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Valuing urban natural capital for health and resilience: a stakeholder-informed system dynamics model for Dublin
No full textUrban natural capital - including trees, soils, grasslands, and waterways - supports flood mitigation, air-quality regulation, carbon storage, and human well-being. However, urban greening interventions such as planting, de-paving, and maintenance are often planned and budgeted in isolation, limiting their long-term effectiveness. We co-produced a system dynamics model for Dublin that integrates seven land-cover classes with hydrological, air-quality, carbon, biodiversity, and access-related services, informed by participatory stakeholder workshops. The model was used to explore four 15-year scenarios (2025–2040), representing policy-aligned investment, no planting, underfunded maintenance, and reduced community engagement pathways, alongside sensitivity analysis of maintenance funding.Results indicate that an integrated strategy - combining sustained planting, gradual conversion of sealed surfaces to permeable green space, adequate operations and maintenance, and community stewardship - produces durable ecosystem-service and health benefits over time. In contrast, scenarios with underfunded maintenance exhibit endogenous failure modes, including declining tree health, stalled canopy growth, and substantially reduced hydrological and health outcomes, despite similar planting efforts. Sensitivity analysis highlights maintenance funding as the dominant driver of long-term performance, with positive economic returns emerging only when funding approaches full requirements.By representing feedbacks, delays, and governance constraints, the model demonstrates how well-documented urban-forestry mechanisms interact dynamically to shape long-term outcomes. The study contributes a transferable, stakeholder-informed system dynamics framework that complements static natural-capital valuation approaches and supports realistic, policy-relevant evaluation of nature-based strategies in cities.</p
Exploration of the Role of EZH2 and BRD4 in the Transcriptional Dysregulation of Epileptogenesis in Epilepsy
No full textTemporal lobe epilepsy (TLE) is the most common form of epilepsy in adults, is characterized by seizures originating in temporal structures and has high rates of drug refractoriness. Acquired TLE often develops following a brain insult e.g. traumatic brain injury, stroke or status epilepticus (SE), triggering widespread gene expression changes which have so far been poorly characterized. These changes may drive the various pathogenic processes involved in the development of the disease; a process known as epileptogenesis.
A key process of the epileptogenic process is the gradual change in cellular properties including neurons, and glial cells. Epigenetic modifications and governance of gene expression are key regulators of cellular identity and function and have been shown to be altered by epileptic triggers. Epigenetics broadly refers to processes such as (i) DNA methylation, (ii) histone modifications and (iii) non-coding RNAs that control gene expression by influencing the accessibility of the chromatin to transcriptional machinery. All three major epigenetic processes have been found to be altered in both experimental and human epilepsies.
EZH2 and BRD4 are two epigenetic regulating enzymes which are critical for cellular identity and function and have profound effects on gene expression patterns in the brain. Although both enzymes have been linked with seizure activity, little is known about how they may regulate the epileptogenic process, and their therapeutic potential as master regulators of the process. The current project sought to fill these knowledge gaps by exploring the effects of epileptogenic insults on the expression of key epigenetic enzymes. By profiling the binding profiles and gene regulatory networks governed by both EZH2 and BRD4 and assessing whether inhibition of BRD4 using small molecule inhibitors holds therapeutic promise as an anti-epileptogenic agent. To do this we used a clinically relevant mouse model of TLE and applied a combination of proteomic analyses, novel CUT&RUN and next generation sequencing approaches and pre-clinical analyses of small molecule inhibitors with long term EEG.
Here, we identified altered expression of EZH2 and BRD4 protein levels and various other epigenetic enzymes in the hippocampus following SE suggesting possible widespread epigenetic reorganization of the genome initiated by epilepsy-inciting events. Additionally, we broadly mapped the protein-DNA binding events involving EZH2 and Brd4 using CUT&RUN, enabling us to further analyze the dynamic interactions between these epigenetic enzymes and DNA driving gene expression changes in epileptogenesis and chronic epilepsy. We then tested a small molecule BET inhibitor to evaluate therapeutic potential, which worsened seizure phenotype, potentially due to altered expression of genes associated with inflammation, microgliosis, and neurotransmission. </p
A mobile craniofacial surgery unit: reconstructing casualties of war in Ukraine
No full textThis paper describes the development and implementation of a mobile craniofacial surgical unit designed to address complex posttraumatic craniofacial deformities in both civilian and military casualties resulting from Russia's invasion of Ukraine. Restricted air space, limited possibilities for transportation of personnel and equipment, frequent interruption of power and water supply, and constant threat of injury to patients and medical personnel from missile and drone strikes, precludes reliable and safe delivery of tertiary care. The Canada Ukraine Surgical Aid Program (CUSAP) addressed these challenges by establishing a mobile craniofacial surgery unit, operating just outside of the war zone. The following report characterizes the civilian and military casualties, highlights the barriers to the provision of adequate tertiary care locally, and provides a detailed description of the measures that were taken to organize the mobile unit. The effectiveness of this program is documented, and specific challenges are illustrated through case examples. We believe this model serves as a template for delivering surgical aid to victims of any global disaster where care cannot be provided locally.</p
Longitudinal relationship between hip displacement and hip function in children and adolescents with cerebral palsy: a scoping review
No full textAim: To identify, describe, and synthesize available evidence on the longitudinal relationship between hip displacement and hip function, using the International Classification of Functioning, Disability and Health (ICF) framework, in children and adolescents with cerebral palsy (CP) aged up to 18 years.Method: Five databases were searched systematically from inception to May 2022. Study and sample characteristics, and hip displacement and hip function measures, mapped to the ICF domains, were extracted for narrative synthesis.Results: Twenty-nine studies were included: four longitudinal registry-based studies; 12 prospective studies; 12 retrospective studies; and one randomized controlled trial. Sample size ranged from 11 to 267. Twenty-seven (93%) studies entailed an intervention: surgery (n = 16); rehabilitation (n = 2); nerve block or botulinum neurotoxin A injection (n = 4); and combined surgery and injection (n = 2). Twenty-six studies (90%) reported outcomes at the body structure and function and impairment domain of the ICF; 17 (59%) reported outcomes in the activity domain; and three (10%) included participation measures. The most common hip displacement measure was Reimers' migration percentage (79%).Interpretation: Because of the inclusion of interventions in most studies, and the preponderance of retrospective studies, the relationship between hip displacement and hip function in CP is unclear. More high-quality prospective evidence on the natural history of hip displacement, and its effect on function, is needed to improve population-wide screening of children with CP.</p
Porphyrin-polymer as a photosensitizer prodrug for antimicrobial photodynamic therapy and biomolecule binding ability
No full textThis study presents the development and characterization of a novel porphyrin-Jeffamine polymer conjugate designed to function as a photosensitizer prodrug for antimicrobial photodynamic therapy (aPDT). The conjugate features a photosensitive porphyrin unit covalently attached to a biocompatible polymer backbone, with enhanced solubility, stability, and bioavailability compared to those of the free porphyrin derivatives. The photophysical properties were studied using transient absorption spectroscopy spanning the fs-μs time scales in addition to emission studies. The production of reactive oxygen species upon photoactivation enabled effective bacterial cell killing. Spectroscopic studies confirmed strong binding of the conjugate to DNA through intercalation, likely disrupting DNA replication and transcription. Interaction studies with bovine serum albumin demonstrated substantial serum protein binding, which may positively impact the pharmacokinetics and biodistribution. Overall, this porphyrin-polymer conjugate offers a multifunctional theranostic platform, combining antimicrobial action with DNA and protein binding potential, positioning it as a promising candidate for aPDT and bioimaging applications.</p
Innovating cancer treatment
No full textDr Jarushka Naidoo is a consultant medical oncologist at Beaumont Hospital, Professor of Oncology at the Royal College of Surgeons in Ireland (RCSI), lung cancer researcher, and certified Pilates instructor.</p
Obesity-related glomerulopathy: how it happens and future perspectives
No full textObesity-related glomerulopathy (ORG) is an emerging complication of excess adiposity. Its incidence rises alongside the obesity pandemic. Up to 40% of individuals can be affected by ORG, irrespective of the status of glomerular filtration rate and albuminuria. ORG is a distinct histological diagnosis based on kidney biopsy, showing classical features of an enlarged glomerulus with and without focal segmental glomerulosclerosis in the perihilar region seen with all categories of obesity. About 10% of individuals with ORG may progress to end-stage kidney disease. The invasive nature of kidney biopsy highlights the need for non-invasive biomarkers for improved screening, diagnosis and risk prediction of ORG. These biomarkers may narrow the gaps in the management of ORG by improving: (1) screening, diagnosis and differentiation of ORG from non-ORG conditions; (2) risk prediction and stratification of individuals at risk of progression to end-stage kidney disease including the detection of trajectories of progression; (3) monitoring of treatment safety and effectiveness and (4) development of novel therapeutic targets. In the present review, we discussed the pathophysiology, emerging biomarkers (such as kidney injury molecule-1 [KIM-1], uromodulin, klotho, circulating microRNA-21 [miR-21]) and future treatment strategies (metabolic surgery, sodium-glucose cotransporter-2 inhibitors, incretin-based therapy and non-steroidal mineralocorticoid antagonists) of ORG.</p
Interventions to increase uptake in a fecal-immunochemical test population-based colorectal cancer screening program: a quasi-experimental study of first-time invitees
No full textBackground: Many countries have established organized colorectal cancer screening programs because they can reduce mortality and incidence from the disease; however, they rely on high participation rates, which are often suboptimal. This study examined the effectiveness of two reminder interventions on uptake rates in Ireland's population-based BowelScreen program.Methods: Employing a quasi-experimental design, one intervention mailed the fecal-immunochemical test (FIT) directly to clients not responding to an initial invitation; the other mailed a reminder letter modified with behavioral insights. Interventions were tested separately and in combination and compared to the standard reminder letter (1: standard reminder letter [SRL]; 2: modified reminder letter [MRL]; 3: SRL + FIT direct [FITD]; and 4: MRL + FITD).Primary outcome: overall uptake rate (test completion at 5 months); Subgroup outcome: uptake rate among only those receiving reminders. Outcomes were modeled using multivariable logistic regression with group allocation as a fixed effect, adjusted for sex and deprivation.Results: Uptake was significantly higher in the FITD groups (SRL: 48%; MRL: 50%; SRL + FITD: 54%; MRL + FITD: 54%; p Conclusion: Mailing the FIT kit directly to nonresponders resulted in improved FIT uptake. Organized FIT-based screening programs not reaching uptake targets should consider implementing this strategy if not already in place.</p
Association of complement proteins with c reactive protein in non-obese women with and without polycystic ovary syndrome
No full textComplement proteins are increased in polycystic ovary syndrome (PCOS), as are markers of inflammation, such as the C-reactive protein (CRP); however, both may be increased in obesity. We hypothesised that body mass index (BMI)-driven CRP would comparably associate with an increase in complement proteins when obesity was accounted for in non-obese women with and without PCOS. In a non-obese, non-insulin-resistant population without inflammation (24 with PCOS and 24 control women), plasma CRP was measured by immunoassay. Slow Off-rate Modified Aptamer (SOMA)-scan plasma proteomic analysis of the classical, lectin, and alternative pathway complement proteins was undertaken. BMI, insulin resistance, and CRP did not differ (p p p p > 0.05). CRP correlated positively (p < 0.05) with C4 of the classical pathways in women with PCOS alone. Hyperandrogenemia did not correlate with CRP or complement in non-obese PCOS. BMI correlated positively with C3, C3adesArg, C3a, iC3b, Factor B, Factor H, and properdin: classical pathway proteins; C1q, C4, C5 and C5a in PCOS women; BMI only correlated negatively with C1q in non-PCOS women. Upregulation of complement proteins occur in non-obese PCOS, and CRP is positively associated with complement protein changes in both women with and without PCOS. This indicates that BMI induces changes in CRP that lead to changes in the complement pathways, particularly the alternate pathway, with increases in CRP (though still within the reference laboratory normal range) leading to upregulation of complement proteins in PCOS. This suggests an enhanced set point for CRP-induced complement protein dysregulation in PCOS.</p
Digital health: what is it & what can it do for outcomes?
No full textA paper presented at the 'Better health outcomes from digital health?’ National Healthcare Outcomes Conference, RCSI University of Medicine and Health Sciences, 8 April 2025.</p