TRY plant trait database – enhanced coverage and open access

Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Impact of granular filtration on ultrafiltration membrane performance as pre-treatment to seawater desalination in presence of algal blooms

International audienc

Performance of a sand filter in removal of algal bloom for SWRO pre-treatment

International audienc

Performances of dead-end ultrafiltration of seawater: from the filtration and backwash efficiencies to the membrane fouling mechanisms

The present work investigates the fouling mechanisms of PVDF hollow fibre membrane (0.03 μm) during the dead end ultrafiltration at a fixed permeate flux (outside to inside configuration) of complex synthetic seawater composed by humic acids, alginic acids, inorganic particles and numerous salts at high concentrations. Short term ultrafiltration experiments at 100 L.h-1.m-2 show that the optimal specific filtered volume seems to be equal to 50 L.m-2. A residual fouling resistance equal to 2.1010 m-1 is added after each cycle of filtration during 8h of ultrafiltration at 100 L.h-1.m-2 and 50 L.m-2. Most of the fouling is reversible (80%). Organics are barely (15% of humic acids) retained by the membrane. Backwash efficiency drops during operation which induces less organics into backwash waters. Humic acids could preferentially accumulate on the membrane early in the ultrafiltration and alginic acids after the build-up of a fouling pre-layer. Colloids and particulates could accumulate inside a heterogeneous fouling layer and/or the concentrate compartment of the membrane module before being more largely recovered inside backwash waters

PACAP-LOADED LIPOSOME DELIVERY ACROSS THE BBB: A LIGHT-SHEET MICROSCOPY STUDY

The blood-brain barrier (BBB) impermeability and selectivity prevent the transport of many therapeutic molecules into the brain, making ineffective their use for treatment of neurological diseases.1 Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuroprotective peptide proposed for treatment of central nervous system (CNS) diseases.2 However, its clinical use is limited by the efflux component of peptide transport system-6 (PTS-6), which reduces its brain uptake3, and also for its low stability in human plasma, rapid degradation and peripheral actions.4 Nanocarrier-mediated method is a non-invasive strategy to explore for brain drug delivery; among them, liposomes are attractive tools that can be easily modified to improve their delivery. 5 We developed liposomes loaded with PACAP and functionalized on the surface with gH625 peptide, a membrane-perturbing domain in glycoprotein H of Herpes simplex virus 1. gH625 can traverse the membrane bilayer and deliver several cargoes across cell membranes in vitro6 and crosses the BBB in vivo.7We evaluated the efficiency of gH625-liposomes to deliver PACAP to the brain in Swiss CD1 mice after intravenous administration using light sheet fluorescence microscopy. Our results show that gH625-liposomes ameliorate both PACAP reaching and crossing the BBB, increasing the number of neuronal cells labeled with PACAP. These data suggest that gH625-liposomes represent a promising strategy to deliver therapeutic agents to CNS for the treatment of neurological diseases but also to provide an effective imaging and/or diagnostic tool for the brain

A NEW STRATEGY TO DELIVER PACAP TO THE BRAIN

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuroprotective peptide, but its brain uptake is limited by the blood-brain barrier (BBB) component, such as peptide transport system-6 (PTS-6) [1]. The liposomes represent an attractive tool to deliver molecules across the BBB; they can be easily modified on surface to improve their delivery. The peptide gH625, a membrane-perturbing domain in glycoprotein H of Herpes Simplex virus 1, has been extensively used for vector-mediated strategies that enable passage of several cargoes across cell membranes in vitro [2] and crosses the BBB [3]. We evaluated the efficiency of liposomes functionalized with gH625 to deliver PACAP to the brain of Swiss CD1 mice after intravenous injection using light sheet fluorescence microscopy. gH625 liposomes improves both PACAP reaching and crossing the BBB, with a higher number of PACAP labeled neuronal cells. This study suggests a promising strategy to deliver PACAP to CNS for brain diseases treatment

Neurotensin receptor 2 is induced in astrocytes and brain endothelial cells in relation to status epilepticus and neuroinflammation following pilocarpine administration in rats

Neurotensin (NT) acts as a primary neurotransmitter and neuromodulator in the CNS and has been involved in a number of CNS pathologies including epilepsy. NT mediates its central and peripheral effects by interacting with the NTSR1, NTSR2 and NTSR3 receptor subtypes. To date, little is known about the precise expression of the NT receptors in brain neural cells and their regulation in pathology. In the present work, we studied expression of the NTSR2 protein in the rat hippocampus using a model of temporal lobe epilepsy induced by pilocarpine and questioned whether NTSR2 was modulated in conditions of neuro-inflammation. This model is characterized by a rapid and intense inflammatory reaction with a pattern of reactive gliosis in the hippocampus. We show that NTSR2 protein is expressed in hippocampal astrocytes and its expression increases together with astrocyte reactivity following induction of status epilepticus. NTSR2 immunoreactivity is also increased in perivascular astrocytes and their end-feet and is apparent in endothelial cells following induction of status epilepticus. Proinflammatory factors such as IL1β and LPS induced NTSR2 in astrocytes, but also in microglia in vitro . Glial NTSR2 expression showed characteristic immediate early gene response under inflammatory conditions. Treating inflamed glial cells with a vectorized NT analogue decreased NTSR2 expression as well as astrocytic and microglial reactivity. Together, these results suggest that NTSR2 is implicated in astroglial and gliovascular inflammation and that targeting the NTSR2 receptor may open new avenues in the regulation of neuroinflammation in CNS diseases