Fecal Microbiome Associated with Both Colon Adenomas and Lifetime Colorectal Cancer Risk.

BACKGROUND: Increasing data indicates the gut flora including bacteria and fungi combined with environmental factors are important in the pathogenesis of colorectal cancer (CRC). Understanding differences in the microbiome in patients with colon neoplasia will foster the development of biomarkers for early detection. AIMS: Determine the association of microbiome with presence of adenomas and predicted CRC risk. METHODS: In subjects referred for colonoscopy, the NCI CRC risk assessment tool was completed and stool for microbiome analysis as well as fecal immunochemical test (FIT) were collected. We calculated the microbiome alpha diversity using the Shannon index as well as individual bacterial and fungal species. RESULTS: Among 34 patients, we identified 10 with one or more adenomas. Only 2 patients were FIT positive. The median predicted lifetime CRC risk was 2.75% and the prevalence of adenoma was higher in the fourth quartile (P < 0.001). The measured alpha diversity was somewhat higher in patients with adenomas (P = 0.07). We identified 4 bacterial species with an increased relative abundance among patients with adenomas [P < 0.5]. Lifetime CRC risk was associated with 2 specific bacterial species, P. distasonis & E. hermannii [P = 0.05 & 0.09, respectively]. No associations were seen with fungal species and adenoma prevalence or lifetime CRC risk. CONCLUSIONS: In addition to a strong correlation of predicted CRC risk and adenoma prevalence, we also found important differences in specific bacterial species and both adenoma prevalence and CRC risk. Larger trials are needed to potentially implement further data in the clinical setting.

Incubatory environment of the scalp impacts pre-emergent hair to affect post-emergent hair cuticle integrity.

OBJECTIVES: To determine whether the oxidative stress transmitted to newly grown hair from an unhealthy scalp has physical consequences to the cuticular condition and function. METHODS: A uniquely designed 24-week clinical study included 8 weeks of pretreatment with a cosmetic shampoo and 16 weeks of treatment with either a potentiated zinc pyrithione (ZPT) antidandruff shampoo or a placebo cosmetic shampoo. This clinical design allowed the growth and acquisition of hair samples under conditions of varying but known scalp health as a result of treating a dandruff/seborrheic dermatitis (D/SD) population. Two complementary methods were used to characterize the integrity of the cuticular surface. Hair surface hydrophobicity was assessed by quantifying water wetting force using a Wilhelmy balance method. Surface structure and porosity were assessed using dynamic vapor sorption (DVS) to gravimetrically quantify water sorption. RESULTS: Chemical oxidative stress to pre-emergent hair has been shown to have negative consequences to hair surface structure. Compared to a placebo shampoo control, use of a potentiated ZPT shampoo improved scalp health and significantly improved the following attributes associated with healthy hair: hair surface hydrophobicity (surface energy) and cuticular moisture barrier effectiveness (dynamic vapor sorption). CONCLUSIONS: Pre-emergent hair can be negatively impacted by the oxidative stress that occurs with an unhealthy scalp, possibly due to metabolic activity of resident microbes. Manifestations of the oxidative stress include altered cuticle surface properties that are responsible for its protective function; these effects are similar in type to those observed by bleaching post-emergent hair. These alterations have the potential to make the hair, once emerged from the scalp, more susceptible to the cumulative physical and chemical insults responsible for hair feel and look, fiber integrity, and overall retention.

Statistical cluster analysis of pharmaceutical solvents.

High efficiency in polymorph screening and crystallization optimization can be gained by judicious selection of solvents for the study design. Examination of all 57 (classes 2 and 3) pharmaceutical solvents may enable a complete study design but is costly in terms of time and resources. Based on a 17 descriptor dataset specifically constructed for all the classes 2 and 3 pharmaceutical solvents recognized by the International Conference of Harmonization (ICH), an optimal two-stage cluster analysis was carried out together with principal component analysis as a dimensionality and colinearity reduction pre-processor. Both hierarchical average linkage cluster analysis and non-hierarchical K-means cluster analysis converged on a 20-cluster solution with strong statistical criteria support and excellent agreement in cluster memberships, which can be reasonably interpreted from a chemical perspective. This 20-cluster solution is offered as an option for design of more efficient solid state screening studies. Rather than designing a polymorph screen to include all 57 solvents, the inclusion of a single member from each of the 20 clusters would be expected to adequately represent the full range of solvent properties exhibited by the entire 57 member solvent set.

A nonrandomized trial of vitamin D supplementation for Barrett's esophagus.

BACKGROUND: Vitamin D deficiency may increase esophageal cancer risk. Vitamin D affects genes regulating proliferation, apoptosis, and differentiation and induces the tumor suppressor 15-hydroxyprostaglandin dehydrogenase (PGDH) in other cancers. This nonrandomized interventional study assessed effects of vitamin D supplementation in Barrett's esophagus (BE). We hypothesized that vitamin D supplementation may have beneficial effects on gene expression including 15-PGDH in BE. METHODS: BE subjects with low grade or no dysplasia received vitamin D3 (cholecalciferol) 50,000 international units weekly plus a proton pump inhibitor for 12 weeks. Esophageal biopsies from normal plus metaplastic BE epithelium and blood samples were obtained before and after vitamin D supplementation. Serum 25-hydroxyvitamin D was measured to characterize vitamin D status. Esophageal gene expression was assessed using microarrays. RESULTS: 18 study subjects were evaluated. The baseline mean serum 25-hydroxyvitamin D level was 27 ng/mL (normal ≥30 ng/mL). After vitamin D supplementation, 25-hydroxyvitamin D levels rose significantly (median increase of 31.6 ng/mL, p<0.001). There were no significant changes in gene expression from esophageal squamous or Barrett's epithelium including 15-PGDH after supplementation. CONCLUSION: BE subjects were vitamin D insufficient. Despite improved vitamin D status with supplementation, no significant alterations in gene expression profiles were noted. If vitamin D supplementation benefits BE, a longer duration or higher dose of supplementation may be needed.

Dehydration of risedronate hemi-pentahydrate: analytical and physical characterization.

Dehydration of hydrates of pharmaceutical active ingredients (pharmaceutical hydrates) may easily occur during storage or manufacturing. Loss of water may have little effect on the crystal lattice, produce less hydrated forms or possibly amorphous forms. Characterizing the effects of water loss on crystal hydrate forms is important for understanding the behavior of pharmaceutical hydrates throughout the manufacturing and storage processes. This study shows that exposure of the hemi-pentahydrate form of risedronate monosodium to gentle heating (60 degrees C) or conditions of low relative humidity (<10% RH) results in the loss of 1 mole of channel-type water. Upon removal of the channel-type water, the crystal lattice adjusts producing a distinct phase characterized by X-ray, thermal, IR, Raman, and NMR data. Adjustment of the crystal lattice appears to compromise crystal integrity and can result in reduced crystallite and particle sizes.

Structural and analytical characterization of three hydrates and an anhydrate form of risedronate.

Four hydration states are reported for Risedronate monosodium. A single-crystal X-ray structure determination is provided as proof of assignment for the monohydrate, hemi-pentahydrate, and variable hydrate forms. The structure provided for the anhydrate form was determined through simulating annealing calculations and subsequent Reitveld refinement of a high-quality X-ray powder diffraction patterns Favorable comparisons of experimentally obtained X-ray powder patterns are made to those generated from the single crystal data. Characteristic infrared, Raman, and NMR spectra are provided and discussed for each form as are thermal analysis profiles. In addition, photomicrographs are provided for each of the forms isolated for this study. The hemi-pentahydrate is demonstrated to be the equilibrium form at room temperature and 37 degrees C, in the presence of water.