Publications by authors named "MCKNIGHT A"

Introduction: Maintaining cognitive health in later life is a global priority. Encouraging individuals to make health behaviour changes, such as regular physical activity, and providing supportive urban environments can help maintain cognitive health, thereby preventing or delaying the progress of dementia and cognitive decline. However, the mechanistic pathways by which the urban environmental exposome influences cognitive health outcomes are poorly understood.

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Background: DNA methylation differences are associated with kidney function and diabetic kidney disease (DKD), but prospective studies are scarce. Therefore, we aimed to study DNA methylation in a prospective setting in the Finnish Diabetic Nephropathy Study type 1 diabetes (T1D) cohort.

Methods: We analysed baseline blood sample-derived DNA methylation (Illumina's EPIC array) of 403 individuals with normal albumin excretion rate (early progression group) and 373 individuals with severe albuminuria (late progression group) and followed-up their DKD progression defined as decrease in eGFR to <60 mL/min/1.

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Aim: Diabetes is increasing in prevalence worldwide, with a 20% rise in prevalence predicted between 2021 and 2030, bringing an increased burden of complications, such as diabetic kidney disease (DKD). DKD is a leading cause of end-stage kidney disease, with significant impacts on patients, families and healthcare providers. DKD often goes undetected until later stages, due to asymptomatic disease, non-standard presentation or progression, and sub-optimal screening tools and/or provision.

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Article Synopsis
  • Current methods for assessing disease severity and progression in Chronic Kidney Disease (CKD) are limited, prompting a study that highlights FERM-domain containing protein 3 (FRMD3) as a key candidate for further research.
  • Using RNA sequencing, the study analyzed CKD biopsies and correlated gene expression with clinical indicators, discovering 93 genes related to CKD severity and progression, including FRMD3.
  • Further investigation into FRMD3 showed its importance in cell structure and health, with knockdown experiments indicating its role in preventing cell death and maintaining cell junction integrity.
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Telomeres are protective structures at the end of eukaryotic chromosomes that are strongly implicated in ageing and ill health. They attrition upon every cellular reproductive cycle. Evidence suggests that short telomeres trigger DNA damage responses that lead to cellular senescence.

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Article Synopsis
  • Age-related macular degeneration (AMD) is a complex eye disease influenced by both genetic factors and involves a subtype called reticular pseudodrusen (RPD), which increases the risk of severe vision loss.* -
  • A genome-wide association study compared genetic data from individuals with AMD and/or RPD to controls, finding significant associations specifically on chromosome 10, while chromosome 1 did not show this correlation in RPD cases.* -
  • The chromosome 10 region includes a long non-coding RNA related to retinal health, highlighting its potential role in retinal thickness and influencing the outer segment of photoreceptors.*
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Background: The Toronto Addis Ababa Academic Collaboration in Emergency Medicine (TAAAC-EM) is a bi-institutional partnership between the University of Toronto (UofT) and Addis Ababa University (AAU) focused on addressing the need for emergency medicine (EM) postgraduate training and care in Ethiopia. Toxicology is a key competency in EM. EM physicians are often the first and sole clinicians to identify and treat patients presenting with a wide range of intoxications.

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Purpose: Epigenetic modifications including DNA methylation (DNAm) are proposed mechanisms by which social or environmental exposures may influence health and behaviours as we age. The Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA) DNAm cohort, established in 2013, is one of several worldwide, nationally representative prospective studies of ageing with biological samples from participants who consented to multiomic analysis.

Participants: NICOLA recruited 8478 participants (8283 aged 50 years or older and 195 spouses or partners at the same address aged under 50 years).

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Introduction: Cardiovascular disease (CVD) is responsible for over 30% of mortality worldwide. CVD arises from the complex influence of molecular, clinical, social, and environmental factors. Despite the growing number of autosomal genetic variants contributing to CVD, the cause of most CVDs is still unclear.

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The most successful obesity therapeutics, glucagon-like peptide-1 receptor (GLP1R) agonists, cause aversive responses such as nausea and vomiting, effects that may contribute to their efficacy. Here, we investigated the brain circuits that link satiety to aversion, and unexpectedly discovered that the neural circuits mediating these effects are functionally separable. Systematic investigation across drug-accessible GLP1R populations revealed that only hindbrain neurons are required for the efficacy of GLP1-based obesity drugs.

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This systematic review investigated the practices that support and hinder the recovery and healing of communities and the environments within which they live, following climate-related environmental disasters. Although the literature focused on recovery is dominated by interventions aimed at the individual and their mental health, a thematic analysis of thirty-six studies established a range of practices that enhance collective recovery and healing. Four narratives were identified from the findings highlighting key practices: (1) collective and community-led recovery; (2) recognising the criticality of context, place, and identity; (3) adopting a holistic conception of well-being and Country-centred practices; and (4) decolonising and Indigenising the literature.

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Background: Chronic kidney disease (CKD) is a complex disorder that has become a high prevalence global health problem, with diabetes being its predominant pathophysiologic driver. Autosomal genetic variation only explains some of the predisposition to kidney disease. Variations in the mitochondrial genome (mtDNA) and nuclear-encoded mitochondrial genes (NEMG) are implicated in susceptibility to kidney disease and CKD progression, but they have not been thoroughly explored.

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Background And Hypothesis: Kidney grafts from donors who died of stroke and related traits have worse outcomes relative to grafts from both living donors and those who died of other causes. We hypothesise that deceased donors, particularly those who died of stroke, have elevated polygenic burden for cerebrovascular traits. We further hypothesise that this donor polygenic burden is associated with inferior graft outcomes in the recipient.

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Introduction: Electronic nose (E-nose) technology has reported excellent sensitivity and specificity in the setting of lung cancer screening. However, the performance of E-nose specifically for early-stage tumors remains unclear. Therefore, the aim of our study was to assess the diagnostic performance of E-nose technology in clinical stage I lung cancer.

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Background: Despite high rates of cardiovascular disease in Scotland, the prevalence and outcomes of patients with cardiogenic shock are unknown.

Methods: We undertook a prospective observational cohort study of consecutive patients with cardiogenic shock admitted to the intensive care unit (ICU) or coronary care unit at 13 hospitals in Scotland for a 6-month period. Denominator data from the Scottish Intensive Care Society Audit Group were used to estimate ICU prevalence; data for coronary care units were unavailable.

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Post-transplant diabetes mellitus (PTDM) is a common complication of solid organ transplantation. PTDM prevalence varies due to different diabetes definitions. Consensus guidelines for the diagnosis of PTDM have been published based on random blood glucose levels, glycated hemoglobin (HbA1c), and oral glucose tolerance test (OGTT).

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Background: Brain tumours are known to have a high mortality and morbidity rate due to their localised and frequent invasive growth. The concept that glioma resistance could originate from the dissimilarity in the vulnerability of clonogenic glial stem cells to chemotherapeutic drugs and radiation has driven the scientific community to reexamine the comprehension of glioma growth and strategies that target these cells or modify their stemness.

Methods: Based on the enrichment scores of 12 stemness signatures, we identified glioma subtypes in both tumour bulks and single cells by clustering analysis.

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Aims: This study describes a program co-created with Aboriginal communities to strengthen cultural ties with the children. Food data are reported from two knowledge systems (lenses): Western and Aboriginal relational, focused on Country, community, and kinship.

Methods: A cultural program was undertaken with primary school children of Aboriginal heritage, on Yuin nation, over 10 weeks including culturally appropriate practices (painting, bushtucker, and dance).

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Immunological determinants favouring emergence of broadly neutralising antibodies are crucial to the development of HIV-1 vaccination strategies. Here, we combined RNAseq and B cell cloning approaches to isolate a broadly neutralising antibody (bnAb) ELC07 from an individual living with untreated HIV-1. Using single particle cryogenic electron microscopy (cryo-EM), we show that the antibody recognises a conformational epitope at the gp120-gp41 interface.

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Background: Having a strong connection to culture and Country is fundamental to the health and wellbeing of Australian Aboriginal children. The aim of the research was to evaluate the feasibility of study methods and programme implementation of a co-created afterschool cultural programme, and identify areas for improvement.

Methods: Aboriginal Relational Research Methodology and mixed methods were applied to evaluate the feasibility of the implementation of the programme and study methods using a non-randomised single-group study design.

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Background: Methotrexate is the first-line treatment for immune-mediated inflammatory diseases and reduces vaccine-induced immunity. We evaluated if a 2-week interruption of methotrexate treatment immediately after COVID-19 booster vaccination improved antibody response against the S1 receptor binding domain (S1-RBD) of the SARS-CoV-2 spike protein and live SARS-CoV-2 neutralisation compared with uninterrupted treatment in patients with immune-mediated inflammatory diseases.

Method: We did a multicentre, open-label, parallel-group, randomised, superiority trial in secondary-care rheumatology and dermatology clinics in 26 hospitals in the UK.

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Article Synopsis
  • Antibiotic resistance is a big problem for global health, and fluoroquinolone resistance is rare even though the drug is often used.
  • * Research found that some bacteria can adapt to survive antibiotics by changing how they use energy, without actually becoming resistant.
  • * This study helps us understand why fluoroquinolone resistance is uncommon, showing that it comes with some disadvantages for bacteria during infections.
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Objective: Determine the incremental yield of prenatal exome sequencing (PES) over chromosome microarray (CMA) and/or karyotype for urinary tract malformations (UTMs).

Method: A prospective cohort study encompassing data from the English Genomic Medicine Service North Thames Laboratory Hub for fetuses with bilateral echogenic kidneys (BEKs) was combined with data from a systematic review. MEDLINE, EMBASE, Web of Science, MedRxiv and GreyLit were searched from 01/2010-02/2023 for studies reporting on the yield of PES over CMA or karyotype in fetuses with UTMs.

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Introduction: Only 5% of rare diseases have an approved treatment available, therefore patients often utilise complementary and integrative medicines (CIMs) to help manage their condition. Limited high-quality evidence-based studies are available which support the effectiveness of CIM, as it is difficult to show that an outcome is a direct result of the CIM intervention and not due to bias. Patients and healthcare professionals must weigh up the evidence quality, safety, efficacy, practical logistics, and financial implications of utilising CIM for rare diseases.

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Introduction: Mucosa-associated lymphoid tissue lymphoma (MALT lymphoma or MALToma) is a prevalent type of primary pulmonary lymphoma. Typically, the primary therapeutic approaches involve surgery or chemotherapy, although there have been instances of radiation therapy being employed.

Case Report: We present a case of pulmonary MALToma that exhibited progression despite rituximab therapy.

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