Neurodevelopmental disorders in children aged 2-9 years: Population-based burden estimates across five regions in India.

BACKGROUND: Neurodevelopmental disorders (NDDs) compromise the development and attainment of full social and economic potential at individual, family, community, and country levels. Paucity of data on NDDs slows down policy and programmatic action in most developing countries despite perceived high burden. METHODS AND FINDINGS: We assessed 3,964 children (with almost equal number of boys and girls distributed in 2-<6 and 6-9 year age categories) identified from five geographically diverse populations in India using cluster sampling technique (probability proportionate to population size). These were from the North-Central, i.e., Palwal (N = 998; all rural, 16.4% non-Hindu, 25.3% from scheduled caste/tribe [SC-ST] [these are considered underserved communities who are eligible for affirmative action]); North, i.e., Kangra (N = 997; 91.6% rural, 3.7% non-Hindu, 25.3% SC-ST); East, i.e., Dhenkanal (N = 981; 89.8% rural, 1.2% non-Hindu, 38.0% SC-ST); South, i.e., Hyderabad (N = 495; all urban, 25.7% non-Hindu, 27.3% SC-ST) and West, i.e., North Goa (N = 493; 68.0% rural, 11.4% non-Hindu, 18.5% SC-ST). All children were assessed for vision impairment (VI), epilepsy (Epi), neuromotor impairments including cerebral palsy (NMI-CP), hearing impairment (HI), speech and language disorders, autism spectrum disorders (ASDs), and intellectual disability (ID). Furthermore, 6-9-year-old children were also assessed for attention deficit hyperactivity disorder (ADHD) and learning disorders (LDs). We standardized sample characteristics as per Census of India 2011 to arrive at district level and all-sites-pooled estimates. Site-specific prevalence of any of seven NDDs in 2-<6 year olds ranged from 2.9% (95% CI 1.6-5.5) to 18.7% (95% CI 14.7-23.6), and for any of nine NDDs in the 6-9-year-old children, from 6.5% (95% CI 4.6-9.1) to 18.5% (95% CI 15.3-22.3). Two or more NDDs were present in 0.4% (95% CI 0.1-1.7) to 4.3% (95% CI 2.2-8.2) in the younger age category and 0.7% (95% CI 0.2-2.0) to 5.3% (95% CI 3.3-8.2) in the older age category. All-site-pooled estimates for NDDs were 9.2% (95% CI 7.5-11.2) and 13.6% (95% CI 11.3-16.2) in children of 2-<6 and 6-9 year age categories, respectively, without significant difference according to gender, rural/urban residence, or religion; almost one-fifth of these children had more than one NDD. The pooled estimates for prevalence increased by up to three percentage points when these were adjusted for national rates of stunting or low birth weight (LBW). HI, ID, speech and language disorders, Epi, and LDs were the common NDDs across sites. Upon risk modelling, noninstitutional delivery, history of perinatal asphyxia, neonatal illness, postnatal neurological/brain infections, stunting, LBW/prematurity, and older age category (6-9 year) were significantly associated with NDDs. The study sample was underrepresentative of stunting and LBW and had a 15.6% refusal. These factors could be contributing to underestimation of the true NDD burden in our population. CONCLUSIONS: The study identifies NDDs in children aged 2-9 years as a significant public health burden for India. HI was higher than and ASD prevalence comparable to the published global literature. Most risk factors of NDDs were modifiable and amenable to public health interventions.

Protective Effects of Eugenol against Hepatotoxicity Induced by Arsenic Trioxide: An Antileukemic Drug.

BACKGROUND: Arsenic trioxide (As2O3) has shown effectiveness in the treatment of leukemia, but it is also associated with hepatotoxicity. Given antileukemic drug-induced oxidative stress and toxicity, this study focused on the mitigatory role of eugenol, a monoterpene compound from clove oil, in the hepatic tissue of Wistar rats. METHODS: Twenty-four male Wistar rats (180-250 g) were randomly divided into 4 groups (6 rats per group): normal control rats, rats treated with As2O2 (4 mg/kg bwt), rats treated with eugenol (5 mg/kg bwt), and rats receiving co-treatment with As2O3 (4 mg/kg bwt) and eugenol (5 mg/kg bwt), all of which orally administered for a period of 30 days. The Tukey test (Origin version 7, Origin Lab Corporation, Northampton, USA) was applied to analyze the one-way analysis of variance (ANOVA) between the different groups. A P value less than 0.05 was considered significant. RESULT: Oral administration of As2O3 significantly induced hepatic damage, evident from increased levels of aspartate transaminase and alanine transaminase (P=0.01 and P<0.001, respectively). Moreover, a decrease in the activities of enzymatic and nonenzymatic antioxidants altered electrolyte concentration and increased the rate of lipid peroxidation (P=0.04) and the level of nitric oxide (P=0.01). Accumulation studies and histopathological analyses confirmed the biochemical variations. Co-treatment with eugenol (5 mg/kg bwt) exhibited hepatoprotective effects as manifested by the decreased rate of arsenic accumulation, lipid peroxidation, and nitric oxide level along with normalized levels of antioxidants and maintained histology of the liver. CONCLUSION: Eugenol may be used in combination with arsenic trioxide in chemotherapy to reduce oxidative damage to the hepatic system.

Comparative diagnostic test evaluation of serum procalcitonin and C-reactive protein in suspected bloodstream infections in children with cancer.

PURPOSE: To compute diagnostic test properties of C-reactive protein (CRP) and serum procalcitonin (PCT) levels in bloodstream infections in children with cancer and suspected sepsis, in comparison with blood culture as the gold standard. METHODOLOGY: Consecutive paediatric cancer patients, aged ≤14 years, with clinically suspected bloodstream infections were evaluated with blood culture and assay of PCT and CRP levels. Blood culture was taken as the gold standard for comparison. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), likelihood ratio (LR) and receiver operating characteristic (ROC) with area under ROC curve (AUC) were calculated to assess the diagnostic test performance for PCT and CRP.Results/Key findings. The ROC curve for PCT was better than that for CRP, with an AUC of 0.751 for PCT at a cut-off of 2.25 ng ml-1. The AUC for CRP was 0.638 at a cut-off of 8.0 mg dl-1. Among the three cut-off values of PCT selected from the ROC curve applicable to the patients under study, the cut-off value of ≥0.49 ng ml-1 had the maximum sensitivity of 81.4 % and an NPV of 94.67 %; ≥2.25 ng ml-1 had a sensitivity and specificity of 65.12 and 71.6 %, respectively, and ≥6.47 ng ml-1 had a maximum specificity of 82.10 %. For CRP, the cut-off value of ≥5.3 mg dl-1 had the maximum sensitivity of 72.09 %; ≥8.0 mg dl-1 had a sensitivity and specificity of 58.14 and 68.09 %, respectively, and ≥8.4 mg dl-1 had the maximum specificity of 70.04 %. CONCLUSION: PCT is a better serological marker for excluding bloodstream infections than CRP. The cut-off value of 0.49 ng ml-1 with a negative predictive value of 94.67 % will be ideal in a clinical setting of immune-compromised children with suspected sepsis.

Single oral acute fluoride exposure causes changes in cardiac expression of oxidant and antioxidant enzymes, apoptotic and necrotic markers in male rats.

Several studies have shown that acute fluoride (F(-)) exposure impairs cardiac function, but the molecular mechanism is not clear. In order to study this, male Wistar rats were treated with single oral doses of 45 and 90 mg/kg F(-) for 24 h. A significant accumulation of F(-) was found in the serum and myocardium of experimental rats. F(-) treatment causes myocardial necrosis as evident from increased levels of myocardial troponin I, creatine kinase, lactate dehydrogenase and aspartate transaminase. In addition, F(-) induces myocardial oxidative stress via increased reactive oxygen species, lipid peroxidation, protein carbonyl content and nitrate levels along with decreased in the levels of enzymatic (superoxide dismutase 2, catalase, glutathione peroxidase and glutathione s transferase pi class) and non-enzymatic (reduced glutathione) antioxidants. Notably, F(-) triggers myocardial apoptosis through altered Bax/Bcl2 ratio and increased cytochrome c, caspase 3p20 and terminal deoxynucleotidyl transferase dUTP nick end labeled positive cells. An increased cardiac expression of Nox4 and p38α MAPK in F(-) treated rats indicates the oxidative and apoptotic damage. Moreover, ultra-structural changes, histopathological and luxol fast blue staining demonstrates the degree of myocardial damage at subcellular level. Taken together, these findings reveal that acute F(-) exposure causes cardiac impairment by altering the expression of oxidative stress, apoptosis and necrotic markers.

Ameliorative effect of α-tocopherol on monosodium glutamate-induced cardiac histological alterations and oxidative stress.

BACKGROUND: Chronic oral intake of high doses of monosodium glutamate (MSG) causes oxidative stress. Oxidative stress plays an important role in the development of cardiac dysfunction and injury. Supplementation with α-tocopherol protects the body against oxidative stress and its related complications. This study was proposed to examine the protective effect of α-tocopherol against MSG-induced biochemical and histological alterations in blood and cardiac tissue of rats for a period of 180 days. RESULTS: Chronic oral administration of MSG (4 g kg(-1)) caused oxidative stress that was manifested by significant increase (P < 0.05) in malondialdehyde, conjugated dienes and by the decrease in the activities of superoxide dismutase, catalase, reduced glutathione, glutathione peroxidase and glutathione S-transferase in cardiac tissue. The significantly increased (P < 0.05) activities of aspartate transaminase, creatine phosphokinase and lactate dehydrogenase in serum suggested a cardiac functional disorder. Moreover, heart muscle fibers showed cloudy swelling, fiber separation and vascular congestion. Administration of α-tocopherol (200 mg kg(-1)) significantly (P < 0.05) attenuated the MSG-induced biochemical alterations in serum and cardiac tissue. α-Tocopherol also prevented the pathological changes in cardiac tissue when compared with the MSG-treated group. CONCLUSION: Our findings suggest that α-tocopherol may have a protective effect against MSG-induced cardiotoxicity, possibly through its antioxidant activity.