College of Medicine and Health - Masters by Research Theses

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Predicting expressive vocabulary change in young children growing up in Ireland
(University College Cork, 2018-06) Bowles, Caoimhe; O'Toole, Ciara; Lee, Alice
During the preschool years expressive vocabulary development is highly variable, which makes it difficult for healthcare and education professionals to identify children with delays that require early intervention services. Previous research has highlighted the need to identify a reliable set of risk and protective factors which predict expressive vocabulary outcomes. The current study explored patterns of expressive vocabulary development between 3 and 5 years using a large population-based sample of 8,266 children. Expressive vocabulary was measured using the naming vocabulary subtest of the British Abilities Scales (BAS) and information relating to additional risk factors was gathered through questionnaires with the primary caregiver. Four patterns of expressive vocabulary development were identified, 89.9% of children had no expressive vocabulary delay, 2.8% of children were delayed at 3 years only (resolving delay), 5.0% were delayed at 5 years only (late onset delay) and 2.3% had a persisting expressive vocabulary delay. Five factors differentiated between the no delay and late onset delay groups. These factors were, learning English as an additional language, low parent education levels, low frequency of book reading, low frequency of home learning activities and few children’s books in the home. Learning English as an additional language was the only factor which differentiated between resolving delay group and children with a persisting delay. The information gleaned from the current study has implications for clinical practice and identifies the need for a service delivery model which incorporates monitoring over time and providing intervention on the basis of language abilities and associated risks.
The impact of variation in freezing and thawing process parameters on the critical quality attributes of a monoclonal antibody
(University College Cork, 2019-09-23) Day, Neil; Crean, Abina; Vucen, Sonja
Therapeutic proteins or biopharmaceuticals have been playing an ever-increasing role in the treatment of human diseases over last 40 years. One of the main challenges with manufacture of these proteins is the stabilization of both the finished product and its processing intermediates during storage. Freezing and frozen storage is widely applied to improve stability of the bulk drug substance. The process of freezing a protein results in stresses that can cause protein degradation and subsequent aggregation. The aim of this project was to evaluate the effect of parameters involved with freezing and thawing of a formulated monoclonal antibody solution in polycarbonate bottles and to assess the scalability of these experiments to the respective full-scale commercial process. Initial experiments were performed to characterise the formulation and develop analytical methods that can detect change in unfolding and aggregation of a fully human IgG1 monoclonal antibody (‘Protein Y’). A designed set of experiments were then executed to understand the effect of parameters involved in freezing and thawing steps of a formulated therapeutic protein solution on protein aggregation and perturbations in tertiary structure. Results showed that the processing parameters studied caused significant variation in freeze and thaw process times, with the factors causing slower rates of freeze and thaw also shown to cause changes in the tertiary structure of Protein Y. Despite the observed changes in tertiary structure, the effect on aggregation was less pronounced, with only a significant change noted for the polydispersity index (PdI), as measured by dynamic light scattering (DLS).
Bowel symptom management following sphincter-sparing surgery for rectal cancer
(University College Cork, 2019-10-07) O'Sullivan, Mairéad; Landers, Margaret; Hegarty, Josephine
Aims: The aim of this study is to determine the content, format and mode of delivery of an intervention for patients following sphincter-sparing surgery who have experienced altered bowel function. Background: The treatment of rectal cancer often causes the development of life-altering bowel symptoms. Healthcare professionals play a pivotal role in supporting patients in their management of symptoms but increasingly it is recognised that care often becomes the patients’ sole responsibility. Numerous studies have identified the need to support patients in the self-care of their bowel symptoms and to develop interventions to facilitate same. Yet there is a dearth of literature around interventions to support patients with the symptoms specific to rectal cancer treatment, to self-care for their bowel symptoms, which do not involve the use of invasive techniques or continuous health-care professional input. Design: A qualitative descriptive design. Methods: To determine the content, format and mode of delivery of an intervention a purposeful sample of five patients and ten healthcare professionals were interviewed through individual semi-structured, audio-recorded interviews. Participants included those who had undergone sphincter-sparing surgery for rectal cancer and those involved in their care. An initial pilot study was carried out prior to conducting the main study. Data were analysed utilising deductive content analysis and data coded according to pre-determined categories. The research was underpinned by the Symptom Management Theory and also utilised the Medical Research Council Framework Guidance for the Development of Complex Interventions. Findings: Participants acknowledged the existence and impact of bowel dysfunction following surgery for rectal cancer, often continuing for a number of years post-treatment and varying from frequency, urgency and tenesmus to skin irritation and pain, in addition data analysis revealed multiple symptoms which occurred and in addition the variability of these symptoms in relation to severity, duration and associated degree of bother. The psychological and social impact of symptoms was also evident. All participants (n=15) acknowledged issues within the current practice around educating patients about the incidence, treatment and self-care of bowel symptoms, often resulting in prolonged periods of symptom experience or use of unhelpful or unsafe self-care strategies. Additionally, participants identified the need for the development of an intervention to support patients. Patients and healthcare professionals identified a phone application as a convenient and accessible method but also acknowledged the need for a booklet/written mode to cater for those less able to utilise technological formats. Of interest some healthcare professionals felt that a leaflet format would be preferable as a means of intervention delivery, this contrasted with the views of patients who felt an online or phone application format would allow greater accessibility and convenience. The intervention proposed is a multi-modal format which provided patients with information around medication, diet, skin care, resources, alternative therapies and pelvic floor exercises. Finally, throughout all interviews the need for a human contact, i.e. ability to access a healthcare professional, was highlighted as a pivotal and important feature of any intervention. Conclusion: This research has provided insights into the bowel symptoms experienced by patients following sphincter-sparing surgery for rectal cancer, the impact of these symptoms, the strategies utilised to manage these symptoms. Importantly, this study identified the need to create an intervention to allow patients to manage their symptoms in a safe and evidence-based manner and determined the appropriate content, format and mode of delivery using the findings of interviews with both affected patients and those involved in their care.
Preparation for clinical practice in radiology: a survey of interns and radiologists
(University College Cork, 2019-11-05) Simelane, Thabisile; O'Connor, Owen; Ó Tuathaigh, Colm
Objective: The purpose of this study was to evaluate interns’ preparedness to deal with radiology departments, and to identify knowledge gaps which will facilitate the design of simplified evidence-based radiology orientation course for students or newly qualified doctors, to ease the transition from theory to practice. Methods: A cross-sectional, mixed-methods approach was employed. A sample of Irish interns and practicing radiologists were asked to complete a quantitative survey regarding perceptions of intern readiness to interact with the radiology department. A mixed quantitative/qualitative analysis using group concept mapping was also conducted involving perspectives of doctors in various categories, including NCHDs, and consultants, to evaluate what topics should be covered in a related preparatory course. Pearson’s Chi Square analysis was employed to examine the association between socio-demographic and educational variables and selected categorical item responses. Kruskal-Wallis analysis of variance (ANOVA) and/or Mann–Whitney U tests were employed to carry out univariate comparisons. Results: The majority of interns 66%( N=66) and radiologists 52%(N=26) felt that undergraduate medical training did not prepare the interns to interact with radiology department. More than half of the intern respondents 52%( N=52) were frequently uncertain about radiology exam indication when completing a request form. Most interns identified challenges in choosing appropriate examinations and communicating with the radiology department. A significant number also regarded the radiology department as unapproachable. Most radiologists 92%( N=92) felt that intern understanding of indications for imaging modalities is inadequate, reflecting intern uncertainty regarding exam indications. Most radiologists 86%(N=43) perceived that interns’ understanding of contrast medium was inadequate, and 78%( N=39) perceived that interns were lacking in the knowledge of (N=39) radiation protection. Results of the group concept analysis suggested the following topics to be included in the intern radiology preparatory module: ordering investigations; clinical decision support; radiology department IT and communication; adverse reactions and risks; urgent imaging; interpretation of radiology results. Conclusion: This study has highlighted vital topics to be included if one were to design a preparatory module in radiology which would promote smooth transition from theory to practice. Future research would be to design, implement, and evaluate an appropriate preparatory module.
Assessment of the potential environmental impacts arising from mercury-free dental restorative materials
(University College Cork, 2019-12) Binner, Hannah; Sullivan, Timothy; Harding, Mairead; Environmental Protection Agency
The field of dentistry and with it, the application of dental filling materials, is currently undergoing changes to adopt sustainability and environmental considerations into the clinical environment. This was largely triggered by the reduction of all products in use that contain Hg (mercury), including dental amalgam, through the Minamata Convention of 2013, which has in turn caused a rise in Hg-free dental filling materials that are now becoming increasingly nano-filled. The focus of this study is on the particles released from Hg-free dental fillings. Knowledge gaps regarding the particle load and potential ecotoxicity of the particulate matter resulting from Hg-free materials exist. Moreover, the widely known environmental and human health impacts of Hg contained in dental amalgam have led to the widespread introduction of an amalgam capture device, the amalgam separator. Amalgam separators capture Hg and dental amalgam particles before wastewater discharge occurs. These amalgam separators are required to be installed in Ireland since the 1st of January 2019 in accordance with EU Directive 2017/852. The overarching objective of this thesis has been to assess whether existing amalgam separators are also effective in capturing particulate matter resulting from the use of Hg-free dental filling materials. In order to meet this objective, this study has assessed the wastewater and amalgam separator capture efficiency in three dental practices in Cork, Ireland. Three dental practices were selected based on the type of amalgam separator in use and focus of service based on private or public practice and high, medium or low utilisation. Physical and chemical parameters of dental wastewater (DWW), including pH, temperature, conductivity, Total suspended solids (TSS) and Total Dissolved Solids (TDS) have been measured. Detailed analysis of particles found in these wastewater streams has been conducted using optical and scanning electron microscopy. The potential ecotoxicity of these waste streams has also undergone preliminary assessment by conducting standardised Daphnia magna immobilisation tests. The results indicate that variation in the discharged DWWs exists, which is likely linked to the use of disinfection products, and has led to extreme observations of pH, conductivity, Total suspended solids and Total dissolved solids. Ecotoxicity results confirmed this and showed that the raw DWW caused an EC50 response at concentrations between 0.1 to 6.69 % DWW/L medium. The particulate load in the three DPs was substantial. A high abundance of microparticles was identified and trends were consistent across the three DPs. It was therefore concluded that amalgam separators may not be sufficient in capturing the particulate matter released from Hg-free dental filling materials. Further research is needed to identify the environmental fate of the particles that are released, particularly nanomaterials, as they have the potential to remain in the water after wastewater treatment has occurred.
Children’s voices: participation in decision-making within the goal setting process in occupational therapy
(University College Cork, 2019-12-17) O'Connor, Deirdre; Lynch, Helen; Boyle, Bryan
Introduction: Children’s participation in decision-making remains an under-researched area, especially in the context of Occupational Therapy. Therefore, the principal aim of this research was to explore the experience of children in relation to having their voices heard within goal-setting in Occupational Therapy. This is consistent with Article 12 of the United Nations Convention on the Rights of the Child, 1989) and with Occupational Therapy’s commitments to client-centred practice (World Federation of Occupational Therapy, 2019). Study Design: Informed by the approaches of ethnography, this qualitative study had 17 participants including 6 children, 5 parent(s)/guardian(s) and 6 occupational therapists to gain multiple perspectives from those involved in goal-setting. Semi-structured interviews were conducted with all participants, while a mosaic approach offered children multiple methods to communicate their experience. Findings were analysed using a thematic analysis approach. Findings: On analysis, 3 themes emerged: 1) Where goal setting exists: Experiences of paediatric Occupational Therapy services in an Irish context; 2) Children’s right to be heard: Knowledge, views, attitudes and power and 3) Goal setting processes … power and influence. Findings suggest that Occupational Therapy goals are, for the most part, adult directed and as such children’s voices are subsumed by adult agendas, priorities, and adult-led services. Conclusion: Findings illustrate that despite healthcare professionals valuing the voice of children, children and their parent(s)/guardian(s) are not consistently included in goal-setting. Numerous factors impacting children’s participation in decision-making were found such as awareness and attitudes towards children and their rights as well as the age and ability of children, for example. Few formal guidelines or standards exist as to how to operationalise a child’s right-based approach in practice.
An effectiveness study of a parent-child interaction therapy with children with Down syndrome
(University College Cork, 2020-04) Cronin, Sarah Marie; Frizelle, Pauline; O'Toole, Ciara; Down Syndrome Ireland
Background: Parents of children with Down syndrome (DS) often demonstrate directive parenting styles which can impede on their child’s communication development. For that reason, parent-child interaction therapies have shown to be an effective form of early intervention for children with DS as it facilitates parent coaching while also addressing the specific communication needs of children with DS. This study aimed to explore the effectiveness of the PELD (Promotion of Early Language Development) intervention offered by a speech and language therapy (SLT) service for individuals with DS. The study aimed to explore the impact this programme had on the language development and communicative interactions of children with DS, while also exploring the change in the interaction and communication strategies employed by their parents. Methodology: A single-subject multiple-baseline design was employed to evaluate the effectiveness of the PELD intervention. Seven child participants and their mothers took part in the study. All participants were aged between 10-17 months at the time of entry. Three terms of the intervention were offered over a 10 month period and families had the option of completing all or some of the terms. Data was collected over three to five time points depending on when the child commenced the intervention. Standardised assessments, parental report and observational measures were used to capture change for both the parent and child. Results: Improvements in receptive vocabulary, use of key word signs, gesture use and a child’s ability to respond to joint attention were noted in the majority of child participants. Children who attended all three terms of the intervention seemed to benefit the most from the PELD programme as they demonstrated a wide range of gestures, understood the most words and used the most Lámh signs post-intervention as reported by their parents. With regards to parent outcomes, all parents were successful in adapting their parenting style and a notable increase in each parents’ ability to follow their child’s lead, join in and play and incorporate a time delay into parent-child interactions was observed. Parents also used language that was developmentally appropriate for their children and increased their use of labelling and repetition of key words post-intervention. Conclusions: The PELD programme is the first parent-child interaction therapy to be tailored specifically to children with DS who are of a very young age. There was some indication that the PELD intervention can support the development of early language skills and the communicative intentions of young children with DS while also upskilling their parents in specific communication and interaction strategies that promote the language development of their child.
Occupation, identity and belonging within community: experiences of mental health disability
(University College Cork, 2020-04-18) Cassidy, Caoileann; Jackson, Jeanne; Lynch, Helen
Background: This is a qualitative research study exploring the perspectives of Irish people with self-reported mental health disability in participating in occupation within their community environments. The relatedness of occupation to health and the concept of belonging requires further research and understanding within the discipline of Occupational Science and within the practice of Occupational Therapy. Methodology: Purposive sampling was employed to recruit three participants, from one national mental health support organisation. A phenomenological and narrative framework was adopted in this research. This informed the use of narrative interviews and observation methods to gather data about occupations enacted by participants within their community environments. Open ended narrative interviews were adopted to encourage storied accounts of participants’ experiences, with each participant engaging in two interviews. Following the first interview, each participant collaborated with the researcher in planning an observation session, with the researcher as complete participant, in a chosen occupation within their local, familiar environment. Following this each participant engaged in a second interview with the researcher. Data Collection and Analysis: Digital audio recordings were transcribed anonymously and verbatim from interviews, coupled with field notes from observations, using thematic analysis. This analysis upheld the integrity of each story while illuminating shared meaning of participants’ chosen occupations. Findings: In answer to the research questions, two primary themes were identified, with each theme encompassing two subthemes. The first theme “Experiencing Normality and Promoting Health” explores how participants in this study experienced feeling or anticipated feeling normal through their participation in occupation. Additionally, they chose occupations to promote their physical and mental health when navigating changes to their identities as a result of their mental health distress or disability. The second theme was “Meaning Making and Experiences of Inclusion and Exclusion within Community” exploring participants meaning making through occupation in their local environments, within places and amongst others. The first subtheme captures how participants participated in meaning making with others. The second focuses on their experiences of inclusion and exclusion with stigma emerging from their surrounding environments, impacting feelings of belonging. Discussion: The findings of this study inform understanding of occupation and expand knowledge of its relationship to health, specifically mental health. It contributes to existing research concerning the impact of the social world on a person’s occupational choices, possibilities and resultant identities. Further these findings have elicited greater understanding about the meaning of these occupations to participants and how this enabled their participation through “being” and “belonging” in their communities. Conclusion: The results of this study contribute to theory generation of occupation within the discipline of occupational science and to the clinical practice of occupational therapy. The findings of the current research indicate that stigma and experiences of exclusion prevail for people with mental health disabilities. Results also find that participation in occupation, within affirming environments can create experiences of normality and promote health. Further, participation in occupation fosters experiences of inclusion and belonging.
Caregiver readiness for hospital discharge of an older adult
(University College Cork, 2020-04-30) Galvin, Eileen; Wills, Teresa; O'Mahony, Mairin; University College Cork
Aim: To explore caregiver readiness for the hospital discharge of an older adult. Background: Older adults rely on their caregivers during hospital discharge. However, caregivers are not routinely included in discharge preparation. Caregivers’ experiences of hospital discharge have been studied retrospectively between one week and three months. However, no study used the attributes of readiness to guide the research and none of the caregivers were interviewed within twenty-four hours of hospital discharge when experiences are foremost in their minds. Method: The study was qualitative descriptive. Using the attributes of readiness for hospital discharge to develop an interview guide, nine semi-structured interviews with caregivers took place within 24 hours of hospital discharge during the summer of 2017. Data were analysed using content analysis. Findings: The findings that emerged from the data are presented under the four attributes of readiness for hospital discharge: Caregivers’ physical readiness, Caregivers’ psychological readiness, Support for caregivers and Information and knowledge. An overarching category of “Wanting to do what’s best” also emerged. Findings highlight that overall, caregivers are not ready to take the older adult home from hospital. In addition, low referral rates of older adults to PHN services were highlighted. Conclusion: The results of this unique study provide a picture of the current state of caregiver readiness for the hospital discharge of an older adult. In addition, the need for early preparation of caregivers for the hospital discharge of an older adult is highlighted which includes early referral to PHN services. Impact: Nursing staff require focused education on the preparation of caregivers for hospital discharge. In addition, development of a tool to assess caregiver physical and psychological readiness is necessary. Further research and assessment of caregivers longitudinally will give more insight into caregiver needs, experience and progress. Ultimately, ensuring caregivers are ready for hospital discharge of an older adult will assist older adults remaining at home, which is ultimately where they want to be.
Regional and developmental profile of hippocampal neuroplasticity in adolescence: lessons from animal studies
(University College Cork, 2020-07) Cusack, Kevin; Nolan, Yvonne M.; English, Jane
Adolescence, the period between childhood and adulthood is a sensitive period of development, open to social and environmental influences. Neuroplasticity, which includes the processes of neurogenesis, synaptogenesis, myelination, and synaptic pruning, is the ability of the brain to change continuously throughout the lifespan. During adolescence, an increased bout of synaptogenesis and myelination occurs, followed by synaptic pruning. The hippocampus, which plays a key role in learning and memory, as well as emotional regulation, is particularly sensitive to influences that change neuroplasticity. However, little is known about the differential expression of specific neuroplasticity proteins in the hippocampus at early, mid and late adolescence, and between males and females. Three timepoints which mimic human adolescence development in rats (PND 28, PND 42 and PND 56) were selected. Male and female Sprague-Dawley rats were used; 8 males and 8 females at each of the three timepoints. Mass spectrometry was used to analyse the hippocampal samples to determine the differential expression of proteins between the three timepoints and between males and females at each adolescent period. Neuroplasticity-related proteins implicated in neurogenesis, axon development and myelination were most prominent early in adolescence with a consistent trajectory of developmental change through adolescence. Differential expression of neuroplasticity-related proteins was observed between the sexes at each time point, indicating differences in the timing of hippocampal development processes between males and females at the same age. This study found evidence for a difference in the timing of hippocampal development between the sexes with females possibly at a more advanced stage of hippocampal development compared to males of the same age.
Patients’ and carers’ experience and perceptions of the pilot Integrated Care Programme for Older Persons in Cork City (ICPOP): a qualitative evaluation
(University College Cork, 2020-07-23) Shinkwin, Claire; McCullagh, Ruth; McVeigh, Joseph
Introduction: The older adult population is increasing dramatically. Older adults experience prolonged hospital admissions and are at a higher risk of experiencing hospital-associated decline, with frail older adults being even more vulnerable. This increases their risk of mortality, readmission, and care-dependency. The Integrated Care Programme for Older Persons (ICPOP) was introduced in Ireland in response to these demanding demographic changes, with an aim of improving quality of life for older adults by supporting them to live well in their homes. The framework for the ICPOP places an emphasis on the importance of evaluating the structural, process and patient outcomes in order to achieve the service objectives. This thesis addresses patient outcomes, with an overall aim of exploring patients’ and carers’ experiences and perceptions of the ICPOP in Cork city. The participants’ feedback will be used to further refine the service. Method: In order to approach this research question, it was necessary for the researcher to gain a more in-depth knowledge on the characteristics of similar models of care worldwide, and their effectiveness compared to usual inpatient care. Therefore, this project was divided into two phases. Phase 1 consisted of a systematic review. The main objective of this review was to determine whether hospital at home is an effective model of care for acutely unwell older adults, compared to usual inpatient care. A secondary aim was to further explore the optimal parameters (i.e. frequency, intensity, duration, and type of care provided) in the delivery of care, to improve patient outcomes. The findings of this review were also used to inform the interview schedule which was used in Phase 2. In Phase 2, the researcher addressed the main research question using qualitative research methods. Semi-structured interviews were carried out with patients and carers in their own homes. The interview guide was developed with guidance from the themes, as listed by Proctor et al (2011), exploring implementation, service, and client outcomes. Data was analysed using thematic analysis. The resulting categories were then organised using the constructs of the conceptual framework for implementation outcomes. Results: In phase 1, a total of 917 studies were screened. Among these, 23 studies were identified as highly relevant, with 16 studies ultimately fulfilling the inclusion and exclusion criteria and being included for review. The systematic review was limited by a lack of newly published randomised controlled trials and a high risk of bias across many studies. In the context of these limitations, there was evidence to support hospital at home in the areas of patient and carer satisfaction and carer burden, compared to usual inpatient care. It was not possible to determine optimal parameters in the delivery of care due to the under-reporting of interventions across many of the studies. The qualitative study revealed service users’ overwhelming satisfaction with the ICPOP. Key elements contributing to this included the accelerated discharge from hospital and home-based rehabilitation, caring personnel, the positive, therapeutic relationships developed with staff, reassurance for patients and carers and the patient’s functional recovery. Some uncertainties regarding the duration of care, end of care and rehabilitative element of the service were also highlighted. Conclusion: This study has made an important contribution to the topic of hospital at home models of care for the older adult. This study demonstrated that the patients’ and carers’ satisfaction with this service is largely due to receiving care in the home environment, the social aspect of care, reassurance for both the patient and carer, and the patients’ functional recovery. The importance of continuity of care and social relationships was also highlighted. Further high quality RCTs are necessary in order to determine the effectiveness of hospital at home care compared to usual inpatient care for the older adult, with accurate reporting of interventions in order to explore the optimal characteristics for the delivery of this model of care to improve patient outcomes.
Preclinical evaluation of a novel AAV-GDF5 vector in a 6-OHDA model of Parkinson’s disease and evaluation of the effect of 6-OHDA on the expression of HDACs
(University College Cork, 2020-08-17) Shanahan, Sarah Elizabeth; Sullivan, Aideen M.; O'Keeffe, Gerard W.
Neurotrophic factors have shown promising results as potential disease-altering treatment methods for Parkinson’s disease (PD). However, there are many risks associated with surgically accessing such deeply located regions of the brain as the striatum or substantia nigra. Directly administered proteins will be broken down, meaning that such an intervention would have short-lived benefits. For this reason, the use of viral vectors to deliver neurotrophic factor genes has become a popular alternative, as this would allow for prolonged expression of the neurotrophic factor. In this study, we used an AAV2/5 vector to deliver GDF5 to the substantia nigra of rats, both at the same time as striatal administration of 6-OHDA and two weeks prior to 6-OHDA administration. We found that those animals which received AAV2/5-GDF5 had similar levels of TH immunopositive cell body loss in the substantia nigra and similar decreases in TH immunstaining in the striatum as those animals which had just received 6-OHDA. The 6-OHDA rodent model is commonly used in PD research. As such, it is important to understand the characteristics of this model in order to best interpret observations made when using this model. In this study we examined how 6-OHDA administration affects HDAC3, 5 and 9 expression in the rat brain. HDAC5 and HDAC9 are of particular interest to our group as our group has shown that their expression correlates with three markers of dopaminergic neurons in both the mouse and human substantia nigra. HDAC3 was also selected as an example of a different HDAC class. We found that striatal administration of 6-OHDA resulted in bilaterally increased expression of HDAC3 and 9 in the striatum, no changes were seen in HDAC3 in the midbrain, while HDAC9 was unilaterally upregulated in the midbrain. HDAC5 is known to shuttle between the nucleus and the cytoplasm of the cell. For this reason, we examined nuclear and cytop-lasmic levels of HDAC5. HDAC5 was also found to be upregulated bilaterally in the midbrain and it was observed that this increase was restricted to the nucleus.
The development of a dementia communication intervention for undergraduate nurses based on the VERA framework
(University College Cork, 2020-08-17) Sisk, Ali-Rose; Naughton , Corina; University College Cork
Background: Patients with dementia experience emotional distress due to difficulties communicating physical and social needs. This is compounded by inadequate dementia communication skills among qualified nurses and student nurses. Aim: The project aims were to adapt a dementia communication training intervention, examine acceptability among undergraduate nursing students and test the feasibility of designing a randomized controlled trial (RCT) to evaluate the intervention. Methods: The intervention involved a 1.5-hour dementia communication workshop based on the VERA framework and used information giving, role play, discussion and student manual. Study Design: A quasi-experimental pre-post control trial was used with mixed-methods data collection (student survey, semi-structured interview and non-participatory observations of students in clinical practice). Results: In total, 49 students completed the post intervention survey (i=26, c=23). There was a significant increase in awareness of person-centred response scores in the intervention group 13.1 (SD1.95), compared to the control group 10.6 (SD3.0), p=0.03, there was no other significant differences. Eleven students were observed interacting with patients with dementia (n=219 interactions). There was no significant difference between the groups with missed opportunity for positive interactions observed in both groups. Qualitative interviews with students (n=8) that received the intervention indicated they valued the training but inconsistently used the dementia communication skills in practice. Barriers to implementing the new skills were a lack of role modelling from qualified staff, busy environment and little emphasis on person-centred interactions in clinical practice. Conclusion: The VERA dementia communication intervention was well received by students and may increase their ability to identify person-centred responses, but this may not change communication behaviour. This feasibility study, suggest that a RCT may not be possible and other pragmatic trail designs should be used to evaluate this education intervention.
Epitope mapping of the E2 glycoprotein, including the hypervariable region 1, of the hepatitis C virus genotype 3a, in the context of humoral immune pressure
(University College Cork, 2020-12) Walsh, Nicole Ellen; Fanning, Liam J.; O'Farrelly, Cliona; Bristol-Myers Squibb
The hepatitis C virus (HCV) is an enveloped +ssRNA virus, belonging to the family Flaviviridae. HCV is notable for displaying extraordinary genetic diversity and variability, having seven recognised genotypes and over sixty subtypes. HCV is responsible for the disease known as hepatitis C, which is associated with cirrhosis and hepatocellular carcinoma (HCC). The Global Hepatitis Report released by the World Health Organisation (WHO) in 2017 estimated that viral hepatitis was responsible for 1,340,000 deaths in 2015. The report also estimated that 71,000,000 people have ongoing HCV infections. HCV is largely transmitted via exposure to infected blood, with intravenous drug use accounting for approximately 55% of cases. HCV infections can be categorised as acute or chronic. During chronic HCV infections, antibodies (Abs) are produced against HCV - however, the host Abs are unable to neutralise HCV and only accelerate the evolution of circulating HCV variants. HCV variants resistant to the current generation of host Abs become the dominant variant through selective pressure. The variants of HCV within a host are known as quasispecies. Although the host Ab response is not able to resolve the chronic HCV infection, some Abs can bind to particular HCV variants. These Abs form complexes with virus particles and are known as AAVs (antibody-associated virus). AAVs are detectable in the blood of patients with chronic HCV infections and examination of these AAVs could reveal conserved viral structures and vulnerable HCV epitopes. Twenty genotype 3a serum and plasma samples from patients with chronic HCV infections were obtained from the National Virus Registry Laboratory (NVRL) and from the Molecular Virology Research and Diagnostic Laboratory (MVDRL). HCV genotype 3a was chosen for this research project given its prevalence (estimated to account for 17.9% of chronic HCV infections), resistance to treatment, and increased risk of causing severe steatosis and HCC when compared to other genotypes. Building on previous research carried out by the MVDRL, the patient samples were screened for the presence of AAVs. Initially, AAV+ samples were going to be processed and used to generate HCV pseudoparticles (HCVpp). The HCVpp system is a model system that incorporates the E1E2 glycoprotein from HCV into a plasmid. The E1E2 glycoprotein is responsible for HCV entry and infection, meaning the HCVpp can be used to infectivity and Ab neutralisation assays. However, the E1E2 glycoproteins could not be extracted from the AAV+ patient samples. Instead, the IgG from the AAV+ samples was extracted and used for a series of neutralisation experiments on HCV pseudoparticles generated using the HCV H77 isolate. H77 (GenBank: AAB67037.1) is an infectious genotype 1a isolate that has undergone complete genome sequencing. The Abs that showed the greatest neutralisation potential against the H77 pseudoparticles were selected for epitope mapping. The epitope mapping procedure tested the selected Ab samples against a synthesised H77 E2 glycoprotein structure, and characterised the sites where the patient Abs bound to the synthesised E2. This revealed vulnerable epitopes on the HCV E2 glycoprotein. The epitope mapping also revealed a large number of glycosylation sites around the vulnerable epitopes – a phenomenon known as glycan shielding. Glycan shielding is used by a number of viruses (including HCV and HIV) to protect conserved and vulnerable epitopes from Abs. However, strategies are being developed to counter viral glycosylation, including modifications to glycosylation sites and the use of polysaccharides derived from non-mammalian sources as therapeutic agents against glycosylated viruses.
Determining the biopsychosocial factors of chronic pain in older adults to inform the development of a risk appraisal checklist for use in long term care: a Delphi study
(University College Cork, 2021) Clifford, Michelle; Cornally, Nicola; Fitzgerald, Serena
Background: In long term care (LTC), the prevalence of pain is 43% (van Kooten et al., 2017), and this, coupled with the high prevalence of dementia (Zimmerman et al., 2014), lends itself to complex practice issues in terms of pain assessment. The American Society of Pain Management Nursing published the hierarchy of pain assessment techniques developed by Pasero and McCaffery (2011) to guide pain assessment in people unable to self-report. The first step of this framework focuses on awareness of potential causes of pain, hence the importance of identifying the biopsychosocial factors associated with chronic pain in older adults. Improving pain assessment can improve older adults' quality of care and the ultimate quality of life. However, very little research has supported the early identification of older persons at risk of unreported chronic pain due to communication impairment or a neurodegenerative disease such as dementia. Using a multi-dimensional lens, this research aims to identify the biopsychosocial factors of chronic pain in older adults to inform the development of a risk appraisal checklist for use in long-term care. Methods: Chen et al. (2016) proposed a four-phase process when employing a Delphi technique to develop a quality instrument. These phases include identifying an expert panel, generating initial factors, and identifying the final factors and instrument development. The first three phases were the focus of this study. Following the identification of an expert panel in chronic pain, phase two involved completing a scoping review to create a list of the initial factors. There was a total of fifty-nine biopsychosocial factors identified from the empirical literature. These factors were used to inform round one of the modified e-Delphi surveys. A consensus agreement rate of 50% was applied for this study for round one, median ≥4 for round 2 and ≥90% agreement for inclusion in round three. Thematic analysis of open-ended responses also took place. Results: Thirteen experts in gerontology and chronic pain participated in a minimum of two rounds. There was a desirable international spread from eight countries, and 68.4% of the experts had >21 years of experience in their field of expertise. The 59 initial factors identified from the scoping review were presented to the experts in round one. Fifty (84.7%) biopsychosocial factors achieved a 50% or greater agreement of factor importance. Sixty-three factors were presented to the expert panel in round two, 33 factors were rerated from round one, nine factors were modified, and the experts identified 21 new factors. The results from round two, a total of fifty-one factors, achieved a median of ≥4 and were presented in round three. The final twenty-two factors that achieved ≥90% consensus agreement in round three for inclusion included; age, female gender, arthritis, lower back pain, malignancy, family history of chronic pain, multiple comorbidities, trauma and/or accident, multiple sites, anxiety and depression, social isolation/loneliness, post-traumatic stress, childhood physical/sexual abuse, maladaptive beliefs, poor sleep hygiene and/or insomnia, substance abuse, low socioeconomic background, chemotherapy medication, history of opioid use and poor access to health care. Conclusion: This study has laid the foundations for future research and innovation in comprehensive pain assessment in older adults, focusing on identifying risk factors in older persons for whom accurate self-report of chronic pain is challenging due to communication and/or cognitive impairment. The twenty-two factors identified from this study will inform the development and testing of the Chronic Pain Risk Appraisal Checklist (C-PRAC) for LTC use.
The development of a core school-based Lámh vocabulary to facilitate effective communication between children with Down syndrome and their communication partners in the first year of mainstream primary school
(University College Cork, 2021-01-08) Lyons, Caoimhe; Frizelle, Pauline; Irish Research Council
Background: In Ireland, the entry-level key word sign (KWS) training for teachers and school staff is the Lámh Module 1 training course, which does not contain vocabulary specifically chosen to support school-age Lámh users. However, if KWS is to be used successfully by children with Down syndrome (DS) in a mainstream school environment, it is essential that communication partners have access to a meaningful, contextually appropriate sign vocabulary. Aim: To identify the Lámh vocabulary needs of children with DS and their communication partners over the course of the first year of mainstream primary school, with the aim of developing a core school-based Lámh vocabulary. Method: Five key groups contributed signs to the core vocabulary: participants with DS in junior infants (n=6), their teachers (n=5), special needs assistants (n=8), and peers (n=9), and the researcher (a Speech and Language Therapist). The researcher contributed signs based on observations of the classroom, the participants with DS contributed signs during guided tours of the school environment, and the teachers, SNAs and peers contributed signs by means of structured interviews. This data collection took place at four time points over the school year. Signs were considered to be part of the core vocabulary if they were contributed five times or more over the course of the year, and by three or more of the groups. Results: The core school-based Lámh vocabulary contained 140 words, including 132 Lámh signs and eight words that do not currently have a Lámh sign. Only 55 (39%) of the 140 signs recommended as core vocabulary for schools are part of the training currently most commonly accessed by school staff. The remaining 77 signs (55%) are part of more advanced training. Conclusion: The current study provides new insights into the complex process of vocabulary selection for children who use Lámh in a mainstream school environment. In addition, it highlights the importance of access to a functional sign vocabulary in facilitating an inclusive approach to education, and enhanced communicative practice by all of those engaging with children with DS in mainstream primary school.
Deciphering the role of microbially-derived metabolites on the microbiota-gut-brain axis
(University College Cork, 2021-01-25) Spichak, Simon; Cryan, John; Dinan, Timothy G.; Science Foundation Ireland; Irish Research Council
The trillions of microbial organisms residing in the gut, microbiota, are now recognized as major modulators of physiology and health, quickly becoming one of the most exciting emerging areas in neuroscience. Preclinical and clinical research alike suggests that the metabolites produced by these gut microbes modulate brain, behavior and disease. Short-chain fatty acids, tryptophan metabolites and bile acids are promising targets for new microbiome-based therapies. But, little is known about their mechanisms. To this end, the second chapter of the thesis collates 278 studies relating to the human microbiota-gut-brain axis, identifying trends and technical/bioinformatics limitations. These studies across different disorders of the brain as well as healthy human behavioral functions. Then a 35 of these studies was reanalyzed with an up-to-date bioinformatics pipeline. New tools, mainly the gut-brain modules provide a predictive framework for identifying whether these gut microbial metabolic pathways are dysregulated in brain diseases and disorders. We uncovered evidence of disease-related alterations in microbial metabolic pathways in Alzheimer’s Disease, schizophrenia, anxiety and depression. Previous human studies suggest that astrocyte immunity and metabolism is affected by short-chain fatty acids. Thus we grew primary male and female mouse astrocyte cultures, treating them with acetate, butyrate and propionate. Butyrate treatment (0 – 25μM) increased gene expression of Bdnf and Pgc1-α expression, implicating histone-deacetylase inhibitor pathways only in female cells. Acetate (0 – 1500 μM) positively correlated with Ahr and Gfap expression in males, suggesting an immune modulatory role. These findings show a novel sex-dependent impact of acetate and butyrate, but not propionate on astrocyte gene expression. These studies increase understanding of microbial metabolites and how they might impact the brain. It also provides guidance to improve and direct future investigations aimed at identifying the mechanisms of other metabolites.
Sensitising pancreatic cancer cell lines to electrochemotherapy by modulation of the cell cycle
(University College Cork, 2021-03) Cooke, Katie Deniese; Forde, Patrick; Collins, Dearbhaile; Breakthrough Cancer Research
We chose to research pancreatic cancer as pancreatic adenocarcinoma (PAC) is quite the aggressive disease, which even with the vast improvements in cancer treatments over recent years still has limited treatment options. Monotherapy treatment of pancreatic cancer with chemotherapy drugs initially show hopeful results, decreased disease symptoms and can lead to a slight improvement in survival but unfortunately does often ends in recurrence (1–3). Surgery has shown to be successful for respectable tumours followed by chemotherapy. Chemotherapy alone has proven to be associated with chemoresistance and can be quite intense, often patients are not able to continue with strong treatment regimes. FOLFIRINOX is classed as the gold standard for treating PAC, however, patient fitness ultimately determines suitability. Electrochemotherapy (ECT) is a new and emerging cancer therapy which allows for decreased doses of chemotherapy drugs to be used. We have evaluated pancreatic cancer cell lines response to low dose chemotherapy and Electrochemotherapy. The human pancreatic cell lines BxPC-3, PANC-1, and MIAPaCa-2 were used for all experiments in this thesis. Based on previous studies we predicted that PANC-1 cells would be most resistant to drug treatment followed by BxPC-3 and MIAPaCa-2 cells. All cell lines survived treatment with Gemcitabine (GEM) and Nab-paclitaxel (Nab), however, they had decreased survival when treated with 5’Fluorouracil (5’FU). When Electrochemotherapy (ECT) was applied to the cell line using GEM, Nab and 5’FU, cells survived and recovered but again had decreased survival and recovery with 5’FU ECT. Cells were also treated with Oxaliplatin (Ox) ECT, this had more of an impact to cell survival than with GEM/Nab/5’FU ECT. Bleomycin and cisplatin are the conventional drugs used with ECT due to their effectiveness (4,5), but we chose Ox as it is part of the FOLFIRONOX cocktail which is the gold standard for treating patients with PAC. Electrochemotherapy (ECT) has emerged as a promising treatment strategy for patients with pancreatic cancer (PC). ECT is safe for patients and has reduced side effects of systemic chemotherapy as drugs are concentrated to treatment site(6). ECT has shown to be very effective in treating melanoma (7). ECT has recently been used to treat locally advanced PC (8). Development of preclinical and clinical agents that inhibit cell cycle progression have proven effective in the treatment of cancer. Targeting cyclin dependent kinases (CDKs) and cell cycle checkpoint proteins can induce cell cycle arrest and apoptosis in cancer cells. Cell cycle deregulation is regularly seen in pancreatic cancer. Cells grow out of control and can lead to mortality. Controlling the deregulation with cell cycle inhibitors has shown to be beneficial for survival. Our study aimed to investigate CDK4/6 inhibitors and their ability to inhibit cell cycle progression. We specifically chose CDK4/6 inhibitors as they have proven to be quite effective in previous studies of breast cancer(9). Our hypothesis was that using a cell cycle inhibitor as a pre-treatment to ECT would make cells more susceptible to treatment. We used Palbociclib (PAL), a CDK4 inhibitor which causes cell cycle arrest at G1 and prevents cells progressing to S phase. We carried out experiments to investigate CDK4 levels in cells treated with PAL and cell cycle profiles of these cells post treatment. PAL prevents cell from passing to S phase of the cell cycle. We could not finish our planned work due to time, ceased funding and the COVID-19 global pandemic. We theorise that this combination treatment could enhance the efficiency of ECT and could potentially be translated into a clinical study as a new treatment option and improve patient quality of life.
Assessment of respiratory motor units in the mdx mouse model of Duchenne muscular dystrophy
(University College Cork, 2021-03-22) Murphy, Kevin H.; O'Halloran, Ken D.; Burns, David
Duchenne muscular dystrophy (DMD) is a fatal neuromuscular disease characterised by the absence of the structural protein dystrophin. Respiratory failure is the leading cause of premature death in DMD. Although respiratory insufficiency is recognized as a hallmark of DMD, respiratory control is relatively understudied. We hypothesized that enhanced drive in respiratory motor pathways preserves ventilatory capacity compensating for severe respiratory muscle weakness. Male wild-type (n=23) and mdx (n=23) mice were studied. Breathing was examined during normoxia and chemo-challenge with hypercapnic-hypoxia. In urethane (1.7 g/kg i.p.) anaesthetised mice, diaphragm, external intercostal and genioglossus electromyogram (EMG) and motor unit recordings were performed during baseline conditions and in response to chemo-stimulation. Diaphragm muscle function was examined ex vivo. Diaphragm muscle function is severely impaired in young mdx mice. Despite substantial diaphragm muscle weakness, freely-behaving mdx mice can increase ventilation during chemostimulation with hypercapnic-hypoxia. Motor unit recordings revealed an increase in the number of active units for diaphragm and genioglossus muscle. There were no major differences in the firing frequency of motor units in the respiratory muscles. Diaphragm EMG activity was depressed in mdx mice during baseline and maximum chemostimulation, compared to wild-type. In conclusion, severe mechanical disadvantage of the diaphragm is evident across a range of stimulation frequencies, yet there is a preserved capacity to raise ventilation in young mdx mice indicating a significant ventilatory reserve. Motor unit remodelling is evident in the diaphragm of mdx mice, but ultimately diaphragm EMG activity is impaired. The combination of reduced neural activation of the diaphragm and intrinsic weakness reveals major compromise in the neuromuscular function of the diaphragm in mdx mice as early as 8 weeks of age. The novel observations of this study coupled with other work by our group suggest that support from accessory muscles is critical to the support of respiratory performance in mdx mice, which may have relevance to DMD.
The effects of stressors during early life on hippocampal neurogenesis and microglial activation in the male and female brain
(University College Cork, 2021-04-05) McGovern, Andrew Joseph; Nolan, Yvonne M.; O'Leary, Olivia
Stress during critical periods of brain development and maturation such as adolescence is associated with an increased risk of developing stress-related psychiatric disorders which are more common in women than men. Early life stress such as maternal separation (MS), juvenile stress (JS) and inflammatory insults like lipopolysaccharide (LPS), have been found to induce anxiety and depressive-like behaviours and decrease adult hippocampal neurogenesis in rodents. However, the effects of early life stress on adult hippocampal neurogenesis and associated function have been mostly assessed in male rodents. The impact of early life stress on microglia, which are involved in the regulation of adult hippocampal neurogenesis and dendritic remodelling, has also been predominantly examined in male rodents. Thus, in this study we assessed adult hippocampal neurogenesis and hippocampal microglia following LPS administration in MS juvenile female Sprague-Dawley rats and following JS in male and female Sprague-Dawley rats in adulthood. MS increased the number of newly born hippocampal neurons in the ventral hippocampus, reduced the dendritic complexity of newly born neurons in the whole hippocampus and increased the soma size of microglia, indicating activation. LPS reduced newly born hippocampal dendritic complexity and increased the number of microglia in the dorsal hippocampus. Conversely, LPS administration in MS rats reduced the number of microglia in the dorsal hippocampus and MS attenuated microglial activation in response to LPS. LPS administration in MS increased dendritic complexity in the granule cell layer (GCL) and further reduced dendritic complexity in the ventral but not dorsal hippocampus of juvenile female rats. JS did not affect hippocampal neurogenesis in adult male or female rats but reduced the cell soma size of microglia in the GCL in the dorsal hippocampus of females. We observed significant sex differences in adult rats; females had fewer newly born neurons with less dendritic complexity in the dorsal hippocampus than males. There were also fewer microglia in the molecular layer (ML) of the hippocampus in adult female than male rats. Together the data here shows that the effect of early life stressors differentially affects hippocampal neurogenesis and hippocampal microglia dependent on age, sex and subregion of the hippocampus analysed.

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