Publications by authors named "Kavanagh T"

Objectives: Pediatric status epilepticus (SE) carries a high risk of morbidity and mortality and can result in neurologic injury. Establishing seizure activity on conventional EEG (cEEG) is essential but can delay treatment of seizures due to technician limitations. Rapid response EEG (rrEEG) device Ceribell and its Brain Stethoscope function can be used and interpreted rapidly by bedside providers with minimal training.

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SMOC1 has emerged as one of the most significant and consistent new biomarkers of early Alzheimer's disease (AD). Recent studies show that SMOC1 is one of the earliest changing proteins in AD, with levels in the cerebrospinal fluid increasing many years before symptom onset. Despite this clear association with disease, little is known about the role of SMOC1 in AD or its function in the brain.

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SMOC1 has emerged as one of the most significant and consistent new biomarkers of early Alzheimer's disease (AD). Recent studies show that SMOC1 is one of the earliest changing proteins in AD, with levels in the cerebrospinal fluid increasing many years before symptom onset. Despite this clear association with disease, little is known about the role of SMOC1 in AD or its function in the brain.

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Article Synopsis
  • Tau is a protein that interacts with special helpers called hnRNPs, which help manage RNA in our cells.
  • Researchers studied how these hnRNP proteins behave in different brain diseases like Alzheimer's, but found they didn't stick together with the bad tau proteins as expected.
  • They discovered that the hnRNP proteins did get mixed up and moved to the wrong places in the cells during these diseases, which might affect how RNA works in the brain.
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Cerebral amyloid angiopathy (CAA) is characterized by amyloid beta (Aβ) deposition in cerebrovasculature. It is prevalent with aging and Alzheimer's disease (AD), associated with intracerebral hemorrhage, and contributes to cognitive deficits. To better understand molecular mechanisms, CAA(+) and CAA(-) vessels were microdissected from paraffin-embedded autopsy temporal cortex of age-matched Control (n = 10), mild cognitive impairment (MCI; n = 4), and sporadic AD (n = 6) cases, followed by label-free quantitative mass spectrometry.

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Matrix remodeling plays central roles in a range of physiological and pathological processes and is driven predominantly by the activity of matrix metalloproteinases (MMPs), which degrade extracellular matrix (ECM) proteins. Our understanding of how MMPs regulate cell and tissue dynamics is often incomplete as approaches are lacking and many strategies cannot provide high-resolution, quantitative measures of enzyme activity within tissue-like 3D microenvironments. Here, we incorporate a Förster resonance energy transfer (FRET) sensor of MMP activity into fully synthetic hydrogels that mimic many properties of the native ECM.

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Context.—: Mutant KRAS is the main oncogenic driver in pancreatic ductal adenocarcinomas (PDACs). However, the clinical and phenotypic implications of harboring different mutant KRAS alleles remain poorly understood.

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The prevalence of epilepsy is increased among Alzheimer's Disease (AD) patients and cognitive impairment is common among people with epilepsy. Epilepsy and AD are linked but the shared pathophysiological changes remain poorly defined. We aim to identify protein differences associated with epilepsy and AD using published proteomics datasets.

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Proteomic studies of human Alzheimer's disease brain tissue have potential to identify protein changes that drive disease, and to identify new drug targets. Here, we analyse 38 published Alzheimer's disease proteomic studies, generating a map of protein changes in human brain tissue across thirteen brain regions, three disease stages (preclinical Alzheimer's disease, mild cognitive impairment, advanced Alzheimer's disease), and proteins enriched in amyloid plaques, neurofibrillary tangles, and cerebral amyloid angiopathy. Our dataset is compiled into a searchable database (NeuroPro).

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•Primary retroperitoneal mucinous tumors (PRMTs) are a rare group of cystic neoplasms consisting of three subtypes.•PRMTs are histologically similar to ovarian mucinous tumors but lack true ovarian tissue.•PRMTs should be considered in the differential diagnosis when encountering retroperitoneal cystic lesions.

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Pathological tau aggregation is a primary neuropathological feature of many neurodegenerative diseases. Intriguingly, despite the common presence of tau aggregates in these diseases the affected brain regions, clinical symptoms, and morphology, conformation, and isoform ratio present in tau aggregates varies widely. The tau-mediated disease mechanisms that drive neurodegenerative disease are still unknown.

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Background: The coronavirus disease 2019 (COVID-19) pandemic has spread globally leading to over 3,700,000 deaths. As COVID-19 cases stabilized, the re-opening of endoscopy centers potentially exposed patients and healthcare workers to viral infection. This study aims to determine risk of COVID-19 exposure among patients undergoing outpatient endoscopies in a tertiary care setting during the COVID-19 pandemic.

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Background: Euglycemic diabetic ketoacidosis is a metabolic condition characterized by relative euglycemia, ketonemia, and metabolic acidosis that occurs through mechanisms resembling starvation. Pancreaticoduodenectomy is a complex abdominal operation that subjects patients to a prolonged fasting and an inflammatory state. This study examined the incidence of euglycemic diabetic ketoacidosis and potential opportunities for early diagnosis and management in patients undergoing pancreaticoduodenectomy.

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Phthalate exposure is widespread, and studies suggest an adverse relationship with asthma morbidity, including some support for oxidative stress as an underlying pathophysiological mechanism. Urinary phthalate metabolites have been associated with biomarkers of oxidative stress, but data are few in children diagnosed with asthma. We used participant data from the Home Air in Agriculture Pediatric Intervention Trial (HAPI) to examine longitudinal relationships between phthalates and oxidative stress in a cohort of Latino children with asthma residing in an agricultural community.

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Phthalates are a class of widely used synthetic chemicals found in commonly used materials and products. Epidemiological studies suggest phthalate exposure is associated with asthma outcomes, though most studies have not investigated phthalates as triggers of exacerbations in children diagnosed with asthma. This study used data from the Home Air in Agriculture Pediatric Intervention Trial (HAPI) to examine relationships between phthalate exposure and outcomes related to childhood asthma exacerbation.

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Background: The reason why Black and South Asian healthcare workers are at a higher risk for SARS-CoV-2 infection remain unclear. We aimed to quantify the risk for SARS-CoV-2 infection among healthcare staff who belong to the ethnic minority and elucidate pathways of infection.

Methods: A one-year follow-up retrospective cohort study has been conducted among National Health Service employees who were working at 123 facilities in Lincolnshire, UK.

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Amyloid plaques contain many proteins in addition to beta amyloid (Aβ). Previous studies examining plaque-associated proteins have shown these additional proteins are important; they provide insight into the factors that drive amyloid plaque development and are potential biomarkers or therapeutic targets for Alzheimer's disease (AD). The aim of this study was to comprehensively identify proteins that are enriched in amyloid plaques using unbiased proteomics in two subtypes of early onset AD: sporadic early onset AD (EOAD) and Down Syndrome (DS) with AD.

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Antioxidant signaling/communication is among the most important cellular defense and survival pathways, and the importance of redox signaling and homeostasis in aging has been well-documented. Intracellular levels of glutathione (GSH), a very important endogenous antioxidant, both govern and are governed by the Nrf2 pathway through expression of genes involved in its biosynthesis, including the subunits of the rate-limiting enzyme (glutamate cysteine ligase, GCL) in GSH production, GCLC and GCLM. Mice homozygous null for the Gclm gene are severely deficient in GSH compared to wild-type controls, expressing approximately 10% of normal GSH levels.

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Background: The NLST reported a significant 20% reduction in lung cancer mortality with three annual low-dose CT (LDCT) screens and the Dutch-Belgian NELSON trial indicates a similar reduction. We present the results of the UKLS trial.

Methods: From October 2011 to February 2013, we randomly allocated 4 055 participants to either a single invitation to screening with LDCT or to no screening (usual care).

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Aims: To investigate the experiences of parents caring for young children with type 1 diabetes type 1 diabetes using a do-it-yourself continuous glucose monitor (DIYrtCGM) in a supported setting.

Methods: Exit interviews were conducted with parents from 11 families at the end of the MiaoMiao study: a randomised cross-over trial focusing on parental fear of hypoglycaemia. Technical support was provided to participants while using DIYrtCGM during the trial.

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It has been demonstrated that elamipretide (SS-31) rescues age-related functional deficits in the heart but the full set of mechanisms behind this have yet to be determined. We investigated the hypothesis that elamipretide influences post-translational modifications to heart proteins. The S-glutathionylation and phosphorylation proteomes of mouse hearts were analyzed using shotgun proteomics to assess the effects of aging on these post-translational modifications and the ability of the mitochondria-targeted drug elamipretide to reverse age-related changes.

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Recent evidence suggests that complex diseases can result from early life exposure to environmental toxicants. Polybrominated diphenyl ethers (PBDEs), and polychlorinated biphenyls (PCBs) are persistent organic pollutants (POPs) and remain a continuing risk to human health despite being banned from production. Developmental BPA exposure mediated-adult onset of liver cancer via epigenetic reprogramming mechanisms has been identified.

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Non-human animals serve as sentinels for numerous issues affecting humans, including exposure to toxic heavy metals like lead. Lead plays a role in perpetuating cycles of poverty in low-income communities due to the inequitable distributions of indoor health risks from lower-quality housing and outdoor health risks from industry and polluters, compounded by inequitable distributions of heath care and education. In this pilot study, we explore the potential for studying lead in low-income populations by partnering with nonprofit veterinary outreach programs.

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The Adverse Outcome Pathway (AOP) framework is serving as a basis to integrate new data streams in order to enhance the power of predictive toxicology. AOP development for engineered nanomaterials (ENM), including silver nanoparticles (AgNP), is currently lagging behind other chemicals of regulatory interest due to our limited understanding of the mechanism by which underlying genetics or diseases directly modify host response to AgNP exposures. This also highlights the importance of considering the Aggregate Exposure Pathway (AEP) framework, which precedes the AOP framework and outlines source to target site exposure.

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