Undernutrition in children & critical windows of opportunity in Indian context.

It is intriguing to note that majority of the wasting among the under 5 yr in India is present at birth. The National Family Health Survey 4 (NFHS-4) data analysis shows 31.9 per cent wasting at birth, which is decreasing to 17.7 per cent in the under five children; clearly suggesting that any reduction in wasting should come from improvement in foetal growth. In addition, children with both severe wasting and severe stunting, in whom the risk of mortality increases many folds, are <1 per cent in almost all the States; and these are the children in whom special care is required under the community-based management of severe acute malnutrition. This article presents an overview of nutrition status in children, their antecedents, and the critical phases; especially, nutrition status before pregnancy that plays a crucial role in all the nutrition status indicators of children. More attention on the critical phases is crucial to maximize the benefits from national programmes.

Evaluation of a Biologic Formulation Using Customized Design of Experiment and Novel Multidimensional Robustness Diagrams.

Formulation development includes selection of appropriate excipients to stabilize the active pharmaceutical ingredient throughout its recommended shelf life, against potential excursions in its life cycle and sometimes to aid in the delivery of therapeutics into the patient. Identity and quantity of every ingredient in a therapeutic formulation are critical to achieve their intended purpose. Deviations from a target composition can result in manufacturing, safety, and efficacy challenges. It is mandatory to establish robustness of a formulation for the expected changes in its composition arising from the qualified "process variability" of the impacting process steps during manufacture. The approach for carrying out a robustness study evolved through improved understanding of a therapeutic stability and exploration of new tools, including the quality by design elements strongly recommended by regulatory agencies. An approach is presented here to study formulation robustness in multidimensional space using a customized experimental design and novel multidimensional diagrams, which present a unique way of identifying robustness limits. The concept is universally applicable to any multivariate analysis and such diagrams would be useful to comprehend the outcome on all variables at a glance. Interpretation of these diagrams is discussed, some of which are applicable in general to any statistical design of experiment.

Secular Trends in Heights and Weights in Boys and Girls Over 3 Decades in Rural India.

BACKGROUND: Secular trends in height reported from developing countries are few and scarce. OBJECTIVE: To assess secular trends in linear growth in boys and girls from birth to 18 years of life in rural households of India based on periodical cross-sectional surveys conducted over a period of 35 years. MATERIALS AND METHODS: The present study uses data from baseline and final surveys of National Nutrition Monitoring Bureau from 1975 to 1979 (N = 6043) to 2012 to 2013 (N = 11 910) on anthropometry from birth to 18 years from 7 states in households of rural India. RESULTS: The overall improvement in 18+ boys and girls was 3.1 and 1.0 cm, respectively, over a period of 35 years. The increments in height of 18+ were highest for both boys (7.4 cm) and girls (4.8 cm) in the state of Kerala followed by Tamil Nadu (boys, 7.3 cm and girls, 3.8 cm). Under-5 stunting rates reduced from 82% in the baseline survey to 45.7% in the final survey at 1.35% per year in the pooled states and was similar in both boys and girls. The recovery in stunting was highest in Tamil Nadu (1.63% per year) followed by Kerala (1.46% per year). CONCLUSION: The pattern of secular trends in height in rural India seen over 3 decades was strikingly similar to that of developed countries. The phenomenal improvement in linear growth in Kerala and Tamil Nadu in children younger than 5 years and adolescents suggests that growth potential for Indians is similar to that of developed countries.

Urban-Rural Differences in Bone Mineral Density: A Cross Sectional Analysis Based on the Hyderabad Indian Migration Study.

BACKGROUND: Fracture risk is rising in countries undergoing rapid rural to urban migration, but whether this reflects an adverse effect of urbanization on intrinsic bone strength, as reflected by bone mineral density (BMD), is currently unknown. METHODS: Lumbar spine (LS) and total hip (TH) BMD, and total body fat and lean mass, were obtained from DXA scans performed in the Hyderabad arm of the Indian Migration Study (54% male, mean age 49 years). Sib-pair comparisons were performed between rural-urban migrants (RUM) and rural non-migrated (RNM) siblings (N = 185 sib-pairs). RESULTS: In analyses adjusted for height, gender, age and occupation, rural to urban migration was associated with higher lumbar and hip BMD and greater predicted hip strength; ΔLS BMD 0.030 (0.005, 0.055) g/cm2, ΔTH BMD 0.044 (0.024; 0.064) g/cm2, Δcross-sectional moment of inertia 0.162 (0.036, 0.289) cm4. These differences were largely attenuated after adjusting for body composition, insulin levels and current lifestyle factors ie. years of smoking, alcohol consumption and moderate to vigorous physical activity. Further analyses suggested that differences in lean mass, and to a lesser extent fat mass, largely explained the BMD differences which we observed. CONCLUSIONS: Rural to urban migration as an adult is associated with higher BMD and greater predicted hip strength, reflecting associated alterations in body composition. It remains to be seen how differences in BMD between migration groups will translate into fracture risk in becoming years.

Is the Association between Vitamin D and Cardiovascular Disease Risk Confounded by Obesity? Evidence from the Andhra Pradesh Children and Parents Study (APCAPS).

BACKGROUND: Evidence of an association between serum vitamin D and cardiovascular disease risk is inconsistent and comes predominantly from studies in high-income settings. We assessed the association between serum levels of 25-hydroxyvitamin D3 (25(OH)D) and cardiovascular disease risk factors in a population of young Indian adults. METHODS: Cross-sectional analyses of data from APCAPS (Andhra Pradesh Children and Parents Study); a prospective birth cohort study in rural south India. Participants were 1038 (40.3% females) adults aged 18-24 years. Main outcome measures were blood pressures, fasting serum lipids (cholesterols and triglycerides), fasting glucose, insulin, measures of arterial stiffness (aortic augmentation index and aortic pulse wave velocity (aPWV)), carotid intima-media thickness, body mass index (BMI) and body fat (dual X-ray absorptiometry). RESULTS: Vitamin D deficiency (≤20ng/ml) was observed in 41.1% of this lean (mean BMI: 19.5) and active (mean minutes of moderate or vigorous physical activity per day: 186) population. Vitamin D deficiency was associated with higher median body fat in both males (15.9% body fat in vitamin D deficient males vs. 14.6% in non-deficient males, p<0.05) and females (29.1% body fat in vitamin D deficient females vs. 27.8% in non-deficient females, p<0.05) but no associations were observed between vitamin D deficiency and mean BMI or median fat mass index (FMI). Except a weak inverse association with fasting insulin in males, there was no clear association between serum vitamin D levels and cardiovascular disease risk factors in fully adjusted models. CONCLUSIONS: We did not find clear evidence for an association between serum vitamin D levels and cardiovascular disease risk factors. Our results, consistent with the limited evidence from randomised trials of vitamin D supplementation and Mendelian randomisation experiments, suggest that the postulated link between serum vitamin D and cardiovascular disease may be non-causal. Instead, it may be attributable to confounding by lifestyle factors such as obesity and physical inactivity which may provide more fruitful targets for cardiovascular disease prevention.

Technology, applications and modelling of ohmic heating: a review.

Ohmic heating or Joule heating has immense potential for achieving rapid and uniform heating in foods, providing microbiologically safe and high quality foods. This review discusses the technology behind ohmic heating, the current applications and thermal modeling of the process. The success of ohmic heating depends on the rate of heat generation in the system, the electrical conductivity of the food, electrical field strength, residence time and the method by which the food flows through the system. Ohmic heating is appropriate for processing of particulate and protein rich foods. A vast amount of work is still necessary to understand food properties in order to refine system design and maximize performance of this technology in the field of packaged foods and space food product development. Various economic studies will also play an important role in understanding the overall cost and viability of commercial application of this technology in food processing. Some of the demerits of the technology are also discussed.

Moisture sorption characteristics of freeze dried whey-grape beverage mix.

Moisture sorption isotherms of freeze dried whey-grape beverage powder were determined at 20, 30 and 40 °C. A gravimetric static method was used under 0.11-0.85 water activity range and the sorption isotherms were found to be Type II. Various mathematical models were fitted to experimental data and it was found that Peleg model suits best in describing the equilibrium moisture content-equilibrium relative humidity relationships of instant whey-grape beverage mix over the range of temperatures studied. The net isosteric heat of sorption varied between 5.22 and 1.12 KJ/mol at moisture level varying between 1 and 9 % db. At moisture content below 1 % (db) the isosteric heat of sorption increased sharply for freeze dried whey-grape beverage powder and value of 49.08 KJ/mol was estimated.

Assessment of body composition in Indian adults: comparison between dual-energy X-ray absorptiometry and isotope dilution technique.

Dual-energy X-ray absorptiometry (DXA) and isotope dilution technique have been used as reference methods to validate the estimates of body composition by simple field techniques; however, very few studies have compared these two methods. We compared the estimates of body composition by DXA and isotope dilution (18O) technique in apparently healthy Indian men and women (aged 19-70 years, n 152, 48 % men) with a wide range of BMI (14-40 kg/m2). Isotopic enrichment was assessed by isotope ratio mass spectroscopy. The agreement between the estimates of body composition measured by the two techniques was assessed by the Bland-Altman method. The mean age and BMI were 37 (sd 15) years and 23·3 (sd 5·1) kg/m2, respectively, for men and 37 (sd 14) years and 24·1 (sd 5·8) kg/m2, respectively, for women. The estimates of fat-free mass were higher by about 7 (95 % CI 6, 9) %, those of fat mass were lower by about 21 (95 % CI - 18, - 23) %, and those of body fat percentage (BF%) were lower by about 7·4 (95 % CI - 8·2, - 6·6) % as obtained by DXA compared with the isotope dilution technique. The Bland-Altman analysis showed wide limits of agreement that indicated poor agreement between the methods. The bias in the estimates of BF% was higher at the lower values of BF%. Thus, the two commonly used reference methods showed substantial differences in the estimates of body composition with wide limits of agreement. As the estimates of body composition are method-dependent, the two methods cannot be used interchangeably.

Raloxifene preserves phenytoin and sodium valproate induced bone loss by modulating serum estradiol and TGF-ß3 content in bone of female mice.

Antiepileptic drugs (AEDs)-induced adverse consequences on bone are now well recognized. Despite this, there is limited data on the effect of anti-osteoporotic therapies on AEDs-induced bone loss. We hypothesize that estrogen deprivation following phenytoin (PHT) and sodium valproate (SVP) therapy could lead to adverse bony effects. Both PHT and SVP inhibit human aromatase enzyme and stimulate microsomal catabolism of oestrogens. Estrogen deficiency states are known to reduce the deposition of transforming growth factor-ß (TGF-ß3), a bone matrix protein, having anti-osteoclastic property. Thus, an attempt was made to investigate the effect of raloxifene, a selective oestrogen receptor modulator, in comparison with calcium and vitamin D3 (CVD) supplementation, on PHT and SVP-induced alterations in bone in mice and to unravel the role of estradiol and TGF-ß3 in mediation of bony effects by either AEDs or raloxifene. Further, the effect of raloxifene on seizures and on the antiepileptic efficacy of PHT and SVP was investigated. Swiss strains of female mice were treated with PHT (35 mg/kg, p.o.) and SVP (300 mg/kg, p.o.) for 120 days to induce bone loss as evidenced by reduced bone mineral density (BMD) and altered bone turnover markers (BTMs) in lumbar bones (alkaline phosphatase, tartarate resistant acid phosphatase, hydroxyproline) and urine (calcium). The bone loss was accompanied by reduced serum estradiol levels and bone TGF-ß3 content. Preventive and therapeutic treatment with raloxifene ameliorated bony alterations and was more effective than CVD. It also significantly restored estradiol and TGF-ß3 levels. Deprived estrogen levels (that in turn reduced lumbar TGF-ß3 content) following PHT and SVP, thus, might represent one of the various mechanisms of AEDs-induced bone loss. Raloxifene preserved the bony changes without interfering with antiepileptic efficacy of these drugs, and hence raloxifene could be a potential therapeutic option in the management of PHT and SVP-induced bone disease if clinically approved.

Potential applications of plant based derivatives as fat replacers, antioxidants and antimicrobials in fresh and processed meat products.

Growing concern about diet and health has led to development of healthier food products. In general consumer perception towards the intake of meat and meat products is unhealthy because it may increase the risk of diseases like cardiovascular diseases, obesity and cancer, because of its high fat content (especially saturated fat) and added synthetic antioxidants and antimicrobials. Addition of plant derivatives having antioxidant components including vitamins A, C and E, minerals, polyphenols, flavanoids and terpenoids in meat products may decrease the risk of several degenerative diseases. To change consumer attitudes towards meat consumption, the meat industry is undergoing major transformations by addition of nonmeat ingredients as animal fat replacers, natural antioxidants and antimicrobials, preferably derived from plant sources.

Phenytoin and sodium valproate but not levetiracetam induce bone alterations in female mice.

Adverse effects on the bone are amongst the potentially adverse clinical consequences with antiepileptic drugs (AEDs). This study compared the effects of 3 AEDs (phenytoin (PHT), sodium valproate (SVP), and levetiracetam (LTM)) on the bones of a Swiss strain of albino female mice. Drugs were administered daily for 4 months at doses that produced plasma concentrations corresponding to the clinically relevant therapeutic ranges. PHT and SVP (but not LTM) significantly lowered the bone mineral density (BMD) of lumbar vertebrae (L2-L4) as evaluated by dual-energy X-ray absorptiometry (DEXA) scan. The findings were supported by histopathology of vertebral (lumbar) bone and analysis of bone turnover markers. While both PHT and SVP reduced alkaline phosphatase (ALP) and hydroxyproline (HxP) in lumbar vertebrae, and elevated tartarate-resistant acid phosphatase (TRAP) and urinary excretion of calcium, LTM did not affect any of these markers of bone turnover, indicating that the drug might be a safer option in female epileptic patients prone to bone changes.

Life-course determinants of bone mass in young adults from a transitional rural community in India: the Andhra Pradesh Children and Parents Study (APCAPS).

BACKGROUND: Undernutrition and physical inactivity are both associated with lower bone mass. OBJECTIVE: This study aimed to investigate the combined effects of early-life undernutrition and urbanized lifestyles in later life on bone mass accrual in young adults from a rural community in India that is undergoing rapid socioeconomic development. DESIGN: This was a prospective cohort study of participants of the Hyderabad Nutrition Trial (1987-1990), which offered balanced protein-calorie supplementation to pregnant women and preschool children younger than 6 y in the intervention villages. The 2009-2010 follow-up study collected data on current anthropometric measures, bone mineral density (BMD) measured by dual-energy X-ray absorptiometry, blood samples, diet, physical activity, and living standards of the trial participants (n = 1446, aged 18-23 y). RESULTS: Participants were generally lean and had low BMD [mean hip BMD: 0.83 (women), 0.95 (men) g/cm²; lumbar spine: 0.86 (women), 0.93 (men) g/cm²]. In models adjusted for current risk factors, no strong evidence of a positive association was found between BMD and early-life supplementation. On the other hand, current lean mass and weight-bearing physical activity were positively associated with BMD. No strong evidence of an association was found between BMD and current serum 25-hydroxyvitamin D or dietary intake of calcium, protein, or calories. CONCLUSIONS: Current lean mass and weight-bearing physical activity were more important determinants of bone mass than was early-life undernutrition in this population. In transitional rural communities from low-income countries, promotion of physical activity may help to mitigate any potential adverse effects of early nutritional disadvantage.

Body composition assessment in infancy and early childhood: comparison of anthropometry with dual-energy X-ray absorptiometry in low-income group children from India.

BACKGROUND/OBJECTIVE: Anthropometry is a simple, inexpensive method of body composition assessment, but its validity has not been examined adequately in young children. The study therefore compared the body composition estimates using anthropometry with those using dual-energy X-ray absorptiometry (DXA) in infants and young children. METHODS: Body composition estimates using anthropometry and DXA were assessed and compared at 6, 12 and 18 months in a cohort of 137 infants enrolled at birth. RESULTS: Fat mass (FM) and body fat percent (%BF) estimates by anthropometry were lower than those using DXA. Mean differences (DXA-skinfold thickness) in FM, fat free mass (FFM) and %BF were highest at 6 months (350 g, -226 g and 4%, respectively); the differences reduced with increase in age and were lowest at 18 months (46 g, 56 g and 0%, respectively). Bland-Altman analyses showed good agreement between the FM, FFM and %BF estimates by the two methods only at 18 months. Accretion of FM and FFM during follow-up, estimated by the two methods, was significantly different, with agreement between the methods seen only for increment in FFM from 6 to 12 months. CONCLUSIONS: Substantial differences were found in the body composition estimates by anthropometry compared with DXA and also in the longitudinally assessed tissue accretion patterns by the two methods. As the body composition patterns may be influenced by the method used for body composition assessment, results of studies assessing body composition by anthropometry during infancy should be interpreted with caution.

The association of early life supplemental nutrition with lean body mass and grip strength in adulthood: evidence from APCAPS.

In the present study, we examined the associations of early nutrition with adult lean body mass (LBM) and muscle strength in a birth cohort that was established to assess the long-term impact of a nutrition program. Participants (n = 1,446, 32% female) were born near Hyderabad, India, in 29 villages from 1987 to 1990, during which time only intervention villages (n = 15) had a government program that offered balanced protein-calorie supplementation to pregnant women and children. Participants' LBM and appendicular skeletal muscle mass were measured using dual energy x-ray absorptiometry; grip strength and information on lifestyle indicators, including diet and physical activity level, were also obtained. Ages (mean = 20.3 years) and body mass indexes (weight (kg)/height (m)(2); mean = 19.5) of participants in 2 groups were similar. Current dietary energy intake was higher in the intervention group. Unadjusted LBM and grip strength were similar in 2 groups. After adjustment for potential confounders, the intervention group had lower LBM (ß = -0.75; P = 0.03), appendicular skeletal muscle mass, and grip strength than did controls, but these differences were small in magnitude (<0.1 standard deviation). Multivariable regression analyses showed that current socioeconomic position, energy intake, and physical activity level had a positive association with adult LBM and muscle strength. This study could not detect a "programming" effect of early nutrition supplementation on adult LBM and muscle strength.

Commentary: acetaldehyde and epithelial-to-mesenchymal transition in colon.

Elamin and colleagues in this issue report that acetaldehyde activates Snail, a transcription factor involved in epithelial-to-mesenchymal transition, in an intestinal epithelium. Snail mediates acetaldehyde-induced tight junction disruption and increase in paracellular permeability. Results of this study and other previous studies raise several important questions. This commentary addresses these questions by discussing the acetaldehyde concentration in colon, disruption of epical junctional complexes in the intestinal epithelium by acetaldehyde, and the consequence of long-term exposure to acetaldehyde on colonic epithelial regeneration, carcinogenesis, and metastases. The precise role of acetaldehyde in colonic epithelial modifications and promotion of colorectal cancers still remains to be understood.

The effect of rural-to-urban migration on renal function in an Indian population: cross-sectional data from the Hyderabad arm of the Indian Migration Study.

BACKGROUND: Urban migration is associated with an increased risk of hypertension, obesity and diabetes in Indian migrants. This study assessed the relationship between internal migration and renal function in the Hyderabad arm of the Indian Migration Study. METHODS: We assessed 841 subjects; urban non-migrants (n = 158), urban migrants (n = 424) and rural non-migrants (n = 259). Muscle mass was ascertained from DXA scanning. We derived urban life years for urban migrants and rural non-migrants. Multivariable linear regression was used to examine the association between tertiles of urban life years and 4-variable MDRD eGFR using Stata 11. RESULTS: Mean eGFR was lower in urban non-migrants and urban migrants compared to rural non-migrants. The prevalence of CKD 3-5 was higher in the rural non-migrant population (5.0%) than in the urban non-migrant populations (2.5%) due to a negatively skewed distribution of eGFR in rural non-migrants. As urban life years increased, eGFR declined (p = 0.008) though there was no obvious dose response effect. After adjustment for muscle mass, the association was attenuated and the trend was consistent with chance (p = 0.08). Further adjustment for vascular risk factors weakened the association to a small degree (p = 0.11). CONCLUSIONS: The high prevalence of reduced eGFR in rural areas requires further research. Urbanization was associated with reduced eGFR. This association appears mostly to be due to higher muscle mass with a small contribution from adverse vascular disease risk factors.

Development and validation of anthropometric prediction equations for estimation of lean body mass and appendicular lean soft tissue in Indian men and women.

Lean body mass (LBM) and muscle mass remain difficult to quantify in large epidemiological studies due to the unavailability of inexpensive methods. We therefore developed anthropometric prediction equations to estimate the LBM and appendicular lean soft tissue (ALST) using dual-energy X-ray absorptiometry (DXA) as a reference method. Healthy volunteers (n = 2,220; 36% women; age 18-79 yr), representing a wide range of body mass index (14-44 kg/m(2)), participated in this study. Their LBM, including ALST, was assessed by DXA along with anthropometric measurements. The sample was divided into prediction (60%) and validation (40%) sets. In the prediction set, a number of prediction models were constructed using DXA-measured LBM and ALST estimates as dependent variables and a combination of anthropometric indices as independent variables. These equations were cross-validated in the validation set. Simple equations using age, height, and weight explained >90% variation in the LBM and ALST in both men and women. Additional variables (hip and limb circumferences and sum of skinfold thicknesses) increased the explained variation by 5-8% in the fully adjusted models predicting LBM and ALST. More complex equations using all of the above anthropometric variables could predict the DXA-measured LBM and ALST accurately, as indicated by low standard error of the estimate (LBM: 1.47 kg and 1.63 kg for men and women, respectively), as well as good agreement by Bland-Altman analyses (Bland JM, Altman D. Lancet 1: 307-310, 1986). These equations could be a valuable tool in large epidemiological studies assessing these body compartments in Indians and other population groups with similar body composition.

Effectiveness of zinc supplementation to full term normal infants: a community based double blind, randomized, controlled, clinical trial.

UNLABELLED: The study was aimed to test whether zinc supplementation, if initiated early, can prevent stunting and promote optimum body composition in full term infants. For this, full term pregnant women from low income urban community were enrolled and were followed-up for 24 months postpartum. Body mass index (BMI) was calculated from maternal weight and height that were collected one month after delivery. Infants' weight, and length, head, chest and mid upper arm circumferences and skin fold thicknesses at triceps, biceps and subscapular area were collected at baseline (before randomization) and once in three months up till 24 months. Three hundred and twenty four infants were randomized and allocated to zinc (163) or placebo (161) groups respectively. Supplementation of zinc was initiated from 4 months of age and continued till children attained 18 months. The control (placebo) group of children received riboflavin 0.5 mg/day, whereas the intervention (zinc) group received 5 mg zinc plus riboflavin 0.5 mg/day. When infants were 18 months old, dietary intakes (in 78 children) were calculated by 24 hour diet recall method and hemoglobin, zinc, copper and vitamin A were quantified in blood samples collected from 70 children. The results showed prevalence of undernutrition (body mass index <18.5) in 37% of the mothers. Mean±SD calorie consumption and zinc intakes from diets in infants were 590±282.8 Kcal/day and 0.97±0.608 mg/day respectively. Multiple linear regression models demonstrated maternal weight as a strong predictor of infants' weight and length at 18 months of age. As expected, diarrhea duration impacted infants' linear growth and weight gain adversely. Zinc supplementation for a mean period of 190 days, starting from 4 months up to 18 months of age, in full term normal infants, consuming an average energy of 590 Kcal/day, had significant effect on the skin fold thicknesses, but not on their linear growth. TRIAL REGISTRATION: Clinical Trail Registration India (CTRI) CTRI/2012/08/002884.