Exploring the most promising anti - Depressant drug targeting Microtubule Affinity Receptor Kinase 4 involved in Alzheimer's Disease through molecular docking and molecular dynamics simulation.

Alzheimer's Disease (AD) is the prevailing type of neurodegenerative illness, characterised by the accumulation of amyloid beta plaques. The symptoms associated with AD are memory loss, emotional variability, and a decline in cognitive functioning. To date, the pharmaceuticals currently accessible in the marketplace are limited to symptom management. According to several research, antidepressants have demonstrated potential efficacy in the management of AD. In this particular investigation, a total of 24 anti-depressant medications were selected as ligands, while the Microtubule Affinity Receptor Kinase 4 (MARK4) protein was chosen as the focal point of our study. The selection of MARK4 was based on its known involvement in the advancement of AD and other types of malignancies, rendering it a highly prospective target for therapeutic interventions. The initial step involved doing ADMET analysis, which was subsequently followed by molecular docking of 24 drugs. This was succeeded by molecular dynamics simulation and molecular mechanics generalised Born surface area (MMGBSA) calculations. Upon conducting molecular docking experiments, it has been determined that the binding affinities observed fall within the range of -5.5 kcal/mol to -9.0 kcal/mol. In this study, we selected six anti-depressant compounds (CID ID - 4184, 2771, 4205, 5533, 4543, and 2160) based on their binding affinities, which were determined to be -9.0, -8.7, -8.4, -8.3, -8.2, and -8.2, respectively. Molecular dynamics simulations were conducted for all six drugs, with donepezil serving as the control drug. Various analyses were performed, including basic analysis and post-trajectory analysis such as free energy landscape (FEL), polarizable continuum model (PCM), and MMGBSA calculations. Based on the findings from molecular dynamics simulations and the MMGBSA analysis, it can be inferred that citalopram and mirtazapine exhibit considerable potential as anti-depressant agents. Consequently, these compounds warrant further investigation through in vitro and in vivo investigations in the context of treating AD.

Incidence, patterns, and management of frontal sinus fractures: A 10-year retrospective study at a tertiary medical center, Saudi Arabia.

OBJECTIVES: To assess the prevalence of various frontal sinus fractures (FSF) and examine the relationships between these fractures, types of treatments, and potential complications. METHODS: A retrospective study was carried out in King Saud Medical City, Riyadh, Saudi Arabia. The study analyzed the records of patients who were diagnosed and treated with FSF from 2011-2021. Files with missing documents or incomplete treatment were excluded. The retrieved data includes: patients age, gender, types, locations, treatment, and complications of FSF. Data was analyzed by the statistical Package for the Social Sciences Statistics, version 23.0 using descriptive statistics and Chi-square test. RESULTS: A total of 72 cases were included, 94.4% males and 5.6% females. Road traffic accidents were the common cause of trauma (91%). Frontal sinus fractures were unilateral in 59.7% and associated other injuries in 80.6% of cases. Anterior table fractures were the largest proportion (58.3%), followed by anterior and posterior table (37.5%). The carried out surgical procedures were obliteration (23.9%), cranialization and obliteration (23.9%), and fixation only (52.2%). The post-operative complications were categorized into; neurological (22.2%), ophthalmic (15.3%), infection (2.8%), and deformity (16.7%). Anterior and posterior table had the highest percentage among these categories. CONCLUSION: Frontal sinus fractures were mostly required surgical treatment (63.9%) and post-operative complications occurred especially the neurological and ophthalmic. We recommend studies on the association of complications and different types of obliteration materials.

What You Should Know About Vasitis: A Case Report.

Even though infected vasitis is rarely reported in the literature, there are other diagnoses that share the same clinical signs, including testicular torsion, epididymo-orchitis, epididymitis, trauma, and incarcerated hernia. A 27-year-old man was brought to the emergency department by his brother with right inguinal and testicular pain for one day. The history was not significant with fever, lower urinary tract symptoms, urethral discharge, change in bowel habits, previous history of inguinal swelling, or surgical intervention. On presentation, the patient was vitally stable, and right infra-inguinal and inguinal vas deferens were tender and swollen; however, both testes and epididymis were normal, and no urethral discharge. Vasitis, or inflammation of the vas deferens, is an uncommon illness that Chan PT and Schlegel classified as either asymptomatic vasitis nodosa or severely painful infectious vasitis. Acute infective vasitis is a really uncommon illness, with only a few occurrences documented in the literature. However, the retrograde transmission of urinary pathogens such as Escherichia coli and Haemophilus influenza is thought to cause acute vasitis. Because of its rarity and ambiguous imaging findings, diagnosing vasitis can be difficult. Epididymitis, orchitis, and testicular torsion can all be ruled out with ultrasound and duplex Doppler screening. Inguinal hernia is difficult to distinguish from vasitis with ultrasound; hence, CT and MRI are more commonly used to confirm the diagnosis. Since this is the first occurrence in our city that we are aware of, it was reported. A few cases from Saudi Arabia have also been documented, and by doing so, we may raise clinicians' awareness of this disease and ensure that they can treat patients without making an incorrect diagnosis.

Pesticides impacts on human health and the environment with their mechanisms of action and possible countermeasures.

Pesticides are chemical constituents used to prevent or control pests, including insects, rodents, fungi, weeds, and other unwanted organisms. Despite their advantages in crop production and disease management, the use of pesticides poses significant hazards to the environment and public health. Pesticide elements have now perpetually entered our atmosphere and subsequently contaminated water, food, and soil, leading to health threats ranging from acute to chronic toxicities. Pesticides can cause acute toxicity if a high dose is inhaled, ingested, or comes into contact with the skin or eyes, while prolonged or recurrent exposure to pesticides leads to chronic toxicity. Pesticides produce different types of toxicity, for instance, neurotoxicity, mutagenicity, carcinogenicity, teratogenicity, and endocrine disruption. The toxicity of a pesticide formulation may depend on the specific active ingredient and the presence of synergistic or inert compounds that can enhance or modify its toxicity. Safety concerns are the need of the hour to control contemporary pesticide-induced health hazards. The effectiveness and implementation of the current legislature in providing ample protection for human health and the environment are key concerns. This review explored a comprehensive summary of pesticides regarding their updated impacts on human health and advanced safety concerns with legislation. Implementing regulations, proper training, and education can help mitigate the negative impacts of pesticide use and promote safer and more sustainable agricultural practices.

Deciphering the Enigma of Neuron-Glial Interactions in Neurological Disorders.

Innate lymphocytes, including microglial cells, astrocytes, and oligodendrocytes, play a crucial role in initiating neuroinflammatory reactions inside the central nervous system (CNS). The prime focus of this paper is on the involvement and interplay of neurons and glial cells in neurological disorders such as Alzheimer's Disease (AD), Autism Spectrum Disorder (ASD), epilepsy, and multiple sclerosis (MS). In this review, we explore the specific contributions of microglia and astrocytes and analyzes multiple pathways implicated in neuroinflammation and disturbances in excitatory and inhibitory processes. Firstly, we elucidate the mechanisms through which toxic protein accumulation in AD results in synaptic dysfunction and deregulation of the immune system and examines the roles of microglia, astrocytes, and hereditary factors in the pathogenesis of the disease. Secondly, we focus on ASD and the involvement of glial cells in the development of the nervous system and the formation of connections between neurons and investigates the genetic connections associated with these processes. Lastly, we also address the participation of glial cells in epilepsy and MS, providing insights into their pivotal functions in both conditions. We also tried to give an overview of seven different pathways like toll-like receptor signalling pathway, MyD88-dependent and independent pathway, etc and its relevance in the context with these neurological disorders. In this review, we also explore the role of activated glial cells in AD, ASD, epilepsy, and MS which lead to neuroinflammation. Even we focus on excitatory and inhibitory imbalance in all four neurological disorders as imbalance affect the proper functioning of neuronal circuits. Finally, this review concludes that there is necessity for additional investigation on glial cells and their involvement in neurological illnesses.

Prevalence of Depressive Symptoms and Its Correlates among Male Medical Students at the University of Bisha, Saudi Arabia.

BACKGROUND: Identifying the potential factors of depression among medical students is the first step towards academic excellence and future safe medical practice. METHODS: A cross-sectional study was conducted from December 2019 to February 2020 at the University of Bisha, College of Medicine (UBCOM), Bisha Province, Saudi Arabia. Male medical students from year one to year six were involved. A self-administered questionnaire was used to collect data about students' socio-demographic and academic characteristics. The Arabic version of the PHQ-9 scale with a score of ≥10 was used to identify depression. Logistic regression analysis was used to assess the prevalence and correlates of depression. RESULTS: Of the 190 male students enrolled, 26.8% had depressive symptoms, of whom 45.1% were experiencing moderate to severe symptoms. The significantly highest depression rate was found among the second-year students, at 43.8% (OR = 2.544; 95% CI 1.178-5.714; p = 0.018), and the lowest rate was found among year one students, at 8.9% (OR = 0.203; 95% CI 0.075-0.560; p = 0.002). Univariate regression revealed a significant correlation between depression and dissatisfaction with family income, loss of family members, having psychological illness, difficulties in personal relationships, regretting studying medicine, failure in an academic year, a lower grade than expected, conflict with tutors, lack of college facilities and heavy academic load. In multivariate analysis, loss of family members (AOR = 3.69; 95% CI 1.86-7.413), difficulties in personal relationships (AOR = 2.371; 95% CI 1.009-5.575), regretting studying medicine (AOR = 3.764; 95% CI 1.657-8.550), and failing an academic year (AOR = 2.559; 95% CI 1.112-5.887) were independently correlated with depression. CONCLUSIONS: The study concluded that medical students at UBCOM experience depressive symptoms associated with various risk indicators. Optimizing the educational and social environment and infrastructure facilities at UBCOM might promote students' mental health and well-being.

Comprehensive review of melatonin as a promising nutritional and nutraceutical supplement.

Background: Melatonin is an indoleamine hormone secreted by the pineal gland at night and has an essential role in regulating human circadian rhythms (the internal 24-h clock) and sleep-wake patterns. However, it has recently gained considerable attention for its demonstrated ability in disease management. This review discusses the major biological activities of melatonin, its metabolites as nutritional supplements, and its bioavailability in food sources. Methods: The information acquisition process involved conducting a comprehensive search across academic databases including PubMed, Scopus, Wiley, Embase, and Springer using relevant keywords. Only the most recent, peer-reviewed articles published in the English language were considered for inclusion. Results: The molecular mechanisms by which melatonin induces its therapeutic effects have been the subject of various studies. Conclusion: While melatonin was initially understood to only regulate circadian rhythms, recent studies indicate that it has a far-reaching effect on various organs and physiological systems, such as immunity, cardiovascular function, antioxidant defense, and lipid hemostasis. As a potent antioxidant, anti-cancer, anti-inflammatory, and immunoregulatory agent, multiple therapeutic applications have been proposed for melatonin.

Itraconazole halts hepatocellular carcinoma progression by modulating sonic hedgehog signaling in rats: A novel therapeutic approach.

Liver cancer stands as the fourth leading global cause of death, and its prognosis remains grim due to the limited effectiveness of current medical interventions. Among the various pathways implicated in the development of hepatocellular carcinoma (HCC), the hedgehog signaling pathway has emerged as a crucial player. Itraconazole, a relatively safe and cost-effective antifungal medication, has gained attention for its potential as an anticancer agent. Its primary mode of action involves inhibiting the hedgehog pathway, yet its impact on HCC has not been elucidated. The main objective of this study was to investigate the effect of itraconazole on diethylnitrosamine-induced early-stage HCC in rats. Our findings revealed that itraconazole exhibited a multifaceted arsenal against HCC by downregulating the expression of key components of the hedgehog pathway, shh, smoothened (SMO), and GLI family zinc finger 1 (GLI1), and GLI2. Additionally, itraconazole extended survival and improved liver tissue structure, attributed mainly to its inhibitory effects on hedgehog signaling. Besides, itraconazole demonstrated a regulatory effect on Notch1, and Wnt/ß-catenin signaling molecules. Consequently, itraconazole displayed diverse anticancer properties, including anti-inflammatory, antiangiogenic, antiproliferative, and apoptotic effects, as well as the potential to induce autophagy. Moreover, itraconazole exhibited a promise to impede the transformation of epithelial cells into a more mesenchymal-like phenotype. Overall, this study emphasizes the significance of targeting the hedgehog pathway with itraconazole as a promising avenue for further exploration in clinical studies related to HCC treatment.

The emerging role of miRNAs in myocardial infarction: From molecular signatures to therapeutic targets.

Globally, myocardial infarction (MI) and other cardiovascular illnesses have long been considered the top killers. Heart failure and mortality are the results of myocardial apoptosis, cardiomyocyte fibrosis, and cardiomyocyte hypertrophy, all of which are caused by MI. MicroRNAs (miRNAs) play a crucial regulatory function in the progression and advancement of heart disease following an MI. By consolidating the existing data on miRNAs, our aim is to gain a more comprehensive understanding of their role in the pathological progression of myocardial injury after MI and to identify potential crucial target pathways. Also included are the primary treatment modalities and their most recent developments. miRNAs have the ability to regulate both normal and pathological activity, including the key signaling pathways. As a result, they may exert medicinal benefits. This review presents a comprehensive analysis of the role of miRNAs in MI with a specific emphasis on their impact on the regeneration of cardiomyocytes and other forms of cell death, such as apoptosis, necrosis, and autophagy. Furthermore, the targets of pro- and anti-MI miRNAs are comparatively elucidated.

Estimation of Vitamin D Levels Using a Chairside Diagnostic Test Kit in Patients with Gingivitis and Periodontitis: A Cross-Sectional Study.

Aim: Periodontitis is an inflammatory condition of the periodontium that is instigated by microbial biofilms developed on the teeth. The purpose of the study was to ascertain the vitamin D status of gingivitis and periodontitis patients while maintaining a healthy group as the control using simple low-cost chairside pre-coated with 25-OH Vitamin D antigen rapid test kits. Materials and Methods: From outpatients visiting the college's periodontics clinics, a total of 101 patients were screened. The study sample includes 38 patients in the periodontitis group, 32 in the gingivitis group, and 31 in the healthy group. A middle-digit needle was used to collect blood samples, which were put into a test cassette with membrane that had been coated with 25-OH Vitamin D antigen on the test line area of the strip. Vitamin D Quick Test (Natejah) Semi-quantitatively detects 25-hydroxyvitamin D (25 (OH) D) in human finger-stick complete blood at a cutoff convergence of 30 ± 4 ng/mL. Vitamin D blood levels below 80 nmol/L are considered to have deficient vitamin 25(OH)D levels. Clinical parameters between healthy, gingivitis, and different stages of periodontitis subjects were compared using one-way ANOVA and Tukey's multiple comparison. Fisher's exact test was done to compare vitamin D levels in the three groups. Results: Fisher's exact test revealed that there was a statistically significant increase in the number of subjects with stages 4 and stage 3 periodontitis who lacked vitamin D levels (less than 80 nmol/L). Whereas least deficient in Vit D were noticed among Healthy and Gingivitis subjects. When compared to healthy individuals, gingivitis, and various stages of periodontitis had significantly higher mean PI values in a Tukey's multiple comparison. Vitamin D deficiency was found to be 27.5% in subjects with gingivitis and 71.5% in subjects with periodontitis. Conclusion: Periodontitis is associated with vitamin D deficiency, in contrast to gingivitis and healthy subjects. The severity of periodontitis was likewise linked to the amount of vitamin D in the individual's blood. When compared to expensive, time-consuming, and laborious laboratory methods, the findings of this study suggest that a simple inexpensive chairside pre-coated with 25-OH Vitamin D antigen rapid test kits can be considered a viable alternative for determining vitamin D levels.

Predictors of Patients' Satisfaction with Primary Health Care Services in the Kingdom of Saudi Arabia: A Systematic Review.

BACKGROUND: Understanding the factors influencing patients' satisfaction with primary healthcare services in the Kingdom of Saudi Arabia is essential for improving healthcare outcomes and patient experiences. OBJECTIVES: This research work is concerned with the identification of the patient satisfaction predictors with the primary health care services by conducting a systematic review in the Kingdom of Saudi Arabia. METHODS: The three databases in the form of Google Scholar, PubMed, and Medline have been used for article extraction. Keywords have been used to search the articles related to this work, such as the predictors of patient satisfaction. The different journals selected were associated with the selected data basis. The research studies selected for the systematic review were evaluated with the help of PRISMA and JBI assessments. The cross-sectional studies have been included in this systematic review. RESULTS: The 3125 articles identified were from the three databases PubMed (1352), Medline (1103), and Google Scholar (670). All the selected studies were evaluated and screened with the help of PRISMA. After extracting the 25 articles for the systematic review, the JBI assessment was applied to the methodologies. The overall quality satisfaction indicated that all the selected studies were suitable for the systematic review. CONCLUSION: Studies have consistently identified five key predictors of patient satisfaction in primary healthcare: availability, accessibility, communication, rational conduct, technical skills, and personal qualities. Policymakers, healthcare providers, and researchers can use these insights to inform strategies to optimize healthcare services and foster higher levels of patient satisfaction in the Kingdom.

Risk and diagnostic factors and therapy outcome of neonatal early onset sepsis in ICU patients of Saudi Arabia: a systematic review and meta analysis.

Background: Neonatal early onset sepsis (NEOS) is a serious and potentially life-threatening condition affecting newborns within the first few days of life. While the diagnosis of NEOS was based on clinical signs and symptoms in the past, recent years have seen growing interest in identifying specific diagnostic factors and optimizing therapy outcomes. This study aims to investigate the diagnostic and risk factors and therapy outcomes of neonatal EOS in ICU patients in Saudi Arabia, with the goal of improving the management of neonatal EOS in the country. Methods: This method outlines the protocol development, search strategy, study selection, and data collection process for a systematic review on neonatal early onset sepsis in Saudi Arabian ICU patients, following the PRISMA 2020 guidelines. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) is a well-established guideline that provides a framework for conducting systematic reviews and meta-analyses in a transparent and standardized manner. It aims to improve the quality and reporting of such research by ensuring clear and comprehensive reporting of study methods, results, and interpretations. The search strategy included electronic databases (PubMed, Embase, Google Scholar, Science Direct, and the Cochrane Library) and manual search of relevant studies, and data were extracted using a standardized form. Results: The systematic review included 21 studies on neonatal sepsis in Saudi Arabia, with varying study designs, sample sizes, and prevalence rates of sepsis. Group B streptococcus and E. coli were the most commonly isolated pathogens. Various diagnostic factors and risk factors were reported, including hematological parameters, biomarkers, and blood cultures. The quality of the included studies was assessed using the Newcastle-Ottawa Scale and Joanna Briggs Institute critical checklist. Conclusions: The review identified a number of risk and diagnostic factors and therapy outcomes for neonatal sepsis. However, most of the studies were having small scale cohort groups. Further research with controlled study designs is needed to develop effective prevention and management strategies for neonatal sepsis in Saudi Arabia.

Ganoderma lucidum: Novel Insight into Hepatoprotective Potential with Mechanisms of Action.

Ganoderma lucidum (G. lucidum) has been widely used for its health benefits as an edible and traditional medicinal mushroom for thousands of years in Asian countries. It is currently used as a nutraceutical and functional food owing to its major bioactive compounds, polysaccharides and triterpenoids. G. lucidum exhibits a broad range of hepatoprotective impacts in various liver disorders, such as hepatic cancer, nonalcoholic fatty liver disease (NAFLD), alcohol-induced liver disease, hepatitis B, hepatic fibrosis, and liver injury induced by carbon tetrachloride (CCl4) and α-amanitin. G. lucidum protects the liver through a broad range of mechanisms that include the modulation of liver Phase I and II enzymes, the suppression of ß-glucuronidase, antifibrotic and antiviral actions, the regulation of the production of nitric oxide (NO), the maintenance of hepatocellular calcium homeostasis, immunomodulatory activity, and scavenging free radicals. G. lucidum could signify an encouraging approach for the management of various chronic hepatopathies, and its potential mechanisms make it a distinctive agent when used alone or with other drugs and applied as a functional food, nutraceutical supplement, or adjuvant to modern medicine. This review summarizes the hepatoprotective properties of G. lucidum with its various mechanisms of action on different liver ailments. Biologically active substances derived from G. lucidum are still being studied for their potential benefits in treating different liver ailments.

In-silico approaches for identification of compounds inhibiting SARS-CoV-2 3CL protease.

The world has witnessed of many pandemic waves of SARS-CoV-2. However, the incidence of SARS-CoV-2 infection has now declined but the novel variant and responsible cases has been observed globally. Most of the world population has received the vaccinations, but the immune response against COVID-19 is not long-lasting, which may cause new outbreaks. A highly efficient pharmaceutical molecule is desperately needed in these circumstances. In the present study, a potent natural compound that could inhibit the 3CL protease protein of SARS-CoV-2 was found with computationally intensive search. This research approach is based on physics-based principles and a machine-learning approach. Deep learning design was applied to the library of natural compounds to rank the potential candidates. This procedure screened 32,484 compounds, and the top five hits based on estimated pIC50 were selected for molecular docking and modeling. This work identified two hit compounds, CMP4 and CMP2, which exhibited strong interaction with the 3CL protease using molecular docking and simulation. These two compounds demonstrated potential interaction with the catalytic residues His41 and Cys154 of the 3CL protease. Their calculated binding free energies to MMGBSA were compared to those of the native 3CL protease inhibitor. Using steered molecular dynamics, the dissociation strength of these complexes was sequentially determined. In conclusion, CMP4 demonstrated strong comparative performance with native inhibitors and was identified as a promising hit candidate. This compound can be applied in-vitro experiment for the validation of its inhibitory activity. Additionally, these methods can be used to identify new binding sites on the enzyme and to design new compounds that target these sites.

Assessment of food labeling knowledge and associated reading barriers among patients with diabetes.

Background: The most challenging part of diabetes management for a patient with diabetes is selecting a healthy diet. The purpose of this study is to evaluate participants' knowledge of food labels, to find out the relationship between the type of diabetes mellitus (DM) and knowledge score of food labels, and to explore the barriers that prevent patients from reading food labels. Methodology: This observational study was conducted on patients with type 1 or type 2 diabetes using a validated self-administered questionnaire. The study was conducted at diabetes clinics at King Khalid University Hospital and King Abdul-Aziz University Hospital, Riyadh, Saudi Arabia, from November 2019 to February 2020. Data were analyzed using SPSS. Results: A total of 310 participants were enrolled in this study, of which 50.3% had type 1 DM, and more than half of them were female (51.6%). Patients with type 1 DM had higher mean declarative and applied knowledge scores than those with type 2 DM, regardless of whether they were taking pre meals insulin or not. The highest proportion (39.9%) had difficulty in understanding the content of the nutrition labels, and some of them (37.2%) did not receive any educational session about it. Only 9.5% of the participants did not have any difficulties in reading food labels. Conclusion: Patients with both types of diabetes tended to have poor total knowledge about food labels and faced difficulties in reading them. Provided educational sessions by primary health care and specialized physician and DM educator about food labels are recommended to help them to choose food properly.

Acute pancreatitis after intragastric balloon insertion: case report.

The intragastric balloon (IGB) is a relatively recent non-surgical weight loss technique that is now widely used in the world to treat obesity. However, IGB causes a wide range of adverse effects that range from minor ones, such as nausea, stomach pain and gastroesophageal reflux, to serious ones, such as ulceration, perforation, intestinal blockage and compression of adjusting structures. A 22-year-old Saudi woman presented to the emergency department (ED) with a history of upper abdominal pain that started 1 day before admission. The patient's surgical background was unremarkable, and no other obvious pancreatitis risk factors were present. The patient underwent a minimally invasive treatment after being diagnosed with obesity (class 1), in which an IGB was inserted one and a half months prior to her ED presentation. She consequently began to lose weight (around 3 kg). The hypothesis states that pancreatitis following IGB insertion can be caused either by stomach distention and pancreatic compression at the tail or body or by ampulla obstruction due to balloon catheter migration at the duodenum. Heavy meal consumption, which may cause an increase in pancreatic compression, is another potential cause of pancreatitis in such patients. We believe that the IGB-induced compression of the pancreas at its tail or body was the likely cause of pancreatitis in our case. This case was reported because it is the first one from our city as far as we know. A few cases from Saudi Arabia have also been reported, and reporting them will help to improve doctors' awareness of this complication, which can cause pancreatitis symptoms to be mistaken for something else because of the balloon-related effects on gastric distention.

Molecular Epidemiology of Carbapenem-Resistant K. pneumoniae Clinical Isolates from the Adult Patients with Comorbidities in a Tertiary Hospital, Southern Saudi Arabia.

Hospitalized patients are likely to have chronic illnesses and are at an increased risk of mortality due to infection caused by MDR bacteria. We aimed to identify carbapenem-resistant genes carrying Klebsiella pneumoniae (K. pneumoniae) isolates and their risk factors recovered from adult patients with comorbidities. A cross-sectional study was carried out between April 2021 and December 2021 at King Abdullah Hospital (KAH) in Bisha province, Saudi Arabia. Seventy-one multi-drug resistant K. pneumoniae recovered from clinical samples and screened for carbapenemase genes of blaOXA-48-like, blaNDM-1, blaKPC, blaVIM, and blaIMP. Of 71 MDR K. pneumoniae examined, 47 (66.2%) isolates harbored various carbapenemase genes. The most prevalent single resistance gene was blaOXA-48-like (62.5%; n = 25), and 33.3% of them were recovered from sputum isolates. The blaNDM-1 gene was detected in 12 (30.0%) isolates, and eight of them were recovered from urine (n = 4) and blood (n = 4). Two (5.0%) single blaKPC genes were recovered from the sputum (n = 1) and blood (n = 1) isolates. In contrast, no blaIMP- and blaVIM-carrying isolates were detected. The co-existence of two resistance genes between blaOXA-48-like and blaNDM-1 was found in six strains, whereas only one strain was found to be produced in the three genes of blaNDM-1, blaKPC, and blaOXA-48-like. There were statistically significant associations between the presence of carbapenem-gene-carrying K. pneumoniae and patients' gender (χ2(1) = 5.94, p = 0.015), intensive care unit admission (χ2(1) = 7.649, p = 0.002), and chronic obstructive pulmonary disease (χ2(1) = 4.851, p = 0.028). The study highlighted the existence of carbapenemase-producing K. pneumoniae, particularly blaOXA-48-like and blaNDM-1, in patients with comorbidities. Our findings emphasize the importance of the molecular characterization of resistance-determinant-carrying bacterial pathogens as a part of infection control and prevention in hospital settings.

Preparedness for the Dengue Epidemic: Vaccine as a Viable Approach.

Dengue fever is one of the significant fatal mosquito-borne viral diseases and is considered to be a worldwide problem. Aedes mosquito is responsible for transmitting various serotypes of dengue viruses to humans. Dengue incidence has developed prominently throughout the world in the last ten years. The exact number of dengue cases is underestimated, whereas plenty of cases are misdiagnosed as alternative febrile sicknesses. There is an estimation that about 390 million dengue cases occur annually. Dengue fever encompasses a wide range of clinical presentations, usually with undefinable clinical progression and outcome. The diagnosis of dengue depends on serology tests, molecular diagnostic methods, and antigen detection tests. The therapeutic approach relies completely on supplemental drugs, which is far from the real approach. Vaccines for dengue disease are in various stages of development. The commercial formulation Dengvaxia (CYD-TDV) is accessible and developed by Sanofi Pasteur. The vaccine candidate Dengvaxia was inefficient in liberating a stabilized immune reaction toward different serotypes (1-4) of dengue fever. Numerous promising vaccine candidates are now being developed in preclinical and clinical stages even though different serotypes of DENV exist that worsen the situation for a vaccine to be equally effective for all serotypes. Thus, the development of an efficient dengue fever vaccine candidate requires time. Effective dengue fever management can be a multidisciplinary challenge, involving international cooperation from diverse perspectives and expertise to resolve this global concern.

Factors associated with the prevalence of malnutrition among adult hemodialytic patients: A two-center study in the Jeddah region, Saudi Arabia.

Chronic kidney disease, one of the most common diseases in the world, is characterized by irreversible impairment of the kidney's metabolic, excretory, and endocrine functions. During end-stage renal disease, patients require renal replacement therapy, such as hemodialysis (HD). Protein-energy wasting is a common health problem among HD patients. This study aims to assess the nutritional status of HD patients at two HD centers in Jeddah, Saudi Arabia, and to determine its associated factors. A cross-sectional study was conducted at two different dialysis centers in Jeddah, Saudi Arabia; 211 female and male HD patients. Malnutrition was recognized using the modified-subjective global assessment (M-SGA) comprising two parts: medical history and physical examination. Sociodemographic and health status for all patients were also determined. Patients were classified based on their M-SGA score into two groups: normal and malnourished. Overall, 54.5% of the participants showed malnutrition. Unemployment, low muscle strength and mass, high level of medication use, and high dialysis vintage were positively (P < .05) associated with malnutrition. In conclusion, the M-SGA score indicates a high prevalence of malnutrition among HD patients. These results show the importance of regular assessment and follow-ups for HD patients ensuring better health and nutritional status.

Use of gold nanoparticle-silibinin conjugates: A novel approach against lung cancer cells.

Lung cancer presents one of the most challenging carcinomas with meager 5-year survival rates (less than 20%), high metastasis and high recurrence due to chemo- and radio- resistance. An alternative or complementation to existing prognosis modalities is the use of phytochemicals such as silibinin, which targets essential cytokines, angiogenic factors and transcription factors for a profound anti-tumor effect. However, the problems of low solubility in an aqueous physiological environment, poor penetration, high metabolism and rapid systemic clearance limit the therapeutic use of silibinin. Conjugation of gold nanoparticles (GNPs) with silibinin may overcome the above challenges along with distinct advantages of biocompatibility, optical properties for monitoring and causation of cytotoxicity in cancer cells. The current study thus aims to develop silibinin conjugated gold nanoparticles (Sb-GNPs) with pH responsive release in the cancer microenvironment, optimizing several parameters for its higher activity and further evaluate the nanoplatform for their efficacy in inducing cell death in vitro against A549 lung cancer cells. GNPs was synthesized using trisodium citrate dihydrate as the reducing agent and further used for the conjugation of silibinin. The synthesized GNPs were found to be monodispersed and spherical in shape. The silibinin was successfully conjugated with gold nanoparticles and long-term stability of GNPs and Sb-GNPs nanoconjugates in suspension phase was confirmed by FTIR and DLS. Anticancer properties of Sb-GNPs were confirmed by different assay using MTT, Trypan blue dye exclusion assay and cell cycle analysis assay. After conjugation of silibinin with GNPs, the efficacy of silibinin increased 4-5 times in killing the cancer cells. This is the first report on using silibinin gold nanoconjugate system for lung cancer therapy with promising future applications.