Lumbar Kinematics, Functional Disability and Fear Avoidance Beliefs Among Adults with Nonspecific Chronic Low Back Pain

Objectives: This study aimed to examine correlations between lumbar kinematics, functional disability and fear avoidance beliefs among adults with nonspecific chronic low back pain (LBP). Methods: This crosssectional study was conducted between March and December 2014. A total of 32 adults diagnosed with nonspecific chronic LBP were recruited from outpatients attending either an orthopaedic clinic at a university hospital or a private physiotherapy clinic in Malaysia. Lumbar kinematics were measured using sensors attached at the first lumbar (L1) and second sacral (S2) vertebrae levels. The Oswestry Disability Index (ODI) and Fear-Avoidance Beliefs Questionnaire (FABQ) were used to assess degree of functional disability and fear avoidance beliefs, respectively. Results: For maximum range of motion, positive correlations were observed between ODI scores and right lateral flexion and right rotation (P = 0.01 each), although there was a negative correlation with left rotation (P = 0.03). With maximum angular velocity, ODI scores were positively correlated with right and left lateral flexion L1 (P = 0.01 and <0.01, respectively) but negatively correlated with left lateral flexion L2 (P= 0.04). Regarding minimum angular velocity, ODI scores were positively correlated with left lateral flexion S2 (P <0.01) but negatively correlated with right and left lateral flexion L1 (P = 0.02 each), right rotation L1 (P = 0.02) and left rotation S2 (P = 0.01). No significant correlations were found between lumbar kinematics and FABQ scores. Conclusion: These findings suggest that certain lumbar kinematic parameters are correlated with functional disability, but not with fear avoidance beliefs

Adherence to subcutaneous interferon beta-1a treatment using an electronic injection device:a prospective open-label Scandinavian noninterventional study (the ScanSmart study)

Background: Disease modifying drugs help control the course of relapsing remitting multiple sclerosis (RRMS); however, good adherence is needed for long-term outcomes. Objective: To evaluate patient adherence to treatment with subcutaneous interferon beta-1a using RebiSmart® and assess injection-site reactions and treatment satisfaction. Methods: This prospective, single-arm, open-label, noninterventional multicenter Phase IV trial included disease modifying drug-experienced mobile patients with RRMS. Adherence was measured over 12 weeks. Items 13–23, 35, 37, and 38 of the Multiple Sclerosis Treatment Concerns Questionnaire (injection-site reactions and treatment satisfaction) were recorded at 12 weeks. Results: Sixty patients were recruited (mean age 43.7 [±SD 7.9] years; 83% female; mean years since multiple sclerosis diagnosis 6.7 [SD 4.5]). Adherence data were obtained in 54 patients only due to technical problems with six devices. Over 12 weeks, 89% (n=48) of patients had ≥90% adherence to treatment. Most patients experienced mild influenza-like symptoms and injection-site reactions, and global side effects were minimal. Most patients (78%) rated the convenience as the most important aspect of the device, and most experienced no or mild pain. Conclusion: RRMS patients treated with subcutaneous interferon beta-1a, administered with RebiSmart, demonstrated generally good adherence, and the treatment was generally well tolerated

Atopic dermatitis and risk of atrial fibrillation or flutter: A 35-year follow-up study.

BACKGROUND: Atopic dermatitis is characterized by chronic inflammation, which is a risk factor for atrial fibrillation. OBJECTIVE: To examine the association between hospital-diagnosed atopic dermatitis and atrial fibrillation. METHODS: Using linked population-based Danish registries, we identified persons with an inpatient or outpatient hospital diagnosis of atopic dermatitis during 1977-2013 and a comparison cohort individually matched to the atopic dermatitis cohort. We followed cohorts until death, emigration, atrial fibrillation diagnosis, or end of study (January 1, 2013). We compared 35-year risk of atrial fibrillation and estimated hazard ratios with 95% confidence intervals using Cox regression, adjusting for birth year and sex. We validated 100 atopic dermatitis diagnoses from a dermatologic department through medical record review. RESULTS: We included 13,126 persons with atopic dermatitis and 124,211 comparators and followed them for a median of 19.3 years. The 35-year risk of atrial fibrillation was 0.81% and 0.67%, respectively. The positive predictive value of atopic dermatitis diagnoses was 99%. The hazard ratio was 1.2 (95% confidence interval 1.0-1.6) and remained increased after adjusting for various atrial fibrillation risk factors. LIMITATIONS: Analyses were limited to persons with moderate-to-severe atopic dermatitis, and we had no lifestyle data. CONCLUSION: Patients with hospital-diagnosed atopic dermatitis have a 20% increased long-term risk of atrial fibrillation, but the absolute risk remains low

Influence of wild-type MLL on glucocorticoid sensitivity and response to DNA-damage in pediatric acute lymphoblastic leukemia

<p>Abstract</p> <p>Background</p> <p>Rearrangement of the mixed-lineage leukemia gene (<it>MLL</it>) is found in 80% of infant acute lymphoblastic leukemia (ALL) and is associated with poor prognosis and resistance to glucocorticoids (GCs). We have recently observed that GC resistance in T-ALL cell lines is associated with a proliferative metabolism and reduced expression of <it>MLL</it>. In this study we have further explored the relationship between <it>MLL </it>status and GC sensitivity.</p> <p>Results</p> <p>Negative correlation of <it>MLL </it>expression with GC resistance in 15 T-ALL cell lines was confirmed by quantitative RT-PCR. The absence of <it>MLL</it>-rearrangements suggested that this relationship represented expression of wild-type <it>MLL</it>. Analysis of <it>MLL </it>expression patterns revealed a negative relationship with cellular metabolism, proliferation and anti-apoptotic transcriptional networks. <it>In silico </it>analysis of published data demonstrated that reduced levels of <it>MLL </it>mRNA are associated with relapse and prednisolone resistance in T-ALL patients and adverse clinical outcome in children with <it>MLL</it>-rearranged ALL. RNAi knockdown of <it>MLL </it>expression in T-ALL cell lines significantly increased resistance to dexamethasone and gamma irradiation indicating an important role for wild-type <it>MLL </it>in the control of cellular apoptosis.</p> <p>Conclusions</p> <p>The data suggests that reduced expression of wild-type <it>MLL </it>can contribute to GC resistance in ALL patients both with and without <it>MLL</it>-translocations.</p

SVM recursive feature elimination analyses of structural brain MRI predicts near-term relapses in patients with clinically isolated syndromes suggestive of multiple sclerosis

Esclerosi múltiple; Classificació d'aprenentatge automàtic; Selecció de funcionsEsclerosis múltiple; Clasificación de aprendizaje automático; Selección de característicasMultiple sclerosis; Machine learning classification; Feature selectionMachine learning classification is an attractive approach to automatically differentiate patients from healthy subjects, and to predict future disease outcomes. A clinically isolated syndrome (CIS) is often the first presentation of multiple sclerosis (MS), but it is difficult at onset to predict who will have a second relapse and hence convert to clinically definite MS. In this study, we thus aimed to distinguish CIS converters from non-converters at onset of a CIS, using recursive feature elimination and weight averaging with support vector machines. We also sought to assess the influence of cohort size and cross-validation methods on the accuracy estimate of the classification. We retrospectively collected 400 patients with CIS from six European MAGNIMS MS centres. Patients underwent brain MRI at onset of a CIS according to local standard-of-care protocols. The diagnosis of clinically definite MS at one-year follow-up was the standard against which the accuracy of the model was tested. For each patient, we derived MRI-based features, such as grey matter probability, white matter lesion load, cortical thickness, and volume of specific cortical and white matter regions. Features with little contribution to the classification model were removed iteratively through an interleaved sample bootstrapping and feature averaging approach. Classification of CIS outcome at one-year follow-up was performed with 2-fold, 5-fold, 10-fold and leave-one-out cross-validation for each centre cohort independently and in all patients together. The estimated classification accuracy across centres ranged from 64.9% to 88.1% using 2-fold cross-validation and from 73% to 92.9% using leave-one-out cross-validation. The classification accuracy estimate was higher in single-centre, smaller data sets than in combinations of data sets, being the lowest when all patients were merged together. Regional MRI features such as WM lesions, grey matter probability in the thalamus and the precuneus or cortical thickness in the cuneus and inferior temporal gyrus predicted the occurrence of a second relapse in patients at onset of a CIS using support vector machines. The increased accuracy estimate of the classification achieved with smaller and single-centre samples may indicate a model bias (overfitting) when data points were limited, but also more homogeneous. We provide an overview of classifier performance from a range of cross-validation schemes to give insight into the variability across schemes. The proposed recursive feature elimination approach with weight averaging can be used both in single- and multi-centre data sets in order to bridge the gap between group-level comparisons and making predictions for individual patients.This project received funding from the European Union's Horizon2020 Research and Innovation Program EuroPOND under grant agreement number 666992, and it was supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. We thank all participating partners of the MAGNIMS study group for sharing their data with us

Cytokine expression in mice exposed to diesel exhaust particles by inhalation. Role of tumor necrosis factor

BACKGROUND: Particulate air pollution has been associated with lung and cardiovascular disease, for which lung inflammation may be a driving mechanism. The pro-inflammatory cytokine, tumor necrosis factor (TNF) has been suggested to have a key-role in particle-induced inflammation. We studied the time course of gene expression of inflammatory markers in the lungs of wild type mice and Tnf-/- mice after exposure to diesel exhaust particles (DEPs). Mice were exposed to either a single or multiple doses of DEP by inhalation. We measured the mRNA level of the cytokines Tnf and interleukin-6 (Il-6) and the chemokines, monocyte chemoattractant protein (Mcp-1), macrophage inflammatory protein-2 (Mip-2) and keratinocyte derived chemokine (Kc) in the lung tissue at different time points after exposure. RESULTS: Tnf mRNA expression levels increased late after DEP-inhalation, whereas the expression levels of Il-6, Mcp-1 and Kc increased early. The expression of Mip-2 was independent of TNF if the dose was above a certain level. The expression levels of the cytokines Kc, Mcp-1 and Il-6, were increased in the absence of TNF. CONCLUSION: Our data demonstrate that Tnf is not important in early DEP induced inflammation and rather exerts negative influence on Mcp-1 and Kc mRNA levels. This suggests that other signalling pathways are important, a candidate being one involving Mcp-1

Effect of virtual reality training on laparoscopic surgery: randomised controlled trial

Objective To assess the effect of virtual reality training on an actual laparoscopic operation

Topiramate add-on therapy for drug-resistant focal epilepsy

Background The majority of people with epilepsy have a good prognosis and their seizures are controlled by a single antiepileptic drug. However, up to 20% of patients from population‐based studies, and up to 30% from clinical series (not population‐based), develop drug‐resistant epilepsy, especially those with focal‐onset seizures. In this review, we summarise the current evidence regarding topiramate, an antiepileptic drug first marketed in 1996, when used as an add‐on treatment for drug‐resistant focal epilepsy. This is an update of a Cochrane Review first published in 1999, and last updated in 2014. Objectives To evaluate the efficacy and tolerability of topiramate when used as an add‐on treatment for people with drug‐resistant focal epilepsy. Search methods For the latest update of this review we searched the following databases on 2 July 2018: Cochrane Register of Studies (CRS Web), which includes the Cochrane Epilepsy Group Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE (Ovid, 1946‐ ); ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP). We imposed no language restrictions. We also contacted the manufacturers of topiramate and researchers in the field to identify any ongoing or unpublished studies. Selection criteria Randomised, placebo‐controlled add‐on trials of topiramate, recruiting people with drug‐resistant focal epilepsy. Data collection and analysis Two review authors independently selected trials for inclusion and extracted the relevant data. We assessed the following outcomes: (1) 50% or greater reduction in seizure frequency; (2) seizure freedom; (3) treatment withdrawal (any reason); (4) adverse effects. Primary analyses were intention‐to‐treat (ITT), and summary risk ratios (RRs) with 95% confidence intervals (95% CIs) are presented. We evaluated dose‐response in regression models. We carried out a 'Risk of bias' assessment for each included study using the Cochrane 'Risk of bias' tool and assessed the overall certainty of evidence using the GRADE approach. Main results We included 12 trials, representing 1650 participants. Baseline phases ranged from four to 12 weeks and double‐blind phases ranged from 11 to 19 weeks. The RR for a 50% or greater reduction in seizure frequency with add‐on topiramate compared to placebo was 2.71 (95% CI 2.05 to 3.59; 12 studies; high‐certainty evidence). Dose regression analysis showed increasing effect with increasing topiramate dose demonstrated by an odds ratio (OR) of 1.45 (95% CI 1.28 to 1.64; P < 0.001) per 200 mg/d increase in topiramate dosage. The proportion of participants achieving seizure freedom was also significantly increased with add‐on topiramate compared to placebo (RR 3.67, 95% CI 1.79 to 7.54; 8 studies; moderate‐certainty evidence). Treatment withdrawal was significantly higher for add‐on topiramate compared to placebo (RR 2.37, 95% CI 1.66 to 3.37; 12 studies; high‐certainty evidence). The RRs for the following adverse effects indicate that they are significantly more prevalent with topiramate, compared to placebo: ataxia 2.29 (99% CI 1.10 to 4.77; 4 studies); concentration difficulties 7.81 (99% CI 2.08 to 29.29; 6 studies; moderate‐certainty evidence); dizziness 1.52 (99% CI 1.07 to 2.16; 8 studies); fatigue 2.08 (99% CI 1.37 to 3.15; 10 studies); paraesthesia 3.65 (99% CI 1.58 to 8.39; 7 studies; moderate‐certainty evidence); somnolence 2.44 (99% CI 1.61 to 3.68; 9 studies); 'thinking abnormally' 5.70 (99% CI 2.26 to 14.38; 4 studies; high‐certainty evidence); and weight loss 3.99 (99% CI 1.82 to 8.72; 9 studies; low‐certainty evidence). Evidence of publication bias for the primary outcome was found (Egger test, P = 0.001). We rated all studies included in the review as having either low or unclear risk of bias. Overall, we assessed the evidence as moderate to high certainty due to the evidence of publication bias, statistical heterogeneity and imprecision, which was partially compensated for by large effect sizes. Authors' conclusions Topiramate has efficacy as an add‐on treatment for drug‐resistant focal epilepsy as it is almost three times more effective compared to a placebo in reducing seizures. The trials reviewed were of relatively short duration and provided no evidence for the long‐term efficacy of topiramate. Short‐term use of add‐on topiramate was shown to be associated with several adverse events. The results of this review should only be applied to adult populations as only one study included children. Future research should consider further examining the effect of dose

'Sexercise': Working out heterosexuality in Jane Fonda’s fitness books

This is an Author's Accepted Manuscript of an article published in Leisure Studies, 30(2), 237 - 255, 2011, copyright Taylor & Francis, available online at: http://www.tandfonline.com/10.1080/02614367.2010.523837.This paper explores the connection between the promotion of heterosexual norms in women’s fitness books written by or in the name of Jane Fonda during the 1980s and the commodification of women’s fitness space in both the public and private spheres. The paper is set in the absence of overt discussions of normative heterosexuality in leisure studies and draws on critical heterosexual scholarship as well as the growing body of work theorising geographies of corporeality and heterosexuality. Using the principles of media discourse analysis, the paper identifies three overlapping characteristics of heterosexuality represented in Jane Fonda’s fitness books, and embodied through the exercise regimes: respectable heterosexual desire, monogamous procreation and domesticity. The paper concludes that the promotion and prescription of exercise for women in the Jane Fonda workout books centred on the reproduction and embodiment of heterosexual corporeality. Set within an emerging commercial landscape of women’s fitness in the 1980s, such exercise practices were significant in the legitimation and institutionalisation of heteronormativity