Targeting SIRT1, NLRP3 inflammasome, and Nrf2 signaling with chrysin alleviates the iron-triggered hepatotoxicity in rats.

Blood transfusion-requiring diseases such as sickle cell anemia and thalassemia are characterized by an imbalance between iron intake and excretion, resulting in an iron overload (IOL) disorder. Hepatotoxicity is prevalent under the IOL disorder because of the associated hepatocellular redox and inflammatory perturbation. The current work was devoted to investigate the potential protection against the IOL-associated hepatotoxicity using chrysin, a naturally-occurring flavone. IOL model was created in male Wistar rats by intraperitoneal injection of 100 mg/kg elemental iron subdivided on five equal injections; one injection was applied every other day over ten days. Chrysin was administered in a daily dose of 50 mg/kg over the ten-day iron treatment period. On day eleven, blood and liver samples were collected and subjected to histopathological, biochemical, and molecular investigations. Chrysin suppressed the IOL-induced hepatocellular damage as revealed by decreased serum activity of the intracellular liver enzymes and improved liver histological picture. Oxidative damage biomarkers, and pro-inflammatory cytokines were significantly suppressed. Mechanistically, the levels of the redox and inflammation-controlling proteins SIRT1 and PPARγ were efficiently up-regulated. The liver iron load, NLRP3 inflammasome activation, and NF-κB acetylation and nuclear shift were significantly suppressed in the iron-intoxicated rats. Equally important, the level of the antioxidant protein Nrf2 and its target HO-1 were up-regulated. In addition, chrysin significantly ameliorated the IOL-induced apoptosis as indicated by reduction in caspase-3 activity and modulation of BAX and Bcl2 protein abundance. Together, these findings highlight the alleviating activity of chrysin against the IOL-associated hepatotoxicity and shed light on the role of SIRT1, NLRP3 inflammasome, and Nrf2 signaling as potential contributing molecular mechanisms.

Feasibility Study of the Boston Naming Test for the Arab Population.

Introduction The Boston Naming Test (BNT) is a widely used US neuropsychological evaluation of confrontation naming for the examination of adults and children with learning disabilities and diagnosis of communication disorders, aphasia, dementia, and acquired brain injury or dysfunction. The purpose of the present study is to evaluate the practicality of the original English version of the 60-item BNT (BNT-60) on an Arab population and the need for a new adaptive Arabic version sensitive to cultural biases and to offer normative data that can serve as a reference for researchers and clinicians in the Gulf region, especially the Kingdom of Saudi Arabia (KSA). Data relating to the familiarity degree of the BNT-60 were also collected. Methods This research involved 105 randomly selected and cognitively healthy college students who were native Arabic speakers recruited in Jeddah. The Montreal Cognitive Assessment (MOCA) was administered with a cutoff score of 26. The participants were examined for naming accuracy, naming agreement, and familiarity in using the BNT-60. The data were then analyzed and compared with the findings from studies conducted in the United States. Results The BNT-60 was administered to 105 university students from the KSA, and the results were compared with the BNT-60 booklet norms (second edition). Their average performance was noticeably below the norms established by the original test standards. Compared with the participants in the US studies, the participants made approximately 65% more errors on the items including pretzel, wreath, beaver, harmonica, acorn, stilts, harp, hammock, knocker, pelican, muzzle, unicorn, funnel, accordion, asparagus, tripod, yoke, and trellis and 25% more errors on the items including seahorse, dart, igloo, sphinx, palette, and abacus. The item "boomerang" was not compared with the US sample because of differences in the version of the BNT, but the errors in naming this item were as frequent as those in naming the other misrecognized items. The internal consistency among the items' degrees of familiarity was also very high (α = 0.966), and a significant connection (r = 0.837, P < 0.001) was observed between object familiarity and naming accuracy. The Arabic-speaking population in the KSA and English-speaking population in the United States showed very different levels of familiarity with numerous items. Conclusion The participants' familiarity with the BNT objects varied depending on their culture and impacted their naming accuracy and overall scores on the test. Accordingly, the possibility of cultural biases should be considered when administering the BNT to the population of the KSA and the possibility of making changes so that the test better reflects the Arab culture as suggested.

The Impact of Recombinant Human Erythropoietin Administration in Critically ill COVID-19 Patients: A Multicenter Cohort Study.

The use of erythropoietin-stimulating agents (ESAs) as adjunctive therapy in critically ill patients with COVID-19 may have a potential benefit. This study aims to evaluate the effect of ESAs on the clinical outcomes of critically ill COVID-19 patients. A multicenter, retrospective cohort study was conducted from 01-03-2020 to 31-07-2021. We included adult patients who were ≥ 18 years old with a confirmed diagnosis of COVID-19 infection and admitted to intensive care units (ICUs). Patients were categorized depending on ESAs administration during their ICU stay. The primary endpoint was the length of stay; other endpoints were considered secondary. After propensity score matching (1:3), the overall included patients were 120. Among those, 30 patients received ESAs. A longer duration of ICU and hospital stay was observed in the ESA group (beta coefficient: 0.64; 95% CI: 0.31-0.97; P = < .01, beta coefficient: 0.41; 95% CI: 0.12-0.69; P = < .01, respectively). In addition, the ESA group's ventilator-free days (VFDs) were significantly shorter than the control group. Moreover, patients who received ESAs have higher odds of liver injury and infections during ICU stay than the control group. The use of ESAs in COVID-19 critically ill patients was associated with longer hospital and ICU stays, with no survival benefits but linked with lower VFDs.

Adoption of antenatal care conversation mapping among health care providers in Saudi Arabia: Application of the diffusion innovation theory.

AIM: To measure the factors influencing on the adoption of antenatal care conversation mapping among health care providers in Riyadh (Saudi Arabia), using the diffusion innovation theory. METHODS: 88 healthcare providers (Riyadh) were recruited using a non-probability convenient sampling technique were trained on how to use a newly developed antenatal care conversation map. Data was collected by self-administrated questionnaire on health education services, adoption of conversation map and diffusion of innovation variables. The JMP statistical software from SAS version 14 was used to perform data analysis. RESULTS: Printable tools were most common as used by 72.7% of participants and 83.0% of them did not hear about conversation map. The total mean score of diffusion of innovation variables showed was in general high. The total mean score of relative advantage and observability was high in participants aged between 40 to less than 50 years, while the total mean score of compatibility, complexity, and trialability was high in participants aged from 50 years and more. Significant differences were obtained in both compatibility and trialability considering the health educators specialty, p = 0.03 and p = 0.027 respectively. The linear correlations between diffusion of innovation variables was significantly positive (p-value <0.01). CONCLUSION: All of diffusion of innovation variables were positive as per the opinion of the participants. Applying the conversation map on other health topics in Saudi Arabia and other Arabic-speaking countries is warranted. Measuring and evaluating the adoption rate of conversation mapping among health care providers on other health topics should be explored.

The Level of Burden among Caregivers of Patients with Alzheimer's Disease in Saudi Arabia.

BACKGROUND: Caregiver burden is a serious global issue associated with the growing number of older adult patients with Alzheimer's disease (AD). AD patients become more dependent on their caregivers and require assistance with basic daily life activities. This study aims to measure the caregiver burden of informal caregivers of AD patients and to determine their characteristics. In addition, it intends to understand caregiver coping techniques and assess their medication knowledge. METHODS: This was a cross-sectional study including 148 informal caregivers mainly recruited by the Saudi Alzheimer's Disease Association (SADA). A four-part study questionnaire was used for data collection in the Arabic Language and included the following: socio-demographic characteristics of AD patients and their caregivers, the 12-item version of the Zarit Burden Interview (ZBI), and adapted questions on coping techniques and medication knowledge. RESULTS: A total of 148 caregivers (62% were female) participated in this study, and 79.06% were between 30 and 60 years old. The ZBI average score was 27, indicating a moderate to high burden. Caregivers reported their need for services to improve their quality of life. The medication knowledge was insufficient in most aspects except that more than half were aware of medications' side effects. CONCLUSION: Our study revealed that the average burden among informal caregivers of AD patients was moderate-high.

Endoscopic appearance of duplicated middle turbinate, case series and literature review.

INTRODUCTION AND IMPORTANCE: Duplication of the middle turbinate is an extremely rare condition encountered in rhinology clinic. Knowledge and awareness of the nasal turbinates' variations are important to perform a safe endoscopic surgery and evaluate patients with inflammatory sinus diseases. CASE PRESENTATION: Case series of two patients who visited rhinology clinic in academic university hospital. Case 1: presented with 6-month history of nasal blockage. Nasal endoscopy revealed bilateral duplication of the middle nasal turbinates. Computed tomography scans showed bilateral medially curved and anteriorly folded uncinate process, and right middle turbinate concha bullosa and its superior end of the middle turbinate was turned medially. Case 2: A 29-year-old gentleman presented with nasal obstruction mainly to the left side for several years. Nasal endoscopy showed bifid right middle turbinate and severe deviated nasal septum to the left. Upon imaging, a sinus computed tomography scan demonstrated a duplication of the right middle turbinates in the form of two middle nasal concha. CLINICAL DISCUSSION: Different rare anatomical variations can occur at different points during the embryological development. These rare variations include double middle turbinate, accessory middle turbinate, secondary middle turbinate, and bifid inferior turbinate. The appearance of double middle turbinate can be encountered in rhinology clinic only 2 % of the time. Upon reviewing the literature, only few case reports were found regarding the double middle turbinate. CONCLUSION: A double middle turbinate has important clinical implications. Anatomical variation may lead to narrowing in the middle meatus which makes the patient vulnerable to sinusitis or maybe associated with secondary symptoms. We report rare cases of middle turbinate duplication. Awareness of the nasal turbinates' variations is important for detection and management of inflammatory sinus diseases. Further studies are needed to identify the association of other pathology.

Postmortem Genetic Testing in Sudden Unexpected Death: A Narrative Review.

Sudden unexpected death (SUD) is one of the challenging situations encountered in forensic medicine. As a rule, a comprehensive forensic assessment is performed to identify the cause of death in such cases; however, the absence of findings suggestive of a cause, i.e., a negative autopsy, warrants further investigation such as a molecular autopsy. In this review, we aim to highlight the genetic causes of SUD, tools used in a molecular autopsy, and the role of screening in surviving relatives. As per several guidelines, the most preferred samples for DNA extraction are whole blood and fresh frozen tissues. Furthermore, Sanger sequencing and next-generation sequencing are the technologies that are used for genetic analysis; the latter overcomes the former's drawbacks in terms of cost-effectiveness, time consumption, and the ability to sequence the whole exome. SUD have diverse etiologies; we can generally classify them into cardiac and non-cardiac causes. Regarding cardiac causes, many conditions having an underlying genetic basis are included, such as channelopathies and cardiomyopathies. Regarding non-cardiac causes of SUD, the main etiologies are epilepsy and metabolic disorders. Nevertheless, it has been proposed that there is a genetic overlap between channelopathies, especially long QT syndromes and epilepsy. Additionally, fatty acid oxidation disorders are major metabolic conditions that are caused by certain genetic mutations that can lead to SUD in infancy. Since many SUD causes have an underlying genetic mutation, it is important to understand the genetic variations not only to recognize the cause of death but also to undertake further preventive measures for surviving relatives. In conclusion, a molecular autopsy has a major role in the forensic examination of cases of SUD.

Overview of Methotrexate Toxicity: A Comprehensive Literature Review.

Methotrexate (MTX) is significantly more effective than and has a considerable advantage over placebo in patients with severe and persistent rheumatoid arthritis (RA). The drug is used to treat a variety of malignant disorders (leukemia and cancer of the lung, breast, and uterus) and ectopic pregnancy. As its side effects are outweighed by its effectiveness, MTX is a first-line antirheumatic drug in many countries. MTX is found in extracellular compartments, such as the synovium, as well as other organs, such as the kidney and liver. To improve treatment, increase adherence, and decrease mortality in MTX therapy, it is essential to reduce its toxicity and understand its side effects. Therefore, this comprehensive review was conducted to assist physicians and researchers in better understanding the toxicity of MTX and how to deal with this toxicity. MTX is eliminated via the kidneys, which are capable of excretion and reabsorption within the renal tubules. Although higher doses of MTX (known as high-dose MTX (HD-MTX), defined as doses of 500 mg/m2 or greater) are often more beneficial, they can produce toxicity and side effects such as bone marrow suppression, pulmonary toxicity, nephrotoxicity, hematologic toxicity, and an increased risk of infections. Treatment of severe MTX toxicity has three main goals: clearance of MTX from the bloodstream, folinic acid therapy, and organ treatment. Leucovorin is highly beneficial in preventing myelosuppression, gastric toxicity, and neurotoxic effects after HD-MTX therapy. The preferred antidote for MTX poisoning is folinic acid. Glucarpidase has been licensed for the treatment of high plasma MTX levels of >1 µmol/L in patients with compromised renal function who have delayed MTX elimination. In patients with renal deficiency, a lower initial dose is considered with an estimated glomerular filtration rate (eGFR) between 30 and 59 mL/minute. These patients need to be monitored, and a more gradual dosage increase and a lower weekly maximum should be considered regarding their general health situation. MTX is contraindicated in patients with RA if the eGFR is <30 mL/minute.

Readability of information imprinted in patient information leaflets (PILs) in Saudi Arabia: The case of antihypertensive medications.

Background: The Saudi Food and Drug Authority (SFDA) requires marketing authorization holders to submit a PIL in both Arabic and English language. However, the readability of imprinted and disseminated Patient information leaflets (PILs) was not assessed extensively in Saudi Arabia. This study aims to assess the readability of PIL of antihypertensive drugs in both Arabic and English languages. Method: This study was a descriptive quantitative analysis conducted in Saudi Arabia in August 2021. PILs of all oral antihypertensive medications in Saudi Arabia were included in the study. The Arabic and English PILs were extracted from the Saudi Drugs Information System (SDI) and pharmaceutical companies' registration documents. The study used Flesch-Kincaid grade level to assess the readability of English and sentence length to assess the Arabic texts. Descriptive analyses were used to assess the readability scores and the mean differences. Results: It was found that almost 88% of English PILs were above recommended readability level compared to 79% of Arabic PILs. About 89% of English PILs of generic and 86% of brand-name medications were above the readability cutoff point compared with 83% of Arabic PILs of generic and 68% of brand-name medications. The means of grade level for readability of PILs for the widely used antihypertensive medications including angiotensin II receptor blockers (ARBs), antiadrenergic, diuretics, Beta-blockers (BBs), calcium channel blockers (CCBs), and combination antihypertensive medications, and CCBs were higher than the recommended readability level (p < 0.05). The highest mean grade level for readability among English PILs was for combinations of antihypertensive agents (9.35 ± 1.38, p 0.01) and among Arabic PILs was for ARBs (6.15 ± 1.62, p < 0.01). Conclusions: The majority of PILs of antihypertensive medications were above the recommended readability level that can be understood by the majority of the public, especially among generic medications and the most widely used antihypertensive medications. The study findings highlight the need of implementing guidelines to improve the readability of information imprinted in PILs and adopt new regulations requiring readability assessment for manufactures before submitting the PILs to the SFDA.

Urinary Tract Infection as the Diagnosis for Admission Through the Emergency Department: Its Prevalence, Seasonality, Diagnostic Methods, and Diagnostic Decisions.

Background Urinary tract infections (UTIs) affect millions of people of all ages around the world. It constitutes one of the most common conditions encountered in emergency departments (EDs). In this study, we aimed to inquire into the prevalence of UTIs as the hospitalization primary diagnosis through the emergency department and to research the seasonal pattern, accuracy of the diagnostic methods used, and final diagnosis. Methods A retrospective cross-sectional study was undertaken that included all patients admitted with a primary diagnosis of UTIs through the ED over a four-month period (January, April, June, and September) in the emergency department of King Abdulaziz Medical City (KAMC) in Riyadh. The prevalence, diagnostics, and outcomes of UTIs were evaluated, and their association with seasonality was assessed after obtaining data from the Hospital Information System BestCare of King Abdullah National Guard Hospital. The variables that have been collected were analyzed using the Statistical Package for Social Sciences software version 26 (IBM Corp., Armonk, NY, USA). Results A total of 315 patients were admitted with a diagnosis of UTI. The prevalence of UTI among patients admitted through the ED was 10.5% with a significantly higher prevalence noted in January (13.3%) than in April (8.5%) or September (8.8%) (Fisher's exact test: 0.009 and 0.01, respectively). As would be expected, the cohort was made up of elderly individuals with a mean age of 70.6 years, and the male/female ratio was 1:2. UTI symptoms including dysuria, frequency, urgency, rigors, and loin pain were noted in only 41% of cases or less, and urinalysis was the basis of making the diagnosis (87.9% had positive leukocyte esterase (LE) and 90.5% had positive urine WBC/HPF). Furthermore, 4.4% required urgent treatment, and 3.1% required intensive care unit (ICU) admission. Urine culture was negative in 30.8% of the cases (30.8% false positives among those admitted with UTI). The commonest organisms isolated were Escherichia coli (33%), Klebsiella pneumoniae (14.3%), and Pseudomonas aeruginosa (5.1%). The median length of hospital stay (LOS) was 3.5 days, and the Charlson Comorbidity Index (CCI) score was 5.7. The mean hemoglobin (Hb), creatinine, C-reactive protein (CRP), procalcitonin, and lactic acid were 108 gm/L, 131.3 umol/L, 38.3 mg/L, 0.28 ng/mL, and 2.07 mmol/L, respectively. Conclusion This research found that the prevalence of UTI cases as an admission diagnosis through the emergency department was high, despite some cultures being negative or contaminated, thus probably indicating an increase in the rates of false positives. The admission rate is linked to factors such as oxygen saturation and RDW, but this is not entirely understood. In addition, the study also displayed a seasonal pattern linked to the highest number of confirmed cases in January, while the lowest was in April.

Splenic Heterogeneity in Focused Assessment With Sonography for Trauma (FAST) Scan Led to the Diagnosis of Grade 2 Splenic Injury in a Pediatric Blunt Abdominal Trauma.

Splenic injuries are one of the most common injuries following blunt abdominal trauma. It occurs in 32% of blunt abdominal trauma, with motor vehicle accidents being the most common cause. The patient may present with generalized abdominal pain or left upper quadrant pain associated with left shoulder pain. Hemodynamic instability is one of the most reliable signs of splenic injuries. A focused assessment with sonography for trauma (FAST) scan is the initial imaging used to assess for solid organ injury in the abdomen, followed by computed tomography (CT) scans. Evidence of free fluid in the abdomen in the FAST scan indicates a solid organ injury. However, the absence of the before-mentioned finding does not rule out the presence of solid organ injury. Hereby a case of a 13-year-old Saudi male with left-sided abdominal pain after falling from a motorbike. A set of the investigation was done with insignificant results. However, FAST revealed a heterogenous appearance in the spleen. Thus, the patient subsequently underwent abdominal CT scans. The patient was managed conservatively and then discharged against medical advice (DAMA). Previously documented cases have mentioned the presence of free fluid in the abdomen in FAST scan in a stable patient leading to undergoing a CT scan and further managing trauma victim patients, which was absent in the present case.

Short- and Long-Term Effects of Vitamin D Treatment on Bacillus Calmette-Guerin-Induced Depressive-Like Behavior in Mice.

PURPOSE: Depression is one of the most common psychological disorders. The nutritional etiology of the depression proposes that vitamin D may play a significant role in the pathogenesis of depression. Further, vitamin D deficiency has been found to aggravate depression in animals. Therefore, vitamin D treatment might be a potential therapeutic aid in depression management. This study aimed to explore the antidepressant effects of vitamin D in a Bacillus Calmette-Guerin (BCG)-induced depression model. METHODS: Thirty-six mice were randomly assigned to short-term and long-term experimental groups. In each group, mice were randomly subcategorized into three subgroups: 1. control (received vehicle), 2. BCG (received BCG [107 CFU/mouse]), and 3. BCG + vitamin D (received vitamin D [60.000 IU/kg] before BCG [107 CFU/mouse] inoculation). After completion of the two experimental periods (3 days for the short-term group and 2 weeks for the long-term group), the mice underwent three behavioral tests: locomotor activity, the forced swimming test (FST), and the tail suspension test (TST). RESULTS: Locomotor activity did not significantly differ among the subgroups in either the long-term or short-term groups. In the short-term group, the total immobility time on the FST was decreased in the vitamin D-treated group compared to the BCG group. However, in the TST, no significant difference was found between the vitamin D-treated group and the BCG group. In the long-term group, the immobility time on the FST was decreased in the vitamin D-treated group compared to the BCG group. Similarly, the total immobility time on the TST was also significantly lower in the vitamin D-treated mice than in the BCG-treated mice. CONCLUSION: Vitamin D is useful in the management of depressive behavior. The potential role of vitamin D in the etiology of depression should be investigated in future work.

Association between type 2 diabetes mellitus and Helicobacter pylori infection among Saudi patients attending National Guard Primary Health Care Centers in the Western Region, 2018.

BACKGROUND: Reports on Helicobacter pylori infection in diabetics are inconsistent and contradictory. This study attempted to identify the possible association between type 2 diabetes and H. pylori infection. MATERIALS AND METHODS: Following a cross-sectional design, participants were recruited from four National Guard Primary Health Care Centers in Jeddah City, Saudi Arabia. The study was conducted from December 2017 to November 2018. All participants underwent hemoglobin A1C (HbA1c) assessment and stool antigen test for H. pylori. RESULTS: A total of 212 type 2 diabetic patients aged 40 years or more, and 209 age-matched nondiabetic subjects were included in the study. About one-quarter of the diabetics and nondiabetics were positive for H. pylori (26.9% and 26.3%, respectively). There was no significant difference. The prevalence of H. pylori did not differ significantly in the type 2 diabetics, with regard to their age groups, gender, smoking status, body mass index, chronic diseases, their HbA1c level, duration of diabetes, or received type of therapy. The prevalence of H. pylori was significantly higher in overweight and obese nondiabetic subjects (P = 0.013). Obese participants in both groups had the highest prevalence of infection (57.9% and 54.5%, respectively, P = 0.038). CONCLUSION: About one-quarter of type 2 diabetics and nondiabetics in Jeddah City have H. pylori infection. There is no association between diabetes and H. pylori infection. H. pylori was significantly higher in patients with a high body mass index.

Familial non-syndromic macular pseudocoloboma secondary to homozygous CLDN19 mutation.

PURPOSE: The purpose of this study is to uncover the genetic cause for non-syndromic macular "coloboma" (pseudocoloboma) in three brothers from a consanguineous family. METHODS: Homozygosity mapping for the three affected brothers and whole-exome sequencing in one affected brother, followed by confirmatory Sanger sequencing and segregation analysis of the candidate gene for all immediate family members; molecular modeling of the candidate mutation; and review of clinical, imaging, and laboratory findings. RESULTS: Three otherwise-healthy brothers (age 10, 10, and 6 years) had macular pseudocoloboma. Both parents and the fourth brother were not affected. Parents were first cousins. A novel homozygous missense variant in claudin 19 (CLND19: NM_148960.2:c. 263T>A; p.Val88Glu) segregated with the phenotype, and molecular modeling predicts an unfavorable effect to protein function. All prior reported biallelic CLND19 mutations cause symptomatic hypomagnesemia with hypercalciuria and nephrocalcinosis, often with concurrent macular pseudocoloboma. However, general physical assessment, metabolic profile, and renal imaging for the three affected brothers were normal. CONCLUSIONS: A homozygous CLDN19 mutation can cause macular pseudocoloboma without evidence for systemic disease in children. This is the first reported family with CLDN19 mutations to have an ocular phenotype only; however, those identified to harbor biallelic CLDN19 mutations should be considered at risk for the extraocular manifestations that have previously been associated with mutations in the gene.