131 Works

Novel Antibiotic-Free Scaffold for the Treatment of Infection and Regeneration of Bone

Emily J. Ryan
The bone infection osteomyelitis (typically caused by Staphylococcus aureus) usually requires a multistep procedure – long term administration of high-dose systemic antibiotics combined with surgical debridement and bone grafting. However, the disease remains notoriously difficult-to-treat due to the poor penetration of systemic antibiotics into the necrotic bone, antibiotic resistance, and the steep decline in antibiotic discovery. Therefore, osteomyelitis treatment has a dual challenge: ensuring an effective and non-toxic dose of antimicrobial, while ensuring bone regeneration...

Progressive Resistance Training in a Post-Acute, Older, Inpatient Population

Sinéad Coleman
Introduction Many older adults are at risk of functional decline following an acute hospital admission. Many of these older adults are pre-sarcopenic or sarcopenic and are extremely vulnerable to a further deterioration of function and dependence in Activities of Daily Living ability. Progressive Resistance Training (PRT) is an intervention that involves exercising a muscle against a load that is progressively increased as the muscle strengthens. PRT has been shown to successfully target both functional decline...

The role of viral regulatory protein ICP0 in herpes simplex type 1 keratitis

David Shahnazaryan
Herpes simplex keratitis (HSK) is the commonest cause of infectious blindness in the developed world. It is caused by herpes simplex virus type 1 (HSV‐1) and is characterised by recurrent episodes of infection and immune‐mediated corneal inflammation that lead to significant loss of vision. Following transmission of HSV‐1 the virus is initially suspended in the tear film, where it encounters a multi‐pronged defence comprising enzymes, complement, immunoglobulins and crucially, a range of anti‐viral and pro‐inflammatory...

Reducing Hospital Attendances for New Vascular Referrals While Improving Risk Factor Investigation

Jason Ridge
Vascular disease is strongly associated with advancing age. As Ireland’s population gets older and the prevalence of other risk factors such as diabetes increase so too does the incidence of vascular disease. In an already heavily burdened system it is important that all processes operate efficiently without sacrificing quality of care provided to the patient. A key metric of quality care provision is patient satisfaction. Something which is negatively impacted by repeated hospital attendances. This...

Secondary risk factor management 5-years post ischaemic stroke - The ASPIRE-S2 study

Eva Gaynor
Numerous guidelines have been published outlining evidence-based best
practice in secondary stroke prevention, including optimal target control of risk
factors. Despite these guidelines failure to achieve these recommendations in
clinical practice is common. This study, ASPIRE-S2 is a 5-year follow-up study
of the ASPIRE-S Study (Action on Secondary Prevention Interventions and
Rehabilitation in Stroke). The primary aim of this study was to prospectively
assess secondary prevention profiles of Irish ischaemic stroke patients at 5-
years and compare them to that measured at...

Improving the Patient Journey for Hip Fracture Patients from Arrival in the Emergency Department to Admission to the Orthopaedic Ward

Mary Jones
This Quality Improvement (QI) Project focuses on the admission pathway of hip fracture patients in a large acute hospital in Dublin. Hip fractures are the most common fragility fracture in the over 50’s in Ireland, accounting for 36.5% of orthopaedic admissions and 46.7% of orthopaedic bed days (Kelly et al 2018). It is a common injury but its effects on patients and carers is often underestimated by clinical staff (Saletti-Cuesta et al 2018)The National Office...

Development of an injectable nanomedicine-loaded hydrogel for sustained delivery of angiogenic growth factors to the ischaemic myocardium

Joanne O'Dwyer
Myocardial ischaemia, primarily occurring during and after a myocardial infarction (MI), results in cardiomyocyte death, tissue damage and eventually heart failure. A previous clinical trial identified that delivery of the angiogenic growth factor Vascular Endothelial Growth Factor (VEGF) could improve patient symptoms following MI. However, the clinical efficacy of the delivered growth factors (GFs) is hampered by their rapid in vivo clearance and degradation. Nanoparticle-based drug delivery systems that facilitate sustained growth factor delivery offer...

Development of an injectable nanomedicine-loaded hydrogel for sustained delivery of angiogenic growth factors to the ischaemic myocardium

Joanne O'Dwyer
Myocardial ischaemia, primarily occurring during and after a myocardial infarction (MI), results in cardiomyocyte death, tissue damage and eventually heart failure. A previous clinical trial identified that delivery of the angiogenic growth factor Vascular Endothelial Growth Factor (VEGF) could improve patient symptoms following MI. However, the clinical efficacy of the delivered growth factors (GFs) is hampered by their rapid in vivo clearance and degradation. Nanoparticle-based drug delivery systems that facilitate sustained growth factor delivery offer...

Pressure ulcer risk assessment: risk factors and risk screening in older persons – a validation study


Background: Mobility is acknowledged in the literature as the highest predictorof pressure ulcer development, however most of clinical studies assess mobilitysubjectively. The few studies that have analysed mobility objectively usingtechnology have the limitation of not measuring small postural changes, whichare important for pressure relief. A more comprehensive analysis of mobility,including all types of movement is needed to better understand mobility andpressure ulcer development, and to further correlate it with other risk factors.Therefore, a quantitative, prospective,...

Pressure ulcer risk assessment: risk factors and risk screening in older persons – a validation study


Background: Mobility is acknowledged in the literature as the highest predictorof pressure ulcer development, however most of clinical studies assess mobilitysubjectively. The few studies that have analysed mobility objectively usingtechnology have the limitation of not measuring small postural changes, whichare important for pressure relief. A more comprehensive analysis of mobility,including all types of movement is needed to better understand mobility andpressure ulcer development, and to further correlate it with other risk factors.Therefore, a quantitative, prospective,...

Characterisation of the effect of genetic deletion of MicroRNA-22 on brain structure and functional outcomes in experimental epilepsy

Epilepsy is a serious chronic neurological disease that affects over 65 millionpeople worldwide. Temporal lobe epilepsy is the most common form of epilepsy inadults and patients are often refractory to available pharmacotherapy.Unfortunately, antiepileptic drugs only treat the symptoms and do not exertdisease-modifying effects in patients. It is crucial to develop new pharmacologicalapproaches to aid patients with drug-resistant epilepsy as well as the developmentof pharmacotherapy with disease-modifying capability. The pathomechanismsinvolved in the development and maintenance of...

Characterisation of the effect of genetic deletion of MicroRNA-22 on brain structure and functional outcomes in experimental epilepsy

Epilepsy is a serious chronic neurological disease that affects over 65 millionpeople worldwide. Temporal lobe epilepsy is the most common form of epilepsy inadults and patients are often refractory to available pharmacotherapy.Unfortunately, antiepileptic drugs only treat the symptoms and do not exertdisease-modifying effects in patients. It is crucial to develop new pharmacologicalapproaches to aid patients with drug-resistant epilepsy as well as the developmentof pharmacotherapy with disease-modifying capability. The pathomechanismsinvolved in the development and maintenance of...

Design and Development of Multi-Targeted Metallodrugs as Potential Chemotherapeutic Agents

Reece G. Kenny
Cancer remains a major global health burden despite significant advances in treatmentregimens. Current drug treatments, including those involving platinum drugs, havedrawbacks including dose limiting toxic side effects and either acquired or intrinsicdrug resistance. The development of safer and more effective drug treatments remainsa major research focus. The platinum drugs in clinical use primarily target DNA.Our Group previously developed novel multi-targeted platinum(II) complexes capableof not only binding cancer cell DNA but also possessing the ability to...

Cognitive impairment and medication adherence in stroke

Daniela Rohde
Aim The overarching aim of this thesis was to explore the bidirectional association between adherence to secondary prevention medications and cognitive impairment in stroke survivors. A secondary aim was to provide an updated account of the longer-term outcomes of cognitive impairment post-stroke. Methods and results Five interrelated studies were conducted to address these aims. Study 1 explored the association between cognitive impairment and cardiovascular medication use in an Irish sample of the general population aged...

Effects of Alpha-1 Antitrypsin on the Neutrophil Plasma Membrane Proteome

Thomas McEnery
Alpha-1 antitrypsin (AAT) deficiency (AATD) results in early onset emphysema and liver disease and represents a common indication for lung transplant. Patients homozygous for the mutant Z allele (Pi*ZZ) are the most commonly affected by AATD-related disease. Treatment with weekly infusion of pooled human AAT has been shown to slow the progression of emphysema in these individuals. AAT is an important anti-protease and the primary mechanism for lung disease in AATD is via unopposed action...

Effects of Alpha-1 Antitrypsin on the Neutrophil Plasma Membrane Proteome

Thomas McEnery
Alpha-1 antitrypsin (AAT) deficiency (AATD) results in early onset emphysema and liver disease and represents a common indication for lung transplant. Patients homozygous for the mutant Z allele (Pi*ZZ) are the most commonly affected by AATD-related disease. Treatment with weekly infusion of pooled human AAT has been shown to slow the progression of emphysema in these individuals. AAT is an important anti-protease and the primary mechanism for lung disease in AATD is via unopposed action...

The Genetic Structure and Landscape of Ireland Reveals Footprints of History

Edmund Gilbert
Ireland has a fascinating history of ancient kingdoms and more modern migrations. Furthermore, Ireland’s island location at the north-western edge of Europe makes it conducive to genetic homogeneity and isolation. The impact of historical migrations on the island is largely unknown, as is the extent of genetic structure in Ireland, despite successful efforts to characterise such genetic ancestry and structure with uniparental data, and efforts within the neighbouring British Isles.The description of the impact of...

Responsive polypeptide containing block copolymers and polymer particles

Elena Bobbi
The synthesis and characterisation of novel stimuli-responsive polymers designed for biomedical applications is described. The first system is temperature-sensitive and is foreseen as useful for the study of the influence of particle shape on cellular uptake while the second one for the redox-sensitive delivery of drugs. Chapter 1 contains a background on the field of synthetic polymers for biomedical applications and on the polymerisation techniques applied by researchers and particularly in this work, namely RAFT...

Molecular mechanisms of biofluid microRNA transfer in human and experimental epilepsy

Elizabeth Brindley
Epilepsy is a common neurological disease characterised by recurring seizures. Diagnosing epilepsy is both difficult and expensive. A molecular biomarker to aid with diagnosis would be a major advance in the field. Plasma microRNAs (miRNAs) could provide a potential solution as a molecular biomarker. MiRNAs are small non-coding RNAs that regulate protein expression. MiRNAs are enriched in the brain and are also found in biofluids; typically bound to the Ago2 protein and encapsulated in exosomes....

Enantiospecific preparation of alkyl phenyl chlorides, bromides and acetates via sulfuranes

Daniele Canestrari
Chapter 1 This chapter offers an extensive introduction about alkyl halides, an important class of intermediates in organic chemistry and biologically active compounds in nature and drug discovery. In particular, we have reviewed their physical and chemical properties, their methods of synthesis, highlighting the stereoselective procedures of their preparation and the relevant limitations. Finally, a brief overview about the organocatalytic reactions involved in the stereospecific carbon-sulfur bond formation was discussed in order to present the...

Enantiospecific preparation of alkyl phenyl chlorides, bromides and acetates via sulfuranes

Daniele Canestrari
Chapter 1 This chapter offers an extensive introduction about alkyl halides, an important class of intermediates in organic chemistry and biologically active compounds in nature and drug discovery. In particular, we have reviewed their physical and chemical properties, their methods of synthesis, highlighting the stereoselective procedures of their preparation and the relevant limitations. Finally, a brief overview about the organocatalytic reactions involved in the stereospecific carbon-sulfur bond formation was discussed in order to present the...

Bone Health in Psychotic Disorders, and Risk Factors for Decreased Bone Health in Established and Early Psychosis

John Lally
Both schizophrenia and osteoporosis are prevalent and disabling disorders. Risk factors for osteoporosis are highly prevalent in people with psychotic disorders. It remains unclear to date as to what are the main drivers of reduced bone mineral density (BMD) in schizophrenia. In this PhD I reviewed risk factors associated with reduced bone mineral density and osteoporosis in schizophrenia. In cross sectional and longitudinal studies in first episode psychosis (FEP) and established psychosis cohorts, I investigated...

Material development and characterisation of a functionalised biomaterial to support pancreatic islet viability.

Liam McDonough
Diabetes mellitus is a chronic disease which affects over 425 million people worldwide (2017), a number which is expected to rise to 629 million people by 2045. Diabetes mellitus occurs when the pancreas does not produce enough insulin to meet the demands of the body, due to the malfunction or immune-mediated destruction of the insulin producing β-cells. The bio-artificial pancreas approach aims to return endogenous insulin production to the patient, by delivering donor pancreatic islets...

Identifying New Drug Targets to Treat Breast Cancer Brain Metastasis

Siobhan Purcell
Breast cancer brain metastasis (BrM) is indicative of poor prognosis, with a short median survival time and limited disease management strategies. Current treatment options are restricted to surgical resection, radiation therapy and limited targeted therapies. Therefore, there is an urgent need to uncover alterations responsible for BrM and to define novel effective therapeutic targets. RNA-sequencing (RNA-Seq) was performed to analyse gene expression differences between patient-matched breast tumours and their associated resected BrM. Importantly, common transcriptional...

Aldosterone-Mineralocorticoid Receptor: Cell Biology to Translational Medicine

Brian Harvey
This book is an open access dissemination of the EU COST Action ADMIRE in Aldosterone/Mineralocorticoid Receptor (MR) physiology and pathophysiology. Aldosterone is the major hormone regulating blood pressure. Alterations in blood levels of aldosterone and genetic mutations in the MR receptor are major causes of hypertension and comorbidities. Many of the drugs in clinical use, and in development for treating hypertension, target aldosterone and MR actions in the kidney and cardiovascular system. The ADMIRE book...

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