Immunosuppression-independent role of regulatory T cells against hypertension-driven renal dysfunctions

Hypertension-associated cardiorenal diseases represent one of the heaviest burdens for current health systems. In addition to hemodynamic damage, recent results have revealed that hematopoietic cells contribute to the development of these diseases by generating proinflammatory and profibrotic environments in the heart and kidney. However, the cell subtypes involved remain poorly characterized. Here we report that CD39+ regulatory T (TREG) cells utilize an immunosuppression-independent mechanism to counteract renal and possibly cardiac damage during angiotensin II (AngII)-dependent hypertension. This mechanism relies on the direct apoptosis of tissue-resident neutrophils by the ecto-ATP diphosphohydrolase activity of CD39. In agreement with this, experimental and genetic alterations in TREG/TH cell ratios have a direct impact on tissue-resident neutrophil numbers, cardiomyocyte hypertrophy, cardiorenal fibrosis, and, to a lesser extent, arterial pressure elevation during AngII-driven hypertension. These results indicate that TREG cells constitute a first protective barrier against hypertension-driven tissue fibrosis and, in addition, suggest new therapeutic avenues to prevent hypertension-linked cardiorenal diseases.This work has been supported by grants from the Castilla-León Autonomous Government (CSI101U13), the Spanish Ministry of Economy and Competitiveness (SAF2012-31371, RD12/0036/0002), Worldwide Cancer Research, the Solórzano Foundation, and the Ramón Areces Foundation to X.R.B. P.M. is funded by the Spanish Ministry of Economy and Competitiveness (SAF2011-27330). S.F., M.M.-M., J.R.-V., and A.M.-M. were supported by the Spanish Ministry of Economy and Competitiveness through BES-2010-031386, CSIC JAE-Doc, Juan de la Cierva, and BES-2009-016103 contracts, respectively. Spanish government-sponsored funding to X.R.B. is partially supported by the European Regional Development Fund.Peer Reviewe

Novel post-processing procedure to enhance casting molds manufactured by binder jetting am

This work was supported by the Spanish Ministry of Science, Innovation and Universities and FEDER, through a research project with the reference DPI2017–89840-R

Novel post-processing procedure to enhance casting molds manufactured by binder jetting AM

The significant improvements made in additive manufacturing (AM) techniques since their beginnings, coupled with its intrinsic advantages, have resulted in a technology that stands out as most suitable for applications in leading sectors today. In addition to some of the properties of the parts, there are also some inherent aspects of AM techniques that hinder their applicability. In this respect, the application of calcium sulfate parts manufactured by binder jetting (BJ), as expendable casting elements, is limited by both the high quantity of volatile substances, due to the BJ process, and their low compression resistance. In this work, a novel part post-processing procedure is presented. This procedure consists of applying various heat treatments, in combination with a vacuum infiltration process using an Epsom salt solution. The procedure reduces the volatile content of BJ AM parts and enhances the compression strength with little modification to the part geometry. This post-processing substantially improves the applicability of BJ AM parts as expendable casting elements. After presenting this novel procedure and analyzing the significant enhancement of the properties of the AM calcium sulfate parts (i.e. permeability, the reduction of volatile content and reduction of compressive strength), a case study is presented with an expendable mold for aluminum casting. This procedure allows for a safer casting process, improves the part’s surface quality and reduces the internal porosity of the cast parts.S

Search for chargino-neutralino production with mass splittings near the electroweak scale in three-lepton final states in √s=13 TeV pp collisions with the ATLAS detector

A search for supersymmetry through the pair production of electroweakinos with mass splittings near the electroweak scale and decaying via on-shell W and Z bosons is presented for a three-lepton final state. The analyzed proton-proton collision data taken at a center-of-mass energy of √s=13  TeV were collected between 2015 and 2018 by the ATLAS experiment at the Large Hadron Collider, corresponding to an integrated luminosity of 139  fb−1. A search, emulating the recursive jigsaw reconstruction technique with easily reproducible laboratory-frame variables, is performed. The two excesses observed in the 2015–2016 data recursive jigsaw analysis in the low-mass three-lepton phase space are reproduced. Results with the full data set are in agreement with the Standard Model expectations. They are interpreted to set exclusion limits at the 95% confidence level on simplified models of chargino-neutralino pair production for masses up to 345 GeV

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

MTOC translocation modulates IS formation and controls sustained T cell signaling

The translocation of the microtubule-organizing center (MTOC) toward the nascent immune synapse (IS) is an early step in lymphocyte activation initiated by T cell receptor (TCR) signaling. The molecular mechanisms that control the physical movement of the lymphocyte MTOC remain largely unknown. We have studied the role of the dynein–dynactin complex, a microtubule-based molecular motor, in the process of T cell activation during T cell antigen–presenting cell cognate immune interactions. Impairment of dynein–dynactin complex activity, either by overexpressing the p50-dynamitin component of dynactin to disrupt the complex or by knocking down dynein heavy chain expression to prevent its formation, inhibited MTOC translocation after TCR antigen priming. This resulted in a strong reduction in the phosphorylation of molecules such as ζ chain–associated protein kinase 70 (ZAP70), linker of activated T cells (LAT), and Vav1; prevented the supply of molecules to the IS from intracellular pools, resulting in a disorganized and dysfunctional IS architecture; and impaired interleukin-2 production. Together, these data reveal MTOC translocation as an important mechanism underlying IS formation and sustained T cell signaling

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Efectos fisiológicos, agronómicos y económicos del riego con agua marina desalinizada en un cultivo de pomelo

La escasez de recursos hídricos para regadío en zonas áridas y semiáridas como el sureste español ha fomentado el uso de recursos hídricos no convencionales, entre los cuales el agua marina desalinizada (AMD) se ha convertido en el más prometedor para paliar la sobredemanda de agua. Sin embargo, las ventajas e inconvenientes de su uso complementario en el riego agrícola deben ser consi‐deradas. Este estudio evaluó la respuesta agrofisiológica de un cultivo de pomelo al riego con AMD durante tres años consecutivos. Se observaron diferencias significativas al comparar la calidad del AMD con los recursos convencionales de agua dulce disponibles, mayoritariamente procedentes del Trasvase Tajo‐Segura. Además, el estudio determinó el posible riesgo de sodicidad del suelo, las diferencias no significativas en las relaciones hídricas foliares y la elevada acumulación de boro en las hojas derivado del riego con AMD, comparado con el uso de recursos hídricos superficiales convencionales. Finalmente, una evaluación económica permitió analizar la rentabilidad de implantar total o parcialmente este re‐curso en el riego, considerando el coste del agua y del fertilizante y los ingresos obtenidos por la venta de la fruta. Los resultados proporcionan orientación para el uso y la gestión del AMD en zonas con escasez de recursos hídricos

Evaluation of large language model-generated medical information on idiopathic pulmonary fibrosis

BackgroundIdiopathic Pulmonary Fibrosis (IPF) information from AI-powered large language models (LLMs) like ChatGPT-4 and Gemini 1.5 Pro is unexplored for quality, reliability, readability, and concordance with clinical guidelines.Research questionWhat is the quality, reliability, readability, and concordance to clinical guidelines of LLMs in medical and clinically IPF-related content?Study design and methodsChatGPT-4 and Gemini 1.5 Pro responses to 23 ATS/ERS/JRS/ALAT IPF guidelines questions were compared. Six independent raters evaluated responses for quality (DISCERN), reliability (JAMA Benchmark Criteria), readability (Flesch–Kincaid), and guideline concordance (0–4). Descriptive analysis, Intraclass Correlation Coefficient, Wilcoxon signed-rank test, and effect sizes (r) were calculated. Statistical significance was set at p < 0.05.ResultsAccording to JAMA Benchmark, ChatGPT-4 and Gemini 1.5 Pro provided partially reliable responses; however, readability evaluations showed that both models were difficult to understand. The Gemini 1.5 Pro provided significantly better treatment information (DISCERN score: 56 versus 43, p < 0.001). Gemini had considerably higher international IPF guidelines concordance than ChatGPT-4 (median 3.0 [3.0–3.5] vs. 3.0 [2.5–3.0], p = 0.0029).InterpretationBoth models gave useful medical insights, but their reliability is limited. Gemini 1.5 Pro gave greater quality information than ChatGPT-4 and was more compliant with worldwide IPF guidelines. Readability analyses found that AI-generated medical information was difficult to understand, stressing the need to refine it.What is already known on this topicRecent advancements in AI, especially large language models (LLMs) powered by natural language processing (NLP), have revolutionized the way medical information is retrieved and utilized.What this study addsThis study highlights the potential and limitations of ChatGPT-4 and Gemini 1.5 Pro in generating medical information on IPF. They provided partially reliable information in their responses; however, Gemini 1.5 Pro demonstrated superior quality in treatment-related content and greater concordance with clinical guidelines. Nevertheless, neither model provided answers in full concordance with established clinical guidelines, and their readability remained a major challenge.How this study might affect research, practice or policyThese findings highlight the need for AI model refinement as LLMs evolve as healthcare reference tools to help doctors and patients make evidence-based decisions