Braggmcfadden5386

Recently, several research groups have reported a newly recognized clinical entity of choroidal neovascularization, termed pachychoroid neovasculopathy. However, its characteristics have yet to be well described. The purpose of this study was to investigate the clinical and genetic characteristics of pachychoroid neovasculopathy regardless of treatment modality. This study included 99 eyes of 99 patients with treatment-naïve pachychoroid neovasculopathy. Mean initial best-corrected visual acuity (BCVA) was 0.20 ± 0.32 logMAR, and did not change (P = 0.725) during follow-up period (mean ± SD, 37.0 ± 17.6 months). Subretinal hemorrhage (SRH) (≥ 4 disc areas in size) occurred in 20 eyes (20.2%) during follow-up. Age, initial BCVA, central retinal thickness, SRH (≥ 4 disc areas in size) and treatment (aflibercept monotherapy) were significantly associated with the final BCVA (P = 0.024,  less then  0.001, 0.031,  less then  0.001, and 0.029, respectively). Multiple regression analysis showed initial BCVA and presence of SRH to be significant predictors of final BCVA (both P  less then  0.001). Polypoidal lesions were more common in the SRH group than in the non-SRH group (85.0% vs 48.1%, P = 0.004). see more There was no significant difference in the frequency of the risk allele in ARMS2 A69S, CFH I62V, CFH Y402H between these groups (P = 0.42, 0.77, and 0.85, respectively). SRH (29.1% vs 9.1%, P = 0.014) and choroidal vascular hyperpermiability (65.5% vs 43.2%, P = 0.027) were seen more frequently in the polypoidal lesion (+) group than in the polypoidal lesion (-) group. There was considerable variation in lesion size and visual function in patients with pachychoroid neovasculopathy, and initial BCVA and presence of SRH at the initial visit or during the follow-up period were significant predictors of final BCVA.Optic atrophy resulting from retinal ganglion cell (RGC) degeneration is a prominent ocular manifestation of mitochondrial dysfunction. Although transgenic mice lacking the mitochondrial complex I accessory subunit NDUFS4 develop early-onset optic atrophy, severe systemic mitochondrial dysfunction leads to very early death and makes this mouse line impractical for studying the pathobiology of mitochondrial optic neuropathies. Theoretically, RGC-specific inactivation of ndufs4 would allow characterization of RGC degeneration over a longer time course, provided that RGC death from mitochondrial dysfunction is a cell-autonomous process. We demonstrate that the vesicular glutamate transporter VGLUT2 may be exploited to drive robust Cre recombinase expression in RGCs without any expression observed in directly neighboring retinal cell types. Deletion of ndufs4 in RGCs resulted in reduced expression of NDUFS4 protein within the optic nerves of Vglut2-Cre;ndufs4loxP/loxP mice. RGC degeneration in Vglut2-Cre;ndufs4loxP/loxP retinas commenced around postnatal day 45 (P45) and progressed to loss of two-thirds of RGCs by P90, confirming that intrinsic complex I dysfunction is sufficient to induce RGC death. The rapidly-developing optic atrophy makes the Vglut2-Cre;ndufs4loxP/loxP mouse line a promising preclinical model for testing therapies for currently untreatable mitochondrial optic neuropathies such as Leber Hereditary Optic Neuropathy.Pyroptosis is a kind of necrotic and inflammatory programmed cell death induced by inflammatory caspases. SENP7 is a SUMO-specific protease, which mainly acts on deconjugation of SUMOs from substrate proteins. We evaluated the effect of SENP7 knockdown on pyroptosis, NF-κB signaling pathway, and NLRP3 inflammasome in Raw 264.7 cells. The results showed that the GSDMD protein mainly expressed in the cytoplasm nearby nuclei of Raw 264.7 cells. It migrated to cytomembrane with the numbers of Raw 264.7 cell decreased when LPS + ATP were administrated. Which was inhibited by SENP7 knockdown. In addition, not only the pyroptosis of Raw 264.7 cells was inhibited, the activation of NF-κB signaling pathway and NLRP3 inflammasome were also attenuated by SENP7 knockdown. The mechanism may be associated with the over SUMOylation of proteins induced by SENP7 knockdown.Piezoelectric (PZT) components are one of the most popular elements in vibration sensing and also energy harvesting. They are very well established, cost effective and available in different geometries however there are still several challenges in their application particularly in vibration energy harvesting. They are normally narrow-band elements and work in high-frequency range. Their efficiency and power extraction density are also generally low compared with different electromagnetic techniques. Auxetic structures are proposed here to enhance efficiency of the piezoelectric circular patches in vibration energy harvesting. These kinds of patches namely PZT buzzers are inexpensive (less than 10 USD) elements and easily available. Two novel circular auxetic substrates are proposed to improve power extraction capacity of the conventional piezoelectric buzzers. Negative Poison's ratio of the proposed meta-structure helps in efficiency enhancement. The concept is introduced, analyzed and verified through the finite element modeling and experimental testing. The idea is proved to work by comparing the harvested electrical power in the auxetic design against the conventional plain system. A parametric study is then carried out and effects of important electrical and geometrical parameters as well as the material property on the power extraction efficiency are assessed to arrive at optimum parameters. It is shown that by employing the auxetic design, a remarkable improvement in the harvested power is achievable. It is shown that for the two proposed auxetic designs, at the resonance frequency, we could reach to 10.2 and 13.3 magnification factor with respect to the plain energy harvester. Another important feature is that the resonant frequency in these new designs is very much lower than the conventional resonators. Results of this study can open a new path to application of inexpensive PZT buzzers in large-scale vibration energy harvesting.