MYB24 orchestrates terpene and flavonol metabolism as light responses to anthocyanin depletion in variegated grape berries.

Variegation is a rare type of mosaicism not fully studied in plants, especially fruits. We examined red and white sections of grape (Vitis vinifera cv. 'Béquignol') variegated berries and found that accumulation of products from branches of the phenylpropanoid and isoprenoid pathways showed an opposite tendency. Light-responsive flavonol and monoterpene levels increased in anthocyanin-depleted areas in correlation with increasing MYB24 expression. Cistrome analysis suggested that MYB24 binds to the promoters of 22 terpene synthase (TPS) genes, as well as 32 photosynthesis/light-related genes, including carotenoid pathway members, the flavonol regulator HY5 HOMOLOGUE (HYH), and other radiation response genes. Indeed, TPS35, TPS09, the carotenoid isomerase gene CRTISO2, and HYH were activated in the presence of MYB24 and MYC2. We suggest that MYB24 modulates ultraviolet and high-intensity visible light stress responses that include terpene and flavonol synthesis and potentially affects carotenoids. The MYB24 regulatory network is developmentally triggered after the onset of berry ripening, while the absence of anthocyanin sunscreens accelerates its activation, likely in a dose-dependent manner due to increased radiation exposure. Anthocyanins and flavonols in variegated berry skins act as effective sunscreens but for different wavelength ranges. The expression patterns of stress marker genes in red and white sections of 'Béquignol' berries strongly suggest that MYB24 promotes light stress amelioration but only partly succeeds during late ripening.

The ethylene-responsive transcription factor ERF024 is a novel regulator of climacteric fruit ripening in melon.

Fruit ripening is an essential developmental stage in Angiosperms triggered by hormonal signals such as ethylene, a major player in climacteric ripening. Melon is a unique crop showing both climacteric and non-climacteric cultivars, offering an ideal model for dissecting the genetic mechanisms underpinning this process. The major quantitative trait locus ETHQV8.1 was previously identified as a key regulator of melon fruit ripening. Here, we narrowed down ETHQV8.1 to a precise genomic region containing a single gene, the transcription factor CmERF024. Functional validation using CRISPR/Cas9 knock-out plants unequivocally identified CmERF024 as the causal gene governing ETHQV8.1. The erf024 mutants exhibited suppression of ethylene production, leading to a significant delay and attenuation of fruit ripening. Integrative multi-omic analyses encompassing RNA-seq, DAP-seq, and DNase-seq revealed the association of CmERF024 with chromatin accessibility and gene expression dynamics throughout fruit ripening. Our data suggest CmERF024 as a novel regulator of climacteric fruit ripening in melon.

The transcription factor VviNAC60 regulates senescence- and ripening-related processes in grapevine.

Grapevine (Vitis vinifera L.) is one of the most widely cultivated fruit crops because the winemaking industry has huge economic relevance worldwide. Uncovering the molecular mechanisms controlling the developmental progression of plant organs will prove essential for maintaining high-quality grapes, expressly in the context of climate change, which impairs the ripening process. Through a deep inspection of transcriptomic data, we identified VviNAC60, a member of the NAC transcription factor family, as a putative regulator of grapevine organ maturation. We explored VviNAC60 binding landscapes through DNA affinity purification followed by sequencing and compared bound genes with transcriptomics datasets from grapevine plants stably and transiently overexpressing VviNAC60 to define a set of high-confidence targets. Among these, we identified key molecular markers associated with organ senescence and fruit ripening. Physiological, metabolic, and promoter activation analyses showed that VviNAC60 induces chlorophyll degradation and anthocyanin accumulation through the upregulation of STAY-GREEN PROTEIN 1 (VviSGR1) and VviMYBA1, respectively, with the latter being upregulated through a VviNAC60-VviNAC03 regulatory complex. Despite sharing a closer phylogenetic relationship with senescence-related homologs to the NAC transcription factor AtNAP, VviNAC60 complemented the nonripening(nor) mutant phenotype in tomato (Solanum lycopersicum), suggesting a dual role as an orchestrator of both ripening- and senescence-related processes. Our data support VviNAC60 as a regulator of processes initiated in the grapevine vegetative- to mature-phase organ transition and therefore as a potential target for enhancing the environmental resilience of grapevine by fine-tuning the duration of the vegetative phase.

Direct regulation of shikimate, early phenylpropanoid, and stilbenoid pathways by Subgroup 2 R2R3-MYBs in grapevine.

The stilbenoid pathway is responsible for the production of resveratrol in grapevine (Vitis vinifera L.). A few transcription factors (TFs) have been identified as regulators of this pathway but the extent of this control has not been deeply studied. Here we show how DNA affinity purification sequencing (DAP-Seq) allows for the genome-wide TF-binding site interrogation in grape. We obtained 5190 and 4443 binding events assigned to 4041 and 3626 genes for MYB14 and MYB15, respectively (approximately 40% of peaks located within −10 kb of transcription start sites). DAP-Seq of MYB14/MYB15 was combined with aggregate gene co-expression networks (GCNs) built from more than 1400 transcriptomic datasets from leaves, fruits, and flowers to narrow down bound genes to a set of high confidence targets. The analysis of MYB14, MYB15, and MYB13, a third uncharacterized member of Subgroup 2 (S2), showed that in addition to the few previously known stilbene synthase (STS) targets, these regulators bind to 30 of 47 STS family genes. Moreover, all three MYBs bind to several PAL, C4H, and 4CL genes, in addition to shikimate pathway genes, the WRKY03 stilbenoid co-regulator and resveratrol-modifying gene candidates among which ROMT2-3 were validated enzymatically. A high proportion of DAP-Seq bound genes were induced in the activated transcriptomes of transient MYB15-overexpressing grapevine leaves, validating our methodological approach for delimiting TF targets. Overall, Subgroup 2 R2R3-MYBs appear to play a key role in binding and directly regulating several primary and secondary metabolic steps leading to an increased flux towards stilbenoid production. The integration of DAP-Seq and reciprocal GCNs offers a rapid framework for gene function characterization using genome-wide approaches in the context of non-model plant species and stands up as a valid first approach for identifying gene regulatory networks of specialized metabolism.

Aggregated gene co-expression networks predict transcription factor regulatory landscapes in grapevine.

Gene co-expression networks (GCNs) have not been extensively studied in non-model plants. However, the rapid accumulation of transcriptome datasets in certain species represents an opportunity to explore underutilized network aggregation approaches. In fact, aggregated GCNs (aggGCNs) highlight robust co-expression interactions and improve functional connectivity. We applied and evaluated two different aggregation methods on public grapevine RNA-Seq datasets from three different tissues (leaf, berry, and 'all organs'). Our results show that co-occurrence-based aggregation generally yielded the best-performing networks. We applied aggGCNs to study several transcription factor gene families, showing their capacity for detecting both already-described and novel regulatory relationships between R2R3-MYBs, bHLH/MYC, and multiple specialized metabolic pathways. Specifically, transcription factor gene- and pathway-centered network analyses successfully ascertained the previously established role of VviMYBPA1 in controlling the accumulation of proanthocyanidins while providing insights into its novel role as a regulator of p-coumaroyl-CoA biosynthesis as well as the shikimate and aromatic amino acid pathways. This network was validated using DNA affinity purification sequencing data, demonstrating that co-expression networks of transcriptional activators can serve as a proxy of gene regulatory networks. This study presents an open repository to reproduce networks in other crops and a GCN application within the Vitviz platform, a user-friendly tool for exploring co-expression relationships.

Corticosteroid Pulses for Hospitalized Patients with COVID-19: Effects on Mortality.

OBJECTIVES: To assess the influence of corticosteroid pulses on 60-day mortality in hospitalized patients with severe COVID-19. METHODS: We designed a multicenter retrospective cohort study in three teaching hospitals of Castilla y León, Spain (865,096 people). We selected patients with confirmed COVID-19 and lung involvement with a pO2/FiO2<300, excluding those exposed to immunosuppressors before or during hospitalization, patients terminally ill at admission, or those who died in the first 24 hours. We performed a propensity score matching (PSM) adjusting covariates that modify the probability of being treated. Then, we used a Cox regression model in the PSM group to consider factors affecting mortality. RESULTS: From 2933 patients, 257 fulfilled the inclusion and exclusion criteria. 124 patients were on corticosteroid pulses (250 mg of methylprednisolone for three days), and 133 were not. 30.3% (37/122) of patients died in the corticosteroid pulse group and 42.9% (57/133) in the nonexposed cohort. These differences (12.6%, 95% CI [8·54-16.65]) were statically significant (log-rank 4.72, p = 0, 03). We performed PSM using the exact method. Mortality differences remained in the PSM group (log-rank 5.31, p = 0.021) and were still significant after a Cox regression model (HR for corticosteroid pulses 0.561; p = 0.039). CONCLUSIONS: This study provides evidence about treatment with corticosteroid pulses in severe COVID-19 that might significantly reduce mortality. Strict inclusion and exclusion criteria with that selection process set a reliable frame to compare mortality in both the exposed and nonexposed groups.

Effects of Heat Treatment on the Physicochemical Properties and Electrochemical Behavior of Biochars for Electrocatalyst Support Applications.

The present work reports the synthesis and the physicochemical characterization of biochar from the organic wastes of nopal (Opuntia Leucotricha), coffee grounds (Coffea arabica) and Ataulfo mango seeds (Mangifera indica) as alternative electrocatalyst supports to Vulcan XC-72 carbon black. The biochars were prepared using pyrolysis from organic wastes collected at three temperatures, 600, 750 and 900 °C, under two atmospheres, N2 and H2. The synthesized biochars were characterized using Raman spectroscopy and scanning electron microscopy (SEM) to obtain insights into their chemical structure and morphological nature, respectively, as a function of temperature and pyrolysis atmosphere. A N2 adsorption/desorption technique, two-point conductivity measurements and cyclic voltammetry (CV) were conducted to evaluate the specific surface area (SSA), electrical conductivity and double-layer capacitance, respectively, of all the biochars to estimate their physical properties as a possible alternative carbon support. The results indicated that the mango biochar demonstrated the highest properties among all the biochars, such as an electrical conductivity of 8.3 S/cm-1 at 900 °C in N2, a specific surface area of 829 m2/g at 600 °C in H2 and a capacitance of ~300 mF/g at 900 °C in N2. The nopal and coffee biochars exhibited excellent specific surface areas, up to 767 m2/g at 600 °C in N2 and 699 m2/g at 750 °C in H2, respectively; nonetheless, their electrical conductivity and capacitance were limited. Therefore, the mango biochar at 900 °C in N2 was considered a suitable alternative carbon material for electrocatalyst support. Additionally, it was possible to determine that the electrical conductivity and capacitance increased as a function of the pyrolysis temperature, while the specific surface area decreased for some biochars as the pyrolysis temperature increased. Overall, it is possible to conclude that heat treatment at a high temperature of 900 °C enhanced the biochar properties toward electrocatalyst support applications.

Effect of the tri-sodium citrate as a complexing agent in the deposition of ZnS by SILAR.

Using the SILAR method Zinc sulfide coatings were deposited on glass slices. The physical properties and the chemical mechanism throughout the variation in concentration of tri-sodium citrate (TSC) as a chelating agent in the synthesis of thin films were investigated. Results shows that ZnS thin films exhibit an average transmittance of 16% in visible light spectra region and a zinc blende structure. The ZnS films synthesized using TSC as a complexing agent, present a smaller average particle size, an average transmittance of 85%, and an adsorption edge at 300-340 nm. Based on our experimental data and analysis, we conclude that the contribution of the oxychloride species, a subproduct in the chemical deposition, is suggested to be related as an impurity level former in the synthesis of ZnS thin films. TSC as a complexing agent in the SILAR technique is a non-toxic option to reduce the generation of the oxychloride species and synthesize a wide band gap semiconductor. Moreover, the use of complexing agents could be extended to other types of semiconductors deposited by SILAR.

Use of Telemonitoring for CPAP Therapy Control in OSA Patients: Impact on Cost and Process Improvements.

Introduction: In Spain, 2 million people are treated for obstructive sleep apnoea. Continuous positive airway pressure, the gold-standard therapy, requires regular follow-up and periodic evaluation of the efficacy of the treatment via a titration examination, i.e. autoCPAP test. Telemonitoring use is increasing and this study aims to evaluate the cost impact of its use for therapy evaluation instead of the standard ambulatory autoCPAP test. Methods: This prospective observational study includes 100 OSA patients under CPAP therapy who volunteered to test telemonitoring as an alternative therapy control tool. Costs for both the patients and the Sleep Unit were calculated and compared for the standard of care (ambulatory autoCPAP (SoC)), vs alternative telemonitoring option (TM). Results: More than half (54%) of the patients preferred the TM option vs only 47.5% of the SoC patients. Patients inclining towards telemonitoring option were mainly reported to be more than 10 years youngers, mainly active workers (63%), travelling more distance to the Sleep Unit (16 vs 8 km) and spending more expenses in travel than those who preferred SoC (median 30€). 29% of active workers left their jobs to attend the SoC. The costs related to the use of the Sleep Unit resources were found to be lower in the TM option compared to the SoC option (0.47 vs 3.09 euros per patient attended). Conclusions: The use of TM for follow-up CPAP therapy enables the patient to save travel costs and to reduce absenteeism but also to save assistential burden and therefore to reduce the Sleep Unit workload and optimize the care activity.

Transcriptomic and metabolomic integration as a resource in grapevine to study fruit metabolite quality traits.

Transcriptomics and metabolomics are methodologies being increasingly chosen to perform molecular studies in grapevine (Vitis vinifera L.), focusing either on plant and fruit development or on interaction with abiotic or biotic factors. Currently, the integration of these approaches has become of utmost relevance when studying key plant physiological and metabolic processes. The results from these analyses can undoubtedly be incorporated in breeding programs whereby genes associated with better fruit quality (e.g., those enhancing the accumulation of health-promoting compounds) or with stress resistance (e.g., those regulating beneficial responses to environmental transition) can be used as selection markers in crop improvement programs. Despite the vast amount of data being generated, integrative transcriptome/metabolome meta-analyses (i.e., the joint analysis of several studies) have not yet been fully accomplished in this species, mainly due to particular specificities of metabolomic studies, such as differences in data acquisition (i.e., different compounds being investigated), unappropriated and unstandardized metadata, or simply no deposition of data in public repositories. These meta-analyses require a high computational capacity for data mining a priori, but they also need appropriate tools to explore and visualize the integrated results. This perspective article explores the universe of omics studies conducted in V. vinifera, focusing on fruit-transcriptome and metabolome analyses as leading approaches to understand berry physiology, secondary metabolism, and quality. Moreover, we show how omics data can be integrated in a simple format and offered to the research community as a web resource, giving the chance to inspect potential gene-to-gene and gene-to-metabolite relationships that can later be tested in hypothesis-driven research. In the frame of the activities promoted by the COST Action CA17111 INTEGRAPE, we present the first grapevine transcriptomic and metabolomic integrated database (TransMetaDb) developed within the Vitis Visualization (VitViz) platform (https://tomsbiolab.com/vitviz). This tool also enables the user to conduct and explore meta-analyses utilizing different experiments, therefore hopefully motivating the community to generate Findable, Accessible, Interoperable and Reusable (F.A.I.R.) data to be included in the future.

The Grape Gene Reference Catalogue as a Standard Resource for Gene Selection and Genetic Improvement.

Effective crop improvement, whether through selective breeding or biotech strategies, is largely dependent on the cumulative knowledge of a species' pangenome and its containing genes. Acquiring this knowledge is specially challenging in grapevine, one of the oldest fruit crops grown worldwide, which is known to have more than 30,000 genes. Well-established research communities studying model organisms have created and maintained, through public and private funds, a diverse range of online tools and databases serving as repositories of genomes and gene function data. The lack of such resources for the non-model, but economically important, Vitis vinifera species has driven the need for a standardised collection of genes within the grapevine community. In an effort led by the Integrape COST Action CA17111, we have recently developed the first grape gene reference catalogue, where genes are ascribed to functional data, including their accession identifiers from different genome-annotation versions (https://integrape.eu/resources/genes-genomes/). We present and discuss this gene repository together with a validation-level scheme based on varied supporting evidence found in current literature. The catalogue structure and online submission form provided permits community curation. Finally, we present the Gene Cards tool, developed within the Vitis Visualization (VitViz) platform, to visualize the data collected in the catalogue and link gene function with tissue-specific expression derived from public transcriptomic data. This perspective article aims to present these resources to the community as well as highlight their potential use, in particular for plant-breeding applications.

Effect of the Graded Silicon Content in SRN/SRO Multilayer Structures on the Si Nanocrystals and Si Nanopyramids Formation and Their Photoluminescence Response.

Two multilayer (ML) structures, composed of five layers of silicon-rich oxide (SRO) with different Si contents and a sixth layer of silicon-rich nitride (SRN), were deposited by low pressure chemical vapor deposition. These SRN/SRO MLs were thermally annealed at 1100 °C for 180 min in ambient N2 to induce the formation of Si nanostructures. For the first ML structure (MLA), the excess Si in each SRO layer was about 10.7 ± 0.6, 9.1 ± 0.4, 8.0 ± 0.2, 9.1 ± 0.3 and 9.7 ± 0.4 at.%, respectively. For the second ML structure (MLB), the excess Si was about 8.3 ± 0.2, 10.8 ± 0.4, 13.6 ± 1.2, 9.8 ± 0.4 and 8.7 ± 0.1 at.%, respectively. Si nanopyramids (Si-NPs) were formed in the SRO/Si substrate interface when the SRO layer with the highest excess silicon (10.7 at.%) was deposited next to the MLA substrate. The height, base and density of the Si-NPs was about 2-8 nm, 8-26 nm and ~6 × 1011 cm-2, respectively. In addition, Si nanocrystals (Si-ncs) with a mean size of between 3.95 ± 0.20 nm and 2.86 ± 0.81 nm were observed for the subsequent SRO layers. Meanwhile, Si-NPs were not observed when the excess Si in the SRO film next to the Si-substrate decreased to 8.3 ± 0.2 at.% (MLB), indicating that there existed a specific amount of excess Si for their formation. Si-ncs with mean size of 2.87 ± 0.73 nm and 3.72 ± 1.03 nm were observed for MLB, depending on the amount of excess Si in the SRO film. An enhanced photoluminescence (PL) emission (eight-fold more) was observed in MLA as compared to MLB due to the presence of the Si-NPs. Therefore, the influence of graded silicon content in SRN/SRO multilayer structures on the formation of Si-NPs and Si-ncs, and their relation to the PL emission, was analyzed.

Binding and removal of sulfate, phosphate, arsenate, tetrachloromercurate, and chromate in aqueous solution by means of an activated carbon functionalized with a pyrimidine-based anion receptor (HL). Crystal structures of [H3L(HgCl4)]·H2O and [H3L(HgBr4)]·H2O showing anion-π interactions.

Binding of anions of great environmental concern such as SO(4)(2-), PO(4)(3-), AsO(4)(3-), HgCl(4)(2-), and CrO(4)(2-) by the protonated forms of a tren-like (tren = tris(2-aminoethyl)amine) ligand (HL) functionalized with a pyrimidine residue was studied by means of potentiometric measurements and isothermal titration calorimetry (ITC) affording log K, ΔH°, and TΔS° values for the formation of the relevant complexes. The complexes show high to very high stability due to the particular topology and electronic properties of the ligand which is able to use two separated coordination environments to host the anions, the protonated tren site where electrostatic and hydrogen bond interactions are operating, and the pyrimidine ring which may act via anion-π interaction. A contribution of -8.9 ± 0.4 kJ/mol for pyrimidine-anion interaction in water was derived for SO(4)(2-) binding. The crystal structures of [H(3)L(HgCl(4))]·H(2)O (1), [H(3)L(HgBr(4))]·H(2)O (2), and that previously reported for [H(3)L(CdI(4))], clearly show these binding features in the solid state. A hybrid AC-HL material obtained by adsorption of HL on commercial activated carbon (AC) was used to study the removal of these anions from water. AC-HL shows enhanced adsorption capacity toward all the anions studied with respect to AC. This behavior is ascribed to the stronger interaction of anions with the HL function of AC-HL than with the Cπ-H(3)O(+) sites of the unfunctionalized AC.

Quantification of the Antioxidant Activity of Plant Extracts: Analysis of Sensitivity and Hierarchization Based on the Method Used.

Plants have a large number of bioactive compounds with high antioxidant activity. Studies for the determination of the antioxidant activity of different plant species could contribute to revealing the value of these species as a source of new antioxidant compounds. There is a large variety of in vitro methods to quantify antioxidant activity, and it is important to select the proper method to determine which species have the highest antioxidant activity. The aim of this work was to verify whether different methods show the same sensitivity and/or capacity to discriminate the antioxidant activity of the extract of different plant species. To that end, we selected 12 species with different content of phenolic compounds. Their extracts were analyzed using the following methods: 2,2-di-phenyl-1-picrylhydrazyl (DPPH) radical scavenging capacity assay, ferric reducing (FRAP) assay, Trolox equivalent antioxidant capacity (ABTS) assay, and reducing power (RP) assay. The four methods selected could quantify the antioxidant capacity of the 12 study species, although there were differences between them. The antioxidant activity values quantified through DPPH and RP were higher than the ones obtained by ABTS and FRAP, and these values varied among species. Thus, the hierarchization or categorization of these species was different depending on the method used. Another difference established between these methods was the sensitivity obtained with each of them. A cluster revealed that RP established the largest number of groups at the shortest distance from the root. Therefore, as it showed the best discrimination of differences and/or similarities between species, RP is considered in this study as the one with the highest sensitivity among the four studied methods. On the other hand, ABTS showed the lowest sensitivity. These results show the importance of selecting the proper antioxidant activity quantification method for establishing a ranking of species based on this parameter.

Platelet-Activating Factor (PAF) in Allergic Rhinitis: Clinical and Therapeutic Implications.

Platelet-activating factor (PAF) is a lipid mediator involved in several allergic reactions. It is released from multiple cells of the immune system, such as eosinophils, neutrophils, and mast cells, and also exerts its effect on most of them upon specific binding to its receptor, becoming a pleiotropic mediator. PAF is considered a potential relevant mediator in allergic rhinitis, with a key role in nasal congestion and rhinorrhoea due to its effect on vascular permeability. Interestingly, despite its potential relevance as a therapeutic target, no specific PAF inhibitors have been studied in humans. However, rupatadine, a second-generation antihistamine with dual antihistamine and anti-PAF effects has shown promising results by both blocking nasal symptoms and inhibiting mast cell activation induced by PAF, in comparison to antihistamine receptor drugs. In conclusion, the inhibition of PAF may be an interesting approach in the treatment of allergic rhinitis as part of a global strategy directed at blocking as many relevant inflammatory mediators as possible.

Subcutaneous immunotherapy with depigmented-polymerized allergen extracts: a systematic review and meta-analysis.

BACKGROUND: Double-blind, placebo-controlled trials (DBPCTs) have confirmed the efficacy of allergen-specific immunotherapy (AIT) with depigmented-polymerized allergen extracts (DPAEs). This systematic review evaluates the efficacy of AIT using different allergens in different severity stages of rhinoconjunctivitis with or without asthma in the pollen studies and asthma and rhinitis in the house dust mite studies in comparison to placebo. METHODS: We used MEDLINE, Embase, CENTRAL and LILACS databases to review DBPCTs published until July 2016. The combined symptom and medication score (cSMS) served as primary endpoint. The total rhinoconjunctivitis symptom score (RCSS) and total score in Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) were secondary efficacy endpoints. Solicited local and systemic adverse events were secondary safety endpoints. We assumed a random effects model with standardized mean differences (SMDs) or mean differences as summary statistics. In a subgroup analysis, we classified the studies following the GINA (Global Initiative for Asthma) and ARIA (Allergic Rhinitis and its Impact on Asthma) guidelines for rhinoconjunctivitis and asthma severity. RESULTS: Six DBPCTs in pollen and 2 trials in house dust mites (HDM) were selected. Patients (N = 915) with intermittent or mild persistent asthma were included in 3 (37.5%) and 5 (62.5%) trials, respectively. Two (25%) HDM studies included patients with moderate persistent asthma, 4 trials patients with moderate-to-severe rhinoconjunctivitis. Treatment periods ranged from 12 to 24 months. AIT with DPAEs yielded significantly lower cSMS (SMD: 1.9, 95% CI: 0.9-2.8) and RQLQ (SMD: 0.3, 95% CI: 0.1-0.5) values than did placebo. An exploratory analysis of cSMS and RCSS suggested that the efficacy of AIT treatment with DPAEs was higher in trials including patients with more severe rhinoconjunctivitis and asthma. A publication bias was not detected. Heterogeneity between individual studies was explained by differences in severity. Patients receiving DPAEs did not experience a significantly higher risk of local (OR: 1.55, 95% CI: 0.86-2.79) or systemic reactions (OR: 1.94, 95% CI: 0.98-3.84). CONCLUSIONS: Compared to placebo, AIT with DPAEs is effective in patients with pollen- or HDM-induced rhinoconjunctivitis with or without allergic asthma and improves health-related quality of life. It does not differ significantly in safety and tolerability.

High expression of anti-apoptotic genes in grade I and II meningiomas.

Objective: To evaluate the expression of c-FLIP, XIAP, Bcl-2, caspase 3, 8 and 9, cytochrome c, APAF 1 and Smac/DIABLO genes related to apoptosis pathways. Methods: The gene expression was evaluated in 30 meningiomas (WHO grades I and II) and in 10 normal samples (from arachnoid tissue) through PCR-RT. Results: The results showed higher expression of anti-apoptotic genes in meningiomas when compared to the control group, which had a low expression of pro-apoptotic genes. Conclusion: There is a possible block in the activation of caspases through the intrinsic apoptosis pathway in meningiomas. c-FLIP modulates caspase 8 and, by inhibiting its activation due to the lack of connection with the receiver, there is a block to the FAS activation of apoptosis by its extrinsic pathway.

Evaluación de la intervención "Malnutrición por exceso de peso en la primera infancia" con base en el modelo de teoría del cambio, Medellín, Colombia, 2017 / Evaluation of the "Early Childhood Malnutrition due to Overweight" Intervention Based on the Theory of Change Model, Medellín, Colombia, 2017 / Avaliação da intervenção "Má nutrição por excesso de peso na primeira infância" baseada no modelo de teoria da mudança, Medellín, Colômbia, 2017

Resumen Objetivo: Evaluar una intervención de base poblacional denominada "Malnutrición por exceso de peso en la primera infancia", implementada con recursos del programa de Presupuesto Participativo en Salud de Medellín, Colombia, en 2017. Método: Perspectiva de investigación de tipo evaluativa, con base en el modelo de teoría del cambio, utilizado en el campo de la evaluación de programas y proyectos en salud. Se desarrolló un estudio de caso de método mixto convergente e igualdad de estatus. El caso de análisis fue la implementación y los resultados de la intervención "Malnutrición por exceso de peso en la primera infancia". La evaluación se dio en dos fases: 1) la planeación de la evaluación, y 2) la evaluación de los procesos durante su implementación y de los efectos al finalizar la intervención. Resultados: Al finalizar la intervención, no se observaron efectos significativos para los indicadores antropométricos de los niños y las niñas. En el peso para la talla, la mediana al iniciar el tratamiento era de 2,52, y al finalizarlo, de 2,49 (p (0,174) > 0,05). Para el índice de masa corporal, la mediana al iniciar el tratamiento era de 2,4, y al finalizarlo, de 2,3 (p (0,236) > 0,05). Sin embargo, de forma individual hubo variaciones en las desviaciones estándar de los valores Z antropométricos de los niños y las niñas; esto se explica porque en la evaluación de los procesos se identificó el compromiso, la aceptabilidad y la adopción de las recomendaciones nutricionales y psicosociales por parte de los padres y cuidadores. También se encontraron cambios no previstos en el modelo de teoría del cambio, los cuales hacen referencia a variaciones antropométricas en los cuidadores de los niños y las niñas. Conclusión: Los efectos individuales a corto plazo que se dieron en la intervención "Malnutrición por exceso de peso en la primera infancia" favorecieron variaciones antropométricas y el mejoramiento del estado nutricional de niños, niñas y cuidadores, lo cual se explica por la adopción de estilos de vida saludables, lo que permitió alcanzar el cambio global definido para la intervención en el modelo de teoría del cambio.

Abstract Objective: To evaluate a population-based intervention named "Early Childhood Malnutrition due to Overweight" implemented with resources of the Participatory Budget for Health program of Medellín, Colombia, in 2017. Methodology: Evaluative research perspective, based on the theory of change model, used in the field of health projects and programs evaluation. A case study of the convergent mixed method and equality of status was conducted. The case under analysis was the implementation and the results of the intervention "Early Childhood Malnutrition due to Overweight". The evaluation was made in two stages: 1) evaluation planning, and 2) evaluation of the processes during their implementation and the effects at the end of the intervention. Results: At the end of the intervention, significant effects in the anthropometric index of the children were not observed. The median weight-for-height at the beginning of the treatment was 2.52; at the end it was 2.49 (p (0.174) > 0.05). The median body mass index at the beginning of the treatment was 2.4, and at the end, it was (p (0.236) > 0.05). Nevertheless, there were individual variations in the standard deviations of the anthropometric Z-score of children, which is explained due to commitment, acceptability, and adoption of the nutritional and psychosocial recommendations by parents and child caregivers, which were identified during the evaluation of the processes. Changes not expected according to the theory of change model were also found. Those changes refer to the anthropometric variations in the child caregivers. Conclusion: The short-term individual effects that occurred during the "Early Childhood Malnutrition due to Overweight" intervention contributed to the anthropometric variations and the nutritional status improvement of the children and child caregivers. This is explained by the adoption of healthy lifestyles, which allow to reach the global change established for the intervention in the theory of change model.

Resumo Objetivo: Avaliar uma intervenção de base populacional denominada "Má nutrição por excesso de peso na primeira infância" implantada com recursos do programa de Orçamento Participativo em Saúde de Medellín, Colômbia, em 2017. Metodologia: Perspectiva de estudo do tipo avaliativo, com base no modelo de teoria da mudança, utilizado no campo da avaliação de programas e projetos em saúde. Foi desenvolvido um estudo de caso de método misto convergente e igualdade de status. O caso analisado foi a implantação e os resultados da intervenção "Má nutrição por excesso de peso na primeira infância". A avaliação foi feita em duas etapas: 1) O planejamento da avaliação, e 2) A avaliação dos processos durante sua implantação e dos efeitos ao terminar tal intervenção. Resultados: Ao concluir a intervenção, não se observaram efeitos significativos para os indicadores antropométricos das crianças. No quesito para o tamanho, a média ao iniciar o tratamento era de 2,52 e ao finalizá-lo, de 2,49 (p (0,174) > 0,05). Para o índice de massa corporal a média ao iniciar o tratamento era de 2,4 e ao finalizá-lo, de 2,3 (p (0,236) > 0,05). Porém, de maneira individual houve variações nos desvios padrão dos valores Z antropométricos das crianças; isto se explica porque na avaliação dos processos foi identificado o compromisso, a aceitação e a adoção das recomendações nutricionais e psicossociais por parte dos pais e cuidadores. Também foram encontradas mudanças não previstas no modelo de teoria da mudança, as quais se referem a variações antropométricas nos cuidadores das crianças Conclusão: Os efeitos individuais em curto prazo que se deram na intervenção "Má nutrição por excesso de peso na primeira infância" foram favoráveis às variações antropométricas e ao melhoramento do estado nutricional das crianças e cuidadores, o qual se explica pela implantação de estilos de vida saudáveis, o que permitiu alcançar a mudança global definida para a intervenção no modelo de teoria da mudança