Publications by authors named "Amy Lynch"

We report on a new methodology for the stereoselective synthesis of β-anomeric -glycosyl amides from unprotected carbohydrates via the reaction of generated carbohydrate oximes with acylsilanes. By variation of the acylsilane, -glycosyl amides with azide and chloride conjugation handles are prepared in excellent yield and β-selectivity from unprotected sugars.

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Neovascular age-related macular degeneration and diabetic macular edema are leading causes of vision loss evoked by retinal neovascularization and vascular leakage. The glycoprotein microfibrillar-associated protein 4 (MFAP4) is an integrin αβ ligand present in the extracellular matrix. Single-cell transcriptomics reveal MFAP4 expression in cell types in close proximity to vascular endothelial cells, including choroidal vascular mural cells, retinal astrocytes, and Müller cells.

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Article Synopsis
  • Clinicians often prefer antiplatelet therapy over direct oral anticoagulants (DOACs) for atrial fibrillation due to concerns about higher risks of intracranial bleeding despite DOACs being more effective in preventing strokes.
  • The study aimed to compare the risks of intracranial and major hemorrhage between DOAC therapy and single-agent antiplatelet therapy using data from nine randomized clinical trials with nearly 45,500 participants.
  • Results showed no significant difference in the risk of intracranial hemorrhage between the two therapies; however, the analysis indicated variability in results among different DOACs, with rivarox
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Purpose: Comprehensive geriatric assessment (CGA) is the cornerstone of high-quality care for older adults. There is no current gold standard to guide what should be included as the baseline measure for CGAs. We examined what metrics are being captured in CGA baseline assessments completed by community based integrated care teams in Ireland.

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As technology development drives the thickness of thin film depositions down into the nano regime, understanding and controlling the dewetting of thin films has become essential for many applications. The dewetting of ultra-thin Ag (9 nm) films with Ti (0.5 nm) adhesion and capping layers on glass substrates was investigated in this work.

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Background: To compare functional and health related quality of life outcomes post-transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) in patients with critical aortic stenosis (AS) across low to high-risk surgical candidates. These patient-centred factors will be compared between both groups in the short to medium term time frames and will aid in shared decision making between patients and healthcare workers.

Materials And Methods: We conducted a systematic review and meta-analysis of randomised controlled trials which compared TAVI with SAVR and reported on quality of life (QoL) and functional scores.

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Context: Burnout, a state of physical or emotional exhaustion, is a concern within athletic training, as between 17% and 40% of athletic trainers (ATs) report high levels of burnout. Adverse childhood experiences (ACEs) are linked with higher levels of burnout in other health professions.

Objective: To compare burnout with ACEs in ATs.

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Bronchopneumonia is a common respiratory disease in livestock. Mannheimia haemolytica is considered the main causative pathogen leading to lung damage in sheep, with Mycoplasma ovipneumoniae and ParaInfluenza virus type 3, combined with adverse physical and physiological stress, being predisposing factors. A balance of humoral and cellular immunity is thought to be important for protection against developing respiratory disease.

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The Adverse Childhood Experiences (ACEs) study was conducted to advance understanding of psychological trauma in early life as a possible determinant of adult health. In the past decade, there has been a movement to use the ACEs research questionnaire in a variety of clinical settings to screen individuals and assess their trauma score. But critics argue that the ACEs questionnaire was never intended to be used for individual-level screening, and even that harm can be done by using the questionnaire for this purpose.

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Cell transfection using short interfering RNAs (siRNAs) is a widely used technique to perform loss of function studies by "knocking down" genes of interest. Oftentimes, primary cells can be difficult to transfect, but here we provide a simple and robust method using cultured endothelial cells and routine transfection reagents. Knockdown studies can be used to complement overexpression studies and validate biochemical pathway analysis, as well as functional assays.

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Murine laser-induced laser choroidal neovascularization is a widely used and robust model of wet (exudative) age-related macular degeneration (wAMD). wAMD is one of the leading causes of blindness in the Western world. In brief, a focused laser beam is used to penetrate Bruch's membrane, which separates the choriocapillaris (well-vascularized choroid layer) from the pigmented layers of the retina.

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Lipidated derivatives of the natural product brartemicin show much promise as vaccine adjuvants due to their ability to signal through the Macrophage Inducible C-type Lectin (Mincle). We synthesised three lipophilic amide-linked brartemicin derivatives and compared their agonist activity to that of their ester-linked counterparts in vitro. We demonstrate that the brartemicin amide derivatives activate bone-marrow-derived macrophages (BMDMs) in a Mincle-dependent manner, as evidenced by the production of the pro-inflammatory cytokine IL-1β in wildtype but not Mincle cells.

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Many studies have investigated how trehalose glycolipid structures can be modified to improve their Macrophage inducible C-type lectin (Mincle)-mediated adjuvanticity. However, in all instances, the ester-linkage of α,ά-trehalose to the lipid of choice remained. We investigated how changing this ester-linkage to an amide influences Mincle signalling and agonist activity and demonstrated that Mincle tolerates this functional group change.

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Alternatives to donor cornea transplantation based on tissue engineering are desirable to overcome the current severe donor tissue shortage. Many natural polymers have good biological properties but poor mechanical properties and degradation resistance; while synthetic polymers have good mechanical properties but do not contain biochemical molecules normally found in the real tissue. In addition, both fiber orientation and composition play a key role in dictating cell behavior within a scaffold.

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The Notch ligand delta-like ligand 4 (Dll4), upregulated by VEGF, is a key regulator of vessel morphogenesis and function, controlling tip and stalk cell selection during sprouting angiogenesis. Inhibition of Dll4 results in hypersprouting, nonfunctional, poorly perfused vessels, suggesting a role for Dll4 in the formation of mature, reactive, functional vessels, with low permeability and able to restrict fluid and solute exchange. We tested the hypothesis that Dll4 controls transvascular fluid exchange.

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Objective: We investigated the mental health impact of participation for youth with disabilities (YWD) in the child welfare system who had experienced victimization in the previous year.

Method: Nationally representative data were obtained from the second National Survey of Child and Adolescent Well-Being. Our sample consisted of 247 YWD ages 11-17 yr.

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Effective Th1-stimulating vaccine adjuvants typically activate antigen presenting cells (APCs) through pattern recognition receptors (PRRs). Macrophage inducible C-type lectin (Mincle) is a PRR expressed on APCs and has been identified as a target for Th1-stimulating adjuvants. Herein, we report on the synthesis and adjuvanticity of rationally designed brartemicin analogues containing long-chain lipids and demonstrate that they are potent Mincle agonists that activate APCs to produce inflammatory cytokines in a Mincle-dependent fashion.

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Attention is increasingly being focussed on probiotics as potential agents to restore or improve gastrointestinal (GI) transit. Determining mechanism of action would support robust health claims. The probiotic bacterium HN019 reduces transit time, but its mechanisms of action and effects on motility patterns are poorly understood.

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Purpose: All-trans retinoic acid (RA) supplementation was investigated as a method of enhancing the differentiation of human adipose-derived stem cells (ASCs) to corneal keratocytes in vitro, in combination with a chemically defined serum-free medium.

Methods: Adipose-derived stem cells were cultured in monolayer and supplemented with 0.1, 1, or 10 μM RA for 14 days.

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In order to expand cells quickly and in high numbers for corneal tissue engineering applications corneal stromal cells, or keratocytes, are often cultured in the presence of serum. However, keratocytes become fibroblastic when exposed to serum leading to a downregulation of corneal stromal specific markers. The purpose of this current study was to determine if corneal stromal cells, made fibroblastic by serum, could display native quiescent keratocyte characteristics when cultured under serum-free conditions supplemented by different growth factors.

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Low adherence to antihypertensive medication has been hypothesized to increase visit-to-visit variability (VVV) of blood pressure (BP). We assessed the association between antihypertensive medication adherence and VVV of BP in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). VVV of BP was calculated using SD independent of mean, SD, and average real variability across study visits conducted 6 to 28 months after randomization.

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Corneal decellularization has become an increasingly popular technique for generating scaffolds for corneal regeneration. Most decellularization procedures result in tissue swelling, thus limiting their application. Here, the use of a polysaccharide, dextran, to reduce swelling and conserve the native corneal structure during decellularization was investigated.

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Background And Objectives: Increased visit-to-visit variability of BP is associated with cardiovascular disease risk. We examined the association of visit-to-visit variability of BP with renal outcomes among 21,245 participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.

Design, Setting, Participants, & Measurements: We measured mean BP and visit-to-visit variability of BP, defined as SD, across five to seven visits occurring 6-28 months after participants were randomized to chlorthalidone, amlodipine, or lisinopril.

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Cartilage defects resulting from osteoarthritis (OA) or physical injury can severely reduce the quality of life for sufferers. Current treatment options are costly and not always effective in producing stable hyaline cartilage. Here we investigated a new treatment option that could potentially repair and regenerate damaged cartilage tissue.

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