Role of epac in the pathogenesis of ischemic stroke

Poster Presentations: Theme 2published_or_final_version15th Research Postgraduate Symposium, Hong Kong, China, 1-2 December 2010. In Abstract - Poste Presentations (Theme II) of 15th Research Postgraduate Symposium, 2010, p. 8

Roles of the CHADS2 and CHA2DS2-VASc scores in post-myocardial infarction patients: Risk of new occurrence of atrial fibrillation and ischemic stroke

Background: Patients with myocardial infarction (MI) are at risk of the development of atrial fibrillation (AF) and ischemic stroke. We sought to evaluate the prognostic performance of the CHADS2 and CHA2DS2-VASc scores in predicting new AF and/or ischemic stroke in post-ST segment elevation MI (STEMI) patients. Six hundred and seven consecutive post-STEMI patients with no previously documented AF were studied.Methods and Results: After a follow-up of 63 months (3,184 patient-years), 83 (13.7%) patients developed new AF (2.8% per year). Patients with a high CHADS2 and/or CHA2DS2-VASc score were more likely to develop new AF. The annual incidence of new AF was 1.18%, 2.10%, 4.52%, and 7.03% in patients with CHADS2 of 0, 1, 2, and ≥ 3; and 0.39%, 1.72%, 1.83%, and 5.83% in patients with a CHA2DS2-VASc score of 1, 2, 3 and ≥ 4. The CHA2DS2-VASc score (C-statistic = 0.676) was superior to the CHADS2 (C-statistic = 0.632) for discriminating new AF. Ischemic stroke occurred in 29 patients (0.9% per year), the incidence increasing in line with the CHADS2 (0.41%, 1.02%, 1.11%, and 1.95% with score of 0, 1, 2, and ≥ 3) and CHA2DS2-VASc scores (0.39%, 0.49%, 1.02%, and 1.48% with score of 1, 2, 3 and ≥ 4). The C-statistic of the CHA2DS2-VASc score as a predictor of ischemic stroke was 0.601, superior to that of CHADS2 score (0.573). CHADS2 and CHA2DS2-VASc scores can identify post-STEMI patients at high risk of AF and stroke.Conclusions: The CHADS2 and CHA2DS2-VASc scores can identify post-STEMI patients at high risk of AF and ischemic stroke. This enables close surveillance and prompt anticoagulation for stroke prevention

Wnt activation downregulates olfactomedin-1 in Fallopian tubal epithelial cells:a microenvironment predisposed to tubal ectopic pregnancy

Ectopic pregnancy (EP) occurs when the embryo fails to transit to the uterus and attach to the luminal epithelium of the Fallopian tube (FT). Tubal EP is a common gynecological emergency and more than 95% of EP occurs in the ampullary region of the FT. In humans, Wnt activation and downregulation of olfactomedin-1 (Olfm-1) occur in the receptive endometrium and coincided with embryo implantation in vivo. Whether similar molecular changes happen in the FT leading to EP remains unclear. We hypothesized that activation of Wnt signaling downregulates Olfm-1 expression predisposes to EP. We investigated the spatiotemporal expression of Olfm-1 in FT from non-pregnant women and women with EP, and used a novel trophoblastic spheroid (embryo surrogate)-FT epithelial cell co-culture model (JAr and OE-E6/E7 cells) to study the role of Olfm-1 on spheroid attachment. Olfm-1 mRNA expression in the ampullary region of non-pregnant FT was higher (P0.05) in the follicular phase than in the luteal phase. Ampullary tubal Olfm-1 expression was lower in FT from women with EP compared to normal controls at the luteal phase (histological scoring (H-SCORE)1.30.2 vs 2.40.5; P0.05). Treatment of OE-E6/E7 with recombinant Olfm-1 (0.2-5 g/ml) suppressed spheroid attachment to OE-E6/E7 cells, while activation of Wnt-signaling pathway by Wnt3a or LiCl reduced endogenous Olfm-1 expression and increased spheroid attachment. Conversely, suppression of Olfm-1 expression by RNAi increased spheroid attachment to OE-E6/E7 cells. Taken together, Wnt activation suppresses Olfm-1 expression, and this may predispose a favorable microenvironment of the retained embryo in the FT, leading to EP in humans. © 2012 USCAP, Inc All rights reserved.link_to_OA_fulltex

Is acupuncture effective in controlling gagging when taking an alginate impressions?

Our community health project aimed to (1) identify the prevalence of gagging among patients attending the Prince Philip Dental Hospital; and to identify socio-demographic variations in reported gagging experiences; and (2) perform a pilot study to evaluate the effectiveness of acupuncture in the control of gagging in the dental setting. Methods: A survey on reported gagging experiences was conducted among patients attending our hospital involving a convenience sample of 225 patients. Participants who reported to previously gag in the dental setting were invited to participate in a pilot study to evaluate the effectiveness of acupuncture in controlling gagging when taking an upper alginate impression. Participants were randomized to receive acupuncture stimulation at a site reported to be effective in the control of gagging on the lower lip (point CV 24) or at a sham site on the upper lip (point GV 26) on their first visit and at their second visit to receive the alternative acupuncture stimulation. Results: The response rate to the survey was 81.3% (183/225). Approximately a third (58/183) reported to have experienced gagging in the dental setting and most frequently encountered this when having a dental impression (among approximately a quarter of participants - 44/183). Half (95/183) reported gagging while performing oral self-care. Four in ten participants (73/183) reported some stress visiting the dentist related to gagging. Sociodemographic variations in reported gagging experiences were evident with respect to age, gender and education level. The response rate to the pilot study was 92.3% (36/39). There was no significant difference in the prevalence of gagging when acupuncture was applied to the test site compared to when acupuncture was applied to the sham site on dental examination (p>0.05) or when taking an upper alginate impression (p>0.05). Conclusions: Gagging in a relative common experience reported by patients attending our hospital – in daily life, in the dental setting and in performing oral self-care. Socio-demographic variations in the prevalence of gagging were apparent. The pilot study does not support the use of acupuncture in controlling gagging in the dental setting.published_or_final_versio

Differential actions of glycodelin-A on Th-1 and Th-2 cells: A paracrine mechanism that could produce the Th-2 dominant environment during pregnancy

Background: The maternalfetal interface has a unique immunological response towards the implanting placenta. It is generally accepted that a T-helper type-2 (Th-2) cytokine prevailing environment is important in pregnancy. The proportion of Th-2 cells in the peripheral blood and decidua is significantly higher in pregnant women in the first trimester than in non-pregnant women. Glycodelin-A (GdA) is a major endocrine-regulated decidual glycoprotein thought to be related to fetomaternal defence. Yet the relationship between its immunoregulatory activities and the shift towards Th-2 cytokine profile during pregnancy is unclear. Methods GdA was immunoaffinity purified from human amniotic fluid. T-helper, T-helper type-1 (Th-1) and Th-2 cells were isolated from the peripheral blood. The viability of these cells was studied by XTT assay. Immunophenotyping of CD4/CD294, cell death and GdA-binding were determined by flow cytometry. The mRNA expression, surface expression and secretion of Fas/Fas ligand (FasL) were determined by quantitative polymerase chain reaction, flow cytometry and ELISA, respectively. The activities of caspase-3, -8 and -9 were measured. The phosphorylation of extracellular signal-regulated kinases (ERK), p38 and, c-Jun N-terminal kinase was determined by western blotting. Results Although GdA bound to both Th-1 and Th-2 cells, it had differential actions on the two cell-types. GdA induced cell death of the Th-1 cells but not the Th-2 cells. The cell death was mediated through activation of caspase -3, -8 and -9 activities. GdA up-regulated the expression of Fas and inhibited ERK activation in the Th-1 cells, which might enhance the vulnerability of the cells to cell death caused by a trophoblast-derived FasL. Conclusions The data suggest that GdA could be an endometrial factor that contributes to the Th-2/Th-1 shift during pregnancy. © 2011 The Author.postprin

Cumulus cells and their extracellular matrix affect the quality of the spermatozoa penetrating the cumulus mass

Objective: To investigate the role of the cumulus cells and the cumulus matrix in affecting the penetrability, morphology, acrosome reaction, and motility of human spermatozoa penetrating the cumulus oophorus. Design: Controlled experimental laboratory study. Setting: University gynecology unit. Patient(s): Women undergoing assisted reproduction treatment and men visiting the subfertility clinics. Intervention(s): Human spermatozoa were allowed to penetrate through the cumulus oophorus and cell-depleted cumulus matrix in a capillary, and were treated with cumulus cell extract or hyaluronic acid. Main Outcome Measure(s): The morphology, acrosomal status, and motility of human spermatozoa were determined. Result(s): Fewer spermatozoa could penetrate the fresh cell-depleted matrix compared with intact cumulus oophorus. Spermatozoa that penetrated through the cumulus oophorus had higher percentages of normal morphology and acrosome reaction and had specific motility pattern. These effects were lost or reduced in the cell-depleted matrix that had been stored overnight. Hyaluronic acid, a main component of the cumulus matrix at concentration found in the cumulus oophorus, modulated sperm motility but did not affect spontaneous acrosome reaction. Cumulus cell extract did not affect sperm motility, but induced acrosome reaction. Conclusion(s): Both the cumulus matrix and the cumulus cells contribute to the effect of cumulus oophorus on spermatozoa penetrating through it. © 2009 American Society for Reproductive Medicine.postprin

Towards a global partnership model in interprofessional education for cross-sector problem-solving

Objectives A partnership model in interprofessional education (IPE) is important in promoting a sense of global citizenship while preparing students for cross-sector problem-solving. However, the literature remains scant in providing useful guidance for the development of an IPE programme co-implemented by external partners. In this pioneering study, we describe the processes of forging global partnerships in co-implementing IPE and evaluate the programme in light of the preliminary data available. Methods This study is generally quantitative. We collected data from a total of 747 health and social care students from four higher education institutions. We utilized a descriptive narrative format and a quantitative design to present our experiences of running IPE with external partners and performed independent t-tests and analysis of variance to examine pretest and posttest mean differences in students’ data. Results We identified factors in establishing a cross-institutional IPE programme. These factors include complementarity of expertise, mutual benefits, internet connectivity, interactivity of design, and time difference. We found significant pretest–posttest differences in students’ readiness for interprofessional learning (teamwork and collaboration, positive professional identity, roles, and responsibilities). We also found a significant decrease in students’ social interaction anxiety after the IPE simulation. Conclusions The narrative of our experiences described in this manuscript could be considered by higher education institutions seeking to forge meaningful external partnerships in their effort to establish interprofessional global health education

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London