ASSOCIATION OF BIRTH WEIGHT AND TIME OF BREASTFEEDING WITH CURRENT NUTRITIONAL STATUS OF CHILDREN

Objetivo: Analisar a relação entre o peso ao nascer (PN) e o tempo de aleitamento materno (AM) com o atual estado nutricional de crianças de dois a seis anos de idade. Métodos: Estudo observacional, quantitativo e do tipo transversal, realizado com crianças, independentemente do sexo, com idades entre dois a seis anos, matriculadas em sete escolas de educação infantil da rede municipal de um município do interior do Rio Grande do Sul (RS), no período de junho a agosto de 2014. Participaram 353 crianças, aferindo-se peso e altura, após os pais terem respondido a um questionário de Peso ao Nascer (PN) e tempo de aleitamento materno. Resultados: A média de aleitamento materno exclusivo foi de 3,47 ± 2,81 meses. A maioria das crianças (50,7%, n=179) encontrou-se em risco de sobrepeso ou sobrepeso para a idade, conforme o Índice de Massa Corporal (IMC). O PN apresentou correlação positiva com a altura atual (r=0,164, p=0,002) e com o peso atual (r=0,180, p=0,001). O PN foi significativamente maior entre os meninos (p=0,003), e o tempo de AM associado à alimentação complementar foi significativamente maior entre as meninas (p=0,024). Conclusão: Os resultados sugerem que o peso ao nascer influencia o ganho de peso nos seis primeiros anos de vida, com maior destaque para os meninos; e o tempo de amamentação associado à alimentação complementar foi maior entre as meninas.

Low-Molecular-Weight Fucoidan Induces Endothelial Cell Migration via the PI3K/AKT Pathway and Modulates the Transcription of Genes Involved in Angiogenesis

Low-molecular-weight fucoidan (LMWF) is a sulfated polysaccharide extracted from brown seaweed that presents antithrombotic and pro-angiogenic properties. However, its mechanism of action is not well-characterized. Here, we studied the effects of LMWF on cell signaling and whole genome expression in human umbilical vein endothelial cells and endothelial colony forming cells. We observed that LMWF and vascular endothelial growth factor had synergistic effects on cell signaling, and more interestingly that LMWF by itself, in the absence of other growth factors, was able to trigger the activation of the PI3K/AKT pathway, which plays a crucial role in angiogenesis and vasculogenesis. We also observed that the effects of LMWF on cell migration were PI3K/AKT-dependent and that LMWF modulated the expression of genes involved at different levels of the neovessel formation process, such as cell migration and cytoskeleton organization, cell mobilization and homing. This provides a better understanding of LMWF's mechanism of action and confirms that it could be an interesting therapeutic approach for vascular repair.

Low molecular weight compounds from mushrooms as potential Bcl-2 inhibitors: docking and virtual screening studies

Mushrooms have the ability to promote apoptosis in tumor cell lines, but the mechanism of action is not quite well understood. Inhibition of the interaction between Bcl-2 and pro-apoptotic proteins could be an important step that leads to apoptosis. Therefore, the discovery of compounds with the ability to inhibit Bcl-2 is an ongoing research topic in drug discovery. In this study, we started by analyzing Bcl-2 experimental structures that are currently available in Protein Data Bank database. After analysis of the more relevant Bcl-2 structures, 4 were finally selected. An analysis of the best docking methodology was then performed using a cross-docking and re-docking approach while testing 2 docking softwares: AutoDock 4 and AutoDock Vina. Autodock4 provided the best docking results and was selected to perform a virtual screening study applied to a dataset of 40 Low Molecular Weight (LMW) compounds present in mushrooms, using the selected Bcl-2 structures as target. Results suggest that steroid are the more promising family, among the analyzed compounds, and may have the ability to interact with Bcl-2 and this way promoting tumor apoptosis. The steroids that presented lowest estimated binding energy (ΔG) were: Ganodermanondiol, Cerevisterol, Ganoderic Acid X and Lucidenic Lactone; with estimated ΔG values between -8,45 and -8,23 Kcal/mol. A detailed analysis of the docked conformation of these 4 top ranked LMW compounds was also performed and illustrates a plausible interaction between the 4 top raked steroids and Bcl-2, thus substantiating the accuracy of the predicted docked poses. Therefore, tumoral apoptosis promoted by mushroom might be related to Bcl-2 inhibition mediated by steroid family of compounds.

Cost-effectiveness analysis of apixaban compared to low-molecular-weight heparins and vitamin k antagonists for treatment and secondary prevention of venous thromboembolism

Objective: Cost-effectiveness analysis of a 6-month treatment of apixaban (10 mg/12h, first 7 days; 5 mg/12h afterwards) for the treatment of the first event of venous thromboembolism (VTE) and prevention of recurrences, versus low-molecular-weight heparins/vitamin K antagonists treatment (LMWH/VKA). Material and methods: A lifetime Markov model with 13 health states was used for describing the course of the disease. Efficacy and safety data were obtained from AMPLIFY and AMPLIFY-EXT clinical trials; health outcomes were measured as life years gained (LYG) and quality-adjusted life years (QALY). The chosen perspective of this analysis has been the Spanish National Health System (NHS). Drugs, management of VTE and complications costs were obtained from several Spanish data sources (€, 2014). A 3% discount rate was applied to health outcomes and costs. Univariate and probabilistic sensitivity analyses (SA) were performed in order to assess the robustness of the results. Results: Apixaban was the most effective therapy with 7.182 LYG and 5.865 QALY, versus 7.160 LYG and 5.838 QALYs with LMWH/VKA. Furthermore, apixaban had a lower total cost (€13,374.70 vs €13,738.30). Probabilistic SA confirmed dominance of apixaban (led to better health outcomes with less associated costs) in 89% of the simulations. Conclusions: Apixaban 5 mg/12h versus LMWH/VKA was an efficient therapeutic strategy for the treatment and prevention of recurrences of VTE from the NHS perspective.

Drinking water disinfection by-products, genetic polymorphisms, and birth outcomes in a european mother-child cohort study

International audience

Effects of Low Molecular Weight Sulfated Galactan Fragments From Botryocladia Occidentalis on the Pharmacological and Enzymatic Activity of Spla2 From Crotalus Durissus Cascavella

Low molecular weight fragments of sulfated galactans (Boc-5 and Boc-10) from the red algae Botryocladia occidentalis significantly inhibited Crotalus durissus cascavella sPLA2 enzymatic activity. Equimolar ratios of sPLA2 to Boc-5 or Boc-10 resulted in allosteric inhibition of sPLA2. Under the conditions tested, we observed that both Boc-5 and Boc-10 strongly decreased edema, myonecrosis, and neurotoxicity induced by native sPLA2.

Very low risk ST-segment elevation myocardial infarction? It exists and may be easily identified

Early discharge protocols have been proposed for ST-segment elevation myocardial infarction (STEMI) low risk patients despite the existence of few but significant cardiovascular events during mid-term follow-up. We aimed to identify a subgroup of patients among those considered low-risk in which prognosis would be particularly good. We analyzed 30-day outcomes and long-term follow-up among 1.111 STEMI patients treated with reperfusion therapy. Multivariate analysis identified seven variables as predictors of 30-day outcomes: Femoral approach; age > 65; systolic dysfunction; postprocedural TIMI flow < 3; elevated creatinine level > 1.5 mg/dL; stenosis of left-main coronary artery; and two or higher Killip class (FASTEST). A total of 228 patients (20.5%), defined as very low-risk (VLR), had none of these variables on admission. VLR group of patients compared to non-VLR patients had lower in-hospital (0% vs. 5.9%; p < 0.001) and 30-day mortality (0% vs. 6.25%: p < 0.001). They also presented fewer in-hospital complications (6.6% vs. 39.7%; p < 0.001) and 30-day major adverse events (0.9% vs. 4.5%; p = 0.01). Significant mortality differences during a mean follow-up of 23.8 ± 19.4 months were also observed (2.2% vs. 15.2%; p < 0.001). The first VLR subject died 11 months after hospital discharge. No cardiovascular deaths were identified in this subgroup of patients during follow-up. About a fifth of STEMI patients have VLR and can be easily identified. They have an excellent prognosis suggesting that 24–48 h in-hospital stay could be a feasible alternative in these patients.

The Effect of Feed and Gonadotrophin Hormone on The Litter Size and Birth Weight of Local Goat

A study was conducted to determine the effect of ration and gonadotrophin hormone on the reproductive performance of breeding goat. Twenty-three does and six bucks having a similar age (1.5-2.0 years old) were exposed in this experiment. An amount of 200 gram of concentrate consisting of yellow corn (30%), rice brand (50%) and commercial concentrate CP 235 (20%) has been given to each experimental animal. The experimental animals were divided into two groups. The group was fed (12 animals) with M1 (roughage + concentrate) and the other group was fed (11 animals) with M2 (roughage). Moreover, each group were divided into four treatment namely: T1 (PGF2α), T2 (PGF2α + PMSG), T3 (PGF2α + HCG) and T4 (PGF2α + PMSG + HCG). The same treatment was applied to the other group. The data such as litter size and birth weight were collected from each experimental goat. Those data were analyzed using a 2 x 4 factorial experiment with unequal repetition. A composition between to treatment group was done using Least Significant Design (LSD). The result of the study showed that the effect of ration and gonadotrophin hormone on litter size and birth weight didn’t show any significant difference (P>0.05). The average of litter size and birth weight from roughage + concentrate treated animal (goat) were 1.92 and 1.51 kilogram respectively. However, the average of litter size and birth weight from roughage treated group were 1.58 and 1.48 kilogram respectively. (Animal Production 5(1): 5-10 (2003) Key words : Gonadotrophin, PGF2α, PMSG, Hormone, Goat

Children with special health care needs : social and learning competence in the early years

The number of children with special health care needs surviving infancy and attending school has been increasing. Due to their health status, these children may be at risk of low social-emotional and learning competencies (e.g., Lightfoot, Mukherjee, & Sloper, 2000; Zehnder, Landolt, Prchal, & Vollrath, 2006). Early social problems have been linked to low levels of academic achievement (Ladd, 2005), inappropriate behaviours at school (Shiu, 2001) and strained teacher-child relationships (Blumberg, Carle, O‘Connor, Moore, & Lippmann, 2008). Early learning difficulties have been associated with mental health problems (Maughan, Rowe, Loeber, & Stouthamer-Loeber, 2003), increased behaviour issues (Arnold, 1997), delinquency (Loeber & Dishion, 1983) and later academic failure (Epstein, 2008). Considering the importance of these areas, the limited research on special health care needs in social-emotional and learning domains is a factor driving this research. The purpose of the current research is to investigate social-emotional and learning competence in the early years for Australian children who have special health care needs. The data which informed this thesis was from Growing up in Australia: The Longitudinal Study of Australian Children. This is a national, longitudinal study being conducted by the Commonwealth Department of Families, Housing, Community Services and Indigenous Affairs. The study has a national representative sample, with data collection occurring biennially, in 2004 (Wave 1), 2006 (Wave 2) and 2008 (Wave 3). Growing up in Australia uses a cross-sequential research design involving two cohorts, an Infant Cohort (0-1 at recruitment) and a Kindergarten Cohort (4-5 at recruitment). This study uses the Kindergarten Cohort, for which there were 4,983 children at recruitment. Three studies were conducted to address the objectives of this thesis. Study 1 used Wave 1 data to identify and describe Australian children with special health care needs. Children who identified as having special health care needs through the special health care needs screener were selected. From this, descriptive analyses were run. The results indicate that boys, children with low birth weight and children from families with low levels of maternal education are likely to be in the population of children with special health care needs. Further, these children are likely to be using prescription medications, have poor general health and are likely to have specific condition diagnoses. Study 2 used Wave 1 data to examine differences between children with special health care needs and their peers in social-emotional competence and learning competence prior to school. Children identified by the special health care needs screener were chosen for the case group (n = 650). A matched case control group of peers (n = 650), matched on sex, cultural and linguistic diversity, family socioeconomic position and age, were the comparison group. Social-emotional competence was measured through Social/Emotional Domain scores taken from the Growing up in Australia Outcome Index, with learning competence measured through Learning Domain scores. Results suggest statistically significant differences in scores between the two groups. Children with special health care needs have lower levels of social-emotional and learning competence prior to school compared to their peers. Study 3 used Wave 1 and Wave 2 data to examine the relationship between special health care needs at Wave 1 and social-emotional competence and learning competence at Wave 2, as children started school. The sample for this study consisted of children in the Kindergarten Cohort who had teacher data at Wave 2. Results from multiple regression models indicate that special health care needs prior to school (Wave 1) significantly predicts social-emotional competence and learning competence in the early years of school (Wave 2). These results indicate that having special health care needs prior to school is a risk factor for the social-emotional and learning domains in the early years of school. The results from these studies give valuable insight into Australian children with special health care needs and their social-emotional and learning competence in the early years. The Australia population of children with special health care needs were primarily male children, from families with low maternal education, were likely to be of poor health and taking prescription medications. It was found that children with special health care needs were likely to have lower social-emotional competence and learning competence prior to school compared to their peers. Results indicate that special health care needs prior to school were predictive of lower social-emotional and learning competencies in the early years of school. More research is required into this unique population and their competencies over time. However, the current research provides valuable insight into an under researched 'at risk' population.

Australian children with special health care needs: Social-emotional and learning competencies in the early years

This study examined the relationship between special health care needs and social-emotional and learning competence in the early years, reporting on two waves of data from the Kindergarten Cohort of Growing up in Australia: The Longitudinal Study of Australian Children (LSAC). Six hundred and fifty children were identified through the 2-question Special Health Care Needs Screener as having special health care needs. Children with special health care needs were more likely to be male, to have been of low birth weight, to be taking prescription medications, to be diagnosed with a specific health condition and to be from families where the mother was less well educated. These children scored significantly lower on teacher-rated social-emotional and learning competencies prior to school compared to a control group of children without special health care needs. Multiple regression analyses indicated that being identified with a special health care need prior to school predicted lower social-emotional and learning competencies in the early years of school. Results are discussed in terms of the implications for policy and practice.

Interactions of ingested food, beverage, and tobacco components involving human cytochrome P4501A2, 2A6, 2E1, and 3A4 enzymes

Human cytochrome P450 (P450) enzymes are involved in the oxidation of natural products found in foods, beverages, and tobacco products and their catalytic activities can also be modulated by components of the materials. The microsomal activation of aflatoxin B1 to the exo-3,9-epoxide is stimulated by flavone and 7,8-benzoflavone, and attenuated by the flavonoid naringenin, a major component of grapefruit. P4502E1 has been demonstrated to play a potentially major role in the activation of a number of very low-molecular weight cancer suspects, including ethyl carbamate (urethan), which is present in alcoholic beverages and particularly stone brandies. The enzyme (P4502E1) is also known to be inducible by ethanol. Tobacco contains a large number of potential carcinogens. In human liver microsomes a significant role for P4501A2 can be demonstrated in the activation of cigarette smoke condensate. Some of the genotoxicity may be due to arylamines. P4501A2 is also inhibited by components of crude cigarette smoke condensate. The tobacco-specific nitrosamines are activated by a number of P450 enzymes. Of those known to be present in human liver, P4501A2, 2A6, and 2E1 can activate these nitrosamines to genotoxic products.

Estimating the burden of disease attributable to childhood and maternal undernutrition in South Africa in 2000

OBJECTIVES To estimate the disease burden attributable to being underweight as an indicator of undernutrition in children under 5 years of age and in pregnant women for the year 2000. DESIGN World Health Organization comparative risk assessment (CRA) methodology was followed. The 1999 National Food Consumption Survey prevalence of underweight classified in three low weight-for-age categories was compared with standard growth charts to estimate population-attributable fractions for mortality and morbidity outcomes, based on increased risk for each category and applied to revised burden of disease estimates for South Africa in 2000. Maternal underweight, leading to an increased risk of intra-uterine growth retardation and further risk of low birth weight (LBW), was also assessed using the approach adopted by the global assessment. Monte Carlo simulation-modeling techniques were used for the uncertainty analysis. SETTING South Africa. SUBJECTS Children under 5 years of age and pregnant women. OUTCOME MEASURES Mortality and disability-adjusted life years (DALYs) from protein- energy malnutrition and a fraction of those from diarrhoeal disease, pneumonia, malaria, other non- HIV/AIDS infectious and parasitic conditions in children aged 0 - 4 years, and LBW. RESULTS Among children under 5 years, 11.8% were underweight. In the same age group, 11,808 deaths (95% uncertainty interval 11,100 - 12,642) or 12.3% (95% uncertainty interval 11.5 - 13.1%) were attributable to being underweight. Protein-energy malnutrition contributed 44.7% and diarrhoeal disease 29.6% of the total attributable burden. Childhood and maternal underweight accounted for 2.7% (95% uncertainty interval 2.6 - 2.9%) of all DALYs in South Africa in 2000 and 10.8% (95% uncertainty interval 10.2 - 11.5%) of DALYs in children under 5. CONCLUSIONS The study shows that reduction of the occurrence of underweight would have a substantial impact on child mortality, and also highlights the need to monitor this important indicator of child health.

Neonatal intestinal obstruction associated with oral calcium supplementation

A case report of a 920 g infant developing a small intestinal obstruction following therapy for congestive cardiac failure is presented. Although the causation was thought to be milk curd obstruction, subsequent analysis revealed high concentration of calcium and phosphate in the stools. The possible pathogenesis is discussed in relation to the inspissated milk syndrome.

Early growth and adult health: focus on blood pressure, glucose tolerance status and body composition

Theory of developmental origins of adult health and disease proposes that experiences during critical periods of early development may have consequences on health throughout a lifespan. Thesis studies aimed to characterize associations between early growth and some components of the metabolic syndrome cluster. Participants belong to two epidemiological cohorts with data on birth measurements and, for the younger cohort, on serial recordings of weight and height during childhood. They were born as singletons between 1924-33 and 1934-44 in the Helsinki University Central Hospital, and 500 and 2003 of them, respectively, attended clinical studies at the age of 65-75 and 56-70 years, respectively. In the 65-75 year old men and women, the well-known inverse relationship between birth weight and systolic blood pressure (SBP) was confined to people who had established hypertension. Among them a 1-kg increase in birth weight was associated with a 6.4-mmHg (95% CI: 1.0 to 11.9) decrease in SBP. This relationship was further confined to people with the prevailing Pro12Pro polymorphism of the peroxisome proliferator-activated receptor-γ2 (PPARγ2) gene. People with low birth weight were more likely to receive angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers (ACEI/ARB, p=0.03), and, again, this relationship was confined to the carriers of the Pro12Pro (p=0.01 for interaction). These results suggest that the inverse association between birth weight and systolic BP becomes focused in hypertensive people because pathological features of BP regulation, associated with slow fetal growth, become self-perpetuating in adult life. Insulin resistance of the Pro12Pro carriers with low birth weight may interact with the renin-angiotensin system leading to raised BP levels. Habitual physical activity protected men and women who were small at birth, and thus at increased risk for the development of type 2 diabetes, against glucose intolerance more strongly. Among subjects with birth weight ≤3000 g, the odds ratio (OR) for glucose intolerance was 5.2 (95% CI: 2.1 to 13) in those who exercised less than 3 times per week compared to regular exercisers; in those who scored their exercise light compared with moderate exercisers (defined as comparable to brisk walking) the OR was 3.5 (1.5 to 8.2). In the 56-70 year old men a 1 kg increase in birth weight corresponded to a 4.1 kg (95% CI: 3.1 to 5.1) and in women to a 2.9 kg (2.1 to 3.6) increase in adult lean mass. Rapid gain in body mass index (BMI), i.e. crossing from an original BMI percentile to a higher one, before the age of 2 years increased adult lean mass index (LMI, lean mass/height squared) without excess fat accumulation whereas rapid gain in BMI during later childhood, despite the concurrent rise in LMI, resulted in a relatively higher increase in adult body fat mass. These findings illustrate how genes, the environment and their interactions, early growth patterns, and adult lifestyle modify adult health risks which originate from early life.