Development of In-Needle SPME Devices for Microextraction Applied to the Quantification of Pesticides in Agricultural Water.

The chemical industry explosion in the 20th century has led to increased environmental pollution, affecting fauna, flora, and waterways. These substances alter water's taste, color, and smell, making it unfit for consumption or toxic. Agricultural water networks face threats from pollution before and after treatment. Some chemical contaminants, like pesticides, are embedded in natural biogeochemical cycles. In this study, we developed a simple and low-cost procedure for the fabrication of needles coated with polydimethylsiloxane (PDMS) as an efficient sorbent for the microextraction of organic pollutant traces from water. The prepared needles were used as an alternative for commercial solid-phase micro-extraction (SPME) devices in analytical chemistry. The PDMS polymeric phase was characterized by Fourier-transform infrared spectroscopy (FT-IR), thermogravimetry (TGA), and scanning electron microscopy (SEM). The PDMS-coated needles were used for extraction of thirteen pesticides by direct-immersion solid-phase microextraction (DI-SPME) from contaminated waters, followed by determination with gas chromatography-mass spectrometry (GC-MS). The developed analytical method showed limits of detection (LODs) between 0.3 and 2.5 ng mL-1 and RSDs in the range of 0.8-12.2%. The homemade needles were applied for the extraction of pesticides in surface and ground aqueous samples collected from an agricultural area. Several target pesticides were identified and quantified in the investigated water samples.

Nivolumab as Second-Line Therapy Improves Survival in Patients with Unresectable Hepatocellular Carcinoma.

BACKGROUND: Limited data exists for the efficacy and outcomes of nivolumab as a second-line treatment for unresectable hepatocellular carcinoma (uHCC). We aimed to assess the efficacy and safety of nivolumab in patients with uHCC who experienced disease progression during sorafenib treatment. METHODS: In this retrospective, observational, multicenter study, adult Child-Turcotte-Pugh A/7B patients with uHCC who tolerated sorafenib therapy but showed disease progression switched to second-line intravenous nivolumab (n = 42). A similar number of consecutive, unselected patients who were maintained on sorafenib therapy, regardless of tumoral response or progression, served as historical controls (n = 38). The primary endpoint was overall survival (OS, defined as the time from starting sorafenib in either group up to death due to any cause) and analyzed by intention-to-treat. RESULTS: The mean age of the overall cohort was 72.4 ± 10.1 years, of whom 87.5% were males and 58.8% had underlying viral etiology. Patients in the two cohorts were similar, except those who received nivolumab had more co-morbidities (70.0% vs. 15.4%), ECOG-2 status (21.4% vs. 15.8%), BCLC stage C (81.0% vs. 47.4%), and extravascular invasion (54.4% vs. 21.8%) (p < 0.05 for all). More patients in the nivolumab arm were Child-Turcotte-Pugh B (35.7% vs. 21.1%, p = 0.15). Median OS was 22.2 months (95% CI: 8.9-49.8) on second-line nivolumab and 11.0 months (95% CI: 3.6-18.4) on sorafenib alone (HR 1.93; 95% CI: 1.1-3.3, p = 0.014). Median OS after starting nivolumab was 10.2 months, and time-to-progression was 4.9 months (95% CI: 3.2-6.3). CONCLUSION: Nivolumab is an effective second-line treatment option in patients with uHCC who progress on sorafenib, with significantly improved OS. These early real-life data offer encouraging results, similar to those shown in Phase I/IIa clinical trials. Further investigations are warranted for the use of nivolumab as a monotherapy.

Discovery of new anti-diabetic potential agents based on paracetamol incorporating sulfa-drugs: Design, synthesis, α-amylase, and α-glucosidase inhibitors with molecular docking simulation.

Uncontrolled diabetes can lead to hyperglycemia, which causes neuropathy, heart attacks, retinopathy, and nervous system damage over time, therefore, controlling hyperglycemia using potential drug target inhibitors is a promising strategy. This work focused on synthesizing new derivatives via the diazo group, using a hybridization strategy involving two approved drugs, paracetamol and several sulfonamides. The newly designed diazo-paracetamols 5-12 were fully characterized and then screened for in vitro α-amylase and α-glucosidase activities and exhibited inhibitory percentages (IP) = 92.5-96.5 % and 91.0-95.7 % compared to Acarbose IP = 96.5 and 95.8 %, respectively at 100 µg/mL. The IC50 values of the synthesized derivatives were evaluated against α-amylase and α-glucosidase enzymes, and the results demonstrated moderate to potent activity. Among the tested diazo-paracetamols, compound 11 was found to have the highest potency activity against α-amylase with IC50 value of 0.98 ± 0.015 µM compared to Acarbose IC50 = 0.43 ± 0.009 µM, followed by compound 10 (IC50 = 1.55 ± 0.022 µM) and compound 9 (IC50 = 1.59 ± 0.023 µM). On the other hand, for α-glucosidase, compound 10 with pyrimidine moiety demonstrated the highest inhibitory activity with IC50 = 1.39 ± 0.021 µM relative to Acarbose IC50 = 1.24 ± 0.029 µM and the order of the most active derivatives was 10 > 9 (IC50 = 2.95 ± 0.046 µM) > 11 (IC50 = 5.13 ± 0.082 µM). SAR analysis confirmed that the presence of 4,5-dimethyl-isoxazole or pyrimidine nucleus attached to the sulfonyl group is important for activity. Finally, the docking simulation was achieved to determine the mode of binding interactions for the most active derivatives in the enzyme's active site.

Discovery of novel 6-(piperidin-1-ylsulfonyl)-2H-chromenes targeting α-glucosidase, α-amylase, and PPAR-γ: Design, synthesis, virtual screening, and anti-diabetic activity for type 2 diabetes mellitus.

A new series of 2H-chromene-based sulfonamide derivatives 3-12 has been synthesized and characterized using different spectroscopic techniques. The synthesized 2H-chromenes were synthesized by reacting activated methylene with 5-(piperidin-1-ylsulfonyl)salicylaldehyde through one-step condensation followed by intramolecular cyclization. Virtual screening of the designed molecules on α-glucosidase enzymes (PDB: 3W37 and 3A4A) exhibited good binding affinity suggesting that these derivatives may be potential α-glucosidase inhibitors. In-vitro α-glucosidase activity was conducted firstly at 100 µg/mL, and the results demonstrated good inhibitory potency with values ranging from 90.6% to 96.3% compared to IP = 95.8% for Acarbose. Furthermore, the IC50 values were determined, and the designed derivatives exhibited inhibitory potency less than 11 µg/mL. Surprisingly, two chromene derivatives 6 and 10 showed the highest potency with IC50 values of 0.975 ± 0.04 and 0.584 ± 0.02 µg/mL, respectively, compared to Acarbose (IC50 = 0.805 ± 0.03 µg/mL). Moreover, our work was extended to evaluate the in-vitro α-amylase and PPAR-γ activity as additional targets for diabetic activity. The results exhibited moderate activity on α-amylase and potency as PPAR-γ agonist making it a multiplet antidiabetic target. The most active 2H-chromenes 6 and 10 exhibited significant activity to PPAR-γ with IC50 values of 3.453 ± 0.14 and 4.653 ± 0.04 µg/mL compared to Pioglitazone (IC50 = 4.884±0.29 µg/mL) indicating that these derivatives improve insulin sensitivity by stimulating the production of small insulin-sensitive adipocytes. In-silico ADME profile analysis indicated compliance with Lipinski's and Veber's rules with excellent oral bioavailability properties. Finally, the docking simulation was conducted to explain the expected binding mode and binding affinity.

Innovation of 6-sulfonamide-2H-chromene derivatives as antidiabetic agents targeting α-amylase, α-glycosidase, and PPAR-γ inhibitors with in silico molecular docking simulation.

A new series of 2-imino or 2-oxo-2H-chromene-6-sulfonamide derivatives 2-9 with potential anti-diabetic activity were designed and synthesized. The new 6-sulfonamide chromenes were synthesized by reacting 3-formyl-4-hydroxybenzenesulfonyl chloride with activated methylene derivatives in the presence of ammonium acetate as a catalyst. The structure of the products was confirmed by spectroscopic analysis. All the designed derivatives 2-9 were evaluated for their activity against α-amylase and exhibited inhibitory percentage values higher than 93% at 100 µg mL-1. Additionally, the IC50 values represented a variable degree of activity with two derivatives 2 and 9 exhibiting the most promising derivative results with IC50 values of 1.76 ± 0.01 and 1.08 ± 0.02 µM, respectively, compared to Acarbose (IC50 = 0.43 ± 0.01 µM). Additionally, these derivatives showed potency against the α-glucosidase enzyme with IC50 values of 0.548 ± 0.02 and 2.44 ± 0.09 µg mL-1, compared to Acarbose (0.604 ± 0.02 µg mL-1). Moreover, the in vitro PPAR-γ transactivation assay revealed that chromene-6-sulfonamide derivatives 2 and 9 exhibited potential PPAR-γ activity with IC50 values of 3.152 ± 0.03 and 3.706 ± 0.32 µg mL-1, respectively, compared to Pioglitazone (4.884 ± 0.29 µg mL-1). This indicates that these derivatives have insulin sensitivity and glucose metabolism activity. The in silico ADMET prediction showed that these derivatives have an acceptable range of oral bioavailability, drug-likeness, and a safe toxicity profile, including being non-cytotoxic, non-mutagenic, non-immunotoxic, and non-carcinogenic. Finally, computational docking analysis demonstrated the ability of these derivatives to interact with α-amylase, α-glucosidase, and PPAR-γ enzymes, with confirmed successful placement due to good binding energy values and various interactions within the pocket.

Computer-aided drug discovery of c-Abl kinase inhibitors from plant compounds against chronic myeloid leukemia.

Chronic myeloid leukemia (CML) is a hematological malignancy characterized by the neoplastic transformation of hematopoietic stem cells, driven by the Philadelphia (Ph) chromosome resulting from a translocation between chromosomes 9 and 22. This Ph chromosome harbors the breakpoint cluster region (BCR) and the Abelson (ABL) oncogene (BCR-ABL1) which have a constitutive tyrosine kinase activity. However, the tyrosine kinase activity of BCR-ABL1 have been identified as a key player in CML initiation and maintenance through c-Abl kinase. Despite advancements in tyrosine kinase inhibitors, challenges such as efficacy, safety concerns, and recurring drug resistance persist. This study aims to discover potential c-Abl kinase inhibitors from plant compounds with anti-leukemic properties, employing drug-likeness assessment, molecular docking, in silico pharmacokinetics (ADMET) screening, density function theory (DFT), and molecular dynamics simulations (MDS). Out of 58 screened compounds for drug-likeness, 44 were docked against c-Abl kinase. The top hit compound (isovitexin) and nilotinib (control drug) were subjected to rigorous analyses, including ADMET profiling, DFT evaluation, and MDS for 100 ns. Isovitexin demonstrated a notable binding affinity (-15.492 kcal/mol), closely comparable to nilotinib (-16.826 kcal/mol), showcasing a similar binding pose and superior structural stability and reactivity. While these findings suggest isovitexin as a potential c-Abl kinase inhibitor, further validation through urgent in vitro and in vivo experiments is imperative. This research holds promise for providing an alternative avenue to address existing CML treatment and management challenges.Communicated by Ramaswamy H. Sarma.

Treatment Patterns and Recommendations for Improving the Management of Hepatocellular Carcinoma in Saudi Arabia.

Hepatocellular carcinoma (HCC) is the sixth most common type of cancer in the world associated with high morbidity and mortality. Despite being a significant healthcare burden there is limited information on the unmet needs and current treatment practices for intermediate and advanced-stage HCC in Saudi Arabia. This article analyzes the gaps and provides expert consensus on the management strategies for unresectable HCC in Saudi Arabia. A pre-meeting online questionnaire, comprising 20 objective questions about the treatment landscape and diagnosis of HCC in Saudi Arabia, was distributed to experts in the field of HCC management. An advisory board meeting including a panel of 13 experts was held in September 2022 where the responses to the survey questionnaire were reviewed and discussed. The survey results and experts' discussion highlighted the growing incidence of liver cancer in Saudi Arabia. HCC comprised the majority of all liver cancer cases due to rising rates of chronic viral infections and lifestyle-related risk factors. Most physicians in Saudi Arabia follow the Barcelona Clinic Liver Cancer guidelines as a prognostic tool for the detection and staging of patients with HCC. Most of the patients with HCC in Saudi Arabia are diagnosed in the intermediate or advanced stages with poor prognoses and limited therapeutic options. Establishing evidence-based surveillance techniques, a multidisciplinary approach to diagnosis, and better accessibility of treatment options is vital for the management of HCC in Saudi Arabia.

An analysis of the intention of female pharmacy students to work in community pharmacy settings in Saudi Arabia using the theory of planned behavior.

Objective: This study aimed to determine the intention of female Saudi pharmacy students to work in community pharmacies and the factors associated with this intention. Methods: This cross-sectional study was conducted between April 2022 and June 2022 and included female students from pharmacy colleges in Saudi Arabia. The survey was created based on the Theory of Planned Behavior. It included items that measure student intentions, attitudes, subjective norms, and perceived behavioral control regarding working in community pharmacies in Saudi Arabia. The study also included items that assessed sociodemographic characteristics, pharmacy program degrees, training, and job preferences of students. Results: A total of 407 participants completed the survey. The average age was 21.8 (±1.6) years, and most participants were Saudi nationals (97.79 %). The intention of participants to work in community pharmacies after graduation was low (mean = 3.2 ± 1.8; range: 1-7). Slightly positive attitudes toward working in a community pharmacy after graduation were revealed as participants showed an overall attitude mean of 4.5 ± 1.6 (range: 1-7). Furthermore, the participants perceived a low social pressure toward working in a community pharmacy after graduation (mean of 3.3 ± 1.9; range: 1-7). The intention of female pharmacy students to work in community pharmacies was significantly predicted by attitudes (p-value < 0.0001), perceived behavioral control (p-value = 0.0017), nationality (p-value = 0.0151), residence in the Saudi Arabian region (p-value = 0.0013), monthly income (p-value = 0.0231), pharmacy degree program (p-value = 0.0035), training received in community pharmacies (p-value = 0.0145), had a relative working in a community pharmacy (p-value = 0.0257), and preference to work in community pharmacies after graduation (p-value = 0.0001). Conclusion: Female pharmacy students in Saudi Arabia had a low intention to work in community pharmacies, a positive attitude toward working in community pharmacies, and perceived no social pressure to work in them. A positive attitude and behavioral perception of control toward working in community pharmacies were demonstrated among pharmacy students who study at a university outside Riyadh, undertaking a bachelor's degree in pharmacy, have a monthly income higher than 5000 Saudi riyals (USD 1,333.3), previously received training in community pharmacies, having a relative working in a community pharmacy, prefer to work in community pharmacies after graduation.

Investigation of natural compounds as methyltransferase inhibitors against dengue virus: an in silico approach.

The global challenge posed by Dengue virus (DENV) infection persists, exacerbated by the absence of specific antiviral therapies. The viral methyltransferase (MTase) enzyme, crucial for viral RNA methylation and immune system evasion, has emerged as a promising drug target for combating Dengue fever. In this study, a comprehensive exploration of natural compounds derived from the COCONUT database was conducted, selecting 224 compounds based on their structural similarity to the native substrate of the MTase enzyme, S-adenosyl-L-methionine (SAM). Employing virtual screening techniques, four natural compounds (CNP0307160, CNP0082902, CNP0449158, and CNP0296775) with acceptable docking scores were selected for further re-docking after geometry optimization by the DFT method. Re-docking analyses unveiled significant interactions, including hydrogen bonds and hydrophobic interactions, between these selected ligands and the MTase protein. To gain deeper insights into the dynamic stability of these complexes, we conducted molecular dynamics simulations which showed lower RMSD values for CNP0307160, CNP0082902, and CNP0296775 when compared to the reference molecule. Furthermore, we assessed the structural and dynamic stability of the protein-ligand complexes through free binding energy calculations and Principal Component Analysis (PCA) of the simulation trajectories. In these analyses, the CNP0296775 compound exhibited promising results compared to the other three compounds. The cumulative findings of these investigations underscore the potential of CNP0296775 as a strong inhibitor of DENV MTase, thus offering a promising starting point for its further experimental validation and optimization.Communicated by Ramaswamy H. Sarma.

The influence of telemedicine in primary healthcare on diabetes mellitus control and treatment adherence in Riyadh region.

Several studies have found that telemedicine has the potential to enhance the outcomes of patients with diabetes. This study aimed to determine the impact of telemedicine on the clinical outcomes of patients with type 2 diabetes mellitus (T2DM) in Saudi Arabia. We conducted a cross-sectional study among T2DM patients in selected primary healthcare centers in Riyadh, Saudi Arabia, from March 1, 2023, to August 20, 2023. We looked at how telemedicine affected HbA1c control, adherence, the number of diabetic complications, and polypharmacy using adjusted multivariable logistic regression models. Among the 583 patients, 140 (24.05 %) received care via telemedicine, while 442 (75.95 %) received in-person care. Patients who utilized telemedicine had significantly better glycemic control than those who received in-person care only (AOR = 5.123, 95 % CI = 3.107-8.447). Telemedicine also showed positive effects on treatment adherence (AOR = 2.552, 95 % CI = 1.6284-4.2414). Telemedicine can effectively reduce diabetic complications (AOR = 0.277, 95 % CI = 0.134-0.571). Regarding polypharmacy, patients with telemedicine use were less likely to report polypharmacy (AOR = 0.559, 95 % CI = 0.361-0.866). Telemedicine is considered one of the factors that improve HbA1c management and might increase therapeutic adherence and reduce diabetic complications and polypharmacy.

Antidiabetic and antioxidant potential of Crocin in high-fat diet plus streptozotocin-induced type-2 diabetic rats.

OBJECTIVES: Crocin, the principal water-soluble active constituent of saffron, possesses numerous pharmacological activities. The present investigation examined the potential antidiabetic and antioxidant characteristics of Crocin in rats with type-2 diabetes by administering it orally and intraperitoneally (i.p.). METHODS: After 2 weeks of a high-fat diet, streptozotocin (STZ) (i.p., 40 mg/kg) was administered to male adult rats to induce type-2 diabetes mellitus. Body weight and fasting blood glucose (FBG) were measured on days zero, weeks 1, and 2. At the end of 2 weeks of drug administration in their respective groups, fasting insulin and glucose levels were estimated, and insulin resistance (HOMA-IR) was determined. Intraperitoneal glucose (IPGTT) and insulin tolerance tests (ITT) were carried out. Histopathological investigation and biochemical parameters were estimated in pancreatic tissues. RESULTS: The Crocin (100 mg/kg) treatment has significantly improved body weight, abatement of FBG, fasting insulin, and HOMA-IR. Likewise, Crocin treatment significantly improved the glucose and insulin challenges. We observed a significantly marked elevation in endogenous antioxidant enzymes in Crocin-treated groups. Similarly, Crocin treatment reversed the histopathological changes and restored the normal integrity and function of the pancreas. CONCLUSION: The overall finding indicates that intraperitoneal administration of Crocin demonstrated better control of glycemic level and body weight. Further, it has improved insulin levels in the serum and potentiated antioxidant properties.

Transplantation of heterozygous familial hypercholesterolemia living donor liver resulting in early myocardial infarction: a possible dangerous link.

Living donor liver transplantation (LDLT) is a lifesaving procedure that is often curative for several liver diseases. Familial hypercholesterolemia (FH) is a metabolic disease that results from an autosomal dominant mutation in the low-density lipoprotein receptor; yet, young patients with FH can live years without detection. Herein, we report a case of a patient who developed early myocardial infarction (MI) after having a transplant from a donor with undetected heterozygous FH. This was a 67-year-old female with non-alcoholic steatohepatitis-related liver cirrhosis, free from coronary artery disease, who underwent LDLT from her daughter, a 45-year-old female with no past medical history. One year post-transplant, she presented with an acute MI with a large atherosclerotic burden. Genetic analysis confirmed heterozygous FH in the donor but not in the recipient. This case emphasizes the importance of incorporating a thorough clinical history and lipid profile into pre-transplant testing for both the recipient and donor, as well as aggressive lipid-lowering therapy post-transplantation to avoid cardiovascular complications.

Beliefs, awareness, use, and factors associated with herbal supplements usage among patients with chronic diseases-A cross-sectional insight from Alkharj, Saudi Arabia.

BACKGROUND: Herbal supplements (HSs) are used to treat a variety of diseases and ailments. Individuals with chronic diseases are at a higher risk of having adverse events and drug interactions from the use of HSs. AIM: This study determined the beliefs, awareness, use, and factors associated with HSs usage among patients with chronic diseases in Alkharj, Saudi Arabia. METHOD: A cross-sectional study was conducted among patients with chronic diseases between February and June 2019. Face-to-face interviews were conducted at various out-patient clinics in different hospitals. Patients diagnosed with chronic diseases were included in the study. Data were analyzed by descriptive, comparative, and inferential statistics using SAS ver. 9.4. RESULTS: The study participants were consisted of 533 patients, with mean age 53.6 ±12.9 years. The most prevalent chronic diseases were diabetes mellitus (67.7%), followed by hypertension (54.8%), and hyperlipidemia (53.8%). Among the studied participants, 336 (63%) had used at least one HS, whereby the most commonly used HSs were ginger (74.7%), mint (72%), and cumin (66.7%). Almost 78% of HSs users did not consult any healthcare provider about their use. HSs use varied significantly between female and male participants (p<0.05), whereby 61.5% of female participants used HSs in comparison to the male participants (38.5%). Gender (AOR 0.328; 95% CI 0.139-0.772; p = 0.0107), number of chronic diseases (AOR 1.585; 95% CI 1.084-2.318; p = 0.0312), and hyperlipidemia (AOR 2.818; 95% CI 1.507-5.269; p = 0.0.0012) were the pure factors of HSs use among the studied patients. CONCLUSION: The results of this study showed that HSs usage was high among patients with chronic diseases in Saudi Arabia. Concurrent usage of HSs with drugs should be well-discussed with healthcare providers to avoid potential adverse events or drug interactions especially among patients with chronic diseases.

Repurposing the inhibitors of MMP-9 and SGLT-2 against ubiquitin specific protease 30 in Parkinson's disease: computational modelling studies.

Ubiquitin specific protease 30 (USP30) has been attributed to mitochondrial dysfunction and impediment of mitophagy in Parkinson's disease (PD). This happens once ubiquitin that supposed to bind with deformed mitochondria at the insistence of Parkin, it's been recruited by USP30 via the distal ubiquitin binding domain. This is a challenge when PINK1 and Parkin loss their functions due to mutation. Although, there are reports on USP30s' inhibitors but no study on the repurposing of inhibitors approved against MMP-9 and SGLT-2 as potential inhibitors of USP30 in PD. Thus, the highlight therein, is to repurpose approved inhibitors of MMP-9 and SGLT-2 against USP30 in PD using extensive computational modelling framework. 3D structures of Ligands and USP30 were obtained from PubChem and protein database (PDB) servers respectively, and were subjected to molecular docking, ADMET evaluation, DFT calculation, molecular dynamics simulation (MDS) and free energy calculations. Out of the 18 drugs, 2 drugs showed good binding affinity to the distal ubiquitin binding domain, moderate pharmacokinetic properties and good stability. The findings showed canagliflozin and empagliflozin as potential inhibitors of USP30. Thus, we present these drugs as repurposing candidates for the treatment of PD. However, the findings in this current study needs to be validated experimentally.Communicated by Ramaswamy H. Sarma.

Novel ibuprofen prodrug: A possible promising agent for the management of complications of Alzheimer's disease.

Background: Alzheimer's disease (AD) is a severe, varied, and complex brain condition that gradually impairs memory and cognitive function. Epidemiological studies have shown that patients who have a history of long-term NSAID use have a decreased risk of developing AD. The objective of this study is to conduct the structural analysis of a novel ibuprofen prodrug and test its anti-Alzheimer's properties. Methods: Computational and docking studies were conducted using AMBER 18 package. The in-vivo studies were performed using aluminum chloride-induced experimental AD in rats. Adult Wistar rats of either sex were used and treated with aluminum chloride (32.5 mg/kg, p.o) and ibuprofen prodrug (50 mg/kg, p.o) daily for 30 days. The hole-board test and elevated plus maze were conducted on 10th, 20th and 30th day. Further, on 31st day, animals were euthanized and the brain tissue was used for histopathology. The results obtained were subjected to statistical analysis by one-way ANOVA and Dunnet's test, p < 0.05 was considered to indicate the significance. Results: The structural configuration of the novel compound indicated the presence of several structures such as aliphatic, aromatic, and asymmetry in the compound. The geometrical analysis indicated that the ibuprofen conjugate has dreiding energy of 51.22 kcal/mol with a van der waals radius of 62.56 A. The Huckel analysis confirmed the presence of aromatic rings in the compound. The molecular docking studies suggested affinity towards beta-secretase and acetylcholinesterase, besides indicating that the compound has ideal characteristics for the oral route (Log P = 2.33), cellular absorption (TPSA = 95.50), and oral bioavailability (number of rotatable bonds = 10). The toxicity profile indicated devoid of major systemic toxicity with mild possibility of cytotoxicity. The in-vivo analysis showed that the Ibu-prodrug significantly (P < 0.001) reversed the changes induced by aluminum chloride and restored histomorphological features in brain tissue. Conclusion: The findings suggested that the ibuprofen conjugate might possess the potential to manage the complications of AD. The action appears to be mediated through inhibition of beta-secretase and acetylcholinesterase activities. More studies might aid in identifying a specific therapeutic intervention that is still lacking in the treatment of AD.

Antibiotic resistance genes prediction via whole genome sequence analysis of Stenotrophomonas maltophilia.

BACKGROUND: Stenotrophomonas maltophilia (S. maltophilia) is the first dominant ubiquitous bacterial species identified from the genus Stenotrophomonas in 1943 from a human source. S. maltophilia clinical strains are resistance to several therapies, this study is designed to investigate the whole genome sequence and antimicrobial resistance genes prediction in Stenotrophomonas maltophilia (S. maltophilia) SARC-5 and SARC-6 strains, isolated from the nasopharyngeal samples of an immunocompromised patient. METHODS: These bacterial strains were obtained from Pakistan Institute of Medical Sciences (PIMS) Hospital, Pakistan. The bacterial genome was sequenced using a whole-genome shotgun via a commercial service that used an NGS (Next Generation Sequencing) technology called as Illumina Hiseq 2000 system for genomic sequencing. Moreover, detailed in-silico analyses were done to predict the presence of antibiotic resistance genes in S. maltophilia. RESULTS: Results showed that S. maltophilia is a rare gram negative, rod-shaped, non sporulating bacteria. The genome assembly results in 24 contigs (>500 bp) having a size of 4668,850 bp with 65.8% GC contents. Phylogenetic analysis showed that SARC-5 and SARC-6 were closely related to S. maltophilia B111, S. maltophilia BAB-5317, S. maltophilia AHL, S. maltophilia BAB-5307, S. maltophilia RD-AZPVI_04, S. maltophilia JFZ2, S. maltophilia RD_MAAMIB_06 and lastly with S. maltophilia sp ROi7. Moreover, the whole genome sequence analysis of both SARC-5 and SARC-6 revealed the presence of four resistance genes adeF, qacG, adeF, and smeR. CONCLUSION: Our study confirmed that S. maltophilia SARC-5 and SARC-6 are one of the leading causes of nosocomial infection which carry multiple antibiotic resistance genes.

Access and Disparities in the Use of Telemedicine Among Patients with Chronic Conditions in Saudi Arabia: A Cross-Sectional Study.

Purpose: This study investigated the access to and disparities in telemedicine use among patients with chronic conditions in Riyadh, Saudi Arabia. Patients and Methods: A cross-sectional study of randomly selected primary healthcare centers was conducted to ensure that each of the 17 municipalities in Riyadh were represented. Three hundred and forty-two participants who completed the questionnaire were interviewed using a standardized questionnaire. The relationship between demographic and socioeconomic factors and telemedicine utilization was evaluated using the chi-square test and multivariable mixed-effects logistic regression model. Results: Among the 342 participants, the study revealed that 25.73% of the patients utilized telemedicine. Older participants had lower odds of telemedicine use than did those aged ≤ 30 years [adjusted odds ratio (AOR) = 0.112, 95% confidence interval (CI) = 0.045-0.279 for 50-59 years; AOR = 0.19, 95% CI = 0.076-0.474 for 60-69 years; AOR = 0.223, 95% CI = 0.092-0.542 for ≥ 70 years]. Female sex (AOR = 2.519, 95% CI = 1.44-4.408), having a higher education level (AOR = 3.434, 95% CI = 1.037-7.041 for secondary education and AOR = 5.87, 95% CI = 2.761-8.235 for higher education), and living in urban areas (AOR = 2.721, 95% CI = 1.184-6.256) were associated with higher odds of telemedicine use. Among socioeconomic factors, employed participants had higher odds of telemedicine use (AOR = 4.336, 95% CI = 2.3-8.174). Furthermore, compared to those with the highest socioeconomic status (SES) index, those with the lowest SES were less likely to use telemedicine than those with the highest SES index (AOR = 0.193, 95% CI = 0.055-0.683 for the lower bottom (poorest). Conclusion: This study highlights a significant disparity in the utilization of telemedicine services across different populations, primarily due to demographic and socioeconomic factors.

Antibiotics for preventing infection at the surgical site: Single dose vs. multiple doses.

Background: Surgical site infections are common and expensive infections that can cause fatalities or poor patient outcomes. To prevent these infections, antibiotic prophylaxis is used. However, excessive antibiotic use is related to higher costs and the emergence of antimicrobial resistance. Objectives: The present meta-analysis aimed to compare the effectiveness of a single dosage versus several doses of antibiotics in preventing the development of surgical site infections. Methods: PubMed was used to find clinical trials evaluating the effectiveness of a single dosage versus several doses of antibiotics in avoiding the development of surgical site infections. The study included trials that were published between 1984 and 2022. Seventy-four clinical trials were included in the analysis. Odds ratios were used to compare groups with 95% confidence intervals. The data were displayed using OR to generate a forest plot. Review Manager (RevMan version 5.4) was used to do the meta-analysis. Results: Regarding clean operations, there were 389 surgical site infections out of 5,634 patients in a single dose group (6.90%) and 349 surgical site infections out of 5,621 patients in multiple doses group (6.21%) (OR = 1.11, lower CI = 0.95, upper CI = 1.30). Regarding clean-contaminated operations, there were 137 surgical site infections out of 2,715 patients in a single dose group (5.05%) and 137 surgical site infections out of 2,355 patients in multiple doses group (5.82%) (OR = 0.87, lower CI = 0.68, upper CI = 1.11). Regarding contaminated operations, there were 302 surgical site infections out of 3,262 patients in a single dose group (9.26%) and 276 surgical site infections out of 3,212 patients in multiple doses group (8.59%) (OR = 1.11, lower CI = 0.84, upper CI = 1.47). In general, there were 828 surgical site infections out of 11,611 patients in a single dose group (7.13%) and 762 surgical site infections out of 11,188 patients in multiple doses group (6.81%) (OR = 1.05, lower CI = 0.93, upper CI = 1.20). The difference between groups was not significant. Conclusion: The present study showed that using a single-dose antimicrobial prophylaxis was equally effective as using multiple doses of antibiotics in decreasing surgical site infections.

Continuity of care in primary healthcare settings among patients with chronic diseases in Saudi Arabia.

Introduction: Maintaining continuity of care is one of the most critical components of providing great care in primary health care. This study aimed to explore continuity of care and its predictors in primary healthcare settings among patients with chronic diseases in Saudi Arabia. Method: Face-to-face cross-sectional interviews were conducted with patients with chronic diseases who had at least four visits to primary care facilities in Riyadh, Saudi Arabia, between November 1, 2022 and March 3, 2023. We determined patients' continuity of care levels using the Bice-Boxerman continuity of care index. A Tobit regression model was used to determine the effects of several factors on the continuity of care index. Results: The interviews were conducted with 193 respondents with chronic diseases of interest. The mean continuity of care index of the entire sample was 0.54. Those with asthma had the highest median continuity of care index at 0.75 (interquartile range, 0.62-0.75), whereas those diagnosed with thyroid disease had a much lower continuity of care index (0.47) (interquartile range, 0.3-0.62). Tobit regression model findings showed that employed respondents with poorer general health had a negative effect on continuity of care index levels. By contrast, a higher continuity of care index was significantly associated with elderly respondents, urban residents, and those diagnosed with dyslipidemia, diabetes, hypertension, or asthma. Conclusions: According to our findings, the continuity of care level in Saudi Arabia's primary healthcare setting is low. The data demonstrate how continuity of care varies among study group characteristics and that improving continuity of care among chronic disease patients in Saudi Arabia is multifaceted and challenging, necessitating a coordinated and integrated healthcare delivery approach.

Knowledge about Emergency Management of Orofacial Injuries among School Teachers at Alkharj Saudi Arabia.

Background: Children suffer from orofacial injuries during sport activities in schools. School teacher's knowledge about managing emergency during orofacial injuries will help in treatment prognosis. Aim: To assess and compare school teacher's knowledge about management of orofacial injuries at alkharj Saudi Arabia. Materials and Methods: Cross-sectional study was planned among school teacher working in various schools at alkharj. Questionnaire consisted of Demographic details such as age and year of experience and knowledge-related questions about management of orofacial injuries. Questionnaire was distributed and collected on the same day. Results: All participants were aware that sport activities results in injuries to head, orofacial structures, or teeth. 15.6% participants have undergone training. 84.4% of study participants have told they don't know to manage avulsed tooth. 92.8% of study participants are interested to get training on orofacial injury management. Conclusion: Knowledge of school teachers about management of orofacial injury is insufficient. Teachers are primary level of contact in schools during sports injuries, measures should be taken to improve their knowledge about orofacial injuries.