Isolation of GLP-1 enhancing indolizidine alkaloids from Boehmeria formosana.

Boehmeria formosana, with its related species, demonstrates anti-glycemic effect, inhibition of HBV production, anti-cancer activities, etc. Some indolizidine alkaloids from the same genus are bioactive but sensitive to light. To overcome this problem and obtain more phenanthroindolizidine alkaloids, isolation was performed in darkness, yielding 10 new indolizidine alkaloids and 17 known compounds. Among them, seven enhanced glucagon-like receptor 1 (GLP-1) activity at 50 mM, especially 14 and 6 (3.5- and 2.3-fold than the negative control). This procedure yielded bioactive indolizidine alkaloids with novel structures.

Impact of Palliative Care Consultation Service on Terminally Ill Cancer Patients: A 9-Year Observational Cohort Study in Taiwan.

The palliative care consultation service (PCCS) that has been enthusiastically promoted in Taiwan since 2005 was designed to provide comprehensive end-of-life care for terminally ill patients with qualified interdisciplinary specialists in acute care ward setting. This study aims to evaluate the impact of PCCS on terminally ill cancer patients.A total of 10,594 terminal cancer patients who were referred to PCCS from a single medical center in Taiwan between 2006 and 2014 were enrolled. The percentages of patients' and their families' disease awareness, do-not-resuscitate (DNR) designation, refusal and acceptance of palliative care among terminally ill cancer patients were analyzed retrospectively.At the beginning of PCCS, the percentages of disease awareness among patients and their family were increased from 25.4% to 37.9% (P = 0.007) and from 61.2% to 84.7% between 2006 and 2014 (P = 0.001), respectively. Patients' disease awareness after PCCS referral between 2006 and 2014 was increased from 47.1% to 64.5% (P = 0.016). Family's awareness of diagnosis and prognosis after PCCS referral researched to a steady plateau, 94.1% to 97.8% in different year cohort (P = 0.34). The percentage of DNR designation rate at the beginning of PCCS (in 2006) was 15.5%, and the designation rate was increased annually and finally reached to 42.0% in 2014 (P = 0.004). The percentage of DNR consents after PCCS was also improved from 44.0% in 2006 up to 80.0% in 2014 (P = 0.005). PCCS refusal rate decreased gradually and dropped to 1.6% in 2014 (P = 0.005). The percentage of PCCS utilization was increased 5-fold during the 9-year period after the promotion of PCCSIn the program of PCCS promotion, an increasing trend of PCCS utilization, better patients' and their families' awareness of diagnosis and prognosis, more consent to DNR, more patients were discharged with stable condition at the end of PCCS and a decrease refusal rate of end-of-life palliative care among terminal cancer patients were observed in Taiwan between 2006 and 2014.

Combination of initial palliative prognostic index and score change provides a better prognostic value for terminally ill cancer patients: a six-year observational cohort study.

CONTEXT: The Palliative Prognostic Index (PPI) is among the most popular scores used to predict life expectancy in terminally ill patients worldwide. PPI assessed on the first day of palliative care might be inappropriate because the contribution from subsequent changes in a patient's condition are not taken into account. OBJECTIVES: The aim of this study is to determine the utility of sequential PPI assessments as a better prognostic tool for patients with terminal cancer. METHODS: In total, 2392 terminally ill cancer patients with initial and one-week PPI assessments under the palliative care consultation service between January 2006 and December 2011 at a single medical center in Taiwan were selected. Patients were categorized into initial PPI, Week 1 PPI, score change (initial PPI - Week 1 PPI; Δscore), and combined initial PPI and Δscore subgroups for survival analysis. RESULTS: Overall median survival was 32 days (range eight to 180 days), and 2183 patients (91.3%) died within 180 days of palliative care consultation service care. A significant difference in survival was observed among patient subgroups (P < 0.001). Subgroup survival analysis showed significant difference in patients with Δscores >0, 0, and <0 in each prognostic group categorized by initial PPI. The c-statistic for predicting life expectancy <30 days was significantly higher with the combined initial PPI and Δscore (c-statistic, 0.71; 95% CI, 0.694-0.731) than with the initial PPI (c-statistic, 0.63; 95% CI, 0.61-0.65), Week 1 PPI (c-statistic, 0.67; 95% CI, 0.652-0.690), or Δscore (c-statistic, 0.64; 95% CI, 0.62-0.66). CONCLUSION: Combination of initial PPI and score change is more useful than initial PPI for identifying patients with poor outcomes in good prognostic groups and patients with better outcomes in poor prognostic groups.

Effect of extracorporeal magnetic energy stimulation on bothersome lower urinary tract symptoms and quality of life in female patients with stress urinary incontinence and overactive bladder.

AIMS: The aim of this study was to investigate the efficacy of extracorporeal magnetic stimulation (EMS) for the treatment of bothersome and severe symptoms of stress urinary incontinence (SUI) and overactive bladder syndrome (OAB) in female patients. MATERIAL AND METHODS: A retrospective review was conducted on patients with SUI and OAB who were referred to EMS therapy. Successful treatment for the bothersome symptoms of OAB and SUI was defined as score ≤1 for questions 2 and 3 on the Urodynamic Distress Inventory-6. The objective cure of SUI and OAB was defined as no urinary leakage during the cough stress test and any urgency, urge incontinence and voiding frequency of less than eight times per 24 h based on the 3-day bladder diary, after the 9 weeks of treatment, respectively. RESULTS: Ninety-three patients with SUI or OAB underwent a 9-week course of EMS at 20 min twice weekly. Seventy-two (77%) patients completed EMS treatment. Geographical factor and poor economic status were two main factors for dropout. A total of 94.1% (32 of 34) and 86.8% (33 of 38) of subjects had successful treatment for the bothersome symptoms of OAB and SUI, respectively. In contrast, the cure rate for OAB and SUI was only 61.7% and 42.1%, respectively. There was also a significant improvement in both Urogenital Distress Inventory Short Form (bothersome on lower urinary tract symptoms) and the Incontinence Impact Questionnaire Short Form (quality of life) total score in both groups after EMS. CONCLUSIONS: EMS is a safe and effective alternative method for treating SUI and OAB. Further studies are needed to evaluate the long-term efficacy.

Perturbation of ATP-induced tetramerization of human cytosolic thymidine kinase by substitution of serine-13 with aspartic acid at the mitotic phosphorylation site.

Human cytosolic thymidine kinase (TK1) is tightly regulated in the cell cycle by multiple mechanisms. Our laboratory has previously shown that in mitotic-arrested cells human TK1 is phosphorylated at serine-13, accompanied by a decrease in catalytic efficiency. In this study we investigated whether serine-13 phosphorylation regulated TK1 activity and found that substitution of serine-13 with aspartic acid (S13D), which mimics phosphorylation, not only diminished the ATP-activating effect on the enzyme, but also decreased its thymidine substrate affinity. Our experimental results further showed that the S13D mutation perturbed ATP-induced tetramerization of TK1. Given that the dimeric form of TK1 is less active than the tetrameric, we propose that mitotic phosphorylation of serine-13 is of physiological importance, in that it may counteract ATP-dependent activation of TK1 by affecting its quaternary structure, thus attenuating its enzymatic function at the G2/M phase.