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Acute psychological stress (PS) mobilizes metabolic responses that are of immediate benefit to the host, but the current medical paradigm holds that PS exacerbates systemic and cutaneous inflammatory disorders. Although the adverse consequences of PS are usually attributed to neuroimmune mechanisms, PS also stimulates an increase in endogenous glucocorticoids (GCs) that compromises permeability barrier homeostasis, stratum corneum cohesion, wound healing, and epidermal innate immunity in normal skin. Yet, if such PS-induced increases in GC were uniformly harmful, natural selection should have eliminated this component of the stress response. Hence, we hypothesized here instead that stress-induced elevations in endogenous GC could benefit, rather than aggravate, cutaneous function and reduce inflammation in three immunologically diverse mouse models of inflammatory diseases. Indeed, superimposed exogenous (motion-restricted) stress reduced, rather than aggravated inflammation and improved epidermal function in all three models, even normalizing serum IgE levels in the atopic dermatitis model. Elevations in endogenous GC accounted for these apparent benefits, because coadministration of mifepristone prevented stress-induced disease amelioration. Thus, exogenous stress can benefit rather than aggravate cutaneous inflammatory dermatoses through the anti-inflammatory activity of increased endogenous GC.

Humans with darkly pigmented skin display superior permeability barrier function in comparison with humans with lightly pigmented skin. The reduced pH of the stratum corneum (SC) of darkly pigmented skin could account for enhanced function, because acidifying lightly pigmented human SC resets barrier function to darkly pigmented levels. In SKH1 (nonpigmented) versus SKH2/J (pigmented) hairless mice, we evaluated how a pigment-dependent reduction in pH could influence epidermal barrier function. Permeability barrier homeostasis is enhanced in SKH2/J versus SKH1 mice, correlating with a reduced pH in the lower SC that colocalizes with the extrusion of melanin granules. Darkly pigmented human epidermis also shows substantial melanin extrusion in the outer epidermis. Both acute barrier disruption and topical basic pH challenges accelerate reacidification of SKH2/J (but not SKH1) SC, while inducing melanin extrusion. SKH2/J mice also display enhanced expression of the SC acidifying enzyme, secretory phospholipase A2f (sPLA2f). Enhanced barrier function of SKH2/J mice could be attributed to enhanced activity of two acidic pH-dependent, ceramide-generating enzymes, β-glucocerebrosidase and acidic sphingomyelinase, leading to accelerated maturation of SC lamellar bilayers. Finally, organotypic cultures of darkly pigmented human keratinocytes display enhanced barrier function in comparison with lightly pigmented cultures. Together, these results suggest that the superior barrier function of pigmented epidermis can be largely attributed to the pH-lowering impact of melanin persistence/extrusion and enhanced sPLA2f expression. © 2014 The Society for Investigative Dermatology.

In the framework of the Forum for Air Quality Modelling in Europe (FAIRMODE), a modelling intercomparison exercise for computing NO 2 long-term average concentrations in urban districts with a very high spatial resolution was carried out. This exercise was undertaken for a district of Antwerp (Belgium). Air quality data includes data recorded in air quality monitoring stations and 73 passive samplers deployed during one-month period in 2016. The modelling domain was 800 × 800 m 2 . Nine modelling teams participated in this exercise providing results from fifteen different modelling applications based on different kinds of model approaches (CFD - Computational Fluid Dynamics-, Lagrangian, Gaussian, and Artificial Intelligence). Some approaches consisted of models running the complete one-month period on an hourly basis, but most others used a scenario approach, which relies on simulations of scenarios representative of wind conditions combined with post-processing to retrieve a one-month average of NO 2 concentrations. The objective of this study is to evaluate what type of modelling system is better suited to get a good estimate of long-term averages in complex urban districts. This is very important for air quality assessment under the European ambient air quality directives. The time evolution of NO 2 hourly concentrations during a day of relative high pollution was rather well estimated by all models. Relative to high resolution spatial distribution of one-month NO 2 averaged concentrations, Gaussian models were not able to give detailed information, unless they include building data and street-canyon parameterizations. The models that account for complex urban geometries (i.e. CFD, Lagrangian, and AI models) appear to provide better estimates of the spatial distribution of one-month NO 2 averages concentrations in the urban canopy. Approaches based on steady CFD-RANS (Reynolds Averaged Navier Stokes) model simulations of meteorological scenarios seem to provide good results with similar quality to those obtained with an unsteady one-month period CFD-RANS simulations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Urban air pollution is one of the most important environmental problems for human health and several strategies have been developed for its mitigation. The objective of this study is to assess the impact of single and combined mitigation measures on concentrations of air pollutants emitted by traffic at pedestrian level in the same urban environment. The effectiveness of different scenarios of green infrastructure (GI), the implementation of photocatalytic materials and traffic low emission zones (LEZ) are investigated, as well as several combinations of LEZ and GI. A wide set of scenarios is simulated through Computational Fluid Dynamics (CFD) modelling for two different wind directions (perpendicular (0°) and 45° wind directions). Wind flow for the BASE scenario without any measure implemented was previously evaluated using wind-tunnel measurements. Air pollutant concentrations for this scenario are compared with the results obtained from the different mitigation scenarios. Reduction of traffic emissions through LEZ is found to be the most effective single measure to improve local air quality. However, GI enhances the effects of LEZ, which makes the combination of LEZ + GI a very effective measure. The effectiveness of this combination depends on the GI layout, the intensity of emission reduction in the LEZ and the traffic diversion in streets surrounding the LEZ. These findings, in line with previous literature, suggest that the implementation of GI may increase air pollutant concentrations at pedestrian level for some cases. However, this study highlights that this negative effect on air quality can turn into positive when used in combination with reductions of local traffic emissions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Downy mildew is one of the most destructive diseases affecting grapevines ( Vitis vinifera L.). Caused by the oomycete Plasmopara viticola (Berk. and Curt.) Berl. and de Toni, it can appear anywhere where vines are cultivated. It is habitually controlled by the application of phytosanitary agents (copper-based or systemic) at different stages of the vine growth cycle. This, however, is costly, can lead to reduced yields, has a considerable environmental impact, and its overuse close to harvest can cause fermentation problems. All grapevines are susceptible to this disease, although the degree of susceptibility differs between varieties. Market demands and European legislation on viticulture and the use of phytosanitary agents (art. 14 of Directive 128/2009/EC) now make it important to know the sensitivity of all available varieties, including minority varieties. Such knowledge allows for a more appropriate use of phytosanitary agents, fosters the commercial use of these varieties and thus increases the offer of wines associated with different terroirs , and helps identify material for use in crop improvement programmes via crossing or genetic transformation, etc. Over 2020-2021, the susceptibility to P. viticola of 63 minority vine varieties from different regions of Spain was examined in the laboratory using the leaf disc technique. Some 87% of these varieties were highly susceptible and 11% moderately susceptible; just 2% showed low susceptibility. The least susceptible of all was the variety Morate (Madrid, IMIDRA). Those showing intermediate susceptibility included the varieties Sanguina (Castilla la Mancha, IVICAM), Planta Mula (Comunidad Valenciana, ITVE), Rayada Melonera (Madrid, IMIDRA), Zamarrica (Galicia, EVEGA), Cariñena Roja (Cataluña, INCAVI), Mandrègue (Aragón, DGA) and Bastardo Blanco (Extremadura, CICYTEX). The highly susceptible varieties could be differentiated into three subgroups depending on sporulation severity and density.

Background: A genome-wide association study (GWAS) in kidney transplant recipients reported the association of two polymorphisms located in the PTPRO gene and upstream of the CCDC67 (DEUP1) gene with increased risk of acute T cell-mediated rejection (TCMR). We aimed at replicating the assessment of mentioned associations and additionally ascertaining the influence of treatment and clinical features of the patients., Methods: The polymorphisms, PTPRO-rs7976329 and CCDC67-rs10765602 were genotyped by TaqMan chemistry in 641 consecutive kidney transplant recipients. The diagnosis of rejection was confirmed by biopsy and categorized according to the Banff classification. Associations were evaluated by Chi-square test or Fisher's exact test when necessary and multivariate logistic regression., Results: Considering the GWAS study we only replicated the association of the PTPRO-rs7976329*C allele in the Banff grade < II subjects. However, the homozygous mutant genotypes of both polymorphism seemed to increase the risk of TCMR Banff grade < II in the overall cohort and after stratification by Thymoglobulin induction therapy. In the multivariate analysis, we confirmed the association of PTPRO-rs7976329 with TCMR Banff grade < II, independently of the Thymoglobulin induction therapy and of CCDC67-rs10765602 only in the group of patients not receiving Thymoglobulin induction therapy. No association of these polymorphisms with TCMR Banff grade ≥ II was observed in either the overall cohort or in the subgroups stratified by Thymoglobulin therapy., Conclusions: Our study shows that the increased risk of TCMR related to polymorphisms PTPRO-rs7976329 and CCDC67-rs10765602 previously reported in a GWAS was replicated only in homozygous patients who presented TCMR Banff grade < II and for the minor allele of either polymorphism., (© 2022. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Background: We compared the probability of hospitalization and death caused by COVID-19 in patients with comorbidities during three periods defined for this study: first-wave (FW), interwave period (IP), and second-wave (SW) observed in Mexico City., Methods: In this registry-based study, we included individuals over 20 years of age. During the FW (symptomatic), the IP, and the SW (symptomatic and asymptomatic), participants were diagnosed using nasopharyngeal swabs. Symptomatic individuals with risk factors for serious disease or death were referred to the hospital. SARS-CoV-2 infection was defined by RT-qPCR in all hospitalized patients. All data were added to the SISVER database. Bayesian analysis and False Discovery Rate were used for further evaluation., Results: The study included 2 260 156 persons (mean age of 43.1 years). Of these, 8.6% suffered from DM, 11.6% arterial hypertension, and 9.7% obesity. Of the total, 666 694 persons tested positive (29.5%). Of the infected persons, a total of 85 587 (12.8%) were hospitalized: 24 023 in the FW; 16 935 in the IP, and 44 629 in the SW. Of the hospitalized patients, there were 42 979 deaths (50.2%), in the FW, 11 964 (49.8%), in the IP, 6794 (40.1%), and in the SW 24 221 (54.3%). The probability of death among individuals hospitalized with or without comorbidities increased consistently in all age groups. A significant increase in the Fatality Rate was observed in individuals with comorbidities (1.36E-19< = FDR< = 3.36E-2). A similar trend was also observed in individuals without comorbidities (1.03E-44< = FDR< = 5.58E-4)., Conclusions: The data from this study show a considerable increase in the number of detected cases of infection between the FW and SW. In addition, 12.8% of those infected were hospitalized for severe COVID-19. A high mortality rate was observed among hospitalized patients (>50%). An age-dependent probability of death was observed with a positive trend in hospitalized patients with and without comorbidities., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose no conflicts of interest., (Copyright © 2022 by the Journal of Global Health. All rights reserved.)

Non-melanoma skin cancer has recently seen an increase in prevalence, and it is estimated that this grow will continue in the coming years. In this sense, the importance of therapy effectiveness has increased, especially photodynamic therapy. Photodynamic therapy has attracted much attention as a minimally invasive, selective and repeatable approach for skin cancer treatment and prevention. Although its high efficiency, this strategy has also faced problems related to tumor resistance, where the tumor microenvironment has gained a well-deserved role in recent years. Tumor microenvironment denotes a wide variety of elements, such as cancer-associated fibroblasts, immune cells, endothelial cells or the extracellular matrix, where their interaction and the secretion of a wide diversity of cytokines. Therefore, the need of designing new strategies targeting elements of the tumor microenvironment to overcome the observed resistance has become evident. To this end, in this review we focus on the role of cancer-associated fibroblasts and tumor-associated macrophages in the resistance to photodynamic therapy. We are also exploring new approaches consisting in the combination of new and old drugs targeting these cells with photodynamic therapy to enhance treatment outcomes of non-melanoma skin cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cerro, Mascaraque, Gallego-Rentero, Almenara-Blasco, Nicolás-Morala, Santiago, González, Gracia-Cazaña, Juarranz and Gilaberte.)

This paper introduces a new method of compressing digital images by using the Difference Transform applied in medical imaging. The Difference Transform algorithm performs the decorrelation process of image data, and in this way improves the encoding process, achieving a file with a smaller size than the original. The proposed method proves to be competitive and in many cases better than the standards used for medical images such as TIFF or PNG. In addition, the Difference Transform can replace other transforms like Cosine or Wavelet.

Health impacts of atmospheric pollution is an important issue in urban environments. Its magnitude depends on population exposure which have been frequently estimated by considering different approaches relating pollutant concentration and population exposed to it. However, the uncertainties due to the spatial resolution of the model used to estimate the pollutant concentration or due to the lack of representativeness of urban air quality monitoring station (AQMS) have not been evaluated in detail. In this context, NO 2 annual average concentration at pedestrian level in the whole city of Pamplona (Spain) modelled at high spatial resolution (~1 m) by Computational Fluid Dynamic (CFD) simulations is used to estimate the total population exposure and health-related externalities by using different approaches. Air pollutant concentration and population are aggregated at different spatial resolutions ranging from a horizontal grid cell size of 100 m × 100 m to a coarser resolution where the whole city is covered by only one cell (6 km × 5 km). In addition, concentrations at AQMS locations are also extracted to assess the representativeness of those AQMS. The case with a spatial resolution of 100 m × 100 m for both pollutant-concentration distribution and population data is used as a reference (Base case) and compared with those obtained with the other approaches. This study indicates that the spatial resolution of concentration and population distribution in the city should be 1 km × 1 km or finer to obtain appropriate estimates of total population exposure (underestimations <13%) and health-related externalities (underestimations <37%). For the cases with coarser resolutions, a strong underestimation of total population exposure (>31%) and health-related externalities (>76%) was found. On the other hand, the use of AQMS concentrations can induce important errors due to the limited spatial representativeness, in particular in terms of population exposure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The COVID-19 pandemic has caused an exponential increase in the demand for medical care worldwide. In Mexico, the COVID Medical Units (CMUs) conversion strategy was implemented., Objective: To evaluate the CMU coverage strategy in the Mexico City Metropolitan Area (MCMA) by territory., Materials: The CMU directory was used, as were COVID-19 infection and mobility statistics and Mexican 2020 census information at the urban geographic area scale. The degree of urban marginalization by geographic area was also considered., Method: Using descriptive statistics and the calculation of a CMU accessibility index, population aggregates were counted based on coverage radii. In addition, two regression models are proposed to explain (1) the territorial and temporal trend of COVID-19 infections in the MCMA and (2) the mobility of the COVID-infected population visiting medical units., Results: The findings of the evaluation of the CMU strategy were (1) in the MCMA, COVID-19 followed a pattern of contagion from the urban center to the periphery; (2) given the growth in the number of cases and the overload of medical units, the population traveled greater distances to seek medical care; (3) after the CMU strategy was evaluated at the territory level, it was found that 9 out of 10 inhabitants had a CMU located approximately 7 km away; and (4) at the metropolitan level, the lowest level of accessibility to the CMU was recorded for the population with the highest levels of marginalization, i.e., those residing in the urban periphery.

The need to develop an environmentally friendly, sustainable viticulture model has led to numerous grapevine improvement programmes aiming to increase resistance to downy and powdery mildew. The success of such programmes relies on the availability of protocols that can quantify the resistance/susceptibility of new genotypes, and on the existence of molecular markers of resistance loci that can aid in the selection process. The present work assesses the degree of phenotypic resistance/susceptibility to downy and powdery mildew of 28 new genotypes obtained from crosses between "Monastrell" and "Regent." Three genotypes showed strong combined resistance, making them good candidates for future crosses with other sources of resistance to these diseases (pyramiding). In general, laboratory and glasshouse assessments of resistance at the phenotype level agreed with the resistance expected from the presence of resistance-associated alleles of simple sequence repeat (SSR) markers for the loci Rpv3 and Ren3 (inherited from "Regent"), confirming their usefulness as indicators of likely resistance to downy and powdery mildew, respectively, particularly so for downy mildew., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ruiz-García, Gago, Martínez-Mora, Santiago, Fernádez-López, Martínez and Boso.)

Emotional intelligence (EI) refers to the ability to perceive, express, understand, and manage emotions. Current research indicates that it may protect against the emotional burden experienced in certain professions. This article aims to provide an updated systematic review of existing instruments to assess EI in professionals, focusing on the description of their characteristics as well as their psychometric properties (reliability and validity). A literature search was conducted in Web of Science (WoS). A total of 2761 items met the eligibility criteria, from which a total of 40 different instruments were extracted and analysed. Most were based on three main models (i.e., skill-based, trait-based, and mixed), which differ in the way they conceptualize and measure EI. All have been shown to have advantages and disadvantages inherent to the type of tool. The instruments reported in the largest number of studies are Emotional Quotient Inventory (EQ-i), Schutte Self Report-Inventory (SSRI), Mayer-Salovey-Caruso Emotional Intelligence Test 2.0 (MSCEIT 2.0), Trait Meta-Mood Scale (TMMS), Wong and Law's Emotional Intelligence Scale (WLEIS), and Trait Emotional Intelligence Questionnaire (TEIQue). The main measure of the estimated reliability has been internal consistency, and the construction of EI measures was predominantly based on linear modelling or classical test theory. The study has limitations: we only searched a single database, the impossibility of estimating inter-rater reliability, and non-compliance with some items required by PRISMA.

Chronic ultraviolet B (UV-B) irradiation is known to be one of the most important hazards acting on the skin and poses a risk of developing photoaging, skin with cutaneous field cancerization (CFC), actinic keratosis (AKs), and squamous cell carcinomas (SCCs). Most of the UV-B light is absorbed in the epidermis, affecting the outermost cell layers, the stratum corneum, and the stratum granulosum, which protects against this radiation and tries to maintain the permeability barrier. In the present work, we show an impairment in the transepidermal water loss, stratum corneum hydration, and surface pH after chronic UV-B light exposure in an immunologically intact mouse model (SKH1 aged mice) of skin with CFC. Macroscopic lesions of AKs and SCCs may develop synchronically or over time on the same cutaneous surface due to both the presence of subclinical AKs and in situ SCC, but also the accumulation of different mutations in keratinocytes. Focusing on skin with CFC, yet without the pathological criteria of AKs or SCC, the presence of p53 immunopositive patches (PIPs) within the epidermis is associated with these UV-B-induced mutations. Reactive epidermis to chronic UV-B exposure correlated with a marked hyperkeratotic hyperplasia, hypergranulosis, and induction of keratinocyte hyperproliferation, while expressing an upregulation of filaggrin, loricrin, and involucrin immunostaining. However, incidental AKs and in situ SCC might show neither hypergranulosis nor upregulation of differentiation markers in the upper epidermis. Despite the overexpression of filaggrin, loricrin, involucrin, lipid enzymes, and ATP-binding cassette subfamily A member 12 (ABCA12) after chronic UV-B irradiation, the permeability barrier, stratum corneum hydration, and surface pH were severely compromised in the skin with CFC. We interpret these results as an attempt to restore the permeability barrier homeostasis by the reactive epidermis, which fails due to ultrastructural losses in stratum corneum integrity, higher pH on skin surface, abundant mast cells in the dermis, and the common presence of incidental AKs and in situ SCC. As far as we know, this is the first time that the permeability barrier has been studied in the skin with CFC in a murine model of SCC induced after chronic UV-B irradiation at high doses. The impairment in the permeability barrier and the consequent keratinocyte hyperproliferation in the skin of CFC might play a role in the physiopathology of AKs and SCCs.

Prostate (PC) and breast cancer (BC) are heterogeneous hormonal cancers. Treatment resistance and adverse effects are the main limitations of conventional chemotherapy treatment. The use of sensitizing agents could improve the effectiveness of chemotherapeutic drugs as well as obviate these limitations. This study analyzes the effect of single catechin (CAT), procyanidin B2 (ProB2) treatment as well as the co-adjuvant treatment of each of these compounds with docetaxel (DOCE). We used PC- and BC-derived cell lines (PC3, DU-145, T47D, MCF-7 and MDA-MB-231). The short and long-term pro-apoptotic, anti-proliferative and anti-migratory effects were analyzed. RT-qPCR was used to discover molecular bases of the therapeutic efficacy of these compounds. ProB2 treatment induced a two- to five-fold increase in anti-proliferative and pro-apoptotic effects compared to single DOCE treatment, and also had a more sensitizing effect than DOCE on DU145 cells. Regarding BC cells, ProB2- and CAT-mediated sensitization to DOCE anti-proliferative and pro-apoptotic effects was cell-independent and cell-dependent, respectively. Combined treatment led to high-efficacy effects on MCF-7 cells, which were associated to the up-regulation of CDKN1A, BAX, caspase 9 and E-cadherin mRNA under combined treatment compared to single DOCE treatment. CAT and ProB2 can enhance the efficacy of DOCE therapy on PC and BC cells by the sensitizing mechanism.

Mesoionic N-heterocyclic olefins (mNHOs) were first reported last year and their reactivity remains largely unexplored. Herein we report the reaction of unprotected mNHOs and organic azides as a novel synthetic route to a variety of pyrazolo[3,4-d][1,2,3]triazoles, an important structural motif in drug candidates and energetic materials. The only byproduct aniline can be easily recycled and converted back to the starting organic azide, in compliance with the green chemistry principle. The reaction mechanism has been explored through experimental and computational studies.

The genes CD28 , CD86 and CTLA-4 conform the costimulatory (CD28-CD86) or inhibitory (CTLA-4-CD86) signal in T-cell activation. T-cell immune response has a critical role in allograft rejection, and single nucleotide polymorphisms (SNPs) located in these genes have been widely analyzed with controversial results. We analyzed a group of SNPs located in the three genes: CD28 : rs3116496; CD86 : rs1129055; and CTLA-4 : rs231775 and rs3087243 in a cohort of 632 consecutively recruited kidney transplanted subjects. All polymorphisms were genotyped by TaqMan chemistry and the diagnosis of rejection was confirmed by biopsy and categorized according to the Banff classification. The analyses showed a statistically significant protective effect to T cell-mediated rejection (TCMR) in carriers of the CTLA-4 rs3087243*G allele, especially in patients with TCMR Banff ≥2 in the overall cohort and in patients without thymoglobulin induction therapy. Both associations were corroborated as independent factors in the multivariate analysis. Interestingly, associations with rejection were not found for any SNP in patients with thymoglobulin induction therapy. As expected, considering the major role of these genes in T-cell activation, no effect was observed for antibody-mediated rejection (ABMR). In conclusion, the SNP rs3087243 located in the CTLA-4 gene may be considered a useful independent biomarker for TCMR risk especially for severe TCMR in patients who did no received thymoglobulin induction therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Santiago, Sánchez-Pérez, Pérez-Flores, de la Higuera, Romero, Querol-García, Urcelay and Sánchez-Fructuoso.)

Introduction: Spain is one of the countries with the highest number of COVID-19 patients. Unfortunately, few data for regions are available., Objectives: This study aimed to describe the characteristics and independent risk factors associated with COVID-19 mortality in Castilla-La Mancha, Spain., Methods: Cohort and multicenter study in all 14 public hospitals of the Castilla-La Mancha Health Service. Baseline characteristics, preexisting comorbidities, symptoms, clinical features and treatments were included. Multivariable logistic regression was used to evaluate factors associated with death and Kaplan-Meier test to examine survival probability. Statistical significance was considered with p  < 0.05 (95% CI). SPSS (version 24.0 for Windows) and R 4.0.2 (R Statistics) software were used., Results: The cohort comprised 12,126 patients sequentially attended between February 11 and May 11, 2020. The mean age of patients was 66.4 years; 5667 (46.7%) were women. Six protective factors against exitus were defined: female sex, anosmia, cough, chloroquine and azithromycin. The risk factors were: age over 50, obesity, cardiac pathology, fever, dyspnea, lung infiltrates, lymphopenia, D-dimer above 1000 ng/mL, and mechanical ventilation requirement. Survival analysis showed higher survival rate in women (75.7%) than men (72.1%). Cumulative survival was 87.5% for non-hospitalized patients, 70.2% for patients admitted to hospital and 61.2% in ICU patients. Additionally, survival probability decreased with increasing age range., Conclusion: Determination of protective or death-promoting factors could be useful to stratify patients by severity criteria and to improve COVID-19 care management., (© 2021 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Atmospheric pollution is a very relevant risk for the human health, in particular in urban environments, where most people lives and high levels of pollution are found. Population exposure is traditionally estimated through concentration recorded at air quality monitoring stations (AQMS) or modelled at a spatial resolution of the order of 1 km 2 . However, these methodologies have limitations in urban areas where strong gradients of concentration, even in the same street, exist. In addition, the movements of pedestrians make difficult to compute reliable estimates of pollutant concentration to which people are exposed to. In this context, the main objective of this study is to estimate the exposure of pedestrians to ambient nitrogen oxides (NOx) concentrations with high spatial resolution in a real urban traffic hot-spot under different methodologies. To achieve this objective, a novel methodology which combines high-resolution NOx concentrations from computational fluid dynamic (CFD) simulations with the pedestrian flows obtained by pedestrian mobility microsimulations is applied to an urban area of Madrid, Spain. High-resolution maps show pedestrian exposure peaks, at bus stops and crosswalks, that cannot be captured by the simpler methods based on spatial average concentration (SAC) or concentration measured in an AQMS. Total daily exposure obtained is 1.19 · 10 9 person s μg m -3 , while SAC and AQMS concentration methods yielded 9-23% and 30-40% lower values. In conclusion, the proposed methodology allows to determine the areas with higher exposure in order to design local strategies to reduce the impact on human health. In addition, from a more general point of view, the total exposure in the studied area is better estimated by using spatial average concentration than through concentration recorded by AQMS. The assessment of the spatial representative of AQMS becomes necessary to use AQMS concentration to evaluate air quality and population exposure of an urban area., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The aim of this study is to analyze the concentrations of cytokines in tear of hospitalized COVID-19 patients compared to healthy controls. Tear samples were obtained from 41 healthy controls and 62 COVID-19 patients. Twenty-seven cytokines were assessed: interleukin (IL)-1b, IL-1RA, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL9, IL-10, IL-12, IL-13, IL-15, IL-17, eotaxin, fibroblast growth factor basic, granulocyte colony-stimulating factor (G-CSF), granulocyte-monocyte colony-stimulating factor (GM-CSF), interferon (IFN)-γ, interferon gamma-induced protein, monocyte chemo-attractant protein-1, macrophage inflammatory protein (MIP)-1a, MIP-1b, platelet-derived growth factor (PDGF), regulated on activation normal T cell expressed and secreted, tumor necrosis factor-α and vascular endothelial growth factor (VEGF).
In tear samples of COVID-19 patients, an increase in IL-9, IL-15, G-CSF, GM-CSF, IFN-γ, PDGF and VEGF was observed, along with a decrease in eotaxin compared to the control group (p < 0.05). A poor correlation between IL-6 levels in tear and blood was found. IL-1RA and GM-CSF were significantly lower in severe patients and those who needed treatment targeting the immune system (p < 0.05). Tear cytokine levels corroborate the inflammatory nature of SARS-CoV-2., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: To determine whether topical applications of thiosulfinate-enriched Allium sativum extract (TASE) can accelerate acute cutaneous wound healing (WH) in a murine model., Methods: Keratinocyte viability and in vitro wound closure were assessed in keratinocyte cultures. Effects of topical TASE (0.5 μg/mL of allicin in 97% ethanol) on acute cutaneous WH were determined in a murine model of acute cutaneous wound. Twelve mice were alternately assigned to the vehicle- and TASE-treated groups (n=6 per group). Expression levels of mRNA for keratinocyte differentiation marker-related proteins (filaggrin, loricrin and involucrin) and lipid synthetic enzymes (elongation of very long chain fatty acids protein 4 (ELOVL4), fatty acid synthase (FA2H), 3-hydroxy- 3-methyl-glutaryl-coenzyme A reductase (HMGCoA), and serine palmitoyltransferase (SPT)) were assessed using real-time quantitative polymerase chain reaction on day 3 and 8 after wounding, while transepidermal water loss (TEWL) rates were measured in wounded areas., Results: TASE accelerated WH both in vivo (40% vs. 22% reduction in wound area, P<0.01) and in vitro (90% vs. 65% reduction in wound area, P<0.01). Moreover, topical applications of TASE upregulated the expression levels of epidermal mRNA for ELOVL4, HMGCoA, SPT, filaggrin, loricrin and involucrin (P<0.05 vs. vehicle-treated controls) on day 3 after wounding. Likewise, TASE significantly lowered TEWL rates in comparison with vehicle alone on day 8 (33.06±2.09 g/(m 2 ·h) vs. 24.60±2.04 g/(m 2 ·h), P<0.01)., Conclusions: Topical applications of TASE stimulated keratinocyte proliferation and formation of epidermal permeability barrier function, leading to acceleration of acute cutaneous WH. Topical products containing TASE could be used to manage acute cutaneous WH.

The present work reports the discovery and the complete characterisation of an ancient cultivated rose variety found growing in a private garden in the southwest of the Principality of Asturias (northern Spain). The variety is here given the name Narcea. The majority of roses currently cultivated belong to the so-called group of 'Modern Roses', all of which were obtained after 1867 via artificial crosses and improvement programmes. All are destined for ornamental use. Until the 19th century, the great majority of the many ancient cultivated roses in Europe were used in perfumery and cosmetics, or had medicinal uses. Rosa damascena and Rosa centifollia are still grown and used by the French and Bulgarian perfume industries. The Asturian Massif of the Cantabrian Mountain Range provides a natural habitat for some 75% of the wild members of the genus Rosa , but until now there was no evidence that this area was home to ancient cultivated roses. A complete botanical description is here provided for a discovered ancient rose. It is also characterised according to a series of sequence tagged microsatellite sites, and its agronomic features are reported. In addition, a histological description (optical and scanning electronic microscope studies) of the petals is offered, along with an analysis of the volatile compounds present in these organs as determined by solid phase microextraction and gas chromatography-mass spectroscopy. The results reveal the uniqueness of this ancient type of rose and suggest it may be of interest to the perfume industry., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s) 2020.)

Objective: The aim of the study was to develop a model of abdominal sepsis in the experimental animal., Methods: Sprague-Dawley male rats of 5 weeks (N=39) were used. Initially, a pilot study (N = 9) was performed and distributed in 3 groups with 1cc inoculum of Escherichia coli ATCC 25922 intraperitoneally at concentrations of 10E8, 10E9 and 10E10 CFU. Subsequently, concentrations of 10E10 CFU are used in two groups of 3 rats with dilutions of 10 cc and 15 cc of distilled water respectively. Finally, a randomized trial of 24 rats was started in three treatment groups after intraperitoneal infection: Group I with physiological serum (N = 6), Group II with ceftriaxone (N = 9), Group III with ceftriaxone plus allicin (N = 9). Microbiological samples of blood and peritoneal fluid were made, as well as histopathological study of intraperitoneal organs (liver, diaphragm and peritoneum)., Results: Death of 100% of the rats infected with 10E10 E. coli UFC concentration with the dilution of 15 ml of distilled water and without antibiotic was oberved. The blood culture and peritoneal fluid culture was positive for the same strain in all of them. The formation of abscesses on the liver surface and polymorphonuclear infiltration in tissues were observed., Conclusions: The lethal dose of E. coli is 10E10 CFU diluted in 15 cc distilled water by intraperitoneal injection., (©The Author 2020. Published by Sociedad Española de Quimioterapia. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)(https://creativecommons.org/licenses/by-nc/4.0/).)

The +874 A/T polymorphism in the interferon gamma ( IFNG ) gene has been associated with Cytomegalovirus (CMV) infection risk in lung and kidney transplant recipients. To replicate this association, we performed a retrospective observational study of this polymorphism and immunosuppressive therapies considering the prophylactic treatment in 600 consecutive kidney transplanted recipients. We found no association of the aforementioned polymorphism with CMV infection in univariate and multivariate analyses regardless of the prophylactic treatment. In addition, the immunosuppressive treatment with mammalian target of rapamycin inhibitors (imTOR) showed a protective effect in all patients independently of prophylaxis. Moreover, in the adjusted model, we found interactions between prophylaxis with high-risk (Donor+/Recipient-, D+/R-) status ( p -interaction = 0.01), with thymoglobulin induction therapy ( p -interaction = 0.03) and with thymoglobulin anti-rejection therapy ( p -interaction = 0.002). Data also revealed that prophylaxis was not an advantage in the not D+/R- and without thymoglobulin therapy group (HR = 0.98, p = 0.95). The benefit of prophylaxis was observed in all groups with thymoglobulin therapy, but it was maximal in the high-risk CMV infection group with both thymoglobulin induction therapy and thymoglobulin anti-rejection therapy (HR = 0.01, p < 0.001). In conclusion, the IFNG +874 polymorphism is not a predictive marker of CMV infection. The protective effect of imTOR is not improved with prophylaxis. Interestingly, the thymoglobulin therapy associated with prophylaxis is not a risk factor for CMV infection, and prophylaxis is not effective in recipients with no high-risk CMV status and without thymoglobulin therapy., (Copyright © 2020 Santiago, Pérez-Flores, Sánchez-Pérez, Moreno de la Higuera, Calvo-Romero, Querol-García, Culebras, Urcelay, Fernández-Pérez and Sánchez-Fructuoso.)

Background: The incidence of cytomegalovirus (CMV) infection in solid organ transplant recipients may be reduced by antiviral prophylaxis, but this strategy may lead to delayed-onset CMV infection. The proinflammatory cytokine interleukin (IL)-18 plays a major role in viral host defense responses. This study examines the impacts of 2 single-nucleotide polymorphisms (SNPs) in the promoter region of the IL-18 gene, -607C/A (rs1946518) and -137G/C (rs187238), on the incidence of delayed-onset CMV infection in patients undergoing kidney transplant., Methods: This retrospective study analyzed 2 IL-18 SNPs in consecutive adult kidney transplant recipients using real-time polymerase chain reaction with TaqMan probes. Participants were enrolled over the period 2005-2013 and stratified according to their IL-18 SNP genotype. The concordance index (Harrell's c-index) was used as a measure of the discriminatory power of the predictive models constructed with bootstrapping to correct for optimistic bias., Results: Seven hundred nine patients received transplants in the study period, and 498 met selection criteria. Cytomegalovirus infection and disease incidence were 38% and 7.5%, respectively. In multivariate competing risk regression models, carriers of the -607C/-137G haplotype who received prophylaxis showed a higher incidence of CMV replication after antiviral agent discontinuation (hazard ratio = 2.42 [95% confidence interval, 1.11-5.26]; P = .026), whereas CMV disease was not observed in those given prophylaxis who were noncarriers of this polymorphism ( P = .009)., Conclusions: Our findings suggest that the -607C/-137G IL-18 haplotype is associated with a higher incidence of postprophylaxis CMV replication. The prior identification of this polymorphism could help select alternative measures to prevent delayed-onset CMV infection in these patients., (© The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Introduction: Introduction: worldwide, hospital malnutrition constitutes an important issue of morbidity and mortality. Although the prevalence of malnutrition has been calculated as between 7% and 27% in hospitalized patients, its real prevalence remains unknown or underestimated because of the different criteria for its identification and diagnosis. The aim of this study was to determine the prevalence of nutritional risk in a cohort of hospitalized patients and to identify the significance of the predictors associated with nutritional risk. Methods: the evaluation of the presence of nutritional risk was carried out in 247 individuals hospitalized at the second-level care institution Instituto de Seguridad y Servicios Sociales para los Trabajadores del Estado (ISSSTE) Zacatecas, Hospital General Nº 26, in Mexico. Nutritional screening was evaluated during the first 24 hours of stay with the NRS 2002. The weighing of associated variables with nutritional risk was calculated statistically using the software Sigma Plot v11. Results: forty-two percent of patients were at risk of malnutrition. Significant associations between nutritional risk and a reduction in food ingestion (during the last week), the illness severity of the patient, as well as age and sex (p < 0.05), were observed. A reduction in food ingestion during the previous week increased the likelihood of having nutritional risk 6.67 times more (95% CI: 3.4-13.2; p < 0.001) in the studied population. Conclusion: the risk of malnutrition in hospitalized patients at ISSSTE-Zacatecas, Hospital General Nº 26 is frequent (42%). Therefore, early detection of nutritional risk is important to offer for proper nutritional intervention with the objective of decreasing the associated morbidity and mortality.

Vitis vinifera is very susceptible to downy mildew ( Plasmopara viticola ) . A number of authors have suggested different genetic populations of this fungus exist in Europe, each showing a different degree of virulence. Work performed to date indicates this diversity to be the result of different factors. In areas where gene flow is greater and recombination more frequent, the diversity of P. viticola appears to be wider. In vineyards isolated by geographic barriers, a race may become dominant and produce clonal epidemics driven by asexual reproduction. The aim of the present work was to identify the conditions that influence the genetic diversity of P. viticola populations in the vineyards of northwestern Spain, where the climatic conditions for the growth of this fungus are very good. Vineyards situated in a closed, narrow valley of the interior, in more open valleys, and on the coast were sampled and the populations of P. viticola detected were differentiated at the molecular level through the examination of microsatellite markers. The populations of P. viticola represented in primary and secondary infections were investigated in the same way. The concentration of airborne sporangia in the vegetative cycle was also examined, as was the virulence of the different P. viticola populations detected. The epidemiological characteristics of the fungus differed depending on the degree of isolation of the vineyard, the airborne spore concentration, and on whether the attack was primary or secondary. Strong isolation was associated with the appearance of dominant fungal races and, therefore, reduced populational diversity.

A methodology based on CFD-RANS simulations (WA CFD-RANS, Weighted Averaged Computational Fluid Dynamic-Reynolds-Averaged Navier-Stokes simulations) which includes appropriate modifications, has been applied to compute the annual, seasonal, and hourly average concentration of NO 2 and NO X throughout the city of Pamplona (Spain) at pedestrian level during 2016. The results have been evaluated using measurements provided both by the city's network of air quality monitoring stations and by a network of mobile microsensors carried around by cyclists during their daily commutes, obtaining a maximum relative error lower than 30% when computing NO 2 annual average concentrations. The model has taken into account the actual city layout in three dimensions, as well as the traffic emissions. The resulting air pollution maps provided information critical for studying the traffic-related health effects of NO 2 and their associated external costs in the city of Pamplona and the spatial representativeness of the current network of air quality monitoring stations (it has not been carried out for an entire city to date). The developed methodology can be applied to similar cities, providing useful information for the decision-makers., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Air pollution continues to be one of the main issues in urban areas. In addition to air quality plans and emission abatement policies, additional measures for high pollution episodes are needed to avoid exceedances of hourly limit values under unfavourable meteorological conditions such as the Madrid's short-term action NO 2 protocol. In December 2016 there was a strong atmospheric stability episode that turned out in generalized high NO 2 levels, causing the stage 3 of the NO 2 protocol to be triggered for the first time in Madrid (29th December). In addition to other traffic-related measures, this involves access restrictions to the city centre (50% to private cars). We simulated the episode with and without measures under a multi-scale modelling approach. A 1 km 2 resolution modelling system based on WRF-SMOKE-CMAQ was applied to assess city-wide effects while the Star-CCM+ (RANS CFD model) was used to investigate the effect at street level in a microscale domain in the city centre, focusing on Gran Vía Avenue. Changes in road traffic were simulated with the mesoscale VISUM model, incorporating real flux measurements during those days. The corresponding simulations suggest that the application of the protocol during this particular episode may have prevented concentrations to increase by 24 μg·m -3 (14% respect to the hypothetical no action scenario) downtown although it may have cause NO 2 to slightly increase in the city outskirts due to traffic redistribution. Speed limitation and parking restrictions alone (stages 1 and 2 respectively) have a very limited effect. The microscale simulation provides consistent results but shows an important variability at street level, with reduction above 100 μg·m -3 in some spots inside Gran Vía. Although further research is needed, these results point out the need to implement short-term action plans and to apply a consistent multi-scale modelling assessment to optimize urban air quality abatement strategies., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Plant oils have been utilized for a variety of purposes throughout history, with their integration into foods, cosmetics, and pharmaceutical products. They are now being increasingly recognized for their effects on both skin diseases and the restoration of cutaneous homeostasis. This article briefly reviews the available data on biological influences of topical skin applications of some plant oils (olive oil, olive pomace oil, sunflower seed oil, coconut oil, safflower seed oil, argan oil, soybean oil, peanut oil, sesame oil, avocado oil, borage oil, jojoba oil, oat oil, pomegranate seed oil, almond oil, bitter apricot oil, rose hip oil, German chamomile oil, and shea butter). Thus, it focuses on the therapeutic benefits of these plant oils according to their anti-inflammatory and antioxidant effects on the skin, promotion of wound healing and repair of skin barrier., Competing Interests: The authors declare no conflict of interest.

The hypothalamic-pituitary-adrenal (HPA) axis is one of the body's neuroendocrine networks that responds to psychological stress (PS). In the skin, there exists a peripheral HPA axis similar to the central axis. Glucocorticoids (GCs) are key effector molecules of the HPA axis and are essential for cutaneous homeostasis. Atopic dermatitis (AD) is a condition typically characterized by a chronic relapsing course that often results in PS. HPA dysfunction is present in AD patients by the decreased response of GCs elevation to stress as compared to those unaffected by AD. Nevertheless, in skin, acute PS activates several metabolic responses that are of immediate benefit to the host. During the acute phase of PS, increased endogenous GCs have been shown to provide benefit rather than by aggravating cutaneous inflammatory dermatoses. However, a chronic T helper cell type 2 (Th2) predominant cytokine profile acts as a negative feedback loop to blunt the HPA axis response in AD. In this article, we reviewed the role of CRF, pro-opiomelanocortin (POMC)-derived peptides, GCs of the HPA, and 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) in AD, with a discussion of the pathogenetic mechanisms of inflammation and skin barrier functions, including antimicrobial defense, and their association with PS., Competing Interests: The authors declare no conflict of interest.

Purpose: To determine variations in cytokine levels of glaucoma patients treated either with preservative-free latanoprost or preserved latanoprost, relative to healthy individuals., Methods: Tear samples were collected from 39 healthy subjects, 20 glaucoma patients treated with preserved latanoprost, and 20 patients treated with preservative-free latanoprost. A set of 27 inflammatory cytokines was analyzed in each group, including interleukin (IL)-1β, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL9, IL-10, IL-12 (p70), IL-13, IL-15, IL-17, eotaxin, fibroblast growth factor (FGF) basic, granulocyte colony stimulating factor (G-CSF), granulocyte monocyte colony stimulating factor (GM-CSF), interferon (IFN)-γ, interferon gamma-induced protein (IP)-10, monocyte chemo attractant protein (MCP)-1MCAF, macrophage inflammatory protein (MIP)-1α, MIP-1β, platelet-derived growth factor (PDGF)-BB, regulated on activation, normal T cell expressed and secreted (RANTES), tumor necrosis factor (TNF)-α and vascular endothelial growth factor (VEGF). Cytokine concentrations were obtained by the Bio-Plex Human Cytokine Immunoassay. Non-invasive tear breakup time (NI-TBUT), tear meniscus height, corneal fluorescein staining, conjunctival hyperemia and ocular surface disease index (OSDI) were assessed in patients treated with preservative-free and preserved latanoprost., Results: The levels of IL-2, IL-5, IL-10, IL-12 (p70), IL-13, IL-15, IL-17, FGF basic, PDGF-BB, and TNF-α were significantly higher in patients receiving preserved latanoprost, compared to normal controls (p < 0.05). The expression of all the cytokines studied remained statistically invariable in patients receiving preservative-free latanoprost, compared to healthy subjects (p > 0.05). Ocular surface parameters were not significantly different in both glaucoma groups, and no correlation between these clinical parameters and cytokine levels was observed., Conclusions: Treatment with preserved latanoprost has a direct impact on tear cytokine levels, whereas this effect is not observed upon preservative-free latanoprost instillation., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: One of the risk factor to develop progressive multifocal leukoencephalopathy (PML) among natalizumab-treated patients is the presence and high levels of anti-JCV antibodies. Our purpose was to test the association of different clinical and demographic variables with the presence and levels of anti-JCV antibodies in a Spanish cohort of patients with multiple sclerosis (MS) during natalizumab treatment., Materials and Methods: All patients with MS from two hospitals with at least one measure of the anti-JCV antibodies levels (2011-2014) were recruited, among them were two PML cases. Anti-JCV antibody levels were assessed using two-step ELISA., Results: A total of 1061 patients (16·3% natalizumab-treated) participated in this study. The seropositivity rate of anti-JCV antibodies was 58·2%. It increased with age (P corrected = 0·00005) and was lower among HLA-DRB1*15:01 carriers (P corrected = 0·049). The two patients with PML were HLA-DRB1*15:01 carriers. We had at least three quarterly anti-JCV antibody measurements (index value) from 137 patients, whose levels did not increase during natalizumab treatment. However, 5·8% of these patients had an increase of the index value higher of one point in a maximum of 6 months, something that was more frequently observed (P = 0·054) among patients treated with immunosuppressant prior to natalizumab onset., Conclusions: Old age and HLA-DRB1*15:01 were the factors that influence positively and negatively, respectively, our anti-JCV antibody prevalence, although our both PML cases were HLA-DRB1*15:01carriers. Most of our patients showed a stable anti-JCV antibody index values during natalizumab treatment., (© 2016 Stichting European Society for Clinical Investigation Journal Foundation.)

The distribution of pollutants is spatially heterogeneous within urban streets making difficult to build a realistic concentration map. In this paper, a methodology based on computational fluid dynamic modeling with Reynolds-averaged Navier-Stokes approach is used to compute maps of concentration for a period of several weeks. The methodology is evaluated by comparing simulation results against experimental data from two different campaigns where a large number of passive samplers deployed in an area with heavy vehicular traffic in Madrid (Spain). The evaluation shows that the methodology is able to reproduce the general pattern of several-week averaged pollutant distribution in an urban area with heavy vehicular traffic, resolving the spatial variability up to a resolution of 1-2m. In addition, the model results fit satisfactorily the time evolution of the pollutant concentration measured at an air quality station deployed in the studied area. However, problems were detected close to zones with complex emissions patterns (tunnels, street forks, etc.), where the model compared poorly against passive sampler measurements. A preliminary assessment of the uncertainties induced in the numerical methodology due to consider NO 2 as non-reactive pollutant under winter conditions indicates that it would be an acceptable approach for this particular case study. Overall, our analysis contributes to raise the confidence in that approached similar to the one presented in this study can be adopted for dealing with several aspects of the air quality management such as air quality assessment, optimization of the location of measurement stations, and the evaluation of air pollution reduction strategies., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Idiopathic achalasia is a severe motility disorder of the esophagus and is characterized by a failure of the lower esophageal sphincter to relax due to a loss of neurons in the myenteric plexus. Most recently, we identified an eight-amino-acid insertion in the cytoplasmic tail of HLA-DQβ1 as strong achalasia risk factor in a sample set from Central Europe, Italy and Spain. Here, we tested whether the HLA-DQβ1 insertion also confers achalasia risk in the Polish and Swedish population. We could replicate the initial findings and the insertion shows strong achalasia association in both samples (Poland P=1.84 × 10(-04), Sweden P=7.44 × 10(-05)). Combining all five European data sets - Central Europe, Italy, Spain, Poland and Sweden - the insertion is achalasia associated with Pcombined=1.67 × 10(-35). In addition, we observe that the frequency of the insertion shows a geospatial north-south gradient. The insertion is less common in northern (around 6-7% in patients and 2% in controls from Sweden and Poland) compared with southern Europeans (~16% in patients and 8% in controls from Italy) and shows a stronger attributable risk in the southern European population. Our study provides evidence that the prevalence of achalasia may differ between populations.

Behavioral interventions preceded by a functional analysis have been proven efficacious in treating severe problem behavior associated with autism. There is, however, a lack of research showing socially validated outcomes when assessment and treatment procedures are conducted by ecologically relevant individuals in typical settings. In this study, interview-informed functional analyses and skill-based treatments (Hanley et al. in J Appl Behav Anal 47:16-36, 2014) were applied by a teacher and home-based provider in the classroom and home of two children with autism. The function-based treatments resulted in socially validated reductions in severe problem behavior (self-injury, aggression, property destruction). Furthermore, skills lacking in baseline-functional communication, denial and delay tolerance, and compliance with adult instructions-occurred with regularity following intervention. The generality and costs of the process are discussed.

The -308G/A SNP of tumor necrosis factor-alpha (TNF-α) gene affects TNF- α production. As its impact on transplant outcome remains open to debate, we decided to genotype it in a cohort of transplant subjects. A retrospective analysis of 439 first kidney recipients randomly divided into two subgroups (discovery and validation cohorts) was performed to identify the best predictors of acute rejection (AR). The effect on transplant outcome was analyzed by an adjusted logistic regression model. Carriers of the A allele, associated with elevated TNF- α production, presented a higher risk of AR (OR = 2.78; 95% CI = 1.40-5.51). Logistic regression analyses for AR showed an interaction between the polymorphism and treatment with thymoglobulin (p-interaction = 0.03). In recipients who did not receive thymoglobulin, carriers of A allele had higher risk of AR (OR = 4.05; 95% CI = 1.76-9.28). Moreover, carriers of A allele not treated with thymoglobulin presented higher risk of AR than those who received thymoglobulin (OR = 13.74; 95% CI = 1.59-118.7). The AUC of the model in the discovery cohort was 0.70 and in the validation cohort was 0.69. Our findings indicate that the -308G/A TNF-α polymorphism is associated with AR risk and it modulates the effectiveness of thymoglobulin treatment. This pharmacogenetic effect lets us propose this SNP as a useful predictor biomarker to tailor immunosuppressive regimens.

Background and Purpose: Progressive multifocal leukoencephalopathy (PML) cases have arisen amongst multiple sclerosis patients treated with natalizumab. Our objective was to gain a better understanding of the mechanisms that underlie the John Cunningham virus (JCV) infection which causes PML., Methods: A study was made of (i) the quarterly JCV DNA levels in peripheral blood mononuclear cells (PBMCs), serum and urine samples in 100 multiple sclerosis patients during their natalizumab treatment (3-39 months), (ii) the association between human leukocyte antigen (HLA) class II and the previous viral detection and (iii) the identification of the JCV variants in those patients suspected of having PML., Results: (i) JCV DNA in PBMCs and/or serum was detected in 23% of our cohort. Patients with an intermittent JCV excretion in urine had a significant increase of the viral load and prevalence in this compartment during natalizumab treatment. (ii) The frequency of the DRB1*07/DQA1*02:01/DQB1*02:02 haplotype tended to be higher in patients with detectable versus undetectable JCV DNA in PBMCs (P(corrected) = 0.108). (iii) The variants in PBMCs and serum of the non-PML patient matched the archetype. In the patient with non-fatal PML, the archetype and the same neurotropic variant in PBMCs, serum and cerebrospinal fluid was identified at the time PML was diagnosed, whereas in the patient with a worse PML prognosis, four neurotropic variants in the three previous compartments were found by the PML diagnosis., Conclusions: The detection of the neurotropic variant in blood during natalizumab treatment could be critical in the prevention of the development of severe PML, since this variant appears simultaneously with the clinical symptoms of PML and mutates quickly., (© 2015 EAN.)

We review novel technologies with diagnostic and therapeutic applications in dermatology. Among the diagnostic techniques that promise to become part of dermatologic practice in the future are optical coherence tomography, multiphoton laser scanning microscopy, Raman spectroscopy, thermography, and 7-T magnetic resonance imaging. Advances in therapy include novel light-based treatments, such as those applying lasers to new targets and in new wavelengths. Devices for home therapy are also appearing. We comment on the therapeutic uses of plasma, ultrasound, radiofrequency energy, total reflection amplification of spontaneous emission of radiation, light stimulation, and transepidermal drug delivery. Finally, we mention some basic developments in nanotechnology with prospects for future application in dermatology., (Copyright © 2014 Elsevier España, S.L.U. and AEDV. All rights reserved.)

Background: The presence of oligoclonal IgM bands (OCMB) in cerebrospinal fluid (CSF) is an unfavourable prognostic marker in multiple sclerosis. There is no commercial test to investigate OCMB status. However, a sensitive and specific isoelectrofocusing (IEF) and western blot method was described. We aimed to study the inter-centre reproducibility of this technique, a necessary condition for a reliable test to be incorporated into clinical practice., Methods: The presence of OCMB was analysed by IEF and western blot with prior reduction of pentameric IgM. We assayed the reproducibility of this test in a blinded multicentre study performed in 13 university hospitals. Paired-CSF and serum samples from 52 neurological patients were assayed at every centre., Results: Global analysis rendered a concordance of 89.8% with a kappa value of 0.71., Conclusion: These data indicate that OCMB detection by means of IEF and western blot with IgM reduction shows a good interlaboratory reproducibility and thus can be used in daily clinical setting., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: The aim of the present study was to analyze whether absolute BNP and relative BNP change values during follow-up of elderly patients with chronic HF could predict the development of acute decompensated episodes., Methods and Results: A total population of 108 elderly outpatients with the diagnosis of HF was retrospectively reviewed. Available BNP levels after at least one stable visit and one acute decompensated episode were required. Follow-up period was 12 months (343 visits, 42.6% decompensated HF episodes). Relative BNP changes were analyzed: "CC period" (patients who remained stable) and "CD period" (patient who suffered from a decompensated HF episode). Changes in BNP levels were significantly higher in CD than in CC periods (mean and median differences 138% and 85%, vs 16% and 0%, respectively; p<0.001). The clinical model (AUC=0.83) had a sensitivity of 67.06%, and a specificity of 80.36%. Relative BNP change (29%) showed by itself, a similar AUC (0.83) and specificity (79%) and an improved sensitivity (0.80) than the clinical model. When relative BNP change was introduced at the clinical model, a similar specificity was obtained and the diagnostic accuracy, AUC (0.89 vs 0.83, p=0.01) and sensitivity were improved. Absolute BNP changes showed worse AUC than that derived from relative BNP changes or clinical assessment., Conclusions: Percent BNP change values during the follow-up showed better results than absolute BNP values and improved the clinical assessment for diagnostic of decompensated HF episodes in elderly outpatients., (Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Aims: The aim of this article was to determine the importance of neuroendocrine and inflammatory biomarkers in elderly patients (>70 years) with heart failure (HF)., Methods: In this retrospective and observational study, TNF-α, IL-6, IL-18, Fas (Apo1), BNP, C-reactive protein and cystatin C values were calculated, as well as the relationship between them and the clinical evolution of patients., Results: A total of 124 patients (mean age ± standard deviation: 83±5 years) were included. After a mean follow-up of 2.4 years, 40.3% of patients were hospitalized for HF and 15.3% of patients died. Those patients who were hospitalized for HF compared with those that did not were hospitalized for HF showed higher values of IL-6 (9.8±13.1 vs 4.65±5.8 pg/ml; p=0.003) and those who died compared with those who are alive higher values of IL-18 (437.1±137.4 vs 299.7±167.2 pg/ml; p=0.01), C-reactive protein (12.6±19.4 vs 6.1±9.4 mg/l; p=0.03), BNP (704.2±428.6 vs 418.5±410.6 pg/ml; p=0.008) and cystatin C (1.76±0.6 vs 1.45±0.5 mg/l; p=0.04). In the multivariate analysis, only IL-18 (hazard ratio: 1.4; 95% CI: 1.05-1.8; p=0.027) remained as an independent predictor for mortality., Conclusion: In elderly patients with HF, the determination of biomarkers may be helpful to establish those patients at higher risk.