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Objective:The aim of this study was to identify disaster medical operation improvements from the 2016 Kumamoto Earthquake (Kumamoto Prefecture, Japan) and to extract further lessons learned to prepare for future expected major earthquakes.Methods:The records of communications logs, chronological transitions of chain of command, and team registration logs for the Disaster Medical Assistant Team (DMAT), as well as other disaster medical relief teams, were evaluated.Results:A total of 466 DMAT teams and 2,071 DMAT team members were deployed to the Kumamoto area, and 1,894 disaster medical relief teams and 8,471 disaster medical relief team member deployments followed. The DMAT established a medical coordination command post at several key disaster hospitals to designate medical coverage areas. The DMAT evacuated over 1,400 patients from damaged hospitals, transported medical supplies to affected hospitals, and coordinated 14 doctor helicopters used for severe patient transport. To keep constant medical and public health operations, DMAT provided medical coordination management until the local medical coordination was on-track. Several logistic teams, which are highly trained on operation and management of medical coordination command, were dispatched to assist management operation. The DMAT also helped to establish Disaster Coordination and Management Council at the prefectural- and municipal-level, and also coordinated command control for public health operations. The DMAT could provide not only medical assistance at the acute phase of the disaster, but also could provide medical coordination for public health and welfare.Conclusion:During the 2016 Kumamoto Earthquake, needs of public health and welfare increased enormously due to the sudden evacuation of a large number of residents. To provide constant medical assistance at the disaster area, DMAT, logistic teams, and other disaster medical relief teams must operate constant coordination at the medical headquarter command. For future expected major earthquakes in Japan, it will be required to educate and secure high enough numbers of disaster medical assistance and health care personnel to provide continuous medical and public health care for the affected area residents.Kondo H, Koido Y, Kawashima Y, Kohayagawa Y, Misaki M, Takahashi A, Kondo Y, Chishima K, Toyokuni Y. Consideration of medical and public health coordination – experience from the 2016 Kumamoto, Japan Earthquake. Prehosp Disaster Med. 2019;34(2):149–154

To assess the value of the texture analysis of fluorine-A total of 14 patients undergoingThe SHAPEHigher MTV, GLRLM

Unsupervised machine learning has received increased attention in clinical research because it allows researchers to identify novel and objective viewpoints for diseases with complex clinical characteristics. In this study, we applied a deep phenotyping method to classify Japanese patients with age-related macular degeneration (AMD), the leading cause of blindness in developed countries, showing high phenotypic heterogeneity. By applying unsupervised deep phenotype clustering, patients with AMD were classified into two groups. One of the groups had typical AMD features, whereas the other one showed the pachychoroid-related features that were recently identified as a potentially important factor in AMD pathogenesis. Based on these results, a scoring system for classification was established; a higher score was significantly associated with a rapid improvement in visual acuity after specific treatment. This needs to be validated in other datasets in the future. In conclusion, the current study demonstrates the usefulness of unsupervised classification and provides important knowledge for future AMD studies.

To describe the distribution of ocular biometry and refraction in Japanese adults.Cross-sectional analysis of a prospective cohort study.A total of 9850 individuals participated in the first follow-up of the Nagahama Prospective Cohort for Comprehensive Human Bioscience (the Nagahama Study) conducted between 2013 and 2016. Participants were between 34 and 80 years of age.All participants underwent axial length (AL; in millimeters), anterior chamber depth (ACD; in millimeters), corneal diameter (white to white; in millimeters), and central corneal thickness (CCT; in micrometers) measurement (IOL Master; Carl Zeiss Meditec, Dublin, CA) and refraction (spherical equivalent [SE]; in diopters [D]) and corneal curvature (CC; in millimeters) measurement (ARK-530A; Nidek, Aichi, Japan). Distribution of these ocular biometric parameters and prevalence of myopia, high myopia, and extreme myopia were summarized.Distribution of ocular biometry and refraction.After standardization to the national population of 2015, estimates of mean AL and SE were 24.21 mm and -1.44 D, respectively. Estimates of mean CC, corneal diameter, CCT, and ACD were 7.69 mm, 12.01 mm, 543.96 μm, and 3.21 mm, respectively. After standardization of age and gender, the prevalence of myopia (SE, ≤-0.5 D) and high myopia (SE, ≤-6.0 D) were 49.97% and 7.89%, respectively. Approximately 70% of the younger participants (34-59 years of age) showed myopia, whereas high myopia was observed in approximately 10%. Although the number of individuals with myopia or high myopia was higher in the younger age groups, the prevalence of more extreme phenotypes remained stable across all ages, especially in women. Axial length of more than 30 mm was observed only in older women (n = 5 [0.05%]).We showed detailed distributions of various ocular biometry and refraction parameters using a large general Japanese cohort. Prevalences of myopia and high myopia from 2013 through 2016 were higher than those in earlier studies, which reflects recent environmental change. However, constant prevalence of extreme myopia across all ages suggests high genetic predisposition of the extreme phenotype.

Quality of single optical coherence tomography angiography (OCTA) images of myopic choroidal neovascularisation (mCNV) is poorer than in averaged images, although obtaining averaged images takes much time. This study evaluated the clinical usefulness of novel denoising process for depicting mCNV. This study included 20 eyes of 20 patients with mCNV. Ten en face images taken in a 3 × 3 mm macular cube were obtained from outer-retina-to-choriocapillaris layer. Three image types were prepared for analysis; single images before and after the denoising process accomplished deep learning (single and denoising groups, respectively) and up to 10 images were averaged (averaging group). Pairwise comparisons showed vessel density, vessel length density, and fractal dimension (FD) were higher; whereas, vessel density index (VDI) was lower in single group than in denoising and averaging groups. Detectable CNV indices, contrast-to-nose ratio, and CNV diagnostic scores were higher in denoising and averaging groups than in single group. No significant differences were detected in VDI, FD, or CNV diagnostic scores between denoising and averaging groups. The denoising process can utilise single OCTA images to provide results comparable to averaged OCTA images, which is clinically useful for shortening examination times with quality similar to averaging.

Purpose To explore novel prognostic factors associated with visual function and number of anti–vascular endothelial growth factor (VEGF) treatments in eyes with active myopic choroidal neovascularization (mCNV) using OCT angiography (OCTA). Design Prospective case series. Participants Twenty-eight treatment-naive eyes with active mCNV from 27 consecutive patients (mean age, 64.4 ± 11.1 years). Methods All eyes received through injection a single loading dose of intravitreal aflibercept (IVA), followed by additional IVA on a pro re nata (PRN) basis during the subsequent 12 months. At baseline, OCTA images of a 3 × 3-mm macular cube were acquired using an OCTA scanner. On binarized and skeletonized OCTA images of the outer retinal layer, OCTA-derived baseline parameters of mCNV—including lesion size, vessel density, vessel length density (VLD), vessel diameter index, and fractal dimension (FD)—were measured and evaluated for correlation with 12-month best-corrected visual acuity (BCVA) and number of additional injections. Main Outcome Measures The primary and secondary outcomes were BCVA 12 months after initial treatment and number of additional injections, respectively. Results There was no significant difference between baseline and 12-month BCVA (0.37 ± 0.30 and 0.30 ± 0.35 logarithm of the minimal angle of resolution, respectively; P = 0.23). The number of additional injections was 0.93 ± 1.02 (mean ± standard deviation). Baseline VLD, FD, and BCVA were correlated with 12-month BCVA (P = 0.02, r = 0.46; P = 0.02, r = 0.46; and P = 0.02, r = 0.45, respectively), and VLD also was correlated with the number of additional injections (P = 0.03, r = 0.42). Conclusions Exuberant mCNV, which is characterized by high VLD and FD derived using OCTA, is a predictor of poor visual outcomes after a single IVA injection followed by a PRN regimen. Only baseline VLD was correlated with the number of additional IVA injections, which indicates that this parameter could help to determine the optimal anti-VEGF treatment regimen for individual eyes with mCNV.

To investigate the incidence and predictors of macular atrophy during treatment with aflibercept for neovascular age-related macular degeneration in Japanese patients.This study included patients with treatment-naive subfoveal neovascular age-related macular degeneration treated from December 2012 through January 2015. Patients were treated with bi-monthly aflibercept injections after 3 monthly loading injections for the first year. Diagnosis of retinal pigment epithelial atrophy was made based on color fundus photography, spectral-domain optical coherence tomography, and fundus autofluorescence. Baseline characteristics and morphological features were analyzed for their association with the development of macular atrophy.This study included 123 eyes that had no baseline macular atrophy and treated with aflibercept injections for 12 months. Thirteen eyes (10.6%) developed new macular atrophy at 12 months. Logistic regression analysis showed that the presence of intraretinal fluid and thinner subfoveal choroidal thickness at baseline were associated with the development of macular atrophy after aflibercept treatment.Macular atrophy developed in about 10% of eyes with neovascular age-related macular degeneration during 12 months of treatment with a fixed regimen of aflibercept. Intraretinal fluid and subfoveal choroidal thickness seem to be predictors for development of macular atrophy after anti-vascular endothelial growth factor (VEGF) therapy.

Purpose To describe the clinical and genetic characteristics of pachychoroid geographic atrophy (GA) and to compare them with those of conventional GA associated with age-related macular degeneration (AMD). Design Observational case series. Participants Ninety-two eyes of 92 consecutive patients with GA who underwent a full ophthalmologic examination, including best-corrected visual acuity measurement, spectral-domain OCT, and fundus autofluorescence imaging. Their blood samples were genotyped for the major AMD-associated single nucleotide polymorphisms. Methods Pachychoroid GA was diagnosed if all of the following criteria were met: (1) GA in either eye; (2) clinical and anatomic features of the pachychoroid phenotype, such as reduced fundus tessellation and dilated choroidal vessels; and (3) no drusen in both eyes. Drusen-related GA was defined as conventional GA. Main Outcomes and Measures Comparison of clinical and genetic characteristics between pachychoroid GA and conventional GA. Results Twenty-one patients (22.8%) were diagnosed with pachychoroid GA. These patients were significantly younger than those with conventional GA (mean age, 70.5 vs. 78.5 years; P Conclusions Pachychoroid GA was diagnosed in 23% of patients with GA. Differences in the phenotypic and genetic characteristics of pachychoroid GA and conventional GA were identified. These 2 conditions should be differentiated when considering prevention and therapeutic strategies.

Rationale: Bilateral diffuse uveal melanocytic proliferation (BDUMP) is an extremely rare retinal exudative disease with physical disorders and no established treatment standard. We describe treatment courses in 3 cases of BDUMP. Patients concerns: Three male patients complained active vision loss. One male patient in his 70s (patient 1) was treated with prednisolone, mesalazine, and ciclosporin for hypoplastic anemia and ulcerous colitis. One male patient in his 60s (patient 2) was on prednisolone therapy for adult Still disease. Another male patient in his 70s (patient 3) was on prednisolone therapy for polymyalgia rheumatica, giant cell arteritis, and pancreatic body tumor. Diagnoses: Retinal specialists diagnosed these patients with BDUMP based on characteristic fundus findings of multiple red patches and retinal exudate. Interventions: Two patients (patients 1 and 2) with poor response to anti-vascular endothelial growth factor (VEGF) monotherapy and/or triamcinolone acetonide sub-Tenon injection were treated with combined anti-VEGF therapy and photodynamic therapy. One patient (patient 3) was treated with 3 rounds of monthly anti-VEGF monotherapy. Outcomes: Retinal exudates were resolved in all patients. No recurrence of retinal exudates was observed for at least 10 months, 2 years, or 4 months after the therapy in patients 1, 2, and 3, respectively. However, best-corrected visual acuity of the right eye was low (20/200) compared with that of the left eye (20/22) in patient 2 despite exudate resolution, due to permanent outer retinal damage secondary to long-term retinal exudate. Lessons subsections: Combined anti-VEGF therapy and photodynamic therapy may be a feasible therapeutic option for treatment-resistant exudate in patients with BDUMP. Early diagnosis of BDUMP and prompt administration of combination therapy are crucial.

PURPOSE To examine the recurrence rate of choroidal neovascularization (CNV) lesion activity in age-related macular degeneration (AMD) and associated factors after 1-year aflibercept treatment. METHODS Age-related macular degeneration eyes with 1-year aflibercept fixed-regimen treatment and a follow-up period of at least 18 months from the initial aflibercept injection for treatment-naive exudative AMD were retrospectively evaluated. The recurrence rate was examined. Age, gender, visual acuity, AMD subtype, greatest linear dimension, and retinal and choroidal thicknesses at the 12th month examination were compared between eyes with and without recurrence. Presence of remnant polyps and pigment epithelial detachment (PED) morphology were also compared in polypoidal choroidal vasculopathy (PCV) eyes. RESULTS Of the 98 eyes studied, 69 displayed a dry macula at the 12th month examination; 43.7% exhibited recurrence during the subsequent 12-month period in Kaplan-Meier analysis. Although no factors associated with recurrence were detected in AMD, remnant polyps and pigment epithelial detachment morphology at the 12th month examination were significantly associated with recurrence in polypoidal choroidal vasculopathy (P = 0.018 and 0.048, respectively). CONCLUSION Continuous, proactive treatment would be considered overtreatment for more than half of the AMD eyes that achieved a dry macula. Angiography and optical coherence tomography analyses may be useful for predicting recurrence in polypoidal choroidal vasculopathy eyes.

PURPOSE To investigate associations between parafoveal microcirculatory status and foveal pathomorphology in eyes with macular edema (ME) secondary to retinal vein occlusion (RVO). METHODS Ten consecutive patients (10 eyes) with acute retinal vein occlusion were enrolled, 9 eyes of which received intravitreal ranibizumab (IVR) injections. Foveal morphologic changes were examined via optical coherence tomography (OCT), and parafoveal circulatory status was assessed via adaptive optics scanning laser ophthalmoscopy (AO-SLO). RESULTS The mean parafoveal aggregated erythrocyte velocity (AEV) measured by adaptive optics scanning laser ophthalmoscopy in eyes with retinal vein occlusion was 0.99 ± 0.43 mm/second at baseline, which was significantly lower than that of age-matched healthy subjects (1.41 ± 0.28 mm/second, P = 0.042). The longitudinal adaptive optics scanning laser ophthalmoscopy examinations of each patient showed that parafoveal AEV was strongly inversely correlated with optical coherence tomography-measured central foveal thickness (CFT) over the entire observation period. Using parafoveal AEV and central foveal thickness measurements obtained at the first and second examinations, we investigated associations between differences in parafoveal AEV and central foveal thickness, which were significantly and highly correlated (r = -0.84, P = 0.002). CONCLUSION Using adaptive optics scanning laser ophthalmoscopy in eyes with retinal vein occlusion macular edema, we could quantitatively evaluate the parafoveal AEV. A reduction or an increase in parafoveal AEV may be a clinical marker for the resolution or development/progression of macular edema respectively.

To evaluate peripheral retinal hemorrhagic patterns in eyes with acute central retinal vein occlusion, and to explore their clinical relevance in differentiating for the retinal perfusion status, through a prospective, and cross-sectional study.Fifty eyes with acute central retinal vein occlusion were included. Retinal hemorrhagic patterns at the equator and retinal perfusion status were evaluated by ultra-wide field fundus photography and fluorescein angiography.Retinal perfusion was categorized as nonischemic in 29 eyes, ischemic in 18 eyes, and undeterminable in 3 eyes. None of the examined eyes had flame-shaped retinal hemorrhages in the periphery. All hemorrhages were rounded-dot or blot and were variable in size. Particle analysis was performed to quantify hemorrhage size, and showed higher values in eyes having larger blot hemorrhages, and lower values in eyes having dot or smaller blot hemorrhages. Mean size of maximum peripheral dot or blot hemorrhage was larger in eyes classified as ischemic (10,763.0 ± 5,946.3 pixels) than as nonischemic (2,839.9 ± 1,153.6 pixels, P0.001). The authors calculated area under the curve to investigate the ability of continuous variables to discriminate retinal perfusion status, which was 0.963 (P0.001) for mean size of maximum peripheral blot hemorrhages.The authors objectively evaluated retinal hemorrhagic patterns at the equator in eyes with acute central retinal vein occlusion using particle analysis. The resulting hemorrhage size measurement was considered to be often useful in determining retinal perfusion status. Because they can be noninvasively evaluated with readily available equipment, peripheral hemorrhagic patterns might be good clinical markers of retinal perfusion.

Genetic studies have investigated the pathogenesis of age-related macular degeneration (AMD). The pachychoroid concept has recently garnered attention as a possible explanation for AMD pathogenesis; the genetic characteristics of pachychoroid diseases have also been elucidated. In this review, we summarize previously reported genetic characteristics of AMD and pachychoroid diseases, and analyze these data to understand the pathogenesis of AMD and pachychoroid diseases. Previous studies show that VIPR2 and the CFH I62V A allele promote development of pachychoroid and central serous chorioretinopathy (CSC), while the CFH I62V G allele promotes development of drusen, pachychoroid neovasculopathy (PCN/PNV), and AMD. ARMS2/HTRA1 also promotes development of drusen, PCN/PNV, and AMD. TNFRSF10A and GATA5 are associated with CSC but not with pachychoroid, and TNFRSF10A is associated with AMD that includes PCN/PNV. These genetic characteristics suggest the following mechanisms of developing AMD and pachychoroid diseases. VIPR2 and the CFH I62V A allele promote pachychoroid development, which can result in CSC development. The CFH I62V G allele promotes a common step during PCN/PNV and AMD development induced by pachychoroid or drusen, such as damage of Bruch's membrane or retinal pigment epithelium (RPE). ARMS2/HTRA1 also promotes damage of Bruch's membrane or RPE, while the association with drusen formation is stronger in ARMS2/HTRA1 than in CFH. TNFRSF10A and GATA5 promote blood-retinal-barrier breakdown to induce CSC, which could lead to PCN/PNV development. Furthermore, recently reported genetic associations with the natural course of CSC suggest the importance of reconsidering the subtype classification of CSC. These associations would enable the development of personalized/precision medicine for CSC and.

Catalytic methane steam reforming was conducted at low temperature using a Pd catalyst supported on Ce

Low temperature ( Nb2O5 > Ta2O5. Surface proton conductivity has a key role for the activation of methane in an electric field. Proton hopping ability on the oxide surface was estimated using electrochemical impedance measurements. Proton transport ability on the oxide surface at 473 K was in the order of CeO2 > Nb2O5 > Ta2O5. The OH group amounts on the oxide surface were evaluated by measuring pyridine adsorption with and without H2O pretreatment. Results indicate that the surface OH group concentrations on the oxide surface were in the order of CeO2 > Nb2O5 > Ta2O5. These results demonstrate that the surface concentrations of OH groups are related to the proton hopping ability on the oxide surface. The concentrations reflect the catalytic activity of low-temperature methane steam reforming in the electric field.

Introduction:Having experienced the Tokyo subway sarin attack in 1995, Japan has established extremely strict rules on handling injured victims before they are sent to a hospital. As a result, it takes a long time before rescue actions are taken. This report aims to propose a reform to change the system that focuses on saving lives.Methods:First, the issues in firefighting on sites that currently present problems in Japan were identified. Then, Japanese guidelines were compared with those that were considered in other countries. Based on this, an ideal way of running rescue operations was examined, and a proposal to save many lives was made. This research was conducted with funding from the Ministry of Health, Labour, and Welfare of Japan (MHLW; Chiyoda, Tokyo, Japan).Results:In addition to preventing secondary injuries, the temporal aspect of rescuing people early with the clear goal of saving many lives was emphasized. Priority was given to measures against nerve agents to prevent secondary injuries, which put the rescuers’ lives at risk. Possible decontamination methods were pursued before choosing the one that was most appropriate. A linear algorithm was used to determine which decontamination method could be started immediately, and then the gradual use of equipment was recommended. Even if Level A personal protective equipment (PPE) and other dedicated equipment and materials cannot be procured, the possibility of starting rescue activities under certain condition using regular equipment was pointed out. The need for a system for possible victims who would require support, such as foreigners, the handicapped, and elderly people, was also identified. Japan limits the scope of activities that can be undertaken by emergency medical technicians (EMTs) on-site. The way in which on-site medical care can be provided with future legal revisions in mind was also discussed.Conclusion:There is an urgent need to build a framework in which rescue activities can take place so that the number of deaths would not rise, even if sarin and other poisons are scattered.

Background and aims Ultrasound-guided peripheral nerve block (USGPNB) is a safe and reliable procedure. However, it is not easy for the novice to perform an appropriate procedure from the start. The aim of this study was to evaluate whether laser-guided ultrasound probe facilitated the performance of USGPNB for the novice practitioners compared with standard ultrasound probe. Methods 32 medical students and residents who have never performed USGPNB were enrolled in this study. The participants were randomly allocated into two groups: GroupL using laser-guided probe and GroupS using standard probe. Each participant performed USGPNB with each probe of the group on porcine phantom a total of six times, three times with linear probe for the simulated nerve embedded in the shallow layer and three times with convex probe for the nerve in the deep layer. A blinded researcher measured the time required for each procedure. Finally, the participants answered a 5-point impression scale of the difficulty for USGPNB. We evaluated the differences in the time required for the procedure and in the impression scale of the difficulty. The date was statistically analyzed with Mann-Whitney U test. Results The time required for the procedure (min, median[IQR]) was significantly shorter in GroupL than GroupS in using linear probe (GroupL: 65[37.5–96.5], GroupS: 92.5[55.5–162.25], P=0.013) and convex probe (GroupL: 54.5[34.5–88.5], GroupS: 93.5[61.25–143], P=0.003). There was no difference between two groups about the impression scale of the difficulty for USGPNB. Conclusions Our study demonstrated that laser-guided ultrasound probe might facilitate the performance of USGPNB from the start of their training for the novice.

To assess whether optical coherence tomography angiography (OCTA) can be used as an alternative to conventional fundus fluorescein angiography (FFA) for the detection of myopic choroidal neovascularization (CNV).Validity and reliability analysis.Twenty-eight eyes of 26 consecutive Japanese patients with exudative lesions associated with pathologic myopia were included in this institutional study. Myopic CNV was detected in 23 eyes of 22 patients; 5 eyes exhibited simple hemorrhage. The main outcome measure was CNV detection by OCTA and FFA. The CNV area was individually measured by FFA and OCTA. Intraclass correlation coefficients (ICCs) for the CNV area, independently measured by 2 investigators using OCTA and FFA, were determined.OCTA images with sufficient quality for CNV assessment were obtained for 17 eyes with CNV and 4 without. FFA alone detected CNV in all 17 eyes, while OCTA alone detected CNV in 16 (94.1%). The 1 eye for which CNV was not detected by OCTA exhibited a 0.01 mm(2) area on FFA. Both FFA and OCTA did not detect CNV in eyes with simple hemorrhage. The mean CNV areas on FFA and OCTA were 0.59 ± 0.56 mm(2) and 0.51 ± 0.55 mm(2), respectively; the 2 values were significantly correlated (P.001, r = .86). The ICC (2, 1) values for FFA and OCTA were 0.944 and 0.997, respectively.Our results indicate that OCTA can detect most myopic CNVs if high-quality images are acquired and can preclude the requirement for FFA in these settings.

The recently emerged pachychoroid concept has changed the understanding of age-related macular degeneration (AMD), which is a major cause of blindness; recent studies attributed AMD in part to pachychoroid disease central serous chorioretinopathy (CSC), suggesting the importance of elucidating the CSC pathogenesis. Our large genome-wide association study followed by validation studies in three independent Japanese and European cohorts, consisting of 1546 CSC samples and 13, 029 controls, identified two novel CSC susceptibility loci: TNFRSF10A-LOC389641 and near GATA5 (rs13278062, odds ratio = 1.35, P = 1.26 × 10−13; rs6061548, odds ratio = 1.63, P = 5.36 × 10−15). A T allele at TNFRSF10A-LOC389641 rs13278062, a risk allele for CSC, is known to be a risk allele for AMD. This study not only identified new susceptibility genes for CSC, but also improves the understanding of the pathogenesis of AMD., 特殊な網膜剥離の発症に関わる遺伝子変異を発見 --中心性漿液性脈絡網膜症のゲノムワイド関連解析--. 京都大学プレスリリース. 2019-12-13.

Purpose To compare the efficacy of photodynamic therapy (PDT) in eyes with polypoidal choroidal vasculopathy (PCV) associated with and without pachychoroid phenotypes (pachychoroid PCV and nonpachychoroid PCV, respectively). Design Retrospective chart review. Participants Patients previously diagnosed with PCV and initially treated with PDT. Methods Patients were classified as having pachychoroid- or nonpachychoroid-driven conditions. The long-term visual outcome and its associated factors were investigated. Main Outcome Measures Visual acuity (VA) outcomes at 1, 2, 3, 4, and 5 years after initial PDT in pachychoroid and nonpachychoroid PCV. Results Of the 158 eyes, 88 (55.7%) met the criteria for pachychoroid PCV; 70 (44.3%) did not (nonpachychoroid PCV). In cases of pachychoroid PCV, VA improved significantly at 1 year (P = 0.042) and maintained baseline level at 5 years (P = 0.38). By contrast, VA continued to deteriorate in the nonpachychoroid PCV group during the follow-up period and had already declined significantly by the second year (P = 0.022, compared with baseline). Despite no difference in baseline VA between pachychoroid and nonpachychoroid PCV groups (P = 0.11), the VA at 5 years was significantly better in the pachychoroid PCV group compared with the nonpachychoroid PCV group (0.54±0.47 vs. 0.93±0.63, respectively; P = 0.23 × 10–3). The incidence of massive submacular hemorrhage (SMH) or vitreous hemorrhage (VH) was not different between groups at 5 years (P = 0.67), and their occurrence was associated with decreased VA in both the nonpachychoroid and pachychoroid PCV groups (coefficient β, 0.361 and 0.481; P = 0.59 × 10–3 and P Conclusions Five years after PDT treatment, VA was maintained at the baseline level in the pachychoroid PCV group but not in the nonpachychoroid PCV group. Massive SMH or VH during the follow-up period affected the final visual outcomes in both conditions.

Immunogenicity is a key factor capable of influencing the efficacy and safety of therapeutic antibodies. A recently developed method called MHC-associated peptide proteomics (MAPPs) uses liquid chromatography/mass spectrometry to identify the peptide sequences derived from a therapeutic protein that are presented by major histocompatibility complex class II (MHC II) on antigen-presenting cells, and therefore may induce immunogenicity. In this study, we developed a MAPPs technique (called Ab-MAPPs) that has high throughput and can efficiently identify the MHC II-presented peptides derived from therapeutic antibodies using magnetic nanoparticle beads coated with a hydrophilic polymer in the immunoprecipitation process. The magnetic beads could identify more peptides and sequence regions originating from infliximab and adalimumab in a shorter measurement time than Sepharose beads, which are commonly used for MAPPs. Several sequence regions identified by Ab-MAPPs from infliximab corresponded to immunogenic sequences reported by other methods, which suggests the method’s high potential for identifying significant sequences involved in immunogenicity. Furthermore, our study suggests that the Ab-MAPPs method can recognize the difference of a single amino acid residue between similar antibody sequences with different levels of T-cell proliferation activity and can identify potentially immunogenic peptides with high binding affinity to MHC II. In conclusion, Ab-MAPPs is useful for identifying the immunogenic sequences of therapeutic antibodies and will contribute to the design of therapeutic antibodies with low immunogenicity during the drug discovery stage.

Intravitreal injections of anti-vascular endothelial growth factor agents such as ranibizumab and aflibercept are the first-line treatment for neovascular age-related macular degeneration (AMD). However, data about long-term outcome in real-world clinical practice is scarce. We recruited 98 AMD patients and investigated four-year visual outcome. During the four years, 25 patients dropped out. The survivors received 7.0 ± 0.1 injections during the first year and 8.0 ± 7.4 injections in the following three years. The logarithm of minimum angle of resolution (logMAR) at baseline, year one, and year four was 0.28, 0.14 (P = 0.033), and 0.22 (P = 0.697), respectively. The gain of vision was not different among AMD subtypes (typical AMD, polypoidal choroidal vasculopathy, and retinal angiomatous proliferation; P = 0.513) Among the investigated factors, the presence of external limiting membrane (ELM), the absence of vitreoretinal adhesion, and thicker choroid at baseline were associated with better logMAR values at year four (coefficient beta = −0.388, 0.201, and −0.001; P = 7.34 × 10−6; 0.01, and 0.028, respectively). In the present study, vision was retained at baseline level after the four-year treatment with aflibercept. The status of ELM, vitreoretinal adhesion, and choroidal thickness were predictive factors for final vision.

Resveratrol is a natural polyphenol produced by plants in response to environmental stress. This compound has been shown to have pharmacological effects against a wide range of diseases including neurological, hepatic, cardiovascular and autoimmune conditions. The non-obese diabetic (NOD) mouse, in which loss of lacrimal and salivary gland function occurs, has been studied as an animal model for Sjögren’s syndrome. In this study, we confirmed that administration of resveratrol results in increased secretion of saliva in NOD mice. Although resveratrol enhanced Sirt1 activity, inflammatory cell infiltration was not affected. Moreover, expression of the anti-inflammatory cytokine IL-10 in salivary glands was enhanced in the resveratrol-administered group. Thus, we confirmed a novel therapeutic effect for resveratrol on salivary dysfunction in Sjögren’s syndrome.

In Drosophila, mature sperm are transferred from males to females during copulation, stored in the sperm storage organs of females, and then utilized for fertilization. Here, we report a gene named sheepish (shps) of Drosophila melanogaster that is essential for sperm storage in females. shps mutant males, although producing morphologically normal and motile sperm that are effectively transferred to females, produce very few offspring. Direct counts of sperm indicated that the primary defect was correlated to failure of shps sperm to migrate into the female sperm storage organs. Increased sperm motion parameters were seen in the control after transfer to females, whereas sperm from shps males have characteristics of the motion parameters different from the control. The few sperm that occasionally entered the female sperm storage organs showed no obvious defects in fertilization and early embryo development. The female postmating responses after copulation with shps males appeared normal, at least with respect to conformational changes of uterus, mating plug formation, and female remating rates. The shps gene encodes a protein with homology to amine oxidases, including as observed in mammals, with a transmembrane region at the C-terminal end. The shps mutation was characterized by a nonsense replacement in the third exon of CG13611, and shps was rescued by transformants of the wild-type copy of CG13611. Thus, shps may define a new class of gene responsible for sperm storage.

To describe the clinical and genetic characteristics of pachychoroid geographic atrophy (GA) and to compare them with those of conventional GA associated with age-related macular degeneration (AMD).Observational case series.Ninety-two eyes of 92 consecutive patients with GA who underwent a full ophthalmologic examination, including best-corrected visual acuity measurement, spectral-domain OCT, and fundus autofluorescence imaging. Their blood samples were genotyped for the major AMD-associated single nucleotide polymorphisms.Pachychoroid GA was diagnosed if all of the following criteria were met: (1) GA in either eye; (2) clinical and anatomic features of the pachychoroid phenotype, such as reduced fundus tessellation and dilated choroidal vessels; and (3) no drusen in both eyes. Drusen-related GA was defined as conventional GA.Comparison of clinical and genetic characteristics between pachychoroid GA and conventional GA.Twenty-one patients (22.8%) were diagnosed with pachychoroid GA. These patients were significantly younger than those with conventional GA (mean age, 70.5 vs. 78.5 years; P0.001), had a smaller GA area (mean, 0.9 mmPachychoroid GA was diagnosed in 23% of patients with GA. Differences in the phenotypic and genetic characteristics of pachychoroid GA and conventional GA were identified. These 2 conditions should be differentiated when considering prevention and therapeutic strategies.

PURPOSE To compare therapeutic responses to intravitreal aflibercept and ranibizumab in neovascular age-related macular degeneration (AMD)-affected eyes with and without choroidal vascular hyperpermeability (CVH). METHODS Medical records of 216 consecutive patients (216 eyes) with treatment-naive exudative AMD who had received three monthly intravitreal injections of aflibercept (2 mg) and ranibizumab (0.5 mg) at a single institution were analyzed. The associations of CVH with functional and morphologic changes were compared between the treatment groups. RESULTS Although foveal thickness (P = 0.85) and visual acuity (P = 0.13) changes were not significantly different between the treatment groups, subfoveal choroidal thickness (CT) (P = 0.001) and pigment epithelial detachment (PED) height (P = 0.043) decreased more profoundly in the aflibercept-treated group. The incidence of dry macula after treatments was lower in the ranibizumab-treated eyes with CVH than in those without CVH (P = 0.043), but it showed no significant difference between the aflibercept-treated eyes with and without CVH (P = 0.74). The aflibercept-treated eyes with CVH showed a higher incidence of dry macula (P = 0.04) and greater decrease in subfoveal CT (P = 0.002) than the ranibizumab-treated eyes with CVH. CONCLUSIONS Intravitreal aflibercept can achieve remission of exudative retinal changes in eyes with AMD even in the presence of CVH. In addition, it showed greater effects on the choroid and PED than intravitreal ranibizumab. The possible relationship between CVH suppression and decrease in CT warrants further study.

To investigate the 2-year outcomes of intravitreal injections of ranibizumab in typical neovascular age-related macular degeneration (tAMD) and polypoidal choroidal vasculopathy (PCV). Factors associated with visual outcomes are examined. We retrospectively reviewed medical records of 128 consecutive eyes with treatment-naive subfoveal AMD treated with ranibizumab and followed for ≥24 months. The association between visual outcomes and single nucleotide polymorphisms (SNPs) in ARMS2 A69S and CFH I62V genes were examined. Fifty-eight eyes were diagnosed with tAMD and 70 eyes with PCV. In tAMD eyes, visual acuity (VA) improved at 3 months (P = 0.020) but returned to the baseline level at 6 months. Thereafter, VA was maintained until 24 months. In PCV eyes, VA significantly improved at 3 months (P = 0.015) and persisted at 12 months (P = 0.025), but the VA improvement dissipated by 24 months. With regard to genetic associations with VA and VA change, neither VA nor VA change showed significant associations with these SNPs at all time points in tAMD. In the PCV eyes, there were significant associations between ARMS2 A69S and VA at baseline and 1 year (P = 0.017 and P = 0.025, respectively). However, VA change showed no significant difference among these genotypes in PCV. Intravitreal ranibizumab significantly improved the VA initially, but this improvement did not persist at 2 years post-treatment. In PCV, ARMS2 A69S polymorphism is associated with the baseline and 12-month VA, but is not associated with the visual prognosis at 24 months.

Objective: To investigate the role of transporter proteins in gadolinium (Gd) distribution and retention in the brain after one high-dose injection of Gd-based contrast agent (GBCA). Methods and materials: 30 ddY mice were randomly divided into three treatment groups to be intravenously injected with either Gadodiamide (linear GBCA), Gadobutrol (macrocyclic GBCA), or Gadoterate (macrocyclic GBCA) at a dose of 5 mmol/kg, while five mice in the control group received 250 µL saline. Five minutes (5 min) and ten days (10d) post-injection, the cerebrospinal fluid (CSF), choroid plexus (CP), and meninges and associated vasculature (MAV) were collected. The brain was then dissected to obtain the olfactory bulb, cerebral cortex, hippocampus, cerebellum, and brainstem. Proteins were extracted and separated by a size-exclusion high-performance liquid chromatography (SEC) system, and Gd concentrations were quantified by inductively coupled plasma mass spectrometry (ICP-MS). Results: 5 m post-injection, the Gadodiamide group had the highest Gd concentration, while Gadoterate had the lowest Gd concentration in all parts of the brain (p < .05). Gd concentration was highest in the cerebrospinal fluid (CSF) of the Gadodiamide group (578.4 ± 135.3 nmol), while Gd concentration was highest in MAV in the Gadobutrol group (379.7 ± 75.4 nmol) at 5 min post-injection. At 10d, in spite of the significant decrease of Gd from all GBCAs ( p < 0.01), retained Gd from Gadodiamide was detected all over the brain in several molecules that varied in size. Gd from Gadobutrol detected in the olfactory bulb (8.7 ± 4.5 nmol) was significantly higher than in other parts of the brain. Although most Gd from Gadobutrol was found in molecules similar in size to Gadobutrol, it was also found in several protein molecules of molecular size larger than the contrast agents. Only a small amount of Gd from Gadoterate was found in the brain. Conclusion: GBCAs may be able to pass through intact brain barriers, and the chemical structures of GBCAs may affect the penetration capability of Gd into the brain. Retained Gd in the brain tissue from Gadodiamide and Gadobutrol may be bound to some organic molecules, including proteins. Advances in knowledge: Intact GBCA are able to penetrate a series of brain barrier immediately after administration regardless the type of the chelate. Gd may be bound with macromolecules that may cause Gd retention in the brain.

Introduction:Japan experienced several major disasters in 2018.Aim:Evaluation of medical response was conducted and problems determined to solve for future response.Methods:An evaluation conducted on DMAT responding report of Northern Osaka Earthquake, West Japan Torrential Rain Disaster, Typhoon Jebi, and Hokkaido Iburi East Earthquake.Results:DMAT responded 58 teams for Osaka Northern Earthquake, 119 teams for West Japan Torrential Rain Disaster, 17 teams for Typhoon Jebi, 67 teams for Hokkaido Iburi East Earthquake. At the Osaka Northern Earthquake, by comparing the report of seismic diagnosis, results and, a magnitude of each region, hospital damage was evaluated. At the West Japan Torrential Rain Disaster, a flood hazard map was used to expect inundation at hospitals. At the Hokkaido Iburi East Earthquake, information of hospital generator was gathered and planned assistance for loss of power. Water supply cessation in the West Japan Torrential Rain Disaster and loss of power in the Hokkaido Iburi East Earthquake influenced hospital functionality. More precise preparation for hospital management in the event of a loss of power and water supply situation required in not only in local government but also each hospital. For the West Japan Torrential Rain Disaster, we experienced the same type of major disasters in the past, but could not manage accordingly. For the Hokkaido Iburi East Earthquake, we applied what was learned from the West Japan Torrential Rain Disaster.Discussion:Disaster medical operation was supposed to be managed with information from the Emergency Medical Information System (EMIS). However, 2018 disasters provided lessons that require a full understanding of disaster prior information and expected disaster damage information to manage disaster assistance. To accomplish effective disaster assistance, information must be gathered of supplies and assistance required by hospitals. An effective system to facilitate lessons learned needs to be developed

Incretin hormones, including glucagon-like peptide-1 (GLP-1), a target for diabetes mellitus (DM) treatment, are associated with cardioprotection. As dipeptidyl-peptidase IV (DPP-IV) inhibition increases plasma GLP-1 levels in vivo, we investigated the cardioprotective effects of the DPP-IV inhibitor vildagliptin in a murine heart failure (HF) model. We induced transverse aortic constriction (TAC) in C57BL/6J mice, simulating pressure-overloaded cardiac hypertrophy and HF. TAC or sham-operated mice were treated with or without vildagliptin. An intraperitoneal glucose tolerance test revealed that blood glucose levels were higher in the TAC than in sham-operated mice, and these levels improved with vildagliptin administration in both groups. Vildagliptin increased plasma GLP-1 levels in the TAC mice and ameliorated TAC-induced left ventricular enlargement and dysfunction. Vildagliptin palliated both myocardial apoptosis and fibrosis in TAC mice, demonstrated by histological, gene and protein expression analyses, and improved survival rate on day 28 (TAC with vildagliptin, 67.5%; TAC without vildagliptin, 41.5%; P < 0.05). Vildagliptin improved cardiac dysfunction and overall survival in the TAC mice, both by improving impaired glucose tolerance and by increasing GLP-1 levels. DPP-IV inhibitors represent a candidate treatment for HF patients with or without DM.

To investigate the incidence rate and risk factors for development of retinal pigment epithelial (RPE) atrophy during anti-vascular endothelial growth factor (anti-VEGF) treatment for retinal angiomatous proliferation.This study included 46 eyes with treatment-naive retinal angiomatous proliferation. All patients were treated with ranibizumab or aflibercept injections. Color fundus photography, spectral-domain optical coherence tomography, and fundus autofluorescence were evaluated for RPE atrophy diagnosis. Baseline characteristics and gene polymorphisms of ARMS2 A69S, and CFH I62V were analyzed for association with development and progression of RPE atrophy.Among 21 eyes treated with ranibizumab without preexisting RPE atrophy at baseline, 5 eyes (23.8%) developed RPE atrophy at 12 months. Among 20 eyes treated with aflibercept without preexisting RPE atrophy at baseline, 10 eyes (50.0%) developed RPE atrophy at 12 months. Refractile drusen at baseline was associated with RPE atrophy development at 12 months (P = 0.014), and the progression rate of RPE atrophy area was negatively correlated with subfoveal choroidal thickness at baseline (R = -0.595, P = 0.019). Gene polymorphisms were not associated with RPE atrophy.Retinal pigment epithelial atrophy developed in 36.6% during 12 months after anti-VEGF treatment for retinal angiomatous proliferation. The presence of refractile drusen at baseline was identified as a novel significant risk factor for RPE atrophy development.

Decreased gamma-aminobutyric acid (GABA)-mediated phasic inhibitory transmission in the spinal cord is thought to be responsible for the development of neuropathic pain. However, the role of GABAergic tonic current in substantia gelatinosa (SG) neurons remains to be fully elucidated. Using real-time polymerase chain reaction, we investigated the expression of the GABAA receptor δ subunit, which contributes to tonic current in the SG, in chronic constriction injury (CCI; a well-known model of neuropathic pain) and naive mice. The expression of the δ subunit mRNA was reduced by 40% in the ipsilateral SG of the dorsal horn of CCI mice compared to naive mice. We also performed behavioral experiments to assess the effect of the δ subunit-preferring agonist 4,5,6,7- tetrahydroisoxazolo(5,4-c)pyridine-3-ol (THIP) on thermal hypersensitivity with the Hargreaves test. Intrathecal administration of THIP significantly improved thermal thresholds of the ipsilateral hindpaw (4.55 ± 0.78 to 6.56 ± 1.09 s from baseline to after injection, respectively, P 0.1). GABAA receptor δ subunit-mediatedtonic current contributes to thermal hypersensitivity of CCI mice, and THIP may represent a therapeutic tool to improve thermal hypersensitivity.

To investigate the incidence rate, risk factors, and final outcomes of patients with age-related macular degeneration (AMD) who have experienced vision loss despite periodic aflibercept treatment. Subjects with treatment-naive AMD were prospectively recruited and treated with three monthly injections followed by two monthly injections of aflibercept. The incidence rate and risk factors of more than two lines of vision loss at any visit were investigated. We included 196 eyes of 196 patients. Vision loss was observed in 16 patients (8.2%). Eleven of 16 patients developed vision loss during the initial 3 months (68.8%). Vision loss remained in 11 eyes (68.8%) at the final visit. The maximum pigment epithelium detachment (PED) height (odds ratio = 1.46 for a 100-μm increase in the PED height) and disruption of the external limiting membrane (odds ratio = 4.45) were identified as risk factors for developing vision loss on logistic regression analysis. The incidence rate of vision loss during aflibercept treatment was relatively low. Identifying high-risk patients, those with a high PED height and disruption of the external limiting membrane, would be helpful in ensuring appropriate informed consent before treatment. Further studies are needed to establish optimal treatment for these patients.

To compare the 12-month-efficacy of 1 initial intravitreal ranibizumab injection (IVR) followed by pro re nata (PRN) dosing with that of three initial monthly IVR followed by PRN dosing in patients with macular edema (ME) after branch retinal vein occlusion.Prospective, interventional study.Of 81 eyes, 42 received 1 initial IVR injection (1+PRN group) and 39 eyes received 3 monthly IVRs (3+PRN). Pro re nata injections were performed when fovea exudative changes were evident.At Month 12, the visual acuity (VA) changes from baseline were -0.245 ± 0.227 and -0.287 ± 0.222, in the 1+PRN and 3+PRN groups, respectively; there were no significant difference between groups (P = 0.728). The stratified analysis showed that patients with better VA (baseline VA20/40) had similar significant improvement in VA at Month 12 (P0.001) to that of those with poorer VA (≤20/40). Better VA at Month 12 was significantly associated with younger age, better baseline VA, and thinner baseline central foveal thickness (P = 0.003,0.001, and0.001, respectively). Mean total number of IVR injections in the 1+PRN and 3+PRN groups were 3.8 ± 1.8 and 4.6 ± 1.4, respectively (P = 0.060). In both groups, shorter durations to the first PRN injection were associated with greater total PRN injection number (1+PRN, P = 0.006; 3+PRN; group, P0.001).In IVR treatment for ME after branch retinal vein occlusion, 1+PRN and 3+PRN regimens achieved similar 12-month functional outcomes. Patients with shorter durations to initial PRN injection may require more PRN treatments.

This prospective study included 63 eyes with acute branch retinal vein occlusion (BRVO) to evaluate the retinal hemorrhagic patterns at the posterior poles and explore their clinical relevance in macular perfusion differentiation. Retinal hemorrhagic patterns and macular perfusion status were evaluated via fundus photography and fluorescein angiography, respectively. Macular perfusion was judged as nonischemic in 30, ischemic in 28 and undeterminable in 5 among the 63 eyes. Predominant hemorrhagic patterns were flame-shaped in 39 (67.2%) and non-flame-shaped in 19 (32.8%) eyes. All 39 eyes with a flame-shaped hemorrhage showed a nonischemic macula. Of the 19 eyes classified as having a non-flame-shaped hemorrhage, 13 (68.4%) had an ischemic macula and 6 (31.6%) had a nonischemic macula (P P P P

To quantify the area of photoreceptor damage surrounding geographic atrophy (GA) and evaluate the relationship between structural abnormalities and retinal function in eyes with GA.Prospective cross-sectional study.Twenty-five eyes of 25 patients with GA associated with age-related macular degeneration underwent a full ophthalmologic examination, including spectral-domain optical coherence tomography (SDOCT), fundus autofluorescence (FAF), and microperimetry. ImageJ software was used to quantify the disruption of the ellipsoid zone on SDOCT images. Hypofluorescent areas of the FAF images indicated areas of retinal pigment epithelium (RPE) loss. Areas of interest graded by SDOCT (photoreceptor damage) and FAF (RPE loss) were registered with microperimetry within a 6-mm circle centered on the fovea.The mean area of photoreceptor damage was 7.69 ± 5.36 mm(2), which was significantly greater than the mean area of RPE loss (4.57 ± 4.07 mm(2), P.001). The average retinal sensitivity of the area with photoreceptor damage outside the area of RPE loss was lower than that of the area without photoreceptor damage (6.57 ± 4.13 dB vs 11.27 ± 3.78 dB, P.001). The area of photoreceptor damage surrounding the area of RPE loss was larger in eyes with pseudodrusen than in eyes without pseudodrusen (4.96 mm(2) vs 1.91 mm(2), P = .008). The only significant predictor of decreased retinal sensitivity was the area of the photoreceptor damage (P.001).Widespread photoreceptor damage surrounding sites of RPE loss occurred in eyes with GA, and it correlated with visual function. Evaluation of photoreceptor damage surrounding sites of RPE loss using OCT is important in patients with GA associated with AMD.

Background and Purpose— The majority of patients with ventricular wall motion abnormality (WMA) associated with subarachnoid hemorrhage (SAH) are postmenopausal women. In addition to elevated catecholamine, the role of estrogen in the pathogenesis of WMA has recently been implicated. The objective of this study is to clarify the interrelation among catecholamine, estrogen, and WMA in patients with SAH. Methods— A retrospective analysis was performed on the medical records of 77 patients with SAH (23 men, 54 women) whose plasma levels of epinephrine, norepinephrine, and estradiol had been measured and echocardiograms had been obtained within 48 hours of SAH onset. Results— Twenty-four patients (31%) were found to sustain WMA on admission. Multivariate regression analysis revealed that decreased estradiol ( P =0.018; OR, 0.902) and elevated norepinephrine levels ( P =0.027; OR, 1.002) were associated with WMA. After quadrichotomization of 77 patients based on sex/WMA, plasma norepinephrine levels were markedly elevated in men with WMA, whereas estradiol levels were markedly decreased in women with WMA. Plasma norepinephrine and estradiol levels were not correlated. Fifty-four female patients with SAH were further quadrichotomized based on norepinephrine/estradiol levels with a threshold value of 1375 pg/mL for norepinephrine and 11 pg/mL for estradiol. The incidence of WMA in the high-norepinephrine/low-estradiol group was significantly higher than the low-norepinephrine/high-estradiol group. Conclusions— To our knowledge, this is the first study to evaluate the interrelation among catecholamine, estrogen, and SAH-induced WMA. Lack of estradiol in postmenopausal women may predispose them to develop WMA after poor-grade SAH. However, the precise role of multiple sex hormones in SAH-induced WMA should be evaluated in future prospective studies.

To review the published reports concerning the apparent diffusion coefficient (ADC) value evaluation for the differentiation between malignant and benign breast tumors, articles were searched with the inclusion criteria: (a) a 1.5-T unit was used; (b) the diagnostic criteria were clearly stated; (c) diffusion-weighted images (DWIs) were obtained, and ADC value was calculated; (d) ADC values of breast tumors were reported with mean +/- standard deviation (SD). Meta-analysis from 12 articles revealed that the pooled sensitivity and specificity were 0.89 (95% confidence interval [CI], 0.85-0.91) and 0.77 (95% CI, 0.69-0.84), respectively, and that only the maximum b factor correlated with the mean ADC values of malignant and benign tumors, and the noncancerous breast tissue (P< 0.05,P < 0.01,P< 0.05, respectively). In conclusion, ADC evaluation is useful for the differentiation between malignant and benign breast tumors.

全身麻酔は意識消失, 不動化, 鎮痛などさまざまな要素が組み合わさった現象である. 近年の麻酔メカニズム研究では, 麻酔薬は神経細胞表面の受容体蛋白質に作用し, その効果を発揮すると考えられている. 神経細胞にはさまざまな受容体蛋白質が存在するが, その中でも特にGABAA受容体は麻酔メカニズム研究の中心的存在である. 最近, GABAA受容体を介する抑制性電流にはPhasic電流とTonic電流の2種類が存在することが明らかにされ, 特にTonic電流は麻酔メカニズムの新しいターゲットとして非常に注目を浴びている. 本稿では, Tonic電流を含むGABAA受容体を中心とした麻酔メカニズム研究の新しい知見についてまとめる.