The Utility of the Platelet-Albumin-Bilirubin Score as a Non-invasive Predictor of Esophageal Varices and Variceal Hemorrhage in Patients With Liver Cirrhosis Compared to Child-Turcotte-Pugh and Model of End-Stage Liver Disease-Sodium Scores.

Introduction Research on non-invasive tools for detecting gastro-esophageal varices is underway. We investigated the Platelet-Albumin-Bilirubin (PALBI) score in comparison with the Child-Turcotte-Pugh (CTP) and MELD-Na (MELD-Na) scores in patients with liver cirrhosis. Methods Three hundred and twenty-three patients with liver cirrhosis were studied. The PALBI, CTP and MELD-Na scores were calculated and analyzed for gastroesophageal varices and their characteristics using SPSS version 26 (IBM Corp., Armonk, NY, USA). Results Two hundred and sixty-four patients had esophageal varices and 102 presented with variceal hemorrhage. Mean PALBI, CTP and MELD-Na scores were significantly higher for patients with varices versus without varices (p < 0.05). Unlike the mean MELD-Na score, the mean PALBI and CTP scores were significantly higher in patients with large high-risk varices as compared to patients with small low-risk varices (p < 0.05). The mean CTP scores were significantly higher in patients with variceal hemorrhage than those without hemorrhage (p < 0.05), while the difference between mean PALBI and MELD-Na was insignificant, in this regard. The PALBI score had better sensitivity than the CTP and MELD-Na scores in indicating the presence of varices but was similar to the CTP score in predicting high-risk varices. Conclusion The PALBI score proves to have good utility and efficiency in predicting varices in comparison to CTP and MELD-Na scores. It can determine high-risk stigmata of variceal hemorrhage with similar performance as the CTP Score.

Variants of NAV3, a neuronal morphogenesis protein, cause intellectual disability, developmental delay, and microcephaly.

Microtubule associated proteins (MAPs) are widely expressed in the central nervous system, and have established roles in cell proliferation, myelination, neurite formation, axon specification, outgrowth, dendrite, and synapse formation. We report eleven individuals from seven families harboring predicted pathogenic biallelic, de novo, and heterozygous variants in the NAV3 gene, which encodes the microtubule positive tip protein neuron navigator 3 (NAV3). All affected individuals have intellectual disability (ID), microcephaly, skeletal deformities, ocular anomalies, and behavioral issues. In mouse brain, Nav3 is expressed throughout the nervous system, with more prominent signatures in postmitotic, excitatory, inhibiting, and sensory neurons. When overexpressed in HEK293T and COS7 cells, pathogenic variants impaired NAV3 ability to stabilize microtubules. Further, knocking-down nav3 in zebrafish led to severe morphological defects, microcephaly, impaired neuronal growth, and behavioral impairment, which were rescued with co-injection of WT NAV3 mRNA and not by transcripts encoding the pathogenic variants. Our findings establish the role of NAV3 in neurodevelopmental disorders, and reveal its involvement in neuronal morphogenesis, and neuromuscular responses.

Association of Genetic Polymorphism rs 77630697(Gly64Asp) of Multidrug and Toxin Extrusion -1 with glycemic response to metformin in patients with Type 2 Diabetes Mellitus.

Objective: To determine the relationship between Gly64Asp (rs77630697) polymorphism of multidrug and toxin extrusion-1 (MATE-1) and therapeutic response of metformin in Type-2 diabetic patients. Methods: A longitudinal study was conducted at Riphah International Hospital, Islamabad from June 2020 to December 2021. Type-2 diabetic patients (n=200) on metformin monotherapy fulfilling the inclusion criteria were enrolled and followed up till three months. Based on change in HbA1c, they were divided into responders and non-responders. DNA was extracted and genotyping was done by TETRA ARMS PCR. Data was entered and association was analyzed by SPSS 22. Results: Out of 200 participants, 104 were categorized as responders and 96 as non-responders. The genotype and allelic distribution of rs77630697 was significantly different between responders and non-responders. The variant genotype (GG) was most prevalent among the study population and among responders. After follow up of three months, difference in glycemic response was found to be statistically significant (p < 0.05) among three genotypes (GG, GA and AA). The decline in HbA1c was highest in GG genotype with almost two-fold reduction in comparison with GA and AA. Carriers of allele A were significantly associated with impaired response to metformin. Conclusion: The variable therapeutic response to metformin in the responders and non-responders may be contributed to rs77630697 isoform variation of MATE-1.

Radiographic Evaluation of Regenerative Endodontic Procedures and Apexification Treatments with the Assessment of External Root Resorption.

INTRODUCTION: This multi-centered cohort study evaluated the radiographic outcomes of regenerative endodontic procedures (REPs) and apexification treatments (APEX) of immature teeth with endodontic disease. MATERIALS AND METHODS: This cohort study included a retrospective record review and prospective data collection of pediatric patients with teeth treated with REPs or APEX between 2005-2014. Data including the presence of a periapical lesion, external root resorption (ERR), obliteration, apical hard tissue, apical closure, intracanal calcifications, and radiographic root area (RRA) change based on measurements were collected/measured from radiographic images. Univariate and multivariate analyses were conducted. RESULTS: The cohort included 190 subjects (204 teeth (92 REPs; 112 APEX)). The frequency of pre-treatment periapical pathology was similar between cases in which the clinical treatment failed versus successful treatment cases. However, the frequency of pre-treatment ERR was higher in failed cases than in successful cases (p=0.007). The mean RRA change was greater than twenty percent in 21% of the REPs cases. In traumatized teeth, REP treatment resulted in less hard tissue formation than other endodontic disease etiologies measured by RRA (p=0.001). 53% of cases with ERR (16/30) showed signs of healing/arrest and were mostly treated with REPs (11/16). CONCLUSIONS: The presence of ERR negatively affected the treatment outcome. There was significant variability in RRA change in REPs. Signs of healing/arrest of the resorptive lesion were radiographically visible in many cases treated with REPs.

Reverse Koebner Phenomenon in a Vitiligo Patient Treated With Radiotherapy.

Radiation-induced hypopigmentation resulting in a skin condition similar to vitiligo is evident in limited studies. In contrast to the typical Koebner phenomenon where new lesions develop at the site of injury, the trauma-induced disappearance of a specific rash in a patient with an already-developed skin disease is seen very rarely. This phenomenon is called "reverse Koebnerization" or "Koebner non-reaction." Herein, we submit a case of a 51-year-old female with already-developed vitiligo who came for treatment for carcinoma of the tongue with radiation therapy. Later, after the treatment, the patient developed a re-pigmentation of her skin.

A Missense Variant in HACE1 Is Associated with Intellectual Disability, Epilepsy, Spasticity, and Psychomotor Impairment in a Pakistani Kindred.

Intellectual disability (ID), which affects around 2% to 3% of the population, accounts for 0.63% of the overall prevalence of neurodevelopmental disorders (NDD). ID is characterized by limitations in a person's intellectual and adaptive functioning, and is caused by pathogenic variants in more than 1000 genes. Here, we report a rare missense variant (c.350T>C; p.(Leu117Ser)) in HACE1 segregating with NDD syndrome with clinical features including ID, epilepsy, spasticity, global developmental delay, and psychomotor impairment in two siblings of a consanguineous Pakistani kindred. HACE1 encodes a HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1 (HACE1), which is involved in protein ubiquitination, localization, and cell division. HACE1 is also predicted to interact with several proteins that have been previously implicated in the ID phenotype in humans. The p.(Leu117Ser) variant replaces an evolutionarily conserved residue of HACE1 and is predicted to be deleterious by various in silico algorithms. Previously, eleven protein truncating variants of HACE1 have been reported in individuals with NDD. However, to our knowledge, p.(Leu117Ser) is the second missense variant in HACE1 found in an individual with NDD.

Generation of induced pluripotent stem cell lines from two unrelated patients affected by intellectual disability carrying homozygous variants in SGIP1.

Intellectual disability (ID) is a diverse neurodevelopmental condition and almost half of the cases have a genetic etiology. SGIP1 acts as an endocytic protein that influences the signaling of receptors in neuronal systems related to energy homeostasis through its interaction with endophilins. This study focuses on the generation and characterization of induced pluripotent stem cells (iPSC) from two unrelated patients due to a frameshift variant (c.764dupA, NM_032291.4) and a splice donor site variant (c.74 + 1G > A, NM_032291.4) in the SGIP1 gene.

Assessment of Prevalence and Causative Factors for Replacement of Composite and Amalgam Restorations: An Observational Study.

Aim: This study intends to evaluate the frequency and causes of replacement for failed amalgam and composite dental restorations. Methodology: A cross-sectional study comprising female patients with failed permanent composite and amalgam restorations aged 15-60 years old was carried out at the dental clinics of Qassim University. Using a self-structured proforma, demographic data and causes for restoration failure were recorded. The effectiveness of the restorations was assessed by using the Ryge criteria after performing clinical and radiographic examinations. The Statistical Package for Social Science was used for the statistical analysis. Results: It is found that 84.6% of the 299 unsuccessful restorations examined were composite, and 15.4% were amalgam. The main reason for dental failure for both amalgam (95.6%) and composite (93.28%) restorations was secondary caries. Failure of amalgam restoration was largely caused by poor marginal adaptation. With varied incidences between amalgam and composite restorations, typical complaints included discomfort, sensitivity, pain, and food impaction with soreness. The main justification for replacement in amalgam restorations was sensitivity. Repair and replacement rates were similar for amalgam, composite, and mandibular/maxillary restorations. Moreover, 21.1% of individuals overall reported no symptoms, with 8.7% in the amalgam group and 23.3% in the composite group with significant differences (χ2 = 34.28, P = 0.001). Conclusion: According to the current study, secondary caries was found to be the main reason for both amalgam and composite restoration failure. The main problems reported were sensitivity, discomfort, and pain with amalgam showing more sensitivity-related failures.

Homozygous novel truncating variant of CLPP associated with severe Perrault syndrome.

A female proband and her affected niece are homozygous for a novel frameshift variant of CLPP. The proband was diagnosed with severe Perrault syndrome encompassing hearing loss, primary ovarian insufficiency, abnormal brain white matter and developmental delay.

AI-Enabled Crop Management Framework for Pest Detection Using Visual Sensor Data.

Our research focuses on addressing the challenge of crop diseases and pest infestations in agriculture by utilizing UAV technology for improved crop monitoring through unmanned aerial vehicles (UAVs) and enhancing the detection and classification of agricultural pests. Traditional approaches often require arduous manual feature extraction or computationally demanding deep learning (DL) techniques. To address this, we introduce an optimized model tailored specifically for UAV-based applications. Our alterations to the YOLOv5s model, which include advanced attention modules, expanded cross-stage partial network (CSP) modules, and refined multiscale feature extraction mechanisms, enable precise pest detection and classification. Inspired by the efficiency and versatility of UAVs, our study strives to revolutionize pest management in sustainable agriculture while also detecting and preventing crop diseases. We conducted rigorous testing on a medium-scale dataset, identifying five agricultural pests, namely ants, grasshoppers, palm weevils, shield bugs, and wasps. Our comprehensive experimental analysis showcases superior performance compared to various YOLOv5 model versions. The proposed model obtained higher performance, with an average precision of 96.0%, an average recall of 93.0%, and a mean average precision (mAP) of 95.0%. Furthermore, the inherent capabilities of UAVs, combined with the YOLOv5s model tested here, could offer a reliable solution for real-time pest detection, demonstrating significant potential to optimize and improve agricultural production within a drone-centric ecosystem.

Toward a Vision-Based Intelligent System: A Stacked Encoded Deep Learning Framework for Sign Language Recognition.

Sign language recognition, an essential interface between the hearing and deaf-mute communities, faces challenges with high false positive rates and computational costs, even with the use of advanced deep learning techniques. Our proposed solution is a stacked encoded model, combining artificial intelligence (AI) with the Internet of Things (IoT), which refines feature extraction and classification to overcome these challenges. We leverage a lightweight backbone model for preliminary feature extraction and use stacked autoencoders to further refine these features. Our approach harnesses the scalability of big data, showing notable improvement in accuracy, precision, recall, F1-score, and complexity analysis. Our model's effectiveness is demonstrated through testing on the ArSL2018 benchmark dataset, showcasing superior performance compared to state-of-the-art approaches. Additional validation through an ablation study with pre-trained convolutional neural network (CNN) models affirms our model's efficacy across all evaluation metrics. Our work paves the way for the sustainable development of high-performing, IoT-based sign-language-recognition applications.

Identifying the Incidence, Predictors, Outcomes, and Prevention of Stent Thrombosis (ST) in Post-percutaneous Coronary Revascularization Patients With Drug-Eluting Stents (DES): A Systematic Review.

Stent thrombosis (ST) is a rare but catastrophic event to happen to a stented coronary artery. The incidence of ST has greatly been reduced after the advent of modern drug-eluting stent (DES) implants, which have become the most preferred treatment option in the stenting category for coronary artery disease (CAD). Although the risk reduction by newer category implant provides substantial benefits, the possibility of thrombosis still exists mostly during the early stage of DES implantation. The development of ST after percutaneous coronary intervention (PCI) can be predicted by multiple factors, but advancements in early diagnostic techniques and modified stent types have greatly reduced the occurrence of this complication. Mortality, which is one of the complications of ST, is primarily influenced by patient-related factors such as incomplete treatment duration of dual antiplatelet therapy (DAPT). The duration of DAPT after DES implantation in patients with acute coronary syndrome (ACS) is determined based on individual characteristics, mainly considered in view of bleeding or ischemia risk. Risk evaluation systems like DAPT/precise-DAPT scores help tailor and personalize the duration of DAPT for each individual patient. This systematic review contains pertinent articles extracted from the PubMed database. We retrieved articles from various study categories, encompassing publications from the period spanning 2014 to 2022. Our analysis highlighted results from studies investigating different aspects contributing to ST development. The most favorable prevention option was the use of customized DAPT intervention based on patient-specific predictable factors. Several complications associated with ST were identified, including recurrent ST, major adverse cardiovascular events (MACE) encompassing all-cause mortality (including cardiac and non-cardiac mortality), cerebrovascular accidents (CVA) or transient ischemic attacks (TIA), hospitalization due to heart failure, and myocardial infarction requiring revascularization. Mortality was also observed as a significant outcome. The umbrella term of ST includes multiple causative factors. Although DES has improved patient survival rates vastly with its usage, careful risk factor assessment and required follow-up, in each individual being stented, further guarantee a more promising reduction in late adverse outcomes.

Undergraduate Students' and Interns' Perception towards Learning Environment at Dental Clinics, Qassim University, Saudi Arabia.

Background: Dental clinical educational environment plays a critical part in the inculcation of skills and enhancement of knowledge for the dental students. The objective was to assess undergraduate dental students' and interns' perceptions towards the clinical learning environment. Methods: Current cross-sectional study was conducted from December 2020 to February 2021, using the 24-item dental clinical learning environment inventory (DECLEI) on a six point Likert scale. The possible range of cumulative score for DECLEI was from 0 to 100 (interpretation poor to excellent). The inventory was emailed to 111 students and interns at College of Dentistry, Qassim University. The relationship between the independent variables and DECLEI scores was determined by using Pearson correlation test. SPSS version-23 was used for statistical analysis. Results: Overall response rate was 78.37%. The mean DECLEI score was noted as 67.5 ± 17.98. Among the factors, the highest mean score was documented for the systematic self-evaluation and the lowest mean score was observed for the item related to patients' punctuality for appointments. A factor-wise analysis of three subscales of DECLEI demonstrated the respondents had good perception towards all subscales with the highest mean score (72.3 ± 18.06) for Factor III and lowest mean score (61.3 ± 19.81) for Factor II. Overall, the DECELI was found to be reliable with the Cronbach's Alpha value of 0.94. The Pearson's correlation test showed the weak positive insignificant correlation of mean DECLEI score with gender and categories. Conclusions: Present study indicated more positive than negative perceptions of the dental students related to their clinical learning environment. The DECLEI helped in recognizing both strengths and shortcomings of the dental clinical learning environment.

Fingolimod-Associated Macular Edema in the Treatment of Multiple Sclerosis.

Multiple sclerosis is a neurological disorder categorized by inflammatory processes with a high prevalence worldwide. It affects both motor and sensory pathways and is also associated with the visual pathway. Fingolimod is a commonly used drug for relapsing-remitting multiple sclerosis. It is a sphingosine 1-phosphate modulator acting on its receptors for immune cell accumulation, neuronal function, embryological development, vascular permeability, smooth muscle cell function, and endothelial barrier maintenance. This review aims to understand the processes, mechanisms, risks, and management of fingolimod-associated macular edema. Due to the anti-inflammatory properties of fingolimod, it decreases various cytokines, including interleukin (IL)-1B and IL-6, spike wave, and spike amplitude, in electrophysiological activities and decreases insoluble receptors for advanced glycation end product ligand. A daily dosage of 0.5 mg of fingolimod has an increased association with macular edema. The serious adverse events of fingolimod are lymphopenia, cardiovascular events, ocular events, and carcinoma. Fingolimod decreases brain volume and increases vascular permeability, resulting in increased macular volume and damage to the blood-retinal barrier, which causes an increased risk for macular edema. Cystoid macular edema is more common in older individuals suffering from comorbidities affecting the retina, such as diabetes, or those undergoing ophthalmological surgeries. This review also highlights the importance of regular ophthalmology examinations on patients consuming fingolimod both in the initial stages and chronic use. The treatment options for macular edema include nonsteroidal anti-inflammatory drugs, acetazolamide, triamcinolone, ketorolac, corticosteroids, and intravitreal procedures.

Anxiety and depression amongst youth as adverse effects of using social media : A Review.

Social media use has become widely popularized in modern society and because of that, human interactions have drastically changed. In parallel, depression and anxiety have reached unprecedented levels among the youth, and concerns have emerged on social media use compromising mental health. The objectives of our review are to explore if there is a relation between social media and the development of those two disorders among youth, to highlight the patterns that could lead to them, and to give recommendations for future research. Methods: Based on the Scale for the Assessment of Narrative Review Articles (SANRA) Criteria, the authors performed a search of all-time articles published in the Medline database using terms such as social media, social media use, problematic social media use, depression, anxiety, suicidality, self-harm, fear of missing out, cyberchondria, cyberbullying, sexting, and online shopping. The initial search yielded 184 924 articles. After review, 77 articles were included for discussion. Results: Social media use is often associated with depression and anxiety. Different patterns are thought to predict poorer mental health outcomes like multitasking, emotional investment, appearance-based activities, passive media use, problematic social media use, cyberbullying, sexting, and disaster awareness. Conclusion: Specific patterns of engagement with social media appear to be associated with poor mental health outcomes in youth. It is important for physicians to address social networks exposure in well-visits and for parents to communicate about it openly. However, more in-depth research needs to be done to determine a relation of causality.

Evaluation of Efficacy of Cannabis Use in Patients With Attention Deficit Hyperactivity Disorder: A Systematic Review.

Cannabis is frequently used by people who self-medicate for the signs of mental health conditions. Attention-deficit/hyperactivity disorder (ADHD), a neurodevelopmental illness, has been linked to increased cannabis use. However, compared to other mental disorders, cannabis use by people with ADHD has received much less research. The main goal of this systematic review was to understand the nature of the relationships between cannabis use and ADHD symptoms. We used Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to conduct the systematic review. We included papers published within the previous ten years from online searches on PubMed, PubMed Central (PMC), Google Scholar, and ScienceDirect until January 1st, 2023. The inclusion-exclusion criteria led to the initial selection of 136 studies. We selected twenty research articles after screening and assessing them using quality assessment techniques. These articles included two non-randomized control trials, one cross-sectional study, one meta-analysis, and sixteen observational cohorts. It can be advantageous for people with ADHD and their medical professionals to understand better how ADHD patients use cannabis and its potential risks and advantages on cannabis use disorder, ADHD symptoms, and executive dysfunction. This article further emphasizes the necessity of thorough research to comprehend cannabis use in ADHD patients.

In vivo effects of the alpha-synuclein misfolding inhibitor minzasolmin supports clinical development in Parkinson's disease.

Direct targeting of alpha-synuclein (ASYN) has emerged as a disease-modifying strategy for Parkinson's disease and other synucleinopathies which is being approached using both small molecule compounds and ASYN-targeted biologics. Minzasolmin (UCB0599) is an orally bioavailable and brain-penetrant small molecule ASYN misfolding inhibitor in clinical development as a disease-modifying therapeutic for Parkinson's disease. Herein the results of preclinical evaluations of minzasolmin that formed the basis for subsequent clinical development are described. Pharmacokinetic evaluations of intraperitoneal 1 and 5 mg/kg minzasolmin in wildtype mice revealed parallel and dose-proportional exposures in brain and plasma. Three-month administration studies in the Line 61 transgenic mouse model of PD were conducted to measure ASYN pathology and other PD-relevant endpoints including markers of CNS inflammation, striatal DAT labeling and gait. Reductions in ASYN pathology were correlated with improved aspects of gait and balance, reductions in CNS inflammation marker abundance, and normalized striatal DAT levels. These findings provide support for human dose determinations and have informed the translational strategy for clinical trial design and biomarker selection for the ongoing clinical studies of minzasolmin in patients living with early-stage Parkinson's disease (ClinicalTrials.gov ID: NCT04658186; EudraCT Number 2020-003265).

A comparative study on effect of heat stress on physiological and cellular responses of crossbred cattle and riverine buffalo in subtropical region of India.

The study was carried out to compare the in vitro and in vivo heat shock responses of cattle and buffaloes. The expression of heat responsive genes (HSP70 and HSF family) were studied in vitro in peripheral blood mononuclear cells (PBMCs) of cattle and buffalo. In vivo observations on animals were carried out to investigate the physiological responses of cattle and buffalo at different THI over a period of 14 months. The study indicated that onset and severity of heat stress at different THI varied significantly between cattle and buffalo. Rectal temperature (RT) showed a significant (p < 0.05) increase at THI 67 in buffaloes and at THI 68 in cattle. Significant (p < 0.01) differences in RT between the species were observed at THI 71, 72, and 73. Respiration rate (RR) significantly (p < 0.05) increased at THI 70 in both the species and significant (p < 0.05) differences in RR were observed between the species at THI 65, 68, 69, and 74. THI had significant (p < 0.05) effect on blood glucose and blood electrolytes of the species with increased levels at higher THI. Serum AST and ALT levels showed less pronounced changes over increasing THI. Heat stress-associated expressions of HSP 70 genes followed temporal changes with incremental THI. The expression of HSPA8 was consistent at lower THI whereas upregulation of HSPA1A and HSPA1L was evident at higher THI. The study concludes that changes in physiological parameters such as RT and RR occur in a phasic pattern in both species and onset of heat stress was early in buffalo as compared to cattle.

Outcomes of Neurorehabilitation Among Patients With Prolonged Disorders of Consciousness.

BACKGROUND:  The impact of neurorehabilitation on patients with prolonged disorders of consciousness (PDOC) is not well known. We assessed the range of motion (ROM), muscle girth and power, level of consciousness, development of musculoskeletal deformity, and superficial sensation. METHODS:  A retrospective observational record-based study was done, which included the data of patients diagnosed with PDOC admitted at Thumbay Physical Therapy & Rehabilitation Hospital, Ajman, UAE, between 2020 and 2022. Data on the "range of motion", "muscle girth and power", "level of consciousness", "development of musculoskeletal deformity", and "superficial sensation" were collected and analyzed. The SPSS software version 27 (IBM Corp., Armonk, NY, USA) was used for analysis. The chi-square test was used to assess association, and the t-test was used to test the mean difference. RESULTS:  We assessed the data of 21 patients with PDOC. The superficial sensation was found to have increased significantly (p<0.025). There was a decrease in the proportion of patients with musculoskeletal deformities during the follow-up period. The ROM, muscle girth, and muscle power were also preserved without significant deterioration. However, the level of consciousness measured by the Glasgow coma scale (GCS) showed no improvement. CONCLUSIONS: Our research showed that neurorehabilitation significantly improves superficial sensation and prevents the development of musculoskeletal deformities. However, the mean level of consciousness remained the same. There was also no decrease in ROM. Both muscle girth and power were preserved over two years.