Is E-Version Transition of the Medication Adherence Scale Feasible for CKD Management? A Pilot Study.

BACKGROUND: To transfer a paper-version Chinese and Western medication adherence scale for CKD into an electronic scale, and evaluate its validity, internal consistency and clinical implementation, and assess whether the transition is feasible in clinic. METHODS: We built an e-version Chinese and Western medication adherence scale based on the Wen-JuanXing platform. CKD subjects' responses were applied to test the scale's validity and internal consistency. We retested some of the participants two weeks later randomly. We also tested the clinical application. RESULTS: Of the 434 recruited patients, 228 responded. In exploratory factor analysis (EFA), the Kaiser-Meyer-Olkin (KMO) measure of sampling adequacy = 0.8 and Bartlett's approx. Chi-Square = 1340.0 (df = 105, p < 0.001). We extracted four common factors which could explain 61.47% of the variance. However, Item 15 "Have you changed a traditional Chinese medicine prescription yourself within the past month?" had factor loading = 0.3 and measure of sampling adequacy (MSA) = 0.5, meaning we could not enter it into the factor analysis. The internal consistency reliability for medication adherence was 0.9, with a Guttman split-half coefficient = 0.5 and a Spearman-Brown coefficient = 0.6. Cronbach's α was 0.9, 0.4 and 0.5 for the knowledge, belief and behavior domains, respectively. The correlation coefficient r of the test-retest reliability was -0.8 and was -0.8, 0.4, -0.3 in the knowledge, belief and behavior domains, respectively. Patients with comorbidities were more likely to respond. We detected no other significant differences in the clinical profiles between respondents and non-respondents. CONCLUSION: The e-version Chinese and Western medication adherence scales have undesirable construct validity and internal consistency. Thus, caution is needed in transitioning the paper-version scale into an e-version.

Refinement and Evaluation of a Chinese and Western Medication Adherence Scale for Patients with Chronic Kidney Disease: Item Response Theory Analyses.

PURPOSE: This study aimed to simplify the version-1 Chinese and Western medication adherence scale for patients with chronic kidney disease (CKD) to a version-2 scale using item response theory (IRT) analyses, and to further evaluate the performance of the version-2 scale. MATERIALS AND METHODS: Firstly, we refined the version-1 scale using IRT analyses to examine the discrimination parameter (a), difficulty parameter (b) and maximum information function peak (Imax). The final scale refinement from version-1 to version-2 scale was also decided upon clinical considerations. Secondly, we analyzed the reliability and validity of version-2 scale using classical test theory (CTT), as well as difficulty, discrimination and Imax of version-1 and version-2 scale using IRT in order to conduct scale evaluation. RESULTS: For scale refinement, the 26-item version-1 scale was reduced to a 15-item version-2 scale after IRT analyses. For scale evaluation using CTT, internal consistency reliability (total Cronbach α = 0.842) and test-rest reliability (r = 0.909) of version-2 scale were desirable. Content validity indicated 3 components of knowledge, belief and behaviors. We found meritorious construct validity with 3 detected components as the same construct of medication knowledge (items 1-9), medication behavior (items 13-15), and medication belief (items 10-12) based upon exploratory factor analysis. The correlation between the version-2 scale and Morisky, Green and Levine scale (MGL scale) was weak (Pearson coefficient = 0.349). For scale evaluation with IRT, the findings showed enhanced discrimination and decreased difficulty of most retained items (items 1, 2, 3, 4, 5, 6, 7, 9, 10, 11, 12, 13, 14, 15), decreased Imax of items 1, 2, 3, 4, 6, 11, 14, as well as increased Imax of items 5, 7, 8, 9, 10, 12, 13, 14, 15 in the version-2 scale than in the version-1 scale. CONCLUSION: The original Chinese and Western medication adherence scale was refined to a 15-item version-2 scale after IRT analyses. The scale evaluation using CTT and IRT showed the version-2 scale had the desirable reliability, validity, discrimination, difficulty, and information providedoverall. Therefore, the version-2 scale is clinically feasible to assess the medication adherence of CKD patients.

Curcumin synergizes with 5-fluorouracil by impairing AMPK/ULK1-dependent autophagy, AKT activity and enhancing apoptosis in colon cancer cells with tumor growth inhibition in xenograft mice.

BACKGROUND: Chemoresistance is a major obstacle that limits the benefits of 5-Fluorouracil (5-Fu)-based chemotherapy for colon cancer patients. Autophagy is an important cellular mechanism underlying chemoresistance. Recent research advances have given new insights into the use of natural bioactive compounds to overcome chemoresistance in colon cancer chemotherapy. As one of the multitargeted and safer phytomedicines, curcumin has been reported to work as cancer-specific chemosensitizer, presumably via induction of autophagic signaling pathways. The precise therapeutic effect of curcumin on autophagy in determining tumorous cells' fate, however, remains unclear. This study was conducted to investigate the differential modulations of the treatments either with 5-Fu alone or 5-Fu combined with curcumin on cellular autophagic responses and viabilities in the human colon cancer cells HCT116 and HT29, and explore molecular signaling transductions underlying the curcumin-mediated autophagic changes and potentiation of 5-Fu's cytotoxicity in vitro and in vivo. METHODS: Cell proliferation assay and morphology observation were used to identify the cytotoxicity of different combinations of curcumin and 5-Fu in HCT116 and HT29 cells. Cell immunofluorescence assay, Flow cytometry and Western blot were employed to detect changes of autophagy and the autophagy-related signaling pathways in the colon cancer cells and/or xenograft mice. RESULTS: Curcumin could significantly augment the cytotoxicity of 5-Fu to the tumorous cells, and the pre-treatment with curcumin followed by 5-Fu (pre-Cur) proved to be the most effective one compared to other two combinations. The chemosensitizing role of curcumin might attribute to the autophagy turnover from being activated in 5-Fu mono-treatment to being inhibited in the pre-Cur treatment as indicated by the changes in expression of beclin-1, p62 and LC3II/LC3I and the intensity of Cyto-ID Green staining. The autophagic alterations appeared to be contributed by down-regulation of not only the phospho-Akt and phospho-mTOR expressions but the phospho-AMPK and phospho-ULK1 levels as well. The cellular activation of AMPK by addition of A-769662 to the pre-Cur combination resulted in reversed changes in expressions of the autophagy protein markers and apoptotic status compared to those of the pre-Cur combination treatment. The findings were validated in the xenograft mice, in which the tumor growth was significantly suppressed in the mice with 25-day combination treatment, and meanwhile expressions of the autophagy markers, P-AMPK and P-ULK1 were all reversely altered in line with those observed in HCT116 cells. CONCLUSION: Pre-treatment with curcumin followed by 5-Fu may mediate autophagy turnover both in vitro and in vivo via AMPK/ULK1-dependent autophagy inhibition and AKT modulation, which may account for the increased susceptibility of the colon cancer cells/xenograft to the cytotoxicity of 5-Fu.

Alkaloids from Pandanus amaryllifolius: Isolation and Their Plausible Biosynthetic Formation.

Pandanus amaryllifolius Roxb. (Pandanaceae) is used as a flavor and in folk medicine in Southeast Asia. The ethanolic crude extract of the aerial parts of P. amaryllifolius exhibited antioxidant, antibiofilm, and anti-inflammatory activities in previous studies. In the current investigation, the purification of the ethanolic extract yielded nine new compounds, including N-acetylnorpandamarilactonines A (1) and B (2); pandalizines A (3) and B (4); pandanmenyamine (5); pandamarilactones 2 (6) and 3 (7), and 5(E)-pandamarilactonine-32 (8); and pandalactonine (9). The isolated alkaloids, with either a γ-alkylidene-α,ß-unsaturated-γ-lactone or γ-alkylidene-α,ß-unsaturated-γ-lactam system, can be classified into five skeletons including norpandamarilactonine, indolizinone, pandanamine, pandamarilactone, and pandamarilactonine. A plausible biosynthetic route toward 1-5, 7, and 9 is proposed.

Design, simulation and experimental validation of a novel flexible neural probe for deep brain stimulation and multichannel recording.

An implantable micromachined neural probe with multichannel electrode arrays for both neural signal recording and electrical stimulation was designed, simulated and experimentally validated for deep brain stimulation (DBS) applications. The developed probe has a rough three-dimensional microstructure on the electrode surface to maximize the electrode-tissue contact area. The flexible, polyimide-based microelectrode arrays were each composed of a long shaft (14.9 mm in length) and 16 electrodes (5 µm thick and with a diameter of 16 µm). The ability of these arrays to record and stimulate specific areas in a rat brain was evaluated. Moreover, we have developed a finite element model (FEM) applied to an electric field to evaluate the volume of tissue activated (VTA) by DBS as a function of the stimulation parameters. The signal-to-noise ratio ranged from 4.4 to 5 over a 50 day recording period, indicating that the laboratory-designed neural probe is reliable and may be used successfully for long-term recordings. The somatosensory evoked potential (SSEP) obtained by thalamic stimulations and in vivo electrode-electrolyte interface impedance measurements was stable for 50 days and demonstrated that the neural probe is feasible for long-term stimulation. A strongly linear (positive correlation) relationship was observed among the simulated VTA, the absolute value of the SSEP during the 200 ms post-stimulus period (ΣSSEP) and c-Fos expression, indicating that the simulated VTA has perfect sensitivity to predict the evoked responses (c-Fos expression). This laboratory-designed neural probe and its FEM simulation represent a simple, functionally effective technique for studying DBS and neural recordings in animal models.