Las organizaciones no gubernamentales de desarrollo y el régimen fiscal de las entidades sin fin de lucro

This paper examines, on the one hand, the question of whether, in the specific case of non-governmental development organizations (NGDOs) set up as associations, it is necessary for them to be declared to be of public utility in order to be considered “non-profit entities” and enjoy the benefits recognized by Law 49/2002, of 23 December, or whether, on the contrary, it is sufficient for them to be registered in the NGDO Register, as has been maintained —not without contradiction— by the Administration itself. On the other hand, an analysis is made of whether registration in said Register constitutes an “indispensable condition” for them to be able to enjoy the aforementioned benefits (as provided for in Law 23/1998, of 7 July, with respect to those established in Law 30/1994 -which previously regulated the tax regime of non-profit organizations-), or whether, distinctly, it is a requirement that, after Law 49/2002, can no longer be maintained. To this debate has been added the latest regulation of the NGDO Register, approved in 2015, which has opened up new fronts of controversy, in that it incurs certain excesses in relation to the concept of NGDOs, their accessibility to the said register or the sufficiency or otherwise of their registration in others.En el presente trabajo se examina, por un lado, la cuestión de si, en el concreto caso de las Organizaciones no gubernamentales de desarrollo (ONGDs) constituidas como asociaciones, les resulta necesario estar declaradas de utilidad pública para poder ser consideradas «entidades sin fines lucrativos» y disfrutar de los beneficios que les reconoce la Ley 49/2002, de 23 de diciembre, o si, por el contrario, les basta con su inscripción en el Registro de ONGDs, como se ha llegado a mantener —no sin contradicciones— por la propia Administración. Por otro, se analiza si la inscripción en dicho Registro constituye una «condición indispensable» para que puedan disfrutar de los aludidos beneficios (como disponía la Ley 23/1998, de 7 de julio, respecto de los establecidos en la Ley 30/1994 —que anteriormente regulaba el régimen fiscal de las entidades sin fin de lucro—), o si, distintamente, se trata de una exigencia que, tras la Ley 49/2002, ya no cabe mantener. A este debate se ha añadido el último reglamento del Registro de ONGDs, aprobado en 2015, que ha abierto nuevos frentes de polémica, por cuanto incurre en ciertos excesos en relación al concepto de ONGD, su accesibilidad a dicho registro o la suficiencia o no de su inscripción en otros

Integrative assessment of coastal marine pollution in Santander Bay and Galician Rías.

Sediments from Rías of A Coruña, Ferrol, Betanzos and Ares (n = 26) and the Bay of Santander (n = 11) were sampled. The concentration of organic contaminants in sediment elutriates (CBs, PAHs, pesticides and pharmaceutical drugs) and sea urchin (Paracentrotus lividus) embryotoxicity were assessed. The concentration of organic pollutants in the elutriates were relatively low (ΣContaminants < 400 ng/L) and their interpretation in terms of the observed toxicity was not straightforward. A clear gradient of toxicity from the inner part to the outer side of the Santander Bay was observed. Sediment elutriates from two stations situated close to the city of A Coruña showed moderate toxicity values, whereas sediment elutriates from the Rías of Ares and Betanzos showed no marked toxicity. Stations located close to the city of Ferrol showed moderate to high toxicity, which is indicative of a nearby source of contamination. On the contrary, the outer side of the Ría of Ferrol was classified as clean according to the calculated toxic units. These results allowed for an integrative assessment of the environmental quality in the studied areas, which highlights the usefulness of embryo-larval test to monitor the coastal pollution

Effectiveness and safety of a microcrystalline tyrosine‐adjuvanted <i>Dermatophagoides pteronyssinus</i> allergoid immunotherapy in adult patients with allergic asthma and rhinitis: A real‐life prospective observational study

Introduction: Although clinical trials have shown the efficacy and safety of allergen-specific immunotherapy (AIT) in the treatment of allergic asthma, there is a need for real-life studies. We aimed to assess the effectiveness and safety of a microcrystalline tyrosine-adjuvanted Dermatophagoides pteronyssinus allergoid (Acarovac Plus (R)) in patients with house dust mite (HDM)-induced allergic asthma in a real-life study. Methods: A subanalysis of a multicenter, prospective, observational, real-life study. Patients with rhinitis and allergic asthma caused by HDMs were assessed before AIT with Acarovac Plus (R) and at 6 and 12 months after this treatment. Assessment parameters were percentage of days with asthma symptoms, percentage of days on asthma medication, classification of asthma according to Spanish guidelines for the management of asthma, asthma-related quality of life (quality of life in adults with asthma questionnaire [QLAAQ]), perception of symptoms (visual analog scale [VAS]), and treatment satisfaction (treatment satisfaction questionnaire for medication [TSQM]). Safety was assessed by the number and severity of adverse reactions. Results: This subanalysis included 55 patients. Treatment with Acarovac Plus (R) showed significant differences in the analyzed variables when the baseline visit was compared with the 12-month visit: reduction of the mean (SD) percentage of days with asthma symptoms (23.9 [9.2] vs. 5.1 [12.8]; p = .002), of the mean [SD] percentage of days on asthma medication (67.6 [42.9] vs. 45.1 [46.8]; p = .002), and of the percentage of patients with persistent asthma (78.2% vs. 38.9%; p = .009). Acarovac Plus (R) significantly improved asthma-related quality of life, as shown by a decrease of 1.39 points in QLAAQ score at 12 months (p < .001), and in the subjective perception of symptoms on the VAS (-3.50, p < .0001). Patients showed high treatment satisfaction according to the TSQM, and it was well tolerated. No serious adverse events were reported. Conclusions: Acarovac Plus (R) was effective and safe for the treatment of patients with HDM-induced allergic asthma in a real-life study

Immunological parameters as biomarkers of response to MicroCrystalline Tyrosine-adjuvanted mite immunotherapy

Despite the effectiveness of allergen immunotherapy (AIT), some patients are unresponsive for reasons still unknown; yet validated response biomarkers remain unavailable. To analyze immunological parameters as biomarkers to monitor and predict clinical response to a MicroCrystalline Tyrosine-adjuvanted house dust mite (HDM) AIT in patients with allergic rhinitis (AR). Observational, prospective, multicenter study including adult patients (aged 18-65 years) with AR, with and without asthma, sensitized to the HDM Dermatophagoides pteronyssinus (DP) and prescribed Acarovac Plus® DP 100% in the routine practice. Serum concentrations of total IgE, specific IgE, specific IgG4, IL-4, IL-5, IL-10, IL-13, and IFN-γ were compared between baseline and 12 months after AIT. The relationship between patients' baseline immunological profiles and classification as low, high, and non-responders and between their sensitization profile to DP allergens and effectiveness were analyzed. Of 141 patients recruited, 118 (mean [SD] age of 33.6 [9.5] years) were evaluable. One year after treatment, Der p 1-specific IgE, DP-specific IgG4, and IL-10 increased by a mean (SD) of 3.4 (13.6) kU/L (p = 0.016), 0.43 (0.55) mg/L (p < 0.0001), and 1.35 (7.56) pg/mL (p = 0.033), respectively. Non-responders showed increased baseline levels of IL-13 compared to high responders (p = 0.037). Changes in effectiveness variables between baseline and after AIT were similar regardless of the sensitization profile. Non-responsive patients to AIT showed increased baseline IL-13 concentrations, suggesting its value as prognostic biomarker. DP-specific AIT increased Der p 1-specific IgE, DP-specific IgG4, and IL-10 concentrations in patients with AR. All patients benefited from treatment regardless of their sensitization profile to major DP allergens

Spill-in counts in the quantification of 18 F-florbetapir on Aβ-negative subjects: the effect of including white matter in the reference region

Background: We aim to provide a systematic study of the impact of white matter (WM) spill-in on the calculation of standardized uptake value ratios (SUVRs) on Aβnegative subjects, and we study the effect of including WM in the reference region as a compensation. In addition, different partial volume correction (PVC) methods are applied and evaluated. Methods: We evaluated magnetic resonance imaging and 18F-AV-45 positron emission tomography data from 122 cognitively normal (CN) patients recruited at the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Cortex SUVRs were obtained by using the cerebellar grey matter (CGM) (SUVRCGM) and the whole cerebellum (SUVRWC) as reference regions. The correlations between the different SUVRs and the WM uptake (WM-SUVRCGM) were studied in patients, and in a well-controlled framework based on Monte Carlo (MC) simulation. Activity maps for the MC simulation were derived from ADNI patients by using a voxel-wise iterative process (BrainViset). Ten WM uptakes covering the spectrum of WM values obtained from patient data were simulated for different patients. Three different PVC methods were tested (a) the regional voxel-based (RBV), (b) the iterative Yang (iY), and (c) a simplified analytical correction derived from our MC simulation. Results: WM-SUVRCGM followed a normal distribution with an average of 1.79 and a standard deviation of 0.243 (13.6%). SUVRCGM was linearly correlated to WM-SUVRCGM (r = 0.82, linear fit slope = 0.28). SUVRWC was linearly correlated to WM-SUVRCGM (r = 0.64, linear fit slope = 0.13). Our MC results showed that these correlations are compatible with those produced by isolated spill-in effect (slopes of 0.23 and 0.11). The impact of the spill-in was mitigated by using PVC for SUVRCGM (slopes of 0.06 and 0.07 for iY and RBV), while SUVRWC showed a negative correlation with SUVRCGM after PVC. The proposed analytical correction also reduced the observed correlations when applied to patient data (r = 0.27 for SUVRCGM, r = 0.18 for SUVRWC). Conclusions: There is a high correlation between WM uptake and the measured SUVR due to spill-in effect, and that this effect is reduced when including WM in the reference region. We also evaluated the performance of PVC, and we proposed an analytical correction that can be applied to preprocessed data.This work was partially supported by the project PI16/01416 (ISCIII co-funded FEDER) and RYC-2015/17430(Ramón y Cajal, PA)S

Serum micrornas as tool to predict early response to benralizumab in severe eosinophilic asthma

Severe eosinophilic asthma poses a serious health and economic problem, so new therapy approaches have been developed to control it, including biological drugs such as benralizumab, which is a monoclonal antibody that binds to IL-5 receptor alpha subunit and depletes peripheral blood eosinophils rapidly. Biomarkers that predict the response to this drug are needed so that microRNAs (miRNAs) can be useful tools. This study was performed with fifteen severe eosinophilic asthmatic patients treated with benralizumab, and serum miRNAs were evaluated before and after treatment by semi-quantitative PCR (qPCR). Patients showed a clinical improvement after benralizumab administration. Additionally, deregulation of miR-1246, miR-5100 and miR-338-3p was observed in severe asthmatic patients after eight weeks of therapy, and a correlation was found between miR-1246 and eosinophil counts, including a number of exacerbations per year in these severe asthmatics. In silico pathway analysis revealed that these three miRNAs are regulators of the MAPK signaling pathway, regulating target genes implicated in asthma such as NFKB2, NFATC3, DUSP1, DUSP2, DUSP5 and DUSP16. In this study, we observed an altered expression of miR-1246, miR-5100 and miR-338-3p after eight weeks of benralizumab administration, which could be used as early response markers.This manuscript was funded by Fondo de Investigación Sanitaria–FIS and FEDER (Fondo Europeo de Desarrollo Regional) [PI15/00803, PI18/00044, and FI16/00036], CIBER de Enfermedades Respiratorias (CIBERES), Merck Health Foundation funds, and Ministerio de Ciencia, Innovación y Universidades (RTC-2017-6501-1

Hypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance

Thyroid hormones (THs) act in the brain to modulate energy balance. We show that central triiodothyronine (T3) regulates de novo lipogenesis in liver and lipid oxidation in brown adipose tissue (BAT) through the parasympathetic (PSNS) and sympathetic nervous system (SNS), respectively. Central T3 promotes hepatic lipogenesis with parallel stimulation of the thermogenic program in BAT. The action of T3 depends on AMP-activated protein kinase (AMPK)-induced regulation of two signaling pathways in the ventromedial nucleus of the hypothalamus (VMH): decreased ceramide-induced endoplasmic reticulum(ER) stress, which promotes BAT thermogenesis, and increased c-Jun N-terminal kinase (JNK) activation, which controls hepatic lipid metabolism. Of note, ablation of AMPK alpha 1 in steroidogenic factor 1 (SF1) neurons of the VMH fully recapitulated the effect of central T3, pointing to this population in mediating the effect of central THs on metabolism. Overall, these findings uncover the underlying pathways through which central T3 modulates peripheral metabolism.Peer reviewe

A New Integrated Variable Based on Thermometry, Actimetry and Body Position (TAP) to Evaluate Circadian System Status in Humans

The disruption of the circadian system in humans has been associated with the development of chronic illnesses and the worsening of pre-existing pathologies. Therefore, the assessment of human circadian system function under free living conditions using non-invasive techniques needs further research. Traditionally, overt rhythms such as activity and body temperature have been analyzed separately; however, a comprehensive index could reduce individual recording artifacts. Thus, a new variable (TAP), based on the integrated analysis of three simultaneous recordings: skin wrist temperature (T), motor activity (A) and body position (P) has been developed. Furthermore, we also tested the reliability of a single numerical index, the Circadian Function Index (CFI), to determine the circadian robustness. An actimeter and a temperature sensor were placed on the arm and wrist of the non-dominant hand, respectively, of 49 healthy young volunteers for a period of one week. T, A and P values were normalized for each subject. A non-parametric analysis was applied to both TAP and the separate variables to calculate their interdaily stability, intradaily variability and relative amplitude, and these values were then used for the CFI calculation. Modeling analyses were performed in order to determine TAP and CFI reliability. Each variable (T, A, P or TAP) was independently correlated with rest-activity logs kept by the volunteers. The highest correlation (r = −0.993, p<0.0001), along with highest specificity (0.870), sensitivity (0.740) and accuracy (0.904), were obtained when rest-activity records were compared to TAP. Furthermore, the CFI proved to be very sensitive to changes in circadian robustness. Our results demonstrate that the integrated TAP variable and the CFI calculation are powerful methods to assess circadian system status, improving sensitivity, specificity and accuracy in differentiating activity from rest over the analysis of wrist temperature, body position or activity alone

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group