonstrate strong antioxidant potential, including reducing capability and H 2 O 2 radical scavenging activity, particularly at high concentrations (240 µg mL -1 ). Overall, these results emphasize the potential of A. lanata plant metabolite-driven NPs as effective agents against infectious diseases and cancer., (© 2024. The Author(s).)

Haem oxygenase-1 (HO-1) is a ubiquitously expressed gene involved in cellular homoeostasis, and its imbalance in expression results in various disorders. To alleviate such disorders, HO-1 gene expression needs to be modulated. Codon usage bias results from evolutionary forces acting on any nucleotide sequence and determines the gene expression. Like codon usage bias, codon pair bias also exists, playing a role in gene expression. In the present study, HO-1 gene was recoded by manipulating codon and codon pair bias, and four such constructs were made through codon/codon pair deoptimization and codon/codon pair optimization to reduce and enhance the HO-1 gene expression. Codon usage analysis was done for these constructs for four tissues brain, heart, pancreas and liver. Based on codon usage in different tissues, gene expression of these tissues was determined in terms of the codon adaptation index. Based on the codon adaptation index, minimum free energy, and translation efficiency, constructs were evaluated for enhanced or decreased HO-1 expression. The analysis revealed that for enhancing gene expression, codon pair optimization, while for reducing gene expression, codon deoptimization is efficacious. The recoded constructs developed in the study could be used in gene therapy regimens to cure HO-1 over or underexpression-associated disorders., Competing Interests: The authors declare no conflict of interest.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Thymidylate kinase (TMPK) of monkeypox virus (MPXV) has emerged as a promising target for potential therapeutics due to its significant role in pyrimidine metabolism. While smallpox drugs are advised for treating monkeypox, the European Medicine Agency has sanctioned Tecovirimat due to its potent nanomolar activity. Nonetheless, there is a need for monkeypox-specific therapeutic options. In this work, we employed docking-based virtual screening and molecular dynamics (MD) simulations to identify myxobacterial secondary metabolites as promising anti-viral natural compounds capable of inhibiting thymidylate kinase. The computational pharmacokinetics and manual curation of top-scoring compounds identified six lead compounds that were compared in terms of protein-ligand contacts and protein-essential dynamics. The study shows that among the six candidates, Aurachin A and the Soraphinol analogues such as Soraphinol A and Soraphinol C remain very stable compared to other compounds, enabling the active site integrity via a stable dynamics pattern. We also show that other compounds such as Phenoxan, Phenylnannolone C, and 8E-Aurafuron B remain unstable and have a negative impact on the active site integrity and may not be suitable binders for TMPK protein. Analyzing the Aurachin A and Soraphinol A binding, the established hydrogen bonds with Arg93 and the conserved hydrophobic interaction with Tyr101 are consistent with previous experimental interactions. Additionally, a deeper insight into the indole and the aromatic ring interaction through π-π stacking and π-cation interactions, as well as the background of Aurachin A and Soraphinol A as a bioactive compound, has significant implications not only for its potential as a promising drug but also for directing future drug discovery efforts targeting the TMPK protein., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Herpes simplex virus type 1 (HSV-1) is associated with Alzheimer's disease, which goes into a cycle of latency and reactivation. The present study was envisaged to understand the reasons for latency and specific molecular patterns present in the HSV-1., Objective: The objective is the molecular dissection of Herpes simplex virus type 1 to elucidate molecular mechanisms behind latency and compare its codon usage patterns with genes modulated during Alzheimer's disease as a part of host-pathogen interaction., Methods: In the present study, we tried to investigate the potential reasons for the latency of HSV-1 virus bioinformatically by determining the CpG patterns. Also, we investigated the codon usage pattern, the presence of rare codons, codon context, and protein properties., Results: The top 222 codon pairs graded based on their frequency in the HSV-1 genome revealed that with only one exception (CUG-UUU), all other codon pairs have codons ending with G/C. Considering it an extension of host-pathogen interaction, we compared HSV-1 codon usage with that of codon usage of genes modulated during Alzheimer's disease, and we found that CGT and TTT are only two codons that exhibited similar codon usage patterns and other codons showed statistically highly significant different codon preferences. Dinucleotide CpG tends to mutate to TpG, suggesting the presence of mutational forces and the imperative role of CpG methylation in HSV-1 latency., Conclusions: Upon comparison of codon usage between HSV-1 and Alzheimer's disease genes, no similarities in codon usage were found as a part of host-pathogen interaction. CpG methylation plays an imperative role in latency HSV-1.

Objective: The aim of the study was to assess the disinfection efficacy, bond integrity, and nano hardness of caries-affected dentin (CAD) surface bonded to resin cement when disinfected with chlorhexidine (CHX), Methylene blue activated by Photodynamic therapy (MB-PDT), chitosan, silver diamine fluoride (SDF), chitosan activated by PDT, and SDF-diode laser against S. mutans., Materials and Methods: A total of 60 human mandibular molars were extracted non-traumatically and gathered using ICDAS criteria. The dentin surface was prepared, leaving CAD to receive a disinfection procedure. After inoculation with S. mutans, the CAD samples were divided into six groups and disinfected with various disinfectants (n = 10) CHX, MB-PDT, chitosan, chitosan-PDT, SDF, and SDF+ diode laser. Survival rates of S. mutans were analyzed following the restoration of samples with resin cement via the etch and rinse method to assess SBS. Also, nano hardness was analyzed. Statistical analysis was performed by using the ANOVA and the Tukey multiple test (p<0.05). The Kruskal-Wallis test was used to evaluate the change in survival rate., Results: Related to the survival rates, the SDF+ diode laser displayed the highest reduction in S. mutans levels and chitosan presented the lowest level of disinfection. The intergroup comparison revealed that CHX and chitosan-PDT displayed comparable outcomes of S. mutans survival rate to that of SDF+ diode laser (p>0.05). Likewise, MB-PDT and SDF displayed a comparable survival rate of S. mutans to Chitosan disinfection (p>0.05). Considering SBS and nano hardness, the highest SBS and NH were exhibited by the SDF+ diode laser, and the lowest SBS and NH values were exhibited by MB-PDT. The intragroup comparison revealed that CAD specimens disinfected with Chitosan-PDT showed comparable SBS and NH values to the SDF+ diode laser (p>0.05). CHX, chitosan, and SDF exhibited bond values and NH comparable to MB-PDT (p<0.05)., Conclusions: Synergistic use of Silver diamine fluoride with diode laser and chitosan activated by PDT can be used as an alternative to CHX for controlling S. mutans growth, promoting enhanced bond efficacy and nano hardness for bonding resin cement to the caries-affected dentin.

The ongoing Russian-Ukrainian conflict has caused a significant displacement of individuals, with an estimated five million Ukrainians seeking temporary refuge in other countries. We conducted a survey among Ukrainians in various countries worldwide using a convenience sample and analyzed 144 responses. The participants were divided into two groups: group 1, consisting of 92 Ukrainian refugees who were forced to leave their country due to the conflict, and group 2, comprising 52 individuals who did not change their place of residence. Data were collected through a structured online questionnaire consisting of socio-demographic questions, Depression, Anxiety, and Stress Scale-21, Insomnia Severity Index, and Symptom Checklist-90 during May-November 2022. We found that there were statistically significantly higher levels of obsessive-compulsive symptoms, depression, hostility, and overall distress in group 1. Group 1 had a higher risk of depression, anxiety, and stress, but not insomnia. In our study, refugee status, dissatisfaction with the state of health, job loss, suffering due to hostilities, and the received support from volunteers, friends, or relatives were the most important factors for the mental disorders. A bi-directional relationship was discovered between anxiety and insomnia, with both symptoms being associated with COVID-19 and subsequent psychiatric disorders. This study highlights the mental health and sleep problems faced by Ukrainian refugees as a result of the conflict linked to numerous social factors. Ukrainian refugees need social support programs and special attention to their mental health to facilitate their post-migration adaptation and integration into the host society., Competing Interests: Declaration of competing interest All authors declare that no conflict of interest of this study., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Individuals with diabetes are at risk of developing diabetic retinopathy, a vision-threatening complication. Regular eye examinations are crucial for early detection and management. Ensuring adherence to eye examination guidelines is essential to prevent visual impairment and blindness in this at-risk population., Methods: This was cross-sectional study, and a validated questionnaire was physically administered among adult individuals with diabetes (both males and females) in Saudi Arabia. The data were gathered and analyzed using Statistical Product and Service Solutions (SPSS, version 26.0) software (IBM SPSS Statistics for Windows, Armonk, NY). This study took approximately three months from the period August 2023 to November 2023., Results: This study found that most participants had type 1 diabetes (46.1%, n=83) and had been diagnosed for more than 10 years (49.4%, n=89). The most used management strategy (48.9%, n=88) was lifestyle changes and anti-diabetic medications. Most of the participants (93.3%, n=168) were fully aware of the severe eye complications of diabetes, as well as diabetic retinopathy and its complications (48.9%, n=88). The most common source of information about the importance of eye exams was healthcare professionals (56.7%, n=102). Most of the participants had annual eye exams (58.3%, n=105) and within the previous year, specifically related to their diabetes (62.8%, n=113). Adherence to eye examination guidelines was higher in those who had diabetes for more than 10 years (p=0.009), those who were on lifestyle changes and insulin therapy or anti-diabetic medications (p=0.030), those who were fully aware of severe eye complications and diabetic retinopathy (p=0.017 and p=0.020, respectively), and those with type 2 diabetes (p=0.001). In addition, participants who understood the importance of eye examinations had better glucose control (p=0.017), had eye examinations within the previous year (p=0.001), and had heard about the importance of eye examinations from healthcare professionals (p=0.020). The findings revealed the most common reasons for not getting an eye exam were a lack of awareness (37.8%) and distance from the hospital., Conclusion: To summarize, many people with diabetes do not get regular eye exams often because they are unaware of how important these exams are. Long-term diabetics who are aware of the dangers of diabetic retinopathy are more likely to heed this advice. However, adherence was linked to more frequent eye exams and better glucose control. Adherence and wide awareness must be created to improve retinopathy outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Alhujaili et al.)

Background Testicular torsion is a serious condition that requires immediate medical attention. It occurs when the spermatic cord, which carries blood to the testicles, twists, reducing blood flow and oxygen to the testicle. This can lead to tissue death and loss of the testis if not treated promptly. It is important to seek medical attention immediately when symptoms of testicular torsion arise, as prompt treatment can help prevent permanent damage to the testicle. This study aimed to explore the level of knowledge about testicular torsion among the general population in the Kingdom of Saudi Arabia. Methodology A descriptive cross-sectional study was conducted using a convenience sample recruited from the general population who fulfilled the inclusion criteria. The data were collected from participants using an electronic pre-structured questionnaire. The researchers developed the questionnaire through expert consultation and after an intensive literature review. The questionnaire was reviewed by a panel of three experts for validation and applicability. After a pilot study, the reliability coefficient (Cronbach's alpha) was 0.74. The data were analyzed using SSPS version 25 (IBM Corp., Armonk, NY, USA) and presented as percentages and frequencies. Chi-square and logistic regression were conducted. P-values ≤0.05 were considered statistically significant. Results A total of 732 participants were recruited, most of whom were male (486, 66.4%), with ages ranging between 18 and 30 years (452, 61.7%). Regarding testicular torsion knowledge, more than half of the participants had good knowledge (406, 55.5%) and knew about the signs, symptoms, and risk factors of testicular torsion. There was a statistically significant relationship between age and knowledge (p < 0.001) and an insignificant relationship between sex and knowledge (p > 0.05). Conclusions The study participants were found to have good knowledge. Fortunately, most participants knew that testicular torsion is an emergency and they must immediately visit the hospital. With further awareness programs, the overall knowledge level can be improved., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Alghuyaythat et al.)

Introduction: The worldwide prevalence of type 2 diabetes mellitus (T2DM) and obesity has been steadily increasing over the past four decades, with projections indicating a significant rise in the number of affected individuals by 2045. Therapeutic interventions in T2DM aim to control blood glucose levels and reduce the risk of complications. Dietary and lifestyle modifications play a crucial role in the management of T2DM and obesity. While conventional medical nutritional therapy (MNT) often promotes a high-carbohydrate, low-fat Mediterranean diet as an elective treatment, low-carbohydrate diets (LCDs), specifically those restricting carbohydrate intake to less than 130 g/day, have gained popularity due to their multifaceted benefits. Scientific research supports the efficacy of LCDs in improving glycemic control, weight loss, blood pressure, lipid profiles, and overall quality of life. However, sustaining these benefits over the long term remains challenging. This trial aimed to compare the effects of a Mediterranean diet vs. a low-carbohydrate diet (carbohydrate intake < 130 g/day) on overweight/obese patients with T2DM over a 16-week period. The study will evaluate the differential effects of these diets on glycemic regulation, weight reduction, lipid profile, and cardiovascular risk factors., Methods: The study population comprises 100 overweight/obese patients with poorly controlled T2DM. Anthropometric measurements, bioimpedance analysis, and blood chemistry assessments will be conducted at baseline and after the 16-week intervention period. Both dietary interventions were hypocaloric, with a focus on maintaining a 500 kcal/day energy deficit., Results: After 16 weeks, both diets had positive effects on various parameters, including weight loss, blood pressure, glucose control, lipid profile, and renal function. However, the low-carbohydrate diet appears to result in a greater reduction in BMI, blood pressure, waist circumference, glucose levels, lipid profiles, cardiovascular risk, renal markers, and overall metabolic parameters compared to the Mediterranean diet at the 16-week follow up., Conclusions: These findings suggest that a low-carbohydrate diet may be more effective than a Mediterranean diet in promoting weight loss and improving various metabolic and cardiovascular risk factors in overweight/obese patients with T2DM. However, it is important to note that further research is needed to understand the clinical implications and long-term sustainability of these findings.