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Background: Reconstruction the skull base defect of an widely opened frontal sinus following extensive tumor resection in the anterior cranial fossa needs to be addressed to prevent postoperative cerebrospinal fluid (CSF) leakage or tension pneumocephalus. Case description: A 51-year-old man presented with headache and epileptic seizure. Magnetic resonance imaging (MRI) showed a cystic and solid extra-axial tumor with homogenous enhancement adhering the planum sphenoidale. Since the frontal sinus was widely opened following gross total resection of the tumor, the sinus was filled and covered with the adipose tissue. Thereafter, DuraGen overlaid the adipose tissue and was covered with the vascularized pericranium. Additionally, the edge of the pericranium flap was sutured to the dura, and further DuraGen overlaid by “sandwich” technique to protect against CSF leakage and tension pneumocephalus. Three months after operation, CT revealed that complete obliteration of the frontal sinus was confirmed and neither CSF leakage nor meningitis were observed. Conclusion: The present study demonstrated that closure of the widely opened frontal sinus using DuraGen inserted between the skull and the pericranium flap is an effective and promising method for the frontal sinus isolation. Keywords: DuraGen, Anterior cranial fossa, Frontal sinus, Skull base surgery, Duraplasty, Cerebrospinal fluid leakage

Summary: High-mobility group box-1 (HMGB1) protein has been postulated to play a pathogenic role in severe sepsis. Histidine-rich glycoprotein (HRG), a 75 kDa plasma protein, was demonstrated to improve the survival rate of septic mice through the regulation of neutrophils and endothelium barrier function. As the relationship of HRG and HMGB1 remains poorly understood, we investigated the effects of HRG on HMGB1-mediated pathway in endothelial cells, focusing on the involvement of specific receptors for HRG. HRG potently inhibited the HMGB1 mobilization and effectively suppressed rHMGB1-induced inflammatory responses and expression of all three HMGB1 receptors in endothelial cells. Moreover, we first clarified that these protective effects of HRG on endothelial cells were mediated through C-type lectin domain family 1 member A (CLEC-1A) receptor. Thus, current study elucidates protective effects of HRG on vascular endothelial cells through inhibition of HMGB1-mediated pathways may contribute to the therapeutic effects of HRG on severe sepsis.

Vogt-Koyanagi-Harada (VKH) disease is a systemic inflammatory disorder that affects pigment cell-containing organs such as the eye (e.g., chronic and/or recurrent granulomatous panuveitis). While the exact etiology and pathogenic mechanism of VKH disease are unclear, HLA-DR4 alleles have been documented to be strongly associated with VKH disease in various ethnic groups. Recently, a genome-wide association study (GWAS) found two new genetic risk factors (IL23R-C1orf141 and ADO-ZNF365-EGR2) in a non-HLA region from a Han Chinese population. In this study, we replicated these GWAS findings in a Japanese population. A total of 1,643 Japanese samples (380 cases with VKH disease and 1,263 healthy controls) were recruited. We assessed four single nucleotide polymorphisms (SNPs) shown in previous GWAS: rs78377598 and rs117633859 in IL23R-C1orf141, and rs442309 and rs224058 in ADO-ZNF365-EGR2. A significant allelic association with VKH disease was observed for all of the four SNPs (rs78377598: pc = 0.0057; rs117633859: pc = 0.0017; rs442309: pc = 0.021; rs224058: pc = 0.035). In genotypic association analysis, the minor alleles of IL23R-C1orf141 rs78377598 and rs117633859 had the strongest association with disease susceptibility under the additive model (pc = 0.0075 and pc = 0.0026, respectively). The minor alleles of ADO-ZNF365-EGR2 rs442309 and rs224058 were most strongly associated with disease susceptibility under the dominant model (pc = 0.00099 and pc = 0.0023, respectively). The meta-analysis of the current and previous studies found that all of the four SNPs exhibited a significantly strong association with VKH disease (meta-p < 0.00001: rs78377598, meta-odds ratio (OR) = 1.69; rs1176338, meta-OR = 1.82; rs442309, meta-OR = 1.34; rs224058, meta-OR = 1.33). In summary, our study replicated significant associations with VKH disease susceptibility reported in a previous GWAS. Thus, the IL23R-C1orf141 and ADO-ZNF365-EGR2 loci may play important roles in the development of VKH disease through genetic polymorphisms.

Takeshi Teshigawara,1–3 Akira Meguro,3 Nobuhisa Mizuki3 1Yokosuka Chuoh Eye Clinic, Yokosuka, Kanagawa, Japan; 2Tsurumi Chuoh Eye Clinic, Yokohama, Kanagawa, Japan; 3Department of Ophthalmology, Yokohama City University School of Medicine, Yokohama, Kanagawa, Japan Purpose: To evaluate the influence of pupil dilation on predicted postoperative refraction (PPR) and recommended intraocular lens (IOL) power to obtain target postoperative refraction calculated by using the third- and fourth-generation IOL power calculation formulas with a new optical biometer.Methods: This retrospective study included 162 eyes with cataract that underwent uneventful phacoemulsification with IOL implantation. PPR, recommended IOL power, anterior chamber depth (ACD), and lens thickness (LT) were measured pre- and post-pupil dilation. The change in PPR detected by using third-generation (Hoffer Q and SRK/T) and fourth-generation formulas (Haigis and Holladay 2) and the changes in ACD and LT were evaluated pre- and postdilation. The influence of dilation on the recommended IOL power calculated by each formula was analyzed.Result: ACD and LT significantly changed from pre- to postdilation. The mean absolute change in PPR between pre- and postdilation was significantly higher for fourth-generation formulas compared with third-generation formulas. The change in PPR between pre- and postdilation showed a significantly positive correlation with change in ACD and a significantly negative correlation with change in LT with fourth-generation formulas, but not with third-generation formulas. The discrepancy rate of recommended IOL power between pre- and postdilation calculated by fourth-generation formulas was significantly higher than that calculated by third-generation formulas.Conclusion: ACD and LT significantly changed by dilation. PPR and recommended IOL power significantly changed more by dilation when using fourth-generation formulas compared with third-generation formulas. Given the significant correlations of the change in PPR (between the pre- and postdilation) in the fourth-generation formulas and the changes in ACD and LT, the latter changes may be key in influencing dilation in the fourth-generation power calculation. Knowledge of the influence of dilation on fourth-generation formulas could help improve IOL calculation. Keywords: pupil dilation, IOL power calculation, predicted postoperative refraction

Takeshi Teshigawara,1–3 Akira Meguro,3 Kazuro Yabuki,4 Seiichiro Hata,5 Nobuhisa Mizuki3 1Yokosuka Chuoh Eye Clinic, Yokosuka, Kanagawa, Japan; 2Tsurumi Chuoh Eye Clinic, Yokohama, Kanagawa, Japan; 3Department of Ophthalmology, Yokohama City University School of Medicine, Yokohama, Kanagawa, Japan; 4Department of Ophthalmology, Saiseikai Yokohamashi Nanbu Hospital, Yokohama, Kanagawa, Japan; 5Yokohama Sky Eye Clinic, Yokohama Kanagawa, Japan Abstract: At present, only one design is available for trifocal intraocular lens (IOL); unfortunately, this particular design is not suitable for implantation in the sulcus with optic capture when posterior capsule rupture (PCR) occurs. Although three-piece bifocal IOLs can be implanted in the sulcus, this form of IOL can be vulnerable to tilt and decentration, thus causing aberration and photopic phenomena, such as halos and glares. However, visual axis centered optic capture using femtosecond laser-assisted cataract surgery (FLACS) is able to manage such complex operations. In the present study, we implanted a three-piece +4.0 D bifocal IOL into the sulcus of a patient who experienced PCR using optic capture and FLACS following the straightforward implantation of a one-piece trifocal IOL in the other eye. Defocus curves showed that the weakness of the trifocal IOL (nearest distances) was compensated for by the strength of the +4.0 D bifocal IOL, whereas the weakness of the +4.0 D bifocal IOL (middle distance) was compensated for by the strength of the trifocal IOL. Therefore, this combination provided the patient with a wider range of depth of focus. The contrast sensitivity in both eyes was within the normal range. Photopic phenomena were comparable with the bilateral implantation of the trifocal IOL. Anterior segment optical coherence tomography showed that tilt and decentration in the trifocal IOL implanted in the bag was significantly higher than the +4.0 D bifocal IOL implanted in the visual axis centered optic capture. This case showed that the intraindividual implantation of a single-piece trifocal IOL in the bag and a three-piece +4.0 D bifocal IOL in the sulcus, using a combination of optic capture and FLACS, is promising particularly in cases of PCR and can provide a wider range of vision without losing visual quality. Keywords: multifocal intraocular lens, mixing and matching, optic capture, femtosecond laser-assisted cataract surgery, posterior capsule rupture

Abstract: The plasma levels of inter-α inhibitor proteins (IAIPs) are decreased in patients with sepsis and the reduced levels correlate with increased mortality. In the present study, we examined the effects of IAIPs on human neutrophils to better understand the beneficial effects of IAIPs in the treatment of sepsis. We demonstrated that IAIPs induced a spherical shape that was smaller in size with a smooth cellular surface in a concentration-dependent manner. These changes were inhibited by a specific antibody against IAIPs. In contrast, bikunin, light chain of IAIP, had no effect on neutrophil morphology. The neutrophils treated with IAIPs could easily pass through the artificial microcapillaries and were prevented from entrapment inside the capillaries. Coincubation of human blood neutrophils with a confluent human vascular endothelial monolayer showed that adhesion of neutrophils on endothelial cells was suppressed by treatment with IAIPs. IAIPs inhibited the spontaneous release of reactive oxygen species (ROS) in a concentration-dependent fashion. ROS inhibition was associated with reductions in p47phox phosphorylation on Ser328. These results suggest that IAIP-induced morphological changes that render neutrophils quiescent, facilitate passage through the microvasculature, and reduce adhesion to vascular endothelial cells and production of ROS. Thus, IAIP plays a key role in controlling neutrophil activation.

The apoptotic process of erythrocytes is known as eryptosis, and is characterized by phosphatidylserine (PS) expression on the outer membrane. PS-positive erythrocytes are increased in sepsis, and PS is believed to facilitate coagulation of erythrocytes and activate macrophages. However, the relationship between eryptosis and abnormal coagulation in sepsis is still not fully understood.Histidine-rich glycoprotein (HRG) inhibits immunothrombus formation by regulating neutrophils and vascular endothelial cells. In the present study, we subjected isolated erythrocytes to Zn2+ stimulation, which activated their aggregation and PS expression. We then determined the Zn2+ contents in septic lung and kidney tissues, and found that they were elevated, suggesting that eryptosis was enhanced in these tissues. Erythrocyte adhesion to endothelial cells was also significantly increased after Zn2+ stimulation, and this effect was inhibited by HRG. Finally, we examined HRG treatment in septic model mice, and found that HRG decreased hemolysis, possibly due to its ability to bind heme.Our study demonstrated a novel Zn2+-initiated aggregation/thrombus formation pathway. We also showed the regulatory role of HRG in this pathway, together with the ability of HRG to inhibit hemolysis under septic conditions. HRG supplementation might be a novel therapeutic strategy for inflammatory disorders, especially sepsis. Keywords: Eryptosis, Aggregation, Hemolysis, Sepsis, Histidine-rich glycoprotein (HRG)

A silver-indium-cadmium (Ag-In-Cd, or AIC) alloy with a 1 eV high neutron cut-off energy was originaly developed as a decoupler to provide a narrow neutron pulse width with a short tail for the J-PARC 1-MW short-pulsed spallation neutron source. As a result of later studies, gold (Au) was chosen as a substitute for Ag for the production of spare decoupled moderators and reflector in order to reduce residual radioactivity thus easing handling and disposal of the spent moderator and reflector. The decoupler material Au-In-Cd (AuIC) was therefore investigated and developed. To implement it into an actual moderator-reflector assembly many critical engineering issues needed to be resolved with regard to large-sized bonding between AuIC and aluminum alloy A5083 by the hot isostatic pressing process (HIP). The HIP process for AuIC and aluminum was investigated in terms of surface condition, size, and heat capacity. Implementation of an AuIC decoupler into a spare reflector assembly was successfuly achieved and will result in a remarkable reduction of radioactivity compared to AIC without sacrificing neutronic performance.

Tatsukata Kawagoe,1 Masao Ota,1,2 Akira Meguro,1 Masaki Takeuchi,1 Takahiro Yamane,1 Haruna Shimazaki,3 Masaru Takeuchi,3 Eiichi Okada,4 Takeshi Teshigawara,1,5,6 Nobuhisa Mizuki1 1Department of Ophthalmology and Visual Science, Yokohama City University Graduate School of Medicine, Yokohama, 2Department of Medicine, Division of Gastroenterology and Hepatology, Shinshu University School of Medicine, Matsumoto, 3Department of Ophthalmology, National Defense Medical College, Tokorozawa, 4Okada Eye Clinic, Yokohama, 5Yokosuka Chuoh Eye Clinic, Yokosuka, 6Tsurumi Chuoh Eye Clinic, Yokohama, Japan Purpose: The crystallin beta A4 (CRYBA4) gene variant, rs2009066, was previously reported to be associated with high myopia in a southern Chinese population. In the present study, we investigated whether CRYBA4 variants were associated with high myopia in a Japanese population.Methods: We recruited 1,063 Japanese patients with high myopia (spherical equivalent [SE] ≤–9.00 D in both eyes) and 1,009 healthy Japanese subjects (SE >–1.00 D). We genotyped rs2009066 and three tagging single-nucleotide polymorphisms (SNPs), rs16982456, rs2071861, and rs4276, in the CRYBA4 region.Results: We did not find any significant association between these four SNPs and high myopia in an allele analysis. However, rs2009066 and rs2071861, which were in strong linkage disequilibrium (LD; r2=0.86), showed a marginal association with high myopia in the recessive genotype model of risk alleles (rs2009066 G allele: P=0.032, odds ratio [OR] =1.31; rs2071861 A allele: P=0.037, OR =1.31). Nevertheless, this association became insignificant after correcting for multiple testing (Pc >0.05).Conclusion: This study showed no significant association between CRYBA4 variants and high myopia in a Japanese population. Our findings did not correspond with a previous study. Further genetic studies with other populations are needed to elucidate a potential contribution of the CRYBA4 region in the development of high myopia. Keywords: high myopia, CRYBA4, association study, polymorphism

The CFA ratio, calculated using pretreatment C‐reactive protein (CRP), fibrinogen, and albumin levels (CRP × fibrinogen/albumin), was previously reported to be a significant prognostic factor for acute myeloid leukemia (AML). This multicenter retrospective study evaluated the prognostic value of the CFA ratio in 328 adult patients with newly diagnosed AML from April 2000 to March 2018. The median age was 49.5 years (range, 15–75 years), and 60.7% of the population were males. According to the European LeukemiaNet (ELN) risk classification, 67 patients (20.4%) were in the favorable‐risk group, 197 patients (60.1%) in the intermediate‐risk group, and 58 patients (17.7%) in the adverse‐risk group. The median CFA ratio was 1.07 (0–67.69). Based on the calculated cutoff CFA ratio of 1.44, the cohort included 176 and 152 patients with low and high CFA ratios, respectively. At a median follow‐up of 91.2 months, the 7‐year overall survival (OS) and disease‐free survival (DFS) rates were 51.2% and 48.6%, respectively, in the overall cohort. The 7‐year OS rates were 61.7% and 39.0% in the low and high CFA ratio groups, respectively (p < 0.001). The 7‐year DFS rates were 58.1% and 37.0% in the low and high CFA ratio groups, respectively (p = 0.004). In univariate analysis, age ≥50 years, male sex, ELN risk class, and comorbidities were associated with poor OS. Age, ELN risk class, comorbidities, and high CFA ratio were associated with poor OS in multivariate analysis. Subgroup analysis revealed that the CFA ratio was significant in the intermediate and adverse ELN risk classes. These findings indicate the prognostic significance of the CFA ratio in AML. [ABSTRACT FROM AUTHOR]

Advanced glycation end-products (AGEs) are produced by non-enzymatic glycation between protein and reducing sugar such as glucose. Although glyceraldehyde-derived AGEs (Glycer-AGEs), one of the AGEs subspecies, have been reported to be involved in the pathogenesis of various age-relating diseases such as diabetes mellitus or arteriosclerosis, little is known about the pathological and physiological mechanism of AGEs in vivo. In present study, we produced 4 kinds of polyclonal antibodies against AGEs subspecies and investigated the localization of AGEs-modified proteins in rat peripheral tissues, making use of these antibodies. We found that Glycer-AGEs and methylglyoxal-derived AGEs (MGO-AGEs) were present in pancreatic islets of healthy rats, distinguished clearly into the pancreatic α and β cells, respectively. Although streptozotocin-induced diabetic rats suffered from remarkable impairment of pancreatic islets, the localization and deposit levels of the Glycer- and MGO-AGEs were not altered in the remaining α and β cells. Remarkably, the MGO-AGEs in pancreatic β cells were localized into the insulin-secretory granules. These results suggest that the cell-specific localization of AGEs-modified proteins are presence generally in healthy peripheral tissues, involved in physiological intracellular roles, such as a post-translational modulator contributing to the secretory and/or maturational functions of insulin.

Abstract Inflammatory processes in brain tissue have been described in human epilepsy of various etiologies and in experimental models of seizures. High mobility group box-1 (HMGB1) is now recognized as representative of damage-associated molecular patterns (DAMPs). In the present study, we focused on whether anti-HMGB1 antibody treatment could relieve status epilepticus- triggered BBB breakdown and inflammation response in addition to the seizure behavior itself. Pilocarpine and methyl-scopolamine were used to establish the acute seizure model. Anti-HMGB1 mAb showed inhibitory effects on leakage of the BBB, and on the HMGB1 translocation induced by pilocarpine. The expression of inflammation-related factors, such as MCP-1, CXCL-1, TLR-4, and IL-6 in hippocampus and cerebral cortex were down-regulated by anti-HMGB1 mAb associated with the number of activated astrocytes, microglial cells as well as the expression of IL-1β. Both hematoxylin & eosin and TUNEL staining showed that the apoptotic cells could be reduced after anti-HMGB1 mAb treatment. The onset and latency of Racine stage five were significantly prolonged in the anti-HMGB1 mAb group. These results suggested that anti-HMGB1 mAb prevented the BBB permeability, reduced HMGB1 translocation while inhibiting the expression of inflammation-related factors, protected against neural cell apoptosis and prolonged Racine stage 5 seizure onset and latency.

Background. Tracheostomy is a necessary procedure for patients who require long-term mechanical ventilation support. There are two methods for tracheostomy in current use: surgical tracheostomy (ST) and percutaneous dilational tracheostomy (PDT). In the current study, we retrospectively compared the safety of both procedures performed in our intensive care unit (ICU). Methods. In this study, we enrolled subjects who underwent tracheostomy in our ICU between January 2012 and March 2016. We excluded subjects who were

Evaluating the performance of reinforced concrete (RC) structures during earthquakes and the resultant damage in the structures depends on an accurate load–displacement relationship. Several experimental and analytical evaluation methods for load–displacement relationships have been proposed and specified in current design standards. However, there have been few quantitative studies on the impact of drying on the yielding behavior of RC members, including evaluations of the effective stiffness of members. In this study, to investigate changes in the mechanical properties of RC beam–slab members due to drying of the concrete, cyclic loading tests are conducted on two RC beam–slab members with and without drying. It is found that the lateral structural stiffness of the specimen with drying decreased to 77% that of the specimen without drying. This is verified in the calculation of the flexural stiffness. In this calculation, it is assumed that drying shrinkage decreases the moment of inertia of the slab in tension but not in compression. Meanwhile, no difference is observed in the flexural capacity and yield displacement between the two specimens. Thus, there is no significant impact from drying shrinkage in RC beam–slab members on the lateral structural performance, while the shrinkage instead induces greater flexural cracking, which reduces the residual stresses in the specimen with drift leading to a gradual decrease in the impact of drying.