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1.
Proc Natl Acad Sci U S A ; 121(32): e2402726121, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39083420

RESUMO

Since prion diseases result from infection and neurodegeneration of the central nervous system (CNS), experimental characterizations of prion strain properties customarily rely on the outcomes of intracerebral challenges. However, natural transmission of certain prions, including those causing chronic wasting disease (CWD) in elk and deer, depends on propagation in peripheral host compartments prior to CNS infection. Using gene-targeted GtE and GtQ mice, which accurately control cellular elk or deer PrP expression, we assessed the impact that peripheral or intracerebral exposures play on CWD prion strain propagation and resulting CNS abnormalities. Whereas oral and intraperitoneal transmissions produced identical neuropathological outcomes in GtE and GtQ mice and preserved the naturally convergent conformations of elk and deer CWD prions, intracerebral transmissions generated CNS prion strains with divergent biochemical properties in GtE and GtQ mice that were changed compared to their native counterparts. While CWD replication kinetics remained constant during iterative peripheral transmissions and brain titers reflected those found in native hosts, serial intracerebral transmissions produced 10-fold higher prion titers and accelerated incubation times. Our demonstration that peripherally and intracerebrally challenged Gt mice develop dissimilar CNS diseases which result from the propagation of distinct CWD prion strains points to the involvement of tissue-specific cofactors during strain selection in different host compartments. Since peripheral transmissions preserved the natural features of elk and deer prions, whereas intracerebral propagation produced divergent strains, our findings illustrate the importance of experimental characterizations using hosts that not only abrogate species barriers but also accurately recapitulate natural transmission routes of native strains.


Assuntos
Encéfalo , Cervos , Príons , Doença de Emaciação Crônica , Animais , Doença de Emaciação Crônica/transmissão , Camundongos , Encéfalo/metabolismo , Encéfalo/patologia , Príons/metabolismo , Príons/genética , Príons/patogenicidade , Camundongos Transgênicos
2.
Vet Pathol ; 60(4): 420-433, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37199487

RESUMO

Chronic wasting disease (CWD) is an infectious transmissible spongiform encephalopathy of cervids associated with the presence of a misfolded prion protein (PrPCWD). Progression of PrPCWD distribution has been described using immunohistochemistry and histologic changes in a single section of brain stem at the level of the obex resulting in scores from 0 (early) to 10 (terminal) in elk with naturally occurring CWD. Here we describe the spread and distribution of PrPCWD in peripheral tissues and spinal cord in 16 wild and 17 farmed Rocky Mountain elk (Cervus elaphus nelsoni) with naturally occurring CWD and correlate these findings with obex scores. Spinal cord and approximately 110 peripheral tissues were collected, processed, stained with hematoxylin and eosin, and immunolabeled with the anti-prion protein monoclonal antibody F99/97.6.1. The medial retropharyngeal and tracheobronchial lymph nodes were the first tissues to accumulate PrPCWD, followed by other lymphoid tissues, myenteric plexus, spinal cord, and finally tissues outside of the lymphatic and neural systems. However, the only significant histological lesion observed was mild spongiform encephalopathy in the dorsal column of the lower spinal cord in elk with an obex score of ≥9. Initial exposure to CWD prions may be through the respiratory system and spread appears to occur primarily via the autonomic nervous system. Therefore, we suggest using obex scores as a proxy for stage of disease progression and verifying with key peripheral tissues.


Assuntos
Cervos , Doenças Priônicas , Príons , Doença de Emaciação Crônica , Animais , Doença de Emaciação Crônica/patologia , Proteínas Priônicas , Doenças Priônicas/veterinária , Medula Espinal/patologia , Isoformas de Proteínas/metabolismo
3.
Horiz. enferm ; 32(3): 297-305, 2021.
Artigo em Espanhol | LILACS | ID: biblio-1353302

RESUMO

INTRODUCCIÓN: Ser adulto mayor conlleva a cambios físicos, psicológicos y sociales que se ven aún más afectados por comorbilidades como las enfermedades crónicas y el dolor. El propósito es interpretar las experiencias de vivir con dolor de los adultos mayores con enfermedades crónico-degenerativas. METODOLOGÍA: Diseño cualitativo de tipo fenomenológico, recolectado mediante un muestreo intencional a través de una entrevista semi estructurada, en la cual se seleccionó a la población adulta mayor con una patología crónico-degenerativa que haya experimentado dolor crónico; se analizaron los datos con el proceso cognitivo de Janice Morse, hasta llegar a la saturación de la información. Participaron 8 personas entre los 66 y 72 años, habiendo siete mujeres y un hombre. RESULTADOS: Se encontraron cuatro categorías: 1. El desgaste de vivir con dolor; 2. Cotidianidad del vivir con dolor; 3. Alternativas para aliviar el dolor, y 4. Afectación en el entorno social. CONCLUSIÓN: Ser adulto mayor trae muchos cambios en todas las esferas de la vida, sin embargo, el padecer una enfermedad crónica acelera toda esta transición, viéndose afectados la salud mental, físico y social, adaptando esta situación a su cotidianidad, buscando a su vez medios alternos que mitiguen o disminuya el dolor.


INTRODUCTION: Being an older adult leads to physical, psychological, and social changes that are further affected by comorbidities such as chronic diseases and pain. The purpose is to interpret the experiences of living in pain of older adults with chronic-degenerative diseases. METHOD: Qualitative phenomenological research, recollected by an intentional sampling through a semi-structured interview in which was selected the adult population with a chronic-degenerative pathology that have experienced an state of chronic pain. The data was analyzed with the cognitive process of Janice Morse and reached to a saturation of 8 participants. There were 8 participants between the ages of 66 and 72, with seven women and one man. RESULTS: Four categories were found: 1. Wearing of living with pain; 2. Daily Living with Pain; 3. Alternatives for Pain Relief, and 4. Social Affectation. CONCLUSION: Being an older adult brings many changes in all spheres of life, however, suffering from a chronic disease accelerates this whole transition, being affected mental, physical and social health, adapting this situation to its daily life, seeking in turn alternate means to mitigate or decrease pain.


Assuntos
Humanos , Masculino , Feminino , Idoso , Idoso/psicologia , Idoso Fragilizado/psicologia , Doença de Emaciação Crônica/psicologia , Dor Crônica/psicologia , Dor/prevenção & controle , Cognição , Doença de Emaciação Crônica/enfermagem , Dor Crônica/enfermagem , México
4.
Lab Anim (NY) ; 45(4): 140-2, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27003353

RESUMO

In a continuing effort to better understand the transmission and persistence of chronic wasting disease in wild populations of cervids, Colorado State University, Fort Collins houses two species of deer indoors to study the pathogenesis of chronic wasting disease. Here we report key aspects regarding the husbandry and medication of Reeves' muntjac and white-tailed deer in captivity for research purposes.


Assuntos
Experimentação Animal , Criação de Animais Domésticos/métodos , Cervos , Doença de Emaciação Crônica , Animais , Modelos Animais de Doenças , Feminino , Abrigo para Animais , Masculino
5.
San Salvador; s.n; 2016. 23 p. tab.
Tese em Espanhol | BISSAL, LILACS | ID: biblio-1247356

RESUMO

La presente investigación desarrolla un análisis acerca del grado de funcionalidad de las familias con paciente con enfermedad crónico degenerativa. El objetivo fue determinar el grado de funcionalidad familiar de las familias con paciente con enfermedad crónica degenerativa de la Comunidad Minerva durante el año 2015. Se realizó un estudio de tipo observacional descriptivo, se visitaron en su domicilio la población de la comunidad Minerva que tiene 100 familias inscritas en las fichas familiares, de las cuales se estudiaron a las que cumplieron los criterios de inclusión que fueron 40, los resultados obtenidos: según tipología familiar fue de familias extensas en un 45 % , 30% y 25% de las mixtas y nucleares, respectivamente, en relación con la prevalencia de enfermedades se encontró que un 65 % padece de Hipertensión arterial, un 25 % de diabetes mellitus y 5 % para cáncer y enfermedad renal, el grado de funcionalidad presente en las familias de los sujetos estudiados fue funcional en la mayoría con un 60%.En cuanto a cohesión 82.5% de semirelacionada. En cuanto a adaptabilidad un 82.5 % de familias son flexibles. En relación a los resultados del FACES III, se encontró a un 15 % de familias en rango medio, un 82.5% a familias balanceadas y un 2.5 % a familias extremas. Conclusiones: el grado de funcionalidad fue de un 82.5 % con familias balanceadas


Assuntos
Doença de Emaciação Crônica , Medicina de Família e Comunidade
6.
Rio de Janeiro; s.n; 2007. 211 p.
Tese em Português | LILACS | ID: lil-510710

RESUMO

Esta tese pretende contribuir para o desenvolvimento de respostas públicas rumo à diminuição do impacto do HIV/Aids nos campos, econômico, político e social tanto no nível coletivo quanto no individual. Discute aspectos téorico-conceituais das noções de risco e vulnerabilidade, mostrando que a atual aplicação e apropriação dessas noções na resposta à essa epidemia dificulta o reconhecimento dos problemas adicionais enfrentados após o diagnóstico. Apresenta as diversas formas de pobreza, desigualdade e exclusão a partir dos indicadores sociais comumente usados e respectivas lógicas construtivas. Questiona as afirmações recentes sobre a queda da desigualdade, da pobreza e da indigência no país; e considera que a desigualdade e a exclusão que afetam a população em geral é a mesma a afetar pessoas que vivem com HIV/Aids. Porém, aponta a existência de vulnerabilidade potencial, conceito desenvolvido nesta tese, na ausência de rede de suporte social. Para identificar e inferir sobre o que ocorre nas vidas das pessoas que vivem em situação de desigualdade ou exclusão após a infecção pelo HIV utiliza dados coletados em pesquisa de survey, discursos, estórias e memórias de casos reais da prática profissional desta autora. O objetivo desta tese é demonstrar que o conceito de vulnerabilidade aplicado após o diagnóstico é importante ferramenta para reconhecer e intervir sobre as dificuldades e problemas adicionais enfrentados. Ressalta a evolução da resposta brasileira à essa epidemia e demonstra as lacunas existentes como desafios a seu aperfeiçoamento. Conclui que o reconhecimento dos problemas adicionais após o diagnóstico e o uso do conceito de vulnerabilidade potencial abre novas possibilidades de enfrentamento do HIV/Aids e exige respostas públicas interligadas e intersetoriais.


This thesis aims to contribute to the development of public responses geared towards the reduction of the impact of HIV/Aids in economic, political and social terms, as well as at the individual level. It discusses theoretic and conceptual aspects of different notions ofrisk and vulnerability, showing that the current application of such notions to the response to that epidemic makes it difficult to acknowledge the additional problems faced after the diagnosis is made. It presents the different forms of poverty, inequality and exclusion taking the social indicators usually employed and their respective constructive logics as a starting point. It brings into question the recent statements made on the decline of inequality, poverty and indigence in the country; and it considers that the inequality andexclusion faced by the population in general is the same that affects the people who live with HIV/Aids. It points out, though, to the presence of a potentiation of vulnerability in this group, in the absence of a social protection network. In order to identify an infer about what happens in the lives of the people who live in a situation of inequality or exclusion after the HIV infection the thesis uses data collected in a survey, discourses, stories andmemories of real cases of the professional practice of the author. The goal of this thesis is to demonstrate that the concept of vulnerability applied after the diagnosis is an important tool to acknowledge and intervene on the additional difficulties and problems that are faced by people in that situation. The thesis stresses the evolution of the Brazilian response to that epidemic and demonstrates its existing gaps as challenges to its improvement. Itfinally concludes that acknowledging the problems faced after diagnosis and the utilization of the concept of potential vulnerability opens new possibilities to the fight against HIV/Aids and demands interconnected and intersectorial responses.


Assuntos
Humanos , Masculino , Feminino , Epidemiologia/tendências , HIV , Fatores Socioeconômicos/análise , Fatores Socioeconômicos/etnologia , Fatores Socioeconômicos/políticas , Pobreza/etnologia , Pobreza/psicologia , Políticas de Controle Social/tendências , Vulnerabilidade Social , Brasil/epidemiologia , Brasil/etnologia , Doença de Emaciação Crônica/epidemiologia , Doença de Emaciação Crônica/imunologia , Doença de Emaciação Crônica/sangue , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Infecções por HIV/sangue , Previdência Social/economia , Previdência Social/tendências
7.
Med Hypotheses ; 65(1): 47-54, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15893117

RESUMO

Prion diseases are rare neurodegenerative diseases of humans and animals with a lethal evolution. Animal prion infections, such as chronic wasting disease (CWD) and scrapie (sheep) have shown a pattern of horizontal transmission. CWD is an endemic disease that has been affecting thousands of domestic and wild cervids in US for the last three decades. The mode of contamination is not known, although direct contact between infected and non-infected animals via saliva, urine and feces have been considered. Increasing spread of CWD has raised concerns about the potential transmission to humans and the conversion of human prion protein by CWD-associated prions has been demonstrated in laboratory experiments. Fly larvae exposed to brain infected material were able to readily transmit scrapie to hamsters. Prion rods were identified in both larvae and fly pupae. New lines of evidence confirmed that adult flies are also able to express prion proteins. The most prevalent species of myiasis in cattle, sheep and wild cervids (Hypoderma spp.) present a very different life cycle from human myiasis, with a long contact with neurologic structures, such as the spinal canal and epidural fat, that are potentially rich in prion rods. Considering the huge amount of fly larvae that affects each animal, it is important to discuss the possibility that these ectoparasites could theoretically act as reservoirs and vectors for CWD and other prion diseases. It is critical to recognize all the possible factors involved in CWD transmission since ectoparasites could be handled in an easier way than the environmental persistence of infectious prions.


Assuntos
Dípteros/crescimento & desenvolvimento , Transmissão de Doença Infecciosa , Vetores de Doenças , Ectoparasitoses/parasitologia , Estágios do Ciclo de Vida , Doença de Emaciação Crônica/transmissão , Animais , Animais Domésticos , Animais Selvagens , Cervos , Reservatórios de Doenças , Larva , Modelos Biológicos , Miíase , Príons/fisiologia , Pupa , Medição de Risco , Fatores de Risco , Scrapie/transmissão , Carneiro Doméstico , Estados Unidos/epidemiologia , Doença de Emaciação Crônica/epidemiologia
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