Screening for diabetes among tuberculosis patients registered under revised national tuberculosis control program, Bhopal, India.

CONTEXT: Tuberculosis (TB) and diabetes mellitus (DM) remain a global public health problem. India has the largest number of TB cases; in 2015, out of total global annual incidence of 9.6 million TB cases, 2.2 million were estimated from India. There are 62.4 million people with type 2 diabetes and 77 million people with prediabetes in India, and these numbers are projected to increase to 101 million by the year 2030. Diabetes and TB affect each other at many levels. Screening for diabetes in patients with TB will not only help in early case detection but also better management of both comorbidities. AIMS: (i) To determine the prevalence of diabetes and prediabetes among diagnosed cases of TB registered under RNTCP in Bhopal district. (ii) To determine additional yield of previously unknown DM and the number needed to screen (NNS) to find out a new case of DM. (iii) To find out the factors associated with diabetes among patients diagnosed with TB registered under RNTCP in Bhopal district. SETTINGS AND DESIGN: This study was a cross-sectional study conducted on registered patients with TB under RNTCP in two TB units of Bhopal district. MATERIALS AND METHODS: Participants were contacted and interview was conducted after obtaining consent using predesigned and pretested performa during the period of 1st October 2014 to 30th March 2015 for a period of 6 months. STATISTICAL ANALYSIS USED: Continuous variable were summarized as frequency, mean, and standard deviation. All variables were analyzed using Chi-square test of significance; P < 0.05 was taken as statically significant. RESULT: Of the total 528 patients with TB, 296 was male and 232 were female. Of the total, 63 (11.9%) patients were diagnosed as diabetic. NNS to diagnose a new case of DM was 22.1. Significant association was found with six variables which are age, sex, body mass index, type of TB, category of TB, and smoking. CONCLUSION: This study shows feasibility and importance of screening of patients with TB in existing program settings.

Epilepsy-associated GRIN2A mutations reduce NMDA receptor trafficking and agonist potency - molecular profiling and functional rescue.

Mutations in the N-methyl-D-aspartate receptor (NMDAR) gene GRIN2A cause epilepsy-aphasia syndrome (EAS), a spectrum of epileptic, cognitive and language disorders. Using bioinformatic and patient data we shortlisted 10 diverse missense mutations for characterisation. We used high-throughput calcium-flux assays and patch clamp recordings of transiently transfected HEK-293 cells for electrophysiological characterization, and Western blotting and confocal imaging to assay expression and surface trafficking. Mutations P79R, C231Y, G483R and M705V caused a significant reduction in glutamate and glycine agonist potency, whilst D731N was non-responsive. These mutants, along with E714K, also showed significantly decreased total protein levels and trafficking to the cell surface, whilst C436R was not trafficked at all. Crucially this reduced surface expression did not cause the reduced agonist response. We were able to rescue the phenotype of P79R, C231Y, G483R and M705V after treatment with a GluN2A-selective positive allosteric modulator. With our methodology we were not able to identify any functional deficits in mutations I814T, D933N and N976S located between the glutamate-binding domain and C-terminus. We show GRIN2A mutations affect the expression and function of the receptor in different ways. Careful molecular profiling of patients will be essential for future effective personalised treatment options.

Epilepsy in patients with GRIN2A alterations: Genetics, neurodevelopment, epileptic phenotype and response to anticonvulsive drugs.

OBJECTIVE: To delineate the genetic, neurodevelopmental and epileptic spectrum associated with GRIN2A alterations with emphasis on epilepsy treatment. METHODS: Retrospective study of 19 patients (7 females; age: 1-38 years; mean 10.1 years) with epilepsy and GRIN2A alteration. Genetic variants were classified according to the guidelines and recommendations of the American College of Medical Genetics (ACMG). Clinical findings including epilepsy classification, treatment, EEG findings, early childhood development and neurodevelopmental outcome were collected with an electronic questionnaire. RESULTS: 7 out of 19 patients fulfilled the ACMG-criteria of carrying "pathogenic" or "likely pathogenic variants", in twelve patients the alterations were classified as variants of unknown significance. The spectrum of pathogenic/likely pathogenic mutations was as follows: nonsense n = 3, missense n = 2, duplications/deletions n = 1 and splice site n = 1. First seizures occurred at a mean age of 2.4 years with heterogeneous seizure types. Patients were treated with a mean of 5.6 AED. 4/5 patients with VPA had an improved seizure frequency (n = 3 with a truncation: n = 1 missense). 3/5 patients with STM reported an improvement of seizures (n = 2 truncation, n = 1 splicing). 3/5 CLB patients showed an improvement (n = 2: truncation; n = 1 splicing). Steroids were reported to have a positive effect on seizure frequency in 3/5 patients (n = 1 each truncation, splicing or deletion). CONCLUSIONS: Our data indicate that children with epilepsy due to pathogenic GRIN2A mutations present with different clinical phenotypes and a spectrum of seizure types in the context of a pharmacoresistant epilepsy providing information for clinicians treating children with this form of genetically determined epileptic syndrome.

New SMARCA2 mutation in a patient with Nicolaides-Baraitser syndrome and myoclonic astatic epilepsy.

We report a de novo SMARCA2 missense mutation discovered on exome sequencing in a patient with myoclonic astatic epilepsy, leading to reassessment and identification of Nicolaides-Baraitser syndrome. This de novo SMARCA2 missense mutation c.3721C>G, p.Gln1241Glu is the only reported mutation on exon 26 outside the ATPase domain of SMARCA2 to be associated with Nicolaides-Baraitser syndrome and adds to chromatin remodeling as a pathway for epileptogenesis. © 2016 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals, Inc.

Clinical characteristics of renal cell carcinoma: Five years review from a tertiary hospital in Eastern India.

BACKGROUND: Renal cell carcinoma (RCC) is the one of the dreadful urological carcinoma. In comparison to the West, it is very rarely seen in Asia as well in India. Very small number of studies is available in this geographical area. AIMS: We studied the demographic pattern, presentation, risk factors and survival of RCC in an Eastern Indian institution. We characterized and compared these data with available literature Settings and Design: Retrospective study. MATERIALS AND METHODS: A total of 81 patients of RCC from January 2008 to December 2012 were enrolled. Their pre-operative data were reviewed. They were followed as per institutional follow-up protocol. STATISTICAL ANALYSIS USED: Kaplan-Meier plot was constructed for survival analysis. Comparison of survival curves was performed by Logrank test. P < 0.05 was considered to be significant. RESULTS: A total of 75 patients were analyzed with a mean follow-up of 26.3 ± 17.7 months. The mean age of presentation in our study was 52.79 years with a peak at 5th decade. Nearly 73.33% patients having one or more risk factors. 9 out of 10 had presented with some symptoms. The survival for localized RCC was 100% and significantly greater than advanced RCC (P < 0.0001). Similarly in the stage III, significant greater survival (P < 0.0001) was noted compare to stage IV. CONCLUSIONS: The age of presentation of RCC in India has been found in 5th decade, which is a decade earlier than the western countries. Symptomatic RCC is still majority in India. Organ confined tumors have good prognosis. When it metastasizes to lymph node or distant organ, the outcome is poor. Our results may form the basis for further studies and it may be used as future reference.

Evidence for linkage of migraine in Rolandic epilepsy to known 1q23 FHM2 and novel 17q22 genetic loci.

Migraine headaches are a common comorbidity in Rolandic epilepsy (RE) and familial aggregation of migraine in RE families suggests a genetic basis not mediated by seizures. We performed a genome-wide linkage analysis of the migraine phenotype in 38 families with RE to localize potential genetic contribution, with a follow-up in an additional 21 families at linked loci. We used two-point and multipoint LOD (logarithm of the odds) score methods for linkage, maximized over genetic models. We found evidence of linkage to migraine at chromosome 17q12-22 [multipoint HLOD (heterogeneity LOD) 4.40, recessive, 99% penetrance], replicated in the second dataset (HLOD 2.61), and suggestive evidence at 1q23.1-23.2, centering over the FHM2 locus (two-point LOD 3.00 and MP HLOD 2.52). Sanger sequencing in 14 migraine-affected individuals found no coding mutations in the FHM2 gene ATP1A2. There was no evidence of pleiotropy for migraine and either reading or speech disorder, or the electroencephalographic endophenotype of RE when the affected definition was redefined as those with migraine or the comorbid phenotype, and pedigrees were reanalyzed for linkage. In summary, we report a novel migraine susceptibility locus at 17q12-22, and a second locus that may contribute to migraine in the general population at 1q23.1-23.2. Comorbid migraine in RE appears genetically influenced, but we did not obtain evidence that the identified susceptibility loci are consistent with pleiotropic effects on other comorbidities in RE. Loci identified here should be fine-mapped in individuals from RE families with migraine, and prioritized for analysis in other types of epilepsy-associated migraine.

Genito-urinary tuberculosis revisited--13 years' experience of a single centre.

BACKGROUND: Tuberculosis had been declared by the World Health Organization (WHO) as 'public health emergency' in 1993. Extra pulmonary tuberculosis (E.P.T.B.) comprises 20-25% total burden of the disease in which genitourinary tuberculosis (GU.T.B.) is 4%. Timely diagnosis and treatment will prevent the sequelae of this disease. AIMS: To know the varied clinical presentations, diagnostic modalities and management of G.U.T.B. METHODS: During a 13-year-period, 117 retrospective cases of GUTB were admitted in the tertiary care centre. They were analyzed for clinical presentation, diagnostic modalities and management. RESULTS: Young patients mainly in third decade of life were commonly affected with higher incidence in females. In our study, the most common presentation was irritative voiding symptoms (66.47%) followed by haematuria (47.60%). Although it can affect the entire organ in genito-urinary system but, in the present study, kidney was the most affected organ (64.9%) following ureter (27.35%), urinary bladder (17.09%), prostate (3.4%) and epididymis (5.19%). In this study, we had not encountered any case of testicular and penile tuberculosis. Among the different diagnostic modalities in this study, the diagnostic positivity rate was 41.6% for the urine AFB test, 55.4% for the urine M. tuberculosis culture test and 67.7% for PCR. Chest x-ray was positive in 25.6% (30). ESR was raised in 62.5% and Mantoux test was positive in 61.2% patients. CONCLUSION: A high index of suspicion and a wide range of investigations may be required to achieve a complete diagnosis of genitourinary tuberculosis. Though short course chemotherapy with four-drug-regimen for six-month-duration is the mainstay of treatment, surgical interventions were required in 60% of cases of this study.

Risk factors for breast cancer among women in Bhopal urban agglomerate: a case-control study.

BACKGROUND: Breast cancer is the most common cancer in females worldwide, and the second leading cause of cancer deaths in women. The incidence is on the rise in India, and breast cancer is the second most common malignancy in Indian women. OBJECTIVE: To assess the risk factors for breast cancer patients living in Bhopal. STUDY DESIGN AND METHOD: This case-control study was conducted in Bhopal urban agglomerate for a period of a year from October 2008 to August 2009. Demographic data and reproductive risk factor related information was collected using a structured questionnaire with analyses by Epi-info and SPSS 16. RESULTS: A history of oral contraceptive pill use (OR=2.77, 95% CI: 1.15-6.65), history of not having breastfeeding (OR=3.49, 95% CI:1.22-9.97), over weight (OR=0.11, 95%CI:0.02-0.49), obese women (OR=0.24, 95%CI: 0.06-0.88) and family history of breast cancer (OR=3.89, 95% CI: 1.01-14.92) were associated significantly with the occurrence of breast cancer on multivariate analysis. CONCLUSIONS: The findings of the present study suggests that positive family history of breast cancer and history of using OCP may be the epigenetic factors promoting the occurrence of breast cancer while breastfeeding reduces the possibility of acquiring breast cancer.

Inverted papilloma of the urinary bladder: Rigorous surveillance needed? An Indian experience.

AIMS: Inverted papilloma (IP) is an uncommon benign neoplasm of the urinary tract. Its multiplicity, recurrence, and association with transitional cell carcinoma (TCC) leads to conflicting clinical conclusions regarding its biological behavior, and hence, the need for rigorous follow-up protocols. In this study, we review all cases of urinary bladder IP in our institution and determine the need for strict follow-up. MATERIALS AND METHODS: We included consecutive patients from August 2004 to August 2008 with IP of the urinary bladder in this study who did not have prior or concurrent urothelial carcinoma. A single pathologist performed the histologic review. The patients had undergone strict a follow-up schedule every 6 months. RESULTS: In our study of the 24 patients, the mean age at presentation was 53.5 (range 22-81) years. The mean follow-up period was 25.8 months (range 6-58 months). Of the 24 patients, 21 were men and 3 were women. No patient had a synchronous or previous bladder tumor. The most common presenting symptoms were macroscopic hematuria and dysuria. All were solitary tumors except one, most commonly found at the bladder neck and trigone. The average follow-up period was 2.5 years without any evidence of recurrence. CONCLUSIONS: We conclude that when diagnosed by strictly defined criteria, IP as benign urothelial neoplasm was with extremely low incidence of recurrence and good prognosis. It does not seem to be a risk factor for TCC, especially if located in the bladder. Therefore, a good transurethral resection is adequate therapy and follow-up protocol as rigorous as those for TCC may not be necessary.

Pleiotropic effects of the 11p13 locus on developmental verbal dyspraxia and EEG centrotemporal sharp waves.

We recently showed genomewide linkage of centrotemporal sharp waves (CTS) in classic Rolandic epilepsy (RE) families to chromosome 11p13, and fine-mapped this locus to variants in the ELP4 gene. Speech sound disorder (SSD) is a common comorbidity in RE subjects, of unknown etiology, which co-aggregates in family members in a manner that could hypothetically be explained by shared underlying genetic risk with CTS. Furthermore, the neural mechanism of SSD is unknown, although individuals with rare, Mendelian forms of RE are described with severe verbal and oromotor apraxia. We therefore first performed genomewide linkage analysis for SSD, operationally defined as clinical history consistent with ICD-10 speech articulation disorder, in 38 families singly ascertained through a proband with RE. We tested the hypothesis of shared genetic risk with CTS at the 11p13 locus. In the second part of the study we used computerized acoustic analysis of recorded speech to test the hypothesis of dyspraxia as a mechanism for SSD in a smaller subset of RE probands and relatives. In two-point and multipoint LOD score analysis, we found that evidence for linkage to the 11p13 locus increased substantially when the phenotype was broadened from CTS to CTS/SSD. In multipoint analysis, the LOD score rose by 3.2 to HLOD 7.54 at D11S914 for CTS/SSD, the same marker at which multipoint linkage maximized for CTS alone. Non-parametric, affected-only methods in a sub-set of the data provide further confirmatory evidence for pleiotropy. In acoustic analysis there were voice-onset time abnormalities in 10/18 RE probands, 8/16 siblings and 5/15 parents, providing evidence of breakdown in the spatial/temporal properties of speech articulation consistent with a dyspraxic mechanism. The results from genetic and physiological studies suggest a pleiotropic role for the 11p13 locus in the development of both SSD and CTS, and also indicate a dyspraxic mechanism for the SSD linked to 11p13. Taken together, these data strongly support a neurodevelopmental origin for classic RE.

A rapid appraisal of functioning of district programme management units under NRHM in Madhya Pradesh.

OBJECTIVES: To study the functioning of District Programme Management Units in the delivery of health services in various districts of Madhya Pradesh. METHODOLOGY: A cross-sectional descriptive study was conducted in seven districts of Madhya Pradesh selected randomly. The study subjects were Chief Medical and Health Officers, programme managers, assistant managers and data officers at state and district levels. Datawas collected from the respondents in a pre-designed, pre-tested in-depth interview schedule. RESULTS: Around 70% of districts submitted their Programme Implementation Plan (PIP) on time, 30% were unable to do so because of inadequate staff and frequent changing of the reporting format. The District Programme Managers (DPMs) were not satisfied with their fixed salary. But they were satisfied with their job. In some districts the space available for the functioning of District Programme Management Unit (DPMU) are rather too small. CONCLUSION: Standardized uniform formats and guidelines should be made available to all DPMUs at the beginning of planning process. A comprehensive pre-service training for the DPMU staff including practical sessions, field exposure on district health planning, financial management, technical and administrative issues needs to be ensured.

A Survey of Deaf Mutes.

BACKGROUND: Detection of hearing loss at birth or early childhood is difficult. This bears on the rehabilitation of the child as the golden period of learning is lost. Reliable statistics relating the average age for detection of hearing loss and fitting of hearing aids in children are not available in our country. A survey of 52 deaf mutes was therefore conducted to ascertain the probable causes that lead to deafness. METHODS: The study subjects were 42 deaf mutes from the Government run school for deaf mutes and 10 from ASHA School run by the Army Wives Welfare Association. A questionnaire prepared in Hindi was filled by the parents and data analysed. RESULTS: The average age of detection of hearing loss was 2.8 years and the average age for receiving a hearing aid was 7.6 years. Thus due to the significant reduction of sensory input at the 'golden period of learning' only 50% of those fitted with a hearing aid found it useful. In 42.3% the cause of deafness could not be identified. CONCLUSION: Greater emphasis is required on early diagnosis of childhood deafness and fitment of hearing aid.

Antibacterial activity of Cuscuta reflexa stem and Corchorus olitorius seed.

The methanol extracts of Cuscuta reflexa stem and Corchorus olitorius seed showed a broad spectrum of antibacterial activity.

Is social support sometimes a mixed blessing?

BACKGROUND: Child behavioural problems in epilepsy originate from a poorly understood interplay between intrinsic, family and social factors. METHODS: We re-analysed data from a randomized controlled trial of antiepileptic treatment in rural India, using regression analysis to find risk factors for behavioural problems. RESULTS: Parental satisfaction with social support was positively and independently correlated with child behavioural problems (P=0.03). CONCLUSION: Our findings suggest parents' interactions within their informal social support network, contrary to expectation, may increase risk for behavioural problems in their children. We suggest a possible explanation for this correlation as well as follow-up studies to investigate the social support-as-risk factor hypothesis.

Separation of 90Y from 90Sr using zirconium vanadate as the ion exchanger.

The sorption and desorption behaviour of several radionuclides, including 241Am, 152,154Eu, 233U, 137Cs, 90Sr and 90Y was studied under varying acidities using zirconium vanadate as ion exchanger. The sorption follows the order: Cs > Eu > Am >Y > U, while Sr was not taken up by the ion exchanger. A radiochemical separation scheme for the 90Y daughter from its 90Sr parent using zirconium vanadate ion exchanger has been developed. The exchanger was synthesized and characterized in our laboratory.

Onset of puberty and ovarian steroidogenesis following adminstration of methanolic extract of Cuscuta reflexa Roxb. stem and Corchorus olitorius Linn. seed in mice.

The effect of methanolic extract (ME) of Cuscuta reflexa stem Roxb. and Corchorus olitorius Linn. seed on the onset of reproductive maturity and the ovarian steroidogenesis was studied by means of biochemical techniques. ME of Cuscuta reflexa stem and Corchorus olitorius seed treatment causes a remarkable delay in sexual maturation as evidenced by the age at vaginal opening and appearance of first estrus (cornified smear). The same treatment also results in a significant diminution of Delta(5)-3beta-hydroxysteroid dehydrogenase (HSD) and glucose-6-phosphate dehydrogenase (G-6-PD) activity along with a reduction in the weight of ovary, uterus and pituitary. On the basis of above data, it is assumed that the probable cause of delayed maturation in ME of Cuscuta reflexa stem and Corchorus olitorius seed treated mice is due to the suppressed ovarian steroidogenesis.

Anti-steroidogenic activity of methanolic extract of Cuscuta reflexa roxb. stem and Corchorus olitorius Linn. seed in mouse ovary.

Methanolic extract (ME) of both C. reflexa stem and C. olitorius seed arrested the normal oestrus cycle of adult female mouse and significantly decreased the weight of ovaries and uterus. The cholesterol and ascorbic acid contents in ovaries were significantly increased in the treated mice. Two key enzymes, delta5-3beta-hydroxysteroid dehydrogenase and glucose-6-phosphate dehydrogenase, were decreased significantly in ME of both C. reflexa stem and C. olitorius seed after 17 days of treatment. High level of substrates and low level of enzymes indicate the inhibition of steroidogenesis in treated mice and may be due to the presence of flavonoids.

Synthesis of a new ion exchanger, zirconium vanadate, and its application to the separation of barium and cesium radionuclides at tracer levels.

A new inorganic ion exchanger, zirconium vanadate, has been synthesized and characterized. Elemental analysis suggests that the probable formula of the compound is ZrO2, V2O5, 2H2O. The exchanger is highly stable in thermal, radiation and chemical environments. Radiochemical separation schemes for the 134Cs and 133Ba pair and also for separating the short-lived daughter 137Ba from its parent 137Cs using this newly synthesized ion exchanger have been developed.