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Porter Chandler posted an update 6 months ago
Moreover, the knockdown or overexpression of PSMD11 was sufficient to change the oxidative state caused by D-Gal. Our results also demonstrated that PSMD11 could bond to AMPKα1/2 in the auditory cortex and PC12 cells, and AMPKα2 but not AMPKα1 was efficient to regulate the function of PSMD11. Deeper insights into the mechanisms of regulating PSMD11 for the anti-aging process are needed, and may offer novel therapeutic methods for central presbycusis.The process of ischemia/reperfusion (IR) in ischemic stroke often leads to significant cell death and permanent neuronal damage. Safe and effective treatments are urgently needed to mitigate the damage caused by IR injury. The naturally occurring pleiotropic peptide phoenixin 14 (PNX-14) has recently come to light as a potential treatment for IR injury. In the present study, we examined the effects of PNX-14 on several key processes involved in ischemic injury, such as pro-inflammatory cytokine expression, oxidative stress, and the related cascade mediated through the toll-like receptor 4 (TLR4) pathway, using BV2 microglia exposed to oxygen-glucose deprivation and reoxygenation (OGD/R). Our results demonstrate an acute ability of PNX-14 to regulate the expression levels of proinflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). PNX-14 also prevented oxidative stress by reducing the generation of reactive oxygen species (ROS) and increasing the level of the antioxidant glutathione (GSH). Importantly, PNX-14 inhibited high-mobility group box 1 (HMGB1)/TLR4/myeloid differentiation primary response 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway, by inhibiting the activation of TLR4 and preventing the nuclear translocation of p65 protein. We further confirmed the cerebroprotective effects of PNX-14 in an MCAO rat model, which resulted in reduced infarct volume and decreased microglia activation. Together, the results of this study implicate a possible protective role of PNX-14 against various aspects of IR injury in vitro.Purpose To investigate rates of structural and functional change in a large clinical population of glaucoma and glaucoma suspect patients. Design Retrospective cohort. Methods 29,548 spectral-domain optical coherence tomography (SDOCT) and 19,812 standard automated perimetry (SAP) tests from 6,138 eyes of 3,669 patients with at least 6 months of follow-up, 2 good quality SDOCT peripapillary retinal nerve fiber layer (RNFL) and 2 reliable SAP tests were included. Data were extracted from the Duke Glaucoma Registry, a large database of electronic medical records of patients from the Duke Eye Center and satellite clinics. Rates of change for the two metrics were obtained using linear mixed models, categorized according to pre-established cut-offs, and analyzed according to the severity of the disease. Results Average rates of change were -0.73±0.80μm/year for global RNFL thickness and -0.09±0.36dB/year for SAP mean deviation (MD). 26.6% of eyes were classified as having at least a moderate rate of change by SDOCT versus 9.1% by SAP (P less then 0.001). In eyes with severe disease, 31.6% were classified as progressing at moderate or faster rates by SAP versus 26.5% by SDOCT (P=0.055). Most eyes classified as fast by SDOCT were classified as slow by SAP and vice-versa. Conclusion Although most patients under routine care had slow rates of progression, a substantial proportion had rates that could potentially result in major losses if sustained over time. Both structural and functional tests should be used to monitor glaucoma, and SDOCT still has a relevant role in detecting fast progressors in advanced disease.Purpose To discuss the evolution in retinopathy of prematurity (ROP) since its first description as retrolental fibroplasia in the US, including the changes in the understanding of pathophysiology; methods of diagnosis; destructive, anti-VEGF, and supportive treatments; and differences in ROP manifestations worldwide. The overall goal is to clarify ROP currently and formulate questions to optimize future care. Study design Literature Review and Synthesis METHODS Critical review and consideration of the literature with inclusion of historical articles and those regarding pathophysiologic risk factors, ROP worldwide, basic and clinical science particularly regarding anti-VEGF mechanisms and agents tested in clinical trials. Results ROP has evolved from affecting infants about 2 months premature to affecting extremely premature infants. MLN7243 Worldwide, ROP differs and in emerging countries, has features similar to that experienced in the US when ROP first manifested. Treatments have evolved from destruction of the peripheral avascular retina to inhibit angiogenic stimuli to anti-VEGF agents, which inhibit pathologic angiogenesis but also extend normal intraretinal angiogenesis by ordering the development of intraretinal vessels. Clinical trial evidence is accruing with the goal to develop less destructive treatments to optimize vision and that are protective to the retina and infant. Conclusions Goals for ROP are to optimize prenatal and perinatal care, improve diagnostic acumen worldwide and refine treatment strategies, including with anti-VEGF agents, to inhibit intravitreal angiogenesis and facilitate vascularization of the previously avascular retina, which include supporting neural and vascular development of the premature infant and retina.Objective To determine the effect of a removable rigid dressing (RRD) on the time to residual limb maturation compared with elastic bandage (EB) in transtibial amputees. Design Experimental single-blinded (assessor-blinded) randomized controlled trial. Setting Department of Rehabilitation Medicine, King Chulalongkorn Memorial Hospital. Participants Twenty-five transtibial amputees with immature residual limb. Interventions Participants were allocated to use RRD or EB to achieve residual limb maturation, and all participants in both groups were trained with the same pre-prosthetic program. Main outcome measures The time to residual limb maturation, patient satisfaction and complications were compared between the two groups. Results Median time to residual limb maturation was significantly lower in the RRD group (28 days, IQR 17-51 days) than in the EB group (54 days, IQR 30-77 days; P=0.020). After accounting for time since amputation, maturation time remained significantly lower in the RRD group (adjusted HR=3.