Resilience And Biomarkers Of Health Risk In Black Smokers And Nonsmokers Pdf
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- Resilience and biomarkers of health risk in Black smokers and nonsmokers.
- Publications by authors named "J Alan Payne"
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Recent media reporting on healthy living and longevity highlights the ever-increasing public interest on the effects of lifestyle choices on disease risk. A majority of the people in Loma Linda belong to the Seventh-day Adventist faith, which advocates healthy living and a life of service. This lifestyle encourages a vegetarian diet, exercise, reducing stress, promoting social connections, and the practice of faith, which is at the core of the Adventist community. The vast majorities of Adventists are non-smokers and avoid alcohol, and many follow a predominantly vegetarian dietary pattern.
Resilience and biomarkers of health risk in Black smokers and nonsmokers.
Memory resilience occurs when genetically at-risk adults perform at high and sustained levels. We investigated whether a memory resilience to AD genetic risk is predicted by biological and other risk markers and b the prediction profiles vary by sex and AD risk variant. Growth mixture models classified resilience. For both sexes, younger age, higher education, stronger grip, and everyday novel cognitive activity predicted memory resilience.
For women, 9 factors from functional, health, mobility, and lifestyle domains were also predictive. For men, only fewer depressive symptoms was an additional important predictor. Although several factors predicted resilience in both sexes, a greater number applied only to women.
Sex-specific mechanisms and intervention targets are implied. However, sporadic AD is a multifactorial neurodegenerative condition and not all genetic risk carriers convert to clinical diagnosis. This phenomenon of cognitive resilience may be influenced and predicted by other factors that contribute to brain and cognitive risk reduction or exacerbation.
Candidates for such factors may be found among key domains of AD risk and protection. These include markers from biological, functional, health, environmental, lifestyle, and demographic domains, as discovered in neuro-epidemiological research Anstey et al. Determining the factors that predict or support cognitive resilience in at-risk older adults will help identify the mechanisms and pathways that can lead to differential neurocognitive outcomes Ferrari et al.
Episodic memory EM is a sensitive indicator of the neurobiological outcomes of typical aging, producing differential aging changes as it is associated with aging risk and protective factors and showing exacerbated decline in mild cognitive impairment MCI and AD Josefsson et al.
We define memory resilience as EM performance that is relatively high and is maintained over time despite the presence of specified AD risk alleles. However, AD differentially affects women as a function of neurobiological mechanisms that are beginning to be understood. Clearly, examining sex differences in resilience to AD genetic risk in nondemented older adults may have implications for potentially timely interventions to delay or reduce risk for neurodegenerative disease.
A related genetic risk factor in a single nucleotide polymorphism within the CLU gene rs is also significantly associated with AD Carrasquillo et al.
For CLU , the major C allele increases the risk of AD and is associated with steeper memory decline in cognitively normal, presymptomatic individuals that later progress to MCI Thambisetty et al.
We then examined two research goals. Research goal 1 was to investigate sex differences in predictors of resilience in terms of a specific risk factors from five nongenetic domains and b relative importance of prediction. We hypothesized that factors predictive of resilience to AD genetic risk would differ between women and men. Furthermore, we expected generalizability of sex-specific differences across the two genes given their mechanistic similarities.
Based on previous aging, dementia, and epidemiological research, we identified a pool of predictors derived from demographic, functional, health, mobility, and lifestyle domains Anstey et al. One team Ferrari et al. A second team Kaup et al. The present study focuses on memory resilience to two AD genetic risk variants and tests the extent to which there are similarities and differences across the sexes.
Participants were community-dwelling older adult volunteers of the Victoria Longitudinal Study VLS , an ongoing, multicohort, longitudinal-sequential study of genetic, biomedical, cognitive, biological, lifestyle, and neuropsychological aspects of human aging. All participants provided written informed consent and all data collection procedures were in full and certified compliance with human research ethics. The source sample for the present study is a group of active and continuing nondemented participants who were genotyped in — With these data, an accelerated longitudinal design covers a year band of aging.
As with previous research Kaup et al. In this study, the longitudinal design was used to develop memory trajectories for resilience classification. Saliva samples for genotyping were collected and prepared according to Oragene DNA Genotek technology and protocol. DNA extraction and genotyping procedures are detailed elsewhere McFall et al. One participant did not have their CLU genotype successfully extracted. Mobility measures included baseline a timed turn degree turn, in seconds and b timed walk 20 feet, in seconds.
We originally included current smoking status smoker or nonsmoker , but it was excluded from the final list due to insufficient participant rates. EM was assessed with two standard tests McFall et al. See Supplementary material for further description. We used standard procedures to test 1- to 3-class GMM models.
Given the sample size restrictions, we expected to differentiate a relatively higher-performing group of women and men by having the 2- or 3-class solution outperform the 1-class model. The empirical results of GMM defined resilient and nonresilient groups on the basis of level and slope of the EM latent variable. See Supplementary material for more information about model assessment and selection.
Notably, chronological age not wave was the metric of longitudinal change. This procedure accounts for variability associated with age as if it were a covariate. RFA in R 3. We selected RFA over logistic regression for five main reasons: a given our sample sizes, it was the best option to test all 22 predictors of interest in single models, b although correlations between variables were small in number and magnitude Supplementary Tables S1 and S2 , we could adjust our model parameters to obtain completely unbiased predictors e.
RFA robustly copes with large numbers of predictor variables and restricting the number of variables used in each tree can reveal important predictors that would have otherwise been overshadowed by a stronger competitor Strobl et al. Final results are combined across all trees to rank relative variable importance.
Categorical variables with too few cases in the minority cell i. Model strength was reported as the area under the receiver operating characteristic curve C statistic. In addition, the importance measure is unbiased considers continuous and categorical variables equally and conditional accounts for correlations between variables.
Those variables with negative, zero, or small positive values left of the dotted line are not important predictors of resilience. Variables beyond this range right of the dotted line are informative and interpreted with a descriptive ranking of relative importance Strobl et al.
GMM analyses revealed that, for both women and men, the two-class model fit the data best Supplementary Table S4. A Higher performing women purple, top cluster and lower performing women blue, bottom cluster. B Higher performing men red, top cluster and lower performing men blue, bottom cluster. Only participants with at least two waves of data were included.
Significant sex differences for level of performance or response were observed for multiple factors across all five risk domains Supplementary Table S6. As can be seen in Figure 2 Supplementary Tables S7 and S8 , we observed four predictors that were common for men and women. The demographic variables age and education emerged within the top three overall most important predictors of resilience in both sexes.
From the functional biomarker domain, grip strength was an important predictor of resilience. From the lifestyle domain, everyday novel cognitive activity was a top predictor of resilience for both sexes. Predictors of resilience specific to women arose from the demographic i.
Men had one unique predictor of resilience from the health domain i. Dotted black line represents cut-off for variable importance, which indicates the importance of each factor in predicting memory resilience relative to other factors. As can be seen in Figure 3 Supplementary Tables S9 and S10 , we observed six predictors for both men and women. The demographic variables age and education predicted resilience for both sexes.
Both factors were of high importance, with the exception of age in women which was lower in the prediction hierarchy. One functional biomarker grip strength and three lifestyle characteristics everyday cognitive activity, volunteering, and social visits predicted resilience in both sexes.
However, for both volunteering and social visits, more participation in these social activities predicted resilience in women whereas less participation predicted resilience in men. Men had two unique predictors of resilience from the demographic i. Random forest analysis results to identify the strongest predictors of episodic memory resilience in CLU CC carriers who were either A women or B men.
Among women, 18 Specifically, 13 factors were reported as important predictors of both APOE - and CLU -based resilience and five factors were not important for both analyses. The 13 important and genetically robust predictors derived from all five domains: demographic i. The remaining three factors were important predictors of resilience to only one risk status i. Among men, 16 Specifically, five factors were reported as important predictors of both APOE - and CLU -based resilience and 11 factors were unimportant.
The important and genetically robust predictors arose from demographic i. We ran two additional sets of RFA to supplement and check our main results. Second, we re-computed the female analyses after down-sampling the majority class to more closely resemble the male sample sizes.
This permitted us to determine if differences in sample size substantially influenced the observed sex prediction effects. In both cases, the conformational RFA results were very similar to those from our original analyses Supplementary material. Although similar, these results were not as complete or sensitive.
For women, a age was a significant predictor of APOE -based resilience and b education, subjective health, and pulse pressure were significant predictors of CLU -based resilience. Research goal 1 was to investigate predictors of resilience as stratified by sex. We found several similarities in predictors of resilience but also a numerous factors from all five domains that differentially predicted resilience in women and b relatively few unique factors from the demographic and health domains that predicted resilience in men.
Within the demographic domain, younger age and higher education emerged as a important predictors of resilience across both sexes and b genetically robust. Our design with a year band of aging permitted a strong test of chronological age predictions within an older adult sample. We found that younger age strongly predicted memory resilience. Conceivably, EM trajectories may be more systematically distributed and sensitive to subtle age changes within a broad band of aging.
Two additional demographic factors—being married and living with someone—were genetically robust predictors of resilience in women. Above-average global cognition and EM ability have both been associated with living with someone Josefsson et al. Such measures may be more salient for females because, on average, they outlive males. Stronger grip strength emerged as a genetically robust predictor of resilience across both sexes. Sarcopenia and declines in grip strength have been associated with cognitive impairment Hsu et al.
The relationship between cognition and fine muscle strength suggests that a grip strength is a useful and simple biomarker of cognitive performance or change and b interventions involving strength training may be associated with sustained memory performance in at-risk older adults, possibly in conjunction with cardiovascular physical activity.
Publications by authors named "J Alan Payne"
Previous attempts to locate hydrothermal vent fields and unravel the nature of venting at the ultraslow spreading and magma starved parts of the Arctic Mid Ocean Ridge AMOR have been unsuccessful. A black smoker vent field was eventually discovered at the Mohns-Knipovich bend at Fluid compositions are anomalous to other basalt-hosted fields and indicate interactions with sediments at depths. The vent field is associated with an unusually large hydrothermal deposit, which documents that extensive venting occurs at ultraslow spreading ridges despite the strongly reduced magmatic heat budget. ROV surveys have shown that venting occurs in two areas separated by around m. Micro-bathymetry acquired by a Hugin AUV documents that two tall mounds that coalesce at the base have developed around the vent sites.
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DNA damage risk assessment in comet assay by the use of buccal mucosa cells has great advantages in comparison with other cell type sample due to more safely, easier, cheaper, and non-invasive method for in vivo studies. According to the OECD Guidelines, the in vivo mammalian alkaline comet assay is well-established and validated method for measuring DNA strand breaks in single eukaryotic cells. Considering exposure to xenobiotics and endogenous damage inductors, buccal mucosa cells are the first to be in direct contact after exposure and this makes them an ideal biomatrices in evaluation of the level of individual genotoxicity to several compounds already mentioned. Their clinical diagnostic applicability confers a potential use in patients across time. However, the number of publications referring to the human buccal comet assay is low in the last two decades. This low growing interest may be explained by several factors, including its relative technical problems. Different procedures have been used in collecting and processing the samples.
The ability of some individuals to reach extreme old age in the presence of clearly high exposure to damaging factors may signal an innate biological advantage. For this study we used data on 4, current and never smokers, ages 50 and above, from NHANES III to examine whether long-lived smokers represent a biologically resilient phenotype that could facilitate our understanding of heterogeneity in the aging process.
Health, environment and working conditions in tobacco cultivation: a review of the literature. This study presents a review of the literature published between and on health and working conditions in tobacco cultivation, with particular emphasis on the Brazilian context. Articles published in English, Spanish and Portuguese were analyzed.
Electronic address:. Arcturus Therapeutics Inc. Toggle navigation. Login Categories Journals.
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