Dissertationen: „Diseases of Tea“

1

Chen, Juhua, und 陳菊華. „Green tea polyphenols modulate carbon tetrachloride-induced liver injury in mice“. Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2002. http://hub.hku.hk/bib/B31242935.

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2

Bursill, Christina. „Green tea and its catechins modulate cholesterol metabolism in cultured human liver (HepG2) cells and the hypercholesterolaemic rabbit“. Title page, contents and introduction only, 2000. http://web4.library.adelaide.edu.au/theses/09PH/09pdb9725.pdf.

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Includes bibliographical references (21 leaves). Previous studies have found that green tea and its antitoxidant constituents, the catechins, are hypocholesterolaemic in both epidemiological and animal intervetion studies. The main objectives of the present study were to investigate the mechanism by which green tea and its most abundant catechin constituent epigallocatechin gallate increase the low-density lipoprotein (LDL) receptor of HepG2 cells. In addition, it was hoped to determine if a crude catechin extract from green tea could lower plasma cholesterol levels in the hypercholesterolaemic rabbit and ascertain if this effect was due to an increase in the LDL receptor. The study provides evidence that green tea and its catechins exhibit hypocholesterolaemic properties and may therefore provide protection against heart disease.

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3

Kobese, Nokubonga. „Synthesis of silver doped titanium dioxide nanocomposites using tea extract from Aspalathus linearis and evaluation of their antibacterial effects“. University of the Western Cape, 2018. http://hdl.handle.net/11394/6779.

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>Magister Scientiae - MSc
Despite the wide success of antimicrobial agents against waterborne pathogens, waterborne disease continues to pose a threat to both mankind and animals. A major concern is that certain bacteria have developed resistance to antimicrobial agents, as a result of their overuse. Silver (Ag) nanoparticles are widely used for antibacterial purposes such as medical dressings. However, they are highly toxic to human cells. Hence, there is a great interest in developing next generation antibacterial nanoparticles that are as effective as Ag nanoparticles for antibacterial functions, while having less toxicity to human cells. Several methods can be used to generate these antimicrobial nanoparticles, one of which is green nanotechnology. Green nanotechnology uses natural plants such as tea to synthesise nanoparticles rather than chemicals, thus reduce human and animal harm and improve sustainability of antibacterial agents. Silver-titanium nano-composites (Ag-TiO2 NCs) were synthesised with the hydrothermal method using a tea extract from Aspalathus linearis (Rooibos, RB), and distilled water in the presence of nitrogen. The resulting structures were characterised with high resolution transmission electron microscopy (HRTEM), energy-dispersive spectroscopy (EDS) analysis X-Ray Diffraction (XRD) and Thermogravimetric Analysis (TGA). The antibacterial characteristics of these new NCs were evaluated against 3 bacteria: Bacillus cereus, Cupriavidus metallidurans, and Escherichia coli. The optimum processing conditions to produce 6-nm spherical NPs included maintaining the temperature at 90 °C, the pH at 4.35, and using RB extract at a concentration of 2 mg/mL. The size of silver NPs was reduced in acidic conditions, agglomerated in neutral conditions, and highly reduced in alkaline conditions. Increasing the pH decreased the particle size and narrowed the particle size distribution. Gram-positive B. cereus showed slight resistance or tolerance to the Ag-TiO2 nanocomposite compared to the gram-negative bacteria E. coli and C. metallidurans. The treatment concentration required for total inhibition of E. coli and C. metallidurans growth was 100 mg/mL. Supported silver nanoparticles has shown to be a suitable way to obtain highly dispersed silver over higher surface area. This approach allowed Ag-TiO2 nanocomposite to be an efficient bactericide, with less silver amount employed.

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Spies, Christoffel F. J. (Christoffel Frederik Jakobus). „The inoculum ecology of Botrytis cinerea in Rooibos nurseries“. Thesis, Stellenbosch : Stellenbosch University, 2005. http://hdl.handle.net/10019.1/20943.

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Thesis (MScAgric)--University of Stellenbosch, 2005.
ENGLISH ABSTRACT: Grey mould, caused by Botrytis cinerea, is the most important foliar disease of rooibos seedlings. Although the disease is primarily controlled with applications of fungicides, the improvement of cultural methods of disease management should lessen this dependence on chemical control. Such improvements would, however, not be possible without knowledge of the inoculum sources and dispersal of the pathogen. The aim of this study was to investigate the inoculum ecology of B. cinerea in rooibos nurseries in order to identify primary sources of inoculum and to improve the environmentally friendly management of the disease. The study was conducted in four nurseries over two production seasons (March to July 2003 and 2004). Levels of airborne inoculum of B. cinerea were monitored on a monthly basis inside and around the nurseries with spore traps. Samples of plant material and organic debris were taken in the corresponding areas to determine the incidence of plant material infected by the pathogen and the incidences of grey mould in the nurseries were recorded. Low numbers of B. cinerea colonies were observed on the spore traps. Similar levels of airborne inoculum were observed inside and around the nurseries. The incidence of plant material yielding B. cinerea was higher outside the nurseries than inside, indicating the importance of such materials as potential sources of inoculum. Since patterns of airborne inoculum observed in this study confirmed reports of the local dispersal of B. cinerea, the removal of possible hosts outside the nurseries could aid in the management of grey mould in rooibos nurseries. Resistance to dicarboximide fungicides is a genetically stable trait in B. cinerea, and therefore has the potential to be used as a phenotypic marker. This marker can be used to gain knowledge on the dispersal of B. cinerea inoculum inside and outside rooibos nurseries. Isolates of B. cinerea collected from the air and from plant material in and around four rooibos nurseries were assessed for resistance to iprodione at 1 and 3 μg/ml a.i. Some of the isolates showed resistance to iprodione at 1 μg/ml a.i. However, none of the isolates showed resistance at 3 μg/ml a.i. iprodione. The initial incidence of dicarboximide-resistance at the nurseries was slightly higher than expected. As the season progressed, the incidence of iprodione-resistant isolates decreased towards May, after which an increase was observed towards July. A relatively high percentage of isolates collected outside the nurseries was found to be dicarboximide-resistant. Two of the nurseries had a significant higher incidence of resistant isolates on plant material collected inside, than on plant material collected outside the nursery. However, when looking at resistance levels of airborne isolates, no significant differences were found in the incidence of resistant isolates sampled inside and outside the four nurseries. The data indicated the importance of organic debris and seed-borne infections in the survival and dispersal of dicarboximide-resistant isolates of the pathogen. With the current emphasis on organic agriculture the knowledge gained in this study presents valuable possibilities of improving the cultural management of grey mould in rooibos nurseries.
AFRIKAANSE OPSOMMING: Vaalvrot, veroorsaak deur Botrytis cinerea, is die belangrikste bo-grondse siekte van rooibossaailinge. Alhoewel die beheer van die siekte hoofsaaklik op die gebruik van fungisiede berus, behoort die verbetering van verbouingspraktyke hierdie afhanklikheid van chemiese beheer te verminder. Sulke verbeteringe sal egter slegs moontlik wees indien voldoende kennis van die inokulumbronne en verspreiding van die patogeen beskikbaar is. Die doel van hierdie ondersoek was om die inokulum ekologie van B. cinerea in rooibos kwekerye te ondersoek sodat primêre inokulumbronne opgespoor en omgewingsvriendelike siektebestuurspraktyke verbeter kan word. Die ondersoek is in vier kwekerye oor twee produksie seisoene (Maart tot Julie 2003 en 2004) uitgevoer. Vlakke van luggedraagde inokulum van B. cinerea is op ’n maandelikse basis met behulp van spoorvangers binne en buite die kwekerye gemonitor. Monsters van plantmateriaal en organiese materiaal is in ooreenstemmende areas geneem om die voorkoms van B. cinerea geïnfekteerde plantmateriaal vas te stel en die voorkoms van vaalvrot in die kwekerye is aangeteken. Min B. cinerea kolonies is op die spoorvangers waargeneem. Soortgelyke vlakke van luggedraagde inokulum is binne en buite die kwekerye waargeneem. Die hoër voorkoms van B. cinerea geïnfekteerde plantmateriaal buite die kwekerye as binne, dui op die belang van sulke materiaal as potensiële inokulumbronne. Aangesien die patrone van luggedraagde inokulum, soos waargeneem in hierdie ondersoek, ander berigte van B. cinerea se beperkte verspreidingsvermoë bevestig, kan die verwydering van moontlike alternatiewe gashere buite die kwekerye die bestuur van die siekte binne die kwekerye verbeter. Weerstand teen dikarboksimied fungisiede is ’n geneties-stabiele kenmerk in B. cinerea en het daarom potensiaal om as ’n fenotipiese merker gebruik te word. Hierdie merker kan gebruik word om kennis aangaande die verspreiding van B. cinerea in en om rooibos kwekerye in te samel. Botrytis cinerea isolate in lug en op plantmateriaal in en om vier rooibos kwekerye is gedurende 2003 en 2004 versamel. Die isolate is vir weerstandbiedendheid teen iprodioon by konsentrasies van 1 en 3 μg/ml aktiewe bestandeel (a.b.) getoets. Isolate met weerstand teen 1 μg/ml a.b. iprodioon is waargeneem, maar nie teen 3 μg/ml nie. Die aanvanklike voorkoms van dikarboksimiedweerstand by die kwekerye was hoër as verwag. Hierdie vlak het egter gedaal met die verloop van die seisoen tot in Mei, waarna ’n toename tot in Julie waargeneem is. Die persentasie dikarboksimied-weerstandbiedende isolate buite die kwekerye was relatief hoog. In twee van die kwekerye was die voorkoms van weerstandbiedende isolate op plantmateriaal in die kwekerye betekenisvol hoër as op plantmateriaal buite die kwekerye. Daar was egter geen betekenisvolle verskille in die voorkoms van luggedraagde weerstandbiedende isolate nie, ongeag van die kwekery of posisie. Die data dui op die belang van organiese materiaal en saadgedraagde infeksies in die oorlewing en verspreiding van dikarboksimied-weerstandbiedende isolate van die patogeen. Met die huidige klem op organiese landbou bied die inligting wat in hierdie ondersoek versamel is moontlike praktyke wat geïmplementeer kan word om die beheer van vaalvrot in kwekerye met behulp van verbouingspraktyke te verbeter.

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Kirana, Chandra. „Bio-active compounds isolated from mistletoe (Scurulla oortiana (Korth.) Danser) parasitizing tea plant (Camellia sinensis L.)“. Title page, contents and summary only, 1996. http://web4.library.adelaide.edu.au/theses/09A/09ak58.pdf.

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Bibliography: leaves 87-96. This thesis investigates non-proteinaceous low molecular weight flavonoid and alkaloid compounds in Scurulla oortiana (Korth.) Danser grown on Camellia sinens. Three flavonols are identified in S. oortiana (Korth.) Danser growing on different hosts. The identification and characterisation of these flavonoids are carried out using various chromatographic and spectrometric procedures. Two purine alkaloids are isolated from and identified in S. oortiana (Korth.) Danser parasitizing tea plant, C. Sinensis. The antifungal activity of the phenolic compounds isolated from mistletoe parasitizing tea plant is examined.

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Kunsevi-Kilola, Carine. „The effect of Rooibos on trace elements absorption and biochemical parameters : a murine model“. Thesis, Cape Peninsula University of Technology, 2014. http://hdl.handle.net/20.500.11838/2248.

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Thesis (MTech (Biomedical Technology))--Cape Peninsula University of Technology, 2014.
Over the past few decades, it has been shown that various critical diseases including heart disease, cancer, and diabetes associated with free radical generation and low endogenous antioxidant capacity, lead to oxidative stress and cell injury. In recent years, numerous studies have also reported that antioxidants, present in various beverages, vegetables and some foods have attracted a significant research interest due to their potential benefits to human health. However, epidemiological evidence shows a correlation between the intake of food rich in antioxidants and the reduced incidence of some mortality of chronic diseases, certain cancers and coronary heart disease. The aims of this study were to determine the effects of rooibos teas (fermented and unfermented) and green tea as a comparison on the biochemical parameters and the trace element absorption in a rat model. In this study 4 groups of experimental animals were used. All groups had ad libitum access to standard rat chow. Group A, the controls (11 animals), were fed with tap water; group B (11 animals) were fed with the liquid extract of fermented rooibos tea; group C (9 animals) were fed with the liquid extracts of unfermented rooibos and group 0 (9 animals) were fed with the liquid extract of green tea. All groups were fed for a period of 10 weeks. After the feeding period, the animals were sacrificed by euthanization with intraperitoneal injections of pentobarbital. Blood was sampled by cardiac puncture and centrifuged to obtain the serum. Some elemental analyses were performed with X-ray emission and backscattering. ICP-OES was used to determine the magnesium content. For X-ray emission, backscattering and ICP-OES analyses, 100 µL of each serum sample in a group were added to 2 ml freeze-drying tube. Of the combined specimen, 100 µL was used for the magnesium determination by ICP-OES. The remainder of the combined serum specimens for each group were freeze-dried at -80°C and then pressed into a pellet. The pellet was coated with carbon and analyzed using X-ray emission and backscattering. The elemental X-rays of P, S, Ca, Mn, Fe, Cu, Co, Zn, Mo, Ca and Se emitted were quantified to obtain the respective concentrations. Biochemical chemistry analyses were performed on each serum sample of each animal. The biochemical parameters tested for were total protein, albumin, globulin, total bilirubin, lactate dehydrogenase, blood urea nitrogen, uric acid, total cholesterol, aspartate aminotransferase, alanine aminotransferase, creatine phosphokinase and creatinine.

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7

朱雯 und Wen Zhu. „The potential roles of nitric oxide in carbon tetrachloride induced liver injury of mice and the protective effects of green teapolyphenols“. Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1999. http://hub.hku.hk/bib/B31241426.

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8

Thamahane-Katengua, Emma Tutu Masechela. „Effect of rooibos and red palm oil supplementation, alone or in combination, on cardiac function after exposure to hypertension and inflammation in an ischaemial/reperfusion injury model“. Thesis, Cape Peninsula University of Technology, 2013. http://hdl.handle.net/20.500.11838/1520.

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Thesis submitted in fulfilment of the requirement for the degree Doctor of Technologiae (Biomedical Technology) in the Faculty of Health and Wellness Sciences at the Cape Peninsula University of Technology Supervisor: Prof J van Rooyen Co-supervisor: Prof JL Marnewick Bellville October 2013
Cardiovascular disease (CVD) is without a doubt one of the most challenging health issues of our time and accounts for the highest number of deaths in both developed and developing countries. Despite the huge strides that have been achieved in the diagnosis and therapeutic intervention of CVD, the disease burden still remains enormous. Therefore, this calls for novel and innovative interventions to curb the surge of CVD. The use of plant based food with bioactive phytochemicals,has a great potential to reduce the incidence of CVD, specifically in resource-strained countries. Red palm oil (RPO) and the indigenous herbal tea, rooibos have previously been shown to exhibit potential cardioprotective effects. Their health promoting properties have largely been attributed to their antioxidant and anti-inflammatory activities and emerging evidence also showed that they have the potential to modulate cell signalling events. Substancial scientific evidence proposes oxidative stress and inflammation to play an important role in the pathogenesis of cardiovascular disease. Hence, natural plant extracts such as RPO and rooibos could be recommended as adjuvants to clinical therapy to reduce the morbidity and mortality associated with CVD. This thesis reports on three studies investigating the cardiovascular protective effects that chronic feeding of either RPO, rooibos or their combination have on 1) antioxidant enzymes and the NO-cGMP pathway in myocardial tissue of spontaneous hypertensive rats, 2) the modulation of systemic and myocardial inflammation and 3) the myocardial ischaemic/reperfusion tolerance in a rat model of lypopolysaccharide induced inflammation. The aim of the first study was to investigate the effect of RPO on cardiac function in sponteneously hypertensive rats. The role of the nitric oxide cyclic-guanosine monophosphate(NO-cGMP) pathway, (as determined by the nitric oxide (NOS) activity) and the antioxidant defence system (selected antioxidant enzymes) were also investigated. Cardiac function was monitored at stabilization and reperfusion using the Langendorff perfusion system. Antioxidant enzymes were determined from left ventricular tissue, while total NOS activity was determined in the aorta and left ventricular tissue. The results show that RPO offered cardiac protection as evidenced by improved left ventricular developed pressure (LVDevP), maximum velocity of pressure rise (+dp/dt) max and fall (-dp/dt) max during reperfusion in sponteneously hypertensive rats (SHR) compared to their control counterparts. Improved function in SHR was associated with increased myocardial superoxide dismutase 2 (SOD2) protein expression compared to the normotensive rats. There was differential modulation of the NOS activity by RPO, an increase in NOS activity was observed in the aorta while a reduction in the activity of NOS was observed in the left ventricular tissue of both RPO supplemented normotensive and hypertensive rats compared to their respective control groups. These results argue a role for elevated NO production in the aorta for endothelial function maintenance. Increased SOD2 protein might lead to reduced oxidative stress. Thus, NO-cGMP pathway and antioxidant defense systems synergistically acted to restore cardiovascular function in SHR. The aim of the second study was to investigate the effect of RPO and rooibos supplementation on the modulation of systemic and myocardial inflammation in a rat model. As RPO and rooibos contain different types of antioxidants which reside and exert their biological effects in different cellular compartments, the combination of these two natural food compounds has the potential to enhance the spectrum of available dietary antioxidants in different cellular compartments, which could result in a better protection against certain pathological conditions such as inflammation. The Langendorff system and the lypopolysaccharide (LPS)-induced inflammatory model were used to determine if RPO and rooibos could protect against the negative effect of LPS-induced inflammation on baseline cardiac function. Both inflammation and dietary supplementation did not have any effect on baseline cardiac functional parameters. Our results show that administration of LPS resulted in elevated plasma levels of IL-1β in supplemented and non-supplemented rats indicating that an inflammatory response was triggered in the LPS-treated rats. However, this increase in IL-1β was counteracted by concurrent elevation of plasma IL-10 in LPS-induced rats consuming either rooibos or RPO alone. Furthermore the combination of RPO and rooibos enhanced myocardial IL-10 levels in LPS-induced rats. This data shows a difference in response to LPS injection between the myocardium and the systemic circulation. The results indicate that the combination of these two natural food substances exhibit potential anti-inflammatory properties which could be beneficial in clinically relevant conditions where inflammation plays a role. Having shown that dietary intervention with RPO and rooibos had the potential to modulate the inflammatory response in the model of inflammation at basal conditions, we then proceeded to the third study to specifically establish if dietary RPO when supplemented alone will improve functional recovery and reduce infarct size in LPS-treated hearts. The Langendorff perfusion system was employed for determination of cardiac function and infarct size. The roles of NFkB, p38 MAPK and the myocardial antioxidant defence systems were investigated as potential mechanisms of protection. LPS-treatment caused significant increases in myocardial IL-1 β indicating that inflammation was induced. However, the levels of myocardial IL-10 was reduced in LPS-treated hearts compared to the non-treated hearts. Intervention with dietary RPO resulted in improved functional recovery and reduced infarct size, in both healthy hearts and in the LPS-treatment group. The RPO-induced cardio-protection was associated with increases in myocardial protein expression of the antioxidant enzymes, SOD1, SOD2, GPX1 as well as increased p38 phosphorylation during reperfusion. LPS treatment increased myocardial protein expression of NFkB p65 which was reversed by RPO supplementation. Reduction of myocardial NFkB protein expression, increased p38 phosphorylation and elevated mitochondrial antioxidant (SOD2 and GPX1) as well as cytosolic enzymes (SOD 1) are proposed as potential mechanisms underlying the RPO-induced cardio-protection in this model. Based on these study results, for the first time, having included vasculature aspects in the cardio-protective effects of RPO we have shown that the NO-cGMP pathway and antioxidant defense systems may act synergistically to restore cardiovascular function in spontaneously hypertensive rats. Results from the second study also provide the first scientific evidence that RPO in combination with rooibos (a flavonoid rich endemic herbal tea) could have potential anti-inflammatory activities at systemic as well as myocardial level, which may be beneficial in clinically relevant conditions where inflammation plays a role. From the third study it can be concluded that dietary RPO improved myocardial tolerance to ischaemia-reperfusion injury in a model of inflammation.

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Deikun, Larissa Loryn. „The Health and Growth of Veal Calves Provided a Fatty Acid Supplement and a Dry Teat“. The Ohio State University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu1563380406594548.

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10

Ehrnhöfer, Dagmar Elisabeth. „Green tea catechins change the aggregation behavior of proteins associated with neurodegenerative disease“. Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2007. http://dx.doi.org/10.18452/15624.

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Eine Gemeinsamkeit verschiedener neurodegenerativer Erkrankungen ist die abnormale Ansammlung von Proteinen im Gehirn, wie z. B. von alpha-Synuclein (Syn)-Aggregaten bei der Parkinson''schen Krankheit (PD) oder von Huntingtin (Htt)-Aggregaten bei Chorea Huntington (HD). Am Anfang dieser Studie wurde eine Bibliothek von ca. 5000 natürlichen Substanzen nach Inhibitoren der Htt-Aggregation durchsucht. Eine der wirksamen Substanzen war (-)-Epigallocatechingallat (EGCG), eine Verbindung, die in grünem und schwarzem Tee vorkommt. Die antioxidativen Eigenschaften von EGCG wurden bereits mit einer neuroprotektiven Wirkung in Verbindung gebracht, was EGCG zu einem vielversprechenden Kandidaten für die Entwicklung einer neuen Behandlungsmethode macht. Eine inhibierende Wirkung auf Proteinaggregation wurde jedoch bis jetzt noch nicht nachgewiesen. Diese Studie zeigt, dass EGCG die Aggregation von Htt und Syn hemmt, indem es dosisabhängig eine oligomere Proteinkonformation stabilisiert. Diese Oligomere wirken jedoch nicht als Keime in Aggregationsreaktionen. Zusätzlich verändert EGCG die Exposition bestimmter Epitope, die von konformationsspezifischen Antikörpern im Laufe der Aggregation erkannt werden. Daher könnte die Substanz Proteine, die zur Aggregation neigen, auf einen alternativen Faltungspfad in der Missfaltungskaskade führen. Weiterhin legen die Ergebnisse nahe, dass eine direkte Wechselwirkung zwischen EGCG und Proteinen in einer ungefalteten Konformation stattfindet. In verschiedenen Zellkultur-Modellsystemen verringerte EGCG die Toxizität, die von missgefalteten Proteinen ausgeht, was nahelegt, dass die neu geformten oligomeren Spezies nicht toxisch sind. EGCG könnte daher ein chemisches Chaperon darstellen, das die Missfaltung und Toxizität von Proteinen, die mit neurodegenerativen Krankheiten assoziiert sind, verringert. Die Substanz könnte daher die Basis zur Entwicklung einer neuen Therapie für diese unheilbaren Krankheiten darstellen.
A common feature of neurodegenerative disorders is the abnormal accumulation of aggregated protein the brain, such as alpha-Synuclein (Syn) aggregates in Parkinson''s disease (PD) and Huntingtin (Htt) aggregates in Huntington''s disease (HD). In this study, a library of approximately 5000 natural compounds was screened for inhibitors of Htt aggregation. One of the hits was (-)- Epigallocatechin gallate (EGCG), a compound present in green and black tea. The antioxidant properties of this substance have been linked to neuroprotection before, making it a promising candidate for the development of a treatment for neurodegenerative diseases. Inhibition of protein aggregation by EGCG, however, has not been demonstrated so far. This study shows that EGCG inhibits the aggregation of Htt and Syn by stabilizing an oligomeric conformation of the respective proteins in a dose-dependent manner. These oligomers do not seed the aggregation of Htt and Syn. Also, EGCG modifies the exposure of different epitopes recognized by conformation-specific antibodies during the aggregation process. The compound might therefore lead aggregation-prone proteins on an alternative folding pathway in the misfolding cascade. The results furthermore suggest that direct interaction occurs between EGCG and proteins in an unfolded conformation. EGCG also reduces toxicity caused by misfolded Htt or Syn in cell culture model systems, suggesting that the oligomeric protein species formed in the presence of EGCG are not toxic to living cells. EGCG might therefore represent a chemical chaperone that can modulate misfolding and toxicity of proteins associated with neurodegenerative diseases and could provide the basis for the development of a novel pharmacotherapy for these fatal disorders.

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Brantman, Karen Renee. „Tear Film VEGF in Dogs with Vascularizing Corneal Disease“. Thesis, Virginia Tech, 2013. http://hdl.handle.net/10919/23166.

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This body of work encompasses two studies: the collection of canine tears via a novel polyester
rod and the comparison of VEGF-A concentrations in tears from dogs with normal and
vascularized corneas. The first study used polyester rods for tear collection in dogs. Fluid volume and VEGF recovery characteristics, as well as potential binding of VEGF to the rod, were determined. Tears were harvested from normal dogs using rods and glass capillary tubes. Tears were assayed for tear film VEGF using a commercial canine VEGF sandwich ELISA kit. Dilutions of VEGF standard were wicked into the rods or drawn into capillary tubes, eluted, and assayed. Percent volume recovery is adequate for polyester rods as is percent VEGF recovery. VEGF is detectable in normal canine tears.The second study harvested tear samples from eyes of dogs with vascularizing corneal disease, as well as the contralateral unaffected eye of unilaterally diseased dogs, and normal dogs. Vascularization scores were assigned to diseased eyes and tear film VEGF concentration was assayed as above. Mean tear film VEGF concentration of diseased eyes did not differ from control eyes, and was not correlated with disease process, extent of vascularization, or other parameters. Tear film VEGF in unaffected eyes was significantly higher than control and vascularized eyes. Canine tear film VEGF exceeds biologically active concentrations, but does not correlate with state of corneal vascularization. VEGF-related control of corneal vascularization may be mediated by other proangiogenic factors.
Master of Science

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Roy, Elise. „Cell disorders in lysosomal storage diseases“. Phd thesis, Université René Descartes - Paris V, 2012. http://tel.archives-ouvertes.fr/tel-00683248.

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Mucopolysaccharidosis type IIIB (MPSIIIB) is a lysosomal storage disease (LSD) characterized by accumulation of heparan sulfate oligosaccharides (HSO), which results in progressive mental retardation, neurodegeneration and premature death in children. The underlying mechanisms are poorly understood. Coming to a better understanding of the pathophysiology of MPSIIIB has become a necessity to assess the efficacy of gene therapy treatment regarding loss of neuronal plasticity, and to define the best conditions for treatment. To address the link between HSO accumulation and downstream pathological events, new cell models of MPSIIIB were created. First, induced pluripotent stem cells (iPSc) were generated from fibroblasts of affected children, followed by differentiation of patient-derived iPSc into a neuronal progeny. Second, a HeLa cell model was created in which expression of shRNAs directed against a-N-acetylglucosaminidase (NAGLU), the deficient enzyme in MPSIIIB, is induced by tetracycline. Success in the isolation of these different models was pointed by the presence of cardinal features of MPSIIIB cell pathology. Studies in these models showed that: I) HSO excreted in the extracellular matrix modifies cell perception of environmental cues, affecting downstream signalling pathways with consequences on the Golgi morphology. II) Accumulation of intracellular storage vesicles, a hallmark of LSDs is due to overexpression of the cis-Golgi protein GM130 and subsequent Golgi alterations. It is likely that these vesicles are abnormal lysosomes formed in the cis- and medial-Golgi which are misrouted at an early step of lysosome biogenesis, giving rise to a dead-end compartment. III) Other cell functions controlled by GM130 are affected, including centrosome morphology and microtubule nucleation. These data point to possible consequences on cell polarization, cell migration and neuritogenesis.

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Macharia, Muiruri. „Modulation of oxidative stress biomarkers by rooibos in adults at risk of developing coronary heart disease /“. [S.l. : s.n.], 2008. http://dk.cput.ac.za/cgi/viewcontent.cgi?article=1024&context=td_cput.

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Cioe, Patricia A. „Cardiovascular Risk Factor Knowledge, Risk Perception, and Actual Risk in HIV-Infected Patients: A Dissertation“. eScholarship@UMMS, 2012. https://escholarship.umassmed.edu/gsn_diss/26.

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Background: Cardiovascular disease (CVD) has emerged as a major cause of morbidity and mortality in HIV-infected adults. Research in noninfected populations suggests that knowledge of CVD risk factors significantly influences perception of risk. Understanding the level of risk factor knowledge and risk perception can inform the development of innovative interventions to reduce risk. The purpose of this study was to describe cardiovascular risk factor knowledge and risk perception in a cohort of HIV-infected adults. Specific aims included (a) describing the estimated risk of CVD, the perceived risk of CVD, and the level of CVD risk factor knowledge; (b) describing the relationship between estimated and perceived risk, and (c) examining the influence of risk factor knowledge on perceived risk of CVD. The Health Belief Model was the theoretical framework that guided the study. Methods: A prospective observational cohort; cross-sectional design. A convenience sample of 130 HIV-infected adults was recruited from two hospital-based HIV clinics. Each participant had one study visit in which all data were collected by direct interview. Results: Results: Mean age of enrollees was 48 years (SD 8.4); 62% were male; 41.5% White, 32% Black, 23% Hispanic; 56% current smokers; mean years since HIV diagnosis were 14.7; mean BMI 27 (SD 5.5); 48.5% had prehypertension. Higher scores on the Heart Disease Fact Questionnaire indicate a higher degree of knowledge. In this sample, the Mean was 19, (S.D. 3.5; range 6–25), indicating a fair degree of knowledge. Estimated and perceived risk were significantly, though weakly, correlated r (126) = .24, p = .01. Controlling for age, risk factor knowledge was not predictive of perceived risk (F[1,117] = 0.13, p > .05). Conclusions: HIV-infected adults are at increased risk for cardiovascular disease. Traditional CVD risk factors such as smoking, prehypertension, and being overweight are highly prevalent. Despite having a fair level of risk factor knowledge, knowledge did not influence perception of risk for CVD. Research to improve risk perception and to develop innovative interventions that reduce CVD risk is needed for this population.

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Rezai-Zadeh, Kavon. „Flavonoids as Modulators of Amyloid Precursor Protein Metabolism and Alzheimer Disease Pathology“. [Tampa, Fla] : University of South Florida, 2008. http://purl.fcla.edu/usf/dc/et/SFE0002683.

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16

Wickwar, Sadie. „The psychosocial and clinical outcomes of surgery for Thyroid Eye Disease (TED)“. Thesis, City University London, 2014. http://openaccess.city.ac.uk/14502/.

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This study aimed to investigate whether quality of life in patients with thyroid eye disease (TED) improves as a result of having orbital decompression surgery and whether any demographic, clinical or psychosocial factors can predict which patients might benefit from this surgery. One hundred and twenty three adults with TED were recruited from Moorfields Eye Hospital (MEH), London. Clinical measurements were taken by the clinical team at MEH and participants completed a range of psychosocial questionnaires prior to surgery and again 6 weeks and 6 months after surgery. The Appearance Research Collaboration’s (ARC) framework of adjustment to living with a disfiguring condition was used to guide the study’s measures and analysis. The Graves’ Ophthalmopathy Quality of Life Questionnaire (GO-QOL; Terwee et al., 1998) was completed by participants at each time point and was the dependent variable in each hierarchical multiple regression model. Semi-structured interviews were conducted with fourteen patients from Birmingham and Midland Eye Centre (BMEC) to explore expectations of orbital decompression and thematic analysis was performed. Prior to surgery, the regression model explained 55% of the variance in GO-QOL visual function scores and 75% of the variance in GO-QOL appearance scores. Although vision-related quality of life was associated with age and asymmetrical disease, it was intervening psychosocial processes that were more consistently associated with both vision- and appearance-related quality of life. Patients had high expectations for surgery to return them to the “normality” of their lives, and appearance, before TED. High expectations were often a result of great confidence and trust in surgeons and information they had accessed about the surgery online. Significant improvements were found in all clinical characteristics following surgery and in most psychosocial variables. Vision-related quality of life did not change significantly until 6 months after surgery whilst appearance-related quality of life significantly improved 6 weeks post-surgery and continued to significantly increase 6 months post-surgery reaching a minimal clinically important difference (MCID). Ethnicity and a small number of clinical factors patients presented for surgery were unique predictors of the variance in change in vision-related quality of life and appearance-related quality of life. None of the changes in clinical or psychosocial outcomes significantly predicted change in vision-related quality of life. The hierarchical regression model explained 81% of the variance in change in appearance-related quality of life however, with improvement in personal evaluation of appearance uniquely predicting improvement in appearance-related quality of life. Further research is required to establish whether expectations are met after surgery. Recommendations for clinical practice include routine psychological assessment and the provision of clear and comprehensible information about surgery. Patients with TED in the future would benefit from interventions targeting the intervening psychosocial processes identified by this thesis as amenable to change.

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Gartner, Coral Elizabeth. „Environmental risk factors for Parkinson's disease“. Queensland University of Technology, 2006. http://eprints.qut.edu.au/16393/.

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Parkinson's disease (PD) is a progressive, degenerative, neurological disease. The progressive disability associated with PD results in substantial burdens for those with the condition, their families and society in terms of increased health resource use, earnings loss of affected individuals and family caregivers, poorer quality of life, caregiver burden, disrupted family relationships, decreased social and leisure activities, and deteriorating emotional well-being. Currently, no cure is available and the efficacy of available treatments, such as medication and surgical interventions, decreases with longer duration of the disease. Whilst the cause of PD is unknown, genetic and environmental factors are believed to contribute to its aetiology. Descriptive and analytical epidemiological studies have been conducted in a number of countries in an effort to elucidate the cause, or causes, of PD. Rural residency, farming, well water consumption, pesticide exposure, metals and solvents have been implicated as potential risk factors for PD in some previous epidemiological studies. However, there is substantial disagreement between the results of existing studies. Therefore, the role of environmental exposures in the aetiology of PD remains unclear. The main component of this thesis consists of a case-control study that assessed the contribution of environmental exposures to the risk of developing PD. An existing, previously unanalysed, dataset from a local case-control study was analysed to inform the design of the new case-control study. The analysis results suggested that regular exposure to pesticides and head injury were important risk factors for PD. However, due to the substantial limitations of this existing study, further confirmation of these results was desirable with a more robustly designed epidemiological study. A new exposure measurement instrument (a structured interviewer-delivered questionnaire) was developed for the new case-control study to obtain data on demographic, lifestyle, environmental and medical factors. Prior to its use in the case-control study, the questionnaire was assessed for test-retest repeatability in a series of 32 PD cases and 29 healthy sex-, age- and residential suburb-matched electoral roll controls. High repeatability was demonstrated for lifestyle exposures, such as smoking and coffee/tea consumption (kappas 0.70-1.00). The majority of environmental exposures, including use of pesticides, solvents and exposure to metal dusts and fumes, also showed high repeatability (kappas >0.78). A consecutive series of 163 PD case participants was recruited from a neurology clinic in Brisbane. One hundred and fifty-one (151) control participants were randomly selected from the Australian Commonwealth Electoral Roll and individually matched to the PD cases on age (± 2 years), sex and current residential suburb. Participants ranged in age from 40-89 years (mean age 67 years). Exposure data were collected in face-to-face interviews. Odds ratios and 95% confidence intervals were calculated using conditional logistic regression for matched sets in SAS version 9.1. Consistent with previous studies, ever having been a regular smoker or coffee drinker was inversely associated with PD with dose-response relationships evident for packyears smoked and number of cups of coffee drunk per day. Passive smoking from ever having lived with a smoker or worked in a smoky workplace was also inversely related to PD. Ever having been a regular tea drinker was associated with decreased odds of PD. Hobby gardening was inversely associated with PD. However, use of fungicides in the home garden or occupationally was associated with increased odds of PD. Exposure to welding fumes, cleaning solvents, or thinners occupationally was associated with increased odds of PD. Ever having resided in a rural or remote area was inversely associated with PD. Ever having resided on a farm was only associated with moderately increased odds of PD. Whilst the current study's results suggest that environmental exposures on their own are only modest contributors to overall PD risk, the possibility that interaction with genetic factors may additively or synergistically increase risk should be considered. The results of this research support the theory that PD has a multifactorial aetiology and that environmental exposures are some of a number of factors to contribute to PD risk. There was also evidence of interaction between some factors (eg smoking and welding) to moderate PD risk.

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Gartner, Coral Elizabeth. „Environmental risk factors for Parkinson's disease“. Thesis, Queensland University of Technology, 2006. https://eprints.qut.edu.au/16393/1/Coral_Gartner_Thesis.pdf.

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Parkinson's disease (PD) is a progressive, degenerative, neurological disease. The progressive disability associated with PD results in substantial burdens for those with the condition, their families and society in terms of increased health resource use, earnings loss of affected individuals and family caregivers, poorer quality of life, caregiver burden, disrupted family relationships, decreased social and leisure activities, and deteriorating emotional well-being. Currently, no cure is available and the efficacy of available treatments, such as medication and surgical interventions, decreases with longer duration of the disease. Whilst the cause of PD is unknown, genetic and environmental factors are believed to contribute to its aetiology. Descriptive and analytical epidemiological studies have been conducted in a number of countries in an effort to elucidate the cause, or causes, of PD. Rural residency, farming, well water consumption, pesticide exposure, metals and solvents have been implicated as potential risk factors for PD in some previous epidemiological studies. However, there is substantial disagreement between the results of existing studies. Therefore, the role of environmental exposures in the aetiology of PD remains unclear. The main component of this thesis consists of a case-control study that assessed the contribution of environmental exposures to the risk of developing PD. An existing, previously unanalysed, dataset from a local case-control study was analysed to inform the design of the new case-control study. The analysis results suggested that regular exposure to pesticides and head injury were important risk factors for PD. However, due to the substantial limitations of this existing study, further confirmation of these results was desirable with a more robustly designed epidemiological study. A new exposure measurement instrument (a structured interviewer-delivered questionnaire) was developed for the new case-control study to obtain data on demographic, lifestyle, environmental and medical factors. Prior to its use in the case-control study, the questionnaire was assessed for test-retest repeatability in a series of 32 PD cases and 29 healthy sex-, age- and residential suburb-matched electoral roll controls. High repeatability was demonstrated for lifestyle exposures, such as smoking and coffee/tea consumption (kappas 0.70-1.00). The majority of environmental exposures, including use of pesticides, solvents and exposure to metal dusts and fumes, also showed high repeatability (kappas >0.78). A consecutive series of 163 PD case participants was recruited from a neurology clinic in Brisbane. One hundred and fifty-one (151) control participants were randomly selected from the Australian Commonwealth Electoral Roll and individually matched to the PD cases on age (± 2 years), sex and current residential suburb. Participants ranged in age from 40-89 years (mean age 67 years). Exposure data were collected in face-to-face interviews. Odds ratios and 95% confidence intervals were calculated using conditional logistic regression for matched sets in SAS version 9.1. Consistent with previous studies, ever having been a regular smoker or coffee drinker was inversely associated with PD with dose-response relationships evident for packyears smoked and number of cups of coffee drunk per day. Passive smoking from ever having lived with a smoker or worked in a smoky workplace was also inversely related to PD. Ever having been a regular tea drinker was associated with decreased odds of PD. Hobby gardening was inversely associated with PD. However, use of fungicides in the home garden or occupationally was associated with increased odds of PD. Exposure to welding fumes, cleaning solvents, or thinners occupationally was associated with increased odds of PD. Ever having resided in a rural or remote area was inversely associated with PD. Ever having resided on a farm was only associated with moderately increased odds of PD. Whilst the current study's results suggest that environmental exposures on their own are only modest contributors to overall PD risk, the possibility that interaction with genetic factors may additively or synergistically increase risk should be considered. The results of this research support the theory that PD has a multifactorial aetiology and that environmental exposures are some of a number of factors to contribute to PD risk. There was also evidence of interaction between some factors (eg smoking and welding) to moderate PD risk.

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Harris, Bertha J. „Veteran Administration Disease Model to an Interdisciplinary Healthcare Model“. ScholarWorks, 2019. https://scholarworks.waldenu.edu/dissertations/6574.

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There is a growing need for healthcare teams within the Veterans Administration (VA) healthcare system to effectively collaborate and communicate to improve patient outcomes. The need to improve patient care in the Patient Aligned Care Team (PACT) has been well established. The scholarly literature does not provide evidence whether using the primary care PACT model on communication and teamwork by an interdisciplinary medical team ameliorates these communication breakdowns. Bronstein's design for interdisciplinary collaboration provided the overarching framework for this study. The purpose of this qualitative case study was to investigate the use of the PACT model on communication and teamwork by an interdisciplinary medical team as well as the perceived processes and results that the interdisciplinary collaborative approach has on production data. 18 participants consisted of licensed medical professionals and other licensed and non-licensed support personnel who were part of the PACT team. There were several challenges associated with the model, such as (a) a lack of clearly defined roles, (b) lack of communication and collaboration, and (c) division between the clerical and medical staff that created a hostile work environment. Other participants felt there were benefits associated with the PACT model, included (a) improved communication between team members, (b) increased collaboration among team members, and (c) enhanced care for patients using a comprehensive team approach. These findings may help leaders create policies, improve patient care, and create perceived processes to affect successful long-term programs for the future implementation of the PACT model.

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Giancardo, Luca. „Automated fundus images analysis techniques to screen retinal diseases in diabetic patients“. Phd thesis, Université de Bourgogne, 2011. http://tel.archives-ouvertes.fr/tel-00692354.

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In this Ph.D. thesis, we study new methods to analyse digital fundus images of diabetic patients. In particular, we concentrate on the development of the algorithmic components of an automatic screening system for diabetic retinopathy. The techniques developed can be categorized in: quality assessment and improvement, lesion segmentation and diagnosis. For the first category, we present a fast algorithm to numerically estimate the quality of a single image by employing vasculature and colour-based features; additionally, we show how it is possible to increase the image quality and remove reflection artefacts by merging information gathered in multiple fundus images (which are captured by changing the stare point of the patient). For the second category, two families of lesion are targeted: exudate and microaneurysms; two new algorithms which work on single fundus images are proposed and compared with existing techniques in order to prove their efficacy; in the microaneurysms case, a new Radon transform-based operator was developed. In the last diagnosis category, we have developed an algorithm that diagnoses diabetic retinopathy and diabetic macular edema based on the lesions segmented; starting from a single unseen image, our algorithm can generate a diabetic retinopathy and ma cular edema diagnosis in _22 seconds on a 1.6 GHz machine with 4 GB of RAM; additionally, we show the first results of a macular edema detection algorithm based on multiple fundus images, which can potentially identify the swelling of the macula even when no lesions are visible.

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Mahmood, Dler Faieeq Darweesh. „Thioredoxin-1 (Trx1) : a new target in the treatment of cardiovascular diseases“. Phd thesis, Université Pierre et Marie Curie - Paris VI, 2014. http://tel.archives-ouvertes.fr/tel-01069096.

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The cardiovascular diseases (CVDs), resulting from complications of atherosclerosis, remain the leading cause of morbidity and death worldwide. Atherosclerosis as a chronic inflammatory disease, involves both innate and adaptive arms of immunity in which macrophages play the orchestral role in modulating lesion initiation, progression, and potentially devastating thrombotic complications. Available evidences support the notion of a central role of oxidative stress, due mainly to the imbalance between antioxidants and reactive oxygen species (ROS) in CVDs. Furthermore, the pathology is frequently associated with dynamic changes in macrophage activation, with classically activated M1 cells implicated in initiating and sustaining inflammation and M2 or M2-like cells associated with resolution or smoldering chronic inflammation. Among endogenous antioxidants, the thiordoxine-1 (Trx1) plays a central role in several diseases including CVD. Thus, the ubiquitous Trx1 has been reported to exert a myriad of beneficial roles. Indeed, it regulates not only cellular redox homeostasis and acts as a principal antioxidant defense system, but it also affects energy metabolism, modulates the immunological and inflammatory responses, and controls cell growth and survival. In contrast, its truncated form (Trx-80), exerts an opposite effects. However, several studies reported the beneficial role of Trx system in CVDs but the detailed molecular mechanism is not addressed yet. Therefore, the present study aims to investigate the role of both Trx1 and Trx80 in the biology of atherosclerosis through the modulation of macrophage polarization and the implicated signaling pathways as well. Our in vitro major findings, using human macrophages and murine peritoneal macrophages, revealed that Trx1 on one hand promoted the polarization of anti-inflammatory M2 macrophages through downregulation of p16INK4a and suppressing nuclear translocation of activator protein-1 (AP-1) and Ref-1 as evidenced by the expression of the CD206 and IL-10 markers. On the other hand Trx1 also reduced the lipopolysaccharide (LPS)-induced differentiation of inflammatory M1 macrophages, as indicated by the decreased expression of the M1 cytokines, tumor necrosis factor-α (TNF-) and monocyte chemoattractant protein-1 (MCP¨-1). By contrast, Trx80 treatment attenuated the polarization of anti-inflammatory M2 macrophages induced by IL-4 or IL-4/IL-13 even it potentiated LPS-induced M1 activation. To validate our obtained in vitro results, hyperlipoproteinemic C57Bl/6.ApoE2.ki mice and human atherosclerotic vessel specimens from patients undergoing vascular surgery were used. Consistently, Trx1 and Trx80 affected macrophage phenotype in thymus, liver and atherosclerotic lesions. As a consequence, Trx1 reduced whereas Trx80 increased the aortic lesion area in mice. Plasma levels of cholesterol and triglycerides did not changed by the treatment. To further explore our results, the implicated signaling pathways has been studied and it was found that both Trx1 and Trx80 activated Akt. Furthermore, Trx80 uses mTOR signaling pathway to exert its effect in polarizing macrophages toward M1 phenotype since it activated mTOR in a dose-dependent manner as demonstrated by the increased phosphorylation of P70S6K. Based on our results, Trx1 antagonizes whereas Trx80 potentiates atherosclerosis through changing M1/M2 phenotypes. Therefore, Trx1 represents a promising target for therapeutic interventions.

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Kaffashian, Sara. „Cognitive Aging : Role of Cardiovascular Disease Risk Factors“. Phd thesis, Université Paris Sud - Paris XI, 2013. http://tel.archives-ouvertes.fr/tel-00940586.

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Several cardiovascular disease risk factors including, dyslipidemia, high blood pressure, and diabetes have been proposed as important modifiable risk factors for cognitive decline and dementia. These risk factors often co-occur and their aggregation is associated with increased risk of cardiovascular disease and dementia. However, studies of composite measures of cardiovascular disease risk in relation to cognitive outcomes in non-elderly populations are scarce. The aim of this thesis was to examine composite measures of risk in relation to cognition and longitudinal cognitive change amongmiddle-aged adults. Data from the Whitehall II study were used to study the associations between the metabolic syndrome, two Framingham risk scores; the Framingham stroke and general cardiovascular disease risk scores, and cognition, based on three cognitive assessments over 10 years. In addition, these two (cardio)vascular risk scores were compared with the CAIDE dementia risk score. Of all composite measures of risk examined, the two Framingham risk scores were the best predictors of 10-year cognitive decline. Higher cardiovascular risk was associated with faster 10-year decline inmultiple cognitive tests including verbal fluency, vocabulary and global cognition. These results suggest that multiple cardiovascular disease risk factors contribute to cognitive decline starting in midlife and that multi-risk factor models such as cardiovascular risk scores may be better suited to assessing risk of cognitive decline. Early identification and treatment of cardiovascular disease risk factors may offer the possibility of markedly delaying or preventing cognitive decline.

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Brambilla, Davide. „Polymeric nanoparticles as original theranostic approach for alzheimer‟s disease“. Phd thesis, Université Paris Sud - Paris XI, 2012. http://tel.archives-ouvertes.fr/tel-00692581.

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The proof of concept of an original nanotechnology-based theranostic approach for Alzheimer‟s disease has been explored. Novel fluorescently tagged nanoparticles have been designed and employed for internalization and transcytosis studies across a recently developed human in vitro blood-brain barrier model. A small library of polymeric nanoparticles have been designed and their ability to capture the Amyloid β1-42 peptide, considered one of the causes of the Alzheimer‟s disease, has been investigated and quantified using an on purpose designed method.

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Laveneziana, Pierantonio. „Dynamic lung hyperinflation as the common pathway for exercise-induced dyspnoea in cardio-respiratory diseases“. Phd thesis, Université Pierre et Marie Curie - Paris VI, 2012. http://tel.archives-ouvertes.fr/tel-00831616.

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Les patients atteints de BPCO de stade I, d'ICC et d'HTAP peuvent présenter une diminution des débits aériens à bas volume pulmonaire. Il s'agit d'un déterminant majeur de la distension thoracique dynamique, particulièrement délétère, et facteur important de la dyspnée d'exercice. Nos travaux montrent sans ambiguïté une forte association entre la distension thoracique dynamique (limitant l'augmentation du volume courant) et la dyspnée à l'effort chez ces patients. Le corollaire de ces constatations est que des interventions thérapeutiques qui réduisent la distension thoracique devraient diminuer la dyspnée d'effort et améliorer la tolérance à l'exercice, et ce y compris dans des situations cliniques où les anomalies de la mécanique respiratoire ne sont a priori pas le primum movens de la maladie. Et en effet, la réduction de la dyspnée d'effort est bien corrélée avec la réduction du volume pulmonaire induite directement par des interventions pharmacologiques ou indirectement par des interventions non-pharmacologiques. De plus, du point de vue thérapeutique, la mise en évidence dans la troisième étude d'une propension à la distension thoracique induite par l'exercice chez certains patients atteints d'HTAP qui présentent une nette diminution des débits aériens à bas volume pulmonaire peut elle fournir une base théorique à l'adjonction de bronchodilatateurs aux traitements à visée hémodynamique. En conclusion, cette thèse contribue à une meilleure connaissance de la physiopathologie de la dyspnée d'exercice dans le contexte de la BPCO à un stade précoce, de l'ICC et de l'HTAP, en mettant en évidence le rôle d'un mécanisme pathogénétique qui n'avait pas été décrit auparavant.

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Pan, Xiaoxi. „Towards FDG-PET image characterization and classification : application to Alzheimer's disease computer-aided diagnosis“. Thesis, Ecole centrale de Marseille, 2019. http://www.theses.fr/2019ECDM0008.

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La maladie d’Alzheimer (MA) est la maladie neurodégénérative--incurable et irréversible pour le moment--la plus répandue chez les personnes âgées. On s’attend à ce qu’elle soit diagnostiquée à son stade précoce, Mild Cognitive Impairment (MCI), pour pouvoir intervenir et retarder son apparition. La tomographie par émission de positons au fluorodésoxyglucose (TEP-FDG) est considérée comme une modalité efficace pour diagnostiquer la MA et la phase précoce correspondante, car elle peut capturer les changements métaboliques dans le cerveau, indiquant ainsi des régions anormales. Cette thèse est consacrée à identifier et distinguer, sur des images TEP, les sujets atteints de MA de ceux qui sont sains. Ce travail vise également à prédire la conversion de MCI sous la modalité d’imagerie TEP-FDG. A cette fin, trois nouvelles méthodes indépendantes sont proposées.La première méthode est axée sur le développement de connectivités entre les régions anatomiques impliquées dans les images au TEP-FDG, qui sont rarement abordées dans les méthodes déjà publiées. Ces connectivités sont représentées par des similarités ou des mesures graphiques entre régions. Combinées ensuite aux propriétés de chaque région, ces caractéristiques sont intégrées dans un cadre de classification d’ensemble conçu pour résoudre les problèmes de diagnostic MA et de prédiction de conversion MCI.La seconde méthode étudie les caractéristiques permettant de caractériser les images au TEP-FDG à partir de gradients spatiaux, ce qui permet de lier les caractéristiques couramment utilisées, voxel ou régionales. Le gradient spatial est quantifié par un histogramme 2D d’orientation et exprimé sous forme multi-échelle. Les résultats sont obtenus en intégrant différentes échelles de gradients spatiaux dans différentes régions.La troisième méthode applique le Convolutional Neural Network (CNN) sur les trois axes des données 3D de TEP-FDG, proposant ainsi la principale architecture CNN à vues multiples. Une telle architecture peut faciliter les opérations de convolution, de la 3D à la 2D, tout en tenant compte des relations spatiales, qui bénéficient d’une nouvelle couche de cartographie. Ensuite, le traitement sur les trois axes sont combinées et prennent une décision conjointement.Les expériences menées sur des ensembles de données publics montrent que les trois méthodes proposées peuvent atteindre des performances significatives et, de surcroît, dépasser les approches les plus avancées
Alzheimer's disease (AD) is becoming the dominant type of neurodegenerative brain disease in elderly people, which is incurable and irreversible for now. It is expected to diagnose its early stage, Mild Cognitive Impairment (MCI), then interventions can be applied to delay the onset. Fluorodeoxyglucose positron emission tomography (FDG-PET) is considered as a significant and effective modality to diagnose AD and the corresponding early phase since it can capture metabolic changes in the brain thereby indicating abnormal regions. Therefore, this thesis is devoted to identify AD from Normal Control (NC) and predict MCI conversion under FDG-PET modality. For this purpose, three independent novel methods are proposed. The first method focuses on developing connectivities among anatomical regions involved in FDG-PET images which are rarely addressed in previous methods. Such connectivities are represented by either similarities or graph measures among regions. Then combined with each region's properties, these features are fed into a designed ensemble classification framework to tackle problems of AD diagnosis and MCI conversion prediction. The second method investigates features to characterize FDG-PET images from the view of spatial gradients, which can link the commonly used features, voxel-wise and region-wise features. The spatial gradient is quantified by a 2D histogram of orientation and expressed in a multiscale manner. The results are given by integrating different scales of spatial gradients within different regions. The third method applies Convolutional Neural Network (CNN) techniques to three views of FDG-PET data, thereby designing the main multiview CNN architecture. Such an architecture can facilitate convolutional operations, from 3D to 2D, and meanwhile consider spatial relations, which is benefited from a novel mapping layer with cuboid convolution kernels. Then three views are combined and make a decision jointly. Experiments conducted on public dataset show that the three proposed methods can achieve significant performance and moreover, outperform most state-of-the-art approaches

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Boman, Åse. „Fathers involved in children with type 1 diabetes : finding the balance between disease control and health promotion“. Doctoral thesis, Högskolan Väst, Avd för vårdvetenskap på avancerad nivå, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:hv:diva-5808.

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Background: Type I diabetes is a chronic disease that places great demands on the child and family. Parental involvement has been found to be essential for disease outcome. However, fathers’ involvement has been less studied, even though high paternal involvement has been correlated with less disease impact on the family and higher quality of life among adolescents. Aim: The overall aim of the study was to explore and analyze constructions of fathers’ involvement in their child’s everyday life with type 1 diabetes from an ecological and health promotion perspective. Four specific aims were applied: 1) explore and describe discourses in health care guidelines for children with type 1 diabetes in Nordic countries, focusing on parents' positioning (I), 2) analyze how Swedish pediatric diabetes teams perceived and discussed fathers’ involvement in the care of their child with type 1 diabetes, and to discuss how the teams’ attitudes toward the fathers’ involvement developed during a focus group process (II), 3) explore and discuss how fathers involved in caring for their child with type 1 diabetes experience support from their pediatric diabetes team in everyday life with their child (III), and 4) analyze how involved fathers to children with type 1 diabetes understand their involvement in their child’s daily life and to discuss their perceptions from a health promotion perspective (IV). Material and methods: A qualitative and inductive approach was applied. Data were collected and analyzed during 2010-2012. The sample consisted of three pediatric guidelines originating from Norway, Denmark and Sweden (I), three Swedish pediatric diabetes teams (PDTs) (II), and 11 (III) and 16 (IV) fathers of children with type 1 diabetes who scored high involvement on the Parental Responsibility Questionnaire. Data were collected through repeated focus group discussions with the PDTs (II), online focus group discussions (III) and individual interviews (III, IV) with the fathers. Three analysis methods were applied: analysis of discourses (I), Constructivist Grounded Theory (II, III) and content analysis (IV). Findings: The findings illuminated the complex interaction between the pediatric guidelines, the PDTs and the fathers. Fathers highly involved in their child’s daily life experienced different levels of tension between the general recommendations and their personal experiences of living with a child with type 1 diabetes (III). The fathers regarded their involvement in their child’s diabetes care as additional to their general parenting, and a fine balance was identified between a health promotion perspective and a controlling involvement. The common denominator between the highly involved fathers was their use of parental leave (IV). The PDTs initially perceived fathers’ involvement as gendered and balanced on the mother’s agement, but as focus was set on fathers’ engagement the PDTs increased their awareness of this and started to identify and encourage their engagement II). At the macro-level, parents’ voices were diminished in Nordic pediatric diabetes guidelines in favor of an expert discourse (I). Conclusions: Fathers’ involvement concerning a child with type 1diabetes is constructed in a complex way, based on an interaction between the fathers’ perceptions of their additional involvement and the support provided by the PDTs; the PDTs’ perceptions of the fathers’ involvement; and how parents/fathers are constructed in pediatric diabetes guidelines. In order to promote the health and well-being of children with type 1 diabetes, fathers’ involvement needs to be taken into account in the pediatric guidelines as well as in clinical practice.

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Zheng, Sang Guo. „Therapeutic effects of TGT-β induced regulatory T cells on the established autoimmune and inflammatory diseases“. Phd thesis, Université d'Orléans, 2011. http://tel.archives-ouvertes.fr/tel-00698579.

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Recent studies revealed that nTregs has less therapeutic effects on established autoimmune diseases. Current study asks if iTregs induced ex-vivo with TGF- can treat the established autoimmune diseases. In allergic asthma we observed that adoptive transfer of iTreg significantly suppressed airway and peri-vascular inflammation, reduced airway résistance, eosinophil recruitment, mucus hyper-production, airway remodeling and IgE levels. This therapeutic effect was associated with increase of Tregs (CD4+Foxp3+) in the draining LNs, and with reduction of Th1, Th2, and Th17 responses. In collagen-induced arthritis (CIA) both antigen-specific iTregs and expanded nTregs prevented CIA. However, only iTregs transfer suppressed established CIA. nTregs but not iTregs were converted into Th17 and lost Foxp3 in vitro and in vivo in established CIA. iTregs suppressed Th17 cell differentiation that paralleled with improved clinical scores and symptoms. In the chronic GVHD model mimicking lupus the iTregs infusion significantly decreased lupus symptoms. Blocking of TGF- !"#$- %&'(&)*-10 signaling pathways significantly abolished the therapeutic effects. iTregs induced the formation of tolerogenic DCs through TGF- but not IL-10 signaling on DC. DC isolated from lupus mice receiving iTregs can suppress lupus development through TGF- & but not IL-10 signaling. Thus, iTregs target DC in the inflammatory milieu and newly formed tolerogenic DC suppress disease progression through its direct or indirect effect (inducing new iTregs) in autoimmune disease settings. Moreover, we demonstrated that all-trans retinoic acid (atRA) promotes and sustains the Foxp3+ regulatory T cells. atRA increased histone methylation and acetylation within Foxp3 gene locus, while DNA methylation in Foxp3 gene was not significantly altered. These results may provide novel insights into clinical cell therapy for patients with autoimmune diseases and those needing organ transplantation.

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Shen, Kai-kai. „Automatic segmentation and shape analysis of human hippocampus in Alzheimer's disease“. Phd thesis, Université de Bourgogne, 2011. http://tel.archives-ouvertes.fr/tel-00703099.

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The aim of this thesis is to investigate the shape change in hippocampus due to the atrophy in Alzheimer's disease (AD). To this end, specific algorithms and methodologies were developed to segment the hippocampus from structural magnetic resonance (MR) images and model variations in its shape. We use a multi-atlas based segmentation propagation approach for the segmentation of hippocampus which has been shown to obtain accurate parcellation of brain structures. We developed a supervised method to build a population specific atlas database, by propagating the parcellations from a smaller generic atlas database. Well segmented images are inspected and added to the set of atlases, such that the segmentation capability of the atlas set may be enhanced. The population specific atlases are evaluated in terms of the agreement among the propagated labels when segmenting new cases. Compared with using generic atlases, the population specific atlases obtain a higher agreement when dealing with images from the target population. Atlas selection is used to improve segmentation accuracy. In addition to the conventional selection by image similarity ranking, atlas selection based on maximum marginal relevance (MMR) re-ranking and least angle regression (LAR) sequence are developed for atlas selection. By taking the redundancy among atlases into consideration, diversity criteria are shown to be more efficient in atlas selection which is applicable in the situation where the number of atlases to be fused is limited by the computational resources. Given the segmented hippocampal volumes, statistical shape models (SSMs) of hippocampi are built on the samples to model the shape variation among the population. The correspondence across the training samples of hippocampi is established by a groupwise optimization of the parameterized shape surfaces. The spherical parameterization of the hippocampal surfaces are flatten to facilitate the reparameterization and interpolation. The reparameterization is regularized by viscous fluid, which is solved by a fast implementation based on discrete sine transform. In order to use the hippocampal SSM to describe the shape of an unseen hippocampal surface, we developed a shape parameter estimator based on the expectationmaximization iterative closest points (EM-ICP) algorithm. A symmetric data term is included to achieve the inverse consistency of the transformation between the model and the shape, which gives more accurate reconstruction of the shape from the model. The shape prior modeled by the SSM is used in the maximum a posteriori estimation of the shape parameters, which is shown to enforce the smoothness and avoid the effect of over-fitting. In the study of the hippocampus in AD, we use the SSM to model the hippocampal shape change between the healthy control subjects and patients diagnosed with AD. We identify the regions affected by the atrophy in AD by assessing the spatial difference between the control and AD groups at each corresponding landmark. Localized shape analysis is performed on the regions exhibiting significant inter-group difference, which is shown to improve the discrimination ability of the principal component analysis (PCA) based SSM. The principal components describing the localized shape variability among the population are also shown to display stronger correlation with the decline of episodic memory scores linked to the pathology of hippocampus in AD.

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Pemberton, Samantha. „Molecular chaperones in the assembly of α-Synuclein and Parkinson's Disease“. Phd thesis, Université Paris Sud - Paris XI, 2011. http://tel.archives-ouvertes.fr/tel-00762970.

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The formation and deposition of α-Synuclein fibrils in the human brain is at the origin of Parkinson's disease. The objective of my thesis was to document the role of two molecular chaperones on the assembly of α-Syn into fibrils: Hsc70, a constitutively expressed human heat shock protein, and Ssa1p, its yeast equivalent. The aim was to expand the catalogue of known effects of molecular chaperones on the PD implicated protein, which could have therapeutic significance. We showed that Hsc70 inhibits the assembly of α-Syn into fibrils, by binding with high affinity to the soluble form of α-Syn. We documented that Hsc70 binds preferentially to α-Syn fibrils and that this binding has a cytoprotective effect, as it renders the fibrils less toxic to cultured mammalian cells. Similarly to Hsc70, Ssa1p inhibits the assembly of α-Syn into fibrils, and has a higher affinity for fibrils than for the soluble form of α-Syn. On the other hand, binding of Ssa1p to α-Syn fibrils does not have a cytoprotective effect, almost certainly due to differences in the amino acid sequences of the peptide binding sites of the two molecular chaperones, which mean that Ssa1p has a lower affinity than Hsc70 for α-Syn fibrils. We stabilized the complex between Ssa1p and α-Syn using chemical cross-linkers, to then map the interaction site between the two proteins. This is indispensable if a "mini" Ssa1p, comprised of only what is necessary and sufficient of Ssa1p, is to be used as a therapeutic agent to decrease the toxicity of α-Syn fibrils. A therapeutic agent based on exogenous protein Ssa1p is less likely to trigger an autoimmune response than for example the endogenous protein Hsc70.

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Dudley, Alicia A. „An Investigation of the Multifaceted Platelet Dysfunction in Dogs with Naturally-Occurring Chronic Kidney Disease“. The Ohio State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=osu1405012077.

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31

Tollefson, Stacy Joy. „Compost Water Extracts And Suppression Of Root Rot (F. Solani F. Sp. Pisi) In Pea: Factors Of Suppression And A Potential New Mechanism“. Diss., The University of Arizona, 2014. http://hdl.handle.net/10150/338972.

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One of the motivating reasons for the development of hydroponics was avoidance of root pathogens. Hydroponics involves growing crops in relatively sterile media, isolated from the underlying soil which may have disease pressure. However, even when hydroponics is coupled with controlled environments such as high tunnels and climate-controlled greenhouses, soil-borne pathogens can enter the growing area and proliferate due to optimal environmental conditions for pathogen growth. Control of root pathogens is difficult and usually achieved through synthetic fungicides since few biocontrol options are available. Compost water extracts (CWE) have recently been gaining the attention of greenhouse growers because they may be a low-cost, environmentally friendly approach to control root disease. CWE are mixtures of compost and water incubated for a defined period of time, either with or without aeration, and with or without additives intended to increase microbial populations, which in turn suppress disease. Much anecdotal, but very little scientific, evidence exists describing CWE effect on suppressing soil-borne pathogens. The present study 1) examined the effect of an aerated CWE on disease suppression at the laboratory scale and in container studies using different soilless substrates, 2) investigated a phenotypic change at the root level caused by CWE that may be associated with disease suppression, and 3) isolated some factors in the production of CWE that affect the ability of a CWE to suppress disease. The common model pathogen-host system of Fusarium solani f.sp. pisi and pea was used to examine CWE-induced disease suppression, with information then being translatable to similar patho-systems involved in greenhouse crop production. In the first study, laboratory-based root growth and infection assays resulted in 100% suppression of F. solani when roots were drenched in CWE. These protected seedlings were then taken to a greenhouse and transplanted into fine coconut coir, watered with hydroponic nutrient solution, and grown for five weeks. At the end of the experiment, 23% of the shoots of the pathogen-inoculated, CWE-drenched seedlings remained healthy while only 2% of the inoculated seedlings without CWE drench remained healthy. All of the roots of the inoculated seedlings developed lesions, even those drenched in CWE. However, 29% of the CWE drenched roots were able to recover from disease, growing white healthy roots past the lesion, while only 2% recovered naturally. A shorter-term container study was conducted in the laboratory to determine the effects of CWE-induced suppression when peas were grown in different substrates and to determine if the hydroponic nutrient solution had an effect on the suppression. Peas were grown in sterilized fine and coarse coconut coir fiber and sand irrigated with water, with a second set of fine coir irrigated with hydroponic nutrient solution. Pea seeds with 20-25mm radicles were inoculated with pathogen and sown directly into CWE-drenched substrate and grown for three weeks. At the end of the experiment, 80%, 60%, 90%, and 50% of the shoots of the inoculated, CWE-drenched seedlings remained healthy when grown in fine coir, coarse coir, sand, and fine coir irrigated with hydroponic nutrient solution, respectively. Nearly 100% of the roots grown in coconut coir substrates again developed necrotic lesions but 83%, 87%, 100%, and 87% grew healthy roots beyond the disease region. The hydroponic nutrient solution had a negative effect on suppression, with a reduction of at least 30 percentage points. Sand demonstrated a natural ability to suppress F. solani. Only 23% of inoculated seedlings had dead or dying shoots by the end of the experiment (compared to 77-80% in coir substrates) and although all but one of the roots developed lesions, all were able to recover on their own with CWE. CWE further increased shoot health and also prevented 57% of the roots from developing lesions. In a second study, two different CWE were used to examine the effect on root border cell dispersion and dynamics in pea, maize, cotton, and cucumber and its relation to disease suppression. Dispersal of border cells after immersion of roots into water or CWE was measured by direct observation over time using a compound microscope and stereoscope. Pictures were taken and the number of border cells released into suspension were enumerated by counting the total number of cells in aliquots taken from the suspension. Border cells formed a mass surrounding root tips within seconds after exposure to water, and most cells dispersed into suspension spontaneously. In CWE, >90% of the border cell population instead remained appressed to the root surface, even after vigorous agitation. This altered border cell phenomena was consistent for pea, maize, and cotton and for both CWE tested. For most cucumber roots (n=86/95), inhibition of border cell dispersal in both CWE was similar to that observed in pea, maize, and cotton. However, some individual cucumber roots (8±5%) exhibited a distinct phenotype. For example, border cells of one root immersed into CWE remained tightly adhered to the root tip even after 30 minutes while border cells of another root immersed at the same time in the same sample of CWE expanded significantly within 5 minutes and continued to expand over time. In a previous study, sheath development over time in growth pouches also was distinct in cucumber compared with pea, with detachment of the sheaths over time, and root infection was reduced by only 38% in cucumber compared with 100% protection in pea (Curlango-Rivera et al. 2013). Further research is needed to evaluate whether this difference in retention of border cell sheaths plays a role in the observed difference in inhibition of root infection. In the third study, a series of investigations were conducted to isolate different factors that contribute to the suppression ability of a CWE by changing incrementally changing some aspect of the CWE production process. The basic aerated CWE recipe (with molasses, kelp, humic acid, rock phosphate, and silica) provided 100% protection of pea from root disease while the non-aerated basic recipe CWE provided 72% protection. Aerated CWE made of only compost and water resulted in 58% protection. It was found that molasses did not contribute to the suppression ability of the ACWE, while kelp contributed strongly. When soluble kelp was added by itself to the compost and water, the CWE provided 80% suppression. However, when all additives were included except molasses and kelp, suppression remained high (93%) indicating that humic acids, rock phosphate, and/or silica were also major contributors toward the suppression effect. Optimal fermentation time for ACWE was 24 hr to achieve 100% suppression, with increased time resulting in inconsistent suppression results. Optimal fermentation time for NCWE was 3 days or 8 days. These studies are important contributions to understanding the differences that might be expected in CWE suppression when growing in different substrates, some of the factors in the production of CWE that affects the ability of a CWE to suppress disease, and the phenotypic effect CWE has on the root zone of plants and the possible relationship between that effect and disease suppression.

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Laval, Julie. „Metabolic adaptation of inflammatory neutrophils in human diseases revealed by retroviral envelope-derived ligands : focus on cystic fibrosis“. Phd thesis, Université Montpellier II - Sciences et Techniques du Languedoc, 2013. http://tel.archives-ouvertes.fr/tel-01021456.

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The present study focuses on adaptive metabolic steps adopted by neutrophils during inflammation, particularly during their recruitment into the cystic fibrosis (CF) airways. In CF, we previously described that airway neutrophils are alive and undergo reprogramming, featuring notably the activation of the anabolic mTOR pathway. The present work is based on specific properties of soluble ligands derived from the receptor-binding domains (RBD) of retroviral glycoprotein envelopes, which can be used for the detection of metabolite transporters at the cell surface. First, we validated the use of this new set of markers for the identification and characterization of the metabolic phenotype of CF leukocytes obtained from distinct compartments (blood and sputum). Second, by studying the metabolite transporter expression on blood neutrophils from CF or rheumatoid arthritis patients and control subjects, we distinguished metabolic phenotypes characteristic of specific inflammatory states. Then, we compared metabolite transporter expression between CF blood and airway neutrophils and showed that neutrophils undergo significant metabolic adaptation upon recruitment into the lungs. Finally, we demonstrated that CF airway neutrophils display significant transcriptional modulation and that despite their metabolic reprogramming, they remain functionally competent, thus adding an additional angle of approach to neutrophil studies with regard to inflammation, notably during CF airway disease.

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Widy, Sarah, Andrea Bisceglia, Emily Bradley, Sanjana Kumari Vyda Srinivasa Kumar, Andrea McDowell, Amanda Murr, Blake Nowicki, Elisha Reed, Alexandria Staples und Brenda Louw. „Young Adults with Cleft Lip and Palate: Are They Receiving Team Services?“ Digital Commons @ East Tennessee State University, 2017. https://dc.etsu.edu/etsu-works/2151.

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It is widely acknowledged that a team approach is preferred practice and contributes to optimizing the surgical, dental, speech and psychosocial outcomes for individuals with CLP. Young adulthood often marks the transition from child-centered interdisciplinary care to adult-centered care. There is a paucity in literature relating to the transition of care for young adults with CLP. The purpose of this survey research is therefore to explore the CLP team practices regarding young adults with CLP.

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Mallett, Susan Veronica. „The clinical utility of viscoelastic tests of coagulation (TEG® & ROTEM®) in liver disease and liver surgery“. Thesis, University College London (University of London), 2016. http://discovery.ucl.ac.uk/1476864/.

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This thesis focuses on what is currently known about the haemostatic changes that occur in liver disease, and also those that follow major liver resection. Although there has been considerable work on the changes in coagulation in both acute and chronic liver disease in recent years, there has been far less attention to hepatic resection. This is also an important area for study as an elevation of PT/INR is common in the first few days after resection, yet these patients are known to have a high incidence of thromboembolic complications in the early post operative period, and this risk appears to increase with the extent of liver parenchyma resected. It is the central hypothesis of this thesis that global viscoelastic tests (TEG/ROTEM) by facilitating assessment of all the cellular components of the coagulation process in an integrated manner, and their summative effect on ultimate clot formation, strength and stability, provide more clinically relevant information than do conventional coagulation tests which only assess single end points of coagulation in plasma rather than in whole blood. Chapter one focuses on models of coagulation (traditional cascade model and the newer cell based model of haemostasis) and the limitations of traditional coagulation tests in liver disease. Chapter two discusses the principles of viscoelastic tests, their limitations and also their correlation with conventional coagulation tests. It also highlights that these tests can detect 'hypercoagulability' which may relate to an increased thrombotic risk, and also fibrinolysis, neither of which is readily detected using conventional tests of coagulation. Chapter three is a review and critical appraisal of the available literature on the utility of viscoelastic tests of coagulation in patients with both acute and chronic liver disease. The majority of patients with liver disease have 'normal' coagulation as assessed by these tests, and this may be seen as supporting the hypothesis of 're-balanced' haemostasis. Aspects such as hypercoagulability and the relation to thrombotic risk, and endogenous heparinoids as markers of infection and endothelial injury are highlighted. Chapter four is a review and critical appraisal of the available literature on the utility of viscoelastic tests of coagulation in patients undergoing liver transplantation. The literature is reviewed to determine their efficacy in predicting bleeding risk, and also to guide haemostatic therapy in the presence of active bleeding. Chapter five is a retrospective study to assess the prevalence of fibrinolysis in patients undergoing liver transplantation, and how this relates to subsequent need for blood transfusion. Historically aprotinin (Trasylol) was given to high risk liver transplant patients to minimise the bleeding associated with fibrinolysis. Aprotinin was withdrawn from clinical practice in 2008, and since that time treatment with antifibrinolytic therapy has generally moved towards a treatment only regime, rather than prophylaxis. Comparing retrospective propensity matched cohorts (prophylactic versus treatment only with anti-fibribrinolytics agents) the impact of fibrinolysis on transfusion requirements was investigated, and also whether the timing of the appearance of fibrinolysis at different stages of the operation has different prognostic significance. Chapter six describes the prevalence of hypercoagulability during liver transplantation, as determined by thromboelastography performed at the start of the procedure, and at various time points during the operation, in a series of 100 consecutive patients undergoing liver transplantation. This information gives an indication of the association of hypercoagulability with underlying disease aetiology, and also whether there are changes in this baseline profile, or de-novo appearance of hypercoagulability during the intraoperative period. Chapter seven describes the sequential changes in coagulation parameters (conventional coagulation tests, pro and anticoagulant factor levels, thrombin generation, and thromboelastometry (ROTEM)) in a prospective series of patients undergoing major hepatic resection. Given that the INR is frequently prolonged in the early post operative period, the question is whether this represents a true bleeding risk, as is currently assumed, or if other tests of coagulation suggest that this assumption should be re-evaluated. Chapter eight describes the efficacy in vitro of two different dose regimes of fresh frozen plasma (FFP) to correct coagulopathy, as determined by a prolonged INR, after major hepatic resection, and also the effect of FFP on viscoelastic tests in the same group of patients. These patients will frequently receive prophylactic FFP prior to procedures, but there is little data on the effect of typical dose regimes on either conventional or viscoelastic coagulation tests. This information could be of value in determining if FFP is useful, or indeed even necessary, in these patients prior to undergoing an invasive procedure. Chapter nine summarises the findings from these chapters, and discusses whether viscoelastic coagulation tests do indeed give more valuable oversight of the haemostatic profile in patients with liver disease and following major hepatic resection. Directions for future research based on these findings are also considered.

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Grano, Maldonado Mayra Ixchel. „The biological and behavioural basis of host selection in the transmission of Gyrodactylus (Monogenea)“. Thesis, University of Stirling, 2010. http://hdl.handle.net/1893/3700.

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The ectoparasitic monogenean fluke, Gyrodactylus salaris, is a parasite known to be highly pathogenic to Atlantic salmon (Salmo salar). Although present in the environment of several neighbouring European countries, the UK is thought to be G. salaris-free, but, if national contingency plans to control this parasite are to be effective, it is vital that we understand the factors underlying its transmission from host to host. This study demonstrates that the majority of parasites transferring to new hosts are mature parasites that have reproduced at least once. Since, exploration and host transfer strategies pose a risk to survival; the parasite will endeavour to pass on its genes before attempting to transfer from one host to another. This study has also shown that when pregnant parasites are forced to leave their hosts, their offspring are aborted prematurely to ensure the survival of the mature parasite. Gyrodactylids do not possess a free-swimming stage in their life cycle, which allows for their migration between hosts. In spite of this, they are able to rapidly colonise naïve hosts, even in non-shoaling populations of fish. This study investigates the transmission strategies employed by detached parasites in the colonisation of new hosts. Observations of gyrodactylids collected from 3-spine sticklebacks, Gasterosteus acuelatus, suggest that their activity increases as a stickleback approaches, alerting the host to its presence. The parasite is then ingested directly by the prospective host. A time series of experimental exposures and specimens prepared for Scanning Electron Microscopy (SEM) suggest that once ingested, the parasites attach to the lining of the buccal cavity and then migrate out to their preferred colonisation site on the outer surface of the fish. It is proposed that this may be an alternative route for host infection. Similarly, direct ingestion by the scavenging on infected hosts by 3-spine sticklebacks suggests another route of infection of new hosts. Although these routes of transmission may be of lesser significance, infections in the buccal cavity may be an important indicator for detection of infection and those personnel involved in screening fish for gyrodactylids should be aware that this is an area in which infections can occur. This study also demonstrated that the use of the anaesthetic 2-phenoxyethanol does not affect the number of gyrodactylids which leave the host to colonise a new host. Additionally, observations of the transmission process suggest that turbulence produced by the movement of the fish’s fins may facilitate the transfer of detached parasites from the substrate. While this hypothesis appears to be supported by video evidence and photographic stills gathered throughout the duration of this study, further work should be conducted using particle tracking techniques to determine the efficacy of using a vortex effect as a means of colonising new hosts. Field sampling processes may have an effect on this type of research, giving rise to problems with the accurate diagnosis, management and control of gyrodactylids in a variety of fish. Gyrodactylus infected specimens of 3-spine stickleback (Gasterosteus aculeatus L.), minnows (Phoxinus phoxinus L.) and stone loach (Barbatula barbatula L.) from one Scottish river were cohabited. The study found that small numbers of Gyrodactylus do transfer to atypical hosts. This study highlights that personnel involved in fish disease surveillance programmes should be aware of the consequences of transporting multiple species in the same transport vessel as gyrodactylids may infect species previously thought to be resistant. Equally, diagnosticians should be aware of the fact that atypical species may act as temporary hosts and that their gyrodactylid fauna should not be assumed. Non-feeding life-cycle stages, such as the dispersal stages of parasites, are dependant for survival upon finite energy reserves gathered during feeding phases. Thus, those individuals with more limited reserves will die sooner and consequently have less time available to find a new host once detached. At this stage, the principal energy reserves in gyrodactylids are stored as large lipids droplets. Confocal laser scanning microscopy (CLSM) has been used to investigate the distribution of lipid droplets in Gyrodactylus, which have migrated off their fish host, testing the hypothesis that these droplets function as a proxy for the nutritional state. This study, demonstrated that the lipid droplets were particularly associated with the gut and that there is a significant variability in the volume of stored lipid carried out by each individual. Transmission Electron Microscopy (TEM) showed that gyrodactylids carry lipid droplets at all stages of their life cycle, including at release from the birth pore. It is likely that transferring worms require stored energy reserves to survive in the event of failure to establish contact with a new host. These reserves could allow the parasite to survive without a host for several days. As gyrodactylids appear to respond to a range of stimuli including vibration and chemicals released from the host, the presence or absence of such cues may have consequences on the rates of Gyrodactylus transmission. If these chemical stimuli can be identified and then mimicked or blocked, then this may offer potential opportunities for the control of gyrodactylid behaviour and for disrupting their transmission to new hosts. Baseline gyrodactylid behaviour, in the absence of a host, was determined under white light and infrared. This was achieved using a specially constructed arena and purpose written image analysis software to analyse parasite movement under different lighting conditions. The study found that gyrodactylids were more active in the dark than in light conditions, typically displaying longer, more sinuous tracks under red light than under white light. To begin investigating the effect of chemical presence on gyrodactylid behaviour, the activity of octopaminergic agonists and antagonist which bind to muscle receptors and alter muscle activity, were assessed. The impact of octopamine hydrochloride, clonidine hydrochloride, amitraz and, a toxic reference, chlordimeform, over a range of concentrations (0.2 to 3.2µM/L) were assessed on gyrodactylid behaviour. All of the four chemicals affected Gyrodactylus and produced muscle tetanus, causing muscle spasms when extension was attempted. Prolonged exposure resulted in death. Only the highest concentration of chlordimeform, the toxic reference, affected 100% of Gyrodactylus after 24 hours. After 48 hours, all of the Gyrodactylus treated with chlordimeform were either affected, moribund or dead. Amitraz was more toxic than chlordimeform with 80% of Gyrodactylus being dead after 24 hours at the highest concentration. After 48 hours 100% of Gyrodactylus exposed to 3.2 µm/L amitraz were dead, and up to 80% were dead in those exposed to lower concentrations; with no parasites being left unaffected. Although these particular compounds are toxic to fish, the effect of these agonistic chemicals on Gyrodactylus behaviour and survival is interesting and suggests that a closely related compound that is safe for use against fish may offer a potential treatment for the control of G. salaris infections in rivers. An ultrastructure study was undertaken to contribute to the current understanding of gyrodactylid ultrastructure. The findings of this research require broad understanding of gyrodactylid behaviour for their interpretation. Photographic evidence was gathered using transmission and electron microscopy. From these results, it is clear that Gyrodactylus gasterostei on a three-spine stickleback host will respond to a range of stimuli (i.e. vibration or chemical cues released from the host) in their assessment of host suitability.

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Sharma, Meenu. „Interactions cellulaires et moléculaires entre basophiles et lymphocytes T CD4+“. Phd thesis, Université de Technologie de Compiègne, 2014. http://tel.archives-ouvertes.fr/tel-01066885.

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Les basophiles sont les granulocytes les plus rares. Ils sont impliqués dans la polarisation des réponses immunitaires de type Th2, dans la différenciation des lymphocytes B et dans la protection contre les infections helminthiques. Les basophiles sont impliqués dans la modulation des réponses immunitaires, en particulier dans les maladies auto-immunes et inflammatoires. Des études récentes ont montré que les basophiles murins sont cellules présentatrices d'antigène (CPA) et induisent des réponses Th2 et IgE contre les allergènes et les infections helminthiques.Par conséquent, Nous avons exploré les fonctions des basophiles humains, en particulier comme CPA professionnelles. Les résultats montrent que les basophiles, contrairement aux cellules dendritiques et monocytes, n'expriment pas HLA-DR et les marqueurs de co-stimulations CD80 et CD86. De plus, la stimulation des basophiles par divers allergènes, comme des ligands de TLR et IgE, n'induit pas des changements dans l'expression de ces marqueurs. Enfin, nos résultats montrent que les basophiles ne favorise pas les réponses immunitaire de type Th2 ou Th17. Ainsi,notre étude montre que les basophiles humains circulant ne possèdent pas des fonctions de CPA professionnelles. Des plus, les basophiles sont impliqués dans la pathogenèse de maladies auto-immunes et inflammatoires dépendantes des réponses Th2 et médiées par les lymphocytes B. Puisque la dérégulation des basophiles joue un rôle important dans le développement des réponses immunitaires dans différentes conditions pathologiques, nous avons exploré les mécanismes de régulations qui modulent les fonctions les basophiles. En particulier, nous avons étudié le rôle suppresseur des lymphocytes T régulateurs (Tregs) CD4+CD25+FoxP3, des cellules clés dans la maintenance de l'homéostasie immune, sur les fonctions des basophiles. Nos résultats montrent que les fonctions des basophiles, contrairement à la majorité des cellules immunes, ne sont pas régulées par les Tregs. Bien au contraire, nos résultats montrent que les lymphocytes T favorisent l'activation des basophiles. En résumé, nous avons exploré de nouveaux mécanismes cellulaires et moléculaires impliqués dans la régulation des fonctions des basophiles humains. Ces résultats nous permettent de mieux comprendre le rôle des basophiles dans les conditions inflammatoires et dans le développement de nouvelles stratégies thérapeutiques.

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Lorenzi, Marco. „Deformation-based morphometry of the brain for the development of surrogate markers in Alzheimer's disease“. Phd thesis, Université de Nice Sophia-Antipolis, 2012. http://tel.archives-ouvertes.fr/tel-00844577.

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The aim of the present thesis is to provide an e ffective computational framework for the analysis and quantifi cation of the longitudinal structural changes in Alzheimer's disease (AD). The framework is based on the diffeomorphic non-rigid registration parameterized by stationary velocity fields (SVFs), and is hierachically developed to account for the diff erent levels of variability which characterize the longitudinal observations of T1 brain magnetic resonance images (MRIs). We developed an effi cient and robust method for the quantifi cation of the structural changes observed between pairs of MRIs. For this purpose, we propose the LCC-Demons registration framework which implements the local correlation coeffi cient as similarity metric, and we derived consistent and numerically stable measures of volume change and boundary shift for the regional assessment of the brain atrophy. In order to consistently analyze group-wise longitudinal evolutions, we then investigated the parallel transport of subject-specifi c deformation trajectories across di fferent anatomical references. Based on the SVF parametrization of diffeomorphisms, we relied on the Lie group theory to propose new and effective strategies for the parallel transport of SVFs, with particular interest into the practical application to the registration setting. These contributions are the basis for the defi nition of qualitative and quantitative analysis for the pathological evolution of AD. We proposed several analysis frameworks which addressed the di fferentiation of pathological evolutions between clinical populations, the statistically powered evaluation of regional volume changes, and the clinical diagnosis at the early/prodromal disease stages.

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Addo, Emilia K. „Chronic Care Model Staff Education and Adherence with End-Stage Renal Disease Patients“. ScholarWorks, 2015. https://scholarworks.waldenu.edu/dissertations/1813.

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The management and treatment of chronic diseases, such as end-stage renal disease, is often unproductive because of patients' poor adherence to treatment. The chronic care model toolkit is an Agency for Healthcare Research and Quality supported framework, associated with improved outcomes in patients living with chronic disease. The purpose of this project was to develop and plan an educational program using the chronic care model toolkit for the interdisciplinary clinical staff of a renal hemodialysis center. The goal of this project was to adapt team building between patients and their clinicians through the use of the chronic care model in order to improve patients' adherence to treatment. The educational program materials were developed, including a plan for future implementation over 6 weeks in 2-hour twice-weekly sessions. Program planning accounted for the mixed roles and responsibilities of the interdisciplinary clinical team members, who will share their knowledge among the team and act as patient advisors. The pretest and posttest materials were developed from the toolkit Team Health Audit Questionnaire, which can be used to evaluate staff learning after the program is delivered. Existing clinical metrics are tracked through a Quality Assessment Performance Improvement measure, which will be used to evaluate potential long term influences of the program on patient adherence and outcomes. The project may contribute to social change in practice by enhancing teamwork that has the potential to improve clinical outcomes. Future research should include longitudinal studies on team building using the chronic care model toolkit to determine if its adaption enhances team effort and contributes to a collaborative workforce that improves clinical outcomes.

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BERTOLDI, GIOVANNI. „Assessment of oxidative stress and cardiovascular-renal remodelling in the X-linked rare Fabry disease. Evaluation of the antioxidant effect of green tea treatment on top of Enzyme Replacement Therapy“. Doctoral thesis, Università degli studi di Padova, 2022. http://hdl.handle.net/11577/3456146.

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La malattia di Fabry è una rara disfunzione metabolica conseguente ad una mutazione nel gene galattosidasi alpha (GLA) localizzato nel cromosoma X che codifica per l’enzima α-galattosidasi A (α-galA) implicato nel metabolismo dei glicosfingolipidi, in modo particolare della globotriaosilceramide (Gb3) e derivati. Le differenti mutazioni comportano un’alterata espressione ed attività dell’enzima α-galA con il conseguente accumulo dei suoi substrati all’interno dei lisosomi e l’insorgenza di una malattia sistemica. L'attuale linea di trattamento è la terapia enzimatica sostitutiva (ERT) la quale, nel lungo termine, non è in grado di alterare il progressivo decorso della malattia. Questo pone l’attenzione sulla possibilità che le complicanze a livello cardiovascolare e renale siano dovute a meccanismi secondari all’accumulo di Gb3, suggerendo la necessità di affiancare l’ERT con terapie aggiuntive. Tra gli induttori di rimodellamento cardiovascolare-renale, lo stress ossidativo ha un ruolo primario. Considerato che nei pazienti con malattia di Fabry è stato dimostrato che l’accumulo di Gb3 induce stress ossidativo in termini di incremento di citochine proinfiammatorie e riduzione della produzione di ossido nitrico, è ragionevole pensare ad un importante coinvolgimento dello stress ossidativo nella malattia di Fabry. A tal scopo, nella prima fase di questo studio è stato valutato lo stato di attivazione dello stress ossidativo nei pazienti Fabry in trattamento con ERT, a confronto con un gruppo di pazienti sani. Nella seconda fase invece è stata valutata la variazione del profilo ossidativo prima dell’inizio della terapia, dopo 12 mesi di trattamento con la terapia enzimatica sostitutiva e dopo 6 mesi di trattamento antiossidante aggiuntivo con tè verde. Queste valutazioni sono state condotte ex vivo su 10 pazienti trattati e 10 controlli sani nella prima fase e, nella seconda fase, su 10 pazienti Fabry arruolati prima dell’inizio della terapia. Nello specifico è stata valutata: l’espressione proteica di p22phox ed HO-1, la fosforilazione della MYPT-1 e delle ERK 1/2, i livelli plasmatici di MDA. Da questo studio emerge chiaramente come nei pazienti Fabry ci sia uno stato di stress ossidativo attivo. Questo sbilancio ossidativo sembra essere parzialmente alleviato dalla terapia con ERT, ma la somministrazione sinergica di tè verde porta ad una significativa riduzione dei marker ossidativi analizzati. Infatti, l’espressione proteica di p22phox, i livelli di MDA e la fosforilazione della MYPT-1 risultano significativamente maggiori nei pazienti rispetto ai soggetti sani. p22phox e fosforilazione di MYPT-1 che si riducono significativamente in seguito alla terapia a differenza dei livelli di MDA; tuttavia, l’integrazione antiossidante contribuisce ad una significativa riduzione dei tre marker. Al contrario, l’espressione proteica di HO-1 e la fosforilazione di ERK 1/2 sono significativamente più basse nei soggetti trattati rispetto ai controlli. Il confronto con i primi 12 mesi di trattamento dimostra una riduzione dei livelli di HO-1 rispetto al baseline ma non della fosforilazione delle ERK 1/2, entrambi valori che significativamente diminuiscono dopo 6 mesi di trattamento antiossidante. In conclusione, da questo studio emerge un’alterata reazione dello stress ossidativo nei pazienti affetti da malattia di Fabry che dovrebbe essere tenuta in considerazione nella gestione e nel follow-up dei pazienti. Da questi dati preliminari emerge inoltre un parziale ruolo protettivo dell’ERT nella riduzione dello stress ossidativo, in seguito amplificato dalla terapia antiossidante con tè verde. Questo da un lato evidenzia ulteriormente l'importanza di una diagnosi precoce e di un inizio tempestivo del trattamento enzimatico, dall'altro suggerisce la necessità di trattamenti antiossidanti adiuvanti per prevenire o risolvere specifiche manifestazioni della malattia.
Fabry disease (FD) is an X-linked rare metabolic disorder due to a mutation in the galactosidase alpha gene (GLA) that encodes for the lysosomal enzyme alpha-galactosidase A (α-galA) involved in the metabolism of glycosphingolipid as globotriaosylceramide (Gb3) and derivatives. The deficient expression and activity of α-galA cause lysosomal accumulation of its substrates in various organs arising a systemic disease. The current available treatment for all FD patients is the enzyme replacement therapy (ERT) which consist in an intravenous administration of recombinant α-galA in order to replace the impaired enzymatic activity and reduce intracellular storage of Gb3. Nevertheless, long-term studies showed no clear evidence that ERT could alter the natural course of cardiac, cerebrovascular and renal disease, suggesting on one hand that these adverse outcomes do not entirely depend on the single accumulation of glycosphingolipids, on the other that additional therapies targeted at specific secondary mechanisms can halt the progress of cardiac and cerebrovascular disease and the nephropathy that occur in Fabry patients. Oxidative stress has a primary role in the induction of cardiovascular-renal remodelling. It has been shown that Gb3 accumulation induces oxidative stress in terms of increased proinflammatory cytokines and reduced nitric oxide production. Therefore, it could also be involved in the onset of cardiovascular-renal complications in FD. Hence, in the first phase of this study we aimed to evaluate the status of oxidative stress in Fabry patients under ERT, compared with a group of healthy patients as control. In the second phase, we evaluated the changes in the oxidative profile in FD before the start of the enzymatic therapy, after 12 months of ERT and after 6 months of additional treatment with green tea. These evaluations were performed ex vivo on 10 treated patients and 10 healthy controls in the first phase and, in the second phase, on 10 Fabry patients enrolled before the start of therapy. Specifically, we evaluated the protein expression of p22phox and HO-1, the phosphorylation of MYPT-1 and ERK 1/2, plasma levels of malondialdehyde (MDA). The results of this project showed that OxSt is clearly present and active in Fabry patients and that the treatment with ERT, and particularly with the adjunctive antioxidant therapy with green tea, led to an attenuation of the oxidative profile. In fact, protein expression of p22phox, MDA levels, and MYPT-1 phosphorylation were significantly higher in patients compared to healthy subjects. p22phox and MYPT-1 phosphorylation that significantly decreased after ERT, unlike MDA levels that were not statistically reversed by the enzymatic treatment. However, the antioxidant supplementation significantly reduced the levels of these markers. In contrast, protein expression of HO-1 and phosphorylation of ERK 1/2 were significantly lower in treated subjects than controls. Compared to baseline, the first 12 months of ERT resulted in a reduction of HO-1, while the phosphorylation state of ERK 1/2 remained unchanged; markers that however significantly decreased after 6 months of green tea supplementation. In conclusion, this study showed an altered oxidative stress response in FD that should be taken into consideration in the management and follow-up of these patients. Our preliminary data also documented an antioxidant effect exerted by ERT itself, which was further amplified by the treatment with green tea on top of ERT. These data while on one hand highlight the fundamental importance of an early diagnosis and treatment of FD, on the other suggest the need of adjuvant antioxidant treatments to prevent or improve specific disease manifestations.

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Cope, Julie K. „Exploring the Effect of an Interdisciplinary Teamwork Intervention in Acute Rehabilitation“. BYU ScholarsArchive, 2016. https://scholarsarchive.byu.edu/etd/6459.

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Purpose: The purpose of this study was to explore the efficacy of an interdisciplinary intervention on interdisciplinary teamwork and patient functional outcomes in an acute inpatient rehabilitation unit at a mid-sized regional hospital. Design: Pilot mixed-methods pre-post intervention study. Methods: Interdisciplinary teamwork and patient functional outcomes were measured before and after a teamwork intervention. Interdisciplinary teamwork was measured with the Healthcare Team Vitality Instrument (HTVI) and a qualitative staff questionnaire developed by a content expert. Patient functional outcomes were measured by aggregated Functional Independence Measure (FIM®) scores. Findings: Post-intervention FIM® gain scores increased significantly (p = .008). Staff questionnaire revealed improvement in interdisciplinary teamwork, with the major themes of teamwork and appreciation/respect. Post-intervention HTVI showed no significant change (p=.528). Conclusions: Initial results of this intervention are promising; additional research is needed to study the effectiveness of this intervention in a variety of acute rehabilitation settings. Clinical Relevance: Rehabilitation leaders can implement low-cost teamwork interventions to improve interdisciplinary teamwork and patient outcomes.

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Li, Cheng-Rui Michael. „The Role of Tec Kinases in CD4⁺ T Cell Activation: A Dissertation“. eScholarship@UMMS, 2005. https://escholarship.umassmed.edu/gsbs_diss/3.

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The Tec family tyrosine kinases Itk, Tec and Rlk are expressed in T cells. Previous studies have established that these kinases are critical for TCR signaling, leading to the activation of PLCγ1. To further understand the functions of Tec kinases in T cell activation, we took three different approaches. First, we performed a thorough analysis of CD28-mediated signaling events and functional responses with purified naïve T cells from Itk-/- mice and a highly controlled stimulation system. Data from this set of studies definitively demonstrate that CD28 costimulation functions efficiently in naïve CD4+ T cells in the absence of Itk. Second, in order to further study the functions of Tec kinases in vivo, we generated transgenic mouse lines expressing a kinase-dead (KD) mutant of Tec on the Itk-/-Rlk-/- background, hoping to study mice that are functionally deficient for all three Tec kinases. The results hint the importance of the Tec kinases in T cell development and/or survival. Finally, in order to identify potential transcriptional targets of Itk, we used microarray technology to compare global gene expression profiles of naïve and stimulated Itk-/- versus Itk+/- CD4+ T cells. This analysis provided a short list of differentially expressed genes in Itk-/- versus Itk+/- CD4 T cells, providing a starting point for further studies of Itk in T cell activation. Collectively, these studies clarified the role of Itk in CD28 signaling, revealed some unexpected aspects of Tec family kinases in T cells, and indicated potential targets of Itk-dependent signaling pathways in T cells.

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Topham, Maren. „Parental Attitudes of Immunization in Children with Special Healthcare Needs: A Qualitative Study“. BYU ScholarsArchive, 2017. https://scholarsarchive.byu.edu/etd/7271.

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Background and Purpose: Just over 15% of children under 18 years of age in the UnitedStates, or approximately 11.2 million children, are estimated to have special healthcare needs.Although children with special healthcare needs (CSHCN) make up a small percentage of thepediatric population, they account for over one third of pediatric medical care. Parental attitudesregarding immunization play a significant role in vaccination rates among children. The purposeof this research is to explore parental attitudes regarding immunization of CSHCN.Methods: This qualitative study focused on parental perceptions and beliefs aboutimmunizations for CSHCN. Sixteen participants, who were parents of CSHCN from onepediatric specialty care clinic participated in focus groups. Institutional review board approvalwas received prior to data collection.Results: While the purpose of this study was to determine the attitudes of parents ofCSHCN regarding immunizations, analysis revealed parents simply wanted to share their lifeexperiences rearing these children, with issues of immunization being secondary. Participantsdescribed the experience of caring for their CSHCN related to isolationism and the weight ofresponsibility as leader of their child<'>s care. Additionally, the majority of parents thatparticipated viewed childhood vaccinations in a positive light. Parents acknowledged that it wasimportant for their own children to receive vaccines. Participants also recognized that it wasimportant for the community to be vaccinated in order to protect their child. However, the desirefor individualized care, at times, caused parents to disregard the immunization schedulerecommended by Center for Disease Control and Prevention.Conclusions: Health care providers can be effective and influential members of the healthcare team by engaging in community based education about vaccines, building trustingrelationships with parents and helping parents understand the need to follow the recommendedschedule for immunizations.

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Manoharan, Malini. „Genomic, structural and functional characterization of odorant binding proteins in olfaction of mosquitoes involved in infectious disease transmission“. Phd thesis, Université de la Réunion, 2011. http://tel.archives-ouvertes.fr/tel-00979587.

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The role of odorant binding proteins in the olfaction of mosquitoes, the primary mechanism of human host recognition, has been an important focus of biological research in the field of infectious disease transmission by these insects. This thesis provides an in depth knowledge of these proteins in three mosquito species Anopheles gambiae, Aedes aegypti and Culex quinquefasciatus. A large scale analysis on these genomes has been carried out towards the identification of the odorant binding proteins in the mosquito genomes. Identification of many new OBP members, in particular in the Aedes aegypti and Culex quinquefasciatus species, and an extensive phylogenetic analysis presenting a novel classification of the OBP subfamilies of these mosquito species has been proposed. This results further demonstrates the extraordinary multiplicity and diversity of the OBP gene repertoire in these three mosquito genomes and highlights the striking sequence features that are nevertheless highly conserved across all mosquito OBPs. Owing to the availability of homologous structures from mosquitoes or related species, the 3D structure modelling of all the Classic OBPs from the three genomes (representing in total 137 structures) has been performed. This was completed by large scale docking studies on these structures by screening a large set of compounds that are known to be mosquito attractants or repellents. These provide many exciting new insights into the structural and functional aspects towards understanding the efficacy of some repellents and of some attractants from human emanations. Through molecular dynamics simulation, the structural changes observed in an OBP bounded to an odorant when pH conditions are modified were characterized and the probable mechanism of ligand binding and release is presented. This work provides the first insights to many of the long awaited questions on the genomic, structural and functional characterization of mosquito OBPs and can be viewed as a reliable starting point for further experimental research focussed on these aspects.

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Vellaiswamy, Manohari. „Characterization of mechanisms involved in rickettsia pathogenicity“. Phd thesis, Université de la Méditerranée - Aix-Marseille II, 2011. http://tel.archives-ouvertes.fr/tel-00640585.

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Les rickettsies sont de petites bactéries à Gram-négatif associées à différentes espèces d'arthropodes. Leur nature intracellulaire stricte a longtemps été un obstacle à la compréhension des mécanismes moléculaires responsables de leur pathogénicité qui restent mal connus. L'adhésion bactérienne, qui est une étape clef de l'invasion des tissus de l'hôte, met en jeu les protéines rOmpA et rOmpB (rickettsial outer membrane proteins), identifiées depuis longtemps comme des antigènes de surface majeurs des rickettsies. L'objectif de cette thèse a été de caractériser une autre adhésine potentielle de Rickettsia prowazekii récemment identifiée, soit Adr2. La stratégie mise en œuvre a été basée sur la production d'anticorps monoclonaux spécifiques de cette protéine, dont une forme recombinante a été exprimée. Cet outil a permis, non seulement de localiser Adr2 à la surface des rickettsies, mais aussi d'apporter la preuve de son rôle dans le phénomène invasif puisque les anticorps anti-Adr2 diminuent significativement la cytotoxicité des rickettsies sur les cellules épithéliales. Un autre aspect de la pathogénicité que nous avons abordé concerne la mobilité des rickettsies du groupe boutonneux, fonction attribuée à la protéine RickA lorsque ce travail a été initié. La résolution des images obtenues par immunofluorescence, ou par microscopie électronique après marquage immunogold, montrent que l'expression de RickA est non-polarisée et répartie sur la surface entière de Rickettsia conorii. Enfin, plusieurs protéines recombinantes ont été utilisées dans des tests de screening sérologiques avec des sérums de patients infectés par diverses rickettsies, avec des résultats encourageants. L'ensemble de ces résultats contribue à une meilleure connaissance de la pathogénicité des bactéries du genre Rickettsia.

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Weisenberger, Kimberly R. „Tear Lipid Layer Thickness and Symptoms in Patients with Dry Eye Disease following the use of Emollient versus Non-Emollient Artificial Tears“. The Ohio State University, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=osu158694773242849.

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Loucoubar, Cheikh. „Statistical genetic analysis of infectious disease (malaria) phenotypes from a longitudinal study in a population with significant familial relationships“. Phd thesis, Université René Descartes - Paris V, 2012. http://tel.archives-ouvertes.fr/tel-00685104.

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Long term longitudinal surveys have the advantage to enable several sampling of the studied phenomena and then, with the repeated measures obtained, find a confirmed tendency. However, these long term surveys generate large epidemiological datasets including more sources of noise than normal datasets (e.g. one single measure per observation unit) and potential correlation in the measured values. Here, we studied data from a long-term epidemiological and genetic survey of malaria disease in two family-based cohorts in Senegal, followed for 19 years (1990-2008) in Dielmo and for 16 years (1993-2008) in Ndiop. The main objectives of this work were to take into account familial relationships, repeated measures as well as effect of covariates to measure both environmental and host genetic (heritability) impacts on the outcome of infection with the malaria parasite Plasmodium falciparum, and then use findings from such analyses for linkage and association studies. The outcome of interest was the occurrence of a P. falciparum malaria attack during each trimester (PFA). The two villages were studied independently; epidemiological analyses, estimation of heritability and individual effects were then performed in each village separately. Linkage and association analyses used family-based methods (based on the original Transmission Disequilibrium Test) known to be immune from population stratification problems. Then to increase sample size for linkage and association analyses, data from the two villages were used together.

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Seifert, Elena. „Metabolic Changes in Pulmonary Arterial Smooth Muscle Cells Exposed to Increased Mechanical Forces from an Ovine Model of Congenital Heart Disease with Increased Pulmonary Blood Flow“. Scholarship @ Claremont, 2019. https://scholarship.claremont.edu/cmc_theses/2094.

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An important cause of pulmonary arterial hypertension (PAH) in children with congenital heart disease (CHD) is increased pulmonary blood flow (PBF). To gain a better understanding of the disease process, the changes in biochemical pathways and metabolism of pulmonary arterial smooth muscle cells (PASMCs) were studied using a unique surgical ovine model of increased pulmonary blood flow. PASMCs isolated from 4-week-old lambs with increased PBF (shunt) showed lower oxygen consumption rates and lower extracellular acidification rates linked to glutamine metabolism when compared to controls. Shunt and control PASMCs both exhibited a switch into the reverse tricarboxylic acid (TCA) cycle, while only shunt cells showed a decrease of glucose being transformed into Acetyl CoA to enter the forward TCA cycle. Shunt PASMCs also demonstrated increased levels of yes-associated protein 1 (YAP1) expression in the nucleus. These results indicate changes in glutamine metabolism, glucose metabolism, and protein signaling cascades associated with increased mechanical forces in the setting of increased PBF, as seen in PAH in children with CHD.

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Samper, González Jorge Alberto. „Learning from multimodal data for classification and prediction of Alzheimer's disease“. Electronic Thesis or Diss., Sorbonne université, 2019. http://www.theses.fr/2019SORUS361.

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La maladie d’Alzheimer (MA) est la première cause de démence dans le monde, touchant plus de 20 millions de personnes. Son diagnostic précoce est essentiel pour assurer une prise en charge adéquate des patients ainsi que pour développer et tester de nouveaux traitements. La MA est une maladie complexe qui nécessite différentes mesures pour être caractérisée : tests cognitifs et cliniques, neuroimagerie, notamment l’imagerie par résonance magnétique (IRM) et la tomographie par émission de positons (TEP), génotypage, etc. Il y a un intérêt à explorer les capacités discriminatoires et prédictives à un stade précoce de ces différents marqueurs, qui reflètent différents aspects de la maladie et peuvent apporter des informations complémentaires. L’objectif de cette thèse de doctorat était d’évaluer le potentiel et d’intégrer différentes modalités à l’aide de méthodes d’apprentissage statistique, afin de classifier automatiquement les patients atteints de la MA et de prédire l’évolution de la maladie dès ses premiers stades. Plus précisément, nous visions à progresser vers une future application de ces approches à la pratique clinique. La thèse comprend trois études principales. La première porte sur le diagnostic différentiel entre différentes formes de démence à partir des données IRM. Cette étude a été réalisée à l’aide de données de routine clinique, ce qui a permis d’obtenir un scénario d’évaluation plus réaliste. La seconde propose un nouveau cadre pour l’évaluation reproductible des algorithmes de classification de la MA à partir des données IRM et TEP. En effet, bien que de nombreuses approches aient été proposées dans la littérature pour la classification de la MA, elles sont difficiles à comparer et à reproduire. La troisième partie est consacrée à la prédiction de l’évolution de la maladie d’Alzheimer chez les patients atteints de troubles cognitifs légers par l’intégration de données multimodales, notamment l’IRM, la TEP, des évaluations cliniques et cognitives, et le génotypage. En particulier, nous avons systématiquement évalué la valeur ajoutée de la neuroimagerie par rapport aux seules données cliniques/cognitives. Comme la neuroimagerie est plus coûteuse et moins répandue, il est important de justifier son utilisation dans les algorithmes de classification
Alzheimer's disease (AD) is the first cause of dementia worldwide, affecting over 20 million people. Its diagnosis at an early stage is essential to ensure a proper care of patients, and to develop and test novel treatments. AD is a complex disease that has to be characterized by the use of different measurements: cognitive and clinical tests, neuroimaging including magnetic resonance imaging (MRI) and positron emission tomography (PET), genotyping, etc. There is an interest in exploring the discriminative and predictive capabilities of these diverse markers, which reflect different aspects of the disease and potentially carry complementary information, from an early stage of the disease. The objective of this PhD thesis was thus to assess the potential and to integrate multiple modalities using machine learning methods, in order to automatically classify patients with AD and predict the development of the disease from the earliest stages. More specifically, we aimed to make progress toward the translation of such approaches toward clinical practice. The thesis comprises three main studies. The first one tackles the differential diagnosis between different forms of dementia from MRI data. This study was performed using clinical routine data, thereby providing a more realistic evaluation scenario. The second one proposes a new framework for reproducible evaluation of AD classification algorithms from MRI and PET data. Indeed, while numerous approaches have been proposed for AD classification in the literature, they are difficult to compare and to reproduce. The third part is devoted to the prediction of progression to AD in patients with mild cognitive impairment through the integration of multimodal data, including MRI, PET, clinical/cognitive evaluations and genotyping. In particular, we systematically assessed the added value of neuroimaging over clinical/cognitive data only. Since neuroimaging is more expensive and less widely available, this is important to justify its use as input of classification algorithms

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Tims, Steve. „A redemptive ministry to a family living with AIDS a project to recruit, train, and implement a care team in an effort to minister to a person living with AIDS and his family in the Wilshire Park Baptist Church /“. Online full text .pdf document, available to Fuller patrons only, 2000. http://www.tren.com.

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Yates, Martin T. „Effect of ESC/EACTS guidelines on myocardial revascularisation on heart team discussion of patients with severe coronary artery disease in the United Kingdom“. Thesis, St George's, University of London, 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.675936.

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Joint European Society of Cardiology and European Association for Cardiothoracic Surgery (ESC/EACTS) Guidelines on Myocardial Revascularisation advocate Heart Team discussion of all patients with severe coronary artery disease. Furthermore, incomplete revascularisation is known to increase morbidity and mortality following intervention. The guidelines suggest that patients with left main stem, proximal LAD or three vessel disease (3VD) should be discussed with a surgeon prior to percutaneous coronary intervention (PCI). The aim of this project is to assess the impact of the guidelines on referral patterns to the Heart Team and myocardial revascularisation outcomes in the United Kingdom. Methods All patients undergoing revascularisation at three major cardiothoracic centres in London were studied. Patients undergoing PCI were identified from the British Cardiovascular Intervention Society Database. Data was collected prospectively from January to June 2010, prior to the guidelines and January to June 2012 following its publication. Heart team discussion or direct referral for surgery, for all patients with surgical disease, was determined from database and electronic patient records. Primary outcomes were Heart Team discussion and method of revascularisation. Results In 2010, 621 patients underwent elective PCI before the guidelines, of which 224 had potentially surgical disease. Of these, only 37 (15%) were discussed by the Heart Team prior to intervention. Furthermore, 41 (18%) of patients had three vessel coronary disease and only 10 (25%) of these were discussed. In 2012, following introduction of the guidelines, 686 elective PCI were performed, of which 272 had surgical disease. Again only 47 (17%) were discussed by the Heart Team prior to intervention (p = NS). Similarly, 43 (16%) had three vessel disease and only 16 (37%) were discussed. Of those patients undergoing elective PCl for severe coronary disease in 2010, only 98 (44%) were fully revascularised. In 2012, 133 (48%) received complete revascularisation. However, of those with 3VD, in 2010 only 7 (17%) were fully revascularised. Similarly, in 2012 only 4 (11 %) received full revascularisation. Conclusion Despite joint ESC/EACTS guidelines and attention given to this subject by the professional bodies, a significant number of patients with severe coronary artery disease who would clearly benefit from surgical revascularization are not being discussed by the Heart Team and receiving optimal treatment.

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Dissertationen zum Thema „Diseases of Tea“

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