DODAB and DODAC bilayer-like aggregates in the micromolar surfactant concentration domain

In the millimolar concentration domain (typically 1 mM), dioctadecyldimethylammonium bromide and chloride (DODAX, X representing Br- or Cl- counterions) molecules assemble in water as large unilamellar vesicles. Differential scanning calorimetry (DSC) is a suitable technique to obtain the melting temperature (Tm) characteristic of surfactant bilayers, while fluorescence spectroscopy detects formation of surfactant aggregates, like bilayers. These two techniques were combined to investigate the assemble of DODAX molecules at micromolar concentrations, from 10 to 100 micromolar. At 1 mM surfactant, Tm ~ 45 ºC and 49 oC, respectively for DODAB and DODAC. DSC and fluorescence of Nile Red were used to show the formation of DODAX aggregates, at the surfactant concentration as low as 10 micromolar, whose Tm decreases monotonically with increasing DODAX concentration to attain the value for the ordinary vesicles. The data indicate that these aggregates are organized as bilayer-like structures.Fundação para a Ciência e a Tecnologia (FCT

Non-Cardiac Surgery in Developing Countries: Epidemiological Aspects and Economical Opportunities – The Case of Brazil

Background: Worldwide distribution of surgical interventions is unequal. Developed countries account for the majority of surgeries and information about non-cardiac operations in developing countries is scarce. The purpose of our study was to describe the epidemiological data of non-cardiac surgeries performed in Brazil in the last years. Methods and Findings: This is a retrospective cohort study that investigated the time window from 1995 to 2007. We collected information from DATASUS, a national public health system database. The following variables were studied: number of surgeries, in-hospital expenses, blood transfusion related costs, length of stay and case fatality rates. The results were presented as sum, average and percentage. The trend analysis was performed by linear regression model. There were 32,659,513 non-cardiac surgeries performed in Brazil in thirteen years. An increment of 20.42% was observed in the number of surgeries in this period and nowadays nearly 3 million operations are performed annually. The cost of these procedures has increased tremendously in the last years. The increment of surgical cost was almost 200%. The total expenses related to surgical hospitalizations were more than $10 billion in all these years. The yearly cost of surgical procedures to public health system was more than$1.27 billion for all surgical hospitalizations, and in average, U$445.24 per surgical procedure. The total cost of blood transfusion was near$98 million in all years and annually approximately $10 million were spent in perioperative transfusion. The surgical mortality had an increment of 31.11% in the period. Actually, in 2007, the surgical mortality in Brazil was 1.77%. All the variables had a significant increment along the studied period: r square (r(2)) = 0.447 for the number of surgeries (P = 0.012), r(2) = 0.439 for in-hospital expenses (P = 0.014) and r(2) = 0.907 for surgical mortality (P = 0.0055). Conclusion: The volume of surgical procedures has increased substantially in Brazil through the past years. The expenditure related to these procedures and its mortality has also increased as the number of operations. Better planning of public health resource and strategies of investment are needed to supply the crescent demand of surgery in Brazil.Scholarship Program of Cardiology Society of Sao Paulo (SOCESP)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP

Intestinal strongyloidiasis and hyperinfection syndrome

In spite of recent advances with experiments on animal models, strongyloidiasis, an infection caused by the nematode parasite Strongyloides stercoralis, has still been an elusive disease. Though endemic in some developing countries, strongyloidiasis still poses a threat to the developed world. Due to the peculiar but characteristic features of autoinfection, hyperinfection syndrome involving only pulmonary and gastrointestinal systems, and disseminated infection with involvement of other organs, strongyloidiasis needs special attention by the physician, especially one serving patients in areas endemic for strongyloidiasis. Strongyloidiasis can occur without any symptoms, or as a potentially fatal hyperinfection or disseminated infection. Th(2 )cell-mediated immunity, humoral immunity and mucosal immunity have been shown to have protective effects against this parasitic infection especially in animal models. Any factors that suppress these mechanisms (such as intercurrent immune suppression or glucocorticoid therapy) could potentially trigger hyperinfection or disseminated infection which could be fatal. Even with the recent advances in laboratory tests, strongyloidiasis is still difficult to diagnose. But once diagnosed, the disease can be treated effectively with antihelminthic drugs like Ivermectin. This review article summarizes a case of strongyloidiasis and various aspects of strongyloidiasis, with emphasis on epidemiology, life cycle of Strongyloides stercoralis, clinical manifestations of the disease, corticosteroids and strongyloidiasis, diagnostic aspects of the disease, various host defense pathways against strongyloidiasis, and available treatment options

Diploids in the Cryptococcus neoformans Serotype A Population Homozygous for the α Mating Type Originate via Unisexual Mating

The ubiquitous environmental human pathogen Cryptococcus neoformans is traditionally considered a haploid fungus with a bipolar mating system. In nature, the α mating type is overwhelmingly predominant over a. How genetic diversity is generated and maintained by this heterothallic fungus in a largely unisexual α population is unclear. Recently it was discovered that C. neoformans can undergo same-sex mating under laboratory conditions generating both diploid intermediates and haploid recombinant progeny. Same-sex mating (α-α) also occurs in nature as evidenced by the existence of natural diploid αADα hybrids that arose by fusion between two α cells of different serotypes (A and D). How significantly this novel sexual style contributes to genetic diversity of the Cryptococcus population was unknown. In this study, ∼500 natural C. neoformans isolates were tested for ploidy and close to 8% were found to be diploid by fluorescence flow cytometry analysis. The majority of these diploids were serotype A isolates with two copies of the α MAT locus allele. Among those, several are intra-varietal allodiploid hybrids produced by fusion of two genetically distinct α cells through same-sex mating. The majority, however, are autodiploids that harbor two seemingly identical copies of the genome and arose via either endoreplication or clonal mating. The diploids identified were isolated from different geographic locations and varied genotypically and phenotypically, indicating independent non-clonal origins. The present study demonstrates that unisexual mating produces diploid isolates of C. neoformans in nature, giving rise to populations of hybrids and mixed ploidy. Our findings underscore the importance of same-sex mating in shaping the current population structure of this important human pathogenic fungus, with implications for mechanisms of selfing and inbreeding in other microbial pathogens

Proteases of haematophagous arthropod vectors are involved in blood-feeding, yolk formation and immunity : a review

Ticks, triatomines, mosquitoes and sand flies comprise a large number of haematophagous arthropods considered vectors of human infectious diseases. While consuming blood to obtain the nutrients necessary to carry on life functions, these insects can transmit pathogenic microorganisms to the vertebrate host. Among the molecules related to the blood-feeding habit, proteases play an essential role. In this review, we provide a panorama of proteases from arthropod vectors involved in haematophagy, in digestion, in egg development and in immunity. As these molecules act in central biological processes, proteases from haematophagous vectors of infectious diseases may influence vector competence to transmit pathogens to their prey, and thus could be valuable targets for vectorial control

A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure

Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify BP loci and extend our knowledge of its genetic architecture. We performed genome-wide association meta-analyses of systolic and diastolic BP incorporating gene-smoking interactions in 610,091 individuals. Stage 1 analysis examined similar to 18.8 million SNPs and small insertion/deletion variants in 129,913 individuals from four ancestries (European, African, Asian, and Hispanic) with follow-up analysis of promising variants in 480,178 additional individuals from five ancestries. We identified 15 loci that were genome-wide significant (p <5 x 10(-8)) in stage 1 and formally replicated in stage 2. A combined stage 1 and 2 meta-analysis identified 66 additional genome-wide significant loci (13, 35, and 18 loci in European, African, and trans-ancestry, respectively). A total of 56 known BP loci were also identified by our results (p <5 x 10(-8)). Of the newly identified loci, ten showed significant interaction with smoking status, but none of them were replicated in stage 2. Several loci were identified in African ancestry, highlighting the importance of genetic studies in diverse populations. The identified loci show strong evidence for regulatory features and support shared pathophysiology with cardiometabolic and addiction traits. They also highlight a role in BP regulation for biological candidates such as modulators of vascular structure and function (CDKN1B, BCAR1-CFDP1, PXDN, EEA1), ciliopathies (SDCCAG8, RPGRIP1L), telomere maintenance (TNKS, PINX1, AKTIP), and central dopaminergic signaling MSRA, EBF2).Peer reviewe