ItemMicrobial regulation of barrier function in the gut-brain axis(University College Cork, 2023) Sánchez Díaz, Paula; Clarke, Gerard; Cryan, John; Leigh, Sarah-Jane; Advancement in Neurosciences (Geneva, Switzerland)The gut microbiome plays a critical role in host health through modulation of gut and blood-brain barrier integrity, responding to factors such as diet, stress, and medication. A key pathway by which the gut microbiota affects gut and bloodbrain barrier integrity is through the production of bioactive metabolites. This thesis explores the role of barriers in the microbiota-gut-brain axis, which are essential for the proper functioning of body systems and homeostasis. Chapter 2 investigates how fermenting infant nutrient formulations with different bifidobacteria strains isolated from infant gut microbiome can influence the integrity of gut and blood-brain barriers in vitro. The study found that the presence of bifidobacteria strains, in some cases, had protective effects on the barriers, and these effects sometimes differed depending on the barrier studied. Chapter 3 explores the effects of indole and two of its derivates, indole-3-acetate and indole- 3-propionate, on gut barrier function in vitro. The results indicate that indole has a protective effect on barrier function, particularly at higher concentrations, and indole-3-acetate has a protective effect at the lowest concentrations tested. Surprisingly, indole-3-propionate was not protective and at higher concentrations exacerbated the effects of LPS-induced disruption. Finally, Chapter 4 focuses on the effect of cancer therapy, specifically cisplatin, on gut and blood-brain barrier structure in mice, to further explore the role of gut microbiome in cancer-related cognitive impairment. The study used mice treated with cisplatin to investigate the expression of genes involved in the structural function of barriers and inflammation, as well as gene expression of receptors activated by microbial ligands in the ileum, colon, and hippocampus. The results showed that cisplatin affected gene expression in a region- and dose-dependent manner, leading to changes in anxiety-like and fatigue behaviours in mice. Overall, this research highlights the critical role of the gut microbiome in gut barrier and blood-brain barrier function. Microbial metabolite supplementation may present a useful therapeutic option for disease processes involving disruption of the gut and/or blood-brain barriers. ItemMajor trauma in older Irish adults(University College Cork, 2023) Junker, Kate; Ó Tuathaigh, Colm; Deasy, ConorIntroduction: The world’s population is rapidly ageing. In Ireland, the population over sixty five years is expected to increase from 629,800 to 1.6 million by 2051. Such changes in demographics pose a challenge for healthcare and all areas of our service must adapt to meet the needs of this cohort. Major trauma is a leading cause of death and disability worldwide. Recent literature has shown that low falls are the biggest contributor to major trauma. Major trauma in older Irish adults is an area about which little research has been done. The primary aim of this study was to determine the prevalence of major trauma in older Irish adults and describe injuries sustained and their management. This study also explores outcomes for older adults who experience major trauma and makes comparison with younger counterparts. Methods: This is a retrospective secondary analysis of data from the Major Trauma Audit (MTA). The MTA prospectively gathers data on patient care and outcomes following trauma from twenty six participating hospitals in Ireland. This study included all patients who presented to a single centre in Ireland with an injury severity score (ISS) indicative of major trauma over five years. Data was divided into the following age groups; 0-24 years, 25-49 years, 50-64 years, 65-74 years, 75-84 years, and 85 years or older. Data was analysed using SPSS version 28. Descriptive statistics were used to define demographics and injury characteristics and chi-square test was used to make comparisons between groups. Univariate and multivariate logistic regression analysis was used to consider factors associated with specific outcomes. A p-value of <0.05 was considered statistically significant. Results: In the five year period studied, 1,123 cases of major trauma were identified in Cork University Hospital. Of these, 659 were aged less than sixty five years and 464 were aged greater than sixty five years meaning that 41.3% were older adults. The majority of older adults presenting with major trauma were male (56%) but the proportion of females presenting increased with age. Low falls were the most common mechanism of injury (74.1%). 80.6% of older adults were alive thirty days post injury and 47.2% had a good recovery. Conclusion: Major trauma in older Irish adults is becoming an important public health issue. Specialist education and training is required to ensure the needs of this cohort are appropriately met. This study highlights the burden of major trauma in older Irish adults. ItemDefining the patient safety trajectory of breast cancer at a National Cancer Centre(University College Cork, 2023) Forrest, Clara; Ó Tuathaigh, Colm; Health Service Executive; University College CorkIntroduction: One in seven Irish women will develop breast cancer in their lifetime. A well-researched management pathway commences thereafter, involving multiple treatment modalities and specialities. In contrast, there is sparse research examining the patient safety trajectory that mirrors this clinical journey. Learnings from previous events can illuminate this otherwise unknown patient safety trajectory of those with breast cancer. Furthermore, there is little known of patients’ and doctors’ views and experiences of this patient safety trajectory. Aims: This study aimed to characterise patient safety incidents that have occurred during breast cancer care, their contributory and preventative factors, outcome and impact. Using this data, patient safety trajectories were created. In addition, this paper aimed to explore the patient safety views and concerns of patients receiving and doctors providing breast cancer care. Methods: Anonymous, quantitative patient and doctor questionnaires were used. In addition, data related to medical negligence claims involving breast cancer and handled by the State Claims Agency was analysed. Pearson chi-squared test and Fisher’s exact test were utilised for categorical data. The median degrees of harm were used to construct trajectories. Results: 83 patient safety incidents were included (61 medical errors and 22 medical negligence claims). Failure or delay to correctly diagnose was the most commonly implicated adverse event type overall (n=32/83, 38.6%) and was involved in a higher proportion of medical negligence claims than medical errors (p=0.01). Forty percent of events occurred in the outpatient department (n=33/83) and 31% of events took place before a patient’s formal breast cancer diagnosis (n=26/83). Inadequate communication was the most common contributory factor. Events during neoadjuvant chemotherapy and after discharge from follow-up had the highest median degree of harm of 4 (Q1-Q3:3.5-4.5 and Q1-Q3:4.0-4.5). More doctors felt patient safety has worsened in the past five years compared to patients (41.4% vs 13.0%) (p<0.001). Twice as many doctors reported that there were inadequate measures in place to prevent medical error compared to patients (54.3% vs 27.2%) (p<0.001). Conclusion: Patient safety incidents during breast cancer care occur in a variety of settings and during all clinical stages but often occur before diagnosis and involve inadequate communication. Doctors who provide breast cancer care have a more pessimistic outlook on patient safety compared to patients and are more concerned about medical error in breast cancer care. Addressing and acting on the experiences and concerns of those involved in breast cancer care is vital to improve patient safety trajectories for breast cancer patients. ItemExploring the daily life experiences of UCC registered doctoral [PhD/ MD/ Practitioner Doctorate] students and how the UCC “Everyday Matters: Healthy Habits for University Life” digital badge impacted their daily life and well-being(University College Cork, 2022) Skipp Prendergast, Alison; Hunt, Eithne; Usher, Ruth; Bank of IrelandBackground - Poor mental health and well-being among university students, including doctoral students, is a growing concern globally. Engaging in occupations every day and maintaining occupational balance is believed to improve health and increase well-being. However, little is currently known about the daily life, occupational balance, and well-being of doctoral students. Whole university approaches to promoting student well-being and success are urgently needed, along a continuum of support including universal, targeted, and intensive interventions. The “Everyday Matters: Healthy Habits for University Life” digital badge (EMDB) is an occupation-based time-use and well-being universal intervention offered to doctoral students as a cocurricular micro-credential at University College Cork (UCC). This study explored and described the daily life experiences of doctoral students and how pursuing their degree impacted their occupational balance and well-being, as well as examined doctoral students’ experience of participating in the EMDB. Method - Purposive sampling methods were used in this qualitative interpretive descriptive study to recruit 10 UCC PhD/MD/Practitioner Doctorate students who completed the EMDB. Data were generated through individual semi-structured interviews and thematic analysis was completed. Findings - Doctoral students have a range of roles, responsibilities, and occupations that they need to and want to engage in on a daily basis. For many, balancing their daily occupations and roles alongside their doctoral degree is challenging. Undertaking a doctoral degree can have both a positive and negative impact on well-being. The EMDB successfully supported the daily lives and well-being of doctoral students. Conclusion - Obtaining an insight into the perspectives and experiences of students allows a better understanding of the students’ doctoral journey. Supporting the well-being of doctoral students is essential to enhance their doctoral journey and assist them in successfully completing their degree. ItemNovel models for understanding traumatic stress(University College Cork, 2022-09-30) Lannon, Adam; Moloney, Rachel; Cryan, John; Brain and Behavior Research FoundationUndergoing trauma, be it physical, psychological, or observed, can induce pathological alterations leading to disorders such as Post-Traumatic Stress Disorder (PTSD). PTSD is highlighted by negative cognitive alterations, behavioural changes, and interruptions in arousal and sociability. PTSD is comorbid with disorders such as anxiety and depression, gastrointestinal disturbances, pain, and the gut microbiome is hypothesized to play a role in this trauma-related disorder. Direct experience of traumatic events is the most common method of generating traumatic-stress related pathologies, however indirect exposure through witnessing another endure a traumatic event can also lead to PTSD-like symptoms. This method of traumatic transference is called secondary traumatic stress (STS). While PTSD and STS are clinically relevant, and ever-growing in importance due to the recent COVID-19 pandemic, there is still a lot to be learned about their molecular underpinning, mechanisms, and biomarkers. In order to appropriately investigate these neurobiological features of traumatic stress, valid and effective animal models are absolutely essential. Utilizing the most appropriate animal models for the representation of neuropathologies is essential for extracting critical information in the process of developing novel therapeutic options. In chapter 2, we aim to develop the knowledge of secondary traumatic stress, we investigated whether a novel observational model, combining visceral pain, a common comorbidity of traumatic stress related disorders, and observed stress could result in a suitable phenotype. Utilizing colo-rectal distension (CRD) to induce visceral pain behaviours, we had rodents observe another rodent undergoing this procedure. These observer rodents then underwent the CRD themselves 24 hours later in order to assess whether they had visceral hypersensitivity. Indeed, it was seen that observer animals had hyperalgesia measured in visceral pain threshold and total behaviours, an impacted HPA axis, and altered neuronal activation in key brain regions. Our results suggest that this novel model was effective in producing secondary traumatic stress-like phenotypes, and would be well suited for further research into the social transference of pain and developing therapeutic options for traumatic-stress induced disorders and visceral pain comorbidity. In chapter 3, we look at Single prolonged stress (SPS), which is a well-validated and commonly used model however there are ethical concerns that limit its widespread use. The classical SPS model involves a 2-hour restraint, immediately followed by a 20-minute forced swim, a 15-minute rest and culminates with diethyl ether exposure until loss of consciousness. Recent focus on ethical standards and interests in refining animal models has led to concerns in the usage of diethyl ether, leading us to investigate whether the model would still be effective using isoflurane as a replacement for diethyl ether. Our findings suggest that this model is effective in recapitulating a key PTSD phenotype in the contextual fear conditioning paradigm. Impaired fear learning has been repeatedly found to be a key component of PTSD phenomenology, and our model induced significantly impaired fear learning in stress rats. Further to this, we found that SPS with isoflurane caused significant reduction in learned helplessness in rodents, paired with time specific changes in corticosterone concentration. Anxiety-like behaviours also appear to be implicated by this model, with Isoflurane exposure leading to reduced anxiety-like behaviour, suggesting its potential as an adequate PTSD model. The encouraging results from these two models of traumatic stress provide a significant interest in further studies using them. With the future intention of developing novel and effective therapeutics for undermedicated sufferers of these disorders, the hope is that these models can help provide valuable insights into the mechanisms of action behind the pathologies, illuminating potential therapeutic avenues.