Golden Hour Intravenous Thrombolysis for Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

OBJECTIVES: The benefits of intravenous thrombolysis are time-dependent, with maximum efficacy when administered within the first "golden" hour after onset. Nevertheless, the impact of golden hour thrombolysis has not been well quantified. METHODS: Medline, Embase, and Web of Science databases were systematically searched from inception to August 27, 2023. We included studies that reported safety and efficacy outcomes of ischemic stroke patients treated with intravenous thrombolysis in the golden hour versus later treatment window. The primary outcome was an excellent functional outcome, defined as a modified Rankin Scale score of 0-1 at 90 days. The secondary efficacy outcome was a good functional outcome (defined as modified Rankin Scale score of 0-2). The main safety outcome was symptomatic intracerebral hemorrhage. RESULTS: Seven studies involving 78,826 patients met the selection criteria. Golden hour thrombolysis was associated with higher odds of 90-day excellent functional outcomes (OR 1.40, 95% CI 1.16-1.67) and 90-day good functional outcomes (OR 1.38, 95% CI 1.13-1.69) compared with thrombolysis outside the golden hour. The number needed to treat to benefit for golden hour thrombolysis to reduce disability by at least 1 level on the modified Rankin Scale per patient was 2.6. Rates of symptomatic intracerebral hemorrhage and mortality were similar between groups. INTERPRETATION: Golden hour thrombolysis significantly improved acute ischemic stroke outcomes. The findings provide rationale for intensive efforts aimed at expediting thrombolytic therapy within the golden hour window following the onset of acute ischemic stroke. ANN NEUROL 2024;96:582-590.

Mechanisms of DNA Damage Response in Mammalian Oocytes.

DNA damage poses a significant challenge to all eukaryotic cells, leading to mutagenesis, genome instability and senescence. In somatic cells, the failure to repair damaged DNA can lead to cancer development, whereas, in oocytes, it can lead to ovarian dysfunction and infertility. The response of the cell to DNA damage entails a series of sequential and orchestrated events including sensing the DNA damage, activating DNA damage checkpoint, chromatin-related conformational changes, activating the DNA damage repair machinery and/or initiating the apoptotic cascade. This chapter focuses on how somatic cells and mammalian oocytes respond to DNA damage. Specifically, we will discuss how and why fully grown mammalian oocytes differ drastically from somatic cells and growing oocytes in their response to DNA damage.

First Measurement Using Elliptically Polarized Photons of the Double-Polarization Observable E for γp→pπ

We report the measurement of the helicity asymmetry E for the pπ^{0} and nπ^{+} final states using, for the first time, an elliptically polarized photon beam in combination with a longitudinally polarized target at the Crystal Ball experiment at MAMI. The results agree very well with data that were taken with a circularly polarized photon beam, showing that it is possible to simultaneously measure polarization observables that require linearly (e.g., G) and circularly polarized photons (e.g., E) and a longitudinally polarized target. The new data cover a photon energy range 270-1400 MeV for the pπ^{0} final state (230-842 MeV for the nπ^{+} final state) and the full range of pion polar angles, θ, providing the most precise measurement of the observable E. A moment analysis gives a clear observation of the pη cusp in the pπ^{0} final state.

The ruminant gut microbiome vs enteric methane emission: The essential microbes may help to mitigate the global methane crisis.

Ruminants release enteric methane into the atmosphere, significantly increasing greenhouse gas emissions and degrading the environment. A common focus of traditional mitigation efforts is on dietary management and manipulation, which may have limits in sustainability and efficacy, exploring the potential of essential microorganisms as a novel way to reduce intestinal methane emissions in ruminants; a topic that has garnered increased attention in recent years. Fermentation and feed digestion are significantly aided by essential microbes found in the rumen, such as bacteria, fungi, and archaea. The practical implications of the findings reported in various studies conducted on rumen gut concerning methane emissions may pave the way to understanding the mechanisms of CH4 production in the rumen to enhance cattle feed efficiency and mitigate CH4 emissions from livestock. This review discussed using essential bacteria to reduce intestinal methane emissions in ruminants. It investigates how particular microbial strains or consortia can alter rumen fermentation pathways to lower methane output while preserving the health and productivity of animals. We also describe the role of probiotics and prebiotics in managing methane emissions using microbial feed additives. Further, recent studies involving microbial interventions have been discussed. The use of new methods involving functional metagenomics and meta-transcriptomics for exploring the rumen microbiome structure has been highlighted. This review also emphasizes the challenges faced in altering the gut microbiome and future directions in this area.

A potent formula against triple-negative breast cancer-sorafenib-carbon nanotubes-folic acid: Targeting, apoptosis triggering, and bioavailability enhancing.

Triple-negative breast cancer (TNBC) has short survival rates. This study aimed to prepare a novel formula of sorafenib, carbon nanotubes (CNTs), and folic acid to be tested as a drug delivery system targeting versus TNBC compared with free sorafenib and to evaluate the formula stability, in vitro pharmacodynamic, and in vivo pharmacokinetic properties. The formula preparation was done by the synthesis of polyethylene glycol bis amine linker, CNT PEGylation, folic acid attachment, and sorafenib loading. The prepared formula has been characterized using X-ray diffraction, Flourier-transform infrared, 1HNMR, UV, high resolution-transmission electron microscope, field emission scanning electron microscopy, and Zeta potential. In vitro studies included drug release determination, MTT assay, flow cytometry to determine the apoptotic stage with percent, cell cycle analysis, and apoptotic marker assays for caspase-3, 8, 9, cytochrome c, and BCL-2. The in vivo study was performed to determine bioavailability and half-life in rats. The in vitro MTT antiproliferative assay revealed that the formula was threefold more cytotoxic toward TNBC cells than free sorafenib, and the flow cytometry showed a significant increase in apoptosis and necrosis. The formula has a greater inhibitory effect on BCL-2 and a lessening effect on cytochrome c and caspases 3, 8, and 9 than free sorafenib. In vivo experiments proved that our novel formula was superior to free sorafenib by increasing bioavailability by eight times and prolonging the half-life by three times. These results confirmed the successful preparation of the desired formula with better pharmacodynamic and pharmacokinetic properties. These promising results may show a novel therapeutic strategy for TNBC patients.

Periostin's role in uterine leiomyoma development: a mini-review on the potential periostin poses as a pharmacological intervention for uterine leiomyoma.

Uterine leiomyomas, also known as fibroids or myomas, occur in an estimated 70-80% of reproductive aged women. Many experience debilitating symptoms including pelvic pain, abnormal uterine bleeding (AUB), dyspareunia, dysmenorrhea, and infertility. Current treatment options are limited in preserving fertility, with many opting for sterilizing hysterectomy as a form of treatment. Currently, surgical interventions include hysterectomy, myomectomy, and uterine artery embolization in addition to endometrial ablation to control AUB. Non-surgical hormonal interventions, including GnRH agonists, are connotated with negative side effects and are unacceptable for women desiring fertility. Periostin, a regulatory extra cellular matrix (ECM) protein, has been found to be expressed in various gynecological diseases including leiomyomas. We previously determined that periostin over-expression in immortalized myometrial cells led to the development of a leiomyoma-like cellular phenotype. Periostin is induced by TGF-ß, signals through the PI3K/AKT pathway, induces collagen production, and mediates wound repair and fibrosis, all of which are implicated in leiomyoma pathology. Periostin has been linked to other gynecological diseases including ovarian cancer and endometriosis and is being investigated as pharmacological target for treating ovarian cancer, post-surgical scarring, and numerous other fibrotic conditions. In this review, we provide discussion linking pathological inflammation and wound repair, with a TGF-ß-periostin-collagen signaling in the pathogenesis of leiomyomas, and ultimately the potential of periostin as a druggable target to treat leiomyomas.

A novel urease-assisted ratiometric fluorescence sensing platform based on pH-modulated copper-quenched near-infrared carbon dots and methyl red-quenched red carbon dots for selective urea monitoring.

A novel and sensitive fluorescence ratiometric method is developed for urea detection based  on the pH-sensitive response of two fluorescent carbon dot (CD) systems: R-CDs/methyl red (MR) and NIR-CDs/Cu2+. The sensing mechanism involves breaking down urea using the enzyme urease, releasing ammonia and increasing pH. At higher pH, the fluorescence of NIR-CDs is quenched due to the enhanced interaction with Cu2+, while the fluorescence of R-CDs is restored as the acidic MR converts to its basic form, removing the inner filter effect. The ratiometric signal (F608/F750) of the R-CDs/MR and NIR-CDs/Cu2+ intensities changed in response to the pH induced by urea hydrolysis, enabling selective and sensitive urea detection. Detailed spectroscopic and morphological investigations confirmed the fluorescence probe design and elucidated the sensing mechanism. The method exhibited excellent sensitivity (0.00028 mM LOD) and linearity range (0.001 - 8.0 mM) for urea detection, with successful application in milk samples for monitoring adulteration, demonstrating negligible interference and high recovery levels (96.5% to 101.0%). This ratiometric fluorescence approach offers a robust strategy for selective urea sensing in complicated matrices.

Effect of Salvadora persica on resin-dentin bond stability.

BACKGROUND: The stability of resin-dentin interfaces is still highly questionable. The aim of this study was to evaluate the effect of Salvadora persica on resin-dentin bond durability. MATERIALS AND METHODS: Extracted human third molars were used to provide mid-coronal dentin, which was treated with 20% Salvadora persica extract for 1 min after acid-etching. Microtensile bond strength and interfacial nanoleakage were evaluated after 24 h and 6 months. A three-point flexure test was used to measure the stiffness of completely demineralized dentin sticks before and after treatment with Salvadora persica extract. The hydroxyproline release test was also used to measure collagen degradation by endogenous dentin proteases. Statistical analysis was performed using two-way ANOVA followed by post hoc Bonferroni test and unpaired t-test. P-values < 0.05 were considered statistically significant. RESULTS: The use of Salvadora persica as an additional primer with etch-and-rinse adhesive did not affect the immediate bond strengths and nanoleakage (p > 0.05). After 6 months, the bond strength of the control group decreased (p = 0.007), and nanoleakage increased (p = 0.006), while Salvadora persica group showed no significant difference in bond strength and nanoleakage compared to their 24 h groups (p > 0.05). Salvadora persica increased dentin stiffness and decreased collagen degradation (p < 0.001) compared to their controls. CONCLUSION: Salvadora persica extract pretreatment of acid-etched dentin preserved resin-dentin bonded interface for 6 months. CLINICAL SIGNIFICANCE: Durability of resin-dentin bonded interfaces is still highly questionable. Endogenous dentinal matrix metalloproteinases play an important role in degradation of dentinal collagen within such interfaces. Salvadora persica may preserve resin-dentin interfaces for longer periods of time contributing to greater clinical success and longevity of resin composite restorations.

Detecting white spot lesions on post-orthodontic oral photographs using deep learning based on the YOLOv5x algorithm: a pilot study.

BACKGROUND: Deep learning model trained on a large image dataset, can be used to detect and discriminate targets with similar but not identical appearances. The aim of this study is to evaluate the post-training performance of the CNN-based YOLOv5x algorithm in the detection of white spot lesions in post-orthodontic oral photographs using the limited data available and to make a preliminary study for fully automated models that can be clinically integrated in the future. METHODS: A total of 435 images in JPG format were uploaded into the CranioCatch labeling software and labeled white spot lesions. The labeled images were resized to 640 × 320 while maintaining their aspect ratio before model training. The labeled images were randomly divided into three groups (Training:349 images (1589 labels), Validation:43 images (181 labels), Test:43 images (215 labels)). YOLOv5x algorithm was used to perform deep learning. The segmentation performance of the tested model was visualized and analyzed using ROC analysis and a confusion matrix. True Positive (TP), False Positive (FP), and False Negative (FN) values were determined. RESULTS: Among the test group images, there were 133 TPs, 36 FPs, and 82 FNs. The model's performance metrics include precision, recall, and F1 score values of detecting white spot lesions were 0.786, 0.618, and 0.692. The AUC value obtained from the ROC analysis was 0.712. The mAP value obtained from the Precision-Recall curve graph was 0.425. CONCLUSIONS: The model's accuracy and sensitivity in detecting white spot lesions remained lower than expected for practical application, but is a promising and acceptable detection rate compared to previous study. The current study provides a preliminary insight to further improved by increasing the dataset for training, and applying modifications to the deep learning algorithm. CLINICAL REVELANCE: Deep learning systems can help clinicians to distinguish white spot lesions that may be missed during visual inspection.

Treatment with onion bulb extract both prevents and reverses allergic inflammation in a murine model of asthma.

CONTEXT: Asthma presents a global health challenge. The main pharmacotherapy is synthetic chemicals and biological-based drugs that are costly, and have significant side effects. In contrast, use of natural products, such as onion (Allium cepa L., Amaryllidaceae) in the treatment of airway diseases has increased world-wide because of their perceived efficacy and little safety concerns. However, their pharmacological actions remain largely uncharacterized. OBJECTIVE: We investigated whether onion bulb extract (OBE) can (1) reverse established asthma phenotype (therapeutic treatment) and/or (2) prevent the development of the asthma phenotype, if given before the immunization process (preventative treatment). MATERIALS AND METHODS: Six groups of male Balb/c mice were established for the therapeutic (21 days) and five groups for the preventative (19 days) treatment protocols; including PBS and house dust mite (HDM)-challenged mice treated with vehicle or OBE (30, 60, and 100 mg/kg/i.p.). Airways inflammation was determined using cytology, histology, immunofluorescence, Western blot, and serum IgE. RESULTS: Therapeutic (60 mg/kg/i.p.) and preventative (100 mg/kg/i.p.) OBE treatment resulted in down-regulation of HDM-induced airway cellular influx, histopathological changes and the increase in expression of pro-inflammatory signaling pathway EGFR, ERK1/2, AKT, pro-inflammatory cytokines and serum IgE. DISCUSSION AND CONCLUSION: Our data show that OBE is an effective anti-inflammatory agent with both therapeutic and preventative anti-asthma effects. These findings imply that onion/OBE may be used as an adjunct therapeutic agent in established asthma and/or to prevent development of allergic asthma. However, further studies to identify the active constituents, and demonstrate proof-of-concept in humans are needed.

Closing the loop: Strengthening course quality of Pharm.D. program via applying a comprehensive four-step review approach.

This study explores the course review process implemented by the College of Pharmacy at King Saud University for its Pharm.D. program. Through a qualitative research design, a dedicated course review committee was established to oversee the evaluation process. The committee gathered and analyzed data from various sources, including course reports, student evaluations, and exam center reports, to achieve a holistic understanding of each course's effectiveness. The evaluation process was structured into a Four-Step Course Evaluation Approach: data collection, data review and recommendations, taking appropriate action, and communicating the outcomes. The "closing the loop" stage ensured that recommendations were effectively implemented, and course evaluation data were systematically archived for future reference. The results of this study, based on the evaluation of 25 courses, revealed significant improvements in course quality, alignment with program learning outcomes, and adherence to accreditation standards. Key findings included the identification of gaps and discrepancies, leading to targeted interventions and enhanced course content. Overall, this study highlights the effectiveness of a structured course review process in enhancing the quality of education and ensuring continuous improvement within the college. The committee focuses on refining evaluation criteria, conducting workshops, and providing training to stay current with emerging accreditation standards and best practices. This systematic course review process demonstrates the College's commitment to providing high-quality education and preparing students for successful careers in pharmacy, with significant implications for the improvement of pharmacy education and the overall student learning experience.

The effect of inhibiting hindbrain A2 noradrenergic neurons by 6-Hydroxydopamine on lipopolysaccharide-treated male rats autistic animal model.

Autism spectrum disorder (ASD) is a complex neurodevelopmental illness that often emerges in early childhood. The incidence of ASD has shown a notable rise in recent years. ASD is defined by deficits in social communication, and presence of rigid and repetitive behaviors and interests. The underlying mechanisms of ASD remain elusive. Multiple studies have documented the presence of neuroinflammation and increased levels of inflammatory cytokines, specifically, IL-6, TNF, and NF-κB, in various brain regions, including the prefrontal cortex (PFC) and hippocampus in individuals with ASD. Noradrenergic neurons play a crucial role in brain development and the regulation of motor, behavioral, and memory functions. This study sought to examine the impact of intracerebroventricular (icv.) injection of the neurotoxin, 6-hydroxydopamine (6-OHDA), in the caudal dorsal vagal complex A2 neurons on various neuroinflammatory pathways at the hippocampus and PFC in valproic acid (VPA) autistic animal model. This was done in conjunction with an intraperitoneal (i.p.) injection of Lipopolysaccharides (LPS) in animal models with VPA-induced autism. We specifically examined the impact of the caudal fourth ventricle 6-OHDA icv. injection and LPS (i.p.) injection on self-grooming behavior. We measured the mRNA expression of IL-6, TNF-a, and NF-κB using qRT-PCR, and the protein expression of COX-2, GPX-1, p-AMPK, and AMPK using western blot analysis. The self-grooming activity was considerably higher in the combined treatment group (6-OHDA icv. + LPS i.p.) compared to the control group. A substantial increase observed in the expression of IL-6, TNF-α, and NF-κB genes in the PFC of the treatment group that received icv. Administration of 6-OHDA, compared to the control group. The VPA-autism rats that received the combo treatment exhibited a slight increase in the expression level of NF-κB gene in the hippocampus, compared to the control group. At the PFC, we noticed a substantial drop in the expression of the antioxidant protein GPX-1 in the group that received the combo treatment compared to the control group. Our data investigates a novel aspect that the 6-OHDA-induced inhibition of hindbrain A2 neurons could be influencing the neuroinflammatory pathways in the PFC and hippocampus of autistic animal models.

Time to involve the multiple sclerosis expert community at large when revising the McDonald diagnostic criteria.

Prof. Kurtzke once said, "Multiple sclerosis is what a good clinician would call multiple sclerosis." Recent McDonald's diagnostic criteria revisions have allowed for earlier diagnoses over the past decades. Revisions often allowed increasing sensitivity but at the expense of lowering specificity. In this correspondence, I suggest that the multiple sclerosis expert community worldwide should be given the opportunity to comment and provide feedback on the proposed revisions of the diagnostic criteria before their publication via providing a duration where open commentaries are welcomed to allow for the expert panel to incorporate diverse feedback to improve the final product.

Fostering innovation and sustainable thinking in surgery: an evaluation of a surgical hackathon.

INTRODUCTION: Surgery represents a major source of carbon emissions, with numerous initiatives promoting more sustainable practices. Healthcare innovation and the development of a digitally capable workforce are fundamental in leveraging technologies to tackle challenges, including sustainability in surgery. METHODS: A surgical hackathon was organised with three major themes: (1) how to make surgery greener, (2) the future of plastic surgery in 10 years, and (3) improving healthcare outcomes using machine learning. Lectures were given on sustainability and innovation using the problem, innovation, market size, strategy and team (PIMST) framework to support their presentations, as well as technological support to translate ideas into simulations or minimum viable products. Pre- and post-event questionnaires were circulated to participants. RESULTS: Most attendees were medical students (65%), although doctors and engineers were also present. There was a significant increase in delegates' confidence in approaching innovation in surgery (+20%, p < 0.001). Reducing waste packaging (70%), promoting recyclable material usage (56%) and the social media dimension of public perceptions towards plastic surgery (40%) were reported as the most important issues arising from the hackathon. The top three prizes went to initiatives promoting an artificial intelligence-enhanced operative pathway, instrument sterilisation and an educational platform to teach students research and innovation skills. CONCLUSIONS: Surgical hackathons can result in significant improvements in confidence in approaching innovation, as well as raising awareness of important healthcare challenges. Future innovation events may build on this to continue to empower the future workforce to leverage technologies to tackle healthcare challenges such as sustainability.

A unified exponential-H family for modeling real-life data: Properties and inference.

The exponential distribution is one of the most widely used statistical distribution for reliability issues. In this paper, we introduce a novel family based on the exponential model, called the new exponential-H (NEx-H) family. The sub-models of the NEx-H family are capable of accommodating variable failure rates, as well as unimodal, bimodal, left-skewed, symmetric, right-skewed, and J-shape densities. The mathematical features of the NEx-H family are derived. The parameters of the NEx-Weibull distribution are estimated by using seven estimation methods. Detailed numerical simulations are presented. Based on our study, the maximum likelihood is the best estimation method for estimating the NEx-Weibull parameters. Three real-life data sets are fitted using the NEx-Weibull distribution. The NEx-Weibull model provides better fit as compared to some competing Weibull models.

Identification of some variable parameters in serum of COVID-19 patients in comparison with control group.

The study intended to determine the correlation among coronavirus disease 2019 (COVID-19) infection and variable abnormalities in liver function test, lipids, and thyroid hormones. The study included 160 infected COVID-19 patients (80 females and 80 male) and 100 subjects as a control group (50 females and 50 males), attended the Al-Sader Medical City in Al-Najaf, Iraq during the period between January 2021 to October 2021. The patients' age ranged from 16-80 years old. Liver enzymes, lipid profile and thyroid hormone were tested. The results revealed a significant increase in liver function levels including alanine transaminase, aspartate aminotransferase, alkaline phosphatase, and Albumin (p < 0.05). Also, there was an increase in lipids levels including total cholesterol, low-density lipoprotein, and triglycerides. The result showed significant difference in levels of thyroid hormones triiodothyronine, thyroxine and thyroid stimulating hormone between COVID-19 infected patients and the control group. As well the antithyroid antibodies (thyroglobulin antibody, thyroid peroxidase antibody and thyrotropin receptor antibodies) were increased. There was a correlation between increasing thyroid hormones and their antibodies with infection by COVID-19. This study concluded that COVID-19 infection can induce disturbances in liver and thyroid function tests and changes in the lipid metabolism.

Increased healthcare utilization in the year before multiple sclerosis diagnosis.

BACKGROUND: Studies have suggested possible multiple sclerosis (MS) prodrome with non-routine healthcare utilization as an indicator. The objective of this project was to compare utilization in the four years (years -1, -2, -3, -4) before clinically definite diagnosis and examine demographic associations. METHODS: i2B2 database search at the Medical College of Wisconsin Comprehensive MS center yielded 613 patients between 07/01/2018 and 07/01/2022. Patients with established MS diagnosis, MS mimicker diagnoses, and pediatric-onset MS were excluded; 108 met the criteria for adult patients ≥ 18 years of age newly diagnosed with clinically definite MS after manual chart review. Utilization score for each of the four years before diagnosis was calculated; demographic variables were also collected. Adjusted repeated measures mixed model and Pearson correlation analysis were performed; P value was set at <0.05 for statistical significance. RESULTS: Utilization was greatest for year -1 compared to years -2, -3, and -4 after demographics adjustment (p < 0.001). Utilization was greater (p < 0.05) for older age and unmarried, patients. CONCLUSIONS: Utilization increased a year before formal MS diagnosis, suggestive of prodromal presentation.

Impact of neuromyelitis optica spectrum disorder on employment and income in the United States.

BACKGROUND AND OBJECTIVES: We aim to characterize the sociodemographic and clinical factors associated with loss of jobs, income, and work hours in people with neuromyelitis optica spectrum disorder (NMOSD) in the United States. METHODS: A REDCap-based survey was administered to working-age NMOSD patients (18-70 years old) querying demographic information, symptoms, immunosuppression, work hours, income, and caregiver work (11/2022-07/2023). Regression models were developed using MATLAB. RESULTS: Of 127 participants (97 female; 55% AQP4-antibody, 19% MOG antibody; 69% Caucasian, 7% Hispanic), with an average diagnosis age of 38.7 years, average disease duration of 6.4 years, mean 3.1 attacks, and 94% of whom were treated with immune system-directed therapy (53% rituximab, 8% satralizumab, 7% eculizumab, 6% mycophenolate mofetil, 4% inebilizumab, 2% azathioprine, 10% IVIg, 10% other), 56% lost a job due to NMOSD. Employment decreased 12% (80% pre- to 68% post-diagnosis). Thirty-six percent of participants said they no longer worked outside the home. Significant predictors for post-NMOSD diagnosis employment status included younger age, lower pain level, no walking aids, and having a job prediagnosis. Sixty-eight percent of those employed prediagnosis reduced their work hours, dropping an average of 18.4 h per month since being diagnosed (±10.1 h). Average annual income grew slowly at $1998 during the average 6.4 years of disease duration (14% of the value predicted by the U.S. Bureau of Labor Statistics). Sixty percent of participants had a regular unpaid caregiver; 34% of caregivers changed their work hours or job to help manage NMOSD. DISCUSSION: We provide a structured analysis of the impact of NMOSD on employment, work hours, and income in the United States, demonstrating its major effect on the livelihoods of patients and their caregivers.

An analysis of suicidal and self-injurious behavior reports with antiseizure medications in the FDA adverse event database.

BACKGROUND: Pharmacovigilance systems such as the FDA Adverse Event Reporting System (FAERS), are established models for adverse event surveillance that may have been missed during clinical trials. We aimed to analyze twenty-five anti-seizure medications (ASMs) in FAERS to assess for increased reporting of suicidal and self-injurious behavior. METHODS: Twenty-five ASMs were analyzed: brivaracetam, cannabidiol, carbamazepine, clobazam, clonazepam, diazepam, eslicarbazepine, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, perampanel, phenobarbital, phenytoin, pregabalin, primidone, rufinamide, stiripentol, tiagabine, topiramate, valproate, vigabatrin, zonisamide. Reports of "suicidal and self-injurious behavior" were collected from January 1, 2004, to December 31, 2020, using OpenVigil 2.1 tool with indication as "Epilepsy". Relative reporting ratio, proportional reporting ratio, and reporting odds ratio were calculated utilizing all other drug reports for epilepsy patients as a control. RESULTS: Significant relative operating ratio, ROR (greater than 1, p<0.05) were observed for diazepam (2.909), pregabalin (2.739), brivaracetam (2.462), gabapentin (2.185), clonazepam (1.649), zonisamide (1.462), lacosamide (1.333), and levetiracetam (1.286). CONCLUSIONS: Of the 25 ASMs that were analyzed in this study, 4 (16%) were identified to have been linked with a likely true adverse event. These drugs included diazepam, brivaracetam, gabapenetin, and pregabalin. Although several limitations are present with the FAERS database, it is imperative to closely monitor patient comorbidities for increased risk of suicidality with the use of several ASMs.

Craniofacial and Airway Morphology in Down Syndrome: A Cone Beam Computed Tomography Case Series Evaluation.

Background: Down syndrome (DS) is a genetic condition characterized by an extra copy of chromosome 21, resulting in various physical and cognitive features. This study aimed to comprehensively analyze the dental and craniofacial morphology of individuals with DS using Cone Beam Computed Tomography (CBCT). Methods: Six individuals with DS, comprising five males and one female aged 17 to 35 years, underwent CBCT scanning. Radiographic assessments included dentition, occlusion, paranasal sinuses, airway, skull bones, and suture calcification. Linear and angular cephalometric measurements were performed, and airway analysis was conducted using Dolphin 3D imaging software v.11. Results: The study revealed prognathic maxilla in five patients, prognathic mandible in four, and bimaxillary protrusion in two. Dental findings included microdontia, enamel hypoplasia, and congenitally missing teeth, with maxillary and mandibular third molars most commonly absent. Sinus abnormalities, delayed suture closure, and cervical spine anomalies were also observed. Conclusion: These findings contribute to a deeper understanding of DS-related craniofacial characteristics and emphasize the importance of considering these morphometric features in clinical management strategies for individuals with DS. This study's limited sample size underscores the significance of radiographic assessment in planning interventions such as cosmetic reconstructions, prosthetic rehabilitation, or orthodontic treatment for individuals with DS.