Development and initial validation of the Bristol Impact of Hypermobility questionnaire

© 2016 Chartered Society of Physiotherapy Objectives Stage 1 – to identify the impact of joint hypermobility syndrome (JHS) on adults; Stage 2 – to develop a questionnaire to assess the impact of JHS; and Stage 3 – to undertake item reduction and establish the questionnaire's concurrent validity. Design A mixed methods study employing qualitative focus groups and interviews (Stage 1); a working group of patients, clinicians and researchers, and ‘think aloud’ interviews (Stage 2); and quantitative analysis of questionnaire responses (Stage 3). Setting Stages 1 and 2 took place in one secondary care hospital in the UK. Members of a UK-wide patient organisation were recruited in Stage 3. Participants In total, 15, four and 615 participants took part in Stages 1, 2 and 3, respectively. Inclusion criteria were: age ≥18 years; diagnosis of JHS; no other conditions affecting physical function; able to give informed consent; and able to understand and communicate in English. Interventions None. Main outcome measures The development of a questionnaire to assess the impact of JHS. Results Stage 1 identified a wide range of impairments, activity limitations and participation restrictions In Stage 2, a draft questionnaire was developed and refined following ‘think aloud’ analysis, leaving 94 scored items. In Stage 3, items were removed on the basis of low severity and/or high correlation with other items. The final Bristol Impact of Hypermobility (BIoH) questionnaire had 55 scored items, and correlated well with the physical component score of the Short Form 36 health questionnaire (r=−0.725). Conclusions The BIoH questionnaire demonstrated good concurrent validity. Further psychometric properties need to be established

Baddies in the classroom: media education and narrative writing

When teachers allow pupils to write stories that include elements of popular media, we must ask what to do with media once it has entered the classroom. This article relates findings from a classroom study which focuses on children’s media-based story writing. The study looks at children as producers of new media texts and describes their activities as a form of ‘media education’. The research shows that through their production of media-based stories, children are reflecting on their consumption of media. Furthermore, children’s media-based stories make explicit some of their implicit knowledge of new media forms. Finally, children’s stories provide ample opportunities for teachers to engage in important discussions about media within the framework of existing writing programmes

Two novel human cytomegalovirus NK cell evasion functions target MICA for lysosomal degradation

NKG2D plays a major role in controlling immune responses through the regulation of natural killer (NK) cells, αβ and γδ T-cell function. This activating receptor recognizes eight distinct ligands (the MHC Class I polypeptide-related sequences (MIC) A andB, and UL16-binding proteins (ULBP)1–6) induced by cellular stress to promote recognition cells perturbed by malignant transformation or microbial infection. Studies into human cytomegalovirus (HCMV) have aided both the identification and characterization of NKG2D ligands (NKG2DLs). HCMV immediate early (IE) gene up regulates NKGDLs, and we now describe the differential activation of ULBP2 and MICA/B by IE1 and IE2 respectively. Despite activation by IE functions, HCMV effectively suppressed cell surface expression of NKGDLs through both the early and late phases of infection. The immune evasion functions UL16, UL142, and microRNA(miR)-UL112 are known to target NKG2DLs. While infection with a UL16 deletion mutant caused the expected increase in MICB and ULBP2 cell surface expression, deletion of UL142 did not have a similar impact on its target, MICA. We therefore performed a systematic screen of the viral genome to search of addition functions that targeted MICA. US18 and US20 were identified as novel NK cell evasion functions capable of acting independently to promote MICA degradation by lysosomal degradation. The most dramatic effect on MICA expression was achieved when US18 and US20 acted in concert. US18 and US20 are the first members of the US12 gene family to have been assigned a function. The US12 family has 10 members encoded sequentially through US12–US21; a genetic arrangement, which is suggestive of an ‘accordion’ expansion of an ancestral gene in response to a selective pressure. This expansion must have be an ancient event as the whole family is conserved across simian cytomegaloviruses from old world monkeys. The evolutionary benefit bestowed by the combinatorial effect of US18 and US20 on MICA may have contributed to sustaining the US12 gene family

Avoiding philosophy as a trump-card in sociological writing. A study from the discourse of evidence-based healthcare

In this article I explore a situation where health sociologists encounter pure-philosophical reasoning in the fabric of social life. Accounts of the relationship between philosophy and sociology tend to be framed in abstract theory, so there is a need for practical ways to anchor philosophical reasoning in sociological writing. I consider the use of philosophies as strategic tools for socially grounded understanding, rather than rhetorical trump-cards which bypass socio-political questions. I present my understanding in two stages: first, I discuss my example topic of Evidence-Based Healthcare (EBHC), reviewing some philosophical contributions by writers in that discourse. These niche-writings I contextualise briefly in relation to other academic meetings between philosophy and sociology. Second, I offer three philosophical perspectives on the topic of EBHC, and outline their significance for understanding it sociologically. I conclude that to navigate the difficult ground where philosophy and sociology meet, sociologists can entrain pure-philosophical argumentation to the purpose of critical, socially situated understandings.PostprintPeer reviewe

Automated mass spectrometric analysis of urinary and plasma serotonin

Serotonin emerges as crucial neurotransmitter and hormone in a growing number of different physiologic processes. Besides extensive serotonin production previously noted in patients with metastatic carcinoid tumors, serotonin now is implicated in liver cell regeneration and bone formation. The aim was to develop a rapid, sensitive, and highly selective automated on-line solid-phase extraction method coupled to high-performance liquid chromatography–tandem mass spectrometry (XLC-MS/MS) to quantify low serotonin concentrations in matrices such as platelet-poor plasma and urine. Fifty microliters plasma or 2.5 μL urine equivalent were pre-purified by automated on-line solid-phase extraction, using weak cation exchange. Chromatography of serotonin and its deuterated internal standard was performed with hydrophilic interaction chromatography. Mass spectrometric detection was operated in multiple reaction monitoring mode using a quadrupole tandem mass spectrometer with positive electrospray ionization. Serotonin concentrations were determined in platelet-poor plasma of metastatic carcinoid patients (n = 23) and healthy controls (n = 22). Urinary reference intervals were set by analyzing 24-h urine collections of 120 healthy subjects. Total run-time was 6 min. Intra- and inter-assay analytical variation were <10%. Linearity in the 0–7300 μmol/L calibration range was excellent (R2 > 0.99). Quantification limits were 30 and 0.9 nmol/L in urine and plasma, respectively. Platelet-poor serotonin concentrations in metastatic carcinoid patients were significantly higher than in controls. The urinary reference interval was 10–78 μmol/mol creatinine. Serotonin analysis with sensitive and specific XLC-MS/MS overcomes limitations of conventional HPLC. This enables accurate quantification of serotonin for both routine diagnostic procedures and research in serotonin-related disorders

Release of tryptophan and serotonin into the portal vein of the isolated perfused rat small intestine

To investigate the release of serotonin from intestinal enterochromaffin cells, we used an in vitro technique which allows studies excluding overlapping influences from outside the gut. The entire small intestine of rats fed a standard or tryptophan-enriched (3% of total) diet was totally isolated by ligatures with the exception of the superior mesentric artery and portal vein that supply and drain the intestine. Simultaneously to the vascular perfusion (Krebs-Ringer bicarbonate buffer, 0,4% human albumin, 5 m M glucose, 0.6 m M glutamine) the gut lumen was infused (buffer or 0.1 N HCL). Acidification of the gut lumen resulted in an increment of venously released tryptophan and serotonin. After feeding tryptophan-enriched food the release of tryptophan was increased. However, the total amount of released serotonin after tryptophan diet did not differ as compared to that after standard diet. Addition of a monoamino-oxidase inhibitor (pargyline) to the arterial perfusate enhanced the released amount of serotonin 3-fold in the portal venous effluent (at a concentration of 1 m M but not 0.1 m M ). Recovery studies done by arterial infusions of serotonin (1 µ M , 10µ M ) and evaluation of the amounts venously released revealed a high loss of infused serotonin (40%–70%). Our data suggest gut-born serotonin to more likely play a paracrine role than a role as a classical hormone.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47538/1/433_2005_Article_BF01852260.pd

Effects of Alcohol on the Acquisition and Expression of Fear Potentiated Startle in Mouse Lines Selectively Bred for High and Low Alcohol Preference

Rationale: Anxiety disorders and alcohol-use disorders frequently co-occur in humans perhaps because alcohol relieves anxiety. Studies in humans and rats indicate that alcohol may have greater anxiolytic effects in organisms with increased genetic propensity for high alcohol consumption. Objectives and Methods: The purpose of this study was to investigate the effects of moderate doses of alcohol (0.5, 1.0, 1.5 g/kg) on the acquisition and expression of anxiety-related behavior using a fear-potentiated startle (FPS) procedure. Experiments were conducted in two replicate pairs of mouse lines selectively bred for high- (HAP1 and HAP2) and low- (LAP1 and LAP2) alcohol preference; these lines have previously shown a genetic correlation between alcohol preference and FPS (HAP\u3eLAP; Barrenha and Chester 2007). In a control experiment, the effect of diazepam (4.0 mg/kg) on the expression of FPS was tested in HAP2 and LAP2 mice. Results: The 1.5 g/kg alcohol dose moderately decreased the expression of FPS in both HAP lines but not LAP lines. Alcohol had no effect on the acquisition of FPS in any line. Diazepam reduced FPS to a similar extent in both HAP2 and LAP2 mice. Conclusions: HAP mice may be more sensitive to the anxiolytic effects of alcohol than LAP mice when alcohol is given prior to the expression of FPS. These data collected in two pairs of HAP/LAP mouse lines suggest that the anxiolytic response to alcohol in HAP mice may be genetically correlated with their propensity toward high alcohol preference and robust FPS