dried-blood-spot-collection-health-biomarkers-to-maximize

Dried Blood Spot Collection of Health Biomarkers to Maximize Participation in Population Studies

Biomarkers are directly-measured biological indicators of disease, health, exposures, or other biological information. In population and social sciences, ...

Harvard School of Public Health

Brigham and Women's Hospital

Limited nutritional information exists on diets of free-ranging orangutans, Pongo abelii and P. pygmaeus. Although they are classified as frugivores, the chemical composition of their diet and their gastrointestinal anatomy suggest that they rely on fiber fermentation for a substantial portion of energy. However, the extent to which they can ferment fiber is not known. Continuous culture systems, inoculated with orangutan fecal bacteria, were established to determine the fiber-digesting capacity of orangutan hindgut microflora. The cultures received one of four treatments: soybean hulls, ground corncobs, corn starch, or no food. Neither dry matter nor neutral detergent fiber digestibilities differed significantly among treatments. However, neutral detergent fiber digestibilities were high for both the soybean hull (88.4%) and ground corncob (86.1%) treatments, indicating that the microflora had a strong fibrolytic capability. To determine whether the same fiber-degrading capacity occurred in vivo, two adult orangutans and one juvenile were fed four gel-matrix diets containing soybean hulls, ground corncobs, or ground primate biscuits. Neutral detergent fiber concentrations (dry matter basis) of the gel matrices were 52.9% with soybean hulls, 46.8% and 63.7% with ground corncobs, and 31.3% with ground primate biscuits. A fifth diet consisted of primate biscuits with 27.3% neutral detergent fiber (dry matter basis) and was considered the baseline diet. Neutral detergent fiber digestibility (74.5%) was greatest (P < 0.05) for the soybean hull gel diet and least (57.5% and 45.0%, respectively; P < 0.05) for the 63.7% neutral detergent fiber (dry matter basis) corncob gel diet and the baseline primate biscuit diet. Total volatile fatty acid concentrations in orangutan feces were not significantly different among diets; however, molar proportions of acetic, propionic, and butyric acid differed (P < 0.05) among diets. The results from both studies indicated that orangutans are capable of extensive fiber fermentation.

Fiber digestibility by the orangutan (Pongo abelii): in vitro and in vivo.

Black lemurs, Eulemur macaco, are classified as generalist feeders, consuming a proportion of fruits and leaves that varies with seasonal availability. It is hypothesized that black lemurs are capable of using neutral detergent fiber (NDF) as a source of energy through fiber fermentation in the cecum and large intestine. In captivity, they are typically fed a diet of commercially available primate biscuits and readily available produce, both of which are limited in NDE Digestibility trials were conducted on 14 black lemurs; 12 were housed in groups (four, three, three, and two) and 2 were individually housed. The lemurs were fed four manufactured feeds differing in fiber form and content. A commercially available primate biscuit, containing approximately 27% NDF, served as the control diet. The second diet contained the same primate biscuits, which were ground and then incorporated into a fiber-based gel matrix. The third and fourth diets were formulated using soybean hulls or ground corncobs as the fiber source, resulting in 53% and 47% NDF, respectively. Produce was added to the diet at 36% (dry matter basis). Dry matter digestibility differed significantly among all diets. Neutral detergent fiber digestibility was highest for the ground biscuit in gel and lowest for the two high-fiber gel diets, with biscuit digestibility values falling between the two extremes. The high-fiber gel diets were successful in increasing the NDF concentrations of the primate diets; however, black lemurs were capable of only limited fiber digestion.

Fiber digestibility by black lemurs (Eulemur macaco macaco).

Aging is associated with insulin resistance, often attributable to obesity and inactivity. Recent evidence suggests that skeletal muscle insulin resistance in aging is associated with mitochondrial alterations. Whether this is true of the senescent myocardium is unknown. Twelve young (Y, 4 years old) and 12 old (O, 11 years old) dogs, matched for body mass, were instrumented with left-ventricular pressure gauges, aortic and coronary sinus catheters, and flow probes on left circumflex artery. Before surgery, all dogs participated in a 6-wk exercise program. Dogs underwent measurements of hemodynamics and plasma substrates before and during a 2-h hyperinsulinemic-euglycemic clamp to measure whole body and myocardial glucose and nonesterified fatty acid uptake. Following the protocol, myocardial and skeletal samples were obtained to measure components of the insulin-signaling cascade and mitochondrial structure. There was no difference in plasma glucose (Y, 90 +/- 4 mg/dl; O, 87 +/- 4 mg/dl), but old dogs had higher (P < 0.02) nonesterified fatty acids (Y, 384 +/- 48 micromol/l; O, 952 +/- 97 micromol/l) and plasma insulin (Y, 39 +/- 11 pmol/l; O, 108 +/- 18 pmol/l). Old dogs had impaired total body glucose disposition (Y, 11.5 +/- 1 mg x kg(-1) x min(-1); O, 8.0 +/- 0.5 mg x kg(-1) x min(-1); P < 0.05) and insulin-stimulated myocardial glucose uptake (Y, 3.5 +/- 0.3 mg x min(-1) x g(-1); O, 1.8 +/- 0.3 mg x min(-1) x g(-1); P < 0.05). The impaired insulin action was associated with altered insulin signaling and glucose transporter (GLUT4) translocation. There were myocardial mitochondrial structural changes observed in association with decreased expression of uncoupling protein-3. Aging is associated with both whole body and myocardial insulin resistance, independent of obesity and inactivity, but involving altered mitochondrial structure and impaired cellular insulin action.

Aging is associated with myocardial insulin resistance and mitochondrial dysfunction.

The rumen, the foregut of herbivorous ruminant animals such as cattle, functions as a bioreactor to process complex plant material. Among the numerous and diverse microbes involved in ruminal digestion are the ruminal protozoans, which are single-celled, ciliated eukaryotic organisms. An activity-based screen was executed to identify genes encoding fibrolytic enzymes present in the metatranscriptome of a bovine ruminal protozoan-enriched cDNA expression library. Of the four novel genes identified, two were characterized in biochemical assays. Our results provide evidence for the effective use of functional metagenomics to retrieve novel enzymes from microbial populations that cannot be maintained in axenic cultures.

Activity-based metagenomic screening and biochemical characterization of bovine ruminal protozoan glycoside hydrolases.

Epidemiological studies link short sleep duration and circadian disruption with higher risk of metabolic syndrome and diabetes. We tested the hypotheses that prolonged sleep restriction with concurrent circadian disruption, as can occur in people performing shift work, impairs glucose regulation and metabolism. Healthy adults spent >5 weeks under controlled laboratory conditions in which they experienced an initial baseline segment of optimal sleep, 3 weeks of sleep restriction (5.6 hours of sleep per 24 hours) combined with circadian disruption (recurring 28-hour "days"), followed by 9 days of recovery sleep with circadian re-entrainment. Exposure to prolonged sleep restriction with concurrent circadian disruption, with measurements taken at the same circadian phase, decreased the participants' resting metabolic rate and increased plasma glucose concentrations after a meal, an effect resulting from inadequate pancreatic insulin secretion. These parameters normalized during the 9 days of recovery sleep and stable circadian re-entrainment. Thus, in humans, prolonged sleep restriction with concurrent circadian disruption alters metabolism and could increase the risk of obesity and diabetes.

Adverse metabolic consequences in humans of prolonged sleep restriction combined with circadian disruption.

Health care workers are at high risk of developing musculoskeletal symptoms and pain. This study tested the hypothesis that sleep deficiency is associated with pain, functional limitations, and physical limitations that interfere with work.

Article	Year
Fiber digestibility by the orangutan (Pongo abelii): in vitro and in vivo. Journal of zoo and wildlife medicine : official publication of the American Association of Zoo Veterinarians\| PubMed ID: 17312712	2005
Fiber digestibility by black lemurs (Eulemur macaco macaco). Journal of zoo and wildlife medicine : official publication of the American Association of Zoo Veterinarians\| PubMed ID: 17323560	2005
Aging is associated with myocardial insulin resistance and mitochondrial dysfunction. American journal of physiology. Heart and circulatory physiology\| PubMed ID: 17873028	2007
Activity-based metagenomic screening and biochemical characterization of bovine ruminal protozoan glycoside hydrolases. Applied and environmental microbiology\| PubMed ID: 21948825	2011
Adverse metabolic consequences in humans of prolonged sleep restriction combined with circadian disruption. Science translational medicine\| PubMed ID: 22496545	2012
Relationship of sleep deficiency to perceived pain and functional limitations in hospital patient care workers. Journal of occupational and environmental medicine / American College of Occupational and Environmental Medicine\| PubMed ID: 22796931	2012

James H. Porter

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