Phenotypic and Molecular Spectrum of Guanidinoacetate N-Methyltransferase Deficiency: An Analytical Study of a Case Series and a Scoping Review of 53 Cases of Guanidinoacetate N-Methyltransferase.

Background: Guanidinoacetate methyltransferase deficiency (GAMT) is an autosomal recessive inborn error of metabolism. A condition that results from a pathogenic variant in the GAMT gene that maps to 19p13.3. The prevalence can be estimated to be up to 1:2,640,000 cases; countries such as Saudi Arabia could have a higher prevalence due to high consanguinity rates. The clinical manifestations that a patient could obtain are broad and start to manifest in the patients' early childhood years. Materials and Methods: A thorough review of case reports in January 2022 was conducted. The retrieved literature was screened for demographic data. Patients of all ages were included. Qualitative variables were described as number and percentage (%), and quantitative data were described by the mean and standard deviation. In bivariate data, Chi-square test (χ2) was used and t-test for nonparametric variables. Results: Gender distribution was 53% of males and 47% females. Reported age ranged from 8 to 31 months. At the age of onset, 50% of the cases were infants, 28% were toddlers, and 15% were children, concluding that 79% of the reported cases developed symptoms before 5 years old. 68% of the cases developed generalized seizures throughout their life. 84% of the cases expressed a form of developmental delay. 43% of the cases had intellectual disabilities and mental retardation that affected their learning process; most cases required special care. 23% of the affected cases were of consanguineous marriages, and 7% had affected relatives. Conclusion: We described four novel case reports, the first to be reported in Saudi Arabia. Seizure was a leading finding in the majority of the cases. Developmental delay was broadly observed. Intellectual delay and language impairments are primary hallmarks. Further understanding and early diagnosis are recommended. Premarital testing of neurogenetic diseases using whole-exome sequencing is probably a future direction, especially in populations with high consanguinity rates.

Diagnostic Accuracy of Molecular Imaging Techniques for Detecting Prostate Cancer: A Systematic Review.

Molecular imaging modalities show valuable non-invasive techniques capable of precisely and selectively addressing molecular markers associated with prostate cancer (PCa). This systematic review provides an overview of imaging markers utilized in positron emission tomography (PET) methods, specifically focusing on the pathways and mediators involved in PCa. This systematic review aims to evaluate and analyse existing literature on the diagnostic accuracy of molecular imaging techniques for detecting PCa. The PubMed, EBSCO, ScienceDirect, and Web of Science databases were searched, identifying 32 studies that reported molecular imaging modalities for detecting PCa. Numerous imaging modalities and radiotracers were used to detect PCa, including 68Ga-prostate-specific membrane antigen (PSMA) PET/computed tomography (CT), 68Ga-PSMA-11 PET/magnetic resonance imaging (MRI), 18F-PSMA-1007 PET/CT, 18F-DCFPyL PET/MRI, 18F-choline PET/MRI, and 18F-fluoroethylcholine PET/MRI. Across 11 studies, radiolabelled 68Ga-PSMA PET/CT imaging had a pooled sensitivity of 80 (95% confidence interval [CI]: 35-93), specificity of 90 (95% CI: 71-98), and accuracy of 86 (95% CI: 64-96). The PSMA-ligand 68Ga-PET/CT showed good diagnostic performance and appears promising for detecting and staging PCa.

Virtual Objective Structured Clinical Examination (OSCE) Training in the Pandemic Era: Feasibility, Satisfaction, and the Road Ahead.

INTRODUCTION: Objective Structured Clinical Examinations (OSCEs) are essential assessments for evaluating the clinical competencies of medical students. The COVID-19 pandemic caused a significant disruption in medical education, prompting institutions to adopt virtual formats for academic activities. This study analyzes the feasibility, satisfaction, and experiences of pediatric board candidates and faculty during virtual or electronic OSCE (e-OSCE) training sessions using Zoom video communication (Zoom Video Communications, Inc., San Jose, USA). METHODS: This is a post-event survey assessing the perceptions of faculty and candidates and the perceived advantages and obstacles of e-OSCE. RESULTS: A total of 142 participants were invited to complete a post-event survey, and 105 (73.9%) completed the survey. There was equal gender representation. More than half of the participants were examiners. The overall satisfaction with the virtual e-OSCE was high, with a mean score of 4.7±0.67 out of 5. Most participants were likely to recommend e-OSCE to a friend or colleague (mean score 8.84±1.51/10). More faculty (66.1%) than candidates (40.8%) preferred e-OSCE (P=0.006). CONCLUSION: Transitioning to virtual OSCE training during the pandemic proved feasible, with high satisfaction rates. Further research on virtual training for OSCE in medical education is recommended to optimize its implementation and outcomes.

Inhibiting Interfacial Nonradiative Recombination in Inverted Perovskite Solar Cells with a Multifunctional Molecule.

Interface-induced nonradiative recombination losses at the perovskite/electron transport layer (ETL) are an impediment to improving the efficiency and stability of inverted (p-i-n) perovskite solar cells (PSCs). Tridecafluorohexane-1-sulfonic acid potassium (TFHSP) is employed as a multifunctional dipole molecule to modify the perovskite surface. The solid coordination and hydrogen bonding efficiently passivate the surface defects, thereby reducing nonradiative recombination. The induced positive dipole layer between the perovskite and ETLs improves the energy band alignment, enhancing interface charge extraction. Additionally, the strong interaction between TFHSP and the perovskite stabilizes the perovskite surface, while the hydrophobic fluorinated moieties prevent the ingress of water and oxygen, enhancing the device stability. The resultant devices achieve a power conversion efficiency (PCE) of 24.6%. The unencapsulated devices retain 91% of their initial efficiency after 1000 h in air with 60% relative humidity, and 95% after 500 h under maximum power point (MPP) tracking at 35 °C. The utilization of multifunctional dipole molecules opens new avenues for high-performance and long-term stable perovskite devices.

Synchronized Glioma Insights: Trends, Blood Group Correlations, Staging Dynamics, and the Vanguard of Liquid Biopsy Advancements.

BACKGROUND: Gliomas are the most frequent, heterogeneous group of tumors arising from glial cells, characterized by difficult monitoring, poor prognosis, and fatality. Tissue biopsy is an established procedure for tumor cell sampling that aids diagnosis, tumor grading, and prediction of prognosis. MATERIALS AND METHODS: We studied and compared the levels of liquid biopsy markers in patients with different grades of glioma. Also, we tried to prove the potential association between glioma and specific blood group antigens. RESULTS: 78 patients were found, among whom the maximum percentage with glioblastoma had blood group O+ (53.8%). The second highest frequency had blood group A+ (20.4%), followed by B+ (9.0%) and A- (5.1%), and the least with O-. Liquid biopsy biomarkers included Alanine Aminotransferase (ALT), Lactate Dehydrogenase (LDH), lymphocytes, Urea, Alkaline phosphatase (AST), Neutrophils, and C-Reactive Protein (CRP). The levels of all the components increased significantly with the severity of the glioma, with maximum levels seen in glioblastoma (grade IV), followed by grade III and grade II, respectively. CONCLUSION: Gliomas have significant clinical challenges due to their progression with heterogeneous nature and aggressive behavior. A liquid biopsy is a non-invasive approach that aids in setting up the status of the patient and figuring out the tumor grade; therefore, it may show diagnostic and prognostic utility. Additionally, our study provides evidence to prove the role of ABO blood group antigens in the development of glioma. However, future clinical research on liquid biopsy will improve the sensitivity and specificity of these tests and confirm their clinical usefulness to guide treatment approaches.

Unknotting tech neck by breaking the cycle of pain and disability: Comparing the impact of instrument assisted soft tissue mobilization on specific muscles and superficial back arm line.

BACKGROUND: Computer professionals often develop a forward head posture due to prolonged hours of computer use, leading to neck pain. Instrument-assisted soft tissue mobilization (IASTM), an advanced technique for treating myofascial trigger points, has become increasingly popular for addressing these musculoskeletal issues. OBJECTIVES: The study aimed to compare the effectiveness of IASTM mobilization on SBAL (superficial back arm line) and SM(specific muscles-upper trapezius, levator scapulae, and sternocleidomastoid) in managing chronic neck pain among computer professionals. PARTICIPANTS & METHODS: The study involved 62 computer professionals, randomly divided into two groups. Group A received IASTM on SBAL and group B received IASTM on SM for neck pain each receiving three sessions weekly for four weeks. Outcome variables like Neck Disability Index (NDI), NPRS(Neck Pain Rating Scale), Craniovertebral angle (CVA), and range of motion (ROM) for flexion, and side flexion (right & left side) were evaluated at baseline, 2 weeks and 4 weeks. RESULTS: Significant improvement in NPRS were observed in both the SBAL and SM groups after 2 weeks of IASTM, wth the SBAL group demonstrating greater improvement. At 4 weeks, IASTM on SBAL showed significantly higher improvements in NPRS, CVA, NDI, and flexion compared to the SM group. The repeated measures ANOVA indicated a significant main effect of both time and group, along with a significant interaction between time and group for all outcome variables, except for CVA. CONCLUSION: The study indicates that IASTM on SBAL may offer a more effective treatment for chronic neck pain in computer professionals compared to targeting specific muscles.

Black Seed Oil-Based Curcumin Nanoformulations Ameliorated Cuprizone-Induced Demyelination in the Mouse Hippocampus.

Multiple sclerosis (MS) is a neurodegenerative disease characterized by the demyelination of nerves, axonal damage, and neuroinflammation. Cognition impairment, pain, and loss of mobility are some of the usual complications of MS. It has been postulated that the overproduction of proinflammatory cytokines and reactive oxygen species (ROS) are the main factors that contribute to MS pathology. Among various animal models, the cuprizone model is the most widely used model for investigating MS-related pathology. We assessed the effects of cuprizone along with the protective effects of some black seed oil-based nanoformulations of curcumin with and without piperine, in mice hippocampus in terms of the changes in antioxidant enzymes, transcription factors, and cytokines during demyelination and remyelination processes. The results of behavioral studies point toward impairment in working memory following the feeding of cuprizone for 5 weeks. However, in treatment groups, mice seemed to prevent the toxic effects of cuprizone. Nanoformulations used in this study were found to be highly effective in lowering the amount of ROS as indicated by the levels of antioxidant enzymes like catalase, superoxide dismutase, glutathione, and glutathione peroxidase. Moreover, nanoformulations CCF and CCPF were observed resisting the toxic effects of cuprizone. We observed greater expression of NFκB-p65 in the CPZ group than in the control group. CCF nanoformulation had a better inhibitory effect on NFκB-p65 than other formulations. Histological examination of the hippocampus was also conducted. Nanoformulations used here were found effective in reversing MS-related pathophysiology and hence have the potential to be applied as adjuvant therapy for MS treatment.

Phytotherapeutic options for the treatment of epilepsy: pharmacology, targets, and mechanism of action.

Epilepsy is one of the most common, severe, chronic, potentially life-shortening neurological disorders, characterized by a persisting predisposition to generate seizures. It affects more than 60 million individuals globally, which is one of the major burdens in seizure-related mortality, comorbidities, disabilities, and cost. Different treatment options have been used for the management of epilepsy. More than 30 drugs have been approved by the US FDA against epilepsy. However, one-quarter of epileptic individuals still show resistance to the current medications. About 90% of individuals in low and middle-income countries do not have access to the current medication. In these countries, plant extracts have been used to treat various diseases, including epilepsy. These medicinal plants have high therapeutic value and contain valuable phytochemicals with diverse biomedical applications. Epilepsy is a multifactorial disease, and therefore, multitarget approaches such as plant extracts or extracted phytochemicals are needed, which can target multiple pathways. Numerous plant extracts and phytochemicals have been shown to treat epilepsy in various animal models by targeting various receptors, enzymes, and metabolic pathways. These extracts and phytochemicals could be used for the treatment of epilepsy in humans in the future; however, further research is needed to study the exact mechanism of action, toxicity, and dosage to reduce their side effects. In this narrative review, we comprehensively summarized the extracts of various plant species and purified phytochemicals isolated from plants, their targets and mechanism of action, and dosage used in various animal models against epilepsy.

Europinidin Attenuates Methamphetamine-induced Learning and Memory Impairments and Hippocampal Alterations in Rodents: Based on Molecular Docking through a Mechanism of Neuromodulatory Cytokines/ Caspases-3/ CREB/BDNF Pathway.

BACKGROUND: Methamphetamine (MA) is well recognized as a psychostimulant that can cause neurotoxicity and neurodegeneration, which is associated with cognitive decline, has been confirmed experimentally. OBJECTIVE: The research aimed to investigate the neuroprotective properties of europinidin (Eu) in rodents affected by methamphetamine (MA)-induced cognitive impairments and hippocampal alterations. This was achieved by inhibiting lipid peroxidation and pro-inflammatory markers. METHODS: Rats were exposed to cognitive impairment produced by MA. The Morris water maze (MWM) is utilized for evaluating behavioral parameters. Tests were conducted on malondialdehyde (MDA), catalase (CAT), interleukins-1ß (IL-1ß), reduced glutathione (GSH), tumor necrosis factor-α (TNF-α), superoxide dismutase (SOD), and the expression of neurotransmitters (Norepinephrine [NE], dopamine [DA], glutamate, and gamma-aminobutyric acid [GABA]) as well as cAMP response element-binding protein (CREB), IL-6, brain-derived neurotrophic factor (BDNF), and caspase 3 proteins. An investigation was carried out using docking methodology to ascertain whether Eu interacts with relevant molecular targets. RESULTS: Significant decline in the transfer latency and there were significant changes in the amount of SOD, GSH, CAT, and MDA and alterations in levels of IL-6, IL-1ß, CREB, TNF-α, BDNF, and Caspase 3 proteins expression, as well as considerably alterations in level of neurotransmitters (NE, DA, Glutamate, and GABA) were observed in the Eu-treated rats compared to the MA-induced rats. Eu had a favorable affinity towards BDNF with docking scores of -9.486 kcal/mol. CONCLUSION: The experiment found that administering Eu to rats improved cognitive abilities by changing antioxidant enzymes, reducing cytokines, and modifying neurotransmitter levels, compared to rats in the control group treated with MA.

Echocardiography to predict left ventricular filling pressure for long-term paediatric heart transplant patients.

OBJECTIVES: Left ventricular diastolic dysfunction is a recognised sequela following transplantation in paediatric heart transplant patients. Traditional echocardiographic indices do not correlate well with left ventricular filling pressure immediately after transplantation. This study aimed to assess whether these indices have any long-term correlation after transplantation in paediatric patients. METHODS: A retrospective chart review of 41 patients who had a heart transplant before the age of 24 years was performed. The median time since the transplantation was 11 years. Data obtained from surveillance cardiac catheterisation and echocardiographic examination were reviewed. Traditional echocardiographic indices of diastolic function were compared with the pulmonary capillary wedge pressure and left ventricular end-diastolic pressure obtained from cardiac catheterisation. RESULTS: The median age at transplant was 12.1 years, and the median time since transplant was 11 years. Eighteen patients (43%) had a history of at least one rejection episode and 12 patients (29%) had a history of cardiac allograft vasculopathy. There was no correlation between mitral inflow E velocity, mitral E/A ratio, tissue Doppler velocities, mitral E/e' (mitral inflow E velocity to mitral annular velocity), and elevated pulmonary capillary wedge pressure or elevated left ventricular end-diastolic pressure. There was no correlation between mitral valve deceleration time or isovolumetric relaxation time with elevated pulmonary capillary wedge pressure or elevated left ventricular end-diastolic pressure. CONCLUSION: Our findings suggest that traditional echocardiographic indices of diastolic function do not correlate well with elevated invasive pulmonary capillary wedge pressure or elevated left ventricular end-diastolic pressure in paediatric heart transplant patients' long-term post-transplantation.

Unveiling the Molecular Interactions Between Human Transferrin and Limonene: Natural Compounds in Alzheimer's Disease Therapeutics.

Background: Neurodegeneration is a term describing an irreversible process of neuronal damage. In recent decades, research efforts have been directed towards deepening our knowledge of numerous neurodegenerative disorders, with a particular focus on conditions such as Alzheimer's disease (AD). Human transferrin (htf) is a key player in maintaining iron homeostasis within brain cells. Any disturbance in this equilibrium gives rise to the emergence of neurodegenerative diseases and associated pathologies, particularly AD. Limonene, a natural compound found in citrus fruits and various plants, has shown potential neuroprotective properties. Objective: In this study, our goal was to unravel the binding of limonene with htf, with the intention of comprehending the interaction mechanism of limonene with htf. Methods: Binding was scrutinized using fluorescence quenching and UV-Vis spectroscopic analyses. The binding mechanism of limonene was further investigated at the atomic level through molecular docking and extensive 200 ns molecular dynamic simulation (MD) studies. Results: Molecular docking uncovered that limonene interacted extensively with the deep cavity located within the htf binding pocket. MD results indicated that binding of limonene to htf did not induce substantial structural alterations, ultimately forming stable complex. The findings from fluorescence binding indicated a pronounced interaction between limonene and htf, limonene binds to htf with a binding constant (K) of 0.1×105 M-1. UV spectroscopy also advocated stable htf-limonene complex formation. Conclusions: The study deciphered the binding mechanism of limonene with htf, providing a platform to use limonene in AD therapeutics in context of iron homeostasis.

The Role of Tele-Exercise for People with Type 2 Diabetes: A Scoping Review.

BACKGROUND: Supervised exercise interventions tend to be more effective than unsupervised exercises or physical activity advice alone. However, people with type 2 diabetes may find it difficult to attend supervised exercise interventions due to several obstacles. Tele-exercise, or utilizing technology to deliver home-based exercise, might be a solution. OBJECTIVE: This scoping review aimed to explore clinical trials investigating the impact of tele-exercise interventions in individuals with type 2 diabetes Methods: Four electronic databases were searched for the period up to January 2024 for clinical trials investigating the impact of tele-exercise on health-related outcomes in adults with type 2 diabetes. RESULTS: Seven trials involving 460 individuals with type 2 diabetes met the inclusion criteria. In these trials, combined aerobic and resistance exercise programs were the main types delivered remotely. To deliver such programs, both synchronous (n = 4) and asynchronous (n = 3) delivery modes were adopted. Regardless of the delivery mode, all tele-exercise interventions led to improvements in various factors related to type 2 diabetes and its complications, including glycemic control, blood lipids, body composition, functional capacity, muscle strength, and quality of life. The improvements were also found to be as effective as those of supervised exercise. CONCLUSIONS: Tele-exercise interventions seem to be feasible and as effective as supervised exercise interventions in terms of improving glycemic control, blood lipids, functional capacity, muscle strength, body composition, and quality of life for people with type 2 diabetes.

Annona squamosa Fruit Extract Ameliorates Lead Acetate-Induced Testicular Injury by Modulating JAK-1/STAT-3/SOCS-1 Signaling in Male Rats.

Lead (Pb) is a common pollutant that is not biodegradable and gravely endangers the environment and human health. Annona squamosa fruit has a wide range of medicinal uses owing to its phytochemical constituents. This study evaluated the effect of treatment with A. squamosa fruit extract (ASFE) on testicular toxicity induced in male rats by lead acetate. The metal-chelating capacity and phytochemical composition of ASFE were determined. The LD50 of ASFE was evaluated by probit analysis. Molecular docking simulations were performed using Auto Dock Vina. Forty male Sprague Dawley rats were equally divided into the following groups: Gp1, a negative control group; Gp2, given ASFE (350 mg/kg body weight (b. wt.)) (1/10 of LD50); Gp3, given lead acetate (PbAc) solution (100 mg/kg b. wt.); and Gp4, given PbAc as in Gp3 and ASFE as in Gp2. All treatments were given by oro-gastric intubation daily for 30 days. Body weight changes, spermatological parameters, reproductive hormone levels, oxidative stress parameters, and inflammatory biomarkers were evaluated, and molecular and histopathological investigations were performed. The results showed that ASFE had promising metal-chelating activity and phytochemical composition. The LD50 of ASFE was 3500 mg/kg b. wt. The docking analysis showed that quercetin demonstrated a high binding affinity for JAK-1 and STAT-3 proteins, and this could make it a more promising candidate for targeting the JAK-1/STAT-3 pathway than others. The rats given lead acetate had defective testicular tissues, with altered molecular, biochemical, and histological features, as well as impaired spermatological characteristics. Treatment with ASFE led to a significant mitigation of these dysfunctions and modulated the JAK-1/STAT-3/SOCS-1 axis in the rats.

Various pharmacological agents in the pipeline against intractable epilepsy.

Epilepsy is a noncommunicable chronic neurological disorder affecting people of all ages, with the highest prevalence in low and middle-income countries. Despite the pharmacological armamentarium, the plethora of drugs in the market, and other treatment options, 30%-35% of individuals still show resistance to the current medication, termed intractable epilepsy/drug resistance epilepsy, which contributes to 50% of the mortalities due to epilepsy. Therefore, the development of new drugs and agents is needed to manage this devastating epilepsy. We reviewed the pipeline of drugs in "ClinicalTrials. gov," which is the federal registry of clinical trials to identify drugs and other treatment options in various phases against intractable epilepsy. A total of 31 clinical trials were found regarding intractable epilepsy. Among them, 48.4% (15) are about pharmacological agents, of which 26.6% are in Phase 1, 60% are in Phase 2, and 13.3% are in Phase 3. The mechanism of action or targets of the majority of these agents are different and are more diversified than those of the approved drugs. In this article, we summarized various pharmacological agents in clinical trials, their backgrounds, targets, and mechanisms of action for the treatment of intractable epilepsy. Treatment options other than pharmacological ones, such as devices for brain stimulation, ketogenic diets, gene therapy, and others, are also summarized.

Influence of different printing orientations and post-polymerization time on the translucency of three-dimensional (3D) printed denture base resins.

PURPOSE: To evaluate the effect of different printing orientations and post-polymerization time with thermal cycling on the translucency of 3D-printed denture base resins. METHODS: Heat-polymerized (HP) acrylic resin specimens were fabricated and 3D-printed denture base materials (NextDent, ASIGA, FormLabs) were printed with different printing orientations (0, 45, 90 degrees) and subjected to different post-polymerization times (15-, 30-, 60-, and 90-min). All specimens were polished and immersed in distilled water for 1 day at 37°C. CIEDE2000 was used to measure the translucency parameters (TP00) before and after thermal cycling (5000 cycles) recording the color parameters (L*, a*, b*) against a black and white background using a spectrophotometer. k-factors ANOVA followed by post hoc Tukey's test (α = .05) was performed for statistical analysis. RESULTS: The k-factors ANOVA test showed a significant effect of resin material, post-polymerization time, and printing orientation on translucency (p < 0.001). In comparison to HP, all 3D-printed resins showed lower translucency with all post-polymerization times and printing orientation (p < 0.001) except FormLabs resin (p > 0.05). For all 3D-printed resins, the translucency increased, with increasing the post-polymerization time (p < 0.001) and 60- and 90-min showed the highest translucency. For printing orientation, 90 and 45 degrees significantly showed high translucency in comparison to 0 degrees (p < 0.001). FormLabs showed significantly higher translucency when compared with NextDent and ASIGA per respective printing orientation and post-polymerization time. The translucency significantly decreased after thermal cycling for all tested resins (p < 0.001). CONCLUSION: The findings of this study demonstrated that the translucency of 3D-printed resins is influenced by the printing orientation, post-polymerization time, and resin type. As a result, choosing a resin type, and printing orientation, with a longer post-polymerization time should be considered since it may improve the esthetic appearance of the 3D-printed resins.

Comprehensive spectroscopic and computational insight into the binding of vanillin with human transferrin: targeting neuroinflammation in Alzheimer's disease therapeutics.

In present times, vanillin stands out as a promising therapeutic molecule that can be implicated in the treatment of neurodegenerative disorders (NDs), notably Alzheimer's disease (AD). This can be attributed to the highly potent scavenging activity of vanillin against reactive oxygen species (ROS). Oxidative stress leads to generation of ROS that serves a critical role in AD's pathological progression. It is apparent from various studies that diets rich in polyphenols prevent oxidative stress associated with AD development, implying the crucial role of vanillin in AD therapeutics. It is crucial to maintain iron balance to manage AD associated oxidative stress, unveiling the significance of human transferrin (hTf) that maintains iron homeostasis. Here, we have performed an integrated study of spectroscopic and computational approaches to get insight into the binding mechanism of vanillin with hTf. In the preliminary study, molecular docking deciphered that vanillin primarily occupies the hTf binding pocket, forming multiple interactions with its key residues. Moreover, the binding mechanism was evaluated at an atomistic level employing comprehensive molecular dynamic (MD) simulation. MD analysis demonstrated that binding of vanillin to hTf stabilizes its structure, without inducing any significant alterations in its native conformation. The docked complex was maintained throughout the simulations without changing its original conformation. Essential dynamics analysis further confirms that hTf achieved a stable conformation with vanillin. The outcomes were further supplemented by fluorescence spectroscopy which confirms the formation of stable hTf-vanillin complex. Taken together, the current study unveils the interaction mechanism of vanillin with hTf and providing a platform to use vanillin in AD therapeutics in the context of iron homeostasis.

Prevalence of Electronic Cigarette Smoking Among Students of Shaqra University, Saudi Arabia.

Background Electronic cigarettes are devices that use a flavored nicotine solution instead of burning tobacco leaves. Since their emergence, e-cigarettes have gained popularity in Saudi Arabia, particularly among young adults. Recently, many non-smoking youths have begun to use e-cigarettes as an alternative social behavior. Recent studies have confirmed that e-cigarettes have harmful effects on the respiratory system. Approximately 48.5 million Europeans have used an e-cigarette at least once while 7.5 million Europeans currently use e-cigarettes. This study aims to assess the prevalence of e-cigarette use and possible addictiveness among Shaqra University students. Methodology This is a cross-sectional study conducted at Shaqra University in 2021. A total of 290 students (18 years old and older) from Shaqra University were included in our study. The subjects were selected through simple random sampling. A self-administered online questionnaire related to e-cigarettes was used. Results Completed questionnaires were obtained from 290 students (average age of 20.2 ± 1.8 years). A total of 58 (20.1%) of the respondents were e-cigarette users. The obtained results showed that the mean age of e-cigarette smokers was 20.5 years, e-cigarette usage significantly differed between age groups (p < 0.001), and the highest prevalence of e-cigarette smoking was in Shaqra Governorate (i.e., 13.1%). Conclusion It's vital to acknowledge that the capacity for addiction to e-cigarettes is comparable to traditional smoking and other nicotine-containing items. It's essential to consistently observe students and smokers to better understand the effects of vaping patterns on this specific group.

A comprehensive investigation on alleviating oxidative stress and inflammation in hyperglycaemic conditions through in vitro experiments and computational analysis.

Protein glycation, hyper-inflammatory reactions, and oxidative stress play a crucial role in the pathophysiology of numerous diseases. The current work evaluated the protective ability of ethyl alcohol extract of leaves from holy basil (Ocimum sanctum Linn) against inflammation, oxidative stress, glycation and advanced glycation endproducts formation. Various in vitro assays assessed prementioned properties of holy basil. In addition, molecular docking was conducted. The highest hydrogen peroxide reduction activity (72.7 %) and maximum percentage of DPPH scavenging (71.3 %) depicted its vigorous antioxidant abilities. Furthermore, it showed the most excellent protection against proteinase activity (67.247 %), prevention of denaturation of egg albumin (65.29 %), and BSA (bovine serum albumin) (68.87 %) with 600 µg/ml. Percent aggregation index (57.528 %), browning intensity (56.61 %), and amyloid structure (57.0 %) were all reduced significantly using 600 µg/ml of extract. Additionally, the antimicrobial potential was also confirmed. According to a molecular docking study, active leaf extract ingredients were found to bind with superoxide dismutase, catalase, and carbonic anhydrase. As a conclusion, O. sanctum has a variety of health-promoting properties that may reduce the severity of many diseases in diabetic patients. However, in order to ascertain the mechanisms of action of the components of its leaves in disease prevention, more thorough research based on pharmacological aspects is needed.

Case Report: A rare treatable metabolic syndrome (Brown-Vialetto-Van Laere syndrome) masquerading as chronic inflammatory demyelinating polyneuropathy from Saudi Arabia.

Background: Brown-Vialetto-Van Laere (BVVL) syndrome is an extremely rare autosomal recessive progressive motoneuron disease that is caused by a defect in the riboflavin transporter genes SLC52A2 and SLC52A3. BVVL syndrome has a variable age of presentation, and it is characterized by progressive auditory neuropathy, bulbar palsy, stridor, muscle weakness, and respiratory compromise secondary to diaphragmatic and vocal cord paralysis. BVVL syndrome has a poor prognosis in the absence of treatment, including morbidity with quadriparesis and sensorineural hearing loss, with mortality in the younger age group. Early administration of riboflavin is associated with prolonged survival, low morbidity, and reversal of some clinical manifestations. Case presentation: We describe an 18-month-old male infant with progressive pontobulbar palsy, loss of developmental milestones, and a clinical picture suggestive of chronic inflammatory demyelinating neuropathy. A nerve conduction study revealed axonal neuropathy, while molecular analysis revealed a homozygous mutation in one of the riboflavin transporter genes, SLC52A3, confirming BVVL syndrome. The patient needed long-term respiratory support and a gastrostomy tube to support feeding. With high-dose riboflavin supplementation, he experienced moderate recovery of motor function. Conclusion: This report highlights the importance of considering BVVL syndrome in any patient who presents with the clinical phenotype of pontobulbar palsy and peripheral axonal neuropathy, as early riboflavin treatment may improve or halt disease progression, thus reducing the associated mortality and morbidity.

Terpenes from Cannabis sativa induce antinociception in a mouse model of chronic neuropathic pain via activation of adenosine A2A receptors.

ABSTRACT: Terpenes are small hydrocarbon compounds that impart aroma and taste to many plants, including Cannabis sativa. A number of studies have shown that terpenes can produce pain relief in various pain states in both humans and animals. However, these studies were methodologically limited and few established mechanisms of action. In our previous work, we showed that the terpenes geraniol, linalool, ß-pinene, α-humulene, and ß-caryophyllene produced cannabimimetic behavioral effects via multiple receptor targets. We thus expanded this work to explore the potential antinociception and mechanism of these Cannabis terpenes in a mouse model of chronic pain. We first tested for antinociception by injecting terpenes (200 mg/kg, IP) into male and female CD-1 mice with mouse models of chemotherapy-induced peripheral neuropathy (CIPN) or lipopolysaccharide-induced inflammatory pain, finding that the terpenes produced roughly equal antinociception to 10 mg/kg morphine or 3.2 mg/kg WIN55,212. We further found that none of the terpenes produced reward as measured by conditioned place preference, while low doses of terpene (100 mg/kg) combined with morphine (3.2 mg/kg) produced enhanced antinociception vs either alone. We then used the adenosine A2A receptor (A2AR) selective antagonist istradefylline (3.2 mg/kg, IP) and spinal cord-specific CRISPR knockdown of the A2AR to identify this receptor as the mechanism for terpene antinociception in CIPN. In vitro cAMP and binding studies and in silico modeling studies further suggested that the terpenes act as A2AR agonists. Together these studies identify Cannabis terpenes as potential therapeutics for chronic neuropathic pain and identify a receptor mechanism for this activity.