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

The sensory detection of water borne vibrational stimuli and their motor effects in the Norway lobster, Nephrops norvegicus (L.)

The morphology and distribution of cuticular setae on the uropods and walking legs of the Norway lobster Nephrops norvegicus (L.) has been studied using both light microscopy and Scanning Electron Microscopy. Three types of setae are present on the uropods, plumose setae, simple setae and guard hairs. Hair peg and hair fan organs were also seen.The propodus and dactyl of the 2nd and 3rd legs of Nephrops are similar in both their structure and in the form and distribution of their cuticular setae. Three main areas of setal distribution are found: squamous setae are distributed 1) in bunches on the flat surfaces of the propodus and dactyl and 2) along the lateral edges of the propodus and dactyl and 3) hedgehog hairs line the inner edges of the propodus and dactyl.Most of the setae on the 4th and 5th legs are found around the propodus-dactyl (P-D) joint. Three rows of simple setae are found on the dactyl, and both serrate setae with simple scales and squamous setae are found overlapping the P-D joint. Also found near the joint are CAP organs and hedgehog hairs.All of the setae on the uropods show responses to tactile and vibratory stimulation as do the hedgehog hairs, the serrate setae, the simple setae and the squamous setae on the legs.The responses of afferents from the uropods and walking legs and of the abdominal interneurones have been tested in response to water borne vibrations of different frequences produced both as surface waves and in an acoustic tube. The uropod afferents show range fractionation and have therefore been divided into three nested categories based on the upper limit of their frequency response. Low frequency units respond from 2-20Hz, intermediate units from 2-50Hz and high frequency units from 2-100Hz. The leg afferents also show range fractionation and have also been divided into three nested categories: low frequency units respond from 20-60Hz, intermediate units from 20-200Hz and high frequency units from 20-450Hz. Preliminary studies have indicated that the leg afferents show directional sensitivity. The abdominal interneurones have been categorised as either intermediate or high frequency; intermediate interneurones respond from 2-100Hz and high frequency interneurones from 2-200Hz. The receptive fields of mechanosensory interneurones have also been determined.The postural responses of Nephrops to water borne vibrations have been studied using video analysis. An abdominal extension response is reliably elicited which varies with the frequency of stimulation in a distinct way. From 20-80Hz the animals respond immediately, and abdominal extension is accompanied by rapid leg movements, swimmeret beating and very occasionally tail flipping. From 100-180Hz the response occurs with a delay, the duration of which seems unrelated to frequency within this range. No responses were seen above 180Hz.The nervous control of the abdominal extension response has been studied by recording from abdominal motor roots (superficial root three and root two) which supply the two muscles involved (the superficial flexor and extensordmuscles). It has been shown that abdominal extension is produced by both central and peripheral inhibition of flexor muscle activity in combination with excitation of the extensor muscle. The neuronal basis of the delay seen in the behavioural experiments has been investigated, and a number different patterns of nervous activity have been found which might produce this delay.Behavioural studies have been conducted in the field to investigate the responses of freely moving animals to sound in their natural environment. Investigations have been conducted of changes in the emergence rhythm and changes in the transient behaviour of the animals. Tests to investigate changes in the burrow emergence rhythm with the underwater loudspeakers at 10m from the animal failed to produce any response. However small changes occur in the transient behaviour of Nephrops when they are very close to the loundspeaker even though the sound pressure levels are similar to those used at 10m. These tests have been repeated in laboratory tanks where clear locomotory responses, predominantly backwards walking, are seen in response to stimuli from 20-80Hz in both blind and sighted animals.Tests have been conducted in a free acoustic field to determine the behavioural response threshold of Nephrops to sound using the postural response as a monitor. The animals showed no responses with the loudspeaker at 1m but showed clear responses with the speaker at 0.09m even when the sound pressure levels were similar, yielding a threshold in terms of particle displacement of the water of 0.874m which is independent of frequency. This indicates that the Nephrops is sensitive to the particle motion component of sound rather than the pressure component

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

Violence brief interventions : a rapid review

This research was funded by the Violence Reduction Unit (Police Scotland).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.PostprintPeer reviewe

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

Allelic expression mapping across cellular lineages to establish impact of non-coding SNPs

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Mutations in CHMP2B in lower motor neuron predominant amyotrophic lateral sclerosis (ALS)

Background: Amyotrophic lateral sclerosis (ALS), a common late-onset neurodegenerative disease, is associated with fronto-temporal dementia (FTD) in 3-10% of patients. A mutation in CHMP2B was recently identified in a Danish pedigree with autosomal dominant FTD. Subsequently, two unrelated patients with familial ALS, one of whom also showed features of FTD, were shown to carry missense mutations in CHMP2B. The initial aim of this study was to determine whether mutations in CHMP2B contribute more broadly to ALS pathogenesis. Methodology/Principal Findings: Sequencing of CHMP2B in 433 ALS cases from the North of England identified 4 cases carrying 3 missense mutations, including one novel mutation, p. Thr104Asn, none of which were present in 500 neurologically normal controls. Analysis of clinical and neuropathological data of these 4 cases showed a phenotype consistent with the lower motor neuron predominant (progressive muscular atrophy (PMA)) variant of ALS. Only one had a recognised family history of ALS and none had clinically apparent dementia. Microarray analysis of motor neurons from CHMP2B cases, compared to controls, showed a distinct gene expression signature with significant differential expression predicting disassembly of cell structure; increased calcium concentration in the ER lumen; decrease in the availability of ATP; down-regulation of the classical and p38 MAPK signalling pathways, reduction in autophagy initiation and a global repression of translation. Transfection of mutant CHMP2B into HEK-293 and COS-7 cells resulted in the formation of large cytoplasmic vacuoles, aberrant lysosomal localisation demonstrated by CD63 staining and impairment of autophagy indicated by increased levels of LC3-II protein. These changes were absent in control cells transfected with wild-type CHMP2B. Conclusions/Significance: We conclude that in a population drawn from North of England pathogenic CHMP2B mutations are found in approximately 1% of cases of ALS and 10% of those with lower motor neuron predominant ALS. We provide a body of evidence indicating the likely pathogenicity of the reported gene alterations. However, absolute confirmation of pathogenicity requires further evidence, including documentation of familial transmission in ALS pedigrees which might be most fruitfully explored in cases with a LMN predominant phenotype