Development of thresholds and a visualization tool for use of a blood test in routine clinical dementia practice.

INTRODUCTION: We developed a multimarker blood test result interpretation tool for the clinical dementia practice, including phosphorylated (P-)tau181, amyloid-beta (Abeta)42/40, glial fibrillary acidic protein (GFAP), and neurofilament light (NfL). METHODS: We measured the plasma biomarkers with Simoa (n = 1199), applied LASSO regression for biomarker selection and receiver operating characteristics (ROC) analyses to determine diagnostic accuracy. We validated our findings in two independent cohorts and constructed a visualization approach. RESULTS: P-tau181, GFAP, and NfL were selected. This combination had area under the curve (AUC) = 83% to identify amyloid positivity in pre-dementia stages, AUC = 87%-89% to differentiate Alzheimer's or controls from frontotemporal dementia, AUC = 74%-76% to differentiate Alzheimer's or controls from dementia with Lewy bodies. Highly reproducible AUCs were obtained in independent cohorts. The resulting visualization tool includes UpSet plots to visualize the stand-alone biomarker results and density plots to visualize the biomarker results combined. DISCUSSION: Our multimarker blood test interpretation tool is ready for testing in real-world clinical dementia settings. HIGHLIGHTS: We developed a multimarker blood test interpretation tool for clinical dementia practice. Our interpretation tool includes plasma biomarkers P-tau, GFAP, and NfL. Our tool is particularly useful for Alzheimer's and frontotemporal dementia diagnosis.

Breaking new ground: Exploring de novo chromosomal rearrangements in 1p36 microdeletion.

Chromosomal structural variations (SVs) are linked to a wide range of phenotypes and arise due to disruptions during DNA replication, which can affect gene function within the SV regions. This case report details a patient diagnosed with neurodevelopmental delay. Detailed investigation through array comparative genomic hybridization revealed two pathogenic SVs on chromosome 1, which align with a 1p36 microdeletion, and a microduplication at 2p35.3, the latter being classified as a variant of unknown significance. The patient's clinical presentation is consistent with the 1p36 deletion syndrome, characterized by specific developmental delays and physical anomalies. Further genetic analysis suggests that these terminal rearrangements might stem from an unbalanced translocation between the short arms of chromosomes 1 and 2. This case underscores the complexity of interpreting multiple concurrent SVs and their cumulative effect on phenotype. Ongoing research into such chromosomal abnormalities will enhance our understanding of their clinical manifestations and guide more targeted therapeutic strategies.

Insights into bioactive constituents of onion (Allium cepa L.) waste: a comparative metabolomics study enhanced by chemometric tools.

BACKGROUND: Onion waste was reported to be a valuable source of bioactive constituents with potential health-promoting benefits. This sparked a surge of interest among scientists for its valorization. This study aims to investigate the chemical profiles of peel and root extracts of four onion cultivars (red, copper-yellow, golden yellow and white onions) and evaluate their erectogenic and anti-inflammatory potentials. METHODS: UPLC-QqQ-MS/MS analysis and chemometric tools were utilized to determine the chemical profiles of onion peel and root extracts. The erectogenic potential of the extracts was evaluated using the PDE-5 inhibitory assay, while their anti-inflammatory activity was determined by identifying their downregulating effect on the gene expression of IL-6, IL-1ß, IFN-γ, and TNF-α in LPS-stimulated WBCs. RESULTS: A total of 103 metabolites of diverse chemical classes were identified, with the most abundant being flavonoids. The organ's influence on the chemical profiles of the samples outweighed the influence of the cultivar, as evidenced by the close clustering of samples from the same organ compared to the distinct separation of root and peel samples from the same cultivar. Furthermore, the tested extracts demonstrated promising PDE-5 and anti-inflammatory potentials and effectively suppressed the upregulation of pro-inflammatory markers in LPS-stimulated WBCs. The anti-inflammatory activities exerted by peel samples surpassed those of root samples, highlighting the importance of selecting the appropriate organ to maximize activity. The main metabolites correlated with PDE-5 inhibition were cyanidin 3-O-(malonyl-acetyl)-glucoside and quercetin dimer hexoside, while those correlated with IL-1ß inhibition were γ-glutamyl-methionine sulfoxide, γ-glutamyl glutamine, sativanone, and stearic acid. Taxifolin, 3'-hydroxymelanettin, and oleic acid were highly correlated with IL-6 downregulation, while quercetin 4'-O-glucoside, isorhamnetin 4'-O-glucoside, and p-coumaroyl glycolic acid showed the highest correlation to IFN-γ and TNF-α inhibition. CONCLUSION: This study provides a fresh perspective on onion waste as a valuable source of bioactive constituents that could serve as the cornerstone for developing new, effective anti-PDE-5 and anti-inflammatory drug candidates.

Bioethics and Neurosurgery: An Overview of Existing and Emerging Topics for the Practicing Neurosurgeon.

Neurosurgery is field with complex ethical issues. In this article, we aim to provide an overview of key and emerging ethical issues in neurosurgery with a focus on issues relevant to practicing neurosurgeons. These issues include those of informed consent, capacity, clinical trials, emerging neurotechnology, innovation, equity and justice, and emerging bioethics areas including community engagement and organizational ethics. We argue bioethics can help neurosurgeons think about and address these issues, and in turn, the field of bioethics can benefit from engagement by neurosurgeons. Several ideas for increasing engagement in bioethics are proposed.

Workforce estimate to treat mental disorders in the Kingdom of Saudi Arabia.

BACKGROUND: Mental, neurological, and substance abuse (MNS) disorders describe a range of conditions that affect the brain and cause distress or functional impairment. In the Middle East and North Africa (MENA), MNS disorders make up 10.88 percent of the burden of disease as measured in disability-adjusted life years. The Kingdom of Saudi Arabia (KSA) is one of the main providers of mental health services and one of the largest contributors to mental health research in the region. Within the past decade, mental health resources and services has increased. METHODS: We employ a needs-based workforce estimate as a planning exercise to arrive at the total number of psychiatrists, nurses, and psychosocial care providers needed to meet the epidemiological need of mental health conditions of the population of KSA. Estimates for a potential mental health workforce gap were calculated using five steps: Step 1-Quantify target population for priority mental health conditions. Step 2-Identify number of expected cases per year. Step 3-Set target service coverage for each condition. Step 4-Estimate cost-effective health care service resource utilization for each condition. Step 5-Estimate service resources needed for each condition. RESULTS: The planning exercise indicates an epidemiologic need for a total of 17,100 full-time-equivalent (FTE) health care providers to treat priority MNS disorders. KSA appears to have a need-based shortage of 10,400 health workers to treat mental disorders. A total of 100 psychiatrists, 5700 nurses, and 4500 psychosocial care providers would be additionally needed (that is, above and beyond current levels) to address the priority mental health conditions. The shortfall is particularly severe for nurses and psychosocial workers who make up 98.9 percent of the shortfall. This shortage is substantial when compared to other high-income countries. Overall, the workforce needed to treat MNS conditions translates to 49.2 health workers per 100,000 population. CONCLUSION: Challenges to addressing the shortfall are Saudi specific which includes awareness of cultural customs and norms in the medical setting. These challenges are compounded by the lack of Saudi nationals in the mental health workforce. Saudi nationals make up 29.5 percent of the physician workforce and 38.8 percent of the nursing workforce. Policymakers and planners supplement this shortfall with non-Saudi providers, who must be mindful of Saudi-specific cultural considerations. Potential solutions to reducing the shortfall of mental health care workers includes nurse task shifting and training of general practitioners to screen for, and treat, a subset of MNS disorders.

Higher incidence of venous thromboembolism associated with increasing lines of treatment in heavily treated ovarian cancer patients.

OBJECTIVE: Ovarian cancer is associated with a high rate of venous thromboembolism. Our objective is to report the incidence of venous thromboembolism in recurrent ovarian cancer, assess the impact on morbidity and mortality, and evaluate predictors of venous thromboembolism. METHODS: A retrospective single institution cohort study was performed. Patients with a diagnosis of recurrent ovarian cancer between 2007 and 2020 and no previous history of venous thromboembolism were identified. Demographic and clinical variables were collected. Univariate and multivariable analyses were performed to identify predictors of venous thromboembolism. RESULTS: Of the 345 patients included in this study, 77 (22.3%) developed a venous thromboembolism. Most (n=56, 72.7%) were actively receiving treatment at the time of diagnosis of venous thromboembolism, of whom 44 (78.6%) had received three or more lines of treatment. In total, 42 (54.5%) were admitted to hospital on diagnosis and one mortality (1.3%) occurred secondary to venous thromboembolism. An intermediate/high risk Khorana score was not predictive of venous thromboembolism (p=0.24). The risk of venous thromboembolism was significantly higher with increasing lines of chemotherapy (odds ratio 1.14, 95% confidence interval 1.02 to 1.28 per line, p=0.026). There was no significant difference in overall survival (62.9 vs 49.1 median months, p=0.29) between patients with and without venous thromboembolism. CONCLUSIONS: More than 20% of patients with recurrent ovarian cancer developed a venous thromboembolism, and most occurred after three or more lines of treatment. The risk of venous thromboembolism was higher with increasing lines of chemotherapy. While venous thromboembolism did not appear to impact survival in this population, nearly half required hospitalization, emphasizing the morbidity of venous thromboembolism and potential impact on healthcare costs. Further studies are needed to improve risk stratification for venous thromboembolism in this high risk population.

Prevalence of Hepatitis B Virus Infection in Tanzania: A Systematic Review and Meta-Analysis.

Methods: We systematically searched the PubMed, Web of Science, African Journals Online, Embase, Cochrane Library, and Google Scholar databases for studies conducted up to March 1, 2023, that estimated the prevalence of HBV in Tanzania based on HBV surface antigen measurements. The DerSimonian-Laird random effects model was used to estimate the overall prevalence of HBV with 95% confidence intervals (CIs). Potential sources of heterogeneity were also investigated. Results: Thirty-one studies with a total sample size of 37,988 were included in the meta-analysis. The overall average HBV prevalence estimate in Tanzania was 6.91% (95% CI = 5.18-8.86%). Subgroup analysis revealed the highest prevalence in the northern zone (9.32%, 95% CI; 2.24-20.36%), among the blood donors (18.72%, 95% CI: 17.43-20.05%) and among the community volunteers (8.76%, 95% CI: 4.55-14.15%). The lowest prevalence was observed in the lake zone at 4.66% (95% CI: 3.49-5.99) and in pregnant women at 4.72% (95% CI: 3.42-6.21). The overall between-study variability showed significant heterogeneity (I 2 = 97.41%, P < 0.001). Conclusions: Our results showed that Tanzania is a country with moderately high HBV endemicity, with large interregional differences and significantly high numbers of HBV infections within the community. This underscores the need for immediate development of targeted prevention strategies and further epidemiological studies to better understand the pattern of the disease.

Tailoring a facile electronic and ionic pathway to boost the storage performance of Fe3O4 nanowires as negative electrode for supercapacitor application.

Today, high-energy applications are devoted to boosting the storage performance of asymmetric supercapacitors. Importantly, boosting the storage performance of the negative electrodes is a crucial topic. Fe3O4-based active materials display a promising theoretical storage performance as a negative electrode. Thus, to get a high storage performance of Fe3O4, it must be tailored to have a higher ionic and electronic conductivity and outstanding stability. Functionalized graphite felt (GF) is an excellent candidate for tailoring Fe3O4 with a facile ionic and electronic pathway. However, the steps of the functionalization of GF are complex and time-consuming as well as the energy loss during this step. Thus, the in-situ functionalization of the GF surface throughout the synthesis of Fe3O4 active materials is proposed herein. Fe3O4 is electrodeposited at the in-situ functionalized GF surface with the crystalline nanowires-like structure as revealed from the various analyses; SEM, TEM, Mapping EDX, XPS, XRD, wettability test, and Raman analysis. Advantageously, the synthetic approach introduces full homogeneous and uniform coverage of the large surface area of the GF. Thus, Fe3O4 nanowires with high ionic and electronic conductivity are characterized by a higher storage performance. Interestingly, Fe3O4/GF possesses a high specific capacity of 1418 mC cm-2 at a potential scan rate of 10 mV s-1 and this value retained to 54% at a potential scan rate of 50 mV s-1 at an extended potential window of 1.45 V. Remarkably, the diffusion-controlled reaction is the main contributor of the storage of Fe3O4/GF electrode as revealed by the mechanistic studies.

Evaluating the public's readiness to combat vector-borne disease threats in Jazan, Saudi Arabia: A cross-sectional survey.

Vector-borne diseases (VBDs) pose a significant public health challenge in Saudi Arabia, particularly in the Jazan region. This study aimed to assess the knowledge, attitudes, and practices regarding VBDs among the population of Jazan and to identify factors associated with these variables. A cross-sectional survey was conducted among 642 adult residents of Jazan using a convenience random sampling technique. The survey tool consisted of 6 domains: demographics, knowledge of VBDs, preventive practices, care-seeking behavior, knowledge of specific VBDs, and attitudes towards VBDs. Data were analyzed using descriptive statistics, chi-square tests, t tests, ANOVA, and multivariable logistic regression. The majority of participants (60.0%) had high knowledge scores, while (75.5%) and (77.7%) had high attitude and practice scores, respectively. However, knowledge gaps were identified in specific areas, such as the transmission of leishmaniasis and Rift Valley fever. Gender was a significant predictor of both knowledge and practice scores, with males having higher knowledge and females demonstrating higher levels of preventive practices. Age, education, income, and working status were also associated with knowledge scores. The findings highlight the need for targeted interventions and educational campaigns to address the identified gaps in knowledge, attitudes, and practices. Future research should focus on exploring the effectiveness of different intervention strategies and investigating the integration of VBD prevention and control measures into existing healthcare systems. By employing a multi-disciplinary approach, evidence-based strategies can be developed to prevent and control VBDs, ultimately improving public health outcomes in Jazan and other endemic regions worldwide.

The reprotoxic adverse side effects of neurogenic and neuroprotective drugs: current use of human organoid modeling as a potential alternative to preclinical models.

The management of neurological disorders heavily relies on neurotherapeutic drugs, but notable concerns exist regarding their possible negative effects on reproductive health. Traditional preclinical models often fail to accurately predict reprotoxicity, highlighting the need for more physiologically relevant systems. Organoid models represent a promising approach for concurrently studying neurotoxicity and reprotoxicity, providing insights into the complex interplay between neurotherapeutic drugs and reproductive systems. Herein, we have examined the molecular mechanisms underlying neurotherapeutic drug-induced reprotoxicity and discussed experimental findings from case studies. Additionally, we explore the utility of organoid models in elucidating the reproductive complications of neurodrug exposure. Have discussed the principles of organoid models, highlighting their ability to recapitulate neurodevelopmental processes and simulate drug-induced toxicity in a controlled environment. Challenges and future perspectives in the field have been addressed with a focus on advancing organoid technologies to improve reprotoxicity assessment and enhance drug safety screening. This review underscores the importance of organoid models in unraveling the complex relationship between neurotherapeutic drugs and reproductive health.

Additional blood meals increase sporozoite infection in Anopheles mosquitoes but not Plasmodium falciparum genetic diversity.

The availability of nutrients from mosquito blood meals accelerates the development of Plasmodium falciparum laboratory strains in artificially infected Anopheles gambiae mosquitoes. The impact of multiple blood meals on the number of P. falciparum genotypes developing from polyclonal natural human malaria infections (field-isolates) remains unexplored. Here, we experimentally infect An. gambiae with P. falciparum field-isolates and measure the impact of an additional non-infectious blood meal on parasite development. We also assess parasite genetic diversity at the blood stage level of the parasite in the human host and of the sporozoites in the mosquito. Additional blood meals increase the sporozoite infection prevalence and intensity, but do not substantially affect the genetic diversity of sporozoites in the mosquito. The most abundant parasite genotypes in the human blood were transmitted to mosquitoes, suggesting that there was no preferential selection of specific genotypes. This study underlines the importance of additional mosquito blood meals for the development of parasite field-isolates in the mosquito host.

Understanding the effects of COVID-19 on patients with diabetic nephropathy: a systematic review.

Background: Diabetic nephropathy is one of the consequences of diabetes mellitus that causes a continuous decline in the eGFR. After the COVID-19 pandemic, studies have shown that patients with diabetic nephropathy who had contracted COVID-19 have higher rates of morbidity and disease progression. The aim of this study was to systematically review the literature to determine and understand the effects and complications of SARS-CoV-2 on patients with diabetic nephropathy. Materials and methods: The authors' research protocol encompassed the study selection process, search strategy, inclusion/exclusion criteria, and a data extraction plan. A systematic review was conducted by a team of five reviewers, with an additional reviewer assigned to address any discrepancies. To ensure comprehensive coverage, the authors employed multiple search engines including PubMed, ResearchGate, ScienceDirect, SDL, Ovid, and Google Scholar. Results: A total of 14 articles meeting the inclusion criteria revealed that COVID-19 directly affects the kidneys by utilizing ACE2 receptors for cell entry, which is significant because ACE2 receptors are widely expressed in the kidney. Conclusion: COVID-19 affects kidney health, especially in individuals with diabetic nephropathy. The mechanisms include direct viral infection and immune-mediated injury. Early recognition and management are vital for improving the outcomes.

International Newborn Screening: Where Are We in Saudi Arabia?

Newborn screening (NBS) programs are believed to play an important role in the decrease of infant mortality rates in many countries. This is achieved through offering early detection and treatment of many genetic as well as metabolic disorders prior to the onset of symptoms. Our paper examines NBS across seven diverse nations: Saudi Arabia, the United States, Japan, Singapore, Canada, Australia, and the United Kingdom. This paper discusses the diseases screened for by each country, latest additions, as well as future recommendations, when applicable. Employing a comparative approach, we conducted a comprehensive review of the most recent published literature on NBS programs in each country and subsequently examined their latest implemented NBS guidelines as outlined on their respective official government health sector websites. We then reviewed the economic feasibility of each of these programs and factors that affect implementation and overall benefit. While all six countries employ well-developed programs, variations are observed. Those variations are mainly attributed to disparities in access, resource scarcity, financial availability, as well as ethical and cultural considerations. From a local perspective, we recommend conducting further population-based studies to assess the epidemiological data in relation to the disease burden on the country's economy. Moreover, we recommend updating national and international guidelines to contain a more comprehensive approach on policies, operation, and sustainability to deliver a service through the lens of value-based healthcare.

Melatonin and resveratrol alleviate molecular and metabolic toxicity induced by Bisphenol A in endometrial organoids.

Bisphenol A (BPA), a widespread environmental contaminant, poses concerns due to its disruptive effects on physiological functions of the uterine endometrium. In contrast, melatonin (MT) and Resveratrol (RSV) are under scrutiny for their potential protective roles against BPA-induced damage. For the efficacy and ethical concerns in the animal test, endometrial organoids, three-dimensional models mimicking endometrium, serve as crucial tools for unraveling the impact of environmental factors on reproductive health. This study aimed to comprehensively characterize the morphological, molecular and metabolic responses of porcine endometrial organoids to BPA and assess the potential protective effects of MT and RSV. Porcine uteri were prepared, digested with collagenase, mixed with Matrigel, and incubated at 38°C with 5 % CO2. Passaging involved dissociation through trypsin-EDTA treatment and subculturing. The culture medium was refreshed every 2-3 days. To investigate the environmental impact on reproductive health, endometrial organoids were treated with BPA (0.5 µM), MT (with/without BPA at 0.1 µM), and/or RSV (10 µM). Various molecular screening using gene expression, western blotting, immunofluorescence staining, and metabolites profiling were assessed the effects of BPA, MT, and RSV in terms of cell viability, morphology, reproductivity, and metabolism alteration in the endometrial organoids. As expected, BPA induced structural and molecular disruptions in organoids, affecting cytoskeletal proteins, Wnt/ß-catenin signaling, and epithelial/mesenchymal markers. It triggered oxidative stress and apoptotic pathways, altered miRNA expression, and disrupted the endocannabinoid system. The level of glucose, galactose, and essential amino acids were increased or decreased by approximately 1.5-3 times in BPA-treated groups compared to the control groups (p-value < 0.05), indicating metabolic changes. Moreover, MT and RSV treated groups exhibited protective effects, mitigating BPA-induced disruptions across multiple pathways. For the first time, our study models endometrial organoids, advancing understanding of environmental impacts on reproductive health.

Thymol's modulation of cellular macromolecules, oxidative stress, DNA damage, and NF-kB/caspase-3 signaling in the liver of imidacloprid-exposed rats.

We evaluated whether thymol (THY) (30 mg/kg b.wt) could relieve the adverse effects of the neonicotinoid insecticide imidacloprid (IMD) (22.5 mg/kg b.wt) on the liver in a 56-day oral experiment and the probable underlying mechanisms. THY significantly suppressed the IMD-associated increase in hepatic enzyme leakage. Besides, the IMD-induced dyslipidemia was considerably corrected by THY. Moreover, THY significantly repressed the IMD-induced hepatic oxidative stress, lipid peroxidation, DNA damage, and inflammation. Of note, the Feulgen, mercuric bromophenol blue, and PAS-stained hepatic tissue sections analysis declared that treatment with THY largely rescued the IMD-induced depletion of the DNA, total proteins, and polysaccharides. Moreover, THY treatment did not affect the NF-kB p65 immunoexpression but markedly downregulated the Caspase-3 in the hepatocytes of the THY+IMD-treated group than the IMD-treated group. Conclusively, THY could efficiently protect against IMD-induced hepatotoxicity, probably through protecting cellular macromolecules and antioxidant, antiapoptotic, and anti-inflammatory activities.

Dried blood spot sampling coupled with liquid chromatography-tandem mass for simultaneous quantitative analysis of multiple cardiovascular drugs.

Dried Blood Spots (DBS) revolutionize therapeutic drug monitoring using LC-MS for the precise quantification of cardiovascular drugs (CDs), enabling personalized treatment adapted to patient-specific pharmacokinetics with minimal invasiveness. This study aims to achieve simultaneous quantification of eight CDs in DBS, overcoming physicochemical challenges. A two-step protein precipitation method was used for simple and precise sample preparation. The drugs were analyzed using LC-MS/MS in ESI positive-ion mode, showing high sensitivity and linearity, with a correlation coefficient (r2) exceeding 0.999, after being separated on a reversed-phase chromatography by gradient elution of DW-acetonitrile containing 0.1 % formic acid + 2 mM ammonium formate. The validation results indicate good selectivity, with no observed matrix effect and carry-over. The intra- and inter-day accuracy and precision were within 6 % for most drugs, except for digoxin and deslanoside at low therapeutic levels where the variation was within 20 %. Stability tests confirmed suitable DBS handling and storage conditions, indicating drug stability for at least 30 days at room temperature. The analysis of whole spot has demonstrated remarkable precision and reliability in all target drugs. The analysis of 3 mm internal diameter discs, punched in and out of DBS, presumed to contain 3 µL of blood, showed acceptable accuracy for most drugs, with less polar drugs like digoxin and deslanoside showing lower accuracy, indicating a need for further correction due to non-uniform drug distribution. Consequently, the developed LC-MS/MS method enables the quantification of multiple CDs in a single DBS analysis, while suggesting the potential for accuracy-based analysis.

The perception of genetic diseases and premarital screening tests in the central region of Saudi Arabia.

The prevalence of consanguineous marriages (CMs) varies worldwide from one country to another. However, the Middle East stands out as a region with a notably high rate of CMs. CM is particularly widespread in Saudi Arabia, where the prevalence of autosomal recessive genetic diseases has increased. This study aims to identify the Saudi population's awareness of genetic diseases and premarital screening tests (PMSTs). It also seeks to understand couples' perceptions of genetic diseases before and after marriage and their attitudes towards PMSTs and genetic counselling (GC) in reducing the risk of CM. Through the administration of online questionnaires, this cross-sectional study surveyed 2,057 participants to assess their awareness of genetic diseases and their understanding of testing and preventive measures for inherited diseases. Descriptive analysis, nonparametric chi-square tests and logistic regressions were performed to assess the association of categorical responses. This study included 2,035 Saudi Arabian respondents. A significant correlation was found between positive family history and partner selection (p = 0.001), as well as between partnering within the same tribe (p = 0.000139), with a different tribe (p = 0.000138) and from another family (p = 0.000489). About 91.3% of participants expressed agreement regarding the need to enhance public awareness and knowledge concerning genetic disorders, while 87% agreed that increased government regulations are required to prevent the spread of genetic diseases in affected families. Despite increased awareness of genetic diseases and PMSTs, there appears to be a lack of understanding regarding the limitations of PMSTs. The persistently high rate of CM underscores the challenge of altering marriage customs. Further governmental efforts are required to promote awareness of alternative reproductive options, establish new regulations and expand screening programmes.

Zeolitic imidazolate framework-8 encapsulated with Mo-based polyoxometalates as surfaces with antibacterial activity against Escherichia coli.

Bacterial infections represent a major global health concern, causing millions of deaths and a significant economic burden. The development of antibacterial nanoporous surfaces with potential mechano-bactericidal effects can revolutionize infection control practices. In this study, a hybrid material of zeolitic imidazolate framework-8 (ZIF-8) doped with phosphomolybdic acid (PMA) was synthesized and characterized by field emission scanning electron microscopy (FESEM), energy-dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and N2 sorption isotherms. PMA@ZIF-8 performance as an antibacterial agent against E. coli was superior to that of its individual constituents, suggesting a synergistic effect of PMA and ZIF-8. The incorporation of PMA into ZIF-8 significantly enhanced its antibacterial efficacy, as evidenced by a twofold reduction in MIC (375 µg mL-1 vs. 750 µg mL-1) and a 4.35 times increase in the bactericidal kinetics rate constant. The time-kill curve experiment revealed that PMA@ZIF-8 achieved a 3-log reduction within 7 hours, whereas ZIF-8 required 24 hours to reach the same level of reduction. The density functional theory (DFT) calculated bandgap of PMA@ZIF-8 was significantly less than that of ZIF-8. Also, PMA@ZIF-8 has caused the elimination of 56.72% of the thiol group as detected by Ellman's assay. Accordingly, PMA@ZIF-8 can be both computationally and experimentally demonstrated as an oxidative nanozyme. PMA@ZIF-8's surface topology revealed nanorod protrusions, suggesting a potential mechano-bactericidal effect, which was confirmed by live/dead assay on PMA@ZIF-8-coated glass. This study highlights the potential of the PMA@ZIF-8 hybrid as a highly effective antibacterial agent, holding promise for creating multifunctional antibacterial surfaces.

Simultaneous quantification of 11 antiepileptic drugs using limited isotope-labeled internal standards in LC-MS/MS: An accuracy assessment.

This study aims to establish an LC-MS/MS method to simultaneously analyze 11 antiepileptic drugs with a particular focus on maintaining accuracy while reducing the number of isotope-labeled internal standards employed for cost-effectiveness. By applying a water/acetonitrile gradient elution containing 0.1 % formic acid and 2 mM ammonium formate as the mobile phase, optimal sensitivity for the target drugs could be obtained in positive ESI mode in LC-MS/MS. After optimizing various extraction techniques, extraction with 70 % acetonitrile was selected as it provided good recoveries (>93 %) for all targets without matrix effects. Accuracies within 3 % were achieved from the combination of six internal standards, while accuracies of 5 % and 10 % were obtained by reducing the number of internal standards to four and two, respectively, for more economical analysis. The accuracy of the established method was maintained in hyperglycemia, hyperlipidemia, and hyperalbuminemia sera, suggesting that it can be successfully applied to individual serum samples with various properties.

Diabetic retinopathy: Knowledge, awareness, and practices in primary-care centers in the Kingdom of Bahrain.

Background: With the growing incidence of diabetic-related complications such as retinopathy and the well-understood role of screening and telemedicine around the world in preventing and managing this potentially blinding disease, there comes the importance of awareness toward this silent eye condition. Awareness ideally should be raised both from the patients' and physicians' perspectives. This study aims to assess the awareness of primary care physicians (PCPs) towards diabetic retinopathy (DR) and its management. Materials and Methods: A survey considering professional background, knowledge, and practices was distributed electronically to all PCPs in the Kingdom of Bahrain and analyzed using SPSS Vs 21. Results: A total of 83 physicians completed the survey; 81.9% were female and 96.4% were Bahraini. More than 60% of them accurately knew screening guidelines for type 1 and 2 DR. Of the total, 72.5% would refer patients to the ophthalmologist even if asymptomatic, and 97.6% correctly stated that a dilated eye exam is the method of choice most efficient for assessing DR. Nearly 60% knew about the current treatment modalities for DR and 91.3% knew about the presence of a national screening program in the Kingdom. Conclusion: The overall knowledge of DR was good with some potential gaps in information about screening. PCPs could benefit from regular refresher courses for more precise practices on screening and referral of retinopathy.