Changes of Soluble CD40 Ligand in the Progression of Acute Myocardial Infarction Associate to Endothelial Nitric Oxide Synthase Polymorphisms and Vascular Endothelial Growth Factor But Not to Platelet CD62P Expression

Reported in vitro data implicated soluble CD40 ligand (sCD40L) in endothelial dysfunction and angiogenesis. However, whether sCD40L could exert that influence in endothelial dysfunction and angiogenesis after injury in acute myocardial infarction (AMI) patients remains unclear. In the present study, we evaluated the association of sCD40L with markers of platelet activation, endothelial, and vascular function during a recovery period early after AMI. To achieve this goal, the time changes of soluble, platelet-bound, and microparticle-bound CD40L levels over 1 month were assessed in AMI patients and correlated with endothelial nitric oxide synthase (eNOS) polymorphisms, vascular endothelial growth factor (VEGF) concentrations, and platelet expression of P-selectin (CD62P). The association of soluble form, platelet-bound, and microparticle-bound CD40L with CD62P expression on platelets, a marker of platelet activation, was also assessed to evaluate the role of CD40L in the thrombosis, whereas the association with eNOS and VEGF was to evaluate the role of CD40L in vascular dysfunction. This work shows for the first time that time changes of sCD40L over 1 month after myocardial infarct onset were associated with G894T eNOS polymorphism and with the VEGF concentrations, but not to the platelet CD62P expression. These results indicate that, in terms of AMI pathophysiology, the sCD40L cannot be consider just as being involved in thrombosis and inflammation but also as having a relevant role in vascular and endothelial dysfunction

Stratification of ST-Elevation Myocardial Infarction Patients Based on Soluble CD40L Longitudinal Changes

Involvement of soluble CD40 ligand (sCD40L) in thrombosis and inflammation on the context of coronary artery disease is currently being revised. In that perspective, we had studied the association of sCD40L with markers of platelet activation and markers of endothelial and vascular function. On that cohort, a stratification of patients with acute myocardial infarction (AMI) 1 month after percutaneous coronary intervention (PCI) was observed based on concentrations of sCD40L. The study intended to identify the groups of AMI patients with different profiles of sCD40L concentrations and verify how medication, clinical evolution, biochemical data, and markers of regulation of endothelial function at genetic (endothelial nitric oxide synthase polymorphisms) and post-transcriptional levels (circulating microRNAs) affect sCD40L serum levels. Lower quartiles of sCD40L (<2.3 ng/mL) were associated with higher concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP), high frequency of G894T polymorphism, and altered expression of a set of microRNAs assumed to be involved in the regulation of endothelial and cardiac function and myocardium hypertrophy, relative to patients in sCD40L upper quartiles. A characteristic sCD40L variation pattern in STEMI patients was identified. Low levels of sCD40L 1 month after PCI distinguish STEMI patients with worse prognosis, a compromised cardiac healing, and a persistent endothelial dysfunction, as given by the association between sCD40L, NT-proBNP, G894T polymorphism, and specific profile of miRNA expression. These results suggest sCD40L could have a prognostic value in STEMI patients.info:eu-repo/semantics/publishedVersio

Risk stratification for small for gestational age for the Brazilian population: a secondary analysis of the Birth in Brazil study.

Risk-stratification screening for SGA has been proposed in high-income countries to prevent perinatal morbidity and mortality. There is paucity of data from middle-income settings. The aim of this study is to explore risk factors for SGA in Brazil and assess potential for risk stratification. This population-based study is a secondary analysis of Birth in Brazil study, conducted in 266 maternity units between 2011 and 2012. Univariate and multivariate logistic regressions were performed, and population attributable fraction estimated for early and all pregnancy factors. We calculated absolute risk, odds ratio, and population prevalence of single or combined factors stratified by parity. Factors associated with SGA were maternal lupus (ORadj 4.36, 95% CI [2.32-8.18]), hypertensive disorders in pregnancy (ORadj 2.72, 95% CI [2.28-3.24]), weight gain < 5 kg (ORadj 2.37, 95% CI [1.99-2.83]), smoking at late pregnancy (ORadj 2.04, 95% CI [1.60-2.59]), previous low birthweight (ORadj 2.22, 95% CI [1.79-2.75]), nulliparity (ORadj 1.81, 95% CI [1.60-2.05]), underweight (ORadj 1.61, 95% CI [1.36-1.92]) and socioeconomic status (SES) < 5th centile (ORadj 1.23, 95% CI [1.05-1.45]). Having two or more risk factors (prevalence of 4.4% and 8.0%) was associated with a 2 and fourfold increase in the risk for SGA in nulliparous and multiparous, respectively. Early and all pregnancy risk factors allow development of risk-stratification for SGA. Implementation of risk stratification coupled with specific strategies for reduction of risk and increased surveillance has the potential to contribute to the reduction of stillbirth in Brazil through increased detection of SGA, appropriate management and timely delivery

Soil-atmosphere exchange of nitrous oxide, methane and carbon dioxide in a gradient of elevation in the coastal Brazilian Atlantic forest

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Soils of tropical forests are important to the global budgets of greenhouse gases. The Brazilian Atlantic Forest is the second largest tropical moist forest area of South America, after the vast Amazonian domain. This study aimed to investigate the emissions of nitrous oxide (N2O), carbon dioxide (CO2) and methane (CH4) fluxes along an altitudinal transect and the relation between these fluxes and other climatic, edaphic and biological variables (temperature, fine roots, litterfall, and soil moisture). Annual means of N2O flux were 3.9 (+/- 0.4), 1.0 (+/- 0.1), and 0.9 (+/- 0.2) ng N cm(-2) h(-1) at altitudes 100, 400, and 1000 m, respectively. On an annual basis, soils consumed CH4 at all altitudes with annual means of -1.0 (+/- 0.2), -1.8 (+/- 0.3), and -1.6 (+/- 0.1) mg m(-2) d(-1) at 100 m, 400 m and 1000 m, respectively. Estimated mean annual fluxes of CO2 were 3.5, 3.6, and 3.4 mu mol m(-2) s(-1) at altitudes 100, 400 and 1000 m, respectively. N2O fluxes were significantly influenced by soil moisture and temperature. Soil-atmosphere exchange of CH4 responded to changes in soil moisture. Carbon dioxide emissions were strongly influenced by soil temperature. While the temperature gradient observed at our sites is only an imperfect proxy for climatic warming, our results suggest that an increase in air and soil temperatures may result in increases in decomposition rates and gross inorganic nitrogen fluxes that could support consequent increases in soil N2O and CO2 emissions and soil CH4 consumption.83733742Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP [2005/57549-8]FAPESP [FAPESP 03/12595-7

The CAG repeat at the Huntington disease gene in the Portuguese population : insights into its dynamics and to the origin of the mutation

Huntington disease (HD) is caused by an expansion of a CAG repeat. This repeat is a dynamic mutation that tends to undergo intergenerational instability. We report the analysis of the CAG repeat in a large population sample (2,000 chromosomes) covering all regions of Portugal, and a haplotype study of (CAG)n and (CCG)n repeats in 140 HD Portuguese families. Intermediate class 2 alleles represented 3.0% of the population; and two expanded alleles (36 and 40 repeats, 0.11%) were found. There was no evidence for geographical clustering of the intermediate or expanded alleles. The Portuguese families showed three different HD founder haplotypes associated with 7-, 9- or 10-CCG repeats, suggesting the possibility of different origins for theHDmutation among this population. The haplotype carrying the 7-CCG repeat was the most frequent, both in normal and in expanded alleles. In general, we propose that three mechanisms, occurring at different times,may lead to the evolution from normal CAGs to full expansion: first, a mutation bias towards larger alleles; then, a stepwise process that could explain the CAGdistributions observed in themore recent haplotypes; and, finally, a pool of intermediate (class 2) alleles more prone to give rise to expanded HD alleles.Fundação para a Ciência e a Tecnologia (FCT) - SFRH/BD/9759/ 2003.Instituto de Genética Médica Jacinto Magalhães

Assessment and topographic characterization of locoregional recurrences in head and neck tumours

Purpose: To evaluate the differences between three methods of classification of recurrences in patients with head and neck tumours treated with Radiation Therapy (RT). Materials and methods: 367 patients with head and neck tumours were included in the study. Tumour recurrences were delineated in the CT images taken during patient follow-up and deformable registration was used to transfer this volume into the planning CT. The methods used to classify recurrences were: methodCTV quantified the intersection volume between the recurrence and the Clinical Target Volume (CTV); methodTV quantified the intersection between the Treated Volume and the recurrence (for method CTV and TV, recurrences were classified in-field if more than 95% of their volume were inside the volume of interest, marginal if the intersection was between 20-95% and outfield otherwise); and methodCOM was based on the position of the Centre Of Mass of the recurrence. A dose assessment in the recurrence volume was also made. Results: The 2-year Kaplan-Meier locoregional recurrence incidence was 10%. Tumour recurrences occurred in 22 patients in a mean time of 16.5 ± 9.4 months resulting in 28 recurrence volumes. The percentage of in-field recurrences for methods CTV, TV and COM was 7%, 43% and 50%, respectively. Agreement between the three methods in characterizing individually in-field and marginal recurrences was found only in six cases. Methods CTV and COM agreed in 14. The percentage of outfield recurrences was 29% using all methods. For local recurrences (in-field or marginal to gross disease) the average difference between the prescribed dose and D 98% in the recurrence volume was -5.2 ± 3.5% (range: -10.1%-0.9%). Conclusions: The classification of in-field and marginal recurrences is very dependent on the method used to characterize recurrences. Using methods TV and COM the largest percentage of tumour recurrences occurred in-field in tissues irradiated with high doses. Keywords: Head and neck tumours, Radiation therapy, Characterization of tumour recurrences, Geometric methods, Dosimetric assessmen

Digital subtraction radiographic analysis of the combination of bioabsorbable membrane and bovine morphogenetic protein pool in human periodontal infrabony defects

Objectives: This study assessed the bone density gain and its relationship with the periodontal clinical parameters in a case series of a regenerative therapy procedure. Material and Methods: Using a split-mouth study design, 10 pairs of infrabony defects from 15 patients were treated with a pool of bovine bone morphogenetic proteins associated with collagen membrane (test sites) or collagen membrane only (control sites). The periodontal healing was clinically and radiographically monitored for six months. Standardized presurgical and 6-month postoperative radiographs were digitized for digital subtraction analysis, which showed relative bone density gain in both groups of 0.034 ± 0.423 and 0.105 ± 0.423 in the test and control group, respectively (p>0.05). Results: As regards the area size of bone density change, the influence of the therapy was detected in 2.5 mm2 in the test group and 2 mm2 in the control group (p>0.05). Additionally, no correlation was observed between the favorable clinical results and the bone density gain measured by digital subtraction radiography (p>0.05). Conclusions: The findings of this study suggest that the clinical benefit of the regenerative therapy observed did not come with significant bone density gains. Long-term evaluation may lead to a different conclusions