Validation of the German version of the STarT-Back Tool (STarT-G): a cohort study with patients from primary care practices

Background: Current research emphasizes the high prevalence and costs of low back pain (LBP). The STarT Back Tool was designed to support primary care decision making for treatment by helping to determine the treatment prognosis of patients with non-specific low back pain. The German version is the STarT-G. The cross-cultural translation of the tool followed a structured and widely accepted process but to date it was only partially validated with a small sample. The aim of the study was to test the psychometric properties construct validity, discriminative ability, internal consistency and test-retest-reliability of the STarT-G and to compare them with values given for the original English version. Methods: A consecutive cohort study with a two-week retest was conducted among patients with non-specific LBP, aged 18 to 60 years, from primary care practices. Questionnaires were collected before the first consultation, and two weeks later by post, using the following reference standards: the Roland and Morris disability questionnaire, the Tampa Scale of Kinesiophobia, the Pain Catastrophizing Scale and the Hospital Anxiety and Depression Scale. Psychometric properties examined included the tool’s discriminative abilities, whether the psychosocial subscale was one factor, internal consistency, item redundancy, test-retest reliability and floor and ceiling effects. Results: There were 228 patients recruited with a mean age of 42.2 (SD 11.0) years, and 53 % were female. The areas under the curve (AUC) for discriminative ability ranged from 0.70 (STarT-G Subscale - Pain Catastrophizing Scale; CI95 0.63, 0.78) to 0.77 (STarT-G Total - Composite reference standard, CI95 0.60, 0.94). Factor loadings ranged from 0.49 to 0.74. Cronbach’s alpha testing the internal consistency and redundancy for the total/subscale scores were α = 0.52/0.55 respectively. The STarT-G test-retest reliability Kappa values for the total/subscale scores were 0.67/0.68 respectively. No floor or ceiling effects were present. Conclusions: The STarT-G shows acceptable psychometric properties although not in exact agreement with the original English version. The items previously regarded as a psychosocial subscale may be better seen as an index of different individual psychosocial constructs. The relevance of using the tool at the point of consultation should be further examined

Nanoscale Imaging Reveals a Tetraspanin-CD9 Coordinated Elevation of Endothelial ICAM-1 Clusters

Endothelial barriers have a central role in inflammation as they allow or deny the passage of leukocytes from the vasculature into the tissue. To bind leukocytes, endothelial cells form adhesive clusters containing tetraspanins and ICAM-1, so-called endothelial adhesive platforms (EAPs). Upon leukocyte binding, EAPs evolve into docking structures that emanate from the endothelial surface while engulfing the leukocyte. Here, we show that TNF-α is sufficient to induce apical protrusions in the absence of leukocytes. Using advanced quantitation of atomic force microscopy (AFM) recordings, we found these structures to protrude by 160 ± 80 nm above endothelial surface level. Confocal immunofluorescence microscopy proved them positive for ICAM-1, JAM-A, tetraspanin CD9 and f-actin. Microvilli formation was inhibited in the absence of CD9. Our findings indicate that stimulation with TNF-α induces nanoscale changes in endothelial surface architecture and that—via a tetraspanin CD9 depending mechanism—the EAPs rise above the surface to facilitate leukocyte capture

The functional connectome of 3,4‐methyldioxymethamphetamine‐related declarative memory impairments

The chronic intake of 3,4‐methylenedioxymethamphetamine (MDMA, “ecstasy”) bears a strong risk for sustained declarative memory impairments. Although such memory deficits have been repeatedly reported, their neurofunctional origin remains elusive. Therefore, we here investigate the neuronal basis of altered declarative memory in recurrent MDMA users at the level of brain connectivity. We examined a group of 44 chronic MDMA users and 41 demographically matched controls. Declarative memory performance was assessed by the Rey Auditory Verbal Learning Test and a visual associative learning test. To uncover alterations in the whole brain connectome between groups, we employed a data‐driven multi‐voxel pattern analysis (MVPA) approach on participants' resting‐state functional magnetic resonance imaging data. Recent MDMA use was confirmed by hair analyses. MDMA users showed lower performance in delayed recall across tasks compared to well‐matched controls with moderate‐to‐strong effect sizes. MVPA revealed a large cluster located in the left postcentral gyrus of global connectivity differences between groups. Post hoc seed‐based connectivity analyses with this cluster unraveled hypoconnectivity to temporal areas belonging to the auditory network and hyperconnectivity to dorsal parietal regions belonging to the dorsal attention network in MDMA users. Seed‐based connectivity strength was associated with verbal memory performance in the whole sample as well as with MDMA intake patterns in the user group. Our findings suggest that functional underpinnings of MDMA‐related memory impairments encompass altered patterns of multimodal sensory integration within auditory processing regions to a functional heteromodal connector hub, the left postcentral gyrus. In addition, hyperconnectivity in regions of a cognitive control network might indicate compensation for degraded sensory processing

Conflict monitoring and emotional processing in 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine users – A comparative neurophysiological study

In stimulant use and addiction, conflict control processes are crucial for regulating substance use and sustaining abstinence, which can be particularly challenging in social-affective situations. Users of methamphetamine (METH, “Ice”) and 3,4-methylenedioxymethamphetamine (MDMA, “Ecstasy”) both experience impulse control deficits, but display different social-affective and addictive profiles. We thus aimed to compare the effects of chronic use of the substituted amphetamines METH and MDMA on conflict control processes in different social-affective contexts (i.e., anger and happiness) and investigate their underlying neurophysiological mechanisms. For this purpose, chronic but recently abstinent users of METH (n = 38) and MDMA (n = 42), as well as amphetamine-naïve healthy controls (n = 83) performed an emotional face-word Stroop paradigm, while event-related potentials (ERPs) were recorded. Instead of substance-specific differences, both MDMA and METH users showed smaller behavioral effects of cognitive-emotional conflict processing (independently of emotional valence) and selective deficits in emotional processing of anger content. Both effects were underpinned by stronger P3 ERP modulations suggesting that users of substituted amphetamines employ altered stimulus–response mapping and decision-making. Given that these processes are modulated by noradrenaline and that both MDMA and METH use may be associated with noradrenergic dysfunctions, the noradrenaline system may underlie the observed substance-related similarities. Better understanding the functional relevance of this currently still under-researched neurotransmitter and its functional changes in chronic users of substituted amphetamines is thus an important avenue for future research

microRNA miR-142-3p Inhibits Breast Cancer Cell Invasiveness by Synchronous Targeting of WASL, Integrin Alpha V, and Additional Cytoskeletal Elements

MicroRNAs (miRNAs, micro ribonucleic acids) are pivotal post-transcriptional regulators of gene expression. These endogenous small non-coding RNAs play significant roles in tumorigenesis and tumor progression. miR-142-3p expression is dysregulated in several breast cancer subtypes. We aimed at investigating the role of miR-142-3p in breast cancer cell invasiveness. Supported by transcriptomic Affymetrix array analysis and confirmatory investigations at the mRNA and protein level, we demonstrate that overexpression of miR-142-3p in MDA-MB-231, MDA-MB-468 and MCF-7 breast cancer cells leads to downregulation of WASL (Wiskott-Aldrich syndrome-like, protein: N-WASP), Integrin-αV, RAC1, and CFL2, molecules implicated in cytoskeletal regulation and cell motility. ROCK2, IL6ST, KLF4, PGRMC2 and ADCY9 were identified as additional targets in a subset of cell lines. Decreased Matrigel invasiveness was associated with the miR-142-3p-induced expression changes. Confocal immunofluorescence microscopy, nanoscale atomic force microscopy and digital holographic microscopy revealed a change in cell morphology as well as a reduced cell volume and size. A more cortical actin distribution and a loss of membrane protrusions were observed in cells overexpressing miR-142-3p. Luciferase activation assays confirmed direct miR-142-3p-dependent regulation of the 3’-untranslated region of ITGAV and WASL. siRNA-mediated depletion of ITGAV and WASL resulted in a significant reduction of cellular invasiveness, highlighting the contribution of these factors to the miRNA-dependent invasion phenotype. While knockdown of WASL significantly reduced the number of membrane protrusions compared to controls, knockdown of ITGAV resulted in a decreased cell volume, indicating differential contributions of these factors to the miR-142-3p-induced phenotype. Our data identify WASL, ITGAV and several additional cytoskeleton-associated molecules as novel invasion-promoting targets of miR-142-3p in breast cancer

advancing the evidence base for public policies impacting on dietary behaviour physical activity and sedentary behaviour in europe the policy evaluation network promoting a multidisciplinary approach

Abstract Non-communicable diseases (NCDs) are the leading cause of global mortality. As the social and economic costs of NCDs have escalated, action is needed to tackle important causes of many NCD's: low physical activity levels and unhealthy dietary behaviours. As these behaviours are driven by upstream factors, successful policy interventions are required that encourage healthy dietary behaviours, improve physical activity levels and reduce sedentary behaviours of entire populations. However, to date, no systematic research on the implementation and evaluation of policy interventions related to these health behaviours has been conducted across Europe. Consequently, no information on the merit, gaps, worth or utility of cross-European policy interventions is available, and no guidance or recommendations on how to enhance this knowledge across European countries exists. As part of the Joint Programming Initiative "A Healthy Diet for a Healthy Life" (JPI HDHL), 28 research institutes from seven European countries and New Zealand have combined their expertise to form the Policy Evaluation Network (PEN). PEN's aim is to advance tools to identify, evaluate, implement and benchmark policies designed to directly or indirectly target dietary behaviours, physical activity, and sedentary behaviour in Europe, as well as to understand how these policies increase or decrease health inequalities. Using well-defined evaluation principles and methods, PEN will examine the content, implementation and impact of policies addressing dietary behaviour, physical activity levels and sedentary behaviour across Europe. It will realise the first steps in a bespoke health policy monitoring and surveillance system for Europe, and refine our knowledge of appropriate research designs and methods for the quantification of policy impact. It will contribute to our understanding of how to achieve successful transnational policy implementation and monitoring of these policies in different cultural, demographic or socioeconomic settings. PEN will consider equity and diversity aspects to ensure that policy actions are inclusive and culturally sensitive. Finally, based on three policy cases, PEN will illustrate how best to evaluate the implementation and impact of such policies in order to yield healthy diets and activity patterns that result in healthier lives for all European citizens

SPINN: Synergistic Progressive Inference of Neural Networks over Device and Cloud

Despite the soaring use of convolutional neural networks (CNNs) in mobile applications, uniformly sustaining high-performance inference on mobile has been elusive due to the excessive computational demands of modern CNNs and the increasing diversity of deployed devices. A popular alternative comprises offloading CNN processing to powerful cloud-based servers. Nevertheless, by relying on the cloud to produce outputs, emerging mission-critical and high-mobility applications, such as drone obstacle avoidance or interactive applications, can suffer from the dynamic connectivity conditions and the uncertain availability of the cloud. In this paper, we propose SPINN, a distributed inference system that employs synergistic device-cloud computation together with a progressive inference method to deliver fast and robust CNN inference across diverse settings. The proposed system introduces a novel scheduler that co-optimises the early-exit policy and the CNN splitting at run time, in order to adapt to dynamic conditions and meet user-defined service-level requirements. Quantitative evaluation illustrates that SPINN outperforms its state-of-the-art collaborative inference counterparts by up to 2x in achieved throughput under varying network conditions, reduces the server cost by up to 6.8x and improves accuracy by 20.7% under latency constraints, while providing robust operation under uncertain connectivity conditions and significant energy savings compared to cloud-centric execution.Comment: Accepted at the 26th Annual International Conference on Mobile Computing and Networking (MobiCom), 202

Evaluation of cystatin C as an early biomarker of cadmium nephrotoxicity in the rat

Cadmium (Cd) is a nephrotoxic environmental pollutant that causes insidious injury to the proximal tubule that results in severe polyuria and proteinuria. Cystatin C is a low molecular weight protein that is being evaluated as a serum and urinary biomarker for various types of ischemic and nephrotoxic renal injury. The objective of the present study was to determine if cystatin C might be a useful early biomarker of Cd nephrotoxicity. Male Sprague–Dawley rats were given daily injections of Cd for up to 12 weeks. At 3, 6, 9 and 12 weeks, urine samples were analyzed for cystatin C, protein, creatinine, β2 microglobulin and kidney injury molecule-1. The results showed that Cd caused a significant increase in the urinary excretion of cystatin C that occurred 3–4 weeks before the onset of polyuria and proteinuria. Serum levels of cystatin C were not altered by Cd. Immunolabeling studies showed that Cd caused the relocalization of cystatin C from the cytoplasm to the apical surface of the epithelial cells of the proximal tubule. The Cd-induced changes in cystatin C labelling paralleled those of the brush border transport protein, megalin, which has been implicated as a mediator of cystatin C uptake in the proximal tubule. These results indicate that Cd increases the urinary excretion of cystatin C, and they suggest that this effect may involve disruption of megalin-mediated uptake of cystatin C by epithelial cells of the proximal tubule