Husband's Alcohol Use, Intimate Partner Violence, and Family Maltreatment of Low-Income Postpartum Women in Mumbai, India.

Husbands' alcohol use has been associated with family-level stress and intimate partner violence (IPV) against women in India. Joint family systems are common in India and IPV often co-occurs with non-violent family maltreatment of wives (e.g., nutritional deprivation, deprivation of sleep, blocking access to health care). Alcohol use increases for some parents following the birth of a child. This study examined 1,038 postpartum women's reports of their husbands' alcohol use and their own experiences of IPV (by husband) and non-violent maltreatment from husbands and/or in-laws. We analyzed cross-sectional, quantitative data collected in 2008, from women (ages 15-35) seeking immunizations for their infants <6 months at three large urban health centers in Mumbai, India. Crude and adjusted logistic regression models estimated associations between the independent variable (husbands' past month use of alcohol) and two dependent variables (postpartum IPV and maltreatment). Overall, 15% of husbands used alcohol, ranging from daily drinkers (10%) to those who drank one to two times per week (54%). Prevalence of postpartum IPV and family maltreatment was 18% and 42%, respectively. Prevalence of IPV among women married to alcohol users was 27%. Most abused women's husbands always (27%) or sometimes (37%) drank during violent episodes. Risk for IPV increased with a man's increasing frequency of consumption. Women who lived with a husband who drank alcohol, relative to non-drinkers, were more likely to report postpartum IPV, aOR = 2.0, 95% confidence interval (CI) = [1.3, 3.1]. Husbands' drinking was marginally associated with increased risk for family maltreatment, aOR = 1.4, 95% CI = [1.0, 2.1]. Our findings suggest that men's alcohol use is an important risk factor for postpartum IPV and maltreatment. Targeted services for Indian women contending with these issues are implicated. Postpartum care offers an ideal opportunity to screen for IPV, household maltreatment, and other health risks, such as husband's use of alcohol. There is need to scale up proven successful interventions for reducing men's alcohol use and design strategies that provide at-risk women protection from alcohol-related IPV

Maternal morbidity associated with violence and maltreatment from husbands and in-laws: findings from Indian slum communities.

BackgroundIntimate partner violence (IPV) victimization is linked to a broad range of negative maternal health outcomes. However, it is unclear whether IPV is directly related to poor maternal outcomes or whether IPV is a marker for other forms of chronic, mundane maltreatment of women that stem from the culture of gender inequity that also gives rise to IPV. To determine the prevalence of non-violent forms of gender-based household maltreatment by husbands and in-laws (GBHM), and violence from in-laws (ILV) and husbands (IPV) against women during the peripregnancy period (during and in the year prior to pregnancy); to assess relative associations of GBHM, ILV and IPV with maternal health.MethodsCross-sectional data were collected from women <6 months postpartum (n = 1,039, ages 15-35 years) seeking child immunization in Mumbai, India. Associations of IPV, ILV and GBHM during the peripregnancy period with maternal health (prenatal care in first trimester, no weight gain, pain during intercourse, high blood pressure, vaginal bleeding, premature rupture of membranes, premature birth) were evaluated.ResultsOne in three women (34.0 %) reported IPV, 4.8 % reported ILV, and 48.5 % reported GBHM during the peripregnancy period. After adjusting for other forms of abuse, IPV related to pain during intercourse (AOR = 1.79); ILV related to not receiving first trimester antenatal care (AOR = 0.49), and GBHM remained associated with premature rupture of membranes (AOR = 2.28), pain during intercourse (AOR = 1.60), and vaginal bleeding (AOR = 1.80).ConclusionAfter adjusting for ILV and IPV, peripregnancy GBHM remained significantly associated with multiple forms of maternal morbidity, suggesting that GBHM is a prevalent and reliable indicator of maternal health risk

Variability in gene expression underlies incomplete penetrance

The phenotypic differences between individual organisms can often be ascribed to underlying genetic and environmental variation. However, even genetically identical organisms in homogeneous environments vary, indicating that randomness in developmental processes such as gene expression may also generate diversity. To examine the consequences of gene expression variability in multicellular organisms, we studied intestinal specification in the nematode Caenorhabditis elegans in which wild-type cell fate is invariant and controlled by a small transcriptional network. Mutations in elements of this network can have indeterminate effects: some mutant embryos fail to develop intestinal cells, whereas others produce intestinal precursors. By counting transcripts of the genes in this network in individual embryos, we show that the expression of an otherwise redundant gene becomes highly variable in the mutants and that this variation is subjected to a threshold, producing an ON/OFF expression pattern of the master regulatory gene of intestinal differentiation. Our results demonstrate that mutations in developmental networks can expose otherwise buffered stochastic variability in gene expression, leading to pronounced phenotypic variation.National Institutes of Health (U.S.). Pioneer AwardMathematical Sciences Postdoctoral Research Fellowships (DMS-0603392)National Institutes of Health (U.S.). Ruth L. Kirschstein National Research Service Award (5F32GM080966

DNA index determination with Automated Cellular Imaging System (ACIS) in Barrett's esophagus: Comparison with CAS 200

BACKGROUND: For solid tumors, image cytometry has been shown to be more sensitive for diagnosing DNA content abnormalities (aneuploidy) than flow cytometry. Image cytometry has often been performed using the semi-automated CAS 200 system. Recently, an Automated Cellular Imaging System (ACIS) was introduced to determine DNA content (DNA index), but it has not been validated. METHODS: Using the CAS 200 system and ACIS, we compared the DNA index (DI) obtained from the same archived formalin-fixed and paraffin embedded tissue samples from Barrett's esophagus related lesions, including samples with specialized intestinal metaplasia without dysplasia, low-grade dysplasia, high-grade dysplasia and adenocarcinoma. RESULTS: Although there was a very good correlation between the DI values determined by ACIS and CAS 200, the former was 25% more sensitive in detecting aneuploidy. ACIS yielded a mean DI value 18% higher than that obtained by CAS 200 (p < 0.001; paired t test). In addition, the average time required to perform a DNA ploidy analysis was shorter with the ACIS (30–40 min) than with the CAS 200 (40–70 min). Results obtained by ACIS gave excellent inter-and intra-observer variability (coefficient of correlation >0.9 for both, p < 0.0001). CONCLUSION: Compared with the CAS 200, the ACIS is a more sensitive and less time consuming technique for determining DNA ploidy. Results obtained by ACIS are also highly reproducible

JC Virus T-Antigen Regulates Glucose Metabolic Pathways in Brain Tumor Cells

Recent studies have reported the detection of the human neurotropic virus, JCV, in a significant population of brain tumors, including medulloblastomas. Accordingly, expression of the JCV early protein, T-antigen, which has transforming activity in cell culture and in transgenic mice, results in the development of a broad range of tumors of neural crest and glial origin. Evidently, the association of T-antigen with a range of tumor-suppressor proteins, including p53 and pRb, and signaling molecules, such as β-catenin and IRS-1, plays a role in the oncogenic function of JCV T-antigen. We demonstrate that T-antigen expression is suppressed by glucose deprivation in medulloblastoma cells and in glioblastoma xenografts that both endogenously express T-antigen. Mechanistic studies indicate that glucose deprivation-mediated suppression of T-antigen is partly influenced by 5′-activated AMP kinase (AMPK), an important sensor of the AMP/ATP ratio in cells. In addition, glucose deprivation-induced cell cycle arrest in the G1 phase is blocked with AMPK inhibition, which also prevents T-antigen downregulation. Furthermore, T-antigen prevents G1 arrest and sustains cells in the G2 phase during glucose deprivation. On a functional level, T-antigen downregulation is partially dependent on reactive oxygen species (ROS) production during glucose deprivation, and T-antigen prevents ROS induction, loss of ATP production, and cytotoxicity induced by glucose deprivation. Additionally, we have found that T-antigen is downregulated by the glycolytic inhibitor, 2-deoxy-D-glucose (2-DG), and the pentose phosphate inhibitors, 6-aminonicotinamide and oxythiamine, and that T-antigen modulates expression of the glycolytic enzyme, hexokinase 2 (HK2), and the pentose phosphate enzyme, transaldolase-1 (TALDO1), indicating a potential link between T-antigen and metabolic regulation. These studies point to the possible involvement of JCV T-antigen in medulloblastoma proliferation and the metabolic phenotype and may enhance our understanding of the role of viral proteins in glycolytic tumor metabolism, thus providing useful targets for the treatment of virus-induced tumors

HIV Disclosure, Condom Use, and Awareness of HIV Infection Among HIV-Positive, Heterosexual Drug Injectors in St. Petersburg, Russian Federation

We examined the prevalence of HIV disclosure to sexual partners by HIV-positive drug injectors (IDUs) in St. Petersburg, Russia and compared the magnitude and direction of associations of condom use with awareness of one’s HIV infection and disclosure to partners. Among 157 HIV-infected participants, awareness of infection at time of last intercourse was associated with condom use with partners perceived to be HIV-negative (aOR 6.68, 95% CI 1.60–27.88). Among the 70 participants aware of their infection prior to enrolment, disclosure to potentially uninfected sexual partners was independently and negatively associated with condom use (aOR 0.13, 95% CI 0.02–0.66). Disclosure was independently associated with having injected ≥9 years (aOR 6.04, 95% CI 1.53–23.77) and partnership with another IDU (aOR 3.61, 95% CI 1.44–9.06) or HIV-seropositive (aOR 45.12, 95% CI 2.79–730.46). Scaling up HIV testing services and interventions that increase the likelihood of individuals receiving their test results is recommended

Lung Adenocarcinoma of Never Smokers and Smokers Harbor Differential Regions of Genetic Alteration and Exhibit Different Levels of Genomic Instability

Recent evidence suggests that the observed clinical distinctions between lung tumors in smokers and never smokers (NS) extend beyond specific gene mutations, such as EGFR, EML4-ALK, and KRAS, some of which have been translated into targeted therapies. However, the molecular alterations identified thus far cannot explain all of the clinical and biological disparities observed in lung tumors of NS and smokers. To this end, we performed an unbiased genome-wide, comparative study to identify novel genomic aberrations that differ between smokers and NS

Enhanced Hsp70 Expression Protects against Acute Lung Injury by Modulating Apoptotic Pathways

The Acute respiratory distress syndrome (ARDS) is a highly lethal inflammatory lung disorder. Apoptosis plays a key role in its pathogenesis. We showed that an adenovirus expressing the 70 kDa heat shock protein Hsp70 (AdHSP) protected against sepsis-induced lung injury. In this study we tested the hypothesis that AdHSP attenuates apoptosis in sepsis-induced lung injury

The HAPPY (Healthy and Active Parenting Programmme for early Years) feasibility randomised control trial: acceptability and feasibility of an intervention to reduce infant obesity.

The prevalence of infant obesity is increasing, but there is a lack of evidence-based approaches to prevent obesity at this age. This study tested the acceptability and feasibility of evaluating a theory-based intervention aimed at reducing risk of obesity in infants of overweight/obese women during and after pregnancy: the Healthy and Active Parenting Programme for Early Years (HAPPY).A feasibility randomised controlled trial was conducted in Bradford, England. One hundred twenty overweight/obese pregnant women (Body Mass Index [BMI] ≥25 kg/m(2)) were recruited between 10-26 weeks gestation. Consenting women were randomly allocated to HAPPY (6 antenatal, 6 postnatal sessions: N = 59) or usual care (N = 61). Appropriate outcome measures for a full trial were explored, including: infant's length and weight, woman's BMI, physical activity and dietary intake of the women and infants. Health economic data were collected. Measurement occurred before randomisation and when the infant was aged 6 months and 12 months. Feasibility outcomes were: recruitment/attrition rates, and acceptability of: randomisation, measurement, and intervention. Intra-class correlations for infant weight were calculated. Fidelity was assessed through observations and facilitator feedback. Focus groups and semi-structured interviews explored acceptability of methods, implementation, and intervention content.Recruitment targets were met (~20 women/month) with a recruitment rate of 30 % of eligible women (120/396). There was 30 % attrition at 12 months; 66 % of recruited women failed to attend intervention sessions, but those who attended the first session were likely to continue to attend (mean 9.4/12 sessions, range 1-12). Reaction to intervention content was positive, and fidelity was high. Group clustering was minimal; an adjusted effect size of -0.25 standard deviation scores for infant weight at 12 months (95 % CI: -0.16-0.65) favouring the intervention was observed using intention to treat analyses. No adverse events were reported.The HAPPY intervention appeared feasible and acceptable to participants who attended and those delivering it, however attendance was low; adaptations to increase initial attendance are recommended. Whilst the study was not powered to detect a definitive effect, our results suggest a potential to reduce risk of infant obesity. The evidence reported provides valuable lessons to inform progression to a definitive trial.Current Controlled Trials ISRCTN56735429