Definitions, Criteria and Global Classification of Mast Cell Disorders with Special Reference to Mast Cell Activation Syndromes: A Consensus Proposal

Activation of tissue mast cells (MCs) and their abnormal growth and accumulation in various organs are typically found in primary MC disorders also referred to as mastocytosis. However, increasing numbers of patients are now being informed that their clinical findings are due to MC activation (MCA) that is neither associated with mastocytosis nor with a defined allergic or inflammatory reaction. In other patients with MCA, MCs appear to be clonal cells, but criteria for diagnosing mastocytosis are not met. A working conference was organized in 2010 with the aim to define criteria for diagnosing MCA and related disorders, and to propose a global unifying classification of all MC disorders and pathologic MC reactions. This classification includes three types of `MCA syndromes' (MCASs), namely primary MCAS, secondary MCAS and idiopathic MCAS. MCA is now defined by robust and generally applicable criteria, including (1) typical clinical symptoms, (2) a substantial transient increase in serum total tryptase level or an increase in other MC-derived mediators, such as histamine or prostaglandin D 2, or their urinary metabolites, and (3) a response of clinical symptoms to agents that attenuate the production or activities of MC mediators. These criteria should assist in the identification and diagnosis of patients with MCAS, and in avoiding misdiagnoses or overinterpretation of clinical symptoms in daily practice. Moreover, the MCAS concept should stimulate research in order to identify and exploit new molecular mechanisms and therapeutic targets. Copyright (C) 2011 S. Karger AG, Base

A PSTOL-like gene, TaPSTOL, controls a number of agronomically important traits in wheat

Background Phosphorus (P) is an essential macronutrient for plant growth, and is required in large quantities by elite varieties of crops to maintain yields. Approximately 70% of global cultivated land suffers from P deficiency, and it has recently been estimated that worldwide P resources will be exhausted by the end of this century, increasing the demand for crops more efficient in their P usage. A greater understanding of how plants are able to maintain yield with lower P inputs is, therefore, highly desirable to both breeders and farmers. Here, we clone the wheat (Triticum aestivum L.) homologue of the rice PSTOL gene (OsPSTOL), and characterize its role in phosphate nutrition plus other agronomically important traits. Results TaPSTOL is a single copy gene located on the short arm of chromosome 5A, encoding a putative kinase protein, and shares a high level of sequence similarity to OsPSTOL. We re-sequenced TaPSTOL from 24 different wheat accessions and (3) three T. durum varieties. No sequence differences were detected in 26 of the accessions, whereas two indels were identified in the promoter region of one of the durum wheats. We characterised the expression of TaPSTOL under different P concentrations and demonstrated that the promoter was induced in root tips and hairs under P limiting conditions. Overexpression and RNAi silencing of TaPSTOL in transgenic wheat lines showed that there was a significant effect upon root biomass, flowering time independent of P treatment, tiller number and seed yield, correlating with the expression of TaPSTOL. However this did not increase PUE as elevated P concentration in the grain did not correspond to increased yields. Conclusions Manipulation of TaPSTOL expression in wheat shows it is responsible for many of the previously described phenotypic advantages as OsPSTOL except yield. Furthermore, we show TaPSTOL contributes to additional agronomically important traits including flowering time and grain size. Analysis of TaPSTOL sequences from a broad selection of wheat varieties, encompassing 91% of the genetic diversity in UK bread wheat, showed that there is very little genetic variation in this gene, which would suggest that this locus may have been under high selection pressure

An average/deprivation/inequality (ADI) analysis of chronic disease outcomes and risk factors in Argentina

<p>Abstract</p> <p>Background</p> <p>Recognition of the global economic and epidemiological burden of chronic non-communicable diseases has increased in recent years. However, much of the research on this issue remains focused on individual-level risk factors and neglects the underlying social patterning of risk factors and disease outcomes.</p> <p>Methods</p> <p>Secondary analysis of Argentina's 2005 <it>Encuesta Nacional de Factores de Riesgo </it>(National Risk Factor Survey, <it>N </it>= 41,392) using a novel analytical strategy first proposed by the United Nations Development Programme (UNDP), which we here refer to as the Average/Deprivation/Inequality (ADI) framework. The analysis focuses on two risk factors (unhealthy diet and obesity) and one related disease outcome (diabetes), a notable health concern in Latin America. Logistic regression is used to examine the interplay between socioeconomic and demographic factors. The ADI analysis then uses the results from the logistic regression to identify the most deprived, the best-off, and the difference between the two ideal types.</p> <p>Results</p> <p>Overall, 19.9% of the sample reported being in poor/fair health, 35.3% reported not eating any fruits or vegetables in five days of the week preceding the interview, 14.7% had a BMI of 30 or greater, and 8.5% indicated that a health professional had told them that they have diabetes or high blood pressure. However, significant variation is hidden by these summary measures. Educational attainment displayed the strongest explanatory power throughout the models, followed by household income, with both factors highlighting the social patterning of risk factors and disease outcomes. As educational attainment and household income increase, the probability of poor health, unhealthy diet, obesity, and diabetes decrease. The analyses also point toward important provincial effects and reinforce the notion that both compositional factors (i.e., characteristics of individuals) and contextual factors (i.e., characteristics of places) are important in understanding the social patterning of chronic diseases.</p> <p>Conclusion</p> <p>The application of the ADI framework enables identification of the regions or groups worst-off for each outcome measure under study. This can be used to highlight the variation embedded within national averages; as such, it encourages a social perspective on population health indicators that is particularly attuned to issues of inequity. The ADI framework is an important tool in the evaluation of policies aiming to prevent or control chronic non-communicable diseases.</p

Pemphigus autoimmunity: Hypotheses and realities

The goal of contemporary research in pemphigus vulgaris and pemphigus foliaceus is to achieve and maintain clinical remission without corticosteroids. Recent advances of knowledge on pemphigus autoimmunity scrutinize old dogmas, resolve controversies, and open novel perspectives for treatment. Elucidation of intimate mechanisms of keratinocyte detachment and death in pemphigus has challenged the monopathogenic explanation of disease immunopathology. Over 50 organ-specific and non-organ-specific antigens can be targeted by pemphigus autoimmunity, including desmosomal cadherins and other adhesion molecules, PERP cholinergic and other cell membrane (CM) receptors, and mitochondrial proteins. The initial insult is sustained by the autoantibodies to the cell membrane receptor antigens triggering the intracellular signaling by Src, epidermal growth factor receptor kinase, protein kinases A and C, phospholipase C, mTOR, p38 MAPK, JNK, other tyrosine kinases, and calmodulin that cause basal cell shrinkage and ripping desmosomes off the CM. Autoantibodies synergize with effectors of apoptotic and oncotic pathways, serine proteases, and inflammatory cytokines to overcome the natural resistance and activate the cell death program in keratinocytes. The process of keratinocyte shrinkage/detachment and death via apoptosis/oncosis has been termed apoptolysis to emphasize that it is triggered by the same signal effectors and mediated by the same cell death enzymes. The natural course of pemphigus has improved due to a substantial progress in developing of the steroid-sparing therapies combining the immunosuppressive and direct anti-acantholytic effects. Further elucidation of the molecular mechanisms mediating immune dysregulation and apoptolysis in pemphigus should improve our understanding of disease pathogenesis and facilitate development of steroid-free treatment of patients

The desmosome and pemphigus

Desmosomes are patch-like intercellular adhering junctions (“maculae adherentes”), which, in concert with the related adherens junctions, provide the mechanical strength to intercellular adhesion. Therefore, it is not surprising that desmosomes are abundant in tissues subjected to significant mechanical stress such as stratified epithelia and myocardium. Desmosomal adhesion is based on the Ca2+-dependent, homo- and heterophilic transinteraction of cadherin-type adhesion molecules. Desmosomal cadherins are anchored to the intermediate filament cytoskeleton by adaptor proteins of the armadillo and plakin families. Desmosomes are dynamic structures subjected to regulation and are therefore targets of signalling pathways, which control their molecular composition and adhesive properties. Moreover, evidence is emerging that desmosomal components themselves take part in outside-in signalling under physiologic and pathologic conditions. Disturbed desmosomal adhesion contributes to the pathogenesis of a number of diseases such as pemphigus, which is caused by autoantibodies against desmosomal cadherins. Beside pemphigus, desmosome-associated diseases are caused by other mechanisms such as genetic defects or bacterial toxins. Because most of these diseases affect the skin, desmosomes are interesting not only for cell biologists who are inspired by their complex structure and molecular composition, but also for clinical physicians who are confronted with patients suffering from severe blistering skin diseases such as pemphigus. To develop disease-specific therapeutic approaches, more insights into the molecular composition and regulation of desmosomes are required

Associations of sedentary behavior and physical activity with psychological distress: a cross-sectional study from Singapore

Background: Emerging evidence suggests the adverse association between sedentary behavior (SB) and physical with mental health, but few studies have investigated the relationship between volume of physical activity and psychological distress. The present study examined the independent and interactive associations of daily SB and weekly level of moderate to vigorous physical activity (MVPA) with psychological distress in a multi-ethnic Asian population. Methods. De-identified data of 4,337 adults (18-79 years old) on sedentary behaviors, physical activity patterns, psychological distresses, and other relevant variables were obtained from the Singapore Ministry of Health's 2010 National Health Survey. Psychological distress was assessed using General Health Questionnaire-12 (GHQ-12), whereas total daily SB and total weekly volume (MET/minutes) of MVPA were estimated using the Global Physical Activity Questionnaire version 2 (GPAQ v2). Multivariate logistic regression analyses were carried out to estimate the odds ratios (95% confidence intervals) of the independent and interactive relationships of SB and MVPA with prevalence of psychological distress. Results: The category of high SB was positively associated with increased odds (OR = 1.29, 1.04-1.59) for psychological distress, whereas the category of active was inversely associated with lower odds (OR = 0.73, 0.62-0.86) for psychological distress. Multivariate analyses for psychological distress by combined daily SB and weekly MVPA levels showed inverse associations between middle SB and active categories (OR = 0.58, 0.45 - 0.74) along with low SB and active categories (OR = 0.61, 0.47-0.80). Conclusions: The present population-based cross-sectional study indicated that in the multi-ethnic Asian society of Singapore, a high level of SB was independently associated with psychological distress and meeting the recommended guidelines for physical activity along with ≤ 5 h/day of SB was associated with the lowest odds of psychological distress

Malaria vector species in Colombia: a review

Here we present a comprehensive review of the literature on the vectorial importance of the major Anopheles malaria vectors in Colombia. We provide basic information on the geographical distribution, altitudinal range, immature habitats, adult behaviour, feeding preferences and anthropophily, endophily and infectivity rates. We additionally review information on the life cycle, longevity and population fluctuation of Colombian Anopheles species. Emphasis was placed on the primary vectors that have been epidemiologically incriminated in malaria transmission: Anopheles darlingi, Anopheles albimanus and Anopheles nuneztovari. The role of a selection of local, regional or secondary vectors (e.g., Anopheles pseudopunctipennis and Anopheles neivai) is also discussed. We highlight the importance of combining biological, morphological and molecular data for the correct taxonomical determination of a given species, particularly for members of the species complexes. We likewise emphasise the importance of studying the bionomics of primary and secondary vectors along with an examination of the local conditions affecting the transmission of malaria. The presence and spread of the major vectors and the emergence of secondary species capable of transmitting human Plasmodia are of great interest. When selecting control measures, the anopheline diversity in the region must be considered. Variation in macroclimate conditions over a species' geographical range must be well understood and targeted to plan effective control measures based on the population dynamics of the local Anopheles species