Search results for: dopamine dysfunction

Authors: Zi-Han Li, Lu Fang, Liang Wu, Dong-Yuan Chang, Manyuan Dong, Liang Ji, Qi Zhang, Ming-Hui Zhao, Sydney C. W. Tang, Lemin Zheng, Min Chen

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Uncoupling of mitochondrial respiration by chemical uncouplers has proven effective in ameliorating obesity, insulin resistance, and hyperglycemia, which were risk factors for diabetic nephropathy (DN). Recently, we found that ANXA1 could improve mitochondrial function to mitigate DN progression. However, the underlying mechanism is not fully clear yet. Here, we identified uncoupling protein 1 (UCP1), an inner membrane protein of mitochondria, as a key to mitochondrial homeostasis improved by ANXA1. Specifically, ANXA1 attenuated mitochondrial dysfunction via appropriately upregulating UCP1 by stabilizing its transcription factor GATA binding protein 3 (GATA3) by combining it with thioredoxin. Moreover, specific overexpression of UCP1 in the renal cortex rescued renal injuries in diabetic Anxa1-KO mice. UCP1 deletion aggravated renal injuries in HFD/STZ-induced diabetic mice. Mechanistically, UCP1 reduced mitochondrial fission through the aristaless-related homeobox (ARX)/cardiolipin synthase 1 (CRLS1) pathway. Therapeutically, CL316243, a UCP1 agonist, could attenuate established DN in db/db mice. This work established an alternative principle to harness the power of uncouplers for the treatment of DN.

Keywords: diabetic nephropathy, uncoupling protein 1, mitochondrial homeostasis, cardiolipin metabolism

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Authors: Zohreh Rostami, Arezoo Khosravi, Mohammad Nikpoor Aghdam, Mahmood Salesi

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Background: Cardiovascular mortality in chronic kidney disease (CKD) and end stage renal disease (ESRD) patients have a strong relationship with baseline or progressive left ventricular hypertrophy (LVH) meanwhile in hemodialysis patients 10% decrement in left ventricular mass was associated with 28% reduction in cardiovascular mortality risk. In consonance with these arguments, we designed a study to measure morphological and functional echocardiographic variations early after transplantation. Method: The patients with normal renal function underwent two advanced echocardiographic studies to examine the structural and functional changes in left ventricular mass before and 3-month after transplantation. Results: From a total of 23 participants 21(91.3%) presented with left ventricular hypertrophy, 60.9% in eccentric and 30.4% in concentric group. Diastolic dysfunction improved in concentric group after transplantation. Both in pre and post transplantation global longitudinal strain (GLS)- average in eccentric group was more than concentric (-17.45 ± 2.75 vs -14.3 ± 3.38 p=0.03) and (-18.08 ± 2.6 vs -16.1 ± 2.7 p= 0.04) respectively. Conclusion: Improvement and recovery of left ventricular function in concentric group was better and sooner than eccentric after kidney transplantation. Although fractional shortening and diastolic function and GLS-4C in pre-transplantation in concentric group was worse than eccentric, but therapeutic response to kidney transplantation in concentric was more and earlier than eccentric group.

Keywords: chronic kidney disease, end stage renal disease, left ventricular hypertrophy, global longitudinal strain

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Authors: Zi-Han Li, Lu Fang, Liang Wu, Dong-Yuan Chang, Manyuan Dong, Liang Ji, Qi Zhang, Ming-Hui Zhao, Sydney C.W. Tang, Lemin Zheng, Min Chen

Abstract:

Uncoupling of mitochondrial respiration by chemical uncouplers has proven effective in ameliorating obesity, insulin resistance, and hyperglycemia, which were risk factors for diabetic nephropathy (DN). Recently, it was found that annexin A1(ANXA1) could improve mitochondrial function to mitigate DN progression. However, the underlying mechanism is not fully clear yet. Here, it was identified that uncoupling protein 1 (UCP1), an inner membrane protein of mitochondria, as a key to mitochondrial homeostasis improved by ANXA1. Specifically, ANXA1 attenuated mitochondrial dysfunction via appropriately upregulating UCP1 by stabilizing its transcription factor GATA binding protein 3 (GATA3) through combining with thioredoxin. Moreover, specific overexpression of UCP1 in renal cortex rescued renal injuries in diabetic Anxa1-KO mice. UCP1 deletion aggravated renal injuries in HFD/STZ-induced diabetic mice. Mechanistically, UCP1 reduced mitochondrial fission through the aristaless-related homeobox (ARX)/cardiolipin synthase 1 (CRLS1) pathway. Therapeutically, CL316243, a UCP1 agonist, could attenuate established DN in db/db mice. This work established a novel principle to harness the power of uncouplers for the treatment of DN.

Keywords: diabetic nephropathy, uncoupling protein 1, mitochondrial homeostasis, cardiolipin metabolism

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Authors: Muhammad Mazhar, Yong Zhu, Likang Qin

Abstract:

Foods contain endogenous components known as dietary fibers, which are classified into soluble and insoluble forms. Dietary fibers are resistant to gut digestive enzymes, modulating anaerobic intestinal microbiota (AIM) and fabricating short-chain fatty acids (SCFAs). Acetate, butyrate, and propionate dominate in the gut, and different pathways, including Wood-Ljungdahl and acrylate pathways, generate these SCFAs. In pancreatic dysfunction, the release of insulin/glucagon is impaired, which leads to hyperglycemia. SCFAs enhance insulin sensitivity or secretion, beta-cell functions, leptin release, mitochondrial functions, and intestinal gluconeogenesis in human organs, which positively affect type 2 diabetes (T2D). Research models presented that SCFAs either enhance the release of peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) from L-cells (entero-endocrine) or promote the release of leptin hormone satiation in adipose tissues through G-protein receptors, i.e., GPR-41/GPR-43. Dietary fibers are the components of foods that influence AIM and produce SCFAs, which may be offering beneficial effects on T2D. This review addresses the effectiveness of SCFAs in modulating gut AIM in the fermentation of dietary fiber and their worth against T2D.

Keywords: dietary fibers, intestinal microbiota, short-chain fatty acids, fermentation, type 2 diabetes

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Authors: Vikas Sharma, V. K. Dixit

Abstract:

Anacyclus pyrethrum (A. pyrethrum) has been used as Vajikaran Rasayana (aphrodisiac) in traditional Indian ayurvedic medicine to treat male sexual dysfunction, including infertility. Aphrodisiac activity may be due to an increase in the production or effect of androgens, so this study sought to evaluate the androgenic and spermatogenic potential of the alkylamide-rich ethanol solution extract. Male Wistar strain rats weighing between 150 and 180 g were completely randomized divided into five groups. The ethanol solution extract of A. pyrethrum was administered to groups of rats in 50, 100, and 150 mg/kg doses for a period of 28 days, and the action was compared with control and testosterone-treated rats. Thirteen N-alkylamides were detected in the extract by using HPLC/UV/electrospray ionization mass spectrometry method. Extract administration at all the doses produced significant increase in body weight, sperm count, motility, and viability along with serum testosterone, luteinizing hormone, and follicle-stimulating hormone concentrations. Histoarchitecture of testis revealed increased spermatogenic activities. Seminal fructose content was also significantly increased after 28 days of treatment. Our results suggest that the ethanol solution extract of the roots of A. pyrethrum has androgenic potential and may improve male fertility by enhancing spermatogenesis.

Keywords: N-alkylamides, testosterone, Anacyclus pyrethrum, androgen

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Authors: Azza Gaber Farag, Yasser Atta Shehata, Sara Elsayed Elghazouly, Mustafa Elsayed Elshaib, Nesreen Gamal Elden Elhelbawy

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Background: Androgen receptor (AR) polymorphism in cytosine adenineguanine (CAG) repeat has an effect on the functional capacity of AR in males. However, little researches in this field are available regarding female sexual function. Aim: To investigate the possible link between polymorphism in the CAG repeat of AR gene and female sexual function in a sample of the Egyptian population. Materials and methods: 500 Egyptian married females completed a questionnaire regarding sociodemographic, reproductive, and sexual data. AR CAG repeat length was analyzed for those having female sexual dysfunctions (FSD) using real-time PCR. Results: The most sensitive domain to AR CAG repeat length was the orgasm domain that showed significant positive correlations with short allele (p=0.001), long allele (p=.015), biallellic mean (p=.000), and X weighted biallelic mean (p=.000). The satisfaction domain had significant positive correlations with the biallelic mean (p=.035), and the X weighted biallelic mean (p=. 032). However, the pain domain was of significant negative correlations with AR polymorphism of short allele (p=.002), biallelic mean (p=.013), and X weighted biallelic mean (p = . 011). Conclusions: AR polymorphism could represent a non-negligible aspect in female sexual function. The lower AR CAG repeat polymorphism was of significant impact on FSD, affecting mainly female orgasm followed by pain disorders that finally reflected On her sexual satisfaction.

Keywords: female sexual dysfunction, androgen receptor, CAG repeat polymorphism, androgen

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Authors: Mohammed Alenezy

Abstract:

The function of cardiac motion can be used as an indicator of the heart abnormality by evaluating longitudinal, circumferential, and Radial Strain of the left ventricle. In this paper, the Radial Strain and SR is studied using tagged MRI (tMRI) data during the cardiac cycle on the mid-ventricle level of the left ventricle. Materials and methods: The short-axis view of the left ventricle of five healthy human (three males and two females) and four healthy male rats were imaged using tagged magnetic resonance imaging (tMRI) technique covering the whole cardiac cycle on the mid-ventricle level. Images were processed using Image J software to calculate the left ventricle wall Radial Strain and radial SR. The left ventricle Radial Strain and radial SR were calculated at the mid-ventricular level during the cardiac cycle. The peak Radial Strain for the human and rat heart was 40.7±1.44, and 46.8±0.68 respectively, and it occurs at 40% of the cardiac cycle for both human and rat heart. The peak diastolic and systolic radial SR for human heart was -1.78 s-1 ± 0.02 s-1 and 1.10±0.08 s-1 respectively, while for rat heart it was -5.16± 0.23s-1 and 4.25±0.02 s-1 respectively. Conclusion: This results show the ability of the tMRI data to characterize the cardiac motion during the cardiac cycle including diastolic and systolic phases which can be used as an indicator of the cardiac dysfunction by estimating the left ventricle Radial Strain and radial SR at different locations of the cardiac tissue. This study approves the validity of the tagged MRI data to describe accurately the cardiac radial motion.

Keywords: left ventricle, radial strain, tagged MRI, cardiac cycle

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Authors: Okyu Kwon, Dongho Kang, Byungsik Kim, Seungkwon Jung

Abstract:

We propose a technique to measure the impact of loss of traffic function in a particular area to surrounding areas. The proposed method is applied to the city of Seoul, which is the capital of South Korea, with a population of about ten million. Based on the actual road network in Seoul, we construct an abstract road network between 1kmx1km grid cells. The link weight of the abstract road network is re-adjusted considering traffic volume measured at several survey points. On the modified abstract road network, we evaluate the traffic vulnerability by calculating a network measure of betweenness centrality (BC) for every single grid cells. This study analyzes traffic impacts caused by road dysfunction due to heavy rainfall in urban areas. We could see the change of the BC value in all other grid cells by calculating the BC value once again when the specific grid cell lost its traffic function, that is, when the node disappeared on the grid-based road network. The results show that it is appropriate to use the sum of the BC variation of other cells as the influence index of each lattice cell on traffic. This research was supported by a grant (2017-MOIS31-004) from Fundamental Technology Development Program for Extreme Disaster Response funded by Korean Ministry of Interior and Safety (MOIS).

Keywords: vulnerability, road network, beweenness centrality, heavy rainfall, road impact

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Authors: Chen-Sheng Chen, Tsung-Yi Huang, Pi-Chang Sun

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Chronic stroke patients often have complaints about hand dysfunction due to flexor hypertonia and extensor weakness, which makes it difficult to open their affected hand for functional grasp. Hand rehabilitation after stroke is essential for restoring functional independence. Constraint-induced movement therapy has shown to be a successful treatment for patients who have acquired certain level of wrist and finger extension. The goal of this study was to investigate the feasibility of task-oriented approach incorporating 3D-printed dynamic hand device by evaluating hand functional performance. This study manufactured a hand device using 3d printer for chronic stroke. The experimental group engaged task-oriented approach with dynamic hand device, but the control group only received task-oriented approach. Outcome measurements include palmar pinch force (PPF), lateral pinch force (LPF), grip force (GF), and Box and Blocks Test (BBT). The results of study revealed the improvement of PPF in experimental group but not in control group. Meanwhile, improvement in LPF, GF and BBT can be found in both groups. This study demonstrates that the 3D-printed dynamic hand device is an effective therapeutic assistive device to improve pinch force, grasp force, and dexterity and facilitate motivation during home program in individuals with chronic stroke.

Keywords: 3D printing, biomechanics, hand orthosis, stroke

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Authors: Shahad Alkhalifah, Jonh Wright

Abstract:

Autism spectrum disorder (ASD) is a pervasive developmental disorder associated, for 42% to 88% of people with ASD, with sensory processing disorders. Sensory processing disorders (SPD) impact daily functioning, and it is, therefore, essential to be able to diagnose them accurately. Currently, however, there is no assessment tool available for the Saudi Arabia (SA) population that would cover a wider enough age range. Therefore, this study aimed to assess the psychometric properties of the Sensory Processing Measure Preschool-Home Form (SPM-P) when used in English, with a population of English-speaking Saudi participants. This was chosen due to time limitations and the urgency in providing practitioners with appropriate tools. Using a convenience sampling approach group of caregivers of typically developing (TD) children and a group of caregivers for children with ASD were recruited (N = 40 and N = 16, respectively), and completed the SPM-P Home Form. Participants were also invited to complete it again after two weeks for test-retest reliability, and respectively, nine and five agreed. Reliability analyses suggested some issues with a few items when used in the Saudi culture, and, along with interscale correlations, it highlighted concerns with the factor structure. However, it was also found that the SPM-P Home has good criterion-based validity, and it is, therefore, suggested that it can be used until a tool is developed through translation and cultural adaptation. It is also suggested that the current factor structure of SPM-P Home is reassessed using a large sample.

Keywords: autism, sensory, assessment, reliability, sensory processing dysfunction, preschool, validity

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Authors: I. Boroňová, J. Bernasovská, J. Kmec, E. Petrejčíková

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Dilated cardiomyopathy (DCM) is a severe cardiovascular disorder characterized by progressive systolic dysfunction due to cardiac chamber dilatation and inefficient myocardial contractility often leading to chronic heart failure. Recently, a genome-wide association studies (GWASs) on DCM indicate that the ZBTB17 gene rs10927875 single nucleotide polymorphism is associated with DCM. The aim of the study was to identify the distribution of ZBTB17 gene rs10927875 polymorphism in 50 Slovak patients with DCM and 80 healthy control subjects using the Custom Taqman®SNP Genotyping assays. Risk factors detected at baseline in each group included age, sex, body mass index, smoking status, diabetes and blood pressure. The mean age of patients with DCM was 52.9±6.3 years; the mean age of individuals in control group was 50.3±8.9 years. The distribution of investigated genotypes of rs10927875 polymorphism within ZBTB17 gene in the cohort of Slovak patients with DCM was as follows: CC (38.8%), CT (55.1%), TT (6.1%), in controls: CC (43.8%), CT (51.2%), TT (5.0%). The risk allele T was more common among the patients with dilated cardiomyopathy than in normal controls (33.7% versus 30.6%). The differences in genotype or allele frequencies of ZBTB17 gene rs10927875 polymorphism were not statistically significant (p=0.6908; p=0.6098). The results of this study suggest that ZBTB17 gene rs10927875 polymorphism may be a risk factor for susceptibility to DCM in Slovak patients with DCM. Studies of numerous files and additional functional investigations are needed to fully understand the roles of genetic associations.

Keywords: ZBTB17 gene, rs10927875 polymorphism, dilated cardiomyopathy, cardiovascular disorder

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Authors: Alia Ali, Azeem Taj, Muhammed Joher Amin, Farrukh Iqbal, Zafar Iqbal

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Background: Hypertension is commonly found in patients with Diabetic Kidney Disease (DKD). Microalbuminuria is the first clinical sign of involvement of kidneys in patients with type 2 diabetes. Uncontrolled hypertension induces a higher risk of cardiovascular events, including death, increasing proteinuria and progression to kidney disease. Objectives: To determine the correlation between microalbuminuria and hypertension and their association with other risk factors in type 2 diabetic patients. Methods: One hundred and thirteen type 2 diabetic patients were screened for microalbuminuria and raised blood pressure, attending the diabetic clinic of Shaikh Zayed Hospital, Lahore, Pakistan. The study was conducted from November 2012 to June 2013. Results: Patients were divided into two groups. Group 1, those with normoalbuminuria (n=63) and Group 2, those having microalbuminuria (n=50). Group 2 patients showed higher blood pressure values as compared to Group 1. The results were statistically significant and showed poor glycemic control as a contributing risk factor. Conclusion: The study concluded that there is high frequency of hypertension among type 2 diabetics but still much higher among those having microalbuminuria. So, early recognition of renal dysfunction through detection of microalbuminuria and to start treatment without any delay will confer future protection from end-stage renal disease as well as hypertension and its complications in type 2 diabetic patients.

Keywords: hypertension, microalbuminuria, diabetic kidney disease, type 2 Diabetes mellitus

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Authors: Huafeng Wei

Abstract:

Failures of developing new drugs primarily based on the amyloid pathology hypothesis after decades of efforts internationally lead to changes of focus targeting alternative pathways of pathology in Alzheimer’s disease (AD). Disruption of intracellular Ca2+ homeostasis, especially the pathological and excessive Ca2+ release from the endoplasmic reticulum (ER) via ryanodine receptor (RyRs) Ca2+ channels, has been considered an upstream pathology resulting in major AD pathologies, such as amyloid and Tau pathology, mitochondria damage and inflammation, etc. Therefore, dantrolene, an inhibitor of RyRs that reduces the pathological Ca2+ release from ER and a clinically available drug for the treatment of malignant hyperthermia and muscle spasm, is expected to ameliorate AD multiple pathologies synapse and cognitive dysfunction. Our own studies indicated that dantrolene ameliorated impairment of neurogenesis and synaptogenesis in neurons developed from induced pluripotent stem cells (iPSCs) originated from skin fibroblasts of either familiar (FAD) or sporadic (SAD) AD by restoring intracellular Ca2+ homeostasis. Intranasal administration of dantrolene significantly increased its passage across the blood-brain barrier (BBB) and, therefore its brain concentrations and durations. This can render dantrolene a more effective therapeutic drug with fewer side effects for chronic AD treatment. This review summarizes the potential therapeutic and side effects of dantrolene and repurposes intranasal dantrolene as a disease-modifying drug for future AD treatment.

Keywords: Alzheimer's disease, calcium, drug development, dementia, neurodegeneration, neurogenesis

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Authors: Nandini Mohan, Elayne Ahern

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Neurocognitive deficits, as well as psychosocial dysfunction, are typically observed in major depressive disorder (MDD). These deficits persist even after a significant reduction of symptoms and remission from MDD. These deficits have also been linked to greater relapse rates. The link between neurocognitive deficits, relapse, and psychosocial functioning in MDD, on the other hand, has received little attention. This review aimed to conduct an in-depth review of the literature on the association between neurocognitive deficits, relapse, and psychosocial functioning in MDD remission. We used search terms related to MDD, MDD remission, psychosocial functioning, neurocognitive impairments, and relapse to conduct a systematic review of English-language literature in PubMed, PsycArticles, PsycINFO, Medline, and Web of Science to identify relevant studies in the area from which 15 studies were identified for inclusion following an examination against inclusion/ exclusion criteria. Executive functioning, psychomotor speed, and memory were closely related to the psychosocial deficits in the phase of MDD remission. Similarly, Executive function, divided attention, and inhibition were closely related to the relapse in the phase of MDD remission. The limitations of the present review include limited and contradicting evidence that led to fewer studies being included. The implications of this review include an understanding of the difference between clinical and full-functional recovery. This evidence can be the basis for incorporating treatment measures that focus on neurocognitive and psychosocial deficits along with the affective symptoms of MDD.

Keywords: depression, MDD, remission, relapse, neurocognitive functioning, psychosocial deficits

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Authors: Sakina Fatima, Joseph-Patrick W. E. Clarke, Patricia A. Thibault, Subha Kalyaanamoorthy, Michael Levin, Aravindhan Ganesan

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Heteronuclear ribonucleoprotein (hnRNPA1 or A1) is associated with the pathology of different diseases, including neurological disorders and cancers. In particular, the aggregation and dysfunction of A1 have been identified as a critical driver for neurodegeneration (NDG) in Multiple Sclerosis (MS). Structurally, A1 includes a low-complexity domain (LCD) and two RNA-recognition motifs (RRMs), and their interdomain coordination may play a crucial role in A1 aggregation. Previous studies propose that RNA-inhibitors or nucleoside analogs that bind to RRMs can potentially prevent A1 self-association. Therefore, molecular-level understanding of the structures, dynamics, and nucleotide interactions with A1 RRMs can be useful for developing therapeutics for NDG in MS. In this work, a combination of computational modelling and biochemical experiments were employed to analyze a set of RNA-A1 RRM complexes. Initially, the atomistic models of RNA-RRM complexes were constructed by modifying known crystal structures (e.g., PDBs: 4YOE and 5MPG), and through molecular docking calculations. The complexes were optimized using molecular dynamics simulations (200-400 ns), and their binding free energies were computed. The binding affinities of the selected complexes were validated using a thermal shift assay. Further, the most important molecular interactions that contributed to the overall stability of the RNA-A1 RRM complexes were deduced. The results highlight that adenine and guanine are the most suitable nucleotides for high-affinity binding with A1. These insights will be useful in the rational design of nucleotide-analogs for targeting A1 RRMs.

Keywords: hnRNPA1, molecular docking, molecular dynamics, RNA-binding proteins

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Authors: Brahmi Brahim, Mohammad Habibur Rahman, Maarouf Saad, Cristóbal Ochoa Luna

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A repetitive training movement is an efficient method to improve the ability and movement performance of stroke survivors and help them to recover their lost motor function and acquire new skills. The ETS-MARSE is seven degrees of freedom (DOF) exoskeleton robot developed to be worn on the lateral side of the right upper-extremity to assist and rehabilitate the patients with upper-extremity dysfunction resulting from stroke. Practically, rehabilitation activities are repetitive tasks, which make the assistive/robotic systems to suffer from repetitive/periodic uncertainties and external perturbations induced by the high-order dynamic model (seven DOF) and interaction with human muscle which impact on the tracking performance and even on the stability of the exoskeleton. To ensure the robustness and the stability of the robot, a new nonlinear backstepping control was implemented with designed tests performed by healthy subjects. In order to limit and to reject the periodic/repetitive disturbances, an iterative estimator was integrated into the control of the system. The estimator does not need the precise dynamic model of the exoskeleton. Experimental results confirm the robustness and accuracy of the controller performance to deal with the external perturbation, and the effectiveness of the iterative estimator to reject the repetitive/periodic disturbances.

Keywords: backstepping control, iterative control, Rehabilitation, ETS-MARSE

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Authors: Mariane G. Tadros, Shahira M. Ezzat, Maha M. Salama, Mohamed A. Farag

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In this study, the in vitro anticholinesterase activity of the volatile oils of both O. basilicum and O. africanum was investigated and both samples showed significant activity. As a result, the major constituents of the two oils were isolated using several column chromatography. Linalool, 1,8-cineol and eugenol were isolated from the volatile oil of O. basilicum and camphor was isolated from the volatile oil of O. africanum. The anticholinesterase activity of the isolated compounds were also evaluated where 1,8-cineol showed the highest inhibitory activity followed by camphor. To confirm these activities, learning and memory enhancing effects were tested in mice. Memory impairment was induced by scopolamine, a cholinergic muscarinic receptor antagonist. Anti-amnesic effects of both volatile oils and their terpenoids were investigated by the passive avoidance task in mice. We also examined their effects on brain acetylcholinesterase activity. Results showed that scopolamine-induced cognitive dysfunction was significantly attenuated by administration of the volatile oils and their terpenoids, eugenol and camphor, in the passive avoidance task and inhibited brain acetylcholinesterase activity. These results suggest that O. basilicum and O. africanum volatile oils can be good candidates for further studies on Alzheimer’s disease via their acetylcholinesterase inhibitory actions.

Keywords: Ocimum baselicum, Ocimum africanum, GC/MS analysis, anticholinesterase

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Authors: Zhuohan Li, Jing Yang, Yaoyuan Cui

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The gut-brain axis (GBA), a communication network between gut microbiota and the brain, benefits for investigation of brain diseases. Currently, organ chips are considered one of the potential tools for GBA research. However, most of the available GBA chips have limitations in replicating the three-dimensional (3D) growth environment of cells and lack the required cell types for barrier function. In the present study, a microfluidic chip was developed for GBA interaction. Blood-brain barrier (BBB) module was prepared with HBMEC, HBVP, U87 cells and decellularized matrix (dECM). Intestinal epithelial barrier (IEB) was prepared with Caco-2 and vascular endothelial cells and dECM. GBA microfluidic device was integrated with IEB and BBB modules using 3D printing interconnecting microchannel scaffolds. BBB and IEB interaction on this GBA chip were evaluated with lipopolysaccharide (LPS) exposure. The present GBA chip achieved multicellular three-dimensional cultivation. Compared with the co-culture cell model in the transwell, fluorescein was absorbed more slowly by 5.16-fold (IEB module) and 4.69-fold (BBB module) on the GBA chip. Accumulation of Rhodamine 123 and Hoechst33342 was dramatically decreased. The efflux function of transporters on IEB and BBB was significantly increased on the GBA chip. After lipopolysaccharide (LPS) disrupted the IEB, and then BBB dysfunction was further observed, which confirmed the interaction between IEB and BBB modules. These results demonstrated that this GBA chip may offer a promising tool for gut-brain interaction study.

Keywords: decellularized matrix, gut-brain axis, organ-on-chip, three-dimensional printing.

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Authors: Pranee Suecharoen, Ratchadaporn Soontornpas, Jaturat Kanpittaya

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Background: Contrast media has an important role for disease diagnosis through detection of pathologies. Contrast media can, however, cause adverse reactions after administration of its agents. Although non-ionic contrast media are commonly used, the incidence of adverse events is relatively low. The most common reactions found (10.5%) were mild and manageable and/or preventable. Pharmacists can play an important role in evaluating adverse reactions, including awareness of the specific preparation and the type of adverse reaction. As most common types of adverse reactions are idiosyncratic or pseudo-allergic reactions, common standards need to be established to prevent and control adverse reactions promptly and effectively. Objective: To measure the effect of using tools for symptom evaluation in order to reduce the severity, or prevent the occurrence, of adverse reactions from contrast media. Methods: Retrospective review descriptive research with data collected on adverse reactions assessment and Naranjo’s algorithm between June 2015 and May 2016. Results: 158 patients (10.53%) had adverse reactions. Of the 1,500 participants with an adverse event evaluation, 137 (9.13%) had a mild adverse reaction, including hives, nausea, vomiting, dizziness, and headache. These types of symptoms can be treated (i.e., with antihistamines, anti-emetics) and the patient recovers completely within one day. The group with moderate adverse reactions, numbering 18 cases (1.2%), had hypertension or hypotension, and shortness of breath. Severe adverse reactions numbered 3 cases (0.2%) and included swelling of the larynx, cardiac arrest, and loss of consciousness, requiring immediate treatment. No other complications under close medical supervision were recorded (i.e., corticosteroids use, epinephrine, dopamine, atropine, or life-saving devices). Using the guideline, therapies are divided into general and specific and are performed according to the severity, risk factors and ingestion of contrast media agents. Patients who have high-risk factors were screened and treated (i.e., prophylactic premedication) for prevention of severe adverse reactions, especially those with renal failure. Thus, awareness for the need for prescreening of different risk factors is necessary for early recognition and prompt treatment. Conclusion: Studying adverse reactions can be used to develop a model for reducing the level of severity and setting a guideline for a standardized, multidisciplinary approach to adverse reactions.

Keywords: role of pharmacist, management of adverse reactions, guideline for contrast media, non-ionic contrast media

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Authors: Yu-Chieh Chen, Kuei-Feng Shen, Chia-Ling Chao

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The purpose of this report was to present the nursing experience and case of an unexpected cerebellar hemorrhagic stroke with acute hydrocephalus patient after lumbar spine surgery. The patient had been suffering from an emergent external ventricular drainage and stayed in the Surgical Intensive Care Unit from July 8, 2016, to July 22, 2016. During the period of the case, the data were collected for attendance, evaluation, observation, interview, searching medical record, etc. An integral evaluation of the patient's physiological 'psychological' social and spiritual states was also noted. The author noticed the following major nursing problems including ineffective cerebral perfusion 'physical activity dysfunction' family resource preparation for disability. The author provided nursing care to maintain normal intracranial pressure, along with a well-therapeutic relationship and applied interdisciplinary medical/nursing team to draft an individualized and appropriate nursing plan for them to face the psychosocial impact of the patient disabilities. We also actively participated in the rehabilitation treatments to improve daily activity and confidence. This was deemed necessary to empower them to a more positive attitude in the future.

Keywords: family resourace preparation inability, hemorrhagic sroke, ineffective tissue cerebral perfusion, lumbar spine surgery

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Authors: Yu-Chen Hsu, Kuang C. Lin

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The artificial lung called extracorporeal membrane oxygenation (ECMO) is an important medical machine that supports persons whose heart and lungs dysfunction. Previously, investigation of steady deoxygenated blood flows passing through hollow fibers for oxygen transport was carried out experimentally and computationally. The present study computationally analyzes the effect of biological pulsatile flow on the oxygen transport in blood. A 2-D model with a pulsatile flow condition is employed. The power law model is used to describe the non-Newtonian flow and the Hill equation is utilized to simulate the oxygen saturation of hemoglobin. The dimensionless parameters for the physical model include Reynolds numbers (Re), Womersley parameters (α), pulsation amplitudes (A), Sherwood number (Sh) and Schmidt number (Sc). The present model with steady-state flow conditions is well validated against previous experiment and simulations. It is observed that pulsating flow amplitudes significantly influence the velocity profile, pressure of oxygen (PO2), saturation of oxygen (SO2) and the oxygen mass transfer rates (m ̇_O2). In comparison between steady-state and pulsating flows, our findings suggest that the consideration of pulsating flow in the computational model is needed when Re is raised from 2 to 10 in a typical range for flow in artificial lung.

Keywords: artificial lung, oxygen transport, non-Newtonian flows, pulsating flows

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Authors: Thomas Geninatti, Bruno Giacomo, Alessandro Grattoni

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Nanofluidic devices have been investigated for over a decade as promising platforms for the controlled release of therapeutics. The nanochannel drug delivery system (nDS), a membrane fabricated with high precision silicon techniques, capable of zero-order release of drugs by exploiting diffusion transport at the nanoscale originated from the interactions between molecules with nanochannel surfaces, showed the flexibility of the sustained release in vitro and in vivo, over periods of time ranging from weeks to months. To improve the implantable bio nanotechnology, in order to create a system that possesses the key features for achieve the suitable release of therapeutics, the next generation of nDS has been created. Platinum electrodes are integrated by e-beam deposition onto both surfaces of the membrane allowing low voltage (<2 V) and active temporal control of drug release through modulation of electrostatic potentials at the inlet and outlet of the membrane’s fluidic channels. Hence, a tunable administration of drugs is ensured from the nanochannel drug delivery system. The membrane will be incorporated into a peek implantable capsule, which will include drug reservoir, control hardware and RF system to allow suitable therapeutic regimens in real-time. Therefore, this new nanotechnology offers tremendous potential solutions to manage chronic disease such as cancer, heart disease, circadian dysfunction, pain and stress.

Keywords: nanochannel membrane, drug delivery, tunable release, personalized administration, nanoscale transport, biomems

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Authors: A. Aceranti, L. Moretti, S. Vernocchi, M. Colorato, P. Caristia

Abstract:

Irritable bowel syndrome (IBS) is the association between abdominal pain, abdominal distension and intestinal dysfunction for recurring periods. About 10% of the world's population has IBS at any given time in their life, and about 200 people per 100,000 receive an initial diagnosis of IBS each year. Persistent pain is recognized as one of the most pervasive and challenging problems facing the medical community today. Persistent pain is considered more as a complex pathophysiological, diagnostic and therapeutic situation rather than as a persistent symptom. The low efficiency of conventional drug treatments has led many doctors to become interested in the non-drug alternative treatment of IBS, especially for more severe cases. Patients and providers are often dissatisfied with the available drug remedies and often seek complementary and alternative medicine (CAM), a unique and holistic approach to treatment that is not a typical component of conventional medicine. Osteopathic treatment may be of specific interest in patients with IBS. Osteopathy is a complementary health approach that emphasizes the role of the musculoskeletal system in health and promotes optimal function of the body's tissues using a variety of manual techniques to improve body function. Osteopathy has been defined as a patient-centered health discipline based on the principles of interrelation between body structure and function, the body's innate capacity for self-healing and the adoption of a whole person health approach. mainly by practicing manual processing. Studies reported that osteopathic manual treatment (OMT) reduced IBS symptoms, such as abdominal pain, constipation, diarrhea, and improved general well-being. The focus in the treatment of IBS with osteopathy has gone beyond simple spinal alignment, to directly address the abnormal physiology of the body using a series of direct and indirect techniques. The topic of this study was chosen for different reasons: due to the large number of people involved who suffer from this disorder and for the dysfunction itself, since nowadays there is still little clarity about the best type of treatment and, above all, to its origin. The visceral component in the osteopathic field is still a world to be discovered, although it is related to a large part of patient series, it has contents that affect numerous disciplines and this makes it an enigma yet to be solved. The study originated in the didactic practice where the curiosity of a topic is marked that, even today, no one is able to explain and, above all, cure definitively. The main purpose of this study is to try to create a good basis on the osteopathic discipline for subsequent studies that can be exhaustive in the best possible way, resolving some doubts about which treatment modality can be used with more relevance. The path was decided to structure it in such a way that 3 types of osteopathic treatment are used on 3 groups of people who will be selected after completing a questionnaire, which will deem them suitable for the study. They will, in fact, be divided into three groups where: - the first group was given a visceral osteopathic treatment. - The second group was given a manual osteopathic treatment of neurological stimulation. - The third group received a placebo treatment. At the end of the treatment, questionnaires will be re-proposed respectively one week after the session and one month after the treatment from which any data will be collected that will demonstrate the effectiveness or otherwise of the treatment received. The sample of 50 patients examined underwent an oral interview to evaluate the inclusion and exclusion criteria to participate in the study. Of the 50 patients questioned, 17 people who underwent different osteopathic techniques were eligible for the study. Comparing the data related to the first assessment of tenderness and frequency of symptoms with the data related to the first follow-up shows a significant improvement in the score assigned to the different questions, especially in the neurogenic and visceral groups. We are aware of the fact that it is a study performed on a small sample of patients, and this is a penalizing factor. We remain, however, convinced that having obtained good results in terms of subjective improvement in the quality of life of the subjects, it would be very interesting to re-propose the study on a larger sample and fill the gaps.

Keywords: IBS, osteopathy, colon, intestinal inflammation

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Authors: Mehmet Ali Kisaçam, P. Sema Temizer Ozan, Ayşe Doğan, Gonca Ozan, F. Sarper Türker

Abstract:

Cardiovascular disease which is one of the most common health problems worldwide has crucial importance because of its’ morbidity and mortality rates. Nitric oxide synthase and arginase use L-arginine as a substrate and produce nitric oxide (NO), citrulline and urea, ornithine respectively. Endothelial dysfunction is characterized by reduced bioavailability of vasodilator and anti-inflammatory molecule NO. The purpose of the study to assess endothelial function via arginase activity and NO levels in patients undergoing coronary artery bypass grafting (CABG) surgery. The study was conducted on 26 patients (14 male, 12 female) undergoing CABG surgery. Blood samples were collected from the subjects before surgery, after the termination and after 24 hours of the surgery. Arginase activity and NO levels measured in collected samples spectrophotometrically. Arginase activity decreased significantly in subjects after the termination of the surgery compared to before surgery data. 24 hours after the surgery there wasn’t any significance in arginase activity as it compared to before surgery and after the termination of the surgery. On the other hand, NO levels increased significantly in the subject after the termination of the surgery. However there was no significant increase in NO levels after 24 hours of the surgery, but there was an insignificant increase compared to before surgery data. The results indicate that after the termination of the surgery vascular and endothelial function improved and after 24 hours of the surgery arginase activity and NO levels returned to normal.

Keywords: arginase, bypass, cordiopulmonary, nitric oxide

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Authors: B. Medani Amna, M. A. Elbadwi Samia, E. Amin Ahmed

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Variable plants present in nature are used by simple rural and urban people, researchers and drug manufacturers for medicinal purposes. Garad is one of the most commonly used in Sudan for both treatment and prophylaxis of infections in the respiratory, urinogenital tracts and the skin. Water exctracts from Acacia nilotica bods were used in this very experiment to test for their toxicity to Nubian goats at two dose rates under proper experimental conditions. The clinical, pathological, haematological and biological changes in Nubian goats given daily oral doses of 1 and 5 g/kg body weight of Acacia nilotica to two groups of test goats. The goats of the control group were undosed with Acacia nilotica.Other than the dose co-related mortality rates, the clinical signs were observed to be salivation, staggered gait, intermittent loss of voice and low appetite. On histopathological testing, the main lesions were hepatic centrolobular necrosis and fatty changes associated with the significant changes in GGT and ALP are indicating hepatic dysfunction.Renal malfunction is indicated by haemorrhages in addition to the change in the urea concentration. The congested, haemorrhagic, emphysematous, edematous and cyanotic lungs may contribute to the development of dyspnea. Acacia nilotica poisoning may lead to an immunosuppression pointed out by the lymphocyte infiltration. On evaluation of the above results, Acacia nilotica was considered toxic to Nubian goats at the above mentioned doses. Future work for Acacia nilotica was forwarded and practical implications of the result were highlighted.

Keywords: Acaia nilotica, toxicity data, Nubian goats, Garad

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Authors: Sina Mahdavi

Abstract:

Multiple sclerosis (MS) is a progressive inflammatory autoimmune disease of the CNS that affects the myelination process in the central nervous system (CNS). Complex interactions of various "environmental or infectious" factors may act as triggers in autoimmunity and disease progression. The association between viral infections, especially human immunodeficiency virus (HIV) and MS is one potential cause that is not well understood. This study aims to summarize the available data on human HIV infection in MS disease progression. In this study, the keywords "Multiple sclerosis", "Human immunodeficiency virus ", and "Central nervous system" in the databases PubMed, and Google Scholar between 2017 and 2022 were searched and 15 articles were chosen, studied, and analyzed. Revealed histologic signs of "MS-like illness" in the setting of HIV, which comprised widespread demyelination with reactive astrocytes, foamy macrophages, and perivascular infiltration with inflammatory cells, all of which are compatible with MS lesions. Human immunodeficiency virus causes dysfunction of the immune system, especially characterized by hypergammaglobulinemia and chronic activation of B cells. Activation of B cells leads to increased synthesis of immunoglobulin and finally to an excess of free light chains. Free light chains may be involved in autoimmune responses against neurons. There is a high expression of HIV during the course of MS, which indicates the relationship between HIV and MS, that this virus can play a role in the development of MS by creating an inflammatory state. Therefore, measures to modulate the expression of HIV may be effective in reducing inflammatory processes in demyelinated areas of MS patients.

Keywords: multiple sclerosis, human immunodeficiency virus, central nervous system, autoimmunity

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Authors: Sarah Hamdan Al-Jahdali, Khaled Alsaad, Abdullah Al-Sayyari

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Objectives: To study the prevalence, clinicopathological features, risk factors and outcome of biopsy proven polyoma (BK) virus infection among Saudi kidney transplant recipients and compare them to negative BK virus group. Methods: We retrospectively reviewed the charts of all the patients with biopsy-proven polyoma (BK) virus infection in King Abdulaziz Medical City in Riyadh between 2005 and 2011. The details of clinical presentation, the indication for kidney biopsy, the laboratory findings at presentation, the natural history of the disease, thepathological findings, the prognosis as well as the response to therapy were all recorded. Results: Kidney biopsy was performed in 37 cases of unexplained graft dysfunction. BK virus was found in 10 (27%). Out of those 10, 3 (30%) ended with graft failure. BK virus occurred in all patients who received ATG induction therapy 100% versus 59.3% in the non BK virus patients (p=0.06). Furthermore, the risk of BK virus was much less in those who received acyclovir as an anti-viral prophylaxis as compared to those who did not receive it (p=0.01). Also, patients with BK virus weighed much less (mean 46.7±20.6 Kgs) than those without BK virus at time of transplantation (mean 64.3±12.1). Graft survival was better among deceased donor kidneys compared to living ones (P=0.016) and with older age (P=0.005). Conclusion: Our findings suggest the involvement of ATG induction therapy, the lack of antiviral prophylaxis therapy and lower weight at transplant as significant risk factors for the development of BK virus infection.

Keywords: BKVAN, BKV, kidney transpant, Saudi Arabia

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Authors: Sherif Sabri, Nael Samir, Mohamed Ali, Ahmed ElSakhawy

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Introduction: There is growing evidence to support the hypothesis that serum matrix metalloproteinase -9 in could be an early predictor of mortality in septic patients. Aim of the work: Study the relationship of matrix metalloproteinase 9 in patients with SIRS in comparison to septic patients in day 0 and day 2. Patients and Methods: This is a prospective observational study conducted on 40 adult critically ill patients staying more than 24 hours in ICU either surgical or medical department, El Fayoum General Hospital in the period from November 2014 to March 2015. Patients met at least two of the criteria for severe inflammatory response syndrome (SIRS). Diagnostic criteria include several clinical and laboratory findings of sepsis induced tissue hypoperfusion or organ dysfunction. Samples were grouped as drawn either at admission, or at day 2 after admission. Results: Patients were divided into two groups: The non-sepsis (SIRS) group, which included 15 (37.5%) patients with no later evidence of sepsis were enrolled as controls. The Sepsis group, which included 25 patients diagnosed to have SIRS with later evidence of sepsis with positive culture. Exploring serum level of MMP-9 in non-survivors and survivors, there was significant increase in non-survivors if compared to survivors at admission p-value 0.001 (mean value in survivors 4.4mg/dl±4.1mg/dl at admission versus mean value in non-survivors 11.9mg/dl±5.8mg/dl) and after two days of admission was also significant increase p-value 0.001 (mean value in survivors 10.9mg/dl ±9.4mg/dl versus mean value in non-survivors 22.6mg/dl±10.4). Conclusion: MMP-9 levels in septic patients have a beneficial role in ICU for high-risk stratification as it is an independent marker of mortality in severe sepsis.

Keywords: matrix metalloproteinase (MMP-9), sepsis, septic shock, systemic inflamatory response syndrome

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Authors: Waziri B. I., Elkhashab M. M.

Abstract:

Background: One of the most serious consequences of spinal cord injury (SCI) is progressive deterioration of renal function mostly as a result of urine stasis and ascending infection of the paralyzed bladder. This necessitates for investigation of early changes in serum urea and creatinine and associated sex related differences in response to SCI. Methods: A total of 24 adult albino rats weighing above 150g were divided equally into two groups, a control and experimental group (n = 12) each containing an equal number of male and female rats. The experimental group animals were paralyzed by complete transection of spinal cord below T4 level after deep anesthesia with ketamine 75mg/kg. Blood samples were collected from both groups five days post SCI for analysis. Mean values of serum urea (mmol/L) and creatinine (µmol/L) for both groups were compared. P < 0.05 was considered as significant. Results: The results showed significantly higher levels (P < 0.05) of serum urea and creatinine in the male SCI models with mean values of 92.12 ± 0.98 and 2573 ± 70.97 respectively compared with their controls where the mean values for serum urea and creatinine were 6.31 ± 1.48 and 476. 95 ± 4.67 respectively. In the female SCI models, serum urea 13.11 ± 0.81 and creatinine 519.88 ± 31.13 were not significantly different from that of female controls with serum urea and creatinine levels of 11.71 ± 1.43 and 493.69 ± 17.10 respectively (P > 0.05). Conclusion: Spinal cord injury caused a significant increase in serum Urea and Creatinine levels in the male models compared to the females. This indicated that males might have higher risk of renal dysfunction following SCI.

Keywords: albino rats, creatinine, spinal cord injury (SCI), urea

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Authors: Nino Gogatishvili, Davit Kvernadze, Giorgi Japharidze

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Background and aims: Landau Kleffner syndrome (LKS) is a rare disorder with epileptic seizures and acquired aphasia. It usually starts in initially healthy children. The first symptoms are language regression and behavioral disturbances, and the sleep EEG reveals abnormal epileptiform activity. The aim was to discuss the efficacy of Clobazam for Landau Kleffner syndrome. Case report: We report a case of an 11-year-old boy with an uneventful pregnancy and delivery. He began to walk at 11 months and speak with simple phrases at the age of 2,5 years. At the age of 18 months, he had febrile convulsions; at the age of 5 years, the parents noticed language regression, stuttering, and serious behavioral dysfunction, including hyperactivity, temper outbursts. The epileptic seizure was not noticed. MRI was without any abnormality. Neuropsychological testing revealed verbal auditory agnosia. Sleep EEG showed abundant left fronto-temporal spikes, reaching over 85% during non-rapid eye movement sleep (non-REM sleep). Treatment was started with Clobazam. After ten weeks, EEG was improved. Stuttering and behavior also improved. Results: Since the start of Clobazam treatment, stuttering and behavior improved. Now, he is 11 years old, without antiseizure medication. Sleep EEG shows fronto-temporal spikes on the left side, over 10-49 % of non-REM sleep, bioccipital spikes, and slow-wave discharges and spike-waves. Conclusions: This case provides further support for the efficacy of Clobazam in patients with LKS.

Keywords: Landau-Kleffner syndrome, antiseizure medication, stuttering, aphasia

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