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1.
Science ; 378(6619): 560-565, 2022 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-36264825

RESUMO

Monkeypox is a viral zoonotic disease endemic in Central and West Africa. In May 2022, dozens of non-endemic countries reported hundreds of monkeypox cases, most with no epidemiological link to Africa. We identified two lineages of monkeypox virus (MPXV) among two 2021 and seven 2022 US monkeypox cases: the major 2022 outbreak variant called B.1 and a minor contemporaneously sampled variant called A.2. Analyses of mutations among these two variants revealed an extreme preference for GA-to-AA mutations indicative of human APOBEC3 cytosine deaminase activity among Clade IIb MPXV (previously West African, Nigeria) sampled since 2017. Such mutations were not enriched within other MPXV clades. These findings suggest that APOBEC3 editing may be a recurrent and a dominant driver of MPXV evolution within the current outbreak.


Assuntos
Desaminases APOBEC , Interações Hospedeiro-Patógeno , Monkeypox virus , Mpox , Edição de RNA , Humanos , Mpox/enzimologia , Mpox/virologia , Monkeypox virus/genética , Monkeypox virus/isolamento & purificação , Nigéria/epidemiologia , Estados Unidos/epidemiologia , Mutação , Evolução Molecular , Desaminases APOBEC/metabolismo , Adenosina/genética , Citidina/genética
2.
Emerg Infect Dis ; 27(12): 3030-3035, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34570693

RESUMO

Nearly all cases of melioidosis in the continental United States are related to international travel to areas to which Burkholderia pseudomallei, the bacterium that causes melioidosis, is endemic. We report the diagnosis and clinical course of melioidosis in a patient from the United States who had no international travel history and the public health investigation to determine the source of exposure. We tested environmental samples collected from the patient's home for B. pseudomallei by PCR and culture. Whole-genome sequencing was conducted on PCR-positive environmental samples, and results were compared with sequences from the patient's clinical specimen. Three PCR-positive environmental samples, all collected from a freshwater home aquarium that had contained imported tropical fish, were a genetic match to the clinical isolate from the patient. This finding suggests a novel route of exposure and a potential for importation of B. pseudomallei, a select agent, into the United States from disease-endemic areas.


Assuntos
Burkholderia pseudomallei , Melioidose , Animais , Burkholderia pseudomallei/genética , Água Doce , Humanos , Melioidose/diagnóstico , Melioidose/epidemiologia , Reação em Cadeia da Polimerase , Estados Unidos/epidemiologia , Sequenciamento Completo do Genoma
3.
Schizophr Res ; 195: 74-75, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-28864280

RESUMO

Specialized First Episode Psychosis (FEP) services have been conceptualized in part around the issue of engagement. Creating treatment that is easier to access, with more frequent contacts, assertive outreach to clients between appointments, and an explicit youth-oriented culture could make services more attractive to those most in need of care. However, engagement has remained a mostly fuzzy, peripheral construct rather than the object of study in itself. As we recognize the importance of treatment engagement, we must prepare to address it more rigorously within psychosis and schizophrenia research. At the same time, factors enhancing or obstructing treatment engagement are inevitably local, rather than universal. The availability of care, its associated costs and stigmas, individuals' motivations for seeking treatment, and their beliefs and expectations about providers' roles are determined by local and cultural features. There can be no singular "best practice" for engagement - but curiosity about how culture and locale influence clients' willingness to participate in care, and creativity in how we account for and incorporate these variables into study designs, will help to shed light on the critical issue of engagement in FEP treatment.


Assuntos
Cultura , Gerenciamento Clínico , Transtornos Psicóticos/terapia , Humanos , Transtornos Psicóticos/psicologia
4.
EGEMS (Wash DC) ; 5(2): 1303, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28459085

RESUMO

CONTEXT: Telehealth is a fast-growing sector in health care, using a variety of technologies to exchange information across locations and to improve access, quality, and outcomes across the continuum of care. Thousands of studies and hundreds of systematic reviews have been done, but their variability leaves many questions about telehealth's effectiveness, implementation priorities, and return on investment. OBJECTIVES: There is an urgent need for a systematic, policy-relevant framework to integrate regulatory, operational, and clinical factors and to guide future investments in telehealth research and practice. METHODS: An invited multidisciplinary group of 21 experts from AcademyHealth, the American Telemedicine Association (ATA), Kaiser Permanente Institute for Health Policy (KP), and the Physician Insurers Association of America (PIAA) met to review and discuss the components of a draft framework for policy-relevant telehealth research. The framework was revised and presented in a challenge workshop at Concordium 2016, and some additional refinements were made. The current framework encompasses the regulatory and payment policy context for telehealth, delivery system factors, and outcomes of telehealth interventions. FINDINGS: Based on the feedback at Concordium 2016, the framework seems to have potential to help educate policymakers, payers, and health systems about the value of telehealth and to frame discussions about implementation barriers, including risk management concerns, technology costs, and organizational culture. However, questions remain about how to disseminate and use the framework to help coordinate policy, research, and implementation efforts in the delivery system.

5.
Biosecur Bioterror ; 12(1): 49-62, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24552362

RESUMO

Abrin is a heterodimeric toxin present in the seeds of the Abrus precatorius plant. The easily obtainable seeds can yield a highly toxic product that can be used in various types of biocrimes and terrorism-related activities, including "white-powder" letters. Although the vast majority of these threats are hoaxes, the lack of rapid and reliable detection assays for abrin, such as lateral flow assays (LFAs), can be an impediment to accurate and rapid hazard assessment. One of the complicating factors associated with LFAs is the use of antibodies of poor affinity and specificity that cross-react with near neighbors or that bind to plant lectins, which are capable of nonspecifically cross-linking the capture and detector antibodies. Because of the critical need to promote public safety and public health, we conducted a comprehensive laboratory evaluation of a commercial LFA for the rapid detection of abrin. This study was conducted using comprehensive inclusivity and exclusivity panels of abrin and near-neighbor plant materials, along with panels of lectins, related proteins, white powders, and environmental background material, to determine the sensitivity, specificity, limit of detection, dynamic range, and repeatability of the assay for the specific intended use of evaluating suspicious white powders and environmental samples for the presumptive presence of abrin.


Assuntos
Abrina/isolamento & purificação , Pós/química , Kit de Reagentes para Diagnóstico/normas , Terrorismo Químico , Pós/intoxicação , Fitas Reagentes , Sensibilidade e Especificidade , Estados Unidos
6.
Toxicol Appl Pharmacol ; 239(1): 1-12, 2009 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-19121331

RESUMO

The zebrafish model system is ideal for studying nervous system development. Ultimately, one would like to link the developmental biology to various aspects of behavior. We are studying the consequences of nicotine exposure on nervous system development in zebrafish and have previously shown that chronic nicotine exposure produces paralysis. We also have made observations that the embryos moved in the initial minutes of the exposure as the bend rates of the musculature increased. This nicotine induced behavior manifests as an increase in the rate of spinal musculature bends, which spontaneously begin at approximately 17 h post fertilization. The behavioral observations prompted the systematic characterization of nicotine-induced modulation of zebrafish embryonic motor output; bends of the trunk musculature. We first characterized embryonic motor output in zebrafish embryos with and without their chorions. We then characterized the motor output in embryos raised at 28 degrees C and 25 degrees C. The act of dechorionation along with temperature influenced the embryonic bend rate. We show that nicotine exposure increases embryonic motor output. Nicotine exposure caused the musculature bends to alternate in a left-right-left fashion. Nicotine was able to produce this phenotype in embryos lacking supraspinal input. We then characterize the kinetics of nicotine influx and efflux and demonstrate that nicotine as low as 1 microM can disrupt embryonic physiology. Taken together, these results indicate the presence of nicotinic acetylcholine receptors (nAChRs) associated with embryonic spinal motor circuits early in embryogenesis.


Assuntos
Embrião não Mamífero/efeitos dos fármacos , Nicotina/toxicidade , Agonistas Nicotínicos/toxicidade , Medula Espinal/efeitos dos fármacos , Peixe-Zebra/embriologia , Animais , Comportamento Animal/efeitos dos fármacos , Embrião não Mamífero/metabolismo , Modelos Animais , Atividade Motora/efeitos dos fármacos , Organogênese/efeitos dos fármacos , Receptores Nicotínicos/metabolismo , Medula Espinal/embriologia , Medula Espinal/metabolismo , Fatores de Tempo
7.
Expert Rev Mol Med ; 11: e3, 2009 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-19152719

RESUMO

There is now a large body of data indicating that the cannabinoid receptor type 2 (CB2) is linked to a variety of immune events. This functional relevance appears to be most salient in the course of inflammation, a process during which there is an increased number of receptors that are available for activation. Studies aimed at elucidating signal transduction events resulting from CB2 interaction with its native ligands, and of the role of exogenous cannabinoids in modulating this process, are providing novel insights into the role of CB2 in maintaining a homeostatic immune balance within the host. Furthermore, these studies suggest that the CB2 may serve as a selective molecular target for therapeutic manipulation of untoward immune responses, including those associated with a variety of neuropathies that exhibit a hyperinflammatory component.


Assuntos
Inflamação/imunologia , Sistema Nervoso/imunologia , Sistema Nervoso/patologia , Neuroimunomodulação/fisiologia , Receptor CB2 de Canabinoide/imunologia , Sequência de Aminoácidos , Animais , Humanos , Dados de Sequência Molecular , Receptor CB2 de Canabinoide/química , Pesquisa
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