Dissertations / Theses: 'Diagnostics of diseases'

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Nygren, Malin. "Molecular diagnostics of infectious diseases." Doctoral thesis, KTH, Biotechnology, 2000. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-2906.

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In DNA-based diagnostics, the polymerase chain reaction(PCR) is the most widely used DNA amplification method. Toenable both sensitive and specific detection of agents causinginfectious diseases, the PCR needs to becombined with methodsto prepare the clinical sample containing the genetic materialof the pathogen. Furthermore, methods for detection and DNAsequence analysis of the PCR amplification products are needed.This thesis describes the development of integrated systems fordetection, quantification and characterization ofmicroorganisms.

An immunomagnetic separation (IMS) technique has been usedto isolateBordetella pertussisfrom nasopharyngeal aspiratesamples. The post-PCR detection and typing ofBordetellaspp. was performed by a combination ofrestriction enzyme analysis of the amplified pertussis toxin(PT) promoter region and a solid-phase colorimetric detectionsystem; detection of immobilized amplified nucleic acid(DIANA). To investigate whether this approach could be used forreliable discrimination between the threeBordetellaspp. infecting humans, the PT promoter regionused for diagnostics was sequenced in 33 strains. To determinethe DNA sequence of this polymorphic and repetitive region, anew technique, bidirectional pyrosequencing, was utilized. Thisprocedure was used to resolve the sequence of this DNA region,which is able to form stable secondary structures inconventional Sanger DNA sequencing. A quantitative assay usingcompetitive PCR and the DIANA detection technique was alsodeveloped, for quantification ofB. pertussisin clinical samples.

By arbitrary PCR, a DNA sequence apparently specific forVibrio choleraeO139 Bengal was isolated andcharacterized. A nested PCR assay was developed for sensitiveand specific detection ofV. choleraeO139 Bengal in clinical samples and inenvironmental water samples, where differentiation betweenV. choleraeO139 Bengal andV. choleraO1 is of epidemiological interest.

The magnetic separation approach was also used to capturehuman immunodeficiency virus (HIV-1) RNA from patient plasma. Anested reverse transcription (RT)-PCR with four internalcompetitors was combined with electrophoretic separation andquantification of the PCR amplicons on an automated DNAsequencer. From the internal calibration curve, the amount ofHIV-1 RNA in the sample could be determined. Furthermore, aprimer extension assay was combined with detection andquantification of the competitive PCR products by the samebiochemiluminescent detection technique that is used inpyrosequencing. Quantification of HIV-1 viral load hasimplications in monitoring of antiretroviral therapy and inassessment of disease progression into AIDS.

Key words:bioluminescence,Bordetella, competitive PCR, DNA sequencing, humanimmunodeficiency virus type 1, PCR, pyrosequencing, solid-phasetechnology,Vibrio cholerae

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Jönsson, Björn. "On leg ischaemia : aspects on epidemiology and diagnostics /." Linköping : Univ, 2005. http://www.bibl.liu.se/liupubl/disp/disp2005/med884s.pdf.

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McCoy, G. F. "The role of vibration emission in the diagnosis of internal diseases of the knee." Thesis, Queen's University Belfast, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.233274.

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Tricou, Vianney M. "Dengue diagnostics and therapeutic interventions in Viet Nam." Thesis, University of Oxford, 2011. http://ora.ox.ac.uk/objects/uuid:46dfff8c-f7d2-4c43-b053-a5438531290a.

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Dengue is a major public health problem that affects tens of millions of people annually in tropical and sub-tropical countries. This acute viral infection happens to be severe and even life threatening but there is still no available drug or vaccine. Previous studies have noted early higher viral burden in patients who develop more severe symptoms suggesting that administration of a potent and safe antiviral may prevent progression to severe dengue. To verify this hypothesis, we have conducted the first RCT directed towards reducing the viral burden in vivo by administrating chloroquine (CQ), a cheap and well-tolerated drug that inhibits DENV in vitro with concentrations achievable in vivo, to 307 Vietnamese adults with suspected dengue (257 of them were laboratory-confirmed cases). Unfortunately, we did not see an effect of CQ on the duration of infection. However in patients treated with CQ, we observed a trend towards a lower incidence of severe forms. We did not find any differences in the immune response that can explain this trend. We also found more adverse events, primarily vomiting, with CQ. In addition, we have explored the relationships between clinical features, antibody responses and virological markers in these patients. We found that the early magnitude of viremia is positively associated with disease severity and there are serotype dependent differences in infection kinetics. We found as well that DENV was cleared faster and earlier in patients with secondary infections. To complete this study, we have also evaluated 2 rapid lateral flow tests for the diagnosis of dengue in a panel of plasma samples from 245 RT-PCR confirmed dengue patients and 47 with other febrile illnesses. Our data suggest that the NS1 test component of these tests are highly specific and have similar levels of sensitivity (~60%). Both NS1 assays were significantly more sensitive for primary than secondary dengue. The IgM parameter in the SD Duo test improved overall test sensitivity without compromising specificity. All these findings are of major importance for further anti-viral drug testing.

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Kameda, de Figueiredo Carvalho Koichi. "Testing the Nation : Healthcare policy and innovation in diagnostics for infectious diseases in Brazil." Thesis, Paris, EHESS, 2019. http://www.theses.fr/2019EHES0196.

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Le diagnostic in vitro (DIV) est un segment des biotechnologies de santé pour lequel les principaux acteurs se situent dans les pays développés. Parallèlement, le paysage actuel a contraint les compagnies multinationales à transformer leur modèle économique, tout en obligeant les pays non-occidentaux à devenir de nouveaux marchés et des lieux où de nouveaux savoirs et technologies pourraient être produits. Non seulement le Brésil est un marché important en ce qui concerne les produits de santé, mais il possède aussi une longue histoire en matière de fabrication de produits biologiques et pharmaceutiques. Dans ce contexte que les acteurs brésiliens se sont engagés dans production de DIV pour les maladies infectieuses. Ces initiatives articulent la santé publique et les politiques économiques industrielles, soit l’approche qui a été privilégiée dans le cadre du courant néo-développementaliste (neo-desenvolvimentismo) prôné de 2003 à 2016 dans ce pays. Cette thèse a pour objectif d’éclairer le travail des acteurs qui ont organisé la production et l’innovation de DIV dans un monde en mouvement, et dont le positionnement se situe au croisement de questions relevant de la santé publique, de l’autonomie technologique et de l’économie nationale brésilienne. Cette recherche se fonde sur un travail de terrain conduit entre 2014 et 2017, qui inclut des stages dans deux laboratoires rattachés à la fondation Oswaldo Cruz, ainsi que des entretiens avec de nombreux acteurs impliqués dans la production de ces tests diagnostics nationaux
In vitro diagnostics (IVD) is a segment of the health biotechnology industry for which the major players are situated in developed countries. At the same time, the contemporary landscape has compelled multinational companies to transform their business models and non-Western countries to become both new markets and places where new knowledge and technology can be produced. Not only is Brazil an important market for healthcare products, but it also has a long-standing history of producing pharmaceutical and biological innovations. It is in this context that Brazilian actors have engaged in the manufacturing of IVD for infectious diseases. These initiatives articulate public health and industrial economy policies, a preferred approach of the new developmentalism (neo-desenvolvimentismo) that prevailed in the country from 2003 to 2016. This thesis aims to shed light on how these actors organize IVD production and innovation in such a changing world, and at the crossroads of public health, technological autonomy and the national economy in Brazil. The research draws on fieldwork conducted between 2014 and 2017, which involved internships in two biotechnology laboratories linked to the Oswaldo Cruz Foundation, and on interviews with the various actors involved in the initiatives to produce national diagnostic tests

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Näslund, Jonas. "Rift Valley fever : development of diagnostics and vaccines." Doctoral thesis, Umeå universitet, Klinisk mikrobiologi, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-30676.

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Rift Valley Fever virus (RVFV) causes an infection with severe impact on animal and human health. The disease is endemic throughout almost the entire African continent and large regions of the Arabian Peninsula. During epidemics, high mortality is observed in animals, especially among cattle, goats, and sheep. In humans, the symptoms vary from a benign influenza-like disease to a life-threatening hemorrhagic fever. Due to the devastating effect on communities in endemic regions and the possibility of further spread of this virus, there is an imperative need to improve and develop control measurements against this emerging disease. Therefore, this thesis focuses on diagnostics and vaccines against RVFV. RVFV infection kinetics was studied in a mouse model system by detection and quantification of viral genomes, using a developed quantitative real-time PCR (QRT-PCR) method. This novel QRT-PCR method proved to be reliable and serves as a supplement to standard diagnostics, direct virus isolation and serological methods. High levels of viral RNA were found in blood and liver samples from experimentally infected mice during the first days post infection. Thereafter the levels declined rapidly and dropped below detection limit approximately seven days post infection. The QRT-PCR technique was also used in a study aimed to improve diagnosis of RVFV from field samples collected on filter strips. Today, the available RVFV vaccines are only approved for animal use and these vaccines have several shortcomings. Since RVFV is a highly pathogenic organism requiring bio-safety level 3 laboratories, two different none-replicating vaccine approaches have been applied and evaluated using a mouse model. A DNA based vaccine, administered via gene-gun, and the use of virus-like particles (VLP), by the intra-peritoneal route. RVFV specific and neutralising antibodies were raised with both vaccine approaches. However, VLP vaccination against Rift valley Fever proved to be more promising as a future vaccine, since higher titres of neutralising antibodies and improved survival rate were found upon a lethal RVFV challenge in mice. In conclusion, a sensitive and specific method for quantifying RVFV infection and a promising vaccine candidate against RVFV were developed.

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Keršulytė, Gintarė. "Širdies signalų analizės metodų paieška ir kūrimas." Master's thesis, Lithuanian Academic Libraries Network (LABT), 2007. http://vddb.library.lt/obj/LT-eLABa-0001:E.02~2007~D_20070816_142805-77618.

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Didelė dalis širdies susirgimų diagnostinių kriterijų gaunama registruojant ir analizuojant kardiosignalus, kurie atspindi tiek elektrinės širdies veiklos sutrikimus (EKG), tiek ir hemodinaminės bei mechaninės veiklos pokyčius, t.y. impedanskardiograma (IKG) ir seismokardiograma (SKG). Dar daugiau, efektyvus širdies susirgimų diagnostikos problemų sprendimas yra naujų kardiosignalų analizės technologijų kūrimas. Jau kelis dešimtmečius Furjė transformacija taikoma EKG dažnumų analizei, tuo tarpu kai IKG ir SKG dažnio charakteristikų vertinimui šis metodas nebuvo naudojamas. Darbo tikslas buvo pritaikyti Furjė analizę įvertinant bei palyginant tris sinchroniškai užregistruotus kardiosignalus, nes jie atspindi elektrinės širdies, hemodinaminės bei mechaninės širdies veiklos pokyčius geriau nei vienas EKG signalas. Kitas darbo tikslas buvo pritaikyti Furjė analizę įvertinant bei palyginant trijų sinchroniškai užregistruotų signalų - EKG, IKG ir SKG dažnio charakteristikas ir koherenciją bei klasifikuoti dvi grupes - "sveikas" ir "ligonis". Rezultatai rodo, kad koherencijos vertinimas ir spektrinė analizė gali būti naudinga gali būti naudingas širdies kraujagyslių bei plaučių sistemų ligų diagnostikai.
A big part of heart disease diagnostics criteria is collected by registration and analysis of cardio signals that reflect the disturbances of the electric heart activity – electrocardiogram (EСG), changes of hemodynamic - impedance cardiograms (IСG) and mechanic activity - seismocardiogram (SСG). ECG analysis is generally applying in clinic practice, but usually in visual way only. Due to the development of the technologies, the bigger amount of data could be stored and more exact analysis of information could be carried out. Therefore, a solution of problem of effective diagnostics of heart diseases is the creation of new technologies for analysis of cardio signals. Previously Fourier series were applied to frequency analysis of ECG, but this method was not applied for estimation of ICG and SCG frequency characteristics. In this thesis the frequency analysis method was applied to three cardio signals, because they reflect the electrical and mechanical work of the human heart better as entirely ECG signal. The main aim of this work was to adapt Fourier transformation to assessing and comparing some characteristics of hereinbefore signals, such as coherence and classify two searching groups - “healthy” and “sick”. Results showed that rating of coherence and spectral analysis could be useful for rightly analyzing and classifying the searching groups.

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López, Siles Mireia. "Ecophysiology and philogeny of Faecalibacterium prausnitzii in healthy and diseased gut. Application in Inflamatory Bowel Disease diagnostics." Doctoral thesis, Universitat de Girona, 2016. http://hdl.handle.net/10803/369044.

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In this PhD thesis Faecalibacterium prausnitzii populations of patients with gut disease and healthy individuals have been characterized. First, isolates from healthy volunteers have been phenotypically characterised, which has allowed to gain insight into the physiology of this species. A possible link between F. prausnitzii sensitivity to changes in gut physicochemical conditions and its disappearance in a diseased gut has been revealed. Second, molecular studies on F. prausnitzii populations have allowed to define two phylogroups within this species, and to describe the diversity of phylotypes in healthy individuals and in patients with intestinal disease. The phylotypes specifically compromised in patients suffering some gut disorders have been identified. Finally, new molecular tools for the detection and quantification of this species and its phylogroups have been designed. Their usefulness to be implemented as complementary molecular tools for the diagnosis and prognosis of intestinal diseases has been determined.
En aquesta tesi doctoral s'ha estudiat la població de Faecalibacterium prausnitzii de pacients amb malalties intestinals i individus sans. En primer lloc, es va realitzar una caracterització fenotípica d'aíllats d'aqueta espècie obtinguts d'individus sans, el que ha permès adquirir coneixement sobre la fisiologia d'aquesta espècie. S'ha evidenciat una possible relació entre la sensibilitat de F.prausnitzii a canvis en les condicions fisicoquímiques de l'intestí i la seva desaparició en un intestí malalt. En segon lloc, s'han realitzat estudis moleculars de les poblacions de F. prausnitzii. Això ha permès definir dos filogrups dins d'aquesta espècie, i descriure la diversitat de filotips en individus sans i pacients amb malalties intestinals.Per primera vegada, s'han identificat els filotips especificament compromesos en pacients que pateixen determinades malalties intestinals. Per últim, s’han dissenyat eines moleculars per a la detecció i quantificació d'aquesta espècie i els seus filogrups. S’ha determinat la utilitat d’aquestes eines moleculars per al suport al diagnòstic o prognòstic de malalties intestinals.

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Johansson, Patrik. "Implications of Local Puumala Hantavirus Genetics and Epidemiology for Diagnostics and Vaccine Development." Doctoral thesis, Umeå : Klinisk mikrobiologi, Umeå universitet, 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-532.

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Conrad, K., L. E. C. Andrade, E. K. L. Chan, M. Mahler, P. L. Meroni, G. J. M. Pruijn, G. Steiner, and Y. Shoenfeld. "From autoantibody research to standardized diagnostic assays in the management of human diseases: report of the 12th Dresden Symposium on Autoantibodies." Sage, 2016. https://tud.qucosa.de/id/qucosa%3A35519.

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Testing for autoantibodies (AABs) is becoming more and more relevant, not only for diagnosing autoimmune diseases (AIDs) but also for the differentiation of defined AID subtypes with different clinical manifestations, course and prognosis as well as the very early diagnosis for adequate management in the context of personalized medicine. A major challenge to improve diagnostic accuracy is to harmonize or even standardize AAB analyses. This review presents the results of the 12th Dresden Symposium on Autoantibodies that focused on several aspects of improving autoimmune diagnostics. Topics that are addressed include the International Consensus on ANA Patterns (ICAP) and the International Autoantibody Standardization (IAS) initiatives, the optimization of diagnostic algorithms, the description and evaluation of novel disease-specific AABs as well as the development and introduction of novel assays into routine diagnostics. This review also highlights important developments of recent years, most notably the improvement in diagnosing and predicting the course of rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, and of autoimmune neurological, gastrointestinal and liver diseases; the potential diagnostic role of anti-DFS70 antibodies and tumor-associated AABs. Furthermore, some hot topics in autoimmunity regarding disease pathogenesis and management are described.

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Moreno, Cabrera José Marcos. "A translational bioinformatics approach to improve genetic diagnostics of hereditary cancer using next-generation sequencing data." Doctoral thesis, Universitat de Barcelona, 2021. http://hdl.handle.net/10803/672364.

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This PhD thesis has been carried out with the aim of improving, from a bioinformatic-based approach, the genetic diagnostics of hereditary cancer. More specifically, the aims were: 1. To perform a comprehensive evaluation of tools suitable for detecting CNVs from NGS panel data at single-exon resolution. 2. To select the best candidate tool to implement in the genetic diagnostics pipeline of the ICO-IGTP program on hereditary cancer. 3. After implementing it, to evaluate the impact of including the selected NGS CNV detection tool as a first-tier screening step prior to MLPA validation. 4. To develop a tool to identify false positives produced by germline NGS CNV detection tools. 5. To develop a web-based tool to support the entire diagnostic process during the laboratory routine.

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Yépez, Mora Vicente A. [Verfasser], Julien [Akademischer Betreuer] Gagneur, Julien [Gutachter] Gagneur, and Juliane [Gutachter] Winkelmann. "Improving and upscaling the diagnostics of genetic diseases via gene expression and functional assays / Vicente A. Yépez Mora ; Gutachter: Julien Gagneur, Juliane Winkelmann ; Betreuer: Julien Gagneur." München : Universitätsbibliothek der TU München, 2021. http://d-nb.info/1233428195/34.

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Backus, Keriann Marie. "Incorporation of trehalose analogues into Mycobacterium tuberculosis : antigen 85 and probes of bacterial infection." Thesis, University of Oxford, 2011. http://ora.ox.ac.uk/objects/uuid:882d8560-c0d3-471b-a896-224a6b22a0f0.

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Diagnoses of tuberculosis, 'TB,' currently rely upon non-specific techniques such as X-ray exams and acid-fast microscopy. Improved diagnostics would preferably consider specific bacterial processes to provide real-time readouts of disease burden and response to chemotherapy. This dissertation presents the cell-wall incorporation of trehalose analogues (fluorescent and radioactive) by the mycobacterial antigen 85 enzymes as a novel method to label the causative bacteria of TB, Mycobacterium tuberculosis (Mtb). The trehalose mycolyltransesterase enzymes (antigens 85A, B, and C (Ag85)) serve as essential mediators of cell envelope function and biogenesis in Mtb. We show that the Ag85 enzymes display activities so broad that they allow added non-natural carbohydrate probes to be incorporated into Mtb growing in vitro and within macrophages. Design and synthesis of a library of structurally-diverse analogs of the sugar trehalose (Tre) revealed that Ag85-enzymes catalyze esterification of a wide variety of non-natural Tre structures, even stereoisomers and those appended with charged or bulky groups (Chapter 2). A novel mass-spectrometry based Ag85 enzyme assay was developed and employed to screen the library of compounds against all three isoforms of Ag85 (Chapter 3). This screen revealed that the Ag85 enzymes exhibit preference for dissacharides over monosaccharides and a broad tolerance for most modified trehalose compounds. This activity assay also afforded full kinetic analysis and the discovery of a novel, covalent inhibitor of the Ag85 enzymes. The Ag85 activity assay informed the design of a fluorescent trehalose-based compound (FITC-Tre), which is the first, non-toxic, selective, small molecule probe for mycobacterial infection. FITC-Tre was acylated with mycolyl esters by growing mycobacteria, anchoring the probe in the cell envelope resulting in fluorescent bacteria (Chapter 4). Adding FITC-Tre to Mtb-infected macrophages allowed selective, fluorescent tagging of Mtb in vivo (Chapter 5). Colocalization studies with antibodies against a variety of phagosomal associated components have hinted at the possibility of FITC-Tre as readout of cellular trafficking of bacteria. ¹⁸F-trehalose, biotin-trehalose and rhodamine-trehalose are also substrates of Ag85. ¹⁸F-trehalose shows promise as Mtb selective PET probe in an infected rabbit model of tuberculosis. Future work with these probes may allow for fluorescent tracking of the Mtb during the macrophage infection process, as well as the ability to label Mtb in infected tissue. The functional differences between the three isoforms of Ag85, A, B and C, are not well understood and may have implications for the survival and persistence of mycobacteria within humans. The differences in substrate specificity and catalytic activity between the Ag85 isoforms (discussed in Chapter 3) has been further investigated (Chapter 6). Mutation of three secondary site amino acids from Ag85C into Ag85B afforded nearly a twenty-fold gain in enzyme activity. Mutation of the equivalent Ag85B residues into Ag85C triggered nearly a twenty-fold loss in activity. Dissection of the roles of these three amino acids helps to explain the previously reported large differences in catalytic activity between Ag85A, B and C. Overexpression of Ag85A, B and C under tetracycline regulation revealed that these enzymes differentially modulate incorporation of mycolates into the cell wall. The Ag85 enzymes are not functionally redundant, and instead serve unique purposes in cell wall biosynthesis. In summary, this research has demonstrated that the broad substrate tolerance of Ag85 enzymes, coupled with their extracellular location, opens the door to probes of mycobacterial infection using many imaging modalities.

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Новіков, Олександр Олегович. "Комп’ютерні засоби діагностування захворювань на основі нейронної мережі." Bachelor's thesis, КПІ ім. Ігоря Сікорського, 2021. https://ela.kpi.ua/handle/123456789/43287.

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Кваліфікаційна робота включає пояснювальну записку (50 с., 36 рис., 2 додатки). Об’єкт розробки – створення комп’ютерного засобу для діагностування захворювань на основі нейронної мережі, яка дозволяє визначати наявність недугу. Предмет розробки – автоматизація діагностування діабетичної ретинопатії. Комп’ютерний засоб дозволяє: діагностувати захворювання на основі цифрового зображення, яке завантажене користувачем використовуючи графічний інтерфейс. В процесі розробки було використано мову програмування високого рівня Python та пакети TensorFlow, Keras, NumPy. В ході розробки: - проведено аналіз методів машинного навчання для класифікації цифрових зображення; - розроблено програмну систему для діагностування діабетичної ретинопатії з користувацьким інтерфейсом; - виконано дослідження ефективності розробленої системи; Використання цієї системи дозволить автоматизувати діагностування недугу. Що надає можливість своєчасного лікування пацієнта, економить час і сили лікарів.
The object of development - the creation of a software system for diagnosing diseases based on the neural network, which allows to determine the presence of the disease. The subject of development is the automation of the diagnosis of diabetic retinopathy. The software system allows user to diagnose the disease on the basis of a digital image that is uploaded using a graphical interface. In the development process were using programming language Python and such packages as TensorFlow, Keras, NumPy. During development: - analysis of machine learning methods for the classification of digital images is carried out; - developed a software system for the diagnosis of diabetic retinopathy with a user interface; - studied the efficiency of the developed software. The use of this software system will make it possible to automate the diagnosis of the disease. That can help to timely treat the patient, save the time and effort of doctors.

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Geraldes, Silvano Salgueiro. "Hemodiálise intermitente em cães com doença renal crônica estádio III e IV." Botucatu, 2018. http://hdl.handle.net/11449/158305.

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Orientador: Priscylla Tatiana Chalfun Guimarães [Unesp] Okamoto
Resumo: A Hemodiálise Intermitente (HDI) é uma modalidade de substituição renal, que vem sendo utilizada nas últimas décadas na veterinária nos casos de remoção de drogas, distúrbios hidroeletrolíticos, lesão renal aguda e doença renal crônica (DRC) em crise urêmica. O objetivo do estudo consistiu em avaliar o efeito da hemodiálise intermitente, instituída em cães DRC, em comparação aos manejados apenas com tratamento clínico, sem diálise, visando proporcionar uma melhor qualidade de vida. Foram selecionados 12 cães com DRC no estádio III e 25 cães DRC no estádio IV pelos critérios de inclusão, randomizados em grupo controle (n=6) no estádio III e (n=11) no estádio IV, onde foi preconizado apenas tratamento clínico e fluidoterapia, e grupo hemodiálise (n=6) no estádio III e (n=14) no estádio IV, em que além do tratamento clínico, foi realizada a hemodiálise intermitente. As coletas de sangue para avaliação laboratorial foram realizadas antes e após a fluidoterapia e antes e após a hemodiálise intermitente. As intercorrências e os parâmetros clínicos foram avaliadas a cada 30 minutos durante a HDI. A eficácia das sessões de HDI foi avaliada por meio da mensuração da taxa de remoção da ureia (URR). A instituição do tratamento dialítico promoveu uma eficaz diminuição das concentrações séricas de ureia, creatinina e fósforo em ambos estádios, porém com diminuição da sobrevida dos cães no estádio III. Apesar da evidente remoção dos compostos nitrogenados, é necessária uma constante avalia... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Intermittent Hemodialysis (IHD) is a modality of renal replacement that has been used in the last decades in the veterinarian in cases of drug withdrawal, hydroelectrolytic disorders, acute kidney injury and chronic kidney disease (CKD) in uremic crisis. The objective of the study was to evaluate the effect of intermittent hemodialysis, instituted in dogs CKD, in comparison to those managed only with clinical treatment, without dialysis, in order to provide a better quality of life. Twelve dogs with stage III CKD and 25 stage four CKD dogs were selected by inclusion criteria, randomized in a control group (n = 6) in stage III and (n = 11) in stage IV, where only clinical treatment was recommended and and hemodialysis group (n = 6) in stage III and (n = 14) in stage IV, in which, in addition to clinical treatment, intermittent hemodialysis was performed. Blood samples for laboratory evaluation were performed before and after fluid therapy and before and after intermittent hemodialysis. Intercurrences and clinical parameters were assessed every 30 minutes during IHD. The efficacy of the IHD sessions was assessed by measuring the urea removal rate (URR). The establishment of the dialytic treatment promoted an effective decrease in the serum concentrations of urea, creatinine and phosphorus in both stages, but with a decrease in the survival of dogs in stage III. Despite the obvious removal of the nitrogen compounds, a constant evaluation of the hematological and serum biochemica... (Complete abstract click electronic access below)
Mestre

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Runheim, Hannes, and Kajsa Appelberg. "Värdet av diagnostik vid sällsynta sjukdomar : En hälsoekonomisk undersökning med två fall." Thesis, Linköpings universitet, Nationalekonomi, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-177270.

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I denna studie undersöks värdet av diagnostik vid sällsynta sjukdomar hos unga individer. Då området är mångfacetterat studeras två fall med olika karaktär. Det första fallet undersöker värdet av screening för den sällsynta sjukdomen fenylketonuri (PKU) bland nyfödda, denna screening har utförts sedan 1960-talet. Det andra fallet fokuserar på en mer modern teknologisk utveckling och utvärderar värdet av införandet av helgenomsekvensering (WGS) som genetiskt test vid sökandet efter sällsynta sjukdomar. Båda fallen använder sig av kostnadseffektivitetsanalys som metod där kostnader respektive hälsoeffekter estimeras för de utvärderade insatserna. Fallen skiljer sig åt med avseende på tillgängliga dataunderlag vilket innebär att tillvägagångssättet för att skatta kostnaderna och hälsoeffekterna är olika i de båda fallen. I fallet med PKU-screening används Markovmodellering där data från olika källor syntetiseras i en simuleringsmodell. I fallet med WGS-testning används i större utsträckning ett insamlat empiriskt datamaterial som utgörs av faktiskt uppmätta sjukvårdskostnader. Resultaten i båda fallen indikerar att de diagnostiska metoderna har en rimlig kostnad i förhållande till hälsoeffekterna. Fall ett åskådliggör att dagens screening för PKU genererar ökade hälsoeffekter till lägre kostnader i jämförelse med att inte screena för PKU. För en kohort på 100 000 nyfödda barn blir den sammanlagda hälsoeffekten en ökning med 73 QALYs och screeningen medför samtidigt en besparing på 53 376 602 kr, sett över ett livstidsperspektiv. Fall två visar att WGS som första genetiskt test i genomsnitt minskar sjukvårdskostnaderna med 15 903 kr per individ jämfört med nuvarande vård och ökar samtidigt chansen till diagnos med 9,5 procentenheter (45,7%). Resultaten bör tolkas med viss försiktighet då de är förknippade med osäkerheter, men kan samtidigt användas som en del av det underlag beslutsfattare behöver för att fatta beslut om hur hälso- och sjukvårdens resurser ska prioriteras.
This study examines the value of diagnostics in rare diseases in young individuals. As the field is varied, two cases with different character are studied. The first case examines the value of screening for the rare disease phenylketonuria (PKU) among newborns, this screening has been performed since the 1960s. The second case focuses on a more modern technological development and evaluates the value of the introduction of whole genome sequencing (WGS) as a genetic test in the search for rare diseases. Both cases utilize the method of cost-effectiveness analysis where costs and health effects are estimated for the evaluated measures. The cases differ regarding available data, which means that the approach to estimating costs and health effects is different in the two cases. In the case of PKU- screening, Markov modeling is used where data from different sources are synthesized in a simulation model. In the case of WGS-testing, an empirical data material is used to a greater extent, which is based on actually measured healthcare costs. The results in both cases indicate that the diagnostic methods have a reasonable cost in relation to the health effects. Case one illustrates that today's screening for PKU generates increased health effects at lower costs compared to not screening for PKU. For a cohort of 100 000 newborns, the total health effect will be an increase of 73 QALYs and the screening will also result in cost- savings of SEK 53 376 602, seen from a lifetime perspective. Case two shows that WGS used as an initial genetic test on average reduces healthcare costs by SEK 15 903 per individual compared with current care and at the same time increases the chance of diagnosis by 9.5 percentage points (45.7%). The results should be interpreted with some caution as they are associated with some uncertainties, but can still be used as part of the basis on which decision-makers need to make decisions on how health care resources should be prioritized.

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Wrightson, John M. "Pathogen identification in lower respiratory tract infection." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:30c757ec-99b7-492e-a12e-ff996581863a.

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Treatment of lower respiratory tract infection (pneumonia and pleural infection) relies on the use of empirical broad spectrum antibiotics, primarily because reliable pathogen identification occurs infrequently. Another consequence of poor rates of pathogen identification is that our understanding of the microbiology of these infections is incomplete. This thesis addresses some of these issues by combining the acquisition of high quality lower respiratory tract samples, free from nasooropharyngeal contamination, with novel molecular microbiological techniques in an attempt to increase rates of pathogen identification. Four main areas are examined: (i) The role of so-called ‘atypical pneumonia’ bacteria in causing pleural infection. These pathogens have been previously identified in the pleural space infrequently and routine culture usually fails to isolate such bacteria. High sensitivity nested polymerase chain reaction (PCR) is a culture-independent technique which is used to undertake a systematic evaluation for these pathogens in pleural infection samples. (ii) The role of Pneumocystis jirovecii in pleural infection, either as a co-infecting pathogen or in monomicrobial infection. This fungus causes severe pneumonia, particularly in the immunosuppressed, but is increasingly recognised as a co-pathogen in community-acquired pneumonia, and is frequently isolated in the upper and lower respiratory tract in health. A high sensitivity real-time PCR assay is used to examine for this fungus. (iii) Ultra-deep sequencing of the 16S rRNA gene is used to perform a comprehensive microbial survey in samples taken from the multi-centre MIST2 study of pleural infection. The techniques employed allow analysis of polymicrobial samples and give very high taxonomic resolution, whilst incorporating methods to control for potential contamination. Further, these techniques provide confirmation of the results from the ‘atypical’ bacteria nested PCR study. (iv) Bedside ultrasound-guided percutaneous transthoracic needle aspiration (TNA) of consolidated lung is undertaken in patients with pneumonia, as part of the PIPAP study. An evaluation is undertaken of the efficacy and acceptability of TNA. Aspirate samples acquired are also processed using ultra-deep sequencing of the 16S rRNA gene. Other samples obtained as part of the PIPAP study, such as ‘control’ lung aspirates and ‘control’ pleural fluid samples, are similarly processed to enable calculation of sensitivity and specificity of the sequencing methodology.

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Monaghan, Sean J. "Approaches to DIVA vaccination for fish using infectious salmon anaemia and koi herpesvirus disease as models." Thesis, University of Stirling, 2013. http://hdl.handle.net/1893/17261.

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The expanding aquaculture industry continues to encounter major challenges in the form of highly contagious aquatic viruses. Control and eradication measures targeting the most lethal and economically damaging virus-induced diseases, some of which are notifiable, currently involve ‘stamping out’ policies and surveillance strategies. These approaches to disease control are performed through mass-culling followed by restriction in the movement of fish and fish products, resulting in considerable impacts on trade. Although effective, these expensive, ethically complex measures threaten the sustainability and reputation of the aquatic food sector, and could possibly be reduced by emulating innovative vaccination strategies that have proved pivotal in maintaining the success of the terrestrial livestock industry. DIVA ‘differentiating infected from vaccinated animal’ strategies provide a basis to vaccinate and contain disease outbreaks without compromising ‘disease-free’ status, as antibodies induced specifically to infection can be distinguished from those induced in vaccinated animals. Various approaches were carried out in this study to assess the feasibility of marker/DIVA vaccination for two of the most important disease threats to the global Atlantic salmon and common carp/koi industries, i.e. infectious salmon anaemia (ISA) and koi herpesvirus disease (KHVD), respectively. Antibody responses of Atlantic salmon (Salmo salar L.), following immunisation with an ISA vaccine, administered with foreign immunogenic marker antigens (tetanus toxoid (TT), fluorescein isothiocyanate (FITC) and keyhole limpet hemocyanin (KLH)) were assessed by antigen-specific enzyme linked immunosorbent assay (ELISA). Although antibodies were induced to some markers, these were unreliable and may have been affected by temperature and smoltification. Detectable antibodies to ISAV antigen were also largely inconsistent despite low serum dilutions of 1/20 being employed for serological analysis. The poor antibody responses of salmon to the inactivated ISA vaccine suggested that DIVA vaccination is not feasible for ISA. A similar approach for KHV, utilising green fluorescent protein (GFP) as the marker, similarly failed to induce sufficiently detectable antibody responses in vaccinated carp (Cyprinus carpio L.). However, as high anti-KHV antibody titres were obtained with an inactivated KHV vaccine (≥1/3200), alternative approaches were carried out to assess the feasibility of DIVA vaccination for carp. Investigations of early KHV pathogenesis in vivo and antigen expression kinetics in vitro (0-10 days post infection (dpi)) provided valuable data for the diagnostics necessary for DIVA surveillance strategies. Following viral infection, molecular methods were shown to be the most effective approach for early detection of KHV infected fish prior to sero-conversion, during which time antibodies are not detectable. An experimental immersion challenge with KHV, however, revealed complications in molecular detection during early infection. The KHV DNA was detected in external biopsies of skin and gills, but also internally in gut and peripheral blood leukocytes ≤ 6 hours post infection (hpi), suggesting rapid virus uptake by the host. The gills and gut appeared to be possible portals of entry, supported by detection of DNA in cells by in situ hybridisation (ISH). However, many false negative results using organ biopsies occurred during the first 4 dpi. The gills were the most reliable lethal biopsy for KHV detection by various polymerase chain reaction (PCR) assays, with a PCR targeting a glycoprotein-gene (ORF56) and a real-time PCR assay being the most sensitive of the 7 methods investigated. Importantly, non-lethal mucus samples reduced the number of false negative results obtained by all KHV PCR assays during the earliest infection stages with large levels of viral DNA being detected in mucus (up to 80,000 KHV DNA genomic equivalents 200 μL-1). KHV DNA was consistently detected in the mucus as a consequence of virus being shed from the skin. Determining the expression kinetics of different viral structural proteins can be useful for DIVA serological tests. Analysis of KHV antigen expression in tissues by immunohistochemistry and indirect fluorescent antibody test was inconclusive, therefore 2 novel semi-quantitative immunofluorescence techniques were developed for determining KHV antigen expression kinetics in susceptible cell lines. During the course of KHV infection in vitro, a greater abundance of capsid antigen was produced in infected cells compared to a glycoprotein antigen (ORF56), as determined by detection with antigen-specific monoclonal antibodies (MAbs). The capsid antigen was characterised as a ~100 kDa protein by SDS-PAGE and identified as a product of KHV ORF84 by matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF/TOF MS). This antigen was subsequently detected in the serum of >25% of KHV infected/exposed carp (6/17), as well as in carp vaccinated with a live attenuated vaccine (3/4), but not with an inactivated vaccine (0/7), by Western blot making it a potential DIVA target for an inactivated vaccine. Attempts were made to improve the sensitivity of KHV serological testing by taking advantage of recombinant proteins specific for KHV (CyHV-3), rORF62 and rORF68 and eliminating any interference by cross-reacting antibodies to carp pox (CyHV-1). These proteins successfully reacted with anti-KHV antibodies. The feasibility of DIVA strategies for KHVD was determined using these recombinant antigens to coat ELISA plates. Differential antibody responses were detected from carp sera to an internal virus tegument protein (rORF62) and external region of a transmembrane protein (rORF68). Fish vaccinated with an inactivated vaccine produced significantly lower antibody responses to rORF62 than to rORF68, whereas infected, exposed and live attenuated vaccinated fish recognised both proteins allowing differentiation between vaccinated and infected carp. However, the sensitivity of the assay was limited, possibly by high levels of natural antibodies detected at the relatively low serum dilutions (1/200) used. As the capsid antigen (ORF84) and tegument protein (ORF62) are derived from internal KHV structural proteins, they induce non-neutralising antibodies, which may be useful for DIVA strategies. Such antibodies are longer lasting than neutralising antibodies and often comprise the majority of fish anti-viral antibodies. This was noted in a fish surviving experimental challenge, which had an antibody titre of 1/10,000, but neutralising titre of 1/45. Such antigens may therefore hold potential for developing effective serological diagnostic tests for KHV and provide the potential for DIVA strategies against KHVD. Natural antibodies will, however, continue to present a challenge to the development of sensitive and reliable KHV serological tests, and hence the application of DIVA strategies.

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Сміян, Олександр Іванович, Александр Иванович Смиян, Oleksandr Ivanovych Smiian, Тетяна Парфеніївна Бинда, Татьяна Парфеньевна Бында, and Tetiana Parfeniivna Bynda. "Мультимедійні технології при викладанні дисципліни «Дитячі інфекційні хвороби»." Thesis, Запорізький державний медичний університет, 2015. http://essuir.sumdu.edu.ua/handle/123456789/43294.

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На кафедрі педіатрії післядипломної освіти при викладанні дисципліни «Дитячі інфекції» розроблені і впродовж останніх 7 років успішно використовуються в навчальному процесі тематичні мультимедійні презентації в основі яких лежить використання програми Power Point. Судячи з відгуків студентів та викладачів, введення в практику лекційних презентацій цілком себе виправдало. Інформація по зоровому каналу сприймається швидше і повніше, ніж по слуховому. Мультимедійна презентація дозволяє максимально використовувати ілюстративний матеріал, знайомлячи студентів з логічно структурованим основним змістом навчальної теми, усуває дефіцит традиційних джерел демонстраційного навчального матеріалу. Така наочність підвищує інтерес до навчального змісту лекції, сприяє більш глибокій мотивації для його вивчення.
На кафедре педиатрии последипломного образования при преподавании дисциплины «Детские инфекции» разработаны и в течение последних 7 лет успешно используются в учебном процессе тематические мультимедийные презентации в основе которых лежит использование программы Power Point. Судя по отзывам студентов и преподавателей, введение в практику лекционных презентаций вполне себя оправдало. Информация по зрительному каналу воспринимается быстрее и полнее, чем по слуховому. Мультимедийная презентация позволяет максимально использовать иллюстративный материал, знакомя студентов с логически структурированным основным содержанием учебной темы, устраняет дефицит традиционных источников демонстрационного учебного материала. Такая наглядность повышает интерес к учебному содержания лекции, способствует более глубокой мотивации для его изучения.
At the Department of Pediatrics postgraduate education in the teaching of discipline "Childhood infections" and developed over the last 7 years have been used successfully in the educational process themed multimedia presentations which are based on the use of the program Power Point. Judging by the reviews of students and teachers, an introduction to the practice of lecture presentations is quite justified. Information on visual channel is perceived more quickly and more completely than by hearing. Multimedia presentation maximizes the use of illustrative material, introduces students to the basic content is logically structured learning threads eliminates the deficiency of traditional sources demo teaching material. This increases the visibility of academic interest in the content of the lectures, promotes a deeper motivation to study it.

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Bourgoin, Pénélope. "Recherche de nouveaux tests rapides en cytométrie en flux pour l’établissement de diagnostics « aux lits des patients » : application à la discrimination des infections bactériennes et/ou virales en vue de réduire l’usage inutile des antibiotiques." Thesis, Aix-Marseille, 2020. http://theses.univ-amu.fr.lama.univ-amu.fr/200213_BOURGOIN_959uvzsse391uijk154knph339nyhkrq_TH.pdf.

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Les maladies infectieuses sont des pathologies dont le diagnostic étiologique est souvent complexe. Le clinicien doit baser son diagnostic sur ses observations cliniques et les relier aux mesures biologiques du patient. Plusieurs groupes recherchent activement de nouveaux marqueurs biologiques pour préciser ce diagnostic. C’est dans cette optique que la cytométrie en flux a été utilisée et optimisée pour comparer l’expression de nouveaux biomarqueurs sur les cellules du sang des patients infectés ou des sujets sains. La caractérisation des mécanismes d’expression des marqueurs montre que l’expression du CD64 sur les neutrophiles est amplifiée chez les patients infectés par une bactérie via l’interféron γ, alors que l’expression du CD169 sur les monocytes est amplifiée chez les patients infectés par un virus via la famille des interférons de type I (α, β, ω). De plus, l’expression de l’HLA-DR sur les monocytes semble aider à l’identification étiologique de l’infection. Les travaux suggèrent que le dosage de ces trois biomarqueurs par la technique de cytométrie en flux optimisée pourrait être un candidat intéressant dans les études sur le diagnostic des infections bactériennes et virales
Infectious diseases are pathologies whose etiological diagnosis is often complex. The clinician must base his diagnosis on his clinical observations and link them to the patient's biological measurements. Several groups are actively seeking new biomarkers to clarify this diagnosis. It is for this purpose that flow cytometry has been used and optimized to compare the expression of new biomarkers on blood cells of infected patients or healthy subjects. Characterization of the expression mechanisms of the markers shows that the expression of CD64 on neutrophils is amplified in patients infected by a bacterium via interferon γ, whereas the expression of CD169 on monocytes is amplified in patients infected with a virus via the type I interferon family (α, β, ω). In addition, the expression of HLA-DR on monocytes seems to help the etiological identification of the infection. The work suggests that the assay of these three biomarkers combined into an optimized flow cytometry technique could be an interesting candidate in studies on the diagnosis of bacterial and viral infections

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Boreiko, L. D. "Improved diagnostics for alcoholic liver disease." Thesis, Матеріали 100-ї підсумкової науковової конференції професорсько-викладацького персоналу Вищого державного навчального закладу України "Буковинський державний медичний університет" 2019 року, 2019. http://dspace.bsmu.edu.ua:8080/xmlui/handle/123456789/14891.

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Liefferinckx, Claire. "Evaluation of disease severity in inflammatory bowel diseases: From predictive diagnostic gene markers to treatment optimization based on pharmacokinetics." Doctoral thesis, Universite Libre de Bruxelles, 2019. https://dipot.ulb.ac.be/dspace/bitstream/2013/286479/3/table.docx.

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Inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are chronic inflammatory immune-mediated diseases of the gastrointestinal tract. Two-thirds of IBD patients will develop severe disease, with complications that will require frequent surgeries and hospital admissions, and will seriously impair their quality of life. The ultimate clinical challenge of precision medicine in IBD is to find predictive markers to anticipate the development of severe disease and to monitor treatment in these patients.In the first part of my PhD thesis, we have carried out several studies monitoring the biologics used in IBD patients with severe disease. We have evaluated the pharmacokinetics of the following biologics used in IBD patients: infliximab, vedolizumab, and ustekinumab. We have focused on measuring trough levels (TLs) (defined as the serum drug level measured just before the next drug administration) early on after initiating biologic treatment to predict patient outcomes, including long- term responses in patients treated with infliximab and vedolizumab. In addition, we are currently conducting a prospective multicentric study that aims to design a pharmacokinetic model of infliximab at induction in IBD patients (EudraCT: CT 2015- 004618-10) (End of study expected by December 2019 but interim analysis available in the present work). Moreover, we have reported on the efficacy of ustekinumab in a large national cohort of highly refractory CD patients and have also examined the benefit of early measurement of ustekinumab TLs in these patients. Finally, we have reported novel findings on the impact of different wash-out periods (defined as the time frame between the discontinuation of one biologic and the initiation of a second biologic on the pharmacokinetics of the second-line biologic). Altogether, over the past 3 years, our data suggest the importance of measuring TLs early on during induction to predict long-term response to biologics during maintenance therapyIn the second part of my PhD thesis, we have analysed the inter-variability of the immune response in healthy subjects. Inflammation is the obvious key driver and underlying mechanism of disease severity in IBD. Therefore, the magnitude of inflammation must help define the phenotype of mild to severe disease. Delineating the inter-variability of the immune response in a healthy cohort constitutes a fundamental step to uncovering the genetic factors underlying this variability. We have performed whole blood cell cultures in a highly selected population of more than 400 healthy subjects stimulated with several Toll-like receptor (TLR) agonists and a T-cell receptor (TCR) antagonist. We found that the magnitude of the immune response (the high- or low-cytokine producer phenotype) was independent of the cytokine measured and the TLR agonists used. Thus, a donor exhibits a specific immune (cytokine) response or “immunotype” across cytokines released and TLR stimulation. Importantly, the high- or low-cytokine producer phenotype was different and did not overlap between the TLR and TCR stimulation conditions. In other words, a donor who is ahigh-cytokine producer following TLR stimulation will not be a high-cytokine producer following TCR stimulation (or the inverse). Therefore, we have defined TLR- or TCR- related Immunotypes (IT) as “a grading classification of the magnitude of the cytokine immune response” with IT1, IT2, and IT3 as low, intermediate, and high immunotypes. This suggests that two independent TLR and TCR ITs (TLR IT1 and TCR IT3) can co-exist in the same subject. We are now currently evaluating the genetic markers underlying these ITs before validating them in large cohort of IBD patients with mild-to-moderate and severe disease.This PhD thesis provides some data suggesting that the assessment of the pharmacokinetics of biologics early on at the initiation of treatment could help predict how the patient will respond in the long run. In parallel, this PhD thesis provides some advances in the understanding of the inter-variability of the immune response, a fundamental step before the identification of potential genetic markers underlying the inter-variability of inflammation and, hence, the severity of disease in IBD.
Doctorat en Sciences biomédicales et pharmaceutiques (Médecine)
info:eu-repo/semantics/nonPublished

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Руденко, Максим Сергійович, Максим Сергеевич Руденко, and Maksym Serhiiovych Rudenko. "Intelligence decision support system for diagnostic oncological diseases." Thesis, Сумський державний університет, 2012. http://essuir.sumdu.edu.ua/handle/123456789/28793.

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Valkus, Martin. "Způsoby stanovení a léčení celiakie." Master's thesis, Vysoké učení technické v Brně. Fakulta chemická, 2015. http://www.nusl.cz/ntk/nusl-217168.

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This diploma thesis deals with methods of determining and treatment of coeliac disease. In the theoretical part of the work sums up informations about coeliac disease - history, prevalence, etiopathogenesis, immunopathogenesis, possibilities of diagnosis, discusses about gluten-free diet, mentions legislation of the Czech Republic and the European Union and compares expensiveness of gluten-free diet and normal diet. The experimental part of this thesis compares PCR, ELISA and indirect immunofluorescence methods for assesment of determination of genetic predisposition and antibodies in coeliac disease (greatest emphasis was placed on the comparison of antibodies against gliadin and deamidated gliadin antibodies in IgA and IgG).

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IJzerman, E. P. F. "Progress in diagnostics and prevention of Legionnaires' disease." [S.l. : [Groningen : s.n.] ; University Library Groningen] [Host], 2009. http://irs.ub.rug.nl/ppn/315954442.

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Warren, Andrew David. "Noninvasive disease diagnostics using engineered synthetic urinary biomarkers." Thesis, Massachusetts Institute of Technology, 2016. http://hdl.handle.net/1721.1/104609.

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Thesis: Ph. D. in Biomedical Engineering, Harvard-MIT Program in Health Sciences and Technology, 2016.
Cataloged from PDF version of thesis.
Includes bibliographical references (pages 149-166).
Accurate, timely, and effective diagnosis is the first step in appropriately treating disease. Many diseases have confusing symptoms, nonspecific biomarkers, or require invasive biopsy; these factors and others contribute to the low rates of early diagnosis for noncommunicable diseases like cancer, clotting disorders, or fibrotic diseases. A promising approach is the introduction of pro-diagnostic agents that interact with pathologic processes to produce a readout. In this vein, our group has developed responsive nanomaterials that, upon cleavage by disease-associated proteases, release reporters into the urine. This thesis sought to improve these tools by enabling the noninvasive quantification of disease-associated protease activity, deskilling complex diagnostic procedures, and developing a pipeline for extending these tools to additional diseases. Drawing inspiration from existing diagnostics, we modified our protease nanosensors to release ligand-encoded reporters compatible with clinical ELISA and paper-based lateral flow assays. These detection techniques enable simple and inexpensive quantification of our synthetic disease reporters by ensuring compatibility with existing diagnostic resources and infrastructure. To demonstrate our platform's versatility, we adapted it to a highly sensitive single molecule array (SiMoA) assay and validated disease detection in mice using 1000-fold lower doses of nanosensors. We next used disease-specific protease expression data to develop an inhalable formulation of our protease nanosensors and investigated direct tissue delivery. Finally, we built a pipeline to improve protease substrate sensitivity and specificity. Using liver fibrosis as a model, we identified target proteases, designed a peptide-screening assay, and nominated peptide candidates that efficiently classify diseased tissue. The protease nanosensors developed here provide a noninvasive, quantitative, and otherwise unavailable glimpse of the complex proteolytic milieu of disease and health. These tools form a framework for developing new diagnostics that simply, rapidly, and inexpensively identify protease-driven diseases without complex equipment or specialized personnel.
by Andrew David Warren.
Ph. D. in Biomedical Engineering

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Wons, Jonathan. "Alzheimer's disease--causes, risks, and diagnostic techniques." Thesis, Boston University, 2012. https://hdl.handle.net/2144/12681.

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Thesis (M.A.)--Boston University PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.
Alzheimer's disease is the most significant cause of dementia in the elderly population. The rapid cognitive decline characteristic of this illness, coupled with the lack of a cure and a projected doubling of incidence within the next half century, has placed an impetus on research that focuses on developing early diagnostic tools. Earlier detection during the course of the disease may allow opportunities for the development of preventative and/or pharmaceutical measures that can possibly attenuate the progression or even prevent disease pathology for occurring. This paper outlines the current knowledge on the causes and diagnosis of AD in order to ascertain the most effective protocol for identifying pre-symptomatic individuals with the disease. One such method is to first select those at the highest risk of developing AD, and then performing periodic neuroimaging and cognitive assessments to ascertain the earliest manifestation. High-risk individuals include those with a family history of AD and/or other neurodegenerative disorders, in addition to those who already exhibit genetic markers for the disease, such as the Apolipoprotein Eε4 allele and the mutated protein Tau. Subjects who present with increased levels of cardiovascular risk factors for stroke, particularly hypertension and diabetes, are also at high risk for developing vascular dementia, which is another significant cause of AD. Disease incidence increases exponentially with advancing age. Consequently, individuals past the age of 65 who possess any combination of the above risk factors fall within the highest risk group. Advances in neuroimaging techniques and technology, like Magnetic Resonance Imaging and Positron Emission Tomography (PET), have allowed researchers to pinpoint the earliest pathological characteristics of AD, which includes cortical degeneration, amyloid plaques and neurofibrillary tangles. However, notwithstanding the recent discovery of the Pittsburg Compound B tracer used in PET, AD diagnosis via neuroimaging remains possible only when the pathological features are already present. Neuropsychological assessments, such as the Mini-Mental State Examination, are frequently used to assess the cognitive decline of patients with AD. Recent enhancements within the scoring of these tests, which has allowed for the incorporation of qualitative data, has given fruitful results and hopeful directions for diagnosing AD before pathogenesis occurs. However, due to the failure of clinical trials in discovering a cure, continued research into the realms of diagnosis and prevention of AD is of paramount importance in order to combat the impending epidemic.

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Ben, Aissa Soler Alejandra. "Rapid diagnostic test for the detection of communicable diseases." Doctoral thesis, TDX (Tesis Doctorals en Xarxa), 2020. http://hdl.handle.net/10803/670392.

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La prevenció i el control de les malalties transmissibles depenen, en gran mesura, de la detecció ràpida i eficaç. Els mètodes convencionals per a la detecció d'un patogen, com ara el cultiu microbiològic, generalment requereixen molt de temps, són laboriosos, necessiten personal qualificat i no són aptes com a eines de diagnòstic en el punt d'atenció. El desenvolupament de mètodes de diagnòstic ràpid en el marc dels criteris ASSURED, de l'anglès (A) Affordable, (SS) Sensitive i Didàctiques, (O) User-friendly, (R) Rapid and Robust, (I) Equipment free, and (d) Deliverable to those who need it, Affordable, descrits per l'Organització Mundial de la Salut (OMS), es troben en l'actualitat sota intens estudi. Per tant, la present tesi aborda el disseny i desenvolupament d'estratègies, mètodes i materials per millorar les prestacions analítiques i simplificar el procediment en proves de diagnòstic ràpid, incloses noves estratègies de preconcentració en fase sòlida, mètodes d'amplificació i materials avançats, així com la seva integració en diferents plataformes (principalment biosensors basats en detecció electroquímica i proves en paper amb lectura òptica). En tots els casos, les aplicacions seleccionades es centren en malalties transmissibles, inclosos els patògens transmesos pels aliments i els micobacteris. Amb aquesta finalitat, es comparen dues plataformes basades en paper en diferents configuracions (flux lateral i vertical) en termes de rendiment analític per a la detecció de Mycobacterium. Per aconseguir una millora addicional en el límit de detecció, s'estudia la preconcentració prèvia dels bacteris per separació immunomagnètica. En segon lloc, s'avaluen i es comparen en termes del seu rendiment analític la detecció simultània de Salmonella i E. coli mitjançant flux lateral d'àcid nucleic amb lectura visual i genosensors electroquímics. Si bé aquests mètodes requereixen PCR de doble etiquetatge per a l'amplificació, es poden adaptar fàcilment a termocicladors portàtils que funcionen amb bateries per poder ser realitzats en entorns amb recursos limitats per satisfer les demandes de diagnòstic ASSURED. A més, també es presenta en aquesta tesi la síntesi de polímers magnètics impresos molecularment, per tal de reemplaçar les partícules magnètiques biològicament modificades, i prenent com a model la detecció de biotina i de molècules biotinilades. A més, es realitza la caracterització del material mitjançant diferents tècniques analítiques i es compara, en tots els casos, amb el polímer no imprès. Aquest material biomimètic mostra un gran potencial per a la preconcentració i detecció d'una àmplia gamma d'analits. Malgrat tot els progressos, les tècniques d'amplificació d'àcid nucleic segueixen essent necessàries per assolir els límits de detecció requerits en algunes malalties transmissibles. En aquest sentit, les tècniques d'amplificació isotèrmiques són bons candidats per dur a terme proves de diagnòstic en entorns on la PCR pot ser una barrera. En concret, es descriu en aquest treball la detecció d' E.coli mitjançant un genosensor electroquímic basat en l'amplificació isotèrmica. En aquest cas, s'optimitza la lectura electroquímica per voltamperometria d'ona quadrada en elèctrodes d'un sol ús comparant dues estratègies de marcatge del producte amplificat. És important ressaltar que totes aquestes estratègies apunten a ser utilitzades com a eines per millorar les proves de diagnòstic ràpid en entorns de baixos recursos, per interrompre la cadena d'infecció de malalties transmissibles i permetre, per tant, un tractament precoç.
La prevención y el control de las enfermedades transmisibles dependen, en gran medida, de la detección rápida y eficaz. Los métodos convencionales para la detección de un patógeno, como el cultivo microbiológico, generalmente requieren mucho tiempo, son laboriosos, necesitan personal cualificado y no son aptos como herramientas de diagnóstico en el punto de atención. El desarrollo de métodos de diagnóstico rápido en el marco de los criterios ASSURED, del inglés (A) Affordable, (SS) Sensitive and Specific, (U) User-friendly, (R) Rapid and Robust, (E) Equipment free, and (D) Deliverable to those who need it, Affordable, descritos por la Organización Mundial de la Salud (OMS), se encuentran en la actualidad bajo intenso estudio. Por lo tanto, la presente tesis aborda el diseño y desarrollo de estrategias, métodos y materiales para mejorar las prestaciones analíticas y simplificar el procedimiento en pruebas de diagnóstico rápido, incluidas nuevas estrategias de preconcentración en fase sólida, métodos de amplificación y materiales avanzados, así como su integración en diferentes plataformas (principalmente biosensores basados en detección electroquímica y pruebas en papel con lectura óptica). En todos los casos, las aplicaciones seleccionadas se centran en enfermedades transmisibles, incluidos los patógenos transmitidas por los alimentos y las micobacterias. Con este fin, se comparan dos plataformas basadas en papel en diferentes configuraciones (flujo lateral y vertical) en términos del rendimiento analítico para la detección de Mycobacterium. Para lograr una mejora adicional en el límite de detección, se estudia la preconcentración previa de las bacterias por separación inmunomagnética. En segundo lugar, se evalúan y se comparan en términos de su rendimiento analítico la detección simultánea de Salmonella y E. coli mediante flujo lateral de ácido nucleico con lectura visual y genosensores electroquímicos. Si bien estos métodos requieren PCR de doble etiquetado para la amplificación, se pueden adaptar fácilmente a termocicladores portátiles que funcionan con baterías para poder ser realizados en entornos con recursos limitados para satisfacer las demandas de diagnóstico ASSURED. Además, también se presenta en esta disertación la síntesis de polímeros magnéticos impresos molecularmente, con el objeto de reemplazar las partículas magnéticas biológicamente modificadas, y tomando como modelo la detección de biotina y moléculas biotiniladas. Además, se realiza la caracterización del material mediante diferentes técnicas analíticas y se compara, en todos los casos, con el polímero no impreso. Este material biomimético muestra un gran potencial para la preconcentración y detección de una amplia gama de analitos. A pesar de todo este progreso, las técnicas de amplificación de ácido nucleico siguen siendo necesarias para alcanzar los límites de detección requeridos en algunas enfermedades transmisibles. Las técnicas de amplificación isotérmica son buenos candidatos para llevar pruebas de diagnóstico en entornos donde la PCR puede ser una barrera. En concreto, se describe en esta disertación la detección de E. coli mediante un genosensor electroquímico basada en la amplificación isotérmica. En este caso, se optimiza la lectura electroquímica por voltamperometría de onda cuadrada en electrodos desechables comparando dos estrategias de marcaje del producto amplificado. Es importante resaltar que todas estas estrategias apuntan a ser utilizadas como herramientas para mejorar las pruebas de diagnóstico rápido en entornos de bajos recursos, para interrumpir la cadena de infección de enfermedades transmisibles y permitir, por tanto, un tratamiento precoz.
The prevention and control of communicable disease rely, to a large extent, on effective and early detection approaches. Conventional methods for the detection of a pathogen, such as microbiological culture, are usually time-consuming, laborious, need skilled personnel and are non-amenable to point-of-care diagnostic tools. The development of rapid diagnostic methods in the framework of the ASSURED criteria as (A) Affordable, (SS) Sensitive and Specific, (U) User-friendly, (R) Rapid and Robust, (E) Equipment free, and (D) Deliverable to those who need it, outlined by the World Health Organization (WHO), are under intensive study. Therefore, the present dissertation addresses the design and development of strategies, methods and materials to improve the analytical performance and to simplify the analytical procedure in rapid diagnostic tests, including novel solid-phase preconcentration strategies, amplification methods and advanced materials, as well as their integration in different platforms (mainly biosensors based on electrochemical detection and paper-based strips for optical readout). In all instances, the applications selected are focused on communicable diseases, including foodborne pathogens and mycobacteria. Therefore, two paper-based platforms in different configurations (nucleic acid lateral and vertical flow) are compared in terms of the analytical performance for the detection of Mycobacterium. In order to achieve a further improvement in the limit of detection, the preconcentration of the bacteria is performed by immunomagnetic separation. Secondly, the simultaneous detection of Salmonella and E. coli by nucleic acid lateral flow with visual readout and electrochemical genosensing are evaluated and compared in terms of their analytical performance. Although these methods required double-tagging PCR for amplification, portable, battery-powered thermocyclers can easily be adapted for resource-constrained settings to meet the demands for ASSURED diagnosis. Furthermore, the synthesis of Magnetic Molecularly Imprinted Polymers, in order to replace biological-modified magnetic particles is also presented in this dissertation, taking as a model the detection of biotin and biotinylated molecules with outstanding performance. Moreover, the characterization of the material is performed by different analytical techniques and compared, in all instances, with the non-imprinted polymer. This biomimetic material shows a great potential for the preconcentration and detection of a huge range of analytes. Despite all these progress, nucleic acid amplification techniques are still necessary to reach the challenging limits of detection required in some communicable disease. Isothermal amplification techniques are good candidates to bring sensitive diagnostic tests in places where the PCR can be a barrier. In detail, the electrochemical genosensing of E. coli based on isothermal amplification is also described in this dissertation. In this approach, the electrochemical readout by square-wave voltammetry on disposable electrodes is optimized comparing two different labelling approaches. It is important to highlight that all these strategies aim to be used as tools for the improvement of rapid diagnostic test in low resource settings, to interrupt the chain of infection of communicable diseases and enabling the rapid treatment.

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Cabré, Casares Noemí. "Assessing Diagnostic and Therapeutic Targets in Obesity-Associated Liver Diseases." Doctoral thesis, Universitat Rovira i Virgili, 2019. http://hdl.handle.net/10803/667718.

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Les alteracions hepàtiques, com la malaltia del fetge gras no alcohòlic (NAFLD) i l'esteatohepatitis no alcohòlica, o NASH, s'associen freqüentment amb l'obesitat. L'absència de marcadors no invasius per al diagnòstic de NASH dificulta la pràctica clínica i el desenvolupament de tractaments farmacològics. Per investigar els mecanismes moleculars d'aquestes alteracions i identificar les molècules que podrien usar-se com a possibles dianes terapèutiques, busquem marcadors biològics no invasius d'alteracions hepàtiques en pacients amb obesitat tipus III sotmesos a cirurgia bariàtrica (CB). En el nostre primer estudi, vam demostrar que la funció hepàtica millora significativament després de la CB a través de mecanismes que impliquen la reducció de l'estrès oxidatiu i els processos inflamatoris. En el segon estudi, mitjançant metabolòmica dirigida vam observar que els perfils plasmàtics van identificar connexions entre el metabolisme hepàtic i l'obesitat mòrbida. Els models combinats de mesuraments en plasma simples o aparellades de alpha-cetoglutarat, beta-hidroxibutirat, piruvat i oxalacetat van reduir la incertesa en el diagnòstic clínic de NASH i van predir la seva remissió. En el tercer estudi, es demostra que alpha-cetoglutarat és un metabòlit clau en l'homeòstasi energètica modulant el procés d’apoptosis en pacients amb NASH a través de l'activació de mTORC1. Després de la CB, la desregulació metabòlica i l'autofàgia compromesa en pacients amb NASH va ser restaurada per complet. L'activació d'AMPK en els hepatòcits va anul·lar l'efecte de l'activació de la glutaminolisis i promou l'ús d'inhibidors de mTORC1. Finalment, confirmem que els metabòlits poden promoure canvis epigenètics que afecten la metilació de l'ADN i les possibles modificacions post-traduccionals en els enzims que regulen el metabolisme energètic del fetge. L'estrès oxidatiu, la disfunció mitocondrial i la mort cel·lular estan implicats en la malaltia de la NAFLD mitjançant la reprogramació metabòlica. En conclusió, alpha-cetoglutarat podria ser un nou marcador biològic potencial i una estratègia terapèutica de NASH.
Las alteraciones hepáticas, como la enfermedad del hígado graso no alcohólico (NAFLD) y la esteatohepatitis no alcohólica, o NASH, se asocian frecuentemente con la obesidad. La ausencia de marcadores no invasivos para el diagnóstico de NASH dificulta la práctica clínica y el desarrollo de tratamientos farmacológicos. Para investigar los mecanismos moleculares de estas alteraciones e identificar las moléculas que podrían usarse como posibles dianas terapéuticas, buscamos marcadores biológicos no invasivos de alteraciones hepáticas en pacientes con obesidad tipo III sometidos a cirugía bariátrica (CB). En nuestro primer estudio, demostramos que la función hepática mejora significativamente después de la CB a través de mecanismos que implican la reducción del estrés oxidativo y los procesos inflamatorios. En el segundo estudio, mediante metabolómica dirigida observamos que los perfiles plasmáticos identificaron conexiones entre el metabolismo hepático humano y la obesidad mórbida. Los modelos combinados de mediciones en plasma simples o pareadas de alpha-cetoglutarato, beta-hidroxibutirato, piruvato y oxaloacetato redujeron la incertidumbre en el diagnóstico clínico de NASH y predijeron su remisión. En el tercer estudio, demostramos que alpha-cetoglutarato es un metabolito clave en la homeostasis energética modulando el proceso de apoptosis en pacientes con NASH a través de la activación de mTORC1. Después de la CB, la desregulación metabólica y la autofagia comprometida en pacientes con NASH fue restaurada por completo. La activación de AMPK en los hepatocitos anuló el efecto de la activación de la glutaminolisis y apoya el uso de inhibidores de mTORC1. Finalmente, confirmamos que los metabolitos pueden promover cambios epigenéticos que afectan la metilación del ADN y las posibles modificaciones postraduccionales en las enzimas que regulan el metabolismo energético del hígado. El estrés oxidativo, la disfunción mitocondrial y la muerte celular están implicados en la enfermedad de la NAFLD mediante la reprogramación metabólica. En conclusión, alpha-cetoglutarato podría ser un nuevo marcador biológico potencial y una estrategia terapéutica de NASH.
Hepatic alterations, such as non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are frequently associated with obesity. The absence of non-invasive markers for NASH diagnosis hampers clinical practice and the development of pharmacological treatments. In order to investigate the molecular mechanisms of these alterations and to identify molecules that could be used as potential therapeutic targets we search for noninvasive biomarkers of liver alterations in patients type III obesity undergoing bariatric surgery (BS). In our first study we showed that the liver function of patients with obesity are significantly improved after BS through mechanisms that involve the reduction of oxidative stress and inflammatory processes. In the second study we performed measurements in obese patients undergoing BS to identify specific metabolic patterns and to test the diagnostic ability to distinguish between patients with and without NASH. Targeted plasma metabolic profiles identified connections between liver metabolism and morbid obesity. Combined models of single or paired plasma measurements of alpha-ketoglutarate, beta-hydroxybutyrate, pyruvate and oxaloacetate reduced the uncertainty in clinical diagnosis of NASH and predicted NASH remission. In the third study we demonstrated that alpha-ketoglutarate is a key metabolite of energy homeostasis that modulates hepatocyte death in NASH patients through mammalian TORC1 (mTORC1). After BS, the mitochondrial oxidative metabolism and the autophagy-lysosomal function compromised in NASH patients, were also completely restored. AMPK activation in hepatocytes abrogated the effects of glutaminolysis supports the potential use of mTORC1 inhibitors. Finally, we confirm that metabolites may promote epigenetic changes affecting DNA methylation and likely post-translational modifications on enzymes regulating liver energy metabolism. Oxidative stress, mitochondrial dysfunction and cell death responses are implicated in NAFLD diseases via metabolic reprogramming. In conclusion, alpha-ketoglutarate could be a new potential biomarker and therapeutic strategy of NASH.

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Aquilano, Adelia <1986&gt. "Molecular genetics of inherited cystic kidney diseases: new diagnostic approaches." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2014. http://amsdottorato.unibo.it/6660/.

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Background. Hhereditary cystic kidney diseases are a heterogeneous spectrum of disorders leading to renal failure. Clinical features and family history can help to distinguish the recessive from dominant diseases but the differential diagnosis is difficult due the phenotypic overlap. The molecular diagnosis is often the only way to characterize the different forms. A conventional molecular screening is suitable for small genes but is expensive and time-consuming for large size genes. Next Generation Sequencing (NGS) technologies enables massively parallel sequencing of nucleic acid fragments. Purpose. The first purpose was to validate a diagnostic algorithm useful to drive the genetic screening. The second aim was to validate a NGS protocol of PKHD1 gene. Methods. DNAs from 50 patients were submitted to conventional screening of NPHP1, NPHP5, UMOD, REN and HNF1B genes. 5 patients with known mutations in PKHD1 were submitted to NGS to validate the new method and a not genotyped proband with his parents were analyzed for a diagnostic application. Results. The conventional molecular screening detected 8 mutations: 1) the novel p.E48K of REN in a patient with cystic nephropathy, hyperuricemia, hyperkalemia and anemia; 2) p.R489X of NPHP5 in a patient with Senior Loken Syndrome; 3) pR295C of HNF1B in a patient with renal failure and diabetes.; 4) the NPHP1 deletion in 3 patients with medullar cysts; 5) the HNF1B deletion in a patient with medullar cysts and renal hypoplasia and in a diabetic patient with liver disease. The NGS of PKHD1 detected all known mutations and two additional variants during the validation. The diagnostic NGS analysis identified the patient’s compound heterozygosity with a maternal frameshift mutation and a paternal missense mutation besides a not transmitted paternal missense mutation. Conclusions. The results confirm the validity of our diagnostic algorithm and suggest the possibility to introduce this NGS protocol to clinical practice.

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Workman, R. W. "The development candidate therapeutic and diagnostic ligands for prion diseases." Thesis, University of Nottingham, 2018. http://eprints.nottingham.ac.uk/49078/.

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To date there are no effective treatments for prion diseases, and these diseases are always fatal in both humans and animals. Additionally, the gold standard for diagnosis of these disease remains to be the analysis of biopsied brain tissue obtained post mortem. Consequently, there is a continued demand for therapeutics and ante-mortem diagnostics for prion diseases. This project addresses these demands by investigating candidate therapeutic and diagnostic ligands for prion diseases. This study investigated recombinant prion proteins (rPrPs) as inhibitors in scrapie and bovine spongiform encephalopathy (BSE) in vitro amplification by protein misfolding cyclic amplification (PMCA). Three ovine rPrPs with the polymorphisms VRQ, ARQ and ARR and hamster rPrP were tested against scrapie PMCA in dilution series to calculate IC50 values. The two most potent inhibitors, VRQ and ARQ, were then similarly tested against bovine spongiform encephalopathy (BSE) amplification. The most potent inhibitor of both disease types, the ovine rPrP VRQ, was then observed to inhibit a range of different scrapie and BSE strains at a fixed concentration. It is recommended that further investigation into rPrP inhibitors is performed. Strain characterisation of scrapie was investigated using rPrP inhibitors, following observations that the rPrP inhibitors generate a pattern of inhibition at a set concentration. Although this pattern of inhibition was repeatable in scrapie amplification by PMCA, this was limited to a single round of PMCA. Ultimately, this limited the application of this method to only amplification efficient prion strains and isolates. It is recommended that this method be investigated further in combination with the amplification of different isolates in substrates of different genotypes over multiple rounds of PMCA, as well as the analysis of glycoform ratios by western blotting. Here it was also identified that the imidazole used in the elution buffer for immobilised metal affinity chromatography (IMAC) can inhibit prion amplification in a strain dependent manner. This inhibition could be used in combination with the proposed method as a multi-faceted assay of prion strain characterisation. The use of next generation phage display (NGPD) to map the epitopes of autoantibodies in the sera of scrapie infected sheep was also investigated. This was performed to identify peptides that were immunoreactive to autoantibodies specific to the disease state. The identification of diagnostic peptides would then enable the development of an ante-mortem serological diagnostic test for scrapie. NGPD successfully selected immunoreactive peptides, of which 39 were selected for validation by peptide enzyme-linked immunosorbent assays (ELISAs). Although none of the peptides demonstrated diagnostic specificity by peptide ELISA, an optimised ELISA methodology was developed for future use in the validation of NGPD selected peptides. Further variations in the NGPD method, as well as validation by immunoassay, can be investigated to identify diagnostic peptides immunoreactive to scrapie specific autoantibodies.

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Nag, Sananda. "Development of Conductive Nanocomposite Sensors for Anticipated Diagnostic of Diseases." Thesis, Lorient, 2014. http://www.theses.fr/2014LORIS336/document.

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L'analyse de COV spécifiques dans l'haleine (identifié comme biomarqueurs de maladies telles que lecancer) donne une idée de l’activité métabolique et physiologique d'un individu et peut fournir undiagnostic anticipé non-invasif et potentiellement peu coûteux de plusieurs maladies dont le cancer.Mais avant que des tests médicaux ne puissent devenir une réalité clinique, il est nécessaire dedévelopper une technique d’analyse rapide, fiable, économique et portable. Les réseaux de senseurs(nez électroniques) à base de nanomatériaux qui peuvent satisfaire toutes ces exigences, constituentl’élément clef de l'identification des maladies par leur empreinte de COV dans l'haleine. L'objectif decette thèse est de fabriquer différents senseurs chemo-résistifs à base de nanocomposites conducteursayant la capacité de discriminer un ensemble de maladies (comme le cancer du poumon) par l’analysede leur biomarqueur (COV). Par conséquent, afin de fabriquer des senseurs de haute performance avecune grande sensibilité (ppb) et une sélectivité adaptée aux COV ciblés, différentes méthodologiesd’élaboration de nanocomposites conducteur, ont été implémentées. Des fonctionnalisations covalenteset non-covalentes de ces nanomatériaux de carbone ont été réalisées avec différents types demolécules, i.e., oligomères, polymères ou minérales afin d’ajuster la sélectivité et la sensibilité descapteurs. La nanodéconnection des jonctions du réseau percolé formé par les nanocharges de carbone aainsi pu être contrôlée en faisant varier la fonctionnalité chimique de leur surface. Finalement unensemble de senseurs de vapeur chemorésistifs de hautes performances, ayant une sélectivité pour lesbiomarqueurs du cancer du poumon ont pu être fabriqués et intégrés avec succès dans un nezélectronique.The
The analysis of specific VOC in exhaled breath (identified as biomarkers of specific disease like cancer)give an idea of metabolic and physiological activities of an individual and can provide non-invasive andpotentially inexpensive anticipated diagnosis of several diseases including cancer. The invention of afast, reliable, economic and portable technique is highly required before breath testing become a clinicalreality. Nanomaterial based sensor arrays can fulfill all these requirements and can form a solidfoundation for identification of disease related VOC patterns in exhaled breath. The objective of thisthesis was to fabricate different chemo-resistive sensors based on conductive nanocomposites withability to differentiate and discriminate a set of disease (such as lung cancer) biomarker VOC. Thereforein order to fabricate high performance sensors with high sensitivity and required selectivity towardstargeted VOC, adoption of different methodologies for the synthesis of conductive nanocomposite, wasstrongly emphasized.Covalent and noncovalent functionalizations of these carbon nanomaterials with various oligomeric,polymeric or inorganic molecules were done in order to tune the sensor’s selectivity and sensitivity.Nanoswitching at the junctions of percolated network formed by the carbon nanomaterials could becontrolled by varying the organic functionality on the surface.Finally a set of high performance chemoresistive vapour sensors, with different selectivity towardstargeted lung cancer VOC could be fabricated and successfully integrated in an e-nose with highefficiency towards detection and discrimination of a set of disease specific VOC biomarkers

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Colom, Sanmartí Glòria. "A Multiplexed diagnostic approach for cardiovascular disease biomarkers." Doctoral thesis, Universitat de Barcelona, 2016. http://hdl.handle.net/10803/396304.

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In the course of this thesis, the optimal epitopes for the subsequent polyclonal rabbit antibody production for cTnI and NT-proBNP have been studied and chosen. cTnI and NT-proBNP are the most relevant cardio-specific biomarkers for the diagnosis of cardiovascular diseases. With these antibodies, a sandwich ELISA for the detection of cTnI has been developed together with a competitive ELISA for the detection of NT-proBNP, both in a microplate format. It has been observed that cTnI has an extraordinary tendency to non-specifically adsorb itself onto surfaces and other biomolecules. This, with the inability to achieve the required detectability for this biomarker, have been the main problems to face with. Regarding the non-specific adsorption, different additives in the analyte or sample buffer have been evaluated. Thus, 0.15% casein in PBST combined with the use of low adsorption microplates (ImmulonTM 2HB) helps considerably to solve this problem. However, the sensitivity obtained for this assay in aqueous buffer is much lower than that required corresponding to the basal levels of cTnI in the blood. For the NT-proBNP ELISA development, the required limit of detection was achieved after studying various parameters related to heterology and other physicochemical parameters. Moreover, a good accuracy with NT-proBNP fortified plasma samples was obtained. It has been possible to develop a multiplexed microarray for the simultaneous detection of 5 biomarkers (cTnI, NT-proBNP, very important in the process of developing cardiovascular diseases, CRP, Cys C and H-FABP). Once the microarray is biofunctionalized using a spatial encoding with the corresponding bioconjugates or capture antibodies, immunoreagents and other biomarkers can be used in a cocktail. Neither cooperativity phenomena (union of immunoreagents that are in solution in sites where there are other biomarkers immobilized) nor cross-reactivity (recognition of different biomarkers from those for which immunoreagents have been developed) have been observed in any case. Only Lp(a) immunoreagents produced such interferences and therefore they were discarded. It has been highlighted the fact that the biomarkers present in different concentration ranges remains one of the main challenges for the multiplexed diagnosis when simultaneous measurements are desired. In this research, it was impossible to quantify the CRP and Cys C in the same microarray than H-FABP, cTnI and NT-proBNP employing direct samples. Fortunately, the fact of using glass surfaces in which 24 microarrays can be printed, has allowed making these measurements in a simultaneous and parallel way. With the multiplexed microarray, it has been possible to measure samples from patients with different pathologies. The results show that the efficiency of this microarray is much higher than that of analyzers currently used in clinical laboratories, regarding the ability to measure multiple biomarkers in a large number of samples in a short time and the coherence of the results. Thus, the microarray developed in this PhD thesis has been able to measure all the biomarkers from all patient samples, while analyzers only analyzed some of them, depending on the pathology, due to the cost (financial and time). The microarray was then able to detect high levels of CRP from patient samples that were not analyzed in clinical laboratory. Additionally, the microarray results are coherent with those obtained with analyzers for those cases in which measures had been made, and the disease had been diagnosed. The results have been satisfactory even in the case of NT-proBNP, which had not reached the detectability baseline even though it was very close. Unfortunately, it was not possible to measure cTnI levels with the microarray as it was expected according to previous studies done with the same immunoreagents. Thus, we can consider this multiplexed microarray as a semi-quantitative method useful for improving the diagnosis of cardiovascular disease for patients who are at different stages of the disease. Finally, preliminary studies have been realized to implement the multiplexed immunochemical system in a fluorescent optical sensor based on the evanescent wave. This was done with the aim to achieve a POC (point-of-care) device suitable to be used outside hospital premises, adapted to non-specialist users, and facilitate the diagnosis of cardiovascular diseases. Unfortunately, the results obtained point to the need to make greater efforts to increase the detectability of the system, since the LOD values obtained are worse than those achieved with the ELISA or the microarray, far from the basal levels in the case of NT-proBNP. The main problem in this thesis has been to reach the detection limits required by some biomarkers. Although in the literature and in the market there are assays that have achieved it, this fact mainly lies in the signal acquisition method as well as in the intrinsic sensitivity of the instrument addressed to do so.
En el transcurs d'aquesta tesi s'han escollit els epítops òptims per a la conseqüent producció d'anticossos policlonals de conill per a cTnl i NT-proBNP, dos dels biomarcadors més cardio-específics i rellevants pel diagnòstic de malalties cardiovasculars. Amb aquests anticossos s'ha desenvolupat un ELISA sandvitx per a la detecció de cTnl i un ELISA competitiu per a la detecció de NT-proBNP, tots dos en format de microplaca. S'ha observat que la cTnl te una extraordinària tendència a adsorbir-se de forma inespecífica a superfícies i també a altres biomolècules. Pel que fa a l'adsorció inespecífica s'han avaluat diferents additius en el tampó de la mostra o analit veient-se que la caseïna al 0,15% en PBST combinat amb l'ús de microplaques de baixa adsorció (ImmulonTM 2HB) ajuda considerablement a solucionar aquest problema. Tot i això, la sensibilitat obtinguda per aquest assaig en tampó aquós és molt inferior a la requerida corresponent als nivells basals d'aquest analit a la sang. En el desenvolupament de l'ELISA per NT-proBNP, després d'estudiar diferents paràmetres relacionats amb l'heterologia i altres paràmetres físico-químics, s'ha aconseguit assolir el límit de detecció necessari obtenint una bona exactitud amb mostres de plasma fortificades amb l'analit en qüestió. Ha estat possible desenvolupar un microarray multiplexat per a la detecció de 5 biomarcardors (cTnl, NT-proBNP, CRP, Cys C i H-FABP). Un cop biofuncionalitzat el microarray amb els corresponents bioconjugats o anticossos de captura, la resta d'immunoreactius i biomarcadors poden ser utilitzats en forma de còctel sense que en cap cas s'hagin observat fenòmens de cooperativitat ni de reactivitat creuada. Tant sols els immunoreactius de Lp(a) van produir aquestes interferències i per aquest motiu es van descartar. En aquest treball de recerca va ser impossible quantificar la CRP i Cys C en el mateix microarray que la H-FABP, cTnl i NT-proBNP de mostres directes. Afortunadament, el fet d'utilitzar superfícies de vidre en les quals es podien imprimir fins a 24 microarrays ha permès poder fer aquestes mesures de forma simultània i paral•ela. Amb el microarray multiplexat ha estat possible mesurar mostres de pacients amb diferents patologies. Malauradament, no va ser possible mesurar els nivells de cTnl amb aquest microarray, tal com era de preveure d'acord amb els estudis previs fets amb els immunoreactius utilitzats. Així doncs, podem considerar aquest microarray com un mètode semi-quantitatiu multiplexat útil per a la millora del diagnòstic de malalties cardiovasculars. Finalment, s'han realitzat estudis preliminars per implementar el sistema immunoquímic multiplexat en un sensor òptic fluorescent d'ona evanescent amb l'objectiu d'aconseguir un dispositiu POC (point-of-care). Malauradament, els resultats obtingut apunten a que és necessari fer un major esforç per a incrementar la detectabilitat d'aquest sistema, donat que els valors de LOD assolits són pitjors que els aconseguits amb l'ELISA o el microarray i, per casos com l'NT-proBNP, es troben molt allunyats dels valors basals.

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34

Andreasen, Niels. "Search for reliable diagnostic markers for Alzheimer's disease /." Stockholm, 2000. http://diss.kib.ki.se/2000/91-628-4039-8/.

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35

Voyle, Nicola Joanne. "Creating an early diagnostic test for Alzheimer's Disease." Thesis, King's College London (University of London), 2016. https://kclpure.kcl.ac.uk/portal/en/theses/creating-an-early-diagnostic-test-for-alzheimers-disease(fc5e88d2-7552-44cd-95a4-7eca4c93202f).html.

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The aim of the research in this thesis was to discover and validate blood biomarkers of early Alzheimer's Disease (AD). Existing and novel datasets from cohort studies were used for discovery and to attempt validation of previously reported biomarkers. For example, this thesis presents the first study to investigate associations between brain amyloid and blood metabolites. Further, this thesis presents the first study to combine more than one modality of blood biomarker in AD research and the first study to use a Bayesian methodology in this field. This thesis begins by aiming to validate candidate protein markers of brain amyloid burden in a novel proteomics dataset. Secondly, pathway-based methods are used to investigate the use of gene expression measurements as a potential biomarker of AD diagnosis. In the fourth chapter I generated a novel metabolomics dataset to investigate associations between blood metabolites and brain amyloid burden. A panel is found that predicts dichotomized amyloid burden with reasonable accuracy. The accuracy is improved by the inclusion of a candidate protein in the model. The fifth chapter of this thesis is focused on the use of a Bayesian methodology to predict measurements of amyloid using a variety of omics data. The Bayesian methodology allows incorporation of historical information by placing informative priors on demographic variables. No improvement is seen over demographics alone. The final chapter of this thesis aims to predict amyloid and tau burden using a polygenic risk score and levels of tau in blood. I have also considered a combined amyloid and tau pathology endpoint. The blood markers considered here do not improve predictive ability over demographics alone. Much of the work in this thesis highlights the importance of demographic factors in the diagnosis of early AD. The metabolite discovery work shows an improvement in predictive ability over demographics alone and warrants further investigation and replication. The other chapters of this thesis highlight that (in the settings investigated so far) blood measurements add minimal information above demographics alone.

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Sood, Sanjana. "Developing RNA diagnostics for studying healthy human ageing." Thesis, Loughborough University, 2017. https://dspace.lboro.ac.uk/2134/24708.

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Developing strategies to cope with increase in the ageing population and age-related chronic diseases is one of the societies biggest challenges. The characteristics of the ageing process shows significant inter-individual variation. Building genomic signatures that could account for variation in health outcomes with age may facilitate early prognosis of individual age-correlated diseases (e.g. cancer, coronary artery diseases and dementia) and help in developing better targeted treatments provided years in advance of acquiring disabling symptoms for these diseases. The aim of this thesis was to explore methods for diagnosing molecular features of human ageing. In particular, we utilise multi-platform transcriptomics, independent clinical data and classification methods to evaluate which human tissues demonstrate a reproducible molecular signature for age and which clinical phenotypes correlated with these new RNA biomarkers.

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Slyvka, Nataliia Oleksyivna, G. V. Nataliia, and Igor Antonovych Plesh. "MODERN WAYS TO IMPROVE DIAGNOSIS DIAGNOSTICS FOR ALCOHOLIC LIVER DISEASE." Thesis, МАТЕРИАЛЫ НАУЧНО-ПРАКТИЧЕСКОЙ КОНФЕРЕНЦИИ С МЕЖДУНАРОДНЫМ УЧАСТИЕМ. - Самарканд, 2016, № 2.1 (88), 2016. http://dspace.bsmu.edu.ua:8080/xmlui/handle/123456789/11624.

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何禮明 and Lai-ming Ho. "A study of diagnostic criteria employed in the analysis of lung function of textile workers." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1991. http://hub.hku.hk/bib/B31209749.

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Al-Khalili, Faris. "Coronary heart disease in women : diagnostic and prognostic markers /." Stockholm, 2000. http://diss.kib.ki.se/2000/91-628-4092-4/.

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40

Tilleman, Esther Hendrika Bernardina Maria. "Evaluation of diagnostic guidelines for hepatobiliary and pancreatic disease." [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2002. http://dare.uva.nl/document/62698.

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41

Bernardi, Enrico. "Diagnostic and therapeutic management of venous and arterial disease." [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2003. http://dare.uva.nl/document/68083.

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42

Pal, Suvankar. "Development of novel molecular diagnostic strategies in prion disease." Thesis, University College London (University of London), 2009. http://discovery.ucl.ac.uk/17554/.

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The causal association of variant Creutzfeldt-Jakob disease (vCJD) with bovine spongiform encephalopathy has raised significant concerns of a human epidemic. prolonged disease incubation, the possibility of asymptomatic carrier states, and the recognition of a transfusion-associated vCJD pose further public health concerns. Development of diagnostic tests is challenging as prions appear devoid of nucleic acid and comprised principally of an abnormal isoform (PrPSc) of host encoded prion protein (PrPC) to which there is immune tolerance. Detection of PrPSc can be used diagnostically but reliable detection in blood has yet to be achieved. Novel enrichment strategies have been developed for assaying PrPSc in clinical samples obtained from patients with vCJD and other forms of human prion disease. Firstly, a protocol for selective precipitation of PrPSc using sodium phosphotungstic acid has been developed. A second strategy involves optimisation of an immunoprecipitation protocol to detect PrPSc using a novel monoclonal antibody (ICSM33) with selectivity for disease-associated isoforms of PrP. This method obviates the need for protease pre-treatment of tissues and has been successfully applied to detection of PrPSc in vCJD brain homogenate and peripheral tissue samples. The method has also been successful in diagnosing other forms of human prion disease where conventional assays have failed. Both enrichment techniques have been optimised for recovery of PrPSc from up to 8mls of blood spiked to a dilution of 100ml 10% w/v vCJD brain. Assay of blood from patients with symptomatic vCJD using these techniques yields no immune signal; extrapolation from assays spiked with infected mouse brain dilution series suggests that levels of PrPSc present in symptomatic vCJD blood must represent levels of infectivity less than 2500 LD50 units ml-1. The techniques developed have immediate diagnostic applications and coupling with other high sensitivity methods may provide the increase in sensitivity required for a blood-based assay.

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Kerssens, Marleen Maartje. "Study of calcification formation and disease diagnostics utilising advanced vibrational spectroscopy." Thesis, Cranfield University, 2012. http://dspace.lib.cranfield.ac.uk/handle/1826/7924.

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The accurate and safe diagnosis of breast cancer is a significant societal issue, with annual disease incidence of 48,000 women and around 370 men in the UK. Early diagnosis of the disease allows more conservative treatments and better patient outcomes. Microcalcifications in breast tissue are an important indicator for breast cancers, and often the only sign of their presence. Several studies have suggested that the type of calcification formed may act as a marker for malignancy and its presence may be of biological significance. In this work, breast calcifications are studied with FTIR, synchrotron FTIR, ATR FTIR, and Raman mapping to explore their disease specific composition. From a comparison between vibrational spectroscopy and routine staining procedures it becomes clear that calcium builds up prior to calcification formation. Raman and FTIR indicate the same size for calcifications and are in agreement with routine staining techniques. From the synchrotron FTIR measurements it can be proven that amide is present in the centre of the calcifications and the intensity of the bands depends on the pathology. Special attention is paid to the type of carbonate substitution in the calcifications relating to different pathology grades. In contrast to mammography, Raman spectroscopy has the capability to distinguish calcifications based on their chemical composition. The ultimate goal is to turn the acquired knowledge from the mapping studies into a clinical tool based on deep Raman spectroscopy. Deep Raman techniques have a considerable potential to reduce large numbers of normal biopsies, reduce the time delay between screening and diagnosis and therefore diminish patient anxiety. In order to achieve this, a deep Raman system is designed and after evaluation of its performance tested on buried calcification standards in porcine soft tissue and human mammary tissue. It is shown that, when the calcification is probed through tissue, the strong 960 cm-1 phosphate band can be used as a pseudo marker for carbonate substitution which is related to the pathology of the surrounding tissue. Furthermore, the first study in which human breast calcifications are measured in bulk tissue with a thickness of several millimetres to centimetres is presented. To date, measurements have been performed at 41 specimens with a thickness up to 25 mm. Measurements could be performed through skin and blue dye. The proposed deep Raman technique is promising for probing of calcifications through tissue but will need refinement before being adopted in hospitals.

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Miller, Shelby Lynn. "Current and future strategies of bovine respiratory disease diagnostics and treatments." Kansas State University, 2016. http://hdl.handle.net/2097/34551.

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Master of Science
Department of Diagnostic Medicine/Pathobiology
Alison P. Adams
Bovine respiratory disease (BRD) is the most common and costly disease affecting cattle in the world today. The disease was first described in the late 1800s and is one of the most extensively studied diseases of livestock. BRD accounts for 65 - 80% of the morbidity and 45 - 75% of the mortality in some feedlots. Outbreaks typically occur around 10 days after transportation with the majority of deaths occurring within the first 45 days of arrival. Bacterial pathogens, physiologic stressors, and concurrent viral infections are all important factors causing BRD; other factors include seasonality, heritability, and breed tolerance. Diagnostic and treatment measures are continually being critiqued and researched. Even with continued research and the administration of antibiotics, BRD still continues to be a problem for the beef industry. Remote early detection and previous calf history are two resources that can help feedlots diagnose the disease earlier, or prevent it entirely. Feeding behavior and physical exams of the calves can also aid in early detection. New antibiotics and treatment methods have been developed, but the BRD problem still exists. Since the disease is most problematic in feedlot cattle, treatment of a large number of cattle in this setting can be costly, and often, performance and carcass traits are also affected. New preventative measures will be crucial to the industry with the continued problems and consequences of BRD. Improved treatment options and enhanced diagnostic tools will also be imperative for the control and treatment of BRD in the future.

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45

Bayoumy, Hassan, and L. O. Averyanova. "Actual problems of stroke disease cure in Egypt." Thesis, Харків, ХНУРЕ, 2019. http://openarchive.nure.ua/handle/document/8375.

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The causes of stroke disease in Egypt are considered. The diagnosis of stroke is explained, and the used diagnostic instruments are studied. The prevention liver cancer is explained. The treatment of each of the causes of liver cancer is analyzed.

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46

Zhong, Liang. "Studies on autofluorescence of gastric cancer and imaging of pancreaticobiliary diseases." [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2004. http://dare.uva.nl/document/76170.

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47

Leenaars, Petronella Engelina Maria. "Prevention and early detection of sexually transmitted diseases." Amsterdam : Maastricht : Thesis Publishers ; University Library, Maastricht University [Host], 1994. http://arno.unimaas.nl/show.cgi?fid=6593.

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48

Chiron, Francois. "3D matching of epicardial surface of the left ventricle and arterial structure." Thesis, Georgia Institute of Technology, 1997. http://hdl.handle.net/1853/8486.

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49

Hakuna, Lovemore. "Selective Indicators for Optical Determination of Disease Biomarkers." PDXScholar, 2014. http://pdxscholar.library.pdx.edu/open_access_etds/2053.

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The most abundant biological thiols, homocysteine (Hcy), cysteine (Cys) and glutathione (GSH) have been the subject of intense research due to their association with a wide range of diseases. They play a key role in maintaining the redox status of biological systems. Selective detection methods for these thiols are challenging due to their similar structures and properties. Current commercially available detection methods use separations, fragile and expensive enzymatic or immunogenic materials and complex instrumentation. This has led to a global effort towards developing simple and inexpensive optical probes and indicators selective for specific biological thiols. Highly selective chemical probes and simple methods for detection and potential quantification of Hcy and GSH in their natural biological media have been developed. These indicators and methods are relatively simple and inexpensive for potential application at point of care. The selective detection of Hcy using novel asymmetric viologen chemical probes at room temperature is described as well as the use of commercially available materials under photochemical conditions. These probes respond linearly proportional to increasing Hcy concentrations, potentially enabling the monitoring of Hcy levels in human plasma. Additionally, new methods for the selective determination of GSH in human plasma, as well as its quantification in whole blood deposited on filter paper (dried blood spots), is also presented herein.

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50

Menciotti, Giulio. "Advanced Echocardiographic Imaging In Dogs With Myxomatous Mitral Valve Disease." Diss., Virginia Tech, 2017. http://hdl.handle.net/10919/77704.

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Myxomatous mitral valve degeneration (MMVD) is the most common canine cardiac disease. In the studies presented in this dissertation, we used advanced echocardiographic techniques to elucidate several aspects of MMVD in dogs. Our hypothesis was that the mitral valve (MV) morphology could have a role in the development of MMVD. First, we tested whether we could use real time three-dimensional transthoracic echocardiography (RT-3DTTE), and an offline software for MV analysis to evaluate canine MV. We described that the technique was feasible and repeatable, we evaluated the morphology of the MV in healthy dogs, and we provided reference values for MV morphologic variables in this species. Then, we used the same technique to compare healthy dogs to dogs affected by MMVD. We found that dogs affected by MMVD have more circular and flatter valve. We then analyzed the MV of healthy Cavalier King Charles Spaniels (CKCSs), given the high predisposition of this breed for MMVD. Our findings indicate that compared to healthy dogs of other breeds, the MV of healthy CKCSs is flatter and has less leaflet tenting, corroborating our hypothesis that an altered MV morphology could represent a predisposing factor for disease development. We also used RT–3DTTE to characterize the area of the regurgitant MV orifice of dogs affected with MMVD, finding that the technique requires further standardization in order to become clinically useful. The elevation of pulmonary venous pressure caused by MMVD can, in some dogs, cause pulmonary arterial hypertension (PH), which is a risk factor associated with worse outcome in dogs with MMVD. Diagnosis of PH in dogs with MMVD is usually made by estimating pulmonary pressure using Doppler echocardiography. We are currently evaluating the accuracy of this technique, compared to invasive measurement of pulmonary pressure. Only preliminary data are presented regarding this study, as the disclosure of the blinding would have infringed the power of the study. Our preliminary results demonstrate that there is only moderate agreement between the two techniques, indicating that caution should be used when deriving the non-invasive estimation of systolic pulmonary pressure in order to make clinical decisions.
Ph. D.

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Dissertations / Theses on the topic 'Diagnostics of diseases'

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