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Self-harm is common in mental health facilities, and coercive containment measures are sometimes used to manage it. Nurses' attitudes towards these measures have been investigated in relation to disturbed behaviour in general, but rarely to self-harm specifically. We therefore investigated mental health nurses' use of and attitudes towards coercive measures (seclusion, restraint, intermittent and constant observations, forced intramuscular medication, and PRN medication) for self-cutting management compared with for disturbed behaviours in general using a cross-sectional, repeated measures survey design. Participants were N = 164 mental health nursing staff. Data collection was via a questionnaire comprising validated attitudinal measures. The study is reported in line with STROBE guidelines. Physical restraint (36.6%), forced intramuscular medication (32.3%) and seclusion (48.2%) had reportedly been used by individuals for self-cutting management. Respondents disapproved of using each coercive measure for self-cutting more than they did for disturbed behaviour in general with the exception of PRN medication. Attitudes to coercive measures differed across target behaviours. Hence, nurses who had used each measure for managing self-cutting disapproved of it less for that purpose than those who had not. Nurses who had used coercive techniques for self-cutting management had less desirable attitudes to their use. We cannot say whether prior use of these techniques led to increased approval or whether greater approval led to an increased willingness to use them. Reducing the use of coercive techniques for self-harm will require attitudes that support its use to be challenged. Less coercive techniques should be encouraged. Harm reduction techniques offer one such alternative., (© 2022 The Authors. International Journal of Mental Health Nursing published by John Wiley & Sons Australia, Ltd.)

Persistent viruses cause chronic disease, and threaten the lives of immunosuppressed individuals. Here, we elucidate a mechanism supporting the persistence of human adenovirus (AdV), a virus that can kill immunosuppressed patients. Cell biological analyses, genetics and chemical interference demonstrate that one of five AdV membrane proteins, the E3-19K glycoprotein specifically triggers the unfolded protein response (UPR) sensor IRE1α in the endoplasmic reticulum (ER), but not other UPR sensors, such as protein kinase R-like ER kinase (PERK) and activating transcription factor 6 (ATF6). The E3-19K lumenal domain activates the IRE1α nuclease, which initiates mRNA splicing of X-box binding protein-1 (XBP1). XBP1s binds to the viral E1A-enhancer/promoter sequence, and boosts E1A transcription, E3-19K levels and lytic infection. Inhibition of IRE1α nuclease interrupts the five components feedforward loop, E1A, E3-19K, IRE1α, XBP1s, E1A enhancer/promoter. This loop sustains persistent infection in the presence of the immune activator interferon, and lytic infection in the absence of interferon.

Dysregulated endogenous retroelements (EREs) are increasingly implicated in the initiation, progression, and immune surveillance of human cancer. However, incomplete knowledge of ERE activity limits mechanistic studies. By using pan-cancer de novo transcript assembly, we uncover the extent and complexity of ERE transcription. The current assembly doubled the number of previously annotated transcripts overlapping with long-terminal repeat (LTR) elements, several thousand of which were expressed specifically in one or a few related cancer types. Exemplified in melanoma, LTR-overlapping transcripts were highly predictable, disease prognostic, and closely linked with molecularly defined subtypes. They further showed the potential to affect disease-relevant genes, as well as produce novel cancer-specific antigenic peptides. This extended view of LTR elements provides the framework for functional validation of affected genes and targets for cancer immunotherapy., (© 2019 Attig et al.; Published by Cold Spring Harbor Laboratory Press.)

WHAT IS KNOWN ON THE SUBJECT?: Nurses in mental health inpatient settings use a range of methods to try and help service users who self-harm Harm-reduction approaches are intended to help service users reduce the impact of their self-harm rather than simply to prevent them self-harming Harm-reduction techniques might be helpful for people who cut themselves because there are some clear ways harm can be minimized such as providing advice about cutting No one has previously tried to measure whether harm-reduction techniques are more or less acceptable to mental health practitioners and service users than traditional methods. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: The paper describes the development of the Attitudes to Self-cutting Management scale. It met the criteria required of a good measurement tool. Each method of managing self-cutting has a unique acceptability profile Harm-reduction methods like advising on wound care and providing a first aid kit are endorsed by nurses and former service users Nurses providing sterile razors or remaining present during self-cutting attract more divergent opinions but are preferred to seclusion and restraint. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Nurses should talk through the approaches to management with service users and agree which techniques are preferred. ABSTRACT: Introduction Harm-reduction approaches for self-harm in mental health settings have been under-researched. Aim To develop a measure of the acceptability of management approaches for self-cutting in mental health inpatient settings. Methods Stage one: scale items were generated from relevant literature and staff/service user consultation. Stage two: A cross-sectional survey and statistical methods from classical test theory informed scale development. Results/Findings At stage one, N = 27 staff and service users participated. At stage two, N = 215 people (n = 175 current mental health practitioners and n = 40 people with experience of self-cutting as a UK mental health inpatient) completed surveys. Principal components analysis revealed a simple factor structure such that each method had a unique acceptability profile. Reliability, construct validity and internal consistency were acceptable. The harm-reduction approaches "advising on wound care" and "providing a first aid kit" were broadly endorsed; "providing sterile razors" and "maintaining a supportive nursing presence during cutting" were less acceptable but more so than seclusion and restraint. Discussion The Attitudes to Self-cutting Management scale is a reliable and valid measure that could inform service design and development. Implications for practice Nurses should discuss different options for management of self-cutting with service users. Harm-reduction approaches may be more acceptable than coercive measures., (© 2018 John Wiley & Sons Ltd.)

Cytomegalovirus (CMV) infection elicits a strong T-cell immune response, which increases further during aging in a process termed "memory inflation." CMV downregulates the expression of HLA-A and HLA-B on the surface of infected cells to limit presentation of viral peptides to T-cells although HLA-C is relatively spared as it also engages with inhibitory killer immunoglobulin receptor receptors and therefore reduces lysis by natural killer cells. We investigated the magnitude and functional properties of CMV-specific CD8 + T-cells specific for 10 peptides restricted by HLA-C in a cohort of 53 donors between the age of 23 and 91 years. This was achieved via peptide stimulation of PBMCs followed by multicolor flow cytometry. Three peptides, derived from proteins generated in the immediate-early period of viral replication and restricted by HLA-Cw*0702, elicited strong immune responses, which increased substantially with age such that the average aggregate response represented 37% of the CD8 + T-cell pool within donors above 70 years of age. Remarkably, a single response represented 70% of the total CD8 + T-cell pool within a 91-year-old donor. HLA-Cw*0702-restricted CD8 + T-cell responses were immunodominant over HLA-A and HLA-B-restricted CMV-specific responses and did not show features of exhaustion such as PD-1 or CD39 expression. Indeed, such CTL exhibit a polyfunctional cytokine profile with co-expression of IFN-γ and TNF-α and a strong cytotoxic phenotype with intracellular expression of perforin and granzymeB. Functionally, HLA-Cw*0702-restricted CTL show exceptionally high avidity for cognate peptide-HLA and demonstrate very early and efficient recognition of virally infected cells. These observations indicate that CD8 + T-cells restricted by HLA-C play an important role in the control of persistent CMV infection and could represent a novel opportunity for CD8 + T-cell therapy of viral infection within immunosuppressed patients. In addition, the findings provide further evidence for the importance of HLA-C-restricted T-cells in the control of chronic viral infection.

Practising hand hygiene at the right times to prevent healthcare-associated infections is one of the most important patient care practices health professionals can undertake. However, changing behaviour to ensure staff practise appropriate hand hygiene requires a multifaceted approach. This article highlights two important aspects of the message staff need--the when and the how of hand hygiene.

The aim was to find how to use information and communication technology to present the clinical skills content of an undergraduate medical curriculum. Rapid application design was used to develop the product, and technical action research was used to evaluate the development process. A clinician-educator, two medical students, two computing science masters students, two other project workers, and a hospital education informatics lead, formed a design team. A sample of stakeholders took part in requirements planning workshops and continued to advise the team throughout the project. A university hospital had many features that favoured fast, inexpensive, and successful system development: a clearly defined and readily accessible user group; location of the development process close to end-users; fast, informal communication; leadership by highly motivated and senior end-users; devolved authority and lack of any rigidly imposed management structure; cooperation of clinicians because the project drew on their clinical expertise to achieve scholastic goals; a culture of learning and involvement of highly motivated students. A detailed specification was developed through storyboarding, use case diagramming, and evolutionary prototyping. A very usable working product was developed within weeks. "SkillsBase" is a database web application using Microsoft Active Server Pages, served from a Microsoft Windows 2000 Server operating system running Internet Information Server 5.0. Graphing functionality is provided by the KavaChart applet. It presents the skills curriculum, provides a password-protected portfolio function, and offers training materials. The curriculum can be presented in several different ways to help students reflect on their objectives and progress towards achieving them. The reflective portfolio function is entirely private to each student user and allows them to document their progress in attaining skills, as judged by self, peer and tutor assessment, and examinations. Training materials include web links and materials developed locally using pedagogic principles developed by the SkillsBase team. Although the usability of SkillsBase has been proven, uptake of software that has arisen 'bottom-up' from within the curriculum has proved slow. We plan to incorporate the SkillsBase services into a more comprehensive virtual managed learning environment, anticipating that presenting the functionality in an environment that is routinely used by students and teachers will increase uptake and use.

Aims: The aim of this study was to use information and communications technology to present a curriculum of clinical skills in a user-friendly format., Setting: A UK undergraduate medical school with a problem-based curriculum and a strong emphasis on proficiency in clinical skills., Study Design: Case study describing the qualitative analysis of users' requirements and development of a web-based learning portfolio., Evaluation: The study involved direct observation of users during a 'think-aloud' protocol, a validated software users' measurement inventory and a 17-item questionnaire designed to test whether 'SkillsBase' met its users' requirements., Results: Students wanted a clear and flexible presentation of their skills curriculum that was easy to navigate, offered instructional material and standards for self- and peer assessment, offered useful Internet links, allowed them to compare their progress with school standards and peer norms, and could be used as a learning portfolio. During the think-aloud protocol, students made very few errors in data interpretation or navigation, and found SkillsBase easy to learn and aesthetically pleasing to use. They rated it higher on all measures of usability than standard commercial software. The questionnaire showed that it met most aspects of its design specification, although many students were doubtful that they would use its reflective function. It is available for inspection at http://www.skillsbase.man.ac.uk/., Conclusions: SkillsBase meets the design specification for a training and reflective aid to learning clinical skills and is very usable.

The cholesterol esterase and lipoprotein lipase catalyzed hydrolyses of the water-soluble substrate p-nitrophenyl butyrate are competitively inhibited by butaneboronic acid and phenylboronic acid. Phenyl-n-butylborinic acid has been synthesized and characterized as an ultrapotent transition state analog inhibitor: Ki = 2.9 +/- 0.6 nM and 1.7 +/- 0.3 microM for the cholesterol esterase and lipoprotein lipase reactions, respectively. These results are interpreted in terms of transition state structure and stabilization.

Neither kcat. nor kcat./Km for five aryl alpha-D-glucopyranosides correlates with aglycone pKa, and isotope effects, described according to the convention used by Cleland [(1982) CRC Crit. Rev. Biochem. 13, 385-428], of 18(V) = 1.002 +/- 0.008, alpha D(V) = 1.01 +/- 0.04 and alpha D(V/K) = 0.969 +/- 0.035 are observed for p-nitrophenyl, and one of beta D(V) = 1.02 +/- 0.04 for phenyl alpha-D-glucopyranoside; kcat. but not kcat./Km, correlates with aglycone pKa for five alpha-D-glucopyranosyl pyridinium ions with a Brønsted coefficient of -0.61 +/- 0.06, and isotope effects of alpha D(V) = 1.22 +/- 0.02, beta D(V) = 1.13 +/- 0.01 and alpha D(V/K) = 1.018 +/- 0.046 for the 4-bromoisoquinolinium, and alpha D(V) = 1.15 +/- 0.02 and beta D(V) = 1.085 +/- 0.011 for the pyridinium salts are observed. These data require that a non-covalent event, fast in the case of the N-glycosides but slow in the case of the O-glycosides, precedes bond-breaking, and that bond-breaking involves substantial charge development on the glycone and near-perpendicularity of the C2-H bond to the planar oxocarbonium ion system. A model meeting these requirements is that the non-covalent event is a conjoint change of protein and substrate conformation which puts the pyranose ring in the 2,5B conformation of the bond-breaking transition state. This model also explains the contrast between the powerful inhibition of the enzyme by deoxynojirimycin (Ki = 23 +/- 3 microM) and feeble inhibition by castanospermine [Saul, Chambers, Molyneux & Elbein (1983) Arch. Biochem. Biophys. 221, 593-597], but is directly contrary to the predictions of Deslongchamps' 'Theory of Stereoelectronic Control' [Deslongchamps (1975) Tetrahedron 31, 2463-2490; (1983) Stereoelectronic Effects in Organic Chemistry, p. 39, Pergamon Press, Oxford].