Epigenetic studies in children at risk of stunting and their parents in India, Indonesia and Senegal: a UKRI GCRF Action Against Stunting Hub protocol paper.

INTRODUCTION: In 2020, an estimated 150 million children under the age of 5 years were stunted. Stunting results from early-life adversity and it is associated with significant physical and cognitive deficit, lifelong socioeconomic disadvantage and reduced life expectancy. There is a need to understand the causes of stunting and its effects in order to develop strategies to avoid it and to mitigate the consequences once stunting has occurred. Epigenetics is an important mechanism through which early-life factors are thought to influence biological function, with long-term consequences. We describe a series of epigenetic studies designed to understand how early-life adversity results in stunting and to inform the development of practical tools such as predictive markers and therapeutic targets. This work is part of the UKRI GCRF Action Against Stunting Hub. METHODS AND ANALYSIS: The project-in India, Indonesia and Senegal-comprises an observational study of mothers, fathers, and offspring (n=500) spanning the first 1000 days of life, and an intervention study in each country. Epigenetic status (DNA methylation) is determined in saliva from babies collected within 1 month of birth and again at 18 months of age, and from mothers and fathers around the time of birth. Epigenome-wide analysis is carried out using the Illumina EPIC array, augmented by high-definition sequencing approaches. Statistical analysis is carried out at the level of candidate genes/regions, higher dimensional epigenetic states and epigenome-wide association. Data analysis focuses on the determinants of stunting, the effectiveness of interventions, population comparisons and the link between epigenetics and other thematic areas, which include anthropometry, microbiome, gut health, parasitology, cognition, nutrition, food hygiene and water sanitation, food systems and the home environment. ETHICS AND DISSEMINATION: This study has been approved by the relevant Ethics Committees in Indonesia, India and Senegal, and the UK. Research data will be published and posted in public repositories.

Cinnamon Attenuated Long-Term IGT-Induced Retinal Abnormalities via Regulation of Glucose Homeostasis in Neonatal Streptozotocin Induced Rat Model.

Diabetic retinopathy (DR) is one of the major causes of blindness all over the world. According to the previous studies, impaired glucose tolerance (IGT) has been linked to retinal dysfunction/vascular damage. Decreased retinal function is an initial event of early DR. Although the biochemical and molecular events are not fully understood, glial activation, angiogenesis and oxidative stress are some of the pathways associated with early retinal abnormalities. Since IGT is associated with development of retinal dysfunction/vascular damage; as a preventive strategy, we have studied beneficial effect of Cinnamon as a hypoglycaemic agent on long-term IGT induced retinal abnormalities using neonatal streptozotocin (nSTZ) rat model. Control, IGT rats were maintained on AIN-93M diet alone and another set of IGT rats were maintained on AIN-93M diet with 3% Cinnamon for 8 months. At the end of the study, untreated IGT rats developed retinal functional abnormalities as assessed by electroretinogram (ERG) and the retinal structure did not alter as assessed by H&E staining. Further, increase in expressions of GFAP, VEGF and decreased expression of rhodopsin in untreated IGT rat retinas. 4-HNE, a marker of oxidative stress was also elevated in IGT state. Supplementation of Cinnamon to IGT rats had lowered fasting and postprandial glucose levels and also prevented retinal functional abnormalities. Further, Cinnamon protected photoreceptor cell damage, suppressed glial activation, angiogenesis and oxidative stress as there was an improved rhodopsin expression, inhibited elevated expressions of GFAP, VEGF and 4-HNE respectively. In conclusion, Cinnamon attenuated IGT induced retinal abnormalities probably through its hypoglycemic property.

Prevalence of Nutritional Anemia and Hyperhomocysteinemia in Urban Elderly.

The data on the prevalence of nutritional anemia among the urban elderly population in India was limited. Hence, the present study was carried out with an aim to assess the prevalence of nutritional anemia and its association with vitamin B12, folate, ferritin and homocystine among the urban elderly population. A community- based cross-sectional study was carried out among 282 urban elderly (≥ 60 years) subjects (186 males and 96 females) in Hyderabad. Fasting blood samples were collected and hemoglobin (Hb) was estimated by cyanmethemoglobin method. Plasma Folic acid and vitamin B12 levels were estimated by RIA and homocysteine and ferritin levels were estimated by ELISA methods. The overall prevalence of anemia (Hb < 12 g/dL for females and < 13 g/dL for males) among the urban elderly was 20.6% and the prevalence was found to be increasing with the age. The prevalence of vitamin B12 (< 203 pg/mL), folic acid (< 4 ng/mL), ferritin (< 15 ng/mL) and hyperhomocysteinemia (≥ 12 µmol/L) in these subjects was 36.0%, 8.2%, 1.1% and 24.3% respectively. The prevalence of anemia due to deficiencies of iron (ferritin < 15 ng/mL), folate and vitamin B12 was 5.45%, 9.1% and 42.3% respectively. A significant association was observed between the prevalence of anemia with ferritin and hyperhomocysteinemia. In conclusion, the prevalence of anemia and nutritional anemia among the urban-based elderly was 20.6% and 56.85% respectively. The association of anemia with hyperhomocysteinemia needs further studies.