Remodeling of the Tight Junction During Recovery from Exposure to Hydrogen Peroxide in Kidney Epithelial Cells

Renal ischemia-reperfusion injury results in oxidative stress-induced alterations in barrier function. Activation of the mitogen-activated protein (MAP) kinase pathway during recovery from oxidative stress may be an effector of oxidant-induced tight junction reorganization. We hypothesized that tight junction composition and barrier function would be perturbed during recovery from oxidative stress. We developed a model of short-term H2O2 exposure followed by recovery using Madin Darby canine kidney (MDCK II) cells. H2O2 perturbs barrier function without a significant cytotoxic effect except in significant doses. ERK-1/2 and p38, both enzymes of the MAP kinase pathway, were activated within minutes of exposure to H2O2. Transient exposure to H2O2 produced a biphasic response in the transepithelial electrical resistance (TER). An initial drop in TER at 6 h was followed by a significant increase at 24 h. Inhibition of ERK-1/2 activation attenuated the increase in TER observed at 24 h. Expression of occludin initially decreased, followed by partial recovery at 24 h. In contrast, claudin-1 levels decreased and failed to recover at 24 h. Claudin-2 levels were markedly decreased at 24 h; however, inhibition of ERK-1/2 activation was protective. Occludin and claudin-1 localization at the apical membrane on immunofluorescence images was fragmented at 6 h after H2O2 exposure with subsequent recovery of appropriate localization by 24 h. MDCK II cell recovery after H2O2 exposure is associated with functional and structural modifications of the tight junction that are mediated in part by activation of the MAP kinase enzymes ERK-1/2 and p38

Prophylactic Transfusion Strategies in Children Supported by Extracorporeal Membrane Oxygenation:The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE Consensus Conference

OBJECTIVES: To derive systematic-review informed, modified Delphi consensus regarding prophylactic transfusions in neonates and children supported with extracorporeal membrane oxygenation (ECMO) from the Pediatric ECMO Anticoagulation CollaborativE.DATA SOURCES: A structured literature search was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2020, with an update in May 2021.STUDY SELECTION: Included studies assessed use of prophylactic blood product transfusion in pediatric ECMO.DATA EXTRACTION: Two authors reviewed all citations independently, with a third independent reviewer resolving conflicts. Thirty-three references were used for data extraction and informed recommendations. Evidence tables were constructed using a standardized data extraction form.MEASUREMENTS AND MAIN RESULTS: The evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation system. Forty-eight experts met over 2 years to develop evidence-informed recommendations and, when evidence was lacking, expert-based consensus statements or good practice statements for prophylactic transfusion strategies for children supported with ECMO. A web-based modified Delphi process was used to build consensus via the Research And Development/University of California Appropriateness Method. Consensus was based on a modified Delphi process with agreement defined as greater than 80%. We developed two good practice statements, 4 weak recommendations, and three expert consensus statements.CONCLUSIONS: Despite the frequency with which pediatric ECMO patients are transfused, there is insufficient evidence to formulate evidence-based prophylactic transfusion strategies.</p

Utility of echocardiography in predicting mortality in infants with severe bronchopulmonary dysplasia

This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.Objective: To determine the relationship between interventricular septal position (SP) and right ventricular systolic pressure (RVSP) and mortality in infants with severe BPD (sBPD). Study design: Infants with sBPD in the Children's Hospitals Neonatal Database who had echocardiograms 34-44 weeks' postmenstrual age (PMA) were included. SP and RVSP were categorized normal, abnormal (flattened/bowed SP or RVSP > 40 mmHg) or missing. Results: Of 1157 infants, 115 infants (10%) died. Abnormal SP or RVSP increased mortality (SP 19% vs. 8% normal/missing, RVSP 20% vs. 9% normal/missing, both p < 0.01) in unadjusted and multivariable models, adjusted for significant covariates (SP OR 1.9, 95% CI 1.2-3.0; RVSP OR 2.2, 95% CI 1.1-4.7). Abnormal parameters had high specificity (SP 82%; RVSP 94%), and negative predictive value (SP 94%, NPV 91%) for mortality. Conclusions: Abnormal SP or RVSP is independently associated with mortality in sBPD infants. Negative predictive values distinguish infants most likely to survive

Executive Summary:The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE (PEACE) Consensus Conference

OBJECTIVES: To present recommendations and consensus statements with supporting literature for the clinical management of neonates and children supported with extracorporeal membrane oxygenation (ECMO) from the Pediatric ECMO Anticoagulation CollaborativE (PEACE) consensus conference.DATA SOURCES: Systematic review was performed using PubMed, Embase, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021, followed by serial meetings of international, interprofessional experts in the management ECMO for critically ill children.STUDY SELECTION: The management of ECMO anticoagulation for critically ill children.DATA EXTRACTION: Within each of eight subgroup, two authors reviewed all citations independently, with a third independent reviewer resolving any conflicts.DATA SYNTHESIS: A systematic review was conducted using MEDLINE, Embase, and Cochrane Library databases, from January 1988 to May 2021. Each panel developed evidence-based and, when evidence was insufficient, expert-based statements for the clinical management of anticoagulation for children supported with ECMO. These statements were reviewed and ratified by 48 PEACE experts. Consensus was obtained using the Research and Development/UCLA Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. We developed 23 recommendations, 52 expert consensus statements, and 16 good practice statements covering the management of ECMO anticoagulation in three broad categories: general care and monitoring; perioperative care; and nonprocedural bleeding or thrombosis. Gaps in knowledge and research priorities were identified, along with three research focused good practice statements.CONCLUSIONS: The 91 statements focused on clinical care will form the basis for standardization and future clinical trials.</p

Executive Summary: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE (PEACE) Consensus Conference

OBJECTIVES: To present recommendations and consensus statements with supporting literature for the clinical management of neonates and children supported with extracorporeal membrane oxygenation (ECMO) from the Pediatric ECMO Anticoagulation CollaborativE (PEACE) consensus conference. DATA SOURCES: Systematic review was performed using PubMed, Embase, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021, followed by serial meetings of international, interprofessional experts in the management ECMO for critically ill children. STUDY SELECTION: The management of ECMO anticoagulation for critically ill children. DATA EXTRACTION: Within each of eight subgroup, two authors reviewed all citations independently, with a third independent reviewer resolving any conflicts. DATA SYNTHESIS: A systematic review was conducted using MEDLINE, Embase, and Cochrane Library databases, from January 1988 to May 2021. Each panel developed evidence-based and, when evidence was insufficient, expert-based statements for the clinical management of anticoagulation for children supported with ECMO. These statements were reviewed and ratified by 48 PEACE experts. Consensus was obtained using the Research and Development/UCLA Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. We developed 23 recommendations, 52 expert consensus statements, and 16 good practice statements covering the management of ECMO anticoagulation in three broad categories: general care and monitoring; perioperative care; and nonprocedural bleeding or thrombosis. Gaps in knowledge and research priorities were identified, along with three research focused good practice statements. CONCLUSIONS: The 91 statements focused on clinical care will form the basis for standardization and future clinical trials

Ventilation Strategies During Extracorporeal Membrane Oxygenation for Neonatal Respiratory Failure: Current Approaches Among Level IV Neonatal ICUs

To describe ventilation strategies used during extracorporeal membrane oxygenation (ECMO) for neonatal respiratory failure among level IV neonatal ICUs (NICUs). Design: Cross-sectional electronic survey. Setting: Email-based Research Electronic Data Capture survey. Patients: Neonates undergoing ECMO for respiratory failure at level IV NICUs. Interventions: A 40-question survey was sent to site sponsors of regional referral neonatal ECMO centers participating in the Children\u27s Hospitals Neonatal Consortium. Reminder emails were sent at 2- and 4-week intervals. Measurements and main results: Twenty ECMO centers responded to the survey. Most primarily use venoarterial ECMO (65%); this percentage is higher (90%) for congenital diaphragmatic hernia. Sixty-five percent reported following protocol-based guidelines, with neonatologists primarily responsible for ventilator management (80%). The primary mode of ventilation was pressure control (90%), with synchronized intermittent mechanical ventilation (SIMV) comprising 80%. Common settings included peak inspiratory pressure (PIP) of 16-20 cm H2O (55%), positive end-expiratory pressure (PEEP) of 9-10 cm H2O (40%), I-time 0.5 seconds (55%), rate of 10-15 (60%), and Fio2 22-30% (65%). A minority of sites use high-frequency ventilation (HFV) as the primary mode (5%). During ECMO, 55% of sites target some degree of lung aeration to avoid complete atelectasis. Fifty-five percent discontinue inhaled nitric oxide (iNO) during ECMO, while 60% use iNO when trialing off ECMO. Nonventilator practices to facilitate decannulation include bronchoscopy (50%), exogenous surfactant (25%), and noninhaled pulmonary vasodilators (50%). Common ventilator thresholds for decannulation include PEEP of 6-7 (45%), PIP of 21-25 (55%), and tidal volume 5-5.9 mL/kg (50%). Conclusions: The majority of level IV NICUs follow internal protocols for ventilator management during neonatal respiratory ECMO, and neonatologists primarily direct management in the NICU. While most centers use pressure-controlled SIMV, there is considerable variability in the range of settings used, with few centers using HFV primarily. Future studies should focus on identifying respiratory management practices that improve outcomes for neonatal ECMO patients

Contourite depositional system after the exit of a strait: Case study from the late Miocene South Rifian Corridor, Morocco

Idealized facies of bottom current deposits (contourites) have been established for fine-grained contourite drifts in modern deep-marine sedimentary environments. Their equivalent facies in the ancient record however are only scarcely recognized due to the weathered nature of most fine-grained deposits in outcrop. Facies related to the erosional elements (i.e. contourite channels) of contourite depositional systems have not yet been properly established and related deposits in outcrop appear non-existent. To better understand the sedimentary facies and facies sequences of contourites, the upper Miocene contourite depositional systems of the South Rifian Corridor (Morocco) is investigated. This contourite depositional system formed by the dense palaeo-Mediterranean Outflow Water. Foraminifera assemblages were used for age-constraints (7.51 to 7.35 Ma) and to determine the continental slope depositional domains. Nine sedimentary facies have been recognized based on lithology, grain-size, sedimentary structures and biogenic structures. These facies were subsequently grouped into five facies associations related to the main interpreted depositional processes (hemipelagic settling, contour currents and gravity flows). The vertical sedimentary facies succession records the tectonically induced, southward migration of the contourite depositional systems and the intermittent behaviour of the palaeo-Mediterranean Outflow Water, which is mainly driven by precession and millennial-scale climate variations. Tides substantially modulated the palaeo-Mediterranean Outflow Water on a sub-annual scale. This work shows exceptional examples of muddy and sandy contourite deposits in outcrop by which a facies distribution model from the proximal continental slope, the contourite channel to its adjacent contourite drift, is proposed. This model serves as a reference for contourite recognition both in modern environments and the ancient record. Furthermore, by establishing the hydrodynamics of overflow behaviour a framework is provided that improves process-based interpretation of deep-water bottom current deposits

Properties of natural microlayers on Australian freshwater storages and their potential to interact with artificial monolayers

Microlayers are natural surface films derived from hydrophobic organic compounds that form on most lakes and streams. Holoarctic brown water lakes have been most commonly studied, with Australian research limited to marine microlayers. Artificial monolayers based on long-chain fatty alcohols have been applied to freshwater storages to reduce evaporative loss. As a water conservation strategy, monolayer technology was not widely adopted due to variable field performance. However, the role of natural microlayers in reducing monolayer performance has not previously been investigated. In this study, microlayer and subsurface samples from six water storages in Queensland were characterized for water quality indices including biochemical oxygen demand, permanganate index and ultraviolet light absorbance. Microlayer enrichment in southeast Queensland is comparable to or higher than holoarctic lakes. Results indicate that microlayer compounds have the potential to disrupt monolayers in at least three ways: As substrates for microbes capable of degrading monolayer compounds, as chromophores accelerating photodegradation, and as impurities disrupting the molecular packing required to reduce evaporative loss. The knowledge gained from studying natural microlayers can also be used to benchmark novel monolayer compounds, to minimize their environmental impact on freshwater ecosystems