Viral Pathogen-Specific Clinical and Demographic Characteristics of Children with Moderate-to-Severe Diarrhea in Rural Bangladesh.

Diarrheal disease is a leading cause of childhood morbidity and mortality worldwide, but particularly in low-income countries in sub-Saharan Africa and South Asia. The Global Enteric Multicenter Study (GEMS) examined the infectious etiologies as well as associated demographics, socioeconomic markers, health-care-seeking behaviors, and handwashing practices of the households of children with diarrhea and their age- and gender-matched controls in seven countries over a 3-year period (December 2007-December 2010). Stool studies to determine diarrheal etiologies and anthropometry were performed at baseline and at 60-day follow-up visits, along with surveys to record demographics and living conditions of the children. We performed secondary analyses of the GEMS data derived from the Bangladesh portion of the study in children with diarrhea associated with viral enteropathogens and explored pathogen-specific features of disease burden. Rotavirus and norovirus were the most prevalent pathogens (39.3% and 35%, respectively). Disease due to rotavirus and adenovirus was more common in infants than in older children (P < 0.001 and P = 0.001, respectively). Height for age decreased from baseline to follow-up in children with diarrhea associated with rotavirus, norovirus, and adenovirus (P < 0.001). Based on these analyses, preventive measures targeted at rotavirus, norovirus, and adenovirus will be expected to have meaningful clinical impact. Cost of treatment was highest for rotavirus as well, making it an obvious target for intervention. Association of specific viruses with stunting is particularly notable, as stunting is an attributable risk factor for poor cognitive development and future productivity and economic potential.

Dietary soy protein induces hepatic lipogenic enzyme gene expression while suppressing hepatosteatosis in obese female Zucker rats bearing DMBA-initiated mammary tumors.

Fatty liver is associated with obesity and breast cancer. We used an obese rat model of mammary cancer to examine whether hepatosteatosis is modifiable by diet and associated with altered expression of hepatic lipogenic enzyme genes, thyroid hormone system genes and cholesterol metabolism-related genes. Beginning at the age of 5 weeks, lean and obese female Zucker rats were fed high-isoflavone soy protein- or casein (control protein)-containing diets. Rats were euthanized at 200 days of age [corresponding to 147 days after administration of carcinogen to induce mammary tumors; (Hakkak et al. in, Oncol Lett 2:29-36, 2011)]. Obese rats had a greater degree of liver steatosis than lean rats. Obese casein-fed rats had marked steatosis with small foci of mononuclear infiltration, whereas obese soy protein-fed rats had a significantly lower steatosis index. Comparisons between lean and obese casein-fed rats showed that obesity was associated with significant reductions in hepatic mRNA abundance for Glucose 6-Phosphate Dehydrogenase (G6PD), 6-Phosphogluconate Dehydrogenase (6PGD), Thyroid Receptor Alpha 1 (TRα1), Thyroid Receptor Beta 1 (TRß1) and Iodothyronine Deiodinase 1 (DIO1). The soy protein diet was associated with increased expression of Fatty Acid Synthase (FASN), Malic Enzyme 1 (ME1), 6PGD, Sterol Regulatory Element Binding Protein-1c (SREBP-1c) and SREBP-2 genes in the livers of obese but not lean rats. Western blot analysis showed a significant induction of ME1 protein expression in the livers of obese, soy protein-fed rats, which paralleled the increased serum insulin level in this group. Long-term soy protein consumption can counter hepatic steatosis while coincidently promoting hepatic lipogenic gene expression, the latter likely a consequence of elevated serum insulin. We suggest that elevations in serum insulin, hepatic lipogenesis and cholesterol synthesis all contributed to the increased tumorigenesis previously observed for the obese, soy protein-fed rats.

Metabolic imbalance associated with methylation dysregulation and oxidative damage in children with autism.

Oxidative stress and abnormal DNA methylation have been implicated in the pathophysiology of autism. We investigated the dynamics of an integrated metabolic pathway essential for cellular antioxidant and methylation capacity in 68 children with autism, 54 age-matched control children and 40 unaffected siblings. The metabolic profile of unaffected siblings differed significantly from case siblings but not from controls. Oxidative protein/DNA damage and DNA hypomethylation (epigenetic alteration) were found in autistic children but not paired siblings or controls. These data indicate that the deficit in antioxidant and methylation capacity is specific for autism and may promote cellular damage and altered epigenetic gene expression. Further, these results suggest a plausible mechanism by which pro-oxidant environmental stressors may modulate genetic predisposition to autism.

Causal relationship of Helicobacter pylori with iron-deficiency anemia or failure of iron supplementation in children.

BACKGROUND & AIMS: We investigated Helicobacter pylori (H pylori)-infection as a cause of iron deficiency (ID) and iron-deficiency anemia (IDA) or treatment failure of iron supplementation. METHODS: We randomized 200 Hp-infected children (positive urea breath test) 2-5 years of age with IDA (hemoglobin level <110 g/L; serum ferritin level <12 microg/L; and soluble transferrin receptor >8.3 mg/L) or ID (serum ferritin level <12 microg/L or soluble transferrin receptor level >8.3 mg/L) to 1 of 4 regimens: 2-week anti-Hp therapy (amoxicillin, clarithromycin, and omeprazole) plus 90-day oral ferrous sulfate (anti-Hp plus iron), 2-week anti-Hp therapy alone, 90-day oral iron alone, or placebo. Sixty noninfected children with IDA received iron treatment as negative control. RESULTS: Hp-infected children receiving iron had significantly less frequent treatment failure compared with those with no iron in correcting IDA (11% [95% confidence interval (CI), 2%-20%] for anti-Hp plus iron, 0% for iron alone vs 33% [95% CI, 26%-46%] for anti-Hp and 45% [95% CI, 31%-59%] for placebo; chi(2) = 127; P < .0001), ID (19% [95% CI, 8%-30%] for anti-Hp plus iron, 7% [95% CI, 0%-14%] for iron alone vs 65% [95% CI, 52%-78%] for anti-Hp alone, and 78% [95% CI, 66%-90%] for placebo; chi(2) = 124; P < .0001), or anemia (34% [95% CI, 20%-40%] for anti-Hp plus iron, 27% [95% CI, 14%-40%] for iron alone vs 65% [95% CI, 52%-78%] for anti-Hp alone and 78% [95% CI, 66%-90%] for placebo; chi(2) = 46; P < .0001). Cure rates of IDA, ID, or anemia with iron were comparable with that of the negative control group. Improvements in iron status also were significantly greater in groups with iron. CONCLUSIONS: H pylori is neither a cause of IDA/ID nor a reason for treatment failure of iron supplementation in young Bangladeshi children.

Prevention of malnutrition among young children in rural Bangladesh by a food-health-care educational intervention: a randomized, controlled trial.

BACKGROUND: As a result of inappropriate feeding, poor health and hygiene, and poor caring practices, the nutritional status of many young infants deteriorates with advancing age. OBJECTIVE: To explore the effectiveness of a nutrition education package to prevent malnutrition among young children. METHODS: A community-based, randomized, controlled trial was conducted among 605 normal and mildly malnourished children aged 6 to 9 months in 121 Community Nutrition Centers (CNCs) of the Bangladesh Integrated Nutrition Project (BINP) in four regions of Bangladesh from 2000 to 2002. The intervention group received weekly nutrition education based on the nutrition triangle concept of UNICEF for 6 months, whereas the control group received regular BINP services. Both groups were observed for a further 6 months to assess the sustainability of the effects. Information on socioeconomic status, feeding patterns, morbidity, and anthropometric features was collected. RESULTS: A significant increase in the frequency of complementary feeding was observed in the intervention group as compared with the control group, and the increase was sustained throughout the observation period. The intervention group had a higher weight gain than the control group after the end of the intervention (0.86 vs. 0.77 kg, p = 0.053) and after the end of the observation period (1.81 vs. 1.39 kg, p < .001). The proportion of normal and mildly malnourished children was greater in the intervention group than in the control group after the end of the observations (88.9% vs. 61.5%, p < .001). Nutrition education successfully prevented malnutrition in all the areas. Variation in the outcome of nutrition education among the regions was observed. CONCLUSIONS: This culturally appropriate nutrition education package based on the nutrition triangle model effectively prevented growth faltering and malnutrition among young children.

Obesity promotes 7,12-dimethylbenz(a)anthracene-induced mammary tumor development in female zucker rats.

INTRODUCTION: High body mass index has been associated with increased risk for various cancers, including breast cancer. Here we describe studies using 7,12-dimethylbenz(a)anthracene (DMBA) to investigate the role of obesity in DMBA-induced mammary tumor susceptibility in the female Zucker rat (fa/fa), which is the most widely used rat model of genetic obesity. METHOD: Fifty-day-old female obese (n = 25) and lean (n = 28) Zucker rats were orally gavaged with 65 mg/kg DMBA. Rats were weighed and palpated twice weekly for detection of mammary tumors. Rats were killed 139 days after DMBA treatment. RESULTS: The first mammary tumor was detected in the obese group at 49 days after DMBA treatment, as compared with 86 days in the lean group (P < 0.001). The median tumor-free time was significantly lower in the obese group (P < 0.001). Using the days after DMBA treatment at which 25% of the rats had developed mammary tumors as the marker of tumor latency, the obese group had a significantly shorter latency period (66 days) than did the lean group (118 days). At the end of the study, obese rats had developed a significantly (P < 0.001) greater mammary tumor incidence (68% versus 32%) compared with the lean group. The tumor histology of the mammary tumors revealed that obesity was associated with a significant (P < 0.05) increase in the number of rats with at least one invasive ductal and lobular carcinoma compared with lean rats. CONCLUSION: Our results indicate that obesity increases the susceptibility of female Zucker rats to DMBA-induced mammary tumors, further supporting the hypothesis that obesity and some of its mediators play a significant role in carcinogenesis.

Helicobacter pylori infection, iron absorption, and gastric acid secretion in Bangladeshi children.

BACKGROUND: Nonheme-iron absorption requires an acidic milieu. Reduced gastric acid output as a consequence of Helicobacter pylori infection could be an important limiting factor for iron absorption. OBJECTIVE: We measured gastric acid output and iron absorption from a non-water-soluble iron compound (ferrous fumarate) and a water-soluble iron compound (ferrous sulfate) in children with and without H. pylori infection. DESIGN: Gastric acid output was quantified before (basal acid output, or BAO) and after pentagastrin stimulation (stimulated acid output, or SAO) in 2-5-y-old children with iron deficiency anemia who were (n = 13) or were not (n = 12) infected with H. pylori. Iron absorption was measured by using a double-stable-isotope technique. H. pylori-infected children were studied before and after eradication therapy. RESULTS: BAO and SAO were significantly lower in the H. pylori-infected children (0.2 +/- 0.2 and 1.6 +/- 0.9 mmol/h, respectively) than in the uninfected children (0.9 +/- 0.7 and 3.1 +/- 0.9 mmol/h, respectively; P = 0.01 and P < 0.005). BAO and SAO improved to 0.8 +/- 1.3 and 3.3 +/- 2.4 mmol/h, respectively, after therapy. Iron absorption from ferrous sulfate was significantly greater than that from ferrous fumarate both before (geometric : 19.7% compared with 5.3%; P < 0.0001) and after (22.5% compared with 6.4%; P < 0.0001) treatment in H. pylori-infected children. Corresponding values for uninfected children were 15.6% and 5.4%, respectively (P < 0.001; n = 12). CONCLUSIONS: Iron absorption from ferrous fumarate was significantly lower than that from ferrous sulfate in both H. pylori-infected and uninfected Bangladeshi children. Treatment of H. pylori infection improved gastric acid output but did not significantly influence iron absorption. The efficacy of ferrous fumarate in iron fortification programs to prevent iron deficiency in young children should be evaluated.