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1
Enomoto, Dorathy Ngauwlieng Hendrikje. "Scleroderma: diagnosis and experimental therapy." [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2000. http://dare.uva.nl/document/57061.
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Marti, Pamela. "New perspectives for allergy diagnosis and therapy /." [S.l.] : [s.n.], 2005. http://www.zb.unibe.ch/download/eldiss/06marti_p.pdf.
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Jolley, Clive Joseph. "Radiolabelling of antibodies for tumour diagnosis and therapy." Thesis, University of Kent, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.334038.
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May, Stephen J. "Development of aspects of mechanical diagnosis and therapy." Thesis, Sheffield Hallam University, 2009. http://shura.shu.ac.uk/20757/.
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Mechanical Diagnosis and Therapy is a system of classification, assessment and management applied to all musculoskeletal problems that is used by clinicians worldwide. The first section concerns the up-dating and contextualising of Mechanical Diagnosis and Therapy (MDT). The books, co-authored with the founder of MDT, Robin McKenzie, applied the principles to extremity musculoskeletal problems, and then set MDT in the contemporary evidence-based background for lumbar, cervical and thoracic problems. This involved an up-dating of the classification system, as well as synthesis and analysis of aspects of musculoskeletal medicine. The second section presents a patient perspective on musculoskeletal problems. This involves an exploration of patient opinions about back pain and its management, and an audit of outcomes in a clinical setting in which an active exercise-based treatment approach was applied. The third section relates to a number of publications that sought to validate aspects of MDT. Centralisation is a key finding during the assessment of spinal patients and work on this included a systematic review of the relevant literature and an analysis of centralisation in patients with sciatica. In another study we conducted a secondary analysis of a published trial to see what happened if patients were crossed-over from exercises that were unmatched with directional preference to matched exercises. We published a case-control study that validates the postural syndrome and measured the prevalence rates of MDT classifications in the patient population. Reliability is a keycomponent of any musculoskeletal assessment system in which clinicians are making management decisions based on physical examination procedures - a systematic review that detailed the reliability of MDT compared to other commonly used examination procedures was an important contribution to the literature. Overall these works have led to a significant independent and original contribution to knowledge and understanding of MDT.
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Tse, Tsz Ho. "Medical robots for MRI guided diagnosis and therapy." Thesis, Imperial College London, 2009. http://hdl.handle.net/10044/1/5643.
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Magnetic Resonance Imaging (MRI) provides the capability of imaging tissue with fine resolution and superior soft tissue contrast, when compared with conventional ultrasound and CT imaging, which makes it an important tool for clinicians to perform more accurate diagnosis and image guided therapy. Medical robotic devices combining the high resolution anatomical images with real-time navigation, are ideal for precise and repeatable interventions. Despite these advantages, the MR environment imposes constraints on mechatronic devices operating within it. This thesis presents a study on the design and development of robotic systems for particular MR interventions, in which the issue of testing the MR compatibility of mechatronic components, actuation control, kinematics and workspace analysis, and mechanical and electrical design of the robot have been investigated. Two types of robotic systems have therefore been developed and evaluated along the above aspects. (i) A device for MR guided transrectal prostate biopsy: The system was designed from components which are proven to be MR compatible, actuated by pneumatic motors and ultrasonic motors, and tracked by optical position sensors and ducial markers. Clinical trials have been performed with the device on three patients, and the results reported have demonstrated its capability to perform needle positioning under MR guidance, with a procedure time of around 40mins and with no compromised image quality, which achieved our system speci cations. (ii) Limb positioning devices to facilitate the magic angle effect for diagnosis of tendinous injuries: Two systems were designed particularly for lower and upper limb positioning, which are actuated and tracked by the similar methods as the first device. A group of volunteers were recruited to conduct tests to verify the functionality of the systems. The results demonstrate the clear enhancement of the image quality with an increase in signal intensity up to 24 times in the tendon tissue caused by the magic angle effect, showing the feasibility of the proposed devices to be applied in clinical diagnosis.
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COX, ALYSIA SARAH-MARIE. "Nanoparticles for Therapy and Diagnosis of Neurodegenerative Diseases." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2019. http://hdl.handle.net/10281/241331.
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Nanoparticles (NPs) are studied as a promising tool to efficiently deliver drugs across biological barriers, which can hinder effective pharmacological treatment for a variety of diseases. One of the key issues to evaluate is the corona, a layer of proteins attached to the surface, formed upon contact of NPs with biological fluids. It is well known that the corona affects bioavailability, toxicity and clearance of NPs. Though the corona is relatively well defined under various conditions, its evolution when it crosses biological barriers was unknown. In my research I utilized gold NPs and a transwell cellular model of the BBB (human brain endothelial cells - hCMEC/D3) to investigate this issue. The protein composition of the corona across the “brain” and “blood” compartments was qualitatively and semi-quantitatively analyzed using SDS-PAGE and MS. The protein corona changed dramatically following passage through the BBB, since many proteins were removed, and 15 out of 381 were enriched in the “brain” side compared to the “blood” side, including alpha-2-macroglobulin and fetuin A. This clearly indicates the dynamic nature of the corona, and the ability or inability of specific proteins bound to NPs to traverse the BBB. The research also established that NP corona in the basolateral side is actually an evolution of the one formed on the apical side ruling out that it is formed in situ by interaction with proteins arriving independently from the apical side. Once beyond the barrier, the corona was stable upon incubation with other proteins
Proteins that were enriched upon passage were used to functionalize NPs, demonstrating their ability to boost passage through the BBB and suggesting that physiological proteins could help to more effectively deliver drugs to the central nervous system. Altogether, these results are particularly relevant when developing NPs that are required to traverse any biological barrier and may lead to the more successful design of therapeutic and/or diagnostic nanodevices.Nanoparticles (NPs) are studied as a promising tool to efficiently deliver drugs across biological barriers, which can hinder effective pharmacological treatment for a variety of diseases. One of the key issues to evaluate is the corona, a layer of proteins attached to the surface, formed upon contact of NPs with biological fluids. It is well known that the corona affects bioavailability, toxicity and clearance of NPs. Though the corona is relatively well defined under various conditions, its evolution when it crosses biological barriers was unknown. In my research I utilized gold NPs and a transwell cellular model of the BBB (human brain endothelial cells - hCMEC/D3) to investigate this issue. The protein composition of the corona across the “brain” and “blood” compartments was qualitatively and semi-quantitatively analyzed using SDS-PAGE and MS. The protein corona changed dramatically following passage through the BBB, since many proteins were removed, and 15 out of 381 were enriched in the “brain” side compared to the “blood” side, including alpha-2-macroglobulin and fetuin A. This clearly indicates the dynamic nature of the corona, and the ability or inability of specific proteins bound to NPs to traverse the BBB. The research also established that NP corona in the basolateral side is actually an evolution of the one formed on the apical side ruling out that it is formed in situ by interaction with proteins arriving independently from the apical side. Once beyond the barrier, the corona was stable upon incubation with other proteins Proteins that were enriched upon passage were used to functionalize NPs, demonstrating their ability to boost passage through the BBB and suggesting that physiological proteins could help to more effectively deliver drugs to the central nervous system. Altogether, these results are particularly relevant when developing NPs that are required to traverse any biological barrier and may lead to the more successful design of therapeutic and/or diagnostic nanodevices.
7
SuleÌ-Suso, Josep. "Autologous cell approaches to diagnosis and therapy in oncology." Thesis, Keele University, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.252570.
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Baillie-Hamilton, Paula. "Applications of magnetic resonance in cancer diagnosis and therapy." Thesis, University of Oxford, 1995. http://ora.ox.ac.uk/objects/uuid:72d25d7c-4f5a-4bc4-9fb0-45f758c09d7b.
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Wang, Xueli. "Organic molecules for diagnosis and therapy of Alzheimer's disease." HKBU Institutional Repository, 2020. https://repository.hkbu.edu.hk/etd_oa/883.
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Alzheimer's disease has become one of the most common diseases jeopardizing the health of the human being. The main pathological feature of AD is the accumulation of Aβ in the brain to form senile plaques. Therefore, it is of great significance to develop new and efficient drugs targeting at amyloid-β for the detection, diagnosis and therapeutics for Alzheimer's disease. Xanthohumol (Xn) naturally presents in hops (Humulus lupulus L). Studies have shown that it has anti-lipoperoxidative, anti-inflammatory, anti-proliferative activities, antiangiogenic and antioxidant effects, which further illustrates its potential therapeutic for AD. However, the bio-incompatibility and blood-brain barrier impermeability of Xanthohumol hindered it in vivo efficacy potential for treating Alzheimer's disease. Thus, we designed and prepared a series of Xanthohumol derivatives, namely, Xn-n, (n = 1-9) and its chalcone derivatives C-n, (n = 1-10) to enhance the desirable physical, biological and pharmacological properties, especially the blood-brain barrier permeability for intervention of AD. As an effective technique for in vivo visualization, Near-infrared fluorescence imaging based on organic small molecule probes has a promising application in the diagnosis of Alzheimer's disease. However, most of the reported imaging probes can only visualize Aβ-plaques but do not have therapeutic potential such as neuroprotection against Aβ induced toxicity. Herein, we designed and synthesized a series of oligomeric Aβ targeted near infrared (NIR) fluorescent probes for the diagnosis and therapeutics of Alzheimer's disease, namely DBAN-SLM, DBAN-SLOH, DBAN-OSLM which showed remarkably effective inhibitory effect on Aβ aggregation, significant neuroprotection effect against the Aβ-induced toxicities, and suppression on Aβ-induced ROS generation. indicating its great promise as a useful theragnostic agent for the early diagnosis and therapy of AD. Dual-modal imaging is an important approach to overcome the limitations of single imaging technology in the diagnosis of AD disease. Therefore, based on the dual-modal, we designed and synthesized the NIR/MR dual-modal detection and theragnostic probes namely Dyad-1, Dyad-2, Dyad-3 and NP@SiO2@F-SLOH. More surprising is that the two NIR/MR dual-modal probes show excellent biological properties, including the ability to inhibit Aβ aggregation to a certain extent, neuroprotective effects on cytotoxicity caused by different forms of Aβ species, blood-brain barrier (BBB) permeability, and high stability. All of these newly designed and synthesized molecules were characterized with 1H NMR, 13C NMR, and HRMS and found to show good agreement with the desired structures. The photophysical properties and biological properties of these novel designed and synthesized fluorescent probe such as UV-vis absorption, fluorescence emission, dissociation constant determined by fluorescence titration, cytotoxicity assay, neuroprotection, and inhibition of Aβ aggregation were investigated
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Hembury, Mathew Thomas. "Gold-silica quantum rattles for cancer therapy and diagnosis." Thesis, Imperial College London, 2013. http://hdl.handle.net/10044/1/14493.
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The Holy Grail of cancer research is to find effective treatments that can be easily delivered to diseased cells with minimal collateral damage to healthy tissue. In this context, recent developments in nanoparticle technology have aroused considerable interest with the promise of multifunctional vectors for both diagnostic and treatment of cancer. Recently, new emphasis has been placed on hybrid nanoparticle (NP) systems, where combinations of different types of nanostructured materials are used to create multimodal systems that exhibit the combined beneficial properties of the component modules. In particular, nanorattles, which are NPs with a core-shell structure containing a distinctive void separating the core material from the shell, constitute promising launch platforms for many biomedical applications. Current hybrid NP systems tend to concentrate on adding extra properties by increasing the number of modules and therefore, system complexity. However, added complexity in itself does not guarantee higher effectiveness. Therefore, in this thesis, a more holistic approach is proposed whereby simplicity, efficiency and usefulness of the design are not overlooked. The work presented here describes a gold-silica rattle-type particle, the Quantum Rattle (QR), made of a hollow mesoporous silica shell (HS) hosting two classes of hydrophobic gold nanostructures: gold quantum dots (AuQDs) and gold nanoparticles (AuNPs). The HS stabilises the gold nanostructures, making them dispersible in water and thereby enables biomedical applications. It also allows passive targeting for the QR via the enhanced permeability and retention (EPR) effect. The AuQDs absorb and emit light in the near-infrared (NIR) biological window where blood and soft tissue are relatively transparent (650 nm - 900 nm). With their NIR photonics, the AuQDs mediate both photothermal therapy (PPT) and live infrared imaging. Finally, the hydrophobic AuNPs optimise the system’s drug carrying performance by increasing the payload’s loading efficiency as well as controlling its release profile. This thesis exhibits the first evidence of the intrinsic and efficient therapeutic and diagnostic potential of this new class of hybrid NP system and discusses how these results could have a significant impact on the growing field of nanosystems used for cancer treatment.
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Alaimo, Salvatore. "From diagnosis to therapy: algorithmic methodologies for precision medicine." Doctoral thesis, Università di Catania, 2016. http://hdl.handle.net/10761/3731.
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In recent years, it has become established the idea of a novel medicine where a patient is the center around which multidisciplinary teams (made up of physicians, statisticians and bioinformaticians) sew targeted treatments. Precision medicine involves the use of detailed patient-specific molecular information for diagnosing, categorizing and guiding treatment of a disease, with the main purpose of improving the clinical outcome compared to a more classical approach. In precision medicine it is supposed that the cause of a disease is at least partially attributable to specific genetic or epigenetic characteristics of a patient. Therefore, identifying these specificities helps building the best treatment for each individual. Next-generation sequencing techniques are massively employed, giving the ability to quickly and at relatively low cost analyze whole genomes, epigenomes and transcriptomes. This ability is clinically important since the prediction of treatment effectiveness is usually affected by many factors.
A fundamental function in this new medicine is played by bioinformatics. It has a crucial role in every aspect of precision medicine, such as the accurate classification of patients, the prediction of new therapies based on current knowledge, the identification of possible outcomes of a disease or therapy, and the enrichment of current knowledge on pathogenic processes or on pharmaceuticals.
The aim of this thesis is the development of an integrated framework, based on synergistically operating tools, models and algorithms, which help to fill some of the major gaps in each step of the production of highly customized therapies, overcoming, if possible, the limitations of currently employed techniques, defining a new standard for precision medicine informatics.
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Bettocchi, Ilaria <1976>. "New approach in the diagnosis and therapy of hyperphenylalaninemia." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2012. http://amsdottorato.unibo.it/4593/1/Bettocchi_Ilaria_tesi.pdf.
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Background. Phenylketonuria is the most prevalent inborn error of aminoacid metabolism. Is an autosomal recessive disorder. It results from mutations in the phenylalanine hydroxilase (PAH) gene. Phenotypes can vary from mild hyperphenylalaninemia to a severe phenylketonuria wich, if untreated, results in severe mental retardation. Thanks to neonatal screening programmes, early detection and promp dietetic intervention (phenylalanine restricted diet lifelong) has allowed to avoid neurocognitive complications. Recently, a new therapy is become widely used: the oral supplementation with the PAH cofactor (BH4), wich can alleviate the diet burden. Genotype-phenotype correlation is a reliable tool to predict metabolic phenotype in order to establish a better tailored diet and to assess the potential responsiveness to BH4 therapy.
Aim Molecular analysis of the PAH gene, evaluation of genotype-phenotype correlation and prediction of BH4 responsiveness in a group of HPA patients living in Emilia Romagna.
Patients and methods. We studied 48 patients affected by PAH deficiency in regular follow-up to our Metabolic Centre. We performed the molecular analysis of these patients using genomic DNA extracted from peripheral blood samples
Results. We obtained a full genotipic characterization of 46 patients. We found 87 mutant alleles and 35 different mutations, being the most frequent IVS10-11 G>A (19.3%), R261Q (9.1%), R158Q (9.1%), R408Q (6.8%) and A403V (5.7%), including 2 new ones (L287, N223Y) ever described previously.
Notably, we found 15 mutations already identified in BH4-responsive patients, according to the literature. We found 42 different genotipic combinations, most of them in single patients and involving a BH4-responsive mutation.
Conclusion. BH4 responsiveness is shown by a consistent number of PAH deficient hyperphenylalaninemic patients. This treatment, combined with a less restricted diet or as monotherapy, can reduce nutritional complications and improve the quality of life of these patients.
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Bettocchi, Ilaria <1976>. "New approach in the diagnosis and therapy of hyperphenylalaninemia." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2012. http://amsdottorato.unibo.it/4593/.
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Background. Phenylketonuria is the most prevalent inborn error of aminoacid metabolism. Is an autosomal recessive disorder. It results from mutations in the phenylalanine hydroxilase (PAH) gene. Phenotypes can vary from mild hyperphenylalaninemia to a severe phenylketonuria wich, if untreated, results in severe mental retardation. Thanks to neonatal screening programmes, early detection and promp dietetic intervention (phenylalanine restricted diet lifelong) has allowed to avoid neurocognitive complications. Recently, a new therapy is become widely used: the oral supplementation with the PAH cofactor (BH4), wich can alleviate the diet burden. Genotype-phenotype correlation is a reliable tool to predict metabolic phenotype in order to establish a better tailored diet and to assess the potential responsiveness to BH4 therapy.
Aim Molecular analysis of the PAH gene, evaluation of genotype-phenotype correlation and prediction of BH4 responsiveness in a group of HPA patients living in Emilia Romagna.
Patients and methods. We studied 48 patients affected by PAH deficiency in regular follow-up to our Metabolic Centre. We performed the molecular analysis of these patients using genomic DNA extracted from peripheral blood samples
Results. We obtained a full genotipic characterization of 46 patients. We found 87 mutant alleles and 35 different mutations, being the most frequent IVS10-11 G>A (19.3%), R261Q (9.1%), R158Q (9.1%), R408Q (6.8%) and A403V (5.7%), including 2 new ones (L287, N223Y) ever described previously.
Notably, we found 15 mutations already identified in BH4-responsive patients, according to the literature. We found 42 different genotipic combinations, most of them in single patients and involving a BH4-responsive mutation.
Conclusion. BH4 responsiveness is shown by a consistent number of PAH deficient hyperphenylalaninemic patients. This treatment, combined with a less restricted diet or as monotherapy, can reduce nutritional complications and improve the quality of life of these patients.
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FIORITO, SERGIO. "Multi-materials nano-heterostructures for combined therapy and diagnosis." Doctoral thesis, Università degli studi di Genova, 2020. http://hdl.handle.net/11567/1001111.
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The present dissertation is resulting from the work performed during the Ph.D. research activity carried out at the Italian Institute of Technology (IIT) under the supervision of Dr. Teresa Pellegrino (Nanomaterials for biomedical research line) of the Italian Institute of Technology and Fabio Canepa of the University of Genova. The thesis has been conducted in the framework of the ERC-founded project ICARO (ERC starting grant n° 678109, Principal Investigator: Dr. Teresa Pellegrino), whose main purpose is the development of novel inorganic nanostructures for radiotherapy and chemotherapy of cancer. Thus, this thesis aims to progress the field of nanomedicine. In particular, the first goal of this work is to synthesize innovative water stable chalcogenide nanoparticles, with the purpose of achieving nano-sized platforms capable of incorporating radioactive 64Cu ions, which would make such systems suitable for the use in radiotherapy and for positron emission tomography. The second goal is to explore the coupling of such chalcogenide nanocrystals with magnetic nanoparticles, which are already part of the nanoparticles’ portfolio available in the research group where this thesis was carried out. These nanoparticles have shown great potential for magnetic hyperthermia treatment of cancer and, in combination with radiotherapy, could result in a synergic and more effective cancer treatment. Thus, this thesis provides new ground in the rational design of multifunctional nano-heterostructures for cancer diagnosis and therapy.
The first chapter of this thesis deals with the synthesis, water transfer and radiolabeling of ZnS nanoparticles. A non-hydrolitycal thermal decomposition synthesis route was exploited in order to obtain quasi-spherical nanoparticles. Such nanoparticles have hydrophobic ligands on their surface and thus are stable in organic solvents. In order to successfully transfer them to water phase, the ligands were exchanged through a procedure that employs a multi-dentate amphiphilic polymer (cysteamine-poly(isobutylene-alt-maleic anhydride)-polyethylene glycol, CYS-PIMA-PEG), which resulted in inorganic colloids with perfect stability in aqueous phase. On this system, cation exchange reactions with both radioactive and non-radioactive copper were carried out. The optimized protocol for the radiolabeling of ZnS nanocrystals with 64Cu permitted to obtain high values of radiochemical yield (93%), defined as the percentage of the total activity used that is incorporated in the crystals, without losing colloidal stability during radiolabeling reaction or subsequent concentration and purification process. The results obtained indicate ZnS nanoparticles as an efficient nano-platform for the use in radiotherapy and positron emission tomography, given the fast, reproducible and easily clinical-translatable radiolabeling procedure resulting in quantitative incorporation of 64Cu ions.
In the second chapter we report the research activity carried out to couple in a single nano-heterostructure, the ZnS nanoparticles or copper-deficient copper sulfide nanoparticles (previously reported to be exploitable as radioisotopes carriers) with highly performing magnetic nanoparticles (iron oxide nanocubes, IONCs) or nano-heterostructures (gold-iron oxide dimers, Au@FeOy). Although the direct growth of ZnS domains on IONCs, through colloidal two-pot seeded-growth synthesis procedures, was not possible, this thesis succeeds on merging the different nanoparticles in a single nano-platform by exploiting the use of gold NPs as “linkers” between magnetic iron oxide domains and copper deficient Cu2-xS domains, using Au@FeOy dimers as seeds for the growth of copper sulfide domains. Thus, this procedure resulted in the production of FeOy@Au@Cu2-xS2 trimers, with the additional possibility to tune the size of the Cu2-xS domain by changing precursors’ concentration. These trimers were thoroughly characterized through diverse structural and magnetic analysis techniques (transition electron microscopy, X-ray diffraction, SQUID magnetometry and UV-VIS-NIR spectroscopy). In particular, magnetic properties measurements, allowed to conclude that the magnetic properties of the FeOy@Au@Cu2-xS trimers are comparable to the ones of the Au@FeOy dimers (used as seeds for the subsequent reaction of growth of Cu2-xS domain). In addition, the trimers display two localized surface plasmon resonance absorption bands, one assigned to the gold domain and the other assignable to the copper deficient copper sulfide domain, respectively localized in the first and second NIR biological windows and, consequently, exploitable in photothermal therapy.
In the third chapter, the newly synthesized trimers were transferred to water phase and tested for the application as carriers for 64Cu and as heating probes in magnetic hyperthermia and photothermal therapy. Different strategies were explored in order to develop a reproducible and high-yield water transfer protocol. Among them, a two-step ligand exchange procedure employing methoxy-poly(ethylene glycol)-thiol and poly(catechol)-poly(ethylene glycol) as amphiphilic ligands resulted in aqueous phase stable trimers with high water transfer procedure yield (> 80 %). FeOy@Au@Cu2-xS trimers were also successfully transferred to water, although with lower yields if compared to previous procedure, using a polymer coating procedure and employing commercially available and cost-effective poly-(maleic anhydride-alt-1-octadecene). Lastly, the developed nano-platform showed great relevance in the field of nanomedicine. Indeed, when employed in magnetic hyperthermia, trimers resulted in high SAR values, preserving the excellent hyperthermia performances of the Au@FeOy used as seeds for their synthesis and thus in line with the best magnetic nano-heterostructures reported so far. Radiolabeling reactions were performed on trimers, resulting in a radiochemical yield of 97 %, higher than any value reported so far for 64Cu incorporation in water stable nanocrystals. Furthermore, the stability of the trimers during the radiolabeling and subsequent purification procedures was likewise ensured by the use of CYS-PIMA-PEG as stabilizing agent, permitting to recover quantitatively the nanocrystals and the associated radioactivity. The performances of FeOy@Au@Cu2-xS trimers when used in photothermal heating were also tested under the exposure to 808 nm laser irradiation. Although when using high power density (4.67 W/cm2), a temperature increase of 33°C in five minutes was registered, the performances obtained with lower laser’s power density were limited. However, the possibility to tune the absorption wavelengths by means of changing gold and copper sulfide domain’s properties, gives space to further improvements for these multifunctional nano-heterostructures. To the best of our knowledge, the here described FeOy@Au@Cu2-xS trimers are the first ever reported nano-heterostructures able to combine in one single nano-object the possibility to perform magnetic hyperthermia, photothermal therapy and radiotherapy/positron emission tomography, thus allowing the possible development of more efficient cancer treatments.
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García, Algar Manuel. "Optical methods and nano/microsystems for cancer diagnosis and therapy." Doctoral thesis, Universitat Rovira i Virgili, 2018. http://hdl.handle.net/10803/586091.
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Aquesta tesi es focalitza en el desenvolupament de nous mètodes per a la recerca en el diagnòstic i teràpia contra el càncer. Els fluds biològics de pacients suposen una font de material cancerígen que pot revel·lar informació sobre l'estat de progressió de la malaltia, si els analitzem amb enfocs de biòpsia líquida. Por altra banda, les propietats fisicoquímiques d'aquest material circulant, ja siguin cèl·lules tumorals senceres CTCs, ens poden ajudar a disenyar sistemes tant per a la seva detecció com per al tractament. L' ús de tècniques espectroscòpiques de fluorescència o basades en SERS ja han estat altament emprades en metodologies per microscopia i altres tècniques d'imatge per a l'evaluació del càncer, així que permeten l'avanç per a generar noves eines per aquest propòsit.
En resum, aquest treball proporciona dos mètodes óptics per a biòpsia líquida: un basat en les vies metabòliques universals de las cèl·lules canceroses que s'ha demostrat aplicable en pacients amb càncer de pulmó i un altre que empra un nano/microsistema de reconeixement de proteïnes aplicat en càncer de mama; a més, proporciona un agent terapèutic desenvolupat per al tractament de càncer de mama. Això, evidencia el potencial de la biofotònica i la nanomedicina al camp de la investigació en càncer.Esta disertación se focaliza en el desarrollo de nuevos métodos para la investigación en el diagnóstico y terapia contra el cáncer. Los fluídos biológicos de pacientes suponen una fuente de material cancerígeno que puede revelar información sobre el estado de progresión de la enfermedad, si los analizamos usando enfoques de biopsia líquida. Por otro lado, las propiedades fisicoquímicas de este material circulante, ya sean células tumorales enteras CTCs, nos pueden ayudar a diseñar sistemas tanto para su detección como tratamiento. El uso de técnicas espectroscópicas de fluorescencia o basadas en SERS ya han sido altamente utilizadas en metodologías por microscopía y otras técnicas de imagen para la evaluación del cáncer, así que permiten el avance para generar nuevas herramientas para este propósito. En resumen, este trabajo proporciona dos métodos ópticos para biopsia líquida: uno basado en las vías metabólicas universales de las células cancerosas que se ha demostrado aplicable en pacientes con cáncer de pulmón y otro que usa un nano/microsistema de reconocimiento de proteínas aplicado en cáncer de mama; además, proporciona un agente terapéutico desarrollado para cáncer de mama. Ésto evidencia el potencial de la biofotónica y la nanomedicina en el campo de la investigación en cáncer.
This dissertation is focused on the development of new methods for the investigation of cancer diagnosis and therapy. Since biological fluids from patients represents a source of cancerous material, they can provide valuable information about the disease progression, when analyzing them in a liquid biopsy approach. Additionally, physicochemical properties of this circulating material, as entire tumor cells CTCs, can help to engineer systems for its both detection and therapy. The use of fluorescence and SERS spectroscopy has been widely used in microscopic and imaging techniques for the pathological evaluation of cancer disease, so methods based on them permit the advancement in potential tools for the above mentioned purposes. In summary, this work provides two new optical liquid biopsy methods: one based on a universal metabolic pathway proven in specific human lung cancer samples and another using a protein recognition nano/microsystem applied to breast cancer; and an engineered system, as a therapeutic agent for specific breast cancer, evidencing the potential of biophotonics and nanomedicine in the field of cancer research.
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Hui, Chee-kin, and 許志堅. "Chronic hepatitis C infection: diagnosis, fibrosis progression and interferon therapy." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2003. http://hub.hku.hk/bib/B29756972.
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Patki, Abhay Harishchandra. "Cloning and expression of mycobacterial genes for diagnosis and therapy." Thesis, University of Surrey, 1991. http://epubs.surrey.ac.uk/844303/.
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The first part of the thesis describes the characterization of 19 kDa antigen from M. bovis BCG. The gene was expressed in E. coli and was detected using the monoclonal antibody CMA134.1. It was shown to be inducible in E. coli by performing Western blot analysis of induced and non-induced lysogens. The complete nucleotide sequence of the gene was determined and shown to be identical to that of 19 kDa gene from M. tuberculosis. This gene has the potential to be used as a diagnostic tool for the early detection of bovine tuberculosis. The second part of the thesis describes an attempt to clone, characterize and sequence the two genes, dihydrofolate reductase (DHFR) and thymidylate synthase (TS) from M. tuberculosis. Polymerase chain reaction technique was used to amplify the coding DNA sequences and the amplified DNA product of the reaction was used as the probe to screen the genomic library of M. tuberculosis. Putative genes for dihydrofolate reductase and thymidylate synthase were isolated from the genomic library. Both of these putative genes failed to complement the E. coli deficient strains of DHFR and TS genes. The complete nucleotide sequence of both these genes was determined. CLUSTAL analysis of both sequences showed only low homology with published Dihydrofolate reductase and Thymidylate synthase sequences.
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Hedberg, Rickard. "Preimplantation genetic diagnosis and therapy in humans- Opportunities and risks." Thesis, Örebro universitet, Institutionen för medicinska vetenskaper, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-81532.
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IntroductionPreimplantation Genetic Diagnosis (PGD) was developed in the 1990s and has been used since to diagnose and discard embryos with genetic conditions or chromosomal abnormalities. CRISPR-Cas9 was discovered in 2012 and has been used in research, but has not become clinical practice on humans yet. CRISPR-Cas9 could potentially be applied to treat and prevent genetic disorders.AimThe aim was to investigate the ethical dilemmas of each method through a set of research questions. The ethics of applying PGD according to Swedish guidelines and applying CRISPR-Cas9 on humans was investigated.MethodologyThis was not a systematic literature review. Instead, articles have been selected based on their explanation of each method and uniqueness or volume of ethical arguments surrounding each method, that is of relevance for the discussed issues.ResultsArguments in favour of PGD addressed among other things the somatic and psychological health of future children and parents along with the economical benefits. Arguments against PGD addressed different dilemmas of discarding an embryo and thereby a future individual. Arguments against CRISPR-Cas9 addressed technical limitations, our limited knowledge of genetics and more. Arguments in favour addressed benefits in clinical medicine and research.ConclusionsPGD according to Swedish guidelines was found to be ethically acceptable, since its restrictive use that have not given room for ethically dubious applications. CRISPR-Cas9 was found not to be safe enough for human applications at this moment due to technical limitations. If these were to be solved, caution and restraint must be urged.
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PICCITTO, ALESSANDRA. "New technologies and materials to improve diagnosis, therapy and surgery." Doctoral thesis, Politecnico di Torino, 2019. http://hdl.handle.net/11583/2734826.
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SALVATI, ELISA. "Multi-functionalized nanoparticles for therapy and diagnosis of alzheimer's disease." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2013. http://hdl.handle.net/10281/43984.
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Alzheimer Disease (AD) is the most common form of dementia among the older people and as the population ages, it is estimated to triplicate by 2040. Since an effective therapy and early diagnosis are not available at the date there is an urgent need to develop new methods and tools to treat this huge disease. The abnormal deposition of amyloid-beta peptides (Aβ) on brain tissues is one of the main neuropathological features of AD. Therefore, targeting of cerebral Aβ has been suggested for therapeutic and/or diagnostic purposes for the pathology. One of the main obstacle in the treatment of CNS diseases is the presence of the Blood-Brain Barrier (BBB) that selectively allows nutrients into the brain, while keeping out harmful components. Thus, the majority of drugs and contrast agents do not cross the BBB. Nanoparticle-mediated delivery represents one promising strategy to successfully treat CNS diseases, thanks to the unique properties of materials at the nanometer scale. Among the different nanoparticles (NPs), liposomes are attractive tools in biomedical applications thanks to their biocompatibility, non-immunogenicity, non-toxicity, biodegradability, high physical stability, versatility in surface functionalization.
In this work of thesis liposomes have been functionalized with ligands able to bind Aβ and eventually inhibit its aggregation, or multi-functionalized with both ligands directed to Aβ and molecules (antibodies or peptides) enhancing the BBB crossing. These last ones have been attached on liposome surface by covalent or non-covalent coupling techniques (i.e. maleimide-thiol coupling chemistry or biotin-streptavidin conjugation). The ability of these NPs to bind Aβ has been assessed in vitro by using the Surface Plasmon Resonance (SPR) technology, as principal technique, and the ability to cross the BBB has been studied on a cellular model of barrier (hCMEC/D3). Within this PhD project, functionalized polymeric NPs have been also tested for their binding towards different aggregation forms of Aβ peptide.
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Majem, Cavaller Blanca. "Micro-RNAs in ovarian cancer as tools for diagnosis and therapy." Doctoral thesis, Universitat Autònoma de Barcelona, 2017. http://hdl.handle.net/10803/458601.
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El càncer d'ovari (CO) és la cinquena causa del càncer en dones i la principal causa de mort entre les malalties ginecològiques. Els símptomes inespecífics i les eines diagnòstiques actualment insuficients no detecten la malaltia en estadis inicials, quan la supervivència és del 90%. Així, al voltant del 70% dels pacients es diagnostiquen en estadis avançats, quan la supervivència és <25%. Mentre que el 80% de les pacients són inicialment quimiosensibles, el 85% d'elles desenvolupen resistència i moren per recurrència. Identificar nous biomarcadors de diagnòstic podria millorar la detecció precoç del CO. A més, desenvolupar noves estratègies terapèutiques eficients és primordial. Els micro-ARNs (miARNs) són ARN no codificants de 22nt que regulen múltiples processos silenciant ARNm diana, i s'han trobat alterats en càncer, essent possibles elements terapèutics. A més, són estables en circulació i, podrien ser eines diagnòstiques no invasives, mitjançant la saliva com a font de biomarcadors. Primer objectiu: identificar nous biomarcadors de diagnòstic per al carcinoma serós d'alt grau (HGSC). Així, 32 salives de pacients en estadis inicials i avançats de HGSC i controls van ser sotmeses a seqüenciació d'ARN. Aproximadament, es va obtenir 100 ng d'ARN per mL de saliva, amb qualitat suficient per a la seqüenciació d'ARN. Les anàlisis bioinformàtiques van mostrar al voltant del 36% de l'alineació amb el genoma humà, donant lloc a la detecció de més de 500 miARNs coneguts. L'anàlisi d'expressió diferencial va mostrar que 49 i 45 miARNs es trobàven alterats significativament en salives de les pacients amb HGSC d’estadi inicial i avançat en comparació amb els controls, respectivament. Curiosament, la família miR-34 apareix comunment alterada, amb tres membres de la família sobreexpressats en les salives de pacients amb HGSC, tant en estadis inicials com avançats, suggerint que podrien ser biomarcadors per millorar la detecció precoç de les pacients amb HGSC. Segon objectiu: identificar noves teràpies basades en miARNs pel CO avançat, ja que les teràpies dirigides s'han convertit en el Sant Grial pel tractament del càncer. Aquí, el miR-654 es va trobar significativament disminuit en teixits de CO comparat amb ovaris benignes. La sobreexpressió d'aquest miARN en línies cel·lulars de CO va disminuir significativament la proliferació cel·lular i va augmentar la mort cel·lular per apoptosis in vitro, acompanyada d'una activació de l’apoptosis a nivell molecular. Cal destacar que l'expressió ectòpica del miR-654 reproduïa in vivo les conseqüències fenotípiques descrites. A més, mitjançant un model preclínic amb cèl·lules derivades d’ascitis de pacients amb HGSC, s’ha demostrat que la sobreexpressió del miR-654 disminuïa la capacitat de formació d’esferes i la seva viabilitat. Mitjançant una anàlisi bioinformàtica dels possibles mRNAs diana del miR-654 es van predir diversos gens, entre els quals HAX1, RAB1B, PBX3, CDCP1 i PLAGL2 van disminuir a nivell de mRNA i proteïna amb la sobrexpressió del miR-654. L’assaig luciferasa va confirmar que el mirR-654 s’uneix directament al 3’UTR dels 5 ARNs diana esmentats. El silenciament d’aquests gens va mostrar que la depleció de CDCP1 i PLAGL2 fenocopia els efectes de la sobreexpressió del miR-654. Curiosament, els nivells de proteina d’ambdós gens estaven reduïts amb la sobreexpressió del miR-654 en el model preclínic utilitzant cèl·lules d’ascitis de pacients, suggerint que l'efecte terapèutic del miR-654 podria ser, en part, conseqüència de la inhibició de CDCP1 I PLAGL2. Finalment, l'anàlisi de microarrays va demostrar que la depleció de CDCP1 i PLAGL2 alterava les vies MYC, Wnt/β-cat, AKT i MAPK. En conjunt, s’ha suggerit que l'expressió ectòpica de miR-654 podria alterar vies importants en OC i que l'ús d'aquest miARN com a eina terapèutica podria millorar les teràpies actuals, potencialment en combinació amb la quimioteràpia estàndard.Ovarian cancer (OC) is the fifth cause of cancer in women and the leading cause of death among gynecological malignancies in developed countries. The unspecific symptoms and currently insufficient diagnostic tools fail to detect the disease at an early stage, when the 5-years survival is 90%. Thus, around 70% of the patients are diagnosed at late stage, when the 5-years survival is <25%. Also, while 80% of the patients are initially chemosensitive, 85% of these develop resistance and die of recurrence. Therefore, identifying new diagnostic biomarkers would potentially improve the early detection of OC. Also, developing novel and efficient therapeutic strategies is paramount. Micro-RNAs (miRNAs) are small non-coding RNAs of 22nt that regulate multiple cellular processes by silencing of the specific target mRNAs, and have been found deregulated in cancer, being potential therapeutic elements. In addition, they are stable in circulation therefore being potential non-invasive diagnostic tools by using saliva as source of biomarkers. The first objective was to identify new miRNA diagnostic biomarkers for high-grade serous carcinoma (HGSC). Thus, 32 salivas were subjected for RNA-sequencing, in particular from early- and late-stage HGSC and control patients. Around 100 ng of RNA was found per 1 mL of saliva from control and HGSC patients, which was of sufficient quality for RNA sequencing. First bioinformatic analyses showed around 36% of alignment with the human genome, thereby resulting in a more than 500 known miRNAs and 65 De Novo miRNAs detected on average in the patients’ cohort. Differential expression analysis showed that 49 and 45 miRNAs were significantly deregulated in salivas from early- and late-stage HGSC patients compared to controls, respectively. Interestingly, miR-34 family appeared commonly altered, with three members of the family overexpressed in saliva from HGSC patients, either from early and late-stages, suggesting that they could be potential biomarkers to improve the early detection of HGSC patients, the most fatal subtype of OC. The second objective was to identify new miRNA-based therapies for late-stage OC, since targeted therapies has became the Holy Grail for cancer therapy. In this study, miR-654 was found significantly under-expressed in OC tissues compared to benign ovaries. Overexpression of this miRNA in clinically relevant OC cell lines resulted in a significant decrease in cell proliferation and marked increased apoptotic cell death in vitro, accompanied by an activation of the apoptotic pathway seen at cellular and molecular level. Importantly, ectopic expression of miR-654 reproduced the described phenotypic consequences in vivo. In addition, a pre-clinical model using 4 patient-derived ascitic cells showed that overexpression of miR-654 decreased the sphere forming capacity and reduced spheroid viability. In silico bioinformatics analysis of putative miR-654 targets predicted several genes, among which HAX1, RAB1B, PBX3, CDCP1 and PLAGL2 decreased at mRNA and protein level. A 3’UTR luciferase reporter assay confirmed that miR-654 is a direct of the 5 targets abovementioned. Additionally, silencing of the direct target genes showed that CDCP1 and PLAGL2 depletion phenocopied the effects of miR-654 overexpression, thereby resulting in a reduced proliferation and in an increased apoptosis. Interestingly, both genes were diminished at protein level upon miR-654-5p in the pre-clinical model using patient-derived ascitic cells, suggesting that the therapeutic effect of the miR-654 could be, in part, due to the inhibition of CDCP1 and PLAGL2. Finally, microarray analysis showed that the depletion of CDCP1 and PLALG2 altered MYC, Wnt/β-cat, AKT and MAPK pathways, which has been confirmed by the overexpression of miR-654. Altogether suggested that ectopic expression of miR-654 impaired canonical pathways in OC and that the use of this miRNA as a therapeutic tool might improve the current therapies, potentially in combination with the standard chemotherapy.
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Mumtaz, Hamid. "Magnetic resonance imaging in the diagnosis and therapy of breast cancer." Thesis, University College London (University of London), 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.401825.
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Ivory, Kamal. "Quantification of cellular antigens : biological tool in immunological diagnosis and therapy." Thesis, University College London (University of London), 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.286362.
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Palmer, Scott Gordon. "Development of non-invasive techniques for bladder cancer diagnosis and therapy." Thesis, University of Dundee, 2016. https://discovery.dundee.ac.uk/en/studentTheses/cb8dc9da-ae98-44a0-aa27-56f0bd9376dc.
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Bladder cancer is among the most common cancers in the UK, responsible for significant patient morbidity. Current techniques for detection suffer from low sensitivity, particularly for early stage disease, therefore new techniques are urgently sought. Among the suggested techniques to augment bladder cancer detection is the use of autofluorescence spectroscopy. Autofluorescence arises from a number of molecules in human tissue, giving a wealth of structural and metabolic information. Autofluorescence spectroscopy has previously been applied to the detection of a wide range of cancers, however clinical implementation of the technique to bladder cancer diagnosis is inhibited by a poor understanding of the contributions of individual fluorophores to autofluorescence. I sought primarily to use the multi-functional laser based diagnostic system “LAKK-M” to study the autofluorescence profiles of bladder cancer at the cell and tissue level, with the aim of developing a better understanding of bladder autofluorescence characteristics in health and disease. The significant findings of this research are threefold: 1. Autofluorescence flow cytometry of cell optical redox ratio reveals metabolic abnormalities in bladder cancer cells, specifically a glycolytic switch in bladder cancer cells culminating in an increased optical redox (NADH/flavin, ex360em425-475/ex488em515/545) ratio relative to healthy bladder cells. 2. Lab grown bladder cancer organoids show progressive changes in autofluorescence ratios relative to control samples – specifically reductions in the NADH/flavin (ex365em490/ex365em550), elastin/NADH (ex365em450/ex365em490) and elastin/flavin ratio (ex365em450/ex365em550), suggestive of structural and metabolic changes in developing cancer. 3. Analysis of human bladder tissue reveals significant differences in key fluorophores and diagnostic ratios between healthy and cancer tissue, amounting to increased porphyrin fluorescence and a decreased optical redox ratio (ex365em490/ex365em550) in cancer tissue compared to healthy control. These findings better inform our understanding of the autofluorescence properties of the bladder in health and disease at both the cell and tissue level, contributing to future development of diagnostic techniques. Additionally, in this thesis, I discuss the diagnostic worth of collagen analysis in bladder cancer using second harmonic generation imaging, the application of bladder tissue computer simulation to better elucidate fluorophore properties, and progress in novel laser therapy techniques for bladder cancer. The ultimate goal of this research is the development of a combined laser-based system for bladder cancer diagnosis and therapy.
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VIDETTA, ALESSANDRO DAVIDE. "Molecular analysis: an invaluable approach to improve diagnosis and tailor therapy." Doctoral thesis, Università di Siena, 2017. http://hdl.handle.net/11365/1011505.
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Neoplastic transformation can start in nearly every cell type in the human body. It is recognisable as cells acquiring the ability to divide uncontrollably and to escape aging mechanisms and naturally occurring cell death, resulting in the growth of a tumour. Tumours have different features, depending on the organ of origin and the level of differentiation of the tumour cells. At certain points in development, a tumour will be influencing its microenvironment, ensuring, among other things, vascularisation and cooperation with the immune system. A tumour can progress further, evolving into malignant disease, by invading the surrounding tissue, disseminating into the bloodstream or lymphatic channels, and establishing metastases in other parts of the body, often with fatal consequences for the affected individual.
The diversity of cancer, in both biological and clinical terms, is well acknowledged and has been extensively studied. Today, with increasingly sophisticated technologies at our disposal, highly detailed molecular features of individual tumours can be described. Such features are often referred to as being layered, occurring at the genomic (DNA), transcriptomic (mRNA) and functional proteomic (protein) levels. Proteins are the key functional elements of cells, resulting from transcription of a gene into mRNA, which is further translated into a protein. This simplistic way of describing the relationship between the layers has gradually changed during the past decades of functional and molecular insight. Protein synthesis is no longer perceived as a linear process, but as an intricate network of a multitude of operational molecules. Astonishing progress has been made in the discovery of molecules that are able to influence transcription and translation, such as DNA-modifying enzymes and non-translated RNAs, and of mechanisms that are able to control the processing, localisation and activation of proteins.
A picture is emerging of individual cells within a tumour that can differ at the genomic, epigenomic and transcriptional levels, as well as at the functional level. Mutations and epigenetic alterations create the required phenotypic diversity that, under the influence of shifting selective pressures imposed by the environment, determines the sub-clonal expansion and selection of specific cells. The development of solid tumours thus follows the same basic principles as Darwinian evolution. Most single nucleotide polymorphism (SNP) variants that arise in human evolution are neutral with respect to survival advantage; over a period of time, these variants are typically fixed in or die out from the genome according to chance. Other variants provide a survival advantage and will, over time, dominate the cell population, leading to distinct haploid signatures. Cancer may involve hundreds or thousands of mutations, with each mutation potentially contributing to tumour fitness. Most of these mutations are assumed to be passengers, but a limited number have driver capability, sometimes only in a sub-population of cells.
There is an intricate interplay between sub-populations of tumour cells and among tumour and normal cells in the microenvironment, and tumour topology is likely to play a role in this context. Our knowledge of molecular mechanisms in cancer development and progression are mainly derived from model systems such as in vitro cell cultures and animal models, as well as from descriptive molecular analyses of tissue samples. Model systems have been crucial for understanding molecular interactions and their implications in cancer, but they cannot fully mimic tumour conditions in vivo. Tissue samples, on the other hand, contain both a microenvironment and sub-populations of cancer cells, but they represent only a snapshot in an individual tumour’s life history. Until recently, cancer studies mainly considered only one or a few molecular levels at a time. Altered protein expression can have several causes; it can be due to copy number gain, a translocation event that combines the gene with an active promoter, alteration of factors that modify DNA or influence the transcription machinery, or modifications of mRNA or the protein itself. Revealing the various downstream effects of such alterations is potentially useful for tumour classification and for prediction of treatment response and prognosis.
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PORCU, ELENA PIERA. "Development of novel platforms for diagnosis and therapy in experimental medicine." Doctoral thesis, Università degli studi di Pavia, 2017. http://hdl.handle.net/11571/1215981.
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Murray, Samuel. "Monoclonal antibodies in the diagnosis, staging and therapy of Langerhans cell histiocytosis." Thesis, Imperial College London, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.298803.
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Russell, Brandon S. (Brandon Skylur). "Nucleic acid modifications in bacterial pathogens - impact on pathogenesis, diagnosis, and therapy." Thesis, Massachusetts Institute of Technology, 2014. http://hdl.handle.net/1721.1/90151.
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Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biological Engineering, 2014.Cataloged from PDF version of thesis.
Includes bibliographical references.
Nucleic acids are subject to extensive chemical modification by all organisms. These modifications display incredible structural diversity, and some are essential for survival. Intriguingly, several of these modifications are unique to bacteria, including many human pathogens. Given the enormous global disease burden due to bacterial infections, and the rapidly increasing rates of antibiotic resistance reported across the world, the need for research to address mechanisms of bacterial survival is more pressing than ever. The goal of this thesis was to determine the function of nucleic acid modifications in pathogenic bacteria, and to evaluate their impact on the three major stages of the infectious disease process: pathogenesis, diagnosis, and therapy. We first used quantitative profiling of tRNA modifications to identify novel stress responses that help mediate host invasion in the world's most common pathogen, Helicobacter pylori. This work uncovered potentially novel targets for the development of new compounds that inhibit pathogenesis. We then developed a new animal model of mycobacterial lung infection that enables drug development and biomarker screening studies in standard laboratories without high-containment facilities. We showed that infection with Mycobacterium bovis bacille Calmette-Guérin produces a granulomatous lung disease in rats that recapitulates many of the important pathological features of human tuberculosis. This model also allowed us to test the utility of nucleic acid modifications as diagnostic biomarkers. Finally, we investigated the effect of the common, transferable bacterial DNA modification phosphorothioation on oxidative and antibiotic stress responses in several pathogens. We showed that phosphorothioation can reduce the effectiveness of antibiotic therapy, which may make it an environmental source of acquired antibiotic resistance. These studies show that nucleic acid modifications play diverse roles in pathogenic bacteria, and that their modulation may be a promising target for developing new tools that can disrupt pathogenesis, improve diagnosis, and strengthen therapy.
by Brandon S. Russell.
Ph. D.
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Frangville, Camille. "Functional water soluble polymers and metal ions interactions for diagnosis and therapy." Toulouse 3, 2015. http://www.theses.fr/2015TOU30378.
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Les polymères hydrosolubles fonctionnels regroupent une grande variété d'architectures telles que des polymères linéaires (homopolymères, copolymères à blocs. . . ), ou branchés (dendrimères, polymères hyperbranchés). Ces structures peuvent supporter des fonctions chimiques spécifiques, leur conférant ainsi des propriétés fonctionnelles telles que la biocompatibilité ou des états modulables par stimuli externes comme le pH ou la température. Ces polymères peuvent en outre comporter des fonctions ionisables ou être greffés de ligands permettant d'établir des interactions polymères -ion smétalliques. Ces travaux de thèse portent ainsi sur l'utilisation d'interactions ions - polymères hydrosolubles et fonctionnels dans le cadre de deux applications biomédicales distinctes que sont l'imagerie à résonance magnétique (IRM) pour le diagnostic et la thérapie liée à la maladie d'Alzheimer. Ces colloïdes dopés par des ions métalliques posent de nombreuses questions de physico-chimie mais permettent égalmeent d'élargir de manière considérable le champ des possibles. L'utilisation de mélanges d'ions métalliques pour atteindre des systèmes pour l'imagerie multimodale ou pour la théragnostique.
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ADANTI, SARA. "Molecular mechanisms of carcinogenesis: identification of new targets for diagnosis and therapy." Doctoral thesis, Università degli Studi di Roma "Tor Vergata", 2014. http://hdl.handle.net/2108/203330.
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La proteina Translationally Controlled Tumor Protein (TCTP) svolge un importante ruolo come fattore di sopravvivenza nelle cellule tumorali ed è overespressa nelle cellule di carcinoma mammario scarsamente differenziato. TCTP è un target specifico della Diidroartemisinina (DHA). La DHA è il principale metabolita dell’Artemisinina, il principio attivo estratto dalla Artemisia annua L. La DHA è attualmente utilizzata come farmaco antimalarico. Recentemente, è stata inoltre dimostrata l’efficacia della DHA come antitumorale. In questo studio abbiamo valutato l’effetto antitumorale della DHA su lineee cellulari di carcinoma della mammella presentanti fenotipo altamente aggressivo, come le linee cellulari MDA-MB-231 ed SKBR3. I nostri risultati mostrano che la DHA inibisce la crescita delle cellule tumorali della mammella ed induce apoptosi, attraverso la riduzione dei livelli di espressione della forma fosforilata della TCTP. Inoltre, abbiamo dimostrato che la DHA aumenta l’efficacia dei farmaci comunemente utilizzati nella terapia antitumorale, come la Doxorubicina e il Trastuzumab. I dati ottenuti da questo studio suggeriscono che la fosfo-TCTP può rappresentare un nuovo bersaglio terapeutico per il trattamento del cancro della mammella. Inoltre, il trattamento combinatoriale con la DHA e i convenzionali chemioterapici potrebbe rappresentare una nuova potenziale strategia terapeutica per il cancro della mammella.Translationally Controlled Tumor Protein (TCTP) is a survival factor in tumor cells overexpressed in poorly differentiated breast cancer cells. TCTP is a specific target of Dihydroartemisinin (DHA). DHA is a metabolite of Artemisinin, the active principle of Artemisia annua L. DHA is an anti-malaria drug with antitumor properties. We studied the effect of DHA on human breast cancer cell lines (such as MDA-MB-231 and SKBR3 cells) with more aggressive phenotype. Our results show that DHA inhibits breast cancer cells growth and induces apoptosis by reducing the levels of the phosphorylated form of TCTP. We also show that DHA improves the antitumor effect of the conventional chemotherapy drugs, such as Doxorubicin and Trastuzumab. Altogether, these results suggest that phospho-TCTP is a novel therapeutic target for breast cancer cells. DHA in combination with conventional chemotherapeutics is a novel strategy to treat breast cancer
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PERSICO, ILARIA. "DEALING WITH THE MAIN CHALLENGES OF FANCONI ANEMIA MOLECULAR DIAGNOSIS AND THERAPY." Doctoral thesis, Università degli Studi di Trieste, 2023. https://hdl.handle.net/11368/3042318.
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L’anemia di Fanconi (Fanconi anemia, FA) è una sindrome genetica rara causata da un difetto nella riparazione del danno al DNA con ampia eterogeneità genetica, numerose mutazioni private ed elevato tasso di mosaicismo. Tali fattori compromettono tuttora la formulazione di una diagnosi molecolare in caso di varianti di difficile caratterizzazione o significato patogenetico incerto. La FA è caratterizzata da aplasia midollare e un’aumentata suscettibilità allo sviluppo di tumori ematologici e solidi. Dato che i trattamenti attualmente disponibili si rivolgono ai soli difetti ematopoietici, è essenziale identificare nuove terapie farmacologiche sistemiche per il trattamento dei pazienti FA. Abbiamo cercato di far fronte a tali criticità mediante: i. Progettazione di una strategia di screening mutazionale ottimizzata basata sul sequenziamento mirato di nuova generazione (targeted next generation sequencing, t- NGS) e su tecniche complementari per una diagnosi molecolare di FA più rapida ed esaustiva. ii. Validazione di sistemi cellulari basati sull’espressione di tre proteine FANCA mutanti, ma stabili (Arg951Gln, Thr1131Ala, Phe1263del), per uno screening ad alto contenuto di farmaci (high content screening, HCS) al fine di trovare molecole capaci di correggerne il fenotipo aberrante. iii. Realizzazione di clustered regularly interspaced short palindromic repeats (CRISPR) knockout (KO) screening su scala genomica per identificare nuove interazioni sintetiche (synthetic interactions, SIs) con i geni FA. Il conseguimento degli obiettivi di questo progetto di tesi fornirà una strategia comprensiva per le attuali sfide poste dalla FA, procedendo dal laboratorio al letto del paziente e viceversa.Fanconi anemia (FA) is a rare genetic DNA repair deficiency with vast genetic heterogeneity, multiple private mutations, and high mosaicism rate, still jeopardizing molecular diagnosis in case of variants with difficult characterization or unclear pathogenicity. FA also shows bone marrow failure and enhanced susceptibility to hematologic and solid malignancies. Since current treatments only address hematopoietic defects, it is essential to find new systemic drug-based therapies for FA patients. We sought to cope with these hurdles through: i. Design of an optimized mutation screening strategy based on targeted next generation sequencing and complementary techniques for a faster and exhaustive FA molecular diagnosis. ii. Validation of cellular systems expressing three stable, but defective FANCA proteins (Arg951Gln, Thr1131Ala, Phe1263del) suitable for high content screening (HCS) to identify drug/s able to rescue mutants’ phenotypes. iii. Performance of genome-wide (GW) clustered regularly interspaced short palindromic repeats (CRISPR) knockout (KO) screens to dissect novel synthetic interactions (SIs) with FA deficiency. The achievement of the goals of this thesis project will provide a comprehensive strategy for the current challenges of FA, proceeding from the bench to the bedside and back.
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Guszkowski, Andrea Jean. "Positive Patient Responses Regarding the Multidisciplinary Approach to Treatment of High Risk Pregnancies with Fetal Anomalies." University of Cincinnati / OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1179845686.
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Albers, Jonas [Verfasser]. "Preclinical evaluation of nanoparticle enhanced breast cancer diagnosis and radiation therapy / Jonas Albers." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2021. http://d-nb.info/1237128994/34.
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Martinčić, Markus. "Encapsulation of inorganic payloads into carbon nanotubes with potential application in therapy and diagnosis." Doctoral thesis, Universitat Autònoma de Barcelona, 2017. http://hdl.handle.net/10803/458136.
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Los nanotubos de carbono representan un grupo de materiales relativamente nuevo con potencial aplicación en diferentes áreas científicas. Esta tesis se centra en beneficiarse de sus cavidades internas para encapsular compuestos biomédicamente relevantes. Los nanotubos de carbono permiten el confinamiento de materiales en su interior impidiendo su fuga y, en consecuencia, reduciendo los efectos secundarios, no deseados, de estos materiales en el medio circundante. Esto hace que los nanotubos de carbono sean unos vectores elegantes para el diagnóstico y tratamiento de enfermedades.
Se ha demostrado que el proceso utilizado para purificar muestras de nanotubos de carbono permite no sólo la reducción de impurezas, que podrían causar citotoxicidad, sino también acortar la longitud de los nanotubos. Teniendo en cuenta que el análisis termogravimétrico es una técnica ampliamente utilizada para evaluar la pureza de muestras de nanotubos de carbono, se ha investigado la influencia que tienen diferentes parámetros que controlan este análisis para asegurar que los resultados obtenidos son lo más precisos y representativos posible. El proceso de purificación también ha sido reajustado para minimizar la cantidad de catalizador en muestras de nanotubos de carbono. También hemos desarrollado un protocolo que permite determinar el contenido de catalizador en muestras de nanotubos de carbono mediante espectroscopía ultravioleta-visible de una manera precisa y fiable.
Se ha investigado la preparación de cloruro de samario(III) anhidro a partir de óxido de samario(III), así como la capacidad que ofrece el material preparado para el llenado de nanotubos de carbono, ya que éste tiene interés para el desarrollo de radiotrazadores. El proceso de llenado de nanotubos de carbono resulta en muestras que contienen grandes cantidades de material externo, no encapsulado, lo cual puede comprometer el rendimiento del material en el contexto biológico. Hemos desarrollado un protocolo para monitorizar la eliminación del material no encapsulado a través de espectroscopía de ultravioleta-visible, que a la vez permite mejorar el procedimiento de lavado.
El uso de nanotubos de carbono multicapa tiene algunos beneficios sobre sus homólogos monocapa debido a la presencia de una cavidad interna más grande que puede contener más material. Se ha investigado el cierre espontáneo de las puntas de nanotubos de carbono multicapa a través de su calentamiento térmico a diferentes temperaturas, así como la encapsulación de distintos materiales en el mismo rango de temperaturas. Finalmente, distintas muestras de nanotubos de carbono multicapa llenos han sido examinadas in-vitro con el fin de evaluar su citotoxicidad y la captación celular de los nanosistemas desarrollados.Carbon nanotubes present a relatively novel group of materials with potential application in different scientific fields. The scope of this Thesis is to benefit from their inner cavities to encapsulate biomedically relevant payloads. Carbon nanotubes allow the confinement of selected materials within their walls, preventing their leakage and, as a consequence, undesired effects of such materials to the surrounding media. This makes filled carbon nanotubes very elegant vectors for the diagnosis and therapy of diseases. The process used to purify samples of carbon nanotubes proved to be a valuable asset, not only in the reduction of impurities which might cause cytotoxicity, but also for shortening the length of nanotubes. Thermogravimetric analysis is a widely-used technique in evaluating the purity of carbon nanotube samples. The role of different parameters that control the analysis has been investigated to assure that the most appropriate and representative results are obtained. The purification process has also been readjusted to assure the presence of the lowest amount of catalyst possible in the carbon nanotube samples with the employed purification strategy. We have also introduced a simple UV-Vis spectrophotometric assertion of the catalyst content in samples of nanotubes in a precise and reliable manner. The preparation of dry samarium(III) chloride from samarium(III) oxide was investigated, together with the nanotube filling-ability of the prepared material, of interest for the development of radiotracers. Bulk filling of carbon nanotubes results in samples that contain a large amount of external, non-encapsulated material, which can compromise the performance of the material in the biological context. We have developed a protocol to monitor the removal of the non-encapsulated material by means of UV-Vis, which in turn allows improving the washing procedure. The usage of multi-walled carbon nanotubes has some benefits over their single-walled counterparts, due to the presence of a bigger cavity which can host more material. The spontaneous closure of the tips of multi-walled carbon nanotubes by thermal annealing was investigated at different temperatures, along with the encapsulation of different materials. The prepared filled multi-walled samples were tested in-vitro to assess cytotoxicity and cellular uptake of the developed nanosystems.
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SANTONASTASO, ALICE. "Development of antibodies for diagnosis and therapy of hyperlipoproteinemia(a): targeting apolipoprotein(a) isoforms." Doctoral thesis, Università degli studi di Pavia, 2017. http://hdl.handle.net/11571/1203271.
Full textAbstract:
Cardiovascular diseases (CVDs) represent the leading cause of death in industrialized countries. Lipoprotein(a) [Lp(a)] is an important, yet novel and poorly characterized risk factor for atherosclerotic CVDs in humans, as elevated serum levels (>30-50 mg/dl) of this lipoprotein are strongly and causally associated to increased CVD risk. This circulating LDL-like lipoprotein carries a peculiar glycoprotein, named apolipoprotein(a) [apo(a)]. The fingerprint of Lp(a) is the astonishingly high degree of apo(a) size heterogeneity, which mainly depends on the genetically determined copy number (1-40 units) of its Kringle IV type 2 (KIV-2) domain. Interestingly, this number is inversely associated with Lp(a) levels in serum and with CVD risk, but, at present, there is no clear explanation for the higher pathogenicity of the small apo(a) isoforms compared to their large counterparts.
The research work of my thesis was conceived to address, by a multi-disciplinary approach, two open issues, strictly related one to the other, regarding Lp(a) heterogeneity: (1) the need for improved research, diagnostic and therapeutic tools specific for the study and clinical monitoring of Lp(a), and (2) the need to clarify the role of apo(a) size, as determined by the copy number of KIV-2, in atherosclerosis pathophysiology.
For the first aim of the work, production of an anti-KIV-2 mAb in hybridoma culture and engineering of its scFv format were carried out, with a good expression of the latter obtained in the yeast P. pastoris. KIV-2 single domain and KIV-2-KIV-2 tandem domains were over-expressed in E. coli and P. pastoris hosts, resulting in high yields. Binding of the anti-KIV-2 antibodies to these target antigens was demonstrated through immunoblotting, immunoenzymatic assays and gel filtration. In surface plasmon resonance, the mAb demonstrated very promising affinity properties. Thus, the antibodies here developed will be evaluated as potential key tools in systems dedicated to the diagnosis and therapy of hyperlipoproteinemia(a).
For the second aim of this research, a set of specialized biophysical analyses allowed to highlight some isoform-specific properties of Lp(a) that suggested the identification of a new, isoform-related, threshold of CVD risk. In parallel, some interesting Lp(a)- and isoform-dependent effects on model target cell types were detected using an innovative and sensitive real-time in vitro cell analysis. This system is relevant to determine anti-Lp(a) antibody interference on Lp(a)-mediated biological effects. Preliminary evidence was achieved both on the Lp(a) particle structure by negative staining electron microscopy and on crystallization of the KIV-2, as a background work for future high-resolution structural analyses. Finally, an efficient Golden Gate cloning platform was set-up to allow, upon expression in suitable hosts, the generation of a library of recombinant apo(a)/Lp(a) isoforms, which could constitute reliable starting material to accurately study intrinsic and specific properties of these variants. It is expected that these contributions will be useful towards a better diagnosis and therapy of hyperlipoproteinemia(a).
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SCANO, ALESSANDRA. "Pseudomonas aeruginosa related to Nosocomial and Animal infections. New approaches in diagnosis and therapy." Doctoral thesis, Università degli Studi di Cagliari, 2019. http://hdl.handle.net/11584/260761.
Full textAbstract:
Pseudomonas aeruginosa is a small bacillus gram negative, aerobic, asporogenous, monoflagellate, non-fermenting. P. aeruginosa infections often have a very severe course and are difficult to treat because of its ability to form biofilms characterized by a thick capsule coated with alginate (an exopolysaccharide consisting of D-mannuronic acid and glucuronic acid monomers). Alginate represent the main component of the extracellular matrix of P. aeruginosa biofilm; as a consequence, the alginate lysis facilitates the spread of antimicrobial substances. In fact, this extracellular matrix makes these micro-organisms resistant to antimicrobial agents and leads to the emergence of multidrug resistant clinical isolates (MDR) during therapy. Mutations in the mucA gene encode a protein involved in the production of this exopolysaccharide. In fact, in vitro inactivation of mucA in Pseudomonas aeruginosa PAO1 (non-mucoid) produces Alg+ strains; this seems to indicate, therefore, that mucA acts as a negative regulator of the production of alginate because it can bind and sequester the factor σ22, through the N-terminal cytoplasmic domain. The risk of P. aeruginosa infection may be related to several factors such as: (i) inappropriate therapies or prophylaxis measures, (ii) failure in the environmental monitoring systems (iii) inadequate laboratory protocols for detecting MDR strains. For example, the inappropriate use of peroxides as disinfectants could be increase the mutation rate in mucA gene. In this context, the P. aeruginosa biofilm studies allow to characterize new antimicrobials and to ascertain what are the useful ranges of the disinfectant that do not induce the mucoid phenotype more virulent and more resistant respectively to the not mucoid phenotype. Mutations present in the promoter of the gene or along the amino terminal part of the protein modulate an alginate hyper-expression giving the biofilm a barrier almost impermeable to the antimicrobials, this aspect must be considered during the use of oxidizing microbicides such as hydrogen peroxides, in able to determine mutations in the mucA gene.
This work aims to study P. aeruginosa infections and its environmental contaminations as a global health problem. In fact, this multi-task pathogen can contaminate different areas in human, veterinary and agricultural fields. For this reason, a comprehensive work must be performed by different strategies in these points:
1 Pathogen detection: in this work, we describe a fast-molecular approach to detect the initial pathogen biofilm samples contaminated with Pseudomonas spp. (P. aeruginosa, P. fluorescens and P. putida). This procedure is based on the particular bi-functional FRET oligonucleotide probes named DUAL-FRET.
2 mucA / alginate profile: in P. aeruginosa, mucA genotype resulted essential to reveal high drug-resistant strains due to alginate hyperproduction in the biofilm.
3 Evaluation of potential new antimicrobials: a critical point in anti - P. aeruginosa prophylaxis is represented by the absence of highly performant disinfectant.
4 New cultural systems: design/use of bioreactors able to reproduce, in standard controlled conditions, the initial parameters in the primary contamination area, for example the cold storage implants in the food production
5 Future strategies: following the recent new molecular procedures obtained in biological field could be possible to design new clinical/laboratory strategies against P. aeruginosa, for example the study of miRNAs.
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Starfinger, Christina. "Patient-Specific Modelling of the Cardiovascular System for Diagnosis and Therapy Assistance in Critical Care." Thesis, University of Canterbury. Mechanical Engineering, 2008. http://hdl.handle.net/10092/1718.
Full textAbstract:
Critical care is provided to patients who require intensive monitoring
and often the support of failing organs. Cardiovascular and circulatory
diseases and dysfunctions are extremely common in this group of patients. However, cardiac disease states are highly patient-specific and every patient has a unique expression of the disease or underlying dysfunction. Clinical staff must consider many combinations of different disease scenarios based on frequently conflicting or confusing measured data on a patient’s condition. Successful diagnosis and treatment therefore often rely on the experience and intuition of
clinical staff, increasing the likelihood for clinical errors.
A cardiovascular (CVS) computerized model that uniquely represents
the patient and underlying dysfunction or disease is developed. The CVS model is extended to account for the known physiologic mechanisms during spontaneous breathing and mechanical ventilation, thus increasing the model’s accuracy of representing a critically ill patient in the intensive care unit (ICU). The extended CVS model is validated by correctly simulating several well known circulatory mechanisms and interactions. An integral-based system parameter identification method is refined and extended to account for much smaller subsets of available input data, as usually seen in critical care units. For example, instead of requiring the continuous ventricle pressure and volume waveforms, only the end-systolic (ESV) and end-diastolic (EDV) volume values are needed, which can be even further reduced to only using the global
end-diastolic volume (GEDV) and estimating the ventricle volumes. These changes make the CVS model and its application to monitoring more pplicable to a clinical environment.
The CVS model and integral-based parameter identification approach are validated on data from porcine experiments of pulmonary embolism (PE), positive end-expiratory pressure (PEEP) titrations at different volemic levels, and 2 different studies of induced endotoxic (septic) shock. They are also validated on 3 adrenaline dosing data sets obtained from published studies in humans. Overall, these studies are used to show how the model and realistic clinical measurements may be used to provide a clear clinical picture in real-time. A wide range of clinically measured hemodynamics were successfully
captured over time. The integral-based method identified all model parameters, typically with less than 10% error versus clinically measured pressure and volume signals. Moreover, patient-specific parameter relationships were formulated allowing the forward prediction of the patient’s response towards clinical interventions, such as administering a fluid bolus or changing the dose of an inotrope. Hence, the model and methods are able to provide diagnostic information and therapeutic decision support. In particular, tracking the model parameter changes over time can assist clinical staff in finding the right diagnosis, for example an increase in pulmonary vascular resistance indicates a developing constriction in the pulmonary artery caused by an embolus. Furthermore, using the predictive ability of the model and developed methods, different treatment choices and their effect on the patient can be simulated. Thus, the best individual treatment for each patient can be developed and chosen, and unnecessary or even harmful interventions avoided.
This research thus increases confidence in the clinical applicability and validity of this overall diagnostic monitoring and therapy guidance
approach. It accomplishes this goal using a novel physiological model of the heart and circulation. The integral-based parameter identification methods take dense, numerical data from diverse measurements and aggregate them into a clearer physiological picture of CVS status. Hence, the broader accomplishment of this thesis is the
transformation, using computation and models, of diverse and often confusing measured data into a patient-specific physiological picture - a new model-based therapeutic.
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Schefer, Quirino [Verfasser]. "Generation of new GPCR-antibodies for target validation in tumor diagnosis and therapy / Quirino Schefer." Berlin : Freie Universität Berlin, 2012. http://d-nb.info/1026992249/34.
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Vernon, Howard. "Manual therapy of headaches of spinal origin : an investigation of etiology, mechanisms, diagnosis and treatment." Thesis, University of South Wales, 2003. https://pure.southwales.ac.uk/en/studentthesis/manual-therapy-of-headaches-of-spinal-origin(62c54f22-8e9d-4e49-b2b1-b2b7193d2223).html.
Full textAbstract:
This thesis has proposed the following: "that mechanical disorders of the upper cervical spine are an important cause of headaches". Four hypotheses were developed to investigate this thesis. 1. Upper cervical spine dysfunction plays an important role in headache etiology. 2. The importance of this role is more or less, depending on the type of headache. 3. Cervical dysfunction can be assessed and characterized by a range of standard clinical methodologies employed in manual therapy. 4. The cervical dysfunction involved in these types of headaches is treatable by spinal manipulative therapy and this results in clinical benefit for patients with these conditions. Four areas of evidence from my published work have been summarized to support this thesis. A. An anaesthetized animal model of upper cervical deep somatic inflammation has provided pathophysiologic responses which could be the origins of headaches of cervical origin, particularly the type currently known as "cervicogenic headache". B. Clinical descriptions have been redefined to reveal common features which could be grouped together and attributed to pathologies or dysfunctions in the regions investigated in the animal model. C. A new form of questionnaire was developed which produced evidence of an association between headache and neck pathology or dysfunction. D. An extensive literature review revealed reported associations between headache and neck pathology in diverse works, particularly those involving manual assessment and therapeutic procedures in the cervical spine. The evidence from such diverse sources strongly supports the hypotheses developed here and my thesis, that mechanical disorders of the upper cervical spine are an important cause of headache.
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Moore, Adam Mousley. "Relational Diagnosis and Psychotherapy Treatment Cost Effectiveness." BYU ScholarsArchive, 2011. https://scholarsarchive.byu.edu/etd/2927.
Full textAbstract:
Despite a call by researchers for estimates of the treatment clinical and cost effectiveness for relational problems, very little has been done to answer this call. The present study is an examination of actual treatment costs and recidivism rates for patients treated for a relational problem (either in individual or conjoint therapy sessions) in the CIGNA network. Despite the fact that this study compares treatment provider cost-effectiveness for treating relational problems, analyses do not control for average amounts paid by provider license type. Policymakers and third-party payers may use such clinical-effectiveness and cost-effectiveness data to make decisions regarding treatment of relational problems and funding allocation. The present study is also the first to compare the costs of couples therapy versus family therapy for relational problems.
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Oldfield, Amelia. "Music therapy with children on the autistic spectrum : approaches derived from clinical practice and research." Thesis, Anglia Ruskin University, 2003. http://arro.anglia.ac.uk/613151/.
Full textAbstract:
This thesis focuses on two specific clinical areas: music therapy with pre-school children with autistic spectrum disorder and their parents, and music therapy diagnostic assessments with children between the ages of four and twelve who are suspected of being on the autistic spectrum. Firstly, the literature was examined and the clinical work was described in detail. This process made it possible to determine what characterises the author’s particular approach, and to find out how it may be different to other music therapists’ work. A 45 minute video which illustrates the approach with pre-school children with autism and their parents accompanies this thesis. Two outcome research investigations were carried out. The first involved studying ten pre-school children with autistic spectrum disorder and their parents who received weekly, individual music therapy sessions over a period of 18 to 26 weeks each. The sessions were video-taped and the videos analysed in detail. The parents were interviewed and asked to fill in questionnaires both pre- and post-treatment. Nine out of the ten dyads achieved some or all of the individual aims set out before treatment began. The parents all felt that music therapy had been effective. The author also looked at how she spent her time in music therapy sessions across the ten children and found that she was generally very active and spent a high proportion of her time vocalising. The second investigation compared Music Therapy Diagnostic Assessments (MTDA) with Autistic Diagnostic Observation Schedules (ADOS) carried out on 30 children suspected of being on the autistic spectrum. A scoring system similar to that used for the ADOS was devised for the MTDA especially for this research investigation. In addition, the children were interviewed after both the MTDA and the ADOS and the people carrying out the tests filled in a questionnaire about their perceptions of the assessment tool after every test. The two assessments showed 72 % of agreement between diagnostic categories, indicating that the MTDA was providing similar information as a recognised and established diagnostic tool. However, the two assessments also showed significant differences in scores of individual questions, indicating that the MTDA could serve a useful and distinct purpose in helping the psychiatric team to diagnose children with autism. The children generally enjoyed the assessments and the music therapist felt that the test was easy to carry out and score, indicating that the MTDA was ‘user-friendly’. Throughout this thesis the author has adopted a personal style particularly when describing her own clinical work and when examining the literature. Although the two outcome investigations rigorously examined numerical data, the author also described her own impressions as the research investigation progressed.
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Oldfield, Amelia. "Music therapy with children on the autistic spectrum approaches derived from clinical practice and research." Thesis, Anglia Ruskin University, 2003. https://arro.anglia.ac.uk/id/eprint/613151/1/Amelia%20Oldfield%20-%20PhD%20Thesis%20final.pdf.
Full textAbstract:
This thesis focuses on two specific clinical areas: music therapy with pre-school children with autistic spectrum disorder and their parents, and music therapy diagnostic assessments with children between the ages of four and twelve who are suspected of being on the autistic spectrum.
Firstly, the literature was examined and the clinical work was described in detail. This process made it possible to determine what characterises the author’s particular approach, and to find out how it may be different to other music therapists’ work. A 45 minute video which illustrates the approach with pre-school children with autism and their parents accompanies this thesis.
Two outcome research investigations were carried out. The first involved studying ten pre-school children with autistic spectrum disorder and their parents who received weekly, individual music therapy sessions over a period of 18 to 26 weeks each. The sessions were video-taped and the videos analysed in detail. The parents were interviewed and asked to fill in questionnaires both pre- and post-treatment. Nine out of the ten dyads achieved some or all of the individual aims set out before treatment began. The parents all felt that music therapy had been effective. The author also looked at how she spent her time in music therapy sessions across the ten children and found that she was generally very active and spent a high proportion of her time vocalising.
The second investigation compared Music Therapy Diagnostic Assessments (MTDA) with Autistic Diagnostic Observation Schedules (ADOS) carried out on 30 children suspected of being on the autistic spectrum. A scoring system similar to that used for the ADOS was devised for the MTDA especially for this research investigation. In addition, the children were interviewed after both the MTDA and the ADOS and the people carrying out the tests filled in a questionnaire about their perceptions of the assessment tool after every test. The two assessments showed 72 % of agreement between diagnostic categories, indicating that the MTDA was providing similar information as a recognised and established diagnostic tool. However, the two assessments also showed significant differences in scores of individual questions, indicating that the MTDA could serve a useful and distinct purpose in helping the psychiatric team to diagnose children with autism. The children generally enjoyed the assessments and the music therapist felt that the test was easy to carry out and score, indicating that the MTDA was ‘user-friendly’.
Throughout this thesis the author has adopted a personal style particularly when describing her own clinical work and when examining the literature. Although the two outcome investigations rigorously examined numerical data, the author also described her own impressions as the research investigation progressed.
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Sachse, Sandy. "The effectiveness of mindfulness-based cognitive therapy for individuals with a diagnosis of borderline personality disorder." Thesis, University of Hertfordshire, 2009. http://hdl.handle.net/2299/2805.
Full textAbstract:
This study investigated the discharge practice of a Community Mental Health Team (CMHT) by examining records (electronic and file) of clients discharged between April 2005 and March 2006. Out of a total of 211 discharged clients a random sample of 20 clients was selected to examine the extent to which records and reasons for discharge adhere to current CMHT policies and guidelines. In addition, a sample of clients who had been engaged by the CMHT for 6 months or less was compared to a sample of clients who have been engaged for 1 year or longer to establish whether these differed in sociodemographic characteristics, diagnoses and extent of service provision. The majority of clients discharged during the specified period consisted of clients engaged for 6 months or less. The sampling process revealed that a proportion of these included clients seen for one-off assessments or duty calls, indicating that there is room for improvement to clarify referral criteria (e.g. to GPs) and the role of the CMHT. Similarly, the examination of recording practice also revealed room for improvement in the closing of care packages electronically and inclusion of required information in discharge letters. Almost 50% of clients in the sample were discharged following a decline of any further intervention the reasons for which it will be important to investigate in the form of an audit or survey of service user’s views. Clients engaged for 6 months or less and 1 year or longer seemed to differ mostly in terms of employment rates, diagnosis and previous inpatient admission and mental health act sections. The findings are discussed in relation to the limitations of this study, implications for the service and further research.
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Grifantini, Renata Maria <1962>. "Identification and characterization of novel tumor-associated proteins as potential tumor markers for diagnosis and therapy." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2014. http://amsdottorato.unibo.it/6479/1/Tesi_PhD_Grifantini.pdf.
Full textAbstract:
This study deals with the discovery and characterization of EXN6 and EXN11 as novel tumor-associated proteins. EXN6 is mainly present in breast and ovary cancers (40 and 35%) while EXN11 is mainly detected in primary and metastatic colon cancer (40%). A characterization of the two proteins confirmed that they could be novel targets for cancer therapy.
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Grifantini, Renata Maria <1962>. "Identification and characterization of novel tumor-associated proteins as potential tumor markers for diagnosis and therapy." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2014. http://amsdottorato.unibo.it/6479/.
Full textAbstract:
This study deals with the discovery and characterization of EXN6 and EXN11 as novel tumor-associated proteins. EXN6 is mainly present in breast and ovary cancers (40 and 35%) while EXN11 is mainly detected in primary and metastatic colon cancer (40%). A characterization of the two proteins confirmed that they could be novel targets for cancer therapy.
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Rolim, Isaura LetÃcia Tavares Palmeira. "Interventions analysis of NIC indicated for the diagnosis of nursing âfluid volume excessâ in intensive therapy unit." Universidade Federal do CearÃ, 2008. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=2686.
Full textAbstract:
CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel SuperiorIt is a descriptive study with the objective to analyze the applicability of the interventions proposed by the Classification of nursing interventions (NIC) nursing for the diagnosis of "Fluid volume excess" in an Intensive Therapy Unit (ITU). It was developed in three stages. At first, they were raised, along with nursing care, activities that they indicated for patients with that diagnosis. In the second step, expert nurses conducted a correspondence among the activities listed by nurse clinicians with the activities outlined in the NIC to the referred diagnosis. The third step, on its turn, consisted of two points: a) five interventions for analysis were selected and it was raised up the views of nurses about the applicability of the activities contained in NIC they have no mentioned, as well as, on the applicability of the activities they indicated in caring for adults with a diagnosis of nursing "Fluid volume excess" and not present in the NIC; b) a proposal for intervention developed from the analysis of data from the previous step was subjected to expert nurses who participated in the second stage. As a result, it was obtained a total of 73 activities indicated by nurses for the care to patients with "Fluid volume excess". In the second step, it was found that 71 of the 479 activities in the interventions of the NIC (14.82%), showed correspondence with 49 activities prescribed by nurses. The only intervention completely correspondent by the experts was âVital signs monitoringâ. As for the percentage of activities that present correspondence, the following results were gotten: âelectrolyte managementâ (12%), âfluid monitoringâ (27.27%), âhipervolemia managementâ (37.5%), âfluid managementâ (35.71%) and âelectrolytes monitoringâ (46.87%). For most of the correspondent activities to the NIC it was shown that the actions of nurses represented specific activities developed in the ITU. The five interventions selected for analysis in the third stage totaled 139 activities. Of these, 47 (33.81%) had been considered correspondent to the indicated by nurses in the first stage. Of the remaining 92 activities that were analyzed as to its completion the following results were obtained: âelectrolyte managementâ (54.54%), âfluid monitoringâ (40%), âhipervolemia managementâ (20%), âfluid managementâ (61.11%) and the âelectrolytes monitoringâ (46.87%). Regarding to the ITU implementation, the 24 activities prescribed in the first stage, and for which it was not found the corresponding in the NIC, 11 activities have reached a percentage above 80%. However, it was not noticed an apparent standard attitude among the nurses in doing these. The intervention âClinical evaluation of changes of electrolytes to risk of injuryâ, suggested by this study, included nine activities, of which six had correlation above the pre-established cut off point. It was concluded that many activities in the NIC were held in the unit of study, but there was no standard as to its implementation in the nurses practice. That a great number of interventions and activities for patients with âFluid volume excessâ offer much possibilities for new investigations and reinforces the importance of using the NIC taxonomy as key resource and as relevant to the implementation of a higher quality of care
Trata-se de um estudo descritivo com o objetivo de analisar a aplicabilidade das intervenÃÃes propostas pela ClassificaÃÃo da intervenÃÃes de enfermagem (NIC) para o diagnÃstico de enfermagem âVolume de lÃquido excessivoâ em uma Unidade de Terapia Intensiva (UTI). Foi desenvolvido em trÃs etapas. Na primeira, foram levantadas, junto aos enfermeiros assistenciais, as atividades que os mesmos indicavam para pacientes com o referido diagnÃstico. Na segunda etapa, enfermeiras peritas realizaram uma correspondÃncia entre as atividades indicadas pelos enfermeiros assistenciais com as atividades apresentadas na NIC para o diagnÃstico em questÃo. A terceira etapa, por sua vez, constituiu-se de dois momentos: a) foram selecionadas as cinco intervenÃÃes para anÃlise e levantou-se a opiniÃo dos enfermeiros acerca da aplicabilidade das atividades contidas na NIC por eles nÃo mencionadas, bem como sobre a aplicabilidade das atividades por eles indicadas no atendimento aos adultos com o diagnÃstico de enfermagem âVolume de lÃquido excessivoâ, e nÃo presentes na NIC; b) uma proposta de intervenÃÃo desenvolvida a partir da anÃlise dos dados da etapa anterior foi submetida Ãs enfermeiras peritas que participaram da segunda etapa. Como resultado, obteve-se um total de 73 atividades indicadas pelos enfermeiros para o atendimento ao paciente com âVolume de lÃquido excessivoâ. Na segunda etapa, verificou-se que 71 das 479 atividades constantes das intervenÃÃes da NIC (14,82%), apresentaram correspondÃncia com 49 atividades prescritas pelos enfermeiros. A Ãnica intervenÃÃo completamente correspondente pelas peritas foi âmonitorizaÃÃo dos sinais vitaisâ. Quanto ao percentual de atividades que apresentaram correspondÃncia, obteve-se os seguintes resultados: âcontrole de eletrÃlitosâ (12%), âmonitorizaÃÃo de lÃquidosâ (27,27%), âcontrole da hipervolemiaâ (37,5%), âcontrole de lÃquidosâ (35,71%) e âmonitorizaÃÃo de eletrÃlitos (46,87%). Para a maioria das atividades correspondentes com as da NIC, percebeu-se que as aÃÃes dos enfermeiros representavam atividades especÃficas desenvolvidas na UTI. As cinco intervenÃÃes selecionadas para anÃlise na terceira etapa somaram 139 atividades. Destas, 47 (33,81%) haviam sido consideradas correspondentes Ãs indicadas pelos enfermeiros na primeira etapa. Das 92 atividades restantes que foram analisadas quanto à sua realizaÃÃo, e obteve-se os seguintes resultados: âcontrole de eletrÃlitosâ (54,54%), âmonitorizaÃÃo de lÃquidosâ (40%), âcontrole da hipervolemiaâ (20%), âcontrole de lÃquidosâ (61,11%) e âmonitorizaÃÃo de eletrÃlitos (46,87%). Com relaÃÃo à realizaÃÃo, na UTI, das 24 atividades prescritas na primeira etapa, e para as quais nÃo foram encontrados correspondentes na NIC, 11 atividades atingiram um percentual acima de 80%. No entanto, nÃo se percebeu uma atitude uniforme entre os enfermeiros na realizaÃÃo destas. A intervenÃÃo âAvaliaÃÃo clÃnica de alteraÃÃo de eletrÃlitos para risco de injÃriaâ, sugerida pelo presente estudo, incluiu nove atividades, das quais seis apresentaram concordÃncia acima do ponto de corte prÃ-estabelecido. Concluiu-se que muitas atividades na NIC eram realizadas na unidade do estudo, porÃm nÃo havia uniformidade quanto à sua realizaÃÃo na prÃtica dos enfermeiros. Que o grande nÃmero de intervenÃÃes e atividades para pacientes com âVolume de lÃquido excessivoâ oferecem uma magnitude de possibilidades para novas investigaÃÃes e reforÃa-se a importÃncia do uso da taxonomia da NIC como recurso fundamental e pertinente para a implementaÃÃo de uma assistÃncia de maior qualidade
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Fawcett, David. "Mental Health Treatment for Children and Adolescents: Cost Effectiveness, Dropout, and Recidivism by Presenting Diagnosis and Therapy Modality." BYU ScholarsArchive, 2012. https://scholarsarchive.byu.edu/etd/3860.
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As many as one in five children and adolescents may suffer from a mental health disorder, yet there are barriers that often prevent children from receiving optimal treatment. The current study explores the influence of practitioner license type, therapy modality, diagnosis, age, and gender on mental health therapy for children and adolescents. Data was provided by Cigna, a leading health care insurance provider in the United States. Participants include 106,374 boys (53.2%) and 93,753 girls (46.8%) ages 3 to 18 (M = 12.1, SD = 3.9) who were treated in outpatient facilities throughout the United States of America. Results indicate that there are differences in dropout, recidivism, cost, and treatment length by provider license, therapy modality, diagnosis, age, and gender. Specifically, results suggest that marriage and family therapists have the lowest percent recidivism and are among the lowest in terms of dropout and cost effectiveness. The results also suggest that family therapy is more cost effective than individual or mixed therapy and that mixed therapy has a much lower percent dropout than individual or family therapy. Analysis by diagnosis suggests a potential severity scale based on dropout, recidivism, and number of sessions. There are also significant differences in dropout and recidivism by age suggesting that younger children are more likely to dropout of treatment. These results provide valuable information about mental health treatment of children and adolescents. Specifically, utilizing a family based approach may help reduce the total length of treatment while utilizing a mixed mode approach to therapy may help reduce the risk of dropout from treatment. Also, some diagnoses appear to be more difficult to treat, with higher percentages of dropout and requiring more time and money for successful treatment. Limitations and future directions are discussed.
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Mahloko, Johanna Metja. "Reasons for disclosure and non-disclosure of HIV diagnosis to children on antiretroviral therapy at the paediatric clinic, Odi Hospital." Thesis, University of Limpopo (Medunsa Campus), 2011. http://hdl.handle.net/10386/653.
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Thesis (MPH)-- University of Limpopo, 2011Background The increased access to HAART and increased survival of perinatally HIV-infected children have given rise to challenges that parents and caregivers face of disclosure of HIV serostatus to their infected children. Given the increased number of children on ART in the country health care providers and caregivers are now faced with the challenge of a population of children who have not been disclosed. The issue of disclosure should be viewed as a great public health concern. Aim and objectives The aim of the study was to determine the socio-demographics of caregivers and children and determine caregivers’ reasons for disclosure and non-disclosure of HIV diagnosis to children on antiretroviral therapy. Methodology: A quantitative descriptive study using researcher administered questionnaires was conducted with a sample of 149 disclosed and non-disclosed caregivers of children aged 4-17 enrolled in an antiretroviral treatment programme of a district hospital. Data were cleaned, coded and captured on Microsoft Excel and analysed in STATA version 10. Results Of 149 caregivers, 97.99% were females, and 2.01% were males, age ranged from 19-81 years with a mean age of 42 years, 25% attained primary education, 51% the grade not completed, 21% completed grade 12, and 3% had a tertiary education, 55.7% were unemployed, 27.3% fully employed, 14% were pensioners, 3% were schooling. Of the 149 children, 58% were girls, 42% boys, aged range of 4-17 years, mean age of 8.3 years, mean diagnosis age was 6 years, mean time on ARVs was 3.1years, and mean disclose age was 9.3 years. Majority (52.3%) children were cared for by mothers, (28.2%) by grandparents, and of the rest (17.4%) by other relatives, only 2% by their fathers. About 38% single orphans having lost their biological mothers, 35% were double orphans. About 39.6% of children were disclosed to and 60.4% not disclosed to. For those children to whom disclosure had been made 52.5% were disclosed to between ages 6-10, 35.6% between ages 11-15, 10.2% between ages 1-5. Reasons for disclosure were varied, and most cited were adhere to medication (36.5%), consistent questioning about disease and medications (36.5%), fear of accidental disclosure (9.5%), prompted by health professionals (7.9%), and child reaching puberty (3.2%). Reasons for non disclosure were also varied, most cited were child was too young to understand the disease, child will tell others, fear of stigma and discrimination, and did not have the skills to disclose Conclusions Prevalence of disclosure was much higher (39.5%) than other findings and there was greater involvement of health care providers in disclosing HIV to children. The study found a low disclosure rate among biological mothers who were in majority in the sample. Adherence to medication and persistent questioning about the disease and medication were the most cited reasons for disclosing HIV to children. Majority of caregivers delayed disclosure fearing that children will tell others because they are still too young to understand the implications of the diagnosis. Fear of stigma and discrimination also influenced disclosure. Caregivers delayed disclosure because they did not have the skills to disclose and explain HIV to children. Recommendations We recommend that disclosure guidelines be developed and healthcare providers trained in disclosure counselling to better advice caregivers on how to disclose to, thus making HIV disclosure to children an integral part of the comprehensive care of children on ART. Strengthening of life skills education programs at school to take into account the situation of children living with HIV Key words: Disclosure, non-disclosure, caregiver, children, ART, South Africa
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Panter, Simon J. "Oesophago-gastric cancer : factors influencing presentation and the effects of antisecretory drug therapy on symptoms and diagnosis." Thesis, University of Edinburgh, 2008. http://hdl.handle.net/1842/29311.
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Methods: A retrospective cohort study of 685 patients with oesophago-gastric adenocarcinoma (ACA) diagnosed in South Tees between April 1991-2001 and prospective studies of gastric ulcer disease and chromoendoscopy. Results: The time course to diagnosis was determined and showed a mean time to diagnosis of 30 weeks. Patients with oesophageal cancer took longer to present to their GP and longer to be seen in secondary care once referred. The part of the diagnostic process in primary care was double that in secondary care. Antisecretory drug therapy (AST) prescribed prior to endoscopy resulted in a delay in diagnosis of 18 weeks (mean) but this had no effect on long-term outcome. The Urgent Referral Guidelines for upper GI cancer, known as the “two week rule” guidelines showing they fail to identify 29% of patients. 27% of patients have an endoscopy within 3 years of diagnosis where the diagnosis of cancer is not made. Lesions are often seen at the prior endoscopy, and are often ulcerated. Inadequate biospying seems responsible, which is influenced by the endoscopist’s perception of whether the lesion is malignant. Only 9.2% of cancers are truly “missed”. Chromoendoscopy identified benign minor abnormalities in 14%: an aggressive biopsy policy even in patients “at risk” by virtue of age is therefore hard to justify. Conclusion: There are significant delays in the diagnosis of oesophago-gastric ACA. Treatment with AST delays diagnosis but without affecting outcome. Current endoscopic practice could be improved to reduce that missed cancer rate through the use of a rigorous biopsy protocol especially for ulcerated lesions. As symptoms are used to determine who is endoscoped and are a poor predictor of pathology alternative means of determining “high risk” need to be developed.
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OLIVEIRA, ERICA A. de. "Estudo comparativo de radiofármacos para angioênese na detecção de melanoma." reponame:Repositório Institucional do IPEN, 2011. http://repositorio.ipen.br:8080/xmlui/handle/123456789/10039.
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Dissertação (Mestrado)
IPEN/D
Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP