Induction of WNT16 via peptide-mRNA nanoparticle-based delivery maintains cartilage homeostasis

Osteoarthritis (OA) is a progressive joint disease that causes significant disability and pain and for which there are limited treatment options. We posit that delivery of anabolic factors that protect and maintain cartilage homeostasis will halt or retard OA progression. We employ a peptide-based nanoplatform to deliver Wingless and the name Int-1 (WNT) 16 messenger RNA (mRNA) to human cartilage explants. The peptide forms a self-assembled nanocomplex of approximately 65 nm in size when incubated with WNT16 mRNA. The complex is further stabilized with hyaluronic acid (HA) for enhanced cellular uptake. Delivery of peptide-WNT16 mRNA nanocomplex to human cartilage explants antagonizes canonical β-catenin/WNT3a signaling, leading to increased lubricin production and decreased chondrocyte apoptosis. This is a proof-of-concept study showing that mRNA can be efficiently delivered to articular cartilage, an avascular tissue that is poorly accessible even when drugs are intra-articularly (IA) administered. The ability to accommodate a wide range of oligonucleotides suggests that this platform may find use in a broad range of clinical applications

Research challenges in 5G networks: a HetNets perspective

This paper highlights use cases, emerging machine type communication (MTC) technologies, ongoing research activities, and existing research challenges in 5G networks. 5G networks are faced with the following challenges: (i) handling large amounts of data, (ii) coping with different types of data traffic, i.e., human-type, machine-type, and combined-type (iii) connecting billions of machines, and (iv) severe resource limitations of devices. The ubiquitous nature of cellular networks make them the preferred choice for access networks, but a lack of communication resources is a problem. To address the resource scarcity issue, different wireless access networks may combine to form a heterogeneous network (HetNet) and hence become a single 5G network. For long-term success of 5G networks, we envision the following as important research outputs: (i) a scalable 5G network architecture that can handle a large number of human users and machines considering different constraints, (ii) a comprehensive quality of service (QoS) framework to satisfy heterogeneous users and machines requirements, (iii) a procedure for intelligent access network selection, and (iv) comprehensive inter-network handover mechanisms

Development of a peptide-siRNA nanocomplex targeting NF- κB for efficient cartilage delivery

Abstract Delivery of therapeutic small interfering RNAs (siRNAs) in an effective dose to articular cartilage is very challenging as the cartilage dense extracellular matrix renders the chondrocytes inaccessible, even to intra-articular injections. Herein, we used a self-assembling peptidic nanoparticle (NP) platform featuring a cell penetrating peptide complexed to NF-κB p65 siRNA. We show that it efficiently and deeply penetrated human cartilage to deliver its siRNA cargo up to a depth of at least 700 μm. To simulate osteoarthritis in vitro, human articular cartilage explants were placed in culture and treated with IL-1β, a cytokine with known cartilage catabolic and pro-inflammatory effects. Exposure of peptide-siRNA NP to cartilage explants markedly suppressed p65 activation, an effect that persisted up to 3 weeks after an initial 48 h exposure to NP and in the presence of continuous IL-1β stimulation. Suppression of IL-1β-induced p65 activity attenuated chondrocyte apoptosis and maintained cartilage homeostasis. These findings confirm our previous in vivo studies in a murine model of post-traumatic osteoarthritis and suggest that the ability of peptide-siRNA NP to specifically modulate NF-κB pathway, a central regulator of the inflammatory responses in chondrocytes, may potentially mitigate the progression of cartilage degeneration

RPL-based routing protocols for multi-sink wireless sensor networks

Recent studies demonstrate that the performance of a wireless sensor network (WSN) can be improved by deploying multiple sinks in the network. Therefore, in this paper we present different routing protocols for multi-sink WSNs based on the routing protocol for low-power and lossy networks (RPL). Our protocols use different routing metrics and objective functions (OFs). We use the available bandwidth, delay, MAC layer queue occupancy, and expected transmission count (ETX) as the tie-breaking metrics in conjunction with the shortest hop-count metric. Our OFs use the tie-breaking metrics on a greedy or end-to-end basis. Our simulation results demonstrate that the protocols based on the delay, buffer occupancy, and ETX metrics demonstrate best performance, increasing the packet delivery ratio by up to 25% and decreasing the number of retransmissions by up to 65%, compared to a version of the RPL protocol that only uses the hop-count metric. Another key insight is that, using the tie-breaking metrics on a greedy basis demonstrates a slight performance improvement compared to using the metrics on an end-to-end basis. Finally, our results also demonstrate that multiple sinks inside a WSN improve the RPL-based protocol performance

Evaluation of available bandwidth as a routing metric for delay-sensitive IEEE 802.15.4-based ad-hoc networks

In this paper, we evaluate available bandwidth as a routing metric for IEEE 802.15.4-based ad-hoc networks. The available bandwidth on a data forwarding path is an approximation of the forwarding path’s residual data relaying capacity. High available bandwidth on a data forwarding path implies low data traffic load on the path, therefore data flows may experience low delay and high packet delivery ratio (PDR). Our aim is to evaluate available bandwidth as a routing metric. We present different available-bandwidth-based routing protocols for IEEE 802.15.40-based networks, namely: end-to-end available-bandwidth-based routing protocol (ABR), available bandwidth and contention-aware routing protocol (ABCR), and shortest hop-count and available-bandwidth-based opportunistic routing protocol (ABOR). Moreover, we also present variants of ABR and ABCR capable of distributing a flow’s data packets on multiple paths by maintaining the top K downstream nodes (the downstream nodes that advertised best data forwarding paths towards a sink node) corresponding to each sink node in a routing table. We focus on both single-sink and multi-sink networks. We performed extensive simulations, and the simulation results demonstrate that the available bandwidth routing metric shows better results when combined with a routing metric that helps to limit a data forwarding path’s length, i.e., shortest hop-count or intra-flow contention count. For multi-path data forwarding towards the same sink node, and at high traffic volumes, the available bandwidth metric demonstrates best performance when combined with the shortest hop-count routing metric

Viability of Split Thickness Autogenous Skin Transplantation in Canine Distal Limb Reconstruction – An Experimental Evaluation

Distal limb reconstruction is complicated by the paucity of local tissues and the frequent association of orthopedic injury with cutaneous loss. Though, second-intention healing or skin stretching techniques are used for wounds involving less than a 30% circumference of the limb, however, skin grafts are recommended for reconstruction of larger superficial wounds. The present study was designed to clinically evaluate the viability of split thickness autogenous skin transplantation (STAST) in dogs. Standardized surgical defects of variable size i.e. 3×3, 4×4 and 5×5 sq cm were made on the left middle radial area (forearm) of 15 mongrel dogs assigned to Group A, B and C, respectively having 5 dogs each. Split thickness autogenous skin grafts were harvested from mid thorax and placed in these defects through several simple interrupted sutures. Results indicated a success rate of 80% with no clinical difference in the survival rate of three different sizes of grafts used. Hence, STAST can successfully be used for canine distal limb reconstruction

Anterior Tarsal Tunnel Syndrome With Thrombosed Dorsalis Pedis Artery: A Case Report

Introduction: The aanterior tarsal tunnel syndrome denotes the entrapment of the deep peroneal nerve under the inferior extensor retinaculum. Although various etiological factors have been reported to cause anterior tarsal syndrome, its occurrence with thrombosed dorsalis pedis artery has not been reported in the English literature. Case Presentation: A 40 -year-old male patient was presented with the history of persistent pain along the dorsal surface of right foot, which was aggravated with the activities. Conservative management was tried without much relief. Diagnosis of anterior tarsal tunnel syndrome was made and the patient was planned for surgery. Thrombosed dorsalis pedis artery was found along with two adjacent collateral vessels. Retinaculum was released and nerve was mobilized. Tight compartment got released. Postoperative period was uneventful. No recurrence was seen on follow-up. Conclusion: The anterior tarsal tunnel syndrome is a known disease. A high index of clinical suspicion is required while dealing with the chronic cases. A detailed history to rule out any traumatic event is necessary too. Timely investigations and surgical release give dramatic relief