RESUMO
American Indian and Alaska Native (AI/AN) communities have disproportionately been impacted by the opioid epidemic with the second highest opioid-related overdose death rates compared to other ethnic groups. The diversity among California AI/AN tribes, including regional differences in economic opportunities, tribal affiliation and organization, resources and infrastructure, requires a strong community-based partnership approach to assess global statewide patterns in service availability, acceptability, and utilization, as well as capturing the unique challenges and service needs within each region. This article describes a statewide community-based needs assessment of strengths and weakness among key informants in CA to identify facilitators and barriers to treatment of substance use disorders (SUD) and opioid use disorders (OUD). We conducted structured interviews of 21 healthcare professionals from Urban Indian Health Programs, Tribal clinics and community-based organizations throughout California. The interview assessed (1) barriers to accessing services; (2) risk factors; (3) protective factors; (4) community substance use description; (5) SUD and OUD services available; and (6) service system needs. Findings indicate an overall increase in SUD and OUD in AI/AN communities. Key informants discussed the importance of comprehensive and culturally centered care, wrap-around services, such as treatment of mental health issues alongside substance abuse, and the need for AI/AN-specific treatment facilities that integrate traditional and cultural activities into western health services.
Assuntos
/psicologia , Comportamento Cooperativo , Assistência à Saúde Culturalmente Competente , Indígenas Norte-Americanos/psicologia , Avaliação das Necessidades , Epidemia de Opioides/estatística & dados numéricos , Transtornos Relacionados ao Uso de Opioides , California , Humanos , Entrevistas como Assunto , Epidemia de Opioides/mortalidade , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Transtornos Relacionados ao Uso de Opioides/mortalidadeRESUMO
Nipah virus (NiV), a paramyxovirus in the genus Henipavirus, has a mortality rate in humans of approximately 75%. While several studies have begun our understanding of NiV particle formation, the mechanism of this process remains to be fully elucidated. For many paramyxoviruses, M proteins drive viral assembly and egress; however, some paramyxoviral glycoproteins have been reported as important or essential in budding. For NiV the matrix protein (M), the fusion glycoprotein (F) and, to a much lesser extent, the attachment glycoprotein (G) autonomously induce the formation of virus-like particles (VLPs). However, functional interactions between these proteins during assembly and egress remain to be fully understood. Moreover, if the F-driven formation of VLPs occurs through interactions with host cell machinery, the cytoplasmic tail (CT) of F is a likely interactive domain. Therefore, we analyzed NiV F CT deletion and alanine mutants and report that several but not all regions of the F CT are necessary for efficient VLP formation. Two of these regions contain YXXØ or dityrosine motifs previously shown to interact with cellular machinery involved in F endocytosis and transport. Importantly, our results showed that F-driven, M-driven, and M/F-driven viral particle formation enhanced the recruitment of G into VLPs. By identifying key motifs, specific residues, and functional viral protein interactions important for VLP formation, we improve our understanding of the viral assembly/egress process and point to potential interactions with host cell machinery.IMPORTANCE Henipaviruses can cause deadly infections of medical, veterinary, and agricultural importance. With recent discoveries of new henipa-like viruses, understanding the mechanisms by which these viruses reproduce is paramount. We have focused this study on identifying the functional interactions of three Nipah virus proteins during viral assembly and particularly on the role of one of these proteins, the fusion glycoprotein, in the incorporation of other viral proteins into viral particles. By identifying several regions in the fusion glycoprotein that drive viral assembly, we further our understanding of how these viruses assemble and egress from infected cells. The results presented will likely be useful toward designing treatments targeting this aspect of the viral life cycle and for the production of new viral particle-based vaccines.
Assuntos
Citoplasma/química , Vírus Nipah/química , Vírus Nipah/fisiologia , Proteínas Virais de Fusão/química , Proteínas Virais de Fusão/metabolismo , Vírion/metabolismo , Montagem de Vírus , Liberação de Vírus , Motivos de Aminoácidos , Animais , Citoplasma/metabolismo , Glicoproteínas/química , Humanos , Vírus Nipah/genética , Domínios Proteicos , Vacinas de Partículas Semelhantes a Vírus , Proteínas do Envelope Viral/metabolismo , Proteínas Virais de Fusão/genética , Proteínas da Matriz Viral/genética , Proteínas da Matriz Viral/metabolismo , Internalização do VírusRESUMO
The family Paramyxoviridae includes many viruses that significantly affect human and animal health. An essential step in the paramyxovirus life cycle is viral entry into host cells, mediated by virus-cell membrane fusion. Upon viral entry, infection results in expression of the paramyxoviral glycoproteins on the infected cell surface. This can lead to cell-cell fusion (syncytia formation), often linked to pathogenesis. Thus membrane fusion is essential for both viral entry and cell-cell fusion and an attractive target for therapeutic development. While there are important differences between viral-cell and cell-cell membrane fusion, many aspects are conserved. The paramyxoviruses generally utilize two envelope glycoproteins to orchestrate membrane fusion. Here, we discuss the roles of these glycoproteins in distinct steps of the membrane fusion process. These findings can offer insights into evolutionary relationships among Paramyxoviridae genera and offer future targets for prophylactic and therapeutic development.
RESUMO
Fractures of the scaphoid are uncommon childhood injuries that can usually be successfully managed by standard immobilization techniques. However, scaphoid waist fractures are less frequent in children and may proceed to nonunion. The authors retrospectively reviewed the charts and radiographs of 19 adolescents with 20 scaphoid waist fractures that had required operative intervention for nonunion from January 1975 to December 2000. All cases had undergone a trial of plaster immobilization, averaging 4.2 months, before operative intervention was performed. Operative management resulted in a 100% rate of union. Herbert or AO screw fixation and grafting was performed in 11, 2 had K-wire fixation and bone grafting, 6 had bone grafting and no fixation, and one had screw fixation with no graft. All but three patients were available for telephone interview, with an average follow-up of 6.1 years. One reported having mild pain at rest, 4 had discomfort with heavy activity, and the remaining 12 were pain-free. Only two had restriction of activity because of pain, with the remainder returning to previous levels of function. All but one reported complete satisfaction with the results of their operation. Operative intervention of nonunion of scaphoid waist fractures in children consistently offers successful fusion, with very low rates of nonunion and a high rate of patient satisfaction.
Assuntos
Fraturas não Consolidadas/cirurgia , Osso Escafoide/lesões , Adolescente , Parafusos Ósseos , Transplante Ósseo , Feminino , Consolidação da Fratura , Fraturas não Consolidadas/diagnóstico por imagem , Humanos , Masculino , Radiografia , Estudos Retrospectivos , Osso Escafoide/diagnóstico por imagemRESUMO
We report a retrospective analysis of all cases of acute knee injuries in children presenting to the Winnipeg Children's Hospital, University of Manitoba, between Jan. 1, 1994, and Jan. 1, 1995. The mechanism of injury was recorded and all 3 radiographic views (i.e., anterioposterior, lateral and skyline) were available for 171 of 256 total cases. We found a significant association between mechanism of injury and visualization of damage on skyline view radiographs (p < 0.01). The skyline view showed damage in only 1 of the 158 cases involving direct or indirect injury not involving subluxation or dislocation. However, damage was visualized on skyline view radiographs in 7 (54%) of the 13 cases that included a history of subluxation or dislocation. We conclude that in acute knee trauma in children, a skyline view radiograph of the patella should be obtained only when the mechanism of injury includes subluxation or dislocation. When the mechanism does not suggest subluxation or dislocation, the skyline view is unlikely to reveal damage; it adds unnecessary radiation, cost and possible added discomfort for the child.