Combined Idiopathic Macular Hole Vitrectomy with Phacoemulsification without Face-Down Positioning

Purpose. To evaluate the outcome of combined vitrectomy with phacoemulsification without postoperative face-down positioning for idiopathic macular holes (MHs). Design. Retrospective, observational case series. Participants. Forty-two eyes of 42 patients with MH. Methods. We studied 42 eyes of 42 cases followed up for 6 months postoperatively. MH closure rate and preoperative and postoperative visual acuity (VA) were evaluated. Main Outcome Measures. MH closure rate and VA were evaluated after combined vitrectomy with phacoemulsification without postoperative face-down positioning. Results. Of the 42 holes, 40 (95.2%) were initially closed, and the final closure rate was 100%. Compared with preoperative VA, the mean VA was significantly improved at 1 month and the improvement was maintained for at least 6 months postoperatively. Conclusions. Combined vitrectomy with phacoemulsification without postoperative face-down positioning produced favorable anatomic and functional results for MH repair. Improvement in VA can be expected for up to at least 6 months postoperatively

Targeting cellular calcium homeostasis to prevent cytokine-mediated beta cell death

AbstractPro-inflammatory cytokines are important mediators of islet inflammation, leading to beta cell death in type 1 diabetes. Although alterations in both endoplasmic reticulum (ER) and cytosolic free calcium levels are known to play a role in cytokine-mediated beta cell death, there are currently no treatments targeting cellular calcium homeostasis to combat type 1 diabetes. Here we show that modulation of cellular calcium homeostasis can mitigate cytokine- and ER stress-mediated beta cell death. The calcium modulating compounds, dantrolene and sitagliptin, both prevent cytokine and ER stress-induced activation of the pro-apoptotic calcium-dependent enzyme, calpain, and partly suppress beta cell death in INS1E cells and human primary islets. These agents are also able to restore cytokine-mediated suppression of functional ER calcium release. In addition, sitagliptin preserves function of the ER calcium pump, sarco-endoplasmic reticulum Ca2+-ATPase (SERCA), and decreases levels of the pro-apoptotic protein thioredoxin-interacting protein (TXNIP). Supporting the role of TXNIP in cytokine-mediated cell death, knock down of TXNIP in INS1-E cells prevents cytokine-mediated beta cell death. Our findings demonstrate that modulation of dynamic cellular calcium homeostasis and TXNIP suppression present viable pharmacologic targets to prevent cytokine-mediated beta cell loss in diabetes.</jats:p

A soluble endoplasmic reticulum factor as regenerative therapy for Wolfram syndrome

Endoplasmic reticulum (ER) stress-mediated cell death is an emerging target for human chronic disorders, including neurodegeneration and diabetes. However, there is currently no treatment for preventing ER stress-mediated cell death. Here, we show that mesencephalic astrocyte-derived neurotrophic factor (MANF), a neurotrophic factor secreted from ER stressed cells, prevents ER stress-mediated β cell death and enhances β cell proliferation in cell and mouse models of Wolfram syndrome, a prototype of ER disorders. Our results indicate that molecular pathways regulated by MANF are promising therapeutic targets for regenerative therapy of ER stress-related disorders, including diabetes, retinal degeneration, neurodegeneration, and Wolfram syndrome

Association between Optic Nerve Head Microcirculation and Macular Ganglion Cell Complex Thickness in Eyes with Untreated Normal Tension Glaucoma and a Hemifield Defect

Purpose. We evaluated the association between optic nerve head (ONH) microcirculation and macular ganglion cell complex (mGCC) thickness in patients with untreated normal tension glaucoma (NTG) and a hemifield defect. Methods. The medical records of 47 patients with untreated NTG were retrospectively reviewed. Laser speckle flowgraphy was used to obtain mean blur rate (MBR), a relative measure of blood flow. Average total deviation (TD), mGCC, and the circumpapillary retinal nerve fiber layer (cpRNFL) thickness were also analyzed. Results. All parameters corresponding to the defective hemifield were significantly lower than those corresponding to the normal hemifield. In the defective hemifield, MBR was correlated with TD, mGCC, and cpRNFL thickness. In the normal hemifield, MBR was only correlated with mGCC thickness, and multiple regression analysis showed that mGCC thickness was a significant contributing factor of the MBR. Conclusion. MBR was well correlated with mGCC thickness in eyes with untreated NTG and a hemifield defect. In the normal hemifield, mGCC thickness was a contributing factor of the MBR indicating that ONH circulatory dysfunction may be associated with retinal structural changes in the early stages of glaucoma. A reduction in ONH microcirculation may be an early indicator of the presence and progression of glaucoma

Continuous blood glucose monitoring during pediatric cardiopulmonary bypass

The purpose of this study was to assess the accuracy and efficacy of a continuous blood glucose monitoring system (artificial endocrine pancreas; STG-22, Nikkiso, Co., Ltd., Tokyo, Japan) during pediatric cardiopulmonary bypass. Sixteen pediatric patients scheduled to undergo cardiovascular surgery with cardiopulmonary bypass (6 for atrial septal defects, 8 for ventricular septal defects and 2 for others, age: 7 months to 13 years, body weight 6.4-55.4 kg) were enrolled. The glucose sensor line of the artificial endocrine pancreas was connected to the venous side of the cardiopulmonary bypass circuit and used for continuous blood glucose monitoring. We obtained 66 samples for blood gas assessment from the cardiopulmonary bypass circuit, and i-STAT (Abbott, East Windsor, NJ, USA) was used for conventional blood glucose assessment. Data were analyzed with simple linear regression analysis using the Bland and Altman approach. After cardiopulmonary bypass was started and the aortic artery clamped, the blood glucose level rose markedly to around 300 mg/dl. Blood sampling via the venous side of the cardiopulmonary bypass circuit showed that continuous blood glucose monitoring was stable and reliable even during pediatric cardiovascular surgery with cardiopulmonary bypass. A close correlation (R = 0.97) was observed between continuous glucose measurement and conventional intermittent glucose measurements. The results of this continuous blood glucose monitoring system for cardiopulmonary bypass during pediatric cardiovascular surgery were highly reliable

Current Performance and On-Going Improvements of the 8.2 m Subaru Telescope

An overview of the current status of the 8.2 m Subaru Telescope constructed and operated at Mauna Kea, Hawaii, by the National Astronomical Observatory of Japan is presented. The basic design concept and the verified performance of the telescope system are described. Also given are the status of the instrument package offered to the astronomical community, the status of operation, and some of the future plans. The status of the telescope reported in a number of SPIE papers as of the summer of 2002 are incorporated with some updates included as of 2004 February. However, readers are encouraged to check the most updated status of the telescope through the home page, http://subarutelescope.org/index.html, and/or the direct contact with the observatory staff.Comment: 18 pages (17 pages in published version), 29 figures (GIF format), This is the version before the galley proo

Novel repressor regulates insulin sensitivity through interaction with Foxo1

This study characterizes a novel Foxo1 CoRepressor (FCoR) that regulates insulin sensitivity and energy metabolism as revealed by whole-body knockout. As target of PKA phosphorylation, FCoR modulates Foxo's acetylation known to control Foxo's biological activity

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Incidence and Risk Factors of Iatrogenic Retinal Breaks: 20-Gauge versus 25-Gauge Vitrectomy for Idiopathic Macular Hole Repair

Purpose. We compared the incidences of iatrogenic retinal breaks and postoperative retinal detachment between eyes that underwent 20-gauge vitrectomy and those that underwent 25-gauge vitrectomy for idiopathic macular hole repair. Methods. This retrospective nonrandomized consecutive observational case series included 185 eyes of 183 patients (130 eyes of 129 patients and 55 eyes of 54 patients in the 20- and 25-gauge groups, respectively). We assessed the relationship between the incidence of retinal breaks and postoperative retinal detachment and related this to posterior vitreous detachment and lattice degeneration. Results. The incidences of iatrogenic retinal breaks were 36.9% and 12.7% in the 20-gauge and 25-gauge groups, respectively. These groups did not differ in their respective frequencies of posterior vitreous detachment (the 20-gauge group: 31.5% and the 25-gauge group: 27.3%) and lattice degeneration (the 20-gauge group: 14.6% and the 25-gauge group: 7.3%). Among eyes without lattice degeneration, the 20-gauge group showed a higher incidence of iatrogenic retinal breaks than the 25-gauge group. However, among the eyes with lattice degeneration, the frequency of retinal breaks did not differ between the two surgery types, and four cases of postoperative retinal detachment were reported in both groups. Conclusions. The incidence of retinal breaks related to idiopathic macular hole surgery is higher among patients undergoing 20-gauge vitrectomy than among those undergoing 25-gauge vitrectomy. Posterior vitreous detachment and lattice degeneration are associated with considerably increased incidences of retinal break