A Two-Sample Mendelian Randomization Study of Neuroticism and Sleep Bruxism.

Sleep bruxism (SB) affects a considerable part of the population and is associated with neuroticism, stress, and anxiety in various studies. However, the causal mechanisms between neuroticism and SB have not been examined. Understanding the reasons for SB is important as understanding bruxism may allow improved comprehensive management of the disorders and comorbidities related to it. Previous studies on the association of risk factors to SB have provided important symptomatic insight but were mainly questionnaire based or limited in sample size and could not adequately assess causal relationships. The aim of this study was to elaborate the possible causal relationship of neuroticism as a risk factor for SB through a Mendelian randomization (MR) approach by combining questionnaires, registry data, and genetic information in large scale. We performed a two-sample MR study using instrumental genetic variants of neuroticism, including neuroticism subcategories, in the UK Biobank (n = 380,506) and outcome data of probable SB using FinnGen (n [cases/controls] = 12,297/364,980). We discovered a causal effect from neuroticism to SB (odds ratio [OR] = 1.38 [1.10-1.74], P = 0.0057). A phenotype sensitive to stress and adversity had the strongest effect (OR = 1.59 [1.17-2.15], P = 0.0028). Sensitivity analyses across MR methods supported a causal relationship, and we did not observe pleiotropy between neuroticism and SB (MR-Egger intercept, P = 0.87). Our findings are in line with earlier observational studies that connect stress and SB. Furthermore, our results provide evidence that neurotic traits increase the risk of probable SB.

Effect of foot orthoses vs sham insoles on first metatarsophalangeal joint osteoarthritis symptoms: a randomized controlled trial.

OBJECTIVES: To compare contoured foot orthoses to sham flat insoles for first MTP joint OA walking pain. DESIGN: This was a participant- and assessor-blinded, sham-controlled, multi-centre randomized clinical trial set in community-based private practices. Eighty-eight adults aged ≥45 years with symptomatic radiographic first MTP joint OA were randomized to receive contoured foot orthoses (n = 47) or sham flat insoles (n = 41), worn at all times when wearing shoes for 12 weeks. Primary outcome was change in first MTP joint walking pain (11-point numerical rating scale (NRS), 0-10) over 12 weeks. Secondary outcomes included additional first MTP joint and foot pain measures, physical function, quality of life and physical activity. Separate linear regression models for primary and secondary outcomes on treatment group were fit, adjusting for the outcome at baseline and podiatrist. Other measures included adverse events. RESULTS: 88 participants were randomized and 87 (99%) completed the 12-week primary outcome. There was no evidence foot orthoses were superior to sham insoles for reducing pain (mean difference -0.3 NRS units (95% CI -1.2 to 0.6), p = 0.53). Similarly, foot orthoses were not superior to sham on any secondary outcomes. Sensitivity analyses yielded similar results. Adverse events were generally minor and transient. CONCLUSION: Contoured foot orthoses are no more effective than flat sham insoles for the clinical management of first MTP joint OA. Given the dearth of evidence on treatments for first MTP joint OA, further research is needed to identify effective management approaches for this common and debilitating condition.

Defining performance levels in undergraduate otolaryngology education.

OBJECTIVES: This study seeks the opinions of qualified doctors on what they feel medical students should learn about otolaryngology. It aims to identify both the content deemed relevant and the performance levels for medical students in otolaryngology. METHODS: A national survey developed from a content analysis of undergraduate otolaryngology curricula from the UK was undertaken, accompanied by a review of the literature and input from an expert group. Data were collected from a wide range of doctors. RESULTS: Participants felt that graduating students should be able to: recognise, assess and initiate management for common and life-threatening acute conditions; take an appropriate patient history; and perform an appropriate examination for the majority of otolaryngology clinical conditions but manage only a select few. CONCLUSION: This study reports performance levels for otolaryngology topics at an undergraduate level. Participating doctors felt that a higher level of performance should be expected of students treating life-threatening, acute and common otolaryngology conditions.

"It's the single best thing I've done in the last 10 years": a qualitative study exploring patient and dietitian experiences with, and perceptions of, a multi-component dietary weight loss program for knee osteoarthritis.

OBJECTIVE: Explore patient and dietitian experiences with a multi-component dietary weight loss program for knee osteoarthritis to understand enablers and challenges to success at 6-months. DESIGN: Qualitative study embedded within a randomised controlled trial. Semi-structured individual interviews with 24 patients with knee osteoarthritis who undertook, and five dietitians who supervised, a weight management program (involving a ketogenic very low calorie diet (VLCD), video consultations, educational resources) over 6 months. Data were thematically analysed. RESULTS: Five themes were developed: (1) ease and convenience of program facilitated adherence (structure and simplicity of the meal replacements; not feeling hungry on diet; convenience of consulting via video) (2) social and professional support crucial for success (encouragement from partner, family, and friends; guidance from, and accountability to, dietitian; anxiety around going at it alone) (3) program was engaging and motivating (determination to stick to program; rapid weight loss helped motivation) (4) holistic nature of program was important (suite of high-quality educational resources; exercise important to compliment weight loss) (5) rewarding experience and lifelong impact (improved knee pain and function; positive lifestyle change). CONCLUSIONS: Patients and dietitians described positive experiences with the weight management program, valuing its simplicity, effectiveness, and convenience. Support from dietitians and a comprehensive suite of educational resources, incorporated with an exercise program, were considered crucial for success. Findings suggest this multi-component dietary program is an acceptable weight loss method in people with knee osteoarthritis that may benefit symptoms. Strategies for supporting long-term independent weight management should be a focus of future research.

Supporting mental health service users to stop smoking: findings from a process evaluation of the implementation of smokefree policies into two mental health trusts.

BACKGROUND: Life expectancy is 10-20 years lower among people with a severe mental health disorder. Most of these early deaths are due to chronic conditions, including cardiovascular and respiratory diseases. Smoking is a major risk factor for these conditions and introducing smokefree policies has been recommended to mental health service providers in England by the National Institute for Health and Care Excellence (NICE), in their Public Health Guideline 48: Smoking: acute, maternity and mental health services. This paper reports a process evaluation of introducing these policy recommendations, which were updated in 2013. METHOD: Process data were collected through semi-structured interviews with staff (n = 51), members of partnering organisations (n = 5), service users (n = 7) and carers (n = 2) between November 2016 - April 2017. Normalization Process Theory (NPT) was used to design the data collection tools and analyse the data. A framework approach was taken with the analysis, using the four concepts of NPT: coherence, cognitive participation, collective action and reflexive monitoring. RESULTS: The policy made sense to some staff, patients and carers (coherence) who 'bought-into' the idea (cognitive participation) but other participants disagreed. Although smokefree policies were operationalised (collective action), sometimes they were opposed. Progress was made, especially in some units, but continued to be resisted in others. Informal appraisal of progress (reflexive monitoring) presented a varied picture. CONCLUSION: Some progress has been made in terms of changing an entrenched, smoking culture into one that is smokefree on Trust sites across the region. Perseverance and resourcing over the long-term is required to establish a non-smoking culture in on-site provision of mental health services.

Cognitive processing speed in multiple sclerosis clinical practice: association with patient-reported outcomes, employment and magnetic resonance imaging metrics.

BACKGROUND AND PURPOSE: To analyze the relationship between cognitive processing speed, patient-reported outcome measures (PROMs), employment and magnetic resonance imaging (MRI) metrics in a large multiple sclerosis cohort. METHODS: Cross-sectional clinical data, PROMs, employment and MRI studies within 90 days of completion of the Processing Speed Test (PST), a technology-enabled adaptation of the Symbol Digit Modalities Test, were collected. MRI was analyzed using semi-automated methods. Correlations of PST score with PROMs and MRI metrics were examined using Spearman's rho. Wilcoxon rank sum testing compared MRI metrics across PST score quartiles and linear regression models identified predictors of PST performance. Effects of employment and depression were also investigated. RESULTS: In 721 patients (mean age 47.6 ± 11.4 years), PST scores were significantly correlated with all MRI metrics, including cord atrophy and deep gray matter volumes. Linear regression demonstrated self-reported physical disability, cognitive function, fatigue and social domains (adjusted R2  = 0.44, P < 0.001) as the strongest clinical predictors of PST score, whereas that of MRI variables included T2 lesion volume, whole-brain fraction and cord atrophy (adjusted R2  = 0.42, P < 0.001). An inclusive model identified T2 lesion volume, whole-brain fraction, self-reported upper extremity function, cognition and social participation as the strongest predictors of PST score (adjusted R2  = 0.51, P < 0.001). There was significant effect modification by depression on the relationship between self-reported cognition and PST performance. Employment status was associated with PST scores independent of age and physical disability. CONCLUSION: The PST score correlates with PROMs, MRI measures of focal and diffuse brain injury, and employment. The PST score is a feasible and meaningful measure for routine multiple sclerosis care.

Dormancy dampens the microbial distance-decay relationship.

Much of Earth's biodiversity has the capacity to engage in dormancy, a reversible state of reduced metabolic activity. By increasing resilience to unfavourable conditions, dormancy leads to the accumulation of 'seed banks'. These reservoirs of genetic and phenotypic diversity should diminish the strength of environmental filtering and increase rates of dispersal. Although prevalent among single-celled organisms, evidence that dormancy influences patterns of microbial biogeography is lacking. We constructed geographical and environmental distance-decay relationships (DDRs) for the total (DNA) and active (RNA) portions of bacterial communities in a regional-scale 16S rRNA survey of forested ponds in Indiana, USA. As predicted, total communities harboured greater diversity and exhibited weaker DDRs than active communities. These observations were robust to random resampling and different community metrics. To evaluate the processes underlying the biogeographic patterns, we developed a platform of mechanistic models that used the geographical coordinates and environmental characteristics of our study system. Based on more than 106 simulations, our models approximated the empirical DDRs when there was strong environmental filtering along with the presence of long-lived seed banks. By contrast, the inclusion of dispersal generally decreased model performance. Together, our findings support recent theoretical predictions that seed banks can influence the biogeographic patterns of microbial communities. This article is part of the theme issue 'Conceptual challenges in microbial community ecology'.

Balloon Eustachian tuboplasty for Eustachian tube dysfunction: report of long-term outcomes in a UK population.

BACKGROUND: Balloon Eustachian tuboplasty is a surgical management option for Eustachian tube dysfunction; it has shown promising results in studies worldwide, but has had limited uptake in the UK. This study reports long-term outcomes for patients offered balloon Eustachian tuboplasty for chronic dilatory and baro-challenge-induced Eustachian tube dysfunction, and describes practical experience gained from its implementation. METHODS: Balloon Eustachian tuboplasty was conducted in 25 patients (36 ears) with Eustachian tube dysfunction over three years. Information on presenting symptoms and signs, audiometric findings, tympanometry, and Eustachian Tube Dysfunction Questionnaire-7 scores were recorded pre- and post-operatively with a minimum follow up of one year. RESULTS: Sixteen (64 per cent) of the 25 patients demonstrated symptom resolution after balloon Eustachian tuboplasty according to the Eustachian Tube Dysfunction Questionnaire-7. Fourteen (64 per cent) of the 22 patients with a type B or C tympanogram pre-operatively, had a type A trace post-operatively. Fifteen (75 per cent) of 20 patients with pre-operative conductive hearing loss showed improvement post-operatively, and 11 (50 per cent) of 22 patients with pre-operative middle-ear effusion or tympanic membrane retraction showed resolution. CONCLUSION: Balloon Eustachian tuboplasty can improve subjective and objective measures of Eustachian tube dysfunction, and provide longer-term resolution.

Estimating sleep parameters using an accelerometer without sleep diary.

Wrist worn raw-data accelerometers are used increasingly in large-scale population research. We examined whether sleep parameters can be estimated from these data in the absence of sleep diaries. Our heuristic algorithm uses the variance in estimated z-axis angle and makes basic assumptions about sleep interruptions. Detected sleep period time window (SPT-window) was compared against sleep diary in 3752 participants (range = 60-82 years) and polysomnography in sleep clinic patients (N = 28) and in healthy good sleepers (N = 22). The SPT-window derived from the algorithm was 10.9 and 2.9 minutes longer compared with sleep diary in men and women, respectively. Mean C-statistic to detect the SPT-window compared to polysomnography was 0.86 and 0.83 in clinic-based and healthy sleepers, respectively. We demonstrated the accuracy of our algorithm to detect the SPT-window. The value of this algorithm lies in studies such as UK Biobank where a sleep diary was not used.

Is the use of a bone conduction hearing device on a softband a useful tool in the pre-operative assessment of suitability for other hearing implants?

OBJECTIVE: To assess whether pre-operative assessment with a bone conduction hearing device on a softband is an accurate predictor of performance with one of two transcutaneous hearing implants.Study designCohort study comparing pre-and post-operative speech audiometry using correlation analysis. METHODS: Pre-operative pure tone audiometry and aided half optimum speech recognition thresholds were compared with post-operative aided results for each ear that had undergone implantation. Data were collected prospectively. RESULTS: Full data were available in 24 ears. In 19 out of 24 ears (79 per cent), the difference between pre- and post-operative speech scores was less than 10 dB, demonstrating a good clinical correlation. The Pearson correlation coefficient was calculated at 0.66 (95 per cent confidence interval = 0.357-0.842), indicating a strong statistical correlation. CONCLUSION: Pre-operative softband testing shows good clinical correlation and strong statistical correlation with hearing implant performance. The findings suggest there is value in using the test to predict performance and guide patients' expectations.

Prevalence of Traumatic Findings on Routine MRI in a Large Cohort of Professional Fighters.

BACKGROUND AND PURPOSE: Previous studies investigating MR imaging abnormalities among fighters have had small sample sizes. This investigation assessed a large number of fighters using the same conventional sequences on the same scanner. MATERIALS AND METHODS: Conventional 3T MR imaging was used to assess 499 fighters (boxers, mixed martial artists, and martial artists) and 62 controls for nonspecific WM changes, cerebral microhemorrhage, cavum septum pellucidum, and cavum vergae. The lengths of the cavum septum pellucidum and cavum vergae and the ratio of cavum septum pellucidum to the septum pellucidum lengths were assessed. RESULTS: The prevalence of nonspecific WM changes was similar between groups. Fighters had a prevalence of cerebral microhemorrhage (4.2% versus 0% for controls, P = .152). Fighters had a higher prevalence of cavum septum pellucidum versus controls (53.1% versus 17.7%, P < .001) and cavum vergae versus controls (14.4% versus 0%, P < .001). The lengths of the cavum septum pellucidum plus the cavum vergae (P < .001), cavum septum pellucidum (P = .025), and cavum septum pellucidum to the septum pellucidum length ratio (P = .009) were higher in fighters than in controls. The number of fights slightly correlated with cavum septum pellucidum plus cavum vergae length (R = 0.306, P < .001) and cavum septum pellucidum length (R = 0.278, P < .001). When fighters were subdivided into boxers, mixed martial artists, and martial artists, results were similar to those in the whole-group analysis. CONCLUSIONS: This study assessed MR imaging findings in a large cohort demonstrating a significantly increased prevalence of cavum septum pellucidum among fighters. Although cerebral microhemorrhages were higher in fighters than in controls, this finding was not statistically significant, possibly partially due to underpowering of the study.

Acute Cytotoxic and Vasogenic Edema after Subarachnoid Hemorrhage: A Quantitative MRI Study.

BACKGROUND AND PURPOSE: The mechanism of early brain injury following subarachnoid hemorrhage is not well understood. We aimed to evaluate if cytotoxic and vasogenic edema are contributing factors. MATERIALS AND METHODS: A retrospective analysis was conducted in patients with SAH undergoing diffusion-weighted MR imaging within 72 hours of onset. Apparent diffusion coefficient values derived from DWI were evaluated by using whole-brain histograms and 19 prespecified ROIs in patients with SAH and controls with normal findings on MRI. Cytotoxic edema observed outside the ROIs was assessed in patients with SAH. The average median ADC values were compared between patients with SAH and controls and patients with SAH with mild (Hunt and Hess 1-3) versus severe early brain injury (Hunt and Hess 4-5). RESULTS: We enrolled 33 patients with SAH and 66 controls. The overall average median whole-brain ADC was greater for patients with SAH (808 × 10-6 mm2/s) compared with controls (788 × 10-6 mm2/s, P < .001) and was higher in patients with SAH across ROIs after adjusting for age: cerebral gray matter (826 versus 803 × 10-6 mm2/s, P = .059), cerebral white matter (793 versus 758 × 10-6 mm2/s, P = .023), white matter tracts (797 versus 739 × 10-6 mm2/s, P < .001), and deep gray matter (754 versus 713 × 10-6 mm2/s, P = .016). ADC values trended higher in patients with Hunt and Hess 4-5 versus those with Hunt and Hess 1-3. Early cytotoxic edema was observed in 13 (39%) patients with SAH and was more prevalent in those with severe early brain injury (87.5% of patients with Hunt and Hess 4-5 versus 24.0% of those with Hunt and Hess 1-3, P = .001). CONCLUSIONS: Age-adjusted ADC values were globally increased in patients with SAH compared with controls, even in normal-appearing brain regions, suggesting diffuse vasogenic edema. Cytotoxic edema was also present in patients with SAH and correlated with more severe early brain injury.

Top-down design of magnonic crystals from bottom-up magnetic nanoparticles through protein arrays.

We show that chemical fixation enables top-down micro-machining of large periodic 3D arrays of protein-encapsulated magnetic nanoparticles (NPs) without loss of order. We machined 3D micro-cubes containing a superlattice of NPs by means of focused ion beam etching, integrated an individual micro-cube to a thin-film coplanar waveguide and measured the resonant microwave response. Our work represents a major step towards well-defined magnonic metamaterials created from the self-assembly of magnetic nanoparticles.

Automated MRI Volumetric Analysis in Patients with Rasmussen Syndrome.

BACKGROUND AND PURPOSE: Rasmussen syndrome, also known as Rasmussen encephalitis, is typically associated with volume loss of the affected hemisphere of the brain. Our aim was to apply automated quantitative volumetric MR imaging analyses to patients diagnosed with Rasmussen encephalitis, to determine the predictive value of lobar volumetric measures and to assess regional atrophy differences as well as monitor disease progression by using these measures. MATERIALS AND METHODS: Nineteen patients (42 scans) with diagnosed Rasmussen encephalitis were studied. We used 2 control groups: one with 42 age- and sex-matched healthy subjects and the other with 42 epileptic patients without Rasmussen encephalitis with the same disease duration as patients with Rasmussen encephalitis. Volumetric analysis was performed on T1-weighted images by using BrainSuite. Ratios of volumes from the affected hemisphere divided by those from the unaffected hemisphere were used as input to a logistic regression classifier, which was trained to discriminate patients from controls. Using the classifier, we compared the predictive accuracy of all the volumetric measures. These ratios were used to further assess regional atrophy differences and correlate with epilepsy duration. RESULTS: Interhemispheric and frontal lobe ratios had the best prediction accuracy for separating patients with Rasmussen encephalitis from healthy controls and patient controls without Rasmussen encephalitis. The insula showed significantly more atrophy compared with all the other cortical regions. Patients with longitudinal scans showed progressive volume loss in the affected hemisphere. Atrophy of the frontal lobe and insula correlated significantly with epilepsy duration. CONCLUSIONS: Automated quantitative volumetric analysis provides accurate separation of patients with Rasmussen encephalitis from healthy controls and epileptic patients without Rasmussen encephalitis, and thus may assist the diagnosis of Rasmussen encephalitis. Volumetric analysis could also be included as part of follow-up for patients with Rasmussen encephalitis to assess disease progression.

Re-review of MRI with post-processing in nonlesional patients in whom epilepsy surgery has failed.

Management of MRI-negative patients with intractable focal epilepsy after failed surgery is particularly challenging. In this study, we aim to investigate whether MRI post-processing could identify relevant targets for the re-evaluation of MRI-negative patients who failed the initial resective surgery. We examined a consecutive series of 56 MRI-negative patients who underwent resective surgery and had recurring seizures at 1-year follow-up. T1-weighted volumetric sequence from the pre-surgical MRI was used for voxel-based MRI post-processing which was implemented in a morphometric analysis program (MAP). MAP was positive in 15 of the 56 patients included in this study. In 5 patients, the MAP+ regions were fully resected. In 10 patients, the MAP+ regions were not or partially resected: two out of the 10 patients had a second surgery including the unresected MAP+ region, and both became seizure-free; the remaining 8 patients did not undergo further surgery, but the unresected MAP+ regions were concordant with more than one noninvasive modality in 7. In the 8 patients who had unresected MAP+ regions and intracranial-EEG before the previous surgery, the unresected MAP+ regions were concordant with ictal onset in 6. Our data suggest that scrutiny of the presurgical MRI guided by MRI post-processing may reveal relevant targets for reoperation in nonlesional epilepsies. MAP findings, when concordant with the patient's other noninvasive data, should be considered when planning invasive evaluation/reoperation for this most challenging group of patients.

Pt, Co-Pt and Fe-Pt alloy nanoclusters encapsulated in virus capsids.

Nanostructured Pt-based alloys show great promise, not only for catalysis but also in medical and magnetic applications. To extend the properties of this class of materials, we have developed a means of synthesizing Pt and Pt-based alloy nanoclusters in the capsid of a virus. Pure Pt and Pt-alloy nanoclusters are formed through the chemical reduction of [PtCl4](-) by NaBH4 with/without additional metal ions (Co or Fe). The opening and closing of the ion channels in the virus capsid were controlled by changing the pH and ionic strength of the solution. The size of the nanoclusters is limited to 18 nm by the internal diameter of the capsid. Their magnetic properties suggest potential applications in hyperthermia for the Co-Pt and Fe-Pt magnetic alloy nanoclusters. This study introduces a new way to fabricate size-restricted nanoclusters using virus capsid.

Is endometrial ablation protective against endometrial cancer? A retrospective observational study.

STUDY OBJECTIVES: Endometrial ablation has been increasingly used over the last 30 years to manage patients with dysfunctional uterine bleeding. Of primary concern, however, is the potential of the procedure to mask the presence or delay the diagnosis of endometrial cancer. The aim of this study is to assess the long-term effects of endometrial ablation and its association with the development of endometrial cancer. METHODS: This is a retrospective observational study that was conducted at Bradford Teaching Hospitals in the United Kingdom. The study included all women who had different types of endometrial ablative procedures in the period of January 1994 to December 2011. Analysis of the data was performed using SPSS for windows (V9) software package. RESULTS: Over 18 years period, 1521 women had endometrial ablative procedures for dysfunctional uterine bleeding. During their long-term follow-up, none of the women developed endometrial cancer later in life. This incidence is much lower than the lifetime risk of endometrial cancer in the general population (RR 0.0135; 95 % CI 0.0007-0.2801; P = 0.0054). CONCLUSION: To our knowledge, this is the largest study to examine the long-term incidence of endometrial cancer in women who had endometrial ablative procedures. It shows that the development of endometrial cancer does not seem to be associated with endometrial ablative procedures.

Do postmenopausal women with thickened endometrium on trans-vaginal ultrasound in the absence of vaginal bleeding need hysteroscopic assessment? A Pilot Study.

We aimed to determine the incidence of endometrial cancer in a cohort of postmenopausal women with thickened endometrium but no bleeding referred for hysteroscopy and determine the risk estimate of cancer using a cut-off of > 11 mm. This retrospective study of asymptomatic postmenopausal women with thickened endometrium on trans-vaginal scan referred for hysteroscopy was performed using data from 2008 to 2010. In total 63 women were identified. 2 cases of endometrial cancer were identified with an incidence of 3.17%. 22 cases had endometrial thickness (ET) > 11 mm of which 2 were malignant giving a risk estimate for endometrial cancer of 9.1%. 61 women had benign pathology, 40.98% had atrophic endometrium and 59.02% had benign polyp. In conclusion, the incidence of endometrial cancer in postmenopausal women with thickened endometrium on transvaginal scan without vaginal bleeding is low and ET of 11 mm or more seems realistic to use as a cut-off for referral for hysteroscopy.

On the minimum requirements for otolaryngology clinics in National Health Service hospitals.

OBJECTIVE: This paper, a report by the Clinical Governance and Audit Committee of the Scottish Otolaryngological Society, presents a consensus view of the minimal requirements for ENT clinics in National Health Service hospitals. RESULTS AND CONCLUSION: The provision of adequate equipment and staff has gained increasing importance as the vast majority of ENT procedures can be safely performed in the out-patient or office setting.