Evaluation of ivermectin and vitamin E based combination with antiseizure rufinamide drug for mitigation of pentylenetetrazole-induced kindling, behavioral challenges and histopathological aberrations.

Pentylenetetrazole- (PTZ)-induced kindling is a broadly used experimental model to evaluate the impact of antiseizure drugs and their novel combination on seizure progression. The current study aimed to evaluate the anti-kindling effects of ivermectin (IVM) and rufinamide (RUFI) alone and their combination with vitamin E. The mice were administered 11 injections of PTZ (40 mg/kg) followed by assessment for anxiety-like behavior and cognitive abilities in a series of behavior tests with subsequent brain isolation for biochemical and histopathological evaluation. The outcomes showed a marked protection by IVM + RUFI (P<0.001) from kindling progression, anxiety-like behavior and cognitive deficit. However, additional supplementation with vitamin E worked superior to duo therapy as these mice were noted to be most fearless to visiting open, illuminated and elevated zones of open field, light/dark and elevated-plus maze (P<0.0001). Further, they showed marked remembrance of the familiar milieu in y-maze (P<0.01) and novel objection recognition (P<0.05) tests. Additionally, their recollection of aversive stimuli in passive avoidance and spatial memory in Morris water maze were evident (P<0.0001), in comparison to kindled mice. The IVM + RUFI duo therapy and its co-administration with vitamin E prevented kindling-triggered oxidative stress in brains and neuronal damage in hippocampus. We conclude that the benefits of the co-administration of vitamin E might be the results of antioxidant and anti-inflammatory effects of vitamin E which might be potentiating the antiseizure effects of RUFI and GABA-A modulating potential by ivermectin.

Association between COVID-19 exposure and autonomic nervous system dysfunction in apparently healthy adults: an observational study.

OBJECTIVE: Coronavirus disease (COVID-19) is a respiratory disease caused by SARS-CoV-2, which complicates the functioning of multiple systems, including the autonomic nervous system (ANS), causing dysautonomia. Investigation of dysautonomia and its association with exposure to COVID-19 is limited in healthy people. Therefore, the study aimed to investigate the relationship between ANS dysautonomia and coronavirus exposure and compare the ANS function between exposed and non-exposed to COVID-19. SUBJECTS AND METHODS: The study involved 141 participants, with a mean age of 18-24.5 years, 83% male (49.6% exposed to COVID-19). The ANS was measured using a composite autonomic symptom scale (COMPASS-31) questionnaire and heart rate variability (HRV) using photoplethysmography. Exposure to COVID-19 was investigated using two national health-status tracking and COVID-19 exposure applications, "Sehhaty" and "Twakkalna". RESULTS: A significantly inverse weak correlation between COMPASS-31 scores and COVID-19 exposure (r=-0.2, p=0.04). No significant association was found between HRV and COVID-19 exposure. COMPASS-31 scores for the exposed group (median=15, n=70) were significantly higher than those for the non-exposed group (median=12, n=71), U=1,913.5, p=0.03. Height (r=-0.4, p=0.002) and gender (r=0.3, p=0.001) were moderately correlated with COMPASS-31 among the exposed group. CONCLUSIONS: These findings indicated that exposure to COVID-19 was associated with poorer ANS scores measured via COMPASS-31. Additionally, exposure to COVID-19 resulted in higher dysautonomia symptoms than non-exposed. Height and gender differences contribute to the severity of dysautonomia among exposed people.

Anxiolytic potential of resveratrol and rufinamide combination by modulating GABA-ergic transmission: insights from experiments, molecular docking and dynamics simulations.

Resveratrol is a polyphenolic phytocompound known to possess anxiolytic-like effects but its impact on central gammaaminobutyric acid (GABA) modulation has never been explored. The purpose of this study was to analyze the anxiolytic-like effects of resveratrol alone and in combination with rufinamide, an antiepileptic drug which has never been studied for its anxiolytic potential. The BALB/c mice were tested in a battery of behavior testing after administration of resveratrol (50 mg/kg) and rufinamide (50 mg/kg) alone and in combination. Moreover, molecular docking studies were also carried out to understand the interaction of resveratrol and rufinamide with GABA aminotransferase, GABA receptor and GABA-A transporter type 1. Resveratrol alone exerted notable anxiolytic-like effects and improved outcomes in few experiments but rufinamide alone did not yield any beneficial outcomes. However, the animal co-administered with resveratrol and rufinamide behaved exceptionally well (p<0.05) and preferred open, illuminated and exposed areas of open field, light/dark and elevated plus maze. Further, these animals showed reduced anxiety towards anxiogenic stimuli i.e. holes and marbles in hole board and marble bury tests, respectively. Resveratrol and rufinamide showed moderate to strong binding affinities with GABA proteins, indicating the potential to treat anxiety-like neurological disorders. Moreover, resveratrol and rufinamide were analyzed using molecular docking to determine their interaction with GABA receptors, transporters, and transaminase. The results suggest that their anxiolytic-like effects may be due to inhibiting GABA reuptake transporter 1 protein, leading to increased synaptic levels of GABA neurotransmitter, as seen in stable molecular dynamics results with the 7SK2 GABA transporter protein.

Generative and Discriminative Learning for Lung X-Ray Analysis Based on Probabilistic Component Analysis.

Introduction: The paper presents a hybrid generative/discriminative classification method aimed at identifying abnormalities, such as cancer, in lung X-ray images. Methods: The proposed method involves a generative model that performs generative embedding in Probabilistic Component Analysis (PrCA). The primary goal of PrCA is to model co-existing information within a probabilistic framework, with the intent to locate the feature vector space for X-ray data based on a defined kernel structure. A kernel-based classifier, grounded in information-theoretic principles, was employed in this study. Results: The performance of the proposed method is evaluated against nearest neighbour (NN) classifiers and support vector machine (SVM) classifiers, which use a diagonal covariance matrix and incorporate normal linear and non-linear kernels, respectively. Discussion: The method is found to achieve superior accuracy, offering a viable solution to the class of problems presented. Accuracy rates achieved by the kernels in the NN and SVM models were 95.02% and 92.45%, respectively, suggesting the method's competitiveness with state-of-the-art approaches.

The Use of Chest Radiographs and Machine Learning Model for the Rapid Detection of Pneumonitis in Pediatric.

Pneumonia is a common lung disease that is the leading cause of death worldwide. It primarily affects children, accounting for 18% of all deaths in children under the age of five, the elderly, and patients with other diseases. There is a variety of imaging diagnosis techniques available today. While many of them are becoming more accurate, chest radiographs are still the most common method for detecting pulmonary infections due to cost and speed. A convolutional neural network (CNN) model has been developed to classify chest X-rays in JPEG format into normal, bacterial pneumonia, and viral pneumonia. The model was trained using data from an open Kaggle database. The data augmentation technique was used to improve the model's performance. A web application built with NextJS and hosted on AWS has also been designed. The model that was optimized using the data augmentation technique had slightly better precision than the original model. This model was used to create a web application that can process an image and provide a prediction to the user. A classification model was developed that generates a prediction with 78 percent accuracy. The precision of this calculation could be improved by increasing the epoch, among other subjects. With the help of artificial intelligence, this research study was aimed at demonstrating to the general public that deep-learning models can be created to assist health professionals in the early detection of pneumonia.

Automation of Cephalometrics Using Machine Learning Methods.

Cephalometry is a medical test that can detect teeth, skeleton, or appearance problems. In this scenario, the patient's lateral radiograph of the face was utilised to construct a tracing from the tracing of lines on the lateral radiograph of the face of the soft and hard structures (skin and bone, respectively). Certain cephalometric locations and characteristic lines and angles are indicated after the tracing is completed to do the real examination. In this unique study, it is proposed that machine learning models be employed to create cephalometry. These models can recognise cephalometric locations in X-ray images, allowing the study's computing procedure to be completed faster. To correlate a probability map with an input image, they combine an Autoencoder architecture with convolutional neural networks and Inception layers. These innovative architectures were demonstrated. When many models were compared, it was observed that they all performed admirably in this task.

Evaluation of the mode of failure of abutments supporting implant-supported fixed partial dentures via different retention techniques.

OBJECTIVE: The objective was to in-vitro evaluate the mode of failure of abutments supporting fixed partial dentures (FPDs) via different retention techniques. MATERIALS AND METHODS: Thirty-six implants with diameter and length of 4.5 and 13 mm, respectively, were used to prepare 18 samples of FPDs. Based on the variations on abutment's design, the FPDs were divided into three groups: Group A is cement-based retention; Group B is screw-based retention; and Group C is multiunit screw-based retention. Using a chewing simulator, cyclic loads of 1,250,000 load cycles with the load of 70N were applied on all samples to simulate 5 years of human functional chewing. The samples were loaded until failure using an electromechanical test machine. Sample-size estimation was done and fracture-load values were recorded as means and corresponding standard deviations; and group comparisons were done using one-way analysis of variance and Tukey's post hoc tests. A P value below 0.01 was nominated as an indicator of statistical significance. RESULTS: In total, 36 samples (12 implant-abutment connections per group) were assessed. Abutment bending was observed in 6 (50%), 6 (50%) and 6 (50%) samples in groups A, B and C, respectively. De-attachment of the FPD form the abutment occurred in 5 (41.7%) and 5 (41.7%) samples in groups A and C, respectively. Screw fracture and fracture of FPD at the connector side occurred in 1 (8.3%) and 1 (8.3%) sample in groups A and C, correspondingly. Failure of the FPD was more often encountered in groups A (100%) and C (100%), compared to group B (50%). CONCLUSION: All abutments underwent failures under cyclic loading with abutment bending being the most common failure mode. Cement- and multi-screw-supported abutments fail more often than screw-supported abutments.

Neuropharmacological investigation, ultra-high performance liquid chromatography analysis, and in silico studies of Phyla nodiflora.

The increasing burden of neurological disorders is becoming a worldwide health challenge and researchers are continuously struggling to cure them by utilizing the miraculous medicinal properties of plants. The crude methanolic extract of whole herb of Phyla nodiflora (Pn.Cr) was subjected to phytochemical, antioxidant and neuropharmacological assessment. The Pn.Cr was initially exposed to the in vitro examination for phytocomposition through ultra-high performance liquid chromatography (UHPLC). The Sprague Dawley rats were chronically administered with various doses (100, 200 and 300 mg/kg) of Pn.Cr for one month with subsequent exposure to neurobehavioral and biochemical experimentation. The Pn.Cr exhibited a dose-dependent anxiolytic effect (P < 0.05 in comparison to control) as rats preferred central, illuminated and open arm zones in open field (OFT), light/dark (L/D) and elevated plus maze (EPM) tests. Likewise, scopolamine-induced amnesia was noticeably reversed with P < 0.05 by Pn.Cr as animals showed improved spontaneous alternation, discrimination index and shorter escape latencies in Y-maze, novel object recognition (NOR) and Morris water maze (MWM) tests. Subsequently, in vivo enzymatic assays depicted the reduced acetylcholinesterase and malondialdehyde levels. The levels of oxidative stress combating enzymes (glutathione peroxidase and superoxide dismutase) were increased in a dose-dependent style. The UHPLC detected 22 phytocompounds were further investigated in silico studied to predict the interaction of blood-brain barrier (BBB) crossing phytocompounds with human acetylcholinesterase. The four BBB crossing phytocompounds belonging to flavonoids, chalcones and alkaloids showed possible interaction with the target enzyme. We found that the phytocompounds owned by Pn.Cr might be playing multiple roles in modulation of different pathways to hinder the pathophysiology of neurological disorders including anxiety and Alzheimer's disease.

Time course evaluation of lacosamide alone and in polypharmacy on behavioral manifestations and oxidative stress in lithium-pilocarpine-induced model.

The lithium-pilocarpine model in rats is commonly used to study the characteristic events of acute status epilepticus (SE), epileptogenesis and temporal lobe epilepsy (TLE). Here we investigated the impact of lacosamide alone and in combination with other drugs (pregabalin, piracetam and scopolamine) on spontaneous recurrent seizures (SRSs) and behavioral parameters during the time frame of 6 weeks after SE. In addition, the level of oxidative stress in the hippocampus was accessed by real-time microdialysis study (8-isoprostanes) and antioxidants enzymes in the homogenate. Results revealed severe behavioral deficits with the control epileptic group and animals displayed hyperexcitability, aggression apprehension and memory insufficiency. Pharmacological manipulation for 6 weeks with lacosamide (L) - 80 mg/kg; in polypharmacy with pregabalin (L/P) - 50/50 mg/kg and piracetam (L/Pi) - 50/140 mg/kg significantly (P < 0.05) ameliorated the anxiety-related behavior (open filed, elevated plus maze, light/dark tests), depression (forced swim test) and improved spatial/reference memory (Morris water maze). There were low incidences of seizures in L, L/P and L/Pi groups revealing disease-modifying effects of employed drugs. Furthermore, the chronic use of scopolamine (L/P/S; 50/50/2 mg/kg) as polypharmacy with the concept of antagonizing the cholinergic inputs in the epileptogenic phase aberrated the behavioral situation further worse. Treatments with L/P and L/Pi significantly attenuated (P < 0.05) the oxidative stress by reducing 8-isoprostanes and malondialdehyde (MDA) levels. Furthermore, superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels in the L/P group were significantly (P < 0.05) improved. Overall, our findings support the use of a combination of drugs (L/P and L/Pi) in lithium-pilocarpine model which remarkably ameliorated SRSs, reduced anxiety-related behaviors, retention of spatial/reference memory and lowered oxidative stress in a time-course evaluation 6 weeks post- SE insult.

Maternal and child health after injuries: a two-year follow-up of a nationally representative sample.

OBJECTIVE: The objective of this study was to examine the association between childhood injury and health outcomes among survivors and their mothers using a national survey in the United States (US). STUDY DESIGN: This was a longitudinal analysis of a nationally representative sample. METHODS: Secondary analysis of the 1997-2013 Medical Expenditure Panel Survey (MEPS) was performed. Children (aged 2-18 years) with or without injuries were followed up for two years. Injuries captured in the study were those associated with at least one hospitalization, emergency department visit, or office-based visit. Outcome measures were child and maternal general and mental health status. Multiple mixed-logistic regressions were used with suboptimal health defined as the response of poor or fair health versus good, very good, or excellent health. RESULTS: Of the 63,422 children analyzed, 3251 (4.9%) were injured, representing 3.6 million US children. Injured children were more likely to be male, white, and older than those without injuries (P < 0.01). About a fifth of injured children suffered head injuries. Injuries were strongly associated with suboptimal general and mental health status in children (adjusted odds ratios [AORs], 1.35 and 1.36, respectively, P < 0.05). Mothers of children with injuries were also more likely to report suboptimal mental health (AOR, 1.30, P < 0.05). CONCLUSION: Injuries among children are associated with lasting adverse effects in general and mental health. To improve health outcomes of pediatric injuries, further follow-up care may be needed to ensure that they return to pre-injury health levels. These results highlight the importance of primary prevention and the long-term impact of injuries on the health of children and their mothers.

Prevalence of comorbidities in cases of Middle East respiratory syndrome coronavirus: a retrospective study.

The Middle East respiratory syndrome coronavirus (MERS-CoV) is a life-threatening respiratory disease with a high case fatality rate; however, its risk factors remain unclear. We aimed to explore the influence of demographic factors, clinical manifestations and underlying comorbidities on mortality in MERS-CoV patients. Retrospective chart reviews were performed to identify all laboratory-confirmed cases of MERS-COV infection in Saudi Arabia that were reported to the Ministry of Health of Saudi Arabia between 23 April 2014 and 7 June 2016. Statistical analyses were conducted to assess the effect of sex, age, clinical presentation and comorbidities on mortality from MERS-CoV. A total of 281 confirmed MERS-CoV cases were identified: 167 (59.4%) patients were male and 55 (20%) died. Mortality predominantly occurred among Saudi nationals and older patients and was significantly associated with respiratory failure and shortness of breath. Of the 281 confirmed cases, 160 (56.9%) involved comorbidities, wherein diabetes mellitus, hypertension, ischemic heart disease, congestive heart failure, end-stage renal disease and chronic kidney disease were significantly associated with mortality from MERS-CoV and two or three comorbidities significantly affected the fatality rates from MERS-CoV. The findings of this study show that old age and the existence of underlying comorbidities significantly increase mortality from MERS-CoV.

The variation in quality and content of patient-focused health information on the Internet for otitis media.

BACKGROUND: When symptoms of otitis media appear, parents and patients often access the Internet for health information. We study the content and quality of health information in parent-patient-focused websites for otitis media. METHODS: We searched the 3 search engines (Google, Yahoo, and Bing) using "otitis media" and "middle ear infection" then reviewed the top 30 hits for each search. We included sites that were focused on providing patient-patient information about otitis media. A variety of instruments were used to assess website content and quality. RESULTS: In 35 included websites, there was considerable variation in content, with the average site having 11 out of 15 informational items potentially useful to parents and patients on otitis media (range 4-15). Across included websites, the mean DISCERN score was 47 out of 80 (low to medium quality), 16 (46%) were HONcode certified, and 8 (23%) fulfilled all the JAMA benchmark criteria. The average website was written at a 9th/10th-grade reading level. CONCLUSION: The content and quality of health information for otitis media in parent-and-patient-focused websites is highly variable. Although easy-to-read, high-quality websites with complete content are available, the average website sites is difficult to read without a high school education and is difficult to use. Consideration should be given to adopting a standard approach for presenting disease-specific information to parents and patients.

Evaluation of a semi-automated software program for the identification of vertebral fractures in children.

AIM: To assess observer reliability and diagnostic accuracy in children, of a semi-automated six-point technique developed for vertebral fracture (VF) diagnosis in adults, which records percentage loss of vertebral body height. MATERIALS AND METHODS: Using a semi-automated software program, five observers independently assessed T4 to L4 from the lateral spine radiographs of 137 children and adolescents for VF. A previous consensus read by three paediatric radiologists using a simplified algorithm-based qualitative technique (i.e., no software involved) served as the reference standard. RESULTS: Of a total of 1,781 vertebrae, 1,187 (67%) were adequately visualised according to three or more observers. Interobserver agreement in vertebral readability for each vertebral level for five observers ranged from 0.05 to 0.47 (95% CI: -0.19, 0.76). Intra-observer agreement using the intraclass correlation coefficient (ICC) ranged from 0.25 to 0.61. The overall sensitivity and specificity were 18% (95% CI: 14-22) and 97% (95% CI: 97-98), respectively. CONCLUSION: In contrast to adults, the six-point technique assessing anterior, middle, and posterior vertebral height ratios is neither satisfactorily reliable nor sensitive for VF diagnosis in children. Training of the software on paediatric images is required in order to develop a paediatric standard that incorporates not only specific vertebral body height ratios but also the age-related physiological changes in vertebral shape that occur throughout childhood.

Childhood scurvy: an unusual cause of refusal to walk in a child.

Scurvy, or vitamin C deficiency, is rarely presented to a rheumatology clinic. It can mimic several rheumatologic disorders. Although uncommon, it may present as pseudovasculitis or chronic arthritis. Scurvy still exists today within certain populations, particularly in patients with neurodevelopmental disabilities, psychiatric illness or unusual dietary habits.Scurvy presentation to the rheumatologist varies from aches and mild pains to excruciating bone pain or arthritis. Musculoskeletal and mucocutaneous features of scurvy are often what prompts referrals to pediatric rheumatology clinics. Unless health care providers inquire about nutritional habits and keep in mind the risk of nutritional deficiency, it will be easy to miss the diagnosis of scurvy. Rarity of occurrence as compared to other nutritional deficiencies, combined with a lack of understanding about modern-day risk factors for nutritional deficiency, frequently leads to delayed recognition of vitamin C deficiency. We report a case of scurvy in a mentally handicapped Saudi child, who presented with new onset inability to walk with diffuse swelling and pain in the left leg. Skin examination revealed extensive ecchymoses, hyperkeratosis and follicular purpura with corkscrew hairs, in addition to gingival swelling with bleeding. Clinical diagnosis of scurvy was rendered and confirmed by low serum vitamin C level. The patient did extremely well with proper nutritional support and vitamin C supplementation. It has been noticed lately that there is increased awareness about scurvy in rheumatology literature. A high index of suspicion, together with taking a thorough history and physical examination, is required for diagnosis of scurvy in patient who presents with musculoskeletal symptoms. Nutritional deficiency should also be considered by the rheumatologist formulating differential diagnosis for musculoskeletal or mucocutaneous complaints in children, particularly those at risk.

Physicians' attitudes towards interaction with the pharmaceutical industry.

The relationship between physicians and the pharmaceutical industry has ethical implications for patient care. This study examined knowledge and attitudes towards the pharmaceutical industry, and associations with actual behaviour, among physicians working in Saudi Arabia. In a cross-sectional study in 2012, a 100-point score was created from 17 5-point Likert-scale questions to assess knowledge and attitudes. The overall score of 659 participants was 63.1 (SD 8.5), with a majority holding a generally positive attitude. Higher (i.e. better) scores were significantly associated with a lack of interactions with the pharmaceutical industry and with refusal of gifts but not with education about ethics. In multivariate analysis, refusing gifts, additional income and Saudi nationality remained independently associated with higher scores. Overall, there was suboptimal knowledge and a generally positive attitude towards the pharmaceutical industry among the sample of physicians in Saudi Arabia.

Physicians' attitudes towards interaction with the pharmaceutical industry

The relationship between physicians and the pharmaceutical industry has ethical implications for patient care. This study examined knowledge and attitudes towards the pharmaceutical industry,and associations with actual behaviour, among physicians working in Saudi Arabia. In a cross-sectional study in 2012, a 100-point score was created from 17 5-point Likert-scale questions to assess knowledge and attitudes. The overall score of 659 participants was 63.1 [SD 8.5], with a majority holding a generally positive attitude. Higher [i.e.better] scores were significantly associated with a lack of interactions with the pharmaceutical industry and with refusal of gifts but not with education about ethics. In multivariate analysis, refusing gifts, additional income and Saudi nationality remained independently associated with higher scores. Overall,there was suboptimal knowledge and a generally positive attitude towards the pharmaceutical industry among the sample of physicians in Saudi Arabia

Les relations entre les médecins et l'industrie pharmaceutique ont des implications éthiques pour les soins aux patients. La présente étude a examiné les connaissances et les attitudes envers l'industrie pharmaceutique, ainsi que les associations avec les comportements réels chez des médecins exerçant en Arabie saoudite. Dans une étude transversale menée en 2012, un score sur 100 a été créé à partir de 17 questions sur une échelle de Likert en 5 points visant à évaluer les connaissances et les attitudes. Le score global des 659 participants était de 63,1 [ET 8,5], la majorité ayant généralement une attitude positive. Les scores les plus élevés [c'est-à-dire les meilleurs scores] étaient nettement associés à une absence d'interactions avec l'industrie pharmaceutique et le refus de cadeaux,mais n'étaient pas liés à une formation sur l’éthique.E l'analyse multivariée, le refus de cadeaux,des revenus supplémentaires ainsi que la nationalité saoudienne étaient des facteurs indépendamment associés à des scores plus élevés.Globalement, les connaissances étaient sous-optimales et l'attitude envers l'industrie pharmaceutique était généralement positive au sein de l'échantillon de médecins répondeurs en Arabie saoudite