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Pathophysiologic mechanisms underpinning ongoing pain in whiplash-associated disorder (WAD) are not well understood, however, alterations in brain morphology and function have been observed in this population and in other chronic pain conditions. This study investigated metabolite profiles of brain regions in people with chronic WAD compared with controls.Thirty-eight individuals with chronic WAD (mean [SD] age, 39.5 [11.3] years, 23 female individuals) and 16 pain-free controls (38.9 [12.7] years, 11 female individuals) underwent multivoxel brain magnetic resonance spectroscopy. At the anterior cingulate cortex (ACC), primary motor cortex (1MC), and somatosensory cortex (SSC), ratios of metabolite concentrations were calculated for N-acetylaspartate (NAA), creatine (Cr), choline (Cho), myo-inositol (Ins), and glutamate/glutamine (Glx). Chronic WAD group participants completed clinical questionnaires and cold and pressure pain threshold assessment. Data were analyzed with hypothesis testing and Spearman correlations (P≥0.05), with Benjamini-Hochberg corrections (5% false discovery rate).No group differences were observed for NAA:Cr, NAA:Cho, Cr:Cho, Glx:NAA, Glx:Cr, Glx:Cho, Ins:NAA, Ins:Cr, Ins:Cho or Ins:Glx for left or right ACC, 1MC, or SSC following correction for multiple comparisons. No significant correlations were observed between metabolite ratios and any clinical variable.These results suggest that ongoing pain and disability in this population may not be underpinned by metabolite aberrations in the brain regions examined. Further research is required to progress our understanding of cortical contributions to neurophysiologic mechanisms in chronic WAD.

ObjectivePrimary objectives: to investigate the central neurobiological effects (using MRI) of physical exercise in individuals with chronic pain. Secondary objectives: (1) to investigate the associations between central changes and clinical outcomes and (2) to investigate whether different types and dosages of physical exercise exert different central changes.DesignSystematic review searching four electronic databases up to September 2018: AMED, CINAHL, Embase and MEDLINE. Two reviewers independently assessed the methodological quality of included studies using the Cochrane Collaboration’s Risk of Bias in Non-Randomised Studies-I tool. A standardised extraction table was used for data extraction, which was performed by two reviewers.InterventionsStudies reporting any physical exercise intervention in any chronic musculoskeletal pain condition were included. Eligibility of 4011 records was screened independently by two reviewers, and four studies were included in the review.Primary and secondary outcome measuresPrimary outcome: any brain outcome assessed with any MR technique. Secondary outcomes: any self-reported clinical outcomes, and type and dosage of the exercise intervention.ResultsAll four studies had high risk of bias. There was heterogeneity between the brain areas studied and the types of exercise interventions delivered. All studies reported functional MRI changes in various brain areas following an exercise intervention. Insufficient data were available to conduct a meta-analysis or to answer the secondary aims.ConclusionsOnly a limited number of studies were available and all were at high risk of bias. None of the studies was randomised or included blinded assessment. Exercise may exert effects on brain neurobiology in people with chronic pain. Due to the high risk of bias, future studies should use a randomised study design. Investigation of morphological brain changes could be included.PROSPERO registration numberCRD42018108179.

IntroductionNeck pain is a global burdensome problem, with a large proportion of neck pain cases becoming chronic. Although physical exercise is a commonly prescribed treatment, the evidence on the effectiveness of isolated exercise interventions remains limited. Traditional pairwise randomised controlled trials (RCTs) and meta-analyses are limited in only comparing two interventions. This protocol describes the design of a network meta-analysis, which enables a comparative investigation of all physical exercise interventions for which RCTs are available. We aim to systematically compare the effectiveness of different types of physical exercise in people with chronic non-specific neck pain.Methods and analysisNine electronic databases (AMED, CINAHL, Cochrane Central Register of Controlled Trials, Embase, MEDLINE, Physiotherapy Evidence Database, PsycINFO, Scopus and SPORTDiscus) were searched for RCTs from inception to 12 March 2019. Titles and abstract firstly, and full-text papers secondly, will be screened by two reviewers. Data will be extracted by two reviewers. The primary outcome measure is effectiveness of the intervention. Methodological quality of included studies will be assessed by two reviewers using the PEDro scale. The overall quality of evidence will be assessed with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework, which has been adapted for network meta-analyses. The available evidence will be summarised using a network diagram. A contribution matrix will be presented to allow assessment of direct and indirect evidence. Forest plots will be constructed to visualise effects of all included exercise interventions. Pairwise effect sizes will be calculated by including all evidence available in the network. Effect measures for treatments that have not been compared in a pairwise RCT can be compared indirectly by contrasting effect sizes of comparisons with a common comparator.Ethics and disseminationThis work synthesises evidence from previously published studies and does not require ethics review or approval. A manuscript describing the findings will be submitted for publication in a peer-reviewed scientific journal.PROSPERO registration numberCRD42019126523.

Background In the midst of the coronavirus pandemic, the International Chiropractors Association (ICA) posted reports claiming that chiropractic care can impact the immune system. These claims clash with recommendations from the World Health Organization and World Federation of Chiropractic. We discuss the scientific validity of the claims made in these ICA reports. Main body We reviewed the two reports posted by the ICA on their website on March 20 and March 28, 2020. We explored the method used to develop the claim that chiropractic adjustments impact the immune system and discuss the scientific merit of that claim. We provide a response to the ICA reports and explain why this claim lacks scientific credibility and is dangerous to the public. More than 150 researchers from 11 countries reviewed and endorsed our response. Conclusion In their reports, the ICA provided no valid clinical scientific evidence that chiropractic care can impact the immune system. We call on regulatory authorities and professional leaders to take robust political and regulatory action against those claiming that chiropractic adjustments have a clinical impact on the immune system.

Purpose: To investigate the effectiveness of general, whole-body, physical exercise interventions compared to usual care for individuals with chronic neck pain.Materials and methods: Systematic rev...

The immunopathogenesis of inflammatory bowel disease (IBD) has been attributed to a combination of host genetics and intestinal dysbiosis. Previous work in a small cohort of IBD patients suggested that pro-inflammatory bacterial taxa are highly coated with secretory immunoglobulin IgA. Using bacterial fluorescence-activated cell sorting coupled with 16S rRNA gene sequencing (IgA-SEQ), we profiled IgA coating of intestinal microbiota in a large cohort of IBD patients and identified bacteria associated with disease and treatment. Forty-three bacterial taxa displayed significantly higher IgA coating in IBD compared with controls, including 8 taxa exhibiting differential IgA coating but similar relative abundance. Patients treated with anti-TNF-α therapies exhibited dramatically altered microbiota-specific IgA responses compared with controls. Furthermore, increased IgA coating of Oscillospira was associated with a delay in time to surgery. These results demonstrate that investigating IgA responses to microbiota can uncover potential disease-modifying taxa and reveal improved biomarkers of clinical course in IBD.

Anti-microbial signaling pathways are normally triggered by innate immune receptors when detecting pathogenic microbes to provide protective immunity. Here we show that the inflammasome sensor Nlrp1 aggravates DSS-induced experimental mouse colitis by limiting beneficial, butyrate-producing Clostridiales in the gut. The colitis-protective effects of Nlrp1 deficiency are thus reversed by vancomycin treatment, but recapitulated with butyrate supplementation in wild-type mice. Moreover, an activating mutation in Nlrp1a increases IL-18 and IFNγ production, and decreases colonic butyrate to exacerbate colitis. We also show that, in patients with ulcerative colitis, increased NLRP1 in inflamed regions of the colon is associated with increased IFN-γ. In this context, NLRP1, IL-18 or IFN-γ expression negatively correlates with the abundance of Clostridiales in human rectal mucosal biopsies. Our data identify the NLRP1 inflammasome to be a key negative regulator of protective, butyrate-producing commensals, which therefore promotes inflammatory bowel disease.

The city of Leiden, the Netherlands, is home to a well-known university and several excellent museums. Among them is Museum Boerhaave, the Dutch National Museum for the History of Science and Medic...

In forensic casework it is common that multiple pieces of evidence are obtained in a single case. For the evaluation of such evidence, one cannot simply assume that they originated from the same source. If this can be disputed, one could decide to report the evidential value of the separate pieces by computing likelihood ratios (LRs) for them separately. However, by doing so, information regarding the conditional dependency structure is lost and the potentially difficult step of combining them is left to the trier of fact. Especially in situations where the pieces of evidence are of the same type, a combined evaluation could be substantially more informative. In such situations, it is not unrealistic that the separate evidential values are not optimally combined by the trier of fact. From a scientific point of view, the optimal way is that the forensic scientist combines the forensic evidence in a report using hypotheses at the 'activity level'. In practice, however, this is not always feasible for every case for reasons of efficiency. In this article, we explore what can be done in cases where the optimal solution is too costly. For a combined evaluation, the prior distribution for the number of distinct sources of the pieces of evidence becomes part of the LR. Generally, prior probabilities are beyond the scope of expertise of the forensic specialist and are left to the trier of fact to decide.Wepropose a lower bound LRapproach for such situations that is independent of the prior distribution. Using a set of examples, we present how this method can be applied in practice.