A critical appraisal of the scientific basis of commercial genomic profiles used to assess health risks and personalize health interventions

Predictive genomic profiling used to produce personalized nutrition and other lifestyle health recommendations is currently offered directly to consumers. By examining previous meta-analyses and HuGE reviews, we assessed the scientific evidence supporting the purported gene-disease associations for genes included in genomic profiles offered online. We identified seven companies that offer predictive genomic profiling. We searched PubMed for meta-analyses and HuGE reviews of studies of gene-disease associations published from 2000 through June 2007 in which the genotypes of people with a disease were compared with those of a healthy or general-population control group. The seven companies tested at least 69 different polymorphisms in 56 genes. Of the 56 genes tested, 24 (43%) were not reviewed in meta-analyses. For the remaining 32 genes, we found 260 meta-analyses that examined 160 unique polymorphism-disease associations, of which only 60 (38%) were found to be statistically significant. Even the 60 significant associations, which involved 29 different polymorphisms and 28 different diseases, were generally modest, with synthetic odds ratios ranging from 0.54 to 0.88 for protective variants and from 1.04 to 3.2 for risk variants. Furthermore, genes in cardiogenomic profiles were more frequently associated with noncardiovascular diseases than with cardiovascular diseases, and though two of the five genes of the osteogenomic profiles did show significant associations with disease, the associations were not with bone diseases. There is insufficient scientific evidence to conclude that genomic profiles are useful in measuring genetic risk for common diseases or in developing personalized diet and lifestyle recommendations for disease prevention.     

Microbiological Analysis of Food Contact Surfaces in Child Care Centers

A study of six child care centers was conducted to assess the microbiological quality of three food contact surfaces (one food serving surface and two food preparation surfaces) and one non-food contact surface (diaper changing surface) to determine the effectiveness of cleaning and sanitization procedures within the facilities. Aerobic plate counts (APCs) and Escherichia coli/coliform counts of 50-cm² areas on all surfaces were determined using standard microbiological swabbing methods. Samples were taken three times a day (preopening, lunchtime, and following final cleanup) twice per month for 8 months in each child care center (n = 288 sampling times). Mean log APCs over the survey period were 1.32, 1.71, 1.34, 1.96, 1.50, and 1.81 log CFU/50 cm² for the six centers. Mean log coliform counts were 0.15, 0.40, 0.33, 1.41, 0.28, and 1.12 CFU/50 cm² for the same centers. Coliforms were detected in 283 of 1,149 (24.7%) samples, with counts ranging from 1 to 2,000 CFU/50 cm², while E. coli was detected in 18 of 1,149 (1.6%) samples, with counts ranging from 1 to 35 CFU/50 cm². The findings of this study demonstrated that the extent of bacterial contamination was dependent on the center, time of day, and the area sampled. While no direct correlation between contamination and illness can be made, given the high risk of food-borne illness associated with children, microbial contamination of food contact or non-food contact surfaces is an aspect of food safety that requires more attention. Emphasis on training and the development of modified standard sanitation operating procedures for child care centers are needed to reduce potential hazards.     

Decreased pathology and prolonged survival of human DC-SIGN transgenic mice during mycobacterial infection

Dendritic cell (DC)-specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN: CD209) is a C-type lectin that binds ICAM-2,3 and various pathogens such as HIV, helicobacter, and mycobacteria. It has been suggested that Mycobacterium tuberculosis, the causative agent of pulmonary tuberculosis, interacts with DC-SIGN to evade the immune system. To directly analyze the role of human DC-SIGN during mycobacterial infection, we generated conventional transgenic (tg) mice (termed "hSIGN") using CD209 cDNA under the control of the murine CD11c promoter. Upon mycobacterial infection, DCs from hSIGN mice produced significantly less IL-12p40 and no significant differences were be observed in the secretion levels of IL-10 relative to control DCs. After high dose aerosol infection with the strain M. tuberculosis H37Rv, hSIGN mice showed massive accumulation of DC-SIGN(+) cells in infected lungs, reduced tissue damage and prolonged survival. Based on our in vivo data, we propose that instead of favoring the immune evasion of mycobacteria, human DC-SIGN may have evolved as a pathogen receptor promoting protection by limiting tuberculosis-induced pathology.     

Spacing behaviour and its implications for the mating system of a precocial small mammal: an almost asocial cavyCavia magna ?

Socioecological models for small mammals attempt to explain the causal relations between the spatiotemporal distributions of food resources, females and males. We tested their predictions for a wild population of Cavia magna, a grazing, precocial rodent, by analysing spacing behaviour in relation to various demographic features. Between May 1999 and January 2001 we collected capture-recapture data on 309 individuals and monitored 55 females and 49 males by radiotelemetry in periodically inundated wetland in Uruguay. Cavies showed a nonstationary use of space: monthly home ranges drifted over the whole study site. Female home ranges overlapped with those of several others. Females were randomly distributed and we found no evidence for socially mediated reproductive synchrony. Males ranged over larger areas than females, showing even less site fidelity, and also overlapped with several rivals. This basic spacing system remained stable over a wide range of densities and sex ratios. Independent of sex, animals used overlap zones randomly with respect to each other. Significant dynamic (spatiotemporal) interaction was most frequent between males and females. However, interaction analyses revealed no evidence for stable social bonds between animals, regardless of sex. We suggest that unpredictable female locations prevent males monopolizing females spatially. Because females are solitary, males could monopolize only one female by maintaining close proximity, rendering a roaming mating tactic more successful. Our findings point to a solitary ‘social’ system and overlap promiscuity as the likely mating system for the C. magna population studied. Copyright 2003 Published by Elsevier Ltd on behalf of The Association for the Study of Animal Behaviour.      

The epizoic diatom community on four bryozoan species from Helgoland (German Bight, North Sea)

The composition of the diatom community on the bryozoans Electra pilosa, Membranipora membranacea, Flustra foliacea, and Alcyonidium gelatinosum from the German Bight was studied by light and scanning electron microscopy. In total, members of 26 diatom genera were found, with Cocconeis, Tabularia, Licmophora, Amphora, and Navicula being the most abundant. The amount and the composition of the diatom covering seem to be typical for single bryozoan species. Electra pilosa and Membranipora membranacea showed a rather dense covering with 71–547 cells/mm² and 77–110 cells/mm², respectively. The most prominent genus on Electra pilosa was Cocconeis, reaching up to 58% of all diatoms in one sample, followed by Navicula, Tabularia and Amphora. The most abundant genera on Membranipora membranacea were Tabularia and Licmophora, making up almost 70% of all diatoms in one sample, followed by Navicula, Cocconeis and Amphora. The diatom composition was very stable on all Electra samples, but varied on Membranipora samples. With <1–27 cells/mm², diatoms were much less abundant on Alcyonidium gelatinosum. Members of the genera Tabularia and Navicula were the most frequently found benthic diatoms, whereas the planktonic forms Coscinodiscus, Cyclotella, and Thalassiosira made up 35% of the diatoms. On Flustra foliacea, diatoms were virtually absent, with fewer than 5 cells/mm². The low diatom numbers are probably due to toxic metabolites produced by the host. The same may be true for Alcyonidium gelatinosum, but here they might also be a consequence of the surface properties of the bryozoan. Electronic Publication     

Groups IV, V, and X phospholipases A2s in human neutrophils: role in eicosanoid production and gram-negative bacterial phospholipid hydrolysis.

The bacterial tripeptide formyl-Met-Leu-Phe (fMLP) induces the secretion of enzyme(s) with phospholipase A(2) (PLA(2)) activity from human neutrophils. We show that circulating human neutrophils express groups V and X sPLA(2) (GV and GX sPLA(2)) mRNA and contain GV and GX sPLA(2) proteins, whereas GIB, GIIA, GIID, GIIE, GIIF, GIII, and GXII sPLA(2)s are undetectable. GV sPLA(2) is a component of both azurophilic and specific granules, whereas GX sPLA(2) is confined to azurophilic granules. Exposure to fMLP or opsonized zymosan results in the release of GV but not GX sPLA(2) and most, if not all, of the PLA(2) activity in the extracellular fluid of fMLP-stimulated neutrophils is due to GV sPLA(2). GV sPLA(2) does not contribute to fMLP-stimulated leukotriene B(4) production but may support the anti-bacterial properties of the neutrophil, because 10-100 ng per ml concentrations of this enzyme lead to Gram-negative bacterial membrane phospholipid hydrolysis in the presence of human serum. By use of a recently described and specific inhibitor of cytosolic PLA(2)-alpha (group IV PLA(2)alpha), we show that this enzyme produces virtually all of the arachidonic acid used for the biosynthesis of leukotriene B(4) in fMLP- and opsonized zymosan-stimulated neutrophils, the major eicosanoid produced by these pro-inflammatory cells.