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The potential of L-citrulline as a treatment for persistent pulmonary hypertension of the newborn: a standard review
No full textPersistent pulmonary hypertension of the newborn poses significant challenges in neonatal care, often leading to severe morbidity and mortality among affected infants. This condition, characterised by , can result in compromised pulmonary blood flow and shunting, making timely intervention crucial to long-term health and survival. While inhaled nitric oxide remains a cornerstone of pharmacological management, its limitations highlight the need for alternative therapeutic strategies. L-citrulline, a non-essential amino acid, has emerged as a promising candidate due to its unique pharmacokinetics, which enhance nitric oxide production while bypassing hepatic metabolism. Preclinical studies in animal models have demonstrated the potential of L-citrulline to improve lung function, support endothelial health, and reduce right ventricular strain. Additionally, clinical findings in other populations suggest favourable safety profiles and positive outcomes with L-citrulline supplementation. Despite these encouraging results, a critical gap exists regarding its efficacy in neonatal populations and in human persistent pulmonary hypertension of the newborn populations, underscoring the necessity for focused clinical trials. This review discusses the mechanisms of action, existing evidence, and the potential role of L-citrulline in the management of persistent pulmonary hypertension of the newborn.</p
Building skin health resilience in a changing world: dermatological challenges in the era of climate change
No full textClimate change presents significant threats to skin health through mechanisms such as increased ultraviolet radiation due to ozone depletion, extreme temperature fluctuations, heightened air pollution, proliferation of environmental allergens, and the spread of vector-borne diseases. These factors exacerbate inflammatory skin conditions and elevate the risk of skin cancers and infections. Studies show that vulnerable populations – particularly those with socioeconomic disadvantages, age-related vulnerabilities, and specific genetic predispositions – are disproportionately affected by climate-related skin diseases. This review examines the dermatological impacts of climate change, highlights disparities in skin health outcomes, and discusses mitigation strategies at both individual and public health levels. Emphasis is placed on the need for increased research, innovation, and policy interventions to protect skin health in a changing environment.</p
Exploring the Immune Microenvironment of Cisplatin-Resistant Neuroblastoma via Genetic Profiling in a Range of <i>In Vitro </i>and <i>In Vivo</i> Models
No full textNeuroblastoma (NB) is a paediatric cancer which accounts for 15% of childhood cancer deaths. Despite advances in multimodal therapy, over one-third of patients have a high risk of relapse due to development of multidrug resistance. It is hypothesized that the immune component of the tumour microenvironment (TME) of NB may be a driver in drug resistance. This TME is dominated by tumour associated macrophages (TAMs) which aid in tumour progression, with few effector immune cells. Due to inadequate preclinical models, there is still little known on the precise interactions between TAMs and NB cells and how they may driveresistance.
This thesis aimed to use a range of in vivo and in vitro cisplatin-resistant models, to better our understanding on NB –immune cell interactions. This work proposed a 3D collagen scaffold model and a drug-resistant murine xenograft model, among other in vitro models for studying NB –TAM interactions, paired with previously developed and extensively characterised cisplatin sensitive and resistant cell lines KellyLuc and KellyCis83Luc. Genetic profiling and bioinformatical analysis of the murine xenografts identified 12 clinically relevant genes which are significantly dysregulated in drug-resistant NB. The marker TNFRSF4 was selected for more focussed analysis, which exhibited potential as a prognostic indicator for NB. It was demonstrated that porous collagen scaffolds supplemented with nanohydroxyapatite, chondroitin-6-sulfate and hyaluronic acid, which are naturally present in the TME, support the growth of NB cells. The methods of loading cells on the scaffolds and monitoring their growth were optimised. Finally, macrophage polarisation in response to NB cells in 2D culture and 3D scaffolds was examined, and it was found that gene expression is significantly altered, including expression of FN1, IL6 and IL1b. However, expression trends cannot be simply categorised in the binary M1 and M2 phenotypes as previously suggested by the literature.
This work has identified a potential new prognostic indicator for NB,TNFRSF4, which has also been used as a therapeutic target in other cancers. The use of our scaffold model to bridge the gap between 2D cell culture and in vivo models was validated, demonstrating the strong potential value of this model for therapeutic testing in the future. While our data was obtained using monoculture, the next step to advance our 3D model will be to coculture NB cells and macrophages. This work combined with supporting literature suggests that this model could provide a beneficial platform for testing novel immunotherapeutics for NB and ultimately facilitate personalised medicine to revolutionise the treatment of this cancer going forward.</p
Do psychotic symptoms predict future psychotic disorders in adolescent psychiatry inpatients? A 17-year cohort study
No full textBackground: Individuals with a psychiatric inpatient admission in adolescence have a high risk of schizophrenia-spectrum disorders (SSDs) when followed to adulthood. Whether psychotic symptoms predict subsequent SSDs in inpatient cohorts, however, is an important unanswered question.Methods: The sample consisted of adolescents (aged 13-17) admitted to psychiatric inpatient care (Oulu, Finland) from April 2001 to March 2006. Psychotic symptoms were assessed with the Schedule for Affective Disorders and Schizophrenia. Specialized health care use and diagnoses were followed up in national health care registers until June 2023. Cox regression was used to predict SSDs by the presence of baseline psychotic symptoms.Results: Of 404 adolescent inpatients admitted with non-psychotic mental disorders, 28% (n = 113) reported psychotic symptoms: 17% (n = 68) subthreshold and 11% (n = 45) full threshold. By the end of follow-up, 23% of the total cohort went on to be diagnosed with an SSD. Subthreshold psychotic symptoms did not differentiate patients who would subsequently develop SSDs (cumulative incidence 24%; HR = 1.42, 95%CI = 0.81-2.50). Full-threshold psychotic symptoms, on the other hand, were associated with an increased risk of subsequent SSDs (cumulative incidence 33%; HR = 2.00, 95%CI = 1.12-3.56). Most subsequent SSDs (83%), however, occurred in individuals who had not reported threshold psychotic symptoms during inpatient admission.Conclusions: There was a high risk of subsequent SSDs among adolescent psychiatry inpatients when followed over time. SSDs were not predicted by subthreshold psychotic symptoms. Full-threshold psychotic symptoms were associated with an increased risk of subsequent SSDs, though with low sensitivity.</p
Studies on the isolation and structure elucidation of berberine, (−)-β-hydrastine, and jatrorrhizine from goldenseal root (<i>H</i><i>ydrastis canadensis</i> L.) and <i>Mahonia</i> x<i> </i><i>media</i> ‘Winter sun’ stem bark
No full textGoldenseal (Hydrastis canadensis L., Ranunculaceae) is a traditional North American herbal medicine with a long history of use to treat various illnesses, primarily as a chemotherapeutic agent for microbial infections. Two of its alkaloid constituents, berberine and (−)-β-hydrastine, have well-defined pharmacological effects. In addition to its presence in goldenseal, berberine (and analogues) are found in other plant families. One such is the barberry family (Berberidaceae), encompassing various medicinal and decorative species, including those of the genus Mahonia (Berberis). This 3-h laboratory practical has been devised to allow undergraduate students to isolate berberine and (−)-β-hydrastine from a commercially available root sample of goldenseal, and both berberine and the closely related alkaloid, jatrorrhizine, from the bark of Mahonia x media ‘Winter sun’. Isolation is carried out on a miniature, sustainable and environmentally friendly scale using flash column chromatography. A gradient mobile phase is utilized for the isolation of (−)-β-hydrastine and berberine from goldenseal. A notable feature of the isolation of berberine and jatrorrhizine from Mahonia is the utilization of silica gel loaded with 10% w/w sodium carbonate. In this way, jatrorrhizine, an acidic alkaloid, is significantly retained while berberine elutes effortlessly from the column. A follow-on spectral assignment workshop is undertaken using 1- and 2-D NMR and IR spectra of the isolated alkaloids. Both formative and summative assessment of student comprehension takes place during the practical, workshop and end-of-semester college examinations. The experiment has been fully validated in the class setting, having been completed by circa 160 third year pharmacy students.</p
Conference programme
No full textProgramme of 'Better health outcomes from digital health?’ National Healthcare Outcomes Conference, RCSI University of Medicine and Health Sciences, 8 April 2025.</p
Cognitive outcomes and performance of patients diagnosed and treated for N-Methyl-D-Aspartate receptor antibody-mediated (NMDAR) encephalitis compared with patients with schizophrenia and healthy controls
No full textBackground: Cognitive dysfunction may be a sequelae of N-Methyl-D-Aspartate receptor encephalitis (NMDAR encephalitis) with working memory commonly affected. This study examined cognitive outcomes in patients treated for NMDAR encephalitis using a neurocognitive test battery and a working memory paradigm, compared with healthy controls & patients with schizophrenia.Methods: Adult patients previously treated for NMDAR encephalitis were assessed using the Cambridge Automated Neuropsychological Test Battery (CANTAB) for working memory & episodic memory. Patients completed the N-back task during functional MRI (fMRI) scanning. Results were compared to patients with schizophrenia and healthy controls from a prior study.Results: Twelve patients were recruited [11 women; mean (SD) age 37(12) years; Mean (SD) duration until immunotherapy treatment 7.09 (2.43) weeks]. Data were compared to 14 patients with schizophrenia [10 women; mean (SD) age 39 (12) years] and 14 healthy controls [7 women; mean (SD) age 30 (6) years]. Significant differences in letter number sequencing, spatial working memory, logical memory I, 1-back, and 2-back performance were observed (Cohen's d = 0.766 to 1.254, pConclusions: Study findings suggest cognitive performance in patients treated for NMDAR encephalitis approaches normal over time. Prompt treatment with immunotherapy is associated with improved cognitive outcomes. Psychiatric services should be aware of the clinical features of autoimmune encephalitis.</p
Use of artificial intelligence to support quality of life of people with dementia: a scoping review
No full textBackground: Dementia has an impact on the quality of life (QoL) of people with dementia. Tailored services are crucial for improving their QoL. Advances in artificial intelligence (AI) offer opportunities for personalised care, potentially delaying institutionalisation and enhancing QoL. However, AI's specific role in approaches to support QoL for people with dementia remains unclear. This scoping review aims to synthesise the scientific evidence and grey literature on how AI can support the QoL of people with dementia.Method: Following Joanna Briggs Institute guidelines, we searched PubMed, Scopus, ACM Digital Library, and Google Scholar in January 2024. Studies on AI, QoL (using Lawton's four-domain QoL definition), and people with dementia across various care settings were included. Two reviewers conducted a two-stage screening, and a narrative synthesis identified common themes arising from the individual studies to address the research question.Results: The search yielded 5.467 studies, after screening, thirty studies were included. Three AI categories were identified: monitoring systems, social robots, and AI approaches for performing activities of daily living. Most studies were feasibility studies, with little active involvement of people with dementia during the research process. Most AI-based approaches were monitoring systems targeting Lawton's behavioural competence (capacity for independent functioning) domain.Conclusion: This review highlights that AI applications for enhancing QoL in people with dementia are still in early development, with research largely limited to small-scale feasibility studies rather than demonstrating clinical effectiveness. While AI holds promise, further exploration and rigorous real-world validation are needed before AI can meaningfully impact the daily lives of people with dementia.</p
Breaking the cycle: psychological and social dimensions of pediatric functional gastrointestinal disorders
No full textBackground: Functional gastrointestinal disorders (FGIDs) in children present with chronic symptoms like abdominal pain, diarrhea, and constipation without identifiable structural abnormalities. These disorders are closely linked to gut-brain axis dysfunction, altered gut microbiota, and psychosocial stress, leading to psychiatric comorbidities such as anxiety, depression, and behavioral issues. Understanding this bidirectional relationship is crucial for developing effective, holistic management strategies that address physical and mental health.Aim: To examine the psychiatric impacts of FGIDs in children, focusing on anxiety and depression and their association with other neurodevelopmental disorders of childhood, such as attention-deficit/hyperactivity disorder, emphasizing the role of the gut-brain axis, emotional dysregulation, and psychosocial stress. Key mechanisms explored include neurotransmitter dysregulation, microbiota imbalance, central sensitization, heightening stress reactivity, emotional dysregulation, and symptom perception. The review also evaluates the role of family dynamics and coping strategies in exacerbating FGID symptoms and contributing to psychiatric conditions.Methods: A narrative review was conducted using 328 studies sourced from PubMed, Scopus, and Google Scholar, covering research published over the past 20 years. Inclusion criteria focused on studies examining FGID diagnosis, gut-brain mechanisms, psychiatric comorbidities, and psychosocial factors in pediatric populations. FGIDs commonly affecting children, including functional constipation, abdominal pain, irritable bowel syndrome, gastroesophageal reflux, and cyclic vomiting syndrome, were analyzed concerning their psychological impacts.Results: The review highlights a strong connection between FGIDs and psychiatric symptoms, mediated by gut-brain axis dysfunction, dysregulated microbiota, and central sensitization. These physiological disruptions increase children’s vulnerability to anxiety and depression, while psychosocial factors - such as chronic stress, early-life trauma, maladaptive family dynamics, and ineffective coping strategies - intensify the cycle of gastrointestinal and emotional distress.Conclusion: Effective management of FGIDs requires a biopsychosocial approach integrating medical, psychological, and dietary interventions. Parental education, early intervention, and multidisciplinary care coordination are critical in mitigating long-term psychological impacts and improving both gastrointestinal and mental health outcomes in children with FGIDs.</p
Reflecting digital transformations in public health curricula
No full textDigital technologies promise greater personalisation and precision in public health services, automation of repetitive tasks, and more efficient use of existing resources through rapid management and analysis of big data sets. To seize this opportunity, the public health workforce needs to become sufficiently competent to navigate these novel digital technologies and understand how to apply them across the spectrum of essential public health functions. With few exceptions, however, digital skills are not yet systematically incorporated into public health curricula.</p