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1.
Headache ; 63(10): 1437-1447, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37655667

RESUMO

OBJECTIVE: This observational study aimed to: (i) describe and explore preliminary psychometric properties of a multidimensional sleep health composite score in adolescent females with frequent migraine; and (ii) examine associations between the composite score, headache characteristics, and emotional health. BACKGROUND: Sleep health is a multidimensional construct comprised of various dimensions of sleep and circadian functioning, including Regularity, Satisfaction, Alertness, Timing, Efficiency, and Duration (Ru-SATED framework). The Ru-SATED sleep health composite score may provide a holistic perspective of sleep among adolescents with frequent migraine in the context of neurobiological and psychosocial impacts on sleep unique to this developmental period. METHODS: In all, 60 female adolescents (aged 12-18 years) with high-frequency episodic or chronic migraine completed wrist-worn actigraphy for 10 days and concurrent daily electronic surveys assessing headache, sleep, and emotional health. A sleep health composite score was derived from empirically supported "healthy" versus "unhealthy" ratings on the six Ru-SATED sleep dimensions. RESULTS: Half of participants (27/54 [50%]) had a composite score ≥4 (i.e., at least four of the six dimensions rated as poor). Convergent validity of the composite score was acceptable (rs = 0.30-0.56, all p < 0.05). Internal consistency among the dimensions was low (α = 0.45). Multivariate multiple regression models indicated that worse sleep health was associated with greater headache-related disability (B = 0.71, p = 0.018) and anxiety (B = 0.59, p = 0.010), and trended toward significance for sadness (B = 0.35, p = 0.052). The composite score was not significantly associated with headache frequency or severity. CONCLUSIONS: A multidimensional sleep health composite score may provide an alternative, more comprehensive picture of sleep disturbance among adolescent females with frequent migraine. Larger studies are needed to examine psychometric properties more rigorously and further explore the composite score as a potentially unique predictor of headache outcomes.


Assuntos
Transtornos de Enxaqueca , Humanos , Adolescente , Feminino , Transtornos de Enxaqueca/complicações , Sono , Cefaleia/complicações , Inquéritos e Questionários , Transtornos de Ansiedade
2.
J Clin Nurs ; 31(3-4): 435-444, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33326657

RESUMO

AIMS: The aims of the study were to compare characteristics, resources, benefits and outcomes of academic-clinical collaborations of nursing researcher leaders from academic, clinical and joint-employer sites. BACKGROUND: Few research-based publications addressed academic-clinical research collaborations. New knowledge could increase nursing and multidisciplinary research productivity, including implementation science. DESIGN: An anonymous survey using a 40-item questionnaire. METHODS: Information letters with a link to the questionnaire were emailed to United States nursing research leaders. Data were grouped by institution type: academic, clinical or joint-employer. Analyses included Kruskal-Wallis tests for ordered responses, Pearson's chi-square test or Fisher's exact test for categorical responses and Cohen's Kappa agreement statistic for expected and actual time devoted to research. STROBE guidelines were followed. RESULTS: Of 120 respondents from academic (n = 60; 50.0%), clinical (n = 53; 41.2%) and joint-employer (n = 7; 5.8%) sites, 78.3%, 92.3% and 100%, respectively, were from metropolitan areas. Mean (SD) priority for active collaborations was higher at joint-employer sites; p = .002. Clinical sites were more likely to have directors of evidence-based practice (p = .031) and informatics (p = .008) and librarians (p = .029). Sites with collaborations were more likely to have access to research subjects (p = .008) and post-award research account management (p = .045). By collaboration status, there were no differences in the number of ethics board-approved studies. Collaborating site benefits were perceived to be executive leadership support (p = .003), greater research engagement by clinical nurses (p = .048), more co-authored publications (p = .048) and more abstracts accepted at national meetings (p = .044). Despite more resources and perceived benefits, outcomes did not differ by collaboration status. CONCLUSIONS: Sites with and without academic-clinical research collaborations differed; however, outcomes were similar. Future efforts should focus on nurse scientist collaboration to address important clinical questions aimed at improving clinical outcomes. RELEVANCE TO CLINICAL PRACTICE: Despite some successful outcomes, potential benefits of academic-clinical research collaborations have not been fully actualised.


Assuntos
Liderança , Pesquisa em Enfermagem , Estudos Transversais , Humanos , Estados Unidos
3.
J Nurs Adm ; 49(5): 234-241, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31008833

RESUMO

Academic-clinical research partnerships can benefit academic and clinical partners when goals are clearly articulated and mutually determined and include increased research dissemination and lower research costs. This article explores the history of academic-clinical research partnerships and discusses the drivers of collaborative academic-clinical research relationships, resources from academia and clinical sites, and sustainability of collaborative partnerships. Through collaboration, academic-clinical partners can improve clinical outcomes and reduce healthcare costs.


Assuntos
Centros Médicos Acadêmicos/organização & administração , Comportamento Cooperativo , Relações Interinstitucionais , Pesquisa Metodológica em Enfermagem/organização & administração , Humanos , Projetos de Pesquisa , Estados Unidos
4.
J Biol Chem ; 286(46): 40296-306, 2011 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-21949239

RESUMO

Myotonic dystrophy 1 (DM1) is a multisystemic disease caused by a triplet nucleotide repeat expansion in the 3' untranslated region of the gene coding for myotonic dystrophy protein kinase (DMPK). DMPK is a nuclear envelope (NE) protein that promotes myogenic gene expression in skeletal myoblasts. Muscular dystrophy research has revealed the NE to be a key determinant of nuclear structure, gene regulation, and muscle function. To investigate the role of DMPK in NE stability, we analyzed DMPK expression in epithelial and myoblast cells. We found that DMPK localizes to the NE and coimmunoprecipitates with Lamin-A/C. Overexpression of DMPK in HeLa cells or C2C12 myoblasts disrupts Lamin-A/C and Lamin-B1 localization and causes nuclear fragmentation. Depletion of DMPK also disrupts NE lamina, showing that DMPK is required for NE stability. Our data demonstrate for the first time that DMPK is a critical component of the NE. These novel findings suggest that reduced DMPK may contribute to NE instability, a common mechanism of skeletal muscle wasting in muscular dystrophies.


Assuntos
Células Epiteliais/enzimologia , Proteínas Musculares/metabolismo , Mioblastos Esqueléticos/enzimologia , Distrofia Miotônica/enzimologia , Membrana Nuclear/enzimologia , Proteínas Serina-Treonina Quinases/metabolismo , Células Epiteliais/patologia , Regulação da Expressão Gênica/genética , Células HeLa , Humanos , Laminas/genética , Laminas/metabolismo , Proteínas Musculares/genética , Mioblastos Esqueléticos/patologia , Distrofia Miotônica/genética , Distrofia Miotônica/patologia , Miotonina Proteína Quinase , Membrana Nuclear/genética , Membrana Nuclear/patologia , Proteínas Serina-Treonina Quinases/genética
5.
Environ Toxicol Chem ; 21(8): 1618-27, 2002 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12152761

RESUMO

The Delaware River-Bay system, USA, was the subject of a study by the National Oceanic and Atmospheric Administration that involved chemical and biological analyses, including the use of the biomarker P450 human reporter gene system (HRGS) to document the occurrence and distribution of cytochrome P450 (CYP) 1A1-inducing compounds. Sediment extracts from 81 locations along the Delaware River, Delaware Bay and immediate coastline were tested by utilizing HRGS as an inexpensive screening test, and were also analyzed for polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls, with selected stations analyzed for dioxins and furans. Benthic community degradation has been observed when benzo[a]pyrene equivalents (BaPEq) exceeded 60 microg/g. The average levels of BaPEq for the largely industrialized upper, middle, and lower regions of the Delaware River were 107, 62, and 5 microg/g, respectively, excluding outliers. Tributaries leading into river averaged 21 microg/g BaPEq, whereas the central Bay and open coast had relatively low values (2.0 and 0.5 microg/g BaPEq, respectively). The HRGS values were highly correlated with total PAHs measured in the same sediment samples (r2 = 0.81). Overall, contamination levels consistently decreased from the upper and middle river sites as collection locations progressed down through the lower river and bay to the coast. Thus, despite the relatively high contaminant load in the river system, Delaware Bay and the immediate coastline seem to have relatively low levels of contaminants, and, therefore, impacts on the benthic organisms in the bay and coast would not be expected from these findings.


Assuntos
Biomarcadores/análise , Citocromo P-450 CYP1A1/análise , Citocromo P-450 CYP1A1/biossíntese , Genes Reporter/genética , Sedimentos Geológicos/química , Hidrocarbonetos Policíclicos Aromáticos/análise , Poluentes Químicos da Água/análise , Animais , Bioensaio/métodos , Delaware , Monitoramento Ambiental , Indução Enzimática , Humanos , Hidrocarbonetos Policíclicos Aromáticos/farmacologia , Poluentes Químicos da Água/farmacologia
6.
Pract Radiat Oncol ; 4(2): 130-135, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24890354

RESUMO

PURPOSE: Radiation-induced taste and smell disturbances are prevalent in patients receiving brain radiation therapy, although the mechanisms underlying these toxicities are poorly understood. We report the results of a single institution prospective clinical trial aimed at correlating self-reported taste and smell disturbances with radiation dose delivered to defined areas within the brain and nasopharynx. METHODS AND MATERIALS: Twenty-two patients with gliomas were enrolled on a prospective observational trial in which patients underwent a validated questionnaire assessing taste and smell disturbances at baseline and at 3 and 6 weeks after commencement of brain radiation therapy. Fourteen patients with glioblastoma, 3 patients with grade 3 gliomas, and 5 patients with low grade gliomas participated. Median dose to tumor volume was 60 Gy (range, 45-60 Gy). Dose-volume histogram (DVH) analysis was performed for specific regions of interest that were considered potential targets of radiation damage, including the thalamus, temporal lobes, nasopharynx, olfactory groove, frontal pole, and periventricular stem cell niche. The %v10 (percent of region of interest receiving 10 Gy), %v40, and %v60 were calculated for each structure. Data from questionnaires and DVH were analyzed using stepwise regression. RESULTS: Twenty of 22 patients submitted evaluable questionnaires that encompassed at least the entire radiation therapy course. Ten of 20 patients reported experiencing some degree of smell disturbance during radiation therapy, and 14 of 20 patients experienced taste disturbances. Patients reporting more severe taste toxicity also reported more severe toxicities with sense of smell (r(2) = 0.60, P < .006). Tumor location in the temporal lobe predicted for increased severity of taste toxicity (F3, 16 = 1.44, P < .06). The nasopharynx was the only structure in which the DVH data predicted the presence of radiation-induced taste changes (r(2) = 0.28, P < .02). CONCLUSIONS: Radiation-induced taste toxicity appears to be more common in temporal lobe tumors, and may be related to the dose received by the nasopharynx.


Assuntos
Neoplasias Encefálicas/radioterapia , Glioma/radioterapia , Lesões por Radiação/etiologia , Olfato/efeitos da radiação , Paladar/efeitos da radiação , Adulto , Idoso , Encéfalo/efeitos da radiação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Inquéritos e Questionários , Adulto Jovem
7.
Dev Dyn ; 237(9): 2353-66, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18729234

RESUMO

Myotonic dystrophy (DM1) is a multi-systemic disease caused by a triplet nucleotide repeat expansion in the 3' untranslated region of the gene coding for myotonic dystrophy protein kinase (DMPK). The primary pathophysiology of DM1 is thought to result from RNA transport and processing defects. The function of DMPK in development or any potential role in DM1 remains unknown. Here we report a novel role for DMPK in myogenesis. We have discovered a specific expression pattern of DMPK in mouse and chick embryonic development. DMPK is expressed in postmitotic cardiac and skeletal myocytes and developmental signaling centers. During cardiac myocyte maturation, DMPK migrates from perinuclear to cellular membrane localization. Manipulating DMPK levels in cultured cardiac and skeletal myocytes has revealed a key role for DMPK in myocyte differentiation. Overexpression of DMPK induces cell rounding and apoptosis in myocytes. In addition, DMPK is necessary for myogenin expression in differentiating C2C12 myoblasts.


Assuntos
Células Musculares/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Miócitos Cardíacos/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Animais , Apoptose/fisiologia , Western Blotting , Diferenciação Celular/fisiologia , Linhagem Celular , Células Cultivadas , Embrião de Galinha , Galinhas , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Imuno-Histoquímica , Camundongos , Microscopia Confocal , Células Musculares/citologia , Fibras Musculares Esqueléticas/citologia , Miócitos Cardíacos/citologia , Miotonina Proteína Quinase , Proteínas Serina-Treonina Quinases/genética , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Transfecção
8.
J Mol Recognit ; 19(3): 215-26, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16680721

RESUMO

Myotonic dystrophy protein kinase (DMPK) was the initial representative of a ubiquitous protein kinase family that regulates cell size and shape. DMPK is highly expressed in heart and skeletal muscle and transgenic over-expression induces cardiac hypertrophy. The characterization of DMPK has been limited by the paucity of immunological reagents with high affinity and well-defined specificity. Amino acid sequence data was used to predict the surface exposure of the coil-coiled domain of DMPK. These exposed amino acids were substituted into an extremely stable coiled-coil template to produce a peptide antigen. Sera from mice immunized with the peptide conjugated to keyhole limpet hemocyanin were screened against recombinant DMPK using Western blots. Murine spleens expressing DMPK antibodies were used to produce hybridoma cell lines. Hybridoma supernatants were further screened against recombinant DMPK and four clonal hybridoma cell lines expressing DMPK antibodies were generated. These four monoclonal antibodies recognized recombinant DMPK in Western blots of COS-1 cell lysates expressing high levels of recombinant DMPK and immunoprecipitated recombinant DMPK from COS-1 cell lysates. The identity of the immunoprecipitated DMPK was confirmed by MALDI-TOF mass spectrometry and peptide mass fingerprinting. DMPK was the only protein detected in the immunoprecipitates, indicating the high specificity of the antibodies. Western blots immunostained with two of the monoclonal antibodies specifically recognized the two isoforms of endogenous DMPK, DMPK-1 and DMPK-2, that are expressed at low levels in the human heart. The recognition of low amounts of DMPK-1 and DMPK-2 indicates the high affinity of these antibodies. A human heart lysate was subjected to ammonium sulfate precipitation and column chromatography to produce a fraction that was enriched in DMPK. One of the monoclonal antibodies immunoprecipitated endogenous DMPK from this fraction. This antibody was used for immuno-localization studies of an adenoviral DMPK construct, expressed in adult mouse cardiac myocytes. This construct was localized to the intercalated disc, the site of endogenous DMPK, indicating that this antibody is applicable to immuno-localization studies. This study demonstrates the utility of the described procedure for generation of specific monoclonal antibodies with high affinity for epitopes in coiled-coiled domains of mammalian proteins expressed at low levels.


Assuntos
Anticorpos Monoclonais/imunologia , Proteínas Serina-Treonina Quinases/imunologia , Células 3T3 , Adulto , Sequência de Aminoácidos , Animais , Anticorpos Monoclonais/biossíntese , Anticorpos Monoclonais/isolamento & purificação , Especificidade de Anticorpos/imunologia , Western Blotting , Células COS , Chlorocebus aethiops , Humanos , Imuno-Histoquímica , Isoenzimas/imunologia , Isoenzimas/metabolismo , Masculino , Camundongos , Dados de Sequência Molecular , Miocárdio/enzimologia , Miocárdio/metabolismo , Miotonina Proteína Quinase , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/imunologia , Proteínas Serina-Treonina Quinases/metabolismo , Estrutura Secundária de Proteína , Homologia de Sequência de Aminoácidos , Baço/enzimologia , Baço/metabolismo
9.
Urology ; 67(6): 1257-61, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16765186

RESUMO

OBJECTIVES: To report a prospective trial of lycopene supplementation in biochemically relapsed prostate cancer. METHODS: A total of 36 men with biochemically relapsed prostate cancer were enrolled in a dose-escalating, Phase I-II trial of lycopene supplementation. Six consecutive cohorts of 6 patients each received daily supplementation with 15, 30, 45, 60, 90, and 120 mg/day for 1 year. The serum levels of prostate-specific antigen (PSA) and plasma levels of lycopene were measured at baseline and every 3 months. The primary endpoints were PSA response (defined as a 50% decrease in serum PSA from baseline), pharmacokinetics, and the toxicity/tolerability of this regimen. RESULTS: A total of 36 patients were enrolled. The median age was 74 years (range 56 to 83), with a median serum PSA at entry of 4.4 ng/mL (range 0.8 to 24.9). No serum PSA responses were observed, and 37% of patients had PSA progression. The median time to progression was not reached. Toxicity was mild, with 1 patient discontinuing therapy because of diarrhea. Significant elevations of plasma lycopene were noted at 3 months and then appeared to plateau for all six dose levels. The plasma levels for doses between 15 and 90 mg/day were similar, with additional elevation only at 120 mg/day. CONCLUSIONS: Lycopene supplementation in men with biochemically relapsed prostate cancer is safe and well tolerated. The plasma levels of lycopene were similar for a wide dose range (15 to 90 mg/day) and plateaued by 3 months. Lycopene supplementation at the doses used in this study did not result in any discernible response in serum PSA.


Assuntos
Adenocarcinoma/tratamento farmacológico , Anticarcinógenos/administração & dosagem , Carotenoides/administração & dosagem , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias da Próstata/tratamento farmacológico , Adenocarcinoma/sangue , Adenocarcinoma/terapia , Idoso , Idoso de 80 Anos ou mais , Humanos , Licopeno , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Estudos Prospectivos , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/terapia
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