Depth-Specific Hypoxic Responses to Spreading Depolarizations in Gyrencephalic Swine Cortex Unveiled by Photoacoustic Imaging.

Spreading depolarizations (SDs) are a marker of brain injury and have a causative effect on ischemic lesion progression. The hemodynamic responses elicited by SDs are contingent upon the metabolic integrity of the affected tissue, with vasoconstrictive reactions leading to pronounced hypoxia often indicating poor outcomes. The stratification of hemodynamic responses within different cortical layers remains poorly characterized. This pilot study sought to elucidate the depth-specific hemodynamic changes in response to SDs within the gray matter of the gyrencephalic swine brain. Employing a potassium chloride-induced SD model, we utilized multispectral photoacoustic imaging (PAI) to estimate regional cerebral oxygen saturation (rcSO2%) changes consequent to potassium chloride-induced SDs. Regions of interest were demarcated at three cortical depths covering up to 4 mm. Electrocorticography (ECoG) strips were placed to validate the presence of SDs. Through PAI, we detected 12 distinct rcSO2% responses, which corresponded with SDs detected in ECoG. Notably, a higher frequency of hypoxic responses was observed in the deeper cortical layers compared to superficial layers, where hyperoxic and mixed responses predominated (p < 0.001). This data provides novel insights into the differential oxygenation patterns across cortical layers in response to SDs, underlining the complexity of cerebral hemodynamics post-injury.

Impact of a cuff-based device calibration method on the agreement between invasive and noninvasive aortic and brachial pressure.

INTRODUCTION: Brachial cuff-based methods are increasingly used to estimate aortic systolic blood pressure (aoSBP). However, there are several unresolved issues. AIMS: to determine to what extent the scheme used to calibrate brachial records (1) can affect noninvasive obtained aoSBP levels, and consequently, the level of agreement with the aoSBP recorded invasively, and (2) how different ways of calibrating ultimately impact the relationship between aoSBP and cardiac properties. METHODS: brachial and aortic blood pressure (BP) was simultaneously obtained by invasive (catheterisation) and noninvasive (brachial oscillometric-device) methods (89 subjects). aoSBP was noninvasive obtained using three calibration schemes: 'SD': diastolic and systolic brachial BP, 'C': diastolic and calculated brachial mean BP (bMBP), 'Osc': diastolic and oscillometry-derived bMBP. Agreement between invasive and noninvasive aoSBP, and associations between BP and echocardiographic-derived parameters were analysed. CONCLUSIONS: 'C' and 'SD' schemes generated aoSBP levels lower than those recorded invasively (mean errors: 6.9 and 10.1 mmHg); the opposite was found when considering 'Osc'(mean error: -11.4 mmHg). As individuals had higher invasive aoSBP, the three calibration schemes increasingly underestimated aoSBP levels; and viceversa. The 'range' of invasive aoSBP in which the calibration schemes reach the lowest error level (-5-5 mmHg) is different: 'C': 103-131 mmHg; 'Osc': 159-201 mmHg; 'SD':101-124 mmHg. The calibration methods allowed reaching levels of association between aoSBP and cardiac characteristics, somewhat lower, but very similar to those obtained when considering invasive aoSBP. There is no evidence of a clear superiority of one calibration method over another when considering the association between aoSBP and cardiac characteristics.

Long noncoding RNA-mediated epigenetic regulation of auxin-related genes controls shade avoidance syndrome in Arabidopsis.

The long noncoding RNA (lncRNA) AUXIN-REGULATED PROMOTER LOOP (APOLO) recognizes a subset of target loci across the Arabidopsis thaliana genome by forming RNA-DNA hybrids (R-loops) and modulating local three-dimensional chromatin conformation. Here, we show that APOLO regulates shade avoidance syndrome by dynamically modulating expression of key factors. In response to far-red (FR) light, expression of APOLO anti-correlates with that of its target BRANCHED1 (BRC1), a master regulator of shoot branching in Arabidopsis thaliana. APOLO deregulation results in BRC1 transcriptional repression and an increase in the number of branches. Accumulation of APOLO transcription fine-tunes the formation of a repressive chromatin loop encompassing the BRC1 promoter, which normally occurs only in leaves and in a late response to far-red light treatment in axillary buds. In addition, our data reveal that APOLO participates in leaf hyponasty, in agreement with its previously reported role in the control of auxin homeostasis through direct modulation of auxin synthesis gene YUCCA2, and auxin efflux genes PID and WAG2. We show that direct application of APOLO RNA to leaves results in a rapid increase in auxin signaling that is associated with changes in the plant response to far-red light. Collectively, our data support the view that lncRNAs coordinate shade avoidance syndrome in A. thaliana, and reveal their potential as exogenous bioactive molecules. Deploying exogenous RNAs that modulate plant-environment interactions may therefore become a new tool for sustainable agriculture.

Direct estimation of central aortic pressure from measured or quantified mean and diastolic brachial blood pressure: agreement with invasive records.

Background: Recently it has been proposed a new approach to estimate aortic systolic blood pressure (aoSBP) without the need for specific devices, operator-dependent techniques and/or complex wave propagation models/algorithms. The approach proposes aoSBP can be quantified from brachial diastolic and mean blood pressure (bDBP, bMBP) as: aoSBP = bMBP2/bDBP. It remains to be assessed to what extent the method and/or equation used to obtain the bMBP levels considered in aoSBP calculation may affect the estimated aoSBP, and consequently the agreement with aoSBP invasively recorded. Methods: Brachial and aortic pressure were simultaneously obtained invasively (catheterization) and non-invasively (brachial oscillometry) in 89 subjects. aoSBP was quantified in seven different ways, using measured (oscillometry-derived) and calculated (six equations) mean blood pressure (MBP) levels. The agreement between invasive and estimated aoSBP was analyzed (Concordance correlation coefficient; Bland-Altman Test). Conclusions: The ability of the equation "aoSBP = MBP2/DBP" to (accurately) estimate (error <5 mmHg) invasive aoSBP depends on the method and equation considered to determine bMBP, and on the aoSBP levels (proportional error). Oscillometric bMBP and/or approaches that consider adjustments for heart rate or a form factor ∼40% (instead of the usual 33%) would be the best way to obtain the bMBP levels to be used to calculate aoSBP.

RWP-RK Domain 3 (OsRKD3) induces somatic embryogenesis in black rice.

BACKGROUND: Plants have the unique capability to form embryos from both gametes and somatic cells, with the latter process known as somatic embryogenesis. Somatic embryogenesis (SE) can be induced by exposing plant tissues to exogenous growth regulators or by the ectopic activation of embryogenic transcription factors. Recent studies have revealed that a discrete group of RWP-RK DOMAIN-CONTAINING PROTEIN (RKD) transcription factors act as key regulators of germ cell differentiation and embryo development in land plants. The ectopic overexpression of reproductive RKDs is associated with increased cellular proliferation and the formation of somatic embryo-like structures that bypass the need for exogenous growth regulators. However, the precise molecular mechanisms implicated in the induction of somatic embryogenesis by RKD transcription factors remains unknown. RESULTS: In silico analyses have identified a rice RWP-RK transcription factor, named Oryza sativa RKD3 (OsRKD3), which is closely related to Arabidopsis thaliana RKD4 (AtRKD4) and Marchantia polymorpha RKD (MpRKD) proteins. Our study demonstrates that the ectopic overexpression of OsRKD3, which is expressed preferentially in reproductive tissues, can trigger the formation of somatic embryos in an Indonesian black rice landrace (Cempo Ireng) that is normally resistant to somatic embryogenesis. By analyzing the transcriptome of induced tissue, we identified 5,991 genes that exhibit differential expression in response to OsRKD3 induction. Among these genes, 50% were up-regulated while the other half were down-regulated. Notably, approximately 37.5% of the up-regulated genes contained a sequence motif in their promoter region, which was also observed in RKD targets from Arabidopsis. Furthermore, OsRKD3 was shown to mediate the transcriptional activation of a discrete gene network, which includes several transcription factors such as APETALA 2-like (AP2-like)/ETHYLENE RESPONSE FACTOR (ERF), MYB and CONSTANS-like (COL), and chromatin remodeling factors associated with hormone signal transduction, stress responses and post-embryonic pathways. CONCLUSIONS: Our data show that OsRKD3 modulates an extensive gene network and its activation is associated with the initiation of a somatic embryonic program that facilitates genetic transformation in black rice. These findings hold substantial promise for improving crop productivity and advancing agricultural practices in black rice.

HSFA1a modulates plant heat stress responses and alters the 3D chromatin organization of enhancer-promoter interactions.

The complex and dynamic three-dimensional organization of chromatin within the nucleus makes understanding the control of gene expression challenging, but also opens up possible ways to epigenetically modulate gene expression. Because plants are sessile, they evolved sophisticated ways to rapidly modulate gene expression in response to environmental stress, that are thought to be coordinated by changes in chromatin conformation to mediate specific cellular and physiological responses. However, to what extent and how stress induces dynamic changes in chromatin reorganization remains poorly understood. Here, we comprehensively investigated genome-wide chromatin changes associated with transcriptional reprogramming response to heat stress in tomato. Our data show that heat stress induces rapid changes in chromatin architecture, leading to the transient formation of promoter-enhancer contacts, likely driving the expression of heat-stress responsive genes. Furthermore, we demonstrate that chromatin spatial reorganization requires HSFA1a, a transcription factor (TF) essential for heat stress tolerance in tomato. In light of our findings, we propose that TFs play a key role in controlling dynamic transcriptional responses through 3D reconfiguration of promoter-enhancer contacts.

Predictable and stable epimutations induced during clonal plant propagation with embryonic transcription factor.

Clonal propagation is frequently used in commercial plant breeding and biotechnology programs because it minimizes genetic variation, yet it is not uncommon to observe clonal plants with stable phenotypic changes, a phenomenon known as somaclonal variation. Several studies have linked epigenetic modifications induced during regeneration with this newly acquired phenotypic variation. However, the factors that determine the extent of somaclonal variation and the molecular changes underpinning this process remain poorly understood. To address this gap in our knowledge, we compared clonally propagated Arabidopsis thaliana plants derived from somatic embryogenesis using two different embryonic transcription factors- RWP-RK DOMAIN-CONTAINING 4 (RKD4) or LEAFY COTYLEDON2 (LEC2) and from two epigenetically distinct founder tissues. We found that both the epi(genetic) status of the explant and the regeneration protocol employed play critical roles in shaping the molecular and phenotypic landscape of clonal plants. Phenotypic variation in regenerated plants can be largely explained by the inheritance of tissue-specific DNA methylation imprints, which are associated with specific transcriptional and metabolic changes in sexual progeny of clonal plants. For instance, regenerants were particularly affected by the inheritance of root-specific epigenetic imprints, which were associated with an increased accumulation of salicylic acid in leaves and accelerated plant senescence. Collectively, our data reveal specific pathways underpinning the phenotypic and molecular variation that arise and accumulate in clonal plant populations.

Progress and challenges for the machine learning-based design of fit-for-purpose monoclonal antibodies.

Although the therapeutic efficacy and commercial success of monoclonal antibodies (mAbs) are tremendous, the design and discovery of new candidates remain a time and cost-intensive endeavor. In this regard, progress in the generation of data describing antigen binding and developability, computational methodology, and artificial intelligence may pave the way for a new era of in silico on-demand immunotherapeutics design and discovery. Here, we argue that the main necessary machine learning (ML) components for an in silico mAb sequence generator are: understanding of the rules of mAb-antigen binding, capacity to modularly combine mAb design parameters, and algorithms for unconstrained parameter-driven in silico mAb sequence synthesis. We review the current progress toward the realization of these necessary components and discuss the challenges that must be overcome to allow the on-demand ML-based discovery and design of fit-for-purpose mAb therapeutic candidates.

The lncRNA MARS modulates the epigenetic reprogramming of the marneral cluster in response to ABA.

Clustered organization of biosynthetic non-homologous genes is emerging as a characteristic feature of plant genomes. The co-regulation of clustered genes seems to largely depend on epigenetic reprogramming and three-dimensional chromatin conformation. In this study, we identified the long non-coding RNA (lncRNA) MARneral Silencing (MARS), localized inside the Arabidopsis marneral cluster, which controls the local epigenetic activation of its surrounding region in response to abscisic acid (ABA). MARS modulates the POLYCOMB REPRESSIVE COMPLEX 1 (PRC1) component LIKE HETEROCHROMATIN PROTEIN 1 (LHP1) binding throughout the cluster in a dose-dependent manner, determining H3K27me3 deposition and chromatin condensation. In response to ABA, MARS decoys LHP1 away from the cluster and promotes the formation of a chromatin loop bringing together the MARNERAL SYNTHASE 1 (MRN1) locus and a distal ABA-responsive enhancer. The enrichment of co-regulated lncRNAs in clustered metabolic genes in Arabidopsis suggests that the acquisition of novel non-coding transcriptional units may constitute an additional regulatory layer driving the evolution of biosynthetic pathways.

Severe congenital neutropenia due to G6PC3 deficiency: Case series of five patients and literature review.

BACKGROUND AND OBJECTIVES: Glucose-6-phosphate catalytic subunit 3 (G6PC3) deficiency is characterized by severe congenital neutropenia with recurrent pyogenic infections, a prominent superficial venous pattern and cardiovascular and urogenital malformations caused by an alteration of glucose homeostasis, with increased endoplasmic reticulum stress and cell apoptosis. METHODS: We reviewed our patients with G6PC3 deficiency diagnosed along the last decade in Mexico; we also searched the PubMed/Medline database for the terms ('G6PC3 deficiency' OR 'Dursun syndrome' OR 'Severe congenital neutropenia type 4'), and selected articles published in English from 2009 to 2020. RESULTS: We found 89 patients reported from at least 14 countries in 4 continents. We describe five new cases from Mexico. Of the 94 patients, 56% are male, 48% from Middle East countries and none of them had adverse reactions to live vaccines; all presented with at least 1 severe infection prior to age 2. Seventy-five per cent had syndromic features, mainly atrial septal defect in 55% and prominent superficial veins in 62%. CONCLUSIONS: With a total of 94 patients reported in the past decade, we delineate the most frequent laboratory and genetic features, their treatment and outcomes, and to expand the knowledge of syndromic and non-syndromic phenotypes in these patients.

Individualized VDJ recombination predisposes the available Ig sequence space.

The process of recombination between variable (V), diversity (D), and joining (J) immunoglobulin (Ig) gene segments determines an individual's naive Ig repertoire and, consequently, (auto)antigen recognition. VDJ recombination follows probabilistic rules that can be modeled statistically. So far, it remains unknown whether VDJ recombination rules differ between individuals. If these rules differed, identical (auto)antigen-specific Ig sequences would be generated with individual-specific probabilities, signifying that the available Ig sequence space is individual specific. We devised a sensitivity-tested distance measure that enables inter-individual comparison of VDJ recombination models. We discovered, accounting for several sources of noise as well as allelic variation in Ig sequencing data, that not only unrelated individuals but also human monozygotic twins and even inbred mice possess statistically distinguishable immunoglobulin recombination models. This suggests that, in addition to genetic, there is also nongenetic modulation of VDJ recombination. We demonstrate that population-wide individualized VDJ recombination can result in orders of magnitude of difference in the probability to generate (auto)antigen-specific Ig sequences. Our findings have implications for immune receptor-based individualized medicine approaches relevant to vaccination, infection, and autoimmunity.

Polycomb-dependent differential chromatin compartmentalization determines gene coregulation in Arabidopsis.

In animals, distant H3K27me3-marked Polycomb targets can establish physical interactions forming repressive chromatin hubs. In plants, growing evidence suggests that H3K27me3 acts directly or indirectly to regulate chromatin interactions, although how this histone modification modulates 3D chromatin architecture remains elusive. To decipher the impact of the dynamic deposition of H3K27me3 on the Arabidopsis thaliana nuclear interactome, we combined genetics, transcriptomics, and several 3D epigenomic approaches. By analyzing mutants defective for histone H3K27 methylation or demethylation, we uncovered the crucial role of this chromatin mark in short- and previously unnoticed long-range chromatin loop formation. We found that a reduction in H3K27me3 levels led to a decrease in the interactions within Polycomb-associated repressive domains. Regions with lower H3K27me3 levels in the H3K27 methyltransferase clf mutant established new interactions with regions marked with H3K9ac, a histone modification associated with active transcription, indicating that a reduction in H3K27me3 levels induces a global reconfiguration of chromatin architecture. Altogether, our results reveal that the 3D genome organization is tightly linked to reversible histone modifications that govern chromatin interactions. Consequently, nuclear organization dynamics shapes the transcriptional reprogramming during plant development and places H3K27me3 as a key feature in the coregulation of distant genes.

A Novel Signaling Pathway Required for Arabidopsis Endodermal Root Organization Shapes the Rhizosphere Microbiome.

The Casparian strip (CS) constitutes a physical diffusion barrier to water and nutrients in plant roots, which is formed by the polar deposition of lignin polymer in the endodermis tissue. The precise pattern of lignin deposition is determined by the scaffolding activity of membrane-bound Casparian Strip domain proteins (CASPs), but little is known of the mechanism(s) directing this process. Here, we demonstrate that Endodermis-specific Receptor-like Kinase 1 (ERK1) and, to a lesser extent, ROP Binding Kinase1 (RBK1) are also involved in regulating CS formation, with the former playing an essential role in lignin deposition as well as in the localization of CASP1. We show that ERK1 is localized to the cytoplasm and nucleus of the endodermis and that together with the circadian clock regulator, Time for Coffee (TIC), forms part of a novel signaling pathway necessary for correct CS organization and suberization of the endodermis, with their single or combined loss of function resulting in altered root microbiome composition. In addition, we found that other mutants displaying defects in suberin deposition at the CS also display altered root exudates and microbiome composition. Thus, our work reveals a complex network of signaling factors operating within the root endodermis that establish both the CS diffusion barrier and influence the microbial composition of the rhizosphere.

A transposon surveillance mechanism that safeguards plant male fertility during stress.

Although plants are able to withstand a range of environmental conditions, spikes in ambient temperature can impact plant fertility causing reductions in seed yield and notable economic losses1,2. Therefore, understanding the precise molecular mechanisms that underpin plant fertility under environmental constraints is critical to safeguarding future food production3. Here, we identified two Argonaute-like proteins whose activities are required to sustain male fertility in maize plants under high temperatures. We found that MALE-ASSOCIATED ARGONAUTE-1 and -2 associate with temperature-induced phased secondary small RNAs in pre-meiotic anthers and are essential to controlling the activity of retrotransposons in male meiocyte initials. Biochemical and structural analyses revealed how male-associated Argonaute activity and its interaction with retrotransposon RNA targets is modulated through the dynamic phosphorylation of a set of highly conserved, surface-located serine residues. Our results demonstrate that an Argonaute-dependent, RNA-guided surveillance mechanism is critical in plants to sustain male fertility under environmentally constrained conditions, by controlling the mutagenic activity of transposons in male germ cells.

Sepsis y choque séptico en los servicios de urgencias de México: estudio multicéntrico de prevalencia puntual / Sepsis and septic shock in emergency departments of Mexico: a multicenter point-prevalence study

Resumen Introducción: La sepsis es una de las principales causas de consulta en los servicios de urgencias médicas. Objetivo: Identificar la prevalencia de la sepsis en servicios de urgencias médicas de México. Método: Estudio transversal con seguimiento a 30 días de los pacientes con diagnóstico de sepsis o choque séptico; se analizaron las variables demográficas, el manejo y los desenlaces. Resultados: En 68 servicios de urgencias médicas analizados se atendió a 2379 pacientes, de los cuales 307 presentaron sepsis. La prevalencia de la sepsis fue de 12.9 %, con mortalidad global de 16.93 %, que en los casos de sepsis fue de 9.39 % y en los de choque séptico, de 65.85 %; no se identificaron diferencias significativas en las variables demográficas o tipo de hospital. Se observó balance hídrico alto en las primeras tres horas y falta de apego a las recomendaciones internacionales de reanimación superior en los pacientes que fallecieron. Conclusiones: Se encontró alta prevalencia de la sepsis en los servicios de urgencias médicas mexicanos. La mortalidad de los pacientes con choque séptico fue similar e, incluso, mayor a la reportada internacionalmente.

Abstract Introduction: Sepsis is one of the main reasons for consultation at emergency departments. Objective: To identify the prevalence of sepsis in emergency departments of Mexico. Method: Cross-sectional study with a 30-day follow-up of patients diagnosed with sepsis or septic shock; demographic variables, management and outcomes were analyzed. Results: In 68 emergency departments analyzed, 2379 patients were attended to, out of whom 307 had sepsis. The prevalence of sepsis was 12.9 %, and overall mortality was 16.93 %, which in the cases of sepsis was 9.39 %, and in those of septic shock, 65.85 %; no significant differences were identified in demographic variables or type of hospital. A significantly higher fluid balance was observed within the first three hours in those patients who died, as well as a lack of adherence to international resuscitation recommendations. Conclusions: A high prevalence of sepsis was found in Mexican emergency departments. Mortality of patients with septic shock was similar and even higher than that internationally reported.

A new role for histone demethylases in the maintenance of plant genome integrity.

Histone modifications deposited by the Polycomb repressive complex 2 (PRC2) play a critical role in the control of growth, development, and adaptation to environmental fluctuations of most multicellular eukaryotes. The catalytic activity of PRC2 is counteracted by Jumonji-type (JMJ) histone demethylases, which shapes the genomic distribution of H3K27me3. Here, we show that two JMJ histone demethylases in Arabidopsis, EARLY FLOWERING 6 (ELF6) and RELATIVE OF EARLY FLOWERING 6 (REF6), play distinct roles in H3K27me3 and H3K27me1 homeostasis. We show that failure to reset these chromatin marks during sexual reproduction results in the transgenerational inheritance of histone marks, which cause a loss of DNA methylation at heterochromatic loci and transposon activation. Thus, Jumonji-type histone demethylases play a dual role in plants by helping to maintain transcriptional states through development and safeguard genome integrity during sexual reproduction.

Asociación entre el índice de agua extravascular pulmonar y el balance hídrico en pacientes críticamente enfermos / Association between extravascular lung water index and fluid balance in critically ill patients / Associação entre água extravascular pulmonar indexada e balanço hídrico em pacientes em estado crítico

Resumen: Introducción: El balance hídrico positivo y el agua extravascular pulmonar medida por termodilución transpulmonar son factores independientes de mortalidad. La inclusión del valor de agua extravascular pulmonar indexada (EVLWi) durante la reanimación inicial impacta en la cantidad de líquido administrado. Aunque no existen antecedentes, buscar una asociación entre ambos parámetros puede llevar a un balance hídrico global negativo guiado por la cantidad de EVLWi. En este estudio retrospectivo se buscó la asociación entre EVLWi y balance hídrico y su impacto en la mortalidad. Material y métodos: Se realizó un estudio retrospectivo de cohortes con 20 casos para establecer la asociación entre agua extravascular pulmonar indexada medida por termodilución transpulmonar y balance hídrico total a las 24, 48 y 72 horas, así como con la mortalidad a 30 días. Resultados: Un valor de corte > 11 mL/kg de EVLWi se asoció con un incremento de la mortalidad; a las 24 horas RR 8.0 (95% IC 1.2146-52.6944, p = 0.0306), a las 48 horas RR 4.3778 (95% IC 1.1643-15.7177, p = 0.0286) y a las 72 horas con RR 3.5000 (95% IC 0.9497-12.8983, p = 0.0598). El valor de corte del balance hídrico fue ≥ 3.5 L, sin asociación con la mortalidad RR 0.1789 (95% IC 0.0125-2.5668, p = 0.2054) a las 24 horas, RR 0.5000 (95% IC 0.0854-2.9258, p = 0.4419) a las 48 horas y RR 0.3750 (95% IC 0.0610-2.3059, p = 0.2897) a las 72 horas. La asociación entre balance hídrico total y EVLWi fue r (2) Pearson = 0.01269. Conclusiones: El EVLWi > 11 mL/kg se asoció a un incremento en la mortalidad, a diferencia del balance hídrico. No encontramos correlación entre el balance hídrico y el EVLWi.

Abstract: Introduction: Positive fluid balance and extravascular lung water index (EVLWi) quantified by transpulmonary thermodilution have been important independent mortality prognostic factors. Including EVLWi to guide initial fluid reanimation therapy has a high impact in the amount of administered fluid. Although there is not enough evidence, search for an association between EVLWi and fluid balance could lead to a negative fluid balance driven by EVLWi to improve survival rates. In this retrospective study we search for the association between EVLWi, fluid balance and its impact on mortality. Material and methods: Retrospective, cohort study of 20 cases. We looked for any association between EVLWi by transpulmonary thermodilution and daily fluid balance at 24, 48 and 72 hours and reviewed mortality at 30 days. Results: An EVLWi cutoff value of > 11 mL/kg was associated with a higher mortality; on the first 24 hours with an RR 8.0 (95% CI 1.2146-52.6944, p = 0.0306), at 48 hours RR 4.3778 (95% CI 1.1643-15.7177, p = 0.0286) and at 72 hours RR 3.5000 (95% CI 0.9497-12.8983 p = 0.0598). Fluid balance cutoff value was established at ≥ 3.5 L, but we can't find any association with mortality, RR 0.1789 (95% CI 0.0125-2.5668, p = 0.2054) at 24 hours, RR 0.5000 (95% CI 0.0854-2.9258, p = 0.4419) at 48 hours y RR 0.3750 (95% CI 0.0610-2.3059, p = 0.2897) at 72 hours. The correlation between fluid balance and EVLWi was negative, Pearson's r (2) = 0.01269. Conclusions: EVLWi was associated to a higher mortality. We could not demonstrate an association between fluid balance and EVLWi.

Resumo: Introdução: O balanço hídrico positivo e a água extravascular pulmonar medida por termodiluição transpulmonar são fatores independentes da mortalidade. A inclusão do valor de água extravascular pulmonar indexada (EVLWi) durante a ressuscitação inicial impacta a quantidade de fluido entregue. Embora não haja precedente, buscar uma associação entre os dois parâmetros pode levar a um balanço hídrico global negativo guiado pela quantidade de EVLWi. Neste estudo retrospectivo, buscou-se a associação entre EVLWi e balanço hídrico e seu impacto na mortalidade. Material e métodos: Foi realizado um estudo de coorte retrospectivo com 20 casos para estabelecer a associação entre a água pulmonar extravascular indexada medida por termodiluição transpulmonar e balanço hídrico total em 24, 48 e 72 horas, bem como mortalidade em 30 dias. Resultados: Um valor de corte > 11 mL/kg de EVLWi foi associado a um aumento na mortalidade; às 24 horas RR 8.0 (95% IC 1.2146-52.6944, p = 0.0306), 48 horas RR 4.3778 (95% IC 1.1643-15.7177, p = 0.0286) e 72 horas com RR 3.5000 (95% IC 0.9497-12.8983 p = 0.0598). O valor de corte do balanço hídrico foi ≥ 3.5 L, sem associação com mortalidade RR 0.1789 (IC 95% 0.0125-2.5668, p = 0.2054) em 24 horas, RR 0.5000 (IC 95% 0.0854-2.9258 p = 0.4419) em 48 horas e RR 0.3750 (IC 95% 0.0610-2.3059 p = 0.2897) às 72 horas. A associação entre balanço hídrico total e EVLWi foi r 2 Pearson = 0.01269. Conclusões: EVLWi > 11 mL/kg foi associado a um aumento da mortalidade, em contraste com o balanço hídrico. Não encontramos correlação entre o balanço hídrico e o EVLWi.

Simultaneous mechanical ventilation of several patients with a single ventilator.

INTRODUCTION: Simultaneous mechanical ventilation of several patients with a single ventilator might reduce the deficit of these devices for the care of patients with acute respiratory failure due to Covid-19. OBJECTIVE: To communicate the results of a mechanical ventilation exercise with a ventilator in a lung simulator, and simultaneously in two and four. RESULTS: No statistically significant differences were observed between programmed, recorded and measured positive end-expiratory pressure, mean airway pressure and peak pressure, except when simultaneously ventilating four lung simulators. CONCLUSIONS: Simultaneous mechanical ventilation should be implemented by medical personnel with experience in the procedure, be restricted to two patients and carried out in the intensive care unit.

INTRODUCCIÓN: La ventilación mecánica simultánea a varios pacientes con un solo ventilador podría disminuir el déficit de esos dispositivos para atender a los enfermos con insuficiencia respiratoria aguda por Covid-19. OBJETIVO: Comunicar los resultados de un ejercicio de ventilación mecánica con un ventilador en un simulador de pulmón, y simultáneamente en dos y cuatro. RESULTADOS: No se observaron diferencias estadísticamente significativas entre la presión positiva al final de la espiración, presión media de la vía aérea y presión pico programadas, registradas y medidas, excepto al ventilar simultáneamente cuatro simuladores de pulmón. CONCLUSIONES: La ventilación mecánica simultánea debe ser instaurada por personal médico con experiencia en el procedimiento, restringirse a dos pacientes y ser realizada en la unidad de cuidados intensivos.