To determine the effect of long-term antiepileptic drug on the serum folate and vitamin B12 among epileptic patients.

The purpose of this study was to prevent anaemia caused on long-term phenytoin treatment among Epileptic patients. Therefore, two groups were categorised based on the duration of phenytoin namely, cases and control. The duration of Phenytoin treatment for case was > 2 years while control had < 1 year. The estimation of serum Folate and Vitamin B12 was carried out and the association between the deficiency of Vitamins with the duration of treatment were evaluated using Linear Regression Analysis. The statistical results shown that the mean value of Folate (2.61 ± 1.81) and the mean value of Vitamin B12 (284.68 ± 110.12) were considered to be low as the duration of Phenytoin treatment increases (> 2 years) compare to control with the Folate concentration of (7.01 ± 4.40) which was statistically significant (p < 0.000). The experimental results have proved that a long-term phenytoin treatment significantly affects the concentration of Folate and Vitamin B12 among the Epileptic patients vigorously.

Clinical profile and incidence of microvascular complications of childhood and adolescent onset type 1 and type 2 diabetes seen at a tertiary diabetes center in India.

AIM: To study the clinical characteristics and incidence of microvascular complications among childhood and adolescent onset type 1 (T1DM) and type 2 diabetes (T2DM) seen at a tertiary care diabetes center in India. METHODS: From our electronic medical records, we retrieved clinical and biochemical details of 4555 individuals with childhood and adolescent onset diabetes (diagnosed below the age of 20 years) seen between 1992 and 2017. T1DM was diagnosed if there was history of ketoacidosis or fasting C-peptide <0.3 PMol/mL and stimulated C-peptide <0.6 PMol/mL or if insulin treatment was required from the time of diagnosis. T2DM was diagnosed based on absence of ketosis, or fasting C-peptide ≥0.6 PMol/mL and stimulated >1.0 PMoL/mL, or response to oral hypoglycemic agents for more than 2 years. We calculated the incidence rates of retinopathy (presence of at least one definite microaneurysm by retinal photography), nephropathy (urinary albumin excretion ≥30 µg/mg of creatinine) and neuropathy (vibration perception threshold ≥20 V) per 1000 person-years of follow up. RESULTS: Among the 4555 individuals with childhood and adolescent-onset diabetes, 71.4% had T1DM, 19.5% T2DM and 9.1% other forms of diabetes. Age at first visit and duration of diabetes were significantly higher in T2DM when compared to T1DM. The age adjusted incidence of retinopathy was 52.9/1000 person years (Confidence Intervals [CI]: 42.9-62.8) in T1DM and 49.8/1000 person years (CI 30.8-68.8) in T2DM; nephropathy, 6.2 (CI 3.3-9.0) and 13.8 (CI 5.6-22.0); and neuropathy, 8.8(CI 3.6-14.0) and 24.0 (CI 9.8-38.2) in T1DM and T2DM, respectively. CONCLUSION: The incidence of microvascular complications is high among childhood and adolescent-onset T1DM and T2DM and these calls for more aggressive control of diabetes.

Accuracy of preoperative imaging in predicting optic nerve invasion in retinoblastoma: A retrospective study.

Purpose: Optic nerve invasion is an important cause of mortality in retinoblastoma. We aimed correlate preoperative imaging and surgical histopathology findings in enucleated eyes with retinoblastoma to determine the efficacy of preoperative imaging in predicting optic nerve invasion in retinoblastoma. Methods: A retrospective review of records of all patients undergoing primary enucleation for retinoblastoma at a tertiary eyecare system between March 2013 and December 2017 with all patients having undergone preoperative imaging, either CT scan or MRI. Data was analyzed statistically to determine the correlation between preoperative CT scan/MRI and histopathology. Results: Totally, 97 eyes of 97 patients were included in the study who underwent primary enucleation for unilateral retinoblastoma. The average age at presentation was 27.8 months with the chief complaint being leukocoria in all the cases. 14 patients (14.43%) had evidence of optic nerve involvement in preoperative imaging. 30 patients had optic nerve invasion on histopathology (laminar and retrolaminar). Spearman's rank correlation test revealed a significant correlation between MRI findings and HP and an insignficant correlation between CT findings and HP. The CT scan had a sensitivity of 20%, specificity of 88.89%, 50% positive predictive value and 66.67% negative predictive value. MRI had a sensitivity of 40%, specificity of 93.55%, positive predictive value of 66.67% and a negative predictive value of 82.86%. Conclusion: MRI showed significant moderate correlation with surgical histopathology for predicting optic nerve invasion in retinoblastoma whereas CT shows insignificant correlation with HPE. Therefore, we recommend MRI for predicting optic nerve invasion in cases of retinoblastoma.

Pigmented ciliary body medulloepithelioma in a newborn infant.

Ciliary body medulloepithelioma is a nonpigmented tumor which presents during the first decade of life. It is rarely seen in newborn infants. We report a pigmented medulloepithelioma in a newborn infant, which showed a rapid growth. Ciliary body medulloepithelioma should be considered in the differential diagnosis in a newborn infant presenting with leukocoria.

Changes in nutrients ratio along the central Bay of Bengal coast and its influence on chlorophyll distribution.

Elemental ratio of nutrients and its influence on chlorophyll a distribution was studied along the central coast of Bay of Bengal using multivariate statistical methods. High chlorophyll concentration was observed during summer (1.81 µg l⁻¹) and premonsoon (1.95 µgl⁻¹), however, it was high in top 20 m during premonsoon season in tandem with high nitrate (N) and silicate (Si) concentration. N:P (phosphate) ratio was less than Redfield ratio (16:1) during all seasons, indicating the Bay of Bengal as nitrate limited and confirmed the results of Principal ComponentAnalysis (PCA) with positive loading and multiple regression analysis showing negative correlation between this ratio and chlorophyll concentration during all seasons. Whereas, N:Si ratio was < 1 and Si:P ratio > 7 in top 20 m during all seasons explained the deficiency of phosphorus and enrichment of silicate in the central Bay of Bengal. Regression analysis between Si:P and N:Si ratios with chlorophyll showed negative correlation during premonsoon and summer respectively. Thus, the present results confirmed that nutrient molar ratios such as N:P<16; Si:P>7 and N:Si<1 was indicative of a potential N and Si limitation and are the primary limiting nutrients in the central Bay of Bengal in determining chlorophyll concentration.

Process optimization for bioscouring of cotton and lycra cotton weft knits by Box and Behnken design.

The aim of the study was to discover the effect of experimental parameters like pH, enzyme dosage and temperature, on the removal of natural and accidental impurities from cotton and lycra cotton weft knitted fabrics, to make them suitable for further processing like dyeing and finishing. The optimal experimental conditions and their effects have been ascertained by response surface methodology using the Box-Behnken model. The optimum values were found to be pH 8.5, enzyme dosage 0.4% on weight of fabric and temperature 55°C. The r(2) values and the F values indicate that the effect of all the parameters taken together is significant. Based on the results of the study it can be understood that the bioscouring process performed with these optimal values is suitable for pretreatment of cotton and lycra cotton weft knitted fabrics.

Structure of a DNA repair substrate containing an alkyl interstrand cross-link at 1.65 A resolution.

Chemotherapeutic alkylating agents, such as bifunctional nitrogen mustards and cisplatins, generate interstrand DNA cross-links that inhibit cell proliferation by arresting DNA transcription and replication. A synthetic N4C-ethyl-N4C interstrand cross-link between opposing cytidines mimics the DNA damage produced by this class of clinically important compounds and can be synthesized in large quantities to study the repair, physical properties, and structures of these DNA adducts. The X-ray structure of a DNA duplex d(CCAAC*GTTGG)2 containing a synthetic N4C-ethyl-N4C interstrand cross-link between the cytosines of the central CpG step (*) has been determined at 1.65 A resolution. This structure reveals that the ethyl cross-link in the CpG major groove does not significantly disrupt the B-form DNA helix. Comparison of the N4C-ethyl-N4C cross-linked structure with the structure of an un-cross-linked oligonucleotide of the same sequence reveals that the cross-link selectively stabilizes a preexisting alternative conformation. The conformation preferred by the cross-linked DNA is constrained by the geometry of the ethyl group bridging the cytosine amines. Characteristics of the cross-linked CpG step include subtle differences in the roll of the base pairs, optimized Watson-Crick hydrogen bonds, and loss of a divalent cation binding site. Given that the N4C-ethyl-N4C cross-link stabilizes a preexisting conformation of the CpG step, this synthetically accessible substrate presents an ideal model system for studying the genomic effects of covalently coupling the DNA strands, independent of gross alterations in DNA structure.

Structural basis for polypyrimidine tract recognition by the essential pre-mRNA splicing factor U2AF65.

The essential pre-mRNA splicing factor, U2AF(65), guides the early stages of splice site choice by recognizing a polypyrimidine (Py) tract consensus sequence near the 3' splice site. Since Py tracts are relatively poorly conserved in higher eukaryotes, U2AF(65) is faced with the problem of specifying uridine-rich sequences, yet tolerating a variety of nucleotide substitutions found in natural Py tracts. To better understand these apparently contradictory RNA binding characteristics, the X-ray structure of the U2AF(65) RNA binding domain bound to a Py tract composed of seven uridines has been determined at 2.5 A resolution. Specific hydrogen bonds between U2AF(65) and the uracil bases provide an explanation for polyuridine recognition. Flexible side chains and bound water molecules form the majority of the base contacts and potentially could rearrange when the U2AF(65) structure adapts to different Py tract sequences. The energetic importance of conserved residues for Py tract binding is established by analysis of site-directed mutant U2AF(65) proteins using surface plasmon resonance.

Risk assessment of heterotrophic bacteria from bottled drinking water sold in Indian markets.

One hundred and five samples of bottled drinking water belonging to 30 different brands, collected from six different states of India have been analysed for total heterotrophic bacterial (THB) load and coliforms. Almost all bottlers used multiple treatment procedures such as microfiltration, reverse osmosis and ozonization to treat the water. Around 40% of the samples exceeded the limit of 100 cfu/ml set by the department of health as well as Bureau of Indian Standards (BIS), Government of India. Fourteen percent and 44% of the samples with THB loads between 100 and 1000 cfu/ml or 1000 cfu/ml tested positive for coliforms indicating a linear relationship between THB and coliform bacteria. Gram-positive genera such as Kurthia and Corynebacterium were found to be dominant genera, while members of the family enterobacteriaceae contributed to 7%. Risk assessment of the heterotrophic bacteria revealed that the majority of the strains acquired resistance against ampicillin, nalidixic acid, novobiocin and oxytetracycline. As bottled drinking water is a ready to drink commodity, the high load of heterotrophic bacteria with multiple drug resistance poses significant health hazards to the consumers, especially to immunocompromised individuals.

Evaluation of the aneugenic potential of the fungicide Ferbam in mice.

Ferbam, a potent dithiocarbamate fungicide is used as a protectant against a wide variety of fungal diseases in fruits, vegetables, and ornamental plants. The wide-spread use of this chemical is likely to pollute the environment. Hence, it was planned to test the possible genotoxicity of Ferbam through its aneugenic potential in the in vivo mouse (Mus musculus) test system. Four different doses of Ferbam, namely, 7.5, 15.0, 30.0, 60.0 mg/kg body weight were administered orally to mice Mus musculus suspended in gum tragacanth representing, respectively, 1/16, 1/8, 1/4;, 1/2 th of the LD50 value. They were sacrificed at 6-, 12-, 24-, and 48-h intervals along with a distilled water negative control at 2 mg/kg body weight. Colchicine treated animals were used as positive controls. Bone marrow preparations were made following the standard Hypotonic flame dry Giemsa staining technique to study the dose and time yield effect of Ferbam. The aneugenic potential was evaluated for C-mitotic effects by scoring the mitotic index, c-mitoses frequency, anaphase reduction, and hyper/hypodiploidy induction. Ferbam showed a significant increase in the mitotic index and C-mitoses effects and anaphase decreased at the highest doses of 30 and 60 mg/kg at 12- and 24-h intervals. Colchicine induced significant effects in all the aneugenic parameters observed at all the time intervals. There was no significant induction of either hyperdiploidy or hypodiploidy by Ferbam, unlike colchicine, indicating that the fungicide Ferbam is not aneugenic in the mouse test system.

Epothilone B analogue (BMS-247550)-mediated cytotoxicity through induction of Bax conformational change in human breast cancer cells.

Epothilone B is a novel nontaxane antimicrotubule agent that is active even against paclitaxel (Taxol)-resistant cancer cells. The present study further explores the mechanisms underlying epothilone B-mediated cytotoxicity in human breast cancer cells. We show that BMS-247550 (EpoB), a novel epothilone B analogue, induces cell cycle arrest at the G(2)-M phase transition and subsequent apoptotic cell death of MDA-MB-468 (468) cells. Treating cells with EpoB triggers a conformational change in the Bax protein and its translocation from the cytosol to the mitochondria, which is accompanied by cytochrome c release from the inter-membrane space of mitochondria into the cytosol. Overexpression of Bcl-2 delays Bax conformational change, cytochrome c release, and apoptosis induced by EpoB. Conversely, the Bcl-2 antagonist Bak-BH3 peptide or HA14-1 compound abrogates the antiapoptotic effects of Bcl-2 and enhances apoptosis of 468 cells pretreated with EpoB (to induce mitotic arrest). In synchronized 468 cells, EpoB is more potent in inducing Bax conformational change and apoptosis at G(2)-M phase compared with G(1)-S phase of the cell cycle. Taken together, these findings demonstrate that EpoB induces apoptosis through a Bcl-2-suppressible pathway that controls a conformational change of the proapoptotic Bax protein. The enhanced cytotoxicity of EpoB by blocking Bcl-2 at mitochondria implies a potential application of the combination of EpoB and Bcl-2 antagonists in the treatment of human breast cancer.