Publications by authors named "John O'Sullivan"

Article Synopsis
  • * A study was conducted using mass spectrometry to analyze the differences in metabolome (metabolism) and proteome (proteins) between healthy left and right ventricles, revealing significant metabolic changes.
  • * In advanced heart conditions like dilated and ischemic cardiomyopathy, the distinct metabolic pathways between the ventricles become less pronounced, but the left ventricle shows more adverse changes related to heart failure.
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There is an unmet need for a biomarker of liver fat. We identified dimethylguanidino valeric acid (DMGV) as a circulating biomarker of liver fat. Here, we assess its two isoforms-symmetric (SDGV) and asymmetric (ADGV)-as biomarkers of steatosis.

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  • Pregnancy causes significant changes in a woman’s heart and vascular system, but some women can develop a heart condition called peripartum cardiomyopathy (PPCM) during or after pregnancy which can lead to heart failure.
  • A study used mass spectrometry to compare protein and metabolite profiles from heart tissue of patients with end-stage PPCM against those with dilated cardiomyopathy (DCM) and non-failing heart donors, aiming to understand the molecular differences.
  • Findings revealed two specific proteins (SBSPON and TNS3) were downregulated in PPCM, disrupting tissue remodeling, while certain metabolites showed abnormal levels indicating altered metabolic functions; both PPCM and DCM shared some inflammatory pathways but differed significantly in thyroid
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  • Metabolic inflexibility and substrate constraints in heart failure have been studied for years, but their exact role is still debated, which challenges traditional beliefs about how the heart uses energy.
  • The rise of SGLT2i therapy as a key treatment for heart failure is prompting researchers to re-examine metabolism as an important factor in heart health and a target for new therapies.
  • Advances in technologies like metabolomics and isotopic analysis, alongside discoveries in epigenetics and microbiome interactions, are expected to deepen our understanding of heart metabolism and inform the development of innovative treatment strategies.
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Introduction: A subset of people with Parkinson's disease (PD) develop dementia faster than others. We aimed to profile PD cognitive subtypes at risk of dementia based on their rate of cognitive decline.

Method: Latent class mixed models stratified subtypes in Parkinson's Progression Markers Initiative (PPMI) (= 770) and ICICLE-PD (= 212) datasets based on their decline in the Montreal Cognitive Assessment over at least 4 years.

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The development of small-diameter vascular grafts requires testing in large animal models before advancing to clinical trials. Vascular graft interposition implantation in sheep carotid arteries (CAs) is the most widely used model, but ovine CAs are prone to severe spasm following surgical manipulation, potentially impairing graft performance assessment. There is paucity in the literature on reducing sheep CA spasm using effective vasodilator therapeutic protocols.

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Heart failure (HF) with left ventricular diastolic dysfunction is a growing global concern. This study evaluated myocardial oxidized nicotinamide adenine dinucleotide (NAD) levels in human systolic and diastolic HF and in a murine model of HF with preserved ejection fraction, exploring NAD repletion as therapy. We quantified myocardial NAD and nicotinamide phosphoribosyltransferase levels, assessing restoration with nicotinamide riboside (NR).

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  • * Participants followed either a mostly plant diet (70% plant and 30% animal) or a balanced diet (50% plant and 50% animal) for 4 weeks, with specific foods provided.
  • * Results showed that those on the pro-vegetarian diet had lower blood pressure, cholesterol, and glucose, and overall better health, suggesting that a diet with more fruits and vegetables can help older adults feel healthier!
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Recreational bathing waters are complex systems with diverse inputs from multiple anthropogenic and zoogenic sources of faecal contamination. Faecal contamination is a substantial threat to water quality and public health. Here we present a comprehensive strategy to estimate the contribution of faecal indicator bacteria (FIB) from different biological sources on two at-risk beaches in Dublin, Ireland.

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The American Society for Surgery of the Hand and British Society for Surgery of the Hand produce patient-focused information above the sixth-grade readability recommended by the American Medical Association. To promote health equity, patient-focused content should be aimed at an appropriate level of health literacy. Artificial intelligence-driven large language models may be able to assist hand surgery societies in improving the readability of the information provided to patients.

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Aims: The optimal echocardiographic predictors of cardiovascular outcome in heart failure (HF) with preserved ejection fraction (HFpEF) are unknown. We aimed to identify independent echocardiographic predictors of cardiovascular outcome in patients with HFpEF.

Methods And Results: Systematic literature search of three electronic databases was conducted from date of inception until November 2022.

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The objective of this study was to comprehensively characterise the resistome, the collective set of antimicrobial resistance genes in a given environment, of two rivers, from their source to discharge into the sea, as these flow through areas of different land use. Our findings reveal significant differences in the riverine resistome composition in areas of different land uses, with increased abundance and diversity of AMR in downstream agricultural and urban locations, with the resistome in urban areas more similar to the resistome in wastewater. The changes in resistome were accompanied by changes in microbial communities, with a reduction in microbial diversity in downstream agricultural and urban affected areas, driven mostly by increased relative abundance in the phyla, Bacteroidetes and Proteobacteria.

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Article Synopsis
  • The study compared cardiac metabolite and lipid usage between healthy individuals and those with heart failure with preserved ejection fraction (HFpEF).
  • Findings indicated that hearts with HFpEF use fatty acids less efficiently and that hemodynamic factors, like pulmonary pressures, impact lipid extraction.
  • Additionally, there were notable differences in energy substrate use based on sex, with variations observed between female and male hearts.
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Aim: Frontal and posterior-cortical cognitive subtypes in Parkinson's disease (PD) present with executive/attention and memory/visuospatial deficits, respectively. As the posterior-cortical subtype is predicted to progress rapidly toward dementia, the present study aimed to explore biological markers of this group using resting-state functional magnetic resonance imaging (rs-fMRI).

Methods: K-means cluster analysis delineated subtypes (cognitively intact, frontal, posterior-cortical, and globally impaired) among 85 people with PD.

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Objectives: In people with Parkinson's disease (PwPD), non-motor symptoms such as anxiety are common and have negative impacts on their quality of life. There are currently few interventions that address anxiety in PwPD, and access to diagnosis and treatment is often limited for those living in rural areas. The aim of this study was to evaluate the feasibility and acceptability of a telehealth videoconferencing CBT intervention for anxiety in PwPD.

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Background: Heart failure with preserved ejection fraction (HFpEF) is a common but poorly understood form of heart failure, characterized by impaired diastolic function. It is highly heterogeneous with multiple comorbidities, including obesity and diabetes, making human studies difficult.

Methods: Metabolomic analyses in a mouse model of HFpEF showed that levels of indole-3-propionic acid (IPA), a metabolite produced by gut bacteria from tryptophan, were reduced in the plasma and heart tissue of HFpEF mice as compared with controls.

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Background: Physical activity levels are low in people with Parkinson's disease (PD) and have proved difficult to increase with exercise programs alone. Intervention approaches that address both the capacity to engage in physical activity and self-management strategies to change and maintain exercise behaviours are needed to address this intractable issue.

Methods: This will be an assessor-blinded, randomized controlled trial performed in Brisbane, Australia.

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We initiated a tagging program in 2004 to determine the large-scale and long-term movement patterns of three species of Mobulid Ray (Mobula mobular, M. munkiana, M. thurstoni).

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We have recently determined dimethylguanidino valeric acid (DMGV) to be a novel biomarker of liver injury in non-alcoholic fatty liver disease (NAFLD) and an independent predictor of incident diabetes over a decade in advance. DMGV consists of two stereo-isomers, asymmetric dimethylguanidino valeric acid (ADGV) and symmetric dimethylguanidino valeric acid (SDGV). Here we report, for the first time, the upper limits of normal of both isomers in humans at the accepted 5.

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Background: Modern oncological therapies together with chemotherapy and radiotherapy have broadened the agents that can cause cardiac sequelae, which can manifest for pediatric oncology patients while on active treatment. Recommendations for high-risk patients who should be monitored in a pediatric cardio-oncology clinic have previously been developed by expert Delphi consensus by our group. In 2022 we opened our first multidisciplinary pediatric cardio-oncology clinic adhering to these recommendations in surveillance and management.

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Article Synopsis
  • - The study aims to evaluate the use of the antiepileptic drug levetiracetam to improve memory deficits in patients with amnestic mild cognitive impairment (aMCI) related to Parkinson's disease (PD) by targeting hyperactivation in specific brain areas known to affect episodic memory.
  • - Twenty-eight participants with PD-aMCI will participate in a 12-week trial comparing levetiracetam to a placebo, alongside neuroimaging to assess changes in brain activity related to memory tasks.
  • - This research is groundbreaking as it seeks to link improvement in memory function with the normalization of hippocampal hyperactivity, potentially offering a new therapeutic strategy to mitigate dementia risks in PD patients.
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Pareidolias, or the misperception of ambiguous stimuli as meaningful objects, are complex visual illusions thought to be phenomenologically similar to Visual Hallucination (VH). VH are a major predictor of dementia in Parkinson's Disease (PD) and are included as a core clinical feature in Dementia with Lewy Bodies (DLB). A newly developed Noise Pareidolia Test (NPT) was proposed as a possible surrogate marker for VH in DLB patients as increased pareidolic responses correlated with informant-corroborated accounts of VH.

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The use of probiotics, prebiotics and synbiotics in poultry diets beneficially stimulates the gut microbiome thus promoting the health and welfare of the animals. In this study, we analyzed 7 poultry probiotics ( - B1 and B4, - B3, - B2, - B5, - B6, - B7) and 12 prebiotics, differing in chemical composition and source of origin (fungi, algae, animal, etc.).

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Article Synopsis
  • Reducing standard modifiable cardiovascular risk factors (SMuRFs) is essential for addressing coronary artery disease (CAD), but some patients develop CAD without any SMuRFs.
  • Patients without SMuRFs who have a heart attack tend to have higher early mortality rates compared to those with at least one SMuRF.
  • An international team has created a clinical pathway for managing SMuRFless CAD patients, focusing on confirming their condition, ensuring proper secondary prevention, and identifying other risk factors to improve their healthcare outcomes.
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An important pathogenicity factor of SARS-CoV-2 and related coronaviruses is Non-structural protein 1 (Nsp1), which suppresses host gene expression and stunts antiviral signaling. SARS-CoV-2 Nsp1 binds the ribosome to inhibit translation through mRNA displacement and induces degradation of host mRNAs. Here we show that Nsp1-dependent host shutoff is conserved in diverse coronaviruses, but only Nsp1 from β-Coronaviruses (β-CoV) inhibits translation through ribosome binding.

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