Massey Documents by Type

Permanent URI for this communityhttps://mro.massey.ac.nz/handle/10179/294

Browse

Subject: search.filters.subject.Diseases

Search Results

Now showing 1 - 10 of 120
  • Thumbnail Image
    Item
    Veterinarians' perspectives of neurology : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Veterinary Science at Massey University, Manawatū, New Zealand
    (Massey University, 2024-10-29) Shea, Anita
    Negative perspectives of neurology are commonly reported in medical education and have led to concerns regarding patient care and insufficient numbers of neurologists. Most of the proposed contributors to this “neurophobia” relate to intellectual difficulty learning and applying neurology knowledge. However, most studies to date have explored neurophobia superficially and differences between how neurophobia is defined and how it is measured challenge what the term means and our understanding of why it develops. Despite this lack of clarity, there are increasing numbers of reports that cite educational interventions to combat neurophobia. While the medical and veterinary professions share many similarities, there is very little research exploring neurophobia in veterinary medicine. It is unclear whether negative perspectives of neurology are common in veterinarians, and what contributes to the development of veterinarians’ perspectives of neurology. The overarching aims of this research were to better understand veterinarians’ perspectives of neurology, how and why they develop, and the effect they can have on further learning and clinical experiences. This research investigated veterinarians’ and veterinary students’ perspectives of neurology using a mixed method approach. Thematic analysis of semi-structured interviews explored how veterinarians’ experiences, and their reactions to those experiences, contributed to their overall attitude towards neurology. Statistical analysis of subsequent surveys of veterinarians and undergraduate veterinary students focused on those with negative or positive attitudes towards neurology to further explore these differing perspectives. The findings of all studies were integrated to obtain a holistic understanding of how similar inciting experiences can lead to different attitudes towards neurology. Intellectual difficulty learning and applying neurology was reported by most participants, regardless of their attitude towards neurology. Differences between participants with negative or positive attitudes towards neurology were often dictated by the individual’s affective responses to that difficulty, which in turn were shaped by personality traits, values, professional identity, and the ability of the individual to resolve internal conflict. Resolution of internal conflict could improve one’s attitude towards neurology. In contrast to medical literature on neurophobia, these findings suggest that an individual’s attitude towards neurology is determined by the way they react to intellectual difficulty, not the difficulty itself. This distinction has implications for educational interventions for any difficult subject, not just neurology.
  • Thumbnail Image
    Item
    Loss of production and animal health costs in assessing economic burden of animal disease.
    (World Organisation for Animal Health, 2024-08) Marsh TL; Pendell D; Schrobback P; Shakil G; Tozer P; Rushton J; Cecchini M
    This article focuses on identifying the loss of production and costs (or lack thereof) associated with livestock health as well as animal disease externalities, with the intent to estimate economy-wide burden. It limits its scope to terrestrial livestock and aquaculture, wherein economic burden is predominately determined by market forces. Losses and costs are delineated into both direct losses and costs and indirect losses and costs, as well as ex post costs and ex ante costs. These costs include not only private expenditures but also public expenditures related to the prevention of, treatment of, and response to livestock disease. This distinction is important because a primary role of government is to mitigate externalities. The article then discusses market impacts and investments. Finally, it provides selected examples and illustrative observations and discusses future directions for research and application. Cet article examine les pertes de production et les coûts associés (ou non) à la santé animale ainsi que les externalités liées aux maladies animales, dans le but d’estimer le fardeau pour l’ensemble de l’économie. L’examen se limite à la production d’animaux terrestres et aquatiques, secteurs où le fardeau économique est principalement déterminé par les forces du marché. Les pertes et les coûts sont répartis en pertes et coûts directs et indirects, ainsi qu’en coûts ex post et ex ante. Ces coûts comprennent non seulement les dépenses privées, mais aussi les dépenses publiques liées à la prévention, au traitement et aux réponses aux maladies des animaux d’élevage. Il s’agit d’une distinction importante car l’une des fonctions premières d’un gouvernement est d’atténuer les externalités. Les auteurs examinent ensuite les impacts sur les marchés et les investissements. Pour conclure, à partir d’exemples choisis et d’observations illustrant leur propos, les auteurs proposent des voies d’exploration pour la recherche et ses applications.
  • Thumbnail Image
    Item
    Changing epidemiology of Leptospirosis in New Zealand, with a focus on the novel strain of Leptospira borgpetersenii : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Veterinary Science at Massey University, Palmerston North, New Zealand
    (Massey University, 2024-12-25) Sokolova, Maryna
    In New Zealand, leptospirosis has been a common disease in dairy cattle since the 1940s. Six pathogenic Leptospira serovars from two species have been identified as endemic to New Zealand: Leptospira borgpetersenii serovars (sv.) Hardjobovis (Hardjo), Tarassovi, Ballum, Balcanica, and Leptospira interrogans sv. Pomona and Copenhageni. From these, sv. Pomona and Hardjo are the most commonly reported in cattle, and sv. Ballum, Tarassovi, and Copenhageni are less common. The estimated 99% of the national dairy herd is vaccinated against leptospirosis by vaccines containing antigens to Pomona and Hardjobovis and sometimes vaccines also include Copenhageni antigen. Vaccines for protecting dairy cows against Tarassovi were unavailable in New Zealand before December 2023. Historically, leptospirosis due to Tarassovi infection in New Zealand cattle was considered accidental and clinically unimportant. Serosurveys of apparently healthy cattle in New Zealand showed that over the past fifty years, Tarassovi seroprevalence increased from 6% (50/300) at MAT ≥ 50 to 18% (698/3878) at MAT ≥ 48. More recently, a serology and urine shedding study from 2015- 2016 evaluated the status of 4,000 dairy cows from 200 randomly selected farms, stratified by New Zealand's geographical location and herd size. The study found that on the animal level, 17% of the study animals showed evidence of past infection with Tarassovi, as defined by at least one sample reacting at MAT ≥ 48 for the study's purposes. Moreover, 96% (90/94) of PCR-positive urine samples were sequenced, and 68% (54/80) of those were found to have a novel allele in the sequenced region at the glmU loci. Thus, the use of molecular diagnostic tools, specifically molecular typing targeting a partial region of the glmU gene, allowed New Zealand researchers to identify a novel L. borgpetersenii strain, informally called strain (str.) Pacifica, in the urine of these cows. The 2015-2016 survey reported that dairy cows with Tarassovi titres were associated with urinary shedding, as determined by microscopic agglutination test (MAT) and polymerase chain reaction (PCR) testing, respectively. Because of this association, str. Pacifica is thought to belong to the serogroup Tarassovi. Additionally, the DNA of str. Pacifica has been retrospectively detected in cattle and deer samples dating back as early as 2007. Moreover, the 19-year (1999-2007) average annual incidence of notified human cases of Tarassovi leptospirosis was estimated at 12.59/100,000 in dairy farmers, compared to an overall annual average incidence of 2.01/100,000. These coincidental findings raised public health concerns. Therefore, at least some cases of Tarassovi seropositivity, as identified by MAT and reported before 2021, could partially be attributed to str. Pacifica. To confirm str. Pacifica's serogroup, isolation by culture and complete genetic characterisation of an isolate are required. Since str. Pacifica was only recently detected, its epidemiology, morphology, maintenance, and pathogenicity in the host population, as well as its impact on animal and human health, were not well understood. In this study, we investigated the possibility of isolating str. Pacifica from cow's urine by running a series of laboratory experiments where laboratory-adapted strains were used as a proxy for L. borgpetersenii str. Pacifica in the absence of an isolate to better understand its growth requirements. Laboratory-adapted Leptospira borgpetersenii strains were seeded into different types of media, and Leptospira growth rates were evaluated (Chapter 3). As a result, we ruled out unsuitable media and growth conditions, and this work helped to select the best media and growth conditions for a follow-up field investigation, where freshly collected cow's urine was seeded into selected media. Str. Pacifica was isolated from the urine of a shedding cow using HAN medium at 37°C and 5% CO2. However, this medium failed to sustain str. Pacifica and the culture was lost (Chapter 4). In addition, over the 2020-2021-2022 milking seasons, we collected and tested blood and urine samples from dairy farms, identified as str. Pacifica positive from the 2016 survey. Our results revealed that str. Pacifica was still maintained in the same dairy herds six years after initial detection. Moreover, we reported an estimated prevalence ratio (PR) of 7, indicating that the prevalence of shedders was seven times as high at the beginning than at the end of lactation in primiparous cows (Chapter 4). These findings provide evidence that str. Pacifica is adapted to dairy cows in New Zealand, and the peak shedding in primiparous heifers occurs in early lactation. Since the highest levels of str. Pacifica shedding were detected at the start of the milking season during peak milk production, which also coincides with a relatively short 3-month mating period, the associations between str. Pacifica and milk production and reproductive performance of milking cows were also investigated using herd test data and serological and PCR test results of the 2016 survey. Statistical models, including linear, logistic, and generalised mixed models with fixed and random effects, as well as a shared frailty survival model, were used to evaluate the associations between str. Pacifica positivity and reproduction (Chapter 5) and milk reproduction (Chapter 6) in dairy cows. Results of the statistical analysis of the association between str. Pacifica positivity and reproduction (Chapter 5) of dairy herds showed that str. Pacifica delayed the time from calving to conception (HR = 0.84; 95%: CI 0.74-0.96), although there was no effect on the pregnancy rate (Chapter 5). An analysis of milk production data did not reveal any associations with str. Pacifica at either animal or herd level (Chapter 6). The absence of clinical signs and the lack of association with milk production and reproduction at both the animal and herd levels provides further evidence towards str. Pacifica being well adapted to dairy cows. Therefore, evidence from this thesis suggests that dairy cattle are the maintenance host for str. Pacifica in New Zealand. It is also important to note that str. Pacifica shedders can infect people, especially dairy farmers, milkers, and farm workers who are in regular contact with str. Pacifica-shedding animals. Therefore, the prevention of str. Pacifica transmission via vaccination or the use of appropriate personal protective gear should be prioritised.
  • Thumbnail Image
    Item
    Wild bovid habitat and infectious disease risk in Thailand : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Veterinary Science, School of Veterinary Sciences, Massey University
    (Massey University, 2024-11-07) Horpiencharoen, Wantida
    Wild bovids are a diverse group of typically large, hoofed ruminant mammals that play crucial functions in ecosystems as seed transporters and prey for predators to maintain biodiversity. However, their conservation status varies from least concern to critically endangered with extinction, depending on the regions and remaining population. The expansion of agricultural areas and livestock farming has led to habitat loss and natural resource sharing, likely increasing the risk of disease transmission and pathogen circulation between humans, wildlife, and domestic animals at the shared habitats or the interface areas. This thesis aims to identify the habitat suitability of five wild bovids remaining in Thailand, understand the consequences of introducing infectious disease into the population, and identify where there is a risk of disease transmission. Therefore, three main studies were conducted: 1) identifying suitable areas for five wild bovid species, including gaur, banteng, wild water buffalo, mainland serow and Chinese goral in Thailand; 2) simulating the impact of infectious diseases of cattle on wild bovid populations, and; 3) mapping potential risk areas between wild bovids and cattle. Initially, I used ecological niche modelling to identify the habitat suitability of five wild bovids remaining in Thailand. Due to poor model predictions for two species (mainland serow and Chinese goral), I excluded these two models from further analyses. The results indicated that over 50% of the potentially suitable areas for the three modelled species (gaur, banteng, wild water buffalo) were located outside protected areas close to human populations and agricultural areas. Then, I simulated the number of animals in a model gaur population with and without infections over 100 years with 100 repetitions using stochastic mathematical models. I selected six bovine infectious diseases with different traits, such as incubation and infectious periods or fatality probabilities, including anthrax, bovine tuberculosis, haemorrhagic septicaemia, lumpy skin disease, foot and mouth disease and brucellosis. I introduced an individual infected animal into a closed population for each infectious disease. The disease-free gaur population grew over time, with infections with different traits having different impacts. The populations infected with chronic diseases (e.g. bovine tuberculosis and bovine brucellosis) showed the greatest decline, while diseases with high mortality but acute disease or high transmission rates with low mortality had less impact on the populations. Finally, I mapped the potential risk areas for disease transmission, assuming that high cattle density and habitat suitability increased transmission risk between wild bovids and livestock. The results also indicated that the potential high-risk areas were at the interface areas at the forest edges where interactions between wildlife and cattle occur. All my studies and findings will require further investigation and validation to gain a deeper and better understanding of the complexity of infectious diseases within wildlife populations and the dynamics of their distributions, but they contribute to supporting wildlife conservation and implementing disease mitigation measures to prevent disease transmission among the populations by highlighting where wild bovids might have suitable habitat, what types of infections may be problems and where mitigation may be better targeted.
  • Thumbnail Image
    Item
    Characterising CG5846 (Peep) in Drosophila melanogaster neural function : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Biochemistry at Massey University, Manawatū, New Zealand
    (Massey University, 2024) Wilson, Sarah Jean
    Histone deacetylase 4 (HDAC4) is a transcriptional regulator that has been implicated in a number of neurodevelopmental and neurodegenerative diseases that are associated with intellectual disability, cognitive defects, and/or memory loss. Both the accumulation of nuclear HDAC4 and its loss-of-function have been linked to these conditions, therefore exploring HDAC4’s role in neuronal function is essential to understand the molecular mechanisms underlying these diseases. In Drosophila, overexpression of HDAC4 results in defects in morphogenesis of axons in the mushroom body, a structure essential for memory formation, as well as long-term memory defects and disruption to the development of the compound eye. The molecular mechanisms underlying these HDAC4-induced phenotypes are currently unknown. RNA-sequencing on fly heads in which HDAC4 was overexpressed has previously been performed and showed few genes were transcriptionally regulated by HDAC4. In addition, an enhancer/suppressor rough eye phenotype screen has also been performed which identified a number of genes that interact genetically in the same molecular pathway as HDAC4. To further investigate the molecular mechanisms underlying HDAC4 dysfunction, an RNA interference (RNAi) based candidate screen for potential HDAC4-interactors was performed, which involved quantification of developmental defects in the mushroom body and eye following RNAi knockdown of each candidate. It was hypothesised that if a phenotype resulting from RNAi knockdown was similar to that induced by HDAC4 overexpression, that candidate may function in similar molecular pathways. A single candidate-interactor was selected (CG5846, named Peep) for further investigation. On overexpression, Peep and HDAC4 co- distribute in nuclei of mushroom body neurons, however no physical interaction was detected. Furthermore, overexpression of Peep did not rescue the HDAC4-induced mushroom body or eye defects. Due to the uncharacterised nature of Peep, a thorough investigation was performed to assess the importance of Peep in survival, longevity, motor function, brain development, courtship learning and memory, and wing development. Peep was observed to be essential for survival of glial cells and for normal mushroom body development, which warrants further investigation. Reduced expression of Peep also resulted in a unique severe necrotic eye phenotype, and through this, Peep was shown to play a potential role in processes involved in regulating mitochondrial and proteasomal function, apoptosis and oxidative stress. These data provide the first documented characterisation of the functional role of Peep in Drosophila development and provide the basis for further investigation into the underlying molecular mechanisms involved in mushroom body and eye development.
  • Thumbnail Image
    Item
    Investigating HDAC4 aggregation in a Drosophila model of neuronal development : a dissertation presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Biochemistry at Massey University, Manawatū, New Zealand
    (Massey University, 2024-06-21) Hawley, Hannah Rose
    Histone deacetylase four (HDAC4) is essential in neuronal development and function, and dysregulation of HDAC4 has been observed in a number of neurodevelopmental and neurodegenerative diseases, including Alzheimer’s and Parkinson’s diseases. In particular, its aberrant nuclear accumulation is a common feature among these diseases, and it has been observed that upon upregulation or accumulation in the nucleus, HDAC4 forms punctate foci in neuronal nuclei. Previous research in a Drosophila model determined that overexpression of HDAC4 disrupted both neuronal development and long-term memory, and this was largely mediated by the nuclear pool of HDAC4. Based on these data, it was hypothesised that aggregates of HDAC4 are responsible for the neurotoxicity that leads to disrupted neurodevelopment and memory. Therefore, this study aimed to determine whether the presence of HDAC4 nuclear aggregates correlated with neurodevelopmental deficits in a Drosophila model of neurodevelopment, and if so, how they mediate their toxic effects. The N-terminus of HDAC4 forms homo-oligomers in solution, and it was hypothesised that full-length HDAC4 similarly oligomerises, and that this is required for its aggregation in neuronal nuclei. Mutations predicted to prevent oligomerisation were introduced into the N- terminus of HDAC4 and were shown to significantly reduce aggregation of HDAC4 in Drosophila neurons. Furthermore, their presence also reduced the severity of HDAC4 overexpression-induced impairments in neurodevelopment. Conversely, stabilisation of oligomerisation increased aggregation and the severity of neurodevelopmental phenotypes, together indicating that aggregation positively correlates with the severity of neurodevelopmental deficits. HDAC4 aggregates have been previously shown to sequester the transcription factor MEF2, and further investigation revealed that the presence of MEF2 stabilised aggregation and increased the severity of defects in neuronal development. Importantly, targeting the interaction between HDAC4 and MEF2 reduced the severity of these defects. Other than MEF2, the composition of HDAC4 aggregates is unknown, and therefore immunoprecipitation-coupled mass spectrometry was performed on nuclear HDAC4 to identify candidate interactors of aggregates. This revealed a number of proteins with roles in neuronal development and function, as well as those involved in splicing and protein homeostasis, suggesting that aggregates may be impairing these processes to mediate toxicity. Together these data indicate that nuclear aggregation of HDAC4 impairs neurodevelopment, and may constitute a novel biomarker of disease or therapeutic target. Given the overlap in aetiology between neurodevelopmental and neurodegenerative diseases, further investigation of whether HDAC4 aggregation contributes to the severity and/or progression of neurodegenerative disorders is warranted.
  • Thumbnail Image
    Item
    Host-microbiota interactions underlying functional gastrointestinal disorders and the impact of gold kiwifruit consumption : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Nutritional Science at Massey University, Albany, Manawatū, Palmerston North, New Zealand
    (Massey University, 2023-05-18) Carco, Caterina
    The microbial ecosystem exists in a mutualistic relationship with its host, contributing to a healthy gastrointestinal tract. Growing evidence supports the role of microbial-immune interactions in functional gastrointestinal disorders (FGIDs), including irritable bowel syndrome (IBS). However, these mechanisms are poorly understood. It has been hypothesised that taxonomic and gene abundance in the faecal microbiota and gene expression of peripheral blood mononuclear cells (PBMCs) could discriminate FGID subtypes (functional constipation (FC), IBS constipation, functional diarrhoea (FD), IBS diarrhoea) from each other and healthy subjects (controls). A second hypothesis was that consuming two gold kiwifruit daily for four weeks had a different effect on the microbial composition and gene abundance than psyllium in constipation predominant FGID subjects or controls. A systems biology approach was used to address these hypotheses. Different microbial compositional and gene abundance profiles were associated with constipation and/or diarrhoea, particularly facultative anaerobes and obligate fermenters, and genes related to tyrosine metabolism, secretion systems and micronutrient utilisation. Differentially PBMC expressed immunoglobulin variable domain genes were shared among FGIDs, except for IBS constipation. Increased expression levels of interferon-induced genes and those linked to the complement system and platelet functions characterised the immune signature of functional constipation. Increased expression levels of immunoglobulin variable domain associated with immunoglobulin E/G receptor-mediated pathways characterised the immune signature of IBS diarrhoea and FD. Further analyses showed that computationally selected microbial, immune gene and symptomatic variables were associated with constipation or diarrhoea predominant FGIDs, and that symptoms remain the best way to discriminate among FGIDs or controls than PBMC genes or microbial taxa except for FC, which was best discriminated from other FGIDs or controls by selected PBMC genes. Eggerthella and Bacteroides were the only genera that differed between subjects consuming gold kiwifruit or psyllium or between each intervention compared to pre-intervention levels, regardless of the digestive health status of the subjects. This PhD thesis presents novel insights into the host-microbiota interactions underlying FGIDs and the microbiota responses to daily consumption of two gold kiwifruit over four weeks in constipation predominant FGID subjects. The knowledge generated can be used for future research on food-based treatments supporting gastrointestinal health and comfort.
  • Thumbnail Image
    Item
    ABAtE : active bacteriophages for AFB eradication : a thesis submitted in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Genetics at Massey University, Auckland, New Zealand
    (Massey University, 2023) Kok, Danielle
    The European honey bee (Apis mellifera) is one of the most important livestock animals in New Zealand. Their value comes from a combination of pollination services and the production of honey for export, notably mānuka honey. American Foulbrood (AFB) is a disease of honey bee larvae and pupae and is caused by the bacterial pathogen, Paenibacillus larvae. AFB is the most serious disease that infects honey bees and is present in almost all countries where honey bees are found. AFB has been present in New Zealand since 1877 and spread to all parts of the country within 10 years. Unlike other countries, the use of antibiotics in hives infected with P. larvae is prohibited under New Zealand law and infected hives must be destroyed immediately. Bacteriophages (phages) are a well-studied alternative to antibiotics. Phages are simple viruses that kill specific bacteria and are highly abundant in the environment with an estimated 1031 globally. Phages have been shown to work effectively as a prophylactic to infection from certain diseases. With the growing antimicrobial resistance crisis, phages are becoming a well-studied and promising alternative to antibiotics. The aim of this research was to investigate the use of phages as a preventative measure against AFB. Previous work undertaken in other laboratories around the world has shown that phages can be isolated from healthy hives and nearby soil and that AFB pathogens are susceptible to destruction by these phages. In this work, we collected soil samples using citizen led science from hives throughout New Zealand. From soil samples provided we isolated 26 novel phages that are destructive to P. larvae. Selected phages were combined into a cocktail and tested against vegetative forms of P. larvae in in-lab testing. All phages were also sequenced and annotated and compared to other P. larvae phages that have been isolated around the world. This project: ABAtE (Active Bacteriophages for AFB Elimination), provides the groundwork study for an innovative approach to naturally protecting NZ beehives against AFB.
  • Thumbnail Image
    Item
    Investigation of lameness and claw disorders in New Zealand dairy goats : a multidisciplinary approach : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Animal Science at Massey University, Manawatū, New Zealand
    (Massey University, 2022) Jaques, Natasha
    New Zealand dairy goat farmers have problems preventing and treating lameness caused by claw disorders within their herds. There is scarce information about lameness and claw disorders in commercial dairy goat herds nationally and internationally. The two aims of this thesis were: to acquire information on the level of clinical lameness and the types and level of claw disorders present on three dairy goat farms in New Zealand and to explore the epidemiological, productivity, and genetic aspects of lameness and claw disorders. Information on lameness and claw disorders was collected on herds 4 or 5 times between July 2019 and June 2020. Additional information collected were age, stage of lactation, milk production, pedigree, kidding date, and lactation type. The prevalence of clinical lameness and claw disorders fluctuated across the production year at levels that differed on each farm. Farm A had the highest average of clinical lameness (23%), followed by farms B and C (12 and 10%, respectively). For the investigation of claw disorders, the main claw disorders studied were horn separation, granulomas, and rot. Farm C had the highest prevalence of horn separation (83%), while farm A had the highest prevalence of rot and granulomas (19 and 14%). Rot and granulomas increased the odds of clinical lameness (OR= 2.10-7.02). Compared to goats walking normally, severe lameness had the highest milk production losses of 7.10% and 8.56% in extended and seasonal lactation goats, respectively. The average income losses ranged from NZD 26 to 104 per goat. The heritability (h2) estimates for lameness occurrence and susceptibility were 0.07 and 0.13, respectively, and the h2 estimates of claw disorder susceptibilities ranged from 0.02 to 0.23. This thesis identified that clinical lameness caused by claw disorders is a problem on dairy goat farms in New Zealand and reported the negative impact of severe lameness on milk production. Additionally, breeding for resistance or tolerance of clinical lameness and claw disorder may be possible. Further large-scale studies are needed to understand the risk factors of clinical lameness and claw disorders. Small-scale studies are required to investigate effective treatments to manage claw disorders in dairy goats.
  • Thumbnail Image
    Item
    The gut‐bone axis in coeliac disease : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Nutritional Science at Massey University, Manawatū, New Zealand
    (Massey University, 2022) Schraders, Katie Elizabeth Coad Pedley
    Coeliac Disease (CD) is a lifelong autoimmune disease, highly prevalent in New Zealand, triggered by ingestion of gluten in genetically susceptible individuals. It leads to villous atrophy and nutrient malabsorption which often compromises bone mineral density (BMD). Although a gluten‐free diet (GFD) usually improves symptoms, BMD is often not fully resolved. Persistent low BMD may be due to ongoing gut inflammation and malabsorption, or the uncoupling of bone formation and resorption. Previous research indicates that individuals with CD and low BMD may have altered bone signalling pathways, particularly in the expression of receptor activator of NF‐κβ ligand (RANKL) and osteoprotegerin. RANKL is implicated in both the initiation of the immune response and persistent low BMD because it has a role in bone resorption, via the differentiation of osteoclasts, and a possible role in translocating gluten across the gut, via the expression of microfold cells. The objective of this PhD was to examine underlying mechanisms underpinning low BMD in individuals with CD using a small intestinal organoid model which allows for investigation of otherwise inaccessible gut cells and signalling pathways implicated in the gut‐bone axis. A further study, Close to the Bone, investigated BMD in premenopausal women with CD compared to healthy controls. A third online A Gut Feeling study investigated dietary advice that individuals consuming a GFD in New Zealand receive, focusing on bone health. Although the organoid research was interrupted due to the SARS‐CoV‐2 pandemic, the model was established using murine tissue and future research opportunities were identified. The results of the Close to the Bone study demonstrated no differences in BMD between the coeliac group and healthy controls but identified further research into bone density in people with CD in New Zealand was warranted. This study raised concerns about iodine intake and status in people with CD. The A Gut Feeling study found inconsistencies in advice given to individuals diagnosed with CD. The research identified that the organoid model offers potential for future study of the gut‐bone axis and that individuals with CD are at risk of nutritional deficiencies but often are not advised well or referred for a bonescan.