KCNT1- related epilepsy: An international multicenter cohort of 27 pediatric cases

ObjectiveThrough international collaboration, we evaluated the phenotypic aspects of a multiethnic cohort of KCNT1- related epilepsy and explored genotype- phenotype correlations associated with frequently encountered variants.MethodsA cross- sectional analysis of children harboring pathogenic or likely pathogenic KCNT1 variants was completed. Children with one of the two more common recurrent KCNT1 variants were compared with the rest of the cohort for the presence of particular characteristics.ResultsTwenty- seven children (15 males, mean age = 40.8 months) were included. Seizure onset ranged from 1 day to 6 months, and half (48.1%) exhibited developmental plateauing upon onset. Two- thirds had epilepsy of infancy with migrating focal seizures (EIMFS), and focal tonic seizures were common (48.1%). The most frequent recurrent KCNT1 variants were c.2800G>A; p.Ala934Thr (n = 5) and c.862G>A; p.Gly288Ser (n = 4). De novo variants were found in 96% of tested parents (23/24). Sixty percent had abnormal magnetic resonance imaging (MRI) findings. Delayed myelination, thin corpus callosum, and brain atrophy were the most common. One child had gray- white matter interface indistinctness, suggesting a malformation of cortical development. Several antiepileptic drugs (mean = 7.4/patient) were tried, with no consistent response to any one agent. Eleven tried quinidine; 45% had marked (>50% seizure reduction) or some improvement (25%- 50% seizure reduction). Seven used cannabidiol; 71% experienced marked or some improvement. Fourteen tried diet therapies; 57% had marked or some improvement. When comparing the recurrent variants to the rest of the cohort with respect to developmental trajectory, presence of EIMFS, >500 seizures/mo, abnormal MRI, and treatment response, there were no statistically significant differences. Four patients died (15%), none of sudden unexpected death in epilepsy.SignificanceOur cohort reinforces common aspects of this highly pleiotropic entity. EIMFS manifesting with refractory tonic seizures was the most common. Cannabidiol, diet therapy, and quinidine seem to offer the best chances of seizure reduction, although evidence- based practice is still unavailable.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154940/1/epi16480_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154940/2/epi16480.pd

Genomic Profiling of Advanced-Stage Oral Cancers Reveals Chromosome 11q Alterations as Markers of Poor Clinical Outcome

Identifying oral cancer lesions associated with high risk of relapse and predicting clinical outcome remain challenging questions in clinical practice. Genomic alterations may add prognostic information and indicate biological aggressiveness thereby emphasizing the need for genome-wide profiling of oral cancers. High-resolution array comparative genomic hybridization was performed to delineate the genomic alterations in clinically annotated primary gingivo-buccal complex and tongue cancers (n = 60). The specific genomic alterations so identified were evaluated for their potential clinical relevance. Copy-number changes were observed on chromosomal arms with most frequent gains on 3q (60%), 5p (50%), 7p (50%), 8q (73%), 11q13 (47%), 14q11.2 (47%), and 19p13.3 (58%) and losses on 3p14.2 (55%) and 8p (83%). Univariate statistical analysis with correction for multiple testing revealed chromosomal gain of region 11q22.1–q22.2 and losses of 17p13.3 and 11q23–q25 to be associated with loco-regional recurrence (P = 0.004, P = 0.003, and P = 0.0003) and shorter survival (P = 0.009, P = 0.003, and P 0.0001) respectively. The gain of 11q22 and loss of 11q23-q25 were validated by interphase fluorescent in situ hybridization (I-FISH). This study identifies a tractable number of genomic alterations with few underlying genes that may potentially be utilized as biological markers for prognosis and treatment decisions in oral cancers

Crystal structure of ethyl pyruvate-2-methyl-4-chloro-phenyl hydrazone

Ethyl pyruvate-2-methyl-4-chloro-phenylhydrazone, C12H15N2O2Cl, is an important intermediate for the synthesis of ethyl-5-chloro-7-methyl indole-2-carboxy-late. Crystals are orthorhombic with a=6.99(4), b=23.75(6), c=17.05(6) à and eight molecules per cell in the space group Cmca. The structure was solved by direct methods using film data and refined by block diagonal least squares method to an R-index of 0.052. The molecule occupies the space group mirror(m) special position. The stacking of the molecules is stabilized by van der Waal's contacts. © 1981 the Indian Academy of Sciences

The structure of chloramphenicol

The structure of chloramphenicol, C11H12Cl2N2O5, an important broad-​spectrum antibiotic, was solved by direct methods and refined by Fourier and least-​squares to a R of 0.069. The crystals are orthorhombic, space group C2221, with a 7.335(3)​, b 17.552(8)​, and c 22.159(6) Å; d.(calcd.) = 1.50 and d.(obsd.) = 1.49 for Z = 8. The side chain exists in the 'alicyclic' form, stabilized by H bonding between the hydroxyl groups. The dichloroacetamido moiety is folded back over the Ph ring

The structure of chloramphenicol

The structure of chloramphenicol, an important broadspectrum antibiotic, has been solved by direct methods with X-ray diffraction data collected using Mo K-alpha radiation. The crystals are orthorhombic, with space group C2221, and the structure has been refined by Fourier and least-square techniques to an R of 0.069 for 940 observed reflections. The side chain exists in the 'alicyclic' form, stabilized by hydrogen bonding between the hydroxyl groups. The dichloroacetamido moiety is folded back over the phenyl ring.La structure du chloramph\ue9nicol, un antibiotique \ue0 large spectre largement utilis\ue9, a \ue9t\ue9 r\ue9solue par des m\ue9thodes directes utilisant des donn\ue9es de diffraction des rayons X pr\ue9lev\ue9es avec un rayonnement MoKa. Les cristaux sont orthorhombiques et appartiennent au groupe d'espace C2221. L\u2019affinement de la structure a \ue9t\ue9 effectu\ue9 par les m\ue9thodes de Fourier et des moindres carr\ue9s jusqu\u2019\ue0 une valeur de R \ue9gale \ue0 0,069 pour 940 r\ue9flexions observ\ue9es. La cha\ueene lat\ue9rale est alicyclique et stabilis\ue9e par des liaisons hydrog\ue8ne entre les groupes hydroxyles. Le groupe dichloroac\ue9tamide se trouve repli\ue9 sur le noyau ph\ue9nyle.Peer reviewed: YesNRC publication: Ye

Refinement of the structure of nalidixic acid

Peer reviewed: YesNRC publication: Ye

Not Available

Not AvailableIn the present study, relationship of reproductive disorders with mineral and hormone status in bovines was analyzed. Paired sera samples (160) were collected randomly from four organized dairy farms in Karnataka (Bijapur, Dharwad) and Tamilnadu (Chennai, Cuddalore). Serum estradiol, progesterone in healthy and RP animals were 11.33±0.58 and 5.67±0.10pg/ml, 1.70±0.08 and 0.77±0.04IU/ml, respectively and significant (P<0.05) decrease in RP bovines. Serum copper, zinc, calcium, magnesium, phosphorus in healthy and RP bovines were 1.29±0.03 and 0.91±0.03ppm, 1.09±0.04 and 0.87±0.03ppm, 9.98±0.17 and 9.07±0.21mg/dl, 3.07±0.16 and 2.36±0.08mg/dl, 1.62±0.08 and 1.52±0.06mg/dl, respectively. Significant (P<0.05) correlation between copper and hormones in bovines of organized dairy farms was observed. Logit analysis revealed significant (P<0.05) positive relationship between estradiol, progesterone and zinc levels with animal health status. Thus, supplementation of these microminerals will reduce the incidence of reproductive disorders in animals and also improves the productivity and profitability of dairy farmers in India. (PDF) Reproductive Disorders and its Relationship with Hormones and Mineral Status in Bovines of Organized Dairy Farms. Available from: https://www.researchgate.net/publication/316355708_Reproductive_Disorders_and_its_Relationship_with_Hormones_and_Mineral_Status_in_Bovines_of_Organized_Dairy_Farms [accessed Nov 22 2018].Not Availabl

Dairy animal Fertility

Not AvailableNot AvailableICAR-NIAN