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1
Martínez, Gutiérrez Alfredo. "Regulation of Sirtuin-dependent skin cell Senescence by dermatology-associated compounds." Doctoral thesis, Universitat de Barcelona, 2019. http://hdl.handle.net/10803/668801.
Full textAbstract:
One of the main causal factors of skin aging is ultraviolet radiation as part of sun exposure. This radiation induces many changes at the molecular level that alter the proper function of skin biological processes, being cellular senescence one characteristic process included in this group. Senescence is a cellular state in which the cells enters an irreversible cell cycle arrest and develops a proinflammatory phenotype that contributes to tissue damage and aging. In this context, the aim of this thesis was to find compounds that both activate sirtuins and protect against UV-induced cellular senescence in human dermal fibroblasts. Among the 30 compounds tested, 8 compounds induced sirtuin activation, while 2 compounds protected against UV-induced senescence. Only one of these compounds had positive effects on both processes. Further charaterization of the compound revealed that the protection exerted by this compound against cellular senescence was mediated by SIRT1 activation. Besides, we observed that this compound activates autophagy, one of the stress response pathways of the cell linked to increased longevity and regulated by SIRT1, among other factors. In conclusion, the caracterized compound has proven to be a good candidate as skin anti aging compound through its action on autophagy, sirtuins and senescence.Uno de los principales factores causantes del envejecimiento de la piel es la radiación ultravioleta procedente del sol. Esta radiación induce una serie de cambios que alteran la correcta función biológica de la piel, entre los que destaca la senescencia celular, un proceso en el cual las células dejan de proliferar y desarrollan un fenotipo inflamatorio que incrementa el daño en el tejido. En este contexto, el objetivo de esta tesis era encontrar compuestos que fueran capaces de activar las sirtuínas y de proteger frente a la senescencia inducida por daño ultravioleta en fibroblastos de piel humana. Del total de 30 compuestos testados, 8 fueron capaces de inducir la activación de las sirtuínas, mientras que 2 fueron capaces de proteger frente a la senescencia inducida por ultravioleta. De todos estos compuestos, sólo uno fue capaz de tener un efecto positivo en ambos procesos. En posteriores ensayos para caracterizar la acción de este compuesto, observamos que la protección del éste frente a la senescencia inducida por ultravioleta era mediada por SIRT1. Además, observamos que este compuesto era capaz de activar la autofagia en estas células, una de las respuestas a estrés en la célula que promueve la longevidad celular y esta controlada por SIRT1, entre otros factores. En conclusión, el compuesto caracterizado ha demostrado ser un buen candidato para su uso en la prevención del envejecimiento de la piel a través de su acción sobre sirtuínas, autofagia y protección de la senescencia.
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Azzarello, Lora M. "Psychological Factors Associated with Skin Cancer Detection Behaviors in Individuals with a Family History of Melanoma." [Tampa, Fla.] : University of South Florida, 2003. http://purl.fcla.edu/fcla/etd/SFE0000174.
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Al-Myouf, Abdullah Abdulaziz. "Cadherins, catenins and associated proteins in normal epidermis, basal cell carcinoma and other cutaneous tumours : an immunohistochemical study." Thesis, University of Glasgow, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.341723.
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West, Julie Ann. "Factors Associated With Tuberculin Skin Test Positivity Prevalence in U.S. Medical Laboratory Microbiologists." Thesis, Walden University, 2014. http://pqdtopen.proquest.com/#viewpdf?dispub=3607454.
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Prior research has indicated that healthcare personnel (HCP) who work in areas where Mycobacterium tuberculosis poses an occupational hazard are at high risk of tuberculin skin test (TST) positivity and subsequent conversion to active tuberculosis (TB). U.S. medical laboratory microbiologists confront similar hazards but have not been studied outside of the HCP aggregate. The purpose of this study was to fill this gap by examining the relationships between the predictor variables of self-reported history of bacille Calmette-Guérin (BCG) immunization, place of birth, and years of laboratory experience and the outcomes of self-reported lifetime TST positivity, preventive treatment noninitiation, and barriers to treatment adherence for this subgroup. This quantitative, cross-sectional study was guided by the epidemiologic triad model. A researcher-designed self-administered questionnaire including Part A of the Brief Medication Questionnaire was mailed to 4,335 U.S. microbiologist members of the American Society for Clinical Pathology. From the 1,628 eligible respondents, results showed that prevalence of positive TSTs (17.0%) and treatment noninitiation (9.8%) was low. Multivariate analysis identified BCG and foreign birth, as well as age, nonoccupational exposure, history of TB, work in mycobacteriology, and work outside of microbiology as predictors of a positive TST; foreign birth was a predictor of treatment noninitiation. Additional research is needed to identify other laboratorian groups at increased risk for developing TB. These results enhance positive social change by helping to inform recommendations in the global fight to stop the spread of TB, as well as improve allocation of resources among this specific group of HCP.
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Wu, Ling. "A HYPER TH17 RESPONSE CONNECTS THE PSORIASIS-ASSOCIATED ACT1 VARIANT TO SKIN INFLAMMATION." Case Western Reserve University School of Graduate Studies / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=case1409866338.
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Large, Juliette. "Characterisation of Staphylococci associated with atopic eczema and chronic plaque psoriasis." Thesis, Aston University, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.341358.
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Arnold, Long Mary Caroleen. "Building Expert Consensus on Including Indicators of Moisture-Associated Skin Damagein The National Database of Nursing Quality Indicators (NDNQI)." Otterbein University / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=otbn1461076119.
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Tawadros, Fady, Sakshi Singal, Maria Zayko, and Devapiran Jaishankar. "Mucosal Associated Lymphoid tissue of the Skin, A Common Entity in a Rare Location." Digital Commons @ East Tennessee State University, 2019. https://dc.etsu.edu/asrf/2019/schedule/55.
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Marginal zone (MZ) lymphomas (MZLs) represent a group of lymphomas originating from B lymphocytes of the “marginal zone” which is the external part of the secondary lymphoid follicles. The WHO classifies MZL into 3 entities; extranodal MZL, splenic MZL and nodal MZL. Extranodal marginal zone lymphoma (EMZL) can arise in different tissues, including the stomach, salivary gland, lung, small bowel, thyroid, ocular adnexa and skin. We present a 25 years old female with a history of angioedema and chronic cutaneous eczema who developed an unusual EMZL. Patient presented with a history of rapidly enlarging skin nodule on her left elbow that had been present for almost one year. Over a period of 2-3 weeks she felt the nodule rapidly changed in size and shape. Excisional biopsy of the mass revealed a lymphoid infiltrate based in the reticular dermis and focally extending into the subcutaneous adipose tissue with formation of disrupted lymphoid follicles positive for CD20, CD23 and BCL2 but negative for CD10, Cyclin D1 and SOX11. Diagnosis was consistent with extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). Patient on presentation did not have any B symptoms other cutaneous lesions, lymphadenopathy or hepatosplenomegaly. PET scan revealed no evidence of abnormal uptake leading to a final Stage IE definition. Patient initiated definitive radiation therapy. EMZL accounts for 5 -10 % of non-Hodgkin lymphoma. It has been described often in organs that are normally devoid of germinal centers. It may arise in reactive lymphoid tissue induced by chronic inflammation in extranodal sites. Primary cutaneous marginal zone lymphoma (PCMZL) is associated with infectious etiologies such as Borrelia burgdorferi and less commonly with viral infections or in relation to autoimmune disorders. Autoimmune disorders, specifically Sjögren's syndrome is associated with a 30-fold increased risk of marginal zone lymphoma. Localized disease can be treated by local radiotherapy, intralesional injections or excision. Widespread skin disease is usually treated with a CD20 directed monoclonal antibody-Rituximab. Patients with PCMZL usually have an indolent clinical course. Extracutaneous dissemination of MALT Lymphoma is uncommon and happens in 6-8 % of patients. The 5 years overall survival is between 98-100%. Family physicians and dermatologists should have a high index of suspicion for this rare lymphoma subtype especially in patients with inflammatory chronic skin conditions and atopy.
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Medina, Lopez Daniel Christofer. "Assessing Diversity, Culturability and Context-dependent Function of the Amphibian Skin Microbiome." Diss., Virginia Tech, 2018. http://hdl.handle.net/10919/84855.
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Emergent infectious diseases are a major driver of the accelerated rates of biodiversity loss that are being documented around the world. Global losses of amphibians provide evidence of this, especially those associated with chytridiomycosis, a lethal skin disease caused by the fungus Batrachochytrium dendrobatidis (Bd). Amphibian skin can harbor diverse bacterial communities that, in some cases, can inhibit the growth of Bd. Thus, there is interest in using skin bacteria as probiotics to mitigate Bd infections in amphibians. However, experiments testing this conservation approach have yielded mixed results, suggesting a lack of understanding about the ecology of these microbial communities. My dissertation research aimed to assess basic ecological questions in microbial ecology and to contribute to the development of probiotics using amphibian skin bacteria. First, to assess whether environmental conditions influence the function of amphibian skin bacterial communities, I conducted a field survey across low and high elevation populations of an amphibian host to assess their skin bacterial communities and metabolite profiles. I found that similar bacterial communities produced different metabolites at different locations, implying a potential functional plasticity. Second, since culturing is critical for characterizing bacteria, I aimed to identify the culture media (low vs high nutrient concentration) that recovers the most representative fraction of the amphibian skin bacterial community. I found that media with low nutrient concentrations cultured a higher diversity and recovered a more representative fraction of the diversity occurring on amphibian skin. I also determined that sampling more individuals is critical to maximize culture collections. Third, I assessed the diversity of the amphibian skin fungal community in relation to Bd infection across eight amphibian species. I determined that amphibian species was the most important predictor of fungal diversity and community structure, and that Bd infection did not have a strong impact. My dissertation highlights the importance of environmental conditions in the function of amphibian skin bacteria, expands our knowledge of the understudied fungal component of the amphibian skin microbiome, and complements current efforts in amphibian conservation.Ph. D.
In light of the global losses of amphibian diversity due to, in part, the skin disease chytridiomycosis (caused by the fungus Batrachochytrium dendrobatidis [Bd]); the discovery that some amphibian-skin bacteria can inhibit Bd growth provides hope for amphibian conservation via their use as probiotics to control Bd infections. However, experiments testing these bacteria have yielded inconsistent results, suggesting a limited understanding about the factors influencing the diversity of amphibian-skin microbes and their ability to inhibit Bd. Also, efforts to identify effective candidates for probiotic therapy are still premature. Thus, my dissertation had an ecological emphasis and focused on complementing conservation efforts focused on probiotics. First, I assessed whether environmental conditions influence bacteriallyproduced products, which can have antifungal properties. Specifically, I surveyed low and highelevation populations of an amphibian species to assess the skin-bacteria and their products. I determined that, while skin bacterial communities were similar across an environmental gradient, their products differed, suggesting potential different antifungal properties. Second, I assessed the ability of different culture media types (low vs high nutrient concentrations) to grow a high portion and most representative fraction of the amphibian-skin bacteria. I found that culture media with low nutrient concentrations allowed the growth of a higher diversity of the bacteria occurring on the amphibian-skin, including the abundant members, and also determined that including a large number of amphibians is the best way to improve culture collections. Third, I assessed the fungal diversity occurring in the skin of different amphibian species and how it might response to Bd infections, and examined whether skin-fungi interact with co-occurring bacteria. I found that the amphibian species was the most important driver of the fungal diversity, and that Bd infection did not influence the diversity of these communities. Moreover, I identified the most diverse fungal phyla occurring in the amphibian-skin and determined that these fungi might interact with co-occurring bacteria. My dissertation contributes to our understanding about the influence of the environmental conditions in the amphibian-skin bacteria, expands our limited knowledge on the amphibian-skin fungi, and complement current amphibian conservation efforts.
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Wax, Noah David. "Comparative genomics of bacteria from amphibian skin associated with inhibition of an amphibian fungal pathogen Batrachochytrium dendrobatidis." Thesis, Virginia Tech, 2021. http://hdl.handle.net/10919/103961.
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Chytridiomycosis is a fungal skin disease in amphibians that is primarily caused by Batrachochytrium dendrobatidis (Bd). We analyzed whole genome sequences of 40 bacterial isolates that had been previously cultured from the skin of four amphibian species from Virginia, USA, and tested for their ability to inhibit Bd growth via an in vitro challenge assay. These 40 isolates spanned 11 families and 13 genera. The aim of this study was to identify genomic differences among the amphibian skin bacterial isolates and generate hypotheses about possible differences that could contribute to variation in their ability to inhibit the growth of Bd. We identified sixty-five gene families that were present in all 40 isolates. We also looked for the presence of biosynthetic gene clusters. While this set of isolates contained a wide variety of biosynthetic gene clusters, the two most abundant clusters with potential anti-fungal activity were siderophores (N=17) and Type III polyketide synthases (N=20). We then analyzed the isolates belonging to the phylum Proteobacteria in more detail. We identified 197 gene families that were present in all 22 Proteobacteria. We examined various subsets of the Proteobacteria for genes for specific compounds with known activity against fungi, including chitinase and violacein. We identified a difference in the number, as well as amino acid sequences, of predicted chitinases found in two isolates belonging to the genus Agrobacterium that varied in their inhibition of Bd. After examining the annotated genomes, we identified a predicted chitinase in a Sphingomonas isolate that inhibited the growth of Bd that was absent from the five Sphingomonas isolates that did not inhibit Bd growth. The genes vioA, vioB, vioC, vioD and vioE are necessary to produce violacein, a compound which inhibits the growth of Bd. Differences in these genes were identified in three out of the four Janthinobacterium isolates. Of these three isolates, two showed strong inhibition of Bd growth, while the third inhibited Bd growth to a lesser extent. Using comparative genomics, we generated several testable hypotheses about differences among bacterial isolates that could contribute to variation in ability to inhibit Bd growth. Further work is necessary to test the various mechanisms utilized by amphibian skin bacterial isolates to inhibit Bd.Master of Science
Many amphibian population declines around the world have been caused by chytridiomycosis, a skin disease. This disease is caused by the fungus Batrachochytrium dendrobatidis (Bd). The skin of amphibians is also home to many bacteria that can provide important functions for the amphibian host, like preventing infection by Bd. To understand how these bacteria might provide protection, we examined the entire genomes of 40 bacterial isolates that reside on the skin of four amphibian species from Virginia, USA. These bacteria were previously tested for their ability to prevent Bd growth and 40 of them were chosen for sequencing based on selecting closely related isolates that varied in their ability to inhibit Bd growth. This allowed us to compare their genomes and generate hypotheses about possible genomic differences that could contribute to the variation in Bd growth inhibition. We identified sixty-five gene families that were present in all 40 bacteria. We also looked for sets of genes (biosynthetic gene clusters) that are known to produce secondary metabolites, which are compounds that can include antifungals. The two most abundant clusters we identified that had the potential to produce compounds that inhibit fungal growth were siderophores and Type III polyketide synthases. We then looked for genes that were not part of biosynthetic gene clusters that could produce specific compounds that can inhibit Bd growth, such as chitinase and violacein. We found variation in chitinase genes in several isolates that seemed to be associated with the ability to inhibit Bd growth. In addition, there were some differences in violacein genes that should be examined more in future studies. Overall, we suggest that using comparative genomic approaches can be valuable for identifying key bacterial functions in the microbiome.
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Ita, Kevin Bassey. "Skin delivery of selected hydrophilic drugs used in the treatment of skin diseases associated with HIV/AIDS by using elastic liposomes / Kevin Bassey Ita." Thesis, North-West University, 2003. http://hdl.handle.net/10394/302.
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Due to the immuncompromised status of AIDS patients, secondary infections and
malignancies are common. Conditions secondary to AIDS for which patients require
treatment include Karposi's sarcoma (treated with methotrexate), varicella-zoster (treated
with antivirals such as acyclovir) and herpes simplex (also treated with antivirals like
acyclovir or idoxuridme). However the clinical efficacy of these drugs is limited by poor
skin permeability.
Few reports, however, have dealt with the delivery of low molecular weight hydrophilic
drugs from these vesicles (El Maghraby et al, 2000). The aim of our study was to
investigate in vitro permeation of methotrexate, acyclovir and idoxuridine across human
epidermal membrane from elastic liposomes. The intent was to establish whether
formulation of these hydrophilic drugs into elastic liposomes would enhance their skin
permeation parameters.
We developed and validated high-performance liquid chromatographic techniques for
quantitative analysis of methotrexate, idoxuridine and acyclovir. Elastic liposomes were
prepared from various phospholipids- phosphatidylcholine 78.6%; phosphatidylcholine
50%; hydrogenated phosphatidylcholine 90%; phosphatidylcholine 95% and surfactants -
sodium cholate, sodium deoxycholate, Span 20, 40, 60, 80. These vesicles were
characterised by transmission electron microscopy. The solubilities of methotrexate,
acyclovir and idoxuridine were determined. Phospholipon G (95% phosphatidylcholine)
was chosen for the preparation of the liposomes with different surfactants. Permeation of
methotrexate, acyclovir and idoxuridme from these vesicles across human epidermal
membrane was investigated.
Flux values for methotrexate, acyclovir and idoxuridine values (J) obtained by curve-fitting
of data using Easyplot were compared to those obtained by linear regression. We
used Student's t-test to determine statistically significant differences in the flux values of
the formulations. A computer program http://www.physics.csbsju.edu/stats/ttest-
bulk-form.html was used for this purpose. Our results indicate that there are no
statistically significant differences between flux values from elastic liposomes and
saturated aqueous solutions.Thesis (Ph.D. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2004.
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Abreu, Marcelle Silva de. "Pioglitazone dosage forms for the treatment of inflammation associated with skin, ocular and neurodegenerative diseases." Doctoral thesis, Universitat de Barcelona, 2018. http://hdl.handle.net/10803/650877.
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La pioglitazona (PGZ) es un agonista del peroxisoma proliferador activado del receptor gamma (PPARγ) receptor, pertenece a la clase de las tiazolidindionas y es usado para el tratamiento de la diabetes tipo 2. Muchos estudios han reportado el uso de este fármaco con diferentes funciones, tales como: antiinflamatoria, antiangiogénica, antifibrótica, antitumoral y neuroprotectora. Además, este fármaco ha sido investigado debido a su capacidad de reducir la respuesta inflamatoria por diferentes mecanismos. Con el fin de obtener formulaciones apropiadas de PGZ que mejoren su liberación, esta tesis tuvo como principal objetivo el desarrollo y la caracterización de formas de dosificación de PGZ (nanopartículas (NPs) poliméricas de PLGA-PEG y formulaciones líquidas) capaces de reducir la inflamación asociada con enfermedades dérmicas (rosácea), oculares (uveítis) y neurodegenerativas (Alzheimer). Estos sistemas fueron optimizados y caracterizados fisicoquímicamente, analizando las interacciones fármaco-vehículo por métodos espectroscópicos y térmicos. Estudios de estabilidades fueron llevados a cabo durante 3 meses. Se estudió también la liberación in vitro, la permeación ex vivo en diferentes membranas biológicas, la tolerancia y la distribución del fármaco en los diferentes tejidos. Asimismo, estudios de toxicidad se realizaron en líneas celulares de queratinocitos (HaCat), retinoblastoma (Y-79) y células endoteliales del cerebro (hCMEC/D3). Estudios de internalización, transporte y permeabilidad de las NPs-PGZ fueron llevados a cabo en hCMEC/D3. Para finalizar se evaluó también la eficacia terapéutica in vivo de las formulaciones desarrolladas para rosácea, uveítis y Alzheimer.
Las NPs-PGZ mostraron un tamaño promedio de partícula menor a 200 nm, una polidispersión aproximada de 0.1, carga superficial de -13.6 mV y una eficiencia de asociación en torno al 92 %. Los estudios de interacción fármaco-vehículo confirmaron que la PGZ fue encapsulada en la matriz polimérica. Las formas farmacéuticas fueron estables 3 meses, con un perfil reológico newtoniano. Los estudios de liberación de las formulaciones mostraron perfiles cinéticos de primer orden e hiperbólico. En los ensayos de permeación en la piel, la solución de PGZ con un promotor fue capaz de penetrar en la piel con altos valores para flujo (Jss), cantidad retenida del fármaco (Qret) y concentraciones predichas en estado de equilibrio estacionario (Css). Además, en los estudios de permeación en las distintas mucosas (bucal, sublingual, nasal e intestinal), dependiendo de la forma farmacéutica y en base a los resultados de Css, ha sido posible predecir que pueden proporcionar un efecto farmacológico sistémico tanto a nivel de la mucosa nasal como de la intestinal. Por otro lado, en el ojo la PGZ a partir de las NPs mostró altas concentraciones permeadas a través de la esclera. Los ensayos de tolerancia in vivo (Draize test) indicaron que la solución de PGZ no producía daño en la piel. Además, las NPs-PGZ no indujeron ninguna irritación a nivel ocular tanto in vivo como in vitro por el (HET CAM test). También las fórmulas fueron testadas mostrando no toxicidad a las concentraciones determinadas en las diferentes líneas celulares. Las NPs fueron capaces de internalizar, atravesar y no alterar la permeabilidad en un modelo in vitro de la barrera hematoencefálica con las células hCMEC/D3. Con respecto a la eficacia terapéutica de las formulaciones: la solución de PGZ disminuyó notablemente los niveles de eritema después de la inducción de la inflamación en las espaldas de los ratones BALB/c en todos los intervalos de tiempos analizados, corroborado por estudios histológicos. En los estudios de eficacia ocular en cerdos, las NPs-PGZ fueron capaces de prevenir la inflamación ocular después de la inducción de la inflamación con araquidonato sódico. Las NPs-PGZ también fueron testadas (in vivo) en un modelo de ratón transgénico con la enfermedad del Alzheimer y los resultados mostraron que las NPs fueron capaces de reducir el déficit de memoria cuando se comparan con el vehículo. Además, mostró clara tendencia a reducir las placas de la proteína beta amiloide. En resumen, las formulaciones de PGZ desarrolladas podrían constituir en un futuro, después de ensayos clínicos, una nueva indicación terapéutica para este fármaco.
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Harwood, Catherine Anne. "Human papillomavirus and the molecular pathogenesis of non-melanoma skin cancer associated with organ transplantation." Thesis, Queen Mary, University of London, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.407957.
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Chan, Pui-yan, and 陳培欣. "An evidence-based guideline of skin care management for older adults with incontinence-associated dermatitis." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/193038.
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Background Incontinence-associated dermatitis (IAD) is a common and preventable condition in older adults with incontinence. People suffering from IAD are usually disdained by individuals, professionals, policy makers, caregivers, and communities. To date, a standard guideline on IAD management is still lacking in Hong Kong. Thus, it is important to develop an evidence-based incontinence-associated guideline for older adults with incontinence in Hong Kong.
Objectives This thesis aims to identify the best available evidence for skin care management for people suffering from IAD and to develop an evidence-based practice guideline to reduce the incidence of IAD.
Methods
Review of literature related to the management of IAD was performed on electronic database according to the inclusion and exclusion criteria. The inclusion criteria included randomized controlled trials and quasi-experiments. In addition, the studies should be in English and should contain the full text. The target participants should be patients aged 60 or above who are suffering from urinary, fecal, or double incontinence and are using diapers. Participants should include cognitively impaired patients, as well as those experiencing skin redness or injury at the perineal or thigh area resulting from incontinence. All non-medical regimens, skin care products, and absorbent diapers or pads designed for managing incontinence related to skin breakdown in older adults with incontinence were also included. The quality of the literatures was assessed according to the checklist provided by the Scottish Intercollegiate Guidelines Network (SIGN) (2011), and the data obtained from the reviewed papers were extracted and summarized in eight tables of evidence. Then, an IAD skin care management guideline was developed based on these pieces of evidence. The transferability, the feasibility, and the cost-benefit ratio of implementing the proposed IAD skin care management guideline were assessed. In addition, the communication plan, the evaluation plan, and the pilot study of the proposed guideline were included in this thesis.
Results The proposed IAD skin care management guideline is a structured skin care management program for older adults with incontinence. With the help of the proposed guideline, registered nurses could provide a standard IAD skin care program based on best available evidence. Moreover, reviewed studies show that the IAD severity score, which is used to evaluate the prevalence of IAD, can be reduced by 47 % by implementing the proposed guideline.
In addition, a systematic communication plan with stakeholders, an evaluation plan, and a pilot study were designed to examine the feasibility and the transferability of the proposed guideline. Patient outcome is the main outcome measure, and this measure is directly related to the IAD severity score. In this study, the IAD severity score was reduced, indicating that the proposed IAD skin care management program is effective, feasible, and cost-effective in the local setting.
Conclusion The proposed skin care management guideline for caring for older adults with IAD was developed based on best available evidence. The prevalence of IAD is expected to be reduced after the implementation of this guideline.published_or_final_version
Nursing Studies
Master
Master of Nursing
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Yamakawa, Noriyuki. "A Clinical, Pathological and Genetic Characterization of Methotrexate-Associated Lymphoproliferative Disorders." Kyoto University, 2014. http://hdl.handle.net/2433/188632.
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Clifton, Walter Scott. "Ways to Skin the Zombie Cat: A Look at the Problems Associated with Chalmers's Zombie-Argument." Digital Archive @ GSU, 2006. http://digitalarchive.gsu.edu/philosophy_theses/3.
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In contemporary philosophy of mind, the issue of consciousness has taken center stage. Broadly speaking, those who deal with consciousness fall into two camps: those who prioritize empirical work and those who favor conceptual investigation. One prominent argument has served to deepen the divide: the argument for the possibility of zombies. In this paper I intend to examine closely this argument, as it’s presented by David Chalmers, and some of the attempts to discredit it. In so doing, I present some of my own arguments against it, as well as the claim that if it’s sound, then materialism is false. Finally, I present a sketch of a new way of thinking about consciousness that would, I argue, guard against the threat—real or merely apparent—of arguments such as the zombie-argument.
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Felicetti, David Andrew. "Apple (Malus domestica borkh.) fruit skin disorders and changes in pigment concentrations associated with the disorders." Online access for everyone, 2007. http://www.dissertations.wsu.edu/Dissertations/Spring2007/d_felicetti_041807.pdf.
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Clifton, Walter Scott. "Ways to skin the zombie cat a look at the problems associated with Chalmers's zombie-argument /." unrestricted, 2005. http://etd.gsu.edu/theses/available/etd-11282005-152528/.
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Thesis (M.A.)--Georgia State University, 2005.Title from title screen. Reina Hayaki, committee chair; George Rainbolt, Robert Almeder, committee members. Electronic text (69 p.) : digital, PDF file. Description based on contents viewed May 9, 2007. Includes bibliographical references (p. 68-69).
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Estrada, Lopez Angie Carole. "Understanding the temporal variability of skin-associated bacterial communities for the conservation of threatened amphibian species." Diss., Virginia Tech, 2019. http://hdl.handle.net/10919/95987.
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Amphibians harbor beneficial skin bacteria that can contribute to host defense against chytridiomycosis, an infectious disease caused by the lethal fungal pathogen Batrachochytrium dendrobatidis (Bd). However, while skin-associated microbial communities may alter host infection risk, the structure of these complex microbial communities can be impacted by both biotic and abiotic factors. In a series of three studies, I investigated the natural temporal and spatial variation in bacterial communities on the skin of wild and captive-born amphibians using 16S rRNA gene amplicon sequencing to characterize bacterial community diversity. First, in a study examining the skin bacterial communities of two sympatric treefrog species (Agalychnis callidryas and Dendropsophus ebraccatus) at a single pond over multiple seasons and years, I found that annual, seasonal, and even daily fluctuations in temperature and rainfall changed the skin bacterial communities on these species. Second, I further investigated the impact of seasonality and rainfall on amphibian skin bacterial communities with a study of the bacterial communities on Craugastor fitzingeri, a common terrestrial species, along a rainfall gradient, and five co-occurring amphibian species at a single site. The strong wet and dry seasonality in the tropical lowland forest impacted the bacterial communities of multiple stream-dwelling co-occurring species, but the nature of the changes differed among the frog species. For C. fitzingeri sampled along the rainfall gradient, I found there was variation in bacterial community structure among sites, although this was not correlated with the latitudinal rainfall gradient. Finally, I investigated the challenges faced by captive-reared Atelopus limosus, an endangered amphibian species, after soft-release into natural habitat with the use of mesocosms. I found that the skin bacterial communities reverted to wild-type fairly quickly, body condition decreased to come closer to wild conspecifics, and 15% of the frogs became infected with Bd during the 27 day trial in mesocosms. Overall, I found that skin bacterial communities of lowland amphibians change across time and space, that variation sometimes correlates with environmental conditions at the time and the site of sampling, and that skin bacterial communities on captive-born frogs revert to wild-frog's state soon after soft-release to natural habitat.Doctor of Philosophy
Beneficial bacteria found on amphibian skin can provide protection against an infectious disease caused by the lethal amphibian chytrid fungus (Batrachochytrium dendrobatidis), that has been linked with the decline and extinction of amphibian species worldwide. However, while skin bacterial communities may play a key role in determining disease outcome, these complex microbial communities can be impacted by biological and environmental factors. In a series of three studies, I investigated the natural variation in skin bacterial communities on wild and captive-born amphibians through time and space using modern DNA sequencing technologies to characterize bacterial community diversity. First, in a study examining the skin bacterial communities of two treefrog species at a single pond over multiple years and seasons, I found that annual, seasonal, and even daily fluctuations in temperature and rainfall changed the skin bacterial communities on these species. Second, I further investigated the impact of seasonality and rainfall with a study sampling the skin of one common frog species along a rainfall gradient, and five amphibian species at a single site across seasons. The strong wet and dry seasonality in the tropical lowland forest impacted the bacterial communities of multiple species found near streams, but the nature of the changes differed among the different frogs. For the common species sampled along the rainfall gradient, I found there was variation in bacterial community structure among sites, although this was not correlated with the rainfall gradient. Finally, I investigated the challenges faced by captive-reared Atelopus limosus, an endangered amphibian species from Panama, after release into field enclosures in the natural habitat. I found that the skin bacterial communities reverted to wild-type fairly quickly, body mass decreased to come closer to wild frogs of the same species, and 15% of the frogs became infected with the chytrid fungus during the 27 day trial in the field enclosures. Overall, I found that skin bacterial communities of lowland amphibians change across time and space, that variation is sometimes linked with environmental conditions at the time and site of sampling, and that captive-born frogs revert to wild states soon after release to natural habitat.
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Salmon, Hillbertz Nicolette. "The origin of the ridge and associated anomalies in Rhodesian Ridgebacks /." Uppsala : Dept. of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, 2007. http://epsilon.slu.se/2007133.pdf.
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Strüver, Kay [Verfasser], and Wolfgang [Akademischer Betreuer] Frieß. "Development and characterization of in-vitro models for filaggrin associated skin diseases / Kay Strüver ; Betreuer: Wolfgang Frieß." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2018. http://d-nb.info/1172634173/34.
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Kahn, Julie. "Biomechanics of Patient Handling Slings Associated with Spinal Cord Injuries." Scholar Commons, 2013. http://scholarcommons.usf.edu/etd/4702.
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Pressure ulcers and related skin integrity threats are a significant problem in current transfer/transport systems used for spinal cord injury patients. To understand this problem twenty-three different slings with varying type, material, and features were analyzed in hopes to identify at-risk areas for skin integrity threats such as pressure ulcers. Population samples included non-disabled (otherwise referred to as "healthy") volunteers as well as SCI patients from the James A. Haley Veterans Hospital. High resolution pressure interface mapping was utilized to directly measure the interface pressures between the patient and sling interface. Overall results provide relevant feedback on the systems used and to suggest a particular type of sling that might reduce and possibly minimize skin integrity threats as well as extend safe patient handling guidelines with sling use. It was found that the highest interface pressures convened along the seams of the sling, regardless of manufacturer or type.
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Walls, Joseph. "Can non-contact SIAscopy be used in the diagnosis and quantification of pigmentary skin changes associated with photodamage?" Thesis, University of East Anglia, 2012. https://ueaeprints.uea.ac.uk/42386/.
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Introduction: Non-contact SIAscopy is a new imaging technique where a standard polarised photographic image of the skin is decomposed to produce independent colour, blood and melanin images using SIAscopy (a form of reflectance spectroscopy). Photodamage is a product of the physiological changes caused by chronic sun exposure on the skin. Measuring the extent of photodamage has always been difficult, with most analysis requiring subjective user interpretation of results. No one available method appears better at clearly identifying and quantifying photodamage within the skin and no truly objective method exists which enables automatic measurement of these characteristics without expert evaluation. Methods and results: 1140 images of skin of various ages and levels of damage were acquired using standard digital colour photography obtained through crossed polarising filters. The sample was split into a model and test set and analysis algorithms were employed to quantify features including dyspigmentation, sallowness, erythema and vessel dilation. Relevant features were isolated and the relationship with age was determined using linear regression. From this a predictive skin photodamage age was generated and tested with a sample set of images. Conclusions: Specific pigmentary characteristic of photodamage can be identified and quantified using non-contact SIAscopy. It is an independent, repeatable, robust and inexpensive method of assessing the level of photodamage from a standard digital photograph and the results can be used to identify individuals most at risk of developing skin cancers.
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Hira, Akshay. "TIP60 regulation of DNp63a is associated with cisplatin resistance." Wright State University / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=wright1566585763492406.
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Pak, Fatemeh. "Development of AIDS associated and endemic Kaposi sarcoma: HHV-8/KSHV viral load in cutaneous and oral tumor cells." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-878-9/.
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Krynak, Katherine L. "ENVIRONMENTAL INFLUENCES ONAMPHIBIAN INNATE IMMUNE DEFENSE TRAITS." Case Western Reserve University School of Graduate Studies / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=case1435590530.
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Rapisarda, Valentina. "Mechanisms of epigenetic regulation in epidermal keratinocytes during skin development : role of p63 transcription factor in the establishment of lineage-specific gene expression programs in keratinocytes via regulation of nuclear envelope-associated genes and polycomb chromatin remodelling factors." Thesis, University of Bradford, 2014. http://hdl.handle.net/10454/7164.
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During tissues development multipotent progenitor cells establish tissue-specific gene expression programmes, leading to differentiation into specialized cell types. It has been previously shown that the transcription factor p63, a master regulator of skin development, controls the expression of adhesion molecules and essential cytoskeleton components. It has also been shown that p63 plays an important role in establishing distinct three-dimensional conformations in the Epidermal Differentiation Complex (EDC) locus (Fessing et al., 2011). Here we show that in p63-null mice about 32% of keratinocytes showed altered nuclear morphology. Alterations in the nuclear shape were accompanied by decreased expression of nuclear lamins (Lamin A/C and Lamin B1), proteins of the LINC complex (Sun-1, nesprin-2/3) and Plectin. Plectin links components of the nuclear envelope (nesprin-3) with cytoskeleton and ChIP-qPCR assay with adult epidermal keratinocytes showed p63 binding to the consensus binding sequences on Plectin 1c, Sun-1 and Nesprin-3 promoters. As a possible consequence of the altered expression of nuclear lamins and nuclear envelope-associated proteins, changes in heterochromatin distribution as well as decrease of the expression of several polycomb proteins (Ezh2, Ring1B, Cbx4) has been observed in p63-null keratinocytes. Moreover, recent data in our lab have showed that p63 directly regulates Cbx4, a component of the polycomb PRC1 complex. Here we show that mice lacking Cbx4 displayed a skin phenotype, which partially resembles the one observed in p63-null mice with reduced epidermal thickness and keratinocyte proliferation. All together these data demonstrate that p63-regulated gene expression program in epidermal keratinocytes includes not only genes encoding adhesion molecules, cytoskeleton proteins (cytokeratins) and chromatin remodelling factors (Satb1, Brg1), but also polycomb proteins and components of the nuclear envelope, suggesting the existence of a functional link between cytoskeleton, nuclear architecture and three dimensional nuclear organization. Other proteins important for proper epidermal development and stratification, are cytokeratins. Here, we show that keratin genes play an essential role in spatial organization of other lineage-specific genes in keratinocytes during epidermal development. In fact, ablation of keratin type II locus from chromosome 15 in epidermal keratinocytes led to changes in the genomic organization with increased distance between the Loricrin gene located on chromosome 3 as well as between Satb1 gene located on chromosome 17 and keratin type II locus, resulting in a more peripheral localization of these genes in the nucleus. As a possible consequence of their peripheral localization, reduced expression of Loricrin and Satb1 has also been observed in keratins type II-deficient mice. These findings together with recent circularized chromosome conformation capture (4C) data, strongly suggest that keratin 5, Loricrin and Satb1 are part of the same interactome, which is required for the proper expression of these genes and proper epidermal development and epidermal barrier formation. Taken together these data suggest that higher order chromatin remodelling and spatial organization of genes in the nucleus are important for the establishment of lineage-specific differentiation programs in epidermal progenitor cells. These data provide an important background for further analyses of nuclear architecture in the alterations of epidermal differentiation, seen in pathological conditions, such as psoriasis and epithelial skin cancers.
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Shanaube, Kwame, James Hargreaves, Katherine Fielding, Ab Schaap, Katherine-Anne Lawrence, Bernadette Hensen, Charalambos Sismanidis, et al. "Risk factors associated with positive quantiFERON-TB gold in-tube and tuberculin skin tests results in Zambia and South Africa." Public Library of Science (PLOS), 2011. http://hdl.handle.net/10019.1/11596.
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The original publication is available at http:/www.plosone.orgIntroduction: The utility of T-cell based interferon-gamma release assays for the diagnosis of latent tuberculosis infection remains unclear in settings with a high burden of tuberculosis. Objectives: To determine risk factors associated with positive QuantiFERON-TB Gold In-Tube (QFT-GIT) and tuberculin skin test (TST) results and the level of agreement between the tests; to explore the hypotheses that positivity in QFT-GIT is more related to recent infection and less affected by HIV than the TST. Methods: Adult household contacts of tuberculosis patients were invited to participate in a cross-sectional study across 24 communities in Zambia and South Africa. HIV, QFT-GIT and TST tests were done. A questionnaire was used to assess risk factors. Results: A total of 2,220 contacts were seen. 1,803 individuals had interpretable results for both tests, 1,147 (63.6%) were QFT-GIT positive while 725 (40.2%) were TST positive. Agreement between the tests was low (kappa = 0.24). QFT-GIT and TST results were associated with increasing age (adjusted OR [aOR] for each 10 year increase for QFT-GIT 1.15; 95% CI: 1.06-1.25, and for TST aOR: 1.10; 95% CI 1.01-1.20). HIV positivity was less common among those with positive results on QFT-GIT (aOR: 0.51; 95% CI: 0.39-0.67) and TST (aOR: 0.61; 95% CI: 0.46-0.82). Smear positivity of the index case was associated with QFT-GIT (aOR: 1.25; 95% CI: 0.90-1.74) and TST (aOR: 1.39; 95% CI: 0.98-1.98) results. We found little evidence in our data to support our hypotheses. Conclusion: QFT-GIT may not be more sensitive than the TST to detect risk factors associated with tuberculous infection. We found little evidence to support the hypotheses that positivity in QFT-GIT is more related to recent infection and less affected by HIV than the TST. © 2011 Shanaube et al.
Publishers' Version
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Suppa, Mariano. "Prevalence, determinants and risks associated with sunbed use in Europe: results from the Euromelanoma skin cancer prevention campaign and beyond." Doctoral thesis, Universite Libre de Bruxelles, 2019. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/288640.
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Introduction. Sunbeds emit ultraviolet (UV) radiation to produce a cosmetic tan and are classified by the World Health Organization as first-group carcinogens: they have been significantly associated with increased risk of melanoma and non-melanoma skin cancer. Despite this, controversies still exist: since sunbeds are able to increase serum vitamin D, the sunbed industry relentlessly tries to promote them as a safe therapeutic measure; and some authors have recently expressed scepticism about the carcinogenicity of sunbeds. Moreover, differences between European countries in terms of prevalence of use have not been extensively studied and a better understanding of the determinants of use in Europe is much needed. Similarly, the association of sunbed use with skin cancer risk factors is poorly understood. Euromelanoma is a skin cancer prevention campaign conducted all over Europe. It offers a once-a-year screening during which participants’ data, including sunbed use and phenotype, are collected via questionnaires.Objectives. To thoroughly describe prevalence, determinants, and risks associated with sunbed use in Europe. To this aim we performed literature reviews (3 publications) and an extensive analysis of the Euromelanoma database, which included data from 30 European countries (2 publications).Methods. For the 3 reviews we searched the most used databases for any literature published in English using all pertinent keywords. As for the 2 Euromelanoma studies, participants filled in questionnaires about demographics and risk factors, including type/duration of sunbed use. Multivariate analyses adjusted for all confounders were employed to assess factors independently associated with sunbed use in each country.Results. Our reviews showed that: (i) European sunbed users are typically young women, sun seekers, and smokers, mostly from northern countries, going to tanning studios with aesthetic motives, although exceptions exist; (ii) in case of vitamin D deficiency, the risk/benefit ratio is clearly in favour of vitamin D supplementation instead of sunbed use; (iii) all epidemiological criteria for causality apply to the relationship between sunbed use and melanoma. The Euromelanoma studies included 227,888 individuals (67.4% females, median age 44) from 30 countries. Overall prevalence of sunbed ever use was 10.6%. Prevalence was higher in northern, sun-deprived countries, with the exception of Italy and Spain. Females displayed higher prevalence than males in all countries. Geographic particularities were found in four regions: Iberian (prevalence ten times higher in Spain than Portugal), Balkan (prevalence disproportionately higher among women), Baltic (highest prevalence among young adults), and Scandinavian (highest prevalence among adolescents). Ever sunbed use was independently associated with nevus count >50 [summary odds ratio (SOR)=1.05 (1.01-1.10)], atypical nevi [SOR=1.04 (1.00-1.09)], lentigines [SOR=1.16 (1.04-1.29)], and suspicion of melanoma [SOR=1.13 (1.00-1.27)]. Conclusions. After a thorough literature revision, we concluded that the debate over whether sunbed use contributes to melanoma should be definitively closed and that sunbeds are not a safe option to increase vitamin D levels. The Euromelanoma analysis on sunbeds and skin cancer risk factors suggests that avoidance/discontinuation of sunbed use should always be encouraged, especially, but not exclusively, for individuals with high-risk phenotypes. The data about prevalence/determinants of sunbed use have public health relevance for future, tailored interventions aimed at reducing indoor tanning in Europe.Introduction. Les bancs solaires émettent des radiations ultraviolettes (UV) pour induire un bronzage cosmétique. Ils sont classés par l’Organisation Mondiale de la Santé comme carcinogènes de premier groupe: ils sont significativement associés à un risque accru de mélanome et de cancers cutanés non-mélanome. Malgré ça, des controverses existent toujours :comme leur utilisation permet d’accroitre le taux sérique de vitamine D, l’industrie du bronzage artificiel n’a cessé de les promouvoir comme thérapeutique sans danger et certains auteurs ont récemment mis en doute la carcinogénicité des bancs solaires. Par ailleurs, les différences entre les pays européens en terme de prévalence et de facteurs déterminant l’utilisation des bancs solaires n’ont pas été clairement étudiées. De la même façon, la relation entre bronzage artificiel et facteurs de risque de cancérisation cutanée reste floue. Euromelanoma est une campagne pan-européenne annuelle de prévention de cancers cutanés, où des questionnaires récoltent les données des participants (usage des bancs solaires, phénotype et informations cliniques inclus).Objectifs. Décrire de manière approfondie la prévalence, les déterminants et les risques associés à l’utilisation des bancs solaires en Europe. Dans ce but, nous avons réalisé des revues de littérature (3 publications) et une analyse extensive de la base de données Euromelanoma qui couvre 30 pays européens (2 publications).Méthodes. Pour les 3 revues, nous avons cherché dans toute la littérature publiée en anglais sur les moteurs de recherche les plus utilisés, en employant des mots clés pertinents. Les participants des 2 études Euromelanoma ont rempli des questionnaires colligeant les facteurs démographiques et de risque, le type et la durée d’utilisation des bancs solaires. Des analyses multi-variées ont permis d’évaluer les facteurs indépendamment associés à l’usage des bancs solaire dans chaque pays.Résultats. Les revues de littérature ont montré que :(i) les utilisateurs européens sont typiquement des femmes jeunes/adultes, amatrices de soleil, fumeuses, ressortissantes des pays nordiques, motivées par des raisons esthétiques et préférant les centres de bronzage, même si des exceptions existent ;(ii) dans le cas d’une carence en vitamine D, le rapport risque/bénéfice est clairement en faveur de la supplémentation en vitamine D plutôt que du bronzage artificiel ;(iii) tous les critères épidémiologiques de causalité s’appliquent à la relation entre les bancs solaires et le mélanome. Les études Euromelanoma ont été réalisées sur 227,888 individus (67.4% femmes, âge médian 44 ans) issus de 30 pays. La prévalence globale d’utilisation des bancs solaires était 10.6%, mais était plus élevée dans les pays nordiques et non ensoleillés, l’Italie et l’Espagne faisant exception. Dans tous les cas, les femmes avaient une prévalence d’utilisation plus élevée que les hommes. Des particularités géographiques ont été relevées dans 4 régions :la péninsule ibérique (prévalence 10 fois plus élevée en Espagne qu’au Portugal), les Balkans (disproportions excessives de prévalence entre femmes et hommes), les pays baltiques (la prévalence la plus élevée chez les jeunes/adultes), et scandinaves (la prévalence la plus élevée chez les adolescents). Avoir utilisé au moins une fois un banc solaire était indépendamment associé avec :un nombre de naevi >50 [summary odds ratio (SOR)=1.05 (1.01-1.10)], la présence de naevi atypiques [SOR=1.04 (1.00-1.09)] et des lentigines [SOR=1.16 (1.04-1.29)] et la suspicion de mélanome [SOR=1.13 (1.00-1.27)]. Conclusions. La revue complète de la littérature nous permet d’affirmer que le débat sur la relation causale entre bancs solaires et mélanome doit être clos et que leur utilisation pour corriger un déficit sérique en vitamine D n’est pas sans danger. L’analyse Euromelanoma sur l’utilisation des bancs solaires et les facteurs de risque de cancer cutané suggère que le bronzage artificiel devrait toujours être dissuadé, spécialement mais pas exclusivement chez les individus avec des phénotypes à haut risque. Les données de la prévalence et des facteurs déterminant l’utilisation des bancs solaires constituent un intérêt de santé publique et devraient permettre de cibler les actions nécessaires à la réduction du bronzage artificiel en Europe.
Doctorat en Sciences médicales (Médecine)
info:eu-repo/semantics/nonPublished
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Janefjord, Camilla. "Th1, Th2 and Treg associated factors in relation to allergy." Doctoral thesis, Linköping : Linköpings universitet, 2006. http://www.bibl.liu.se/liupubl/disp/disp2006/med947s.pdf.
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Potrony, Mateu Míriam. "Characterization of genetic factors associated with melanoma susceptibility and prognosis." Doctoral thesis, Universitat de Barcelona, 2018. http://hdl.handle.net/10803/663477.
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Melanoma is the malignant tumor arising from melanocytes and is the most aggressive of the common skin cancers. Melanoma is the tumor with the highest heritability (58%) and around 10% of cases occur in a familial context. Genetic susceptibility can be explained due to the inheritance of low, medium or high-risk variants, or a combination of them. To date, germline mutations in high-risk genes have been detected in 20-30% of melanoma-prone families. Interestingly, there is an important relationship between genetic factors associated with the risk to develop melanoma and genetic factors modulating melanoma outcome.
The thesis hypotheses were:
a) The proper characterization of known melanoma risk genes in a specific population context will facilitate genetic counseling in melanoma
b) The use of genome-wide linkage can allow the identification of new melanoma susceptibility loci in our population.
c) Melanoma susceptibility and nevus-related genes can play a role in melanoma prognosis.
d) Variants in immune checkpoints genes can play a role in melanoma prognosis.
Based on those hypotheses, the aims of this thesis were:
1) To characterize known risk genes in patients at high-risk to develop melanoma in Spain to refine genetic counseling.
2) To identify new familial melanoma loci using genome-wide linkage analysis.
3) To study the role of candidate genes in melanoma prognosis.
To answer those aims we designed six studies. In the first study, we evaluated the prevalence of CDKN2A germline mutations in patients at high risk to develop melanoma in our population and characterize families with mutation. We identified a higher prevalence of lung, breast and pancreatic cancer cases in families with mutation. Based on the study results, CDKN2A mutation carriers, besides sun protection advice and dermatologic surveillance, should receive recommendations on avoiding smoking and can be included in early detection programs for pancreatic, lung and breast cancers. In the second study, we evaluated the prevalence of MITF p.Glu318Lys carriers and assessed their characteristics detecting fast-growing melanoma among carriers. Thus, MITF p.Glu318Lys should be given fast-track visits to dermatology as they may be at risk to develop fast-growing melanomas and can be included in early detection programs for renal cancer. In the third study we identified that POT1 is mutated in a subset of melanoma families in Spain, thus genetic testing in melanoma should include the analysis of this gene. In the fourth study we identified a new melanoma locus at 11q associated with familial melanoma. Next-generation sequencing studies focused on the analysis of this region may allow the identification of new melanoma susceptibility genes or variants. Finally, in the last two studies, we focused on melanoma prognosis. We determined that IRF4 rs12203592 T functional variant, associated with a low melanogenesis (and low nevus count) and immune tolerance, correlates with a worse melanoma survival. Moreover, inherited functional variants of the lymphocyte receptor CD5, associated with more immune reactivity, correlated with better melanoma outcome.
To conclude, we have established the genetic bases of melanoma susceptibility in our population and refined genetic counseling, knowing the mutation prevalence of each gene and adapting secondary prevention measures in melanoma and other tumors according to the genetic testing results. Genome-wide linkage analysis in melanoma-prone families from Spain has allowed the identification of a new locus at 11q involved in familial melanoma. We have identified new genes modulating melanoma outcome based on the study of candidate genes involved in melanoma susceptibility, nevi count, and immune regulation.El melanoma és el més agressiu dels càncers de pell comuns. És el tumor amb una major heretabilitat. La susceptibilitat genètica depèn de variants d’alt, mig o baix risc, o la seva combinació. Hi ha una gran correlació entre factors genètics associats al risc i al pronòstic del melanoma. Els objectius d’aquesta tesi han estat: 1. Caracteritzar gens coneguts en pacients amb alt risc a desenvolupar melanoma per millorar el consell genètic. 2. Identificar nous loci implicats en la susceptibilitat a melanoma mitjançant anàlisi de lligament massiu. 3. Estudiar el paper de gens candidats en el pronòstic del melanoma En els primers tres estudis, es va avaluar la prevalença de mutacions a CDKN2A, POT1, promotor de TERT i la variant p.Glu318Lys a MITF en pacients amb alt risc a desenvolupar melanoma. També es van estudiar les característiques de les famílies i portadors d’aquestes variants. Els resultats observats mostren que els portadors de mutació a CDKN2A, a banda de les mesures de fotoprotecció i seguiment dermatològic, haurien d’evitar el tabac i es poden incloure en programes de detecció precoç de càncer de pàncrees, pulmó o mama. Els portadors de la variant p.Glu318Lys a MITF haurien de tenir accés ràpid a la consulta dermatològica pel risc a desenvolupar melanoma de ràpid creixement. POT1 s’hauria d’incloure en el test genètic. En el quart, hem identificat un nou locus a 11q associat a la susceptibilitat del melanoma familiar. Finalment, en els dos últims treballs, hem observat que la variant funcional d’IRF4 rs12203592 T, associada a un recompte de nevus baix i immunotolerància, correlaciona amb un pitjor pronòstic. A més, variants funcionals de CD5 associades amb una major reactivitat immunològica correlacionen amb un millor pronòstic. En conclusió, hem establert les bases genètiques de la susceptibilitat del melanoma en la nostra població i millorat el consell genètic. Estudis de lligament massiu han permès la identificació d’un nou locus associat al melanoma familiar. Per acabar, hem identificat nous gens que modulen el pronòstic del melanoma basant-nos en l’estudi de candidats relacionats amb la susceptibilitat a melanoma, el recompte de nevus i la regulació del sistema immune.
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Ahmed, Mohammed Ikram. "Exploring molecular mechanisms controlling skin homeostasis and hair growth : microRNAs in hair-cycle-dependent gene regulation, hair growth and associated tissue remodelling." Thesis, University of Bradford, 2010. http://hdl.handle.net/10454/5204.
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The hair follicle (HF) is a cyclic biological system that progresses through stages of growth, regression and quiescence, each being characterized by unique patterns of gene activation and silencing. MicroRNAs (miRNAs) are critically important for gene silencing and delineating their role in hair cycle may provide new insights into mechanisms of hair growth control and epithelial tissue remodelling. The aims of this study were: 1) To define changes in the miRNA profiles in skin during hair cycle-associated tissue remodelling; 2) To determine the role of individual miRNAs in regulating gene expression programs that drive HF growth, involution and quiescence; 3) and to explore the role of miRNAs in mediating the effects of BMP signalling in the skin. To address Aims 1 & 2, global miRNA expression profiling in the skin was performed and revealed marked changes in miRNAs expression during distinct stages of the murine hair cycle. Specifically, miR-31 markedly increased during anagen and decreased during catagen and telogen. Administration of antisense miR-31 inhibitor into mouse skin during the early- and mid-anagen phases of the hair cycle resulted in accelerated anagen development, and altered differentiation of hair matrix keratinocytes and hair shaft formation. Microarray, qRT-PCR and Western blot analyses revealed that miR-31 negatively regulates expression of Fgf10, the components of Wnt and BMP signalling pathways Sclerostin and BAMBI, and Dlx3 transcription factor, as well as selected keratin genes. Luciferase reporter assay revealed that Krt16, Krt17, Dlx3, and Fgf10 serve as direct miR-31 targets. In addition, miR-214 was identified as a potent inhibitor of the Wnt signalling pathway in the keratinocytes. Mutually exclusive expression patterns of miR-214 and β-catenin was observed during HF morphogenesis. MiR-214 decreases the expression of β-catenin and other components of Wnt signalling pathways c-myc, cyclin D1, and Pten in the keratinocytes. Luciferase reporter assay proved that β-catenin serves as a direct target of miR-214. In addition, miR-214 prevented translocation of β-catenin into the nucleus in response to the treatment with an activator of the Wnt signalling pathway lithium chloride, and abrogated the lithium-induced increase of the expression of the Wnt target gene VI Axin2. This suggests that miR-214 may indeed be involved in regulation of skin development and regeneration at least in part, by controlling the expression of β-catenin and the activity of the Wnt signalling pathway. To address Aim 3, the role of miRNAs in mediating the effects of the bone morphogenetic protein (BMP) signalling in the skin was explored. MiRNAs were isolated from the primary mouse keratinocytes treated with BMP4 and processed for analysis of global miRNA expression using the microarray approach. Microarray and real-time PCR analysis revealed BMP4-dependent changes in the expression of distinct miRNAs, including miR-21, which expression was strongly decreased in the keratinocytes after BMP4 treatment. In contrast, miR-21 expression was substantially higher in the skin of transgenic mice over-expressing BMP antagonist Noggin. Transfection of the keratinocytes with miR-21 mimic revealed existence of two groups of the BMP target genes, which are differentially regulated by miR-21. Thus, this suggests a novel mechanism controlling the effects of BMP signalling in the keratinocytes. Thus, miRNAs play important roles in regulating gene expression programs in the skin during hair cycle. By targeting a number of growth regulatory molecules, transcription factors and cytoskeletal proteins, miRNAs are involved in establishing an optimal balance of gene expression in the keratinocytes required for the HF and skin homeostasis.
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Ahmed, Mohammed I. "Exploring Molecular Mechanisms Controlling Skin Homeostasis and Hair Growth. MicroRNAs in Hair-cycle-Dependent Gene Regulation, Hair Growth and Associated Tissue Remodelling." Thesis, University of Bradford, 2010. http://hdl.handle.net/10454/5204.
Full textAbstract:
The hair follicle (HF) is a cyclic biological system that progresses through stages of growth, regression and quiescence, each being characterized by unique patterns of gene activation and silencing. MicroRNAs (miRNAs) are critically important for gene silencing and delineating their role in hair cycle may provide new insights into mechanisms of hair growth control and epithelial tissue remodelling.
The aims of this study were: 1) To define changes in the miRNA profiles in skin during hair cycle-associated tissue remodelling; 2) To determine the role of individual miRNAs in regulating gene expression programs that drive HF growth, involution and quiescence; 3) and to explore the role of miRNAs in mediating the effects of BMP signalling in the skin.
To address Aims 1 & 2, global miRNA expression profiling in the skin was performed and revealed marked changes in miRNAs expression during distinct stages of the murine hair cycle. Specifically, miR-31 markedly increased during anagen and decreased during catagen and telogen. Administration of antisense miR-31 inhibitor into mouse skin during the early- and mid-anagen phases of the hair cycle resulted in accelerated anagen development, and altered differentiation of hair matrix keratinocytes and hair shaft formation. Microarray, qRT-PCR and Western blot analyses revealed that miR-31 negatively regulates expression of Fgf10, the components of Wnt and BMP signalling pathways Sclerostin and BAMBI, and Dlx3 transcription factor, as well as selected keratin genes. Luciferase reporter assay revealed that Krt16, Krt17, Dlx3, and Fgf10 serve as direct miR-31 targets.
In addition, miR-214 was identified as a potent inhibitor of the Wnt signalling pathway in the keratinocytes. Mutually exclusive expression patterns of miR-214 and ¿-catenin was observed during HF morphogenesis. MiR-214 decreases the expression of ¿-catenin and other components of Wnt signalling pathways c-myc, cyclin D1, and Pten in the keratinocytes. Luciferase reporter assay proved that ¿-catenin serves as a direct target of miR-214. In addition, miR-214 prevented translocation of ¿-catenin into the nucleus in response to the treatment with an activator of the Wnt signalling pathway lithium chloride, and abrogated the lithium-induced increase of the expression of the Wnt target gene
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Axin2. This suggests that miR-214 may indeed be involved in regulation of skin development and regeneration at least in part, by controlling the expression of ¿-catenin and the activity of the Wnt signalling pathway.
To address Aim 3, the role of miRNAs in mediating the effects of the bone morphogenetic protein (BMP) signalling in the skin was explored. MiRNAs were isolated from the primary mouse keratinocytes treated with BMP4 and processed for analysis of global miRNA expression using the microarray approach. Microarray and real-time PCR analysis revealed BMP4-dependent changes in the expression of distinct miRNAs, including miR-21, which expression was strongly decreased in the keratinocytes after BMP4 treatment. In contrast, miR-21 expression was substantially higher in the skin of transgenic mice over-expressing BMP antagonist Noggin. Transfection of the keratinocytes with miR-21 mimic revealed existence of two groups of the BMP target genes, which are differentially regulated by miR-21. Thus, this suggests a novel mechanism controlling the effects of BMP signalling in the keratinocytes.
Thus, miRNAs play important roles in regulating gene expression programs in the skin during hair cycle. By targeting a number of growth regulatory molecules, transcription factors and cytoskeletal proteins, miRNAs are involved in establishing an optimal balance of gene expression in the keratinocytes required for the HF and skin homeostasis.
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Lee, Chun-Yuan, Hung-Chin Tsai, Calvin M. Kunin, Susan SJ Lee, and Yao-Shen Chen. "Clinical and microbiological characteristics of purulent and non-purulent cellulitis in hospitalized Taiwanese adults in the era of community-associated methicillin-resistant Staphylococcus aureus." BioMed Central Ltd, 2015. http://hdl.handle.net/10150/610291.
Full textAbstract:
BACKGROUND: The risk factors, microbial etiology, differentiation, and clinical features of purulent and non-purulent cellulitis are not well defined in Taiwan. METHODS: We conducted a retrospective cohort study of hospitalized adults with cellulitis in Taiwan in 2013. The demographic characteristics, underlying diseases, clinical manifestations, laboratory and microbiological findings, treatments, and outcomes were compared for patients with purulent and non-purulent cellulitis. RESULTS: Of the 465 patients, 369 had non-purulent cellulitis and 96 had purulent cellulitis. The non-purulent group was significantly older (p = 0.001) and was more likely to have lower limb involvement (p < 0.001), tinea pedis (p = 0.003), stasis dermatitis (p = 0.025), a higher Charlson comorbidity score (p = 0.03), and recurrence at 6 months post-infection (p = 0.001) than the purulent group. The purulent group was more likely to have a wound (p < 0.001) and a longer hospital stay (p = 0.001) and duration of antimicrobial therapy (p = 0.003) than the non-purulent group. The etiological agent was identified in 35.5 % of the non-purulent cases, with β-hemolytic streptococci the most frequent cause (70.2 %). The etiological agent was identified in 83.3 % of the purulent cases, with Staphylococcus aureus the predominant pathogen (60 %): 50 % of these were methicillin-resistant S. aureus (MRSA). In multivariable analysis, purulent group (odds ratio (OR), 5.188; 95 % confidence interval (CI), 1.995-13.493; p = 0.001) was a positive predictor of MRSA. The prescribed antimicrobial agents were significantly different between the purulent and non-purulent groups, with penicillin the most frequently used antimicrobial agent in the non-purulent group (35.2 %), and oxacillin the most frequent in the purulent group (39.6 %). The appropriate antimicrobial agent was more frequently prescribed in the non-purulent group than in the purulent group (83.2 % vs. 53.8 %, p < 0.001). CONCLUSIONS: The epidemiology, clinical features, and microbiology of purulent and non-purulent cellulitis were significantly different in hospitalized Taiwanese adults. Purulence was a positive predictor of MRSA as the causal agent of cellulitis. These findings provide added support for the adoption of the IDSA guidelines for empirical antimicrobial therapy of cellulitis in Taiwan.
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Powell, Cecil Lamonte. "College men's psychological and physiological responses associated with violent video game play." unrestricted, 2008. http://etd.gsu.edu/theses/available/etd-04212008-155443/.
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Thesis (Ph. D.)--Georgia State University, 2008.Title from file title page. Dominic Parrott, committee chair; Tracie Stewart, Cynthia Hoffner, Heather Kleider, Eric Vanman, committee members. Electronic text (94 p. : ill.) : digital, PDF file. Description based on contents viewed July 2, 2008. Includes bibliographical references (p. 81-88).
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Jarosz, Monika. "The roles of Fibroblast Growth Factor 22 in development, tissue repair and homeostasis, and the associated role of FGF signalling in skin cancer." Thesis, Queen Mary, University of London, 2010. http://qmro.qmul.ac.uk/xmlui/handle/123456789/433.
Full textAbstract:
Fibroblast Growth Factors (FGFs) play critical roles during development, tissue homeostasis and repair and in controlling cell proliferation, survival, migration and differentiation. Of the 22 mammalian FGFs, FGF22, a member of the FGF7/10/22 subfamily, is relatively understudied. I have investigated the in vivo functions of FGF22 in mice engineered to lack Fgf22. Fgf22 null animals were viable, fertile and did not display any obvious abnormalities. No differences in skin histology and pelage hair were observed, demonstrating that FGF22 is dispensable during embryogenesis and in unchallenged adult skin. Mice lacking FGF22 were able to heal acute wounds just as efficiently as wild type mice. However, classical two-step skin carcinogenesis challenge revealed that Fgf22 null mice developed considerably less papillomas than wild type mice. Interestingly, Fgf22 knockout mice displayed a significant reduction in body weight and I identified several novel sites of Fgf22 expression in the gastrointestinal tract. However, the morphology and function of various tested tissues of the digestive system were not affected by Fgf22 deletion and the mechanism underlying metabolic differences between Fgf22 wild type and knockout mice remains unknown. FGF22 signals through FGFR2b, a receptor tyrosine kinase that we recently have shown plays a tumour-suppressive role in the mouse skin. Another aspect of my project was to verify whether FGFR2 plays a similar role in human skin, by investigating squamous cell carcinoma (SCC) sections and cell lines isolated from patient SCCs. I observed differences in the pattern of anti-FGFR2 4 immunostaining of normal skin and tumours. Also, since it is well documented that mutations in FGFR2 arise in patients with different types of cancer, I screened DNA isolated from the cell lines and identified eleven different mutations in FGFR2. This study contributes towards a better understanding of the wide spectrum of FGF/FGFR activities and distinct regulatory functions in the biology of physiological and pathological processes.
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Weideman, Liezel. "An investigation into the antibacterial activities of medicinial plants traditionally used in the Eastern Cape to treat secondary skin infections associated with burn wounds." Thesis, Nelson Mandela Metropolitan University, 2005. http://hdl.handle.net/10948/172.
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Traditional medicine has a long history of being used for treating various ailments ranging in severity. Although traditional medicine has typically been the health care for the poorest levels of society, there is a worldwide growth in popularity. The growing popularity of traditional medicine, termed the green boom, may be ascribed to people taking a more holistic approach to maintain their health. Traditional medicine is widely used on a regular basis by 70% of South Africans. Various indigenous medicinal plants are used for the preparation of traditional herbal medicine. These plants are mostly indigenous to the regions were it is used. In this study four medicinal plants (Bulbine frutescens, Leonotis leounurus, Melianthus major & Zantedecshia aethiopica) that are traditionally used in the Eastern Cape region for treating burn wound infections, were collected for investigation. The in vitro antibacterial activity of these plants was tested against different bacterial strains of eight different bacteria. The bacteria used in this investigation included bacterial strains of four Gram-positive bacteria, S. aureus, methicillin-resistant S. aureus (MRSA), E. feacalis, S. pyogenes and four Gramnegative bacteria, P. aeruginosa, A. baumanii, K. pneumoniae and P. mirabilis. Traditional preparations as well as three different extracts (methanol, aqueous & acetone) of the plants were used for in vitro antibacterial activity testing. The microtitre plate assay and agar dilution assay were used for determining the antibacterial activity of the traditional preparations and plant extracts against the different bacterial strains. In the microtitre plate assay the antibacterial activity was tested using the bacterial growth indicator, INT and a microtitre plate spectrophotometer to determine the minimal inhibitory concentrations of the plant extracts and traditional preparations. The microtitre plate assay was used for testing the antibacterial activity of the plants against the bacterial strains of five bacteria, S. aureus, MRSA, P. aeruginosa, A. baumanii and K. pneumoniae. The bacterial strains of the three bacteria, S. pyogenes, E. feacalis and P. mirabilis were not compatible with the microtitre plate assay using INT and spectrophotometric readings to determine bacterial inhibition. Therefore the agar dilution assay were used as an alternative method for determining the MIC’s of the plant extracts against the bacterial strains of these bacteria. The initial plant extract concentration in the microtitre plate assay differed with the different plant extracts in the microtitre plate assay. Acetone followed by methanol extracted the highest plant extract concentrations with the different medicinal plants. M. major followed by L. leonurus produced the highest plant extract concentrations following extraction with the different extraction solvents. Consequently the acetone extract of M. major had the highest plant extract concentration before serial dilution in the microtitre plate assay. Uniform plant extract concentrations were tested in the agar dilution assay. The methanol extract followed by the acetone extract of the plants gave the highest antibacterial activity against the different bacterial strains. The extracts of M. major followed by L. leonurus inhibited the highest number of bacterial strains in the microtitre plate assay and the extracts of B. frutescens inhibited the lowest number of bacterial strains. The acetone and methanol extracts of M. major were the only extracts that displayed antibacterial activity in the agar dilution assay. The bacterial strains of P. mirabilis were the only bacteria that were inhibited using this method. The bacterial strains of S. pyogenes and E. feacalis were not inhibited at any of the plant extract concentrations in the agar dilution assay.
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Abelius, Martina S., Jan Ernerudh, Göran Berg, Leif Matthiesen, Lennart Nilsson, and Maria Jenmalm. "High cord blood levels of the T-helper 2-associated chemokines CCL17 and CCL22 precede allergy development during the first 6 years of life." Linköpings universitet, Pediatrik, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-74499.
Full textAbstract:
Exposure to a strong T-helper 2 (Th2)-like environment during fetal development may promote allergy development. Increased cord blood (CB) levels of the Th2-associated chemokine CCL22 were associated with allergy development during the first 2 y of life. The aim of the present study was to determine whether CB Th1- and Th2-associated chemokine levels are associated with allergy development during the first 6 y of life, allowing assessment of respiratory allergic symptoms usually developing in this period. The CB levels of cytokines, chemokines, and total IgE were determined in 56 children of 20 women with allergic symptoms and 36 women without allergic symptoms. Total IgE and allergen-specific IgE antibody levels were quantified at 6, 12, 24 mo, and 6 y of age. Increased CB CCL22 levels were associated with development of allergic sensitization and asthma and increased CCL17 levels with development of allergic symptoms, including asthma. Sensitized children with allergic symptoms showed higher CB CCL17 and CCL22 levels and higher ratios between these Th2-associated chemokines and the Th1-associated chemokine CXCL10 than nonsensitized children without allergic symptoms. A pronounced Th2 deviation at birth, reflected by increased CB CCL17 and CCL22 levels, and increased CCL22/CXCL10 and CCL17/CXCL10 ratios might promote allergy development later in life.
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Lorencini, Márcio 1981. "Avaliação global de transcritos associados ao envelhecimento da epiderme humana utilizando microarranjos de DNA = Global evaluation of transcripts associated to human epidermal aging with DNA microarrays." [s.n.], 2014. http://repositorio.unicamp.br/jspui/handle/REPOSIP/317175.
Full textAbstract:
Orientador: Nilson Ivo Tonin ZanchinTese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia
Made available in DSpace on 2018-08-24T14:29:49Z (GMT). No. of bitstreams: 1 Lorencini_Marcio_D.pdf: 16348273 bytes, checksum: 4ed299b197892b0d3297e6e6a65d947c (MD5) Previous issue date: 2014
Resumo: Com o aumento do tempo de vida da população humana muitas modalidades médicas, incluindo a dermatologia, deparam-se com uma revolução na forma de garantir saúde e qualidade de vida aos pacientes. Em contato com o ambiente externo, a pele representa um órgão no qual as mudanças com o envelhecimento causam danos funcionais, além de potencial impacto estético e psicossocial. A epiderme, camada mais externa da pele, constitui uma barreira seletiva com destacada capacidade de renovação e manutenção da homeostasia corporal. Entretanto, o entendimento de diversos mecanismos associados à fisiologia e envelhecimento da epiderme permanece como desafio para a comunidade científica. Com base nesse cenário, o objetivo do presente trabalho foi compreender o atual estado da arte no tema de envelhecimento da epiderme e realizar experimentos voltados para lacunas existentes, com foco na integração de aspectos clínicos, fisiológicos, morfológicos, celulares e moleculares. O capítulo de abertura descreve uma avaliação global de transcritos associados ao envelhecimento da epiderme humana, com a técnica de microarranjos de DNA e coleta não invasiva com fitas adesivas. O estudo indica características moleculares específicas do fotoenvelhecimento epidermal, com alterações relevantes e complementares a dados clínicos e morfológicos prévios, como modulação das vias de organização do citoesqueleto de actina e sinalização de cálcio, expressão gênica alterada de proteínas do envelope córneo, e avaliação de um painel segmentado por décadas de vida que sugere aspectos inéditos de regulação homeostática da epiderme, além de genes com modulação contínua ao longo das idades. O segundo capítulo compara o envelhecimento nas regiões folicular e interfolicular da epiderme. Como um sistema biológico de simples obtenção e fácil manuseio, os bulbos dos folículos pilosos representam uma fonte rica de material epidermal distinto, conforme evidencias na ampla modulação gênica diferenciada. O terceiro capítulo inclui uma avaliação in vitro do envelhecimento da epiderme, com queratinócitos de indivíduos de diferentes idades cultivados em monocamada e no modelo de pele equivalente. Os resultados evidenciam diferenças na expressão de marcadores moleculares de proliferação e diferenciação entre queratinócitos neonatais e adultos, mas não entre adultos de diferentes idades. Não houve diferença nas populações de células tronco, entretanto, observou-se aumento de células na fase proliferativa do ciclo celular em neonatos, assim como predominância de células na fase estacionária do ciclo celular em adultos mais velhos. Concluindo, os resultados obtidos no presente trabalho contribuem de forma significativa para o avanço do entendimento dos mecanismos moleculares afetados pelo avanço da idade da epiderme, possilitando a busca de novas alternativas no tratamento do envelhecimento cutâneo
Abstract: With the increase in lifetime of the human population many medical disciplines, including dermatology, are facing a revolution in the approaches to ensure healthcare and quality of life for patients. In contact with the external environment, the skin is an organ in which the changes of aging cause functional damage, in addition to potential aesthetic and psychosocial impact. Epidermis, the outermost skin layer, is a selective barrier with outstanding capacity for renewal and maintenance of the body homeostasis. However, the understanding of several mechanisms associated with skin physiology and aging remains a challenge for the scientific community. Considering this scenario, the objective of this work was to evaluate the state of the art knowledge on epidermal aging and to conduct experimental approaches to cover gaps that still exist on that theme, focusing on the integration of clinical, physiological, morphological, cellular and molecular aspects of epidermis aging. The opening chapter describes a study based on global transcriptional evaluation associated with aging of the human epidermis, using DNA microarrays and noninvasive tape stripping. This study reveals molecular characteristics specific of epidermal photoaging, with relevant findings complementary to previous clinical and morphological data, such as modulation of the actin cytoskeleton and calcium signaling pathways; altered gene expression of proteins of the cornified envelope; and evaluation of a segmented panel structured by decades of life, which suggests new aspects of homeostatic regulation in the epidermis and unvails genes with continuous modulation throughout different ages. The second chapter compares the gene expression patterns of the follicular and interfollicular regions of epidermis undergoing aging. As a biological system easily sampled and handled, the bulbs of plucked hair follicles represent a rich source of distinct epidermal material, as evidenced by the wide differential gene modulation that was detected. The third chapter includes an experimental in vitro evaluation of skin aging using keratinocytes isolated from individuals of different ages and cultured in monolayer and in skin equivalent models. Differences in the expression of proliferation and differentiation molecular markers between neonatal and adult keratinocytes were observed. No differences were found regarding the stem cell populations, however, neonates showed an increased percentage of cells in the proliferative phase of cell cycle, while older adults presented a predominance of cells in the stationary phase of cell cycle. The results herein presented provide novel insights on the molecular mechanisms affected by epidermal aging, enabling the search of new alternatives in the treatment of aging skin
Doutorado
Genetica Animal e Evolução
Doutor em Genetica e Biologia Molecular
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Affara, Nesrine I. "The role of phosphoinositide 3-kinase/akt signaling pathway in tumor-associated angiogenesis, wound healing, and carcinogenesis." The Ohio State University, 2006. http://rave.ohiolink.edu/etdc/view?acc_num=osu1150469618.
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Graf, Justin T. "Membrane associated transporter protein gene (SLC45A2) and the genetic basis of normal human pigmentation variation." Queensland University of Technology, 2008. http://eprints.qut.edu.au/25913/.
Full textAbstract:
This work is concerned with the genetic basis of normal human pigmentation variation. Specifically, the role of polymorphisms within the solute carrier family 45 member 2 (SLC45A2 or membrane associated transporter protein; MATP) gene were investigated with respect to variation in hair, skin and eye colour ― both between and within populations. SLC45A2 is an important regulator of melanin production and mutations in the gene underly the most recently identified form of oculocutaneous albinism. There is evidence to suggest that non-synonymous polymorphisms in SLC45A2 are associated with normal pigmentation variation between populations. Therefore, the underlying hypothesis of this thesis is that polymorphisms in SLC45A2 will alter the function or regulation of the protein, thereby altering the important role it plays in melanogenesis and providing a mechanism for normal pigmentation variation.
In order to investigate the role that SLC45A2 polymorphisms play in human pigmentation variation, a DNA database was established which collected pigmentation phenotypic information and blood samples of more than 700 individuals. This database was used as the foundation for two association studies outlined in this thesis, the first of which involved genotyping two previously-described non-synonymous polymorphisms, p.Glu272Lys and p.Phe374Leu, in four different population groups. For both polymorphisms, allele frequencies were significantly different between population groups and the 272Lys and 374Leu alleles were strongly associated with black hair, brown eyes and olive skin colour in Caucasians. This was the first report to show that SLC45A2 polymorphisms were associated with normal human intra-population pigmentation variation.
The second association study involved genotyping several SLC45A2 promoter polymorphisms to determine if they also played a role in pigmentation variation. Firstly, the transcription start site (TSS), and hence putative proximal promoter region, was identified using 5' RNA ligase mediated rapid amplification of cDNA ends (RLM-RACE). Two alternate TSSs were identified and the putative promoter region was screened for novel polymorphisms using denaturing high performance liquid chromatography (dHPLC). A novel duplication (c.–1176_–1174dupAAT) was identified along with other previously described single nucleotide polymorphisms (c.–1721C>G and c.–1169G>A). Strong linkage disequilibrium ensured that all three polymorphisms were associated with skin colour such that the –1721G, +dup and –1169A alleles were associated with olive skin in Caucasians. No linkage disequilibrium was observed between the promoter and coding region polymorphisms, suggesting independent effects. The association analyses were complemented with functional data, showing that the –1721G, +dup and –1169A alleles significantly decreased SLC45A2 transcriptional activity. Based on in silico bioinformatic analysis that showed these alleles remove a microphthalmia-associated transcription factor (MITF) binding site, and that MITF is a known regulator of SLC45A2 (Baxter and Pavan, 2002; Du and Fisher, 2002), it was postulated that SLC45A2 promoter polymorphisms could contribute to the regulation of pigmentation by altering MITF binding affinity.
Further characterisation of the SLC45A2 promoter was carried out using luciferase reporter assays to determine the transcriptional activity of different regions of the promoter. Five constructs were designed of increasing length and their promoter activity evaluated. Constitutive promoter activity was observed within the first ~200 bp and promoter activity increased as the construct size increased. The functional impact of the –1721G, +dup and –1169A alleles, which removed a MITF consensus binding site, were assessed using electrophoretic mobility shift assays (EMSA) and expression analysis of genotyped melanoblast and melanocyte cell lines. EMSA results confirmed that the promoter polymorphisms affected DNA-protein binding. Interestingly, however, the protein/s involved were not MITF, or at least MITF was not the protein directly binding to the DNA. In an effort to more thoroughly characterise the functional consequences of SLC45A2 promoter polymorphisms, the mRNA expression levels of SLC45A2 and MITF were determined in melanocyte/melanoblast cell lines. Based on SLC45A2’s role in processing and trafficking TYRP1 from the trans-Golgi network to stage 2 melanosmes, the mRNA expression of TYRP1 was also investigated. Expression results suggested a coordinated expression of pigmentation genes.
This thesis has substantially contributed to the field of pigmentation by showing that SLC45A2 polymorphisms not only show allele frequency differences between population groups, but also contribute to normal pigmentation variation within a Caucasian population. In addition, promoter polymorphisms have been shown to have functional consequences for SLC45A2 transcription and the expression of other pigmentation genes. Combined, the data presented in this work supports the notion that SLC45A2 is an important contributor to normal pigmentation variation and should be the target of further research to elucidate its role in determining pigmentation phenotypes. Understanding SLC45A2’s function may lead to the development of therapeutic interventions for oculocutaneous albinism and other disorders of pigmentation. It may also help in our understanding of skin cancer susceptibility and evolutionary adaptation to different UV environments, and contribute to the forensic application of pigmentation phenotype prediction.
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Roy, Srirupa. "Defining the mechanism of action of silibinin as an anti-cancer and cancer chemopreventive agent /." Connect to full text via ProQuest. Limited to UCD Anschutz Medical Campus, 2008.
Find full textAbstract:
Thesis (Ph.D. in Toxicology) -- University of Colorado Denver, 2008.Typescript. Includes bibliographical references (leaves 144-170). Free to UCD Anschutz Medical Campus. Online version available via ProQuest Digital Dissertations;
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Strathmann, Marc. "Auswirkungen der Bestrahlung mit UVB, UVA-1 und PUVA-1 auf das Funktionsverhalten humaner dermaler Mastzellen nach Stimulation mit anti-IgE und Substanz P." Doctoral thesis, [S.l.] : [s.n.], 2004. http://deposit.ddb.de/cgi-bin/dokserv?idn=972615822.
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Watchman, Alan Leslie, and n/a. "Properties and dating of silica skins associated with rock art." University of Canberra. Applied Science, 1996. http://erl.canberra.edu.au./public/adt-AUC20061110.104443.
Full textAbstract:
Hydrated amorphous silicon dioxide (Si02.nH-,O), or opal-A, is deposited naturally
from seepage and runoff water as white or brown rock surface coatings, called 'skins',
that often partly obscure rock paintings and engravings, but occasionally, a thin
translucent silica skin can form a protective film over rock art. White lustrous silica
skins, less than 1 mm thick, occur where seepage water regularly flows from bedding
and joint planes, whereas much thinner brown skins form on the sides of boulders and
cliffs where runoff water periodically flows. To find the degree of silica skin variability
and to determine how climate and rock type affect the properties of silica skins I
collected samples at seven Australian and two Canadian rock painting sites that were
located in temperate, tropical and sub-arctic regions. The skins had developed on
sandstone, quartzite, schist, gneiss and migmatite. I studied the effects of the skins on
rock art stability, documented their compositions, textures and structures to establish
their common properties, and searched for a way to date the silica which would provide
an indication of the minimum age of the underlying art. 1 also made replication
experiments to determine factors that influence the properties of artificial silica skins
and the rates of their precipitation so that I could propose a mechanism for natural silica
skin formation, and ascertain whether an artificial silica skin could act as a protective
rock art conservation measure.
I was able to subdivide the analysed samples into silica skin Types I, II and III on the
basis of their colour (translucent, white or brown), composition (SiO2, Al2O3 and
absorbed water contents) and texture (smooth vitreous or vermiform). I propose that
silica skins initially begin to form on stable rock surfaces by a process involving a
combination of evaporation- and ionic-induced polymerisation of silicic acid in seepage
and runoff water. Condensation reactions, random clustering of small silica spheres
and deposition of the resulting aggregates eventually produce a thin surficial silica film.
Deposition of silica often traps micro-organisms that live in the damp seepage and
runoff water zones, and these fossils in finely laminated skins enable the radiocarbon
dating of silica deposition, and therefore the dating of rock paintings enclosed by silica.
Micro-excavation of silica layers associated with rock art combined with accelerator
mass spectrometry gave preliminary radiocarbon determinations that were either
consistent with, or contradicted, prevailing opinions about the antiquity of the rock art
at selected sites. Experiments using a laser technique for combusting fossilised microorganisms
in finely laminated skins were unable to generate sufficient carbon for
dating. Catalysis of a mixture of equal proportions of methyl-trimethoxy silane and
water produces a translucent stable film that may be suitable as a consolidant, whereas
other artificial silica skins made from silica glass and tetra-ethoxy silane develop microfractures
on drying, and these are unsuitable as rock art consolidants.
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Imel, Clint J. "Analysis of defects associated with leaks on skid steer loaders." Thesis, Kansas State University, 2008. http://hdl.handle.net/2097/4602.
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Master of AgribusinessDepartment of Agricultural Economics
Ted C. Schroeder
The CNH Wichita Product Center has had a chronic leak problem with the Skid Steer Loaders. The objective of this project was to analyze the manufacturing plant leak data and make improvements to correct the issue. The objective is twofold: 1) to make process or design improvements on current products produced in the plant and 2) to make recommendations for future designs to prevent such leak issues from reoccurring. The manufacturing data had to be transformed into usable form and then it was analyzed mostly by utilizing Pareto Charts. The highest six problem leak points were chosen from the manufacturing data. Process changes were implemented on these particular leak joints and the results were analyzed using two proportions hypothesis tests. The process changes reduced the leak rate by an average percent reduction of 86 percent. The process changes implemented will also be applied to other similar joints, and results documented in the future. The future design recommendations made from the analyzed data included the increased use of o-ring face seal connections at certain locations and where possible, reducing the number of joints per machine.
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Cassir, Nadim. "Culturomique : un nouvel outil d'analyse de microbiotes impliqués dans la pathogenèse ou la transmission de maladies infectieuses." Thesis, Aix-Marseille, 2015. http://www.theses.fr/2015AIXM5038/document.
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Le microbiote digestif humain joue un rôle essentiel et bénéfique pour son hôte mais il est également impliqué dans un nombre croissant de pathologies. Les connaissances sur la composition de cet écosystème ont récemment été révolutionnées grâce à l’utilisation de techniques moléculaires. Cependant, ces techniques comportent des limites importantes. C’est ainsi que le concept de « culturomique » a été introduit ; il consiste en la multiplication de milieux et conditions de culture et l’identification rapide de colonies bactériennes par spectrométrie de masse (MALDITOF) ou par amplification et séquençage du gène de l’ARN ribosomal 16S. Dans la première partie de ce travail, nous avons mis en évidence une association entre la présence de Clostridium butyricum dans les selles et la survenue d’entérocolite ulcéro-nécrosante que ce soit par méthodes de pyroséquençage et culture ou par PCR quantitative en temps réel spécifique de C. butyricum; identifié après séquençage du génome complet de toutes nos souches de C. butyricum, la présence du gène de la β-hémolysine (toxine). Dans la deuxième partie de ce travail, nous avons montré par cuturomique que les bactéries à Gram-négatif (BGN) étaient fréquemment disséminées au sein du microbiote cutané transitoire des patients hospitalisés en réanimation ; le réservoir serait essentiellement digestif. En conclusion, le microbiote digestif constitue un réservoir sousestimé de bactéries pathogènes. La microbiologie moderne incluant les nouvelles méthodes de culture permet d’étendre de manière considérable les connaissances sur la composition de cet écosystème et son implication en pathologie humaineHe human gut microbiota plays an important and beneficial role in its host but it is also involved in a growing number of diseases. Knowledge of the composition of this ecosystem have recently been revolutionized by the use of molecular techniques. However, these techniques have significant limitations. Thus, the concept of "culturomics" has been introduced; it consists of the multiplication of culture conditions and the rapid identification of bacterial colonies by mass spectrometry (MALDI-TOF) or by PCR 16S RNA gene sequencing. In the first part of this work, we have demonstrated an association between the presence of Clostridium butyricum in the stool and the occurrence of necrotizing enterocolitis whether by pyrosequencing methods and Culture or by quantitative PCR specific real time C. butyricum; identified after sequencing the complete genome of all our strains of C. butyricum, the presence of the gene of β-hemolysin (toxin). In the second part of this work, we showed by cuturomics that Gram-negative bacteria (BGN) were frequently spread out over the transitional skin microbiota of patients hospitalized in intensive care; the reservoir would essentially digestive. In conclusion, the gut microbiota is an underestimated reservoir of pathogenic bacteria. Modern microbiology including new culture-based methods is currently extending exponentially our knowledge on gut microbiota giving rise to new insights into the pathogenesis or the transmission of infectious diseases
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Wolf, Horrell Erin M. "Regulation of UV-Protective Pathways Downstream of the Melanocortin 1 Receptor in Melanocytes." UKnowledge, 2016. http://uknowledge.uky.edu/physiology_etds/29.
Full textAbstract:
Malignant cutaneous melanoma is the deadliest form of skin cancer, and a majority of melanoma diagnoses are a result of exposure to ultraviolet (UV) radiation. UV radiation causes DNA damage, which if not repaired correctly via nucleotide excision repair (NER) can result in mutations and melanomagenesis. The melanocortin 1 receptor (MC1R) is a Gs protein coupled receptor located on melanocyte plasma membranes and is involved in protecting the skin from UV induced damage. MC1R signaling results in the activation of two protective pathways: 1) induction of eumelanin synthesis downstream of micropthalmia-associated transcription factor (MITF) and 2) acceleration of NER downstream of ataxia telangiectaseia mutated and Rad3 related (ATR). MC1R signaling, however, also promotes melanocyte proliferation, therefore, the activation of the MC1R pathway must be regulated. The overall hypothesis of this dissertation is that the pathways downstream of MC1R can be manipulated to protect against UV induced damage.
Chapter 2 investigates the regulation of the MC1R neutral antagonist human β-defensin 3 (βD3). UV damage did not induce βD3 mRNA expression in ex vivo human skin explants. The induction of βD3 expression instead correlated with inflammatory cytokines including TNF.
Chapter 3 investigates the interdependence and cross talk between the two protective pathways downstream of MC1R. We directly tested the effect of MITF on the acceleration of NER and the effect of ATR on the induction of eumelanin synthesis following MC1R activation. MITF was not required for the acceleration of NER as mediated by ATR, however, the induction of transcription of enzymes involved in eumelanin synthesis was dependent upon ATR kinase activity.
Finally, Chapter 4 investigates the mechanism by which MC1R promoted proliferation and whether the two UV protective pathways downstream of MC1R could be selectively activated without the risk of melanocyte proliferation. MC1R signaling resulted in activation of the mechanistic target of rapamycin complex 1 (mTORC1), a major regulator of cell growth and proliferation. Inhibition of mTORC1 signaling via rapamycin prevented MC1R induced proliferation in vitro. Rapamycin, however, did not prevent MC1R induced eumelanin synthesis or the acceleration of NER in vitro or in vivo suggesting it is possible to selectively activate the beneficial signaling pathways without the risk of melanocyte proliferation.
The results of this dissertation suggest that MC1R signaling could be augmented in individuals to prevent UV induced damage.
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Donnelly, Steven. "Molecular mechanisms underlying mutations in Connexin 26 associated with genetically inherited skins disorders." Thesis, Glasgow Caledonian University, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.688293.
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Romano, Sara. "Dynamique des populations et communautés bactériennes au cours de l’hospitalisation et des infections associées aux soins : cas particulier de la chirurgie cardiaque." Thesis, Montpellier, 2015. http://www.theses.fr/2015MONT3515.
Full textAbstract:
Les microbiotes humains sont considérés comme des organes supplémentaires impliqués dans des pathologies diverses, y compris infectieuses. Les déséquilibres des microbiotes, ou dysbioses, créent des niches écologiques pathologiques ou pathobiomes. Ce nouveau paradigme de l'infection s'applique tout particulièrement aux infections opportunistes. Dans ce travail, nous considérons des infections associées aux soins (IAS), les infections du site opératoire en chirurgie cardiaque, comme le résultat d'une pathologie de niche et nous étudions la dynamique des communautés et des populations microbiennes comme conditions d'émergence et de succès de l'agent infectieux. La diversité et la dynamique du microbiote chirurgical superficiel et profond de patients opérés pour pontage aorto-coronarien montrent un remplacement partiel du microbiote pré-opératoire par un microbiote spécifique avec une résilience partielle lors de la cicatrisation. Un lien significatif est observé entre la composition microbiotique et les marqueurs de risque infectieux. Le suivi de la structure de population d'un agent pathogène reconnu en chirurgie cardiaque, Propionibacterium acnes, montre des fréquences différentielles de phylotypes selon les phases opératoires. La spécificité du microbiote opératoire consiste en une forte diversité de bactéries à Gram négatif dont certaines ont été décrites dans le microbiote de la peau saine. Nous avons réalisé une identification au niveau de l'espèce de ces bactéries de la peau saine qui s'avèrent atypiques parmi les bactéries humaines connues car elles évoquent une origine environnementale. Le réservoir cutané et non environnemental d'un pathogène opportuniste, Roseomonas mucosa, est démontré et trois populations de pathogène opportuniste à réservoir environnemental et/ou humain (Pseudomonas aeruginosa, Ochrobactrum antropi, O. intermedium) sont étudiés en termes de structure de population pour préciser les conditions de leur transmission et leur succès infectieux dans le contexte général du pathobiome et des niches écologiques perturbées. Ce contexte général permet d'organiser les résultats obtenus à diverses échelles (communauté, populations, espèces, phylotypes) pour proposer une vision intégrée et originale de la microbiologie des IASHuman microbiota are now considered as supplementary organs involved in diseases such as infections. Microbiota disequilibrium named dysbiosis creates impaired ecological niches (pathobiomes). This new paradigm of infection is particularly relevant for opportunistic infections. In this study, we consider one major type of healthcare associated infection (HAI), the surgical site infections after cardiothoracic surgery as a pathology of niche. We study the dynamics of microbial communities and populations as conditions for emergence and success of infectious agents.The diversity and dynamics of superficial and deep surgical microbiota in patients undergoing coronary artery bypass grafting show a partial replacement of the pre-operative microbiota by a specific surgical microbiota with partial resilience during healing. Significant links are found between microbiota composition and scores for infectious risk. The population structure of Propionibacterium acnes, a pathogen complicating cardiac surgery, shows variable frequencies of phylotypes according to operative stages. Surgical microbiota appears specific with high diversity of Gram-negative bacteria, some of them being previously described in healthy skin microbiota. At the species-level, these bacteria appear atypical among known human bacteria because they are related to environmental bacteria. We demonstrate the cutaneous reservoir of the opportunistic pathogen Roseomonas mucosa deemed, until now, to be environmental. Three populations of opportunistic pathogens (Pseudomonas aeruginosa, Ochrobactrum anthropi, O. intermedium) are structured in order to precise their transmission and their infectivity in the general context of impaired ecological niche and pathobiome.The results obtained at various microbiological scale (community, population, species, phylotype) are organized in this general context in order to delineate an original integrative vision of HAI
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Stumpp, Sebastien. "Le ski associatif en Alsace au temps du Reichsland (1896-1914) : tensions nationales, oppositions sociales, jeux institutionnels." Université Marc Bloch (Strasbourg) (1971-2008), 2007. http://www.theses.fr/2007STR20058.
Full textAbstract:
Notre travail s’attache à analyser le processus d’émergence et de diffusion du ski associatif en Alsace entre 1896 et 1914. Annexée au Reich depuis 1871, cette région constitue le lieu d’implantation de nombreux immigrés venus de l’ensemble des provinces de l’Empire. Les rapports qu’ils entretiennent avec les populations locales sont profondément déterminés par l’état des tensions politiques et sociales. L’étude du processus d’autonomisation sportive du ski, appréhendé à travers le concept de « configuration locale » (Elias), représente de ce point de vue une entrée intéressante pour comprendre les liens complexes qui se nouent entre autochtones et immigrés. La première partie (1896-1908) décrit les conditions d’introduction de cette pratique dans la région et les enjeux de fondation d’une Fédération de ski d’Alsace-Lorraine. La seconde partie (1908-1914) analyse le fonctionnement fédéral entre imposition du référent compétitif et revendications nationalesOur work consists in analyzing the process of emergence and spreading of ski clubs in Alsace between 1896 and 1914, This region was annexed to the German Reich in 1871 and became a settling place for immigrants from all the provinces of the empire. The relationship established with the local populations remains, throughout the annexation period (1871-1918), deeply determined by the state of the political and social tensions. The study of the process of sportization of skiing is from that point of view, an interesting entry to understand the complex links established between the locals and the immigrants and, finally, the local configuration (Elias). The first part (1896-1908) describes the conditions of appropriation of the skiing practice and the creation of the Fédération de ski d'Alsace-Lorraine. The second part (1908-1914) describes the consequences of federal development, between the imposition of a competitive reference and national tensions