Circulating immunome fingerprint in eosinophilic esophagitis is associated with clinical response to proton pump inhibitor treatment.

Objectives: The aim of the study was to characterize the circulating immunome of patients with EoE before and after proton pump inhibitor (PPI) treatment in order to identify potential non-invasive biomarkers of treatment response. Methods: PBMCs from 19 healthy controls and 24 EoE patients were studied using a 39-plex spectral cytometry panel. The plasmacytoid dendritic cell (pDC) population was differentially characterized by spectral cytometry analysis and immunofluorescence assays in esophageal biopsies from 7 healthy controls and 13 EoE patients. Results: Interestingly, EoE patients at baseline had lower levels of circulating pDC compared with controls. Before treatment, patients with EoE who responded to PPI therapy had higher levels of circulating pDC and classical monocytes, compared with non-responders. Moreover, following PPI therapy pDC levels were increased in all EoE patients, while normal levels were only restored in PPI-responding patients. Finally, circulating pDC levels inversely correlated with peak eosinophil count and pDC count in esophageal biopsies. The number of tissue pDCs significantly increased during active EoE, being even higher in non-responder patients when compared to responder patients pre-PPI. pDC levels decreased after PPI intake, being further restored almost to control levels in responder patients post-PPI. Conclusions: We hereby describe a unique immune fingerprint of EoE patients at diagnosis. Moreover, circulating pDC may be also used as a novel non-invasive biomarker to predict subsequent response to PPI treatment.

[Depressive symptoms in a sample of women with subclinical hypothyroidism and their relationship to chlorates in tap water]. / Síntomas depresivos en una muestra de mujeres con hipotiroidismo subclínico y su relación con los cloratos del agua del grifo.

Introduction: Introduction: depressive symptoms may develop in subclinical hypothyroidism and their presence usually facilitates recognition and the establishment of replacement treatment; however, recent studies have found no association between the two. Besides, thyroid function can be affected by endocrine disruptors and some of them, such as chlorates, can be found in the water we drink. Objectives: to know if the type of water consumed may influence the development of depressive symptoms in patients with subclinical hypothyroidism. Methods: 96 women with subclinical hypothyroidism, without thyroid treatment, were enrolled. We studied, among other variables, the presence of depressive symptoms, type of water consumption (tap, bottled or spring) and the level of chlorates in the tap water. Results: 41.7 % (40) of women presented depressive symptoms and these were related to the consumption of tap water (p = 0.001), resulting in a reliable predictor (OR, 27.79; p = 0.007). Chlorate level in the tap water was 250 µg/L, a value within the maximum limit allowed by law. Conclusions: chronic exposure to chlorates in water, in women with subclinical hypothyroidism, at levels authorized by law, could favor the inhibition of iodine transport and the appearance of depressive symptoms. It would be interesting to test this hypothesis as well as its possible effect on other population profiles.

Introducción: Introducción: en el hipotiroidismo subclínico pueden aparecer síntomas depresivos y su presencia suele facilitar la instauración de un tratamiento de reemplazo; sin embargo, estudios recientes no han encontrado una asociación entre ambos. Por otra parte, la función tiroidea puede verse afectada por disruptores endocrinos y, algunos de ellos, como los cloratos, pueden encontrarse en el agua que bebemos. Objetivos: conocer si el tipo de consumo de agua puede influir en la aparición de síntomas depresivos en pacientes con hipotiroidismo subclínico. Métodos: participaron 96 mujeres con hipotiroidismo subclínico, sin tratamiento tiroideo, de un área de salud de España. Estudiamos, entre otras variables, la presencia de síntomas depresivos, el tipo de consumo de agua (grifo/embotellada o manantial) y el nivel de cloratos en el agua del grifo. Resultados: el 41,7 % (40) de las mujeres presentaban síntomas depresivos y estos se relacionaban con el consumo de agua del grifo (p = 0,001), resultando este un predictor confiable (OR: 27,79; p = 0,007). El nivel de cloratos en el agua del grifo era de 250 µg/L, valor situado en el límite máximo permitido por la ley. Conclusiones: en mujeres con hipotiroidismo subclínico, la exposición crónica a cloratos en el agua, en niveles autorizados por la ley, podría favorecer la inhibición del transporte de yodo y la aparición de síntomas depresivos. Sería interesante comprobar esta hipótesis, así como su posible efecto sobre otros perfiles poblacionales.

Swallowed topical corticosteroids for eosinophilic esophagitis: Utilization and real-world efficacy from the EoE CONNECT registry.

BACKGROUND: Swallowed topical corticosteroids (tC) are common therapy for patients with eosinophilic esophagitis (EoE). Widely heterogeneous results have occurred due to their active ingredients, formulations and doses. OBJECTIVE: To assess the effectiveness of topical corticosteroid therapy for EoE in real-world practice. METHODS: Cross-sectional study analysis of the multicentre EoE CONNECT registry. Clinical remission was defined as a decrease of ≥50% in dysphagia symptom scores; histological remission was defined as a peak eosinophil count below 15 per high-power field. The effectiveness in achieving clinico-histological remission (CHR) was compared for the main tC formulations. RESULTS: Overall, data on 1456 prescriptions of tC in monotherapy used in 866 individual patients were assessed. Of those, 904 prescriptions with data on formulation were employed for the induction of remission; 234 reduced a previously effective dose for maintenance. Fluticasone propionate formulations dominated the first-line treatment, while budesonide was more common in later therapies. A swallowed nasal drop suspension was the most common formulation of fluticasone propionate. Doses ≥0.8 mg/day provided a 65% CHR rate and were superior to lower doses. Oral viscous solution prepared by a pharmacist was the most common prescription of budesonide; 4 mg/day provided no benefit over 2 mg/day (CHR rated being 72% and 80%, respectively). A multivariate analysis revealed budesonide orodispersible tablets as the most effective therapy (OR 18.9, p < 0.001); use of higher doses (OR 4.3, p = 0.03) and lower symptom scores (OR 0.9, p = 0.01) were also determinants of effectiveness. CONCLUSION: Reduced symptom severity, use of high doses, and use of budesonide orodispersible tablets particularly were all independent predictors of tC effectiveness.

Esophageal biomechanics assessed by impedance planimetry (EndoFLIPTM) in healthy subjects and in patients with eosinophilic esophagitis. Normality values.

BACKGROUND: active eosinophilic esophagitis is associated with esophageal caliber, distensibility and motility changes that may be reversed with treatment. OBJECTIVES: to study esophageal diameter, distensibility and contractility in healthy subjects compared to patients with eosinophilic esophagitis, both before and after treatment. METHODS: a quasi-experimental study, EndoFLIP™, was used to analyze the esophageal body and esophago-gastric junction (EGJ) in all three groups, and a program was designed to obtain esophageal diameter, distensibility and contractility values. RESULTS: ten healthy volunteers (24-61 years, six men) and nine patients with eosinophilic esophagitis (21-52 years, seven men) were included. The esophagogastric junction distensibility index was 5.07 mm2/Hg in the control subjects, 2.40 mm2/Hg in the subjects with eosinophilic esophagitis before treatment and 2.46 mm2/Hg after treatment. The distensibility plateau was 20.02 mm, 15.43 mm and 17.41 mm, respectively, and the diameter was 21.90 mm, 17.73 mm and 18.30 mm, showing significant differences (p < 0.05), except between control subjects and patients after treatment (p = 0.079). Repetitive antegrade contractions developed in 90 % of control subjects, 66.7 % of eosinophilic esophagitis patients before treatment and 88.9 % of the latter after treatment (p > 0.05). CONCLUSIONS: esophago-gastric junction distensibility index, distensibility plateau and diameter values were higher in controls than in patients, although six weeks of treatment seems a short period to observe significant changes in esophageal biomechanics. Repetitive antegrade contractions are the predominant pattern in healthy subjects and eosinophilic esophagitis. We provide normality values for esophageal biomechanics, measured by impedance planimetry in our setting.

Neonatal outcomes after water birth: A retrospective cohort study.

OBJECTIVE: To compare neonatal outcomes between water births, births with immersion only during labour, and births in which immersion was never used. METHODS: A retrospective cohort study was performed including mother-baby dyads attended between 2009 and 2019 at the Hospital do Salnés regional hospital (Pontevedra, Spain). These women were categorised into 3 groups: water birth; immersion only during dilation; and women who never used immersion. Several sociodemographic-obstetric variables were studied and the main outcome was the admission of the neonate to the intensive care unit (NICU). Permission was obtained from the responsible provincial ethics committee. Descriptive statistics were used and between-group comparisons were performed using variance for continuous variables and chi-square for categorical variables. Multivariate analysis was performed with backward stepwise logistic regression and incidence risk ratios with 95%CI were calculated for each independent variable. Data were analysed using IBM SPSS® statistical software. RESULTS: A total of 1191 cases were included. 404 births without immersions; 397 immersions only during the first stage of labor; and 390 waterbirths were included. No differences were found in the need to transfer new-borns to a NICU (p = .735). In the waterbirth cohort, neonatal resuscitation (p < .001, OR: 0,1), as well as respiratory distress (p = .005, OR: 0,2) or neonatal problems during admission (p < .001, OR: 0,2), were lower. In the immersion only during labor cohort, less neonatal resuscitation (p = .003; OR: 0,4) and respiratory distress (p = .019; OR: 0,4) were found. The probability of not breastfeeding upon discharge was higher for the land birth cohort (p < .001, OR: 0,4). CONCLUSIONS: The results of this study indicated that water birth did not influence the need for NICU admission, but was associated with fewer adverse neonatal outcomes, such as resuscitation, respiratory distress, or problems during admission.

Proteomic analysis of the esophageal epithelium reveals key features of eosinophilic esophagitis pathophysiology.

BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic non-IgE-mediated allergic disease of the esophagus. An unbiased proteomics approach was performed to investigate pathophysiological changes in esophageal epithelium. Additionally, an RNAseq-based transcriptomic analysis in paired samples was also carried out. METHODS: Total proteins were purified from esophageal endoscopic biopsies in a cohort of adult EoE patients (n = 25) and healthy esophagus controls (n = 10). Differentially accumulated (DA) proteins in EoE patients compared to control tissues were characterized to identify altered biological processes and signaling pathways. Results were also compared with a quantitative proteome dataset of the human esophageal mucosa. Next, results were contrasted with those obtained after RNAseq analysis in paired samples. Finally, we matched up protein expression with two EoE-specific mRNA panels (EDP and Eso-EoE panel). RESULTS: A total of 1667 proteins were identified, of which 363 were DA in EoE. RNA sequencing in paired samples identified 1993 differentially expressed (DE) genes. Total RNA and protein levels positively correlated, especially in DE mRNA-proteins pairs. Pathway analysis of these proteins in EoE showed alterations in immune and inflammatory responses for the upregulated proteins, and in epithelial differentiation, cornification and keratinization in those downregulated. Interestingly, a set of DA proteins, including eosinophil-related and secreted proteins, were not detected at the mRNA level. Protein expression positively correlated with EDP and Eso-EoE, and corresponded with the most abundant proteins of the human esophageal proteome. CONCLUSIONS: We unraveled for the first time key proteomic features involved in EoE pathogenesis. An integrative analysis of transcriptomic and proteomic datasets provides a deeper insight than transcriptomic alone into understanding complex disease mechanisms.

Encephalartos natalensis, Their Nutrient-Cycling Microbes and Enzymes: A Story of Successful Trade-Offs.

Encephalartos spp. establish symbioses with nitrogen (N)-fixing bacteria that contribute to soil nutrition and improve plant growth. Despite the Encephalartos mutualistic symbioses with N-fixing bacteria, the identity of other bacteria and their contribution to soil fertility and ecosystem functioning is not well understood. Due to Encephalartos spp. being threatened in the wild, this limited information presents a challenge in developing comprehensive conservation and management strategies for these cycad species. Therefore, this study identified the nutrient-cycling bacteria in Encephalartos natalensis coralloid roots, rhizosphere, and non-rhizosphere soils. Additionally, the soil characteristics and soil enzyme activities of the rhizosphere and non-rhizosphere soils were assayed. The coralloid roots, rhizosphere, and non-rhizosphere soils of E. natalensis were collected from a population of >500 E. natalensis in a disturbed savanna woodland at Edendale in KwaZulu-Natal (South Africa) for nutrient analysis, bacterial identification, and enzyme activity assays. Nutrient-cycling bacteria such as Lysinibacillus xylanilyticus; Paraburkholderia sabiae, and Novosphingobium barchaimii were identified in the coralloid roots, rhizosphere, and non-rhizosphere soils of E. natalensis. Phosphorus (P) cycling (alkaline and acid phosphatase) and N cycling (ß-(D)-Glucosaminidase and nitrate reductase) enzyme activities showed a positive correlation with soil extractable P and total N concentrations in the rhizosphere and non-rhizosphere soils of E. natalensis. The positive correlation between soil enzymes and soil nutrients demonstrates that the identified nutrient-cycling bacteria in E. natalensis coralloid roots, rhizosphere, and non-rhizosphere soils and associated enzymes assayed may contribute to soil nutrient bioavailability of E. natalensis plants growing in acidic and nutrient-poor savanna woodland ecosystems.

Differences between childhood- and adulthood-onset eosinophilic esophagitis: An analysis from the EoE connect registry.

BACKGROUND: Direct comparisons of childhood- and adulthood-onset eosinophilic esophagitis (EoE) are scarce. AIM: To compare disease characteristics, endoscopic and histological features, allergic concomitances and therapeutic choices across ages. METHODS: Cross-sectional analysis of the EoE CONNECT registry. RESULTS: The adulthood-onset cohort (those diagnosed at ≥18y) comprised 1044 patients and the childhood-onset cohort (patients diagnosed at <18 y), 254. Vomiting, nausea, chest and abdominal pain, weight loss, slow eating and food aversion were significantly more frequent in children; dysphagia, food bolus impaction and heartburn predominated in adults. A family history of EoE was present in 16% of pediatric and 8.2% of adult patients (p<0.001). Concomitant atopic diseases did not vary across ages. Median±IQR diagnostic delay (years) from symptom onset was higher in adults (2.7 ± 6.1) than in children (1 ± 2.1; p<0.001). Esophageal strictures and rings predominated in adults (p<0.001), who underwent esophageal dilation more commonly (p = 0.011). Inflammatory EoE phenotypes were more common in children (p = 0.001), who also presented higher eosinophil counts in biopsies (p = 0.015) and EREFS scores (p = 0.017). Despite PPI predominating as initial therapy in all cohorts, dietary therapy and swallowed topical corticosteroids were more frequently prescribed in children (p<0.001). CONCLUSIONS: Childhood-onset EoE has differential characteristics compared with adulthood-onset, but similar response to treatment.

Exposure to Morphine and Cocaine Modify the Transcriptomic Landscape in Zebrafish Embryos.

Morphine and other opioid analgesics are the drugs of election to treat moderate-to-severe pain, and they elicit their actions by binding to the opioid receptors. Cocaine is a potent inhibitor of dopamine, serotonin, and noradrenaline reuptake, as it blocks DAT, the dopamine transporter, causing an increase in the local concentration of these neurotransmitters in the synaptic cleft. The molecular effects of these drugs have been studied in specific brain areas or nuclei, but the systemic effects in the whole organism have not been comprehensively analyzed. This study aims to analyze the transcriptomic changes elicited by morphine (10 uM) and cocaine (15 uM) in zebrafish embryos. An RNAseq assay was performed with tissues extracts from zebrafish embryos treated from 5 hpf (hours post fertilization) to 72 hpf, and the most representative deregulated genes were experimentally validated by qPCR. We have found changes in the expression of genes related to lipid metabolism, chemokine receptor ligands, visual system, hemoglobins, and metabolic detoxification pathways. Besides, morphine and cocaine modified the global DNA methylation pattern in zebrafish embryos, which would explain the changes in gene expression elicited by these two drugs of abuse.

Accurate and timely diagnosis of Eosinophilic Esophagitis improves over time in Europe. An analysis of the EoE CONNECT Registry.

BACKGROUND: Poor adherence to clinical practice guidelines for eosinophilic esophagitis (EoE) has been described and the diagnostic delay of the disease continues to be unacceptable in many settings. OBJECTIVE: To analyze the impact of improved knowledge provided by the successive international clinical practice guidelines on reducing diagnostic delay and improving the diagnostic process for European patients with EoE. METHODS: Cross-sectional analysis of the EoE CONNECT registry based on clinical practice. Time periods defined by the publication dates of four major sets of guidelines over 10 years were considered. Patients were grouped per time period according to date of symptom onset. RESULTS: Data from 1,132 patients was analyzed and median (IQR) diagnostic delay in the whole series was 2.1 (0.7-6.2) years. This gradually decreased over time with subsequent release of new guidelines (p < 0.001), from 12.7 years up to 2007 to 0.7 years after 2017. The proportion of patients with stricturing of mixed phenotypes at the point of EoE diagnosis also decreased over time (41.3% vs. 16%; p < 0.001), as did EREFS scores. The fibrotic sub-score decreased from a median (IQR) of 2 (1-2) to 0 (0-1) when patients whose symptoms started up to 2007 and after 2017 were compared (p < 0.001). In parallel, symptoms measured with the Dysphagia Symptoms Score reduced significantly when patients with symptoms starting before 2007 and after 2012 were compared. A reduction in the number of endoscopies patients underwent before the one that achieved an EoE diagnosis, and the use of allergy testing as part of the diagnostic workout of EoE, also reduced significantly over time (p = 0.010 and p < 0.001, respectively). CONCLUSION: The diagnostic work-up of EoE patients improved substantially over time at the European sites contributing to EoE CONNECT, with a dramatic reduction in diagnostic delay.

Small static radiosurgery field dosimetry with small volume ionization chambers.

PURPOSE: To evaluate the response of the four smallest active volume thimble type ionization chambers commercially available (IBA-dosimetry RAZOR Nano Chamber, Standard Imaging Exradin A16, IBA-dosimetry CC01 and PTW T31022) when measuring SRS cone collimated Flattening Filter Free (FFF) fields. METHODS: We employed Monte Carlo simulation for calculating correction factors as defined in IAEA TRS-483. Monte Carlo simulation beam model and ion chamber geometry definitions were supported by an extensive set of measurements. Type A and B uncertainty components were evaluated. RESULTS: Commissioning of Monte Carlo 6 MV and 10 MV FFF beam models yielded relative differences between measured and simulated dose distributions lower than 1.5%. Monte Carlo simulated output factors for 5 mm SRS field agree with experimental values within 1% local relative difference for all chambers. Smallest active volume ion chamber (IBA-dosimetry RAZOR Nano Chamber) exhibits smallest correction, being compatible with unity. Correction factor combined uncertainties range between 0.7% and 0.9%. Smallest uncertainties were recorded for smallest and largest active volume ion chambers, although the latter exhibited largest correction factor. Highest contribution to combined uncertainty was type B component associated with beam model initial electron spatial Full Width Half Maximum (FWHM) uncertainty. CONCLUSIONS: Among the investigated chambers, the IBA RAZOR Nano Chamber was found to be an excellent choice for narrow beam output factor measurement since it requires minimum correction (in line with IAEA TRS-483 recommendations). This is caused by its tiny size and tissue equivalence materials which produce minimum volume averaging and fluence perturbation.

[Effects of the intake of dairy products naturally enriched with selenium and omega-3 polyunsaturated fatty acids in a sample of postmenopausal women with metabolic syndrome: a randomized, triple-blind, placebo-controlled clinical trial]. / Efectos de la ingesta de lácteos enriquecidos de forma natural con selenio y omega-3 en una muestra de mujeres posmenopáusicas con síndrome metabólico: un ensayo clínico aleatorizado, triple ciego y controlado con placebo.

INTRODUCTION: Introduction: metabolic syndrome in postmenopausal women can improve with a healthy diet. Objectives: to evaluate whether a dietary intervention with dairy products naturally enriched with selenium and omega-3 polyunsaturated fatty acids increases selenium plasma levels and improves cardiovascular risk factors in postmenopausal women with metabolic syndrome. Material and methods: a randomized, triple-blind, controlled clinical trial carried out in GP surgeries. Recruitment: April 2018, 46 postmenopausal women with metabolic syndrome who were frequent dairy consumers. Randomization: 23 in control group and 23 in experimental group. Intervention: consumption of dairy products naturally enriched with selenium and omega-3 polyunsaturated fatty acids (milk, yogurt, fresh cheese) for three months. Controls took conventional dairy. Primary endpoint: plasma selenium levels; secondary endpoints: metabolic syndrome criteria. Registration number 2018/256, Galicia Ethics Committee. Results: in all, 23 women in the control group and 21 in the intervention group completed the trial. Selenium increased in the intervention group (7.2 µg/L, 95 % CI, 3.7/10.8) compared to the control group (-4.5 µg/L, 95 % CI, -8/-1) (p < 0.001) and very low-density lipoprotein cholesterol decreased (-2.3 mg/dL, 95 % CI, -5.6/1) compared to the control group (1.9 mg/dL, 95 % CI, -0.7/4.5) (p = 0.043). Waist circumference (p = 0.010), body mass index (p = 0.047) and high-density lipoprotein cholesterol (p < 0.001) in the experimental group improved in comparison to baseline measurements. Conclusions: an intervention with dairy products naturally enriched with selenium and omega-3 in a sample of postmenopausal women with metabolic syndrome can improve plasma selenium levels and very low-density lipoprotein cholesterol.

INTRODUCCIÓN: Introducción: el síndrome metabólico de las mujeres posmenopáusicas puede mejorar con una alimentación saludable. Objetivos: evaluar si una intervención alimentaria con productos lácteos enriquecidos en selenio y ácidos grasos poliinsaturados omega-3 aumenta los niveles de selenio y mejora los factores de riesgo cardiovascular en las mujeres posmenopáusicas con síndrome metabólico. Material y métodos: ensayo clínico aleatorizado, triple ciego y controlado, realizado en atención primaria. Captación: abril 2018, 46 mujeres posmenopáusicas con síndrome metabólico consumidoras habituales de lácteos. Aleatorización: 23 en el grupo de control y 23 en el grupo experimental. Intervención: consumo durante 3 meses de lácteos enriquecidos naturalmente con selenio y ácidos grasos poliinsaturados omega-3 (leche, yogur y queso fresco). Controles: consumo de lácteos convencionales. Variable principal: selenio en plasma; secundarias: criterios del síndrome metabólico. Número de registro 2018/256, Comité de Ética Galicia. Resultados: finalizaron 23 mujeres en el grupo de control y 21 en el grupo de intervención. Aumentó el selenio en el grupo de intervención (7,2 µg/L, IC del 95 %: 3,7/10,8) frente al grupo de control (-4,5 µg/L, IC del 95 %: -8/-1) (p < 0,001) y disminuyó el colesterol unido a lipoproteínas de muy baja densidad (-2,3 mg/dl, IC del 95 %: -5,6/1) respecto al grupo de control (1,9 mg/dl, IC del 95 %: -0,7/4,5) (p = 0,043). Las mujeres del grupo experimental mejoraron respecto a su medición basal en perímetro de cintura (p = 0,010), índice de masa corporal (p = 0,047) y colesterol unido a lipoproteínas de alta densidad (p < 0,001). Conclusiones: una intervención con lácteos enriquecidos naturalmente con selenio y omega-3 en mujeres posmenopáusicas con síndrome metabólico puede mejorar los niveles de selenio en plasma y de colesterol unido a lipoproteínas de muy baja densidad.

[Characteristics and evolution of COVID-19 in an urban Health Center at the pandemic beginning']. / Características y evolución de los pacientes COVID-19 en un centro de salud urbano al inicio de la pandemia.

OBJETIVE: To evaluate SAR-COV-2 pacients' features. To analyse de diferences between those who required hospital care and those who didn't. DESIGN: Observational, descriptive and retrospective study. SETTING: Twomedical practices of an urban health center in Salamanca (Spain). PARTICIPANTS: ≥18 years diagnosed with SAR-CoV-2 between March 11th and April 20th. MAIN MEASUREMENTS: clinical-epidemiological chatacteristics, diagnosis, treatment and outcome at the end of study RESULTS: 122 patients (63.9% female), 19.7% social and health care workers y 4.9% from nursing homes. Predominant age group: 46-60 years. 67.2% without comorbility. Predomint symptoms: low-grade fever (73.5%), cough (65.2%) y fever (43%). Average age of the patients requiring hospital care was higher: 59.85 (DE16.22) versus 50.78 (DE17.88) P=.013. 63.6% of all the patients monitored by Primary Health Care and 14.1% of patients that required assistance did not present dyspnea P=.001. Only 2.5% of the hospital-assisted patients, compared to 61.5% of Primary Health Care, were not tested P=.0001. 26 patients were attendedn at an emergency room: 11(9%) stayed and 2 (1.6%) passed away. No antibiotic or inhaler treatment for 52.5% and 70.5% respectively. The most used antipyretic treatment was paracetamol (78.7%). CONCLUSIONS: Prevalence in females, comorbility-free patients and in age range: 46-60 years. Complementary and confirmatory test were performed mainly in hospital care. Predominance of mild symptoms and favourable evolution. Highliting the role played by Primary Health Care in detection, early intervention and monitoring of severe cases.

Phosphate and phosphite have a differential impact on the proteome and phosphoproteome of Arabidopsis suspension cell cultures.

Phosphorus absorbed in the form of phosphate (H2 PO4- ) is an essential but limiting macronutrient for plant growth and agricultural productivity. A comprehensive understanding of how plants respond to phosphate starvation is essential for the development of more phosphate-efficient crops. Here we employed label-free proteomics and phosphoproteomics to quantify protein-level responses to 48 h of phosphate versus phosphite (H2 PO3- ) resupply to phosphate-deprived Arabidopsis thaliana suspension cells. Phosphite is similarly sensed, taken up and transported by plant cells as phosphate, but cannot be metabolized or used as a nutrient. Phosphite is thus a useful tool for differentiating between non-specific processes related to phosphate sensing and transport and specific responses to phosphorus nutrition. We found that responses to phosphate versus phosphite resupply occurred mainly at the level of protein phosphorylation, complemented by limited changes in protein abundance, primarily in protein translation, phosphate transport and scavenging, and central metabolism proteins. Altered phosphorylation of proteins involved in core processes such as translation, RNA splicing and kinase signaling was especially important. We also found differential phosphorylation in response to phosphate and phosphite in 69 proteins, including splicing factors, translation factors, the PHT1;4 phosphate transporter and the HAT1 histone acetyltransferase - potential phospho-switches signaling changes in phosphorus nutrition. Our study illuminates several new aspects of the phosphate starvation response and identifies important targets for further investigation and potential crop improvement.

An EGS Monte Carlo model for Varian TrueBEAM treatment units: Commissioning and experimental validation of source parameters.

In this work we have created and commissioned a Monte Carlo model of 6FFF Varian TrueBeam linear accelerator using BEAMnrc. For this purpose we have experimentally measured the focal spot size and shape of three Varian TrueBeam treatment units in 6FFF modality with a slit collimator and several depth dose and lateral beam profiles in a water phantom. The Monte Carlo model of a 6FFF TrueBeam machine was implemented with a primary electron source commissioned as a 2D Gaussian with Full Width Half Maximum selected by comparison of simulated and measured narrow beam profiles. The energy of the primary electron beam was optimized through a simultaneous fit to the measured beam depth dose profiles. Special attention was paid to evaluation of uncertainties of the selected Monte Carlo source parameters. These uncertainties were calculated by analysing the sensitivity of the commissioning process to changes in both primary beam size and energy. Both experimental and Monte Carlo commissioned focus size values were compared and found to be in excellent agreement. The commissioned Monte Carlo model reproduces within 1% accuracy the dose distributions of radiation field size from 3 cm × 3 cm to 15 cm × 15 cm.

Phosphorus and Nitrogen Modulate Plant Performance in Shrubby Legumes from the Iberian Peninsula.

We investigated the impact of phosphorus nutrition on plant growth and biological nitrogen fixation in four leguminous plants in the Tribe Genistea. The main objective of the study was to analyze Phosphorus and Nitrogen use efficiency under drought. We also tested for the effects of rhizobial inoculation on plant performance. Plants inoculated with Rhizobium strains isolated from plants of the four species growing in the wild were cropped under controlled conditions in soils with either low P (5 µM) or high P (500 µM). The experiment was replicated in the presence and absence of plant irrigation to test for the effects of drought stress of inoculated and non-inoculated plants under the two P levels of fertilization. Low-P treatments increased nodule production while plant biomass and shoot and root P and N contents where maximum at high P. Low P (5 µM) in the growing media, resulted in greater N accumulated in plants, coupled with greater phosphorus and nitrogen uptake efficiencies. Drought reduced the relative growth rate over two orders of magnitude or more, depending on the combination of plant species and treatment. Genista cinerea had the lowest tolerance to water scarcity, whereas Genista florida and Retama sphaerocarpa were the most resistant species to drought. Drought resistance was enhanced in the inoculated plants. In the four species, and particularly in Echinospartum barnadesii, the inoculation treatment clearly triggered N use efficiency, whereas P use efficiency was greater in the non-inoculated irrigated plants. Nodulation significantly increased in plants in the low P treatments, where plants showed a greater demand for N. The physiological basis for the four species being able to maintain their growth at low P levels and to respond to the greater P supply, is through balanced acquisition of P and N to meet the plants' nutritional needs.

Atherosclerosis in Chronic Kidney Disease: More, Less, or Just Different?

Patients with chronic kidney disease (CKD) are at an increased risk of premature mortality, mainly from cardiovascular causes. The association between CKD on hemodialysis and accelerated atherosclerosis was described >40 years ago. However, more recently, it has been suggested that the increase in atherosclerosis risk is actually observed in early CKD stages, remaining stable thereafter. In this regard, interventions targeting the pathogenesis of atherosclerosis, such as statins, successful in the general population, have failed to benefit patients with very advanced CKD. This raises the issue of the relative contribution of atherosclerosis versus other forms of cardiovascular injury such as arteriosclerosis or myocardial injury to the increased cardiovascular risk in CKD. In this review, the pathophysiogical contributors to atherosclerosis in CKD that are shared with the general population, or specific to CKD, are discussed. The NEFRONA study (Observatorio Nacional de Atherosclerosis en NEFrologia) prospectively assessed the prevalence and progression of subclinical atherosclerosis (plaque in vascular ultrasound), confirming an increased prevalence of atherosclerosis in patients with moderate CKD. However, the adjusted odds ratio for subclinical atherosclerosis increased with CKD stage, suggesting a contribution of CKD itself to subclinical atherosclerosis. Progression of atherosclerosis was closely related to CKD progression as well as to the baseline presence of atheroma plaque, and to higher phosphate, uric acid, and ferritin and lower 25(OH) vitamin D levels. These insights may help design future clinical trials of stratified personalized medicine targeting atherosclerosis in patients with CKD. Future primary prevention trials should enroll patients with evidence of subclinical atherosclerosis and should provide a comprehensive control of all known risk factors in addition to testing any additional intervention or placebo.

Efficacy of baths with mineral-medicinal water in patients with fibromyalgia: a randomized clinical trial.

The layout of this study, designed as a randomized crossover clinical trial, is to evaluate the efficacy of an intervention with mineral-medicinal water from As Burgas (Ourense) in patients suffering from fibromyalgia. This sample was randomly divided into two groups: group A and group B. In phase 1, group A had 14 baths in thermal water for a month and standard pharmacological treatment; group B, standard pharmacological treatment. Washout period is 3 months. In phase 2, group A had standard treatment and group B had 14 baths in thermal water for a month plus standard treatment. The Fibromyalgia Impact Questionnaire (FIQ) was used; this grades the impact of the illness from 1 (minimum) to 10 (maximum), which was measured in both phases. Twenty-five patients were included in each group and the study was concluded with 20 patients in group A and 20 in group B. The intervention group obtained, once the baths finished, a mean score of 60.3 (± 11.8) and the control group of 70.8 (± 13.0) (p < 0.001). Three months later, the intervention group presented a mean score of 64.4 (± 10.6) and the control group of 5.0 (± 11.3) (p < 0.001). We can therefore conclude that the simple baths with mineral-medicinal water from As Burgas can make an improvement on the impact caused by fibromyalgia.