Design and validation of a GMP stem cell manufacturing protocol for MPSII hematopoietic stem cell gene therapy.

Hematopoietic stem cell gene therapy (HSCGT) is a promising therapeutic strategy for the treatment of neurodegenerative, metabolic disorders. The approach involves the introduction of a missing gene into patients' own stem cells via lentiviral-mediated transduction (TD). Once transplanted back into a fully conditioned patient, these genetically modified HSCs can repopulate the blood system and produce the functional protein, previously absent or non-functional in the patient, which can then cross-correct other affected cells in somatic organs and the central nervous system.

Age and Sex Differences in the Genetics of Cardiomyopathy.

Cardiomyopathy has variable penetrance. We analyzed age and sex-related genetic differences in 1,397 cardiomyopathy patients (Ontario, UK) with whole genome sequencing. Pediatric cases (n = 471) harbored more deleterious protein-coding variants in Tier 1 cardiomyopathy genes compared to adults (n = 926) (34.

Oral antimicrobial therapy for cellulitis versus outpatient parenteral antimicrobial therapy: a single-centre audit of cellulitis outcomes.

Background: Cellulitis is a common acute skin and soft tissue infection that causes substantial morbidity and healthcare costs.

Aims: To audit the impact on cellulitis management, regimen tolerability and outcomes of switching from outpatient parenteral antimicrobial therapy (OPAT) using intravenous (i.v.

Repair of Acute Respiratory Distress Syndrome in COVID-19 by Stromal Cells (REALIST-COVID Trial): A Multicenter, Randomized, Controlled Clinical Trial.

Mesenchymal stromal cells (MSCs) may modulate inflammation, promoting repair in coronavirus disease (COVID-19)-related acute respiratory distress syndrome (ARDS). We investigated the safety and efficacy of ORBCEL-C (CD362 [cluster of differentiation 362]-enriched, umbilical cord-derived MSCs) in COVID-19-related ARDS. In this multicenter, randomized, double-blind, allocation-concealed, placebo-controlled trial (NCT03042143), patients with moderate to severe COVID-19-related ARDS were randomized to receive ORBCEL-C (400 million cells) or placebo (Plasma-Lyte 148).

Combined Borderline Acetabular Dysplasia and Increased Femoral Anteversion Is Associated With Worse Outcomes in Female Patients Undergoing Hip Arthroscopy for Femoroacetabular Impingement.

Purpose: To determine the relationship of increased femoral anteversion and borderline acetabular dysplasia on the outcomes of hip arthroscopy for femoroacetabular impingement in a female cohort of patients.

Methods: This is a retrospective study of female patients undergoing hip arthroscopy for femoroacetabular impingement. All patients had preoperative radiographs and computed tomography scans from which lateral center edge angle (LCEA) and femoral anteversion were measured.

Repair of acute respiratory distress syndrome by stromal cell administration (REALIST): a structured study protocol for an open-label dose-escalation phase 1 trial followed by a randomised, triple-blind, allocation concealed, placebo-controlled phase 2 trial.

Background: Mesenchymal stromal cells (MSCs) may be of benefit in ARDS due to immunomodulatory and reparative properties. This trial investigates a novel CD362 enriched umbilical cord derived MSC product (REALIST ORBCEL-C), produced to Good Manufacturing Practice standards, in patients with moderate to severe ARDS due to COVID-19 and ARDS due to other causes.

Methods: Phase 1 is a multicentre open-label dose-escalation pilot trial.

analysis of growth rate evolution during molecular layer deposition of ultra-thin polyurea films using aliphatic and aromatic precursors.

Organic thin films formed by molecular layer deposition (MLD) are important for next-generation electronics, energy storage, photoresists, protective barriers and other applications. This study uses ellipsometry and quartz crystal microbalance to explore growth initiation and growth rate evolution during MLD of polyurea using aromatic -phenylene diisocyanate (PDIC) or aliphatic 1,6-hexamethylene diisocyanate (HDIC) combined with ethylenediamine (ED) or 1,6-hexanediamine (HD) co-reactants. During the first 10-20 cycles of growth, we show the growth rate can increase and/or decrease substantially depending on the substrate as well as the flexibility, length, and structure of the isocyanate and amine reactants used.

Common Genetic Variants Contribute to Risk of Transposition of the Great Arteries.

Rationale: Dextro-transposition of the great arteries (D-TGA) is a severe congenital heart defect which affects approximately 1 in 4,000 live births. While there are several reports of D-TGA patients with rare variants in individual genes, the majority of D-TGA cases remain genetically elusive. Familial recurrence patterns and the observation that most cases with D-TGA are sporadic suggest a polygenic inheritance for the disorder, yet this remains unexplored.

Repair of acute respiratory distress syndrome by stromal cell administration (REALIST) trial: A phase 1 trial.

Background: Mesenchymal stromal cells (MSCs) may be of benefit in acute respiratory distress syndrome (ARDS) due to immunomodulatory, reparative, and antimicrobial actions. ORBCEL-C is a population of CD362 enriched umbilical cord-derived MSCs. The REALIST phase 1 trial investigated the safety and feasibility of ORBCEL-C in patients with moderate to severe ARDS.

Preventing early births in a regional tertiary maternity unit: Evaluating preterm and early term birth rates before and after implementation of the Preterm Birth Prevention Initiative in the Australian Capital Territory.

Background: A multifaceted preterm birth (PTB) prevention initiative was launched in the Australian Capital Territory (ACT) in 2019. The aim of this initiative was to safely lower the rate of early births across the ACT and the surrounding areas in New South Wales. Modelled on the Western Australian PTB Prevention Initiative, the program included new clinical guidelines and a new PTB prevention clinic at the main tertiary hospital.

Repair of Acute Respiratory Distress Syndrome by Stromal Cell Administration in COVID-19 (REALIST-COVID-19): A structured summary of a study protocol for a randomised, controlled trial.

Objectives: The primary objective of the study is to assess the safety of a single intravenous infusion of Mesenchymal Stromal Cells (MSCs) in patients with Acute Respiratory Distress Syndrome (ARDS) due to COVID-19. Secondary objectives are to determine the effects of MSCs on important clinical outcomes, as described below.

Trial Design: REALIST COVID 19 is a randomised, placebo-controlled, triple blinded trial.

Cardiac abnormalities identified with echocardiography in anorexia nervosa: systematic review and meta-analysis.

Background: Anorexia nervosa affects most organ systems, with 80% suffering from cardiovascular complications.

Aims: To define echocardiographic abnormalities in anorexia nervosa through systematic review and meta-analysis.

Method: Two reviewers independently assessed eligibility of publications from Medline, EMBASE and Cochrane Database of Systematic Reviews registries.

Return of genetic and genomic research findings: experience of a pediatric biorepository.

Background: Assess process, uptake, validity and resource needs for return of actionable research findings to biobank participants.

Methods: Participants were prospectively enrolled in a multicenter biorepository of childhood onset heart disease. Clinically actionable research findings were reviewed by a Return of Research Results Committee (RRR) and returned to the physician or disclosed directly to the participant through a research genetic counselor.

Consent, wantedness, and pleasure: Three dimensions affecting the perceived stress of and judgements of rape in sexual encounters.

Participants conflate consent and wantedness when judging situations as rape (Peterson & Muehlenhard, 2007). Pleasure might also affect how such situations might be appraised by victims, perpetrators, and jurors. In four experiments, participants read vignettes describing sexual encounters that were consensual or not, wanted or unwanted, and pleasurable or not pleasurable.

Non-invasive stroke volume estimation by transthoracic electrical bioimpedance Doppler echocardiography in healthy volunteers.

Thoracic electrical bioimpedance (TEB) and transthoracic echocardiography (TTE) are non-invasive methods to estimate stroke volume (SV) and cardiac output (CO). Thoracic electrical bioimpedance is not in widespread clinical use with reports of inaccurate cardiac output estimation compared to invasive monitors, particularly in non-healthy populations. We explore its use as a trend monitor by comparing it against thoracic echocardiography in fifteen healthy volunteers undergoing two physical challenges designed to vary cardiac output.

Non-invasive imaging reveals conditions that impact distribution and persistence of cells after in vivo administration.

Background: Cell-based regenerative medicine therapies are now frequently tested in clinical trials. In many conditions, cell therapies are administered systemically, but there is little understanding of their fate, and adverse events are often under-reported. Currently, it is only possible to assess safety and fate of cell therapies in preclinical studies, specifically by monitoring animals longitudinally using multi-modal imaging approaches.

Impact of salivary enzyme activity on the oral perception of starch containing foods.

Unlabelled: It has long been held that product developers should not rely solely on instrumental measures of texture. This study examined the widely accepted effects of salivary α amylase on mouth thinning during oral processing. To understand this phenomenon, 13 descriptive panelists were trained to manipulate starch thickened semisolid foods and note when changes in the perceived thickness occurred.

An innovative method to generate a Good Manufacturing Practice-ready regulatory T-cell product from non-mobilized leukapheresis donors.

Background Aims: There is real and sustained interest in preparing T-regulatory cells from leukapheresis collections for cellular therapy through the use of simple, effective and reliable methods conforming to Good Manufacturing Practice (GMP). We describe a GMP-ready isolation procedure for CD25(+) products with the use of a sterile docking device, pigtail sampling, a laminar flow hood and the CliniMACS system that uses leukapheresis collections made by two apheresis machines.

Methods: We used CD8/CD19 depletion followed by CD25-positive selection.

Exome sequencing identifies rare variants in multiple genes in atrioventricular septal defect.

Purpose: The genetic etiology of atrioventricular septal defect (AVSD) is unknown in 40% cases. Conventional sequencing and arrays have identified the etiology in only a minority of nonsyndromic individuals with AVSD.

Methods: Whole-exome sequencing was performed in 81 unrelated probands with AVSD to identify potentially causal variants in a comprehensive set of 112 genes with strong biological relevance to AVSD.