Reductions in co-contraction following neuromuscular re-education in people with knee osteoarthritis

Background Both increased knee muscle co-contraction and alterations in central pain processing have been suggested to play a role in knee osteoarthritis pain. However, current interventions do not target either of these mechanisms. The Alexander Technique provides neuromuscular re-education and may also influence anticipation of pain. This study therefore sought to investigate the potential clinical effectiveness of the AT intervention in the management of knee osteoarthritis and also to identify a possible mechanism of action. Methods A cohort of 21 participants with confirmed knee osteoarthritis were given 20 lessons of instruction in the Alexander Technique. In addition to clinical outcomes EMG data, quantifying knee muscle co-contraction and EEG data, characterising brain activity during anticipation of pain, were collected. All data were compared between baseline and post-intervention time points with a further 15-month clinical follow up. In addition, biomechanical data were collected from a healthy control group and compared with the data from the osteoarthritis subjects. Results: Following AT instruction the mean WOMAC pain score reduced by 56% from 9.6 to 4.2 (P<0.01) and this reduction was maintained at 15 month follow up. There was a clear decrease in medial co-contraction at the end of the intervention, towards the levels observed in the healthy control group, both during a pre-contact phase of gait (p<0.05) and during early stance (p<0.01). However, no changes in pain-anticipatory brain activity were observed. Interestingly, decreases in WOMAC pain were associated with reductions in medial co-contraction during the pre-contact phase of gait. Conclusions: This is the first study to investigate the potential effectiveness of an intervention aimed at increasing awareness of muscle behaviour in the clinical management of knee osteoarthritis. These data suggest a complex relationship between muscle contraction, joint loading and pain and support the idea that excessive muscle co-contraction may be a maladaptive response in this patient group. Furthermore, these data provide evidence that, if the activation of certain muscles can be reduced during gait, this may lead to positive long-term clinical outcomes. This finding challenges clinical management models of knee osteoarthritis which focus primarily on muscle strengthening

Extragalactic Radio Continuum Surveys and the Transformation of Radio Astronomy

Next-generation radio surveys are about to transform radio astronomy by discovering and studying tens of millions of previously unknown radio sources. These surveys will provide new insights to understand the evolution of galaxies, measuring the evolution of the cosmic star formation rate, and rivalling traditional techniques in the measurement of fundamental cosmological parameters. By observing a new volume of observational parameter space, they are also likely to discover unexpected new phenomena. This review traces the evolution of extragalactic radio continuum surveys from the earliest days of radio astronomy to the present, and identifies the challenges that must be overcome to achieve this transformational change.Comment: To be published in Nature Astronomy 18 Sept 201

A descriptive study of a manual therapy intervention within a randomised controlled trial for hamstring and lower limb injury prevention

The journal has been informed by its publisher BioMed Central that contrary to the statement in this article [Wayne Hoskins, Henry Pollard, Chiropractic & Osteopathy 2010, 18:23], they have been advised by the authors' institution Macquarie University, that its Human Research Ethics Committee did not approve this study. Because the study was conducted without institutional ethics committee approval it has been retracted

Harmonising data collection from osteoarthritis studies to enable stratification: recommendations on core data collection from an Arthritis Research UK clinical studies group

Objective. Treatment of OA by stratifying for commonly used and novel therapies will likely improve the range of effective therapy options and their rational deployment in this undertreated, chronic disease. In order to develop appropriate datasets for conducting post hoc analyses to inform approaches to stratification for OA, our aim was to develop recommendations on the minimum data that should be recorded at baseline in all future OA interventional and observational studies.Methods. An Arthritis Research UK study group comprised of 32 experts used a Delphi-style approach supported by a literature review of systematic reviews to come to a consensus on core data collection for OA studies.Results. Thirty-five systematic reviews were used as the basis for the consensus group discussion. For studies with a primary structural endpoint, core domains for collection were defined as BMI, age, gender, racial origin, comorbidities, baseline OA pain, pain in other joints and occupation. In addition to the items generalizable to all anatomical sites, joint-specific domains included radiographic measures, surgical history and anatomical factors, including alignment. To demonstrate clinical relevance for symptom studies, the collection of mental health score, self-efficacy and depression scales were advised in addition to the above.Conclusions. Currently it is not possible to stratify patients with OA into therapeutic groups. A list of core and optional data to be collected in all OA interventional and observational studies was developed, providing a basis for future analyses to identify predictors of progression or response to treatment

Altered Neurocircuitry in the Dopamine Transporter Knockout Mouse Brain

The plasma membrane transporters for the monoamine neurotransmitters dopamine, serotonin, and norepinephrine modulate the dynamics of these monoamine neurotransmitters. Thus, activity of these transporters has significant consequences for monoamine activity throughout the brain and for a number of neurological and psychiatric disorders. Gene knockout (KO) mice that reduce or eliminate expression of each of these monoamine transporters have provided a wealth of new information about the function of these proteins at molecular, physiological and behavioral levels. In the present work we use the unique properties of magnetic resonance imaging (MRI) to probe the effects of altered dopaminergic dynamics on meso-scale neuronal circuitry and overall brain morphology, since changes at these levels of organization might help to account for some of the extensive pharmacological and behavioral differences observed in dopamine transporter (DAT) KO mice. Despite the smaller size of these animals, voxel-wise statistical comparison of high resolution structural MR images indicated little morphological change as a consequence of DAT KO. Likewise, proton magnetic resonance spectra recorded in the striatum indicated no significant changes in detectable metabolite concentrations between DAT KO and wild-type (WT) mice. In contrast, alterations in the circuitry from the prefrontal cortex to the mesocortical limbic system, an important brain component intimately tied to function of mesolimbic/mesocortical dopamine reward pathways, were revealed by manganese-enhanced MRI (MEMRI). Analysis of co-registered MEMRI images taken over the 26 hours after introduction of Mn^(2+) into the prefrontal cortex indicated that DAT KO mice have a truncated Mn^(2+) distribution within this circuitry with little accumulation beyond the thalamus or contralateral to the injection site. By contrast, WT littermates exhibit Mn^(2+) transport into more posterior midbrain nuclei and contralateral mesolimbic structures at 26 hr post-injection. Thus, DAT KO mice appear, at this level of anatomic resolution, to have preserved cortico-striatal-thalamic connectivity but diminished robustness of reward-modulating circuitry distal to the thalamus. This is in contradistinction to the state of this circuitry in serotonin transporter KO mice where we observed more robust connectivity in more posterior brain regions using methods identical to those employed here

Use of complementary alternative medicine for low back pain consulting in general practice: a cohort study

<p>Abstract</p> <p>Background</p> <p>Although back pain is considered one of the most frequent reasons why patients seek complementary and alternative medical (CAM) therapies little is known on the extent patients are actually using CAM for back pain.</p> <p>Methods</p> <p>This is a post hoc analysis of a longitudinal prospective cohort study embedded in a RCT. General practitioners (GPs) recruited consecutively adult patients presenting with LBP. Data on physical function, on subjective mood, and on utilization of health services was collected at the first consultation and at follow-up telephone interviews for a period of twelve months</p> <p>Results</p> <p>A total of 691 (51%) respectively 928 (69%) out of 1,342 patients received one form of CAM depending on the definition. Local heat, massage, and spinal manipulation were the forms of CAM most commonly offered. Using CAM was associated with specialist care, chronic LBP and treatment in a rehabilitation facility. Receiving spinal manipulation, acupuncture or TENS was associated with consulting a GP providing these services. Apart from chronicity disease related factors like functional capacity or pain only showed weak or no association with receiving CAM.</p> <p>Conclusion</p> <p>The frequent use of CAM for LBP demonstrates that CAM is popular in patients and doctors alike. The observed association with a treatment in a rehabilitation facility or with specialist consultations rather reflects professional preferences of the physicians than a clear medical indication. The observed dependence on providers and provider related services, as well as a significant proportion receiving CAM that did not meet the so far established selection criteria suggests some arbitrary use of CAM.</p

Pressure pain sensitivity maps of the neck-shoulder and the low back regions in men and women

<p>Abstract</p> <p>Background</p> <p>Musculoskeletal pain in the low back and neck-shoulder regions is a major problem among the working population all over the world. The prevalence of musculoskeletal pain is found to be higher among women. Women also have lower pressure pain thresholds (PPTs) than men. Pressure pain topography aims at mapping the spatial distribution of PPT within a muscle in an attempt to track changes in mechanical sensitivity. In order to assess gender differences in the pain topography, it is necessary to map the distribution in both healthy men and women. The aim of this study was to assess PPT maps from the cervico-thoracic and lumbar regions in men and women.</p> <p>Methods</p> <p>Eleven men and eleven women without any known musculoskeletal disorders participated in the study. PPT was measured twice at 36 points over the trapezius muscle of the dominant arm, at 36 points over the trapezius muscle on the contralateral side and at 12 points over the spine between the left and right trapezius. Further, 11 points were measured over the erector spinae muscle on the left side of the spine between the first and the fifth lumbar vertebrae, 11 on the right side and 5 points on the spine itself. The measurements on each trapezius muscle were divided according to anatomical subdivisions. Three-way and two-way ANOVAs were used to analyse the differences in PPTs with the following factors: gender, locations and sub-divisions (only for cervico-thoracic region).</p> <p>Results</p> <p>There were no differences between left and right side in neither the cervico-thoracic nor the lumbar region, but there were (large effect) differences between the subdivisions in the trapezius with the lowest values in the upper part (P < 0.001; partial η²= 0.19). Women had (small effect) lower PPT in both cervico-thoracic and lumbar regions (P ≤ 0.001; partial η²= 0.02 for both regions), but gender had no effect on neither location nor subdivisions.</p> <p>Conclusions</p> <p>The pain topography was not found to be different between genders in the cervico-thoracic and lumbar regions. This study can be used as basis for further clinical studies on musculoskeletal disorders.</p

Synapsin II Is Involved in the Molecular Pathway of Lithium Treatment in Bipolar Disorder

Bipolar disorder (BD) is a debilitating psychiatric condition with a prevalence of 1–2% in the general population that is characterized by severe episodic shifts in mood ranging from depressive to manic episodes. One of the most common treatments is lithium (Li), with successful response in 30–60% of patients. Synapsin II (SYN2) is a neuronal phosphoprotein that we have previously identified as a possible candidate gene for the etiology of BD and/or response to Li treatment in a genome-wide linkage study focusing on BD patients characterized for excellent response to Li prophylaxis. In the present study we investigated the role of this gene in BD, particularly as it pertains to Li treatment. We investigated the effect of lithium treatment on the expression of SYN2 in lymphoblastoid cell lines from patients characterized as excellent Li-responders, non-responders, as well as non-psychiatric controls. Finally, we sought to determine if Li has a cell-type-specific effect on gene expression in neuronal-derived cell lines. In both in vitro models, we found SYN2 to be modulated by the presence of Li. By focusing on Li-responsive BD we have identified a potential mechanism for Li response in some patients

Text Mining Improves Prediction of Protein Functional Sites

We present an approach that integrates protein structure analysis and text mining for protein functional site prediction, called LEAP-FS (Literature Enhanced Automated Prediction of Functional Sites). The structure analysis was carried out using Dynamics Perturbation Analysis (DPA), which predicts functional sites at control points where interactions greatly perturb protein vibrations. The text mining extracts mentions of residues in the literature, and predicts that residues mentioned are functionally important. We assessed the significance of each of these methods by analyzing their performance in finding known functional sites (specifically, small-molecule binding sites and catalytic sites) in about 100,000 publicly available protein structures. The DPA predictions recapitulated many of the functional site annotations and preferentially recovered binding sites annotated as biologically relevant vs. those annotated as potentially spurious. The text-based predictions were also substantially supported by the functional site annotations: compared to other residues, residues mentioned in text were roughly six times more likely to be found in a functional site. The overlap of predictions with annotations improved when the text-based and structure-based methods agreed. Our analysis also yielded new high-quality predictions of many functional site residues that were not catalogued in the curated data sources we inspected. We conclude that both DPA and text mining independently provide valuable high-throughput protein functional site predictions, and that integrating the two methods using LEAP-FS further improves the quality of these predictions