Assessing the vulnerability of women to sexually transmitted diseases STDS/ HIV: construction and validation of markers

Objective To construct and validate markers of vulnerability of women to STDs/HIV, taking into consideration the importance of STDs/HIV. Method Methodological study carried out in three stages: 1) systematic review and identification of elements of vulnerability in the scientific production; 2) selection of elements of vulnerability, and development of markers; 3) establishment of the expert group and validation of the markers (content validity). Results Five markers were validated: no openness in the relationship to discuss aspects related to prevention of STDs/HIV; no perception of vulnerability to STDs/HIV; disregard of vulnerability to STDs/ HIV; not recognizing herself as the subject of sexual and reproductive rights; actions of health professionals that limit women’s access to prevention of STDs/HIV. Each marker contains three to eleven components. Conclusion The construction of such markers constituted an instrument, presented in another publication, which can contribute to support the identification of vulnerabilities of women in relation to STDs/HIV in the context of primary health care services. The markers constitute an important tool for the operationalization of the concept of vulnerability in primary health care and to promote inter/multidisciplinary and inter/multi-sectoral work processes.


Association between self-reported health and sociodemographic characteristics with cardiovascular diseases in adults

OBJECTIVE To assess the association of sociodemographic and self-rated health in the presence of cardiovascular diseases and the association of this perception with the type of disease. METHODS A cross-sectional population survey study carried out with 1,232 individuals aged between 20 and 59 years of both genders living in the metropolitan region of Maringá-PR. Data were analyzed using multiple and simple logistic regression. RESULTS In multivariate analysis, the age range and self-rated health were associated with cardiovascular disease, and in the univariate analysis self-rated regular health was associated with arterial hypertension, while self-rated poor health was associated to heart failure, stroke, and to acute myocardial infarction (heart attack). CONCLUSION The differences in association of self-rated health with these diseases can indicate how individuals with certain characteristics cope with the disease, allowing for more individualized and specific health care.

Les maladies infectieuses ont encore un bel avenir [Infectious diseases have again a good future!].

Invasive fungal diseases (IFDs) have become major causes of morbidity and mortality among highly immunocompromised patients. Authoritative consensus criteria to diagnose IFD have been useful in establishing eligibility criteria for antifungal trials. There is an important need for generation of consensus definitions of outcomes of IFD that will form a standard for evaluating treatment success and failure in clinical trials. Therefore, an expert international panel consisting of the Mycoses Study Group and the European Organization for Research and Treatment of Cancer was convened to propose guidelines for assessing treatment responses in clinical trials of IFDs and for defining study outcomes. Major fungal diseases that are discussed include invasive disease due to Candida species, Aspergillus species and other molds, Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis. We also discuss potential pitfalls in assessing outcome, such as conflicting clinical, radiological, and/or mycological data and gaps in knowledge.

The inflammasome, autoinflammatory diseases, and gout.

IL-1beta is a cytokine with major roles in inflammation and innate immune responses. IL-1beta is produced as an inactive proform that must be cleaved within the cell to generate biologically active IL-1beta. The enzyme caspase-1 catalyzes the reaction. Recent work showed that caspase-1 must be activated by a complex known as the inflammasome. The inflammasome comprises NALP, which is an intracellular receptor involved in innate immunity, and an ASC adapter that ensures caspase-1 recruitment to the receptor. The most extensively described inflammasome to date is formed by the NALP3 receptor within monocytes. Mutations involving the NALP3 gene cause hereditary periodic fever syndromes in humans. Increased inflammasome activity responsible for uncontrolled IL-1beta production occurs in these syndromes. Inhibition of the IL-1beta pathway by IL-1 receptor antagonist (anakinra) is a highly effective treatment for inherited periodic fever syndromes. A major role for inflammasome activity in the development of gout attacks was established recently. Urate monosodium crystals are specifically detected via the NALP3 inflammasome, which results in marked IL-1beta overproduction and initiation of an inflammatory response. This finding opens up new possibilities for the management of gouty attacks.

Hot vs. cold: Sequential responses and preference stability in experimental games

In experiments with two-person sequential games we analyzewhether responses to favorable and unfavorable actions dependon the elicitation procedure. In our hot treatment thesecond player responds to the first player s observed actionwhile in our cold treatment we follow the strategy method and have the second player decide on a contingent action foreach and every possible first player move, without firstobserving this move. Our analysis centers on the degree towhich subjects deviate from the maximization of their pecuniaryrewards, as a response to others actions. Our results show nodifference in behavior between the two treatments. We also findevidence of the stability of subjects preferences with respectto their behavior over time and to the consistency of theirchoices as first and second mover.

Validation of the New Mix Design Process for Cold In-Place Rehabilitation Using Foamed Asphalt, 2007

Asphalt pavement recycling has grown dramatically over the last few years as a viable technology to rehabilitate existing asphalt pavements. Iowa's current Cold In-place Recycling (CIR) practice utilizes a generic recipe specification to define the characteristics of the CIR mixture. As CIR continues to evolve, the desire to place CIR mixture with specific engineering properties requires the use of a mix design process. A new mix design procedure was developed for Cold In-place Recycling using foamed asphalt (CIR-foam) in consideration of its predicted field performance. The new laboratory mix design process was validated against various Reclaimed Asphalt Pavement (RAP) materials to determine its consistency over a wide range of RAP materials available throughout Iowa. The performance tests, which include dynamic modulus test, dynamic creep test and raveling test, were conducted to evaluate the consistency of a new CIR-foam mix design process to ensure reliable mixture performance over a wide range of traffic and climatic conditions. The “lab designed” CIR will allow the pavement designer to take the properties of the CIR into account when determining the overlay thickness.

Characterization of NALP2 and NALP3 IL-1β processing inflammasomes

Résumé II y a cinq ans, la découverte d'un nouveau domaine, le PYD domaine, lié aux domaines de la mort, a permis la description de la nouvelle famille des NALP protéines. L'analyse structurelle de cette famille de protéines révéla la présence de deux autres domaines, impliqués dans l'oligomerisation, NACHT, et la détection des ligands, Leucine rich repeats ou LRR. Cette architecture protéique est homologue à celle qui est décrite pour les NODs, les Tol1 récepteurs et tes protéines de résistance chez les plantes. Cette homologie suggère une possible implication des NALPs dans la régulation de l'immunité innée. Premièrement, nous avons décrit les composants minimaux qui permettent à l'inflammasomeNALP3 d'activer la caspase pro-inflammatoire, caspase-1. En comparaison à NALP1, NALP3 ne contient pas de FIIND domaine, ni de CARD domaine en C-terminus et n'interagit pas avec caspase-5. Nous avons découvert une protéine très homologue au C-terminus de NALP1, Cardinal, qui se lie au NACHT domaine de NALP2 et NALP3 par l'intermédiaire de son FIIND domaine. Cardinal possède la capacité d'interagir avec caspase-l, mais seul ASC semble être nécessaire à la maturation de la prointerleukine-1β suite à la stimulation de NALP3. Deuxièmement, notre étude s'est concentrée sur la nature du stimulus capable d'induire la formation et l'activation de l'inflammasome-NALP3. Nous avons démontré que l'ajout de muramyl dipeptide (MDP), produit à partir de la digestion enzymatique de peptidoglycaris bactériens, induit à la fois l'expression de la proIL-1β par la voie NOD2 et sa maturation en IL-1β active par la voie NALP3. Bien que le MDP active l'inflammasome-NALP3, il est incapable d'induire la sécrétion de l'IL-1β mature dans la lignée cellulaire THP1, comparé aux monocytes primaires humains. Cette différence pourrait être liée à l'absence, dans les THP1, de la protéine Filamin, qui est proposée d'interagir avec Cardinal. L'implication de NALP3 dans la maturation de l'IL-lb est confirmée suite à la découverte de mutations sur le gène CIAS1/NALP3/cryopyrin associées à trois maladies auto-inflammatoires : le syndrome de Muckle-Wells (MWS), l'urticaire familial au froid (FCU) et le syndrome CINCA/NOMID. Une élévation constitutive de la maturation et de la sécrétion de la proIL-1β en absence de stimulation MDP est détectée dans les macrophages des patients Muckle-Wells. En conclusion, nos études ont démontré que l'inflammasome-NALP3 doit être finement régulé pour éviter une activité incontrôlée qui représente la base moléculaire des symptômes associés aux syndromes auto-inflammatoires liés à NALP3. Summary Five years ago, the description of the NALP family originated from the discovery of a new death-domain fold family, the PYD domain. NALP contains aprotein-protein interaction domain (PYD), an oligomerization domain (NACHT) and a ligand-sensing domain, leucine rich repeats or LRR. This protein architecture shares similarity with receptors involved in immunity, such as NODS, Toll receptors (TLRs) and related plant resistance proteins, and points to an important role of NALPs in defense mechanisms. We first described the minimal complex involved in the pro-inflammatory Interleukin-1beta (IL-1β) cytokine maturation, called the inflammasome, which contains NALP3. In contrast to NALP1, NALP3, like other members of the NALP family, is devoid of C-terminal FIIND and CARD domains and does not interact with the pro-inflammatory caspase-5. Interestingly, a homolog of the C-terminal portion of NALP1 was found in the human genome and was named Cardinal. We found that NALP2 and NALP3 interact with the CARD-containing proteins Cardinal. Cardinal is able to bind to caspase-1 but is not required for IL-1β maturation through NALP3 activation, as demonstrated for the adaptor ASC. Secondly, our study focused on the stimuli involved in the activation of the NALP3 inflammasome. MDP was shown to induce the expression of proIL1β through NOD2 and then the maturation into active IL-1β by activation of the NALP3 inflammasome. However, in the monocytic THP1 cell line, secretion of IL-1β upon MDP stimulation seems to be independent of the inflammasome activation compared to human primary monocytes. This difference might be linked to a Cardinal-interacting protein, filamin. Until now, the role of Cardinal and filamin is still unknown and remains to be elucidated. Finally, mutations in the NALP3/cryopyrin/CIAS1 gene are associated with three autoinflammatory diseases: Muckle-Wells syndrome, familial cold autoinflammatory syndrome, and CINCA. Constitutive, elevated IL-1β maturation and secretion, even in the absence of MDP stimulation, was observed in macrophages from Muckle-Wells patients and confirmed a key role for the NALP3 inflammasome in innate immunity In conclusion, our studies describes the formation of the NALP3 inflammasome and suggests that this complex has to be tightly regulated to avoid an increased deregulated inflammasome activity that is the molecular basis for the symptoms associated with NALP3-dependent autoinflammatory disorders.

Loss of interactions with ants under cold climate in a regional myrmecophilous butterfly fauna

Aim Specialized mutualistic clades may revert and thus increase their autonomy and generalist characteristics. However, our understanding of the drivers that trigger reductions in mutualistic traits and of the consequences for the tolerance of these species to various environmental conditions remains limited. This study investigates the relationship between the environmental niche and the degree of myrmecophily (i.e. the ability to interact with ants) among members of the Lycaenidae. Location The western Swiss Alps. Methods We measured the tolerance of Lycaenidae species to low temperatures by comparing observations from a random stratified field sampling with climatic maps. We then compared the species-specific degree of myrmecophily with the species range limits at colder temperatures while controlling for phylogenetic dependence. We further evaluated whether the community-averaged degree of myrmecophily increases with temperature, as would be expected in the case of environmental filters acting on myrmecophilous species. Results Twenty-nine Lycaenidae species were found during sampling. Ancestral state reconstruction indicated that the 24 species of Polyommatinae displayed both strong myrmecophily and secondary loss of mutualism; these species were used in the subsequent statistical analyses. Species with a higher degree of ant interaction were, on average, more likely to inhabit warmer sites. Species inhabiting the coldest environments displayed little or no interaction with ants. Main conclusions Colder climates at high elevations filter out species with a high degree of myrmecophily and may have been the direct evolutionary force that promoted the loss of mutualism. A larger taxon sampling across the Holarctic may help to distinguish between the ecological and evolutionary effects of climate.

Nouvelles thérapies pour les maladies osseuses de l'enfant [New therapies for children affected by bone diseases].

Considerable progress has been achieved in recent years in treating children affected by bone diseases. Advances in the understanding of the molecular pathophysiology of genetic bone diseases have led to the development of enzyme replacement therapies for various lysosomal storage diseases, following the breakthrough initiated in treating Gaucher disease. Clinical studies are underway with tailored molecules correcting bone fragility and alleviating chronic bone pain and other manifestations of hypophosphatasia, or promoting growth of long bones in achondroplasia patients. We further report our very encouraging experience with intravenous bisphosphonate treatment in children suffering from secondary osteopenia and the high prevalence of calcium and vitamin D deficits in these severely disabled children.

Alterations of bone microarchitecture in young patients with inflammatory bowel diseases are associated with fracture risk during growth

Aims: Inflammatory bowel diseases (IBD) appearing during childhood and adolescence compromise peak bone mass acquisition and increase fracture risk. The structural determinants of bone fragility in IBD however remain unknown. Methods: We investigated volumetric bone mineral density (vBMD), trabecular and cortical bone microstructure at distal radius and tibia by high-resolution pQCT (XtremeCT, Scanco, Switzerland), aBMD at distal radius, hip and spine and vertebral fracture assessment (VFA) by DXA in 107 young patients (mean age 22.8 yrs, range 12.2-33.7 yrs; 62 females and 45 males) with Crohn's disease (n=75), ulcerative colitis (n=25), undetermined colitis (n=2), and no definitive diagnosis (n=5), and in 389 healthy young individuals. Results: Mean disease duration was 6.1 yrs, 89/107 IBD patients received corticosteroids, 83 other immunomodulators, and 59 vitamin D. Clinical fractures were reported by 38 patients (mean age at 1st fracture, 12.6 yrs), the vast majority of the forearm, arm or hand; 5 had vertebral crush fractures (Grade 1 or 2) and 11 had multiple fractures. As compared to healthy controls (matched 2:1 for age, sex, height and fracture history), the 102 patients with established IBD had similar weight but significantly lower aBMD at all sites, lower trabecular (Tb) BV/TV and number, and greater Tb separation and inhomogeneous Tb distribution (1/SD TbN) at both distal radius and tibia, lower tibia cortical thickness (CTh), but no differences in cortical vBMD nor bone perimeter. Among IBD's, aBMD was not associated with fractures (by logistic regression adjusted for age, age square, sex, height, weight and protein intake). However, radius and tibia Tb BV/TV, thickness and SD 1/TbN, as well as radius Tb separation and perimeter, were significantly associated with fracture risk (fully adjusted as above), whereas cortical vBMD and CTh were not. After adjustment for aBMD at radius, respectively at femur neck, radius SD 1/TbN and tibia BV/TV, TbTh and perimeter remained independently associated with fracture risk. Conclusions: Young subjects with IBD have low bone mass and poor bone microarchitecture compared to healthy controls. Alterations of bone microarchitecture, particularly in the trabecular bone compartment, are specifically associated with increased fracture risk during growth.

Genetic Variations and Diseases in UniProtKB/Swiss-Prot: The Ins and Outs of Expert Manual Curation.

During the last few years, next-generation sequencing (NGS) technologies have accelerated the detection of genetic variants resulting in the rapid discovery of new disease-associated genes. However, the wealth of variation data made available by NGS alone is not sufficient to understand the mechanisms underlying disease pathogenesis and manifestation. Multidisciplinary approaches combining sequence and clinical data with prior biological knowledge are needed to unravel the role of genetic variants in human health and disease. In this context, it is crucial that these data are linked, organized, and made readily available through reliable online resources. The Swiss-Prot section of the Universal Protein Knowledgebase (UniProtKB/Swiss-Prot) provides the scientific community with a collection of information on protein functions, interactions, biological pathways, as well as human genetic diseases and variants, all manually reviewed by experts. In this article, we present an overview of the information content of UniProtKB/Swiss-Prot to show how this knowledgebase can support researchers in the elucidation of the mechanisms leading from a molecular defect to a disease phenotype.

Application of the 2008 definitions for invasive fungal diseases to the trial comparing voriconazole versus amphotericin B for therapy of invasive aspergillosis: a collaborative study of the Mycoses Study Group (MSG 05) and the European Organization for Research and Treatment of Cancer Infectious Diseases Group.

BACKGROUND: Strict definition of invasive aspergillosis (IA) cases is required to allow precise conclusions about the efficacy of antifungal therapy. The Global Comparative Aspergillus Study (GCAS) compared voriconazole to amphotericin B (AmB) deoxycholate for the primary therapy of IA. Because predefined definitions used for this trial were substantially different from the consensus definitions proposed by the European Organization for Research and Treatment of Cancer/Mycoses Study Group in 2008, we recategorized the 379 episodes of the GCAS according to the later definitions. METHODS: The objectives were to assess the impact of the current definitions on the classification of the episodes and to provide comparative efficacy for probable/proven and possible IA in patients treated with either voriconazole or AmB. In addition to original data, we integrated the results of baseline galactomannan serum levels obtained from 249 (65.7%) frozen samples. The original response assessment was accepted unchanged. RESULTS: Recategorization allowed 59 proven, 178 probable, and 106 possible IA cases to be identified. A higher favorable 12-week response rate was obtained with voriconazole (54.7%) than with AmB (29.9%) (P < .0001). Survival was higher for voriconazole for mycologically documented (probable/proven) IA (70.2%) than with AmB (54.9%) (P = .010). Higher response rates were obtained in possible IA treated with voriconazole vs AmB with the same magnitude of difference (26.2%; 95% confidence interval [CI], 7.2%-45.3%) as in mycologically documented episodes (24.3%; 95% CI, 11.9%-36.7%), suggesting that possible cases are true IA. CONCLUSIONS: Recategorization resulted in a better identification of the episodes and confirmed the higher efficacy of voriconazole over AmB deoxycholate in mycologically documented IA.

Estimating uncertainty of alcohol-attributable fractions for infectious and chronic diseases.

Background: Alcohol is a major risk factor for burden of disease and injuries globally. This paper presents a systematic method to compute the 95% confidence intervals of alcohol-attributable fractions (AAFs) with exposure and risk relations stemming from different sources.Methods: The computation was based on previous work done on modelling drinking prevalence using the gamma distribution and the inherent properties of this distribution. The Monte Carlo approach was applied to derive the variance for each AAF by generating random sets of all the parameters. A large number of random samples were thus created for each AAF to estimate variances. The derivation of the distributions of the different parameters is presented as well as sensitivity analyses which give an estimation of the number of samples required to determine the variance with predetermined precision, and to determine which parameter had the most impact on the variance of the AAFs.Results: The analysis of the five Asian regions showed that 150 000 samples gave a sufficiently accurate estimation of the 95% confidence intervals for each disease. The relative risk functions accounted for most of the variance in the majority of cases.Conclusions: Within reasonable computation time, the method yielded very accurate values for variances of AAFs.