Liver Transplantation Profile Among Teenagers in the United States.

PURPOSE: Indications for liver transplantation (LT) vary across age groups. We identified predictors of outcomes for teenage LT waitlisted candidates and recipients in the United States from 2008 to 2022. METHODS: The Scientific Registry of Transplant Recipients 2008-2022 provided data (clinical, sociodemographic, indications for LT, outcomes) for all teenagers (13-19 years) waitlisted for LT in the United States. Sociodemographic and clinical characteristics, including primary listing diagnoses, were evaluated and compared by age group (13-16 vs. 17-19 years) among waitlisted teenage candidates. RESULTS: There were 2,813 teenage LT candidates listed between 2008 and 2022. The most common LT indication was acute liver disease (23.5%), followed by biliary atresia or hypoplasia (11.9%), autoimmune hepatitis (11.1%), and primary sclerosing cholangitis (9.7%). In contrast, chronic viral hepatitis, metabolic dysfunction-associated steatotic liver disease, and alcohol-related liver disease (the most common indications in adults) did not exceed 1% each; 2.8% had hepatocellular carcinoma. Excluding the two most recent years, 67.2% of candidates received a transplant; mean time to transplant was 217.0 days (standard deviation 371.6). Independent predictors of receiving a transplant were a more recent calendar year, younger age, higher model for end-stage liver disease score, and an acute liver disease diagnosis (all p < .05). Among the LT group, 3-year survival was 90%, with an improving survival trend. Higher post-transplant mortality was associated with earlier years of transplantation, older age, having Medicaid, being retransplanted, and having hepatocellular carcinoma (adjusted hazard ratios >1, all p < .05). DISCUSSION: Indications for LT among US teenagers are different from adults or younger children. There is a trend toward improved post-transplant outcomes.

The burden of metabolic dysfunction-associated steatotic liver disease and viral hepatitis in Saudi Arabia.

BACKGROUND: Globally, viral hepatitis is decreasing, but nonalcoholic fatty liver disease (NAFLD), now metabolic dysfunction-associated steatotic liver disease (MASLD), is increasing. We assessed the burden and trends of MASLD and viral hepatitis in Saudi Arabia. METHODS: Prevalence, death, and disability data due to MASLD, hepatitis C virus (HCV), and hepatitis B virus (HBV) were obtained from 2019 Global Burden of Disease (GBD) database for Saudi Arabia. Time trends were assessed by annual percent change (APC) from joinpoint regression. RESULTS: From 2012 through 2019, MASLD prevalence in children and adults increased from 28.02% (n = 8.34 million) to 33.11% (n = 11.83 million); APC +2.43% (95% confidence interval: 2.33% to 2.54%). HBV prevalence decreased from 1.83% (n = 0.54 million) to 1.53% (n = 0.55 million); APC -1.74% (-2.66% to -0.81%). HCV prevalence stabilized from 0.72% (n = 0.21 million) to 0.73% (n = 0.26 million): APC +0.32% (-0.13% to 0.78%). Among adults (>20 years), MASLD prevalence increased from 40.64% to 43.95% (APC = +1.15%, 1.12% to 1.18%), HBV prevalence decreased from 2.67% to 2.05% (APC = -2.96%, -3.90% to -2.01%), and HCV leveled from 0.88% to 0.86% (APC = -0.30%, -0.75% to 0.16%). MASLD liver mortality rate from liver cancer and cirrhosis increased: APC of +1.15% (0.82% to 1.48%) from 1.31 to 1.43 (per 100,000). HBV and HCV liver mortality increased at slower rates (APC = +0.78%, 0.38% to 1.19%): 2.07 to 2.20 (per 100,000) and (APC = +0.55%, 0.09% to 0.89%): 6.32 to 6.61 (per 100,000), respectively. CONCLUSIONS: MASLD burden is increasing, while HBV and HCV burden is decreasing/remaining stable. Early prevention and diagnosis health policies for MASLD are needed.

Dulaglutide reduces oxidative DNA damage and hypermethylation in the somatic cells of mice fed a high-energy diet by restoring redox balance, inflammatory responses, and DNA repair gene expressions.

Obesity is an established risk factor for numerous malignancies, although it remains uncertain whether the disease itself or weight-loss drugs are responsible for a greater predisposition to cancer. The objective of the current study was to determine the impact of dulaglutide on genetic and epigenetic DNA damage caused by obesity, which is a crucial factor in the development of cancer. Mice were administered a low-fat or high-fat diet for 12 weeks, followed by a 5-week treatment with dulaglutide. Following that, modifications of the DNA bases were examined using the comet assay. To clarify the underlying molecular mechanisms, oxidized and methylated DNA bases, changes in the redox status, levels of inflammatory cytokines, and the expression levels of some DNA repair genes were evaluated. Animals fed a high-fat diet exhibited increased body weights, elevated DNA damage, oxidation of DNA bases, and DNA hypermethylation. In addition, obese mice showed altered inflammatory responses, redox imbalances, and repair gene expressions. The findings demonstrated that dulaglutide does not exhibit genotoxicity in the investigated conditions. Following dulaglutide administration, animals fed a high-fat diet demonstrated low DNA damage, less oxidation and methylation of DNA bases, restored redox balance, and improved inflammatory responses. In addition, dulaglutide treatment restored the upregulated DNMT1, Ogg1, and p53 gene expression. Overall, dulaglutide effectively maintains DNA integrity in obese animals. It reduces oxidative DNA damage and hypermethylation by restoring redox balance, modulating inflammatory responses, and recovering altered gene expressions. These findings demonstrate dulaglutide's expediency in treating obesity and its associated complications.

Serological markers of transfusion transmissible infections and ABO blood groups in Najran, Saudi Arabia.

OBJECTIVES: To ascertain the prevalence of transfusion transmissible infections (TTIs) across diverse donor groups in the Najran province. Additionally, to establish a potential association between the development of TTI and the donors' blood group, as determined by the ABO/Rh blood grouping system. METHODS: Blood donation data of 4120 donors, spanning from January to December 2020, were retrospectively reviewed. The blood were screened for TTI markers, including hepatitis B surface antigen (HBsAg), anti-hepatitis B core (anti-HBc), anti-hepatitis C virus (anti-HCV), anti-human immunodeficiency viruses 1 and 2 (anti-HIV1&2), anti-human T-lymphotropic virus types 1 and 2 (anti-HTLV-1&2), and syphilis antigen. RESULTS: Positive TTI markers were detected in 10.9% of the donors. The most detected TTI marker was anti-HBc (8.9%), followed by HBsAg (0.7%). Other markers were individually detected in <1% of the donors. Anti-HBc-positive was significantly elevated among non-Saudi blood donors. There was an association between age groups and anti-HCV (p=0.002), anti-HTLV (p=0.004) and syphilis antigen (p=0.02) markers positivity. The AB positive blood group exhibited the most positivity for TTI markers, followed by O positive blood group. Similarly, association was found between ABO group and HBsAg (p=0.01), anti-HBc (p=0.001), and anti-HCV (p<0.001) markers positivity. CONCLUSION: Emphasis on implementing robust screening measures for donated blood is underscored by this study. There is the need for future study to extensively evaluate TTI status to enhance our understanding of the trend in TTI.

Recent developments in the synthesis and applications of terpyridine-based metal complexes: a systematic review.

Terpyridine-based metal complexes have emerged as versatile and indispensable building blocks in the realm of modern chemistry, offering a plethora of applications spanning from materials science to catalysis and beyond. This comprehensive review article delves into the multifaceted world of terpyridine complexes, presenting an overview of their synthesis, structural diversity, and coordination chemistry principles. Focusing on their diverse functionalities, we explore their pivotal roles in catalysis, supramolecular chemistry, luminescent materials, and nanoscience. Furthermore, we highlight the burgeoning applications of terpyridine complexes in sustainable energy technologies, biomimetic systems, and medicinal chemistry, underscoring their remarkable adaptability to address pressing challenges in these fields. By elucidating the pivotal role of terpyridine complexes as versatile building blocks, this review provides valuable insights into their current state-of-the-art applications and future potential, thus inspiring continued innovation and exploration in this exciting area of research.

Blue Toe Syndrome in Behçet's Disease: A Case Report.

BACKGROUND Vascular Behçet's disease (VBD) is a rare but potentially life-threatening subtype of Behçet's disease that is characterized by multisystemic vasculitis. It primarily affects males with ancestry traced back to regions along the ancient Silk Road. Both arteries and veins, regardless of size, may exhibit complications, including aneurysmal degeneration or occlusion. While venous involvement is observed in two-thirds of VBD cases, arterial complications are notably the most severe and lethal. Arterial aneurysmal degeneration is more common than occlusive complications, with larger arteries being predominantly affected in VBD. Data regarding isolated small-vessel arterial occlusive disease in VBD are limited. Given the rarity of this presentation in this patient population, it becomes mandatory to thoroughly evaluate such patients to differentiate small-vessel vasculitis from other similar diseases, such as Raynaud's phenomenon, which has a different etiology and management and generally has a more benign course. Here, we delineate the concept of isolated small-vessel vasculitis as a cause of blue toe syndrome in patients with VBD. CASE REPORT This report describes a distinctive case of vascular Behçet's disease in a 51-year-old man who initially exhibited unilateral blue toe syndrome, which swiftly progressed to dry gangrene of the toes. Despite reports of large-vessel involvement, there is a paucity of data on isolated small-vessel vasculitis-induced digital ischemia in VBD. CONCLUSIONS This atypical case underscores the necessity of clinical discernment in differentiating inflammatory microvascular occlusive disease from vasospastic Raynaud's syndrome, both of which can complicate Behçet's disease.

Barriers to Seeking Mental Health Help in Saudi Arabia: A Systematic Review.

Globally, mental disorders have become a significant burden, affecting a substantial number of individuals. Accessing mental health services is crucial for effective treatment and improving outcomes. However, significant barriers to seeking health services can impede access and contribute to the treatment gap. This systematic review aims to identify and analyze the perceived barriers to seeking mental health services in Saudi Arabia. A comprehensive search was conducted among four databases (PubMed, Web of Science, ProQuest, and Science Direct) to identify relevant studies published between 2018 and 2023. Studies that investigated barriers that could prevent psychiatric patients from seeking mental health services in Saudi Arabia were included. Data extraction and synthesis were performed to identify common themes and barriers. The review included a total of six studies that examined barriers to seeking mental health services in Saudi Arabia. The identified barriers encompassed a range of factors, including stigma, lack of awareness, concerns about confidentiality, limited availability of services, negative attitudes toward professional help, and cultural and religious beliefs. The lack of knowledge, as well as the negative attitude toward mental health care, was a perceived barrier to help-seeking in most studies. Furthermore, stigma was consistently reported as a predominant barrier, preventing individuals from seeking mental health care. This systematic review highlights the barriers to seeking mental health services in Saudi Arabia. Addressing these barriers is essential for improving access to mental healthcare and reducing the treatment gap. Strategies should focus on destigmatization efforts, increasing awareness, ensuring confidentiality and privacy, providing culturally appropriate care, and addressing structural limitations. By implementing these strategies, healthcare systems can improve access to mental health care and the overall well-being of individuals experiencing mental disorders in Saudi Arabia.

Comprehensive pan-cancer analysis reveals VSIR as a candidate immunologic, diagnostic, and prognostic biomarker.

OBJECTIVES: Being a checkpoint, the expression level of V-set immunoregulatory receptor (VSIR) serves as an indicator of the extent of immunosuppression. Our objective was to undertake a pan-cancer analysis to examine the expression, genetic alterations, prognosis, and immunologic features associated with VSIR. METHODS: The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), GEPIA2, UALCAN, OncoDB, Human Protein Atlas (HPA), STRING, DAVID, cell culture, clinical sample collection, and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were used. RESULTS: This study comprehensively assessed VSIR across 33 cancers using TCGA and GTEx databases. Differential expression analysis revealed elevated VSIR in several cancers, notably in cholangiocarcinoma, esophageal carcinoma, kidney renal cell carcinoma, and liver hepatocellular carcinoma, while decreased expression was observed in various others. Prognostic analysis highlighted its significant association with reduced overall survival (OS) in ESCA and LIHC. Investigation into cancer stages demonstrated a correlation between VSIR expression and stage in ESCA and LIHC. Promoter methylation analysis indicated decreased VSIR methylation levels in tumors, implicating a role in oncogenesis. Furthermore, subcellular localization predictions, Tumor Mutational Burden (TMB), and Microsatellite Instability (MSI) correlations revealed intriguing insight into VSIR's function. Notably, a positive correlation was identified between VSIR expression and various immune cells in both cancers. Protein-protein interaction (PPI) network construction and gene enrichment analysis elucidated VSIR-associated dysregulated pathways, emphasizing its possible involvement in diverse pathways. Finally, experimental validation using LIHC clinical samples and cell lines confirmed elevated VSIR expression, supporting its oncogenic role. CONCLUSION: Collectively, these findings present a comprehensive understanding of VSIR's diverse roles and potential clinical implications in ESCA and LIHC.

Association between polycystic ovary syndrome and the risk of malignant gynecologic cancers (ovarian, endometrial, and cervical): A population-based study from the U.S.A. National Inpatient Sample 2016-2019.

OBJECTIVE: This study aimed to systematically examine the relationship between polycystic ovary syndrome and ovarian, endometrial, and cervical cancers using the National Inpatient Sample (NIS) database. METHODS: We utilized the International Classification of Diseases (ICD-10) system to identify relevant codes from the NIS database (2016-2019). Univariate and multivariable regression analyses (adjusted age, race, hospital region, hospital teaching status, income Zip score, smoking, alcohol use, and hormonal replacement therapy) were conducted to evaluate association between PCOS and gynecologic cancers. Results were summarized as odds ratio (OR) with 95% confidence intervals (CI). RESULTS: Overall, 15,024,965 patients were analyzed, of whom 56,183 and 14,968,782 patients were diagnosed with and without PCOS, respectively. Among the patients diagnosed with gynecologic cancers (n = 91,599), there were 286 with PCOS and 91,313 without PCOS. Univariate analysis revealed that PCOS was significantly associated with higher risk of endometrial cancer (OR = 1.39, 95 % CI [1.18-1.63], p < 0.0001), but lower risk of ovarian cancer (OR = 0.55, 95 % CI [0.45-0.67], p < 0.0001) and cervical cancer (OR = 0.68, 95 % CI [0.51-0.91], p = 0.009). In contrast, after Bonferroni correction, multivariable analysis depicted that PCOS remained significantly associated with higher risk of endometrial cancer (OR = 3.90, 95 % CI [4.32-4.59], p < 0.0001). There was no significant correlation between PCOS and risk of ovarian cancer (OR = 1.09, 95 % CI [0.89-1.34], p = 0.409) and cervical cancer (OR = 0.83, 95 % CI [0.62-1.11], p = 0.218). CONCLUSION: This first-ever NIS analysis showed that patients with PCOS exhibited unique gynecologic cancer risk profiles, with higher risk for endometrial cancer, and no significant risk for ovarian or cervical cancers.

Quality of Life in Children With Eosinophilic Esophagitis in Saudi Arabia.

INTRODUCTION: Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus that can adversely affect the quality of life (QOL) in children. We aim to investigate the burden of EoE on the QOL in children aged 2-18 years and identify factors that influence their QOL. METHOD: A multicenter cross-sectional study was conducted in six Saudi pediatric hospitals. Pediatric Quality of Life 3.0 EoE Module was used to measure the QOL of children with EoE. RESULTS: Thirty-six families (36 parents and 33 children) were enrolled. The most reported symptoms were vomiting (50%), dysphagia (44.4%), and food impaction (36.1%). The mean total score of the parent-proxy report of the Pediatric Quality of Life EoE was 82.9 ± 10.3 versus the children's self-reported score of 77.28 ± 13.6 (p = .043). DISCUSSION: Recurrent emergency department visits were associated with a lower QOL, and a positive family history of EoE was associated with a better QOL.

Complicated Spigelian hernia presenting with sigmoid colon strangulation: A unique clinical report.

INTRODUCTION AND IMPORTANCE: Spigelian hernias are rare, constituting about 1-2 % of all abdominal wall hernias. They present clinically significant challenges due to their potential for incarceration and strangulation. This case report highlights a unique presentation of a Spigelian hernia involving sigmoid colon strangulation, emphasizing the critical need for awareness and timely intervention. CASE PRESENTATION: A 60-year-old female with hypertension and diabetes presented with severe left abdominal pain, nausea, and vomiting. Examination revealed leukocytosis, neutrophilia, and signs of acute abdomen. CT imaging showed a complicated left lateral abdominal wall hernia containing the sigmoid colon. Surgical intervention included sigmoidectomy with colorectal anastomosis and hernia repair. Postoperative recovery was successful with subsequent elective ileostomy reversal. CLINICAL DISCUSSION: The rarity of Spigelian hernias and their atypical presentations can complicate diagnosis and management. This case was particularly challenging due to the strangulation of the sigmoid colon within the hernial sac. Surgical management was necessary to address the incarcerated bowel segment and prevent further complications. This case underscores the utility of CT scans in diagnosing complex cases and guiding surgical strategy. CONCLUSION: Despite their rarity, Spigelian hernias carry significant risks of strangulation. Prompt diagnosis and treatment are essential to avoid severe complications. This case highlights the importance of including Spigelian hernia in the differential diagnosis for acute abdominal symptoms, especially when they are nonspecific.

Nivolumab as Second-Line Therapy Improves Survival in Patients with Unresectable Hepatocellular Carcinoma.

BACKGROUND: Limited data exists for the efficacy and outcomes of nivolumab as a second-line treatment for unresectable hepatocellular carcinoma (uHCC). We aimed to assess the efficacy and safety of nivolumab in patients with uHCC who experienced disease progression during sorafenib treatment. METHODS: In this retrospective, observational, multicenter study, adult Child-Turcotte-Pugh A/7B patients with uHCC who tolerated sorafenib therapy but showed disease progression switched to second-line intravenous nivolumab (n = 42). A similar number of consecutive, unselected patients who were maintained on sorafenib therapy, regardless of tumoral response or progression, served as historical controls (n = 38). The primary endpoint was overall survival (OS, defined as the time from starting sorafenib in either group up to death due to any cause) and analyzed by intention-to-treat. RESULTS: The mean age of the overall cohort was 72.4 ± 10.1 years, of whom 87.5% were males and 58.8% had underlying viral etiology. Patients in the two cohorts were similar, except those who received nivolumab had more co-morbidities (70.0% vs. 15.4%), ECOG-2 status (21.4% vs. 15.8%), BCLC stage C (81.0% vs. 47.4%), and extravascular invasion (54.4% vs. 21.8%) (p < 0.05 for all). More patients in the nivolumab arm were Child-Turcotte-Pugh B (35.7% vs. 21.1%, p = 0.15). Median OS was 22.2 months (95% CI: 8.9-49.8) on second-line nivolumab and 11.0 months (95% CI: 3.6-18.4) on sorafenib alone (HR 1.93; 95% CI: 1.1-3.3, p = 0.014). Median OS after starting nivolumab was 10.2 months, and time-to-progression was 4.9 months (95% CI: 3.2-6.3). CONCLUSION: Nivolumab is an effective second-line treatment option in patients with uHCC who progress on sorafenib, with significantly improved OS. These early real-life data offer encouraging results, similar to those shown in Phase I/IIa clinical trials. Further investigations are warranted for the use of nivolumab as a monotherapy.

Study on Regio- and Diastereoselectivity of the 1,3-Dipolar Cycloaddition Reaction of Azomethine Ylide with 2-(Benzo[d]thiazol-2-yl)-3-(aryl)acrylonitrile: Synthesis, Spectroscopic, and Computational Approach.

An unprecedented and efficient three-component 1,3-dipolar cycloaddition reaction using (E)-2-(benzo[d]thiazol-2-yl)-3-(aryl)acrylonitriles 4a-g and an in situ generated azomethine ylide 3 from isatin and N-methylglycine is described. The reaction exhibits exclusive regioselectivity, resulting in the formation of 3'-(benzo[d]thiazol-2-yl)-1'-methyl-2-oxo-4'-(aryl)spiro[indoline-3,2'-pyrrolidine]-3'-carbonitriles regioisomers through exo/endo approaches. The diastereoselectivity of the reaction is highly dependent on the substitution pattern of the phenyl ring in dipolarophiles 4a-g, leading to the formation of exo-/endo-cycloadducts in varying ratios. To understand the stereoselectivity, the transition state structures were optimized using the TS guess geometry with the QST3-based method. The reaction mechanism and regioselectivity were elucidated by evaluating global and local electrophilicity and nucleophilicity descriptors at the B3LYP/cc-pVTZ level of theory, along with considerations based on the HSAB principle. The analysis of global electron density transfer (GEDT) showed that the reactions are polar and electron density fluxes from azomethine ylide 3 toward dipolarophile 4a-g. It was found from the molecular electrostatic potential map (MESP) that at the more favorable transition state, approach of reactants locates the oppositely charged regions over each other resulting in attractive forces between the two fragments. The computational results are consistent with the experimental observations, confirming that the reactions proceed through an asynchronous one-step mechanism.

Effects of nonlinear thermal radiation on the efficiency of building integrated photovoltaic systems with nanofluid cooling.

The nonlinear effects of thermal radiation on the free convection flow of certain nanofluids along a heated wall are studied numerically using an original finite-difference method. Nanofluids are used to improve the performance of flat and curved integrated photovoltaic modules. The partial differential equations governing the flow are difficult to solve due to the strong non-linearity of the radiative term. In contrast to previous studies, the problem is solved directly without linearization by Rosseland's nonlinear approximation. The proposed numerical method is validated with results from the literature. The effects of nonlinearity and various physical parameters such as time, volume fraction and radiation parameter on the velocity, temperature, Nusselt number and skin friction coefficient of the CuO-water nanofluid are analyzed and presented graphically. A comparative study between the solutions given by the linear and non-linear problems reveals that Rosseland's linear approximation is no longer valid when the effect of thermal radiation is significant. On the other hand, the non-linear model better reflects the physical phenomena involved in the cooling process. Finally, a comparison of the performance of five nanofluids (CuO, Ag, Al2O3, Cu and TiO2 in water) shows that the Cu-water nanofluid performs best, with a high heat transfer rate and low shear stresses.

Isolated Neutrophilic Urticarial Dermatosis in a Previously Healthy Male: A Case Report.

Neutrophilic urticarial dermatosis (NUD), a variant falling under the larger umbrella of neutrophilic dermatoses (NDs), is characterized by distinctive clinical and histopathological attributes often associated with systemic conditions. This report presents a case of a 45-year-old male with no prior health issues who exhibits both clinical and pathological hallmarks of NUD without any concurrent systemic illness. This singular case illuminates the intricate aspects of NUD, emphasizing the necessity for accurate diagnostic methods and effective treatment strategies.

Findings on three endocommensal scuticociliates (Protista, Ciliophora) from freshwater mollusks, including their morphology and molecular phylogeny with descriptions of two new species.

Species of the ciliate genera Myxophyllum and Conchophthirus are found as endocommensals of terrestrial and freshwater mollusks, respectively. So far, there have been few studies of these genera and morphological data for most members are often incomplete. In the present work, two new species, Myxophyllum weishanense sp. nov. and Conchophthirus paracurtus sp. nov., and a known species, Conchophthirus lamellidens, were isolated from hosts in Lake Weishan Wetland, China. Taxonomic studies indicate that M. weishanense sp. nov. can be recognized mainly by the combination of about 60 somatic kineties on both ventral and dorsal sides and the presence of caudal cilia. Conchophthirus paracurtus sp. nov. differs from congeners in its body shape and size, having a glabrous area on the posterior right side, and having fewer somatic kineties. In addition, differences in their ITS2 (Internally Transcribed Spacer 2) secondary structures support the discrimination of the two new species from their highly similar congeners. An improved diagnosis for the poorly known species, C. lamellidens is also provided. Phylogenetic analyses reveal that members of the genus Myxophyllum belong to a fully supported clade that is sister to a large, poorly supported clade consisting of Hemispeiridae, Ancistridae, and several lineages of the nonmonophyletic Cyclidiidae. The Myxophyllum clade also includes Protophyra ovicola JQ956552, a possible misidentification. Sequences of the two new Conchophthirus species cluster with other congeners in a fully supported clade that is unrelated to either the 'typical' thigmotrichs or to pleuronematids, thus conflicting with the traditional classification, and may represent an orphan scuticociliate lineage. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-024-00230-4.

Neuroprotective Effect of Brivaracetam and Perampanel Combination on Electrographic Seizures and Behavior Anomalies in Pentylenetetrazole-Kindled Mice.

Pentylenetetrazole (PTZ)-induced kindling is a broadly used experimental model to study the anticonvulsive potential of new and existing chemical moieties with the aim of discovering drugs hindering seizure progression and associated neurological comorbidities. In the present study, the impact of brivaracetam (BRV) (10 and 20 mg/kg) as monotherapy as well as in combination with 0.25 mg/kg of perampanel (PRP) was investigated on seizure progression with simultaneous electroencephalographic changes in PTZ kindling mouse model. Subsequently, mice were experimentally analyzed for anxiety, cognition, and depression after which their brains were biochemically evaluated for oxidative stress. The outcomes demonstrated that BRV alone delayed the kindling process, but BRV + PRP combination significantly (p < 0.0001) protected the mice from seizures of higher severity and demonstrated an antikindling effect. The PTZ-kindled mice exhibited anxiety, memory impairment, and depression in behavioral tests, which were remarkably less (p < 0.001) in animals treated with drug combination (in a dose-dependent manner) as these mice explored central, illuminated, and exposed zones of open-field test, light/dark box, and elevated plus maze. Moreover, memory impairment was demonstrated by kindled mice, which was significantly (p < 0.001) protected by BRV + PRP as animal's spontaneous alteration, object discrimination, and step-through latencies were increased in various tests employed for the assessment of cognitive abilities. The brains of PTZ-kindled mice had increased malondialdehyde and reduced antioxidant enzymes while treatment with BRV + PRP combination prevented kindling-induced elevation in oxidative markers. The outcomes of this study demonstrate that combining the PRP at low dose augmented the antiseizure properties of BRV as both drugs when administered simultaneously hindered the process of kindling by reducing PTZ-induced excessive electrical activity and oxidative stress in the brain.

Unveiling the unexplored novel signatures for osteoporosis via a detailed bioinformatics and molecular experiments based approach.

BACKGROUND: Osteoporosis (OP) stands as a prevalent bone ailment affecting the elderly, globally. The identification of reliable diagnostic markers crucially aids OP clinical management. METHODS: Utilizing the GEO database (GSE35959), we acquired expression profiles for OP and normal samples. Differential expression genes (DEGs) and hub genes were pinpointed through STRING, GEO2R, and Cytoscape. The competing endogenous RNA (ceRNA) network was constructed using miRTarBase, miRDB, and MiRcode databases. Gene Ontology (GO) and KEGG pathway enrichment analyses were performed via DAVID. Validation involved clinical OP samples from the Pakistani population, with Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR) assessing hub gene expression. RESULTS: A total of 2124 differentially expressed genes (DEGs) were identified between OP and normal samples in GSE35959. The selected hub genes among these DEGs were Splicing Factor 3a Subunit 1 (SF3A1), Ataxin 2 Like (ATXN2L), Heat Shock Protein 90 Beta Family Member 1 (HSP90B1), Cluster of Differentiation 74 (CD74), DExH-Box Helicase 29 (DHX29), ALG5 Dolichyl-Phosphate Beta-Glucosyltransferase (ALG5), NudC Domain Containing 2 (NUDCD2), and Ras-related protein Rab-2A (RAB2A). Expression validation of these genes on the Pakistani OP patients revealed significant up-regulation of SF3A1, ATXN2L, and CD74 and significant (P < 0.05) down-regulation of HSP90B1, DHX29, ALG5, NUDCD2, and RAB2A in OP patients. Receiver operating characteristic (ROC) analysis demonstrated that these hub genes displayed considerable diagnostic accuracy for detecting OP. The ceRNA network analysis of the hub genes revealed some important hub genes' regulatory miRNAs and lncRNAs. Via KEGG analysis, hub genes were found to be enriched in N-Glycan biosynthesis, Thyroid hormone synthesis, IL-17 signaling pathway, Prostate cancer, AMPK signaling pathway, Spliceosome, Estrogen signaling pathway, and Fluid shear stress and atherosclerosis, etc., pathways. CONCLUSION: The identified eight hub genes in the present study could reliably distinguish OP patients from normal individuals, which may provide novel insight into the diagnostic research of OP.

Epilepsy first aid awareness among healthcare workers in Saudi Arabia: A cross-sectional study.

Objectives: Epilepsy is a neurological disorder affecting more than 50 million human lives of all ages, its social, physical and psychological implications is of huge concern. The current study and as a continuation of epilepsy knowledge assessment projects conducted by our research team is aimed to assess the knowledge of healthcare workers regarding epilepsy first aid in Saudi Arabia. Methods: A cross-sectional questionnaire-based study was carried out from 2020 to 2021. Results: During the study period, 272 healthcare workers were recruited; participants were males and females from different nationalities in various Saudi Arabian cities, possess diverse qualifications, and belong to several healthcare-related professions. The question, "Did you witness an epileptic seizure"? was answered as "Yes" by 42% of participants, and in response to the question "If you know that this patient struggles during seizure attacks," 58% of respondents stated that they would not call an ambulance. Moreover, the question "Put something in his/her mouth to prevent tongue biting" was incorrectly answered as "Yes" by 42% of respondents, and the question "Try to catch him/her and stop his/her movement" in order to control the attack was answered "Yes" by 21% of respondents. Furthermore, almost 90% of healthcare participants do not know how to use the Vagus Nerve Stimulation device. The mean knowledge score among participants was 23.7; sex, as well as type of higher qualification obtained, was found to be significantly associated with the score of knowledge. Conclusion: Knowledge toward epilepsy and epilepsy first aid among healthcare workers in Saudi Arabia was found fragile. Further research is appreciated to support the current findings.