Baseline Characteristics of Adult Patients Treated and Never Treated with Teduglutide in a Multinational Short Bowel Syndrome and Intestinal Failure Registry.

The Short Bowel Syndrome (SBS) Registry (NCT01990040) is a multinational real-world study evaluating the long-term safety of teduglutide in patients with SBS and intestinal failure (SBS-IF) in routine clinical practice. This paper describes the study methodology and baseline characteristics of adult patients who have (ever-treated) or have never (never-treated) received teduglutide. A total of 1411 adult patients (679 ever-treated; 732 never-treated) were enrolled at 124 sites across 17 countries. The mean (standard deviation [SD]) age at enrollment was 55.4 (15.46) years, and 60.2% of patients were women. Crohn's disease was the most common cause of major intestinal resection in both ever-treated (34.1%) and never-treated patients (20.4%). A similar proportion of ever-treated and never-treated patients had a prior history of colorectal polyps (2.7% vs. 3.6%), whereas proportionally fewer ever-treated patients reported a history of colorectal cancer (1.8% vs. 6.2%) or any malignancy (17.7% vs. 30.0%) than never-treated patients. Never-treated patients received a numerically greater mean (SD) volume of parenteral nutrition and/or intravenous fluids than ever-treated patients (12.4 [8.02] vs. 10.1 [6.64] L/week). Ever-treated patients received a mean teduglutide dosage of 0.05 mg/kg/day. This is the first report of patient baseline characteristics from the SBS Registry, and the largest cohort of patients with SBS-IF to date. Overall, ever-treated and never-treated patients had similar baseline characteristics. Differences between treatment groups may reflect variations in patient selection and degree of monitoring.

Psychometric properties of the Chinese version of the Positive Thinking Scale in individuals after hip fracture surgery.

Positive thinking is a form of positive cognition and a coping strategy. The Positive Thinking Scale (PTS) is used to measure positive thinking, but the reliability and validity of the PTS-Chinese have yet to be tested. This study aims to examine the psychometric properties of the PTS-Chinese. A total of 154 patients post-hip fracture surgery completed the questionnaire in a hospital in Taiwan between April 2020 and December 2020. The scales in the questionnaire included the PTS, Automatic Thoughts Questionnaire-Positive, Automatic Thoughts Questionnaire-Negative, Barthel Index, and items related to happiness, demographics, and disease treatment. The results of the confirmatory factor analysis and average variance extracted show that the PTS-Chinese version exhibits construct validity. Scores on the PTS-Chinese version are positively related to scores on the Automatic Thoughts Questionnaire-Positive and happiness items and negatively related to scores on the Automatic Thoughts Questionnaire-Negative. This finding indicates that the PTS-Chinese demonstrates concurrent, predictive, and discriminant validity. The scale also presents acceptable reliability and test-retest reliability. Overall, the PTS-Chinese can be used to evaluate and track the positive thinking of patients. Further studies are needed to assess the psychometric properties of the PTS-Chinese in different cultures and ethnic groups.

Psychometric properties of the Chinese version of the Positive Thinking Scale in individuals after hip fracture surgery

Positive thinking is a form of positive cognition and a coping strategy. The Positive Thinking Scale (PTS) is used to measure positive thinking, but the reliability and validity of the PTS-Chinese have yet to be tested. This study aims to examine the psychometric properties of the PTS-Chinese. A total of 154 patients post-hip fracture surgery completed the questionnaire in a hospital in Taiwan between April 2020 and December 2020. The scales in the questionnaire included the PTS, Automatic Thoughts Questionnaire-Positive, Automatic Thoughts Questionnaire-Negative, Barthel Index, and items related to happiness, demographics, and disease treatment. The results of the confirmatory factor analysis and average variance extracted show that the PTS-Chinese version exhibits construct validity. Scores on the PTS-Chinese version are positively related to scores on the Automatic Thoughts Questionnaire-Positive and happiness items and negatively related to scores on the Automatic Thoughts Questionnaire-Negative. This finding indicates that the PTS-Chinese demonstrates concurrent, predictive, and discriminant validity. The scale also presents acceptable reliability and test-retest reliability. Overall, the PTS-Chinese can be used to evaluate and track the positive thinking of patients. Further studies are needed to assess the psychometric properties of the PTS-Chinese in different cultures and ethnic groups. (AU)

Downregulation of the tumor-suppressor miR-16 via progestin-mediated oncogenic signaling contributes to breast cancer development.

INTRODUCTION: Experimental and clinical evidence points to a critical role of progesterone and the nuclear progesterone receptor (PR) in controlling mammary gland tumorigenesis. However, the molecular mechanisms of progesterone action in breast cancer still remain elusive. On the other hand, micro RNAs (miRNAs) are short ribonucleic acids which have also been found to play a pivotal role in cancer pathogenesis. The role of miRNA in progestin-induced breast cancer is poorly explored. In this study we explored progestin modulation of miRNA expression in mammary tumorigenesis. METHODS: We performed a genome-wide study to explore progestin-mediated regulation of miRNA expression in breast cancer. miR-16 expression was studied by RT-qPCR in cancer cell lines with silenced PR, signal transducer and activator of transcription 3 (Stat3) or c-Myc, treated or not with progestins. Breast cancer cells were transfected with the precursor of miR-16 and proliferation assays, Western blots or in vivo experiments were performed. Target genes of miR-16 were searched through a bioinformatical approach, and the study was focused on cyclin E. Reporter gene assays were performed to confirm that cyclin E 3'UTR is a direct target of miR-16. RESULTS: We found that nine miRNAs were upregulated and seven were downregulated by progestin in mammary tumor cells. miR-16, whose function as a tumor suppressor in leukemia has already been shown, was identified as one of the downregulated miRNAs in murine and human breast cancer cells. Progestin induced a decrease in miR-16 levels via the classical PR and through a hierarchical interplay between Stat3 and the oncogenic transcription factor c-Myc. A search for miR-16 targets showed that the CCNE1 gene, encoding the cell cycle regulator cyclin E, contains conserved putative miR-16 target sites in its mRNA 3' UTR region. We found that, similar to the molecular mechanism underlying progestin-modulated miR-16 expression, Stat3 and c-Myc participated in the induction of cyclin E expression by progestin. Moreover, overexpression of miR-16 abrogated the ability of progestin to induce cyclin E upregulation, revealing that cyclin E is a novel target of miR-16 in breast cancer. Overexpression of miR-16 also inhibited progestin-induced breast tumor growth in vitro and in vivo, demonstrating for the first time, a role for miR-16 as a tumor suppressor in mammary tumorigenesis. We also found that the ErbB ligand heregulin (HRG) downregulated the expression of miR-16, which then participates in the proliferative activity of HRG in breast tumor cells. CONCLUSIONS: In this study, we reveal the first progestin-regulated miRNA expression profile and identify a novel role for miR-16 as a tumor suppressor in progestin- and growth factor-induced growth in breast cancer.