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Background: Gestational age is often used as a proxy for developmental maturity by clinicians and researchers alike. DNA methylation has previously been shown to be associated with age and has been used to accurately estimate chronological age in children and adults. In the current study, we examine whether DNA methylation in cord blood can be used to estimate gestational age at birth. Results: We find that gestational age can be accurately estimated from DNA methylation of neonatal cord blood and blood spot samples. We calculate a DNA methylation gestational age using 148 CpG sites selected through elastic net regression in six training datasets. We evaluate predictive accuracy in nine testing datasets and find that the accuracy of the DNA methylation gestational age is consistent with that of gestational age estimates based on established methods, such as ultrasound. We also find that an increased DNA methylation gestational age relative to clinical gestational age is associated with birthweight independent of gestational age, sex, and ancestry. Conclusions: DNA methylation can be used to accurately estimate gestational age at or near birth and may provide additional information relevant to developmental stage. Further studies of this predictor are warranted to determine its utility in clinical settings and for research purposes. When clinical estimates are available this measure may increase accuracy in the testing of hypotheses related to developmental age and other early life circumstances. Electronic supplementary material The online version of this article (doi:10.1186/s13059-016-1068-z) contains supplementary material, which is available to authorized users., Version of Record

3-day-old miniature piglets were stimulated in vivo with Bacillus firmus by the intraperitoneal or intragastric route for 1 d. Cells containing IgA and IgG2 were detected in the ileum in all stimulated but not in control animals. The frequency of blood CD3+ cells increased after intraperitoneal administration of B. firmus, the ratio of polymorphonuclears to lymphocytes increased in all stimulated piglets. B. firmus induced antitumor immunity in rats with transplanted Yoshida sarcoma cells. Granular lymphocytes and dead tumor cells were found in peritoneal exudate of stimulated animals. B. firmus induced IFN-γ synthesis in human blood lymphocytes stimulated in vitro for 1 d. The amount of TNF-α produced by these stimulated human peripheral blood mononuclears (PBMC) was lower than that of PBMC stimulated with some other bacterial immunomodulators. Cells containing TGF-β or IL-8 were not found in human PBMC stimulated with B. firmus. [ABSTRACT FROM AUTHOR]

Some bacteria possess the ability to convert cholic acid (CA) to pharmacologically important chenodeoxycholic acid (CDCA) or to its precursor 3α, 7α-dihydroxy-12-oxo-5β-cholan-24-ic acid (12-oxo-CDCA). The ability of several bacterial strains to convert CA to 12-oxo-CDCA was tested in our work. The highest conversion was reached by one strain of Arthrobacter sp. which converted up to 61% CA to 12-oxo-CDCA in a complex medium containing 4% ( W/V) CA under aerobic conditions. 12-Oxo-CDCA was further oxidized to 3,12-dioxo-7ì-hydroxy-5β-cholan-24-ic acid (3,12-dioxo-7-OHCA) that represented up to 10% of total bile acids in the cultivation medium after a 1-d cultivation. The concentration of 12-oxo-CDCA increased rapidly during the first hours of cultivation, maximal yields were achieved between 20 and 24 h of cultivation and they decreased after that due to further bacterial oxidation. [ABSTRACT FROM AUTHOR]

Bacillus firmus strongly stimulates Ig synthesis in the cultures of human peripheral blood mononuclear leukocytes. As apparent from the character of Ig formation and blastic transformation, the stimulation has features of a polyclonal activation of B lymphocytes without substantial participation of T lymphocytes. B. firmus is a strong B cell polyclonal activator even for human cord blood lymphocytes. The most striking feature is the strong stimulation of IgA synthesis in both adult and cord blod lymphocytes. Several crude fractions were isolated from B. firmus. None of them exhibited any remarkable enhancement of activity but the cytoplasmic fraction P-40 was clearly more potent than the intact bacilli. On the other hand, cell wall peptidoglycan, a well known polyclonal activator of B cells, had a much lower activity than whole bacteria. The effect of B. firmus on the stimulation of Ig formation is thus relatively complex; it is not caused mainly by peptidoglycan but rather by some cytoplasmic constituents of the bacterium. [ABSTRACT FROM AUTHOR]

Bacillus firmus is a Gram-positive, aerobic, sporulating, nonpathogenic air contaminant which, according to earlier findings, is a strong polyclonal activator of B lymphocytes. The crude lipids of this microbe induced significant resistance of mice against listerial infection. The administration of bacterin, like that of crude lipids obtained by the extraction of cell suspension with chloroform-methanol to rats, strain AVN Wistar, transplanted later with Yoshida sarcoma, significantly prolonged the survival of the animals in comparison with the control group. At the same time the number of granular lymphocytes was increased. The destruction of tumor cells in the peritoneal exudate of immunostimulated rats was also determined. [ABSTRACT FROM AUTHOR]

B. firmus activates human peripheral blood lymphocytes in vitro. Bacteria inactivated by heat or by formaldehyde were about equally effective, stimulating the blastic transformation of lymphocytes at doses of 10-200 mg/L and Ig formation in the culture at 10-500 mg/L. The action of formaldehyde treated B. firmus was compared with that of analogously inactivated B. subtilis, B. polymyxa, B. coagulans, B. megaterium, B. pumilus, B. cereus and B. lentus at a concentration of 100 mg/L. All these bacilli midly stimulated blastic transformation and most of them substantially stimulated Ig formation, but B. firmus was the most efficient in stimulating the formation of Ig of all classes, in particular IgM and IgA. Its effect on Ig formation was comparable with that of PWM and was unusually high as compared with that of other bacteria. B. firmus is apparently a strong polyclonal activator of B lymphocytes. Its cells or their components could be potentially used for modulating immune reactions. [ABSTRACT FROM AUTHOR]

Crude lipids isolated from Bacillus firmus, but not from other bacilli, were previously found to induce significant resistance against Listeria monocytogenes infection in mice. In this study, formaldehyde-and heat-killed bacterins of eight Bacillus species and some cellular fractions of B. firmus were prepared and tested for further immunomodulatory activities. Crude lipids, their aqueous extract, LTA, Protodyne and Pex-residue preparations exhibited a strong anti-infection activity, whereas Pextract, P40 and all bacterins tested had no effect. Formaldehyde-killed bacterins, live bacteria and the P40 preparation of both B. firmus strains, as well as bacterins of both B. subtilis strains, induced pronounced splenomegaly in mice. Peptidoglycan and Pex-residue induced significant depression of cytochrome P-450 in mouse liver microsomes after application of 0.1 mg per mouse. Optimal conditions for obtaining a bacterial suspension exhibiting these immunomodulatory properties were elaborated. [ABSTRACT FROM AUTHOR]

Using the ELISA method antibodies against the sonicate, teichoic acid (TA) and exoproducts of Staphylococcus aureus were determined in sera and saliva of healthy individuals. Main serum antibodies against all the antigens used were shown to be class IgG antibodies. However, antigens of the sonicate stimulated significantly even the systemic IgA response. In the saliva class IgA antibodies predominated, but IgG antibody levels against TA and exoproducts approached the level of IgA antibodies. Levels of IgM antibodies against all antigens tested were low in both the serum and saliva which corresponds with the anamnestic type of response. On the basis of these results one may assume that not only IgG, but also IgA antibodies are important in the systemic immunity against staphylococcal infection and in the immunity of mucous membranes; besides IgA, even class IgG antibodies play an important role. [ABSTRACT FROM AUTHOR]

Using phenol-water extraction, a lipopeptidopolysacoharide complex (LPPS) was isolated from Listeria monocytogenes. Some biological and immunological properties of LPPS were compared with lipopolysaccharide isolated by the same procedure from Salmonella typhimurium. LPPS possesses low pyrogenicity, but the immunological activity is comparable with LPS: slightly lower adjuvant and polyolonal stimulating effect, almost equal mitogenic effect on mouse spleen cells and higher mitogenic effect oh human peripheral blood cells, The results are discussed in connection with the chemical structure of both substances. [ABSTRACT FROM AUTHOR]

The avirulent strain Listeria monocytogenes (Welshimer) induced upon a single injection 4 weeks prior to challenge with Mycobacterium tuberculosis HR resistance in guinea-pigs, which was manifested by a significant decrease of spleen weight and Feldman's index in immunized animals. The degree of resistance was dependent on the immunizing dose and time of administration. Repeated high doses of Listeria yielded only a low or no effect. Further increase of resistance was obtained using the BCG lipids; however, stimulation of resistance with listeria lipids was not successful and, finally, Freund's incomplete adjuvant was significantly effective in the Feldman index only. The BCG lipids, extracted with ethanol, which contained nitrogen and water-soluble substances, induced a significant resistance against M. tuberculosis infection. The chloroform-methanol BCG lipids were also effective, however, significantly less than the ethanol-extracted material. The listeria factor E itself or together with Freund's incomplete adjuvant possessed only low effectiveness against mycobacterial infection. However, if injected together with ethanol-extracted BCG lipids, it produced a significant degree of resistance which was higher than that induced by lipids only. The degree of resistance was comparable with the effect of living BCG strain which served as a source of isolated lipids. [ABSTRACT FROM AUTHOR]

Epidemiologic evidence on the association of antioxidant intake and prostate cancer incidence is inconsistent. Total antioxidant intake and prostate cancer incidence have not previously been examined. Using the ferric-reducing antioxidant potential (FRAP) assay, the total antioxidant content (TAC) of diet and supplements was assessed in relation to prostate cancer incidence. A prospective cohort of 47,896 men aged 40-75 years was followed from 1986 to 2008 for prostate cancer incidence (N = 5,656), and they completed food frequency questionnaires (FFQs) every 4 years. A FRAP value was assigned to each item in the FFQ, and for each individual, TAC scores for diet, supplements and both (total) were calculated. Major contributors of TAC intake at baseline were coffee (28%), fruit and vegetables (23%) and dietary supplements (23%). In multivariate analyses for dietary TAC a weak inverse association was observed [highest versus lowest quintiles: 0.91 (0.83-1.00, p-trend = 0.03) for total prostate cancer and 0.81 (0.64-1.01, p-trend = 0.04) for advanced prostate cancer]; this association was mainly due to coffee. No association of total TAC on prostate cancer incidence was observed. A positive association with lethal and advanced prostate cancers was observed in the highest quintile of supplemental TAC intake: 1.28 (0.98-1.65, p-trend < 0.01) and 1.15 (0.92-1.43, p-trend = 0.04). The weak association between dietary antioxidant intake and reduced prostate cancer incidence may be related to specific antioxidants in coffee, to nonantioxidant coffee compounds or other effects of drinking coffee. The indication of increased risk for lethal and advanced prostate cancers with high TAC intake from supplements warrants further investigation., Accepted Manuscript

Purpose: To study associations between single nucleotide polymorphisms (SNP) in Ribonuclease L (RNASEL), a gene implicated in inflammation and prostate cancer risk, and outcomes after radiation therapy.Experimental Design: We followed participants in the prospective US Health Professionals Follow-Up Study treated with radiation therapy for early-stage prostate cancer. Three SNPs were genotyped based on previously determined functional and biological significance. We used multivariable Cox proportional hazards models to assess per-allele associations with the primary outcome defined as time to a composite endpoint including development of lethal prostate cancer or biochemical recurrence.Results: We followed 434 patients treated with radiation therapy for a median of 9 years. On multivariate analysis, the rs12757998 variant allele was associated with significantly decreased risk of the composite endpoint [HR: 0.65; 95% confidence interval (CI), 0.45-0.94%; P = 0.02] driven by decreased biochemical recurrence (HR: 0.60; 95% CI, 0.40-0.89%; P = 0.01) and men treated with external beam (HR: 0.58; 95% CI, 0.36-0.93%; P = 0.02). In contrast, in 516 men from the same cohort treated with radical prostatectomy, we found no significant impact of this variant on outcome. Furthermore, the rs12757998 variant allele significantly modified the association between androgen deprivation therapy and outcomes after radiation therapy (p-interaction 0.02).Conclusion: We show an association between RNASEL SNP rs12757998 and outcome after radiation therapy for prostate cancer. This SNP is associated with increased circulating C-reactive protein and interleukin-6, suggesting a potential role for inflammation in the response to radiation. If validated, genetic predictors of outcome may help inform prostate cancer management. Clin Cancer Res; 19(6); 1612-9. (C)2013 AACR., Accepted Manuscript

BACKGROUND Common genetic variants in the Toll-like receptor 4 (TLR4), which is involved in inflammation and immune response pathways, may be important for prostate cancer.METHODS. In a large nested case-control study of prostate cancer in the Physicians' Health Study (1982-2004), 10 single nucleotide polymorphisms (SNPs) were selected and genotyped to capture common variation within the TLR4 gene as well as 5 kb up and downstream. Unconditional logistic regression was used to assess associations of these SNPs with total prostate cancer incidence, and with prostate cancers defined as advanced stage/lethal (T3/ T4, M1/N1(T1-T4), lethal) or high Gleason grade (7 (4 + 3) or greater). Cox-proportional hazards regression was used to assess progression to metastases and death among prostate cancer cases. RESULTS . The study included 1,267 controls and 1,286 incident prostate cancer cases, including 248 advanced stage/lethal and 306 high grade cases. During a median follow-up of 10.6 years, 183 men died of prostate cancer or developed distant metastases. No statistically significant associations between the TLR4 SNPs were found for total prostate cancer incidence, including SNPs for which an association was reported in other published studies. Additionally, there were no significant associations with TLR4 SNPS and the incidence of advanced stage/lethal, or high grade cancers; nor was there evidence among prostate cancer cases for associations of TLR4 SNPs with progression to prostate cancer specific mortality or bony metastases. CONCLUSION S. Results from this prospective nested case-control study suggest that genetic variation across TLR4 alone is not strongly associated with prostate cancer risk or mortality. Prostate 72: 209-216, 2012., Accepted Manuscript

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