Early growth characteristics and the risk of reduced lung function and asthma : a meta-analysis of 25,000 children

Peer reviewed

Early growth characteristics and the risk of reduced lung function and asthma : a meta-analysis of 25,000 children

Peer reviewed

Synthesis & retention mechanisms of novel mixed mode stationary phase for detection of specific polar low molecular weight biological samples

The thesis primarily reports the synthesis, characterization and application of novel mixed mode stationary phases for Hydrophilic Interaction Liquid Chromatography (HILIC). HILIC is a rapidly emerging chromatographic mode that is finding great applicability in the analysis of polar organic molecules. In addition, there is a chapter on the analysis of Bisphenol A and related species using capillary electrophoresis (CE) coupled with boron-doped diamond electrodes for electrochemical detection. The synthesis and characterization of the novel mixed mode stationary phases prepared in this work is an important contribution to the field as the materials prepared exhibited better performance than similar materials obtained commercially. In addition a more thorough characterization of the materials (e.g.,thermogravimetric analysis, various NMR modes, elemental analysis, etc.) and resulting columns (e.g., H) than is typically encountered. The application of these new materials to the analysis of sugars using evaporative light scattering is also novel. In CE studies, electrochemical detection is sufficiently rare that the work is also novel.

(Table 1) Low molecular weight hydrocarbon concentrations and organic carbon contents at DSDP Hole 71-511

C2-C8 hydrocarbons (36 compounds identified) from 56 shipboard sealed, deep-frozen core samples of DSDP Leg 71, Site 511, Falkland Plateau, South Atlantic, were analyzed by a combined hydrogen stripping-thermovaporization method. Concentrations, which represent hydrocarbons dissolved in the pore water and adsorbed to the mineral surfaces of the sediment, vary from 24 ng/g of dry weight sediment in Lithologic Unit 4 to 17,400 ng/g in Lithologic Unit 6 ("black shale" unit). Likewise, the organic carbon normalized C2-C8 hydrocarbon concentrations range from 104 to 3.5 x 105 ng/g Corg. The latter value is more than one order of magnitude lower than expected for petroleum source beds in the main phase of oil generation. The low maturity at 600 meters depth is further supported by light hydrocarbon concentration ratios. The change of the kerogen type from Lithologic Unit 5 (Type III) to 6 (Type II) is evidenced by changes in the C6 and C7 hydrocarbon composition. Redistribution phenomena are observed close to the Tertiary-Cretaceous unconformity and at the contact between the "black shale" unit and the overlying Cretaceous chalks and claystones. Otherwise, the low molecular weight hydrocarbons in Hole 511 are formed in situ and remain at their place of formation. The core samples turned out to be contaminated by large quantities of acetone, which is routinely used as a solvent during sampling procedures onboard Glomar Challenger.

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.

Risk Factors for Neonatal Sepsis and Method for Reduction of Blood Culture Contamination

Background False-positive blood cultures findings may lead to a falsely increased morbidity and increased hospital costs. Method The survey was conducted as retrospective - prospective study and included 239 preterm infants (born before 37 weeks of gestation) who were treated in Neonatal Intensive Care Unit (NICU) in Institute for Child and Youth Health Care of Vojvodina during one year (January 1st, 2012 to December 31st, 2012). The retrospective part of the study focused on examination of incidence of neonatal sepsis and determination of risk factors. In the prospective part of the study infants were sub-divided into two groups: Group 1- infants hospitalized in NICU during the first 6 months of the study; blood cultures were taken by the ‘’clean technique’’ and checklists for this procedure were not taken. Group 2- neonates hospitalized in NICU during last 6 months of the study; blood cultures were taken by ‘’sterile technique’’ and checklists for this procedure were taken. Results The main risk factors for sepsis were prelabor rupture of membranes, low gestational age, low birth weight, mechanical ventilation, umbilical venous catheter placement, and abdominal drainage. Staphylococcus aureus and coagulase negative Staphylococcus were the most frequently isolated microorganisms in false-positive blood samples. Conclusions Education of employees, use of checklists and sterile sets for blood sampling, permanent control of false positive blood cultures, as well as regular and routine monthly reports are crucial for successful reduction of contamination rates.

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.

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.

Role of Serum Levels of Vascular Endothelial Growth Factor and Its Receptor in Retinopathy of Prematurity

Background: Retinopathy of prematurity (ROP) is a disorder of developing retina of low birth weight preterm infants which can lead to blindness. One theory attributes the fibrosis seen in ROP to deregulation of vascularization in the retina. Vascular endothelial growth factor (VEGF) is one of the important mediators involved in vascularization. Objectives: This study was carried out to assess the role of VEGF and its receptor in retinopathy of prematurity. Patients and Methods: Around 200 preterm infants born in SSK hospital were screened at 33 - 34 weeks. These babies were followed up according to the international classification of retinopathy of prematurity (ICROP) criteria. Those infants who developed ROP at 38 - 40 weeks were enrolled in group A while an equal number of infants who did not develop ROP were included in group B. Each group comprised of 30 subjects each. Venous sampling was carried out twice, once at 33 - 34 weeks and then again at 38 - 40 weeks. VEGF and VEGF-R2 were estimated by commercially available ELISA kits. Results: There was no statistically significant difference between the levels of VEGF and VEGF-R2 in both groups at first visit as well as the follow up visit. However, the intra-group difference was significant between the first and the final visit in VEGF and VEGF-R2 levels in the cases with ROP. In the control population, the VEGF levels were significantly lower in the follow up visit as compared to the initial visit. Conclusions: Our study demonstrates that a significant difference is seen in the serum VEGF and VRGF-R2 in the second visit of the infants with ROP demonstrating that VEGF might be responsible for the initiation and aggravation of ROP.

The effects of vitamin D supplementation on maternal and neonatal outcome: A randomized clinical trial

Background: Vitamin D supplementation during pregnancy has been supposed to defend against adverse gestational outcomes. Objective: This randomized clinical trial study was conducted to assess the effects of 50,000 IU of vitamin D every two weeks supplementation on the incidence of gestational diabetes (GDM), gestational hypertension, preeclampsia and preterm labor, vitamin D status at term and neonatal outcomes contrasted with pregnant women that received 400 IU vitamin D daily. Materials and Methods: 500 women with gestational age 12-16 weeks and serum 25 hydroxy vitamin D (25 (OH) D ) less than 30 ng/ml randomly categorized in two groups. Group A received 400 IU vitamin D daily and group B 50,000 IU vitamin D every 2 weeks orally until delivery. Maternal and Neonatal outcomes were assessed in two groups. Results: The incidence of GDM in group B was significantly lower than group A (6.7% versus 13.4%) and odds ratio (95% Confidence interval) was 0.46 (0.24-0.87) (P=0.01). The mean ± SD level of 25 (OH) D at the time of delivery in mothers in group B was significantly higher than A (37.9 ± 19.8 versus 27.2 ± 18.8 ng/ml, respectively) (P=0.001). There were no differences in the incidence of preeclampsia, gestational hypertension, preterm labor, and low birth weight between two groups. The mean level of 25 (OH) D in cord blood of group B was significantly higher than group A (37.9 ± 18 versus 29.7 ± 19ng/ml, respectively). Anthropometric measures between neonates were not significantly different. Conclusion: Our study showed 50,000 IU vitamin D every 2 weeks decreased the incidence of GDM.

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.

Peptide-based low molecular weight gelators for the preparation of self-assembled materials

Low molecular weight gelators (LMWGs) based on pseudo-peptides are here studied for the preparation of supramolecular materials. These compounds can self-assemble through non-covalent interactions such as hydrogen bonds and π-π stacking, forming fibres and gels. A wide variety of materials can be prepared starting from these building blocks, which can be tuned and functionalised depending on the application. In this work, derivatives of the three aromatic amino acids L-Phenylalanine, L-Tyrosine and L-DOPA (3,4-dihydroxiphenylalanine) were synthesised and tested as gelators for water or organic solvents. First, the optimal gelating conditions were studied for each compound, varying concentration, solvent and trigger. Then the materials were characterised in terms of mechanical properties and morphology. Water remediation from dye pollution was the first focus of this work. Organogels were studied as absorbent of dyes from contaminated water. Hydrogels functionalised with TiO2 nanoparticles and graphene platelets were proposed as efficient materials for the photo-degradation of dyes. An efficient method for the incorporation of graphene inside hydrogels using the gelator itself as dispersant was proposed. In these materials a high storage modulus coexists with good self-healing and biocompatibility. The incorporation of a mineral phase inside the gel matrix was then investigated, leading to the preparation of composite organic/inorganic materials. In a first study, the growth of calcium carbonate crystals was achieved inside the hydrogel, which preserved its structure after crystal formation. Then the self-assembled fibres made of LMWGs were used for the first time instead of the polymeric ones as reinforcement inside calcium phosphate cements (CPCs) for bone regeneration. Gel-to-crystal transitions occurring with time in a metastable gel were also examined. The formation of organic crystals in gels can be achieved in multicomponent systems, in which a second gelator constitutes the independent gel network. Finally, some compounds unable to gelate were tested as underwater adhesives.