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Biomedical subjects

Carol M Worthman

Publications and source records attributed to Carol M Worthman.

5 recordsLinked to original sources

Sensitive high-performance liquid chromatographic method using coulometric electrode array detection for measurement of phytoestrogens in dried blood spots.

As the epidemiological and physiological investigation of isoflavones and lignans expands, the need for sensitive methods for analyzing large numbers of samples intensifies. We have developed a method using high-performance liquid chromatography (HPLC) equipped with a coulometric electrode array detector for separation and sensitive detection of daidzein (Da), equol (Eq), genistein (Ge) and enterolactone (Enl) in dried blood spots (DBS). Detection limits ranged from 4.5 pg or 0.09 ng/mL (Eq) to 19 pg or 0.38 ng/mL (Ge) on column. Signal linearities ranged from detection limits to 200 ng/mL (Eq, Enl) and 600 ng/mL (Da, Ge) sample concentration. Correlations between DBS and serum concentrations were 0.66 (Enl), 0.88 (Eq), 0.98 (Ge) and 0.99 (Da). Intra-assay coefficients of variation (CVs) were less than 8% and inter-assay CVs ranged from 2.4 to 20.2% for Da, Eq and Ge for three levels of controls. Enl intra-assay CV was 13.6% for the low pooled control. Analytic recovery ranged from 87% (inter-assay Ge) to 98% (inter-assay Enl). DBS concentrations of Da, Ge and Eq were stable for at least 8 weeks at 4 and 25 degrees C, and at 37 degrees C for at least 5 weeks, with Enl showing greater variability at all temperatures but relative stability for 7 weeks. Measurement of samples from 135 perimenopausal Japanese women consuming habitual diets in Kyoto and Fukushima prefectures showed the former to have the expected lower concentrations of Da and Eq (416 and 87 nM) as well as Enl (49 nM) compared to the latter locale (566, 145 and 72 nM, respectively). This method could be useful in large epidemiological research or detailed physiological studies.

Chromatography, High Pressure Liquid↗

Estimating between- and within-individual variation in cortisol levels using multilevel models.

Cortisol measures often are used to examine variation in hypothalamic-pituitary-adrenal axis (HPA) activity as well as broader patterns of differential health. However, substantial within-individual variation renders single cortisol measurements unreliable as estimates for probing differences between individuals and groups. A standard practice to clarify between-individual differences involves collecting multiple samples from each participant and then deriving person-specific averages. By ignoring information about variation at between- and within-individual levels, this technique impedes cross-study comparison of results, ignores data useful for future study design, and hinders the analysis of cross-level interactions. This report describes how multilevel approaches can simultaneously model between- and within-individual variation in diurnal cortisol levels without using crude averages. We apply these models to data from children in Nepal (n=29, 11-15 samples per child), Mongolia (n=47, 8-12 samples per child) and the US (n=1269, 1-6 samples per child). Using the Nepal data, we show how an analysis of crude time-adjusted aggregates does not detect an association between aggressive behavior and cortisol levels, while a multilevel analysis does. More importantly, we argue that the 'roadmap' to variation generated by these multilevel models provides meaningful information about the predictive accuracy--not just statistical significance--of relationships between cortisol levels and individual-level variables, such as psychopathology, age, and gender. The 'roadmap' also facilitates comparison between the results from different studies and estimation of the necessary number of cortisol measurements for future investigations.

Adolescent↗

Receding horizons of health: biocultural approaches to public health paradoxes.

Worldwide challenges to health reflect a "paradox of success," whereby both the strengths and the weaknesses of current approaches in public health, epidemiology, and biomedicine have determined the nature of the health problems we now face. In detail, we analyze and illustrate five constituent paradoxes that fuel continued health risk even in the face of success, including: (1) unmasking, (2) local biology, (3) socialization, (4) emerging and reemerging disease, and (5) savage inequity. We trace the pathways behind the paradoxes and their effects on health, and demonstrate that biocultural dynamics are involved in each. Furthermore, we track the roots of health paradox to changes that divert or disrupt pathways for production of health. These analyses contribute to an emerging literature of research and praxis on integrative biocultural models of health.

Communicable Diseases, Emerging↗

Testosterone, antisocial behavior, and social dominance in boys: pubertal development and biosocial interaction.

BACKGROUND: Studies linking testosterone and antisocial behavior in humans have produced mixed results. Adolescence offers a promising period to study this relationship; circulating testosterone increases dramatically in boys during puberty, and antisocial behavior increases during the same period. METHODS: Our analyses were based on boys aged 9-15 years who were interviewed during the first three waves of the Great Smoky Mountains Study. Measures included interview assessment of DSM-IV conduct disorder (CD) symptoms and diagnosis, blood spot measurement of testosterone, Tanner staging of pubertal development, and assessment of leadership behaviors and peer deviance. RESULTS: The adolescent rise in CD was primarily attributable to an increase in nonphysically aggressive behaviors. Increasing levels of circulating testosterone and association with deviant peers contributed to these age trends. There was no evidence that physical aggression was related to high testosterone. Evidence of biosocial interactions was identified; testosterone was related to nonaggressive CD symptoms in boys with deviant peers and to leadership in boys with nondeviant peers. CONCLUSIONS: The results are consistent with the hypothesis that testosterone relates to social dominance, with the assumption that behaviors associated with dominance differ according to social context.

Adolescent↗

Life history and the early origins of health differentials.

Current epidemiologic models concerning the fetal origins of later health risk are evaluated from the perspectives of evolutionary and developmental biology. Claims of adaptive value for and biological status of fetal programming are critically examined. Life history theory is applied to identify key trade-offs in adaptive strategies that constrain developmental design to use information from the environment to guide ontogeny and establish cost-benefit trade-offs that weigh early survival advantage against remote or unlikely future costs. Expectable environments of evolutionary adaptedness, particularly of gestation, are characterized and their impact on human adaptive design discussed. The roles of neuroendocrine mechanisms in scaffolding life course development, negotiating ongoing cost-benefit trade-offs, and mediating their long-term impacts on function and health are reviewed in detail. Overviews of gestational biology and the postnatal physiologic, cognitive-affective, and behavioral effects of gestational stress identify a shared central role for the hypothalamic-pituitary-adrenal (HPA) axis. Rather than merely mediating stress responses, the axis emerges an agent of resource allocation that draws a common thread among conditions of gestation, postnatal environments, and functional and health-related outcomes. The preponderance of evolutionary and developmental analysis identifies environments as agents on both sides of the health risk equation, by influencing vulnerabilities and capacities established in early and later life course development, and determining exposures and demands encountered over the life course.

Adaptation, Physiological↗