Anaphylaxis: Mediators, Biomarkers, and Microenvironments.

The life-threatening nature of anaphylactic reactions has increased interest in discovering new biomarkers that could improve diagnosis and prevention. However, the diverse nature of the clinical features and the etiology and pathogenesis of anaphylaxis hinder the identification of valuable molecular indicators of disease. Most studies on anaphylaxis focus on the immune system. Anaphylactic reactions are characterized primarily by IgE-mediated activation of mast cells and basophils and release of mediators. Determination of serum tryptase levels is the main in vitro test used to confirm the reaction, although there are no biomarkers that can predict it. Nevertheless, recent research has postulated that alternative pathways, cell types, and systems are involved. Consequently, various molecular products have been explored and considered potential biomarkers, although none of them are yet used in clinical practice. The products that are altered in patients with anaphylaxis include vasoactive agents, proteases, proteoglycans, lipids, interleukins, cytokines, products of the complement-contact and coagulation systems, circulating proteins, extracellular vesicles, microRNAs, and metabolites. The recognition of biological processes and molecular pathways affecting the microenvironments involved in anaphylaxis will considerably improve clinical practice and the identification of better molecular markers. We offer a broad review of the various mediators described in anaphylaxis, consider their usefulness as potential biomarkers of this pathological event, and examine their role in the molecular basis of the reaction.

Allergen Profile of London Plane Tree Pollen: Clinical and Molecular Pattern in Central Spain.

BACKGROUND AND OBJECTIVES: Platanus acerifolia (London plane tree) is a deciduous tree of the Platanaceae family. Sensitization to this plant varies with geography. Madrid, located in central Spain, has one of the highest London plane tree pollen concentration levels on the Iberian Peninsula. We evaluated both the clinical characteristics and the molecular sensitization pattern of patients with allergy to London plane tree pollen in the region of Madrid. METHODS: Thirty-eight patients allergic to London plane tree pollen were selected according to their clinical symptoms and positive results in skin prick testing and/or specific IgE determination. Serum was collected, and allergen components were evaluated using immunodetection techniques as well as ImmunoCAP. The IgE-binding proteins detected were identified and characterized using mass spectrometry. RESULTS: Analysis of serum samples from allergic patients revealed 9 IgE-binding bands in London plane tree pollen extract. Among these, the 45-kDa protein, which corresponded to Pla a 2, was detected in 76.3% of patients. However, the 18-kDa (Pla a 1) and 9-kDa (Pla a 3) bands were detected in 44.7% and 23.7% of sera, respectively. These results were confirmed using purified proteins. Characterization of the allergen revealed the 27-kDa protein to be glutathione-S-transferase. CONCLUSIONS: The molecular profile of patients sensitized to London plane tree pollen differs from that reported in studies from other locations. In the population we studied, the prevalence of Pla a 2 was higher than that of Pla a 1 and Pla a 3. In addition, the minor allergen previously referred to as Pla a 4 was characterized as glutathione-S-transferase.

Apple bagasse as a substrate for the propagation of Patagonian wine yeast biomass.

AIMS: A culture medium based on apple bagasse was designed and tested as a substrate for biomass production of conventional and unconventional native wine yeasts. METHODS AND RESULTS: The physicochemical characterization of the apple bagasse was carried out and its potential utility as a constituent of a complete culture medium for the production of yeast biomass was analysed using the experimental statistical designs. Growth parameters of conventional and nonconventional Patagonian wine yeasts were analysed with Placket-Burman designs and response surface methodology, comparing in each assay the apple bagasse substrate with the commonly used substrate for biomass development, cane molasses. Culture media composition was optimized and models were validated. CONCLUSIONS: This study demonstrates that, both from a nutritional and from an economic point of view, apple bagasse constitutes a more advantageous substrate than cane molasses for the propagation of native yeasts from Patagonia. SIGNIFICANCE AND IMPACT OF THE STUDY: We used an alternate carbon-rich material, generously available in our region, originally generated as fruit industrial waste, to transform it into a source of sustainable, economically profitable and environmentally friendly energy resource.

Pliocene-Pleistocene ecological niche evolution shapes the phylogeography of a Mediterranean plant group.

Estimating species ability to adapt to environmental changes is crucial to understand their past and future response to climate change. The Mediterranean Basin has experienced remarkable climatic changes since the Miocene, which have greatly influenced the evolution of the Mediterranean flora. Here, we examine the evolutionary history and biogeographic patterns of two sedge sister species (Carex, Cyperaceae) restricted to the western Mediterranean Basin, but with Pliocene fossil record in central Europe. In particular, we estimated the evolution of climatic niches through time and its influence in lineage differentiation. We carried out a dated phylogenetic-phylogeographic study based on seven DNA regions (nDNA and ptDNA) and fingerprinting data (AFLPs), and modelled ecological niches and species distributions for the Pliocene, Pleistocene and present. Phylogenetic and divergence time analyses revealed that both species form a monophyletic lineage originated in the late Pliocene-early Pleistocene. We detected clear genetic differentiation between both species with distinct genetic clusters in disjunct areas, indicating the predominant role of geographic barriers limiting gene flow. We found a remarkable shift in the climatic requirements between Pliocene and extant populations, although the niche seems to have been relatively conserved since the Pleistocene split of both species. This study highlights how an integrative approach combining different data sources and analyses, including fossils, allows solid and robust inferences about the evolutionary history of a plant group since the Pliocene.

Early genetic consequences of defaunation in a large-seeded vertebrate-dispersed palm (Syagrus romanzoffiana).

Plant populations are seriously threatened by anthropogenic habitat disturbance. In particular, defaunation may disrupt plant-disperser mutualisms, thus reducing levels of seed-mediated gene flow and genetic variation in animal-dispersed plants. This may ultimately limit their adaptive potential and ability to cope with environmental change. Tropical forest remnants are typically deprived of medium to large vertebrates upon which many large-seeded plants rely for accomplishing effective seed dispersal. Our main goal was to examine the potential early genetic consequences of the loss of large vertebrates for large-seeded vertebrate-dispersed plants. We compared the genetic variation in early-stage individuals of the large-seeded palm Syagrus romanzoffiana between continuous protected forest and nearby partially defaunated fragments in the Atlantic Forest of South America. Using nine microsatellites, we found lower allelic richness and stronger fine-scale spatial genetic structure in the disturbed area. In addition, the percentage of dispersed recruits around conspecific adults was lower, although not significantly, in the disturbed area (median values: 0.0 vs 14.4%). On the other hand, no evidence of increased inbreeding or reduced pollen-mediated gene flow (selfing rate and diversity of pollen donors) was found in the disturbed area. Our findings are strongly suggestive of some early genetic consequences resulting from the limitation in contemporary gene flow via seeds, but not pollen, in defaunated areas. Plant-disperser mutualisms involving medium-large frugivores, which are seriously threatened in tropical systems, should therefore be protected to warrant the maintenance of seed-mediated gene flow and genetic diversity in large-seeded plants.

Environmental assessment of potential toxic trace element contents in the inundated floodplain area of Tablas de Daimiel wetland (Spain).

Contamination of aquatic systems with potentially toxic trace elements (PTEs) is a major problem throughout the world. The National Park Tablas de Daimiel (NPTD) is considered to make up one of the two most important wetlands in the Biosphere Reserve called "Wet Spot." Since PTEs are good indicator of the prevailing environmental conditions and possible contamination, soil samples collected from 43 sites were analyzed in order to investigate the levels and its distribution of these elements, in the inundated floodplain area of the NPTD wetland. In addition, some physicochemical parameters such as pH, electrical conductivity and organic matter were measured. The total concentrations of 32 trace elements were determined by X-ray fluorescence. The results show that there was accumulation of lead (Pb), tin (Sn), selenium (Se), antimony (Sb), copper (Cu), vanadium (V), nickel (Ni), zinc (Zn), arsenic (As), strontium (Sr) and zirconium (Zr)-in some cases at high concentrations. The interpolated maps showed that the distributions of some of these elements and in some cases the trend in spatial variability are pronounced and decrease from the inlet to the outlet. The values for some elements are higher than the reference values, which is consistent with contamination (some values are higher by a factor of more than 10 compared to the reference). In the case of iodine (I), the levels at some sample points are significantly more than ten times the reference; Se appears in the range from 1.0 to 9.8 mg/kg, with an average value of 3.1 mg/kg, and these can be considered as seleniferous soils. The concentrations found are consistent with the introduction in the wetland of pollution by human activities, such as agricultural non-point sources, uncontrolled fertilization over many years, treatment with urban wastewater and other possible sources.

Determination of fatty acid profile in ram spermatozoa and seminal plasma.

Fatty acids are important in male reproductive function because they are associated with membrane fluidity, acrosome reaction, sperm motility and viability, but limited information exists about the fatty acid profile of ram semen. Our aim was to determine the fatty acid composition in ram spermatozoa and seminal plasma. Sixty ejaculates were obtained from three ram (20 ejaculates/ram) using artificial vagina. Ram spermatozoa (RS) and seminal plasma (SP) were separated using centrifugation, and the fatty acids were analysed by gas chromatography. Total lipids obtained in ram spermatozoa were 1.8% and 1.6% in seminal plasma. Saturated fatty acid (SFA) was proportionally major in SP (66.6%) that RS (49.9%). The highest proportions of SFA corresponded to C4:0 (RS = 16.3% and SP = 28.8%) and C16:0 (RS = 16.3% and PS = 20%). The most important unsaturated fatty acid (UFA) was docosahexaenoic acid (DHA), 44.9% in RS and 31.5% in SP. The profile of fatty acid and their proportions showed differences between spermatozoa and seminal plasma.

Assessment of aortitis by semiquantitative analysis of 180-min 18F-FDG PET/CT acquisition images.

PURPOSE: The aim of this study was to evaluate the contribution of semiquantitative analysis of 180-min (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT images for the assessment of aortitis in cases of suspected large vessel vasculitis (LVV) and to establish a threshold index for application in the clinical setting. METHODS: This prospective study included 43 patients (mean age 67.5 ± 12.9 years) with suspicion of LVV (25 with a final diagnosis of aortitis). (18)F-FDG PET/CT scan was acquired 180 min after injection of 7 MBq/kg of (18)F-FDG. A semiquantitative analysis was performed calculating the aortic wall maximum standardized uptake value (SUVmax) (T), the lumen SUVmax (B) and the target to background ratio (TBR). These results were also compared with those obtained in a control population. RESULTS: The mean aortic wall SUVmax was 2.00 ± 0.62 for patients with aortitis and 1.45 ± 0.31 for patients without aortitis (p < 0.0001). The TBR was 1.66 ± 0.26 for patients with aortitis and 1.24 ± 0.08 for patients without aortitis (p < 0.0001). The differences were also statistically significant when the patients with aortitis and controls were compared. Receiver-operating characteristic (ROC) analysis revealed that the area under the curve was greater for the TBR than for the aortic wall SUVmax (0.997 vs 0.871). The highest sensitivity and specificity was obtained for a TBR of 1.34 (sensitivity 100%, specificity 94.4%). CONCLUSION: Semiquantitative analysis of PET/CT images acquired 180 min after (18)F-FDG injection and the TBR index of 1.34 show very high accuracy and, therefore, are strongly recommended for the diagnosis of aortitis in the clinical setting.

Deltamethrin resistance in the sea louse Caligus rogercresseyi (Boxhall and Bravo) in Chile: bioassay results and usage data for antiparasitic agents with references to Norwegian conditions.

The sea louse Caligus rogercresseyi is a major threat to Chilean salmonid farming. Pyrethroids have been used for anticaligus treatments since 2007, but have shown reduced effect, most likely due to resistance development. Pyrethroid resistance is also a known problem in Lepeophtheirus salmonis in the Northern Hemisphere. This study describes the development of deltamethrin resistance in C. rogercresseyi based on bioassays and usage data for pyrethroids in Chilean aquaculture. These results were compared to bioassays from L. salmonis from Norway and to Norwegian usage data. Available deltamethrin bioassay results from 2007 and 2008, as well as bioassays from Norway, were collected and remodelled. Bioassays were performed on field-collected sea lice in region X in Chile in 2012 and 2013. Bioassays from 2007 were performed prior to the introduction of pyrethroids to the Chilean market. Both the results from 2008 and 2012 showed an increased resistance. Increased pyrethroid resistance was also indicated by the increased use of pyrethroids in Chilean aquaculture compared with the production of salmonids. A similar trend was seen in the Norwegian usage data. The bioassay results from Chile from 2012 and 2013 also indicated a difference in the susceptibility to deltamethrin between male and female caligus.

Efficacy of the treatments used for the control of Caligus rogercresseyi infecting Atlantic salmon, Salmo salar L., in a new fish-farming location in Region XI, Chile.

Caligus rogercresseyi is the most important parasite affecting Atlantic salmon and rainbow trout farming in sea water in Chile. After the outbreaks of the infectious salmon anaemia recorded in Region X from 2007, the salmon industry has expanded southwards to Region XI, where 60% of Atlantic salmon in Chile is now produced. In parallel with the relocation of salmon production, sea lice infestation has also spread to Region XI, and today C. rogercresseyi is the most serious threat to the salmon-farming industry in this region. The results obtained through a year of monitoring between September 2007 and August 2008 on a farm located in the 'Las Guaitecas Archipelago' in Region XI (44°S; 74°W) showed that treatments with emamectin benzoate and deltamethrin did not give the expected control of Caligus. Failures of the treatments were associated with the loss of sensitivity recorded for C. rogercresseyi to emamectin benzoate in Region X. In addition, a major influence was the lack of delousing coordination measures with the neighbouring farms sharing the same area in that period.

Accumulation, distribution pattern and potential contamination of sulphur in vineyard soils of the Valdepeñas protected denomination origin.

Soil is the basis for almost all global agriculture and the medium in which most terrestrial biological activity occurs. Viticulture represents an important agricultural practice in the Castilla-La Mancha (CLM) community. In this region, there are several protected denominations of origin (PDO), the largest being Valdepeñas. This paper describes the accumulation pattern of sulphur (S) in the vineyard soils of this PDO. Samples were collected from 90 vineyard soil profiles. Sulphur content was determined using an X-ray Fluorescence spectrometer in the solid mode on a powdered aliquot of each sample. The results indicated that the total S in soils varied from 0.54 to 6.90 (g·kg-1) in surface soil (0-30 cm) and from 0.39 to 2.80 (g·kg-1) on the subsurface layer (30-80 cm). When comparing the mean values of surface horizons to the subsurface horizons, S content lowered as soil depth increased. Kurtosis exceeded 45 % in all cases, which indicates a wide variability of concentrations. These findings can be explained by the continuous fertiliser and fungicide applications (and therefore S) in these production systems. Using the geoaccumulation index (Igeo), most soils were included in Class 0 (Igeo <0) and were, thus, S uncontaminated; only a few points can be considered pollutants. The obtained results should contribute to extend the scarce existing database on S in Mediterranean regions like that herein studied.

[Evaluation of the research performed in Spanish hospitals]. / Valoración de la investigación que se realiza en los hospitales españoles.

OBJECTIVES: No study that analyzes how the investigators who work in the Spanish hospitals perceived and evaluate the current research system has been performed. This work, carried out by the Scientific Forum of the Lilly Foundation, aims to improve the level of information on the research activity performed in the hospitals. SUBJECTS AND METHODS: By means of a «self-administered¼ interview made up of 34 items and aimed at physicians and other research professionals who work in the Spanish hospitals (272 surveyed), 3 questions were analyzed: a) general situation of biomedical research in Spain; b) administration of available resources: need for better resources, and c) evaluation and giving priority to biomedical research. RESULTS: The use of the data has shown strengths in the system such as the initiatives to promote research through contracts with FIS and post-residency (7.6/10 points); the beneficial effects of research and care quality (7.3/10); or support of the pharmaceutical industry through the sponsoring of clinical trials (6.9/10). However, it has also shown that there are some weaknesses in the organization of the centers, as for example, those referring to the differentiated allocation of the care cost of the research activity (5.1/10); to the coordination between them and the health care centers (2.8/10); to the integration and organization among care, teaching and research (3.6/10); and to decide the priorities (5.2/10) and evaluation (5.2/10) of the research activities. Furthermore, the value of the research as a fundamental activity of the hospitals is emphasized (4.7/10). CONCLUSIONS: The investigators surveyed consider that biomedical research in recent decades in the hospital setting has significantly improved and has had a positive effect in the number of publications. The subjects surveyed consider that research should have greater institutional support and recognition, and a more translational orientation, which would be translated into better quality of life of the citizens and registry of patents.

Epidemiologic trend of pediatric inflammatory bowel disease in Latin America: The Latin American Society for Pediatric Gastroenterology, Hepatology and Nutrition (LASPGHAN) Working Group.

INTRODUCTION AND AIMS: The primary aim was to explore the epidemiologic trend of pediatric inflammatory bowel disease in Latin America, and the secondary aims were to obtain an overview of the diagnostic/therapeutic focus of the members of the LASPGHAN and examine the relation of case frequency to year, during the study period. MATERIALS AND METHODS: Latin American pediatric gastroenterologists participated in an online survey, conducted through the SurveyMonkey platform, that investigated the yearly frequency of new inflammatory bowel disease patients within the time frame of 2005-2016, their disease variety, the gastrointestinal segments affected, and the diagnostic and treatment methods utilized. The correlation of new case frequency with each study year was evaluated. RESULTS: A total of 607 patients were studied. The diagnoses were ulcerative colitis in 475 (78.3%) cases, Crohn's disease in 104 (17.1%), and inflammatory bowel disease D unclassified in 28 (4.6%). The trend in ulcerative colitis was a lineal increase in the frequency of new cases related to each study year, with a significant correlation coefficient. Pancolitis was found in 67.6% of the patients. The diagnostic methods included clinical data, endoscopy, and biopsies in more than 99% of the cases, and imaging studies were indicated selectively. Drug regimens were limited to 5-aminosalicylic acid derivatives, azathioprine, 6-mercaptopurine, infliximab, and adalimumab. CONCLUSIONS: Pediatric inflammatory bowel disease in Latin America appears to have increased during the years included in the study period, with a predominance of moderate or severe ulcerative colitis. That lineal trend suggests the predictive likelihood of a gradual increase in the coming years, with possible epidemiologic and clinical implications.

[Implementation of the Lean Six Sigma in the improvement of the medication dispensing circuit]. / Implementación Lean Six Sigma en la mejora del circuito de dispensación de medicación.

OBJECTIVE: Lean Six Sigma (LSS) methodology is used to increase productivity and to improve performance, by eliminating processes that do not add value to the customer, as well as reducing variability. In recent years, its application in healthcare sector is increasing in order to improve the efficiency of processes. The aim of this study was to evaluate the results obtained in terms of efficiency in the medication dispensing circuit, after application of LSS methodology. MATERIAL AND METHODS: A multidisciplinary team was created in order to analyse and improve the medication dispensing circuit. The main tools used in LSS methodology were the DMAIC cycle (Define, Measure, Analyse, Improve and Control), SIPOC diagram (Suppliers, Inputs, Process, Outputs, and Customers), a root-cause analysis; a survey to determine the "Customer's voice" about the circuit; and the cost of each task in terms of staff time. Two Pilot Nursing Units (Thoracic Surgery and Cardiology) were selected to introduce the improvement actions. The main analysed variables were: urgent medication orders per day, and percentage of medication orders made online. RESULTS: After the application of LSS methodology, a significant reduction was found in urgent medicament orders per day in both nursing units, and a significant improvement in the electronic processing of urgent orders. The performance of medication dispensing circuit was increased from 60% (1.76 sigma) during initial data analysis, to 93% (3 sigma) in Thoracic Surgery, and from 71% (2.11 sigma) to 81% (2.4 sigma) in Cardiology. Six months after the implementation of improvements, the performance values were increased to 94% (3.1 sigma) and 93% (3 sigma), respectively. Estimated cost savings related to staff were 798.2 € (266 € per month) after implementation, ascending to 2, 228.5 € (371.4 € per month) after 6months. CONCLUSION: The use of LSS methodology has improved the performance of medication dispensing circuits, reducing costs in terms of staff time, and obtaining satisfactory results.