Biomarkers of aging associated with past treatments in breast cancer survivors.

Radiation and chemotherapy are effective treatments for cancer, but are also toxic to healthy cells. Little is known about whether prior exposure to these treatments is related to markers of cellular aging years later in breast cancer survivors. We examined whether past exposure to chemotherapy and/or radiation treatment was associated with DNA damage, telomerase activity, and telomere length 3-6 years after completion of primary treatments in breast cancer survivors (stage 0-IIIA breast cancer at diagnosis). We also examined the relationship of these cellular aging markers with plasma levels of Interleukin (IL)-6, soluble TNF-receptor-II (sTNF-RII), and C-reactive protein (CRP). Ninety-four women (36.4-69.5 years; 80% white) were evaluated. Analyses adjusting for age, race, BMI, and years from last treatment found that women who had prior exposure to chemotherapy and/or radiation compared to women who had previously received surgery alone were more likely to have higher levels of DNA damage (P = .02) and lower telomerase activity (P = .02), but did not have differences in telomere length. More DNA damage and lower telomerase were each associated with higher levels of sTNF-RII (P's < .05). We found that exposure to chemotherapy and/or radiation 3-6 years prior was associated with markers of cellular aging, including higher DNA damage and lower telomerase activity, in post-treatment breast cancer survivors. Furthermore, these measures were associated with elevated inflammatory activation, as indexed by sTNF-RII. Given that these differences were observed many years after the treatment, the findings suggest a long lasting effect of chemotherapy and/or radiation exposure

Role of SPARC in Drosophila Melanogaster basal lamina homeostasis

SPARC is a multifunctional, evolutionarily conserved, collagen- and growth factor-binding glycoprotein that is required in Drosophila melanogaster for proper larval development and maintenance of fat body homoeostasis. I have engineered a SPARC RNAi knockdown in the larval fat body, with an emphasis on ultrastructural adipocyte morphology and basal lamina integrity, resulting in adipocyte remodeling characterized by cell rounding and accumulation of fibrous matrix material. SPARC deficient larva show increased deposition of collagen IV and other basal lamina components. How collagen IV assembles into an organized network in basal lamina remains unclear. In seeking to elucidate the potential intra- and extracellular functions of SPARC in this context, I generated five mCherry tagged SPARC constructs which failed to rescue SPARC-null mutants. Together, the data compiled by myself and others in the lab indicate that SPARC is required to maintain adipocyte morphology and basal lamina homeostasis during larval development.M.A.S

Cognitive performance in survivors of breast cancer and markers of biological aging.

BackgroundBiological aging pathways accelerated by cancer treatments may be a mechanism for cognitive impairment in cancer survivors. The goal of the current study was to examine whether indicators of biological aging, namely elevated levels of DNA damage, reduced telomerase enzymatic activity, and shorter peripheral blood mononuclear cell (PBMC) telomere length (TL) would be related to cognitive function in a cohort of survivors of breast cancer.MethodsThe authors evaluated a cross-sectional sample of 94 women aged 36 to 69 years who were treated for early-stage breast cancer 3 to 6 years previously. Leukocyte DNA damage, PBMC telomerase enzymatic activity, PBMC TL, and the inflammatory marker soluble tumor necrosis factor receptor II (sTNF-RII) were determined from blood samples. Cognitive function was assessed using a neuropsychological test battery and self-report. Linear regression models examined the relationship between biological aging predictors and cognitive outcomes.ResultsBoth higher DNA damage and lower telomerase were found to be statistically significantly related to lower executive function scores adjusting for age, body mass index, race, years from treatment, and intelligence score (standardized coefficients [B], -0.23 and 0.30; all P values <.05). In addition, lower telomerase activity was associated with worse attention and motor speed scores (B values, 0.30 and 0.24; P <.05). sTNF-RII and TL were found to be unrelated to any of the neurocognitive domains.ConclusionsThe results of the current study suggest a significant association between measures of biological aging and objective measures of cognitive performance in survivors of breast cancer. Future prospective studies are needed to confirm a causal role of biological aging as a driver of declines in cognitive function after cancer treatment

Cortical microinfarcts detected in vivo on 3 Tesla MRI: clinical and radiological correlates

Item does not contain fulltextBACKGROUND AND PURPOSE: Cortical microinfarcts (CMIs) are a common postmortem finding associated with vascular risk factors, cognitive decline, and dementia. Recently, CMIs identified in vivo on 7 Tesla MRI also proved retraceable on 3 Tesla MRI. METHODS: We evaluated CMIs on 3 Tesla MRI in a population-based cohort of 194 nondemented older people (72-80 years) with systolic hypertension. Using a case-control design, participants with and without CMIs were compared on age, sex, cardiovascular risk factors, and white matter hyperintensity volume. RESULTS: We identified 23 CMIs in 12 participants (6%). CMIs were associated with older age, higher diastolic blood pressure, and a history of recent stroke. There was a trend for a higher white matter hyperintensity volume in participants with CMIs. CONCLUSIONS: We found an association of CMIs with clinical parameters, including age and cardiovascular risk factors. Although the prevalence of CMIs is relatively low, our results suggest that the study of CMIs in larger clinical studies is possible using 3 Tesla MRI. This opens the possibility of large-scale prospective investigation of the clinical relevance of CMIs in older people

Cognitive performance in survivors of breast cancer and markers of biological aging.

BackgroundBiological aging pathways accelerated by cancer treatments may be a mechanism for cognitive impairment in cancer survivors. The goal of the current study was to examine whether indicators of biological aging, namely elevated levels of DNA damage, reduced telomerase enzymatic activity, and shorter peripheral blood mononuclear cell (PBMC) telomere length (TL) would be related to cognitive function in a cohort of survivors of breast cancer.MethodsThe authors evaluated a cross-sectional sample of 94 women aged 36 to 69 years who were treated for early-stage breast cancer 3 to 6 years previously. Leukocyte DNA damage, PBMC telomerase enzymatic activity, PBMC TL, and the inflammatory marker soluble tumor necrosis factor receptor II (sTNF-RII) were determined from blood samples. Cognitive function was assessed using a neuropsychological test battery and self-report. Linear regression models examined the relationship between biological aging predictors and cognitive outcomes.ResultsBoth higher DNA damage and lower telomerase were found to be statistically significantly related to lower executive function scores adjusting for age, body mass index, race, years from treatment, and intelligence score (standardized coefficients [B], -0.23 and 0.30; all P values <.05). In addition, lower telomerase activity was associated with worse attention and motor speed scores (B values, 0.30 and 0.24; P <.05). sTNF-RII and TL were found to be unrelated to any of the neurocognitive domains.ConclusionsThe results of the current study suggest a significant association between measures of biological aging and objective measures of cognitive performance in survivors of breast cancer. Future prospective studies are needed to confirm a causal role of biological aging as a driver of declines in cognitive function after cancer treatment

Student Satisfaction and Learning Outcomes in Asynchronous Online Lecture Videos.

Our study identified online lecture video styles that improved student engagement and satisfaction, while maintaining high learning outcomes in online education. We presented different lecture video styles with standardized material to students and then measured learning outcomes and satisfaction with a survey and summative assessment. We created an iterative qualitative coding scheme, coding online asynchronous lectures (COAL), to analyze open-ended student survey responses. Our results reveal that multimedia learning can be satisfying and effective. Students have strong preferences for certain video styles despite their equal learning outcomes, with the Learning Glass style receiving the highest satisfaction ratings. Video styles that were described as impersonal and unfamiliar were rated poorly, while those that were described as personal and engaging and evoked positive affective responses were rated highly. The students in our study rated lecture video styles that aligned with Mayers multimedia learning principles as highly satisfying, indicating that student feedback can be a valuable resource for course designers to consider as they design their own online courses. Finally, we provide guidelines for creating engaging, effective, and satisfying asynchronous lecture videos to support establishment of best practices in online instruction