Blocking c-MET/ERBB1 Axis Prevents Brain Metastasis in ERBB2+ Breast Cancer

Brain metastasis (BrM) remains a significant cause of cancer-related mortality in epidermal growth factor receptor 2-positive (ERBB2+) breast cancer (BC) patients. We proposed here that a combination treatment of irreversible tyrosine kinase inhibitor neratinib (NER) and the c-MET inhibitor cabozantinib (CBZ) could prevent brain metastasis. To address this, we first tested the combination treatment of NER and CBZ in the brain-seeking ERBB2+ cell lines SKBrM3 and JIMT-1-BR3, and in ERBB2+ organoids that expressed the c-MET/ERBB1 axis. Next, we developed and characterized an orthotopic mouse model of spontaneous BrM and evaluated the therapeutic effect of CBZ and NER in vivo. The combination treatment of NER and CBZ significantly inhibited proliferation and migration in ERBB2+ cell lines and reduced the organoid growth in vitro. Mechanistically, the combination treatment of NER and CBZ substantially inhibited ERK activation downstream of the c-MET/ERBB1 axis. Orthotopically implanted SKBrM3+ cells formed primary tumor in the mammary fat pad and spontaneously metastasized to the brain and other distant organs. Combination treatment with NER and CBZ inhibited primary tumor growth and predominantly prevented BrM. In conclusion, the orthotopic model of spontaneous BrM is clinically relevant, and the combination therapy of NER and CBZ might be a useful approach to prevent BrM in BC

A cross sectional study to measure prevalence of Hepatitis B and HIV and explore the potential risk factors for the acquisition of these and other sexually transmitted infections among antenatal care attendees in a tertiary care center of West Bengal, India

ObjectivesTo estimate the prevalence and socio-demographic and behavioral correlates of HIV and Hepatitis B among ANC attendees in a public tertiary care center in Kolkata, West Bengal, IndiaMethodologyA cross-sectional study was conducted involving consenting adult pregnant women attending the antenatal clinic of a public-sector tertiary care hospital in Kolkata, between January and June, 2016. Anonymous data was collected from 1670 randomly selected subjects, using a color-coded, audio-integrated, tablet-PC assisted, pre-recorded, self-interview system developed in an algorithm based android platform with a non-response rate of 3%. FindingsAmong participants. 1.66% were HIV-positive while 2.74% had Hepatitis-B. Having extra-marital relationship was associated with Hepatitis B infection. Higher age, poor education, higher parity, alcohol consumption by husbands before sex, history of syphilis/genital ulcer or swelling and higher self-perceived HIV risk were associated with HIV sero-positivity. Higher age at marriage and graduation or higher education were the factors negatively associated with ever having sex with someone who consumed alcohol. Relatively older participants had higher while high-school or more educated subjects had lower odds of having extra-marital sexual relationship. Rural respondents were more likely to engage in paid sex. Rural-living husbands, those having high-school or more education and business-owners were less likely to have sex with the respondents always after consuming alcohol. Higher age of respondent was negatively and graduation or above education was positively associated with husband having vaginal sex during respondent’s pregnancy. Odds of verbal abuse/bad behavior during sex by husband was positively associated with wife’s age and lower among high school-educated husband, and wives. Physical abuse during sex was more likely experienced by respondents with higher age of respondent, Muslim religion and less likely among high-school or more educated. Conclusions and RecommendationsHIV/STI related counseling strategy need revisit and re-orientation to shift the focus from individual perspective to couples’ joint responsibilities so that concurrent counseling/treatment of partners receive priority especially the high-risk group. Proper management of STIs during pregnancy needs multifaceted approach which includes quality epidemiological data, good evidence of effectiveness of ongoing interventions, increase accessibility to reproductive health care services, stronger advocacy and commitment to get them implemented

A cross sectional study to measure prevalence of Hepatitis B and HIV and explore the potential risk factors for the acquisition of these and other sexually transmitted infections among antenatal care attendees in a tertiary care center of West Bengal, India

ObjectivesTo estimate the prevalence and socio-demographic and behavioral correlates of HIV and Hepatitis B among ANC attendees in a public tertiary care center in Kolkata, West Bengal, IndiaMethodologyA cross-sectional study was conducted involving consenting adult pregnant women attending the antenatal clinic of a public-sector tertiary care hospital in Kolkata, between January and June, 2016. Anonymous data was collected from 1670 randomly selected subjects, using a color-coded, audio-integrated, tablet-PC assisted, pre-recorded, self-interview system developed in an algorithm based android platform with a non-response rate of 3%. FindingsAmong participants. 1.66% were HIV-positive while 2.74% had Hepatitis-B. Having extra-marital relationship was associated with Hepatitis B infection. Higher age, poor education, higher parity, alcohol consumption by husbands before sex, history of syphilis/genital ulcer or swelling and higher self-perceived HIV risk were associated with HIV sero-positivity. Higher age at marriage and graduation or higher education were the factors negatively associated with ever having sex with someone who consumed alcohol. Relatively older participants had higher while high-school or more educated subjects had lower odds of having extra-marital sexual relationship. Rural respondents were more likely to engage in paid sex. Rural-living husbands, those having high-school or more education and business-owners were less likely to have sex with the respondents always after consuming alcohol. Higher age of respondent was negatively and graduation or above education was positively associated with husband having vaginal sex during respondent’s pregnancy. Odds of verbal abuse/bad behavior during sex by husband was positively associated with wife’s age and lower among high school-educated husband, and wives. Physical abuse during sex was more likely experienced by respondents with higher age of respondent, Muslim religion and less likely among high-school or more educated. Conclusions and RecommendationsHIV/STI related counseling strategy need revisit and re-orientation to shift the focus from individual perspective to couples’ joint responsibilities so that concurrent counseling/treatment of partners receive priority especially the high-risk group. Proper management of STIs during pregnancy needs multifaceted approach which includes quality epidemiological data, good evidence of effectiveness of ongoing interventions, increase accessibility to reproductive health care services, stronger advocacy and commitment to get them implemented

Role of perceived family environment in the pathogenesis of schizophrenia

Background: Family plays an important role in mental health of its member, thus its contribution can also be discerned in pathogenesis. Maintenance and relapse of several mental illnesses have been also attributed to the family environment (FE). This study explores FE as perceived by schizophrenia patients. Methodology: A case–control study was conducted in Chhattisgarh, India, to measure the association of perceived FE with schizophrenia. Between February 2014 and January 2015, 100 paranoid schizophrenia patients and 100 neighborhood-based healthy (based on 28-item General Health Questionnaire) controls were recruited. Minimum school-educated individuals aged 20–35 years were eligible if they/their caregivers provided consent. Interpersonal relationships and FE were assessed by an interviewer-administered 69-item FE scale. Results: The odds of suffering from schizophrenia increased with age, decreased with education, income, and found to be less among married. Schizophrenia risk was negatively associated with mean scores for cohesion, acceptance/caring, active-recreational orientation, and organization. Negative symptoms of schizophrenia were less pronounced among patients belonging to joint families. Conclusion: Thus, to minimize the burden and morbidity associated with schizophrenia, interventions to improve FE by minimizing conflict and improving cohesion, acceptance/caring, active-recreational orientation, and organization, and specifically targeting older, less-educated, poor, and married individuals in nuclear families seemed necessary

Perceived morbidity, healthcare-seeking behavior and their determinants in a poor-resource setting: observation from India.

To control the double burden of communicable and non-communicable diseases (NCDs), in the developing world, understanding the patterns of morbidity and healthcare-seeking is critical. The objective of this cross-sectional study was to determine the distribution, predictors and inter-relationship of perceived morbidity and related healthcare-seeking behavior in a poor-resource setting.Between October 2013 and July 2014, 43999 consenting subjects were recruited from 10107 households in Malda district of West Bengal state in India, through multistage random sampling, using probability proportional-to-size. Information on socio-demographics, behaviors, recent ailments, perceived severity and healthcare-seeking were analyzed in SAS-9.3.2.Recent illnesses were reported by 55.91% (n=24,600) participants. Among diagnosed ailments (n=23,626), 50.92% (n=12,031) were NCDs. Respiratory (17.28%, n=7605)), gastrointestinal (13.48%, n=5929) and musculoskeletal (6.25%, n=2749) problems were predominant. Non-qualified practitioners treated 53.16% (n=13,074) episodes. Older children/adolescents [adjusted odds ratio for private healthcare providers (AORPri)=0.76, 95% confidence interval=0.71-0.83) and for Govt. healthcare provider (AORGovt)=0.80(0.68-0.95)], females [AORGovt=0.80(0.73-0.88)], Muslims [AORPri=0.85(0.69-0.76) and AORGovt=0.92(0.87-0.96)], backward castes [AORGovt=0.93(0.91-0.96)] and rural residents [AORPri=0.82(0.75-0.89) and AORGovt=0.72(0.64-0.81)] had lower odds of visiting qualified practitioners. Apparently less severe NCDs [acid-peptic disorders: AORPri=0.41(0.37-0.46) & AORGovt=0.41(0.37-0.46), osteoarthritis: AORPri=0.72(0.59-0.68) & AORGovt=0.58(0.43-0.78)], gastrointestinal [AORPri=0.28(0.24-0.33) & AORGovt=0.69(0.58-0.81)], respiratory [AORPri=0.35(0.32-0.39) & AORGovt=0.46(0.41-0.52)] and skin infections [AORPri=0.65(0.55-0.77)] were also less often treated by qualified practitioners. Better education [AORPri=1.91(1.65-2.22) for ≥graduation], sanitation [AORPri=1.58(1.42-1.75)] and access to safe water [AORPri=1.33(1.05-1.67)] were associated with healthcare-seeking from qualified private practitioners. Longstanding NCDs [chronic obstructive pulmonary diseases: AORPri=1.80(1.46-2.23), hypertension: AORPri=1.94(1.60-2.36), diabetes: AORPri=4.94(3.55-6.87)] and serious infections [typhoid: AORPri=2.86(2.04-4.03)] were also more commonly treated by qualified private practitioners. Potential limitations included temporal ambiguity, reverse causation, generalizability issues and misclassification.In this poor-resource setting with high morbidity, ailments and their perceived severity were important predictors for healthcare-seeking. Interventions to improve awareness and healthcare-seeking among under-privileged and vulnerable population with efforts to improve the knowledge and practice of non-qualified practitioners probably required urgently

Association of Frontline Worker-Provided Services with Change in Block-Level Complementary Feeding Indicators: An Ecological Analysis from Bihar, India

<div><p>Background</p><p>Insufficiencies in complementary feeding put infants and young children at increased risk of undernutrition. Till now, most Indian studies have looked at the individual level determinants of complementary feeding practices. We aimed to evaluate the association of frontline worker (FLW) provided nutritional counselling services, with change in community level indicators of complementary feeding practices among 9–11 month old children over time.</p><p>Methods</p><p>The study data was obtained from five rounds of ‘Lot Quality Assurance Sampling’ survey in eight districts of Bihar, an impoverished Indian state. The surveys were conducted as evaluation exercises for the ‘Integrated Family Health Initiative (IFHI)’–a multi-faceted program aimed at improving the maternal and child health outcomes in Bihar. The main outcome indicators were—current breastfeeding, age-appropriate minimum frequency of semi-solid food, age-appropriate minimum quantity of semi-solid food, initiation of complementary feeding at the right age, and dietary diversity. Repeated measures analysis was performed to determine the association of changes in the outcome indicators with coverage of FLW-provided counselling services.</p><p>Results</p><p>Visits by FLW, advices on age-appropriate frequency and handwashing were significant predictors of receiving age-appropriate frequency of feeding. The determinants of receiving age-appropriate quantity were—advices on age appropriate frequency and advices on handwashing. Receiving food support from AWC and FLW visits were significantly associated with initiating complementary feeding at the right age.</p><p>Conclusions</p><p>The present study identified the critical elements among the different types of FLW-provided services. The study findings, from an economically and socially underdeveloped region of India, would inform the relevant programs about the nutritional counselling services that need to be emphasized upon for reducing the burden of childhood malnutrition.</p></div

Is hypertension associated with job strain? A meta-analysis of observational studies.

Job strain results from a combination of high workload and few decision-making opportunities in the workplace. There is inconsistent evidence regarding the association between job strain and hypertension, and methodological shortcomings preclude firm conclusions. Thus, a meta-analysis of observational studies on hypertension among occupational groups was conducted to determine whether job strain was associated with hypertension. In January 2012, we carried out a comprehensive, topic-specific electronic literature search of the Ovid MEDLINE, EMBASE and PsychoINFO databases complemented by individual help from non-communicable disease experts. Experimental/interventional studies and studies on personality disorders were excluded. Nine of 894 identified studies met the eligibility criteria and were included in the meta-analysis. The pooled OR of the nine studies was 1.3 (95% CI 1.14 to 1.48; p<0.001), of case-control studies 3.17 (95% CI 1.79 to 5.60; p<0.001) and of cohort studies 1.24 (95% CI 1.09 to 1.41; p<0.001), all of which indicated statistically significant positive associations between job strain and hypertension. In a subgroup analysis, cohort studies of good methodological quality showed significant associations between job strain and hypertension, while those of poor methodological quality showed no association or subgroup differences. We conclude that despite methodological differences, case-control and cohort studies of good methodological quality showed positive associations between hypertension and job strain

Burden and Socio-Behavioral Correlates of Uncontrolled Abnormal Glucose Metabolism in an Urban Population of India.

Progressive burden of diabetes mellitus is a major concern in India. Data on the predictors of poor glycemic control among diabetics are scanty. A population-based cross-sectional study nested in an urban cohort was thus conducted in West Bengal, India to determine the burden and correlates of total and uncontrolled abnormalities in glucose metabolism (AGM) in a representative population.From 9046 adult cohort-members, 269 randomly selected consenting subjects (non-response = 7.24%) were interviewed, examined [blood pressure (BP), anthropometry], tested for fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1C). Those having pre-diagnosed diabetes or FPG ≥126 or HbA1c≥6.5 were defined as diabetic. Among non-diabetics, subjects with FPG (mg/dl) = 100-125 or HbA1C(%) = 5.7-6.4 were defined as pre-diabetic. Pre-diagnosed cases with current FPG ≥126 were defined as uncontrolled AGM. Descriptive and regression analyses were conducted using SAS-9.3.2.Among participants, 28.62% [95% Confidence Interval (95%CI) = 23.19-34.06)] were overweight [body mass index(BMI) = (25-29.99)kg/meter2], 7.81% (4.58-11.03) were obese(BMI≥30kg/meter2), 20.82% (15.93-25.70) were current smokers, 12.64% (8.64-16.64) were current alcohol-drinkers and 46.32% of responders (39.16-53.47) had family history of diabetes. 17.84% (13.24-22.45) had stage-I [140≤average systolic BP (AvSBP in mm of mercury)<160 or 90≤average diastolic BP (AvDBP)<100] and 12.64% (8.64-16.64) had stage-II (AvSBP≥160 or AvDBP≥160) hypertension. Based on FPG and HbA1c, 10.41% (6.74-14.08) were diabetic and 27.88% (22.49-33.27) were pre-diabetic. Overall prevalence of diabetes was 15.61% (11.25-19.98). Among pre-diagnosed cases, 46.43% (26.74-66.12) had uncontrolled AGM. With one year increase in age [Odds Ratio(OR) = 1.05(1.03-1.07)], retired subjects [OR = 9.14(1.72-48.66)], overweight[OR = 2.78(1.37-5.64)], ex-drinkers [OR = 4.66(1.35-16.12)] and hypertensives [ORStage I = 3.75(1.42-9.94); ORStage II = 4.69(1.67-13.17)] had higher odds of diabetes. Relatively older subjects [OR = 1.06(1.02-1.10)], unemployed [OR = 19.68(18.64-20.78)], business-owners [OR = 25.53(24.91-16.18)], retired [OR = 46.53(45.38-47.72)], ex-smokers [OR = 4.75(1.09-20.78)], ex-drinkers [OR = 22.43(4.62-108.81)] and hypertensives [ORStage II = 13.17(1.29-134.03)] were more likely to have uncontrolled AGM.Burden of uncontrolled AGM was high among participants. Efforts to curb the diabetes epidemic in urban India should include interventions targeting appropriate diabetic control among relatively older persons, unemployed, business-owners, retired, ex-smokers, ex-drinkers and hypertensives