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Abstract Background Aberrant expression of small noncoding RNAs called microRNAs (miRNAs) is a common feature of several human diseases. The objective of the study was to identify miRNA modulation in patients with complex regional pain syndrome (CRPS) a chronic pain condition resulting from dysfunction in the central and/or peripheral nervous systems. Due to a multitude of inciting pathologies, symptoms and treatment conditions, the CRPS patient population is very heterogeneous. Our goal was to identify differentially expressed miRNAs in blood and explore their utility in patient stratification. Methods We profiled miRNAs in whole blood from 41 patients with CRPS and 20 controls using TaqMan low density array cards. Since neurogenic inflammation is known to play a significant role in CRPS we measured inflammatory markers including chemokines, cytokines, and their soluble receptors in blood from the same individuals. Correlation analyses were performed for miRNAs, inflammatory markers and other parameters including disease symptoms, medication, and comorbid conditions. Results Three different groups emerged from miRNA profiling. One group was comprised of 60% of CRPS patients and contained no control subjects. miRNA profiles from the remaining patients were interspersed among control samples in the other two groups. We identified differential expression of 18 miRNAs in CRPS patients. Analysis of inflammatory markers showed that vascular endothelial growth factor (VEGF), interleukin1 receptor antagonist (IL1Ra) and monocyte chemotactic protein-1 (MCP1) were significantly elevated in CRPS patients. VEGF and IL1Ra showed significant correlation with the patients reported pain levels. Analysis of the patients who were clustered according to their miRNA profile revealed correlations that were not significant in the total patient population. Correlation analysis of miRNAs detected in blood with additional parameters identified miRNAs associated with comorbidities such as headache, thyroid disorder and use of narcotics and antiepileptic drugs. Conclusions miRNA profiles can be useful in patient stratification and have utility as potential biomarkers for pain. Differentially expressed miRNAs can provide molecular insights into gene regulation and could lead to new therapeutic intervention strategies for CRPS.

Featured Application: Application as a decision-support tool in the management of level crossings. Railway level crossings pose risks to both train passengers and road users, worsened by the complex interaction between rail and road traffic, particularly on local railways. This study introduces a Risk Management (RM) framework designed to enhance safety at level crossings on local railways by providing a decision-support tool. By individually assessing risk factors, the framework allows for a precise evaluation of the current risk levels in terms of both Cumulated and Individual Risk levels, Individual Risk, and the impacts of potential modifications. The framework allows the quantitative assessment of risk and resource optimization, enabling infrastructure managers to identify high-risk crossings and select the most effective safety interventions. The framework was applied to 96 level crossings on an Italian local railway line, demonstrating its ability to support decision-making for targeted interventions as well as broader network-level actions, significantly improving system safety. [ABSTRACT FROM AUTHOR]

In the airport pavement management systems (APMSs), a focus point is the decision-making process. It enables finding the optimal strategy for maintaining a flight infrastructure in adequate condition over a given period, while considering the operating conditions of the airside. In this context, the present study analyzes the factors involved in the optimization processes by investigating how much they influence the solutions. Using the analysis processes connected to the APMS, the present study also includes the identification of specific intervention areas through clustering algorithms, minimizing the fixed operating costs. More specifically, the use of K-means clustering and the heuristic algorithms connected to the choices of the maintenance activities, allow possible scenarios replicating the different needs of managers to be investigated. In this way, the research work analyzes the influence of the alternatives in terms of pavement quality and total activities duration. Through this study it is shown that there is not a unique optimal strategy, but several possible solutions that can be undertaken by the airport managers according to their needs. However, the comparison of the results obtained in this study could become a useful tool for airport managers for better planning and management of the flight infrastructures. [ABSTRACT FROM AUTHOR]

Physical exercise promotes neural plasticity in the brain of healthy subjects and modulates pathophysiological neural plasticity after sensorimotor loss, but the mechanisms of this action are not fully understood. After spinal cord injury, cortical reorganization can be maximized by exercising the non-affected body or the residual functions of the affected body. However, exercise per se also produces systemic changes - such as increased cardiovascular fitness, improved circulation and neuroendocrine changes - that have a great impact on brain function and plasticity. It is therefore possible that passive exercise therapies typically applied below the level of the lesion in patients with spinal cord injury could put the brain in a more plastic state and promote cortical reorganization. To directly test this hypothesis, we applied passive hindlimb bike exercise after complete thoracic transection of the spinal cord in adult rats. Using western blot analysis, we found that the level of proteins associated with plasticity - specifically ADCY1 and BDNF - increased in the somatosensory cortex of transected animals that received passive bike exercise compared to transected animals that received sham exercise. Using electrophysiological techniques, we then verified that neurons in the deafferented hindlimb cortex increased their responsiveness to tactile stimuli delivered to the forelimb in transected animals that received passive bike exercise compared to transected animals that received sham exercise. Passive exercise below the level of the lesion, therefore, promotes cortical reorganization after spinal cord injury, uncovering a brain-body interaction that does not rely on intact sensorimotor pathways connecting the exercised body parts and the brain.

The present paper reports different applications which have a common data source: Automatic Road Analyzer (ARAN) of the Transport Infrastructure Laboratory of the University of Catania. Data surveyed with ARAN were used to develop performance indicators of the road asset. A BIM model makes possible to improve the flexibility in information access and to merge data with the aim to allow a complete Road Asset Management (RAM) application in the same environment Data Collected and stored with high efficiency equipment allows to get high quality and detailed information of the road asset and offers the chance to create georeferenced database which can be used both for safety assessment and for the other RAM related applications. BIM provides a comprehensive approach involving the generation and management of transport infrastructure assets using 3D digital representations of their physical and functional characteristics allowing to produce ad hoc output for investigate in the same environment different parts of the RAM.

Interaction of the chemokine CXCL12 with its receptor CXCR4 promotes neuronal function and survival during embryonic development and throughout adulthood. Previous studies indicated that μ-opioid agonists specifically elevate neuronal levels of the protein ferritin heavy chain (FHC), which negatively regulates CXCR4 signaling and affects the neuroprotective function of the CXCL12/CXCR4 axis. Here, we determined that CXCL12/CXCR4 activity increased dendritic spine density, and also examined FHC expression and CXCR4 status in opiate abusers and patients with HIV-associated neurocognitive disorders (HAND), which is typically exacerbated by illicit drug use. Drug abusers and HIV patients with HAND had increased levels of FHC, which correlated with reduced CXCR4 activation, within cortical neurons. We confirmed these findings in a nonhuman primate model of SIV infection with morphine administration. Transfection of a CXCR4-expressing human cell line with an iron-deficient FHC mutant confirmed that increased FHC expression deregulated CXCR4 signaling and that this function of FHC was independent of iron binding. Furthermore, examination of morphine-treated rodents and isolated neurons expressing FHC shRNA revealed that FHC contributed to morphine-induced dendritic spine loss. Together, these data implicate FHC-dependent deregulation of CXCL12/CXCR4 as a contributing factor to cognitive dysfunction in neuroAIDS., Introduction The chemokine CXCL12 and its cognate receptor CXCR4 perform multiple functions essential for CNS development and function, including guiding migration and differentiation of neuronal precursor cells (1), regulating cell [...]

The development of advanced design tools and the increasing performance of the materials allow realising increasingly complex infrastructures that, as such, make the possible presence of errors made in the different phases of realisation of a work even more amplified. In this context, an efficient and effective design verification service allows identifying possible non-conformities in a phase of the process of the work that still makes "sustainable" modifications possible so as to reduce the onset of disputes and variants as much as possible, with the increase in time and costs associated with them. The in-depth analysis of the main characteristics of verification in terms of attributes, methods and legislation performed in this work allowed defining and representing specific checklists, highlighting their peculiarities and potential in contributing to the quality of a railway infrastructure, also in a context of integration in the wider development of BIM technology. [ABSTRACT FROM AUTHOR]