Physical activity in Hodgkin's lymphoma survivors with and without chronic fatigue compared with the general population – a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Hodgkin's lymphoma survivors (HLSs) commonly report chronic fatigue, defined as high levels of fatigue for 6 months or more. Underlying mechanisms are poorly understood. Based upon knowledge from other populations, lifestyle parameters may be related to this increased and persistent fatigue. The primary objective of the present study was to assess self-reported levels of physical activity, smoking habits and sleep patterns in HLSs with and without chronic fatigue. The secondary objective was to compare these results with data from age and gender adjusted data from the general population (Gen-Pop).</p> <p>Methods</p> <p>The Fatigue Questionnaire (FQ) and questions about daily smoking, sleep patterns and level of physical activity were completed by 476 HLSs treated at Rikshospitalet-Radiumhospitalet Trust (RR). The Gen-Pop data was derived from 56.999 inhabitants in a Norwegian county responding to a mail survey. Fischer's exact test, chi square test and t-tests were used to compare groups. P-values < .05 were considered statistically significant. A logistic regression analysis was performed in comparing the Gen-Pop with the HLSs.</p> <p>Results</p> <p>Level of physical activity, smoking habits and sleep patterns did not differ significantly between HLSs with and without chronic fatigue. The multivariate logistic regression analysis adjusting for different covariates, showed significantly more physically active men among HLSs compared with the Gen-Pop (OR = 1.50, CI 1.04 – 2.17), p = .031. No significant difference was found among females (OR = 1.20, CI = 0.83 – 1.74), p = .33.</p> <p>Conclusion</p> <p>Lifestyle parameters did not seem to be related to increased and persistent fatigue among HLSs. The results may indicate that the experience of Hodgkin's lymphoma increases the level of physical activity among male HLSs.</p

Severe Airway Epithelial Injury, Aberrant Repair and Bronchiolitis Obliterans Develops after Diacetyl Instillation in Rats

Bronchiolitis obliterans (BO) is a fibrotic lung disease that occurs in a variety of clinical settings, including toxin exposures, autoimmunity and lung or bone marrow transplant. Despite its increasing clinical importance, little is known regarding the underlying disease mechanisms due to a lack of adequate small animal BO models. Recent epidemiological studies have implicated exposure to diacetyl (DA), a volatile component of artificial butter flavoring, as a cause of BO in otherwise healthy factory workers. Our overall hypothesis is that DA induces severe epithelial injury and aberrant repair that leads to the development of BO. Therefore, the objectives of this study were 1) to determine if DA, delivered by intratracheal instillation (ITI), would lead to the development of BO in rats and 2) to characterize epithelial regeneration and matrix repair after ITI of DA.Male Sprague-Dawley rats were treated with a single dose of DA (125 mg/kg) or sterile water (vehicle control) by ITI. Instilled DA resulted in airway specific injury, followed by rapid epithelial regeneration, and extensive intraluminal airway fibrosis characteristic of BO. Increased airway resistance and lung fluid neutrophilia occurred with the development of BO, similar to human disease. Despite rapid epithelial regeneration after DA treatment, expression of the normal phenotypic markers, Clara cell secretory protein and acetylated tubulin, were diminished. In contrast, expression of the matrix component Tenascin C was significantly increased, particularly evident within the BO lesions.We have established that ITI of DA results in BO, creating a novel chemical-induced animal model that replicates histological, biological and physiological features of the human disease. Furthermore, we demonstrate that dysregulated epithelial repair and excessive matrix Tenacin C deposition occur in BO, providing new insights into potential disease mechanisms and therapeutic targets

New Binding Mode to TNF-Alpha Revealed by Ubiquitin-Based Artificial Binding Protein

A variety of approaches have been employed to generate binding proteins from non-antibody scaffolds. Utilizing a beta-sheet of the human ubiquitin for paratope creation we obtained binding proteins against tumor necrosis factor (TNF)-alpha. The bioactive form of this validated pharmacological target protein is a non-covalently linked homo-trimer. This structural feature leads to the observation of a certain heterogeneity concerning the binding mode of TNF-alpha binding molecules, for instance in terms of monomer/trimer specificity. We analyzed a ubiquitin-based TNF-alpha binder, selected by ribosome display, with a particular focus on its mode of interaction. Using enzyme-linked immunosorbent assays, specific binding to TNF-alpha with nanomolar affinity was observed. In isothermal titration calorimetry we obtained comparable results regarding the affinity and detected an exothermic reaction with one ubiquitin-derived binding molecule binding one TNF-alpha trimer. Using NMR spectroscopy and other analytical methods the 1∶3 stoichiometry could be confirmed. Detailed binding analysis showed that the interaction is affected by the detergent Tween-20. Previously, this phenomenon was reported only for one other type of alternative scaffold-derived binding proteins – designed ankyrin repeat proteins – without further investigation. As demonstrated by size exclusion chromatography and NMR spectroscopy, the presence of the detergent increases the association rate significantly. Since the special architecture of TNF-alpha is known to be modulated by detergents, the access to the recognized epitope is indicated to be restricted by conformational transitions within the target protein. Our results suggest that the ubiquitin-derived binding protein targets a new epitope on TNF-alpha, which differs from the epitopes recognized by TNF-alpha neutralizing antibodies

Effects of Ambulant Myofeedback Training and Ergonomic Counselling in Female Computer Workers with Work-Related Neck-Shoulder Complaints: A Randomized Controlled Trial

Objective: To investigate the effects of ambulant myofeedback training including ergonomic counselling (Mfb) and ergonomic counselling alone (EC), on work-related neck-shoulder pain and disability. Methods: Seventy-nine female computer workers reporting neck-shoulder complaints were randomly assigned to Mfb or EC and received four weeks of intervention. Pain intensity in neck, shoulders, and upper back, and pain disability, were measured at baseline, immediately after intervention, and at three and six months follow-up. Results: Pain intensity and disability had significantly decreased immediately after four weeks Mfb or EC, and the effects remained at follow up. No differences were observed between the Mfb and EC group for outcome and subjects in both intervention groups showed comparable chances for improvement in pain intensity and disability. Conclusions: Pain intensity and disability significantly reduced after both interventions and this effect remained at follow-up. No differences were observed between the two intervention groups

Localization and broadband follow-up of the gravitational-wave transient GW150914

A gravitational-wave (GW) transient was identified in data recorded by the Advanced Laser Interferometer Gravitational-wave Observatory (LIGO) detectors on 2015 September 14. The event, initially designated G184098 and later given the name GW150914, is described in detail elsewhere. By prior arrangement, preliminary estimates of the time, significance, and sky location of the event were shared with 63 teams of observers covering radio, optical, near-infrared, X-ray, and gamma-ray wavelengths with ground- and space-based facilities. In this Letter we describe the low-latency analysis of the GW data and present the sky localization of the first observed compact binary merger. We summarize the follow-up observations reported by 25 teams via private Gamma-ray Coordinates Network circulars, giving an overview of the participating facilities, the GW sky localization coverage, the timeline, and depth of the observations. As this event turned out to be a binary black hole merger, there is little expectation of a detectable electromagnetic (EM) signature. Nevertheless, this first broadband campaign to search for a counterpart of an Advanced LIGO source represents a milestone and highlights the broad capabilities of the transient astronomy community and the observing strategies that have been developed to pursue neutron star binary merger events. Detailed investigations of the EM data and results of the EM follow-up campaign are being disseminated in papers by the individual teams

Common and distinct neural effects of risperidone and olanzapine during procedural learning in schizophrenia: A randomised longitudinal fMRI study

© 2015 The Author(s). Rationale: Most cognitive domains show only minimal improvement following typical or atypical antipsychotic treatments in schizophrenia, and some may even worsen. One domain that may worsen is procedural learning, an implicit memory function relying mainly on the integrity of the fronto-striatal system. Objectives: We investigated whether switching to atypical antipsychotics would improve procedural learning and task-related neural activation in patients on typical antipsychotics. Furthermore, we explored the differential effects of the atypical antipsychotics risperidone and olanzapine. Methods: Thirty schizophrenia patients underwent functional magnetic resonance imaging during a 5-min procedural (sequence) learning task on two occasions: at baseline and 7-8 weeks later. Of 30 patients, 10 remained on typical antipsychotics, and 20 were switched randomly in equal numbers to receive either olanzapine (10-20 mg) or risperidone (4-8 mg) for 7-8 weeks. Results: At baseline, patients (all on typical antipsychotics) showed no procedural learning. At follow-up, patients who remained on typical antipsychotics continued to show a lack of procedural learning, whereas those switched to atypical antipsychotics displayed significant procedural learning (p = 0.001) and increased activation in the superior-middle frontal gyrus, anterior cingulate and striatum (cluster-corrected p < 0.05). These neural effects were present as a linear increase over five successive 30-s blocks of sequenced trials. A switch to either risperidone or olanzapine resulted in comparable performance but with both overlapping and distinct task-related activations. Conclusions: Atypical antipsychotics restore procedural learning deficits and associated neural activity in schizophrenia. Furthermore, different atypical antipsychotics produce idiosyncratic task-related neural activations, and this specificity may contribute to their differential long-term clinical profiles.Alexander von Humboldt Foundation; Biomedical Research Centre for Mental Health at the Institute of Psychiatry, King’s College London; South London and Maudsley NHS Foundation Trus