Structural Motifs at the Telomeres and Their Role in Regulatory Pathways.

Telomeres are specialized structures, found at the ends of linear chromosomes in eukaryotic cells, that play a crucial role in maintaining the stability and integrity of genomes. They are composed of repetitive DNA sequences, ssDNA overhangs, and several associated proteins. The length of telomeres is linked to cellular aging in humans, and deficiencies in their maintenance are associated with various diseases. Key structural motifs at the telomeres serve to protect vulnerable chromosomal ends. Telomeric DNA also has the ability to form diverse complex DNA higher-order structures, including T-loops, D-loops, R-loops, G-loops, G-quadruplexes, and i-motifs, in the complementary C-rich strand. While many essential proteins at telomeres have been identified, the intricacies of their interactions and structural details are still not fully understood. This Perspective highlights recent advancements in comprehending the structures associated with human telomeres. It emphasizes the significance of telomeres, explores various telomeric structural motifs, and delves into the structural biology surrounding telomeres and telomerase. Furthermore, telomeric loops, their topologies, and the associated proteins that contribute to the safeguarding of telomeres are discussed.

Acetyl-L-Carnitine and Liposomal Co-Enzyme Q10 Attenuate Hepatic Inflammation, Apoptosis, and Fibrosis Induced by Propionic Acid.

Propionic acid (PRA) is a metabolic end-product of enteric bacteria in the gut, and it is commonly used as a food preservative. Despite the necessity of PRA for immunity in the body, excessive exposure to this product may result in disruptive effects. The purpose of this study is to examine the hepatoprotective effects of acetyl-L-carnitine (A-CAR) and liposomal-coenzyme Q10 (L-CoQ10) against PRA-induced injury. Liver injury in rats was induced by oral administration of PRA, and A-CAR and L-CoQ10 were administered concurrently with PRA for 5 days. Oxidative stress, inflammatory, apoptotic, and fibrotic biomarkers were analyzed; the histology of liver tissue was assessed as well to further explore any pathological alterations. PRA caused significant increases in the levels of serum liver enzymes and hepatic oxidative stress, inflammatory, and apoptotic biomarker levels, along with histopathological alterations. Concurrent treatment with A-CAR and/or L-CoQ10 with PRA prevented tissue injury and decreased the levels of oxidative stress, proinflammatory cytokines, and apoptotic markers. Additionally, A-CAR and/or L-CoQ10 modulated the expression of high-mobility group box-1, cytokeratin-18, transforming growth factor-beta1, and SMAD3 in liver tissue. In conclusion, A-CAR and/or L-CoQ10 showed hepatoprotective efficacy by reducing oxidative stress, the inflammatory response, apoptosis, and fibrosis in liver tissue.

Cross-Regulation between Autophagy and Apoptosis Induced by Vitamin E and Lactobacillus Plantarum through Beclin-1 Network.

Autophagy and apoptosis are two important regulatory mechanisms for how the body can respond to diseases. This study was designed to investigate the protective actions of vitamin E (Vit-E) and lactobacillus plantarum (Lac-B) against mercuric chloride (HgCl2)-induced kidney injury. Thirty albino rats were divided into five groups: group 1 served as the normal group; rats in group 2 received high doses of HgCl2; rats in groups 3, 4 and 5 were given Vit-E, Lac-B and the combination of Vit-E and Lac-B, respectively along with HgCl2 for two weeks. HgCl2 provoked renal injury, manifested by elevation in serum urea, urea nitrogen and creatinine. Kidney levels of oxidative stress and inflammation were markedly increased post HgCl2 administration. Moreover, HgCl2 significantly elevated the gene expression levels of VCAM-1 and cystatin C, while podocin was downregulated. Additionally, it markedly decreased the protein expression of Beclin-1 and Bcl-2. Histopathological examination revealed massive degeneration with congested blood vessels following HgCl2 administration. Treatment with Vit-E or/and Lac-B restored the normal levels of the previously mentioned parameters, as well as improved the morphology of kidney tissues. Both Vit-E and Lac-B provided a protective effect against HgCl2-induced kidney damage by regulating autophagy and apoptosis.

Identification and Characterization of Novel Mutations in Chronic Kidney Disease (CKD) and Autosomal Dominant Polycystic Kidney Disease (ADPKD) in Saudi Subjects by Whole-Exome Sequencing.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is a condition usually caused by a single gene mutation and manifested by both renal and extrarenal features, eventually leading to end-stage renal disease (ESRD) by the median age of 60 years worldwide. Approximately 89% of ADPKD patients had either PKD1 or PKD2 gene mutations. The majority (85%) of the mutations are in the PKD1 gene, especially in the context of family history. Objectives: This study investigated the genetic basis and the undiscovered genes that are involved in ADPKD development among the Saudi population. Materials and Methods: In this study, 11 patients with chronic kidney disease were enrolled. The diagnosis of ADPKD was based on history and diagnostic images: CT images include enlargement of renal outlines, renal echogenicity, and presence of multiple renal cysts with dilated collecting ducts, loss of corticomedullary differentiation, and changes in GFR and serum creatinine levels. Next-generation whole-exome sequencing was conducted using the Ion Torrent PGM platform. Results: Of the 11 Saudi patients diagnosed with chronic kidney disease (CKD) and ADPKD, the most common heterozygote nonsynonymous variant in the PKD1 gene was exon15: (c.4264G > A). Two missense mutations were identified with a PKD1 (c.1758A > C and c.9774T > G), and one patient had a PKD2 mutation (c.1445T > G). Three detected variants were novel, identified at PKD1 (c.1758A > C), PKD2L2 (c.1364A > T), and TSC2 (deletion of a'a at the 3'UTR, R1680C) genes. Other variants in PKD1L1 (c.3813_381 4delinsTG) and PKD1L2 (c.404C > T) were also detected. The median age of end-stage renal disease for ADPK patients in Saudi Arabia was 30 years. Conclusion: This study reported a common variant in the PKD1 gene in Saudi patients with typical ADPKD. We also reported (to our knowledge) for the first time two novel missense variants in PKD1 and PKD2L2 genes and one indel mutation at the 3'UTR of the TSC2 gene. This study establishes that the reported mutations in the affected genes resulted in ADPKD development in the Saudi population by a median age of 30. Nevertheless, future protein−protein interaction studies to investigate the influence of these mutations on PKD1 and PKD2 functions are required. Furthermore, large-scale population-based studies to verify these findings are recommended.

Hospital admission trends due to respiratory diseases in England and Wales between 1999 and 2019: an ecologic study.

BACKGROUND: Identifying trends of hospital admissions for respiratory diseases is crucial for public health and research to guide future clinical improvements for better outcomes. This study aims to define the trends of respiratory disease-related hospital admissions (RRHA) in England and Wales between 1999 and 2019. METHODS: An ecological study was conducted using hospital admission data taken from the Hospital Episode Statistics database in England and the Patient Episode Database for Wales. Hospital admissions data for respiratory diseases were extracted for the period between April 1999 and March 2019. The trend in hospital admissions was assessed using a Poisson model. RESULTS: Hospital admission rate increased by 104.7% [from 1535.05 (95% CI 1531.71-1538.38) in 1999 to 3142.83 (95% CI 3138.39-3147.26) in 2019 per 100,000 persons, trend test, p < 0.01]. The most common causes were influenza and pneumonia, chronic lower respiratory diseases, other acute lower respiratory infections, which accounted for 26.6%, 26.4%, and 14.9%, respectively. The age group 75 years and above accounted for 34.1% of the total number of hospital admissions. Males contributed to 50.5% of the total number of hospital admissions. Hospital admission rate in females increased by 119.8% [from 1442.18 (95% CI 1437.66-1446.70) in 1999 to 3169.38 (95% CI 3163.11-3175.64) in 2019 per 100,000 persons, trend test, p < 0.001]. Hospital admission rate increased by 92.9% in males [from 1633.25 (95% CI 1628.32-1638.17) in 1999 to 3149.78 (95% CI 3143.46-3156.09) in 2019 per 100,000 persons, trend test, p < 0.001]. CONCLUSION: During the study period, hospital admissions rate due to respiratory diseases increased sharply. The rates of hospital admissions were higher among males for the vast majority of respiratory diseases. Further observational studies are warranted to identify risk factors for these hospital admissions and to offer relevant interventions to mitigate the risk.

Antioxidant, antiapoptotic, and antifibrotic effects of the combination of liposomal resveratrol and carvedilol against doxorubicin-induced cardiomyopathy in rats.

The use of the cytotoxic antibiotic doxorubicin (DOXR) is limited by its dose-dependent cardiotoxicity. The aim of this study was to evaluate the cardioprotective effect of the combination of carvedilol (CARD) and liposomal resveratrol (LIPO RESV) against DOXR-induced cardiomyopathy in rats. The results of the present study showed that DOXR administration significantly increased heart weight/body weight ratio by 35.6%, creatine kinase-MB (CK-MB) by 40.6%, troponin-I levels by 85%, and decreased reduced glutathione level and superoxide dismutase activity by 47% and 52%, respectively compared to the control group. Moreover, cardiac caspase-3 protein expression was upregulated by 51.6% vs the control group. In contrast, treatment of DOXR-administered rats with CARD, RESV, or LIPO RESV and their combination for 6 weeks improved all the above-mentioned measured parameters. In conclusion, concomitant administration of CARD and LIPO RESV exerted additive pharmacological effects in some measured parameters against DOXR-induced cardiomyopathy and this may be a useful cardioprotective strategy.

Knowledge and Attitude Regarding Cutaneous Leishmaniasis Among Adult Population in Tabuk, Saudi Arabia.

Background Cutaneous leishmaniasis (CL) is a major health problem in Saudi Arabia. It is caused by the protozoa Leishmania. The vector is female sand flies. In order to develop preventive strategies to reduce the burden of this health problem, public awareness of the disease should be assessed. Objective This study aimed to investigate the knowledge and attitude toward CL among the adult population in Tabuk, Saudi Arabia. Methods A cross-sectional survey study was conducted on 385 adult participants of Tabuk between April and May 2022. The investigators assembled the survey questions from peer-reviewed articles with some modifications. Google Forms was used to create the online survey. Social media were used to distribute the survey. Results The study revealed that hearing about CL was much more common among participants older than 61 years and Saudi males. The most prominent sources of information for the participants on which their answers were based were as follows: families and friends, health care professionals, television or radio, and lastly, newspapers. Subjects older than 61 years also showed more knowledge of the risk factors for contracting CL. However, the participants showed overall poor knowledge of the clinical presentation of the disease, which gender or age group was mostly affected, or how the disease was transmitted. Likewise, their knowledge of sand flies was poor. Most participants did not know if CL was a health problem or not. Conclusions The study revealed overall poor awareness of the epidemiological aspects of CL, how it is transmitted, its clinical presentation, and proper management. Our study could help authorities correct the gap in knowledge regarding CL in Tabuk.

Knowledge and Perception of Orthodontic Treatment among General and Non-Orthodontic Dental Specialists: A Comparative Study.

The objective of this study is to discover any possible association of gender or practitioner classification with orthodontic knowledge and attitudes towards orthodontic treatment. Descriptive cross-sectional research was conducted on two groups of dentists in the Ha'il region of Saudi Arabia. Group I included general practitioners, while Group II had non-orthodontic specialists. The findings suggest a statistically significant (p < 0.05) difference between the knowledge and attitudes of general practitioners and non-orthodontic specialists. Independent two tailed t-scores for difference in Knowledge (t-score = 3.19919, p = 0.003) and Attitude (t-score = 2.16314, p = 0.048319), highlight significant disparities in the knowledge and attitudes of general practitioners and non-orthodontic specialists. However, no statistically significant difference was observed in terms of knowledge and attitudes based on gender differences. This study captures and highlights subtle information that is very significant in dealing with critically important orthodontics issues. The study suggests that it is possible that a non-orthodontic specialist may suggest an altogether different line of treatment with different consequences when compared to a general practitioner and vice versa. This may result in unwanted, permanent orthodontic effects, highlighting the significance of the early stage of orthodontic treatment awareness. This research reveals disparities between the perceptions of general practitioners and non-orthodontic specialists about the stage and relevance of orthodontic treatment. It is strongly advised to see an orthodontic expert rather than a general practitioner or non-orthodontic specialist for orthodontic issues.

Sleep Hygiene Practices and Its Impact on Mental Health and Functional Performance Among Adults in Tabuk City: A Cross-Sectional Study.

Background Poor or imperfect sleep hygiene practices include all factors that promote arousal or disrupt the normal balance of the sleep-wake cycle. It is necessary to clarify the relationship between sleep hygiene behaviors and a person's mental health. This may allow a better understanding of this problem and might help design effective awareness programs about good sleep hygiene practices for reducing the serious outcomes of this problem. Therefore, the current study was conducted to evaluate sleep hygiene practices and assess the impact of sleep hygiene on sleep quality and the mental health of the adult population of Tabuk city, Saudi Arabia. Methodology This cross-sectional, survey-based study was conducted in Tabuk city, Saudi Arabia in 2022. All adult residents of Tabuk city, Saudi Arabia were invited to participate. Participants with incomplete data were excluded from the study. A self-administered questionnaire was developed by the researchers to assess sleep hygiene practices and their impact on the sleep quality and mental health of the study participants. Results The study included 384 adults. There was a significant association between the frequency of sleep problems and poor sleep hygiene practices (p < 0.001). The percentage of subjects who had problems sleeping during the past three months was significantly higher among those having poor sleep hygiene practices (76.5%) than their counterparts (56.1%). The rates of excessive or severe daytime sleepiness were significantly higher among individuals with poor hygiene practices (22.5% versus 11.7% and 5.2% versus 1.2%, p = 0.001). Participants with depression were found to be significantly higher among the poor hygiene group (75.8%) in comparison to those having good hygiene practices (59.6%) (p = 0.001). Conclusions The findings of the present study indicate significant associations between poor sleep hygiene practices and sleep problems, daytime sleepiness, and depression among adult residents of Tabuk city, Saudi Arabia.

Epidermolysis Bullosa Simplex With Dystonin Gene Mutation: First Reported Case in Saudi Arabia.

We report a case of a 3-year-old Saudi female patient as the first case reported in Saudi Arabia who is homozygous for dystonin c.3370C>T, p.(Gln1124*). At the age of 3 months, the girl started to develop numerous vesicles and bullae involving the dorsum of the feet that were not on a pressure site, with remission and aggravation, but she had no mucosal lesions or nail affection. The patient was diagnosed with epidermolysis bullosa simplex.

An Overview of the History, Pathophysiology, and Pharmacological Interventions of Multiple Sclerosis.

Multiple sclerosis (MS) is an immune-inflammatory disease that attacks and damages myelinated axons in the central nervous system (CNS) and causes nontraumatic neurological impairment in young people. Historically, Lidwina of Schiedam documented the first MS case. After that, Augustus d'Este wrote for years about how his MS symptoms worsened. Age, sex, genetics, environment, smoking, injuries, and infections, including herpes simplex and rabies, are risk factors for MS. According to epidemiology, the average age of onset is between 20 and 40 years. MS is more prevalent in women and is common in Europe and America. As diagnostic methods and criteria change, people with MS may be discovered at earlier and earlier stages of the disease. MS therapy has advanced dramatically due to breakthroughs in our knowledge of the disease's etiology and progression. Therefore, the efficacy and risk of treatment medications increased exponentially. Management goals include reducing lesion activity and avoiding secondary progression. Current treatment approaches focus on managing acute episodes, relieving symptoms, and reducing biological activity. Disease-modifying drugs such as fingolimod, interferon-beta, natalizumab, and dimethyl fumarate are the most widely used treatments for MS. For proof of the efficacy and safety of these medications, investigations in the real world are necessary.

ChatGPT Conquers the Saudi Medical Licensing Exam: Exploring the Accuracy of Artificial Intelligence in Medical Knowledge Assessment and Implications for Modern Medical Education.

Background The application of artificial intelligence (AI) in education is undergoing rapid advancements, with models such as ChatGPT-4 showing potential in medical education. This study aims to evaluate the proficiency of ChatGPT-4 in answering Saudi Medical Licensing Exam (SMLE) questions. Methodology A dataset of 220 questions across four medical disciplines was used. The model was trained using a specific code to answer the questions accurately, and its performance was assessed using key performance indicators, difficulty level, and exam sections. Results ChatGPT-4 demonstrated an overall accuracy of 88.6%. It showed high proficiency with Easy and Average questions, but accuracy decreased for Hard questions. Performance was consistent across all disciplines, indicating a broad knowledge base. However, an error analysis revealed areas for further refinement, particularly with category (Option) A questions across all sections. Conclusions This study underscores the potential of ChatGPT-4 as an AI-assisted tool in medical education, demonstrating high proficiency in answering SMLE questions. Future research is recommended to expand the scope of training and evaluation as well as to enhance the model's performance on complex clinical questions.

Prevalence and Risk Factors of Allergic Diseases Among School Students in Tabuk: A Cross-Sectional Study.

BACKGROUND: Allergic diseases such as bronchial asthma, allergic rhinitis, and atopic dermatitis are common health problems among children. The prevalence of different allergic diseases is increasing in the Kingdom of Saudi Arabia. OBJECTIVES: This study aimed to estimate the prevalence and risk factors of allergic diseases among school students in Tabuk, Saudi Arabia. METHODS: This cross-sectional analytical study was conducted in Tabuk city, Saudi Arabia, between the first of August and the end of September, 2022. Students from primary, intermediate, and secondary schools were included. A predesigned, structured, self-administered questionnaire in the Arabic language was used to collect data. RESULTS: This study included 384 school students from Tabuk, Saudi Arabia. The age of the recruited students ranged from five to 19 years old. The prevalence of clinically diagnosed bronchial asthma that occurred at any time in the past was 31.8%. The prevalence of asthma symptoms was 51.0% for lifetime wheezing and 45.8% for current wheezing (in the past 12 months). The prevalence rates of clinically diagnosed allergic rhinitis and atopic dermatitis were 56.8% and 30.2%, respectively. Further, 68.2% of the school students had one or more of the diagnosed allergic diseases. The second or more childbirth orders were significantly associated with an increased risk of allergic diseases (adjusted odds ratio [AOR] = 3.140, 95% CI: 1.864-5.288). A family history of asthma or atopic conditions showed 3.118 times increased likelihood of allergic conditions (AOR = 3.118, 95% CI: 1.827-5.320). Other significant risk factors were the father's smoking (AOR = 1.698, 95% CI: 1.024-2.817) and having a dog, cat, or bird at home (AOR = 0.493, 95% CI: 0.257-0.946). CONCLUSION: The prevalence of bronchial asthma and other allergic diseases such as allergic rhinitis and atopic dermatitis among school students in Tabuk city, Saudi Arabia, is alarmingly high. Furthermore, both genetic and environmental components of allergic disease pathogenesis have been identified as risk factors.

Refractory Pyoderma Gangrenosum: Stabilized on Colchicine and Tumor Necrosis Factor (TNF) Inhibitor.

Pyoderma gangrenosum (PG) is a rare ulcerative, painful inflammatory skin condition that is categorized among neutrophilic dermatoses. We report an otherwise healthy female who initially presented to a dermatology clinic with erythematous nodules and pustules scattered over her legs and thigh, which progressed later to multiple painful ulcers. Upon further investigation, it was diagnosed as idiopathic PG. Prednisone was an initial mainstay of treatment. While tapering, mycophenolate mofetil was started as adjunctive therapy but failed to maintain remission. A tumor necrosis factor inhibitor was initiated alongside colchicine with a significant clinical response.

Current Knowledge, Satisfaction, and Use of E-Health Mobile Application (Seha) Among the General Population of Saudi Arabia: A Cross-Sectional Study.

Background: General population knowledge, satisfaction, and barriers to using Seha app have not been evaluated from a large-scale perspective. Therefore, this study aimed to explore current knowledge, satisfaction, and barriers of using Seha app and identify the most common mobile health application used among the general population in Saudi Arabia. Methods: A cross-sectional online survey, consisting of 25 questions, was distributed among the general population of Saudi Arabia. Descriptive statistics were used to describe the respondents' characteristics. Categorical variables were reported as frequencies and percentages. A chi-square (χ2) test was conducted to assess the statistical difference between respondents' demographic characteristics and their knowledge and use of the app. Results: Overall, 5008 respondents, both Saudi (3723: 74%) and non-Saudi (1285: 26%) as well as male 2142 (43%) and female 2866 (57%), across the Kingdom of Saudi Arabia completed the online survey. A total of 2921 (58%) had heard of the Seha app, although only 1286 (25%) had used the app. Higher percentages of users were from the western region, females and those within the age group of ≥51 years old, 388 users (29%: P<0.001), 804 (28%; P<0.001) and 67 (35%; P=0.013), respectively. Consulting a doctor was the most frequently utilized service, 576 users (58%). Respondents strongly agreed 402 (41%) that Seha was easy to use, and 538 (54%) strongly agreed that they would recommend Seha to others. The most common barrier of using Seha was a lack of knowledge about the app and its benefits, at 1556 (35%). Overall, the Tawakkalna app was the most utilized mobile health application provided by MOH used 2170 (48%). Conclusion: Utilization of the Seha app is quite low due to a lack of knowledge about the app and its benefits. Thus, the MOH should promote public awareness about the app and its benefits.

Hematological indices in the adult saudi population: Reference intervals by gender, age, and region.

Introduction: Hematological parameters are critical in disease diagnosis, management, and monitoring; however, complete blood count (CBC) reference intervals vary across populations. The aim of the current study was to provide the reference ranges of hematological parameters/indices in the healthy adult Saudi population. Methods: A multicenter retrospective cross-sectional study was conducted with a sample of employees who were screened pre-employment from January 2015 to December 2019, at tertiary care hospitals in three regions. Demographic and CBC data were extracted from the electronic health system. The 2.5th and 97.5th percentiles were used to determine the reference intervals. Results: Of a total of 1,388 participants, 53.82% were male. The majority 96% was less than 40 years old, and 85% were from the Central region. Gender-related differences were observed for the RBC count, Hb, HCT, MCV, MCH, MCHC, and the platelet count. Age-related differences were observed for the RBC, Hb, HCT, and eosinophils. The WBC parameters did not differ by gender or age categories. Region-related differences were observed for the RBC, hemoglobin, HCT, MCV, WBC, and basophils. The platelet count was higher in the female group, the age group 40 years and above, and in the Western region. The prevalence of anemia was high in the female group and the Eastern region. The overall neutropenia rate was 12.8%. Conclusion: The data from this study provide hematological parameter reference ranges for the adult Saudi population by gender, age, and region. Gender and age-related differences were observed for the hematological parameters. Anemia was more frequent in the female group and the Eastern region. Caution must be taken when comparing or interpreting results from different age groups, gender, region of origin, and ethnicity.

Postpartum depression and health-related quality of life: a Saudi Arabian perspective.

Background and Objectives: The mental and physical functioning of an individual is partly determined by their health-related quality of life (HRQOL), which is a multifaceted component. Women who have recently given birth must have a good quality of life to provide proper care and development for their infant. The purpose of this study was to assess the relationship between postpartum depression (PPD) and HRQOL in Saudi Arabian women and to identify potential risk factors that could influence them. Methods: This study comprised 253 mothers aged 1-24 weeks postpartum from several health centers in Saudi Arabia, recruited by random purposive sampling. The study's questionnaire featured three sections: the first section had demographic information; the second and third sections contained the Edinburgh Postnatal Depression Scale (EPDS) scale and the HRQOL scale (SF-12), respectively. Data were analyzed using descriptive statistics, chi square analyses, independent samples t-tests and binary logistic regression analysis using IBM SPSS 25. Results: Results of current study indicate that 59.68% of the patients exhibited probable post-partum depression symptoms. Participants who were depressed had significantly lower mental component (MCS) and physical component scores than participants who were in good health. When compared to non-smokers, smokers have a 21-fold higher risk of developing depression. Similar to this, mothers who worked had a 3.98 times higher risk of depression, and patients with a history of depression had a 3.6 times higher chance of getting PPD. The probability of developing PPD was also significantly higher in those who lived outside the Riyadh region, had given birth more than twice before this time, and had experienced undesired pregnancies. Conclusion: Our study demonstrated an inverse correlation between postpartum depression and health-related quality of life scores. Treatment for depression, particularly among mothers, is crucial for improving their quality of life and, as a result, creating a favorable environment for the development of newborn babies.

Nano-Resveratrol: A Promising Candidate for the Treatment of Renal Toxicity Induced by Doxorubicin in Rats Through Modulation of Beclin-1 and mTOR.

Background: Although doxorubicin (DXR) is one of the most used anticancer drugs, it can cause life-threatening renal damage. There has been no effective treatment for DXR-induced renal damage until now. Aim: This work aims at examining the potential impact of nano-resveratrol (N-Resv), native resveratrol (Resv), and their combination with carvedilol (Card) against DXR-induced renal toxicity in rats and to investigate the mechanisms through which these antioxidants act to ameliorate DXR nephrotoxicity. Method: DXR was administered to rats (2 mg/kg, i.p.) twice weekly over 5 weeks. The antioxidants in question were taken 1 week before the DXR dose for 6 weeks. Results: DXR exhibited an elevation in serum urea, creatinine, renal lipid peroxide levels, endoglin expression, kidney injury molecule-1 (KIM-1), and beclin-1. On the other hand, renal podocin and mTOR expression and GSH levels were declined. In addition, DNA fragmentation was markedly increased in the DXR-administered group. Treatment with either Resv or N-Resv alone or in combination with Card ameliorated the previously measured parameters. Conclusion: N-Resv showed superior effectiveness relative to Resv in most of the measured parameters. Histopathological examination revealed amelioration of renal structural and cellular changes after DXR by Card and N-Resv, thus validating the previous biochemical and molecular results.

Combined therapy with ivermectin and doxycycline can effectively alleviate the cytokine storm of COVID-19 infection amid vaccination drive: A narrative review.

An unprecedented global health crisis has developed due to the emergence of the mysterious coronavirus-2 of the severe acute respiratory syndrome, which has resulted in millions of deaths around the globe, as no therapy could control the 'cytokine storm'. Consequently, many vaccines have been developed and several others are being developed for this infection. Although most of the approved vaccines have been highly effective, many developing, and economically poor countries are still deprived of vaccination against SARS-CoV-2 due to the unequal distribution of vaccines worldwide. Furthermore, the uncertainty about the effectiveness of the available vaccines against the emerging mutants and variants also remains a matter of concern. Due to the multistep pathogenesis and unique features, combination therapy using safe immunomodulatory and antiviral drugs should be considered as the most effective and acceptable therapeutic regimen for this infection. Based on a thorough assessment of the literature, it was determined that it would be interesting to study the therapeutic potential of ivermectin and doxycycline, given their roles in several biological pathways involved in SARS CoV-2 pathogenesis. Following that, a comprehensive literature search was undertaken using Scopus, Web of Science, and Pubmed, depending on the inclusion and exclusion criteria. The present study provides a mechanism and comprehensive report, highlighting the role of combined therapy with ivermectin and doxycycline in alleviating the 'cytokine storm' of COVID-19 infection.

Diagnostic Test Accuracy of Genetic Tests in Diagnosing Psoriasis: A Systematic Review.

The pathogenesis of psoriasis involves the interaction of several environmental and genetic factors. Predicting the disease risk cannot depend on individual genetic alleles. Consequently, some studies have evaluated the use of genetic risk scores that combine several psoriasis susceptibility loci to increase the accuracy of predicting/diagnosing the disease. This meta-analysis summarizes the evidence regarding using genetic risk scores (GRS) in the diagnosis or prediction of psoriasis. A search of MEDLINE/PubMed, the Latin American Caribbean Health Sciences Literature (LILACS) database, Cochrane Library, Scopus, Web of Science, and ProQuest was conducted in July 2022. The primary objective was to record the area under the curve (AUC) for GRS of psoriasis. Secondary objectives included characteristics of studies and patients. The risk of bias (ROB) was assessed using the PROBAST tool. Five studies fulfilled the eligibility criteria of this review. None of the studies described the clinical criteria (reference standard) that were employed to diagnose psoriasis. The AUCs of the 11 GRS models ranged from 0.6029-0.8583 (median: 0.75). Marked heterogeneity was detected (Cochran Q: 1250.051, p < 0.001, and I2 index: 99.2%). So, pooling of the results of the included studies was not performed. The ROB was high for all studies and clinical application was not described. Genetic risk scores are promising tools for the prediction of psoriasis with fair to good accuracy. However, further research is required to identify the most accurate combination of loci and to validate the scores in variable ethnicities.