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Now days, digital data security over network is a big issue. Digital data security and authentication is a big and challenge able research area in the field of computer science. A lot of security mechanisms are available for data authentication and privacy. For the purpose of data security and secure communication encryption mechanism are available, and also for data authentication several watermarking techniques are available. In this paper authors mainly focus research based on image watermarking approach by using least significant bit substitutions. Here authors represent comparative studies of different LSB based image watermarking approach.This paper mainly focuses on spatial domain based data hiding mechanism. The detail comparison is also given in the tabular form.

Biological pathogen-based illnesses pose a risk to the safety of our food supply. Ralstonia solanacearum is a bacterial pathogen that lives in soil and can infect more than 250 plant species, including significant crop plants like tomato, potato, pepper, and banana, leading to significant crop output losses across the globe (Elphinstone, 2005). R. solanacearum invades host plants' roots and colonises their xylem vessels, where it reproduces in large quantities and eventually kills the plant. R. solanacearum needs a type III secretion system, just as other Gram-negative bacterial pathogens, to introduce effector proteins into host cells and cause illness.&nbsp

International audience; Pure amnestic seizures are defined as self-limited episodes with isolated, anterograde memory loss and have been attributed to bilateral dysfunction of mesial temporal structures. This type of seizure can occur in patients with different forms of temporal lobe epilepsy and has been more recently associated with a late-onset epileptic syndrome, called transient epileptic amnesia (TEA). The mechanisms of such prolonged manifestations are not well known and notably its ictal or post-ictal origin remains poorly understood. We report a case of prolonged anterograde amnesia (lasting several hours) following a brief seizure induced by stimulation of the left entorhinal cortex, recorded during stereo-EEG (SEEG). This episode was associated with prolonged changes in the intracerebral EEG signal complexity (entropy) within bilateral mesial temporal structure, particularly the entorhinal cortices, with a progressive normalization paralleling the clinical recovery. Our case shows that long-lasting (hours) memory impairment may follow brief seizure that led to prolonged electrophysiological signals alterations in bilateral mesial temporal structures

This study was undertaken to characterize clinical expression and intracerebral electroencephalographic (EEG) correlates of emotional expression during prefrontal epileptic seizures.We performed a descriptive analysis of seizure semiology in patients explored with stereo-EEG (SEEG) for pharmacoresistant prefrontal epilepsy, using a semiquantitative score for seizure-related emotional behavior. Two independent observers scored occurrence and intensity of objective emotional features (face/body movements/vocalization/overall appearance), testing interobserver reliability. Intracerebral electrophysiological changes were documented. Cluster analysis and principal component analysis (PCA) compared behavioral signs with neural SEEG correlates. For each patient, the clinical and anatomoelectrophysiological scores were established, based on a prototypical emotional seizure.Forty-two patients (469 seizures) were included. Interobserver correlation for emotional signs was satisfactory (kappa = 0.6-0.8). Prevalence of any subjective and/or objective ictal emotional phenomena was 79% (33/42); objective emotional signs occurred in 27 of 42 subjects (64%). Negatively valenced emotional semiology (ictal feeling of fear, defensive and/or aggressive behaviors) was much more prevalent than positively valenced, prosocial behaviors. Cluster analysis and PCA identified 4 groups with different occurrence of emotional signs and cerebral correlates. Two main clusters of negatively valenced behavior were identified: "active threat response," associated with seizure organizations involving posterior orbitofrontal cortex, anterior cingulate, and dorsolateral and/or ventrolateral prefrontal cortex; and "passive fear," associated with amygdala, other mesial temporal structures, and posterior orbitofrontal cortex.Emotional behaviors, especially fear/threat response, are common in prefrontal seizures, reflecting the role of the prefrontal cortex in emotional control. Different cortical seizure localizations were associated with "passive fear" and "active threat response" seizure behaviors at the group level. ANN NEUROL 2022;92:1052-1065.

Superparamagnetism has been widely used for many biomedical applications, such as early detection of inflammatory cancer and diabetes, magnetic resonance imaging (MRI), hyperthermia, etc., whereas incorporation of superparamagnetism in stimulus-responsive hydrogels has now gained substantial interest and attention for application in these fields. Recently, pH-responsive superparamagnetic hydrogels showing the potential use in disease diagnosis, biosensors, polymeric drug carriers, and implantable devices, have been developed based on the fact that pH is an important environmental factor in the body and some disease states manifest themselves by a change in the pH value. However, improvement in pH sensitivity of magnetic hydrogels is a dire need for their practical applications. In this study, we report the distinctly high pH sensitivity of new synthesized dual-responsive magnetic hydrogel nanocomposites, which was accomplished by copolymerization (free-radical polymerization) of two pH-sensitive monomers, acrylic acid (AA) and vinylsulfonic acid (VSA) with an optimum ratio, in the presence of presynthesized superparamagnetic iron oxide nanoparticles (Fe3O4(OH)x). The monomers contain pH-sensitive functional groups (COO– and SO3– for AA and VSA, respectively), and they have also been widely used as biomaterials because of the good biocompatibility. The pH sensitivity of the superparamagnetic hydrogel, poly(acrylic acid-co-vinylsulfonic acid), PAAVSA/Fe3O4, was investigated by swelling studies at different pH values from pH 7 to 1.4. Distinct pH reversibility of the system was also demonstrated through swelling/deswelling analysis. Thermal stability, chemical configuration, magnetic response, and structural properties of the system have been explored by suitable characterization techniques. Furthermore, the study reveals a pH-responsive significant change in the overall morphology and packing fraction of iron oxide nanoparticles in PAAVSA/Fe3O4 via energy-dispersive X-ray (EDX) elemental mapping with the field emission scanning electron microscopy (FESEM) study (for freeze-dried PAAVSA/Fe3O4, swelled at different pH values), implying a drastic change in susceptibility and induced saturation magnetization of the system. These important features could be easily utilized for the purpose of diagnosis using magnetic probe and/or impedance analysis techniques.

Epithelial ovarian cancer (EOC) is categorized into four major histological subtypes such as clear cell carcinoma (CCC), endometrioid carcinoma (EC), mucinous carcinoma (MC), and serous carcinoma (SC). Heterogeneity of the EOC leads to different clinical outcomes of the disease, although all the subtypes are originated from the same layer of tissue. Therefore, it is of interest to identify the common candidate genes, miRNA and their interaction network in four the subtypes of EOC. A comparative gene expression analysis identified 248 common differentially expressed genes (DEGs) in the four subtypes of EOC. Identified common DEGs were found to be enriched in cancer specific pathways. A protein-protein interaction (PPI) network of the common DEGs were constructed, and subsequent module and survival analyses identified seven key candidate genes (CCNB1, CENPM, CEP55, RACGAP1, TPX2, UBE2C, and ZWINT). We also documented 10 key candidate miRNAs (hsa-mir-16-5p, hsa-mir-23b-3p, hsa-mir-34a-5p, hsa-mir-103a-3p, hsa-mir-107, hsa-mir-124-3p, hsa-mir-129-2-3p, hsa-mir-147a, hsa-mir-205-5p, and hsa-mir-195-5p) linked to the candidate genes. These derived data find application in the understanding of EOC.

Febrile infection-related epilepsy syndrome (FIRES) is a severe epilepsy disorder that affects previously healthy children. It carries high likelihood of unfavourable outcome and putative aetiology relates to an auto-inflammatory process. Standard antiepileptic drug therapies including intravenous anaesthetic agents are largely ineffective in controlling status epilepticus in FIRES. Deep brain stimulation of the centromedian thalamic nuclei (CMN-DBS) has been previously used in refractory status epilepticus in only a few cases. The use of Anakinra (a recombinant version of the human interleukin-1 receptor antagonist) has been reported in one case with FIRES with good outcome. Here we describe two male paediatric patients with FIRES unresponsive to multiple anti-epileptic drugs, first-line immune modulation, ketogenic diet and cannabidiol. They both received Anakinra and underwent CMN-DBS. The primary aim for CMN-DBS therapy was to reduce generalized seizures. CMN-DBS abolished generalized seizures in both cases and Anakinra had a positive effect in one. This patient had a favourable outcome whereas the other did not. These are the first reported cases of FIRES where CMN-DBS has been used.

Zinc oxide (ZnO) was grown on polymer template, namely Poly (methyl methacrylate) (PMMA), by atomic layer deposition (ALD) technique. The detailed structural characterizations of the composite ZnO/PMMA film, through X-ray scattering techniques, indicate that on the PMMA template crystalline ZnO thin film was formed with its c-axis oriented along the surface normal. Combination of X-ray reflectivity (XRR) and atomic force microscopy (AFM) studies demonstrate the formation of high quality ZnO thin film (about 25 nm thick) on PMMA template, with more than 92% coverage and low surface/interface roughness. AFM results clearly show that the ZnO film consists of almost uniform nanoparticles with ∼24-30 nm in-plane size distribution, which is very much consistent with the observed size of the ZnO crystallites obtained from X-ray diffraction (XRD) study.

We report a case of changing semiology of intractable right temporal lobe epilepsy. The patient’s semiology of ictal spitting, altered awareness, automatisms and occasional secondary generalization remained stable for many years. 3T MRI head was normal, and subsequent advanced imaging and neu- rophysiology localised the seizure focus to the right temporal lobe and surrounding regions. He received a right temporal lobectomy, with subsequent redo surgery due to incomplete margins. These did not confer seizure freedom. Subsequently his seizure semiology changed to episodic fluent dysphasia with preserved awareness. This was correlated with scalp EEG changes now showing lateralisation to the bilateral temporal lobes.This case demonstrates that seemingly unilateral temporal lobe epilepsy may arise from bilateral networks, which can manifest for years from one hemisphere. It is also possible that extra-temporal origin seizures (for example from perisylvian, fronto-basal or parietal locations) can manifest with temporal-like semiology and can spread to either temporal lobe, and thus can be a cause of epilepsy surgery failure.nchlasim@doctors.org.uk35

ImportanceStereoelectroencephalography (SEEG) is more frequently being used in the pre-surgical evaluation of children with focal epilepsy. Many factors affect the rate of identification of a definable seizure onset zone (SOZ) and subsequent seizure freedom following SEEG-guided epilepsy surgery, which have not been systematically examined in multi-centre studies.ObjectivesDetermine the rates and factors that predict (a) whether or not a definable putative SOZ was identified on SEEG and (b) subsequent seizure freedom following surgical intervention.DesignRetrospective cohort studySettingMulticentre study involving 6 of 7 UK Children’s Epilepsy Surgery Service centres that perform paediatric SEEG in the UK.ParticipantsAll children undergoing SEEG from 2014 - March 2019 were included. Demographic, non-invasive evaluation, SEEG and operative factors were collected retrospectively from patient records.Main OutcomesThe two main outcome measures were (a) whether or not a definable putative SOZ was identified on SEEG (binary yes/no outcome) and (b) subsequent seizure freedom following surgical intervention (Engel classification)FindingsOne hundred and thirty-five patients underwent 139 SEEG explorations using a total of 1767 electrodes. A definable SOZ was identified in 117 patients (85.7%); odds of successfully finding a SOZ were 6.4x greater for non-motor seizures compared to motor seizures (p=0.02) and 3.6x more if ≥ 4 seizures were recorded during SEEG (p=0.03). Of 100 patients undergoing surgical treatment, 47 (47.0%) had an Engel class I outcome at a median follow-up of 1.3 years; the only factor associated with outcome was indication for SEEG (p=0.03). SEEG was safe with one (0.7%) haematoma requiring surgical evacuation and no long-term neurological deficits as a result of the procedure.Conclusions and RelevanceThis large nationally representative cohort illustrates that, in these patients who may not have otherwise been offered resective surgery, SEEG-guided surgery can still achieve high rates of seizure freedom. Seizure semiology and the number of seizures recorded during SEEG are important factors in the identification of a definable SOZ and the indication for SEEG is an important factor in post-operative outcomes.

International audience; Purpose: Frontal seizures are organized according to anatomo-functional subdivisions of the frontal lobe. Prefrontal seizures have been the subject of few detailed studies to date. The objective of this study was to identify subcategories of prefrontal seizures based on seizure onset quantification and to look for semiological differences.Methods: Consecutive patients who underwent stereoelectroencephalography (SEEG) for drug-resistant prefrontal epilepsy between 2000 and 2018 were included. The different prefrontal regions investigated in our patients were dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC), dorsomedial prefrontal cortex (DMPFC), ventromedial prefrontal cortex (VMPFC), and orbitofrontal cortex (OFC). The seizure onset zone (SOZ) was determined from one or two seizures in each patient, using the epileptogenicity index (EI) method. The presence or absence of 16 clinical ictal manifestations was analyzed. Classification of prefrontal networks was performed using the k-means automatic classification method.Results: A total of 51 seizures from 31 patients were analyzed. The optimal clustering was 4 subgroups of prefrontal seizures: a "pure DLPF" group, a "pure VMPF" group, a "pure OFC" group, and a "global prefrontal" group. The first 3 groups showed a mean EI considered epileptogenic (>0.4) only in one predominant structure, while the fourth group showed a high mean EI in almost all prefrontal structures. The median number of epileptogenic structures per seizure (prefrontal or extrafrontal) was 5 for the "global prefrontal" group and 2 for the other groups. We found that the most common signs were altered consciousness, automatisms/stereotypies, integrated gestural motor behavior, and hyperkinetic motor behavior. We found no significant difference in the distribution of ictal signs between the different groups.Conclusion: Our study showed that although most prefrontal seizures manifest as a network of several anatomically distinct structures, we were able to determine a sublobar organization of prefrontal seizure onset with four groups.

OBJECTIVE Insula epilepsy is rare and can be evaluated effectively by Stereotactic intracerebral EEG (SEEG). Many previous studies of insulo-opercular seizures have been unable to separate insular and opercular onset. With adequate sampling of the insula, this study shows this is possible. METHODS We analyzed intrainsular dynamics and extrainsular propagation in 12 patients with "pure" insula epilepsy (n = 9) or insular and only deepest opercular involvement (n = 3) at seizure onset. Review of semiology defined clinical groups, agglomerative cluster, and principal component analysis of semiological features were performed. Quantitative epileptogenicity, and intrainsular and extrainsular propagation were computed via time frequency analysis and epileptogenicity mapping. RESULTS Seizure onset patterns were heterogeneous; the seizure onset zone was focal. Seizure onset and first ictal change within insula functional subdivision correlated with aura and reflex component. No paninsular spread occurred; contralateral insular spread was very early. While the discharge was intrainsular, clinical signs related to aura or vegetative signs. Extrainsular propagation was early and related to the emergence of the majority of clinical signs. Cluster analysis found an anterior, intermediate, and posterior insula seizure onset group. The largest principal component separated anterior insula manifestations, including early hypermotor signs, early recovery, and no aura from posterior insula features of early dystonia, early tonic motor features, and sensorimotor aura. INTERPRETATION Aura is vital to identifying seizure onset and relates to insula functional subdivision. Seizures are heterogenous; extrainsular propagation occurs early, accounting for most of the semiology. With adequate sampling, "pure" insula epilepsy can be identified and focal curative resection is possible. ANN NEUROL 2020;88:477-488.

Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer. Due to the lack of specific symptoms, ∼80% of epithelial ovarian cancer is diagnosed at an advanced stage and often metastasize to the distant organ. Epithelial ovarian cancer is a heterogeneous disease that is classified into four major histological subtypes namely, serous carcinoma (SC), endometrioid carcinoma (EC), mucinous carcinoma (MC), and clear cell carcinoma (CCC). Ovarian cancer treatment is complicated due to the heterogeneity of the tumors. Patients with different subtypes respond differently to the same treatment and also have different prognoses. This diversity extends to various clinical outcomes of the disease. Thus, identifying new reliable potential biomarkers irrespective of their subtypes is an urgent need for the diagnosis and prognosis of epithelial ovarian cancer. In this study, we performed comparative gene expression analysis for identifying potential biomarkers in four histological subtypes of epithelial ovarian cancer (EOC) that include serous, endometrioid, mucinous, and clear cell carcinomas. Differentially expressed genes (DEGs) between cancerous and normal tissue samples were identified by considering the criteria of absolute logarithmic fold change |log2fc|>1 and adjusted p (padj) value

This article focuses on investigating adults with early-onset epilepsy and intellectual or physical disability within adult neurology services. We aim to guide general neurologists in the diagnostic reassessment of people with epilepsy and complex neurological problems of unknown cause. Following an overview, we address imaging, electroencephalography, genetic studies and metabolic testing, and give examples where diagnosis directly influences treatment. Aetiological diagnosis serves to inform prognosis, guide treatment and provide a framework for genetic counselling

Using spectroscopic ellipsometry from the midinfrared (0.03 eV) to the deep ultraviolet (6.5 eV), the authors determined the thickness dependence of the dielectric function for ZnO thin layers (5–50 nm) on Si and quartz in comparison to bulk ZnO. They observed a small blueshift of the band gap ( ∼80 meV) in thin ZnO layers due to quantum confinement, which is consistent with a simple effective mass theory in an infinite potential well. There is a drastic reduction in the excitonic effects near the bandgap, especially for thin ZnO on Si, which not only affects the excitonic absorption peak but also lowers the high-frequency dielectric constant by up to 40%. No significant change of the phonon parameters (except an increased broadening) in thin ZnO layers was found.

Thickness dependency in the composition ratio of amorphous silicon carbide (SiC) thin films and its effect in optical properties are reported. SiC thin films (~ 20 nm to 450 nm range) with very low surface roughness (

Aluminium and its alloys have excellent characteristics such as low density, high ductility and appropriate strength. In the marine, automotive and high-speed train sector, they find extensive applications. The volume percentage of metal matrix and reinforcement material and also the method of manufacturing the composites are the vital factors in making composite product. Composites of a metal matrix (MMCs), such as SiC and Al strengthened fly ash particles, are most widely used because of their excellent high hardness, high strength, corrosion resistance, stiffness and wear properties. The high strength and rigidity of AA 2024 alloys are well known. The high specific strength of such alloys with suitable reinforcement gives better yield properties and finds various applications at a reasonable cost. This article includes the study on mechanical and microstructural behaviour of AA 2024 metal matrix composites by reinforcing SiC and fly ash particles.

Pharmaceutical and chemical industries have been using transportation of various material/powder through pipes. The bend was punctured in the conveying system during the flow of material and finally stops the production. The scientists and researchers are working on material and mechanism to reduce the material loss of the bends. An experimental investigation have been carried out for erosive wear in pipe bends of a pneumatic conveying pipe line. Six bends has been considered for the investigation of wear at 90° from rotary feeder to air filter. The Comparison of erosive wear was investigated for all six pipe bends. The bend 2 was the most critical place in the pipeline. Other five bends had less erosion than the bend 2 due to maximum velocity of the flow.

Ovarian cancer is the most lethal gynecological cancer affecting women and hence an important public health issue. Identifying the underlying biology and neoplastic progression of ovarian cancer is very important to understand and advancing the treatment of the disease. The aim of this study is to identify the crucial genes which are common in all the cases of ovarian cancer irrespective of their subtypes, suggesting essential neoplastic progression and the common molecular mechanism through which cancer cells progress. These genes might prove to be good therapeutic drug targets. Our analysis revealed 320 genes, which functionally interacted among different subtypes of epithelial ovarian cancer. JUN, FOS, MYC, STAT5B, NR3C1, KRAS, PNN, SFN, SMARCA4, GSK3B, JUND, CAV1, and MAPK13 are genes played crucial role in ovarian cancer progression and thus can act as good therapeutic targets.

An efficient method for the removal of methylene blue dye (MB) (cationic-dye) from aqueous solution under alkaline conditions was explored, by synthesizing and utilizing suitable pH sensitive poly (acrylic acid-co-vinylsulfonic acid) hydrogel (PAAVSA). The hydrogel was synthesized by free radical polymerization reaction using optimum ratio of the acrylic acid and vinylsulfonic acid monomers. The functional groups present in PAAVSA (i.e. COO− and SO3− groups) have strong affinity with positively charged (cationic) dye molecule, enabling absorption and trapping of cationic dyes from aqueous solution. Synthesized PAAVSA was characterized by Raman and Fourier-transform-infrared-spectroscopy techniques, while significant pH response of PAAVSA, was evident through swelling studies, indicating large swelling ratio, ~250, at higher pH values. Field-emission-scanning-electron-microscopy (FESEM) images of the respective freeze-dried PAAVSA samples swelled at different pH, exhibit distinct pH-responsive change in surface morphology of the hydrogel. PAAVSA shows significant efficiency as an adsorbent for the removal of cationic dyes (MB-dye) from aqueous solution at higher pH values (pH 7 and above), along with biocompatibility and excellent reusability, leading to potential application in waste-water treatment. The adsorption kinetics and isotherm analysis indicate that the overall adsorption process was governed by chemisorption through heterogeneous surfaces having different activation energies for adsorption of MB-dye.

Gene identification in epilepsy has mainly been limited to large families segregating genes of major effect and de novo mutations in epileptic encephalopathies. Many families that present with common non-acquired focal epilepsies and genetic generalized epilepsies remain unexplained. We assembled a cohort of 'genetically enriched' common epilepsies by collecting and phenotyping families containing multiple individuals with unprovoked seizures. We aimed to determine if specific clinical epilepsy features aggregate within families, and whether this segregation of phenotypes may constitute distinct 'familial syndromes' that could inform genomic analyses. Families with three or more individuals with unprovoked seizures were studied across multiple international centres. Affected individuals were phenotyped and classified according to specific electroclinical syndromes. Families were categorized based on syndromic groupings of affected family members, examined for pedigree structure and phenotypic patterns and, where possible, assigned specific familial epilepsy syndromes. A total of 303 families were assembled and analysed, comprising 1120 affected phenotyped individuals. Of the 303 families, 117 exclusively segregated generalized epilepsy, 62 focal epilepsy, and 22 were classified as genetic epilepsy with febrile seizures plus. Over one-third (102 families) were observed to have mixed epilepsy phenotypes: 78 had both generalized and focal epilepsy features within the same individual (n = 39), or within first or second degree relatives (n = 39). Among the genetic generalized epilepsy families, absence epilepsies were found to cluster within families independently of juvenile myoclonic epilepsy, and significantly more females were affected than males. Of the 62 familial focal epilepsy families, two previously undescribed familial focal syndrome patterns were evident: 15 families had posterior quadrant epilepsies, including seven with occipito-temporal localization and seven with temporo-parietal foci, and four families displayed familial focal epilepsy of childhood with multiple affected siblings that was suggestive of recessive inheritance. The findings suggest (i) specific patterns of syndromic familial aggregation occur, including newly recognized forms of familial focal epilepsy; (ii) although syndrome-specificity usually occurs in multiplex families, the one-third of families with features of both focal and generalized epilepsy is suggestive of shared genetic determinants; and (iii) patterns of features observed across families including pedigree structure, sex, and age of onset may hold clues for future gene identification. Such detailed phenotypic information will be invaluable in the conditioning and interpretation of forthcoming sequencing data to understand the genetic architecture and inter-relationships of the common epilepsy syndromes.

Amorphous SiC thin films on a silicon substrate (Si) with different film thicknesses (about 20–450 nm) were deposited using dual ion beam sputtering deposition (DIBSD) at room temperature. These SiC thin films were of high quality showing high coverage (>90%) and low surface and interface roughness (

Pregabalin (PGB) is a new antiepileptic drug (AED) which is a structural, non-functional analogue of gamma-aminobutyric acid. It acts at presynaptic calcium channels to modulate neurotransmitter release in the CNS. While the efficacy and tolerability of PGB have been demonstrated in several randomised controlled trials, few studies have addressed long-term outcome in large groups of patients. A cohort of patients attending a tertiary referral centre for epilepsy was identified as having started taking PGB. Patients' data were obtained through medical records. Of 402 patients included, 42% of patients were still taking PGB at last follow-up. The estimated 2.5-year retention rate was 32%. Males appeared more likely to continue on PGB therapy than females. The common adverse experiences (AEs) leading to withdrawal were CNS-related, psychiatric AEs and weight gain. Published retention rates for levetiracetam appear to be higher, and those for gabapentin lower, than the rates estimated for PGB.

Summary Background The Epilepsy Genetics (EPIGEN) Consortium was established to undertake genetic mapping analyses with augmented statistical power to detect variants that influence the development and treatment of common forms of epilepsy. Methods We examined common variations across 279 prime candidate genes in 2717 case and 1118 control samples collected at four independent research centres (in the UK, Ireland, Finland, and Australia). Single nucleotide polymorphism (SNP) and combined set-association analyses were used to examine the contribution of genetic variation in the candidate genes to various forms of epilepsy. Findings We did not identify clear, indisputable common genetic risk factors that contribute to selected epilepsy subphenotypes across multiple populations. Nor did we identify risk factors for the general all-epilepsy phenotype. However, set-association analysis on the most significant p values, assessed under permutation, suggested the contribution of numerous SNPs to disease predisposition in an apparent population-specific manner. Variations in the genes KCNAB1, GABRR2, KCNMB4, SYN2 , and ALDH5A1 were most notable. Interpretation The underlying genetic component to sporadic epilepsy is clearly complex. Results suggest that many SNPs contribute to disease predisposition in an apparently population-specific manner. However, subtle differences in phenotyping across cohorts, combined with a poor understanding of how the underlying genetic component to epilepsy aligns with current phenotypic classifications, might also account for apparent population-specific genetic risk factors. Variations across five genes warrant further study in independent cohorts to clarify the tentative association.

Introduction The EEG, alongside clinical examination, imaging studies, and SSEPs, is used to determine the prognosis following hypoxic encephalopathy postcardiac arrest. Generalized periodic epileptiform discharges (GPEDs) are recognized as a “malignant” EEG pattern associated with very poor outcome with previous studies reporting no or few survivors. We looked at our database of cardiac arrest patients who subsequently developed GPEDs to determine clinical outcome and profile any survivors. Methodology We identified all cardiac arrest patients treated at King's College Hospital between 2011–2014 who developed hypoxic encephalopathy associated with GPEDs, BiPLEDs (bilateral periodic lateralized epileptiform discharges), and periodic discharges on first EEG. We collected clinical data including age, gender, downtime, EEG reactivity, presence of seizures or myoclonus, and outcome. Survivors were defined as patients who were discharged from the hospital to home or a neurorehabilitation unit. Results Thirty-six postcardiac arrest patients with hypoxic encephalopathy were identified, 24/36 with GPEDs, and 12/36 with BiPLEDs on first EEG. The mean age of patients was 62.8 ± 14.5 years old, with 27 males (75%) and 9 females (25%). Ten of thirty-six patients survived, which is slightly higher than previously reported. Statistical tests to compare clinical characteristics between survivors and nonsurvivors demonstrated no significant differences except for trend to significance for the presence of reactivity on first EEG (p = 0.0794). On discharge, one survivor had good functional outcome (and subsequently became independent), but all others were dependent for all ADLs (activities of daily living). Conclusion Generalized periodic epileptiform discharges carry a grave clinical prognosis following cardiac arrest. This study did identify a higher number of survivors compared to previous studies, but most were severely disabled at hospital discharge. Reactivity of the first EEG might predict better prognosis and merit further evaluation. This article is part of a Special Issue entitled “Status Epilepticus”.

Maternally inherited diabetes and deafness and mitochondrial encephalomyopathy, lactic acidosis with stroke-like episodes result from the 3243A>G mitochondrial point mutation. Current methods to detect the presence of the mutation have limited sensitivity and may lead to potential misclassification of patients with low levels of heteroplasmy. Here, we describe development and validation of a rapid real-time polymer- ase chain reaction (PCR) method for detection and quantification of levels of heteroplasmy in a single assay. Standard curve analysis indicated that the sensitivity of detection was less than 0.1%. Time from sample loading to data analysis was 110 minutes. We tested 293 samples including 23 known positives, 40 known negatives, and 230 samples from patients clinically classified as having type 2 diabetes. All positive samples were correctly detected, and of those samples previously quantified, heteroplasmy levels determined using the real-time assay correlated well (r2 = 0.88 and 0.93) with results from fluorescently labeled PCR-restriction fragment length polymorphism and pyrosequencing methods. Screening of 230 patients classified as having type 2 diabetes revealed one patient with 0.6% heteroplasmy who had previously tested negative by PCR-restriction fragment length polymorphism. Real-time PCR provides rapid simultaneous detection and quantification of the 3243A>G mutation to a detection limit of less than 0.1%, without post-PCR manipulation.

Monogenic diabetes accounts for approximately 1 to 2% of diabetes, although it is often mistakenly diagnosed as either type 1 or type 2 diabetes, depending on patient age and mode of presentation. Knowing the genetic etiology of diabetes allows better prediction of disease progression, screening of family members and genetic counselling regarding transmission risk. This review focuses on 2 forms of monogenic diabetes: maturity-onset diabetes of the young (MODY) and permanent neonatal diabetes mellitus (PNDM). Recent research has shown that these forms of diabetes require specific therapy, often with dramatic impact for the patient. Within MODY, the different subtypes can essentially be divided into 2 distinct groups: glucokinase MODY and transcription factor MODY, distinguished by characteristic phenotypic features and pattern on oral glucose tolerance testing. Glucokinase MODY requires no treatment, while transcription factor MODY (i.e. hepatocyte nuclear factor - 1alpha) requires low-dose sulfonylurea therapy and PNDM (caused by Kir6.2 mutation) requires high-dose sulfonylurea therapy.

The HIV-1 reverse transcriptase (RT) inhibitory activity of benzyl/benzoylpyridinones is modeled with molecular features identified in combinatorial protocol in multiple linear regression (CP-MLR) and genetic algorithm (GA). Among the features, nDB and LogP are found to be the most influential descriptors to modulate the activity. Although the coefficient of nDB suggested in favor of benzylpyridinones skeleton, the coefficient of LogP suggested the favorability of hydrophilic nature in compounds for better activity. The partial least squares analysis of the descriptors common to CP-MLR and GA has displayed their predictivity over the total descriptors identified in both the approaches. The back-propagation artificial neural networks model from the five most significant common descriptors (nDB, T(O..O), MATS8e, LogP, and BELp4) has explained 93.2% variance in the HIV-1 RT activity of the training set compounds and showed a test set r(2) of 0.89. The results suggest that the descriptors have the ability to identify the patterns in the compounds to predict potential analogues.

Nongenetic biologic and lifestyle-related factors, including age, sex, hepatic/renal function, diet/exercise practices, illness severity, smoking, and alcohol consumption habits can account for the heterogeneity of treatment effects (HTE). However, even when these factors are taken into account, considerable variation remains unexplained and could potentially be attributable to genetic differences between patients. Drug response may be dictated by variation in genes involved in both pharmacokinetic (PK) (absorption, distribution, metabolism, excretion [ADME]) and pharmacodynamic (PD) (receptors, ion channels, enzymes, immune system) pathways. Functional variants of the ADME genes can result in patients being poor, intermediate, efficient, or ultrarapid metabolizers of specific agents, thereby affecting efficacy and/or susceptibility to adverse drug reaction and necessitating individualized dosing. A well-documented example of ADME gene variation is the debrisoquine polymorphism, which is characterized by markedly different metabolism of numerous commonly prescribed drugs based on variants of the cytochrome P450 2D6 gene. Variants of genes regulating PD pathways cause altering of drug target pathways, which may affect efficacy in a more pronounced manner. Examples of gene variants affecting PD pathways include those coding for dopamine metabolism, synthesis, and transport. These gene variants may act independently, in combination with each other, and/or in combination with PK genes to affect drug response, for example to antipsychotic medications. Increased understanding of a patient's genotype and its corresponding effect on drug response would be useful to the practicing clinician in choosing an effective drug and in optimizing the dose in a timely manner.

A broad range of phenytoin doses is used in clinical practice, with the final 'maintenance' dose normally determined by trial and error. A common functional polymorphism in the SCN1A gene (one of the genes encoding the drug target) has been previously associated with maximum dose of phenytoin used clinically, and also maximum dose of carbamazepine, another antiepileptic drug with the same drug target.We have related variation at the SCN1A IVS5-91 GA polymorphism to maximum dose and to maintenance dose of phenytoin in 168 patients with epilepsy treated with phenytoin. We also related genotype to phenytoin serum levels at maximum dose and at maintenance dose of phenytoin. We genotyped the polymorphism using an Applied Biosystems Taqman assay.The polymorphism is associated with phenytoin serum concentration at maintenance dose (P=0.03). In a reduced cohort of 71 patients receiving phenytoin monotherapy this association is also significant (P=0.03). Neither association remains significant after Bonferroni correction for multiple testing.These results are not a replication of the original study. They do, however, support the hypothesis that this polymorphism influences the clinical use of phenytoin. They also demonstrate the utility of using multiple phenotypes in pharmacogenetics studies, particularly when attempting to separate pharmacokinetic and pharmacodynamic effects. As the SCN1A polymorphism affects phenytoin pharmacodynamics, it is particularly useful to obtain data on serum levels in addition to dose because association of a pharmacodynamic variant may be stronger with serum levels than dose as the serum level may eliminate or reduce pharmacokinetic variability.

Introduction: Use of the antiepileptic drug (AED) vigabatrin is severely limited by irreversible visual field constriction, an adverse reaction to the drug reported in approximately 40% of patients. Given the evidence suggesting an idiosyncratic drug response, we set out to detect genetic variation of strong, clinically relevant effect that might guide clinicians in the safe, controlled prescribing of this otherwise usefuldrug. Methods: Patients with a history of at least 1-year exposure to vigabatrin were enrolled at two independent referral centers. Using Goldmann perimetry, visual fields and the extent of constriction were calculated for each patient. We examined the correlation between the extent of vigabatrin induced visual field constriction and genetic variation across six candidate genes (SLC6A1, SLC6A13, SCL6A11, ABAT, GABRR1 and GABRR2). We availed of HapMap data and used a tagging SNP technique in an effort to efficiently capture all common variation within these genes. We attempted to replicate any positive associations before drawing conclusions from our results. Results: The degree of visual field constriction correlated with three SNPs and one haplotype in a cohort of 73 patients. However we were unable to replicate these findings in a second independent cohort consisting of 58 patients, suggesting the initial results were possibly false positives, or variants of weak effect. Conclusion: Common variants of strong, clinically relevant effect do not appear to reside in the candidate genes studied here. This does not rule out the presence of genetic variants of weak effect in these genes, nor of variants of strong effect in other genes.

Alternative to diesel fuel is very promising in the Indian context, as it is being used in large quantities in transport, agriculture, industrial, commercial and domestic sectors. Varieties of vegetable oils, along with their derivatives are considered a sustainable substitute to diesel. As neat vegetable oils are not suitable as a diesel fuel, their derivative commonly known as methyl ester of vegetable oils or biodiesel are amongst the most promising renewable alternative to diesel. In the present study, amongst the variety of feedstocks biodiesel derived from Jatropha and Karanja oil has been used as a fuel in a medium capacity diesel engine. The performance, emission and combustion characteristics of these biodiesel samples were recorded and results were compared with that of the base line data of diesel. The brake thermal efficiency was lower and brake specific energy consumption was higher for biodiesel fuels as compared to diesel fuel. Exhaust temperature was found to be higher for diesel as compared to biodiesel fuels. CO, smoke opacity and unburnt hydrocarbon have been found lower for biodiesel fuels in comparison to diesel, whereas NOx have been found to be higher for biodiesel fuels. For biodiesel fuels, ignition was found to start earlier as compared to diesel fuel. Maximum in-cylinder gas pressure was found to be lower for biodiesel fuels. The Heat Release Rate for the biodiesel fuels was lower than that of the diesel fuel as diesel was found to have higher ignition delay than biodiesel fuels. From the experimental results, it can be concluded that, biodiesel derived from Jatropha and Karanja oils have a great potential as an alternative diesel fuel.

The antifungal agent itraconazole is considered safe in patients with diabetes (1,2) but has been associated with acute painful neuropathy in patients taking vincristine (3–5). We describe a patient with diabetic neuropathy who developed acute painful neuropathy with itraconazole therapy. A 37-year-old man with poorly controlled type 1 diabetes of 19 years’ duration presented with an excematous rash affecting his lower abdomen. Skin scrapings grew C. albicans . Itraconazole (200 mg/day) was prescribed, but on the 4th day of treatment he developed acute bilateral leg weakness with stabbing pain in the hips and legs and difficulty walking. He …