BMP13 Prevents the Effects of Annular Injury in an Ovine Model

Chronic back pain is a global health problem affecting millions of people worldwide and carries significant economic and social morbidities. Intervertebral disc damage and degeneration is a major cause of back pain, characterised by histological and biochemical changes that have been well documented in animal models. Recently there has been intense interest in early intervention in disc degeneration using growth factors or stem cell transplantation, to replenish the diseased tissues. Bone Morphogenetic Proteins (BMPs) have been approved for clinical use in augmenting spinal fusions, and may represent candidate molecules for intervertebral disc regeneration

BMP-13 Emerges as a Potential Inhibitor of Bone Formation

Bone morphogenetic protein-13 (BMP-13) plays an important role in skeletal development. In the light of a recent report that mutations in the BMP-13 gene are associated with spine vertebral fusion in Klippel-Feil syndrome, we hypothesized that BMP-13 signaling is crucial for regulating embryonic endochondral ossification. In this study, we found that BMP-13 inhibited the osteogenic differentiation of human bone marrow multipotent mesenchymal stromal cells (BM MSCs) in vitro. The endogenous BMP-13 gene expression in MSCs was examined under expansion conditions. The MSCs were then induced to differentiate into osteoblasts in osteo-inductive medium containing exogenous BMP-13. Gene expression was analysed by real-time PCR. Alkaline phosphatase (ALP) expression and activity, proteoglycan (PG) synthesis and matrix mineralization were assessed by cytological staining or ALP assay. Results showed that endogenous BMP-13 mRNA expression was higher than BMP-2 or -7 during MSC growth. BMP-13 supplementation strongly inhibited matrix mineralization and ALP activity of osteogenic differentiated MSCs, yet increased PG synthesis under the same conditions. In conclusion, BMP-13 inhibited osteogenic differentiation of MSCs, implying that functional mutations or deficiency of BMP-13 may allow excess bone formation. Our finding provides an insight into the molecular mechanisms and the therapeutic potential of BMP-13 in restricting pathological bone formation

Global Burden of Aortic Aneurysm and Attributable Risk Factors from 1990 to 2017

Background: To date, our understanding of the global aortic aneurysm (AA) burden distribution is very limited. Objective: To assess a full view of global AA burden distribution and attributable risk factors from 1990 to 2017. Methods: We extracted data of AA deaths, disability-adjusted life years (DALYs), and their corresponding age-standardized rates (ASRs), in general and by age/sex from the 2017 Global Burden of Disease (GBD) study. The current AA burden distribution in 2017 and its changing trend from 1990 to 2017 were separately showed. The spatial divergence was discussed from four levels: global, five social-demographic index regions, 21 GBD regions, and 195 countries and territories. We also estimated the risk factors attributable to AA related deaths. Results: Globally, the AA deaths were 167,249 with an age-standardized death rate (ASDR) of 2.19/100,000 persons in 2017, among which the elderly and the males accounted for the majority. Although reductions in ASRs were observed in developed areas, AA remained an important health issue in those relatively underdeveloped areas and might be much more important in the near future. AA may increasingly affect the elderly and the female population. Similar patterns of AA DALYs burden were noted during the study period. AA burden attributable to high blood pressure and smoking decreased globally and there were many heterogeneities in their distribution. Discussion: AA maintained an incremental public health issue worldwide. The change pattern of AA burden was heterogeneous across locations, ages, and sexes and it is paramount to improve resource allocation for more effective and targeted prevention strategies. Also, prevention of tobacco consumption and blood pressure control should be emphasized

Uric acid predicts recovery of left ventricular function and adverse events in heart failure with reduced ejection fraction: Potential mechanistic insight from network analyses

Background and Aims: Heart failure with reduced ejection fraction (HFrEF) still carries a high risk for a sustained decrease in left ventricular ejection fraction (LVEF) even with the optimal medical therapy. Currently, there is no effective tool to stratify these patients according to their recovery potential. We tested the hypothesis that uric acid (UA) could predict recovery of LVEF and prognosis of HFrEF patients and attempted to explore mechanistic relationship between hyperuricemia and HFrEF. Methods: HFrEF patients with hyperuricemia were selected from the National Inpatient Sample (NIS) 2016-2018 database and our Xianyang prospective cohort study. Demographics, cardiac risk factors, and cardiovascular events were identified. Network-based analysis was utilized to examine the relationship between recovery of LVEF and hyperuricemia, and we further elucidated the underlying mechanisms for the impact of hyperuricemia on HFrEF. Results: After adjusting confounding factors by propensity score matching, hyperuricemia was a determinant of HFrEF [OR 1.247 (1.172-1.328); Conclusion: Lower baseline UA value predicted the LVEF recovery and less long-term adverse events in HFrEF patients. Our results provide new insights into underlying mechanistic relationship between hyperuricemia and HFrEF

Seismic Performance of Base-Isolated Precast Concrete Shear Wall Structure with AHW Connections

To improve the seismic performance and seismic reliability of precast concrete shear wall (PCSW) structure with improved assembly horizontal wall connections (AHW connections), base isolation technology was proposed to be applied in the PCSW structure. Two 1/4-scaled structure models using the improved AHW connections were constructed: a lead-rubber bearing (LRB) base-isolated PCSW structure model and a base-fixed PCSW structure model. Shaking table tests were conducted on these two models with three strong ground motions to assess the seismic performance of the structures. It was found that the improved AHW connections in the base-isolated PCSW structure are useful and effective and that they fulfil the requirements to be met by the connections to withstand an earthquake. In addition, the maximum absolute acceleration and base shear force of the base-isolated PCSW structure model were less than those of the base-fixed PCSW structure model, and the isolation effect on the absolute acceleration responses and base shear responses increased with increase in the intensity of ground motions. In a word, the seismic performance and seismic reliability of PCSW structures can be effectively improved using base isolation technology. After this investigation, the seismic responses of the base-isolated PCSW structure model were numerically simulated using OpenSees software. There was a reasonable agreement between the numerically simulated results and test results; thus, the numerical simulation method and analysis model used for the base-isolated PCSW structure model were verified

Detecting hardware trojan through time domain constrained estimator based unified subspace technique

Hardware Trojan (HT) has emerged as an impending security threat to hardware systems. However, conventional functional tests fail to detect HT since Trojans are triggered by rare events. Most of the existing side-channel based HT detection techniques just simply compare and analyze circuit's parameters and offer no signal calibration or error correction properties, so they suffer from the challenge and interference of large process variations (PV) and noises in modern nanotechnology which can completely mask Trojan's contribution to the circuit. This paper presents a novel HT detection method based on subspace technique which can detect tiny HT characteristics under large PV and noises. First, we formulate the HT detection problem as a weak signal detection problem, and then we model it as a feature extraction model. After that, we propose a novel subspace HT detection technique based on time domain constrained estimator. It is proved that we can distinguish the weak HT from variations and noises through particular subspace projections and reconstructed clean signal analysis. The reconstructed clean signal of the proposed algorithm can also be used for accurate parameter estimation of circuits, e.g. power estimation. The proposed technique is a general method for related HT detection schemes to eliminate noises and PV. Both simulations on benchmarks and hardware implementation validations on FPGA boards show the effectiveness and high sensitivity of the new HT detection technique.Published versio

Hyaluronan: its potential application in intervertebral disc regeneration

Bojiang Shen, Aiqun Wei, Divya Bhargav, Thomas Kishen, Ashish D DiwanOrthopaedic Research Institute, Department of Orthopaedic Surgery, St. George Hospital, The University of New South Wales, Sydney, AustraliaAbstract: Hyaluronan (HA) is a ubiquitous component of extracellular matrix in human tissues with diverse functions in skeletal biology. The biophysical properties of HA, such as high viscosity, elasticity and highly negative charge, make it useful in various therapeutic procedures. Although intra-articular administration of HA has been extensively used in the management of osteoarthritis (OA), there is a paucity of data on the clinical application of HA in intervertebral disc repair. This review discusses the biology and signaling mechanisms of HA, the pathophysiology of disc degeneration and summarises current evidence relating to the role of HA in cell phenotype maintenance, differentiation of chondrocytes, intervertebral disc cells and bone marrow stromal cells, and its application in tissue engineering. Based on recent advances in the clinical outcomes of OA treatment, HA has demonstrated potential as a bio-polymer filler, therapeutic agent and cell carrier in the management of intervertebral disc degeneration.Keywords: hyaluronan, cartilage, intervertebral disc, stromal cells, tissue engineering, back pai

Hyaluronan : its potential application in intervertebral disc regeneration

Hyaluronan (HA) is a ubiquitous component of extracellular matrix in human tissues with diverse functions in skeletal biology. The biophysical properties of HA, such as high viscosity, elasticity and highly negative charge, make it useful in various therapeutic procedures. Although intra-articular administration of HA has been extensively used in the management of osteoarthritis (OA), there is a paucity of data on the clinical application of HA in intervertebral disc repair. This review discusses the biology and signaling mechanisms of HA, the pathophysiology of disc degeneration and summarises current evidence relating to the role of HA in cell phenotype maintenance, differentiation of chondrocytes, intervertebral disc cells and bone marrow stromal cells, and its application in tissue engineering. Based on recent advances in the clinical outcomes of OA treatment, HA has demonstrated potential as a bio-polymer filler, therapeutic agent and cell carrier in the management of intervertebral disc degeneration

On Maximizing the Sum Secret Key Rate for Reconfigurable Intelligent Surface Assisted Multiuser Systems

International audienceChannel reciprocity-based key generation (CRKG) has recently emerged as a new technique to address the problem of key distribution in wireless networks. However, as this approach relies upon the characteristics of fading channels, the corresponding secret key rate may be low when the communication link is blocked. To enhance the applicability of CRKG in harsh propagation scenarios, this paper introduces a novel multiuser key generation scheme, which is referred to as RIS-assisted multiuser key generation (RMK) that leverages the reconfigurable intelligent surface (RIS) technology for appropriately shaping the environment and enhancing the sum secret key rate between an access point and multiple users. In the RMK scheme, an RIS-induced channel, rather than the direct channel, serves as the key source. We derive a general closed-form expression of the secret key rate and optimize the configuration of the RIS to maximize the sum secret key rate over independent and correlated fading channels in the presence of multiple users. In the presence of independent fading, we introduce a low-complexity algorithm based on the Karush-Kuhn-Tucker (KKT) condition. In the presence of correlated fading, the optimization problem is non-convex and challenging to solve. To tackle it, we propose a new optimization algorithm based on the semi-definite relaxation (SDR) and successive convex approximation (SCA) methods. Simulation results demonstrate that the proposed RMK scheme outperforms existing RIS-assisted algorithms and achieves a near-optimal sum secret key rate over independent and correlated fading channels