Publications by authors named "John Riley"

Article Synopsis
  • Severe asthma (SA) has various clinical phenotypes linked to a diverse airway microbiome, and a study focused on identifying phenotypes with low microbial diversity.
  • Metagenomic sequencing of sputum samples from SA participants identified 51 out of 97 samples with relative dominant species (RDS), with Haemophilus influenzae being the most prevalent.
  • The research found that a specific cluster of RDSs associated with Haemophilus influenzae had more severe disease characteristics and indicated a host response linked to neutrophilic inflammation, suggesting potential for antibiotic treatment in this group.
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Monogenic blood diseases are among the most common genetic disorders worldwide. These diseases result in significant pediatric and adult morbidity, and some can result in death prior to birth. Novel ex vivo hematopoietic stem cell (HSC) gene editing therapies hold tremendous promise to alter the therapeutic landscape but are not without potential limitations.

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Article Synopsis
  • In utero gene editing (IUGE) is a new way to fix inherited diseases in babies before they are born.
  • The study found that if a mother has certain antibodies against AAV (a virus used in gene editing), it can block the editing in the baby, especially when the baby is older.
  • However, during earlier stages of pregnancy, this blocking effect is weaker, which could help doctors plan better for treatments in the future.
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In utero hematopoietic cell transplantation is an experimental nonmyeloablative therapy with potential applications in hematologic disorders, including sickle cell disease (SCD). Its clinical utility has been limited due to the early acquisition of T-cell immunity beginning at ∼14 weeks gestation, posing significant technical challenges and excluding treatment fetuses evaluated after the first trimester. Using murine neonatal transplantation at 20 days postcoitum (DPC) as a model for late-gestation transplantation (LGT) in humans, we investigated whether immune modulation with anti-CD3 monoclonal antibody (mAb) could achieve donor-specific tolerance and sustained allogeneic engraftment comparable with that of the early-gestation fetal recipient at 14 DPC.

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, a Brassicaceae family crop, is used for fodder, human food, and biofuels. Its relatively high resistance to abiotic and biotic stresses, as well as being a climate-resilient oilseed crop, has contributed to its popularity. Camelina's seed yield and oil contents have been improved using various technologies like RNAi and CRISPR/Cas9 genome editing.

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Protein translational control is critical for ensuring that the fetus develops correctly and that necessary organs and tissues are formed and functional. We developed an in utero method to quantify tissue-specific protein dynamics by monitoring amino acid incorporation into the proteome after pulse injection. Fetuses of pregnant mice were injected with isotopically labeled lysine and arginine via the vitelline vein at various embyonic days, and organs and tissues were harvested.

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Background: There is increasing evidence that co-design can lead to more engaging, acceptable, relevant, feasible, and even effective interventions. However, no guidance is provided on the specific designs and associated methods or methodologies involved in the process. We propose the development of the Preferred Components for Co-design in Research (PRECISE) guideline to enhance the consistency, transparency, and quality of reporting co-design studies used to develop complex health interventions.

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Rationale: Patients with severe asthma are dependent upon treatment with high doses of inhaled corticosteroids (ICS) and often also oral corticosteroids (OCS). The extent of endogenous androgenic anabolic steroid (EAAS) suppression in asthma has not previously been described in detail. The objective of the present study was to measure urinary concentrations of EAAS in relation to exogenous corticosteroid exposure.

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Probing the transient microstructure of soft matter far from equilibrium is an ongoing challenge to understanding material processing. In this work, we investigate inverse worm-like micelles undergoing large amplitude oscillatory shear using time-resolved dielectric spectroscopy. By controlling the Weissenburg number, we compare the non-linear microstructure response of branched and unbranched worm-like micelles and isolate distinct elastic effects that manifest near flow reversal.

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Introduction: VACTERL is defined as 3 or more of the following congenital defects: vertebral, anorectal, cardiac, tracheoesophageal (TE), renal, and limb. The purpose of this study was to create an easy-to-use assessment tool to help providers counsel expecting families regarding the likelihood of additional anomalies and postnatal outcomes.

Methods: Employing the Kids' Inpatient Database from 2003-2016, neonates (<29 days old) with VACTERL were identified using ICD-9-CM and ICD-10-CM codes.

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Protein translational control is highly regulated step in the gene expression program during mammalian development that is critical for ensuring that the fetus develops correctly and that all of the necessary organs and tissues are formed and functional. Defects in protein expression during fetal development can lead to severe developmental abnormalities or premature death. Currently, quantitative techniques to monitor protein synthesis rates in a developing fetus () are limited.

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Background: Because of altered airway microbiome in asthma, we analysed the bacterial species in sputum of patients with severe asthma.

Methods: Whole genome sequencing was performed on induced sputum from non-smoking (SAn) and current or ex-smoker (SAs/ex) severe asthma patients, mild/moderate asthma (MMA) and healthy controls (HC). Data were analysed by asthma severity, inflammatory status and transcriptome-associated clusters (TACs).

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Article Synopsis
  • The Canadian Institutes of Health Research launched the Strategy for Patient-Oriented Research (SPOR) in 2011 to engage patients in research and improve health outcomes.
  • The Ontario SPOR SUPPORT Unit implemented capacity-building initiatives from 2014 to 2020, training various stakeholders in patient-oriented research through workshops, online curricula, and resource development.
  • The initiatives have reached a wide audience, evidenced by high access rates to resources and the establishment of core competencies for meaningful patient research partnerships across Canada.
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Introduction: Industry reports and anecdotal evidence indicate that the death loss rate in cattle feedlots has increased over time. Such increases in death loss rates impact feedlot cost and thus profitability.

Objectives: The primary objective of this study is to examine whether feedlot death loss rates in cattle have changed over time, to analyze the nature of any identified structural change, and to identify possible catalysts for that change.

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In utero hematopoietic cell transplantation (IUHCT) is an experimental treatment for congenital hemoglobinopathies, including Sickle cell disease and thalassemias. One of the principal advantages of IUHCT is the predisposition of the developing fetus toward immunologic tolerance. This allows for engraftment across immune barriers without immunosuppression and, potentially, decreased susceptibility to graft-versus-host disease (GVHD).

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Background: Interleukin (IL)-33 is an upstream regulator of type 2 (T2) eosinophilic inflammation and has been proposed as a key driver of some asthma phenotypes.

Objective: To derive gene signatures from in vitro studies of IL-33-stimulated cells and use these to determine IL-33-associated enrichment patterns in asthma.

Methods: Signatures downstream of IL-33 stimulation were derived from our in vitro study of human mast cells and from public datasets of in vitro stimulated human basophils, type 2 innate lymphoid cells (ILC2), regulatory T cells (Treg) and endothelial cells.

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Introduction: Asthma is a heterogeneous disease with poorly defined phenotypes. Patients with severe asthma often receive multiple treatments including oral corticosteroids (OCS). Treatment may modify the observed metabotype, rendering it challenging to investigate underlying disease mechanisms.

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Rationale: Asthma phenotyping requires novel biomarker discovery.

Objectives: To identify plasma biomarkers associated with asthma phenotypes by application of a new proteomic panel to samples from two well-characterised cohorts of severe (SA) and mild-to-moderate (MMA) asthmatics, COPD subjects and healthy controls (HCs).

Methods: An antibody-based array targeting 177 proteins predominantly involved in pathways relevant to inflammation, lipid metabolism, signal transduction and extracellular matrix was applied to plasma from 525 asthmatics and HCs in the U-BIOPRED cohort, and 142 subjects with asthma and COPD from the validation cohort BIOAIR.

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The rheology of wormlike micelle (WLM) solutions is tunable by engineering the micellar structure and topology. While much is known about how microscopic properties influence the rheological characteristics, questions remain regarding the quantification of fast relaxation processes, including Rouse and rotational modes. These fast processes are challenging to access using mechanical spectroscopy as bending modes dominate high-frequency mechanical measurements.

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