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Purpose: To evaluate scleral thickness using anterior segment-optical coherence tomography (AS-OCT) in Fuchs endothelial dystrophy (FED) and compare the results with healthy individuals. Methods: Thirty-two eyes of 32 patients with FED and 30 eyes of 30 age, gender, spherical equivalent and axial length matched healthy participants were included. All subjects underwent a detailed ophthalmological examination including endothelial cell density and central corneal thickness (CCT) measurements. Scleral thickness was measured by AS-OCT (Swept Source-OCT, Triton,Topcon,Japan) in 4 quadrants (superior, inferior, nasal, temporal) from 6 mm posterior to the scleral spur. Results: The mean ages were 62.5 ± 13.2 (33–81) for FED group; 64 ± 8.1 (48–81) for control group. CCT was significantly greater in FED group than in the control group (586.8 ± 33.1 (514–635) vs 545.0 ± 20.7 (503–587), respectively)(p = 0.000). In FED group, mean scleral thickness in the superior, inferior, nasal and temporal quadrants were 434.0 ± 30.6 (371–498), 442.8 ± 27.6 (395–502), 447.7 ± 31.4 (382–502), 443.4 ± 30.3 (386–504) μm, respectively. In control group, the mean scleral thickness in the superior, inferior, nasal and temporal quadrants were 381.3 ± 20.0 (341–436), 383.2 ± 16.0 (352–436), 389.2 ± 21.0 (353–440), 383.2 ± 19.2 (349–440) µm, respectively. The mean scleral thickness was significantly higher in all quadrants in FED group than in control group (p = 0.000). Conclusion: In patients with FED, scleral thickness was significantly higher. FED is a progressive corneal disease that results in the accumulation of extracellular material in the cornea. These findings suggest that the accumulation of extracellular deposits may not be limited to the cornea. Due to their functional similarity and anatomical proximity, sclera may also be affected in FED. [ABSTRACT FROM AUTHOR]

The adverse effects of hard contact lenses (HCL) on the corneal endothelium have been studied in the short term; however, long-term effects remain still unclear. In this study, we analyzed the effect of long-term HCL use on corneal endothelial cell density (ECD) and morphology in healthy Japanese individuals. This cross-sectional observational study included individuals using HCL for refractive errors examined at a single specialty eye hospital. Patient age, duration of HCL usage, ECD, coefficient of variation of the cell area (CV), and rate of appearance of hexagonal cells (6A) obtained via non-contact specular microscopy were assessed. We analyzed 8604 eyes (mean age: 35.6 ± 10.0 years, 837 males, 3465 females). The mean duration of HCL usage was 14.7 ± 9.1 (range, 1–50) years. Multivariate analysis revealed that ECD significantly correlated with age (P < 0.001) but not with duration of usage; however, CV and 6A significantly correlated with both factors (P < 0.001). Univariate analysis revealed that CV and 6A correlated with duration of usage (all, P < 0.001). According to our results, CV and 6A correlated with the duration of HCL usage in ophthalmologically healthy Japanese individuals. Therefore, it is important to monitor corneal endothelial morphology in long-term HCL wearers. [ABSTRACT FROM AUTHOR]

Violet light (VL), 360–400 nm wavelength, is contained in the sunlight and is an effective element for myopia suppression. This study is to investigate the safety and efficacy of novel eyeglasses that emit VL from the frames. This is a double-masked, randomized, pilot clinical trial conducted in a clinic in Japan. Forty-three children with myopia were enrolled. Participants were randomly assigned to two groups, wearing VL-emitting eyeglass frames (VLf) that emitted VL of 310 μW/cm2 (VLf group, n = 22) or pseudo-placebo eyeglass frames with a minimal emission of VL (<10 μW/cm2) (control group, n = 21). The exposure time was 3 h per day. The primary outcomes were visual acuity, tear film break-up time, corneal endothelial cell density, and the slit-lamp/fundus examinations. The secondary outcome was the 6-month changes in the axial lengths and cycloplegic refractions. Forty-one (95%) participants were included; twenty-one in the VLf group and twenty in the control group. No significant differences were seen in any safety evaluation. Significant changes were seen in axial elongation, choroidal thickness, and cycloplegic refractions in the subgroup analysis of 8- to 10-year-old children (p < 0.05), but otherwise no significant differences were seen. The VLf showed short-term safety and effectiveness against myopia progression. [ABSTRACT FROM AUTHOR]

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Background: Hemodialysis (HD) is a common renal replacement therapy for patients with renal failure. Cardiovascular and cerebrovascular diseases are known to shorten survival periods and worsen the quality of life of HD patients. Atherosclerosis is a major cause of vascular diseases, and various factors such as abnormality of lipid metabolism and increased macrophage activity, oxidative stress, and endothelial dysfunction are associated with its pathogenesis and progression. Further, endothelial stem cells (ESCs) have been reported to play important roles in endothelial functions. Royal jelly (RJ) affects atherosclerosis- and endothelial function-related factors. The main aim of this trial is to investigate whether oral intake of RJ can maintain endothelial function in HD patients. In addition, the effects of RJ intake on atherosclerosis, ESC count, inflammation, and oxidative stress will be analyzed.Methods: This will be a multicenter, prospective, double-blind, randomized controlled trial. We will enroll 270 participants at Nagasaki Jin Hospital, Shinzato Clinic Urakami, and Maeda Clinic, Japan. The participants will be randomized into RJ and placebo groups. The trial will be conducted according to the principles of the Declaration of Helsinki, and all participants will be required to provide written informed consent. The RJ group will be treated with 3600 mg/day of RJ for 24 months, and the placebo group will be treated with starch for 24 months. The primary endpoint will be the change in flow-mediated dilation (FMD), a parameter of endothelium function, from the time before treatment initiation to 24 months after treatment initiation. The secondary and other endpoints will be changes in FMD; ESC count; serum levels of vascular endothelial cell growth factor, macrophage colony-stimulating factor, 8-hydroxydeoxyguanosine, and malondialdehyde; the incidence of cardiovascular diseases, cerebrovascular diseases, and stenosis of blood access; and safety.Discussion: This trial will clarify whether oral intake of RJ can maintain endothelial function and suppress the progression of atherosclerosis in HD patients. In addition, it will clarify the effects of RJ on ESCs, oxidative stress, and angiogenic activity in blood samples.Trial Registration: The Japan Registry of Clinical Trials  jRCTs071200031 .  Registered on 7 December 2020. [ABSTRACT FROM AUTHOR]

The corneal endothelium plays a key role in maintaining corneal transparency. Its dysfunction is currently treated with penetrating or lamellar keratoplasty. Advanced cell therapy methods seek to address the persistent global deficiency of donor corneas by enabling the renewal of the endothelial monolayer with tissue-engineered grafts. This review provides an overview of recently published literature on the preparation of endothelial grafts for transplantation derived from cadaveric corneas that have developed over the last decade (2010–2021). Factors such as the most suitable donor parameters, culture substrates and media, endothelial graft storage conditions, and transplantation methods are discussed. Despite efforts to utilize alternative cellular sources, such as induced pluripotent cells, cadaveric corneas appear to be the best source of cells for graft preparation to date. However, native endothelial cells have a limited natural proliferative capacity, and they often undergo rapid phenotype changes in ex vivo culture. This is the main reason why no culture protocol for a clinical-grade endothelial graft prepared from cadaveric corneas has been standardized so far. Currently, the most established ex vivo culture protocol involves the peel-and-digest method of cell isolation and cell culture by the dual media method, including the repeated alternation of high and low mitogenic conditions. Culture media are enriched by additional substances, such as signaling pathway (Rho-associated protein kinase, TGF-β, etc.) inhibitors, to stimulate proliferation and inhibit unwanted morphological changes, particularly the endothelial-to-mesenchymal transition. To date, this promising approach has led to the development of endothelial grafts for the first in-human clinical trial in Japan. In addition to the lack of a standard culture protocol, endothelial-specific markers are still missing to confirm the endothelial phenotype in a graft ready for clinical use. Because the corneal endothelium appears to comprise phenotypically heterogeneous populations of cells, the genomic and proteomic expression of recently proposed endothelial-specific markers, such as Cadherin-2, CD166, or SLC4A11, must be confirmed by additional studies. The preparation of endothelial grafts is still challenging today, but advances in tissue engineering and surgery over the past decade hold promise for the successful treatment of endothelial dysfunctions in more patients worldwide. [ABSTRACT FROM AUTHOR]

We aimed to investigate the cell density and morphology of the corneal endothelium in ophthalmologically healthy young Japanese, given the lack of normative data in literature. This observational study included eyes without ophthalmologic diseases, besides refractive errors, examined between 1996 and 2015 at Miyata Eye Hospital. Eyes with a history of ophthalmologic diseases or contact lens usage were excluded. Correlation of corneal endothelial cell density (ECD), coefficient of variation (CV), appearance rate of hexagonal cells (6A), and cell area with age were examined. Multivariate linear regression analysis was performed to determine the predictors of corneal parameters. We included 16842 eyes of 8421 individuals (19.6 ± 8.7 years). ECD was 3109.0 ± 303.7 cells/mm2 and significantly reduced with age (p < 0.001). The ECD reduction rate was 0.42%/year in the total population. On multivariate analysis, age and sex were significantly correlated with ECD, CV, 6A, and cell area (all p < 0.001). ECD, 6A, CV, and cell area are significantly associated with age in healthy young Japanese individuals. Monitoring their corneal endothelium is essential to assess the risk of endothelial damage. [ABSTRACT FROM AUTHOR]

Purpose: To determine the difference in mean corneal endothelial cell density (CECD) between the healthy and diseased eyes of the patients with unilateral pterygium with different morphology patterns by using a non-contact specular microscope (SP2000: Topcon Corporation, Japan) and to find out any relationship between severity of pterygium and daily sunlight exposure with the CECD loss. Methods: A descriptive cross-sectional prospective study was carried out at Al-Shifa Trust Eye Hospital (ASTEH), Rawalpindi, Pakistan from 21st January 2019 to 22nd January 2020. Two hundred eyes (n= 100 patients) of age range18 -68 years with unilateral pterygium were selected. Necessary demographic data and essential variables like age, smoking status, occupation, and daily direct sunlight exposure were determined. The severity of pterygium (grading) based on its morphology was determined by slit-lamp examination. CECD of each patient was carried out using a non-contact Specular Microscope. The healthy eye (without pterygium) of a patient was considered as control. Results: The age range in this study was 18– 68 years, with a mean age of 43.80 ± 24.37 years with a male to female ratio of 1.6:1 (62.00% males vs 38% females). Out of six occupations, the most common occupation was labour/construction work (n=31) followed by farming (n=27). The study reported a mean corneal endothelial cell density (CECD) of 2411.61± 143.64 vs 2751.41 ± 123.674 cells/mm2 in diseased and normal eyes, respectively (p-value = 0.0001). CECD was lower in grade 3 pterygium compared to less severe pterygium { grade 3 (Fleshy) =2261 cells/mm2 vs grade 2 (Intermediate)= 2413 cells/mm2 vs grade 1 (Atrophic)=2459 cells/mm2} although this difference between the groups was not found to be significant (p=0.065). No significant association between sunlight exposure and CECD loss was observed (p=0.065). Conclusion: This study concluded that the mean corneal endothelial cell density in patients with unilateral pterygium using a non-contact specular microscope were 2411.61± 143.64 cells/mm2. [ABSTRACT FROM AUTHOR]

Background: To evaluate the morphological features of corneal endothelial cells and their relationship with the stage of retinopathy in diabetes mellitus (DM).Methods: Patients with type 2 DM and age-matched controls were included in this prospective, cross-sectional study. Patients with diabetic retinopathy (DR) were divided into no-DR, non-proliferative DR and proliferative DR based on the fundus findings. Endothelial measurements were obtained using specular microscopy (Topcon SP-3000P, Japan). Endothelial cell density, average cell area, co-efficient variation of cell area and percentage of hexagonal cells were evaluated. Central corneal thickness (CCT) was measured using an ultrasound pachymeter. Endothelial cell parameters and CCTs of DM and control groups were compared and subgroup analysis of the patients with DM was performed.Results: One hundred and twenty patients (mean age 59.5 ± 8.1 years) were in the DM group, 112 patients (mean age 57.3 ± 7.2 years) were in the control group. Both the endothelial cell density and the hexagonal cell rate were lower, while the CCT was higher in the DM group. There were no significant differences between these two groups in terms of average cell area and co-efficient variation of cell area. Significant differences were detected between endothelial cell density values of subgroups, and endothelial cell density decreased as the stage of the DR increased. The average cell area, co-efficient variation of cell area and CCT measurements were similar across subgroups. Hexagonality values were significantly different between subgroups, with the lowest ratio of hexagonal cells in the proliferative DR group.Conclusion: Additional precautions should be taken to reduce the risk of endothelial decompensation prior to intraocular surgery, especially in patients with proliferative DR. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to evaluate the effect of vitamin D deficiency on corneal endothelial layer using specular microscopy.Methods: Fifty-eight eyes of 58 patients whose vitamin D level was below 15 ng/ml and who had no ocular pathology were included in the study (Group 1). Forty eyes of 40 age-and sex-matched subjects were enrolled as control group (Group 2). Corneal endothelial cell density (CD), coefficient of variation (CV), hexagonal cell ratio (HEX), and central corneal thickness (CCT) were measured using specular microscopy (Konan Medical Inc., Nishinomiya, Japan). The obtained data were compared between the groups.Results: There was no significant difference between the groups in terms of age and gender (P = 0.344, P = 0.399, respectively). The mean CD value was 2772.79 ± 202.21 cells/mm2 in Group 1 and 2954.97 ± 116.89 cells/mm2 in Group 2 (P = 0.001). The mean CV value was 30.31 ± 3.65 in Group 1 and 28.20 ± 2.71 in Group 2 (P = 0.003). The mean HEX value was 46.56 ± 6.32 in Group 1 and 51.07 ± 5.28 in Group 2 (P = 0.001). The mean CCT value was 555.87 ± 36.90 μ in group 1 and 549.0 ± 37.39 μ in Group 2 (P = 0.96).Conclusion: Vitamin D deficiency may affect the corneal endothelial layer. Patients with vitamin D deficiency should be evaluated for endothelial parameters in particular before an intraocular surgery. Further studies are needed to confirm our results. [ABSTRACT FROM AUTHOR]

Japan, along with most other countries in the world, is facing an increasingly aging population with a prolonged life expectancy. Concurrently, the need for medical intervention, including hepatectomy, has also increased for the elderly. Although surgical outcomes for older patients are reported to be comparable with those for younger patients, additional care in the selection of older patients for hepatectomy is considered necessary. Although the effect of aging on human liver regeneration is not fully understood, the regeneration of liver tissue after hepatectomy in elderly patients is shown to be generally worse than in younger patients and, to date, the mechanisms involved in the impairment of liver regeneration have not been fully clarified. Hepatic stellate cells (HSCs) are liver-specific mesenchymal cells that play critical roles in liver physiology and fibrogenesis. Recent studies in liver regeneration have increasingly focused on HSCs rather than on hepatocytes, Kupffer cells, endothelial cells, or infiltrating immune cells and suggest that HSCs might play a critical role in liver regeneration. In this review, we summarize the mechanisms involved in the impairment of liver regeneration in elderly patients, especially focusing on HSCs. We also discuss how HSCs contribute to the impairment of liver regeneration. [ABSTRACT FROM AUTHOR]

Corneal endothelial diseases are common almost everywhere in the world and have 3 main origins: primary diseases, largely dominated by Fuchs' endothelial corneal dystrophy (FECD), iatrogenic diseases which mainly complicate lens surgery, whether cataract or clear lens, but also other surgeries. The frequency of these complications is very low but the number of these surgeries being gigantic (probably around 50 million cases/year/worlwide), the number of post‐surgical bullous keratopathy remains important. Post‐keratoplasty endothelial failure (early or late) is the 3rd cause. All these diseases "consume" 50% of corneal grafts in the world and a large part of the population does not have access to any graft. The number of corneal donors is absolutely insufficient to meet the world demand and corneal bioengineering appears to be a realistic solution to complete the offer. Because of its relative simplicity and the demonstrated effectiveness of endothelial keratoplasty, endothelial bioengineering is logically the first to be developed. The Japanese team of 2 Kyoto universities (Prof. S. Kinoshita, N. Koizumi and N. Okumura) is a pioneer in this field and has demonstrated the effectiveness of injection therapy, which consists of cultivating mature endothelial cells from a small number of corneas from young donors, then injecting them into the anterior chamber of patients. The industrialization of the process is underway in 2 different start‐ups, one in the United States, the other in Japan. In addition to injection therapy, the bioengineering of endothelial grafts (Tissue engineered endothelial keratoplasty, TEEK), which consists of cultivating endothelial cells on a "corneo‐compatible" carrier to exactly reproduce a DMEK or a DSAEK, has passed the preclinical stage. This presentation will detail these different processes, their current limitations and the short, medium and long term perspectives. These Advanced Therapy Medicinal products (ATMP) are clearly revolutionizing corneal transplantation. By offering a new treatment for endothelial diseases, they will make it possible to redirect donor corneas to other corneal diseases that have no therapeutic alternative. Finally, this paper will also discuss the prospects of medical and medico‐surgical treatments for FECD, which are at the frontier of endothelial bioengineering. [ABSTRACT FROM AUTHOR]

Background Placenta praevia is an obstetric complication involving placental implantation in the lower uterine segment. Given the suggested aetiology of placenta praevia, adverse biological effects of air pollutants, such as plasma viscosity increment, endothelial dysfunction, and systemic inflammation, have the potential to induce low implantation. We explored the association between exposure to air pollutants during the pregnancy period up to implantation, and placenta praevia, in pregnant Japanese women. The outcome also included placenta accreta, which often exists in combination with placenta praevia. Methods From the Japan Perinatal Registry Network database, we obtained data on 40,573 singleton pregnant women in western Japan (Kyushu-Okinawa Districts) between 2005 and 2010. We assigned pollutant concentrations (suspended particulate matter [SPM], ozone, nitrogen dioxide [NO 2 ], and sulphur dioxide [SO 2 ]), measured at the nearest monitoring station to the respective delivery hospital of each woman. A logistic regression model was used to adjust for several covariates. Results The odds ratios (ORs) of placenta praevia per 10 units increase were 1.12 (95% confidence interval (CI) = 1.01–1.23) for SPM over 0–4 weeks of gestation, and 1.08 (1.00–1.16) for ozone. The association between exposure to NO 2 and SO 2 , and praevia, was in the direction of increased risk. SPM exposure during 0–4 weeks was associated with placenta accreta without praevia (OR = 1.33, 95% CI = 1.07–1.66). We found no association with exposure to air pollutants during 5–12 weeks and the second trimester. Conclusions Exposure to air pollutants through to implantation was positively associated with placenta praevia and accreta. [ABSTRACT FROM AUTHOR]

Erysipelothrix rhusiopathiae causes swine erysipelas (SE) and is classified –into 16 serovars based on cell surface antigens. Our previous study suggested that recent SE outbreaks were mostly caused by serovar 1a of E. rhusiopathiae with the surface protective antigen (Spa)A protein characterized by methionine and isoleucine at positions 203 and 257 (M203/I257 SpaA). In this study, four recent E. rhusiopathiae isolates comprising two serovar 1a with M203/I257 SpaA strains (2012 Miyazaki and 2012 Chiba), one serovar 1b strain (2015 Miyazaki), and one serovar 2a strain (2012 Nagano) were compared with each other and with the serovar 1a Fujisawa reference strain regarding in vitro phenotypes and in vivo virulence in mice and pigs. The serovar 1b and 2a strains, which are the less prevalent strains in the field in Japan, showed lower growth in liquid culture and lower virulence in animals than the serovar 1a variants. Adhesion of the serovar 2a strain to porcine endothelial cells was weaker than that of the serovar 1a and 1b strains. Several advantages of serovar 1a strains were found, but no plausible cause of the M203/I257 SpaA type variants to be selected for the most prevalent strains among serovar 1a strains was identified in this study. • Serovar 1a M203/I257 SpaA type variants of E. rhusiopathiae are currently the major etiological agent of SE in Japan. • Representative serovar 1b and 2a strains showed lower growth in liquid culture and lower virulence in mice and pig. • Adhesion of the serovar 2a strain to PECs was weaker than that of serovar 1a and 1b strains. • No plausible cause of M103/I257 SpaA type variants to be selected for the major strains in the field was identified. [ABSTRACT FROM AUTHOR]

Background: Elevated level of reactive carbonyl species, such as methylglyoxal, triggers carbonyl stress and activates a series of inflammatory responses leading to accelerated vascular damage. Edaravone is the active substance of a Japanese medicine, which aids neurological recovery following acute brain ischemia and subsequent cerebral infarction. Our aim was to test whether edaravone can exert a protective effect on the barrier properties of human brain endothelial cells (hCMEC/D3 cell line) treated with methylglyoxal. Methodology: Cell viability was monitored in real-time by impedance-based cell electronic sensing. The barrier function of the monolayer was characterized by measurement of resistance and flux of permeability markers, and visualized by immunohistochemistry for claudin-5 and β-catenin. Cell morphology was also examined by holographic phase imaging. Principal Findings: Methylglyoxal exerted a time- and dose-dependent toxicity on cultured human brain endothelial cells: a concentration of 600 µM resulted in about 50% toxicity, significantly reduced the integrity and increased the permeability of the barrier. The cell morphology also changed dramatically: the area of cells decreased, their optical height significantly increased. Edaravone (3 mM) provided a complete protection against the toxic effect of methylglyoxal. Co-administration of edaravone restored cell viability, barrier integrity and functions of brain endothelial cells. Similar protection was obtained by the well-known antiglycating molecule, aminoguanidine, our reference compound. Conclusion: These results indicate for the first time that edaravone is protective in carbonyl stress induced barrier damage. Our data may contribute to the development of compounds to treat brain endothelial dysfunction in carbonyl stress related diseases. [ABSTRACT FROM AUTHOR]

Marbling in beef, measured by Beef Marbling Standard ( BMS) number, is an economically important trait for beef cattle breeding and markets in Japan. We previously detected three single nucleotide polymorphisms ( SNPs) associated with BMS number of Japanese Black in Oita prefecture: c.*188 G> A in AKIRIN2, g.1471620 G> T in EDG1 and g.3109537 C> T in RPL27A. Here, we carried out single and multiple marker association analyses for the three SNPs in a different commercial Japanese Black population of 892 genotyped animals. The single marker analyses with the model including a single SNP showed significant associations of all SNPs with BMS number. The multiple marker analysis with the model including the main effects of the three SNPs and their interactions detected only significant main effects of g.1471620 G> T and g.3109537 C> T and a significant interaction between c.*188 G> A and g.1471620 G> T. These findings suggest the presence of inter-allelic interactions among genes affecting the development of beef marbling. For effective marker-assisted selection for BMS number, interactions among these markers need to be considered. [ABSTRACT FROM AUTHOR]

Objectives: Vasohibin-1 (VASH1) is an endogenous angiogenesis regulator expressed in activated vascular endothelial cells. We previously reported that high VASH1 expression is a predictor of progression in acinar adenocarcinoma of the prostate. In this study, we evaluated the characteristics of ductal adenocarcinoma of the prostate by comparing the level of VASH1 expression between ductal and acinar adenocarcinoma specimens., Design and Setting: A retrospective cohort study at two centres in Japan., Participants: Among the 1495 patients who underwent radical prostatectomy or transurethral resection for the past 15 years, a total of 14 patients diagnosed with ductal adenocarcinoma and 20 patients diagnosed with acinar adenocarcinoma with a Gleason score of 4+4 were included., Interventions: We immunohistochemically examined the CD34 expression as the microvessel density (MVD) and activated endothelial cells as the VASH1 density (vessels per mm 2 )., Primary and Secondary Outcome Measures: The primary outcome was the association of MVD and VASH1 density between ductal and acinar adenocarcinoma, and the secondary outcome was their oncological outcomes., Results: Nine patients (64.3%) with ductal adenocarcinoma were diagnosed at an advanced clinical stage, and five patients (35.7%) died from cancer during a median follow-up of 56.0 months. The VASH1 densities (mean±SD) in ductal and acinar adenocarcinoma were 45.1±18.5 vs 16.1±21.0 (p<0.001), respectively, while the MVD (mean±SD) in ductal and acinar adenocarcinoma were 65.3±21.9 vs 80.8±60.7 (p=0.666), respectively. The 5-year cancer-specific survival rates for high and low VASH1 expression were 70.0% and 100.0% (p=0.006), respectively. High VASH1 expression and a diagnosis of ductal adenocarcinoma were significant predictors of cancer-specific survival., Conclusions: Ductal adenocarcinoma was more aggressive and had higher VASH1 expression than acinar adenocarcinoma, although MVD was equivalent. These results indicate that VASH1 expression may serve as a novel biomarker for the aggressive nature of ductal adenocarcinoma., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: The deswelling of a corneal graft at the end of storage in the eye bank is essential before perforating or deep anterior lamellar keratoplasty to allow good donor/recipient congruence and to accelerate visual recovery. In France, CorneaJet (Eurobio, France) containing 5% Dextran T500 is the most commonly used medium, but its deswelling kinetics is not referenced and the duration of 48 or 72 hr is chosen purely by habit while the increase in endothelial toxicity over time is documented. Aim: To determine the corneal deswelling kinetics in CorneaJet. Methods: 12 corneas discarded by our eye bank were used. They had an endothelial cell density at reception (day 2 to day 4) of 1713 ± 389 cell/mm2 (mean ± SD). All had been stored in organoculture in CorneaMax medium at 31°C for at least 1 week. The corneas were immersed in 50 ml vials of CorneaJet (same batch) and were stored at 31°C. Central corneal thickness (CCT in µm) and central corneal volume (on an 8mm disc, CCV8 in mm3) were measured by optical coherence tomography (OCT, Casia I, Tomey, Japan). Transparency was evaluated on a prototype measuring contrast transmission (relative scale in %). Measurements were performed before immersion in CorneaJet and repeated at hour (H)3, H6, H9, H12, H18, H24, H30, H36 and H48. Results: All data were expressed as mean ± SD respectively at the different times. CCT: 1284 ± 249; 1031 ± 233; 897 ± 22; 773 ± 160; 741 ± 123; 673 ± 75; 626 ± 27; 638 ± 41; 645 ± 49; 652 ± 55. CCV8: 73 ± 9; 61 ± 9; 53 ± 9; 47 ± 8; 44 ± 6; 40 ± 4; 38 ± 3; 37 ± 3; 37 ± 3 and 37 ± 3. Transparency: 13 ± 4; 19 ± 5; 24 ± 6; 29 ± 6; 33 ± 7; 40 ± 7 41 ± 7; 44 ± 9; 45 ± 8 and 44 ± 11. Conclusions: Corneal deswelling in CorneaJet is rapid during the first 12 hr and reaches a plateau at 20 hr. After 20 hr, transparency and thickness are ideal for surgery. [ABSTRACT FROM AUTHOR]

Cell based treatment, as an option in contrast to ordinary donor corneal transplantation, is foreseen to give a not so much intrusive but rather more successful helpful methodology for corneal endothelial dysfunction. The proliferative capacity of human corneal endothelial cells is seriously controlled, in this way making the foundation of ideal conditions for the development of human corneal endothelial cells a basic perspective for the clinical utilization of a cell based treatment. As of late, effective development convention of human corneal endothelial cells for clinical application which incorporates the utilization of Rho kinase (ROCK) inhibitor and the restraint of changing development factor beta flagging were accounted for to advance the cell multiplication and to help human corneal endothelial cell societies that show high cell thickness. Creature tests demonstrated that a cell‐infusion treatment joined with the utilization of a ROCK inhibitor advances developed corneal endothelial cell bond onto the back cornea, at last bringing about the recuperation of corneal straightforwardness. A pilot clinical examination was as of late started in Japan to research the viability of a cell‐infusion treatment for patients with bullous keratopathy. [ABSTRACT FROM AUTHOR]

Purpose: In the field of regenerative medicine, Rho kinase inhibitors (ROCK inhibitors) show a protective effect on the corneal endothelium and promote effective healing in acute surgical wounds. In this study, we investigated the effectiveness of eyedrops containing ripasudil, a ROCK inhibitor approved in Japan for therapeutic use for glaucoma., Methods: In this retrospective observational study, 13 glaucoma patients (16 eyes) were treated with 0.4% ripasudil eyedrops twice a day after cataract surgery. The control group comprised 13 patients (17 eyes). The averaged corneal endothelial cell density from one central and four paracentral points was <1500/mm2 (range, 527 to 1439/mm2)., Results: The mean rate of increase in the thinnest corneal thickness one week after surgery was 1.25% in the ripasudil group, which was significantly lower than the 5.97% increase observed in the control group (P = 0.0037). The mean endothelial cell density loss 90 to 120 days after surgery, excluding bullous keratopathy patients for whom measurements were not possible was -4.5% in the ripasudil group, which was significantly lower than in control group (14.1%; P = 0.0003)., Conclusions: The results suggest that ripasudil may help maintain corneal endothelial functional integrity and reduce cell loss after cataract surgery in patients with low corneal endothelial cell density, suggesting that it may be more broadly useful for protection of the corneal endothelium after intraocular surgery., Translational Relevance: The clinically approved ROCK inhibitor ripasudil formulated as an eye drop for glaucoma has a corneal endothelial protective effect in cataract surgery for patients with low corneal endothelial cell density.

Aims: While most patients with myocardial infarction (MI) have underlying coronary atherosclerosis, not all patients with coronary artery disease (CAD) develop MI. We sought to address the hypothesis that some of the genetic factors which establish atherosclerosis may be distinct from those that predispose to vulnerable plaques and thrombus formation., Methods and Results: We carried out a genome-wide association study for MI in the UK Biobank (n∼472 000), followed by a meta-analysis with summary statistics from the CARDIoGRAMplusC4D Consortium (n∼167 000). Multiple independent replication analyses and functional approaches were used to prioritize loci and evaluate positional candidate genes. Eight novel regions were identified for MI at the genome wide significance level, of which effect sizes at six loci were more robust for MI than for CAD without the presence of MI. Confirmatory evidence for association of a locus on chromosome 1p21.3 harbouring choline-like transporter 3 (SLC44A3) with MI in the context of CAD, but not with coronary atherosclerosis itself, was obtained in Biobank Japan (n∼165 000) and 16 independent angiography-based cohorts (n∼27 000). Follow-up analyses did not reveal association of the SLC44A3 locus with CAD risk factors, biomarkers of coagulation, other thrombotic diseases, or plasma levels of a broad array of metabolites, including choline, trimethylamine N-oxide, and betaine. However, aortic expression of SLC44A3 was increased in carriers of the MI risk allele at chromosome 1p21.3, increased in ischaemic (vs. non-diseased) coronary arteries, up-regulated in human aortic endothelial cells treated with interleukin-1β (vs. vehicle), and associated with smooth muscle cell migration in vitro., Conclusions: A large-scale analysis comprising ∼831 000 subjects revealed novel genetic determinants of MI and implicated SLC44A3 in the pathophysiology of vulnerable plaques., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Serum uric acid (UA) is taken up by endothelial cells and reduces the level of nitric oxide (NO) by inhibiting its production and accelerating its degradation. Cytosolic and plasma xanthine oxidase (XO) generates superoxide and also decreases the NO level. Thus, hyperuricemia is associated with impaired endothelial function. Hyperuricemia is often associated with vascular diseases such as chronic kidney disease (CKD) and cardiovascular disease (CVD). It has long been debated whether hyperuricemia is causally related to the development of these diseases. The 2020 American College of Rheumatology Guideline for the Management of Gout (ACR2020) does not recommend pharmacological treatment of hyperuricemia in patients with CKD/CVD. In contrast, the Japanese Guideline on Management of Hyperuricemia and Gout (JGMHG), 3 rd edition, recommends pharmacological treatment of hyperuricemia in patients with CKD. In a FREED study on Japanese hyperuricemic patients with CVD, an XO inhibitor, febuxostat, improved the primary composite endpoint of cerebro-cardio-renovascular events, providing a rationale for the use of urate-lowering agents (ULAs). Since a CARES study on American gout patients with CVD treated with febuxostat revealed increased mortality, ACR2020 recommends switching to different ULAs. However, there was no difference in the mortality of Japanese patients between the febuxostat-treated group and the placebo or allopurinol-treated groups in either the FEATHER or FREED studies.

Objective: To investigate the expression levels and activation differences of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) gene in bone microvascular endothelial cells (BMECs) in different regions of human femoral head. Methods: Tissue specimens of femoral heads were obtained from hip arthroplasty carried out in China-Japan Friendship Hospital from January 2017 to June 2018. And the BMECs we isolated, purified, identified and cultured from different regions of the human femoral head: in the subchondral and cancellous bone regions. The BMECs from the two regions were intervened by hydrocortisone with a series of low concentration gradients (0, 0.03, 0.06, 0.10 mg/ml) respectively. The cell phenotype and functional status of BMECs and cell migration were detected by scratch experiments, and the angiogenesis in different regions of the femoral head was observed. The mRNA and protein expression of 11beta-HSD1, 11beta-HSD2 in BMECs were detected by real-time fluorescence quantitative polymerase chain reaction (RT-PCR) and Western-blot method, respectively. Results: With the increase of the concentration of hydrocortisone, the 11beta-HSD1 mRNA and protein expression of BMECs in the subchondral and cancellous bone regions of the femoral head increased significantly, and the 11beta-HSD1 mRNA and protein expression of BMECs in the subchondral bone region was significantly lower than those in cancellous bone region (all P< 0.05). The 11beta-HSD2 mRNA and protein expression of BMECs in the cancellous bone region showed a slow decrease first and then increased slightly at 0.10 mg/ml, while the expression in the subchondral bone region was the opposite. The 11beta-HSD2 mRNA and protein expression of BMECs in subchondral bone region was slightly higher than those in cancellous bone region (all P< 0.05), but there was no significant statistical difference between the two regions at 0.10 mg/ml (0.123±0.018 vs 0.126±0.021, 0.577±0.231 vs 0.609±0.174, t= 1.380, 0.409, both P> 0.05). At different times of the 0.06 mg/ml hydrocortisone intervention, there was no significant differences in scratch closure rate, the number of BMECs lumen, the number of buds and the length of tubule branches in different regions of the femoral head (all P> 0.05). Conclusion: The 11beta-HSD expression of BMECs in different regions of human femoral head is significantly different. The 11beta-HSD1 is high-expressed, but 11beta-HSD2 is low-expressed in BMECs of the cancellous bone region, and those are opposite in the subchondral bone region, which helps to explain the pathological characteristics and pathogenesis of hormonal osteonecrosis.

Ripasudil (K-115) is a novel Rho-associated protein kinase (ROCK) inhibitor. The Rho-ROCK pathway regulates key downstream effectors involved in many cellular functions, in particular in the actin cytoskeleton activity. The clinical effects of ripasudil expected on the eye include an intraocular pressure-lowering effect and a wound-healing activity on corneal endothelial cells, but many other functions are currently under investigation. To date, ripasudil has been approved in Japan (2014) for the treatment of glaucoma and ocular hypertension, and several clinical trials are currently investigating its role in the treatment of Fuchs' corneal dystrophy. In this review, we will discuss its pharmacokinetics, pharmacodynamics and clinical efficacy, focusing also on its safety and tolerability profile., (Copyright 2020 Clarivate Analytics.)