Cytomegalovirus antibodies in dried blood spots: a minimally invasive method for assessing stress, immune function, and aging

<p>Abstract</p> <p>Background</p> <p>Cytomegalovirus (CMV) is a prevalent herpesvirus with links to both stress and aging. This paper describes and validates a minimally invasive method for assessing antibodies against CMV in finger stick whole blood spot samples for use as an indirect marker of an aspect of cell-mediated immunity.</p> <p>Results</p> <p>Analysis of CMV in dried blood spot samples (DBS) was based on modifications of a commercially available protocol for quantifying CMV antibodies in serum or plasma. The method was evaluated through analysis of precision, reliability, linearity, and correlation between matched serum and DBS samples collected from 75 volunteers. Correlation between DBS and plasma values was linear and high (Pearson correlation <it>R </it>= .96), and precision, reliability, and linearity of the DBS assay were within acceptable ranges.</p> <p>Conclusions</p> <p>The validity of a DBS assay for CMV antibodies will enable its inclusion in population-based surveys and other studies collecting DBS samples in non-clinical settings, increasing scientific understanding of the interaction of social and biological stress and immune function.</p

Blood spots as an alternative to whole blood collection and the effect of a small monetary incentive to increase participation in genetic association studies

<p>Abstract</p> <p>Background</p> <p>Collection of buccal cells from saliva for DNA extraction offers a less invasive and convenient alternative to venipuncture blood collection that may increase participation in genetic epidemiologic studies. However, dried blood spot collection, which is also a convenient method, offers a means of collecting peripheral blood samples from which analytes in addition to DNA can be obtained.</p> <p>Methods</p> <p>To determine if offering blood spot collection would increase participation in genetic epidemiologic studies, we conducted a study of collecting dried blood spot cards by mail from a sample of female cancer cases (n = 134) and controls (n = 256) who were previously selected for a breast cancer genetics study and declined to provide a venipuncture blood sample. Participants were also randomized to receive either a $2.00 bill or no incentive with the blood spot collection kits.</p> <p>Results</p> <p>The average time between the venipuncture sample refusal and recruitment for the blood spot collection was 4.4 years. Thirty-seven percent of cases and 28$2.00 incentive vs. 26% for no incentive, p = 0.6), it was significantly associated with participation among the breast cancer cases (48% vs. 27%, respectively, p = 0.01). There did not appear to be any bias in response since no differences between cases and controls and incentive groups were observed when examining several demographic, work history and radiation exposure variables.</p> <p>Conclusion</p> <p>This study demonstrates that collection of dried blood spot cards in addition to venipuncture blood samples may be a feasible method to increase participation in genetic case-control studies.</p

Trends in Mortality from Septicaemia and Pneumonia with Economic Development: An Age-Period-Cohort Analysis

<div><h3>Background</h3><p>Hong Kong population has experienced drastic changes in its economic development in the 1940s. Taking advantage of Hong Kong’s unique demographic and socioeconomic history, characterized by massive, punctuated migration waves from Southern China, and recent, rapid transition from a pre-industrialized society to the first ethnic Chinese community reaching “first world” status over the last 60 years (i.e., in two or three generations), we examined the longitudinal trends in infection related mortality including septicemia compared to trends in non-bacterial pneumonia to generate hypotheses for further testing in other recently transitioned economies and to provide generalized aetiological insights on how economic transition affects infection-related mortality.</p> <h3>Methods</h3><p>We used deaths from septicemia and pneumonia not specified as bacterial, and population figures in Hong Kong from 1976–2005. We fitted age-period-cohort models to decompose septicemia and non-bacterial pneumonia mortality rates into age, period and cohort effects.</p> <h3>Results</h3><p>Septicaemia-related deaths increased exponentially with age, with a downturn by period. The birth cohort curves had downward inflections in both sexes in the 1940s, with a steeper deceleration for women. Non-bacterial pneumonia-related deaths also increased exponentially with age, but the birth cohort patterns showed no downturns for those born in the 1940s.</p> <h3>Conclusion</h3><p>The observed changes appeared to suggest that better early life conditions may enable better development of adaptive immunity, thus enhancing immunity against bacterial infections, with greater benefits for women than men. Given the interaction between the immune system and the gonadotropic axis, these observations are compatible with the hypothesis that upregulation of the gonadotropic axis underlies some of the changes in disease patterns with economic development.</p> </div

The potential of neurofilaments analysis using dry-blood and plasma spots

The lack of biomarkers for an early diagnosis of neurodegenerative disorders (NDs) has hampered the development of therapeutics whose effect would be enhanced by a timely intervention. Neurofilaments light chain (Nf-L), an integral part of the axonal structure, has emerged as a robust fluid biomarker for fatal neurodegenerative disorders like amyotrophic lateral sclerosis (ALS). To facilitate large-scale studies into early-stage neurodegeneration, reduce costs of samples collection/processing and cold-chain storage, we describe the measurement of Nf-L in blood fractions obtained from dry blood spots (DBS) and dry plasma spots (DPS), two filter paper-based remote blood collection tools. To test the feasibility of using this approach, Nf-L analysis in DBS/DPS is compared to that in plasma obtained from the same blood sample, looking at Nf-L discriminatory power in the clinical stratification of ALS compared to healthy controls. With the best pre-analytical treatment for total protein recovery and using highly sensitive immunoassays, we report the detection of different Nf-L levels in DBS elute compared to reference plasma and DPS from the same blood samples. However, Nf-L measurement in DBS elutes provides a very good discrimination of ALS from healthy controls which is comparable to that obtained using plasma Nf-L assays. With the available immunodetection methods, we show that Nf-L measurement based on DPS microsampling is similar to that in plasma. The filter-paper biophysical characteristics and the interference of high haemoglobin concentration released by erythrocyte lysis is likely to perturb Nf-L detection in DBS elute. Further studies into DBS-based Nf-L detection and its analytical optimization are needed to make this method suitable for routine Nf-L blood analyses in neurodegeneration

Screening for C3 Deficiency in Newborns Using Microarrays

BACKGROUND: Dried blood spot samples (DBSS) from newborns are widely used in neonatal screening for selected metabolic diseases and diagnostic possibilities for additional disorders are continuously being evaluated. Primary immunodeficiency disorders comprise a group of more than one hundred diseases, several of which are fatal early in life. Yet, a majority of the patients are not diagnosed due to lack of high-throughput screening methods. METHODOLOGY/PRINCIPAL FINDINGS: We have previously developed a system using reverse phase protein microarrays for analysis of IgA levels in serum samples. In this study, we extended the applicability of the method to include determination of complement component C3 levels in eluates from DBSS collected at birth. Normal levels of C3 were readily detected in 269 DBSS from healthy newborns, while no C3 was detected in sera and DBSS from C3 deficient patients. CONCLUSIONS/SIGNIFICANCE: The findings suggest that patients with deficiencies of specific serum proteins can be identified by analysis of DBSS using reverse phase protein microarrays.QC 20120213</p

The Effects of Stress at Work and at Home on Inflammation and Endothelial Dysfunction

This study examined whether stress at work and at home may be related to dysregulation of inflammation and endothelial function, two important contributors to the development of cardiovascular disease. In order to explore potential biological mechanisms linking stress with cardiovascular health, we investigated cross-sectional associations between stress at work and at home with an inflammation score (n's range from 406–433) and with two endothelial biomarkers (intercellular and vascular adhesion molecules, sICAM-1 and sVCAM-1; n's range from 205–235) in a cohort of healthy US male health professionals. No associations were found between stress at work or at home and inflammation. Men with high or medium levels of stress at work had significantly higher levels of sVCAM-1 (13% increase) and marginally higher levels of sICAM-1 (9% increase), relative to those reporting low stress at work, independent of health behaviors. Men with high levels of stress at home had marginally higher levels of both sVCAM-1 and sICAM-1 than those with low stress at home. While lack of findings related to inflammation are somewhat surprising, if replicated in future studies, these findings may suggest that endothelial dysfunction is an important biological mechanism linking stress at work with cardiovascular health outcomes in men

Kowakare: A New Perspective on the Development of Early Mother–Offspring Relationship

The mother–offspring relationship has components of both positivity and negativity. Kowakare is a new concept introduced to explain an adaptive function of the negativity in the early mother-offspring relationship. Kowakare is the psycho-somatic development of the relationship as the process of accumulation in the otherness of offspring. Early human Kowakare has two frameworks, biological inter-body antagonism and socio-cultural allomothering compensating the antagonism. Some features of feeding/weaning, parental aversion to offspring’s bodily products, and transition from dyad to triad relationship (proto–triad relationship) in tactile play are discussed. Early human Kowakare is promoted by allomothering with the nested systems of objects/persons/institutions as interfaces between mother and offspring. Kowakare makes mother–offspring relationship a mutually autonomous and cooperative companionship