Animal models of atherosclerosis.

Atherosclerosis is a significant cause of morbidity and mortality globally. Many animal models have been developed to study atherosclerosis, and permit experimental conditions, diet and environmental risk factors to be carefully controlled. Pathophysiological changes can be produced using genetic or pharmacological means to study the harmful consequences of different interventions. Experiments using such models have elucidated its molecular and pathophysiological mechanisms, and provided platforms for pharmacological development. Different models have their own advantages and disadvantages, and can be used to answer different research questions. In the present review article, different species of atherosclerosis models are outlined, with discussions on the practicality of their use for experimentation.GT was supported by a BBSRC Doctoral Training Award and thanks the Croucher Foundation of Hong Kong for the generous support of his clinical assistant professorship. YC is supported by the ESRC

Animal models of atherosclerosis.

Atherosclerosis is a significant cause of morbidity and mortality globally. Many animal models have been developed to study atherosclerosis, and permit experimental conditions, diet and environmental risk factors to be carefully controlled. Pathophysiological changes can be produced using genetic or pharmacological means to study the harmful consequences of different interventions. Experiments using such models have elucidated its molecular and pathophysiological mechanisms, and provided platforms for pharmacological development. Different models have their own advantages and disadvantages, and can be used to answer different research questions. In the present review article, different species of atherosclerosis models are outlined, with discussions on the practicality of their use for experimentation.GT was supported by a BBSRC Doctoral Training Award and thanks the Croucher Foundation of Hong Kong for the generous support of his clinical assistant professorship. YC is supported by the ESRC

A systematic review of randomised controlled trials on the effectiveness of exercise programs on lumbo pelvic pain among postnatal women

Background: A substantial number of women tend to be affected by Lumbo Pelvic Pain (LPP) following child birth. Physical exercise is indicated as a beneficial method to relieve LPP, but individual studies appear to suggest mixed findings about its effectiveness. This systematic review aimed to synthesise evidence from randomised controlled trials on the effectiveness of exercise on LPP among postnatal women to inform policy, practice and future research. Methods: A systematic review was conducted of all randomised controlled trials published between January 1990 and July 2014, identified through a comprehensive search of following databases: PubMed, PEDro, Embase, Cinahl, Medline, SPORTDiscus, Cochrane Pregnancy and Childbirth Group’s Trials Register, and electronic libraries of authors’institutions. Randomised controlled trials were eligible for inclusion if the intervention comprised of postnatal exercise for women with LPP onset during pregnancy or within 3 months after delivery and the outcome measures included changes in LPP. Selected articles were assessed using the PEDro Scale for methodological quality and findings were synthesised narratively as meta-analysis was found to be inappropriate due to heterogeneity among included studies. Results: Four randomised controlled trials were included, involving 251 postnatal women. Three trials were rated as of ‘good’ methodological quality. All trials, except one, were at low risk of bias. The trials included physical exercise programs with varying components, differing modes of delivery, follow up times and outcome measures. Intervention in one trial, involving physical therapy with specific stabilising exercises, proved to be effective in reducing LPP intensity. An improvement in gluteal pain on the right side was reported in another trial and a significant difference in pain frequency in another. Conclusion: Our review indicates that only few randomised controlled trials have evaluated the effectiveness of exercise on LPP among postnatal women. There is also a great amount of variability across existing trials in the components of exercise programs, modes of delivery, follow up times and outcome measures. While there is some evidence to indicate the effectiveness of exercise for relieving LPP, further good quality trials are needed to ascertain the most effective elements of postnatal exercise programs suited for LPP treatment

Spatial analysis of hemorrhagic fever with renal syndrome in China

BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) is endemic in many provinces with high incidence in mainland China, although integrated intervention measures including rodent control, environment management and vaccination have been implemented for over ten years. In this study, we conducted a geographic information system (GIS)-based spatial analysis on distribution of HFRS cases for the whole country with an objective to inform priority areas for public health planning and resource allocation. METHODS: Annualized average incidence at a county level was calculated using HFRS cases reported during 1994–1998 in mainland China. GIS-based spatial analyses were conducted to detect spatial autocorrelation and clusters of HFRS incidence at the county level throughout the country. RESULTS: Spatial distribution of HFRS cases in mainland China from 1994 to 1998 was mapped at county level in the aspects of crude incidence, excess hazard and spatial smoothed incidence. The spatial distribution of HFRS cases was nonrandom and clustered with a Moran's I = 0.5044 (p = 0.001). Spatial cluster analyses suggested that 26 and 39 areas were at increased risks of HFRS (p < 0.01) with maximum spatial cluster sizes of ≤ 20% and ≤ 10% of the total population, respectively. CONCLUSION: The application of GIS, together with spatial statistical techniques, provide a means to quantify explicit HFRS risks and to further identify environmental factors responsible for the increasing disease risks. We demonstrate a new perspective of integrating such spatial analysis tools into the epidemiologic study and risk assessment of HFRS

Vandetanib (Zactima, ZD6474) Antagonizes ABCC1- and ABCG2-Mediated Multidrug Resistance by Inhibition of Their Transport Function

ABCC1 and ABCG2 are ubiquitous ATP-binding cassette transmembrane proteins that play an important role in multidrug resistance (MDR). In this study, we evaluated the possible interaction of vandetanib, an orally administered drug inhibiting multiple receptor tyrosine kinases, with ABCC1 and ABCG2 in vitro.MDR cancer cells overexpressing ABCC1 or ABCG2 and their sensitive parental cell lines were used. MTT assay showed that vandetanib had moderate and almost equal-potent anti-proliferative activity in both sensitive parental and MDR cancer cells. Concomitant treatment of MDR cells with vandetanib and specific inhibitors of ABCC1 or ABCG2 did not alter their sensitivity to the former drug. On the other hand, clinically attainable but non-toxic doses of vandetanib were found to significantly enhance the sensitivity of MDR cancer cells to ABCC1 or ABCG2 substrate antitumor drugs. Flow cytometric analysis showed that vandetanib treatment significantly increase the intracellular accumulation of doxorubicin and rhodamine 123, substrates of ABCC1 and ABCG2 respectively, in a dose-dependent manner (P<0.05). However, no significant effect was shown in sensitive parental cell lines. Reverse transcription-PCR and Western blot analysis showed that vandetanib did not change the expression of ABCC1 and ABCG2 at both mRNA and protein levels. Furthermore, total and phosphorylated forms of AKT and ERK1/2 remained unchanged after vandetanib treatment in both sensitive and MDR cancer cells.Vandetanib is unlikely to be a substrate of ABCC1 or ABCG2. It overcomes ABCC1- and ABCG2-mediated drug resistance by inhibiting the transporter activity, independent of the blockade of AKT and ERK1/2 signal transduction pathways

A multi-targeted approach to suppress tumor-promoting inflammation

Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-κB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes

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

X-ray emission from the Sombrero galaxy: discrete sources

We present a study of discrete X-ray sources in and around the bulge-dominated, massive Sa galaxy, Sombrero (M104), based on new and archival Chandra observations with a total exposure of ~200 ks. With a detection limit of L_X = 1E37 erg/s and a field of view covering a galactocentric radius of ~30 kpc (11.5 arcminute), 383 sources are detected. Cross-correlation with Spitler et al.'s catalogue of Sombrero globular clusters (GCs) identified from HST/ACS observations reveals 41 X-rays sources in GCs, presumably low-mass X-ray binaries (LMXBs). We quantify the differential luminosity functions (LFs) for both the detected GC and field LMXBs, whose power-low indices (~1.1 for the GC-LF and ~1.6 for field-LF) are consistent with previous studies for elliptical galaxies. With precise sky positions of the GCs without a detected X-ray source, we further quantify, through a fluctuation analysis, the GC LF at fainter luminosities down to 1E35 erg/s. The derived index rules out a faint-end slope flatter than 1.1 at a 2 sigma significance, contrary to recent findings in several elliptical galaxies and the bulge of M31. On the other hand, the 2-6 keV unresolved emission places a tight constraint on the field LF, implying a flattened index of ~1.0 below 1E37 erg/s. We also detect 101 sources in the halo of Sombrero. The presence of these sources cannot be interpreted as galactic LMXBs whose spatial distribution empirically follows the starlight. Their number is also higher than the expected number of cosmic AGNs (52+/-11 [1 sigma]) whose surface density is constrained by deep X-ray surveys. We suggest that either the cosmic X-ray background is unusually high in the direction of Sombrero, or a distinct population of X-ray sources is present in the halo of Sombrero.Comment: 11 figures, 5 tables, ApJ in pres

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns