Entry pathways of herpes simplex virus type 1 into human keratinocytes are dynamin- and cholesterol-dependent

Herpes simplex virus type 1 (HSV-1) can enter cells via endocytic pathways or direct fusion at the plasma membrane depending on the cell line and receptor(s). Most studies into virus entry have used cultured fibroblasts but since keratinocytes represent the primary entry site for HSV-1 infection in its human host, we initiated studies to characterize the entry pathway of HSV-1 into human keratinocytes. Electron microscopy studies visualized free capsids in the cytoplasm and enveloped virus particles in vesicles suggesting viral uptake both by direct fusion at the plasma membrane and by endocytic vesicles. The ratio of the two entry modes differed in primary human keratinocytes and in the keratinocyte cell line HaCaT. Inhibitor studies further support a role for endocytosis during HSV-1 entry. Infection was inhibited by the cholesterol-sequestering drug methyl-beta-cyclodextrin, which demonstrates the requirement for host cholesterol during virus entry. Since the dynamin-specific inhibitor dynasore and overexpression of a dominant-negative dynamin mutant blocked infection, we conclude that the entry pathways into keratinocytes are dynamin-mediated. Electron microscopy studies confirmed that virus uptake is completely blocked when the GTPase activity of dynamin is inhibited. Ex vivo infection of murine epidermis that was treated with dynasore further supports the essential role of dynamin during entry into the epithelium. Thus, we conclude that HSV-1 can enter human keratinocytes by alternative entry pathways that require dynamin and host cholesterol

Comparative assessment of young learners' foreign language competence in three Eastern European countries

This paper concerns teacher practices in, and beliefs about, the assessment of young learners' progress in English in three Eastern European countries (Slovenia, Croatia, and the Czech Republic). The central part of the paper focuses on an international project involving empirical research into assessment of young learners' foreign language competence in Slovenia, Croatia and the Czech Republic. With the help of an adapted questionnaire, we collected data from a non-random sample of primary and foreign language teachers who teach foreign languages at the primary level in these countries. The research shows that English as a foreign language is taught mostly by young teachers either primary specialists or foreign language teachers. These teachers most frequently use oral assessment/interviews or self-developed tests. Other more authentic types of assessment, such as language portfolios, are rarely used. The teachers most frequently assess speaking and listening skills, and they use assessment involving vocabulary the most frequently of all. However, there are significant differences in practice among the three countries

Examining Chemotherapy-Related Cognitive Changes in Colorectal Cancer Patients: A Feasibility Trial

Introduction: Research suggests that chemotherapy may be related to decline in patients’ cognitive functions. Objectives: To assess the feasibility and acceptability of a multi-site study designed to examine the nature and extent of chemotherapy-related cognitive changes in colorectal cancer patients. Method: Data was collected over 8 months using objective and self-reported measures of cognitive functioning and self-reported quality of life, fatigue and mood questionnaires. The assessment battery was administered pre- and mid-chemotherapy treatment to a consecutive sample of colorectal cancer patients across three Londonbased NHS Trusts. Participants included patients who had undergone colorectal surgery and were scheduled to have adjuvant chemotherapy treatment, or no further cancer treatment. Main outcome measures: Recruitment procedures, rate of recruitment, suitability of exclusion/inclusion criteria, acceptability of data collection procedures and the battery, and attrition rates. Results: From 1 April 2014 to 1 December 2014, 42 eligible participants were invited to take part in the trial. Of the 17 that completed pre-chemotherapy assessments, only 1 withdrew at follow-up due to reasons of ill health from disease recurrence. All participants completed the entire battery and indicated that they found the trial acceptable. Conclusions: What went wrong: Strained researcher resources; loss of eligible participants to competing studies, restrictive upper age limit. Possible solutions: Removal of upper age limit, an increased dedicated research team to increase rate of recruitment. The large multi-site study is feasible with suggested amendments and is acceptable to patients and medical teams. Acceptability of trial to medical teams is further evidenced by requests of collaboration from two additional London based NHS Trusts. Lessons learned: This feasibility trial provides evidence to other researchers designing similar studies in this area of an acceptable design and the need for appropriate funding for resources to recruit large enough consecutive samples of patients with solid tumour cancers

What influences withdrawal because of rejection of telehealth - the whole systems demonstrator evaluation

Purpose: The widespread deployment of telehealth (TH) has been conducted in the absence of any clear understanding of how acceptable these devices are to patients. One potential limitation of the widespread deployment of TH is that patients may refuse. Moreover an understanding of the reasons for refusing to use TH devices will provide an understanding of the barriers. Design/methodology/approach: This investigation from the Whole Systems Demonstrator (WSD) programme, a pragmatic cluster randomised controlled trial into the effectiveness of TH, examined reasons for patients in the intervention cohort of the trial refusing TH, and the potential barriers to its deployment. Findings: Active rejection of the TH intervention was the most frequent reason for withdrawal. After examination of trial-related, health, socio-demographic, cognitive, emotional and behavioural factors, patients diagnosed with diabetes, as opposed to heart failure or chronic obstructive pulmonary disease, and patients' beliefs about the acceptability of the intervention predicted whether or not they withdrew from the trial because of the intervention. Originality/value: Beliefs that the TH intervention resulted in increased accessibility to care, satisfaction with equipment and fewer concerns about the privacy, safety and discomfort associated with using TH equipment predicted continued participation in the WSD trial. Findings suggest that potentially modifiable beliefs about TH predict those more likely to reject the intervention. These findings have important implications for understanding individual differences in the acceptance of TH and subsequent success in mainstreaming TH in healthcare services. © Emerald Group Publishing Limited

Short Report : Outcomes for siblings associated with sub-groups of autistic children with intellectual disability identified by latent profile analysis

Background Recent research suggests that having a brother or sister with autism may contribute to increased positive or negative emotional or psychological impact on siblings. Aims To use a novel multidimensional data analysis method to further understand outcomes for siblings of autistic children. Methods and Procedures 318 siblings of children with a recorded autism diagnosis and an intellectual disability were included for latent profile analysis. Five variables (DBC disruptive and anxiety; VABS II communication, daily living, and socialization skills) were used to identify sub-groups of autistic children. Primary carers reported on sibling relationship quality (items from the Sibling Relationship Questionnaire warmth/closeness and conflict scales), and siblings’ behavioral and emotional problems. Outcomes and results The profile groups differed in their levels of ID coupled with disruptive behavior, emotional problems and adaptive skills. Profiles included a severe ID, low behavior and emotional problems and low adaptive skills group; a group with mild ID coupled with high adaptive skills and low emotional and behavioral problems; and a mild ID group with high emotional and behavioral problems. Conflict in the sibling relationship differed across the profile groups (F (4304) = 15.13, p < .001). Conclusions and implications Siblings of autistic children with the highest support needs were reported to have the lowest conflict in their relationships. Conversely, siblings of the autistic children with the highest levels of externalizing behaviors and anxiety were reported to have the highest levels of conflict in the sibling relationship

Cost-effectiveness of telehealth in people with social care needs: the Whole Systems Demonstrator cluster randomised trial

Introduction: The Whole Systems Demonstrator pilots introduced telehealth and telecare into three local authority areas using an integrated approach to deliver health and social care to those with high care needs and long-term conditions. Proponents of these technologies have given cost savings as one rationale for advocating their introduction and widespread implementation; proponents have also advocated their potential to improve the quality of life for their users. Until recently, evaluations of telehealth and telecare in high-income countries have been based on relatively small-scale pilots; few such evaluations have been designed as randomised controlled trials. The WSD study was a pragmatic cluster-randomised control trial, representing the largest-scale trial of telehealth and telecare to be carried out in the UK. This presentation focuses on the results of the WSD telecare questionnaire study. Objectives: To examine the costs and cost-effectiveness of telecare compared to standard support and treatment. Methods: Economic evaluation conducted in parallel with a pragmatic cluster-randomised controlled trial of Telecare. 2600 people with social care needs participated in a trial of a community-based telecare intervention in three English local authority areas. Approximately half of the participants in the telecare trial also consented to participate in the WSD telecare questionnaire study, which collected information on a number of patient-reported outcome measures and also on the self-reported use of a range of health and social services. Health and social costs were calculated by attaching nationally applicable unit costs to self-reported service use data. The unit costs of telecare support and treatment provided were calculated drawing on administrative and financial data sources and interviews with key informants. The primary outcome for the cost-effectiveness analysis was the quality-adjusted life year (QALY). Secondary outcomes included measures of health-related quality of life and well-being. We employed multivariate analyses to explore the cost-effectiveness of the intervention Results: The presentation will describe the results of the economic evaluation of telecare, addressing the cost of care and treatment packages used by those participating in the telecare questionnaire study and the results of the cost-effectiveness analysis. These results will be available by the time of the presentation. Conclusions: These will be available by the time of the presentation

Sibling adjustment and sibling relationships associated with clusters of needs in children with autism : a novel methodological approach

We tested a novel methodological approach to examine associations between characteristics of autistic children and outcomes for siblings. Cluster analysis was used to define five groups of children with autism (n = 168) based on autism symptoms, adaptive behavior, pro-social behavior, and behavior problems. Primary and secondary parent carers, and siblings themselves, reported on sibling relationship quality and psychological adjustment. Siblings of autistic children with a mild symptom profile, high levels of adaptive skills, but high internalizing and externalizing problems had the highest level of these problems themselves and more conflict in their relationship. Siblings of autistic children with the most complex support needs (adaptive skills deficits, severe autism symptoms) reported lower warmth relationships but not elevated internalizing and externalizing problems

Quantifying beliefs regarding telehealth: Development of the Whole Systems Demonstrator Service User Technology Acceptability Questionnaire

Introduction: Telehealth (TH) is a potential solution to the increased incidence of chronic illness in an ageing population.The extent to which older people and users with chronic conditions accept and adhere to using assistive technologies is a potential barrier to mainstreaming the service. This study reports the development and validation of the Whole Systems Demonstrator (WSD) Service User Technology Acceptability Questionnaire (SUTAQ). Methods: Questionnaires measuring the acceptability of TH, quality of life, well-being and psychological processes were completed by 478 users of TH. The 22 acceptability items were subject to principal components analysis (PCA) to determine sub-scales. Scale scores, relationships between scales and other patient reported outcome measures (PROMs), and group differences on scales were utilised to check the reliability and validity of the measure. Results: PCAs of SUTAQ items produced 6 TH acceptability scales: enhanced care, increased accessibility, privacy & discomfort, care personnel concerns, kit as substitution, and satisfaction. Scale scores indicated, individuals with long term conditions held beliefs. Significant correlations within these beliefs and between these scales and additional PROMs were coherent and the SUTAQ subscales were able to predict those more likely to refuse TH. Discussion: The SUTAQ is an instrument that can be used to measure user beliefs about the acceptability of TH, and has the ability to discriminate and predict individual differences in beliefs and behaviour. Measuring acceptability beliefs of TH users can provide valuable information to direct and target provision of services to increase uptake and maintain use of TH

Inner tegument protein pUL37 of herpes simplex virus type 1 is involved in directing capsids to the trans-Golgi network for envelopment

Secondary envelopment of herpes simplex virus type 1 has been demonstrated as taking place at the trans-Golgi network (TGN). The inner tegument proteins pUL36 and pUL37 and the envelope glycoproteins gD and gE are known to be important for secondary envelopment. We compared the cellular localizations of capsids from a virus mutant lacking the UL37 gene with those of a virus mutant lacking the genes encoding gD and gE. Although wild-type capsids accumulated at the TGN, capsids of the pUL37− mutant were distributed throughout the cytoplasm and showed no association with TGN-derived vesicles. This was in contrast to capsids from a gD−gE− mutant, which accumulated in the vicinity of TGN vesicles, but did not colocalize with them, suggesting that they were transported to the TGN but were unable to undergo envelopment. We conclude that the inner tegument protein pUL37 is required for directing capsids to the TGN, where secondary envelopment occurs

Cognitive dysfunction in Adult Congenital Heart Disease with different structural complexity

We carried out a cross-sectional study to assess cognitive function in a sample of adult CHD patients, within the Functioning in Adult Congenital Heart Disease study London. The association between cognitive functioning and disease complexity was examined. A total of 310 patients participated in this study. Patients were classified into four structural complexity groups – tetralogy of Fallot, transposition of the great arteries, single ventricle, and simple conditions. Each patient underwent neuropsychological assessment to evaluate cognitive function, including memory and executive function, and completed questionnaires to assess depression and anxiety. Among all, 41% of the sample showed impaired performance (>1.5 SD below the normative mean) on at least three tests of cognitive function compared with established normative data. This was higher than the 8% that was expected in a normal population. The sample exhibited significant deficits in divided attention, motor function, and executive functioning. There was a significant group difference in divided attention (F=5.01, p=0.002) and the mean total composite score (F=5.19, p=0.002) between different structural complexity groups, with the simple group displaying better cognitive function. The results indicate that many adult CHD patients display impaired cognitive function relative to a healthy population, which differs in relation to disease complexity. These findings may have implications for clinical decision making in this group of patients during childhood. Possible mechanisms underlying these deficits and how they may be reduced or prevented are discussed; however, further work is needed to draw conclusive judgements