A case report: retigabine induced oral mucosal dyspigmentation of the hard palate

Background Dyspigmentation of the oral mucosa has a multitude of aetiological causes. Retigabine, a new antiepileptic drug, has the potential side effect of inducing a blue/purple pigmentation of the oral mucosa in addition to the skin, lips, nails and retina of the eyes. This article presents a unique case of dyspigmentation present in the oral mucosa of the hard palate which has previously been unreported in the dental literature. Case presentation A 70 year old white male presented to a secondary care oral surgery department with an unusual asymptomatic pigmented lesion present in the hard palate of the oral cavity. The pigmentation was remarkable for its distinct blue/purple colouration which was associated with a similar discolouration of the nail beds of the hands. This is believed to be a side effect of the anti-epileptic medication retigabine. Conclusion The dental profession and wider healthcare community should be made fully aware of the potential side effect of oral dyspigmentation associated with the novel anti-epileptic medication retigabine. Enhanced knowledge of the causative role of retigabine in dyspigementation of the oral mucosa will allow the practitioner to make an appropriate diagnosis. As far the authors are aware this is reaction is unreported in the dental literature and should be disseminated to the wider oral health professional’s community

Violence brief interventions: a rapid review

Provision of a Violence Brief Intervention (VBI) to young men undergoing treatment for a violent injury may represent a teachable moment for the prevention of future interpersonal violence in Scotland. Prior to intervention design, a rapid review of the research literature was necessary to examine existing programmes. After title and abstract screening, eight distinct VBIs were identified from full texts. Whilst none of the programmes were a perfect match for our intervention goals, they did demonstrate the potential effectiveness of brief interventions for violence prevention at both cognitive and behavioural levels. Key themes of successful interventions included brief motivational interviewing as an effective method of engaging with at-risk participants and encouraging change, the utility of social norms approaches for correcting peer norm misperceptions, the usefulness of working with victims of violence in medical settings (particularly oral and maxillofacial surgeries), the importance of addressing the role of alcohol after violent injury, the advantages of a computer-therapist hybrid model of delivery, and the need for adequate follow-up evaluation as part of a randomised control trial. This information has been used to design a VBI which is currently under evaluation

Preliminary research informing policy on remote alcohol monitoring in criminal justice : the Scottish experience

This study was funded in part by a grant from the Scottish Violence Reduction Unit to Peter D Donnelly (no grant number) and partly by a grant from the Scottish School of Public Health to Fergus G Neville (no grant number).Objectives. To explore the views of Scottish offenders on the impact of alcohol on their experience of offending and their lives in general. Further, to explore their views on the concept of Remote Alcohol Monitoring (RAM) as a way to address alcohol misuse upon liberation from prison. Methods. A convenience sample of 12 serving offenders participated in one of three focus groups.Data were analysed using the principles of thematic analysis. Results. Analysis of the data revealed the significant impact of alcohol on the lives of the participants. Key themes included the amount and frequency of alcohol consumption; the association of alcohol with harm; the association of alcohol with offending; previous attempts to reduce alcohol consumption and possible reasons for failure; and the views of the participants on the utility of RAM in relation to crime prevention. Conclusions. This group of offenders had significant issues with alcohol misuse prior to incarceration that had impacted on their offending and resulted in a variety of health and social harms. Participants were generally positive but pragmatic about RAM, recognising that technology alone may not be enough to change deeply ingrained and addictive behaviours.PostprintPeer reviewe

Cut-free Calculi and Relational Semantics for Temporal STIT Logics

We present cut-free labelled sequent calculi for a central formalism in logics of agency: STIT logics with temporal operators. These include sequent systems for Ldm , Tstit and Xstit. All calculi presented possess essential structural properties such as contraction- and cut-admissibility. The labelled calculi G3Ldm and G3Tstit are shown sound and complete relative to irreflexive temporal frames. Additionally, we extend current results by showing that also Xstit can be characterized through relational frames, omitting the use of BT+AC frames

Coseismic Throw Variation Across Along-Strike Bends on Active Normal Faults: Implications for Displacement Versus Length Scaling of Earthquake Ruptures

Fault bends, and associated changes in fault dip, play a key role in explaining the scatter in maximum offset versus surface rupture length fault scaling relationships. Detailed field measurements of the fault geometry and magnitude of slip in the 2016–2017 Central Italy earthquake sequence, alongside three examples from large historical normal-faulting earthquakes in different tectonic settings, provide multiple examples in which coseismic throw increases across bends in fault strike where dip also increases beyond what is necessary to accommodate a uniform slip vector. Coseismic surface ruptures produced by two mainshocks of the 2016–2017 Central Italy earthquake sequence (24 August 2016 Mw 6.0 and 30 October 2016 Mw 6.5) cross a ~0.83-km amplitude along-strike bend, and the coseismic throws for both earthquakes increase by a factor of 2–3, where the strike of the fault changes by ~28o and the dip increases by 20–25o. We present similar examples from historical normal faulting earthquakes (1887, Sonora earthquake, Mw 7.5; 1981, Corinth earthquakes, Mw 6.7–6.4; and 1983, Borah Peak earthquake, Mw 7.3). We demonstrate that it is possible to estimate the expected change in throw across a bend by applying equations that relate strike, dip, and slip vector to horizontal strain conservation along a nonplanar fault for a single earthquake rupture. The calculated slip enhancement in bends can explain much of the scatter in maximum displacement (Dmax) versus surface rupture length scaling relationships. If fault bends are unrecognized, they can introduce variation in Dmax that may lead to erroneous inferences of stress drop variability for earthquakes, and exaggerate maximum earthquake magnitudes derived from vertical offsets in paleoseismic data sets

The interview as narrative ethnography : seeking and shaping connections in qualitative research.

Acts of counter-subjectification in qualitative research are always present but are often submerged in accounts that seek to locate the power of subjectification entirely with the researcher. This is particularly so when talking to people about sensitive issues. Based on an interview-based study of infertility and reproductive disruption among British Pakistanis in Northeast England, we explore how we, as researchers, sought and were drawn into various kinds of connections with the study participants; connections that were actively and performatively constructed through time. The three of us that conducted interviews are all female academics with Ph.Ds in anthropology, but thereafter our backgrounds, life stories and experiences diverge in ways that intersected with those of our informants in complex and shifting ways. We describe how these processes shaped the production of narrative accounts and consider some of the associated analytical and ethical implications

Integration of microRNA signatures of distinct mammary epithelial cell types with their gene expression and epigenetic portraits

Introduction: MicroRNAs (miRNAs) have been implicated in governing lineage specification and differentiation in multiple organs; however, little is known about their specific roles in mammopoiesis. We have determined the global miRNA expression profiles of functionally distinct epithelial subpopulations in mouse and human mammary tissue, and compared these to their cognate transcriptomes and epigenomes. Finally, the human miRNA signatures were used to interrogate the different subtypes of breast cancer, with a view to determining miRNA networks deregulated during oncogenesis. Methods: RNA from sorted mouse and human mammary cell subpopulations was subjected to miRNA expression analysis using the TaqMan MicroRNA Array. Differentially expressed (DE) miRNAs were correlated with gene expression and histone methylation profiles. Analysis of miRNA signatures of the intrinsic subtypes of breast cancer in The Cancer Genome Atlas (TCGA) database versus those of normal human epithelial subpopulations was performed. Results: Unique miRNA signatures characterized each subset (mammary stem cell (MaSC)/basal, luminal progenitor, mature luminal, stromal), with a high degree of conservation across species. Comparison of miRNA and transcriptome profiles for the epithelial subtypes revealed an inverse relationship and pinpointed key developmental genes. Interestingly, expression of the primate-specific miRNA cluster (19q13.4) was found to be restricted to the MaSC/basal subset. Comparative analysis of miRNA signatures with H3 lysine modification maps of the different epithelial subsets revealed a tight correlation between active or repressive marks for the top DE miRNAs, including derepression of miRNAs in Ezh2-deficient cellular subsets. Interrogation of TCGA-identified miRNA profiles with the miRNA signatures of different human subsets revealed specific relationships. Conclusions: The derivation of global miRNA expression profiles for the different mammary subpopulations provides a comprehensive resource for understanding the interplay between miRNA networks and target gene expression. These data have highlighted lineage-specific miRNAs and potential miRNA-mRNA networks, some of which are disrupted in neoplasia. Furthermore, our findings suggest that key developmental miRNAs are regulated by global changes in histone modification, thus linking the mammary epigenome with genome-wide changes in the expression of genes and miRNAs. Comparative miRNA signature analyses between normal breast epithelial cells and breast tumors confirmed an important linkage between luminal progenitor cells and basal-like tumors.Bhupinder Pal, Yunshun Chen, Andrew Bert, Yifang Hu, Julie M. Sheridan, Tamara Beck, Wei Shi, Keith Satterley, Paul Jamieson, Gregory J. Goodall, Geoffrey J. Lindeman, Gordon K. Smyth, and Jane E. Visvade

On measuring miRNAs after transient transfection of mimics or antisense inhibitors

The ability to alter microRNA (miRNA) abundance is crucial for studying miRNA function. To achieve this there is widespread use of both exogenous double-stranded miRNA mimics for transient over-expression, and single stranded antisense RNAs (antimiRs) for miRNA inhibition. The success of these manipulations is often assessed using qPCR, but this does not accurately report the level of functional miRNA. Here, we draw attention to this discrepancy, which is overlooked in many published reports. We measured the functionality of exogenous miRNA by comparing the total level of transfected miRNA in whole cell extracts to the level of miRNA bound to Argonaute following transfection and show that the supraphysiological levels of transfected miRNA frequently seen using qPCR do not represent the functional levels, because the majority of transfected RNA that is detected is vesicular and not accessible for loading into Argonaute as functionally active miRNAs. In the case of microRNA inhibition by transient transfection with antisense inhibitors, there is also the potential for discrepancy, because following cell lysis the abundant inhibitor levels from cellular vesicles can directly interfere with the PCR reaction used to measure miRNA level.Daniel W. Thomson, Cameron P. Bracken, Jan M. Szubert, Gregory J. Goodal

Australian long-term care personnel's knowledge and attitudes regarding palliative care for people with advanced dementia.

This study aimed to describe Australian long-term care (LTC) personnel's knowledge and attitudes concerning palliative care for residents with advanced dementia, and explore relationships with LTC facility/personnel characteristics. An analysis was undertaken of baseline data from a cluster randomised controlled trial of facilitated family case conferencing for improving palliative care of LTC residents with advanced dementia (the 'IDEAL Study'). Participants included any LTC personnel directly involved in residents' care. Knowledge and attitudes concerning palliative care for people with advanced dementia were measured using the questionnaire on Palliative Care for Advanced Dementia. Univariate and multivariate analyses explored relationships between personnel knowledge/attitudes and facility/personnel characteristics. Of 307 personnel in the IDEAL Study, 290 (94.5%) from 19/20 LTCFs provided sufficient data for inclusion. Participants included 9 (2.8%) nurse managers, 59 (20.5%) registered nurses, 25 (8.7%) enrolled nurses, 187 (64.9%) assistants in nursing/personal care assistants and 9 (3.1%) care service employees. In multivariate analyses, a facility policy not to rotate personnel through dementia units was the only variable associated with more favourable overall personnel knowledge and attitudes. Other variables associated with favourable knowledge were a designation of nursing manager or registered or enrolled nurse, and having a preferred language of English. Other variables associated with favourable attitudes were tertiary level of education and greater experience in dementia care. Like previous international research, this study found Australian LTC personnel knowledge and attitudes regarding palliative care for people with advanced dementia to be associated with both facility and personnel characteristics. Future longitudinal research is needed to better understand the relationships between knowledge and attitudes, as well as between these attributes and quality of care