Quantification of bile acids: a mass spectrometry platform for studying gut microbe connection to metabolic diseases.

Bile acids (BAs) serve multiple biological functions, ranging from the absorption of lipids and fat-soluble vitamins to serving as signaling molecules through the direct activation of dedicated cellular receptors. Synthesized by both host and microbial pathways, BAs are increasingly understood as participating in the regulation of numerous pathways relevant to metabolic diseases, including lipid and glucose metabolism, energy expenditure, and inflammation. Quantitative analyses of BAs in biological matrices can be problematic due to their unusual and diverse physicochemical properties, making optimization of a method that shows good accuracy, precision, efficiency of extraction, and minimized matrix effects across structurally distinct human and murine BAs challenging. Herein we develop and clinically validate a stable-isotope-dilution LC/MS/MS method for the quantitative analysis of numerous primary and secondary BAs in both human and mouse biological matrices. We also utilize this tool to investigate gut microbiota participation in the generation of structurally specific BAs in both humans and mice. We examine circulating levels of specific BAs and in a clinical case-control study of age- and gender-matched type 2 diabetes mellitus (T2DM) versus nondiabetics. BAs whose circulating levels are associated with T2DM include numerous 12α-hydroxyl BAs (taurocholic acid, taurodeoxycholic acid, glycodeoxycholic acid, deoxycholic acid, and 3-ketodeoxycholic acid), while taurohyodeoxycholic acid was negatively associated with diabetes. The LC/MS/MS-based platform described should serve as a robust, high-throughput investigative tool for studying the potential involvement of structurally specific BAs and the gut microbiome on both physiological and disease processes.

Risk indicators associated with root caries in independently living older adults.

OBJECTIVE: To determine the risk indicators associated with root caries experience in a cohort of independently living older adults in Ireland. METHODS: The data reported in the present study were obtained from a prospective longitudinal study conducted in a cohort of independently living older adults (n=334). Each subject underwent an oral examination, performed by a single calibrated examiner, to determine the root caries index and other clinical variables. Questionnaires were used to collect data on oral hygiene habits, diet, smoking and alcohol habits and education level. A regression analysis with the outcome variable of root caries experience (no/yes) was conducted. RESULTS: A total of 334 older dentate adults with a mean age of 69.1 years were examined. 53.3% had at least one filled or decayed root surface. The median root caries index was 3.13 (IQR 0.00, 13.92). The results from the multivariate regression analysis indicated that individuals with poor plaque control (OR 9.59, 95% CI 3.84-24.00), xerostomia (OR 18.49, 95% CI 2.00-172.80), two or more teeth with coronal decay (OR 4.50, 95% CI 2.02-10.02) and 37 or more exposed root surfaces (OR 5.48, 95% CI 2.49-12.01) were more likely to have been affected by root caries. CONCLUSIONS: The prevalence of root caries was high in this cohort. This study suggests a correlation between root caries and the variables poor plaque control, xerostomia, coronal decay (≥2 teeth affected) and exposed root surfaces (≥37). The significance of these risk indicators and the resulting prediction model should be further evaluated in a prospective study of root caries incidence. CLINICAL SIGNIFICANCE: Identification of risk indicators for root caries in independently living older adults would facilitate dental practitioners to identify those who would benefit most from interventions aimed at prevention.

Self-reported hearing difficulty versus audiometric screening in younger and older smokers and nonsmokers.

BACKGROUND: The high incidence of age-related hearing loss demands accessible, low cost hearing screenings for prevention and hearing health promotion. This study assessed performance of self report (SR) against audiometry, and prevalence of hearing difficulty when screening hearing in middle-aged and younger adults, including smokers and nonsmokers. METHODS: Prospective participants (N = 219) completed a questionnaire providing biographical, health, and smoking information. Their Yes/No responses about hearing or communication difficulty provided data for self-reported hearing loss. Eligible (N = 170) participants received a hearing test including immittance, pure-tone, and speech audiometry. The binaural pure-tone average (PTA) hearing threshold was determined; PTA decibel (dB) level indicated degree (e.g., mild) of hearing loss. All hearing screening data were coded and initially analyzed in an Access database. Statistical analyses based on conditional probability included measures of prevalence, sensitivity, specificity, and predictive value of the SR versus audiometric measures. Participants provided a urine sample for biochemical analysis to confirm smoker/nonsmoker status. RESULTS: Among all participants (N = 170), overall prevalence of self-reported hearing difficulty (15.9%) was in excellent agreement with measured, mild hearing loss (16.5%). However, factoring in age and smoking revealed that SR was incongruent with audiometry because hearing loss was overestimated by smokers and younger participants and underestimated by middle-aged individuals. The SR question yielded high specificity (80-90%) overall. Specificity was highest in nonsmokers (89-94%) and younger (90-91%) individuals with lower performance in smokers and middle-aged participants. SR sensitivity was high (86-100%) only when the hearing impairment cutoff was > 40 dB (moderate loss) and > 60 dB (severe loss). Sensitivity was highest in smokers (100%), supporting SR for screenings. High negative and low positive predictive value (PPV) occurred in smokers, younger, and middle-aged persons. This study reports new sensitivity and specificity data on self-reported hearing difficulty in smokers (N = 98), younger (N = 80), and middle-aged (N = 90) adults, indicating efficacy of SR as an adult hearing screening measure. CONCLUSIONS: SR was effective as few normal-hearing persons were labeled hearing-impaired. However, audiometry should supplement SR to optimize detection of mild hearing loss for at-risk adults. Results may guide community health initiatives for hearing screenings, prevention, and health promotion. KEYWORDS: Aging; Smoking; Self Report; Health Promotion; Hearing Screening.