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1.
PLoS Pathog ; 17(2): e1009285, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33524073

RESUMO

Herpes simplex virus encephalitis (HSE) is the most common cause of sporadic viral encephalitis, and despite targeted antiviral therapy, outcomes remain poor. Although the innate immune system is critical for restricting herpes simplex virus type I (HSV-1) in the brain, there is evidence that prolonged neuroinflammation contributes to HSE pathogenesis. In this study, we investigated the contribution of inflammasomes to disease pathogenesis in a murine model of HSE. Inflammasomes are signaling platforms that activate the pro-inflammatory cytokines interleukin-1ß (IL-1ß) and IL-18. We found that mice deficient in the inflammasome adaptor protein, apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC), had significantly improved survival and lower levels of IL-1ß and IL-18 in the brain. Importantly, this difference in survival was independent of viral replication in the central nervous system (CNS). We found that microglia, the resident macrophages of the CNS, are the primary mediators of the ASC-dependent inflammasome response during infection. Using in vitro glial infections and a murine HSE model, we demonstrate that inflammasome activation contributes to the expression of chemokine (C-C motif) ligand 6 (CCL6), a leukocyte chemoattractant. The lower concentration of CCL6 in the brains of ASC-/- mice correlated with lower numbers of infiltrating macrophages during infection. Together, these data suggest that inflammasomes contribute to pathogenic inflammation in HSE and provide a mechanistic link between glial inflammasome activation and leukocyte infiltration. The contribution of inflammasomes to survival was independent of viral replication in our study, suggesting a promising new target in combating harmful inflammation in HSE.


Assuntos
Proteínas Adaptadoras de Sinalização CARD/imunologia , Encefalite por Herpes Simples/imunologia , Encefalite por Herpes Simples/mortalidade , Inflamassomos/imunologia , Animais , Encéfalo/imunologia , Células Cultivadas , Quimiocinas CC/imunologia , Chlorocebus aethiops , Modelos Animais de Doenças , Feminino , Mediadores da Inflamação/imunologia , Interleucina-1beta/imunologia , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia/imunologia , Células Vero
2.
J Rheumatol ; 48(5): 638-647, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33060316

RESUMO

Knee osteoarthritis (OA) is a serious disease and has no cure to date. Knee OA is a leading cause of functional limitation (e.g., difficulty walking). Walking speed is 1 method of quantifying difficulty with walking and should be assessed in clinical practice for adults with knee OA because it has prognostic value and is modifiable. Specifically, slow walking speed is associated with increased risk of adverse health outcomes, including all-cause mortality in adults with knee OA and can be modified by engaging in physical activity or exercise. However, at present, there is little consensus on the distance and instructions used to conduct the walk test. Distance is often selected based on space availability, and instruction varies, from asking the participants to walk at a comfortable pace versus as fast as possible. Therefore, the purpose of this narrative review is to summarize the measurement properties, strengths, and limitations of a fixed-distance walk test ≤ 40 meters in adults with knee OA. Good measurement properties in terms of reliability and validity were observed across the different testing protocols for fixed-distance walk test (i.e., any distance ≤ 40 m and fast- or self-paced). Therefore, clinicians and researchers can select a testing protocol that can safely and consistently be performed over time, as well as provide a practice trial to acclimatize the patients to the fixed-distance walk test.


Assuntos
Osteoartrite do Joelho , Adulto , Humanos , Osteoartrite do Joelho/diagnóstico , Reprodutibilidade dos Testes , Teste de Caminhada , Caminhada , Velocidade de Caminhada
5.
J Inj Violence Res ; 3(1): 19-23, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21483210

RESUMO

BACKGROUND: Because individual practitioner's commitment to routine screening for IPV is the greatest predictor that women will be screened and referred for services, it is vital that screeners are dedicated, knowledgeable, and confident in their ability to recognize and assist victims of violence. Self-efficacy has been consistently linked in the literature with successful outcomes. OBJECTIVES: Intimate partner violence (IPV) constitutes a major public health problem. In the absence of Federal or State regulation, individual hospitals and systems are left to develop their own policies and procedures. This paper describes the policies and procedures developed by an American domestic violence counseling and resource center. DESIGN: Post test surveys were used. SETTINGS: Hospitals, medical offices, and medical schools surrounding an urban area in Pennsylvania participated. PARTICIPANTS: 320 nurses and medical students participated in training provided by a domestic violence center. METHODS: Post test surveys measured self-efficacy, the perceived usefulness of screening the accessibility of victim services, understanding of obstacles faced by victims, and knowledge-level regarding local IPV services. Participants also self-reported their gender, age, race, and position with the hospital system. RESULTS: Nurses and medical interns exhibit a wide range of self-efficacy regarding their ability to screen victims of intimate partner violence. Intimate partner violence (IPV) training yielded participants who were better informed about IPV services and the obstacles faced by victims. CONCLUSIONS: In the absence of uniform screening guidelines, hospitals, systems, and individual practitioners must be vigilant in screening procedures. Partnerships with women's centers may provide valuable resources and training that may ultimately improve patient care.


Assuntos
Programas de Rastreamento/métodos , Autoeficácia , Maus-Tratos Conjugais/prevenção & controle , Adulto , Serviço Hospitalar de Emergência , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Programas de Rastreamento/psicologia , Pessoa de Meia-Idade , Pennsylvania , Análise de Regressão , Adulto Jovem
6.
Adolescence ; 40(160): 749-60, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16468669

RESUMO

This study furthers the current understanding of optimistic bias regarding youth violence among high school students. Results from a survey of 387 urban high school students indicate a wide range of predictors of optimistic bias, including experience, demographics, and attitudes. Linkages to other developmental frameworks (personal fable and self-efficacy) suggest future directions for additional research.


Assuntos
Comportamento do Adolescente/psicologia , Atitude , Vítimas de Crime/psicologia , Assunção de Riscos , Estudantes/psicologia , Violência/psicologia , Adolescente , Vítimas de Crime/estatística & dados numéricos , Negação em Psicologia , Feminino , Humanos , Masculino , Pennsylvania , Fatores de Risco , Instituições Acadêmicas , Autoeficácia , Estudantes/estatística & dados numéricos , Inquéritos e Questionários , População Urbana , Violência/prevenção & controle , Violência/estatística & dados numéricos
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