scholarly journals A multivariate approach to investigate the combined biological effects of multiple exposures

2018 ◽  
Vol 72 (7) ◽  
pp. 564-571 ◽  
Author(s):  
Pooja Jain ◽  
Paolo Vineis ◽  
Benoît Liquet ◽  
Jelle Vlaanderen ◽  
Barbara Bodinier ◽  
...  

Epidemiological studies provide evidence that environmental exposures may affect health through complex mixtures. Formal investigation of the effect of exposure mixtures is usually achieved by modelling interactions, which relies on strong assumptions relating to the identity and the number of the exposures involved in such interactions, and on the order and parametric form of these interactions. These hypotheses become difficult to formulate and justify in an exposome context, where influential exposures are numerous and heterogeneous. To capture both the complexity of the exposome and its possibly pleiotropic effects, models handling multivariate predictors and responses, such as partial least squares (PLS) algorithms, can prove useful. As an illustrative example, we applied PLS models to data from a study investigating the inflammatory response (blood concentration of 13 immune markers) to the exposure to four disinfection by-products (one brominated and three chlorinated compounds), while swimming in a pool. To accommodate the multiple observations per participant (n=60; before and after the swim), we adopted a multilevel extension of PLS algorithms, including sparse PLS models shrinking loadings coefficients of unimportant predictors (exposures) and/or responses (protein levels). Despite the strong correlation among co-occurring exposures, our approach identified a subset of exposures (n=3/4) affecting the exhaled levels of 8 (out of 13) immune markers. PLS algorithms can easily scale to high-dimensional exposures and responses, and prove useful for exposome research to identify sparse sets of exposures jointly affecting a set of (selected) biological markers. Our descriptive work may guide these extensions for higher dimensional data.

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Glòria Carrasco-Turigas ◽  
Cristina M. Villanueva ◽  
Fernando Goñi ◽  
Panu Rantakokko ◽  
Mark J. Nieuwenhuijsen

Disinfection by-products (DBPs) are ubiquitous contaminants in tap drinking water with the potential to produce adverse health effects. Filtering and boiling tap water can lead to changes in the DBP concentrations and modify the exposure through ingestion. Changes in the concentration of 4 individual trihalomethanes (THM4) (chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM)), MX, and bromate were tested when boiling and filtering high bromine-containing tap water from Barcelona. For filtering, we used a pitcher-type filter and a household reverse osmosis filter; for boiling, an electric kettle, a saucepan, and a microwave were used. Samples were taken before and after each treatment to determine the change in the DBP concentration. pH, conductivity, and free/total chlorine were also measured. A large decrease of THM4 (from 48% to 97%) and MX concentrations was observed for all experiments. Bromine-containing trihalomethanes were mostly eliminated when filtering while chloroform when boiling. There was a large decrease in the concentration of bromate with reverse osmosis, but there was a little effect in the other experiments. These findings suggest that the exposure to THM4 and MX through ingestion is reduced when using these household appliances, while the decrease of bromate is device dependent. This needs to be considered in the exposure assessment of the epidemiological studies.


2008 ◽  
Vol 78 (2) ◽  
pp. 64-69 ◽  
Author(s):  
Choi ◽  
Cho

This study investigated the effect of vitamin B6 deficiency on the utilization and recuperation of stored fuel in physically trained rats. 48 rats were given either vitamin B6-deficient (B6–) diet or control (B6+) diet for 4 weeks and were trained on treadmill for 30 minutes daily. All animals were then subdivided into 3 groups: before-exercise (BE); during-exercise (DE); after-exercise (AE). The DE group was exercised on treadmill for 1 hour just before being sacrificed. Animals in the AE group were allowed to take a rest for 2 hours after being exercised like the DE group. Glucose and free fatty acids were compared in plasma. Glycogen and triglyceride were compared in liver and skeletal muscle. Protein levels were compared in plasma, liver, and skeletal muscle. Compared with the B6+ group, plasma glucose levels of the B6– group were significantly lower before and after exercise. Muscle glycogen levels of the B6– group were significantly lower than those of the B6+ group regardless of exercise. The liver glycogen level of the B6– group was also significantly lower than that of B6+ group during and after exercise. Before exercise, plasma free fatty acid levels were not significantly different between the B6+ and B6– groups, and plasma free fatty acid levels of the B6– group were significantly lower during and after exercise. The muscle triglyceride level of the B6– group was significantly lower than that of the B6+ group before exercise, and there were no differences between B6+ and B6– groups during and after exercise. Liver triglyceride levels were not significantly different between B6+ and B6– groups. Plasma protein levels of the B6– group were lower than those of B6+ before and after exercise. Muscle protein levels of the B6– group were not significantly different from those of the B6+ group. Liver protein levels of the B6– group were significantly lower than that of the B6+ group after exercise. Liver protein levels of both B6+ and B6– groups were not significantly changed, regardless of exercise. Thus, it is suggested that vitamin B6 deficiency may reduce fuel storage and utilization with exercise in physically trained rats.


2015 ◽  
Vol 29 (3) ◽  
pp. 119-129 ◽  
Author(s):  
Richard J. Stevenson ◽  
Deborah Hodgson ◽  
Megan J. Oaten ◽  
Luba Sominsky ◽  
Mehmet Mahmut ◽  
...  

Abstract. Both disgust and disease-related images appear able to induce an innate immune response but it is unclear whether these effects are independent or rely upon a common shared factor (e.g., disgust or disease-related cognitions). In this study we directly compared these two inductions using specifically generated sets of images. One set was disease-related but evoked little disgust, while the other set was disgust evoking but with less disease-relatedness. These two image sets were then compared to a third set, a negative control condition. Using a wholly within-subject design, participants viewed one image set per week, and provided saliva samples, before and after each viewing occasion, which were later analyzed for innate immune markers. We found that both the disease related and disgust images, relative to the negative control images, were not able to generate an innate immune response. However, secondary analyses revealed innate immune responses in participants with greater propensity to feel disgust following exposure to disease-related and disgusting images. These findings suggest that disgust images relatively free of disease-related themes, and disease-related images relatively free of disgust may be suboptimal cues for generating an innate immune response. Not only may this explain why disgust propensity mediates these effects, it may also imply a common pathway.


2021 ◽  
Vol 43 (1) ◽  
Author(s):  
Loïc Le Marchand

AbstractSince Dr. Sugimura’s discovery of heterocyclic aromatic amines (HAA) in broiled fish, many epidemiological studies have been conducted to investigate their role in human cancers, often focusing on colorectal cancer. The difficulty in measuring HAA exposure from meat and fish intake in these studies has resulted in inconsistent findings. Because studying individuals who may be particularly susceptible to the carcinogenic effects of HAA might facilitate the demonstration of a link with cancer, multiple studies have focused on individuals with the high activity phenotype for CYP1A2 and/or NAT2, the two main metabolic enzymes involved in the bioactivation of HAA. These investigations have also yielded inconsistent results. Two recent large pooled analyses of colorectal cancer studies have helped clarify the overall evidence. One was conducted in whites and reported no interaction of red meat intake and NAT2 genotype on risk in Whites. The other was conducted in Japanese and African Americans, two populations with high rates of the disease and a prevalence of the at-risk rapid NAT2 phenotype 10- and 2-fold greater than in whites, respectively. In those groups, a significant interaction was found, with the association of red meat with colorectal cancer being strongest among individuals with the rapid NAT2 phenotype, intermediate among those with the intermediate phenotype and not significant among those with the slow NAT2 phenotype. Recent research on biomarkers has focused on PhIP hair content, as a marker of exposure to HAA, and on DNA adducts using new sensitive quantitative methods, as markers of early biological effects. These advances, when brought to bear, may contribute greatly to the further elucidation of the carcinogenicity of HAA in humans.


Insects ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 475
Author(s):  
Vassilios Sideris ◽  
Maria Georgiadou ◽  
Georgios Papadoulis ◽  
Konstantinos Mountzouris ◽  
Antonios Tsagkarakis

The effect of spent coffee grounds (SCG), brewer’s spent grains (BSG) and their mixtures with the addition of brewer’s yeast (BY) were tested in two rearing densities of the Black Soldier Fly, Hermetia illucens (L.). Different treatments were investigated on larval development, survival, yield, protein conversion (PrCR) and bioconversion rate (BCR), substrate mass reduction and body composition of the insect. BSF larvae were able to develop sufficiently in all diets, except on sole SCG. The addition of BY enhanced the performance properties of diets, especially in the case of SCG, where larvae underperformed. Substrate mass reduction, PrCR and BCR were affected only by feed and exhibited higher values on reference feed, followed by BSG and SCG+BSG enriched with BY. Density did not have a significant effect on various larval nutrients, except for fat, which was higher on larvae fed enriched feeds with BY and in the 300 larval density. The interaction between feed and density strongly affected the nitrogen and protein levels, larval yield and ash. Generally, diets which contained SCG exhibited high larval crude protein levels. Our results illustrate that low value beverage by-products can be successfully utilized as constituents of a successful BSF diet.


1976 ◽  
Vol 13 (4) ◽  
pp. 207-214
Author(s):  
Hiroshi Yamanouchi ◽  
Hideo Tohgi ◽  
Masakuni Kameyama ◽  
Mototaka Murakami ◽  
Tamotsu Matsuda

2016 ◽  
Vol 74 ◽  
pp. 133-143 ◽  
Author(s):  
Lars C. Schrübbers ◽  
Bernal E. Valverde ◽  
Bjarne W. Strobel ◽  
Nina Cedergreen

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Hyrum S. Eddington ◽  
Courtney Carroll ◽  
Randy T. Larsen ◽  
Brock R. McMillan ◽  
John M. Chaston

Abstract Background Mule deer rely on fat and protein stored prior to the winter season as an energy source during the winter months when other food sources are sparse. Since associated microorganisms (‘microbiota’) play a significant role in nutrient metabolism of their hosts, we predicted that variation in the microbiota might be associated with nutrient storage and overwintering in mule deer populations. To test this hypothesis we performed a 16S rRNA marker gene survey of fecal samples from two deer populations in the western United States before and after onset of winter. Results PERMANOVA analysis revealed the deer microbiota varied interactively with geography and season. Further, using metadata collected at the time of sampling, we were able to identify different fecal bacterial taxa that could potentially act as bioindicators of mule deer health outcomes. First, we identified the abundance of Collinsella (family: Coriobacteriaceae) reads as a possible predictor of poor overwintering outcomes for deer herds in multiple locations. Second, we showed that reads assigned to the Bacteroides and Mollicutes Order RF39 were both positively correlated with deer protein levels, leading to the idea that these sequences might be useful in predicting mule deer protein storage. Conclusions These analyses confirm that variation in the microbiota is associated with season-dependent health outcomes in mule deer, which may have useful implications for herd management strategies.


1995 ◽  
Vol 182 (6) ◽  
pp. 1997-2006 ◽  
Author(s):  
H Kishimoto ◽  
R T Kubo ◽  
H Yorifuji ◽  
T Nakayama ◽  
Y Asano ◽  
...  

Recent studies indicate that there may be functional uncoupling of the TCR-CD3 complex and suggest that the TCR-CD3 complex is composed of two parallel signal-transducing units, one made of gamma delta epsilon chains and the other of zeta chains. To elucidate the molecular mechanisms that may explain the functional uncoupling of TCR and CD3, we have analyzed their expression by using flow cytometry as well as immunochemical means both before and after stimulation with anti-TCR-beta, anti-CD3 epsilon, anti-CD2, staphylococcal enterotoxin B, and ionomycin. We present evidence that TCR physically dissociates from CD3 after stimulation of the TCR-CD3 complex. Stimulation with anti-CD3 resulted in down-modulation of TCR within 45 min whereas CD3 epsilon was still expressed on the cell surface as detected by flow cytometry. However, the cell surface expression of TCR and CD3 was not affected when cells were stimulated with anti-TCR-beta under the same conditions. In the case of anti-CD3 treatment of T cells, the TCR down-modulation appeared to be due to the internalization of TCR, as determined by immunoelectron microscopy. Immunochemical analysis of cells after stimulation with either anti-TCR or anti-CD3 mAbs revealed that the overall protein levels of TCR and CD3 were similar. More interestingly, the dissociation of the TCR-CD3 complex was observed with both treatments and occurred in a manner that the TCR and the associated TCR-zeta chain dissociated as a unit from CD3. These results provide the first report of physical dissociation of TCR and CD3 after stimulation through the TCR-CD3 complex. The results also suggest that the signal transduction pathway triggered by TCR may differ from that induced by CD3.


1993 ◽  
Vol 129 (3) ◽  
pp. 225-228 ◽  
Author(s):  
Elizabeth Farish ◽  
Hilary A Rolton ◽  
Judith F Barnes ◽  
Colin D Fletcher ◽  
David J Walsh ◽  
...  

Epidemiological studies have shown that postmenopausal oestrogen therapy substantially reduces the risk of cardiovascular and cerebrovascular disease and this is partly mediated by oestrogen-associated changes in lipoproteins, particularly high-density lipoprotein. In this study, we investigated whether changes in lipoprotein(a) might help to account for the reduction in coronary heart disease and stroke associated with postmenopausal oestrogen therapy. The study group consisted of 18 women who had hysterectomy and bilateral oophorectomy at least 2 months prior to recruitment and had received no previous hormonal therapy. Serum samples were collected for measurement of lipoprotein(a) before and after 4 months of treatment with oestradiol valerate (2 mg/day). Lipoprotein(a) levels ranged from 35 to 720 mg/l (median 180 mg/l) before treatment and from 55 to 780 mg/l (median 1 30 mg/l) after oestradiol treatment and showed no consistent pattern of change. It would appear, therefore, that treatment with unopposed oestrogen in relatively low doses does not have a marked effect on lipoprotein(a), at least in the short term.


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