Long-term prognostic value of protein C activity, erythrocyte aggregation and membrane fluidity in transmural myocardial infarction

The objective of this study was to evaluate the long-term predictive value of the haemostatic, inflammatory and haemorheologic disturbances in transmural myocardial infarction (MI). Sixty-four (59 male) consecutive survivors of a MI, with a mean age of 58.3 +/- 12.0 years, were followed over a period of 36 months. Eighteen patients had a cardiovascular event defined as the composite of death, non-fatal MI, unstable angina and stroke. The haemostatic (protein C activity-PtC, antithrombin III, plasminogen activator inhibitor-1), haemorheologic (blood fluidity and components, erythrocyte membrane fluidity) and inflammatory (polymorphonuclear elastase, leukocyte count) profiles were determined at hospital discharge, using standard methodology. Our results can be summarized as follow: (i) at hospital discharge, the subgroup of patients with events had higher leukoactivity, leukocyte count, membrane fluidity, prognosis cyte count (7833.0 +/- 1696.0 vs. 10294.0 +/- 3129.0; p = 0.011), lower PtC (100.65 +/- 19.08 vs.81.25 +/- 19.95; p = 0.002), and lower erythrocyte aggregation (14.26 +/- 5.94 vs. 11.47 +/- 3.45; p = 0.031) in relation to the ones without events; (ii) By Cox regression the protein C activity lower tertile (OR 0.169; 0.045-0.628; p = 0.008); erythrocyte membrane outer layer fluidity upper tertile (OR 0.067; 95% CI 0.011 - 0.393; p = 0.003); and erythrocyte aggregation lower tertile (OR 0.182; 0.038 - 0.876; p = 0.034) were independent predictors of the composite endpoint. We can conclude that some haemostatic, haemorheologic and inflammatory disturbances, at hospital discharge, are long-term independent predictors of recurrent cardiovascular events in transmural myocardial infarction survivors.     

Synaptic signals mediated by protons and acid‐sensing ion channels

Extracellular pH changes may constitute significant signals for neuronal communication. During synaptic transmission, changes in pH in the synaptic cleft take place. Its role in the regulation of presynaptic Ca²⁺ currents through multivesicular release in ribbon‐type synapses is a proven phenomenon. In recent years, protons have been recognized as neurotransmitters that participate in neuronal communication in synapses of several regions of the CNS such as amygdala, nucleus accumbens, and brainstem. Protons are released by nerve stimulation and activate postsynaptic acid‐sensing ion channels (ASICs). Several types of ASIC channels are expressed in the peripheral and central nervous system. The influx of Ca²⁺ through some subtypes of ASICs, as a result of synaptic transmission, agrees with the participation of ASICs in synaptic plasticity. Pharmacological and genetical inhibition of ASIC1a results in alterations in learning, memory, and phenomena like fear and cocaine‐seeking behavior. The recognition of endogenous molecules, such as arachidonic acid, cytokines, histamine, spermine, lactate, and neuropeptides, capable of inhibiting or potentiating ASICs suggests the existence of mechanisms of synaptic modulation that have not yet been fully identified and that could be tuned by new emerging pharmacological compounds with potential therapeutic benefits.     

Survival After Thoracoscopic Surgery or Open Lobectomy: Systematic Review and Meta-Analysis

1. Download : Download high-res image (260KB)
2. Download : Download full-size image

     

Retrovirally transferred genes inhibit apoptosis in an insulin-secreting cell line: implications for islet transplantation

The transplantation of pancreatic islets for the treatment of type I diabetes is hindered by the enormous loss of cells due to early apoptotic events. Genetic engineering of islets with cytoprotective genes is an important strategy aimed to enhance the survival of these cells in the transplant setting. The present study was designed to evaluate and compare the effects of five genes on a cell line derived from insulin-producing beta-cells, NIT-1. Cells were transduced using a Maloney murine leukemia virus (MLV) vector coding for yellow fluorescent protein (YFP) and for one of the following antiapoptotic genes: cFLIP, FADD-DN, BcL-2, PI-9, and ICAM-2. These genes were able to protect NIT-1 cells from cytokine-induced apoptosis to varying degrees ranging from no protection to significant protection equivalent to an optimal dose of a chemical caspase inhibitor. The data demonstrate that cFLIP, FADD-DN, and PI-9 are significantly more effective in protecting NIT-1 cells than BcL-2 and ICAM-2. Additionally, the data show that despite its weak in vitro inhibition of caspase-3, PI-9 affords significant protection against TNF-alpha-induced apoptosis in these cells. These genes may be ideal candidates to augment islet survival following transplantation.     

Habitats, dispersion and invasion of sylvatic Triatoma dimidiata (Hemiptera: Reduviidae: Triatominae) in Petén, Guatemala

Dispersion and invasion capacity of sylvatic populations of Triatoma dimidiata (Latreille) were investigated during 14 mo by means of experimental chicken coops installed in a nature reserve within the Maya Biosphere, Petén, Guatemala. In addition, palm trees, underground archeological holes (chultunes) and piles of limestones within the forest were inspected as potential sylvatic habitats of T. dimidiata. From the three types of sylvatic habitats we inspected, all served as shelter and breeding sites for T dimidiata. The natural infection of these bugs (n = 72) with Trypanosoma cruzi (Chagas) was high (25%) and represent a risk for humans who colonize the forest. T. dimidiata quickly invaded the experimental chicken coops installed in the primary forest, albeit at very low densities. However, only one adult bug was encountered in the chicken coops installed in a secondary forest. Dispersal of adult T. dimidiata was most apparent at the end of the dry season. Overall, our results indicate a potential risk for invasion by sylvatic T. dimidiata of domestic environments in this area, with a risk of T. cruzi transmission to humans. We suggest that a system of community-based surveillance should be developed to detect new infestations and organize prompt treatment of any new cases of acute Chagas disease that may result.     

Supersensitivity of the cholinergic muscarinic system in the rat's brain is induced by high concentrations of Cu+2

Transition metals have been described as regulators of receptor's function. here, we studied the effects of chronic administration of Cu2+ or the Cu2+ chelator penicillamine (PA) on the functional and binding properties of the muscarinic receptors (MR) on selected areas of rat's brain. Groups of 10 Sprague-Dawley rats were treated daily, for 45 days with either 1) 1 mg/Kg CuSO4 (Cu2+), 2) 100 mg/Kg PA, or 3) saline solution. Double T-maze and motility cages were used for behavioral testing and the binding assays were performed using [3H]-QNB or [3H]-N-MSCP as MR's ligands. Cu2+ brain levels were measured in the cerebral cortex by atomic absorption spectrophotometer. Results showed that PA treated rats displayed a significant decrease of locomotor's activity (LA) and rearing behavior (RB), but a significant increases in memory efficiency (ME). Cu2+ treated rats displayed diminished RB with no significant changes in LA. Cu2+ treated rats displayed higher MR's density (Bmax) in cortex (C), striatum (S), and hippocampus (H). An increase in Bmax was also observed in PA treated rats, but only in C and S. Finally, Cu2+ tissue concentration was significantly higher in C of both Cu2+ and with PA treated animals. In conclusion, 45 days of Cu2+ or PA treatment induced brain hypercuprosis, which was associated with MR binding supersensitivity; however, change in ME was only observed in PA treated rats suggesting that might be still another factor in these experiments besides Cu2+ (i.e., Zn2+ or PA itself) involved in memory modulation.     

Evidence of prolonged disturbances in the haemostatic,hemorheologic and inflammatory profiles in transmural myocardial infarction survivors

Haemostatic, hemorheologic and inflammatory disturbances have been associated with acute coronary syndromes. Most knowledge is reported in cross sectional studies and are without time dependent evolution of these profiles. The aim of this study was to evaluate, during the first year, the evolution of the haemostatic, hemorheologic and inflammatory profiles determined at hospital discharge in survivors with transmural myocardial infarction (MI). Eighty eight (79 male; 9 female) mean age of 58 +/- 11 years, survivors of a transmural MI were prospectively studied at discharge, 6 months and one year after the event. Haemostatic (protein C, antithrombin III and plasminogen activator inhibitor 1), hemorheologic (blood fluidity and components) and inflammatory profiles (polymorphonuclear elastase and leukocyte count) were determined using standard methodology. The results of the study can be summarized as follows: (1) Protein C decreased (p < 0.05) over time while PAI-1 only varied significantly until 6(th) month. (2) Plasma viscosity and fibrinogen (p < 0.001) decrease over time, while erythrocyte aggregation (p < 0.001) and haematocrit increased. Whole blood viscosity did not vary. (3) Leukocyte decreased (p < 0.001) and elastase did not (4). Those patients with cardiovascular events (n = 7) had higher PAI-1 concentration (p < 0.05) and leukocyte count (p < 0.01), at discharge (5) Left ventricle ejection fraction correlated significantly with plasma viscosity (r = 0.35 p < 0.05). The results of this longitudinal study show dynamic modifications of the haemostatic, hemorheologic and inflammatory profiles during the first year of a transmural myocardial infarction. In addition, there are interrelations between them and the clinical profile that could help to explain the clinical evolution of this group of patients.     

RTS,S/AS01E malaria vaccine induces IgA responses against CSP and vaccine-unrelated antigens in African children in the phase 3 trial

BackgroundThe evaluation of immune responses to RTS,S/AS01 has traditionally focused on immunoglobulin (Ig) G antibodies that are only moderately associated with protection. The role of other antibody isotypes that could also contribute to vaccine efficacy remains unclear. Here we investigated whether RTS,S/AS01_E elicits antigen-specific serum IgA antibodies to the vaccine and other malaria antigens, and we explored their association with protection.MethodsNinety-five children (age 5–17 months old at first vaccination) from the RTS,S/AS01_E phase 3 clinical trial who received 3 doses of RTS,S/AS01_E or a comparator vaccine were selected for IgA quantification 1 month post primary immunization. Two sites with different malaria transmission intensities (MTI) and clinical malaria cases and controls, were included. Measurements of IgA against different constructs of the circumsporozoite protein (CSP) vaccine antigen and 16 vaccine-unrelated Plasmodium falciparum antigens were performed using a quantitative suspension array assay.ResultsRTS,S vaccination induced a 1.2 to 2-fold increase in levels of serum/plasma IgA antibodies to all CSP constructs, which was not observed upon immunization with a comparator vaccine. The IgA response against 13 out of 16 vaccine-unrelated P. falciparum antigens also increased after vaccination, and levels were higher in recipients of RTS,S than in comparators. IgA levels to malaria antigens before vaccination were more elevated in the high MTI than the low MTI site. No statistically significant association of IgA with protection was found in exploratory analyses.ConclusionsRTS,S/AS01_E induces IgA responses in peripheral blood against CSP vaccine antigens and other P. falciparum vaccine-unrelated antigens, similar to what we previously showed for IgG responses. Collectively, data warrant further investigation of the potential contribution of vaccine-induced IgA responses to efficacy and any possible interplay, either synergistic or antagonistic, with protective IgG, as identifying mediators of protection by RTS,S/AS01_E immunization is necessary for the design of improved second-generation vaccines.Clinical trial registration: ClinicalTrials.gov: NCT008666191.     

Aversion to geographic inequality and geographic variation in preferences in the context of healthcare

Background

It is now widely accepted that social values have a role to play in terms of healthcare resource allocation decisions. Furthermore, with the recent focus on decentralization, geographic variation in preferences has become a pertinent issue. However, the geographic dimension of inequality in the distribution of health gains across different regions has received little attention in the literature.

Objectives

To elicit the general public’s preferences regarding inequality in the distribution of health gains across regions and to test the assumption of variation in preferences across regions.

Methods

A questionnaire was developed to elicit social and personal preferences. The first preference questions focused on the criteria of maximization of health gain and geographic equality of health gain. Person trade-off questions were used to assess trade-offs and inequality aversion. The latter preference questions focused on attributes of healthcare delivery. The questionnaire was administered in two Portuguese municipalities. Samples from both localities were defined by quotas based on the composition of local populations. Overall, 70 respondents (half from each municipality) self-completed the questionnaire.

Results

Respondents agreed or strongly agreed that both maximization of health gain and geographic equality of health gain should be considered in resource allocation decisions; when they were asked to make trade-offs, 70–80% were prepared to do so. Of those making trade-offs, most people were willing to forego 10–30% of total health gain to keep geographic equality of health gain in return. Regarding inequality aversion, the results indicate that there was some aversion to inequality in the sample. Regarding preference variation, the results do not corroborate the hypothesis of variation in preferences across regions.

Conclusion

These results suggest that the general public supports the principles of maximization of health gain and geographic equality in the distribution of health gain. The results further suggest the existence of aversion to inequality, subject to a maximum opportunity cost. Further research is required into preference variation; in particular, in larger samples, and in other regions of Portugal.     

Resilience in eating disorders: A qualitative study

ABSTRACT

The objectives of the authors in this study were two-fold: (1) to explore the role of resilience in recovery from eating disorders (EDs), and (2) to develop a model of resilience in women with EDs. Semi-structured interviews with ten women were conducted in April 2011, along with two focus groups with women who had recovered from EDs (n = 5 women each; conducted in April 2012 at the University of Deusto, Spain), one focus group with clinical experts (n = 8; conducted in April 2012 at the Foundation Against EDs of Biskay, Spain), and six narratives from primary caregivers of ED patients living in Biskay, Spain (conducted in November 2012). All data were analyzed using a grounded theory approach. All female participants acknowledged experiencing resilience in their recovery. The analysis resulted in a conceptual model of resilience composed of the following categories: deep dissatisfaction with life, turning point, acceptance, hope, determination to change, accountability for the ED, active coping, getting social support, gaining self-knowledge, getting information about EDs, increase well-being, trait resilience, initiating new projects and living in the here and now. According to the model presented, resilience preceded the experience of recovery in women with EDs in this sample and could be a useful asset for future interventions.