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Cervical cancer is one of the most common forms of cancer in the world, and human papillomavirus (HPV) is a cause of the vast majority of these patient cases. With many HPV types being oncogenic in nature, HPV as a whole is responsible for over 5% of all cancers worldwide and 15% of cancer in women in developing countries. HPV is a sexually transmitted infection that is spread through contact with infected genital skin, mucosa, or bodily fluids from a partner with acute or subclinical viral infection. While less frequent, various strains of the virus are also responsible for anal and vaginal warts, anal cancer, and cancer of the vulva and penis – these account for approximately 50,000 cases per year worldwide. Data also suggest a potential implication of HPV in oropharyngeal cancers, especially among younger adults. Various behavioral and prophylactic approaches are recommended for the prevention of HPV infection and cancer. For example, there is evidence that behavioral change can be effective, such as condom use and limitation on the number of sexual partners. Besides this, in recent years we have seen the development of various prophylactic or therapeutic vaccines that are highly effective in the prevention of HPV pathogenesis. Despite this, barriers to treatment and prevention exist, making HPV a continuing threat to individuals most at-risk across the globe. Thus, this study reviewed a large collection of current HPV and related cancer literature to understand the process of infection and pathogenesis in various human sites as well as potential barriers to prevention and treatment that may be perpetuating the survival of the virus across the world. Analyzing current and past research on such barriers, this paper delves into important variables that can affect early detection and treatment of HPV, and also explores a novel and promising therapy currently in development that could be valuable in overcoming many of these issues.

Introduction Malaria retinopathy is a set of visible changes in the retina which are specific to falciparum malaria. Studies to date have been mostly limited to comatose African children. Retinal changes in adults with severe malaria and severely unwell patients without malaria have been less well studied and the specificity, pathogenesis, diagnostic and prognostic value of malarial retinopathy in adults are not known. Methods A series of observational studies of retinopathy in Bangladesh, India and Malaysia were done from 2008-2012. The aims were to describe the spectrum of retinal changes in falciparum and knowlesi malaria in adults, determine their specificity for severe falciparum malaria, quantify the impact of malaria retinopathy on visual function, understand its pathogenesis and assess the potential contribution of retinopathy to confirming diagnosis of malarial coma, predicting prognosis and understanding pathogenesis of cerebral malaria. Results 495 patients were enrolled and underwent retinal photography (305 with P. falciparum malaria (112 cerebral, 68 noncerebral severe, 125 uncomplicated), 44 P. knowlesi, 43 sepsis, 41 encephalopathy and 62 healthy). Retinal whitening and white-centred haemorrhages were common and specific to severe falciparum malaria. Retinopathy was most common and severe in cerebral (88%) and fatal (91%) falciparum malaria. Moderate-severe retinopathy was 95% specific for cerebral malaria in comatose patients, and its severity correlated with depth of coma. Vessel whitening was not seen and papilloedema was rare. In noncerebral severe falciparum malaria, retinopathy predicted increased likelihood of later development of coma and death. Retinal findings in Bangladeshi children were similar to those in adults. Optic nerve sheath diameter was mildly increased and brain swelling minimal on MRI. Severity of retinopathy correlated with plasma lactate, serum bicarbonate, sequestered parasite load and red cell stiffness suggesting a central role for microvascular obstruction in the pathogenesis. Severity of retinal whitening correlated with decreased visual acuity. Conclusions Retinal changes seen in severe P. falciparum malaria in Asian adults is similar, but not identical, to that seen in African children. They have potential to help with diagnosis and prognosis of Asian adults with severe falciparum malaria. Microvascular obstruction is prominent in the pathogenesis of retinopathy and coma in adults whereas raised intracranial pressure is not.

The proposed thesis contributes to the knowledge about tick-borne encephalitis and its pathogenesis. The thesis describes pathogenesis and immunopathogenesis of tick-borne encephalitis, impact of host's genotype in clinical course determination, immune response of patients with acute tick-borne encephalitis, the mechanism of tick-borne encephalitis virus migration into central nervous system and virus interaction with cells of neurovascular unit as well as potential medical interventions.

Submitted by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2015-10-26T14:15:02Z No. of bitstreams: 1 Luciane Amorim Santos. Leptospira... 2015Tese.pdf: 2475098 bytes, checksum: 1cc01b7226dc488ff72bd8c3d6df2c00 (MD5) / Approved for entry into archive by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2015-10-26T14:16:25Z (GMT) No. of bitstreams: 1 Luciane Amorim Santos. Leptospira... 2015Tese.pdf: 2475098 bytes, checksum: 1cc01b7226dc488ff72bd8c3d6df2c00 (MD5) / Made available in DSpace on 2015-10-26T14:16:25Z (GMT). No. of bitstreams: 1 Luciane Amorim Santos. Leptospira... 2015Tese.pdf: 2475098 bytes, checksum: 1cc01b7226dc488ff72bd8c3d6df2c00 (MD5) Previous issue date: 2015 / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / A leptospirose é a zoonose mais disseminada mundialmente por infectar diversas espécies diferentes de animais mamíferos. Apresenta 22 espécies identificadas, sendo dez patogênicas, cinco intermediarias e sete saprofiticas, além de apresentar mais de 250 sorovares diferentes. Em Salvador, Leptospira interrogans sorovar Copenhageni é a causadora da epidemia urbana na cidade e apresenta ratos como seu hospedeiro reservatório. As formas clínicas da leptospirose podem variar de assintomática a formas graves. As manifestações clínicas mais graves envolve o desenvolvimento da síndrome Hemorrágica pulmonar severa, e óbito do paciente. Estudos para entender as diferenças genéticas entre as diferentes espécies e sorovares é de extrema importância para identificar fatores de virulência da bactéria, genes que possam está associado aos diferentes formas clinicas, e sua capacidade de se adaptar aos diferentes ambientes. Neste trabalho foi estudado o genoma de dois importantes serovares de L. interrogans, o sorovar Copenhageni e o serovar Icterohaemorrhagiae, e suas diferenças genéticas e associação com dados clínicos e epidemiológicos. Um total de 141 isolados tiveram seus genomas sequenciados. Foi construindo e validado um pipeline para a o mapeamento e construção dos genomas e a identificação de SNPs e Indels. Os resultados encontrados demostraram um alta similaridade entre os isolados dos dois serovares, de diferentes regiões geográficas e isolados em anos diferentes. As sequências deste estudo se mostram conservadas ao longo do tempo sem apresentar nenhuma mutação associada as diferentes forma clínicas da doença, indicando que outros fatores, tais como os do hospedeiro, podem estar envolvidos na diversidade de sintomatologia. Na comparação do genoma dos isolados de L. interrogans, sorovar Copenhageni e sorovar Icterohaemorrhagiae foi identificado apenas uma mutação que as difere geneticamente. Essa mutação está presente no gene LIC12008 que produz uma proteína hipotética, e que a sua avaliação in silico demostrou estar envolvida na síntese de LPS, justificando assim as diferenças encontradas no teste serológico. Além disto, também foram avaliadas as diferenças entre 20 das 22 espécies de Leptospira, para identificar possíveis fatores de virulência e genes que possam estar envolvidos na patogênese e adaptação da bactéria ao ambiente. Estudos de fatores genéticos da Leptospira pode auxiliar ao manejo da doença, com uma melhor assistência e terapia para os pacientes, desenvolvimento de vacinas e diagnostico desta doença negligenciada. / There are 22 different species of Leptospira spp. in which 10 are pathogenic, 5 intermediate and 7 saprophytic species. In Salvador the Leptospira interrogans sorovar Copenhageni is the main serovar detected, responsible for the urban epidemics, and has rats as their main host. The clinical manifestations of leptospirosis can vary from asymptomatic form to severe disease like pulmonary hemorrhagic syndrome, and death. Studies to understand de genetic differences among the species and serovars are of great importance to identify virulence factors, genes that could be related to the different clinical manifestations and its capacity to adapt in different environments. Here, the genome of two epidemiologically important serovar of the L. interrogans, the serovar Copenhageni and serovar Icterohaemorrhagiae, and their genetic differences and the association of these differences with epidemiological and clinical data were studied. A total of 141 strains were genome sequenced. A pipeline for the genome mapping and variant call were constructed and validated. The results showed a high similarity among the strains from both serovars from different geographic locations and year of isolation. The sequences from this study showed to be very conserved, not presenting any mutation associated with the different clinical outcome, indicating that other factors, like host factors, could be related to the diversity of clinical outcome. Only one genetic mutation was detected in the genome comparison of the strains belonging to the L. interrogans sorovar Copenhageni and sorovar Icterohaemorrhagiae. This mutation was found in the gene LIC12008 that produce a hypothetical protein, in which its in silico analysis reviled that this protein could be related to the LPS synthesis, justifying the serological test differences between the two serovar. Besides that, the differences between 20 of the 22 species of Leptospira identified were evaluated to detect possibly virulence factors and genes that could be involved in the pathogenesis and adaptation. Studies of the Leptospira virulence factors can give support to the disease management, giving a better assistance and treatment to the patients and developing vaccines and better diagnostic for the neglected disease

Made available in DSpace on 2014-06-11T19:33:25Z (GMT). No. of bitstreams: 0 Previous issue date: 2001Bitstream added on 2014-06-13T19:44:12Z : No. of bitstreams: 1 fernandes_cg_dr_botfm.pdf: 3174897 bytes, checksum: e5fb345fc410749c0ccd81aa96d672fb (MD5) / Realizou-se o estudo da patogenia de uma genodermatose mecanobolhosa que acomete búfalos Murrah. Para tal, 5 amostras de pele (íntegra, submetida a 3 graus diferentes de lesão e pele cicatrizada) de cada um dos 5 animais experimentais (4 do rebanho experimental/EMBRAPA-CPACT para obtenção de doentes e um de outro rebanho). As amostras foram destinadas a estudos de Imunofluorescência Direta para a pesquisa das frações do complemento e de auto-anticorpos, de Imuno-histoquímica para desmoplaquinas I e II e de Microscopia Eletrônica de Transmissão. A imunofluorescência foi negativa para frações C1 e C3 do complemento e para IgG nas peles dos búfalos doentes e nos controles negativos. As desmoplaquinas I e II apresentaram marcação idêntica nos doentes e controles. Na Microscopia Eletrônica verificou-se que a perda da adesão célula-célula é o evento primário na doença e que as alterações nos complexos desmossomos-tonofilamentos são conseqüência do primeiro. Os resultados desse trabalho permitem então concluir que a Genodermatose Mecanobolhosa dos Búfalos Murrah não tem caráter auto-imune e é uma doença dos desmossomos, que se deve provavelmente a alterações na estrutura e/ou estabilidade e funcionamento das caderinas desmossômicas e não a defeitos nas proteínas da placa do desmossomo. / The pathogenesis of a Mechanobullous Genodermatosis of Murrah Water Buffalos was studied. Five skin samples (undamaged, mild to severe injured and healed skin) from each one of five animals (4 from an EMBRAPA-CPACT experimental herd and 1 from another one) were collected. In these samples were performed tests of direct immunofluorescence to C1 and C3 complement fractions and IgG autoantibody, of desmoplakin I/II immunohistochemistry and of transmission electron microscopy. The immunofluorescence was negative to C1, C3 and IgG autoantibodies in skin of affected and normal water buffalo. Desmoplakin I/II immunostaining was similar in skin of affected and health. Electron microscopy revealed that the loss of cell-cell adhesion was a primary event in this disease. Disruption of tonofilaments-desmosomes complexes was consequence of the former lesion. With these results was possible to conclude that the Mechanobullous Genodermatosis of Murrah Water Buffalos is not an autoimmune disease. Desmossomos are the key-point in this illness that occur, probably, due to defects on stability, structure or function of desmosomal cadherins and not owing to alterations in desmosomal plaque proteins.

Orientador: Marcelo Brocchi / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-21T03:16:05Z (GMT). No. of bitstreams: 1 Moraes_MarcosHenriquede_M.pdf: 1961086 bytes, checksum: 56f96f9d1cad5160a5c9417fc809b09e (MD5) Previous issue date: 2012 / Resumo: Salmonella enterica é uma bactéria Gram-negativa classificada em diferentes sorovariedades que podem causar desde gastroenterites a infecções sistêmicas. A sorovariedade Enteritidis é predominante nos casos de salmonelose em humanos, tendo produtos derivados do frango como principal fonte de infecção. Uma forma de se controlar infecções por Enteritidis é através da vacinação de frangos, uma estratégia já utilizada, porém com limitações, pois estas vacinas muitas vezes são inativadas ou possuem origem de atenuação desconhecida. Outra limitação é a falta de estudos específicos para Enteritidis, pois maior parte dos estudos feitos com S. enterica se baseiam na sorovariedade Typhimurium. Um alvo para a construção de linhagens vacinais são os genes codificadores de Nucleoid Associated Proteins que são proteínas que se ligam ao DNA alterando sua topologia, afetando a transcrição global dos genes. Neste projeto realizamos a construção de mutantes nulos de S. enterica Enteritidis para alguns destes genes com a finalidade de avaliar seu potencial vacinal e papel na patogênese. As linhagens foram testadas no modelo de infecção sistêmica e de inflamação do ceco. No modelo de infecção sistêmica, a linhagem selvagem e ?fis se apresentaram virulentas ou pouco atenuadas enquanto as linhagens ?ihfA e ?ihfB foram atenuadas. Os testes de proteção foram feitos com os dois mutantes atenuados que induziram 100% de proteção. A linhagem selvagem e o mutante pouco atenuado induziram inflamação neste modelo, mas o mutante induziu de forma mais amena. Analises morfométricas futuras irão elucidar com mais clareza o papel deste gene na inflamação. Este projeto teve como principais realizações: (i) a construção de duas linhagens atenuadas, com alto potencial para uso vacinal e (ii) abriu novas possibilidades para o estudo nas NAP's durante a patogênese de diferentes sorovariedades / Abstract: enterica is a Gram-negative bacterium classified in different sorovars which may causes gastroenteritis and systemic infections. The serovar Enteritidis is responsible for most of the cases of salmonellosis in humans and have poultry based products as its main source of infection. Poultry vaccination has been and effective strategy to control Enteritidis infections and it's already applied, but with limitations, because the vaccines sometimes are inactivated or are attenuated by unknown mechanisms. Another limitation is the lack of studies especific to Enteritidis, most of the research related to S. enterica is based on serovar Typhimurium. A target to vaccine strains development are the genes members of the group called Nucleoid Associeted Proteins, which are proteins that bind to DNA changing its topology and affecting global gene transcription. In this project, we constructed S. enterica null mutants to some of these genes aiming the evaluation of their vaccine potential and and role in pathogenesis. The strains were tested with the systemic infection model and cecum inflamation. In the systemic infection model, the wild and ?fis strain were virulent while the ?ihfA and ?ihfB were attenuated. The protection essays were made with attenuated mutants and provided 100% of protection. The wild and ?fis strains lead to inflammation in this model, but the mutant induced a mild inflammation, morfometrics analysis will clarify the role of this gene in inflammation. This project have as main outcomes: (i) the construction of strains, ?ihfA and ?ihfB, with good potential to be used as vaccines; (ii) New possibilities to the role of fis gene during inflammation / Mestrado / Microbiologia / Mestre em Genética e Biologia Molecular

Submitted in fulfilment of the requirements of Master's Degree in Chemistry, Durban University of Technology, 2017. / DNA damage plays a pivotal role in the pathogenesis of Alzheimer’s disease (AD) therefore, an innovative ss-DNA/dopamine/TiO2/FTO electrode strategy was developed to detect the genotoxicity upon photocatalytic reactions. This study involves a computational and electrochemical investigation towards the direct measurement of DNA damage. Computational chemistry was useful to resolve the intricate chemistry problems behind electrode constructions. The computational protocols were simultaneously carried out comprising of density functional theory (DFT) calculations, Metropolis Monte Carlo (MC) adsorption studies, and molecular dynamics (MD) simulations. The DFT calculations elucidated the structural, electronics, and vibrational properties of the electrode components resulting in a good agreement with the experimental parameters. The MC simulations carried out using simulated annealing predicted the adsorption process within layer-by-layer electrode as well generating reliable inputs prior to MD simulations. A 100 ns MD simulations were performed using a canonical ensemble provided information on the thermodynamics parameters such as total energy, temperature, and potential energy profiles, including radius of gyrations and atomic density profiles. Binding energies calculated from the MD trajectories revealed increasing interaction energies for the layer-by-layer electrode, in agreement with the electrochemical characterization studies (i.e. gradual decrease of cyclic voltammogram (CV) as well as increasing diameter of electrochemical impedance spectroscopy (EIS) semicircle upon electrode modification). The higher binding energies may lead to smaller changes in the electrochemical polarizability which directly affect to the decreasing of redox peak current and charge transfer resistance enhancement. Instead, HOMO-LUMO DFT levels are also taken into account to explain electron transfer phenomena within layer construction leading to the alteration of CV behaviours. Experimentally, the ss-DNA was electronically linked to TiO2/FTO surface through dopamine as a molecular anchor. Electrochemical measurements using cyclic voltammetry and EIS were employed to characterize the electrode modifications. The square wave voltammetry was subsequently used to measure the DNA damage and the potency of antioxidant treatment using ascorbic acid (AA) due to its ability in protecting the DNA from the damages. The presence of AA significantly protected the DNA from the damage, therefore was able to be used as a potential treatment in AD. Theoretically, guanine residues predicted by DFT as the most reactive sites of the ss-DNA involved in the genotoxic reactions. Overall, the theoretical studies successfully validated the experimental study as well as providing the molecular basis of interaction phenomena towards electrode constructions. Our results highlight the potential application of this methodology to screen the genotoxicity in Alzheimer’s, suggesting the important role of theoretical studies to predict the molecular interaction and validation of the DNA-based sensors and bioelectronics. / M

Human Immunodeficiency Virus Type I, or HIV, is one of the most well-known and well-researched viruses in the world. The current standard of care for HIV infected individuals is an antiretroviral drug therapy regiment, or ART, started immediately after diagnosis. While this treatment is generally quite effective at keeping the viral load low and stopping the progression from HIV infection to AIDS, patients receiving ART therapy still have a lower life expectancy than uninfected individuals. Many times, the cause of death in these patients is not the common opportunistic pathogens and cancers linked to HIV and AIDS, but chronic health conditions that develop. One of these conditions that is seen in many of the HIV infected patients undergoing the antiretroviral therapy is cardiovascular disease, such as atherosclerosis and myocardial infarction. Research shows that one of the key players in developing these conditions in HIV patients is the chronic inflammation caused by the immune system attempts to control the level of the virus. By studying the links between HIV, inflammation, and cardiovascular disease, we may be able to find solutions to the development of chronic disease in HIV patients on antiretroviral therapy.

This thesis is an update of the bachelor work entitled "The application of physiotherapeutic tools for some tinnitus types". The original work was complemented with the latest findings in pathogenesis field and in therapy by physiotherapeutic tool. The fundamental of this diploma thesis is a study examining the quality of patients' lives with tinnitus. The study was based upon a research using a modified questionnaire Tinnitus Handicap Inventory by Newman's et. al. (1999). Powered by TCPDF (www.tcpdf.org)