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p58IPK is a multifaceted endoplasmic reticulum (ER) chaperone and a regulator of eIF2α kinases involved in a wide range of cellular processes including protein synthesis, ER stress response, and macrophage-mediated inflammation. Systemic deletion of p58IPK leads to age-related loss of retinal ganglion cells (RGC) and exacerbates RGC damage induced by ischemia/reperfusion and increased intraocular pressure (IOP), suggesting a protective role of p58IPK in the retina. However, the mechanisms remain elusive. Herein, we investigated the cellular mechanisms underlying the neuroprotection action of p58IPK using conditional knockout (cKO) mouse lines where p58IPK is deleted in retinal neurons (Chx10-p58IPK cKO) or in myeloid cells (Lyz2-p58IPK cKO). In addition, we overexpressed p58IPK by adeno-associated virus (AAV) in the retina to examine the effect of p58IPK on RGC survival after ocular hypertension (OHT) in wild type (WT) mice. Our results show that overexpression of p58IPK by AAV significantly improved RGC survival after OHT in WT mice, suggesting a protective effect of p58IPK on reducing RGC injury. Conditional knockout of p58IPK in retinal neurons or in myeloid cells did not alter retinal structure or cellular composition. However, a significant reduction in the b wave of light-adapted electroretinogram (ERG) was observed in Chx10-p58IPK cKO mice. Deletion of p58IPK in retinal neurons exacerbates RGC loss at 14 days after OHT. In contrast, deficiency of p58IPK in myeloid cells increased the microglia/macrophage activation but had no effect on RGC loss. We conclude that deletion of p58IPK in macrophages increases their activation, but does not influence RGC survival. These results suggest that the neuroprotective action of p58IPK is mediated by its expression in retinal neurons, but not in macrophages. Therefore, targeting p58IPK specifically in retinal neurons is a promising approach for the treatment of neurodegenerative retinal diseases including glaucoma. [ABSTRACT FROM AUTHOR]

Background: Cryoneurolysis is a term used to describe the application of extreme cold to targeted nerve tissue. The primary goal of the application of a thermal neurolytic technique is to disrupt the conduction of pain signals from the periphery to the central nervous system and eliminate or diminish the experience of pain. Recent advancements in ultrasound technology coupled with the development and approval of handheld devices specifically designed to deliver cryoneurolysis has expanded the use of this modality in the perioperative setting. Application: Surgical procedures including total knee arthroplasties, shoulder arthroplasties, thoracotomies, and mastectomies have all demonstrated long‐term pain relief benefits when cryoneurolysis has been administered days to weeks prior to the planned procedure. In addition, the newly designed handheld device allows for office‐based clinical use and has been utilized for various chronic pain conditions including neuropathic and phantom limb pain. Conclusion: The evidence clearly demonstrates that cryoneurolysis has a low risk profile and when administered appropriately, provides prolonged analgesia without promoting motor blockade. This narrative review article describes the unique mechanism of action of cryoneurolysis for prolonged pain relief and provides emerging evidence to support its applications in both acute and chronic pain management. [ABSTRACT FROM AUTHOR]

NADPH oxidase 4 (Nox4) is a major source of reactive oxygen species (ROS) in retinal endothelial cells (ECs) and is upregulated under hyperglycemic and hypoxic conditions. However, the role of endothelial Nox4 upregulation in long-term retinal blood vessel damage in diabetic retinopathy (DR) remains undefined. Here, we attempted to address this question using humanized EC-specific Nox4 transgenic (hNox4EC-Tg) and EC-specific Nox4 knockout (Nox4EC-KO) mouse models. Our results show that, hNox4EC-Tg mice at age of 10-12 months exhibited increased tortuosity of retinal blood vessels, focal vascular leakage, and acellular capillary formation. In vitro study revealed enhanced apoptosis in brain microvascular ECs (BMECs) derived from hNox4EC-Tg mice, concomitant with increased mitochondrial ROS, elevated lipid peroxidation, decreased mitochondrial membrane potential (ΔΨm), and reduced mitochondrial respiratory function. In contrast, EC-specific deletion of Nox4 decreased mitochondrial ROS generation, alleviated mitochondrial damage, reduced EC apoptosis, and protected the retina from acellular capillary formation and vascular hyperpermeability in a streptozotocin-induced diabetes mouse model. These findings suggest that sustained upregulation of Nox4 in the endothelium contributes to retinal vascular pathology in diabetes, at least in part, through impairing mitochondrial function. Normalization of Nox4 expression in ECs may provide a new approach for prevention of vascular injury in DR. [ABSTRACT FROM AUTHOR]

This document is a preface to a special issue of the International Journal of Computational Methods on the topic of "Numerical Modelling of Fibre-Reinforced Materials and Structures." The special issue contains selected papers presented at the Fifth Australasian Conference on Computational Mechanics, which focused on the use of computational methods and modelling technology in the field of fibre-reinforced materials and structures. The papers in this special issue cover advanced theory, algorithms, numerical simulations, and novel applications of computational techniques in this area. The research and development of fibre-reinforced materials and structures have been increasing, leading to enhanced structure safety and infrastructure resilience. The preface is written by Sarah (Yixia) Zhang from the School of Engineering, Design and Built Environment at Western Sydney University in Australia. [Extracted from the article]