Regulation of human and mouse bystander T cell activation responses by PD-1.

Bystander activation of memory T cells occurs via cytokine signaling alone in the absence of T cell receptor (TCR) signaling and provides a means of amplifying T cell effector responses in an antigen-nonspecific manner. While the role of Programmed Cell Death Protein 1 (PD-1) on antigen-specific T cell responses is extensively characterized, its role in bystander T cell responses is less clear. We examined the role of the PD-1 pathway during human and mouse non-antigen-specific memory T cell bystander activation and observed that PD-1+ T cells demonstrated less activation and proliferation than activated PD-1- populations in vitro. Higher activation and proliferative responses were also observed in the PD-1- memory population in both mice and patients with cancer receiving high-dose IL-2, mirroring the in vitro phenotypes. This inhibitory effect of PD-1 could be reversed by PD-1 blockade in vivo or observed using memory T cells from PD-1-/- mice. Interestingly, increased activation through abrogation of PD-1 signaling in bystander-activated T cells also resulted in increased apoptosis due to activation-induced cell death (AICD) and eventual T cell loss in vivo. These results demonstrate that the PD-1/PD-Ligand 1 (PD-L1) pathway inhibited bystander-activated memory T cell responses but also protected cells from AICD.

Health, Security and Fire Safety Process Optimisation Using Intelligence at the Edge.

The proliferation of sensors to capture parametric measures or event data over a myriad of networking topologies is growing exponentially to improve our daily lives. Large amounts of data must be shared on constrained network infrastructure, increasing delays and loss of valuable real-time information. Our research presents a solution for the health, security, safety, and fire domains to obtain temporally synchronous, credible and high-resolution data from sensors to maintain the temporal hierarchy of reported events. We developed a multisensor fusion framework with energy conservation via domain-specific "wake up" triggers that turn on low-power model-driven microcontrollers using machine learning (TinyML) models. We investigated optimisation techniques using anomaly detection modes to deliver real-time insights in demanding life-saving situations. Using energy-efficient methods to analyse sensor data at the point of creation, we facilitated a pathway to provide sensor customisation at the "edge", where and when it is most needed. We present the application and generalised results in a real-life health care scenario and explain its application and benefits in other named researched domains.

Wireless Body Area Sensor Networks: Survey of MAC and Routing Protocols for Patient Monitoring under IEEE 802.15.4 and IEEE 802.15.6.

Wireless body area sensor networks (WBASNs) have received growing attention from industry and academia due to their exceptional potential for patient monitoring systems that are equipped with low-power wearable and implantable biomedical sensors under communications standards such as IEEE 802.15.4-2015 and IEEE 802.15.6-2012. The goal of WBASNs is to enhance the capabilities of wireless patient monitoring systems in terms of data accuracy, reliability, routing, channel access, and the data communication of sensors within, on and around the human body. The huge scope of challenges related to WBASNs has led to various research publications and industrial experiments. In this paper, a survey is conducted for the recent state-of-art in the context of medium access control (MAC) and routing protocols by considering the application requirements of patient monitoring systems. Moreover, we discuss the open issues, lessons learned, and challenges for these layers to provide a source of motivation for the upcoming design and development in the domain of WBASNs. This survey will be highly useful for the 6th generation (6G) networks; it is expected that 6G will provide efficient and ubiquitous connectivity to a huge number of IoT devices, and most of them will be sensor-based. This survey will further clarify the QoS requirement part of the 6G networks in terms of sensor-based IoT.

Engineering the gut microbiota to treat hyperammonemia.

Increasing evidence indicates that the gut microbiota can be altered to ameliorate or prevent disease states, and engineering the gut microbiota to therapeutically modulate host metabolism is an emerging goal of microbiome research. In the intestine, bacterial urease converts host-derived urea to ammonia and carbon dioxide, contributing to hyperammonemia-associated neurotoxicity and encephalopathy in patients with liver disease. Here, we engineered murine gut microbiota to reduce urease activity. Animals were depleted of their preexisting gut microbiota and then inoculated with altered Schaedler flora (ASF), a defined consortium of 8 bacteria with minimal urease gene content. This protocol resulted in establishment of a persistent new community that promoted a long-term reduction in fecal urease activity and ammonia production. Moreover, in a murine model of hepatic injury, ASF transplantation was associated with decreased morbidity and mortality. These results provide proof of concept that inoculation of a prepared host with a defined gut microbiota can lead to durable metabolic changes with therapeutic utility.

Fibrous Dysplasia of the Spine - A Case Involving Three Levels of Thoracic Spine.

INTRODUCTION: Involvement of the spinal column in either monostotic or polyostotic form is rare, with fewer than thirty-five cases discussed in the literature. Most of the cases of polyostotic fibrous dysplasia of spine have involvement of the appendicular skeleton. CASE REPORT: We report a case of a 74-year-old Irish man with a two month history of back pain. Investigations revealed a diagnosis of fibrous dysplasia involving three levels of the thoracic spine in isolation. The patient underwent T2-T9 stabilization and bone grafting. CONCLUSION: A case of fibrous dysplasia involving three levels of the thoracic spine in isolation has never previously been reported. The extreme rarity of this type of presentation can pose a diagnostic dilemma, and in cases with spinal involvement, a consensus of management has not yet been achieved.