Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 8 de 8
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Alzheimers Dement ; 19(2): 696-707, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35946590

RESUMO

Clinical trials for Alzheimer's disease (AD) are slower to enroll study participants, take longer to complete, and are more expensive than trials in most other therapeutic areas. The recruitment and retention of a large number of qualified, diverse volunteers to participate in clinical research studies remain among the key barriers to the successful completion of AD clinical trials. An advisory panel of experts from academia, patient-advocacy organizations, philanthropy, non-profit, government, and industry convened in 2020 to assess the critical challenges facing recruitment in Alzheimer's clinical trials and develop a set of recommendations to overcome them. This paper briefly reviews existing challenges in AD clinical research and discusses the feasibility and implications of the panel's recommendations for actionable and inclusive solutions to accelerate the development of novel therapies for AD.


Assuntos
Doença de Alzheimer , Humanos , Doença de Alzheimer/tratamento farmacológico , Seleção de Pacientes
2.
Front Neurol ; 13: 1031091, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36530625

RESUMO

Biomarker discovery, development, and validation are reliant on large-scale analyses of high-quality samples and data. Currently, significant quantities of data and samples have been generated by European studies on Alzheimer's disease (AD) and other neurodegenerative diseases (NDD), representing a valuable resource for developing biomarkers to support early detection of disease, treatment monitoring, and patient stratification. However, discovery of, access to, and sharing of data and samples from AD and NDD research are hindered both by silos that limit collaboration, and by the array of complex requirements for secure, legal, and ethical sharing. In this Perspective article, we examine key challenges currently hampering large-scale biomarker research, and outline how the European Platform for Neurodegenerative Diseases (EPND) plans to address them. The first such challenge is a fragmented landscape filled with technical barriers that make it difficult to discover and access high-quality samples and data in one location. A second challenge is related to the complex array of legal and ethical requirements that must be navigated by researchers when sharing data and samples, to ensure compliance with data protection regulations and research ethics. Another challenge is the lack of broad-scale collaboration and opportunities to facilitate partnerships between data and sample contributors and researchers, in addition to a lack of regulatory engagement early in the research process to enable validation of potential biomarkers. A further challenge facing projects is the need to remain sustainable beyond initial funding periods, ensuring data and samples are shared and reused, thereby driving further research and innovation. In addressing these challenges, EPND will enable an environment of faster and more disruptive research on diagnostics and disease-modifying therapies for Alzheimer's disease and other neurodegenerative diseases.

3.
BMJ Glob Health ; 5(12)2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33272938

RESUMO

This paper introduces a framework for conducting and disseminating mixed methods research on positive outlier countries that successfully improved their health outcomes and systems. We provide guidance on identifying exemplar countries, assembling multidisciplinary teams, collecting and synthesising pre-existing evidence, undertaking qualitative and quantitative analyses, and preparing dissemination products for various target audiences. Through a range of ongoing research studies, we illustrate application of each step of the framework while highlighting key considerations and lessons learnt. We hope uptake of this comprehensive framework by diverse stakeholders will increase the availability and utilisation of rigorous and comparable insights from global health success stories.


Assuntos
Saúde Global , Avaliação de Resultados em Cuidados de Saúde , Humanos
5.
J Bacteriol ; 187(7): 2225-32, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15774863

RESUMO

The toxin-coregulated pilus (TCP) of Vibrio cholerae and the soluble TcpF protein that is secreted via the TCP biogenesis apparatus are essential for intestinal colonization. The TCP biogenesis apparatus is composed of at least nine proteins but is largely uncharacterized. TcpC is an outer membrane lipoprotein required for TCP biogenesis that is a member of the secretin protein superfamily. In the present study, analysis of TcpC in a series of strains deficient in each of the TCP biogenesis proteins revealed that TcpC was absent specifically in a tcpQ mutant. TcpQ is a predicted periplasmic protein required for TCP biogenesis. Fractionation studies revealed that the protein is not localized to the periplasm but is associated predominantly with the outer membrane fraction. An analysis of the amount of TcpQ present in the series of tcp mutants demonstrated the inverse of the TcpC result (absence of TcpQ in a tcpC deletion strain). Complementation of the tcpQ deletion restored TcpC levels and TCP formation, and similarly, complementation of tcpC restored TcpQ. Metal affinity pull-down experiments performed using His-tagged TcpC or TcpQ demonstrated a direct interaction between TcpC and TcpQ. In the presence of TcpQ, TcpC was found to form a high-molecular-weight complex that is stable in 2% sodium dodecyl sulfate and at temperatures below 65 degrees C, a characteristic of secretin complexes. Fractionation studies in which TcpC was overexpressed in the absence of TcpQ showed that TcpQ is also required for proper localization of TcpC to the outer membrane.


Assuntos
Proteínas da Membrana Bacteriana Externa/fisiologia , Proteínas de Fímbrias/fisiologia , Fímbrias Bacterianas/fisiologia , Lipoproteínas/fisiologia , Vibrio cholerae/fisiologia , Sequência de Aminoácidos , Proteínas da Membrana Bacteriana Externa/genética , Proteínas de Fímbrias/genética , Lipoproteínas/genética , Dados de Sequência Molecular , Mutação , Vibrio cholerae/genética , Vibrio cholerae/ultraestrutura
6.
Chem Biodivers ; 1(7): 1036-57, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17191897

RESUMO

Cholera, an enteric disease that can reach pandemic proportions, remains a world-wide problem that is positioned to increase in incidence as changes in global climate or armed conflict spawn the conditions that enhance transmission to humans and, thus, precipitate epidemic cholera. An effective subunit cholera vaccine that can provide protective immunity with one parenteral immunization would be a major advantage over the existing oral vaccines that can require two doses for optimal protection. The existing vaccines are clearly effective in some settings, but are less so in others, especially with respect to specific groups such as young (2-5 years) children. In our efforts to develop a cholera subunit vaccine, we focused on two Vibrio cholerae antigens, LPS (lipopolysaccharide) and TCP (toxin co-regulated pilus), that are known to induce protective antibodies in animal models and, in the case of anti-LPS antibodies, to be associated with clinical protection of V. cholerae exposed or vaccinated individuals. This review discusses the current cholera vaccines and compares the advantages of a cholera subunit vaccine to that of the whole cell vaccines. We discuss the possible subunit antigens and prospective targeted use of a subunit cholera vaccine.


Assuntos
Vacinas contra Cólera/química , Cólera/prevenção & controle , Animais , Cólera/transmissão , Vacinas contra Cólera/uso terapêutico , Humanos , Tecnologia Farmacêutica/tendências , Vacinas Atenuadas/química , Vacinas Atenuadas/uso terapêutico , Vacinas de Produtos Inativados/química , Vacinas de Produtos Inativados/uso terapêutico , Vacinas de Subunidades Antigênicas/química , Vacinas de Subunidades Antigênicas/uso terapêutico
7.
Mol Microbiol ; 49(1): 81-92, 2003 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12823812

RESUMO

Colonization of the human small intestine by Vibrio cholerae requires the type 4 toxin co-regulated pilus (TCP). Genes encoding the structure and biogenesis functions of TCP are organized within an operon located on the Vibrio Pathogenicity Island (VPI). In an effort to elucidate the functions of proteins involved in TCP biogenesis, in frame deletions of all of the genes within the tcp operon coding for putative pilus biogenesis proteins have been constructed and the resulting mutants characterized with respect to the assembly and function of TCP. As a result of this analysis, we have identified the product of one of these genes, tcpF, as a novel secreted colonization factor. Chromosomal deletion of tcpF yields a mutant that retains in vitro phenotypes associated with the assembly of functional TCP yet is severely attenuated for colonization of the infant mouse intestine. Furthermore, we have determined that the mechanism by which TcpF is translocated across the bacterial outer membrane requires the TCP biogenesis machinery and is independent of the type II extracellular protein secretion (EPS) system. These results suggest a dual role for the TCP biogenesis apparatus in V. cholerae pathogenesis and a novel mechanism of intestinal colonization mediated by a soluble factor.


Assuntos
Proteínas de Fímbrias/metabolismo , Fímbrias Bacterianas/metabolismo , Vibrio cholerae/metabolismo , Animais , Antígenos de Bactérias/genética , Antígenos de Bactérias/metabolismo , Proteínas de Fímbrias/genética , Fímbrias Bacterianas/genética , Deleção de Genes , Teste de Complementação Genética , Humanos , Camundongos , Óperon , Vibrio cholerae/genética
8.
J Bacteriol ; 184(8): 2305-9, 2002 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11914364

RESUMO

In Vibrio cholerae, elaboration of toxin-coregulated pilus and protein secretion by the extracellular protein secretion apparatus occurred in the absence of both TonB systems. In contrast, the cognate putative ATPases were required for each process and could not substitute for each other.


Assuntos
Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/fisiologia , Fímbrias Bacterianas/fisiologia , Proteínas de Membrana/fisiologia , Vibrio cholerae/fisiologia , Adenosina Trifosfatases/fisiologia , Trifosfato de Adenosina/metabolismo , Força Próton-Motriz
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...