A general model for vegetation patterns including rhizome growth

Vegetation patterns, a natural phenomenon observed worldwide, are typically driven by spatially distributed feedback. However, the spatial colonization mechanisms of clonal plants, driven by the growth of a rhizome, are usually not considered in prototypical models. Here we propose a general equation for the vegetation density that includes all main clonal-growth features as well as the essential ingredients leading to spatial self-organization. This generic model reproduces the phase diagram of a fully detailed model of clonal growth. The relation of each term of the model with the mechanisms of clonal growth is discussed

Bioelectronic recordings of cardiomyocytes with accumulation mode electrolyte gated organic field effect transistors

Versió postprint del document publicat a: https://doi.org/10.1016/j.bios.2019.111844Organic electronic materials offer an untapped potential for novel tools for low-invasive electrophysiological recording and stimulation devices. Such materials combine semiconducting properties with tailored surface chemistry, elastic mechanical properties and chemical stability in water. In this work, we investigate solution processed Electrolyte Gated Organic Field Effect Transistors (EGOFETs) based on a small molecule semiconductor. We demonstrate that EGOFETs based on a blend of soluble organic semiconductor 2,8-Difluoro-5,11-bis(triethylsilylethynyl)anthradithiophene (diF-TES-ADT) combined with an insulating polymer show excellent sensitivity and long-term recording under electrophysiological applications. Our devices can stably record the extracellular potential of human pluripotent stem cell derived cardiomyocyte cells (hPSCs-CMs) for several weeks. In addition, cytotoxicity tests of pharmaceutical drugs, such as Norepinephrine and Verapamil was achieved with excellent sensitivity. This work demonstrates that organic transistors based on organic blends are excellent bioelectronics transducer for extracellular electrical recording of excitable cells and tissues thus providing a valid alternative to electrochemical transistors

Nanoscale mapping of the conductivity and interfacial capacitance of an electrolyte-gated organic field-effect transistor under operation

Versió postprint del document publicat a: https://doi.org/10.1002/adfm.202008032Probing nanoscale electrical properties of organic semiconducting materials at the interface with an electrolyte solution under externally applied voltages is key in the field of organic bioelectronics. It is demonstrated that the conductivity and interfacial capacitance of the active channel of an electrolyte-gated organic field‐effect transistor (EGOFET) under operation can be probed at the nanoscale using scanning dielectric microscopy in force detection mode in liquid environment. Local electrostatic force versus gate voltage transfer characteristics are obtained on the device and correlated with the global current–voltage transfer characteristics of the EGOFET. Nanoscale maps of the conductivity of the semiconducting channel show the dependence of the channel conductivity on the gate voltage and its variation along the channel due to the space charge limited conduction. The maps reveal very small electrical heterogeneities, which correspond to local interfacial capacitance variations due to an ultrathin non-uniform insulating layer resulting from a phase separation in the organic semiconducting blend. Present results offer insights into the transduction mechanism at the organic semiconductor/electrolyte interfaces at scales down to ≈100 nm, which can bring substantial optimization of organic electronic devices for bioelectronic applications such as electrical recording on excitable cells or label-free biosensing

Efficient long-range conduction in cable bacteria through nickel protein wires

Filamentous cable bacteria display long-range electron transport, generating electrical currents over centimeter distances through a highly ordered network of fibers embedded in their cell envelope. The conductivity of these periplasmic wires is exceptionally high for a biological material, but their chemical structure and underlying electron transport mechanism remain unresolved. Here, we combine high-resolution microscopy, spectroscopy, and chemical imaging on individual cable bacterium filaments to demonstrate that the periplasmic wires consist of a conductive protein core surrounded by an insulating protein shell layer. The core proteins contain a sulfur-ligated nickel cofactor, and conductivity decreases when nickel is oxidized or selectively removed. The involvement of nickel as the active metal in biological conduction is remarkable, and suggests a hitherto unknown form of electron transport that enables efficient conduction in centimeter-long protein structures

Multicentre, randomised, open-label, phase IV–III study to evaluate the efficacy of cloxacillin plus fosfomycin versus cloxacillin alone in adult patients with methicillin-susceptible Staphylococcus aureus bacteraemia: study protocol for the SAFO trial

SAFO study group and the Spanish Network for Research in Infectious Diseases (REIPI).[Introduction] Methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia is a frequent condition, with high mortality rates. There is a growing interest in identifying new therapeutic regimens able to reduce therapeutic failure and mortality observed with the standard of care of beta-lactam monotherapy. In vitro and small-scale studies have found synergy between cloxacillin and fosfomycin against S. aureus. Our aim is to test the hypothesis that cloxacillin plus fosfomycin achieves higher treatment success than cloxacillin alone in patients with MSSA bacteraemia.[Methods] We will perform a superiority, randomised, open-label, phase IV–III, two-armed parallel group (1:1) clinical trial at 20 Spanish tertiary hospitals. Adults (≥18 years) with isolation of MSSA from at least one blood culture ≤72 hours before inclusion with evidence of infection, will be randomly allocated to receive either cloxacillin 2 g/4-hour intravenous plus fosfomycin 3 g/6-hour intravenous or cloxacillin 2 g/4-hour intravenous alone for 7 days. After the first week, sequential treatment and total duration of antibiotic therapy will be determined according to clinical criteria by the attending physician. Primary endpoints: (1) Treatment success at day 7, a composite endpoint comprising all the following criteria: patient alive, stable or with improved quick-Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA at day 7. (2) Treatment success at test of cure (TOC) visit: patient alive and no isolation of MSSA in blood culture or at another sterile site from day 8 until TOC (12 weeks after randomisation). We assume a rate of treatment success of 74% in the cloxacillin group. Accepting alpha risk of 0.05 and beta risk of 0.2 in a two-sided test, 183 subjects will be required in each of the control and experimental groups to obtain statistically significant difference of 12% (considered clinically significant).[Ethics and dissemination] Ethical approval has been obtained from the Ethics Committee of Bellvitge University Hospital (AC069/18) and from the Spanish Medicines and Healthcare Product Regulatory Agency (AEMPS, AC069/18), and is valid for all participating centres under existing Spanish legislation. The results will be presented at international meetings and will be made available to patients and funders.[Trial registration number] The protocol has been approved by AEMPS with the Trial Registration Number EudraCT 2018-001207-37. ClinicalTrials.gov Identifier: NCT03959345; Pre-results.The SAFO trial is supported by a competitive grant awarded by the Fondo de Investigaciones Sanitarias at the Spanish government’s National Institute of Health Research, Instituto de Salud Carlos III (ISCIII), (FIS PI17/01116). This study was supported by Plan Nacional de I+D+i 2017–2021 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0005).Peer reviewe

Multicentre, randomised, open-label, phase IV-III study to evaluate the efficacy of cloxacillin plus fosfomycin versus cloxacillin alone in adult patients with methicillin-susceptible Staphylococcus aureus bacteraemia: study protocol for the SAFO trial

Introduction: Methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia is a frequent condition, with high mortality rates. There is a growing interest in identifying new therapeutic regimens able to reduce therapeutic failure and mortality observed with the standard of care of beta-lactam monotherapy. In vitro and small-scale studies have found synergy between cloxacillin and fosfomycin against S. aureus. Our aim is to test the hypothesis that cloxacillin plus fosfomycin achieves higher treatment success than cloxacillin alone in patients with MSSA bacteraemia. Methods: We will perform a superiority, randomised, open-label, phase IV-III, two-armed parallel group (1:1) clinical trial at 20 Spanish tertiary hospitals. Adults (≥18 years) with isolation of MSSA from at least one blood culture ≤72 hours before inclusion with evidence of infection, will be randomly allocated to receive either cloxacillin 2 g/4-hour intravenous plus fosfomycin 3 g/6-hour intravenous or cloxacillin 2 g/4-hour intravenous alone for 7 days. After the first week, sequential treatment and total duration of antibiotic therapy will be determined according to clinical criteria by the attending physician. Primary endpoints: (1) Treatment success at day 7, a composite endpoint comprising all the following criteria: patient alive, stable or with improved quick-Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA at day 7. (2) Treatment success at test of cure (TOC) visit: patient alive and no isolation of MSSA in blood culture or at another sterile site from day 8 until TOC (12 weeks after randomisation). We assume a rate of treatment success of 74% in the cloxacillin group. Accepting alpha risk of 0.05 and beta risk of 0.2 in a two-sided test, 183 subjects will be required in each of the control and experimental groups to obtain statistically significant difference of 12% (considered clinically significant). Ethics and dissemination: Ethical approval has been obtained from the Ethics Committee of Bellvitge University Hospital (AC069/18) and from the Spanish Medicines and Healthcare Product Regulatory Agency (AEMPS, AC069/18), and is valid for all participating centres under existing Spanish legislation. The results will be presented at international meetings and will be made available to patients and funders

Cloxacillin plus fosfomycin versus cloxacillin alone for methicillin-susceptible Staphylococcus aureus bacteremia: a randomized trial

© The Author(s) 2023. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Treatment failure occurs in about 25% of patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. We assessed whether cloxacillin plus fosfomycin achieves better treatment success than cloxacillin alone in hospitalized adults with MSSA bacteremia. We conducted a multicenter, open-label, phase III–IV superiority randomized clinical trial. We randomly assigned patients (1:1) to receive 2 g of intravenous cloxacillin alone every 4 h or with 3 g of intravenous fosfomycin every 6 h for the initial 7 days. The primary endpoint was treatment success at day 7, a composite endpoint with the following criteria: patient alive, stable or with improved quick Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA, adjudicated by an independent committee blinded to treatment allocation. We randomized 215 patients, of whom 105 received cloxacillin plus fosfomycin and 110 received cloxacillin alone. We analyzed the primary endpoint with the intention-to-treat approach in 214 patients who received at least 1 day of treatment. Treatment success at day 7 after randomization was achieved in 83 (79.8%) of 104 patients receiving combination treatment versus 82 (74.5%) of 110 patients receiving monotherapy (risk difference 5.3%; 95% confidence interval (CI), –5.95–16.48). Secondary endpoints, including mortality and adverse events, were similar in the two groups except for persistent bacteremia at day 3, which was less common in the combination arm. In a prespecified interim analysis, the independent committee recommended stopping recruitment for futility prior to meeting the planned randomization of 366 patients. Cloxacillin plus fosfomycin did not achieve better treatment success at day 7 of therapy than cloxacillin alone in MSSA bacteremia. Further trials should consider the intrinsic heterogeneity of the infection by using a more personalized approach. ClinicalTrials.gov registration: NCT03959345.This study was funded by the Spanish Ministry of Health (grant no. PI17/01116), Instituto de Salud Carlos III, Madrid, Spain, and Laboratorios ERN, Barcelona, Spain (grant no. 19PNJ145). We thank the Spanish Clinical Research Network (SCReN), Instituto de Salud Carlos II, for its support through projects PT17/0017/0010 and PT20/000008, integrated into the ‘Plan Estatal de I + D + I’ 2013–2016 and co-financed by the European Regional Development Fund (FEDER). J.M.M. received a personal 80:20 research grant from Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain, for the 2017–2024 period. O.G. received a research grant from the ‘Pla estratègic de recerca i innovació en salut (PERIS) 2019–2021’ (Departament de Salut, Generalitat de Catalunya).Peer reviewe

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio