Association Between the First-Hour Intravenous Fluid Volume and Mortality in Pediatric Septic Shock.

Study Objective: To determine whether the receipt of more than or equal to 30 mL/kg of intravenous fluid in the first hour after emergency department (ED) arrival is associated with sepsis-attributable mortality among children with hypotensive septic shock.

Methods: This is a retrospective cohort study set in 57 EDs in the Improving Pediatric Sepsis Outcomes quality improvement collaborative. Patients less than 18 years of age with hypotensive septic shock who received their first intravenous fluid bolus within 1 hour of arrival at the ED were propensity-score matched for probability of receiving more than or equal to 30 mL/kg in the first hour.

Machine Learning Approach to Predicting Absence of Serious Bacterial Infection at PICU Admission.

Background And Objectives: Serious bacterial infection (SBI) is common in the PICU. Antibiotics can mitigate associated morbidity and mortality but have associated adverse effects. Our objective is to develop machine learning models able to identify SBI-negative children and reduce unnecessary antibiotics.

Lessons Learned from an HIV Pre-Exposure Prophylaxis Coordination Program in San Francisco Primary Care Clinics.

HIV pre-exposure prophylaxis (PrEP) has shown high efficacy and effectiveness for HIV prevention; however, many individuals with PrEP indications are not receiving PrEP. PrEP Coordinators work closely with patients and health care providers to increase PrEP access, and they provide unique insights into the inner workings of PrEP care and service delivery. In this study, we discuss key challenges and recommendations for improved PrEP service delivery (including training PrEP Coordinators to manage PrEP panels, making PrEP a part of routine care and optimizing electronic health records, designating a PrEP "champion" who can strengthen communication and leadership, using a proactive approach to increase PrEP retention, and training providers and PrEP Coordinators to meet youth-specific needs) from our discussions with the PrEP Coordinators who led PrEP panel management in San Francisco Department of Public Health primary care clinics.

Human brucellosis: Widespread information deficiency hinders an understanding of global disease frequency.

Background: For decades, human brucellosis has been recognized worldwide as a significant cause of morbidity, yet the annual incidence of this disease remains unknown. We analyzed this frequency, using international reports (2005-2019), identifying information gaps, and distinguishing a possible path forward.

Methodology/principal Findings: A novel approach to estimating the incidence of this disease was explored.

Discovering a new part of the phenotypic spectrum of Coffin-Siris syndrome in a fetal cohort.

Purpose: Genome-wide sequencing is increasingly being performed during pregnancy to identify the genetic cause of congenital anomalies. The interpretation of prenatally identified variants can be challenging and is hampered by our often limited knowledge of prenatal phenotypes. To better delineate the prenatal phenotype of Coffin-Siris syndrome (CSS), we collected clinical data from patients with a prenatal phenotype and a pathogenic variant in one of the CSS-associated genes.

The clinical and genetic features of hereditary pancreatitis in South Australia.

Objective: To characterise the clinical phenotypes and genetic variants of hereditary pancreatitis in people diagnosed in South Australia.

Design, Setting, Participants: Cross-sectional study of people who received molecular diagnoses of hereditary pancreatitis from one of four major diagnostic services in South Australia, 1 January 2006 - 30 June 2021.

Main Outcome Measures: Genotypic and clinical features of people with hereditary pancreatitis, including age at onset, attack frequency, pain indices, use of opioid medications, and physical and mental health impact of hereditary pancreatitis.

Validation of the Pediatric Sequential Organ Failure Assessment Score and Evaluation of Third International Consensus Definitions for Sepsis and Septic Shock Definitions in the Pediatric Emergency Department.

Importance: Pediatric sepsis definitions have evolved, and some have proposed using the measure used in adults to quantify organ dysfunction, a Sequential Organ Failure Assessment (SOFA) score of 2 or more in the setting of suspected infection. A pediatric adaptation of SOFA (pSOFA) showed excellent discrimination for mortality in critically ill children but has not been evaluated in an emergency department (ED) population.

Objective: To delineate test characteristics of the pSOFA score for predicting in-hospital mortality among (1) all patients and (2) patients with suspected infection treated in pediatric EDs.

RNA-Based Targeted Gene Sequencing Improves the Diagnostic Yield of Mutant Detection in Chronic Myeloid Leukemia.

Mutation detection is increasingly used for the management of hematological malignancies. Prior whole transcriptome and whole exome sequencing studies using total RNA and DNA identified diverse mutation types in cancer-related genes associated with treatment failure in patients with chronic myeloid leukemia. Variants included single-nucleotide variants and small insertions/deletions, plus fusion transcripts and partial or whole gene deletions.

Structure and Interdigitation of Chain-Asymmetric Phosphatidylcholines and Milk Sphingomyelin in the Fluid Phase.

We addressed the frequent occurrence of mixed-chain lipids in biological membranes and their impact on membrane structure by studying several chain-asymmetric phosphatidylcholines and the highly asymmetric milk sphingomyelin. Specifically, we report trans-membrane structures of the corresponding fluid lamellar phases using small-angle X-ray and neutron scattering, which were jointly analyzed in terms of a membrane composition-specific model, including a headgroup hydration shell. Focusing on terminal methyl groups at the bilayer center, we found a linear relation between hydrocarbon chain length mismatch and the methyl-overlap for phosphatidylcholines, and a non-negligible impact of the glycerol backbone-tilting, letting the -chain penetrate deeper into the opposing leaflet by half a CH group.

The structure of Phocaeicola vulgatus sialic acid acetylesterase.

Sialic acids terminate many N- and O-glycans and are widely distributed on cell surfaces. There are a diverse range of enzymes which interact with these sugars throughout the tree of life. They can act as receptors for influenza and specific betacoronaviruses in viral binding and their cleavage is important in virion release.

Association of SARS-CoV-2 Infection During Pregnancy With Maternal and Perinatal Outcomes.

Importance: There are limited high-quality, population-level data about the effect of SARS-CoV-2 infection on pregnancy using contemporaneous comparator cohorts.

Objectives: To describe maternal and perinatal outcomes associated with SARS-CoV-2 infection in pregnancy and to assess variables associated with severe disease in the pregnant population.

Design, Setting, And Participants: CANCOVID-Preg is an observational surveillance program for SARS-CoV-2-affected pregnancies in Canada.

Model Membrane Systems Used to Study Plasma Membrane Lipid Asymmetry.

It is well known that the lipid distribution in the bilayer leaflets of mammalian plasma membranes (PMs) is not symmetric. Despite this, model membrane studies have largely relied on chemically symmetric model membranes for the study of lipid-lipid and lipid-protein interactions. This is primarily due to the difficulty in preparing stable, asymmetric model membranes that are amenable to biophysical studies.

Interdigitation-Induced Order and Disorder in Asymmetric Membranes.

We studied the transleaflet coupling of compositionally asymmetric liposomes in the fluid phase. The vesicles were produced by cyclodextrin-mediated lipid exchange and contained dipalmitoyl phosphatidylcholine (DPPC) in the inner leaflet and different mixed-chain phosphatidylcholines (PCs) as well as milk sphingomyelin (MSM) in the outer leaflet. In order to jointly analyze the obtained small-angle neutron and X-ray scattering data, we adapted existing models of trans-bilayer structures to measure the overlap of the hydrocarbon chain termini by exploiting the contrast of the terminal methyl ends in X-ray scattering.

Adolescent perspectives of bedtime social media use: A qualitative systematic review and thematic synthesis.

Adolescence is often characterised by changes in sleep patterns, with reports that the average adolescent does not get the recommended sleep time. Recent qualitative research has identified the use of electronics at bedtime and engagement with social media platforms as barriers to gaining sufficient time and quality of sleep during adolescence. A systematic review and thematic synthesis was undertaken following the three-step thematic synthesis framework.

An experimental investigation on the impact of wind turbine noise on polysomnography-measured and sleep diary-determined sleep outcomes.

Study Objectives: Carefully controlled studies of wind turbine noise (WTN) and sleep are lacking, despite anecdotal complaints from some residents in wind farm areas and known detrimental effects of other noises on sleep. This laboratory-based study investigated the impact of overnight WTN exposure on objective and self-reported sleep outcomes.

Methods: Sixty-eight participants (38 females) aged (mean ± SD) 49.

Complement Activation Fragments Are Increased in Critically Ill Pediatric Patients with Severe AKI.

Background: Children who are critically ill with AKI suffer from high morbidity and mortality rates, and lack treatment options. Emerging evidence implicates the role of complement activation in AKI pathogenesis, which could potentially be treated with complement inhibitors. The purpose of this study is to evaluate the association between complement activation fragments and severity of AKI in children who are critically ill.

Simulation-Based Engineering of Time-Delayed Safety Switches for Safer Gene Therapies.

CRISPR-based gene editing is a powerful tool with great potential for applications in the treatment of many inherited and acquired diseases. The longer that CRISPR gene therapy is maintained within a patient, however, the higher the likelihood that it will result in problematic side effects such as off-target editing or immune response. One approach to mitigating these issues is to link the operation of the therapeutic system to a safety switch that autonomously disables its operation and removes the delivered therapeutics after some amount of time.

Does total sleep time substantially increase after cognitive behavioral therapy for insomnia?

Study Objectives: In most standardized approaches to cognitive behavioral therapy for insomnia, it is commonly the case that total wake time is reduced substantially during sleep restriction, but self-reported total sleep time (TST) is minimally affected. By follow-up, however, TST increases by almost 1 hour on average. A secondary analysis was undertaken to assess what percentage of participants meet or appreciably exceed baseline TST after cognitive behavioral therapy for insomnia.

Inhibition of Anti-Inflammatory Macrophage Phenotype Reduces Tumour Growth in Mouse Models of Brain Metastasis.

Breast cancer brain metastasis is a significant clinical problem and carries a poor prognosis. Although it is well-established that macrophages are a primary component of the brain metastasis microenvironment, the role of blood-derived macrophages (BDM) and brain-resident microglia in the progression of brain metastases remains uncertain. The aim of this study, therefore, was to determine the role, specifically, of pro- and anti-inflammatory BDM and microglial phenotypes on metastasis progression.

Low-fidelity simulation for management of postpartum haemorrhage in a Ghanaian teaching hospital.

We conducted a pre/post study of a post-partum hemorrhage (PPH) simulation exercise at Korle Bu Hospital, using a low-fidelity birthing simulator and questionnaires. We aimed to evaluate low-fidelity simulation as a feasible and effective method of improving resident knowledge and confidence in a low-resource setting. Knowledge and confidence in PPH management were measured before and after using 5-point Likert scales and multiple-choice questions.

From outcome measurement to improving health outcomes after lower limb amputation-A narrative review exploring outcome measurement from a clinical practice perspective.

Outcome measurement is essential to understand the impact of clinical interventions and the performance of services. Despite national and professional body encouragement, and successful examples of system level outcome measurement within some health care settings, many barriers still exist preventing outcome measurement from becoming embedded in clinical practice. This paper presents a narrative review which aims to describe the state of the outcome measurement evidence base in prosthetic rehabilitation, as applied in clinical practice, with a view to identifying areas for future work aimed at making outcome measurement in prosthetic rehabilitation a meaningful reality.

Changes Experienced by Low-Concentration Lipid Bicelles as a Function of Temperature.

Differential scanning calorimetry (DSC) of dipalmitoyl phosphatidylcholine (DPPC), dihexanoyl phosphatidylcholine, and dipalmitoyl phosphatidylglycerol bicelles reveals two endothermic peaks. Based on analysis of small angle neutron scattering and small angle X-ray scattering data, the two DSC peaks are associated with the melting of DPPC and a change in bicellar morphology─namely, either bicelle-to-spherical vesicle or oblate-to-spherical vesicle. The reversibility of the two structural transformations was examined by DSC and found to be consistent with the corresponding small angle scattering data.

Feasibility of establishing a Canadian Obstetric Survey System (CanOSS) for severe maternal morbidity: a study protocol.

Introduction: Severe maternal morbidity (SMM)-an unexpected pregnancy-associated maternal outcome resulting in severe illness, prolonged hospitalisation or long-term disability-is recognised by many, as the preferred indicator of the quality of maternity care, especially in high-income countries. Obtaining comprehensive details on events and circumstances leading to SMM, obtained through maternity units, could complement data from large epidemiological studies and enable targeted interventions to improve maternal health. The aim of this study is to assess the feasibility of gathering such data from maternity units across Canadian provinces and territories, with the goal of establishing a national obstetric survey system for SMM in Canada.

A qualitative exploration of decisions about dental recall intervals - part 2: perspectives of dentists and patients on the role of shared decision making in dental recall decisions.

Introduction Patients are sensitive to both the frequency and costs of dental recall visits. Shared decision making (SDM) is a principle of patient-centred care, advocated by the National Institute for Health and Care Excellence and policymakers, whereby joint decisions are made between clinicians and patients.Aims To explore NHS dentists' and patients' attitudes towards SDM in decisions about recall interval.