Changes in water content and distribution in Quercus ilex leaves during progressive drought assessed by in vivo 1H magnetic resonance imaging

12 páginas, 7 figuras.-- Metodología.[Background]: Drought is a common stressor in many regions of the world and current climatic global circulation models predict further increases in warming and drought in the coming decades in several of these regions, such as the Mediterranean basin. The changes in leaf water content, distribution and dynamics in plant tissues under different soil water availabilities are not well known. In order to fill this gap, in the present report we describe our study withholding the irrigation of the seedlings of Quercus ilex, the dominant tree species in the evergreen forests of many areas of the Mediterranean Basin. We have monitored the gradual changes in water content in the different leaf areas, in vivo and non-invasively, by 1H magnetic resonance imaging (MRI) using proton density weighted (ρw) images and spin-spin relaxation time (T2) maps. [Results]: ρw images showed that the distal leaf area lost water faster than the basal area and that after four weeks of similar losses, the water reduction was greater in leaf veins than in leaf parenchyma areas and also in distal than in basal leaf area. There was a similar tendency in all different areas and tissues, of increasing T2 values during the drought period. This indicates an increase in the dynamics of free water, suggesting a decrease of cell membranes permeability. [Conclusions]: The results indicate a non homogeneous leaf response to stress with a differentiated capacity to mobilize water between its different parts and tissues. This study shows that the MRI technique can be a useful tool to follow non-intrusively the in vivo water content changes in the different parts of the leaves during drought stress. It opens up new possibilities to better characterize the associated physiological changes and provides important information about the different responses of the different leaf areas what should be taken into account when conducting physiological and metabolic drought stress studies in different parts of the leaves during drought stress.This research was supported by the European project NEU NITROEUROPE (GOCE017841), by the Spanish Government grants CGL2006-04025/BOS and Consolider-Ingenio Montes CSD2008-00040 and the Catalan Government grant SGR 2009-1458.Peer reviewe

High TGFβ-Smad Activity Confers Poor Prognosis in Glioma Patients and Promotes Cell Proliferation Depending on the Methylation of the PDGF-B Gene

SummaryTGFβ acts as a tumor suppressor in normal epithelial cells and early-stage tumors and becomes an oncogenic factor in advanced tumors. The molecular mechanisms involved in the malignant function of TGFβ are not fully elucidated. We demonstrate that high TGFβ-Smad activity is present in aggressive, highly proliferative gliomas and confers poor prognosis in patients with glioma. We discern the mechanisms and molecular determinants of the TGFβ oncogenic response with a transcriptomic approach and by analyzing primary cultured patient-derived gliomas and human glioma biopsies. The TGFβ-Smad pathway promotes proliferation through the induction of PDGF-B in gliomas with an unmethylated PDGF-B gene. The epigenetic regulation of the PDGF-B gene dictates whether TGFβ acts as an oncogenic factor inducing PDGF-B and proliferation in human glioma

Microsoft Kinect-based Continuous Performance Test: An Objective Attention Deficit Hyperactivity Disorder Assessment

Background: One of the major challenges in mental medical care is finding out new instruments for an accurate and objective evaluation of the attention deficit hyperactivity disorder (ADHD). Early ADHD identification, severity assessment, and prompt treatment are essential to avoid the negative effects associated with this mental condition. Objective: The aim of our study was to develop a novel ADHD assessment instrument based on Microsoft Kinect, which identifies ADHD cardinal symptoms in order to provide a more accurate evaluation. Methods: A group of 30 children, aged 8-12 years (10.3 [SD 1.4]; male 70% [21/30]), who were referred to the Child and Adolescent Psychiatry Unit of the Department of Psychiatry at Fundación Jiménez Díaz Hospital (Madrid, Spain), were included in this study. Children were required to meet the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria of ADHD diagnosis. One of the parents or guardians of the children filled the Spanish version of the Strengths and Weaknesses of ADHD Symptoms and Normal Behavior (SWAN) rating scale used in clinical practice. Each child conducted a Kinect-based continuous performance test (CPT) in which the reaction time (RT), the commission errors, and the time required to complete the reaction (CT) were calculated. The correlations of the 3 predictors, obtained using Kinect methodology, with respect to the scores of the SWAN scale were calculated. Results: The RT achieved a correlation of -.11, -.29, and -.37 with respect to the inattention, hyperactivity, and impulsivity factors of the SWAN scale. The correlations of the commission error with respect to these 3 factors were -.03, .01, and .24, respectively. Conclusions: Our findings show a relation between the Microsoft Kinect-based version of the CPT and ADHD symptomatology assessed through parental report. Results point out the importance of future research on the development of objective measures for the diagnosis of ADHD among children and adolescents.We would like to thank the Instituto de Salud Carlos III, cofounded by Fondo Europeo de Desarrollo Regional - FEDER (PI13/02200 grant)

One Year Overview and Follow-Up in a Post-COVID Consultation of Critically Ill Patients

The long-term clinical management and evolution of a cohort of critical COVID-19 survivors have not been described in detail. We report a prospective observational study of COVID-19 patients admitted to the ICU between March and August 2020. The follow-up in a post-COVID consultation comprised symptoms, pulmonary function tests, the 6-minute walking test (6MWT), and chest computed tomography (CT). Additionally, questionnaires to evaluate the prevalence of post-COVID-19 syndrome were administered at 1 year. A total of 181 patients were admitted to the ICU during the study period. They were middle-aged (median [IQR] of 61 [52;67]) and male (66.9%), with a median ICU stay of 9 (5-24.2) days. 20% died in the hospital, and 39 were not able to be included. A cohort of 105 patients initiated the follow-up. At 1 year, 32.2% persisted with respiratory alterations and needed to continue the follow-up. Ten percent still had moderate/severe lung diffusion (DLCO) involvement (<60%), and 53.7% had a fibrotic pattern on CT. Moreover, patients had a mean (SD) number of symptoms of 5.7 ± 4.6, and 61.3% met the criteria for post-COVID syndrome at 1 year. During the follow-up, 46 patients were discharged, and 16 were transferred to other consultations. Other conditions, such as emphysema (21.6%), COPD (8.2%), severe neurocognitive disorders (4.1%), and lung cancer (1%) were identified. A high use of health care resources is observed in the first year. In conclusion, one-third of critically ill COVID-19 patients need to continue follow-up beyond 1 year, due to abnormalities on DLCO, chest CT, or persistent symptoms.This study was supported in part by ISCIII (CIBERESUCICOVID, COV20/00110), co-funded by ERDF, “Una manera de hacer Europa,” donation program “Estar Preparados,” UNESPA, Madrid, Spain and Fundación Soria Melguizo (Madrid, Spain). DG-C had received financial support from Instituto de Salud Carlos III (Miguel Servet 2020: CP20/00041), co-funded by the European Social Fund (ESF)/“Investing in your future.” JB acknowledged receiving financial support from Instituto de Salud Carlos III (ISCIII; Miguel Servet 2019: CP19/00108), co-funded by the European Social Fund (ESF), “Investing in your future.

Vigilancia epidemiológica de Shigelosis en España, 2016-2021

[ES] Se analizaron los casos y brotes de shigelosis notificados entre los años 2016 y 2021 a la Red Nacional de Vigilancia Epidemiológica (RENAVE), que recoge, entre otra, información relativa a edad y sexo de los casos, posibles mecanismos de transmisión y características microbiológicas de los aislados, aunque no incluye información sobre resistencias antibióticas. Durante el periodo de estudio, se notificaron 1.985 casos y 18 brotes de shigelosis. La incidencia acumulada aumentó en el periodo 2016-2019 (con un máximo de 1,2 casos por 100.000 habitantes en el año 2019), disminuyendo posteriormente durante los años 2020 y 2021, con 0,3 casos por 100.000 habitantes en ambos años. No obstante, en el año 2021, a pesar de que sólo algunas Comunidades Autónomas notificaron casos a la RENAVE, el número de casos fue ligeramente superior al año previo. La enfermedad fue más frecuente en hombres que en mujeres, fundamentalmente en individuos entre 15 y 49 años, siendo estos grupos de edad los que presentaron mayor razón hombre/mujer. La especie de Shigella más aislada durante el periodo de estudio fue S. sonnei, seguida de S. flexneri, aunque no se disponía de información en aproximadamente la mitad de los casos. Únicamente en 9 casos constaba como mecanismo de transmisión las relaciones sexuales, aunque la información sobre el posible mecanismo de transmisión no se recogió en más del 90% de los casos. Es necesario reforzar la notificación de la enfermedad en España, especialmente la información relativa a la transmisión, a la caracterización microbiológica y a las resistencias a los antimicrobianos. [EN] Cases and outbreaks of shigelosis reported from 2016 to 2021 to the National Epidemiological Surveillance Network (RENAVE in Spanish) were analysed, including information about age and sex of cases, possible routes of transmission and microbiological characteristics of isolates, although information about antimicrobial resistance was not reported. During the study period, 1,985 cases and 18 outbreaks of shigelosis were reported. The cumulative incidence raised during 2016-2019 period (with a maximum of 1.2 cases per 100.000 inhabitants in 2019), declining in 2020 and 2021, with 0.3 cases per 100.000 inhabitants both years. Nevertheless, during 2021, although only some Autonomous Regions reported cases to RENAVE, the number of cases was slightly higher than the previous year, due to some regions reporting similar or higher figures than in the pre-pandemic period. The disease was more frequent in men than in women, mainly in individuals from 15 to 49 years old, being these age groups those that presented the highest maleto-female ratio. S. sonnei was the most frequent species of Shigella isolated, followed by S. flexneri, although the information was not available in approximately half of the cases. Sexual transmission was mentioned only in a small percentage of cases, but information about exposure/transmission was not available for more than 90% cases. It is necessary to strengthen the epidemiological surveillance of this disease in Spain, regarding the transmission, microbiological characterization and antimicrobial resistance.N

Multiplex protein profiling of bronchial aspirates reveals disease-, mortality- and respiratory sequelae-associated signatures in critically ill patients with ARDS secondary to SARS-CoV-2 infection

Introduction: Bronchial aspirates (BAS) obtained during invasive mechanical ventilation (IMV) constitutes a useful tool for molecular phenotyping and decision making. Aim: To identify the proteomic determinants associated with disease pathogenesis, all-cause mortality and respiratory sequelae in BAS samples from critically ill patients with SARS-CoV-2-induced ARDS. Methods: Multicenter study including 74 critically ill patients with COVID-19 and non-COVID-19 ARDS. BAS were obtained by bronchoaspiration after IMV initiation. Three hundred sixty-four proteins were quantified using proximity extension assay (PEA) technology. Random forest models were used to assess predictor importance. Results: After adjusting for confounding factors, CST5, NADK, SRPK2 and TGFa were differentially detected in COVID-19 and non-COVID-19 patients. In random forest models for COVID-19, CST5, DPP7, NADK, KYAT1 and TYMP showed the highest variable importance. In COVID-19 patients, reduced levels of ENTPD2 and PTN were observed in nonsurvivors of ICU stay, even after adjustment. AGR2, NQO2, IL-1a, OSM and TRAIL showed the strongest associations with in-ICU mortality and were used to construct a proteinbased prediction model. Kaplan-Meier curves revealed a clear separation in mortality risk between subgroups of PTN, ENTPD2 and the prediction model. Cox regression models supported these findings. In survivors, the levels of FCRL1, NTF4 and THOP1 in BAS samples obtained during the ICU stay correlated with lung function (i.e., DLCO levels) 3 months after hospital discharge. Similarly, Flt3L and THOP1 levels were correlated with radiological features (i.e., TSS). These proteins are expressed in immune and nonimmune lung cells. Poor host response to viral infectivity and an inappropriate reparative mechanism seem to be linked with the pathogenesis of the disease and fatal outcomes, respectively. Conclusion: BAS proteomics identified novel factors associated with the pathology of SARS-CoV-2-induced ARDS and its adverse outcomes. BASbased protein testing emerges as a novel tool for risk assessment in the ICU

Impact of time to intubation on mortality and pulmonary sequelae in critically ill patients with COVID-19: a prospective cohort study

Question: We evaluated whether the time between first respiratory support and intubation of patients receiving invasive mechanical ventilation (IMV) due to COVID-19 was associated with mortality or pulmonary sequelae. Materials and methods: Prospective cohort of critical COVID-19 patients on IMV. Patients were classified as early intubation if they were intubated within the first 48 h from the first respiratory support or delayed intubation if they were intubated later. Surviving patients were evaluated after hospital discharge. Results: We included 205 patients (140 with early IMV and 65 with delayed IMV). The median [p25;p75] age was 63 [56.0; 70.0] years, and 74.1% were male. The survival analysis showed a significant increase in the risk of mortality in the delayed group with an adjusted hazard ratio (HR) of 2.45 (95% CI 1.29-4.65). The continuous predictor time to IMV showed a nonlinear association with the risk of in-hospital mortality. A multivariate mortality model showed that delay of IMV was a factor associated with mortality (HR of 2.40; 95% CI 1.42-4.1). During follow-up, patients in the delayed group showed a worse DLCO (mean difference of - 10.77 (95% CI - 18.40 to - 3.15), with a greater number of affected lobes (+ 1.51 [95% CI 0.89-2.13]) and a greater TSS (+ 4.35 [95% CI 2.41-6.27]) in the chest CT scan. Conclusions: Among critically ill patients with COVID-19 who required IMV, the delay in intubation from the first respiratory support was associated with an increase in hospital mortality and worse pulmonary sequelae during follow-up.The study was supported in part by ISCIII (CIBERESUCICOVID, COV20/00110), co‑funded by ERDF, “Una manera de hacer Europa” and Donation pro‑gram "estar preparados". UNESPA. Madrid. Spain David de Gonzalo Calvo acknowledges receiving financial support from Instituto de Salud Carlos III (ISCIII); Miguel Servet 2020: CP20/00041), co‑funded by the European Social Fund (ESF), “Investing in your future”. JdB acknowledges receiving financial support from Instituto de Salud Carlos III (Miguel Servet 2019: CP19/00108), co‑funded by European Regional European Social Fund (ESF), “Investing in your future

Multiplex protein profiling of bronchial aspirates reveals disease-, mortality- and respiratory sequelae-associated signatures in critically ill patients with ARDS secondary to SARS-CoV-2 infection

IntroductionBronchial aspirates (BAS) obtained during invasive mechanical ventilation (IMV) constitutes a useful tool for molecular phenotyping and decision making.AimTo identify the proteomic determinants associated with disease pathogenesis, all-cause mortality and respiratory sequelae in BAS samples from critically ill patients with SARS-CoV-2-induced ARDSMethodsMulticenter study including 74 critically ill patients with COVID-19 and non-COVID-19 ARDS. BAS were obtained by bronchoaspiration after IMV initiation. Three hundred sixty-four proteins were quantified using proximity extension assay (PEA) technology. Random forest models were used to assess predictor importance.ResultsAfter adjusting for confounding factors, CST5, NADK, SRPK2 and TGF-α were differentially detected in COVID-19 and non-COVID-19 patients. In random forest models for COVID-19, CST5, DPP7, NADK, KYAT1 and TYMP showed the highest variable importance. In COVID-19 patients, reduced levels of ENTPD2 and PTN were observed in nonsurvivors of ICU stay, even after adjustment. AGR2, NQO2, IL-1α, OSM and TRAIL showed the strongest associations with in-ICU mortality and were used to construct a protein-based prediction model. Kaplan-Meier curves revealed a clear separation in mortality risk between subgroups of PTN, ENTPD2 and the prediction model. Cox regression models supported these findings. In survivors, the levels of FCRL1, NTF4 and THOP1 in BAS samples obtained during the ICU stay correlated with lung function (i.e., DLCO levels) 3 months after hospital discharge. Similarly, Flt3L and THOP1 levels were correlated with radiological features (i.e., TSS). These proteins are expressed in immune and nonimmune lung cells. Poor host response to viral infectivity and an inappropriate reparative mechanism seem to be linked with the pathogenesis of the disease and fatal outcomes, respectively.ConclusionBAS proteomics identified novel factors associated with the pathology of SARS-CoV-2-induced ARDS and its adverse outcomes. BAS-based protein testing emerges as a novel tool for risk assessment in the ICU

The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

Background: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation