Multicentre analysis of severe perioperative adverse events in children undergoing surgery who were infected with SARS-CoV-2: a propensity score-adjusted analysis.

Background: The incidence of severe adverse events in children with SARS-CoV-2 undergoing anaesthesia has not been well established. We examined the relationship between SARS-CoV-2 infection and severe perioperative adverse events in children.

Methods: This multicentre (21 North American institutions), retrospective cohort study included children <18 years old, with American Society of Anesthesiologists physical status (ASA PS) of 1-4 and non-severe SARS-CoV-2, who underwent general anaesthesia between April 1, 2020, and March 31, 2021.

Profiling Tel1 Signaling Reveals a Non-Canonical Motif Targeting DNA Repair and Telomere Control Machineries.

The stability of the genome relies on Phosphatidyl Inositol 3-Kinase-related Kinases (PIKKs) that sense DNA damage and trigger elaborate downstream signaling responses. In , the Tel1 kinase (ortholog of human ATM) is activated at DNA double strand breaks (DSBs) and short telomeres. Despite the well-established roles of Tel1 in the control of telomere maintenance, suppression of chromosomal rearrangements, activation of cell cycle checkpoints, and repair of DSBs, the substrates through which Tel1 controls these processes remain incompletely understood.

Multi-step control of homologous recombination via Mec1/ATR suppresses chromosomal rearrangements.

The Mec1/ATR kinase is crucial for genome stability, yet the mechanism by which it prevents gross chromosomal rearrangements (GCRs) remains unknown. Here we find that in cells with deficient Mec1 signaling, GCRs accumulate due to the deregulation of multiple steps in homologous recombination (HR). Mec1 primarily suppresses GCRs through its role in activating the canonical checkpoint kinase Rad53, which ensures the proper control of DNA end resection.

Neuromonitoring of Pediatric and Adult Extracorporeal Membrane Oxygenation Patients: The Importance of Continuous Bedside Tools in Driving Neuroprotective Clinical Care.

Extracorporeal membrane oxygenation (ECMO) is a form of temporary cardiopulmonary bypass for patients with acute respiratory or cardiac failure refractory to conventional therapy. Its usage has become increasingly widespread and while reported survival after ECMO has increased in the past 25 years, the incidence of neurological injury has not declined, leading to the pressing question of how to improve time-to-detection and diagnosis of neurological injury. The neurological status of patients on ECMO is clinically difficult to evaluate due to multiple factors including illness, sedation, and pharmacological paralysis.

Multi-Step Control of Homologous Recombination by Mec1/ATR Ensures Robust Suppression of Gross Chromosomal Rearrangements.

The Mec1/ATR kinase is crucial for genome stability, yet the mechanism by which it prevents gross chromosomal rearrangements (GCRs) remains unknown. Here we find that in cells with deficient Mec1 signaling, GCRs accumulate due to the deregulation of multiple steps in homologous recombination (HR). Mec1 primarily suppresses GCRs through its role in activating the canonical checkpoint kinase Rad53, which ensures the proper control of DNA end resection.

Association between preoperative respiratory symptoms and perioperative respiratory adverse events in pediatric patients with positive viral testing.

Study Objective: To determine the association between the presence of upper respiratory tract viral infection symptoms and occurrence of perioperative respiratory adverse events (PRAE) in children with positive viral screening, and to analyze the risk of PRAE in children with SARS-CoV-2 compared to non-SARS-CoV-2 infection.

Design: A prospective cohort study.

Setting: A tertiary, freestanding pediatric hospital in Dallas, Texas.

Mec1-independent activation of the Rad53 checkpoint kinase revealed by quantitative analysis of protein localization dynamics.

The replication checkpoint is essential for accurate DNA replication and repair, and maintenance of genomic integrity when a cell is challenged with genotoxic stress. Several studies have defined the complement of proteins that change subcellular location in the budding yeast following chemically induced DNA replication stress using methyl methanesulfonate (MMS) or hydroxyurea (HU). How these protein movements are regulated remains largely unexplored.

Hypothermia after extracorporeal cardiopulmonary resuscitation not associated with improved neurologic complications or survival in children: An analysis of the ELSO registry.

Aim: To analyze the association between hypothermia and neurologic complications among children who were treated with extracorporeal cardiopulmonary resuscitation (ECPR) using the Extracorporeal Life Support Organization (ELSO) international registry.

Methods: We conducted a retrospective, multicenter, database study utilizing ELSO data for ECPR encounters from January 1, 2011, through December 31, 2019. Exclusion criteria included multiple ECMO runs and lack of variable data.

Association Between Disrupted Cerebral Autoregulation and Radiographic Neurologic Injury for Children on Extracorporeal Membrane Oxygenation: A Prospective Pilot Study.

Validation of a real-time monitoring device to evaluate the risk or occurrence of neurologic injury while on extracorporeal membrane oxygenation (ECMO) may aid clinicians in prevention and treatment. Therefore, we performed a pilot prospective cohort study of children under 18 years old on ECMO to analyze the association between cerebral blood pressure autoregulation as measured by diffuse correlation spectroscopy (DCS) and radiographic neurologic injury. DCS measurements of regional cerebral blood flow were collected on enrolled patients and correlated with mean arterial blood pressure to determine the cerebral autoregulation metric termed DCSx.

Proximity Labeling Reveals Spatial Regulation of the Anaphase-Promoting Complex/Cyclosome by a Microtubule Adaptor.

The anaphase-promoting complex/cyclosome (APC/C) coordinates advancement through mitosis via temporally controlled polyubiquitination events. Despite the long-appreciated spatial organization of key events in mitosis mediated largely by cytoskeletal networks, the spatial regulation of APC/C, the major mitotic E3 ligase, is poorly understood. We describe a microtubule-resident protein, PLEKHA5, as an interactor of APC/C and spatial regulator of its activity in mitosis.

A field guide to the proteomics of post-translational modifications in DNA repair.

All cells incur DNA damage from exogenous and endogenous sources and possess pathways to detect and repair DNA damage. Post-translational modifications (PTMs), in the past 20 years, have risen to ineluctable importance in the study of the regulation of DNA repair mechanisms. For example, DNA damage response kinases are critical in both the initial sensing of DNA damage as well as in orchestrating downstream activities of DNA repair factors.

Racial/ethnic differences in receipt of surgery among children in the United States.

Background: It is unknown whether racial/ethnic disparities exist in surgical utilization for children. The aim, therefore, was to evaluate the odds of surgery among children in the US by race/ethnicity to test the hypothesis that minority children have less surgery.

Methods: Cross-sectional data were analyzed on children 0-18 years old from the 1999 to 2018 National Health Interview Survey, a large, nationally representative survey.

Fe-NTA Microcolumn Purification of Phosphopeptides from Immunoprecipitation (IP) Eluates for Mass Spectrometry Analysis.

Protein phosphorylation is a nearly universal signaling mechanism. To date, a number of proteomics tools have been developed to analyze phosphorylation. Phosphoproteome-wide analyses using whole cell extracts suffer from incomplete coverage, often missing phosphorylation events from low-abundance proteins.

Anesthetic Complications Associated With Severe Acute Respiratory Syndrome Coronavirus 2 in Pediatric Patients.

Background: Coronavirus disease 2019 (COVID-19) is associated with high perioperative morbidity and mortality among adults. The incidence and severity of anesthetic complications in children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unknown. We hypothesized that there would be an increased incidence of intra- and postoperative complications in children with SARS-CoV-2 infection as compared to those with negative testing.

Phosphoproteomics reveals a distinctive Mec1/ATR signaling response upon DNA end hyper-resection.

The Mec1/ATR kinase is crucial for genome maintenance in response to a range of genotoxic insults, but it remains unclear how it promotes context-dependent signaling and DNA repair. Using phosphoproteomic analyses, we uncovered a distinctive Mec1/ATR signaling response triggered by extensive nucleolytic processing (resection) of DNA ends. Budding yeast cells lacking Rad9, a checkpoint adaptor and an inhibitor of resection, exhibit a selective increase in Mec1-dependent phosphorylation of proteins associated with single-strand DNA (ssDNA) transactions, including the ssDNA-binding protein Rfa2, the translocase/ubiquitin ligase Uls1, and the Sgs1-Top3-Rmi1 (STR) complex that regulates homologous recombination (HR).

Changes in pediatric trauma during COVID-19 stay-at-home epoch at a tertiary pediatric hospital.

Background: Trauma is the leading cause of morbidity and mortality in the pediatric population. However, during the societal disruptions secondary to the coronavirus (COVID-19) stay-at-home regulations, there have been reported changes to the pattern and severity of pediatric trauma. We review our two-institution experience.

In-depth and 3-dimensional exploration of the budding yeast phosphoproteome.

Phosphorylation is one of the most dynamic and widespread post-translational modifications regulating virtually every aspect of eukaryotic cell biology. Here, we assemble a dataset from 75 independent phosphoproteomic experiments performed in our laboratory using Saccharomyces cerevisiae. We report 30,902 phosphosites identified from cells cultured in a range of DNA damage conditions and/or arrested in distinct cell cycle stages.

Maximized quantitative phosphoproteomics allows high confidence dissection of the DNA damage signaling network.

The maintenance of genomic stability relies on DNA damage sensor kinases that detect DNA lesions and phosphorylate an extensive network of substrates. The Mec1/ATR kinase is one of the primary sensor kinases responsible for orchestrating DNA damage responses. Despite the importance of Mec1/ATR, the current network of its identified substrates remains incomplete due, in part, to limitations in mass spectrometry-based quantitative phosphoproteomics.

Protein polyglutamylation catalyzed by the bacterial calmodulin-dependent pseudokinase SidJ.

Pseudokinases are considered to be the inactive counterparts of conventional protein kinases and comprise approximately 10% of the human and mouse kinomes. Here, we report the crystal structure of the effector protein, SidJ, in complex with the eukaryotic Ca-binding regulator, calmodulin (CaM). The structure reveals that SidJ contains a protein kinase-like fold domain, which retains a majority of the characteristic kinase catalytic motifs.

Activity of a ubiquitin ligase adaptor is regulated by disordered insertions in its arrestin domain.

The protein composition of the plasma membrane is rapidly remodeled in response to changes in nutrient availability or cellular stress. This occurs, in part, through the selective ubiquitylation and endocytosis of plasma membrane proteins, which in the yeast is mediated by the HECT E3 ubiquitin ligase Rsp5 and arrestin--related trafficking (ART) adaptors. Here, we provide evidence that the ART protein family members are composed of an arrestin fold with interspersed disordered loops.

Trends in Surgery for Children Younger Than 3 Years From 1998 to 2017.

This study investigates trends in surgical exposure among children younger than 3 years using National Health Interview Survey data.