Making Informed Choices On Incorporating Chemoprevention into carE (MiCHOICE, SWOG 1904): Design and methods of a cluster randomized controlled trial.

INTRODUCTION: Women with atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS) have a significantly increased risk of breast cancer, which can be substantially reduced with antiestrogen therapy for chemoprevention. However, antiestrogen therapy for breast cancer risk reduction remains underutilized. Improving knowledge about breast cancer risk and chemoprevention among high-risk patients and their healthcare providers may enhance informed decision-making about this critical breast cancer risk reduction strategy. METHODS/DESIGN: We are conducting a cluster randomized controlled trial to evaluate the effectiveness and implementation of patient and provider decision support tools to improve informed choice about chemoprevention among women with AH or LCIS. We have cluster randomized 26 sites across the U.S. through the SWOG Cancer Research Network. A total of 415 patients and 200 healthcare providers are being recruited. They are assigned to standard educational materials alone or combined with the web-based decision support tools. Patient-reported and clinical outcomes are assessed at baseline, after a follow-up visit at 6 months, and yearly for 5 years. The primary outcome is chemoprevention informed choice after the follow-up visit. Secondary endpoints include other patient-reported outcomes, such as chemoprevention knowledge, decision conflict and regret, and self-reported chemoprevention usage. Barriers and facilitators to implementing decision support into clinic workflow are assessed through patient and provider interviews at baseline and mid-implementation. RESULTS/DISCUSSION: With this hybrid effectiveness/implementation study, we seek to evaluate if a multi-level intervention effectively promotes informed decision-making about chemoprevention and provide valuable insights on how the intervention is implemented in U.S. TRIAL REGISTRATION: NCT04496739.

Effect of glyphosate, its metabolite AMPA, and the glyphosate formulation Roundup® on brown trout (Salmo trutta f. fario) gut microbiome diversity.

Glyphosate is used worldwide as a compound of pesticides and is detectable in many environmental compartments. It enters water bodies primarily through drift from agricultural areas so that aquatic organisms are exposed to this chemical, especially after rain events. Glyphosate is advertised and sold as a highly specific herbicide, which interacts with the EPSP synthase, an enzyme of the shikimate metabolism, resulting in inhibition of the synthesis of vital aromatic amino acids. However, not only plants but also bacteria can possess this enzyme so that influences of glyphosate on the microbiomes of exposed organisms cannot be excluded. Those influences may result in subtle and long-term effects, e.g., disturbance of the symbiotic interactions of bionts with microorganisms of their microbiomes. Mechanisms how the transformation product aminomethylphosphonic acid (AMPA) of glyphosate might interfere in this context have not understood so far. In the present study, molecular biological fingerprinting methods showed concentration-dependent effects of glyphosate and AMPA on fish microbiomes. In addition, age-dependent differences in the composition of the microbiomes regarding abundance and diversity were detected. Furthermore, the effect of exposure to glyphosate and AMPA was investigated for several fish pathogens of gut microbiomes in terms of their gene expression of virulence factors associated with pathogenicity. In vitro transcriptome analysis with the fish pathogen Yersinia ruckeri revealed that it is questionable whether the observed effect on the microbiome is caused by the intended mode of action of glyphosate, such as the inhibition of EPSP synthase activity.

Quantitative comparisons of potentially cariogenic microorganisms cultured from noncarious and carious root and coronal tooth surfaces.

Potentially cariogenic microorganisms cultured from noncarious and carious root and coronal (enamel) surfaces were quantitatively compared in patients 22 to 84 years of age (mean, 52 years). We collected 150 plaque specimens from 26 in situ teeth with initial root lesions and from 25 extracted teeth with advanced root lesions. The frequencies of isolation of Streptococcus mutans, Actinomyces viscosus, and Lactobacillus spp. were, respectively, 94, 72, and 51% at the noncarious root site; 98, 71, and 54% at the root lesion; 84, 61, and 44% at the noncarious enamel site; and 100, 66, and 90% at the enamel lesion. The streptococci made up the largest mean proportion of the total anaerobic cultivable microflora, ranging from 31.2% at the noncarious enamel site to 37.6% at the root lesion, while S. mutans varied between 18% at the noncarious enamel and root surfaces and approximately 24% at both the enamel and root lesions. The proportion of actinomyces ranged from 12.3% at the root lesion to 23.6% at the noncarious root site, while A. viscosus varied from 7.8% at the root lesion to 15.1% at the noncarious root site. The largest mean proportion of lactobacilli (4.2%) was recovered at the enamel lesion site. Proportions of Candida spp. made up less than 0.1% at all sites. Proportions of microorganisms did not differ significantly between noncarious enamel and root sites, but the noncarious coronal and root sites had higher (P less than 0.05) proportions of actinomyces than did the root lesion. Also, enamel lesions had a greater (P less than 0.05) percentage of Lactobacillus spp. than did root lesions. The number of streptococci recovered from the root lesion was greater (P less than 0.01) than the number of actinomyces at the same site. S. mutans was recovered from initial root lesions in greater numbers (P less than 0.001) than were actinomyces and lactobacilli. The number of S. mutans recovered at the initial root lesions was greater (P less than 0.01) than that recovered from the advanced root lesions.

Extracellular dextranase activity produced by human oral strains of the genus Bifidobacterium.

Three strains of anaerobic, dextranase-producing, gram-positive, rod-shaped bacteria were isolated from human dental plaque associated with root carious lesions. The isolates produced a molar ratio of acetate to lactate from glucose fermentation ranging from 1.1 to 1.9. Each strain also produced fructose-6-phosphate phosphoketolase. The isolates were identified as belonging to the genus Bifidobacterium, but from their carbohydrate fermentation patterns they did not appear to be strains of Bifidobacterium dentium. These microorganisms fermented high-molecular-weight dextrans. A partial characterization of the dextranase activity was included in this study and revealed an extracellular dextranase with a pH optimum of 7.1. Analysis of the dextran degradation products demonstrated the liberation of saccharides larger than 1 glucose unit. It was concluded that this enzyme used an endohydrolytic mode of dextran cleavage.

Selective habitation of bacteria on "intermediate soft" keratin surfaces of the rat tongue.

Scanning and light microscopy reveals a selective and restrictive pattern of indigenous bacterial colonization on the tongue of rats which is accounted for by the preferred attachment of bacteria to an "intermediate soft" keratin substrate. Total intravenous feeding of rats for 10 days did not alter this colonization pattern indicating that oral intake of food is not responsible for maintenance of this pattern.