Lithocholic Acid Amides as Potent Vitamin D Receptor Agonists.

1α,25-Dihydroxyvitamin D3 [1α,25(OH)2D3, 1] is an active form of vitamin D3 and regulates various biological phenomena, including calcium and phosphate homeostasis, bone metabolism, and immune response via binding to and activation of vitamin D receptor (VDR). Lithocholic acid (LCA, 2) was identified as a second endogenous agonist of VDR, though its potency is very low. However, the lithocholic acid derivative 3 (Dcha-20) is a more potent agonist than 1α,25(OH)2D3, (1), and its carboxyl group has similar interactions to the 1,3-dihydroxyl groups of 1 with amino acid residues in the VDR ligand-binding pocket. Here, we designed and synthesized amide derivatives of 3 in order to clarify the role of the carboxyl group. The synthesized amide derivatives showed HL-60 cell differentiation-inducing activity with potency that depended upon the substituent on the amide nitrogen atom. Among them, the N-cyanoamide 6 is more active than either 1 or 3.

Feasibility and preliminary efficacy of a smartphone application intervention for subthreshold depression.

AIM: We developed a motion picture-reproducing smartphone application (app) designed to improve self-confidence in individuals with subthreshold depression (StD) and examined the feasibility and preliminary efficacy of an app intervention for individuals with StD. METHODS: We conducted an open-label, single-arm pre-post study of 22 young adults with StD. Our intervention involved app usage for at least 70 min/wk for 5 weeks. The primary outcome measure was the adherence rate. Secondary outcome measures were safety and Center for Epidemiologic Studies Depression Scale (CES-D) scores. RESULTS: No participants dropped out during the study. The adherence rate was 50%. The mean time of app use over 5 weeks was 124.23 ± 81.94 min/wk. No adverse events were reported. The CES-D scores were significantly improved at 5 weeks post-intervention. CONCLUSIONS: Although this app intervention has the potential to reduce depressive symptoms, the app needs to be improved to increase adherence rates.

Measurement error in the Liebowitz Social Anxiety Scale: results from a general adult population in Japan.

Objective: Although the self-report version of Liebowitz Social Anxiety Scale (LSAS) is frequently used to measure social anxiety, data is lacking on the smallest detectable change (SDC), an important index of measurement error. We therefore aimed to determine the SDC of LSAS. Methods: Japanese adults aged 20-69 years were invited from a panel managed by a nationwide internet research agency. We then conducted a test-retest internet survey with a two-week interval to estimate the SDC at the individual (SDCind) and group (SDCgroup) levels. Results: The analysis included 1300 participants. The SDCind and SDCgroup for the total fear subscale (scoring range: 0-72) were 23.52 points (32.7%) and 0.65 points (0.9%), respectively. The SDCind and SDCgroup for the total avoidance subscale (scoring range: 0-72) were 32.43 points (45.0%) and 0.90 points (1.2%), respectively. The SDCind and SDCgroup for the overall total score (scoring range: 0-144) were 45.90 points (31.9%) and 1.27 points (0.9%), respectively. Conclusions: Measurement error is large and indicate the potential for major problems when attempting to use the LSAS to detect changes at the individual level. These results should be considered when using the LSAS as measures of treatment change.

Smallest detectable change and test-retest reliability of a self-reported outcome measure: Results of the Center for Epidemiologic Studies Depression Scale, General Self-Efficacy Scale, and 12-item General Health Questionnaire.

RATIONALE, AIMS, AND OBJECTIVES: This study aims to examine the smallest detectable change (SDC) and test-retest reliability of the Center for Epidemiologic Studies Depression Scale (CES-D), General Self-Efficacy Scale (GSES), and 12-item General Health Questionnaire (GHQ-12). METHOD: We tested 154 young adults at baseline and 2 weeks later. We calculated the intra-class correlation coefficients (ICCs) for test-retest reliability with a two-way random effects model for agreement. We then calculated the standard error of measurement (SEM) for agreement using the ICC formula. The SEM for agreement was used to calculate SDC values at the individual level (SDCind ) and group level (SDCgroup ). RESULTS: The study participants included 137 young adults. The ICCs for all self-reported outcome measurement scales exceeded 0.70. The SEM of CES-D was 3.64, leading to an SDCind of 10.10 points and SDCgroup of 0.86 points. The SEM of GSES was 1.56, leading to an SDCind of 4.33 points and SDCgroup of 0.37 points. The SEM of GHQ-12 with bimodal scoring was 1.47, leading to an SDCind of 4.06 points and SDCgroup of 0.35 points. The SEM of GHQ-12 with Likert scoring was 2.44, leading to an SDCind of 6.76 points and SDCgroup of 0.58 points. CONCLUSION: To confirm that the change was not a result of measurement error, a score of self-reported outcome measurement scales would need to change by an amount greater than these SDC values. This has important implications for clinicians and epidemiologists when assessing outcomes.

Identification of common words to improve self-confidence in Japanese students with subthreshold depression.

Background Subthreshold depression (StD) is more common than major depressive disorder. Objective The study aimed to identify common words to improve self-confidence in Japanese university students with StD for developing a smartphone application to help those with StD. Methods In this cross-sectional study, words participants used to improve their self-confidence were gathered using self-report questionnaires in 154 university students in Japan. The words used to improve self-confidence were categorized using a computerized text analysis method based on the frequency of appearance. Results Participants were 154 male and females [StD group (n = 82) and healthy control (HC) group (n = 72); median age = 20 years]. A total of 290 words for improving self-confidence were identified. In the StD group, the keywords that appeared with the highest frequencies were "can", "let's try", "good luck", "able", and "don't worry". The keywords that occurred with the highest frequencies (the top eight) were common across both groups. The keywords were grouped into eight categories. The "encouragement" and "praise" categories were found in the responses of more than 80% of participants in both groups. Frequencies of the "determination" and "trust" categories were significantly higher in the StD group than in the HC group. Conclusions We conclude that "can", "let's try", and "good luck" are the most common words that Japanese students with StD use when describing how they improve their self-confidence. Future work will use these common words to develop a smartphone application to help those suffering from StD.