Magnetic Resonance Spectroscopy discriminates the response to microglial stimulation of wild type and Alzheimer's disease models.

Microglia activation has emerged as a potential key factor in the pathogenesis of Alzheimers disease. Metabolite levels assessed by magnetic resonance spectroscopy (MRS) are used as markers of neuroinflammation in neurodegenerative diseases, but how they relate to microglial activation in health and chronic disease is incompletely understood. Using MRS, we monitored the brain metabolic response to lipopolysaccharides (LPS)-induced microglia activation in vivo in a transgenic mouse model of Alzheimers disease (APP/PS1) and healthy controls (wild-type (WT) littermates) over 4 hours. We assessed reactive gliosis by immunohistochemistry and correlated metabolic and histological measures. In WT mice, LPS induced a microglial phenotype consistent with activation, associated with a sustained increase in macromolecule and lipid levels (ML9). This effect was not seen in APP/PS1 mice, where LPS did not lead to a microglial response measured by histology, but induced a late increase in the putative inflammation marker myoinositol (mI) and metabolic changes in total creatine and taurine previously reported to be associated with amyloid load. We argue that ML9 and mI distinguish the response of WT and APP/PS1 mice to immune mediators. Lipid and macromolecule levels may represent a biomarker of activation of healthy microglia, while mI may not be a glial marker

Overall prognosis of preschool autism spectrum disorder diagnoses

Background Autism spectrum disorder is a neurodevelopmental disorder characterised by social communication difficulties, restricted interests and repetitive behaviours. The clinical pathway for children with a diagnosis of autism spectrum disorder is varied, and current research suggests some children may not continue to meet diagnostic criteria over time. Objectives The primary objective of this review was to synthesise the available evidence on the proportion of preschool children who have a diagnosis of autism spectrum disorder at baseline (diagnosed before six years of age) who continue to meet diagnostic criteria at follow‐up one or more years later (up to 19 years of age). Search methods We searched MEDLINE, Embase, PsycINFO, and eight other databases in October 2017 and ran top‐up searches up to July 2021. We also searched reference lists of relevant systematic reviews. Selection criteria Two review authors independently assessed prospective and retrospective follow‐up studies that used the same measure and process within studies to diagnose autism spectrum disorder at baseline and follow‐up. Studies were required to have at least one year of follow‐up and contain at least 10 participants. Participants were all aged less than six years at baseline assessment and followed up before 19 years of age. Data collection and analysis We extracted data on study characteristics and the proportion of children diagnosed with autism spectrum disorder at baseline and follow‐up. We also collected information on change in scores on measures that assess the dimensions of autism spectrum disorder (i.e. social communication and restricted interests and repetitive behaviours). Two review authors independently extracted data on study characteristics and assessed risk of bias using a modified quality in prognosis studies (QUIPS) tool. We conducted a random‐effects meta‐analysis or narrative synthesis, depending on the type of data available. We also conducted prognostic factor analyses to explore factors that may predict diagnostic outcome. Main results In total, 49 studies met our inclusion criteria and 42 of these (11,740 participants) had data that could be extracted. Of the 42 studies, 25 (60%) were conducted in North America, 13 (31%) were conducted in Europe and the UK, and four (10%) in Asia. Most (52%) studies were published before 2014. The mean age of the participants was 3.19 years (range 1.13 to 5.0 years) at baseline and 6.12 years (range 3.0 to 12.14 years) at follow‐up. The mean length of follow‐up was 2.86 years (range 1.0 to 12.41 years). The majority of the children were boys (81%), and just over half (60%) of the studies primarily included participants with intellectual disability (intelligence quotient < 70). The mean sample size was 272 (range 10 to 8564). Sixty‐nine per cent of studies used one diagnostic assessment tool, 24% used two tools and 7% used three or more tools. Diagnosis was decided by a multidisciplinary team in 41% of studies. No data were available for the outcomes of social communication and restricted and repetitive behaviours and interests. Of the 42 studies with available data, we were able to synthesise data from 34 studies (69% of all included studies; n = 11,129) in a meta‐analysis. In summary, 92% (95% confidence interval 89% to 95%) of participants continued to meet diagnostic criteria for autism spectrum disorder from baseline to follow‐up one or more years later; however, the quality of the evidence was judged as low due to study limitations and inconsistency. The majority of the included studies (95%) were rated at high risk of bias. We were unable to explore the outcomes of change in social communication and restricted and repetitive behaviour and interests between baseline and follow‐up as none of the included studies provided separate domain scores at baseline and follow‐up. Details on conflict of interest were reported in 24 studies. Funding support was reported by 30 studies, 12 studies omitted details on funding sources and two studies reported no funding support. Declared funding sources were categorised as government, university or non‐government organisation or charity groups. We considered it unlikely funding sources would have significantly influenced the outcomes, given the nature of prognosis studies. Authors' conclusions Overall, we found that nine out of 10 children who were diagnosed with autism spectrum disorder before six years of age continued to meet diagnostic criteria for autism spectrum disorder a year or more later, however the evidence was uncertain. Confidence in the evidence was rated low using GRADE, due to heterogeneity and risk of bias, and there were few studies that included children diagnosed using a current classification system, such as the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM‐5) or the eleventh revision of the International Classification of Diseases (ICD‐11). Future studies that are well‐designed, prospective and specifically assess prognosis of autism spectrum disorder diagnoses are needed. These studies should also include contemporary diagnostic assessment methods across a broad range of participants and investigate a range of relevant prognostic factors

Performance and Results of the Triple Buffering Built-In in a Raspberry PI to Optimize the Distribution of Information from a Smart Sensor

“ The final publication is available at Springer via http://dx.doi.org/ 10.1007/978-3-319-07593-8_33"Currently, 3D sensors can be considered an evolution of cameras by providing the image with its depth information. These sensors have a generic function and the programmer has to process the received information in order to be adapted and used in a specific environment. In robots navigation, the 3D information can be useful for basic behaviours such as obstacles avoidance or even more complex behaviours such as maps generation . In this article an image management system provided by the xTion intelligent sensor is presented. The xTion sensor provides a VGA image and a 3D depth, which allows it to be used for several purposes. In order to distribute the data, it is acquired, processed and sent to several clients with a triple buffer system modified to serve the most recent image to the client. The system is programmed in C for Linux and built-in in a Raspberry PI. The article exposes the performance and results from monitoring the frame's delay comparing it with a simple and a double buffer system widely used in this kind of systems.Coordinated project COBAMI: Mission-based Hierarchical Control. Education and Science Department, Spanish Government. CICYT: MICINN: DPI2011-28507-C02-01/02 and project “Real time distributed control systems” of the Support Program for Research and Development 2012 UPV (PAID-06-12).Jiménez García, JL.; Poza Luján, JL.; Posadas Yagüe, JL.; Baselga Masiá, D.; Simó Ten, JE. (2014). Performance and Results of the Triple Buffering Built-In in a Raspberry PI to Optimize the Distribution of Information from a Smart Sensor. En Distributed Computing and Artificial Intelligence, 11th International Conference. Springer. 279-286. https://doi.org/10.1007/978-3-319-07593-8_33S279286Brignell, J.E.: The future of intelligent sensors: a problem of technology or ethics? Sensors and Actuators 56, 11–15 (1996)Fernandes, J., Laranjeira, J., Novais, P., Marreiros, G., Neves, J.: A Context Aware Architecture to Support People with Partial Visual Impairments. In: Omatu, S., Neves, J., Rodriguez, J.M.C., Paz Santana, J.F., Gonzalez, S.R. (eds.) Distrib. Computing & Artificial Intelligence. AISC, vol. 217, pp. 333–340. Springer, Heidelberg (2013)Chien-Hui, L., Kuan-Wei, L., Ting-Hua, C., Che-Chen, C., Charles, H.-P.: Fall Detection by a SVM-Based Cloud System with Motion Sensors. In: Yueh-Min, H., Han-Chieh, C., Der-Jiunn, D., James J (Jong Hyuk), P. (eds.) Advanced Technologies, Embedded and Multimedia for Human-centric Computing. LNEE, vol. 260, pp. 37–45. Springer, Heidelberg (2014)Grzejszczak, T., Mikulski, M., Szkodny, T., Jędrasiak, K.: Gesture Based Robot Control. In: Bolc, L., Tadeusiewicz, R., Chmielewski, L.J., Wojciechowski, K. (eds.) ICCVG 2012. LNCS, vol. 7594, pp. 407–413. Springer, Heidelberg (2012)Lee, C.S., Gyu, M.L., Woo, S.R.: Standardization and challenges of smart ubiquitous networks in ITU-T. IEEE Communications Magazine 51(10), 102–110 (2013)Dias, D.M., Mukherjee, R., Sitaram, D., Tewari, R.: Buffering and Caching in Large-Scale Video Servers. In: Prac. of COMPCON (1995)Tagami, Y., Watanabe, M., Yamaguchi, Y.: Development Environment of 3D Graphics Systems. Fujitsu Scientific & Technical Journal 49(1), 64–70 (2013)Khan, S., Bailey, D., Gupta, G.: Simulation of Triple Buffer Scheme. In: Second International Conference on Computer and Electrical Engineering (2009)ASUS: Xtion Pro Live, http://www.asus.comEdwards, C.: Not-so-humble raspberry pi gets big ideas. Engineering & Technology 8(3), 30–33 (2013)Poza-Luján, J.L., Posadas-Yagüe, J.L., Simó-Ten, J.E.: Quality of Control and Quality of Service in Mobile Robot Navigation. International Journal of Imaging and Robotics 8(1) (2014)Norman Villaroman, N., Rowe, D., Swan, B.: Teaching natural user interaction using OpenNI and the Microsoft Kinect sensor. In: Proceedings of the 2011 Conference on Information Technology Education (SIGITE 2011), pp. 227–232. ACM, New York (2011)Bradski, G., Kaehler, A.: Learning OpenCV: Computer vision with the OpenCV library. O’reilly (2008)Ollero, A.: Intelligent mobile robot navigation. STAR, vol. 16. Springer, Heidelberg (2005)Freese, M., Singh, S., Ozaki, F., Matsuhira, N.: Virtual Robot Experimentation Platform V-REP: A Versatile 3D Robot Simulator. In: Ando, N., Balakirsky, S., Hemker, T., Reggiani, M., von Stryk, O. (eds.) SIMPAR 2010. LNCS (LNAI), vol. 6472, pp. 51–62. Springer, Heidelberg (2010

Steady-state modulation of voltage-gated K+ channels in rat arterial smooth muscle by cyclic AMP-dependent protein kinase and protein phosphatase 2B

Voltage-gated potassium channels (Kv) are important regulators of membrane potential in vascular smooth muscle cells, which is integral to controlling intracellular Ca2+ concentration and regulating vascular tone. Previous work indicates that Kv channels can be modulated by receptor-driven alterations of cyclic AMP-dependent protein kinase (PKA) activity. Here, we demonstrate that Kv channel activity is maintained by tonic activity of PKA. Whole-cell recording was used to assess the effect of manipulating PKA signalling on Kv and ATP-dependent K+ channels of rat mesenteric artery smooth muscle cells. Application of PKA inhibitors, KT5720 or H89, caused a significant inhibition of Kv currents. Tonic PKA-mediated activation of Kv appears maximal as application of isoprenaline (a β-adrenoceptor agonist) or dibutyryl-cAMP failed to enhance Kv currents. We also show that this modulation of Kv by PKA can be reversed by protein phosphatase 2B/calcineurin (PP2B). PKA-dependent inhibition of Kv by KT5720 can be abrogated by pre-treatment with the PP2B inhibitor cyclosporin A, or inclusion of a PP2B auto-inhibitory peptide in the pipette solution. Finally, we demonstrate that tonic PKA-mediated modulation of Kv requires intact caveolae. Pre-treatment of the cells with methyl-β-cyclodextrin to deplete cellular cholesterol, or adding caveolin-scaffolding domain peptide to the pipette solution to disrupt caveolae-dependent signalling each attenuated PKA-mediated modulation of the Kv current. These findings highlight a novel, caveolae-dependent, tonic modulatory role of PKA on Kv channels providing new insight into mechanisms and the potential for pharmacological manipulation of vascular tone