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Sökning: WFRF:(Darst Burcu F.)

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1.
  • Schultz, Stephanie A, et al. (författare)
  • Cardiorespiratory fitness alters the influence of a polygenic risk score on biomarkers of AD.
  • 2017
  • Ingår i: Neurology. - 1526-632X. ; 88:17, s. 1650-1658
  • Tidskriftsartikel (refereegranskat)abstract
    • To examine whether a polygenic risk score (PRS) derived from APOE4, CLU, and ABCA7 is associated with CSF biomarkers of Alzheimer disease (AD) pathology and whether higher cardiorespiratory fitness (CRF) modifies the association between the PRS and CSF biomarkers.Ninety-five individuals from the Wisconsin Registry for Alzheimer's Prevention were included in these cross-sectional analyses. They were genotyped for APOE4, CLU, and ABCA7, from which a PRS was calculated for each participant. The participants underwent lumbar puncture for CSF collection. β-Amyloid 42 (Aβ42), Aβ40, total tau (t-tau), and phosphorylated tau (p-tau) were quantified by immunoassays, and Aβ42/Aβ40 and tau/Aβ42 ratios were computed. CRF was estimated from a validated equation incorporating sex, age, body mass index, resting heart rate, and self-reported physical activity. Covariate-adjusted regression analyses were used to test for associations between the PRS and CSF biomarkers. In addition, by including a PRS×CRF term in the models, we examined whether these associations were modified by CRF.A higher PRS was associated with lower Aβ42/Aβ40 (p < 0.001), higher t-tau/Aβ42 (p = 0.012), and higher p-tau/Aβ42 (p = 0.040). Furthermore, we observed PRS × CRF interactions for Aβ42/Aβ40 (p = 0.003), t-tau/Aβ42 (p = 0.003), and p-tau/Aβ42 (p = 0.001). Specifically, the association between the PRS and these CSF biomarkers was diminished in those with higher CRF.In a late-middle-aged cohort, CRF attenuates the adverse influence of genetic vulnerability on CSF biomarkers. These findings support the notion that increased cardiorespiratory fitness may be beneficial to those at increased genetic risk for AD.
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2.
  • Darst, Burcu F., et al. (författare)
  • The Four-Kallikrein Panel Is Effective in Identifying Aggressive Prostate Cancer in a Multiethnic Population
  • 2020
  • Ingår i: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. - : American Association for Cancer Research. - 1538-7755. ; 29:7, s. 1381-1388
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The four-kallikrein (4K) panel has been demonstrated to improve prediction of aggressive prostate cancer compared with prostate-specific antigen (PSA) among men with moderately elevated PSA levels. However, the development and testing of the 4K panel has been conducted primarily in White men, with limited data in African Americans and no studies in other racial and ethnic groups. METHODS: We evaluated the 4K panel in a nested case-control study among African American, Latino, Japanese, Native Hawaiian, and White men in the Multiethnic Cohort. Prediagnostic blood levels of free, intact, and total PSA and human kallikrein-related peptidase 2 were measured among 1,667 incident prostate cancer cases and 691 controls with PSA ≥2 ng/mL. We evaluated the discriminative ability of the 4K panel within and across all racial/ethnic groups. RESULTS: The 4K panel enhanced discrimination of overall prostate cancer compared with free plus total PSA and total PSA alone (AUC 0.748 vs. 0.711 and 0.669, respectively). Discrimination was further enhanced for Gleason 8+ prostate cancer, aggressive prostate cancer, and death due to prostate cancer, and to a lesser degree for nonaggressive prostate cancer. Improvement of the 4K panel over PSA was observed in each population. Adding a prostate cancer polygenic risk score slightly improved upon the discriminative ability of the 4K panel. CONCLUSIONS: The superior discriminative ability of the 4K panel over PSA for overall and aggressive prostate cancer across multiethnic populations indicates the broad clinical applicability of the 4K panel. IMPACT: Our multiethnic investigation suggests potential for the 4K panel to improve current prostate cancer screening practices.
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3.
  • Vogt, Nicholas M, et al. (författare)
  • The gut microbiota-derived metabolite trimethylamine N-oxide is elevated in Alzheimer's disease.
  • 2018
  • Ingår i: Alzheimer's research & therapy. - 1758-9193. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Trimethylamine N-oxide (TMAO), a small molecule produced by the metaorganismal metabolism of dietary choline, has been implicated in human disease pathogenesis, including known risk factors for Alzheimer's disease (AD), such as metabolic, cardiovascular, and cerebrovascular disease.In this study, we tested whether TMAO is linked to AD by examining TMAO levels in cerebrospinal fluid (CSF) collected from a large sample (n = 410) of individuals with Alzheimer's clinical syndrome (n = 40), individuals with mild cognitive impairment (MCI) (n = 35), and cognitively-unimpaired individuals (n = 335). Linear regression analyses were used to determine differences in CSF TMAO between groups (controlling for age, sex, and APOE ε4 genotype), as well as to determine relationships between CSF TMAO and CSF biomarkers of AD (phosphorylated tau and beta-amyloid) and neuronal degeneration (total tau, neurogranin, and neurofilament light chain protein).CSF TMAO is higher in individuals with MCI and AD dementia compared to cognitively-unimpaired individuals, and elevated CSF TMAO is associated with biomarkers of AD pathology (phosphorylated tau and phosphorylated tau/Aβ42) and neuronal degeneration (total tau and neurofilament light chain protein).These findings provide additional insight into gut microbial involvement in AD and add to the growing understanding of the gut-brain axis.
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