Ezrin interacts with the SARS coronavirus spike protein and restrains infection at the entry stage

© 2012 Millet et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Entry of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and its envelope fusion with host cell membrane are controlled by a series of complex molecular mechanisms, largely dependent on the viral envelope glycoprotein Spike (S). There are still many unknowns on the implication of cellular factors that regulate the entry process. Methodology/Principal Findings: We performed a yeast two-hybrid screen using as bait the carboxy-terminal endodomain of S, which faces the cytosol during and after opening of the fusion pore at early stages of the virus life cycle. Here we show that the ezrin membrane-actin linker interacts with S endodomain through the F1 lobe of its FERM domain and that both the eight carboxy-terminal amino-acids and a membrane-proximal cysteine cluster of S endodomain are important for this interaction in vitro. Interestingly, we found that ezrin is present at the site of entry of S-pseudotyped lentiviral particles in Vero E6 cells. Targeting ezrin function by small interfering RNA increased S-mediated entry of pseudotyped particles in epithelial cells. Furthermore, deletion of the eight carboxy-terminal amino acids of S enhanced S-pseudotyped particles infection. Expression of the ezrin dominant negative FERM domain enhanced cell susceptibility to infection by SARS-CoV and S pseudotyped particles and potentiated S-dependent membrane fusion. Conclusions/Significance: Ezrin interacts with SARS-CoV S endodomain and limits virus entry and fusion. Our data present a novel mechanism involving a cellular factor in the regulation of S-dependent early events of infection.This work was supported by the Research Grant Council of Hong Kong (RGC#760208)and the RESPARI project of the International Network of Pasteur Institutes

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

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Using Malmquist Indexes to measure changes in the productivity and efficiency of Fuzzy accounting and before and after the SarbanesOxley Act

There have been many criticisms of the Sarbanes-Oxley (SOX) Act passed in July of 2002 to correct business accountability and performance practices. The act has a major emphasis on accounting and its practices. This paper attempts a response to these criticisms by investigating changes in productive efficiency for 62 of the largest US public accounting firms between the periods (2000)(2001) and (2003)(2004))-the periods before and after enactment of SOX in July of 2002. DEA is used to calculate Malmquist indexes of productivity and efficiency changes. This index is used because it can distinguish between changes in technical efficiency, which limit the possibilities, and changes in the performance efficiencies for each firm. Contrary to many of the criticisms, results indicate that accounting firms have exhibited significant post SOX growth in productive efficiency which is better than pre-SOX performances

Using Malmquist Indexes to measure changes in the productivity and efficiency of US accounting firms before and after the Sarbanes-Oxley Act

There have been many criticisms of the Sarbanes-Oxley (SOX) Act passed in July of 2002 to correct business accountability and performance practices. The act has a major emphasis on accounting and its practices. This paper attempts a response to these criticisms by investigating changes in productive efficiency for 62 of the largest US public accounting firms between the periods (2000-2001) and (2003-2004)--the periods before and after enactment of SOX in July of 2002. DEA is used to calculate Malmquist indexes of productivity and efficiency changes. This index is used because it can distinguish between changes in technical efficiency, which limit the possibilities, and changes in the performance efficiencies for each firm. Contrary to many of the criticisms, results indicate that accounting firms have exhibited significant post SOX growth in productive efficiency which is better than pre-SOX performances.Accounting firms Productivity change Efficiency change Data envelopment analysis Malmquist index

Perceived Quality of Reference Service with WhatsApp

Academic libraries are experiencing significant changes and making efforts to deliver their service in the digital environment. Libraries are transforming from being places for reading to extensions of the classroom and learning spaces. Due to the globalized digital environment and intense competition, libraries are trying to improve their service quality through various evaluations. As reference service is crucial to users, this study explores user satisfaction towards the reference service through WhatsApp, a social media instant messenger, at a major university in Hong Kong and discusses the correlation between the satisfaction rating and three variables. Suggestions and recommendations are raised for future improvements. The study also sheds light on the usage of reference services through instant messaging in other academic libraries

The Hong Kong Version Of The Oxford Cognitive Screen (Hk-Ocs): Validation Study For Cantonese-Speaking Chronic Stroke Survivors

This study reports the validation of the Hong Kong version of Oxford Cognitive Screen (HK-OCS). Seventy Cantonese-speaking healthy individuals participated to establish normative data and 46 chronic stroke survivors were assessed using the HK-OCS, Albert’s Test of Visual Neglect, short test of gestural production, and Hong Kong version of the following assessments: Western Aphasia Battery, MMSE, MoCA, Modified Barthel Index, and Lawton Instrumental Activities of Daily Living scale. The validity of the HK-OCS was appraised by the difference between the two participant groups. Neurologically unimpaired individuals performed significantly better than stroke survivors on the HK-OCS. Positive and significant correlations found between cognitive subtests in the HK-OCS and related assessments indicated good concurrent validity. Excellent intra-rater and inter-rater reliabilities, fair test–retest reliability, and acceptable internal consistency suggested that the HK-OCS had good reliability. Specific HK-OCS subtests including semantics, episodic memory, number writing, and orientation were the best predictors of functional outcomes

Cantonese version of the Oxford Cognitive Screen (OCS): Validation for stroke survivors in Hong Kong

Background Stroke-induced cognitive impairments are critical predictors of poor functional outcomes. They adversely affect recovery and reduce independent performance of basic activities of daily living (ADL) and instrumental ADL (Zinn et al., 2004). Choices of cognitive assessment tools specific to the Cantonese speaking stroke population in Hong Kong are limited. The Cantonese version of the Western Aphasia Battery (Cantonese-WAB) was specifically developed for examining language impairments. The Cantonese version of MMSE (Cantonese-MMSE) and Hong Kong Montreal Cognitive Assessment (HK-MoCA), designed to detect cognitive deficits associated with dementia, lacked important measures of writing, neglect, and praxis where impairments were commonly found in stroke. More critically, most tasks in these two screeners required relatively intact auditory comprehension and verbal responses from participants. Presence of aphasia can, therefore, lead to underestimation of cognitive abilities. Aims Extending Chan et al.’s (2013) development of a Cantonese version of the Birmingham Cognitive Screen (BCoS) to be used in Hong Kong, our first aim was to validate the Oxford Cognitive Screen (OCS), built on similar principles to the BCoS test but is shorter (15 minutes) and can be used in acute settings, for Cantonese-speaking stroke survivors. This tool, including assessment of aphasia, apraxia, attention, memory, and spatial neglect, was designed to be neglect- and aphasia-friendly by using multi-modal presentation, forced-choice testing procedures, and vertical layouts. The second aim was to determine which cognitive domain(s) in HK-OCS would best predict functional outcomes. Procedures Seventy normal individuals were recruited to establish the normative data of HK-OCS. Norm was developed for three age groups (59 years). Direct percentile conversions for each sub-test scores were used and cut-off scores were set at the top 5th percentile. Forty six native Cantonese-speaking stroke participants (aged 21-83 years; 72% left hemispheric stroke) participated and received a short test of gestural production (Goldenberg, 1996), Albert’s test of visual neglect, Chinese version of the Modified Barthel Index, and Hong Kong Chinese version of Lawton Instrumental Activities of Daily Living scale, Cantonese-WAB, Cantonese-MMSE, HK-MoCA, and HK-OCS. Results Cut-off scores for most HK-OCS sections were comparable across the three age groups. Paired-sample t-tests revealed the stroke group achieved significantly lower scores across most sections than matched controls. The tool demonstrated strong concurrent validity with positive and significant correlations across related cognitive subtests in other batteries (Table 1). The HK-OCS also had excellent intra-rater and inter-rater, good test-retest reliability, and acceptable internal consistency. Regarding its predictive values on functional outcomes, while semantics and episodic memory best predicted basic ADL, number writing and orientation best predicted complex ADL. <br/

Effect of sucralfate on gastric mucosal blood flow in rats.

Sucralfate possesses site protective and cytoprotective actions and heals ulcers effectively, but its effect on gastric mucosal blood flow is unknown. Using an ex vivo gastric chamber preparation, we studied the effect of sucralfate on gastric mucosal blood flow in rats by laser doppler flowmetry. Under both fasting and fed states, measurements of gastric mucosal blood flow and damage were made in rats after topical application of absolute ethanol alone or after pretreatment with sucralfate. Gastric mucosal damage was assessed by measuring the total area of haemorrhagic mucosal lesions. Ethanol induced gastric mucosal lesions were significantly less with sucralfate pretreatment than without (p less than 0.008). Mucosal blood flow significantly fell after ethanol application (p less than 0.001). The fall was significantly less in fed than in fasted rats (p less than 0.05), and after pretreatment with sucralfate 100 mg or 200 mg than without in both fasted (p less than 0.0008 and 0.00001, respectively) and fed (p less than 0.002 and 0.001, respectively) rats. Graded doses of sucralfate (25-400 mg) resulted in an increase in gastric mucosal blood flow in a dose dependent manner (r = 0.731, p less than 0.001). In conclusion that sucralfate increases gastric mucosal blood flow in rats and lessens the fall in blood flow in rats treated with ethanol, and this action may contribute to its protection against the vascular damage of mucosa by ethanol

Randomised double-blind controlled trial of non-invasive preimplantation genetic testing for aneuploidy in in vitro fertilisation: a protocol paper

Introduction The success rate of in vitro fertilisation (IVF) treatment for couples with infertility remains low due to lack of a reliable tool in selecting euploid embryos for transfer. This study aims to compare the efficacy in embryo selection based on morphology alone compared with non-invasive preimplantation genetic testing for aneuploidy (niPGT-A) and morphology in infertile women undergoing IVF.Methods and analysis This is a randomised double-blind controlled trial conducted in two tertiary assisted reproduction centres. A total of 500 infertile women will be recruited and undergo IVF as indicated. They will be randomly assigned on day 6 after oocyte retrieval into two groups: the intervention group using morphology and niPGT-A and the control group based on morphology alone. In the control group, blastocysts with the best quality morphology will be replaced first. In the intervention group, blastocysts with the best morphology and euploid result of spent culture medium will be replaced first. The primary outcome is a live birth per the first embryo transfer. The statistical analysis will be performed with the intention to treat and per protocol.Ethics and dissemination Ethics approval was sought from the institutional review board of the two participating units. All participants will provide written informed consent before joining the study. The results of the study will be submitted to scientific conferences and peer-reviewed journals.Trial registration number NCT04474522