Search

Several bacterial taxa enriched in inflammatory bowel diseases and colorectal cancer (CRC) are found in the oral cavity. We conducted a pilot study nested within a six-week aspirin intervention in a randomized placebo-controlled trial to test their response to aspirin intervention. Fifty healthy subjects, 50–75 years old, were randomized to receive 325 mg aspirin (n = 30) or placebo (n = 20) orally once daily for six weeks. Oral tongue swabs were collected at baseline and week six. We estimated the association between aspirin use and the temporal changes in the relative abundance of pre-specified genus level taxa from pre- to post-treatment. The temporal change in relative abundance differed for eight genus level taxa between the aspirin and placebo groups. In the aspirin group, there were significant increases in the relative abundances of Neisseria, Streptococcus, Actinomyces, and Rothia and significant decreases in Prevotella, Veillonella, Fusobacterium, and Porphyromonas relative to placebo. The log ratio of Neisseria to Fusobacterium declined more in the aspirin group than placebo, signaling a potential marker associated with aspirin intervention. These preliminary findings should be validated using metagenomic sequencing and may guide future studies on the role of aspirin on taxa in various oral ecological niches.

Several bacterial taxa enriched in inflammatory bowel diseases and colorectal cancer (CRC) are found in the oral cavity. We conducted a pilot study nested within a six-week aspirin intervention in a randomized placebo-controlled trial to test their response to aspirin intervention. Fifty healthy subjects, 50–75 years old, were randomized to receive 325 mg aspirin (n = 30) or placebo (n = 20) orally once daily for six weeks. Oral tongue swabs were collected at baseline and week six. We estimated the association between aspirin use and the temporal changes in the relative abundance of pre-specified genus level taxa from pre- to post-treatment. The temporal change in relative abundance differed for eight genus level taxa between the aspirin and placebo groups. In the aspirin group, there were significant increases in the relative abundances of Neisseria, Streptococcus, Actinomyces, and Rothia and significant decreases in Prevotella, Veillonella, Fusobacterium, and Porphyromonas relative to placebo. The log ratio of Neisseria to Fusobacterium declined more in the aspirin group than placebo, signaling a potential marker associated with aspirin intervention. These preliminary findings should be validated using metagenomic sequencing and may guide future studies on the role of aspirin on taxa in various oral ecological niches. [ABSTRACT FROM AUTHOR]

The intestinal microbiota produces β-glucuronidase that plays an essential role in the metabolism of the immunosuppressant mycophenolate mofetil (MMF). This drug is commonly used in organ and hematopoietic cell transplantation (HCT), with variations in dosing across transplant types. We hypothesized that β-glucuronidase activity differs between transplant types, which may account for differences in dosing requirements. We evaluated fecal β-glucuronidase activity in patients receiving MMF post-allogeneic HCT and post-kidney transplant. Kidney transplant patients had significantly greater β-glucuronidase activity (8.48 ± 6.21 nmol/hr/g) than HCT patients (3.50 ± 3.29 nmol/hr/g; P = .001). Microbially mediated β-glucuronidase activity may be a critical determinant in the amount of mycophenolate entering the systemic circulation and an important factor to consider for precision dosing of MMF.

Jean-Yves Niemier,1,2 Frédérique Claudot,3,4 Phi Linh Nguyen-Thi,4 Jean-Marie Hubert,5 Hubert Rousselot,2,6 Athanase Benetos,1 Christine Perret-Guillaume1,3 1Department of Geriatric Medicine, CHRU de Nancy, Nancy, France; 2UCOG Lorraine, Nancy, France; 3EA 4360 APEMAC, Faculté de Médecine, Université de Lorraine, Nancy, France; 4PARC, CHRU de Nancy, Nancy, France; 5Spincourt Multidisciplinary MSP, Spincourt, France; 6SISSPO Department, Institut de Cancérologie de Lorraine, Vandœuvre-lès-Nancy, France Objective: The objective of this study was to identify changes in the decision-making criteria of general practitioners (GPs) concerning the care of elderly cancer patients after 1 year of corrective measures for care practices in the Lorraine region, France. Materials and methods: In 2014, a postal mail questionnaire was sent to all GPs in the Lorraine region. This questionnaire was designed to identify GPs’ decision-making criteria. It was based on the results of a literature review and on existing guidelines. During 1 year, corrective measures were implemented to improve practices, especially training sessions for physicians and production of specific tools, including a guide to the accepted ideas in geriatric oncology. In 2015, the same questionnaire was resent to all GPs to compare the answers. Results: In 2014, 430 questionnaires were returned out of 2,048 sent, and in 2015, 378 questionnaires were returned out of 2,066 sent. Our results show for the first time that there exists a significant difference in the overall decision criteria between the two survey periods. This difference mainly concerns criteria related to the cancerous diseases. Physicians tend to consider the principal decision criteria to be less important after the training period. GPs express the importance of accessibility to specialists for additional advice in both 2014 and 2015; the distance between the patient’s home and an adapted care facility and the interval before care begins are viewed as similarly important. Conclusion: Training and information sessions for physicians remain the most important tool for improving care practices. Such training strategies are more effective when carried out at the geographical scale at which the cancer professionals practice, allowing them to exploit their local organizational structure. The analysis of our data makes it possible to further integrate the patient into the care path, which remains a public health issue in terms of cost and organization. Keywords: elderly, cancer, general practitioner, treatment decision-making, care improvement, older people, tumors, physician, management, ethics

We combine sea level records and repeat lidar surveys at 8 sites in the United Kingdom and the United States to explore controls on marsh accretion. We compare marsh elevations relative to sea level as well as lidar-derived marsh accretion rates to simple 0-dimensional settling simulations in order to explore constraints on suspended sediment concentration and particle size. We find that the marsh platforms examined occupy a narrow range of elevations in the upper tidal frame, situated between Mean High Tide MHT and the Observed Highest High Tide OHHT. Under sinusoidal tidal forcing, common in marsh accretion models, marshes at these elevations are never inundated, highlighting the inadequacy of sinusoidal forcing in numerical models of salt marshes. Forcing the model with year-long tidal records, deposition rates follow hyperbolic contour lines when expressed as a function of sediment concentration and median grain size. We also observe that when using a median sediment grain size D50 = 50 μm and sediment concentrations derived from satellite data, modeled deposition rates are much lower than when using field data. We find that the deposition of coarse, concentrated sediment is necessary for platforms in the upper tidal frame to withstand sea level rise, suggesting a strong dependance on infrequent high-deposition events. This is particularly true for marshes that are very high in the tidal frame, making accretion increasingly storm-driven as marsh platforms gain elevation. Finally, we reflect on the capacity of marshes to regenerate after erosion events within a context of changing sediment supply conditions.

Background: The MHC class I chain-related protein A (MICA) and protein B (MICB) participate in tumor immunosurveillance and may be important in colorectal cancer, but have not been examined in colorectal cancer development. Methods: sMICA and sMICB blood levels were measured by SomaScan in Visit 2 (1990-92, baseline) and Visit 3 (1993-95) samples in cancer-free participants in the Atherosclerosis Risk in Communities Study. We selected rs1051792, rs1063635, rs2516448, rs3763288, rs1131896, rs2596542, and rs2395029 that were located in or in the vicinity of MICA or MICB and were associated with cancer or autoimmune diseases in published studies. SNPs were genotyped by the Affymetrix Genome-Wide Human SNP Array. We applied linear and Cox proportional hazards regressions to examine the associations of preselected SNPs with sMICA and sMICB levels and colorectal cancer risk (236 colorectal cancers, 8,609 participants) and of sMICA and sMICB levels with colorectal cancer risk (312 colorectal cancers, 10,834 participants). In genetic analyses, estimates adjusted for ancestry markers were meta-analyzed. Results: Rs1051792-A, rs1063635-A, rs2516448-C, rs3763288-A, rs2596542-T, and rs2395029-G were significantly associated with decreased sMICA levels. Rs2395029-G, in the vicinity of MICA and MICB, was also associated with increased sMICB levels. Rs2596542-T was significantly associated with decreased colorectal cancer risk. Lower sMICA levels were associated with lower colorectal cancer risk in males (HR = 0.68; 95% confidence interval, 0.49-0.96) but not in females (Pinteraction = 0.08). Conclusions: Rs2596542-T associated with lower sMICA levels was associated with decreased colorectal cancer risk. Lower sMICA levels were associated with lower colorectal cancer risk in males. Impact: These findings support an importance of immunosurveillance in colorectal cancer. [ABSTRACT FROM AUTHOR]