Transcranial Doppler Ultrasound Detection of Microemboli as a Predictor of Cerebral Events in Patients with Symptomatic and Asymptomatic Carotid Disease: A Systematic Review and Meta-Analysis.

OBJECTIVE: Identification of patients who will benefit from carotid endarterectomy is not entirely effective, primarily utilising degree of carotid stenosis. This study aimed at determining if microembolic signals (MES) detected by transcranial Doppler ultrasound (TCD) can provide clinically useful information regarding stroke risk in patients with carotid atherosclerosis. METHODS: A meta-analysis of prospective studies was performed. Three analyses were proposed investigating MES detection as a predictor of: stroke or TIA, stroke alone, and stroke or TIA but with an increased positivity threshold. Subgroup analysis was used to compare pre-operative (symptomatic or asymptomatic) patients and peri- or post-operative patients. RESULTS: Twenty-eight studies reported data regarding both MES status and neurological outcome. Of these, 22 papers reported data on stroke and TIA as an outcome, 19 on stroke alone, and eight on stroke and TIA with increased positivity threshold. At the median pre-test probability of 3.0%, the post-test probabilities of a stroke after a positive and negative TCD were 7.1% (95% CI 5-10.1) and 1.2% (95% CI 0.6-2.5), respectively. In addition, the sensitivities and specificities of each outcome showed that increasing the threshold for positivity to 10 MES per hour would make TCD a more clinically useful tool in peri- and post-operative patients. CONCLUSION: TCD provides clinically useful information about stroke risk for patients with carotid disease and is technically feasible in most patients. However, the generally weak level of evidence constituting this review means definitive recommendations cannot be made

The microbiome in chronic inflammatory airway disease: A threatened species

The human body is exposed to a multitude of microbes and infectious organisms  throughout life. Many of these organisms colonise the skin, gastrointestinal tract (GIT) and airway. We now recognise that this colonisation includes the lower airway,   previously thought to be sterile. These colonising organisms play an important role in disease prevention, including an array of chronic inflammatory conditions that are unrelated to infectious diseases. However, new evidence of immune dysregulation suggests that early colonisation, especially of the GIT and airway, by pathogenic micro-organisms, has deleterious effects that may contribute to the potential to induce  chronic inflammation in young children, which may only express itself in adult life

Brain activation during face perception: evidence of a developmental change.

Behavioral studies suggest that children under age 10 process faces using a piecemeal strategy based on individual distinctive facial features, whereas older children use a configural strategy based on the spatial relations among the face's features. The purpose of this study was to determine whether activation of the fusiform gyrus, which is involved in face processing in adults, is greater during face processing in older children (12-14 years) than in younger children (8-10 years). Functional MRI scans were obtained while children viewed faces and houses. A developmental change was observed: Older children, but not younger children, showed significantly more activation in bilateral fusiform gyri for faces than for houses. Activation in the fusiform gyrus correlated significantly with age and with a behavioral measure of configural face processing. Regions believed to be involved in processing basic facial features were activated in both younger and older children. Some evidence was also observed for greater activation for houses versus faces for the older children than for the younger children, suggesting that processing of these two stimulus types becomes more differentiated as children age. The current results provide biological insight into changes in visual processing of faces that occur with normal development

Determinants of the voltage dependence of G protein modulation within calcium channel β subunits

CaVβ subunits of voltage-gated calcium channels contain two conserved domains, a src-homology-3 (SH3) domain and a guanylate kinase-like (GK) domain with an intervening HOOK domain. We have shown in a previous study that, although Gβγ-mediated inhibitory modulation of CaV2.2 channels did not require the interaction of a CaVβ subunit with the CaVα1 subunit, when such interaction was prevented by a mutation in the α1 subunit, G protein modulation could not be removed by a large depolarization and showed voltage-independent properties (Leroy et al., J Neurosci 25:6984–6996, 2005). In this study, we have investigated the ability of mutant and truncated CaVβ subunits to support voltage-dependent G protein modulation in order to determine the minimal domain of the CaVβ subunit that is required for this process. We have coexpressed the CaVβ subunit constructs with CaV2.2 and α2δ-2, studied modulation by the activation of the dopamine D2 receptor, and also examined basal tonic modulation. Our main finding is that the CaVβ subunit GK domains, from either β1b or β2, are sufficient to restore voltage dependence to G protein modulation. We also found that the removal of the variable HOOK region from β2a promotes tonic voltage-dependent G protein modulation. We propose that the absence of the HOOK region enhances Gβγ binding affinity, leading to greater tonic modulation by basal levels of Gβγ. This tonic modulation requires the presence of an SH3 domain, as tonic modulation is not supported by any of the CaVβ subunit GK domains alone

Dynamic calcium-mediated stress response and recovery signatures in the fungal pathogen, Candida albicans

Acknowledgements AB conceived the project and wrote the manuscript. CVG conceived the experimental design. SW designed the GCaMP reporter. AM, KL, LV-M, SC and TB constructed strains and optimised imaging. MF developed the image analysis software. CVG and CP carried out the microfluidics experiments and imaging analysis. NG assisted with preparation of the manuscript. PS, SN and DMR developed and undertook the theoretical data analysis and contributed to the interpretation of the results. Funding AB, CG and TB were funded by the Wellcome Trust [Grant number 206412/A/17/Z]. AB and DR were supported by a Wellcome Trust Institutional Strategic Support Award (WT204909/Z/16/Z). CP was funded by a University of Exeter studentship (113516). This work was also supported by a Royal Society URF (UF080611), an MRC NIRG (G0900211/90671) and the MRC-Centre for Medical Mycology at the University of Exeter (MR/N006364/2). DR was funded by the Medical Research Council (MR/P022405/1). SN was supported by the Medical Research Council via the GW4 BioMed2 DTP (MR/W006308/1). MCA was supported by a European Commission ITN ‘FungiBrain’ studentship (607963). LL and SC were funded by a Wellcome Trust Institutional Strategic Support Award to the University of Aberdeen. NG acknowledges support of Wellcome Trust Investigator, Collaborative, Equipment, Strategic and Biomedical Resource awards (101873, 200208, 215599, 224323). NG and AB thank the MRC (MR/M026663/2) for support. This study/research is funded by the National Institute for Health and Care Research (NIHR) Exeter Biomedical Research Centre (BRC). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.Peer reviewedPublisher PD

Improvements in vision-related quality of life in blind patients implanted with the Argus II Epiretinal Prosthesis

Background: The purpose of this analysis is to report the change in quality of life (QoL) after treatment with the Argus II Epiretinal Prosthesis in patients with end-stage retinitis pigmentosa. Methods: The Vision and Quality of Life Index (VisQoL) was used to assess changes in QoL dimensions and overall utility score in a prospective 30-patient single-arm clinical study. VisQoL is a multi-attribute instrument consisting of six dimensions (injury, life, roles, assistance, activity and friendship) that may be affected by visual impairment. Within each dimension, patients were divided into two groups based on how much their QoL was affected by their blindness at baseline (moderate/severe or minimal). Outcomes were compared within each dimension sub-group between baseline and the combined follow-up periods using the Friedman test. In addition, data from the six dimensions were combined into a single utility score, with baseline data compared to the combined follow-up periods. Results: Overall, 80 per cent of the patients reported difficulty in one or more dimensions preimplant. Composite VisQoL utility scores at follow-up showed no statistically significant change from baseline; however, in three of the six VisQoL dimensions (injury, life and roles), patients with baseline deficits showed significant and lasting improvement after implantation with Argus II. In two of the three remaining dimensions (assistance and activity), data trended toward an improvement. In the final VisQoL dimension (friendship), none of the patients reported baseline deficits, suggesting that patients had largely adjusted to this attribute. Conclusion: Patients whose vision negatively affected them with respect to three VisQoL dimensions (that is, getting injured, coping with the demands of their life and fulfilling their life roles) reported significant improvement in QoL after implantation of the Argus II retinal prosthesis. Furthermore, the benefit did not deteriorate at any point during the 36-month follow-up, suggesting a long-term, durable improvement

A telephone survey of cancer awareness among frontline staff: informing training needs

Background: Studies have shown limited awareness about cancer risk factors among hospital-based staff. Less is known about general cancer awareness among community frontline National Health Service and social care staff. Methods: A cross-sectional computer-assisted telephone survey of 4664 frontline community-based health and social care staff in North West England. Results: A total of 671 out of 4664 (14.4%) potentially eligible subjects agreed to take part. Over 92% of staff recognised most warning signs, except an unexplained pain (88.8%, n=596), cough or hoarseness (86.9%, n=583) and a sore that does not heal (77.3%, n=519). The bowel cancer-screening programme was recognised by 61.8% (n=415) of staff. Most staff agreed that smoking and passive smoking ‘increased the chance of getting cancer.’ Fewer agreed about getting sunburnt more than once as a child (78.0%, n=523), being overweight (73.5%, n=493), drinking more than one unit of alcohol per day (50.2%, n=337) or doing less than 30 min of moderate physical exercise five times a week (41.1%, n=276). Conclusion: Cancer awareness is generally good among frontline staff, but important gaps exist, which might be improved by targeted education and training and through developing clearer messages about cancer risk factors

High cocoa polyphenol rich chocolate may reduce the burden of the symptoms in chronic fatigue syndrome

<p>Abstract</p> <p>Background</p> <p>Chocolate is rich in flavonoids that have been shown to be of benefit in disparate conditions including cardiovascular disease and cancer. The effect of polyphenol rich chocolate in subjects with chronic fatigue syndrome (CFS) has not been studied previously.</p> <p>Methods</p> <p>We conducted a double blinded, randomised, clinical pilot crossover study comparing high cocoa liquor/polyphenol rich chocolate (HCL/PR) in comparison to simulated iso-calorific chocolate (cocoa liquor free/low polyphenols(CLF/LP)) on fatigue and residual function in subjects with chronic fatigue syndrome. Subjects with CFS having severe fatigue of at least 10 out of 11 on the Chalder Fatigue Scale were enrolled. Subjects had either 8 weeks of intervention in the form of HCL/PR or CLF/LP, with a 2 week wash out period followed by 8 weeks of intervention with the other chocolate.</p> <p>Results</p> <p>Ten subjects were enrolled in the study. The Chalder Fatigue Scale score improved significantly after 8 weeks of the HCL/PR chocolate arm [median (range) Exact Sig. (2-tailed)] [33 (25 - 38) vs. 21.5 (6 - 35) 0.01], but that deteriorated significantly when subjects were given simulated iso-calorific chocolate (CLF/CP) [ 28.5 (17 - 20) vs. 34.5 (13-26) 0.03]. The residual function, as assessed by the London Handicap scale, also improved significantly after the HCL/PR arm [0.49 (0.33 - 0.62) vs. 0.64 (0.44 - 0.83) 0.01] and deteriorated after iso-calorific chocolate [00.44 (0.43 - 0.68) vs. 0.36 (0.33 - 0.62)0.03]. Likewise the Hospital Anxiety and Depression score also improved after the HCL/PR arm, but deteriorated after CLF/CP. Mean weight remained unchanged throughout the trial.</p> <p>Conclusion</p> <p>This study suggests that HCL/PR chocolate may improve symptoms in subjects with chronic fatigue syndrome.</p

Ecological implications of a flower size/number trade-off in tropical forest trees

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