Maternal high-cholesterol diet negatively programs offspring bone development and downregulates hedgehog signaling in osteoblasts.

Cholesterol is one of the essential intrauterine factors required for fetal growth and development. Maternal high cholesterol levels are known to be detrimental for offspring health. However, its long-term effect on offspring skeletal development remains to be elucidated. We performed our studies in two strains of mice (C57BL6/J and Swiss Albino) and human subjects (65 mother-female newborn dyads) to understand the regulation of offspring skeletal growth by maternal high cholesterol. We found that mice offspring from high-cholesterol-fed dams had low birth weight, smaller body length, and delayed skeletal ossification at the E18.5 embryonic stage. Moreover, we observed that the offspring did not recover from the reduced skeletal mass and exhibited a low bone mass phenotype throughout their life. We attributed this effect to reduced osteoblast cell activity with a concomitant increase in the osteoclast cell population. Our investigation of the molecular mechanism revealed that offspring from high-cholesterol-fed dams had a decrease in the expression of ligands and proteins involved in hedgehog signaling. Further, our cross-sectional study of human subjects showed a significant inverse correlation between maternal blood cholesterol levels and cord blood bone formation markers. Moreover, the bone formation markers were significantly lower in the female newborns of hypercholesterolemic mothers compared with mothers with normal cholesterolemic levels. Together, our results suggest that maternal high cholesterol levels deleteriously program offspring bone mass and bone quality and downregulate the hedgehog signaling pathway in their osteoblasts.

Comparison of 2006 WHO and Indian Academy of Pediatrics recommended growth charts of under five Indian children.

This cross-sectional study was undertaken to compare WHO and Indian Academy of Pediatrics (IAP) recommended growth charts compiled by Agarwal. 2105 children aged less than 5 years, attending 132 Anganwadi centres in Mysore city, were included by simple random sampling method. Weight and height of all children were recorded and plotted on both WHO and IAP charts. WHO charts detected more boys as underweight compared to IAP charts (P<0.0001). When weight charts of girls were compared there was no difference between the two charts. WHO charts detected more children with stunting than IAP charts, which was true for both boys and girls (P=0.001).

Racecadotril for childhood gastroenteritis: an individual patient data meta-analysis.

BACKGROUND: Racecadotril is an antidiarrhoeal drug with intestinal antisecretory mechanism of action. AIM: To assess racecadotril efficacy as an adjunct to oral rehydration solution, against oral rehydration solution alone or with placebo in childhood acute gastroenteritis. METHODS: Individual patient data meta-analysis following multilevel mixed models testing the significance of the treatment effect adjusted for baseline covariates. RESULTS: Nine randomised clinical trials (n=1384) were identified with raw data. Baseline dehydration level and Rotavirus were found as two essential predictors influencing the outcomes. The proportion of recovered patients was higher in racecadotril groups compared with placebo, Hazard Ratio HR=2.04, 95% CI (1.85; 2.32), p<0.001. For inpatient studies, the ratio of mean stool output racecadotril/placebo was 0.59 (0.51; 0.74), p<0.001. For outpatient studies, the ratio of the mean number of diarrhoeic stools racecadotril/placebo was 0.63 (0.51; 0.74), p<0.001. CONCLUSION: Dehydration level and Rotavirus at baseline are essential adjustments to compare treatments. As an adjunct to oral rehydration solution, racecadotril has a clinically relevant effect in reducing diarrhoea (duration, stool output and stool number), irrespective of baseline conditions (dehydration, Rotavirus or age), treatment conditions (inpatient or outpatient studies) or cultural environment.

Single-nucleotide polymorphisms of NKX2.5 found in congenital heart disease patients of Mysore, South India.

Congenital heart disease (CHD) is a common congenital birth defect, affecting nearly 1% of all live births, and is the most common cause of infant death. NKX2.5 is an important transcription factor expressed during vertebrate heart development and involved in the regulation of septation during cardiac morphogenesis and in the maturation and maintenance of the atrioventricular node throughout life. There are many reports on association of single-nucleotide polymorphisms (SNPs) of NKX2.5 with CHD but none have been reported from Mysore, South India. With informed consent, 150 clinically diagnosed CHD patients and 70 unrelated healthy controls in Mysore, South India, were recruited. In the first phase the DNAs of 50 CHD patients and 20 controls were subjected to polymerase chain reaction amplification of coding regions of NKX2.5 and further sequenced for SNP genotyping. Additionally, mass array analysis of SNPs was performed for 100 CHD and 50 controls. Analysis revealed the occurrence of six SNPs in different types of CHDs. Two were synonymous SNPs, the most common c.239A>G (p.E21E) and newly identified c.896C>A (p.A240A), as well as three nonsynonymous SNPs, c.608A>G (p.E203G), c.646C>T (p.R216C), and c.852G>A (p.N226D). The sixth SNP 1212G>T in the 3'UTR was observed in 40% of the CHD cases. The SNPs c.646C>T and c.608A>G were shown to cause changes in their secondary structure. Ventricular septal defect was the more prominent CHD observed in our study population. The SNPs c.608A>G (p.E203G) and c.852G>A (p.N226D) were present only in CHD patients, indicating their association with CHDs.

Redefining the World Health Organization algorithm for diagnosis of pneumonia with simple additional markers.

OBJECTIVES: WHO to examine the value of additional markers like history of previous respiratory distress and response to bronchodilator (BD) to redefine these guidelines. METHODS: Fifty (50) patients were analysed for presence of fever. Those who were febrile were put on antipyretic to look for resolution of tachypnea. Those who showed persistent tachypnea and those who were afebrile were analyzed for history of previous respiratory distress. Those who gave a positive history were challenged with BD. The association of persistent tachypnea and pulmonary infiltrates was recorded. RESULTS: Persistence of tachypnea after BD therapy was associated with pulmonary infiltrate in 7/8 (87.5%) whereas tachypnea persisted in 9/30 (30%) of those without infiltrates (p < 0.001). The proposed algorithm brings down the overuse of antibiotics from 78.9% to 26.3% (p <0.001) and also brings down the underuse of bronchodilators from 78.9% to 21.1 %(p<0.001). CONCLUSION: Adding simple markers like history of previous respiratory distress and response to BD therapy to the existing WHO guidelines it is possible to reliably differentiate pneumonia from acute exacerbation of asthma.

Essential hypertension in early and mid-adolescence.

OBJECTIVES: To detect prevalence of essential hypertension in early and mid adolescents and to identify various risk factors. METHODS: Blood pressure was recorded in 503 apparently normal school students in 10 to 16 yr age group as per standard guidelines. Detailed clinical examination was done in all cases. A detailed questionnaire was sent to parents. RESULTS: 6.16% of adolescents had high blood pressure at the end of fourth screening. Both systolic and diastolic hypertensions were documented. Increased body mass index and reduced consumption of vegetables and fruits were found to be statistically significant risk factors for hypertension. CONCLUSION: Multiple blood pressure recordings are essential for accurate diagnosis of hypertension. There is a high prevalence of essential hypertension amongst adolescents in Mysore city with modifiable risk factors for hypertension.

Modifiable risk factors for acute lower respiratory tract infections.

OBJECTIVE: Acute respiratory infection is a leading cause of morbidity and mortality in under five children in developing countries. Hence, the present study was undertaken to identify various modifiable risk factors for acute lower respiratory tract infections (ALRI) in children aged 1 mth to 5 yr. METHODS: 104 ALRI cases fulfilling WHO criteria for pneumonia, in the age group of 1 mth to 5 yr were interrogated for potential modifiable risk factors as per a predesigned proforma. 104 healthy control children in the same age group were also interrogated. RESULTS: The significant sociodemographic risk factors were parental illiteracy, low socioeconomic status, overcrowding and partial immunization, [p value < 0.05 in all]. Significant nutritional risk factors were administration of prelacteal feeds, early weaning, anemia, rickets and malnutrition, [p value < 0.05 in all]. Significant environmental risk factors were use of kerosene lamps, biomass fuel pollution and lack of ventilation [p value < 0.05 in all]. On logistic regression analysis, partial immunization, overcrowding and malnutrition were found to be significant risk factors. CONCLUSION: The present study has identified various socio-demographic, nutritional and environmental modifiable risk factors for ALRI which can be tackled by effective education of the community and appropriate initiatives taken by the government.

Self abortion of attacks in patients with Hot Water Epilepsy.

A cross sectional hospital based study was undertaken to find out the various clinical aspects and management of Hot Water Epilepsy (HWE) in children. Of the 71 cases analysed, 67.6% had onset of seizures in the first decade of life. Seizures occurred frequently towards the end of head bath (71.8%). In 14.1% cases, seizures were precipitated with cold-water head bath also. Complex partial seizures (60.6%) and generalized atonic seizures (21.1%) were common. Spontaneous non-reflex epilepsy was seen in 47.9% cases. Self-induction and self-abortion of seizures were seen in 16.9% and 12.7% patients respectively. Family history was available in 32.4% of cases. Majority had good response to continuous prophylactic treatment with antiepileptic drugs. We conclude that high incidence of spontaneous seizures and generalized atonic seizures seem to be peculiar to our geographical area. "Self abortion of attacks"may be of immense help in controlling the attacks.

Myotonia congenita--a successful response to carbamazepine.

Myotonia congenita is a rare disease of skeletal muscle characterized by painless myotonia, generalized muscular hypertrophy and a non-progressive course. We report a 10-year-old girl with myotonia, "Herculean appearance" and electromyographic confirmation of myotonic discharges. There was a dramatic response to carbamazepine. The aim of this report is to make the readers aware of this entity which can be easily controlled with medication and also prevented by genetic counseling.