Changing family structures and self-rated health of India's older population (1995-96 to 2014).

A common view within academia and Indian society is that older Indians are cared for by their families less than in the past. Children are a key source of support in later life and alternatives are limited, therefore declining fertility appears to corroborate this. However, the situation may be more complex. Having many children may be physiologically burdensome for women, sons and daughters have distinct care roles, social trends could affect support provision, and spouses also provide support. We assessed whether the changing structure of families has negatively affected health of the older population using three cross-sectional and nationally representative surveys of India's 60-plus population (1995-96, 2004 and 2014). We described changes in self-rated health and family structure (number of children, sons, and daughters, and marital status) and, using ordinal regression modelling, determined the association between family structure and self-rated health, stratified by survey year and gender. Our results indicate that family structure changes that occurred between 1995-96 and 2014 were largely associated with better health. Though family sizes declined, there were no health gains from having more than two children. In fact, having many children (particularly daughters) was associated with worse health for both men and women. There was some evidence that being sonless or childless was associated with worse health, but it remained rare to not have a son or child. Being currently married was associated with better health and became more common over the inter-survey period. Although our results suggest that demographic trends have not adversely affected health of the older population thus far, we propose that the largest changes in family structure are yet to come. The support available in coming years (and potential health impact) will rely on flexibility of the current system

Childhood socio-economic conditions and risk of cardiovascular disease: results from a pooled sample of 14 011 adults from India.

BACKGROUND: South Asians are at an increased risk of premature cardiovascular disease, but the reasons for this are unclear. Poor socio-economic conditions in childhood are associated with an increased risk of cardiovascular disease in many high-income countries and may be particularly relevant to South Asia, where socio-economic deprivation is more prevalent and severe. However, evidence from South Asia is limited. METHODS: We pooled data from two large population-based studies in India to provide a geographically representative and adequately powered sample of Indian adults. We used multilevel linear regression models to assess associations between standard of living index (SLI) in childhood (measured by recalled household assets at age 10-12 years) and major cardiovascular risk factors including adiposity, blood pressure, and fasting blood lipids, glucose and insulin. RESULTS: Data on 14 011 adults (median age 39 years, 56% men) were analysed. SLI in childhood was inversely associated with systolic and diastolic blood pressure, independent of socio-economic conditions in adulthood, with beta coefficients (95% CIs) of -0.70 mmHg (-1.17 to -0.23) and -0.56 mmHg (-0.91 to -0.22), respectively, per SD increase in SLI in childhood. There was no strong evidence for an association between SLI in childhood and other risk factors of cardiovascular disease. CONCLUSIONS: Poor socio-economic conditions in childhood may contribute to the increased risk of premature cardiovascular disease among South Asians by raising their blood pressure. Elucidating the mechanisms and improving socio-economic conditions for children in South Asia could provide major reductions in the burden of cardiovascular disease

“Day and night people run after money … where is the time to spend chit-chatting with parents?”: Challenges of, and coping strategies for, supporting older relatives in adults of varied socioeconomic backgrounds in Tamil Nadu, India

Fertility has declined significantly across the socioeconomic spectrum in the south Indian state of Tamil Nadu, which has the potential to increase the strains of support provision for family members and to limit support for dependent older people. We used a qualitative approach to explore the challenges that adults (N ​= ​113) from varying socioeconomic backgrounds (urban/rural and socioeconomic status) in Tamil Nadu experience when supporting their older relatives, and to understand how they cope with these challenges. While the broad challenges mirrored those seen elsewhere in India and globally (e.g., role conflict), some were particular to the context of contemporary Tamil Nadu (e.g., difficulties around supporting son/child-less or non-co-resident elders). The challenges experienced were qualitatively similar across socioeconomic groups but affluent families had more coping strategies available to limit the negative outcomes of support provision. We highlight the potential value of universal health coverage for promoting family-based support for older Indians, the urgent need for strategies to ease the challenges for lower socioeconomic status families, and the importance of wider socioeconomic policy to reduce the financial and time pressures that restrict the support that much of the population can provide each other

The Association of Total Meat Intake with Cardio-Metabolic Disease Risk Factors and Measures of Sub-Clinical Atherosclerosis in an Urbanising Community of Southern India: A Cross-Sectional Analysis for the APCAPS Cohort.

AIM: Meat is commonly consumed in India; however, in comparison to Western settings, it is eaten in relatively lower quantities and with minimal processing. The association between meat intake and cardio-metabolic diseases (CMDs) and their risk factors in India is currently uncertain. We examined whether meat intake is associated with risk factors for CMDs and the measures of subclinical atherosclerosis in urbanising villages in southern India. METHODS: We conducted a cross-sectional analysis of 6012 adults (52.3% male) participating in the Andhra Pradesh Children and Parents' Study (APCAPS), which is a large prospective, intergenerational cohort study in Southern India that began with the long-term follow-up of the Hyderabad Nutrition Trial (1987-1990). We used cross-sectional data from the third wave of data collection conducted in 2010-2012, where total meat intake was assessed using 100-item, semi-quantitative validated food frequency questionnaires (FFQ). The FFQs were validated using multiple weighed 24 h dietary recalls. The main predictor, 'total meat intake', was calculated as the sum of chicken, red meat, and fish consumption. The risk factors for CMDs [systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), waist circumference (WC), fasting glucose, total cholesterol, homeostasis model assessment insulin resistance (HOMA-IR), total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, triglycerides, and C-reactive protein] and measures of subclinical atherosclerosis [Carotid Intima-Media Thickness, Pulse Wave Velocity, and Augmentation Index] were assessed using standardised clinical procedures. Stratified by gender, the association of meat intake with the risk factors of CMDs and measures of subclinical atherosclerosis was examined using linear multilevel models with random intercept at the household level. RESULTS: The mean (SD) age of the male (n = 3128) and female participants (n = 2828) was 34.09 years (15.55) and 34.27 years (12.73), respectively. The median (IQR) intake of meat was 17.79 g/day (8.90, 30.26) in males and 8.90 g/day (4.15, 18.82) in females. In males, a 10 g increase in total meat intake/1000 Kcal/day was positively associated with DBP, BMI, WC, total cholesterol, LDL-C, and triglycerides, whereas in females, a 10 g increase in total meat intake/1000 Kcal/day was positively associated with SBP, DBP, fasting glucose, HOMA-IR, total cholesterol, LDL-C, and triglycerides. There was no relationship between meat consumption and measures of subclinical atherosclerosis. CONCLUSIONS: Meat intake had a linear positive association with CMD risk factors among the relatively younger Indian population who were consuming meat at lower levels compared to their European counterparts

Effect of Ku80 Deficiency on Mutation Frequencies and Spectra at a LacZ Reporter Locus in Mouse Tissues and Cells

Non-homologous end joining (NHEJ) is thought to be an important mechanism for preventing the adverse effects of DNA double strand breaks (DSBs) and its absence has been associated with premature aging. To investigate the effect of inactivated NHEJ on spontaneous mutation frequencies and spectra in vivo and in cultured cells, we crossed a Ku80-deficient mouse with mice harboring a lacZ-plasmid-based mutation reporter. We analyzed various organs and tissues, as well as cultured embryonic fibroblasts, for mutations at the lacZ locus. When comparing mutant with wild-type mice, we observed a significantly higher number of genome rearrangements in liver and spleen and a significantly lower number of point mutations in liver and brain. The reduced point mutation frequency was not due to a decrease in small deletion mutations thought to be a hallmark of NHEJ, but could be a consequence of increased cellular responses to unrepaired DSBs. Indeed, we found a substantial increase in persistent 53BP1 and γH2AX DNA damage foci in Ku80−/− as compared to wild-type liver. Treatment of cultured Ku80-deficient or wild-type embryonic fibroblasts, either proliferating or quiescent, with hydrogen peroxide or bleomycin showed no differences in the number or type of induced genome rearrangements. However, after such treatment, Ku80-deficient cells did show an increased number of persistent DNA damage foci. These results indicate that Ku80-dependent repair of DNA damage is predominantly error-free with the effect of alternative more error-prone pathways creating genome rearrangements only detectable after extended periods of time, i.e., in young adult animals. The observed premature aging likely results from a combination of increased cellular senescence and an increased load of stable, genome rearrangements

Alcohol and HIV Disease Progression: Weighing the Evidence

Heavy alcohol use is commonplace among HIV-infected individuals; however, the extent that alcohol use adversely impacts HIV disease progression has not been fully elucidated. Fairly strong evidence suggests that heavy alcohol consumption results in behavioral and biological processes that likely increase HIV disease progression, and experimental evidence of the biological effect of heavy alcohol on simian immunodeficiency virus in macaques is quite suggestive. However, several observational studies of the effect of heavy alcohol consumption on HIV progression conducted in the 1990s found no association of heavy alcohol consumption with time to AIDS diagnosis, while some more recent studies showed associations of heavy alcohol consumption with declines of CD4 cell counts and nonsuppression of HIV viral load. We discuss several plausible biological and behavioral mechanisms by which alcohol may cause HIV disease progression, evidence from prospective observational human studies, and suggest future research to further illuminate this important issue

Tuberculosis mortality and the male survival deficit in rural South Africa:An observational community cohort study

BACKGROUND: Women live on average five years longer than men, and the sex difference in longevity is typically lower in populations with high mortality. South Africa-a high mortality population with a large sex disparity-is an exception, but the causes of death that contribute to this difference are not well understood. METHODS: Using data from a demographic surveillance system in rural KwaZulu-Natal (2000-2014), we estimate differences between male and female adult life expectancy by HIV status. The contribution of causes of death to these life expectancy differences are computed with demographic decomposition techniques. Cause of death information comes from verbal autopsy interviews that are interpreted with the InSilicoVA tool. RESULTS: Adult women lived an average of 10.4 years (95% confidence Interval 9.0-11.6) longer than men. Sex differences in adult life expectancy were even larger when disaggregated by HIV status: 13.1 (95% confidence interval 10.7-15.3) and 11.2 (95% confidence interval 7.5-14.8) years among known HIV negatives and positives, respectively. Elevated male mortality from pulmonary tuberculosis (TB) and external injuries were responsible for 43% and 31% of the sex difference in life expectancy among the HIV negative population, and 81% and 16% of the difference among people living with HIV. CONCLUSIONS: The sex differences in adult life expectancy in rural KwaZulu-Natal are exceptionally large, atypical for an African population, and largely driven by high male mortality from pulmonary TB and injuries. This is the case for both HIV positive and HIV negative men and women, signalling a need to improve the engagement of men with health services, irrespective of their HIV status

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Childhood Socioeconomic Position and Risk of Cardiovascular Disease in Adulthood: Systematic Review of Evidence From Low- and Middle-Income Countries.

INTRODUCTION: Socioeconomic disadvantage in childhood is strongly associated with a higher risk of cardiovascular disease in high-income countries. However, the association in low- and middle-income countries, where childhood poverty remains prevalent, has not been reviewed. METHODS: The authors systematically searched Embase, MEDLINE, and Global Health databases for articles on the association between childhood socioeconomic position and risk of cardiovascular disease in adulthood in low- and middle-income countries until September 2020. Outcomes included measures of cardiovascular disease, its subclinical markers (e.g., carotid intima-media thickness), and its major risk factors (e.g., hypertension, dyslipidemia, diabetes). Where available, associations were extracted before and after adjustment for socioeconomic position in adulthood. Results were synthesized qualitatively by outcome. The study protocol is registered on PROSPERO (CRD42018086984). RESULTS: The search returned 3,568 unique abstracts, from which 29 eligible articles from 14 middle-income countries were identified, representing >150,000 participants. The most commonly reported outcomes were cardiovascular risk factors; very few studies reported prevalent measures of cardiovascular disease, and no studies reported cardiovascular disease incidence or mortality. Of the 46 reported associations between childhood socioeconomic position and risk of cardiovascular disease, 8 were inverse, 0 were positive, and 38 showed no clear evidence of association. All articles had high (16/29) or medium (13/29) risk of bias. CONCLUSIONS: Current evidence from middle-income countries provides little support for an association between childhood socioeconomic position and risk of cardiovascular disease, and evidence from low-income countries is lacking. It would be premature to consider childhood poverty as a target for cardiovascular disease prevention in these settings