The protective effect of Astaxanthin on scopolamine - induced Alzheimer's model in mice.

OBJECTIVES: To investigate the fundamental mechanisms of the neuroprotective impact of Astaxanthin (AST) in a mouse model of Alzheimer's disease (AD) induced by scopolamine. METHODS: This research constituted an in vivo animal study encompassing 36 adult male mice, divided into 6 groups: Control, 100 mg/kg AST, 2 mg/kg scopolamine (AD group), 100 mg/kg AST+2 mg/kg scopolamine, 3 mg/kg galantamine+2 mg/kg scopolamine, and 100 mg/kg AST+3 mg/kg galantamine+2 mg/kg scopolamine. After 14 days, the mice's short-term memory, hippocampus tissue, oxidative and inflammatory markers were evaluated. RESULTS: The AST demonstrated a beneficial influence on short-term memory and a reduction in acetylcholinesterase activity in the brain. It exhibited neuroprotective and anti-amyloidogenic properties, significantly decreased pro-inflammatory markers and oxidative stress, and reversed the decline of the Akt-1 and phosphorylated Akt pathway, a crucial regulator of abnormal tau. Furthermore, AST enhanced the effect of galantamine in reducing inflammation and oxidative stress. CONCLUSION: The findings indicate that AST may offer therapeutic benefits against cognitive dysfunction in AD. This is attributed to its ability to reduce oxidative stress, control neuroinflammation, and enhance Akt-1 and pAkt levels, thereby underscoring its potential in AD treatment strategies.

Machine Learning-Based Prediction of COVID-19 Prognosis Using Clinical and Hematologic Data.

The coronavirus disease 2019 (COVID-19) pandemic is challenging healthcare systems worldwide. The prediction of disease prognosis has a critical role in confronting the burden of COVID-19. We aimed to investigate the feasibility of predicting COVID-19 patient outcomes and disease severity based on clinical and hematological parameters using machine learning techniques. This multicenter retrospective study analyzed records of 485 patients with COVID-19, including demographic information, symptoms, hematological variables, treatment information, and clinical outcomes. Different machine learning approaches, including random forest, multilayer perceptron, and support vector machine, were examined in this study. All models showed a comparable performance, yielding the best area under the curve of 0.96, in predicting the severity of disease and clinical outcome. We also identified the most relevant features in predicting COVID-19 patient outcomes, and we concluded that hematological parameters (neutrophils, lymphocytes, D-dimer, and monocytes) are the most predictive features of severity and patient outcome.

Polymorphisms in the Drug Transporter Gene ABCB1 Are Associated with Drug Response in Saudi Epileptic Pediatric Patients.

Epilepsy is one of the most common chronic neurodisorders in the pediatric age group. Despite the availability of over 20 anti-seizure medications (ASMs) on the market, drug-resistant epilepsy still affects one-third of individuals. Consequently, this research aimed to investigate the association between single-nucleotide polymorphisms (SNPs) of the ATP-binding cassette subfamily B member 1 (ABCB1) gene in epileptic pediatric patients and their response to ASMs. This multicentric, cross-sectional study was conducted among Saudi children with epilepsy in Jeddah, Saudi Arabia. The polymorphism variants of ABCB1 rs1128503 at exon 12, rs2032582 at exon 21, and rs1045642 at exon 26 were genotyped using the Sanger sequencing technique. The study included 85 children with epilepsy: 43 patients demonstrated a good response to ASMs, while 42 patients exhibited a poor response. The results revealed that good responders were significantly more likely to have the TT genotypes at rs1045642 and rs2032582 SNPs compared to poor responders. Additionally, haplotype analysis showed that the T-G-C haplotype at rs1128503, rs2032582, and rs1045642 was only present in poor responders. In conclusion, this study represents the first pharmacogenetic investigation of the ABCB1 gene in Saudi epileptic pediatric patients and demonstrates a significant association between rs1045642 and rs2032582 variants and patient responsiveness. Despite the small sample size, the results underscore the importance of personalized treatment for epileptic patients.

Generalized Anxiety Disorder Associated With Gastroesophageal Reflux Disease Among the Saudi Population.

Objectives In Saudi Arabia, the prevalence of generalized anxiety disorder (GAD) was reported to be 29%. As a result, our goal was to examine the association between GAD and gastroesophageal reflux disease (GERD) within the general Saudi Arabian population, as well as to access the risk factors for GAD in order to gain a better understanding. Method This cross-sectional study involved 4,224 participants who completed a questionnaire. Anxiety was assessed using the General Anxiety Disorder-7 (GAD-7) scale, and the GerdQ tool was used to evaluate GERD. Result The prevalence of anxiety among participants was 29% at cutoff 10, with 73% of anxiety-positive participants being female and only 26.9% being male. Furthermore, the associations between anxiety and GERD were significant as 31.4% of participants with anxiety had GERD, compared to 15.0% of those without anxiety. Conclusion In our finding, there was a significant association between anxiety and GERD among the general Saudi population. In terms of anxiety risk factors, female, younger age, social status, body mass index, eating fried food, caffeinated drinks, diabetes miletus, high blood cholesterol, NSAID use, antidepressants, and anti-anxiety medication were found to have a significant association.

Association of Polymorphism of the Methyl Tetrahydrofolate Reductase (MTHFR) Gene with Anti-Seizure Medication Response in Pediatric Patients in Jeddah, Saudi Arabia.

Background and ObjectivesEpilepsy is a chronic brain disease, with inherent and noninherent factors. Although over 20 anti-seizure medications (ASMs) are commercially available, nearly one-third of patients develop drug-resistant epilepsy. We evaluated the association between the clinical features and the methyl tetrahydrofolate (MTHFR) rs1801133 polymorphism and ASMs response among pediatric patients with epilepsy. Materials and Methods This was a multicenter, retrospective, case-control study of 101 children with epilepsy and 59 healthy children in Jeddah. The MTHFR rs1801133 polymorphism was genotyped using the real-time polymerase chain reaction TaqMan Genotyping Assay. Results Among the patients with epilepsy, 56 and 45 showed good and poor responses to ASMs, respectively. No significant genetic association was noted between the single-nucleotide polymorphism (SNP) rs1801133 within the MTHFR gene and the response to ASMs. However, a significant association was noted between reports of drug-induced toxicity and an increase in allele A frequencies. The MTHFR rs1801133 genotype was significantly associated with the development of electrolyte disturbance among good and poor responders to ASMs. Conclusion This is the first pharmacogenetic study of MTHFR in patients with epilepsy in Saudi Arabia that found no significant association between the MTHFR SNP rs1801133 and gene susceptibility and drug responsiveness. A larger sample size is needed for testing gene polymorphisms in the future.

Mortality Predictors Among COVID-19 Elderly in Taif, Saudi Arabia.

Background: By December 2021, the COVID-19 pandemic had caused more than 266 million cases and 5 million deaths, especially among geriatric patients. Objective: To identify determinants of COVID-19-related death in geriatric patients. Methods: This is a comparative retrospective study involving 145 COVID-19 hospitalized patients who are more than 60 years old, conducted at King Faisal Medical Complex in Taif, Saudi Arabia, from June 2020 to August 2020. The main outcome studied was COVID-19-related death. Results: Out of 145 elderly COVID-19 patients, 11% have died. There was a significant difference between those who died and the surviving group regarding hospital stay duration, with a higher duration median among those who died (22 days vs 12 day respectively, p=0.002). Transfer to ICU, mechanical ventilation, low oxygen saturation, shortness of breath, respiratory support, x-ray trend, and prolonged QT interval showed significant statistical differences between them (p<0.001, <0.001, 0.017, 0.045, <0.001, <0.001, 0.004, respectively). After doing logistic regression of predictors for progression to death, putting patients on oxygen only vs mechanical ventilation was statistically significant, with an adjusted odds ratio (AOR) of 0.038 (p=0.012). Worse x-rays vs constant also were statistically significant and had AOR of 23.459 (p=0.001). There was a significant moderate positive correlation between duration of hospital stay and duration from admission to medication start (SP=0.336 and p<0.001). Conclusion: We recommend accurately monitoring patients using x-rays to determine which patients have worse x-rays. However, the cost-benefit of using radiation must be well assessed and needs further research to determine if its benefit outweighs its risks, especially in high-risk patients. Furthermore, mechanically ventilated patients must be carefully monitored. Finally, the duration of hospital stay was highly correlated with the duration from admission to medication start. Therefore, proper treatment must be started as early as possible.

Nanoparticles of Costus speciosus Ameliorate Diabetes-Induced Structural Changes in Rat Prostate through Mediating the Pro-Inflammatory Cytokines IL 6, IL1ß and TNF-α.

Diabetes mellitus is a common global health problem. Among the complications that are frequently associated with DM are the alternation of sexual function and fertility, especially in young men. This study aimed to assess the efficacy of nanoparticles of Costus speciosus (C. speciosus) in preserving the prostatic structure of diabetic rats and to explore the mechanism behind this effect. A model of DM was induced in male albino rats by a single intraperitoneally injection of streptozotocin (STZ, 60 mg/kg body weight). Five groups (n = 10 each) of rats were included in this study: the control, C. speciosus gold nanoparticles-treated (150 mg/kg body weight through gastric intubation for 30 days), untreated diabetic, metformin-treated diabetic (500 mg/kg/day gastric intubation for 30 days) and the C. speciosus-treated diabetic group. The blood glucose, insulin and testosterone levels as well as oxidants/antioxidants status were assessed in the serum. Gene expression of proinflammatory cytokines TNF-α, IL1ß and IL-6 were assessed in the prostate homogenate. At the end of the experiment, the rats were sacrificed and the prostate was dissected out and prepared for histopathological and immunohistochemistry study using Ki67 and Bcl-2. C. Speciosus nanoparticles significantly decreased (p = 0.03) the blood glucose level while significantly increasing insulin (p = 0.01) and testosterone (p = 0.04) levels compared to the untreated diabetic rats. Oxidants/antioxidants status was markedly improved after administration of C. speciosus. Prostatic expression of the mRNA of pro-inflammatory cytokines IL-6, IL1ß and TNF-α was down-regulated in metformin- and C. speciosus-treated rats. The histological structure of the ventral prostate was preserved in metformin- and C. speciosus-treated diabetic rats with a significantly thicker epithelial cell layer and significant increase immunoexpression in Bcl-2 and Ki67. In conclusion, the protective effect induced by C. speciosus nanoparticles on the prostate of diabetic rats might be directly mediated through the down-regulation of inflammatory cytokines and the up-regulation of antioxidant activity and indirectly mediated through the anti-hyperglycemic effect through enhancing insulin secretion.

Pharmacological basis for the potential role of Azithromycin and Doxycycline in management of COVID-19.

A novel corona virus SARS-CoV-2 has led to an outbreak of the highly infectious pandemic COVID-19 complicated viral pneumonia. Patients with risk factors frequently develop secondary infections where the role of appropriate antibiotics is mandatory. However, the efforts of drug repurposing lead to recognizing the role of certain antibiotics beyond the management of infection. The current review provided the detailed antiviral, immunomodulatory effect, unique pharmacokinetic profile of two antibiotics namely azithromycin (AZ) and doxycycline (DOX). It summarizes current clinical trials and concerns regarding safety issues of these drugs. Azithromycin (AZ) has amazing lung tissue access, wide range antibacterial efficacy, conceivable antiviral action against COVID-19. It also showed efficacy when combined with other antiviral drugs in limited clinical trials, but many clinicians raise concerns regarding cardiovascular risk in susceptible patients. DOX has a considerable role in the management of pneumonia, it has some advantages including cardiac safety, very good access to lung tissue, potential antiviral, and immunomodulation impact by several mechanisms. The pharmacological profiles of both drugs are heightening considering these medications for further studies in the management of COVID-19.

Successive waves of COVID 19: confinement effects on virus-prevalence with a mathematical model.

BACKGROUND: A pandemic outbreak of severe acute respiratory syndrome coronavirus 2 (COVID 19) incidence data are largely available online. Until August 17, COVID 19 has hit more than 22 million individuals all over the globe. So, it is urged to get clear information about the prevalence of the virus. Therefore, one can manipulate easily a suitable mathematical model to fit these published data. METHODS: We propose a mathematical model that considers the total population, in 25 countries, either infected by COVID 19 or confined (safe) during the period from November 17, 2019, to August 17, 2020. The model considers the total population as a complex number; the imaginary part is the number of infected individuals and the real part is the number of confined individuals. This classification combined with mathematical treatments leads to a transmission dynamics of the virus to be as wave-like motion. The virus can hit any country either by one wave or by successive waves (up to 11 waves). FINDINGS: We find net discrimination between the 25 countries investigated in this report. The immediate response to the first attack is a substantial parameter to determine whether the epidemic attack will be in one wave or it can be in successive waves. For example, the best case was such as individuals in China hit by one wave while the individuals in the USA were attacked by nine waves; it is the worst case all over the globe. In addition, the model differentiates between the daily reproduction numbers (Rd0) and the median reproduction number (R0). We have found that Rd0 decreases exponentially with time from high values down to zero at the wave maximum point; and R0 varies from a country to another. For example, the virus hit individuals in Germany in R0 = 1.39 (96% CI 1.01-3.87) and in the USA R0 = 3.81 (91% CI 1.71-5.15). We have found that twice the virus has hit both the USA and Iran. The great protestation of black matter lives in the USA and the great assemblage of the new Iranian year, on March 21, 2020, have been the cause of the second epidemic attack in both countries. INTERPRETATION: Our results show that COVID 19 transmission depends on the prompt reaction against the first viral-wave. The reaction depends on both the social behaviour of individuals and on the swift system-decision by the governmental decision-maker(s). The Chinese strictly follow the decision-maker and therefore the virus hit by only one wave; while in the USA, the system-decision was different and the American-responses were different, therefore ten waves followed the first wave.

Effectiveness and Safety of Favipiravir Compared to Hydroxychloroquine for Management of Covid-19: A Retrospective Study.

BACKGROUND: Coronavirus disease (COVID-19) is an infectious disease due to SARS-COV-2. Patients with risk factors are vulnerable to severe morbidity and mortality. Favipiravir (FPV) and hydroxychloroquine (HCQ) are considered possible COVID-19 treatments. OBJECTIVE: To investigate the effectiveness and safety of FPV compared to HCQ in patients with COVID-19 as the standard of care approved by the national protocol there. METHODS: This is a retrospective cohort study on patients with COVID-19 who were administered either FPV or HCQ at King Faisal Medical Complex, Taif, Saudi Arabia, from June 2020 to August 2020. RESULTS: In total, 508 patients were included in the analysis. Patients were categorized into three groups by medication. Patients enrolled in this study were 244 (55.8%) on FPV, 193 (44.2%) on HCQ and 71 (13.81%) on neither medication. Patients who received FPV had higher age and greater comorbidity. Most of the patients were discharged on day 14 (n = 303, 59.6%), 26 (36.6%) in neither med, 154 (63.1%) in FPV and 123 (63.7%) in HCQ groups with significant difference between groups (P < 0.0001). Mortality rate was 8.2% (n = 20) in FPV and 7.3% (n = 14) in HCQ groups with significant difference between groups (P = 0.048). Regarding drug safety, 19.7% of patients treated with FPV vs 7.8% HCQ have adverse effects with significant difference between groups (P < 0.0001). Most of the side effects were increase ALT and AST. Meanwhile, prolonged Q-T interval was reported only in the HCQ group (2.6%). From Cox regression modeling, only mechanical ventilation due to Covid 19 was predictive for mortality (HR: 16.598, 95% CI: 7.095-38.828, P < 0.0001). Meanwhile, there was no significant difference in the prediction of discharge of FPV (vs HCQ) (HR: 0.933, 95% CI: 0.729-1.195, P = 0.5843), predictors of mortality were HCQ (vs FPV) (HR: 2.3, 95% CI: 0.994-5.487, P = 0.0518). Kaplan-Meier survival curves showed improved survival time and discharged time among patients in the HCQ versus FPV group with an insignificant difference between them (P = 0.85, P = 0.06, respectively). CONCLUSION: The present study concluded that FPV and HCQ showed comparable efficacy in decrease mortality and oxygen requirements. FPV likely has a more favorable safety profile regarding cardiac toxicity. A randomized clinical trial with large patient numbers is recommended to confirm the effectiveness of these drugs in COVID-19 patients.

Yet another function of p53--the switch that determines whether radiation-induced autophagy will be cytoprotective or nonprotective: implications for autophagy inhibition as a therapeutic strategy.

The influence of autophagy inhibition on radiation sensitivity was studied in human breast, head and neck, and non-small cell lung cancer cell lines, in cell lines that were either wild type or mutant/null in p53, and in cells where p53 was inducible or silenced. Whereas ionizing radiation promoted autophagy in all tumor cell lines studied, pharmacological inhibition of autophagy and/or genetic silencing of autophagy genes failed to influence sensitivity to radiation in p53 mutant Hs578t breast tumor cells, HN6 head and neck tumor cells, and H358 non-small cell lung cancer cells. The requirement for functional p53 in the promotion of cytoprotective autophagy by radiation was confirmed by the observation that radiation-induced autophagy was nonprotective in p53 null H1299 cells but was converted to the cytoprotective form with induction of p53. Conversely, whereas p53 wild-type HN30 head and neck cancer cells did show sensitization to radiation upon autophagy inhibition, HN30 cells in which p53 was knocked down using small hairpin RNA failed to be sensitized by pharmacological autophagy inhibition. Taken together, these findings indicate that radiation-induced autophagy can be either cytoprotective or nonprotective, a functional difference related to the presence or absence of function p53. Alternatively, these findings could be interpreted to suggest that whereas radiation can induce autophagy independent of p53 status, inhibition of autophagy promotes enhanced radiation sensitivity through a mechanism that requires functional p53. These observations are likely to have direct implications with respect to clinical efforts to modulate the response of malignancies to radiation through autophagy inhibition.