Study on abnormal uterine bleeding among adult women in a tertiary care hospital in Bihar, India

Background: Abnormal uterine bleeding (AUB) is the most common problem among patients coming to gynaecology outpatient department. There are various pathologies which can lead to AUB. History, blood investigations, ultrasonography, hysteroscopy and endometrial aspiration are the methods to rule out different causes. Later on, they are classified as per PALM-COEIN classification. It helps in better and successful management of AUB patients.Methods: It was a retrospective study done in Obstetrics and Gynaecology Department of AIIMS Patna from March 2014 to March 2016. A total of 272 cases were selected and data were collected in structured proforma on excel sheet.Results: The most common age-group presenting with AUB was 40 to 49 years of age (58%) and the most common histological pattern was secretory (47.7%).  Menorrhagia was found to be the most common problem in AUB patients (58.45%). As per PALM- COEIN classification, the most common type in our study was found to be AUB-E (26.8%). In a sub-set of patients, who underwent hysterectomy, histopathological samples were compared to endometrial samples which were similar in 81.6% cases.Conclusions: Incidence and pattern of AUB varies according to the age of the patient. It is more common in perimenopausal age-group. Classification of AUB as per PALM-COEIN helps in better understanding of disease and successful management of patients.

Genetics of Amyotrophic Lateral Sclerosis

Peer reviewedPublisher PD

Diagnostic accuracy of fine needle aspiration cytology in soft tissue tumors: our institutional experience

Background: Diagnosis of Soft tissue tumors by FNAC (Fine needle aspiration cytology) is one of the diagnostic modality of choice in pathological evaluation of soft tissue neoplasms especially to differentiate from the non-neoplastic soft tissue lesions. It is challenging and controversial. Very few centers rely on simple FNAC for diagnosis which is largely due to a lack of experience, familiarity, confidence and tricky cytological features.Methods:We have studied 140 cases of soft-tissue tumors by simple FNAC procedure done by cytopathologist from 01/01/2012 to 31/12/2012. After considering thorough history, clinical, radiology and other findings all cases were reported by the experienced faculty in cytopathology section of our institute.Results:Out of total 140 cases of soft tissue tumors 131 (93.58%) were benign and 9 (6.42%) were malignant. In benign category maximum numbers were lipoma 105 cases (80.15%) followed by benign neural tumors 5 cases (3.82%), ganglion 4 cases (3.05%), benign fibrohistiocytic lesions 2 cases (1.53%) and others. Conclusions: Current study demonstrates that FNAC is valuable as a primary tool in diagnosing soft tissue tumors specifically benign lesions like lipomatous tumors, high grade malignant sarcoma and recurrent lesions. Findings are well supported by histopathological correlation

Development and testing of a quantitative food frequency questionnaire for use in Kerala, India

Objective: To develop and test a food frequency questionnaire (FFQ) for use in rural areas of Kerala, India. Design: Based on food use and market surveys of the study area, a quantitative 81- item interviewer-administered FFQ was developed. A validation study was conducted consisting of 24-h diet recalls (24HR) administered on 8 days randomly selected over an entire year and two administrations of the FFQ, one at the beginning of the l-year period and the other at the end. FFQ and 24HR-derived nutrient scores were compared using correlation and regression analyses and by examining differences in the nutrient scores. Setting: Rural villages in Ernakulum district, Kerala, South India. Subjecrs: In each of 30 households, the male head of household and female food preparer were enrolled. Results: Pearson (parametric) correlation coefficients (Y,) averaged about 0.50 in comparing nutrient scores derived from the 24HR with those from the first FFQ and about 0.55 in comparing the second FFQ. On average, Spearman correlation coefficients (YJ were slightly lower than the Y, in comparing the scores derived from the first FFQ, but virtually identical for the second FFQ. Regression analyses indicated better agreement in the comparison of the 24HR-derived scores with the first FFQ than the second FFQ. Difference scores, however, tended to be larger in comparing the first FFQ scores with the 24HR. Conclusions: This FFQ produces results broadly comparable to those used in Europe and North America, indicating its suitability for comparing exposures within a study population in reference to health-related endpoints

Astrocyte pathology and the absence of non-cell autonomy in an induced pluripotent stem cell model of TDP-43 proteinopathy

Glial proliferation and activation are associated with disease progression in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar dementia. In this study, we describe a unique platform to address the question of cell autonomy in transactive response DNA-binding protein (TDP-43) proteinopathies. We generated functional astroglia from human induced pluripotent stem cells carrying an ALS-causing TDP-43 mutation and show that mutant astrocytes exhibit increased levels of TDP-43, subcellular mislocalization of TDP-43, and decreased cell survival. We then performed coculture experiments to evaluate the effects of M337V astrocytes on the survival of wild-type and M337V TDP-43 motor neurons, showing that mutant TDP-43 astrocytes do not adversely affect survival of cocultured neurons. These observations reveal a significant and previously unrecognized glial cell-autonomous pathological phenotype associated with a pathogenic mutation in TDP-43 and show that TDP-43 proteinopathies do not display an astrocyte non-cell-autonomous component in cell culture, as previously described for SOD1 ALS. This study highlights the utility of induced pluripotent stem cell-based in vitro disease models to investigate mechanisms of disease in ALS and other TDP-43 proteinopathies

Neuro-Metabolite Changes in a Single Season of University Ice Hockey Using Magnetic Resonance Spectroscopy

Background: Previous research has shown evidence for transient neuronal loss after repetitive head impacts (RHI) as demonstrated by a decrease in N-acetylaspartate (NAA). However, few studies have investigated other neuro-metabolites that may be altered in the presence of RHI; furthermore, the relationship of neuro-metabolite changes to neurocognitive outcome and potential sex differences remain largely unknown.Objective: The aim of this study was to identify alterations in brain metabolites and their potential association with neurocognitive performance over time as well as to characterize sex-specific differences in response to RHI.Methods: 33 collegiate ice hockey players (17 males and 16 females) underwent 3T magnetic resonance spectroscopy (MRS) and neurocognitive evaluation before and after the Canadian Interuniversity Sports (CIS) ice hockey season 2011–2012. The MRS voxel was placed in the corpus callosum. Pre- and postseason neurocognitive performances were assessed using the Immediate Post-Concussion Assessment and Cognitive Test (ImPACT). Absolute neuro-metabolite concentrations were then compared between pre- and postseason MRS were (level of statistical significance after correction for multiple comparisons: p < 0.007) and correlated to ImPACT scores for both sexes.Results: A significant decrease in NAA was observed from preseason to postseason (p = 0.001). Furthermore, a trend toward a decrease in total choline (Cho) was observed (p = 0.044). Although no overall effect was observed for glutamate (Glu) over the season, a difference was observed with females showing a decrease in Glu and males showing an increase in Glu, though this was not statistically significant (p = 0.039). In both males and females, a negative correlation was observed between changes in Glu and changes in verbal memory (p = 0.008).Conclusion: The results of this study demonstrate changes in absolute concentrations of neuro-metabolites following exposure to RHI. Results suggest that changes in Glu are correlated with changes in verbal memory. Future studies need to investigate further the association between brain metabolites and clinical outcome as well as sex-specific differences in the brain's response to RHI

Neuro-Metabolite Changes in a Single Season of University Ice Hockey Using Magnetic Resonance Spectroscopy

Background: Previous research has shown evidence for transient neuronal loss after repetitive head impacts (RHI) as demonstrated by a decrease in N-acetylaspartate (NAA). However, few studies have investigated other neuro-metabolites that may be altered in the presence of RHI;furthermore, the relationship of neuro-metabolite changes to neurocognitive outcome and potential sex differences remain largely unknown. Objective: The aim of this study was to identify alterations in brain metabolites and their potential association with neurocognitive performance over time as well as to characterize sex-specific differences in response to RHI. Methods: 33 collegiate ice hockey players (17 males and 16 females) underwent 3T magnetic resonance spectroscopy (MRS) and neurocognitive evaluation before and after the Canadian lnteruniversity Sports (CIS) ice hockey season 2011-2012. The MRS voxel was placed in the corpus callosum. Pre- and postseason neurocognitive performances were assessed using the Immediate Post-Concussion Assessment and Cognitive Test (ImPACT). Absolute neuro-metabolite concentrations were then compared between pre- and postseason MRS were (level of statistical significance after correction for multiple comparisons: p < 0.007) and correlated to ImPACT scores for both sexes. Results: A significant decrease in NAA was observed from preseason to postseason (p = 0.001). Furthermore, a trend toward a decrease in total choline (Cho) was observed (p = 0.044). Although no overall effect was observed for glutamate (Glu) over the season, a difference was observed with females showing a decrease in Glu and males showing an increase in Glu, though this was not statistically significant (p = 0.039). In both males and females, a negative correlation was observed between changes in Glu and changes in verbal memory (p = 0.008). Conclusion: The results of this study demonstrate changes in absolute concentrations of neuro-metabolites following exposure to RHI. Results suggest that changes in Glu are correlated with changes in verbal memory. Future studies need to investigate further the association between brain metabolites and clinical outcome as well as sex-specific differences in the brain's response to RHI

Stochastic Expression of the Interferon-β Gene

The analysis of stochastic interferon-beta gene expression in virus-infected mammalian cells reveals that the levels of components required for virtually every step in the virus induction pathway are limiting

Yeast Screens Identify the RNA Polymerase II CTD and SPT5 as Relevant Targets of BRCA1 Interaction

BRCA1 has been implicated in numerous DNA repair pathways that maintain genome integrity, however the function responsible for its tumor suppressor activity in breast cancer remains obscure. To identify the most highly conserved of the many BRCA1 functions, we screened the evolutionarily distant eukaryote Saccharomyces cerevisiae for mutants that suppressed the G1 checkpoint arrest and lethality induced following heterologous BRCA1 expression. A genome-wide screen in the diploid deletion collection combined with a screen of ionizing radiation sensitive gene deletions identified mutants that permit growth in the presence of BRCA1. These genes delineate a metabolic mRNA pathway that temporally links transcription elongation (SPT4, SPT5, CTK1, DEF1) to nucleopore-mediated mRNA export (ASM4, MLP1, MLP2, NUP2, NUP53, NUP120, NUP133, NUP170, NUP188, POM34) and cytoplasmic mRNA decay at P-bodies (CCR4, DHH1). Strikingly, BRCA1 interacted with the phosphorylated RNA polymerase II (RNAPII) carboxy terminal domain (P-CTD), phosphorylated in the pattern specified by the CTDK-I kinase, to induce DEF1-dependent cleavage and accumulation of a RNAPII fragment containing the P-CTD. Significantly, breast cancer associated BRCT domain defects in BRCA1 that suppressed P-CTD cleavage and lethality in yeast also suppressed the physical interaction of BRCA1 with human SPT5 in breast epithelial cells, thus confirming SPT5 as a relevant target of BRCA1 interaction. Furthermore, enhanced P-CTD cleavage was observed in both yeast and human breast cells following UV-irradiation indicating a conserved eukaryotic damage response. Moreover, P-CTD cleavage in breast epithelial cells was BRCA1-dependent since damage-induced P-CTD cleavage was only observed in the mutant BRCA1 cell line HCC1937 following ectopic expression of wild type BRCA1. Finally, BRCA1, SPT5 and hyperphosphorylated RPB1 form a complex that was rapidly degraded following MMS treatment in wild type but not BRCA1 mutant breast cells. These results extend the mechanistic links between BRCA1 and transcriptional consequences in response to DNA damage and suggest an important role for RNAPII P-CTD cleavage in BRCA1-mediated cancer suppression

Multi-center feasibility study evaluating recruitment, variability in risk factors and biomarkers for a diet and cancer cohort in India

<p>Abstract</p> <p>Background</p> <p>India's population exhibits diverse dietary habits and chronic disease patterns. Nutritional epidemiologic studies in India are primarily of cross-sectional or case-control design and subject to biases, including differential recall of past diet. The aim of this feasibility study was to evaluate whether a diet-focused cohort study of cancer could be established in India, providing insight into potentially unique diet and lifestyle exposures.</p> <p>Methods</p> <p>Field staff contacted 7,064 households within three regions of India (New Delhi, Mumbai, and Trivandrum) and found 4,671 eligible adults aged 35-69 years. Participants completed interviewer-administered questionnaires (demographic, diet history, physical activity, medical/reproductive history, tobacco/alcohol use, and occupational history), and staff collected biological samples (blood, urine, and toenail clippings), anthropometric measurements (weight, standing and sitting height; waist, hip, and thigh circumference; triceps, sub-scapula and supra-patella skin fold), and blood pressure measurements.</p> <p>Results</p> <p>Eighty-eight percent of eligible subjects completed all questionnaires and 67% provided biological samples. Unique protein sources by region were fish in Trivandrum, dairy in New Delhi, and pulses (legumes) in Mumbai. Consumption of meat, alcohol, fast food, and soft drinks was scarce in all three regions. A large percentage of the participants were centrally obese and had elevated blood glucose levels. New Delhi participants were also the least physically active and had elevated lipids levels, suggesting a high prevalence of metabolic syndrome.</p> <p>Conclusions</p> <p>A high percentage of participants complied with study procedures including biological sample collection. Epidemiologic expertise and sufficient infrastructure exists at these three sites in India to successfully carry out a modest sized population-based study; however, we identified some potential problems in conducting a cohort study, such as limited number of facilities to handle biological samples.</p