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Pietravalle, SteÌphane. "Modelling weather/disease relationships in winter wheat diseases." Thesis, University of Reading, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.402602.
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Haslam, Bryan (Bryan Todd). "Learning diseases from data : a disease space odyssey." Thesis, Massachusetts Institute of Technology, 2017. http://hdl.handle.net/1721.1/114002.
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Thesis: Ph. D., Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, 2017.Cataloged from PDF version of thesis.
Includes bibliographical references (pages 253-280).
Recent commitments to enhance the use of data for learning in medicine provide the opportunity to apply instruments and abstractions from computational learning theory to systematize learning in medicine. The hope is to accelerate the rate at which we incorporate knowledge and improve healthcare quality. In this thesis, we work to bring further clarity to the ways in which computational learning theory can be applied to update the collective knowledge about diseases. Researchers continually study and learn about the complex nature of the human body. They summarize this knowledge with the best possible set of diseases and how those diseases relate to each other. We draw on computational learning theory to understand and broaden this form of collective learning. This mode of collective learning is regarded as unsupervised learning, as no disease labels are initially available. In unsupervised learning, variance is typically reduced to find an optimal function to organize the data. A significant challenge that remains is how to measure variance in the definition of diseases in a comprehensive way. Variance in the definition of a disease introduces a systematic error in both basic and clinical research. If measured, it would also be possible to use computers to efficiently minimize variance, providing a great opportunity for learning by utilizing medical data. In this thesis, we demonstrate that it is possible to estimate variance in the disease taxonomy, effectively estimating an error bar for the current definitions of diseases. We do so using the history of the disease taxonomy and comparing it with a variety of external data sets that relate diseases to attributes such as symptoms, drugs and genes. We demonstrate that variance can be significant over relatively short time periods. We further present methods for updating the disease taxonomy by reducing variance based on external disease data sets. This makes it possible to automatically incorporate information contained in disease data sets into the disease taxonomy. The approach also makes it possible to use expert information encoded in the taxonomy to systematically transfer knowledge and update other biomedical data sets that are often sparse (e.g. - symptoms associated with diseases). A natural question stemming from these results is how granular does data need to be to make improvements? For instance, is patient-level data necessary to enable learning at the macro level of disease? Or are there strategies to extract information from other kinds of data to alleviate the need for very granular data. We show that detailed, patient-level data is not necessarily needed to extract detailed biological data. We do so by comparing disease relationships learned from clinical trial metadata to disease relationships learned from a detailed genetic database and show we can achieve similar results. This result shows that we can use currently available data and take advantage of computational learning to improve disease learning, which suggests a new avenue to improving patient outcomes. By reducing variance within diseases using data available today, we can quickly update the space of diseases to be more precise. Precise diseases lead to better learning in other areas of medicine and ultimately improved healthcare quality.
by Bryan Haslam.
Ph. D.
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Guallar-Hoyas, Cristina. "Prospecting for markers of disease in respiratory diseases." Thesis, Loughborough University, 2013. https://dspace.lboro.ac.uk/2134/12415.
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Asthma, current detection methods and metabolites proposed as asthma markers are described. The limitation of the disease diagnosis is outlined and metabolomics is introduced as the approach carried out within this research with the potential to measure the group metabolites that characterise the metabolic responses of a biological system to a specific disease. Chemistry underlying breathing, current breath collection and analytical techniques are described as well as detection and data processing technology associated within our research. A work-flow for the collection, analysis and processing of exhaled breath samples in respiratory diseases is described. The non-invasive sampling method allows collection of exhaled breath samples on children and adults without experiencing any discomfort. The analysis of exhaled breath samples using thermal desorption gas chromatography mass spectrometry outlines the use of retention index for the alignment of VOCs retention time shifting over time. This methodology enables the creation of a breath matrix for multivariate analysis data processing where each VOC is defined by retention index and most intense fragments of the mass spectrum. This methodology is tested in two cohorts of participants: paediatric asthma and severe asthmatic participants whose breath profiles are compared against healthy controls and within the two asthmatic phenotypes to prospect the markers that differentiate between the different groups. Eight candidate markers are identified to discriminate between asthmatic children and healthy children and seven markers between asthmatics undergoing therapy and healthy controls. The database from severe and paediatric asthma is compared, establishing seven non-age related markers between the two groups. A new interface is developed for the faster analysis of exhaled breath samples using thermal desorption ion mobility mass spectrometry. The interface front end has been modified and optimised to achieve the best sensitivity and resolution of VOCs in exhaled breath. A preliminary study carried out in a small cohort of volunteers shows the feasibility of the technique for the differentiation of asthmatic and healthy adults.
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Mancini, Sabrina. "Assessment of a screening test for MMP-8 activity in the diagnosis of periodontal diseases." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape11/PQDD_0028/MQ40755.pdf.
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Gu, Mei. "Mitochondrial function in Parkinson's disease and other neurodegenerative diseases." Thesis, University College London (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.322371.
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Ullah, Naseem. "Disease modules identification in heterogenous diseases with WGCNA method." Thesis, Högskolan i Skövde, Institutionen för biovetenskap, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-16692.
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The widely collected and analyzed genetic data help in understanding the underlying mechanisms of heterogeneous diseases. Cellular components interact in a network fashion where genes are nodes and edges are the interactions. The failure in individual genes lead to dys-regulation of sub-groups of genes which causes a disease phenotype, and this dys-functional region is called a disease module. Disease module identification in complex diseases such as asthma and cancer is a huge challenge. Despite the development of numerous sophisticated methods there is a still no gold standard. In this study we apply different parameter settings to test the performance of a widely used method for disease module detection in multi-omics data called Weighted Gene Co-expression Network Analysis (WGCNA). A systematic approach is used to identify disease modules in asthma and arthritis diseases. The accuracy of obtained modules is validated by a pathway scoring algorithm (PASCAL) and GWAS SNP enrichment. Our results differ between the tested data sets and therefore we cannot conclude with recommendations for an optimal setting that could perform best for multiple data sets using this method.
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Gadd, Malin. "Cardiovascular diseases in immigrants in Sweden /." Stockholm : Neurotec, Center for family and community medicine, Karolinska institutet, 2006. http://diss.kib.ki.se/2006/91-7140-627-1/.
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Franco, Iborra Sandra. "Mitochondrial quality control in neurodegenerative diseases: focus on Parkinson’s disease and Huntington’s disease." Doctoral thesis, Universitat Autònoma de Barcelona, 2018. http://hdl.handle.net/10803/565668.
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Darrerament s’han produït avanços importants que han contribuït al coneixement dels mecanismes de disfunció cel·lular i mort en la malaltia de Parkinson (MP) i en la malaltia de Huntington (MH). Ambdues malalties són trastorns del moviment que es caracteritzen per la pèrdua específica de neurones dels ganglis basals, les neurones dopaminèrgiques de la substància nigra (SN), en el cas de la MP i les neurones espinoses de l’estriat, en el cas de la MH. Malgrat les diferències, ambdues comparteixen processos patològics comuns com la presència de proteïnes malplegades, l’estrés oxidatiu i disfunció mitocondrial. La mitocòndria és la font d’energia principal en les cèl·lules eucariotes, però també és un orgànul dinàmic relacionat amb una gran quantitat de processos cel·lulars. La disrupció de la homeòstasis mitocondrial i la subseqüent disfunció mitocondrial juguen un paper important en la patofisiologia de les malalties neurodegeneratives. El manteniment de la integritat mitocondrial a través de diferents mecanismes de control és crític per a la superviviència neuronal. Aquesta tesi es centra en l’estudi dels mecanismes de control de qualitat mitocondrial en la MP i la MH, per tal d’entendre millor els mecanismes que duen a la mort cel·lular.
En el primer capítol, he estudiat el transport de proteïnes a la mitocòndria en models in vitro i in vivo de la MP. In vitro, la inhibició del complexe I produeix una alteració del transport de proteïnes a la mitocòndria així com una disminució dels nivells de proteïnes OXPHOS, acumulació de proteïnes agregades i disminució dels nivells de chaperones mitocondrials. Per tal de restablir el transport de proteïnes mitocondrials es van sobreexpressar dos components clau del sistema de translocases: la translocasa de la membrana externa 20 (TOM20) i la translocasa de la membrana interna 23 (TIM23). La sobreexpressió in vitro de TOM20 i TIM23 va restaurar el transport de proteïnes mitocondrials i va alleugerar la disfunció mitocondrial i la mort cel·lular. La inhibició del complexe I en ratolins també dóna lloc a una alteració del transport de proteïnes mitocondrials i produeix neurodegeneració del sistema dopaminèrgic. La sobreexpressió de TIM23 va restaurar parcialment el transport de proteïnes i va protegir lleugerament les neurones dopaminèrgiques de la SN. En canvi, la sobreexpressió de TOM20 va ser incapaç de millorar el transport de proteïnes mitocondrials i, fins i tot, va exacerbar la mort cel·lular. Aquests resultats posen de relleu el paper de la disfunció del transport de proteïnes mitocondrials, en particular de dos dels seus components, en la patogènesis de la MP i suggereixen la necessitat de futurs estudis es centrin en altres elements d’aquest sistema.
En el segon capítol, he estudiat el paper de la proteïna huntingtina en la mitofàgia i com la seva mutació, que dóna lloc a una expansió de glutamines, pot afectar a aquesta funció. Per a tal fi, he treballat en un model in vitro de cèl·lules estriatals ST-Q7 (control) i ST-Q111 (mutant). En condicions fisiològiques, la mitofàgia induïda no es troba mitjançada pel reclutament de parkin als mitocondris despolaritzats. La huntingtina mutada afecta la mitofàgia induïda a través de l’alteració de la seva funció de scaffold en diferents passos del procés de mitofàgia: (i) activació d’ULK1 a través de l’alliberament de mTORC1, (ii) formació del complexe Beclin 1-Vps15,(iii) interacció dels adaptadors de mitofàgia OPTN i NDP52 amb huntingtina i, (iv) amb LC3. Com a resultat, els mitocondris de les cèl·lules ST-Q111 estan més danyats i tenen una respiració mitocondrial deficient. Aquests resultats demostren la presència d’una alteració en la mitofàgia com un mecanisme lligat a la MH. En conclusió, el descobriment de noves dianes mitocondrials en la MP i MH emfatitza el paper important que juga el control de qualitat mitocondrial en la neurodegeneració.In the past years, several important advances have expanded our understanding of the pathways that lead to cell dysfunction and death in Parkinson’s disease (PD) and Huntington’s disease (HD). Both diseases are movement disorders characterized by the loss of a specific subset of neurons within the basal ganglia, dopaminergic neurons in the substantia nigra pars compacta (SNpc), in the case of PD, and medium spiny neurons in the striatum, in the case of HD,. Despite distinct clinical and pathological features, these two neurodegenerative disorders share critical underlying pathogenic mechanisms such as the presence of misfolded and/or aggregated proteins, oxidative stress and mitochondrial anomalies. Mitochondria are the prime energy source in most eukaryotic cells, but these highly dynamic organelles are also involved in a multitude of cellular events. Disruption of mitochondrial homeostasis and the subsequent mitochondrial dysfunction plays a key role in the pathophysiology of neurodegenerative diseases. Therefore, maintenance of mitochondrial integrity through different surveillance mechanisms is critical for neuronal survival. In this thesis I have studied in depth some mitochondrial quality control mechanisms in the context of PD and HD, in order to broaden the knowledge about the pathomechanisms leading to cell death. In the first chapter I have studied mitochondrial protein import in in vitro and in vivo models of PD. In vitro, complex I inhibition, a characteristic pathological hallmark in PD, impaired mitochondrial protein import. This was associated with OXPHOS protein downregulation, accumulation of aggregated proteins inside mitochondria and downregulation of mitochondrial chaperones. Therefore, we aimed to reestablish the mitochondrial protein import by overexpressing two key components of the system: translocase of the outer membrane 20 (TOM20) and translocase of the inner membrane 23 (TIM23). Overexpression of TOM20 and TIM23 in vitro restored protein import into mitochondria and ameliorated mitochondrial dysfunction and cell death. Complex I inhibition also impaired mitochondrial protein import and led to dopaminergic neurodegeneration in vivo. Overexpression of TIM23 partially rescued protein import into mitochondria and slightly protected dopaminergic neurons in the SNpc. On the contrary, TOM20 overexpression did not rescue protein import into mitochondria and exacerbated neurodegeneration in both SNpc and striatum. These results highlight mitochondrial protein import dysfunction and the distinct role of two of their components in the pathogenesis of PD and suggest the need for future studies to target other elements in the system. In the second chapter, I have studied the role of huntingtin in mitophagy and how the polyglutamine expansion present in mutant huntingtin can affect its function. For such, I worked with differentiated striatal ST-Q7 (as control) and ST-Q111 (as mutant) cells, expressing full length huntingtin. In these conditions, induced mitophagy was not mediated by Parkin recruitment into depolarized mitochondria. Mutant huntingtin impaired induced mitophagy by altering wildtype huntingtin scaffolding activity at different steps of mitophagy process: (i) ULK1 activation through its release from the mTORC1, (ii) Beclin1-Vps15 complex formation, (iii) interaction of the mitophagy adapters OPTN and NDP52 with huntingtin and (iv) with LC3. As a result, mitochondria from ST-Q111 cells exhibited increased damage and altered mitochondrial respiration. These results uncover impaired mitophagy as a potential pathological mechanism linked with HD. In conclusion, we have discovered new mitochondrial targets for PD and HD emphasizing the important role that mitochondrial quality control plays in neurodegeneration
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Rodeiro, Carmen Lucia Vidal. "Some issues in disease map modelling and surveillance of diseases." Thesis, University of Aberdeen, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.415553.
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The first part of this thesis is dedicated to the study of edge effects in maps of disease. The aim of the analyses is to find out how the estimation of the risk from a disease near boundaries can be affected by the boundary position. The behaviour of a selection of models for disease mapping is evaluated when different edge conditions exist in the data. Disease mapping plays an important role in monitoring the health of a community. Plotting new cases on a map is a frequently used technique for monitoring the spread of infectious diseases and from a statistical point of view it is relevant to consider how statistical methods can be developed or employed to aid the task of surveillance. In the second part of this thesis, methodological and practical issues in developing a rapid response in a spatial surveillance system are discussed. In particular, I review and propose methods for the detection of changes. A simulation study is set up to assess if these methods are good at detecting changes in risk over space and time. An application to a real data set is also given. Surveillance should be performed as quickly as possible but complex Bayesian models require the use of sampling methods to provide estimates of posterior expectations, and these estimates may be computationally expensive to obtain. To aid this, special computational approaches can be considered. One option is to resample the output form initial iterations to provide reweighted estimates as time protocols. This is known a filtration or sequential Monte Carlo. In the third part of this thesis I review the use of sequential Monte Carlo methods (in particular, the Resample-Move algorithm) for dynamic systems, focusing on their use in a surveillance context. This is followed by an application to a real data set where a comparison between the use of McMC methods and the Resample-Move algorithm is carried out.
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Schwengler, Franziska. "Prion Diseases." Diss., lmu, 2005. http://nbn-resolving.de/urn:nbn:de:bvb:19-36790.
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Kirsch, Florian [Verfasser]. "Economic aspects of disease management programs in chronic diseases / Florian Kirsch." München : Verlag Dr. Hut, 2018. http://d-nb.info/1164293648/34.
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Ryan, Philip. "An Investigation Into Novel Molecular Strategies Targeting Neurodegenerative Diseases." Thesis, Griffith University, 2020. http://hdl.handle.net/10072/395102.
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Neurodegenerative diseases are characterised by the progressive loss of neuron function and structure. The most prevalent neurodegenerative diseases are hypothesized to be due to the misfolding and accumulation of specific proteins in the brain. Alzheimer’s disease (AD) is suspected to result from the aggregation of amyloid-β (Aβ) or tau proteins, Parkinson’s disease (PD) from the aggregation of α-synuclein (α-syn), and so on for numerous other diseases including Huntington’s disease, amyotrophic lateral sclerosis, and Creutzfeldt-Jakob disease. There are no curative therapies for any of these fatal diseases, only palliative care is available in some cases currently. Research is currently focussed on modulating the aggregation processes common amongst the diseases. Various projects are dedicated to targeting the protein monomers, or small oligomeric assemblies, present at the early stages toward therapy. Modern strategies to target these proteins involve the use of peptide-based agents, effective at selectively binding the proteins through engaging with multiple sites along the protein sequences; and multitarget directed ligands (MTDL), which engage with multiple pathological factors to produce an overall beneficial effect.
Here we set out to investigate various novel chemical scaffolds that we envisaged may prove effective at inhibiting protein aggregation mechanisms in the hopes of identifying new strategies and promising leads. Following review of the literature, compound scaffolds were designed based on existing data and then synthetic chemistry was employed to construct panels of candidate inhibitors. The compounds synthesised were then screened against protein aggregation including Aβ, α-syn and prion formation.
Chapter 2 describes the development of a novel strategy to construct selective glycopeptide-based inhibitors of protein aggregation. This strategy employs the peptide sequences that are reported to recognise the target proteins in their monomeric or oligomeric state and then hinder their aggregation via a disruptive glycoside unit. This component of the project led to the identification of an inhibitor of α-syn aggregation and provided proof-of-concept for the design. The rationale was also used for the construction of Aβ and tau-targeted inhibitors, however evaluation of their effectiveness is ongoing.
Chapter 3 describes the use of the quinazoline scaffold to construct MTDLs designed to be capable of modulating the aggregation of α-syn and the formation of prion proteins. This component of the project led to the identification of a panel of highly potent inhibitors of prion formation in yeast, which are undergoing further evaluation currently, as well as a number of leads that are effective α-syn aggregation inhibitors.
Chapter 4 describes investigation into α-syn oligomerisation modulating analogues of anle138b, a promising candidate undergoing preclinical development. The compounds designed and synthesised were found to be as effective as inhibiting α-syn aggregation in vitro as the preclinical candidate.
Chapter 5 describes attempts at investigating the thiazolone scaffold for use in the design of MTDLs targeting protein aggregation. Unfortunately, this objective of the project was hampered by challenging syntheses and unfavourable solubility profiles, discouraging further commitment to the component of the project.
In summary, a number of novel molecular scaffolds were designed, synthesised and found to be effective modulators of protein aggregation implicated in multiple neurodegenerative diseases. This project has culminated in the identification of promising leads against pathological targets for PD, prionopathy, and AD therapy, as well as contributing to the knowledgebase to stimulate future research efforts.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Pharmacy and Pharmac
Griffith Health
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Lopez-Alvarez, Jordi. "Evaluation of early indicators of disease progression in dogs with degenerative mitral valve disease." Thesis, Royal Veterinary College (University of London), 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.669194.
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Mableson, Hayley Elizabeth. "The disease-scape of the new millennium : a review of global health advocacy and its application." Thesis, University of Edinburgh, 2014. http://hdl.handle.net/1842/17855.
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The global disease scape is constantly shifting, influenced by demographic transitions, altering the balance of the burden of infectious and non‐communicable diseases. The epidemiological transitions can be divided into three stages: the first, an increase in infectious disease burden as populations settled, then grew into towns and cities providing conditions for infectious agents to maintain spread; the second transition follows industrialisation, changes in lifestyle, diet and improved sanitation whereby infectious diseases are reduced and non‐communicable disease (NCD) prevalence increases; the third transition describes the re‐emergence of infectious diseases as the AIDS epidemic and other emerging and re‐emerging disease outbreaks lead to an increasing burden of infectious diseases, particularly in developing countries. Analysis of the disease‐scape has been carried out using WHO Global Burden of Disease data and correlation to demographic factors calculated using World Bank Development Indicators. The balance of chronic NCDs and infectious diseases can be represented numerically as the unit rate of infectious to non‐communicable diseases. The rate, which indicates at which end the continuum lies can then be correlated to these demographic development indicators to assess the factors which are influential to the continuum. As the balance of infectious and non‐communicable diseases around the world alters, the focus of the advocacy at the global health level has been examined to assess if the trends follow that of the shifting continuum. This has been carried out through an assessment of the WHO World Health Assembly (WHA) resolutions adopted annually between 1948 and 2013 on the subject of infectious and/or non-communicable diseases. The principle of International health stemmed from the need to contain the international spread of communicable diseases, so it is not surprising that in the first decade of the WHO, 88% of the resolutions adopted for infectious and non‐communicable disease were adopted for infectious diseases. In the latest ten years of the WHO, 72% of the Assembly resolutions for infectious and non‐communicable diseases were focused on infectious diseases; this indicates that while there has been a shift in the balance, the adopted resolutions still focus heavily on infectious diseases. An example of how advocacy can elevate diseases to a higher position on the global health agenda is that of the Neglected Tropical Diseases. Following the Millennium Development Goals, this group of seventeen diseases has been highlighted as being “neglected” in terms of funding, research and political will. A review of the campaign to highlight this shows how global health advocacy can elevate diseases to a prominent position on the global health agenda. With this in mind, the advocacy for a sub‐group of Neglected Zoonotic Diseases has been examined at the WHA level. The results highlight the sporadic nature of support to control these diseases, and that activism for control of some of the major zoonotic diseases remains lacking. Rabies is explored as an example of a disease for which there are recommendations and support at the global level for the control and elimination of the disease, but for which barriers to control exist locally in endemic countries. The advocacy for diseases at the global health level has the possibility to impact the priorities of health care within individual nations. However the advocacy at this level may take time to reflect the changes within the disease‐scape. The impact of such advocacy is also limited by local political will, availability of resources and local cultural implications. Therefore there is a need to ensure that efforts to control diseases are tailored to specific populations and that resources are made available to support the advocacy.
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Chochó, Karen S. "Hispanic migrants and cross-border disease control of Arizona's vaccine preventable diseases." restricted, 2008. http://etd.gsu.edu/theses/available/etd-04222008-151047/.
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Thesis (M.Ph.)--Georgia State University, 2008.Title from file title page. Richard Rothenberg, committee chair; Russ Toal, Karen E. Gieseker, committee members. Electronic text (135 p. : col. ill.) : digital, PDF file. Description based on contents viewed August 12, 2008. Includes bibliographical references (p. 127-135).
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Mekaru, Sumiko Rachel. "Environmental risk factors in infectious diseases: studies in waterborne disease outbreaks, Ebola, and Lyme disease." Thesis, Boston University, 2013. https://hdl.handle.net/2144/11144.
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Thesis (Ph.D.)--Boston UniversityThe resurgence of infectious diseases and global climate change's potential impact on them has refocused public health's attention on the environment's role in infectious disease. The studies in this dissertation utilize the increased availability of satellite image-derived data sets with fine temporal and geographic granularity and the expansion of epidemiologic methods to explore the relationship between the environment and infectious disease in three settings. The first study employed a novel study design and analytic methods to investigate the hypothesis that heavy rainfall is an independent risk factor for waterborne disease outbreaks (WBDOs). We found that a location experiencing a heavy rainfall event had about half the odds of a WBDO two or four weeks later than did a location without a heavy rainfall event. The location-based case-crossover study design utilized in this study may help to expand the research methods available to epidemiologists working in this developing field. The second study employed a location-based case-crossover study design to evaluate standardized differences from historic average of weekly rainfall in locations with a recorded introduction of Ebola into a human. For each 1.0 unit z-score decrease in total rainfall, the odds of an Ebola introduction three weeks later increased by 75%. Given the severity of Ebola outbreaks and the dearth of knowledge about indicators of increased risk, this finding is an important step in advancing our understanding of Ebola ecology. The third study used GIS methods on remote sensing data to estimate the association between peridomestic forest/non-forest interface within 100, 150, 250 meters and Lyme-associated peripheral facial palsy (LAPFP) among pediatric facial palsy patients. After adjustment for sex, age, and socio-economic status, children with the highest level of forest edge in the three radii of analysis had 2.74 (95% CI 1.15, 6.53), 4.58 (1.84, 11.41), and 5.88 (2.11, 16.4) times the odds of LAPFP compared to children with zero forest edge in those radii. This study is the first to examine environmental risk factors for LAPFP. Each of these studies advances the techniques used to investigate environmental risk factors for infectious disease through study design, case definition, data used, or exposure definitions.
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Constable, Fiona Elizabeth. "Biology and epidemiology of Australian grapevine phytoplasmas." Title page, contents and abstract only, 2002. http://web4.library.adelaide.edu.au/theses/09PH/09phc756.pdf.
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Ye, Ping. "Autoimmunity in chronic periodontitis." Thesis, The University of Sydney, 2003. http://hdl.handle.net/2123/4256.
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Profound perturbation of epithelial structure is a characteristic feature of the immunopatholoical response to bacterial antigens considered to be central in the pathogenesis of the destructive lesion of periodontitis. The pathological basis for the disturbance of epithelial structure is not understood. It was demonstrated that the structural integrity and functional differentiation of the lining epithelium is compromised in relation to inflammatory changes associated with destructive periodontitis. In the pathological lining epithelium of the periodontal pocket there was a marked reduction of epithelial cadherin important in intercellular adhesion, of involucrin, a marker of terminal differentiation, and of the gap junction connexions that form intercellular communication channels. These changes were associated with alterations of filamentous actin expression, collectively indicating profound perturbation of epithelial structure. The data reported support the concept that the ability of the pathological lining epithelium to function as an effective barrier against the ingress of microbial products into the tissues is severely compromised (Ye et al., 2000). In addition, a recent study (Ye et al., 2003) by Western analysis of serum IgG from all 22 patients with chronic periodontitis tested indicated recognition of multiple epithelial components in individual patterns. In contrast, subjects with a healthy periodontium displayed only trace recognition of epithelial antigens. Levels of epithelial-reactive antibodies were significantly correlated with attachment loss as an indication of disease activity. To investigate a possible relationship between the bacterial flora adjacent to the diseased sites and the presence of epithelial-reactive antibodies, subgingival plague samples were taken from deep periodontal pockets and cultured anaerobically. Gram positive bacteria containing antigens potentially cross-reactive with epithelial cells were reproducibly isolated by probing membrane colony lifts with affinity-isolated (epitheial-specific) antibodies. The bacteria were identified as streptococci (S. mitis, S. constellatus and two S. intermedius strains) and Actinomyces (A. georgiae, and A. sp. oral clone) by 16S rDNA sequence homology. Recognition by affinity-isolated antibodies of antigens from the captured organisms was confirmed by Western analysis. Conversely, absorption of affinity-isolated antibodies with bacterial species specifically reduced subsequent recognition of epithelial antigens. To identify the auto-antigens, a human keratinocyte cDNA expression library in Lambda phage was probed using a pooled sera. Groups of responders were detected for CD24 (a recently described adhesion molecule also known as P-selectin ligand), antioxidant protein 2 (a newly recognised member of the thiol-dependment anti-oxidant proteins), lavtate dehydrogenase A, the transcription factor NFAT5, and for three genes encoding novel proteins. Six identified bacteria, especially S intermedius were demonstrated to absorb antibodies reaching with identified auto-antigens in patterns varying between individuals. This evidence indicated that during the course of periodontits, subjects develop increased levels of antibodies to common oral bacteria amongst which are included tissue cross-reactive antigens. Periodontitis could therefore present a risk for the subsequent initiation or exacerbation of a broad spectrum of disease processes including autoimmune, inflammatory, proliferative and degenerative disorders.
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Ye, Ping. "Autoimmunity in chronic periodontitis." University of Sydney, 2003. http://hdl.handle.net/2123/4256.
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Doctor of PhilosophyProfound perturbation of epithelial structure is a characteristic feature of the immunopatholoical response to bacterial antigens considered to be central in the pathogenesis of the destructive lesion of periodontitis. The pathological basis for the disturbance of epithelial structure is not understood. It was demonstrated that the structural integrity and functional differentiation of the lining epithelium is compromised in relation to inflammatory changes associated with destructive periodontitis. In the pathological lining epithelium of the periodontal pocket there was a marked reduction of epithelial cadherin important in intercellular adhesion, of involucrin, a marker of terminal differentiation, and of the gap junction connexions that form intercellular communication channels. These changes were associated with alterations of filamentous actin expression, collectively indicating profound perturbation of epithelial structure. The data reported support the concept that the ability of the pathological lining epithelium to function as an effective barrier against the ingress of microbial products into the tissues is severely compromised (Ye et al., 2000). In addition, a recent study (Ye et al., 2003) by Western analysis of serum IgG from all 22 patients with chronic periodontitis tested indicated recognition of multiple epithelial components in individual patterns. In contrast, subjects with a healthy periodontium displayed only trace recognition of epithelial antigens. Levels of epithelial-reactive antibodies were significantly correlated with attachment loss as an indication of disease activity. To investigate a possible relationship between the bacterial flora adjacent to the diseased sites and the presence of epithelial-reactive antibodies, subgingival plague samples were taken from deep periodontal pockets and cultured anaerobically. Gram positive bacteria containing antigens potentially cross-reactive with epithelial cells were reproducibly isolated by probing membrane colony lifts with affinity-isolated (epitheial-specific) antibodies. The bacteria were identified as streptococci (S. mitis, S. constellatus and two S. intermedius strains) and Actinomyces (A. georgiae, and A. sp. oral clone) by 16S rDNA sequence homology. Recognition by affinity-isolated antibodies of antigens from the captured organisms was confirmed by Western analysis. Conversely, absorption of affinity-isolated antibodies with bacterial species specifically reduced subsequent recognition of epithelial antigens. To identify the auto-antigens, a human keratinocyte cDNA expression library in Lambda phage was probed using a pooled sera. Groups of responders were detected for CD24 (a recently described adhesion molecule also known as P-selectin ligand), antioxidant protein 2 (a newly recognised member of the thiol-dependment anti-oxidant proteins), lavtate dehydrogenase A, the transcription factor NFAT5, and for three genes encoding novel proteins. Six identified bacteria, especially S intermedius were demonstrated to absorb antibodies reaching with identified auto-antigens in patterns varying between individuals. This evidence indicated that during the course of periodontits, subjects develop increased levels of antibodies to common oral bacteria amongst which are included tissue cross-reactive antigens. Periodontitis could therefore present a risk for the subsequent initiation or exacerbation of a broad spectrum of disease processes including autoimmune, inflammatory, proliferative and degenerative disorders.
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Nitoiu, Daniela. "Insights into molecular and functional mechanisms behind inherited heart and skin disorders." Thesis, Queen Mary, University of London, 2015. http://qmro.qmul.ac.uk/xmlui/handle/123456789/8911.
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Desmosomes are macromolecular, dynamic and adaptable complexes that connect intermediate filaments of neighboring cells in a variety of tissues, generating a large mechanically resilient structure. The importance of maintaining desmosome homeostasis for tissue integrity and optimal organ function has been revealed through the identification of desmosome-associated disorders and mechanistic studies into desmosome regulation. This thesis focuses on inherited skin and heart conditions linked to mutations in desmosomal genes or in genes believed to be implicated in desmosome regulation. Part of this thesis is focused on the molecular analysis and identification of novel desmosomal mutations in patients clinically diagnosed with Arrhythmogenic Right Ventricular Cardiomyopathy, and the genetic diagnosis of patients with hypotrichosis, hypotrichosis and PPK or acral peeling skin syndrome. Patients were analysed using a number of different genetic techniques including custom capture array, HaloPlex targeted resequencing, exome capture and Sanger sequencing. Both novel and previously reported mutations were identified in DSP, DSC2, DSG2, PKP2, DSG4 or CSTA in patients diagnosed with these disorders. The molecular mechanisms behind mutations in the protease inhibitors cystatin A and calpastatin, leading to the skin disorders exfoliative ichthyosis and PLACK syndrome, were also investigated. In vitro analysis, using siRNA-mediated knockdown in the immortalised keratinocyte cell line HaCaT, demonstrated that these mutations, affecting the structure and function of the protease inhibitors, lead to deficient intercellular adhesion, possibly through the indirect regulation of desmosomal complexes through their target proteases.
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Fu, Pengfei. "Causes of neurological disorders : associations of pm2.5 exposure and intestinal disorders." HKBU Institutional Repository, 2020. https://repository.hkbu.edu.hk/etd_oa/742.
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Objective: The aims of this project were to (a) perform a systematic review and meta-analysis of the associations between multiple neurological disorders (or neurological diseases) and potential influencing factors, including the association between fine particulate matter (PM 2.5) and intestinal dysfunction, and (b) investigate the mechanisms and toxicological effects of PM 2.5 exposure in the brain and intestines using a mouse model of Alzheimer's disease (AD). Design: A systematic review and meta-analysis was conducted to assess the risks of PM 2.5 exposure, as manifested by the incidence of exposure-associate neurological disorders or intestinal dysfunction. An APP/PS1 transgenic mouse model for AD was used to study the brain damage resulting from PM 2.5 exposure, and the miRNA/mRNA regulatory mechanisms contributing to this damage. The inflammatory injuries and bacterial community changes in the intestines of AD mice exposed to PM 2.5 were also investigated. Data sources: Articles for systematic review and meta-analysis were obtained by searching PubMed and China National Knowledge Infrastructure (CNKI), which were published for more than ten years. Animal experiments were conducted at Shanxi University of Taiyuan in China, and toxicological tests were performed according to the stipulated methods and protocols. Review and experimental methods: Data on the risks of incidence of neurological disorders associated with the environmental factor (PM 2.5) and biological factors (intestinal disorders and bacteria) were obtained, and random- or fixed-effects models (depending on the I 2 value) were used to pool the odds ratios (OR) with the 95% confidence intervals (CI) from individual studies. In the animal experiments, mice were divided into four groups of five animals per group, as follows: normal control mice in filtered air, AD mice in filtered air, normal control mice in PM 2.5 air, and AD mice in PM 2.5 air. PM 2.5 mice were exposed to ambient PM 2.5 in a whole-body inhalation exposure device for 8 weeks in Taiyuan, China. Well-established methods were used to explore the toxicological mechanisms by which PM 2.5 exacerbated brain damage in AD mice, namely open-field testing, enzyme-linked immunosorbent assay (ELISA), real-time quantitative RT-PCR, hematoxylin-eosin (HE) staining, and transmission electron microscopy (TEM). Brain damage and related biomarkers in the brains were measured, and miRNA and mRNA profiles were detected using high-throughput sequencing methods. The signaling pathways of miRNAs or mRNAs were predicted and summarized, and specific miRNAs and mRNAs were screened to explore the possible regulatory mechanisms of PM 2.5 -induced brain damage in AD mice. Intestinal and fecal samples from these mice were also subjected to 16S rRNA gene sequencing. HE staining, ELISA, and metagenome bacterial diversity analyses were performed to investigate the effects of PM 2.5 inhalation on intestinal tissue damage, inflammatory responses, and changes of bacterial diversity and communities in AD mice. Results: Long-term PM 2.5 exposure has been associated with increased risks of stroke, dementia, AD, autism spectrum disorder (ASD), and Parkinson's disease (PD) in humans, with the risks of ischemic and hemorrhagic stroke being higher than that of stroke in general. Furthermore, a relatively higher risk of stroke has been observed in heavily polluted countries compared to less polluted countries. It is known that some intestinal disorders and related problems such as constipation, inflammatory bowel disease, irritable bowel syndrome, small intestinal bacterial overgrowth, and diarrhea significantly increase the risks of developing AD or PD. For example, the risk estimates of Helicobacter pylori infection were significantly associated with AD and PD. From another angle, preliminary animal experimental results showed that PM 2.5 promoted brain morphological damage and decreased spatial exploration ability in AD mice, and was concomitant with increases in the concentrations of amyloid-β-42, acetylcholinesterase, tumor necrosis factor-α, and interleukin-6 and decreases in the concentrations of choline acetyltransferase. High-throughput sequencing and bioinformatics analyses revealed that miRNAs and mRNA had differential expression profiles subsequent to PM 2.5 exposure, which suggested that these species are involved in the molecular regulatory mechanisms and possible signal pathways of PM 2.5 -aggravated brain injury in AD mice. These PM 2.5 -aggravated brain injuries were correlated with pathological intestinal injury, inflammatory responses, and changes in bacterial diversity in the intestines and feces of PM 2.5 -exposed AD mice, and decreases in predominant bacteria were identified. These data will assist in delineating the ability of PM 2.5 exposure to induce pathological changes in the brain and gut tissue via the brain-gut axis and thereby aggravate AD. Conclusions: A systematic review and meta-analysis showed that there is a significant association between PM 2.5 exposure and the occurrence of stroke, dementia, AD, ASD, and PD, and a strong association between intestinal disorders and the presence of certain bacteria and the development of AD and PD. PM 2.5 (environmental factors) and intestinal disorders accompanied by changes in bacterial diversity (internal biological factors) appeared to be the two most important factors that increase the risk of developing neurological disorders. Experimental animal data showed that PM 2.5 potently damaged the brain and intestines of AD mice, and that the toxicological mechanisms of this PM 2.5 -mediated brain injury led to morphological changes, inflammation, and perturbation of miRNA/mRNA regulation in the brain. These data suggest that PM 2.5 inhalation also have modulatory effects on the abundance and diversity of intestinal bacteria in AD mice. The findings of this study have clarified positive relationships between environmental and biological factors and neurological disorders and have elucidated the potential mechanisms by which PM 2.5 may mediate the initiation or exacerbation of AD
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梁欣珮 and Yan-pui Irene Leung. "Potential impact of alzheimer's disease on retina." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B42905059.
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Lane, Fiona Mary. "Defining mechanisms of neurodegeneration associated with protein misfolding diseases." Thesis, University of Edinburgh, 2015. http://hdl.handle.net/1842/19542.
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Protein misfolding diseases (PMDs) are a broad group of disorders including Alzheimer’s, Parkinson’s and prion diseases. They are characterised by the presence of aggregated, misfolded host proteins which are thought to cause cell death. Prion diseases are associated with misfolded prion protein (PrPSc), which has a tendency to form fibrillar aggregates. By contrast, Alzheimer’s disease (AD) is associated with misfolded amyloid beta (Aβ), which aggregates to form characteristic Aβ plaques. A feature which is common across PMDs is that small assemblies (oligomers) of the misfolded proteins are thought to be the important neurotoxic species, and it has been proposed that there may be a shared mechanism leading to cell death across PMDs caused by oligomers. In this study, the toxicity of different misfolded forms of recombinant PrP (recPrP) and recombinant Aβ (recAβ) and the mechanisms leading to cell death were investigated using a primary cell culture model. In addition, the importance of the disulphide bond in recPrP in relation to oligomer formation was explored using size exclusion chromatography and mass spectrometry, the toxicity of the different resulting oligomer populations were also investigated. Both recPrP oligomers and fibrils were shown to cause toxicity to mouse primary cortical neurons. Interestingly, oligomers were shown to cause apoptotic cell death, while the fibrils did not, suggesting the activation of different pathways. By contrast, recAβ fibrils were shown to be non-toxic to cortical neurons, Aβ oligomers, however, were shown to cause toxicity. Similar to recPrP, my data showed that it is likely that recAβ 1-42 oligomers also cause apoptosis. However, by contrast this seemed to be caused by excitotoxicity, which was not found to be the case for recPrP. Additionally, I have shown that the presence or absence of the disulphide bond in PrP has a profound effect on the size of oligomers which form. RecPrP lacking a disulphide bond leads to the formation of larger oligomers which are highly toxic to primary neurons. Findings from this study suggest that structural properties such as the disulphide bond in PrP can affect the size and toxicity of oligomers, furthermore, whilst oligomers have been shown to be important in both AD and prion diseases, they may not trigger the same pathways leading to cell death.
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Erdem, Munire Tugba. "Modeling Diseases With Multiple Disease Characteristics: Comparison Of Models And Estimation Methods." Master's thesis, METU, 2011. http://etd.lib.metu.edu.tr/upload/12613531/index.pdf.
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Epidemiological data with disease characteristic information can be modelled in several ways. One way is taking each disease characteristic as a response and constructing binary or polytomous logistic regression model. Second way is using a new response which consists of disease subtypes created by cross-classification of disease characteristic levels, and then constructing polytomous logistic regression model. The former may be disadvantageous since any possible covariation between disease characteristics is neglected, whereas the latter can capture that covariation behaviour. However, cross-classifying the characteristic levels increases the number of categories of response, so that dimensionality problem in parameter space may occur in classical polytomous logistic regression model. A two staged polytomous logistic regression model overcomes that dimensionality problem. In this thesis, study is progressen in two main directions: simulation study and data analysis parts. In simulation study, models that capture the covariation behaviour are compared in terms of the response model parameter estimators. That is, performances of the maximum likelihood estimation (MLE) approach to classical polytomous logistic regression, Bayesian estimation approach to classical polytomous logistic regression and pseudo-conditional likelihood (PCL) estimation approach to two stage polytomous logistic regression are compared in terms of bias and variation of estimators. Results of the simulation study revealed that for small sized sample and small number of disease subtypes, PCL outperforms in terms of bias and variance. For medium scaled size of total disease subtypes situation when sample size is small, PCL performs better than MLE, however when the sample size gets larger MLE has better performance in terms of standard errors of estimates. In addition, sampling variance of PCL estimators of two stage model converges to asymptotic variance faster than the ML estimators of classical polytomous logistic regression model. In data analysis, etiologic heterogeneity in breast cancer subtypes of Turkish female cancer patients is investigated, and the superiority of the two stage polytomous logistic regression model over the classical polytomous logistic model with disease subtypes is represented in terms of the interpretation of parameters and convenience in hypothesis testing.
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Chocho, Karen. "Hispanic Migrants and Cross-border Disease Control of Arizona's Vaccine Preventable Diseases." Digital Archive @ GSU, 2008. http://digitalarchive.gsu.edu/iph_theses/35.
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BACKGROUND: According to the Centers for Disease Control and Prevention and the National Immunization Program, there is an increase in the re-emergence of past diseases. Even with mandatory vaccination practices in the United States, there are still a number of cases of vaccine-preventable diseases (VPDs) reported yearly. It is speculated that the re-emergence of VPDs is in part due to the increase in international travel as well as the influx of immigrants. One particular group of interest includes the Hispanic migrants coming from Central and South America where some of these diseases are endemic. OBJECTIVE: The purpose of this paper is to determine the extent of VPD cases in the border state of Arizona that may be attributed to Hispanic migrant influx using data from the MMWR: Summary of Notifiable Diseases reports for the United States and the ADHS data from all Arizona counties. RESULTS: Since 1995, rates of hepatitis B and pertussis have been increasing in Arizona and have become higher for non-Hispanics than Hispanics. In 2005, hepatitis B rates were 1.53* for the United States and 7.31* for Arizona; pertussis rates were 8.72* for the United States and 21.60* for Arizona. CONCLUSION: The results of this study's analysis show the need to improve immunization efforts within the non-Hispanic populations in all Arizona counties. (*Per 100,000 population)
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Yassin, Khaled. "Unravelling the mystery of liver diseases in Egypt : the burden of disease /." Lage : Jacobs, 2001. http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&doc_number=009222709&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA.
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Adanyeguh, Isaac Mawusi. "Biomarkers Identification and Disease Modeling using Multimodal Neuroimaging Approaches in Polyglutamine Diseases." Thesis, Paris 6, 2017. http://www.theses.fr/2017PA066279/document.
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Les maladies par expansion de polyglutamines sont des maladies neurodégénératives dues à l’expansion du trinucléotide cytosine-adénine-guanine (CAG) dans les gènes correspondants codant pour une expansion d’homopolymère de glutamine dans les protéines mutées. Ce projet concerne les formes les plus courantes qui sont la maladie de Huntington (MH) et les ataxies spinocérébelleuses (SCA) types 1, 2, 3 et 7. Ce sont des maladies autosomiques dominantes, responsables de troubles graves de la motricité partageant des voies physiopathologiques communes, avec un effet notable sur la dysfonction métabolique. La disponibilité des tests génétiques et le fait que la plupart du temps la maladie débute à l’âge adulte offre la possibilité d’une intervention thérapeutique avant l’apparition de symptômes. Toutefois, les échelles cliniques ne sont pas assez sensibles et ne peuvent effectivement être utilisés pour évaluer les personnes au stade présymptomatique de la maladie. Les techniques d’imagerie par résonance magnétique (IRM) et de spectroscopie (SRM) sont des approches non invasives qui permettent de recueillir des informations pertinentes et sensibles. Ainsi, dans ce travail, nous présentons une combinaison de différentes techniques d’IRM et SRM afin d’identifier de robustes biomarqueurs de la MH et des SCA. Nous présentons aussi des approches thérapeutiques prometteuses dans la MH. De la même manière, nous voulons démontrer que des biomarqueurs d’imagerie sont plus sensibles que des échelles cliniques. Pour conclure, nous combinons des données multimodales – volumétrie, SRM, métabolomique et lipidomique – à partir de SCA dans un modèle qui explique mieux la pathologieMutations in different gene loci that lead to the encoding of the unstable and expanded glutamine-encoding cytosine-adenine-guanine (CAG) repeats results in the group of diseases known as the polyglutamine diseases. This project focuses on the most common forms which are Huntington disease (HD) and spinocerebellar ataxia (SCA) types 1, 2, 3 and 7. These are autosomal dominant diseases responsible for severe movement disorders and are thought to share common pathophysiological pathways with a major emphasis on metabolic dysfunction. The availability of genetic testing and their predominantly adult onset opens a window for therapeutic intervention before symptoms onset. However, current clinical scales are not sensitive and cannot effectively be used to evaluate individuals at the presymptomatic stage of the diseases. This prompts the need for biomarkers that are sensitive to macroscopic and microscopic changes that may occur prior to disease onset. Magnetic resonance imaging (MRI) and spectroscopy (MRS) techniques present non-invasive approaches to extract pertinent information that otherwise would not be possible with clinical scales. In this work therefore, we present a combination of different MRI and MRS techniques to identify robust biomarkers in HD and SCA. We also present therapeutic approaches that hold promise in HD. Likewise, we show that imaging biomarkers have higher effect sizes than clinical scales. Finally, we combine multimodal data – volumetry, MRS, metabolomics and lipidomic – from SCA into a model that best explains the pathology
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Dolan, Corrine, and Bill Mannan. "Wildlife Transmitted Diseases." College of Agriculture and Life Sciences, University of Arizona (Tucson, AZ), 2009. http://hdl.handle.net/10150/146750.
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3 pp.Tips for Arizona's Rural Landowners: Wildlife Unit
The Tips for Arizona's Rural Landowners Fact Sheet Series is intended to educate homeowners who have recently purchased small acreages in Arizona. The purpose of the series is to give homeowners information about living in rural settings. The Wildlife Unit includes fact sheets on wildlife habitat enhancement, the legal status of wildlife, venomous wildlife, wildlife transmitted diseases, aggressive wildlife and pet safety, wildlife-human conflicts, fencing, safe pesticide alternatives, and invasive wildlife.
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Nelson, M. R., A. Nadeem, W. Ahmed, and T. V. Orum. "Cotton Virus Diseases." College of Agriculture, University of Arizona (Tucson, AZ), 1998. http://hdl.handle.net/10150/210398.
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Virus diseases of cotton have historically been of only sporadic importance to global cotton production. Recent devastating epidemics in Pakistan and other areas have brought new awareness to the potential for disaster of a pathogen once considered to be of a minor importance. Under changing conditions this pathogen (cotton leaf curl virus) has emerged as a serious problem in Pakistan and India. Cotton leaf curl virus does not occur in the United States or the rest of the western hemisphere but recent experience worldwide is a reminder that pathogens, such as this geminivirus, can be moved easily from one part of the world to another and therefor we need to be aware of the potential impact of such pathogens on local crops.
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Gazzo, Andrea. "Beyond monogenic diseases: a first collection and analysis of digenic diseases." Doctoral thesis, Universite Libre de Bruxelles, 2018. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/272617.
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In the next generation sequencing era many bioinformatics tools have been developed for assisting scientists in their studies on the molecular basis of genetic diseases, often with the aim of identifying the pathogenic variants. As a consequence, in the last decades more than one hundred new disease-gene associations have been discovered. Nevertheless, the genetic basis of many genetic diseases yet remains undisclosed. It has been shown that many diseases considered as monogenic with an imperfect genotype-phenotype correlation or incomplete penetrance are, on the contrary, caused or modulated by more than one mutated gene, meaning that they are in fact oligogenic. Current bioinformatics methods used for identifying pathogenic variants are trained and fine-tuned for identifying a single variant responsible of a disease. This monogenic-oriented approach cannot be used to explore the impact of combinations of variants in different genes on the complexity and genetic heterogeneity of rare diseases. Digenic diseases are the simplest form of oligogenic disease and thus they can provide a conceptual bridge between monogenic and the poorly understood polygenic diseases.The ambition of this thesis is to collect and analyse digenic data, introducing this topic in the bioinformatics field where digenic diseases are still an unexplored branch. This can be divided in two steps: the first consists in the creation of a central repository containing detailed information on digenic diseases; the second is an analysis of their peculiarities, using machine learning methods for studying subclasses of digenic effects.In the first step we developed DIDA (DIgenic diseases DAtabase), a novel database that provides for the first time a curated collection of genes and associated variants involved in digenic diseases. Detailed information related to the digenic mechanism have been manually mined from the medical literature. All instances in DIDA were also assigned to two sub classes of digenic effects, annotated as true digenic (both genes are required for developing the disease) and composite classes (one gene is sufficient to produce the disease phenotype, the second one alters it or change significantly the age of onset).In the second step, we hypothesized that the digenic effect may be related to some biological properties characterizing digenic combinations. Using machine learning methods, we show that a set of variant, gene and higher-level features can differentiate between the true digenic and composite classes with high accuracy. Moreover, we show that a digenic effect decision profile, extracted from the predictive model, motivates why an instance is assigned to either of the two classes.Together, our results show that digenic disease data generates novel insights, providing a glimpse into the oligogenic realm.Doctorat en Sciences
info:eu-repo/semantics/nonPublished
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Emonts, M. "Polymorphisms in immune response genes in infectious diseases and autoimmune diseases." [S.l.] : Rotterdam : [The Author] ; Erasmus University [Host], 2008. http://hdl.handle.net/1765/14316.
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Mabunda, Michael Mucheyeni. "A cultural evaluation of the causes and treatment of diseases and other misfortunes among communities in the Pietersburg and Mankweng areas of the Northern Province." Thesis, University of Limpopo, 1999. http://hdl.handle.net/10386/2353.
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Zhong, Ming. "ABCA4 structure-function relationships : role in Stargardt disease and related retinal degenerative diseases." Thesis, University of British Columbia, 2009. http://hdl.handle.net/2429/7111.
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ABCA4, also known as ABCR or the rim protein, is a member of the family of ATP binding cassette (ABC) proteins expressed in rod and cone photoreceptors. Mutations in ABCA4 have been linked to Stargardt macular degeneration and related retinal degenerative diseases and implicated in the transport of retinoid compounds across the outer segment disk membrane.
This dissertation investigation describes various aspects of the structure and function relationships for ABCA4 and examines the mechanisms by which mutations in ABCA4 lead to various retinal degenerative diseases. A pull-down was employed to identify the retinoid substrate that interacts with ABCA4. When all-trans-retinal was added to ABCA4 in the presence of phosphatidylethanolamine, ~1 mol of N-retinylidene-phosphatidylethanolamine was bound per mol of ABCA4 with an apparent Kd of 5.4 μM. These results provided the first direct biochemical evidence for the identity of the retinoid substrate for ABCA4. To determine the role of that C-terminus of ABCA4 plays in structure and function, a series of deletion and chimera mutants of ABCA4 was expressed, purified by immunoaffinity chromatography, and their biochemical properties analyzed. Removal of the C-terminal 30 amino acids including a conserved VFVNFA motif or substitution of the VFVNFA motif with alanines resulted in the complete loss in N-retinylidene-phosphatidylethanolamine substrate binding, ATP photoaffinity labeling, and retinal stimulated ATPase activity and caused retention of ABCA4 in the endoplasmic reticulum. In contrast mutants lacking the C-terminal 8, 16 or 24 amino acids but retaining the VFVNFA motif were active. These studies indicated that the VFVNFA motif in ABCA4 is required for proper folding of ABCA4 into a functionally active protein. These results provide a molecular rationale for the disease phenotype displayed by individuals with mutations in the C-terminus of ABCA4. Co-IP studies coupled to mass spectrometry were performed to identify novel protein interactors of ABCA4. Rhodopsin and arrestin (including a splice variant of arrestin, p⁴⁴) were identified and confirmed by western blotting. All-trans-retinal was found as a regulator of this interaction.
This study for the first time has identified the retinoid substrate for ABCA4, demonstrated a role for the C-terminus and has found protein partners of ABCA4.
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Pepler, A. "Identification of novel disease-causing variants in rare diseases using trio exome sequencing." Thesis, University College London (University of London), 2017. http://discovery.ucl.ac.uk/1565182/.
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The use of trio exome next-generation sequencing (NGS), an analysis of the entire complement of coding exons within an affected index patient and unaffected parents, is increasingly being utilised in the analysis of patients with congenital diseases. This thesis describes the use of trio exome sequencing in the analysis of three distinct circumstances. First, the analysis of a cohort of eight trios in which the index patients suffer from startle disease, characterized by dysfunction of inhibitory glycinergic synapses. This revealed a single case of allelic drop-out of a known GLRA1 p.Y307C variant in a novel de novo pattern of inheritance, three cases where known or expected pathogenic variants had been identified in genes known to cause a seizure phenotype (DOLK and DMD), and an association with variants in ATRN, a null mutant of which is associated with a seizure phenotype in Mus musculus. Second, whole exome analysis of three individual cases with rare diseases was performed; a case of hypomyelinating leukodystrophy with a homozygous NKX6-2 p.L54Qfs variant, a case of microcephaly and pontocerebellar hypoplasia with a MED14 de novo p.R1162C variant, and a case of syndromic intellectual disability with hypotonia and a homozygous DRG1 p.Y295* variant. None of these genes had yet been implicated in disease, but all show some functional implication in each of the respective disorders. Third, novel de novo GRIN1 p.M818R and GRIN2B p.M824V variants were identified in further cases with developmental delay and hypotonia, adding to recent publications expanding the phenotype of variants within the NMDA receptor subunits. In each of these cases, trio exome sequencing was requested due to unclear disease aetiology and the resulting data indicates, in the majority of these cases, novel or putative genotype-phenotype correlations.
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Cristofani, R. M. "PROTEIN MISFOLDING IN KENNEDY¿S DISEASE AND IN RELATED MOTOR NEURON DISEASES (MNDS)." Doctoral thesis, Università degli Studi di Milano, 2015. http://hdl.handle.net/2434/339901.
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Motor neuron diseases, like spinobulbar muscular atrophy (SBMA) and amyotrophic lateral sclerosis (ALS) are characterized by the presence of inclusions or aggregates of proteinaceous materials. In SBMA, inclusions are formed by testosterone dependent aggregates of mutant androgen receptor (AR) with an elongated polyglutamine tract (ARpolyQ), while in ALS inclusions contain several aggregated proteins including TDP43, ubiquilin, optineurin. Exceptions are familial ALS forms linked to superoxide dismutase 1 (SOD1) mutations, to mutated TDP43 and to C9ORF72 poly-dipeptides (DPRs), in which aggregates are mainly composed of mutant SOD1, mutant TDP43 or DPRs, respectively. In general, protein aggregation is due to generation of aberrant protein conformations (misfolding) combined to a failure, in neuronal cells, of the protein quality control (PQC) system, which may be insufficient to correctly remove the misfolded proteins. In other target tissue, such as the muscles, a different physiological PQC regulation may be helpful to remove misfolded proteins related to MNDs.
The PQC system requires the activities of chaperones, degradative systems ubiquitin- proteasome (UPS) and autophagy. After misfolded protein recognition by chaperones, the dynein motor complex plays a crucial role to efficiently remove these species via autophagy, transporting them to autophagosome and assisting autophagosome- lysosome fusion.
In this thesis, I have investigated the implications of protein misfolding in SBMA and in ALS. Taking advantage of a comparative analysis of misfolded proteins response in skeletal muscle and in spinal cord of SMBA mice, we proved that autophagy is dramatically perturbed in muscles. Indeed, we found the up-regulation of most autophagic markers (Beclin-1, ATG10, p62/SQSTM1, LC3). In addition, the chaperon small Heat Shock Protein B8 (HSPB8) and its co-chaperone BCL2-Associated Athanogene 3 (BAG3), required for autophagy, were robustly up-regulated together with other specific HSPB8 interactors (HSPB2 and HSPB3). Interestingly, the BAG3:BAG1 ratio, increased in muscle, suggesting preferential misfolded proteins routing to autophagy rather than to proteasome. Misfolded proteins, recognized by HSPB8-BAG3 complex, are actively transport by dynein to MTOC to be inserted in autophagosome and degraded by autophagy,
Then, we analysed the role of dynein mediate transport in the autophagic removal of misfolded proteins. In immortalized motoneuronal NSC34 cells, we found that the reduction of dynein protein levels, obtained using a specific siRNA, resulted in autophagy inhibition and in unexpected testosterone dependent ARpolyQ aggregates reduction. Also, we found that pharmacological dynein inhibition, with erythro-9-(2- Hydroxy-3-nonyl) adenine hydrochloride (EHNA), in NSC34 cells expressing ARpolyQ, mutant SOD1, truncated TDP43 form or C9ORF72 DPRs, induced a great reduction of mutant protein aggregates, even in presence of an autophagy inhibitor (3-MA), but not of a proteasome inhibitor (MG132). By performing fractionation studies we found that EHNA increased the ARpolyQ levels in PBS and Triton-X100 fractions. Surprisingly, we found that ENHA effects were paralleled by an increased expression of BAG1, a co- chaperone which routes misfolded proteins to UPS, but not of BAG3 suggesting the prevalence of UPS functions. Indeed, when dynein activity was blocked, BAG3:BAG1 ratio was decreased, thus in favour of BAG1 expression, suggesting the involvement of the pro-degradative activity of BAG1 on ARpolyQ aggregates. Collectively, these data show that mutant ARpolyQ induces a potent autophagic response in muscle cells. This may be useful to evaluate the SBMA progression.
In parallel, dynein blockage perturbs autophagy and modifies the response of PQC system to misfolded protein. This results in reduced aggregation of MNDs-related misfolded proteins, a phenomenon that may occurs via an increase in their solubility and the induction of UPS functions.
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Baird, Todd B. "Oculomotor Deficits in Diseases of the Basal Ganglia: Parkinson's and Huntington's Diseases." VCU Scholars Compass, 1992. http://scholarscompass.vcu.edu/etd/4344.
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Oculomotor deficits are now recognized as being present in several neurological diseases of the basal ganglia. The present report will focus primarily on those observed in Huntington's and Parkinson's diseases. Neuronal cell loss in the pars compacta of the substantia nigra, degeneration of the nigrostriatal pathway, and consequent depletion of the neurotransmitter dopamine is the most obvious etiological abnormality in Parkinson's disease. Huntington's disease, on the other hand, involves the selective genetically-driven atrophy of the striatum (caudate and putamen). In order to attempt to understand oculomotor dysfunction, as a component of basal ganglia disease, it is necessary to first establish a definition of the basal ganglia, its relevant connections, and their associated neurotransmitters and functions.
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O'Connell, Jeffrey R. "Algorithms for linkage analysis, error detection and haplotyping in pedigrees." Thesis, University of Oxford, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.325622.
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Ren, Lei, and Ph D. 任蕾. "Lipopolysaccharide-binding protein and CD14 in human gingiva." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2005. http://hub.hku.hk/bib/B31374281.
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Ramzan, Naveen, Shimin Zheng, Hemang Panchal, Edward Leinaar, Christian Nwabueze, and Timir K. Paul. "Investigating The Association Between Chronic Kidney Disease and Clinical Outcomes." Digital Commons @ East Tennessee State University, 2019. https://dc.etsu.edu/asrf/2019/schedule/21.
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Background
Chronic Kidney Disease (CKD) can be described as the loss of the kidney function over time. Symptoms usually develop slowly, and it may not appear in early stages. Lab tests can confirm a CKD diagnosis. The approximate number of incidents per year is more than 200,000 cases, and approximately 30 million people are living with CKD today in the United States. This long-standing disease ultimately leads to renal failure at the end. At this present time, there are no known cures for CKD, and the only treatment available is dialysis. Objectives
The purpose of this study is to determine the association between CKD and further with hemodialysis (HD) and medical condition such as cardiac complications, cardiogenic shock, hemorrhage, anemia, vascular complication, postop respiratory failure, post op infarct hemorrhage, acute renal failure, new temporary pacemaker, new permanent pacemaker, pericardial complications, and death. Study design
The study employed secondary data in a cross-sectional design. Methods
A sample of 106,969 was drawn from the population. The outcome variables were a diagnosis of CKD and/or CKD with HD. The predictor variables were cardiac complications, cardiogenic shock, hemorrhage, anemia, vascular complication, postop respiratory failure, post op infarct hemorrhage, acute renal failure, new temporary pacemaker, new permanent pacemaker, pericardial complications and death. Logistic regression was conducted to analyze the relationship between outcome variable and each independent variable. Variables with a p-value Results
Analysis shows that subjects with cardiac complications were 17% less likely to have CKD as compared to those who did not have cardiac complications (OR: 0.83, 95% CI: 0.78-0.88). CKD patients who had cardiac complications were 18% more likely to have HD than the subjects who did not have cardiac complications (OR: 1.18, 95% CI: 1.01-1.39). Patients with cardiogenic shock were 86% more likely to have CKD than the subjects who did not have cardiogenic shock (OR: 1.86, 95% CI: 1.82-1.91). CKD patients who had cardiogenic shock were also 18% more likely to have HD than the subjects who did not have cardiogenic shock (OR: 1.18, 95% CI: 1.11-1.25). We have similar results if a patient had other conditions. Conclusion
Chronic kidney disease with hemodialysis is significantly associated by the other medical conditions such as cardiac complications cardiogenic shock, hemorrhage, anemia, vascular complication, postop respiratory failure, post op infarct hemorrhage, acute renal failure, new temporary pacemaker, new permanent pacemaker, pericardial complications and death in the United States. Further studies are needed to confirm the results and to understand the prognosis.
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Sevilla, Cruz Jr. "Long-term Effects of Notch1 Signaling on Neural Stem Cells following Traumatic Brain Injury." VCU Scholars Compass, 2019. https://scholarscompass.vcu.edu/etd/5918.
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Traumatic brain injury (TBI) is a devastating problem which stands as a leading cause of death and disability. The elderly is significantly affected by TBI, typically as the result of falls, and recovery is especially limited. This, in part, is associated with decreased tissue-specific stem cell regeneration and replacement of damaged cells in the aged brain. The diminished ability of the aged brain to recover is especially devastating after TBI, likely leading to permanent loss of sensory, motor, and cognitive functions. Studies have shown that the mature mammalian brain contains Neural Stem Cells (NSCs), found in specific regions of the brain, which can generate functional neurons during normal and pathological conditions. Two of those regions, the Dentate Gyrus (DG) of the hippocampus as well as the Subventricular Zone (SVZ) of the lateral ventricles, have proven to be niches for these multipotent NSCs. A key regulator in the maintenance of these NSCs is the Notch signaling pathway, shown to control proliferation, differentiation, and apoptosis of NSCs during development and throughout adulthood. In the current study, we assessed the regulatory mechanisms that drive the regenerative functions of NSCs in a neuropathological state following TBI. Using the Lateral Fluid Percussion Injury model, we analyzed the diffuse effects of the injury response on 3-month old male Sprague-Dawley rats. Immediately following TBI, Notch agonist, antagonist or vehicle was infused into the lateral ventricle for 7 days to assess the role of Notch signaling on neural stem cell proliferation/survival and neurogenesis at 30 days post-TBI. Dividing cells during infusion time were labeled with BrdU via single daily intraperitoneal injections for 7 days. Animals were sacrificed at 30 days post-injury and brain tissues were processed then immunolabeling for BrdU and Doublecortin. We found a higher number of BrdU-positive cells in the FPI+Notch1 agonist group when compared to Sham and FPI+Jagged-1 Fc antagonist groups in the contralateral granular zone. A significant increase in proliferation/survival was also seen in FPI+Notch1 versus Sham/FPI+Jagged-1 Fc and for FPI+Vehicle versus Sham animals in both the ipsilateral and contralateral hilus. DCX immunolabeling did not establish a significant difference in FPI+Notch1 compared to Sham animals, nor across any other groups, which is consistent with what we know of activation of the Notch pathway. Our results demonstrate that Notch1 signaling is directly involved in cellular proliferation/survival of NSCs in the DG following TBI at 30 days post-injury, but further work must be done to understand the fate of these cells. Thus, drug treatment targeting Notch1 signaling could serve as a potential therapeutic target following TBI to preserve NSCs and limit long-term cognitive deficits.
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Abong'o, Benard Omondi. "Prevalence of Escherichia coli O157:H7 in water and meat and meat products and vegetables sold in the Eastern Cape Province of South Africa and its impact on the diarrhoeic conditions of HIV/AIDS patients." Thesis, University of Fort Hare, 2008. http://hdl.handle.net/10353/87.
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Water and food borne Escherichia coli O157:H7 could be one of the pathogens posing high health risk to patients suffering from Acquired Immunodeficiency Syndrome (AIDS) because of its incrimination in diarrhoea cases in AIDS patients. The present study, which was conducted between March 2005 and August 2006, investigated the prevalence of E. coli O157:H7 in water, meat and meat products and vegetables and its impact on diarrhoeic conditions of confirmed and non-confirmed HIV/AIDS patients in the Amathole District in the Eastern Cape Province of South Africa. The water samples used in the study were obtained from stand pipes supplying treated drinking water to communities residing in Fort Beaufort, Alice, Dimbaza and Mdantsane whereas borehole waters were sampled from Ngwenya and Kwasaki. The meat and meat products and vegetable samples were purchased from shops, butcheries, supermarkets and open air markets in Fort Beaufort, Alice and Mdantsane. The stool swabs used in the study were obtained from HIV/AIDS and outpatient clinics at Frere Hospital in East London. A total of 180 each of water, meat and meat products and vegetable samples and another 360 stool samples were analyzed for E. coli O157:H7. Presumptive E. coli O157 was isolated from the samples by culture-based methods and confirmed using Polymerase Chain Reaction techniques. Anti-biogram as well as risk assessment were also carried out using standard methods. The viable counts of presumptive E. coli O157 for water samples ranged between 3.3 × 104 and 1.71 × 105 CFU/ml, and between 1.8 × 104 and 5.04 × 106 CFU/g for meat and meat products, whereas those for vegetables ranged between 1.3 × 103 and 1.6 × 106 CFU/g. The counts of presumptive E. coli O157 for the water and vegetable samples were not significantly different whereas those for meat and meat products were found to be significantly different (P ≤ 0.05). The prevalence rates of presumptive E coli O157 in meat and meat products was 35.55 percent (64/180), and 25.55 percent (46/180) and 21.66 percent (39/180) for water and vegetables respectively. Prevalence of presumptive E. coli O157 in the stool samples of HIV/AIDS patients was 36.39 percent (131/360), of which 56.5 percent (74/131) and 43.5 percent (57/131) were from stools of confirmed and non-confirmed HIV/AIDS patients, respectively. Molecular analysis of representative presumptive E. coli O157 indicated that 10.29 percent (4/39) of vegetables; 14.81 percent (4/27) of water and 38.46 percent (5/13) of meat and meat products carried E. coli O157:H7. Also 36 percent (9/25) and 17.24 percent (5/29) of the stool samples were positive for E. coli O157:H7. Antimicrobial susceptibility profile revealed that all of the E. coli O157:H7 isolated from water, meat and meat products and vegetables as well as those isolated from stools of confirmed and non-confirmed HIV/AIDS patients were resistant (R) to gentamycin and erythromycin. However, 75 percent (20/27) of these isolates were resistant (R) to ampicillin and tetracycline whereas approximately 25 percent (6/27) were resistant (R) to nalidixic acid, ceftriaxone, and chloramphenicol. All the isolates (27/27) were susceptible (S) to amikacin. Probability of risk of E. coli O157:H7 infection was high for confirmed HIV/AIDS patients than for the non-confirmed HIV/AIDS patients. Estimated probability of risk of E. coli O157:H7 due to ingestion of water was 1.00 for 100 confirmed and non-confirmed HIV/AIDS patients. Risk due to meat and meat products was estimated at 0.27 and 0.20 and for vegetables at 0.21 and 0.15 per 100 confirmed and non-confirmed HIV/AIDS patients. The findings of this study predicted a possible link between E. coli O157:H7 isolated from drinking water, meat and meat products and vegetables and diarrhoeic conditions in both confirmed and non-confirmed HIV/AIDS patients, and concludes that confirmed HIV/AIDS patients can be at higher risk of contracting water and food borne E. coli O157:H7 than nonconfirmed HIV/AIDS patients. It is thus recommended that proper water treatment and food handling, maximum food and water safety and sanitation as well as personal body hygiene should be maintained, in order to prevent E. coli O157:H7 infections. Education initiatives and active surveillance of E. coli O157:H7 should be taken by all the stake-holders working directly or indirectly towards ensuring enduring sound public health.
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Hadian, Mojtaba. "Study of collagen structure in canine myxomatous mitral valve disease." Thesis, University of Edinburgh, 2009. http://hdl.handle.net/1842/4383.
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Myxomatous mitral valve disease (MMVD) is the single most common acquired cardiac disease of dogs, and is a disease of significant veterinary importance. It also bears close similarities to mitral valve prolapse in humans and therefore is a disease of emerging comparative interest. Realising the importance of collagen fibres in mitral heart valves and considering the paramount significance of myxomatous mitral valve disease, a better understanding of the pathogenesis of MMVD is essential. Thus, this study was designed to investigate the changes in collagen molecules, including fibril structure, fibril orientation, d-spacing, collagen density, collagen content, thermal stability, and the status of mature and immature crosslinks. A combination of biophysical and biochemical tools such as x-ray diffraction, neutron diffraction, HPLC were utilised in order to fulfil the objectives. Biochemical assay of hydroxyproline revealed a 10% depletion of collagen in mildly affacted (grade I and II) leaflets, while a 20% depletion of fibrillar collagen was revealed by mapping the collagen fibrils onto the anatomy of cardiac leaflets using x-ray data. Differential scanning calorimetry showed that there were no significant differences in the onset temperature of denaturation of collagen between the healthy and affected leaflets. However, in affected areas of leaflets, the enthalpy of denaturation significantly dropped by 20%. In the affected regions, neutron diffraction results showed an increase in the immature reducible cross-links though the low number of the samples can be considered a limiting factor in this regard. However, the HPLC results showed a 25% decrease in the number of mature cross-links. Additionally, the recently introduced imaging technologies to biology and medicine such as differential enhancing imaging (DEI) and coherent anti-Stokes Raman scattering spectroscopy (CARS) were, to the author’s best knowledge, applied for the first time to this disease. In doing so, this thesis furthers our understanding of the pathogenesis of MMVD, especially in relation to the collagen. The thesis provides new findings about MMVD and demonstrates the potential of biophysical tools for studying similar conditions.
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Maimela, Eric. "Development of an integrated, evidence-based management model for chronic non-communicable diseases and their risk factors, in a rural area of Limpopo Province, South Africa." Thesis, University of Limpopo, 2016. http://hdl.handle.net/10386/1732.
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Thesis(Ph.D.(Medical Science)) -- University of Limpopo, 2016Background: Chronic disease management (CDM) is an approach to health care that keeps people as healthy as possible through the prevention, early detection and management of chronic diseases. This approach offers holistic and comprehensive care, with a focus on rehabilitation, to achieve the highest level of independence possible for individuals.The aim of this study was to develop an integrated, evidence-based model for the management of chronic non-communicable diseases in a rural community of the Limpopo Province, South Africa. Methods: The study was conducted at Dikgale Health and Demographic Surveillance System (HDSS) site is situated in Capricorn District of Limpopo Province in South Africa. This study followed mixed methods methodology with an aim on integrating quantitative and qualitative data collection and analysis in a single study to develop an intervention program in a form of model to improve management of chronic diseases in a rural area. Therefore, this included literature review and WHO STEPwise approach to surveillance of NCD risk factors for quantitative techniques and focus group discussions, semi-structures interviews and quality circles for qualitative techniques. In the surveillance of NCD risk factors standardised international protocols were used to assess behavioural risk factors (smoking, alcohol consumption, fruit and vegetable consumption, physical activity) and physical characteristics (weight, height, waist and hip circumferences, and blood pressure). A purposive sampling method was used for qualitative research to determine knowledge, experience and barriers to chronic disease management in respect of patients, nurses, community health workers (CHWs), traditional health practitioners (THPs) and managers of chronic disease programmes. Data were analysed using STATA 12 for Windows, INVIVO and Excel Spreadsheets. Results: The study revealed that epidemiological transition is occurring in Dikgale HDSS. This rural area already demonstrates a high burden of risk factors for non-communicable diseases, especially smoking, alcohol consumption, low fruit and vegetable intake, physical inactivity, overweight and obesity, hypertension and dyslipidaemia, which can lead to cardiovascular diseases. The barriers mostly mentioned by the nurses, patients with chronic disease, CHWs and THPs include lack of knowledge of NCDs, shortages of medication and shortages of nurses in the clinics which cause patients to stay for long periods of time in a clinic. Lack of training on the management of chronic diseases, supervision by the district and provincial health managers, together with poor dissemination of guidelines, were contributing factors to lack of knowledge of NCDs management among nurses and CHWs. THPs revealed that cultural insensitivity on the part of nurses (disrespect) makes them unwilling to collaborate with the nurses in health service delivery. x The model developed in this study which was the main aim of the study describes four interacting system components which are health care providers, health care system, community partners and patients with their families. The main feature of this model is the integration of services from nurses, CHWs and THPs including a well-established clinical information system for health care providers to have better informed patient care. The developed model also has an intervention such as establishment of community ambassadors. Conclusion: Substantially high levels of the various risk factors for NCDs among adults in the Dikgale HDSS suggest an urgent need for adopting healthy life style modifications and the development of an integrated chronic care model. This highlights the need for health interventions that are aimed at controling risk factors at the population level in order to slow the progress of the coming non-communicable disease epidemic. Our study highlights the need for health interventions that aim to control risk factors at the population level, the need for availability of NCD-trained nurses, functional equipment and medication and a need to improve the link with traditional healers and integrate their services in order to facilitate early detection and management of chronic diseases in the community. The developed model will serve as a contribution to the improvement of NCD management in rural areas. Lastly, concerted action is needed to strengthen the delivery of essential health services in a health care system based on this model which will be tasked to organize health care in the rural area to improve management and prevention of chronic illnesses. Support systems in a form of supervisory visits to clinics, provision of medical equipments and training of health care providers should be provided. Contribution from community partners in a form of better leadership to mobilise and coordinate resources for chronic care is emphasized in the model. This productive interaction will be supported by the district and provincial Health Departments through re-organization of health services to give traditional leaders a role to take part in leadership to improve community participation.
Medical Science Department, University of Limpopo in South Africa,International Health Unit, and Antwerp University
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Blosser, Peter, Remil Simon, and Courtney Ridner. "Differential Diagnosis of Pan-Uveitis: Behçet’s Disease." Digital Commons @ East Tennessee State University, 2018. https://dc.etsu.edu/asrf/2018/schedule/2.
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This report describes the case of a 56-year-old man who presented with blurry vision, increased intraocular pressure, and conjunctival injection after posterior chamber intraocular lens implantation. Initially post-operative endophalmitis and foreign body inflammation were considered as differential diagnoses, but after further examination pan-uveitis was diagnosed. Uveitis is an ocular finding that may indicate several diseases, one of which is Behçet’s Disease. During the interview, the patient mentioned a history of apthous ulcers and genital ulcers which then lead to the clinical diagnosis of Behçet’s Disease. This report emphasizes that Behçet’s Disease is rare in Caucasians. Therefore, is frequently misdiagnosed in North America due to variable presentations and by not exploring the option when analyzing differential diagnoses. Early diagnosis and intervention will prevent the development of blindness and fatality due to complications of the disease.
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Chetty, Runjan. "Oncogenesis of lymphoproliferative diseases." Thesis, University of Oxford, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.308789.
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張嘉能 and Ka-nang Benny Cheung. "Hospital for infectious diseases." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1999. http://hub.hku.hk/bib/B31984496.
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Rabie, S. M. M. "Antioxidants and oral diseases." Thesis, Queen's University Belfast, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.397891.
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Pirim, Ibrahim. "Ubiquitin and neurogenerative diseases." Thesis, University of Nottingham, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.335277.
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Tamimi, S. O. "Stroma of breast diseases." Thesis, University of Manchester, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.374564.
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Gkrania-Klotsas, Effrossyni. "Infections and metabolic diseases." Thesis, University of Cambridge, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.610669.
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