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1.
Proc Natl Acad Sci U S A ; 120(29): e2309250120, 2023 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-37406089
2.
AMIA Jt Summits Transl Sci Proc ; 2023: 562-571, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37350890

RESUMO

Online health forums are used by patients and caregivers as community and information resources, especially for chronic disease management, and could help determine user needs for digital health app design. This study aims to assess the feasibility of using online forum posts on Alzheimer's disease to inform user needs in mobile health application design and whether this process can be automated through text clustering methods. A total of 413 posts were analyzed manually through thematic coding and yielded three themes and nine subthemes for patient and caregiver needs. The external evaluation showed fair to substantial similarity between the automatically and manually derived labels. Four personas were developed to assess the validity of forum-generated needs. These results establish that health forum data can provide sufficient information to understand user needs. However, further refinement of the analysis process and algorithm is necessary to generalize this method to other disease conditions and types of forum data.

3.
J Econ Psychol ; 962023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37092036

RESUMO

Saving disposition, the tendency to save rather than consume, has been found to be associated with economic outcomes. People lacking the disposition to save are more likely to experience financial distress. This association could be driven by other economic factors, behavioral traits, or even genetic effects. Using a sample of 3,920 American twins, we develop scales to measure saving disposition and financial distress. We find genetic influences on both traits, but also a large effect of the rearing family environment on saving disposition. We estimate that 44% of the covariance between the two traits is due to genetic effects. Saving disposition remains strongly associated with lower financial distress, even after controlling for family income, cognitive ability, and personality traits. The association persists within families and monozygotic twin pairs; the twin who saves more tends to be the twin who experiences less financial distress. This result suggest that there is a direct association between saving disposition and financial distress, although the direction of causation remains unclear.

4.
Oncology (Williston Park) ; 32(9): 437-42, 444, 2018 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-30248163

RESUMO

Oxaliplatin-based chemotherapy (FOLFOX [folinic acid, fluorouracil, oxaliplatin] or XELOX [oxaliplatin, capecitabine; also called CAPOX]) for 6 months is the current standard for adjuvant therapy of stage III colon cancer patients with good performance status. However, these regimens are associated with significant toxicities, including myelosuppression, diarrhea, and oxaliplatin-induced, cumulative, dose-dependent neurotoxicity. A reduced duration of adjuvant therapy, which would reduce overall toxicity while maintaining overall clinical efficacy, would be optimal. The goal of the International Duration Evaluation of Adjuvant (IDEA) study was to evaluate the noninferiority of 3-month compared with 6-month adjuvant oxaliplatin-based treatment in stage III colon cancer using a prospectively designed pooled analysis of 6 concurrently conducted phase III randomized trials. Herein, we review the findings of the IDEA study and discuss the optimal duration of oxaliplatin-based adjuvant chemotherapy using patient-based risk factors.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias do Colo , Desoxicitidina/análogos & derivados , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Fluoruracila/análogos & derivados , Conduta do Tratamento Medicamentoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina , Quimioterapia Adjuvante , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Desoxicitidina/farmacologia , Desoxicitidina/uso terapêutico , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Humanos , Leucovorina/farmacologia , Estadiamento de Neoplasias , Compostos Organoplatínicos/farmacologia , Oxaloacetatos , Fatores de Tempo , Resultado do Tratamento
5.
J Allergy Clin Immunol ; 130(3): 587-96, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22935587

RESUMO

BACKGROUND: Eosinophils are blood cells that are often found in high numbers in the tissues of allergic conditions and helminthic parasite infections. The pathophysiologic roles that eosinophils may serve in other human "eosinophil-associated" diseases remain obscure. OBJECTIVE: National Institutes of Health (NIH) Institutes and the Office of Disease Prevention assembled an international taskforce of clinical and basic scientists with the charge to propose and prioritize unmet research needs in eosinophil-associated diseases. METHODS: The taskforce used an organ system approach to identify the different and common themes of eosinophil cell involvement in these diseases. In early 2012, a draft document was circulated for review. The document was amended and the prioritizations were set at a NIH-organized workshop in June 2012. RESULTS: The taskforce identified significant research needs. These needs cross disease entities but some are disease specific. There are substantial shortcomings to the various preclinical animal models, as well as significant gaps in our epidemiologic, pathophysiologic, diagnostic, prognostic, and therapeutic knowledge. The taskforce recognized that recent efforts by patient advocacy groups have played instrumental roles in improving the identification and characterization of these disorders. However, communications among the eosinophil-interested communities, for example, governmental funding and regulatory agencies, and industry and clinician scientists need to be more comprehensive. CONCLUSIONS: Significant efforts are required to address our knowledge gaps to improve the outcomes of eosinophil-associated diseases. NIH Institutes, other federal agencies, lay organizations, and the pharmaceutical industry should consider the taskforce's recommendations in their future research activities.


Assuntos
Eosinofilia/complicações , Eosinófilos/fisiologia , Pesquisa Biomédica , Doenças Cardiovasculares/etiologia , Eosinofilia/diagnóstico , Gastroenteropatias/etiologia , Humanos , Doenças Respiratórias/etiologia , Dermatopatias/etiologia
6.
J Immunol Methods ; 375(1-2): 138-47, 2012 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-22019643

RESUMO

Mouse models of eosinophilic disorders are often part of preclinical studies investigating the underlying biological mechanisms of disease pathology. The presence of extracellular eosinophil granule proteins in affected tissues is a well established and specific marker of eosinophil activation in both patients and mouse models of human disease. Unfortunately, assessments of granule proteins in the mouse have been limited by the availability of specific antibodies and a reliance on assays of released enzymatic activities that are often neither sensitive nor eosinophil specific. The ability to detect immunologically and quantify the presence of a mouse eosinophil granule protein in biological fluids and/or tissue extracts was achieved by the generation of monoclonal antibodies specific for eosinophil peroxidase (EPX). This strategy identified unique pairs of antibodies with high avidity to the target protein and led to the development of a unique sandwich ELISA for the detection of EPX. Full factorial design was used to develop this ELISA, generating an assay that is eosinophil-specific and nearly 10 times more sensitive than traditional OPD-based detection methods of peroxidase activity. The added sensitivity afforded by this novel assay was used to detect and quantify eosinophil degranulation in several settings, including bronchoalveolar fluid from OVA sensitized/challenged mice (an animal model of asthma), serum samples derived from peripheral blood recovered from the tail vasculature, and from purified mouse eosinophils stimulated ex vivo with platelet activating factor (PAF) and PAF + ionomycin. This ability to assess mouse eosinophil degranulation represents a specific, sensitive, and reproducible assay that fulfills a critical need in studies of eosinophil-associated pathologies in mice.


Assuntos
Anticorpos Monoclonais/imunologia , Degranulação Celular/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Proteínas Granulares de Eosinófilos/imunologia , Peroxidase de Eosinófilo/sangue , Peroxidase de Eosinófilo/imunologia , Eosinófilos/imunologia , Animais , Líquido da Lavagem Broncoalveolar/imunologia , Proteínas Granulares de Eosinófilos/metabolismo , Peroxidase de Eosinófilo/análise , Peroxidase de Eosinófilo/metabolismo , Eosinófilos/metabolismo , Humanos , Leucócitos/imunologia , Leucócitos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Sensibilidade e Especificidade
7.
J Leukoc Biol ; 71(6): 1033-41, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12050190

RESUMO

Eosinophil migration from circulation is controlled, in part, by chemokines through a family of G-protein-coupled chemokine receptors (CCR). Studies of human eosinophils have demonstrated that signaling through CCR3 receptors is a prominent pathway leading to chemotaxis, although several other receptor-ligand interactions also appear to mediate eosinophil recruitment. The availability of genetically unique strains of mice permits a reductionist approach to assess the signaling pathways in experimental models of human disease. However, despite similarities in these pathways between mice and humans, significant species differences exist, complicating the translation of results from animal models to humans. Purified mouse eosinophils were used in this study to investigate the chemokine receptor expression and the activities of 18 chemokines. Mouse eosinophils isolated from IL-5 transgenic mice expressed transcripts encoding the chemokine receptors CCR1, CCR2, CCR3, CCR5, CCR8, CXCR2, and CXCR4, but not CCR4. Mouse eosinophils also migrated in response to human and mouse eotaxin-1 and -2, but not human eotaxin-3. In addition, the induced migration of mouse eosinophils by TARC, MIP-1beta, and KC suggests that unidentified receptor-ligand interactions contribute to eosinophil recruitment. It is interesting that the potent chemoattractant of human eosinophils, RANTES, was unable to mediate mouse eosinophil migration. Furthermore, despite the ability of MIP-1alpha to bind receptors on purified mouse eosinophils, it was only able to induce significant eosinophil migration in a mixed splenocyte population and was unable to induce migration of highly purified eosinophils. Collectively, these observations reveal physiologically relevant distinctions in mechanisms mediating human and mouse eosinophil migration that potentially reflect evolutionary disparities between these species.


Assuntos
Quimiotaxia de Leucócito/fisiologia , Eosinófilos/fisiologia , Receptores de Quimiocinas/fisiologia , Sequência de Aminoácidos , Animais , Cálcio/sangue , Quimiocina CCL5/genética , Eosinófilos/imunologia , Humanos , Ligantes , Linfócitos/imunologia , Camundongos , Dados de Sequência Molecular , Filogenia , Receptores CCR3 , Receptores de Quimiocinas/sangue , Receptores de Quimiocinas/química , Receptores de Quimiocinas/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Baço/citologia
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