Search results for: epileptic%20seizures

Authors: Adetoun Adedotun Amubode

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Nigeria's Textile Industry was the second largest in Africa after Egypt, with above 250 vibrant factories and over 50 percent capacity utilization contributing to foreign exchange earnings and employment generation. Currently, multifaceted challenges such as epileptic power supply, inconsistent government policies, growing digitalization, smuggling of foreign textiles, insecurity and the inability of the local industries to compete with foreign products, especially Chinese textile, has created a hostile environment for the sector. This led to the closure of most of the textile industries. China's textile industry has experienced institutional change and industrial restructuring, having 30% of the world's market share. This paper examined the strategies adopted by China in transforming her textile and clothing industries and designed a model for the integration of these strategies to improve the competitive strength and growth of the Nigerian textile and clothing industries in a dynamic and changing market. The paper concludes that institutional support, regional production, export-oriented policy, value-added and branding cultivation, technological upgrading and enterprise resource planning be integrated into the Nigerian clothing and textile industries.

Keywords: clothing, industry, integration, Nigerian, textile, transformation.

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Authors: Anat Achiron

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Background: Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system in young adults. It involves the immune system attacking the protective covering of nerve fibers (myelin), leading to inflammation and damage. MS can result in various neurological symptoms, such as muscle weakness, coordination problems, and sensory disturbances. Seizures are not common in MS, and the frequency is estimated between 0.4 to 6.4% over the disease course. Objective: Investigate the frequency of seizures in individuals with multiple sclerosis and to identify associated risk factors. Methods: We evaluated the frequency of seizures in a large cohort of 5686 MS patients followed at the Sheba Multiple Sclerosis Center and studied associated risk factors and comorbidities. Our research was based on data collection using a cohort study design. We applied logistic regression analysis to assess the strength of associations. Results: We found that younger age at onset, longer disease duration, and prolonged time to immunomodulatory treatment initiation were associated with increased risk for seizures. Conclusions: Our findings suggest that seizures in people with MS are directly related to the demyelination process and not associated with other factors like medication side effects or comorbid conditions. Therefore, initiating immunomodulatory treatment early in the disease course could reduce not only disease activity but also decrease seizure risk.

Keywords: epilepsy, seizures, multiple sclerosis, white matter, age

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Authors: Kedar S. Prabhavalkar, Nimmy Baby Poovanpallil

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Lamotrigine is approved for maintenance treatment of bipolar I disorder. However, its role in the treatment of acute bipolar depression is not well clear. Its efficacy in the treatment of major depressive disorders including refractory unipolar depression suggested the use of lamotrigine as an augmentation drug for acute bipolar depression. The present study aims to evaluate and perform a comparative analysis of the therapeutic effects of lamotrigine, an epileptic mood stabilizer, when used alone and in combination with duloxetine in treating acute bipolar depression at different doses of lamotrigine. Male swiss albino mice were used. For evaluation of efficacy of combination, immobility period was analyzed 30 min after the treatment from forced swim and tail suspension tests. Further amount of sucrose consumed in sucrose preference test was estimated. The combination of duloxetine and lamotrigine showed potentiation of antidepressant activity in acute models. Decrease in immobility time and increase in the amount of sucrose consumption in stressed mice were higher in combined group compared to lamotrigine monotherapy group. Brain monoamine levels were also attenuated more with combination compared to monotherapy. Results of the present study suggest potential role of lamotrigine and duloxetine combination in the treatment of acute bipolar depression.

Keywords: lamotrigine, duloxetine, acute bipolar depression, augmentation

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Authors: Omar Sorour, Michael Leahy, Thomas Irvine, Vladimir Koren

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Introduction: Covid encephalitis is a rare yet dangerous complication, particularly affecting the older and immunocompromised. Symptoms range from confusion to delirium, coma, and seizures. Although neurological manifestations have become more well-characterized in COVID patients, little is known about whether priorneurological abnormalities may predispose patients to COVID encephalopathy. Case Description: A 73 y.o. male with a CT and MRI-confirmed stable, prior 9 mm cavernoma in the right frontal lobe and no past history of seizures was hospitalized with generalized weakness, abdominal pain, nausea, and shortness of breath with subsequent COVID pneumonia. Three days after the initial presentation, the patient developed a spontaneous generalized tonic-clonic seizure consistent with presumed COVID encephalitis, along with somnolence and confusion. A day later, the patient had two other seizure episodes. Follow-up EEG suggested an inter-ictal epileptic focus with sharp waves corresponding to roughly the same location as the patient’s pre-existing cavernoma. The patient’s seizures stopped shortly thereafter, while his encephalopathy continued for days. Conclusion: We illustrate that a pre-existing anatomic cortical abnormality may act as a potential nidus for new-onset seizure activity in the context of suggested COVID encephalopathy. Future studies may further demonstrate that manifestations of COVIDencephalopathy in certain patients may be more predictable than initially assumed.

Keywords: cavernoma, covid, encephalopathy, seizures

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Authors: Mostafa Mohammadpour, Christoph Kapeller, Christy Li, Josef Scharinger, Christoph Guger

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Interictal spikes provide valuable information on electrocorticography (ECoG), which aids in surgical planning for patients who suffer from refractory epilepsy. However, the shape and temporal dynamics of these spikes remain unclear. The purpose of this work was to analyze the shape of interictal spikes and measure their distance to the seizure onset zone (SOZ) to use in epilepsy surgery. Thirteen patients' data from the iEEG portal were retrospectively studied. For analysis, half an hour of ECoG data was used from each patient, with the data being truncated before the onset of a seizure. Spikes were first detected and grouped in a sequence, then clustered into interictal epileptiform discharges (IEDs) and non-IED groups using two-step clustering. The distance of the spikes from IED and non-IED groups to SOZ was quantified and compared using the Wilcoxon rank-sum test. Spikes in the IED group tended to be in SOZ or close to it, while spikes in the non-IED group were in distance of SOZ or non-SOZ area. At the group level, the distribution for sharp wave, positive baseline shift, slow wave, and slow wave to sharp wave ratio was significantly different for IED and non-IED groups. The distance of the IED cluster was 10.00mm and significantly closer to the SOZ than the 17.65mm for non-IEDs. These findings provide insights into the shape and spatiotemporal dynamics of spikes that could influence the network mechanisms underlying refractory epilepsy.

Keywords: spike propagation, spike pattern, clustering, SOZ

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Authors: Murali Munisamy, Gauthaman Karunakaran, Mubarak Al-Gahtany, Vivekanandhan Subbiah, M. Manjari Tripati

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Background: Sodium valproate is a widely prescribed broad-spectrum anti-epileptic drug. It shows high inter-individual variability in pharmacokinetics and pharmacodynamics and has a narrow therapeutic range. We evaluated the effects of polymorphic uridine diphosphate glucuronosyltransferase (UGT1A9) metabolizing enzyme on the pharmacokinetics of sodium valproate in the patients with epilepsy who showed toxicity to therapy. Methods: Genotype analysis of the patients was made with polymerase chain–restriction fragment length polymorphism (RFLP) with sequencing. Plasma drug concentrations were measured with reversed phase high-performance liquid chromatography (HPLC) and concentration–time data were analyzed by using a non-compartmental approach. Results: The results of this study suggested a significant genotypic as well as allelic association with valproic acid toxicity for UGT1A9 polymorphic enzymes. The elimination half-life (t 1/2=40.2 h) of valproic acid was longer and the clearance rate (CL=937 ml/h) was lower in the poor metabolizers group of UGT1A9 polymorphism who showed toxicity than in the intermediate metabolizers group (t1/2=35.5 h, CL=1042 ml/h) or the extensive metabolizers group (t1/2=26. h, CL=1,302 ml/h). Conclusion: Our findings suggest that the UGT1A9 genetic polymorphism plays a significant role in the steady state concentration of sodium valproate, and it thereby has an impact on the toxicity of the sodium valproate used in the patients with epilepsy.

Keywords: UGT1A9, sodium valporate, pharmacogenetics, polymorphism

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Authors: Tomáš Nejedlý, Dominika Mrázková, Jitka Viktorová

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The blood-brain barrier (BBB) serves as a protective shield, preventing the entry of harmful substances into the central nervous system. On the other hand, it also restricts the transport of neuroactive drugs, such as antiepileptics, which mitigate epileptic seizures. Drug-resistant epilepsy is often associated with the overexpression of efflux transporters, including P-glycoprotein (P-gp) or multidrug resistance protein 1 (MRP1), on the BBB. The aim of this work is to find P-gp and MRP1 inhibitors derived from phytocannabinoids and terpenes. The work evaluates whether these compounds interact directly with P-gp or MRP1 by rhodamine 123 or fluorescein efflux assay. The effect of phytocannabinoids on the gene expression of these transporters is also studied using qPCR and Western blot. These transporters are found in BBB cells; however, we decided to use the human ovarian cancer cell line (A2780ADR) due to its overproduction of P-gp and malignant glioma cell line (U87) due to its overproduction of MRP1. The results showed that while terpenes suppressed the activity of efflux transporters, phytocannabinoids tended to decrease their expression. Terpenes demonstrated an average inhibition of 65%, surpassing phytocannabinoids, which exhibited an average inhibition of approximately 30%. Particularly noteworthy was the modulating effect of (-)-α-bisabolol with the highest activity among the compounds tested. Based on these findings, phytocannabinoids and terpenes emerge as promising natural candidates for addressing drug resistance linked to efflux transporters. Acknowledgment: The project was funded by the Grant No 22-20860S of The Czech Science Foundation.

Keywords: drug-resistant epilepsy, efflux transporters, multidrug resistance protein 1, P-glycoprotein, phytocannabinoids, terpens

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Authors: Jun Yang, Ching-Liang Hsieh, Yi-Wen Lin

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Chronic inflammatory pain results from peripheral tissue injury or local inflammation to increase the release of protons, histamines, adenosine triphosphate, and several proinflammatory cytokines. Transient receptor potential vanilloid 1 (TRPV1) is involved in fibromyalgia, neuropathic, and inflammatory pain; however, its exact mechanisms in chronic inflammatory pain are still unclear. We investigate the analgesic effect of EA by injecting complete Freund’s adjuvant (CFA) in the hind paw of mice to induce chronic inflammatory pain ( > 14 d). Our results showed that EA significantly reduced chronic mechanical and thermal hyperalgesia in the chronic inflammatory pain model. Chronic mechanical and thermal hyperalgesia was also abolished in TRPV1−/− mice. TRPV1 increased in the dorsal root ganglion (DRG) and spinal cord (SC) at 2 weeks after CFA injection. The expression levels of downstream molecules such as pPKA, pPI3K, and pPKC increased, as did those of pERK, pp38, and pJNK. Transcription factors (pCREB and pNFκB) and nociceptive ion channels (Nav1.7 and Nav1.8) were involved in this process. Inflammatory mediators such as GFAP (Glial fibrillary acidic protein), S100B, and RAGE (Receptor for advanced glycation endproducts) were also involved. The expression levels of these molecules were reduced in EA (electroacupuncture) and TRPV1−/−mice but not in the sham EA group. The present study demonstrated that EA or TRPV1 gene deletion reduced chronic inflammatory pain through TRPV1 and related molecules. In addition, our data provided evidence to support the clinical use of EA for treating chronic inflammatory pain.

Keywords: auricular electric-stimulation, epileptic seizures, anti-inflammation, electroacupuncture

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Authors: Marija Zulić, Vanda Hájková, Nina Brkić–Jovanović, Srećko Potić, Sanja Tomić

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The name cerebral palsy comes from the word cerebrum, which means the brain and the word palsy, which means seizure, and essentially refers to the movement disorder. In the clinical picture of cerebral palsy, basic neuromotor disorders are associated with other various disorders: behavioural, intellectual, speech, sensory, epileptic seizures, and bone and joint deformities. Motor speech disorders are among the most common difficulties present in people with cerebral palsy. Social participation represents an interaction between an individual and their social environment. Quality of social participation of the students with cerebral palsy at school is an important indicator of their successful participation in adulthood. One of the most important skills for the undisturbed social participation is ability of good communication. The aim of the study was to determine relation between social participation of students with cerebral palsy and presence of their speech impairment in primary schools in the Czech Republic. The study was performed in the Czech Republic in mainstream schools and schools established for the pupils with special education needs. We analysed 75 children with cerebral palsy aged between six and twelve years attending up to sixth grade by using the first and the third part of the school function assessment questionnaire as the main instrument. The other instrument we used in the research is the Gross motor function classification system–five–level classification system, which measures degree of motor functions of children and youth with cerebral palsy. Funding for this study was provided by the Grant Agency of Charles University in Prague.

Keywords: cerebral palsy, social participation, speech disorders, The Czech Republic, the school function assessment

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Authors: Shaban Saad, Syed Ahmed, Suher Aburawi, Isabel Fong

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Ruta graveolens is a plant commonly found in north Africa and south Europe. It is reported that Ruta graveolens is used traditionally for epilepsy and some other illnesses. The acute and sub-acute effects of alcoholic extract residue were tested for possible anti-epileptic and skeletal muscle relaxation activity. The effect of extract on rat spontaneous motor activity (SMA) was also investigated using open filed. We previously proved the anti convulsant activity of the plant against pentylenetetrazol and electrically induced convulsions. Therefore in this study strychnine was used to induce convulsions in order to explore the mechanism of anti-convulsant activity of the plant. The skeletal muscle relaxation activity of Ruta graveolens was studied using pull-up and rod hanging tests in rats. At concentration of 5%w/v the extract protected mice against strychnine induced myoclonic jerks and death. The pull-up and rod hanging tests pointed to a skeletal muscle relaxant activity at higher concentrations. Ruta graveolens extract also significantly decreased the number of squares visited by rats in open field apparatus at all tested concentrations (3.5-20%w/v). However, the significant decrease in number of rearings was only noticed at concentrations of (15 and 20%w/v). The results indicate that Ruta graveolens contains compound(s) capable to inhibit convulsions, decrease SMA and/or diminish skeletal muscle tone in animal models. This data and the previously generated data together point to a general depression trend of CNS produced by Ruta graveolens.

Keywords: Ruta graveolens, open field, skeletal muscle relaxation

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Authors: Sarah K. Amer, Walaa Alaa

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Epilepsy is an important cause of mortality and morbidity, according to WHO statistics. It is characterized by the presence of frequent seizures occurring more than 24 hours apart. Carbamazepine (CBZ) is considered first-line treatment for epilepsy. However, reports have shown that CBZ oral formulations failed to achieve optimum systemic delivery, minimize side effects, and enhance patient compliance. Besides, the literature has signified the lack of therapeutically efficient CBZ transdermal formulation and the urge for its existence owing to its ease and convenient method of application and highlighted capability to attain higher bioavailability and more extended-release profiles compared to conventional oral CBZ tablets. This work aims to prepare CBZ microspheres (MS) that are embedded in a transdermal gel containing Vitamin B to be co-delivered. MS were prepared by emulsion-solvent diffusion method using Eudragit S as core forming polymer and hydroxypropyl methylcellulose (HPMC) polymer. The MS appeared to be spherical and porous in nature, offering a large surface area and high entrapment efficiency of CBZ. The transdermal gel was prepared by solvent-evaporation technique using HPMC that, offered high entrapment efficiency and Eudragit S that provided an extended-release profile. Polyethylene glycol, Span 80 and Pyridoxine were also added. Data indicated that combinations of CBZ with pyridoxine can reduce epileptic seizures without affecting motor coordination. Extended-release profiles were evident for this system. The patches were furthermore tested for thickness, moisture content, folding endurance, spreadability and viscosity measurements. This novel pharmaceutical formulation would be of great influence on seizure control, offering better therapeutic effects.

Keywords: epilepsy, carbamazepine, pyridoxine, transdermal

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Authors: Adebowale Olukayode Efunnowo

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This study was carried out to assess the awareness and utilization of Social Network Tools (SNTs) among agricultural science students in Colleges of Education in Ogun State, Nigeria. Simple random sampling techniques were used to select 280 respondents from the study area. Descriptive statistics was used to describe the objectives while Pearson Product Moment Correlation was used to test the hypothesis. The result showed that the majority (71.8%) of the respondents were single, with a mean age of 20 years. Almost all (95.7%) the respondents were aware of Facebook and 2go as a Social Network Tools (SNTs) while 85.0% of the respondents were not aware of Blackplanet, LinkedIn, MyHeritage and Bebo. Many (41.1%) of the respondents had views that using SNTs can enhance extensive literature survey, increase internet browsing potential, promote teaching proficiency, and update on outcomes of researches. However, 51.4% of the respondents perceived that SNTs usage as what is meant for the lecturers/adults only while 16.1% considered it as mainly used by internet fraudsters. Findings revealed that about 50.0% of the respondents browsed Facebook and 2go daily while more than 80% of the respondents used Blackplanet, MyHeritage, Skyrock, Bebo, LinkedIn and My YearBook as the need arise. Major constraints to the awareness and utilization of SNTs were high cost and poor quality of ICTs facilities (77.1%), epileptic power supply (75.0%), inadequate telecommunication infrastructure (71.1%), low technical know-how (62.9%) and inadequate computer knowledge (61.1%). The result of PPMC analysis showed that there was an inverse relationship between constraints and utilization of SNTs at p < 0.05. It can be concluded that constraints affect efficient and effective utilization of SNTs in the study area. It is hereby recommended that management of colleges of education and agricultural institutes should provide good internet connectivity, computer facilities, and alternative power supply in order to increase the awareness and utilization of SNTs among students.

Keywords: awareness, utilization, social network tools, constraints, students

Procedia PDF Downloads 322

Authors: Sharmin Akhter, M. Salahuddin, Sukalyan Kumar Kundu, Mohammad Fahim Kadir

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Relatively insoluble candidate drug like carbamazepine (CBZ) often exhibit incomplete or erratic absorption; and hence wide consideration is given to improve aqueous solubility of such compound. Solid dispersions were formulated with an aim of improving aqueous solubility, oral bioavailability and the rate of dissolution of Carbamazepine using different hydrophyllic polymer like Polyethylene Glycol (PEG) 6000, Polyethylene Glycol (PEG) 4000, kollidon 30, HPMC 6 cps, poloxamer 407 and povidone k 30. Solid dispersions were prepared with different drug to polymer weight ratio by the solvent evaporation method where methanol was used as solvent. Drug-polymer physical mixtures were also prepared to compare the rate of dissolution. Effects of different polymer were studied for solid dispersion formulation as well as physical mixtures. These formulations were characterized in the solid state by Fourier Transform Infrared (FTIR) spectroscopy and Scanning Electron Microscopy (SEM). Solid state characterization indicated CBZ was present as fine particles and entrapped in carrier matrix of PEG 6000 and PVP K30 solid dispersions. Fourier Transform Infrared (FTIR) spectroscopic studies showed the stability of CBZ and absence of well-defined drug-polymer interactions. In contrast to the very slow dissolution rate of pure CBZ, dispersions of drug in polymers considerably improved the dissolution rate. This can be attributed to increased wettability and dispersibility, as well as decreased crystallinity and increase in amorphous fraction of drug. Solid dispersion formulations containing PEG 6000 and Povidone K 30 showed maximum drug release within one hour at the ratio of 1:1:1. Even physical mixtures of CBZ prepared with both carriers also showed better dissolution profiles than those of pure CBZ. In conclusions, solid dispersions could be a promising delivery of CBZ with improved oral bioavailability and immediate release profiles.

Keywords: carbamazepine, FTIR, kollidon 30, HPMC 6 CPS, PEG 6000, PEG 4000, poloxamer 407, water solubility, povidone k 30, SEM, solid dispersion

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Authors: Rayhana Begum, Manju Sharma

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Careya arborea Roxb. belongs to the Lecythidaceae family, is traditionally used in tumors, anthelmintic, bronchitis, epileptic fits, astringents, inflammation, an antidote to snake-venom, skin disease, diarrhea, dysentery with bloody stools, dyspepsia, ulcer, toothache, and ear pain. The present study was focused on investigating the anti-arthritic effect of coumaroyl lupendioic acid, a new lupane-type triterpene from Careya arborea stem bark in the chronic inflammatory model and further assessing its possible mechanism on the modulation of inflammatory biomarkers. Arthritis was induced by injecting 0.1 ml of Complete Freund’s Adjuvant (5 mg/ml of heat killed Mycobacterium tuberculosis) into the subplantar region of the left hind paw. Treatment with coumaroyl lupendioic acid (10 and 20 mg/kg, p.o.) and reference drugs (indomethacin and dexamethasone at the dose of 5 mg/kg, p.o.) were started on the day of induction and continued up to 28 days. The progression of arthritis was evaluated by measuring paw volume, tibio tarsal joint diameters, and arthritic index. The effect of coumaroyl lupendioic acid (CLA) on the production PGE₂, NO, MPO, NF-κB, TNF-α, IL-1β, and IL-6 on serum level as well as inflamed paw tissue were also assessed. In addition, ankle joints and spleen were collected and prepared for histological examination. CLA in inflamed rats resulted in significant amelioration of paw edema, tibio-tarsal joint swelling and arthritic score as compared to CFA control group. The results indicated that CLA treated groups markedly decreased the levels of inflammatory mediators (PGE₂, NO, MPO and NF-κB levels) and down-regulated the production of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in paw tissue homogenates as well as in serum. However, the more pronounced effect was observed in the inflamed paw tissue homogenates. CLA also revealed a protective effect to the tibio-tarsal joint cartilage and spleen. These results suggest that coumaroyl lupendioic acid inhibits inflammation may be through the suppression of the cascade of proinflammatory mediators via the down-regulation of NF-ҡB.

Keywords: complete Freund’s adjuvant , Coumaroyl lupendioic acid, pro-inflammatory cytokines, prostaglandin E2

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Authors: Željka Rogač, Dejan Stevanović, Sara Bečanović, Ljubica Božić, Aleksandar Dimitrijević, Dragana Bogićević, Dimitrije Nikolić

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Children with epilepsy face changes in cognitive functioning, the appearance of symptoms of psychopathology and a decline in their quality of life. Factors related to epileptic seizures and the side effects of AEDs are considered to be potential causes of these changes.These changes can be prevented by prompt action, replacement of AEDs, psychological and psychiatric treatment, and social support. However, a review of literature has not yielded a conclusion as to when it is best to react, i.e., when changes in the functioning of children with newly-diagnosed epilepsy appears. The primary goal of this study was to investigate the impact of the most commonly used AEDs on cognitive status, behavior, anxiety and depression, as well as quality of life of children with newly-diagnosed epilepsy, during the first six months of treatment. This is a non-interventional, prospective study involving six-month monitoring of cognitive status, internalizing and externalizing symptoms, as well as quality of life of children with newly-diagnosed epilepsy, and the impact of antiepileptic drugs on these domains. Children with new-onset epilepsy and their parents, immediately after the introduction of antiepileptic drugs as well as six months later, filled out appropriate questionnaires (RCADS, NCBRF, CHEQOL-25, KIDSCREEN-10, AEP). At the same time, a psychologist performed the psychological testing of the child (REVISK). At the very beginning of REVISK treatment, a reduced VIQ was established, while after six months there was a significant decrease in IQ, VIQ and especially PIQ, under the influence of primary cognitive potentials and the development of depressive symptoms. All scores of the RCADS and NCBFR questionnaires were significantly elevated after six months while internalizing and externalizing symptoms affected each other. The development of depressive symptoms was significantly influenced by AED. The scores of the CHEQOL25 and KIDSCREEN10 questionnaires were significantly reduced, influenced by the adverse effects of AED and quality of life at the start of treatment. Side effects of AEDs, were significantly associated with depressive symptoms and reduced quality of life and did not significantly affect cognitive decline, anxiety, ADHD, and behavioral disorders during the first six months.

Keywords: epilepsy, children, AEDs, cognition, behavior, ADHD, anxiety, depression, QOL

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Authors: Muhammad Bilal, Amelia Jane Llyod, Habsah Mohamad, Jia Hui Wong, Abdul Aziz Mohamed Yusoff, Jafri Malin Abdullah, Jingli Zhang

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Epilepsy is one of the major brain afflictions occurs with uncontrolled excitation of cortex; disturbed 50 million of world’s population. About 25 percent of patients subjected to adverse effects from antiepileptic drugs (AEDs) such as depression, nausea, tremors, gastrointestinal symptoms, osteoporosis, dizziness, weight change, drowsiness, fatigue are commonly observed indications; therefore, new drugs are required to cure epilepsy. GABA is principle inhibitory neurotransmitter, control excitation of the brain. Mutation or dysfunction of GABA receptor is one of the primary causes of epilepsy, which is confirmed from many acquired models of epilepsy like traumatic brain injury, kindling, and status epilepticus models of epilepsy. GABA receptor has 3 distinct types such as GABA (A), GABA (B), GABA(C).GABA (A) receptor has 20 different subunits, α1β2γ2 subunits composition of GABA (A) receptor is the most used combination of subunits for screening of compounds against epilepsy. We expressed α1β2γ2s subunits of GABA (A) Receptor in Xenopus leavis oocytes and examined the enhancement potential of 4-Hydroxybenzoic acid compound on GABA (A) receptor via two-electrode voltage clamp current recording technique. Bamboo shoots are the young, tender offspring of bamboo, which are usually harvested after a cultivating period of 2 weeks. Proteins, acids, fat, starch, carbohydrate, fatty acid, vitamin, dietary fiber, and minerals are the major constituent found systematically in bamboo shoots. These shoots reported to have anticancer, antiviral, antibacterial activity, also possess antioxidant properties due to the presence of phenolic compounds. Student t-test analysis suggested that 4- hydroxybenzoic acid positively allosteric GABA (A) receptor, increased normalized current amplitude to 1.0304±0.0464(p value 0.032) compared with vehicle. 4-Hydrobenzoic acid, a compound from Dendrocalamus Asper bamboo shoot gives new insights for future studies on bamboo shoots with motivation for extraction of more compounds to investigate their effects on human and rodents against epilepsy, insomnia, and anxiety.

Keywords: α1β2γ2S, antiepileptic, bamboo shoots, epilepsy GABA (A) receptor, two-microelectrode voltage clamp, xenopus laevis oocytes

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Authors: Nouha Bouayed Abdelmoula, Rim Louati, Nawel Abdellaoui, Balkiss Abdelmoula, Oldez Kaabi, Walid Smaoui, Samir Aloulou

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Background and Aims: Cardiofaciocutaneous syndrome (CFC) is an autosomal dominant disorder with the vast majority of cases arising by a new mutation of BRAF, MEK1, MEK2, or rarely, KRAS genes. Here, we report a rare Tunisian case of CFC syndrome for whom we identify SOS1 mutation. Methods: Genomic DNA was obtained from peripheral blood collected in an EDTA tube and extracted from leukocytes using the phenol/chloroform method according to standard protocols. High resolution melting (HRM) analysis for screening of mutations in the entire coding sequence of PTPN11 was conducted first. Then, HRM assays to look for hot spot mutations coding regions of the other genes of the RAS-MAPK pathway (RAt Sarcoma viral oncogene homolog Mitogen-Activated Protein Kinases Pathway): SOS1, SHOC2, KRAS, RAF1, KRAS, NRAS, CBL, BRAF, MEK1, MEK2, HRAS, and RIT1, were applied. Results: Heterozygous SOS1 point mutation clustered in exon 10, which encodes for the PH domain of SOS1, was identified: c.1655 G > A. The patient was a 9-year-old female born from a consanguineous couple. She exhibited pulmonic valvular stenosis as congenital heart disease. She had facial features and other malformations of Noonan syndrome, including macrocephaly, hypertelorism, ptosis, downslanting palpebral fissures, sparse eyebrows, a short and broad nose with upturned tip, low-set ears, high forehead commonly associated with bitemporal narrowing and prominent supraorbital ridges, short and/or webbed neck and short stature. However, the phenotype is also suggestive of CFC syndrome with the presence of more severe ectodermal abnormalities, including curly hair, keloid scars, hyperkeratotic skin, deep plantar creases, and delayed permanent dentition with agenesis of the right maxillary first molar. Moreover, the familial history of the patient revealed recurrent brain malignancies in the paternal family and epileptic disease in the maternal family. Conclusions: This case report of an overlapping RASopathy associated with SOS1 mutation and familial history of brain tumorigenesis is exceptional. The evidence suggests that RASopathies are truly cancer-prone syndromes, but the magnitude of the cancer risk and the types of cancer partially overlap.

Keywords: cardiofaciocutaneous syndrome, CFC, SOS1, brain cancer, germline mutation

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Authors: Sakshi Piplani, Ajit Kumar

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Valproic acid (VPA) is the first synthetic therapeutic agent used to treat epileptic disorders, which account for affecting nearly 1% world population. Teratogenicity caused by VPA has prompted the search for next generation drug with better efficacy and lower side effects. Recent studies have posed HDAC8 as direct target of VPA that causes the teratogenic effect in foetus. We have employed molecular dynamics (MD) and docking simulations to understand the binding mode of VPA and their analogues onto HDAC8. A total of twenty 3D-structures of human HDAC8 isoforms were selected using BLAST-P search against PDB. Multiple sequence alignment was carried out using ClustalW and PDB-3F07 having least missing and mutated regions was selected for study. The missing residues of loop region were constructed using MODELLER and energy was minimized. A set of 216 structural analogues (>90% identity) of VPA were obtained from Pubchem and ZINC database and their energy was optimized with Chemsketch software using 3-D CHARMM-type force field. Four major neurotransmitters (GABAt, SSADH, α-KGDH, GAD) involved in anticonvulsant activity were docked with VPA and its analogues. Out of 216 analogues, 75 were selected on the basis of lower binding energy and inhibition constant as compared to VPA, thus predicted to have anti-convulsant activity. Selected hHDAC8 structure was then subjected to MD Simulation using licenced version YASARA with AMBER99SB force field. The structure was solvated in rectangular box of TIP3P. The simulation was carried out with periodic boundary conditions and electrostatic interactions and treated with Particle mesh Ewald algorithm. pH of system was set to 7.4, temperature 323K and pressure 1atm respectively. Simulation snapshots were stored every 25ps. The MD simulation was carried out for 20ns and pdb file of HDAC8 structure was saved every 2ns. The structures were analysed using castP and UCSF Chimera and most stabilized structure (20ns) was used for docking study. Molecular docking of 75 selected VPA-analogues with PDB-3F07 was performed using AUTODOCK4.2.6. Lamarckian Genetic Algorithm was used to generate conformations of docked ligand and structure. The docking study revealed that VPA and its analogues have more affinity towards ‘hydrophobic active site channel’, due to its hydrophobic properties and allows VPA and their analogues to take part in van der Waal interactions with TYR24, HIS42, VAL41, TYR20, SER138, TRP137 while TRP137 and SER138 showed hydrogen bonding interaction with VPA-analogues. 14 analogues showed better binding affinity than VPA. ADMET SAR server was used to predict the ADMET properties of selected VPA analogues for predicting their druggability. On the basis of ADMET screening, 09 molecules were selected and are being used for in-vivo evaluation using Danio rerio model.

Keywords: HDAC8, docking, molecular dynamics simulation, valproic acid

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Authors: Christine F. Boos, Fernando M. Azevedo

Abstract:

Electroencephalogram (EEG) is a record of the electrical activity of the brain that has many applications, such as monitoring alertness, coma and brain death; locating damaged areas of the brain after head injury, stroke and tumor; monitoring anesthesia depth; researching physiology and sleep disorders; researching epilepsy and localizing the seizure focus. Epilepsy is a chronic condition, or a group of diseases of high prevalence, still poorly explained by science and whose diagnosis is still predominantly clinical. The EEG recording is considered an important test for epilepsy investigation and its visual analysis is very often applied for clinical confirmation of epilepsy diagnosis. Moreover, this EEG analysis can also be used to help define the types of epileptic syndrome, determine epileptiform zone, assist in the planning of drug treatment and provide additional information about the feasibility of surgical intervention. In the context of diagnosis confirmation the analysis is made using long term EEG recordings with at least 24 hours long and acquired by a minimum of 24 electrodes in which the neurophysiologists perform a thorough visual evaluation of EEG screens in search of specific electrographic patterns called epileptiform discharges. Considering that the EEG screens usually display 10 seconds of the recording, the neurophysiologist has to evaluate 360 screens per hour of EEG or a minimum of 8,640 screens per long term EEG recording. Analyzing thousands of EEG screens in search patterns that have a maximum duration of 200 ms is a very time consuming, complex and exhaustive task. Because of this, over the years several studies have proposed automated methodologies that could facilitate the neurophysiologists’ task of identifying epileptiform discharges and a large number of methodologies used neural networks for the pattern classification. One of the differences between all of these methodologies is the type of input stimuli presented to the networks, i.e., how the EEG signal is introduced in the network. Five types of input stimuli have been commonly found in literature: raw EEG signal, morphological descriptors (i.e. parameters related to the signal’s morphology), Fast Fourier Transform (FFT) spectrum, Short-Time Fourier Transform (STFT) spectrograms and Wavelet Transform features. This study evaluates the application of these five types of input stimuli and compares the classification results of neural networks that were implemented using each of these inputs. The performance of using raw signal varied between 43 and 84% efficiency. The results of FFT spectrum and STFT spectrograms were quite similar with average efficiency being 73 and 77%, respectively. The efficiency of Wavelet Transform features varied between 57 and 81% while the descriptors presented efficiency values between 62 and 93%. After simulations we could observe that the best results were achieved when either morphological descriptors or Wavelet features were used as input stimuli.

Keywords: Artificial neural network, electroencephalogram signal, pattern recognition, signal processing

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Authors: Alla Ovsyannikova, Oksana Rymar, Elena Shakhtshneider, Mikhail Voevoda

Abstract:

In Siberia endocrinologists increasingly noted young patients with the course of diabetes mellitus differing from 1 and 2 types. Therefore we did a molecular genetic study for this group of patients to verify the monogenic forms of diabetes mellitus in them and researched the characteristics of this pathology. When confirming the monogenic form of diabetes, we performed a correction therapy for many patients (transfer from insulin to tablets), prevented specific complications, examined relatives and diagnosed their diabetes at the preclinical stage, revealed phenotypic characteristics of the pathology which led to the high significance of this work. Materials and Methods: We observed 5 patients (4 families). We diagnosed MODY (Maturity Onset Diabetes of the Young) during the molecular genetic testing (direct automatic sequencing). All patients had a full clinical examination, blood samples for biochemical research, determination of C-peptide and TSH, antibodies to b-cells, microalbuminuria, abdominal ultrasound, heart and thyroid ultrasound, examination of ophthalmologist. Results: We diagnosed 3 rare types of MODY: two women had MODY8, one man – MODY6 and man and his mother - MODY12. Patients with types 8 and 12 had clinical features. Age of onset hyperglycemia ranged from 26 to 34 years. In a patient with MODY6 fasting hyperglycemia was detected during a routine examination. Clinical symptoms, complications were not diagnosed. The patient observes a diet. In the first patient MODY8 was detected during first pregnancy, she had itchy skin and mostly postprandial hyperglycemia. Upon examination we determined glycated hemoglobin 7.5%, retinopathy, non-proliferative stage, peripheral neuropathy. She uses a basic bolus insulin therapy. The second patient with MODY8 also had clinical manifestations of hyperglycemia (pruritus, thirst), postprandial hyperglycemia and diabetic nephropathy, a stage of microalbuminuria. The patient was diagnosed autoimmune thyroiditis. She used inhibitors of DPP-4. The patient with MODY12 had an aggressive course. In the detection of hyperglycemia he had complaints of visual impairment, intense headaches, leg cramps. The patient had a history of childhood convulsive seizures of non-epileptic genesis, without organic pathology, which themselves were stopped at the age of 12 years. When we diagnosed diabetes a patient was 28 years, he had hypertriglyceridemia, atherosclerotic plaque in the carotid artery, proliferative retinopathy (lacerocoagulation). Diabetes and early myocardial infarction were observed in three cases in family. We prescribe therapy with sulfonylureas and SGLT-2 inhibitors with a positive effect. At the patient's mother diabetes began at a later age (30 years) and a less aggressive course was observed. She also has hypertriglyceridemia and uses oral hypoglycemic drugs. Conclusions: 1) When young patients with hyperglycemia have extrapancreatic pathologies and diabetic complications with a short duration of diabetes we can assume they have one of type of MODY diabetes. 2) In patients with monogenic forms of diabetes mellitus, the clinical manifestations of hyperglycemia in each succeeding generation are revealed at an earlier age. Research had increased our knowledge of the monogenic forms of diabetes. The reported study was supported by RSCF, research project No. 14-15-00496-P.

Keywords: diabetes mellitus, MODY diabetes, monogenic forms, young patients

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