OBJECTIVE: To determine the validity and reliability of the PPCI for physicians in Malaysia.
SETTING: An urban tertiary hospital in Malaysia.
METHODS: This prospective study was conducted from June to August 2014. Doctors were grouped as either a "collaborator" or a "non-collaborator". Collaborators were doctors who regularly worked with one particular clinical pharmacist in their ward, while non-collaborators were doctors who interacted with any random pharmacist who answered the general pharmacy telephone line whenever they required assistance on medication-related enquiries, as they did not have a clinical pharmacist in their ward. Collaborators were firstly identified by the clinical pharmacist he/she worked with, then invited to participate in this study through email, as it was difficult to locate and approach them personally. Non-collaborators were sampled conveniently by approaching them in person as these doctors could be easily sampled from any wards without a clinical pharmacist. The PPCI for physicians was administered at baseline and 2 weeks later.
MAIN OUTCOME MEASURE: Validity (face validity, factor analysis and discriminative validity) and reliability (internal consistency and test-retest) of the PPCI for physicians.
RESULTS: A total of 116 doctors (18 collaborators and 98 non-collaborators) were recruited. Confirmatory factor analysis confirmed that the PPCI for physicians was a 3-factor model. The correlation of the mean domain scores ranged from 0.711 to 0.787. "Collaborators" had significantly higher scores compared to "non-collaborators" (81.4 ± 10.1 vs. 69.3 ± 12.1, p < 0.001). The Cronbach alpha for the overall PPCI for physicians was 0.949, while the Cronbach alpha values for the individual domains ranged from 0.877 to 0.926. Kappa values at test-retest ranged from 0.553 to 0.752.
CONCLUSION: The PPCI for physicians was a valid and reliable measure in determining doctors' views about collaborative working relationship with pharmacists, in Malaysia.
METHODS: Pre- and post-participation questionnaires were distributed to near-peer tutors after their clinical skills teaching sessions with Phase I undergraduate medical students. The Peer Tutor Assessment Instrument questionnaires were distributed to the 1) students, and to the 2) near-peer tutors (junior and senior) after each teaching and learning session for self-evaluation.
RESULTS: The senior near-peer tutors felt that their participation in the programme had enhanced their skills (p=0.03). As a whole, the near-peer tutors were more motivated (Pre 5.32±0.46; Post 5.47±0.50; p=0.210) to participate in future teaching sessions but did not expect that having teaching experiences would make teaching as their major career path in the future (Pre 4.63±1.07; Post 4.54±0.98; p=0.701). The senior near-peer tutors were evaluated significantly higher by the students (p=0.0001). Students' evaluations of near-peer tutors on the domain of critical analysis was higher than self-evaluations (p=0.003).
CONCLUSIONS: Generally, the near-peer tutors perceived that they have benefited most in their skills enhancement and these near-peer tutors were scored highly by the students. However, senior near-peer tutors do not perceive that the programme has a lasting impact on their choice of career path.
MATERIALS AND METHODS: The PBMC (n = 7) were cultured either in RPMI-1640 containing L-glutamine and 50 units/ml Penicillin-Streptomycin (BM) or in BM with either AuHS or FBS. Viability, proliferation and differentiation of PBMC were evaluated. Paracrine factors present in the secretomes (n = 6) were analysed using ProcartaPlex Human Cytokine panel (17 plex). Ingenuity Pathway Analysis (IPA) was performed to predict activation or inhibition of biological functions related to tissue regeneration.
RESULTS: The viability of PBMC that were cultured with FBS supplement was significantly reduced at 96 h compared to those at 0 and 24 h (P
MATERIALS AND METHODS: The inhibitory effects of hexane (LHXN), dichloromethane (LDCM), ethyl acetate (LEA) and methanol (LMEOH) extracts from leaves of PS on Aβ-induced production and mRNA expression of pro-inflammatory mediators in BV-2 microglial cells were assessed using colorimetric assay with Griess reagent, ELISA kit and real-time RT-PCR respectively. Subsequently, MTT reduction assay was used to evaluate the neuroprotective effects of PS leaf extracts against Aβ-induced microglia-mediated neurotoxicity in SH-SY5Y neuroblastoma cells. The levels of tau proteins phosphorylated at threonine 231 (pT231) and total tau proteins (T-tau) were determined using ELISA kits.
RESULTS: Polar extracts of PS leaves (LEA and LMEOH) reduced the Aβ-induced secretion of pro-inflammatory cytokines (IL-1β and TNF-α) in BV-2 cells by downregulating the mRNA expressions of pro-inflammatory cytokines. The inhibition of nitric oxide (NO) production could be due to the free radical scavenging activity of the extracts. In addition, conditioned media from Aβ-induced BV-2 cells pre-treated with LEA and LMEOH protected SH-SY5Y cells against microglia-mediated neurotoxicity. Further mechanistic study suggested that the neuroprotective effects were associated with the downregulation of phosphorylated tau proteins.
CONCLUSIONS: The present study suggests that polar extracts of PS leaves confer neuroprotection against Aβ-induced microglia-mediated neurotoxicity in SH-SY5Y cells by attenuating tau hyperphosphorylation through their anti-inflammatory actions and could be a potential therapeutic agent for Alzheimer's disease.
METHODS: Gene expression of IL-6 and IL-6Rα in PSC and PDAC cells was measured with qRT-PCR. The role of PSC-secreted IL-6, JAK/Stat3 signaling, and Nrf2 mediation on EMT-related genes expression was also examined with qRT-PCR. EMT phenotypes were assessed with morphological change, wound healing, migration, and invasion.
RESULTS: PSC expressed higher mRNA levels of IL-6 but lower IL-6Rα compared to PDAC cells. Neutralizing IL-6 in PSC secretion reduced mesenchymal-like morphology, migration and invasion capacity, and mesenchymal-like gene expression of N-cadherin, vimentin, fibronectin, collagen I, Sip1, Snail, Slug, and Twist2. Inhibition of JAK/Stat3 signaling induced by IL-6 repressed EMT and Nrf2 gene expression. Induction of Nrf2 activity by tert-butylhydroquinone (tBHQ) increased both EMT phenotypes and gene expression (N-cadherin, fibronectin, Twist2, Snail, and Slug) repressed by IL-6 neutralizing antibody. Simultaneous inhibition of Nrf2 expression with siRNA and Stat3 signaling further repressed EMT gene expression, indicating that Stat3/Nrf2 pathway mediates EMT induced by IL-6.
CONCLUSIONS: IL-6 from PSC promotes EMT in PDAC cells via Stat3/Nrf2 pathway.
GENERAL SIGNIFICANCE: Targeting Stat3/Nrf2 pathway activated by PSC-secreted IL-6 may provide a novel therapeutic option to improve the prognosis of PDAC.