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Endothelial fenestrae are the transcellular pores existing on the capillary walls which are organized in clusters referred to as sieve plates. They are also divided by a diaphragm consisting of plasmalemma vesicle-associated protein (PLVAP). In this study, we examined the involvement of fibronectin signaling in the formation of fenestra and diaphragm in endothelial cells. Results showed that Itga5 and Itgb1 were expressed in PECAM1-positive endothelial cells isolated from the anterior lobe (AL) of the rat pituitary, and integrin α5 was localized at the fenestrated capillaries of the rat pituitary and cultured PECAM1-positive endothelial cells isolated from AL (CECAL). Inhibition of both integrin α5β1 and FAK, a key molecule for integrin-microtubule signaling, respectively, by ATN-161 and FAK inhibitor 14, caused the delocalization of PLVAP at the sieve plates and depolymerization of microtubules in CECAL. Paclitaxel prevented the delocalization of PLVAP by the inhibition of integrin α5β1. Microtubule depolymerization induced by colcemid also caused the delocalization of PLVAP. Treatment of CECAL with ATN-161 and colcemid caused PLVAP localization at the Golgi apparatus. The localization of PLVAP at the sieve plates was inhibited by BFA treatment in a time-dependent manner and spread diffusely to the cytoplasm. These results indicate that a constant supply of PLVAP proteins by the endomembrane system via the Golgi apparatus is essential for the localization of PLVAP at sieve plates. In conclusion, the endomembrane transport pathway from the Golgi apparatus to sieve plates requires microtubule cytoskeletons, which are regulated by fibronectin-integrin α5β1 signaling.

The aim of the current study is to identify possible new Ocular Response Analyzer (ORA) waveform parameters related to changes of retinal structure/deformation, as measured by the peripapillary retinal arteries angle (PRAA), using a generative deep learning method of variational autoencoder (VAE). Fifty-four eyes of 52 subjects were enrolled. The PRAA was calculated from fundus photographs and was used to train a VAE model. By analyzing the ORA waveform reconstructed (noise filtered) using VAE, a novel ORA waveform parameter (Monot1-2), was introduced, representing the change in monotonicity between the first and second applanation peak of the waveform. The variables mostly related to the PRAA were identified from a set of 41 variables including age, axial length (AL), keratometry, ORA corneal hysteresis, ORA corneal resistant factor, 35 well established ORA waveform parameters, and Monot1-2, using a model selection method based on the second-order bias-corrected Akaike information criterion. The optimal model for PRAA was the AL and six ORA waveform parameters, including Monot1-2. This optimal model was significantly better than the model without Monot1-2 (p = 0.0031, ANOVA). The current study suggested the value of a generative deep learning approach in discovering new useful parameters that may have clinical relevance.

Background: Bevacizumab (BEV) + Paclitaxel (PTX) and Eribulin represent the most frequently agents for the treatment of HER2-negative metastatic breast cancer (MBC). Eribulin has improved overall survival (OS) in EMBRACE trials. On the other hand, BEV has improved progression free survival (PFS) in several clinical studies, but not revealed prolongation of OS in them. There are difficult situations in making a clinical decision of when to choose which treatment option.Purpose: The purpose of this study is to compare two treatment strategies, Eribulin followed by BEV + PTX versus BEV + PTX followed by Eribulin. We evaluated whether sequential order of treatment affects survival benefit in patients who have been treated with both BEV + PTX and Eribulin in the real world. Methods: All patients who started BEV + PTX and Eribulin treatment for MBC from Aug-2011 to Jun-2018 were selected. Among 264 patients recorded in the TBCRG (14 institutions of Research Group) database, 180 patients had HER2-negative MBC. Of these, 84 patients were treated with both BEV + PTX and Eribulin sequentially regardless of treatment line. To evaluate the influence of sequential order, we compared the efficacy of Eribulin followed by BEV + PTX (arm E-B) to treatment with the reverse sequence (arm B-E). We used the two different analytical approaches to rubstify the findings from this study. Results: 38 patients were treated with E-B and 46 patients with the B-E sequence. We analyzed 60 cases within 3rd-line. In the entire cohort, the median time to failure of strategy (TFS) was 9.9 and 16.8 months in arm E-B and arm B-E, respectively (HR = 0.503, 95%CI 0.298-0.889, p=0.017). The respective median OS was 17.2 and 28.0 months (HR = 0.663, 95%CI 0.349-1.261. p=0.21). Similar HRs were derived from the PSMA and IPTWA cohort in TFS. Using PSMA, TFS was 9.0 and 14.1 months in arm E-B and arm B-E, respectively (HR = 0.406, 95%CI 0.172-0.955, p=0.039). The respective median OS was 12.8 and 24.0 months (HR = 0.61, 95%CI 0.232-1.6, p=0.315). Using IPTWA, TFS was 10.2 and 14.8 months in arm E-B and arm B-E, respectively (HR = 0.621, 95%CI 0.423-0.913, p=0.015). The respective median OS was 17.5 and 24.0 months (HR = 0.86, 95%CI 0.547-1.352, p=0.513).Conclusion: These results suggest that when patients with HER2-negative MBC are treated with both BEV + PTX and Eribulin, patients with prior BEV + PTX treatment is more likely to show more significant difference in results benefit than patients who are treated with prior Eribulin treatment. Citation Format: Koshi Matsui, Mitsuharu Earashi, Takuya Nagata, Akemi Yoshikawa, Wataru Fukushima, Zensei Nozaki, Yasuko Tanada, Kaeko Oyama, Katsuo Shimada, Kaoru Kiyohara, Tetsuro Shimizu, Keiko Iwata, Toru Yoshida, Kiichi Maeda, Akiyoshi Nakakura, Satoshi Morita, Tsutomu Fujii. Effect of Bevacizumab and Eribulin for metastatic breast cancer in the real world evaluated using the propensity score matching analysis (PSMA) and inverse probability of treatment weighting analysis (IPTWA) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-15-12.

Hexagonal cesium tungsten bronze (Cs0.32WO3) nanoparticles are well known as near-infrared (NIR) shielding materials. However, one of the critical issues for industrial applications involves a photochromic instability, i.e., a blue color change of this material under ultraviolet (UV) irradiation. This color change is attributed to the formation of HxWO3 phase through doping of H+ ions into Cs-deficient sites present at the surface of Cs0.32WO3 nanoparticles. Therefore, a new approach was adopted to prevent the color change by synthesizing a Cs0.32WO3 nanoparticle with less Cs-deficient sites using spray pyrolysis followed by heat treatment and short-time milling. The Cs0.32WO3 nanoparticles of spray pyrolysis route exhibited an improved photochromic stability under UV irradiation compared to those synthesized through a solid-state-reaction route. Detailed analysis using atomic resolution transmission electron microscopy revealed that the Cs0.32WO3 nanoparticles of spray pyrolysis route retain Cs ions up to a depth of less than 1 nm from the surface. This work demonstrates that the less-Cs-deficient Cs0.32WO3 nanoparticles are beneficial to improve the photochromic stability.

BACKGROUND Several studies have demonstrated that non-osmotic antidiuretic hormone activity contributes to the development of hyponatremia in children with common febrile diseases. However the relationship between hyponatremia and body temperature has remained unclear. Therefore, we examined this relationship in children with common diseases. METHODS In this retrospective case study based on chart review, 1,973 children presenting with acute illnesses at Hirakata City Hospital between November 2008 and October 2009, and for whom blood test data were available, were enrolled. The median age of this cohort was 2.7 years and the mean serum sodium concentration was 136.4 mEq/L; 454 patients showed hyponatremia (

The adenohypophysis is composed of the anterior and intermediate lobes (AL and IL), and secretes important hormones for growth, sexual development, metabolism, and reproduction. In the marginal cell layer (MCL) facing Rathke's cleft between the IL and AL, cluster of differentiation (CD) 9-, CD81-, S100β-, and SOX2-quadruple positive (CD9/CD81/S100β/SOX2-positive) cells in the adult IL are settled as tissue-resident stem/progenitor cells supplying hormone-producing cells to the AL. However, it is unclear how CD9/CD81/S100β/SOX2-positive cells in the IL-side MCL migrate into the AL across Rathke's cleft. In the present study, we performed chimeric pituitary tissue culture using S100β/GFP-transgenic rats and Wistar rats, and traced the footprint of S100β/GFP-expressing cells. We detected IL-side S100β/GFP-expressing cells in the AL tissue, demonstrating that these cells migrate from the IL to the AL. However, the cells failed to migrate in the opposite direction. Consistently, scanning electron microscopic analysis revealed well-developed cytoplasmic protrusions in the IL-side MCL, but not in the AL-side MCL, suggesting that IL-side CD9/CD81/S100β/SOX2-positive cells had higher migratory activity. We also searched for a specific marker for IL-side CD9/CD81/S100β/SOX2-positive cells and identified tetraspanin 1 (TSPAN1) from microarray analysis. Downregulation of Tspan1 by specific siRNA impaired cell migration and significantly reduced expression of snail family transcriptional repressor 2 (Slug), a marker of epithelial-mesenchymal transition (EMT). Therefore, CD9/CD81/S100β/SOX2-positive cells in the IL-side MCL can be stem/progenitor cells that provide stem/progenitor cells to the AL-side MCL via SLUG-mediated EMT and cell migration.

Glaucoma leads to irreversible blindness. Numerous anti-glaucoma eye drops have been developed. Unfortunately, many patients with glaucoma still suffer from progressive visual disorders. Recently, ripasudil hydrochloride hydrate, a selective Rho-associated protein kinase inhibitor, was launched for the treatment of glaucoma. However, adverse events, such as conjunctival hyperemia, are often noted in clinical trials using healthy subjects. Therefore, we investigated the onset, offset, and kinetic changes of conjunctival hyperemia induced by ripasudil ophthalmic solution in patients with open-angle glaucoma or ocular hypertension who had already been treated with anti-glaucoma eye drops other than ripasudil. Conjunctival hyperemia was evaluated by both clinical grading by 3 ophthalmic physicians and pixel coverage of conjunctival blood vessels determined by conjunctival hyperemia-analyzing software. Conjunctival hyperemia appeared within 10 min post-instillation in most of the participants. Clinical grade and pixel coverage increased significantly 10 min post-instillation and then decreased. In most of the participants, hyperemia resolved within 2 h. Median conjunctival hyperemia offset was 90 min. A tendency of monotonic increase was observed between clinical grade and pixel coverage. Taken altogether, hyperemia induced by ripasudil was transient in glaucoma patients who had already been treated with anti-glaucoma eye drops other than ripasudil.

The metastable state hexagonal-tungsten oxide (h-WO3) has been attracting attention over the past decade because of its high reactivity that arises from the hexagonal channels in its crystal structure. Simplification of the process used to synthesize h-WO3 is an important step to facilitate the industrial applications of this material. In this study, we addressed this challenge by developing a spray pyrolysis process to synthesize highly crystalline h-WO3. The ratio of the monoclinic to the hexagonal phase was controlled by adjusting the segregation time. Single-phase h-WO3 nanorods were synthesized using a carrier gas flow rate of 1 L/min, which was equivalent to a segregation time of 18.4 s. The ability of the h-WO3 nanorods to adsorb nitrogen and carbon dioxide was evaluated to confirm the presence of hexagonal channels in the crystal structure.

ObjectivesWe evaluated early medication persistence with new topical antiglaucoma eyedrops, omidenepag isopropyl 0.002% (a selective prostaglandin EP2 agonist).Design and settingRetrospective two-institute study in Himeji and Akashi in Japan.ParticipantsWe analysed patients with glaucoma who were prescribed topical omidenepag isopropyl from November 2018 to December 2019. From the last outpatient visit of patients until February 2020, 235 patients were prescribed a new solution of omidenepag isopropyl (129 patients in the initial monotherapy group, 85 in the switching group (switched from another topical antiglaucoma eyedrops), 19 added to another topical antiglaucoma eyedrops group, and 2 were lost to follow-up)). Additionally, we recruited 98 patients (3 were lost to follow-up) who received initial latanoprost 0.005% monotherapy during the same period as a control group.OutcomesMedication persistence failure was defined as drug discontinuation due to any adverse effects or change of therapy. Kaplan-Meier survival analysis was performed with a Cox regression analysis.ResultsAmong 233 patients, 48 (20%) showed failure of treatment; the median persistence time of all patients was 165 days, and the median time until discontinuation of omidenepag isopropyl was 45 days. The total persistence rates were 85%, 80% and 70% at 3, 6 and 12 months, respectively. Risk factors for failure were male gender (HR: 1.45, p=0.023) and monotherapy/switching (HR: 1.715, p=0.002). Comparison between latanoprost and omidenepag isopropyl monotherapy, only male gender (HR: 1.43, p=0.016) was a significant risk factor. Failures associated with omidenepag isopropyl were due to insufficient intraocular pressure-lowering efficiency (n=26, observed during all the period), followed by conjunctival hyperaemia (n=10) and visual acuity disturbance (n=5) in patients who were observed until 3 months.ConclusionMedication persistence with omidenepag isopropyl is mostly positive; however, clinicians should also be cautious of early failure.

Cesium tungsten bronze (Cs0.32WO3) nanoparticles (NPs) have attracted attention as a transparent near-infrared (NIR) absorbing material. In this study, a solvent-free aerosol method, namely solid-fed spray pyrolysis, was applied for the synthesis of Cs0.32WO3 NPs. Optimising the reaction temperature and H2 concentration in the carrier gas led to highly crystalline Cs0.32WO3 NPs with well controlled stoichiometry. The obtained Cs0.32WO3 NPs exhibited 13.7% NIR transmittance at 1425 nm with 80% visible light transmittance; these NIR absorption properties were superior to those of the Cs0.32WO3 NPs produced by a liquid-fed spray pyrolysis method. This improvement was examined in terms of the crystal structure and the mechanism of particle formation.

Background Cosmetic problems induced by conventional prostaglandin F2α (PGF2α) analogs are common. We prospectively evaluated the improvement of patients with prostaglandin-associated periorbital syndrome (PAPS) for whom the treatment regimen was switched from conventional PGF2α analogs to a new selective prostaglandin-EP2 agonist (i.e., omidenepag isopropyl). Methods We finally evaluated 12 patients with follow-up for one year who changed the therapy from conventional PGF2α drugs to omidenepag isopropyl. Digital facial images of the patients were captured prior to the initiation of therapy with omidenepag isopropyl and after approximately three, six, and 12 months. Three independent observers judged the recovery according to the five signs of PAPS - deepening of the upper eyelid sulcus (DUES), flattening of the lower eyelid bags, upper eyelid ptosis, ciliary hypertrichosis, and periorbital skin hyperpigmentation - by comparing images at baseline and each month. Results The mean age of patients (eight females; four males) was 61 years. The original PGF2α drugs were bimatoprost (N = 7), latanoprost (N = 3), travoprost (N = 1), and tafluprost (N = 1). The mean duration of treatment with PGF2α was 61 months. PAPS signs were evaluated in 11 patients after three months and in all 12 patients after six and 12 months. After three, six, and 12 months, DUES improved in five, six, and six patients, respectively; flattening of the lower eyelid bags improved in two, two, and three patients, respectively; upper eyelid ptosis improved in zero, one, and two patients, respectively; ciliary hypertrichosis improved in zero, one, and zero patients, respectively; and eyelid pigmentation improved in one, five, and three patients, respectively. Recovery of DUES was the most observed sign at ≤50%, whereas the recovery of ciliary hypertrichosis was the least sign at ≤8% at 12 months. All patients with improved DUES at one year had been receiving bimatoprost or travoprost. Conclusions Some PAPS signs improved after the administration of omidenepag isopropyl for one year. Our findings are useful for patients suffering from cosmetic problems induced by conventional PGF2α analogs.

Purpose: To evaluate the pattern of conjunctival hyperemia induced by omidenepag isopropyl 0.002% and ripasudil 0.4%, and its correlation with the degree of hyperemia. Subjects and Methods: We previously reported the time course of conjunctival hyperemia induced by administering one drop of omidenepag isopropyl to one eye and one drop of ripasudil to the other eye in 34 healthy subjects (mean age: 29.7 years; 22 females, 12 males). We assessed the degree of hyperemia by slit-lamp photography of the frontal and temporal conjunctiva 0, 15, 30, 60, 120, 180, and 360 min after the administration of one drop of omidenepag isopropyl and ripasudil. The data were used to compare the frontal photographs before and at the peak of hyperemia according to the clinical hyperemia score (0-3) and classify the pattern of developing hyperemia due to both drugs. We also examined the correlation between the degree of hyperemia by comparing the images captured at the peak of hyperemia in both groups, using clinical hyperemia score and “percent coverage” of conjunctival hyperemia by using an automated hyperemia analysis software program; this program provides the pixel coverage of the conjunctival vessels in the region of interest. Results: There were significant differences in the developmental pattern of hyperemia between omidenepag isopropyl-administered and ripasudil-administered eyes (P

Objective We investigated the detailed time course of conjunctival hyperemia induced by omidenepag isopropyl ophthalmic solution 0.002% (omidenepag), a selective prostaglandin E2 receptor 2 agonist. Methods and analysis We recruited 34 healthy subjects and administered omidenepag in the right eye and ripasudil 0.4% in the left eye. We evaluated conjunctival hyperemia using slit-lamp photography at baseline and after 15, 30, 60, 120, 180 and 360 min. The conjunctival hyperemia score was graded by three independent observers using a scale from 0 (none) to 3 (severe). We also evaluated conjunctival hyperemia by the pixel coverage of conjunctival blood vessels (per cent coverage) determined using a conjunctival hyperemia-analysing software. Results In omidenepag, the conjunctival hyperemia score and per cent coverage peaked at both 30 min (mean score±SD: 1.57±0.67 and 11.90%±3.66%, respectively) and then gradually decreased at 60 min (10.79%±3.32%) and 120 min (1.10±0.52) when they reached a level that was not significantly different from the baseline values. For ripasudil 0.4%, the peak time of the conjunctival hyperemia score and per cent coverage were both at 15 min (score: 2.42±0.54 and 15.26%±3.38%). The degree of conjunctival hyperemia was significantly higher for ripasudil 0.4% than that for omidenepag from 15 to 30 min in both the conjunctival hyperemia score and per cent coverage (p, The article has been presented at the 30th Annual Meeting of the Japanese Glaucoma Society on 7 September 2019.

Purpose We evaluated the recovery of patients with PAPS for whom the treatment regimen switched from conventional prostaglandin F2α analogues to a new selective prostaglandin-EP2 agonist: omidenepag isopropyl. Patients and methods From November 2018 to July 2019, we prospectively evaluated 11 patients who had been using conventional PGF2α drugs. Digital photographs of the patients were taken before the start of omidenepag isopropyl therapy and ~3 and 6 months after. Three independent observers used the photographs to judged recovery according to the 5 signs of PAPS: deepening of the upper eyelid sulcus (DUES), flattening of the lower eyelid bags, upper eyelid ptosis, ciliary hypertrichosis, and periorbital skin hyperpigmentation. Results The mean age of patients was 61, and 7 patients were female. The original PGF2α drugs were bimatoprost, latanoprost, travoprost, and tafluprost. The mean duration of PGF2α treatment was 65 months. PAPS signs were evaluated in 10 patients after 3 months and in all 11 patients after 6 months: After 3 and 6 months, DUES improved in 3 and 3 patients, respectively; flattening of the lower eyelid bags improved in 1 and 2 patients, respectively; upper eyelid ptosis did not improve in any patients; ciliary hypertrichosis improved in 0 and 2 patients, respectively; and eyelid pigmentation improved in 2 and 8 patients, respectively. The 3 patients who showed improvement in DUES at 6 months had all previously used bimatoprost. Conclusions Some PAPS signs improved after patients started taking omidenepag isopropyl. Our findings will be useful for patients taking antiglaucoma eye drops.

Highly crystalline and hexagonal single-phase cesium tungsten bronze (Cs0.32WO3) nanoparticles were successfully synthesized by a flame-assisted spray pyrolysis followed by annealing under a reducing gas atmosphere. The resulting Cs0.32WO3 nanoparticles featured a pure hexagonal Cs0.32WO3 phase with a high crystallinity and homogeneous chemical composition. Unlike conventional methods, the proposed process in this paper has several advantages, including a short reaction time and the ability to yield products with high purity and good energy efficiency. Furthermore, the Cs0.32WO3 nanoparticles produced in this research showed a remarkable near-infrared shielding ability with a 97.7% cut-off at 1500 nm.

Background Tuberous sclerosis complex is an autosomal dominant genetic disorder that affects multiple organ systems and can result in tumors in the brain, skin, heart, and kidneys; it may also cause neurological symptoms. About 1 to 7% of patients develop end-stage renal disease due to bilateral renal angiomyolipoma. We herein describe a patient with a bilateral large kidney angiomyolipoma whose residual renal function was temporarily improved with everolimus treatment. Case presentation A 39-year-old man was diagnosed with tuberous sclerosis complex associated with an angiomyolipoma that was first detected at 12 years of age and had enlarged to a size that completely filled the bilateral kidneys. Although his kidney function was poor at the start of everolimus treatment as indicated by a creatinine-based estimated glomerular filtration rate of 13.7 mL/min/1.73 m2, his kidney function recovered with an annual increase in the glomerular filtration rate of 4.57 mL/min/1.73 m2 without morphological changes or a reduction in the size of the angiomyolipoma after everolimus treatment. As a result, we were able to delay the initiation of renal replacement therapy for more than 1 year. Conclusions Even in patients with tuberous sclerosis complex who exhibit decreased renal function, everolimus treatment can retain the renal function and delay introduction of dialysis without a reduction in the size of the renal angiomyolipoma. The pathophysiological mechanisms for the deterioration of renal function in patients with tuberous sclerosis complex may not involve renal parenchymal loss secondary to angiomyolipoma growth only but may also involve other mechanisms including glomerular hypertrophy and hyperfiltration associated with mTOR complex 1 overactivity.

This paper describes a volumetric solar receiver that is vertically integrated with beam-down optics for condensed light irradiation. The heat-transfer performance of a silicon carbide honeycomb receiver was investigated using a 30-kW th solar simulator and numerical simulation. The experiments achieved an air temperature of 840 K at the receiver outlet by varying the operational parameters. Numerical simulations were performed for a vertical honeycomb block with beam-down irradiation and a horizontal honeycomb block with tower-type irradiation to elucidate the effects of buoyancy. Three blocks with different sizes were simulated for a variety of operational parameters. When the block was oriented vertically, the flow and temperature fields remained nearly symmetric in and near the receiver. In contrast, when it was oriented horizontally, the flow and temperature became asymmetric, with the hot spot moving toward the receiver's side wall and the stream in the receiver being reversed. The vertical orientation's robustness to buoyancy effects prevented any reduction in the receiver efficiency or outlet temperature and suppressed the thermal leakage.

To quantify the resolution limits of scanning microwave impedance microscopy (sMIM), we created scanning tunneling microscope (STM)-patterned donor nanostructures in silicon composed of 10 nm lines of highly conductive silicon buried under a protective top cap of silicon, and imaged them with sMIM. This dopant pattern is an ideal test of the resolution and sensitivity of the sMIM technique, as it is made with nm-resolution and offers minimal complications from topography convolution. It has been determined that typical sMIM tips can resolve lines down to ∼80 nm spacing, while resolution is independent of tip geometry as extreme tip wear does not change the resolving power, contrary to traditional scanning capacitance microscopy (SCM). Going forward, sMIM is an ideal technique for qualifying buried patterned devices, potentially allowing for quantitative post-fabrication characterization of donor structures, which may be an important tool for the study of atomic-scale transistors and state of the art quantum computation schemes.

Hideaki Okumichi,1 Yoshiaki Kiuchi,1 Tetsuya Baba,2 Takashi Kanamoto,3 Tomoko Naito,4,5 Shunsuke Nakakura,6 Hitoshi Tabuchi,6 Hiroki Nii,7 Chie Sueoka,7 Yosuke Sugimoto1,8 1Department of Ophthalmology and Visual Science, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan; 2Shirai Eye Hospital, Mitoyo, Japan; 3Department of Ophthalmology, Hiroshima Memorial Hospital, Hiroshima, Japan; 4Department of Ophthalmology, Okayama University Graduate School of Medicine, Okayama, Japan; 5Department of Ophthalmology, Konko Hospital, Asakuchi, Japan; 6Department of Ophthalmology, Saneikai Tsukazaki Hospital, Himeji, Japan; 7Department of Ophthalmology, Hiroshima General Hospital, Hiroshima, Japan; 8Department of Ophthalmology, Hiroshima Prefectural Hospital, Hiroshima, Japan Purpose: To evaluate the ocular-surface safety of a 0.001% benzalkonium chloride-containing tafluprost/timolol fixed combination (TTFC) in patients with primary open-angle glaucoma (POAG) or ocular hypertension who have inadequate intraocular pressure (IOP) control with latanoprost monotherapy.Methods: This study is a multicenter, prospective, single-arm, open-label clinical study. Patients with POAG or ocular hypertension who have inadequate IOP control with latanoprost monotherapy were considered eligible. After providing informed consent, patients continued latanoprost monotherapy for 12 weeks, followed by a switch to TTFC. We evaluated the extent of ocular-surface damage using superficial punctate keratopathy (SPK) score, tear breakup time (TBUT), hyperemia score, IOP, systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate at 0, 4, and 12 weeks after switching.Results: A total of 68 patients were enrolled, of whom, 64 patients were included in the final analysis. No significant changes in SPK score, TBUT, or hyperemia score were observed at 4 and 12 weeks compared with week 0. IOP decreased significantly at 4 (13.9±2.5 mmHg) and 12 (14.1±2.5 mmHg) weeks, relative to week 0 (15.3±2.7 mmHg). No significant changes in either SBP or DBP were observed during the study, although patients’ mean heart rate decreased significantly after switching to TTFC. Adverse drug reactions to TTFC occurred in seven patients including two incidences of asthma and one of arrhythmia, and no events were serious.Conclusion: The ocular-surface safety of TTFC is not significantly different to that of latanoprost. Furthermore, switching from latanoprost to TTFC in patients with insufficient IOP control has additive IOP-lowering effects. TTFC is an effective approach for patients receiving latanoprost monotherapy who require more intensive IOP reduction. Keywords: tafluprost/timolol fixed combination, latanoprost, glaucoma, ocular-surface safety, intraocular pressure

We previously reported that a shallow circumpapillary retinal nerve fiber layer (cpRNFL) peak angle as measured by optical coherence tomography (OCT) suggests the temporal retina is stretched around the optic disc from the papillo-macular bundle (Yamashita T et al. Investigative Ophthalmol Vis Sci 2013). The purpose of the current study was to investigate the relationship between CorvisST tonometry (CST) corneal measurements, axial length (AL) and the change in OCT-measured cpRNFL peak angle, in young healthy subjects. OCT and CST measurements were carried out in 97 eyes of 97 young healthy volunteers. The relationship between cpRNFL peak angle and 12 CST parameters, adjusted for AL, was investigated using linear modelling. The mean ± standard deviation cpRNFL peak angle of the 97 healthy volunteers was 130.6 ± 25.4 (range: 77.8 to 207.0) degrees. The optimal linear model to explain cpRNFL peak angle (chosen from 216 different models) included three CST variables related to the speed and size of energy absorption (namely, A1 time, A1 length and A2 time), in addition to AL. In eyes with longer AL and shorter energy absorption in CST measurement, temporal retina is stretched around the optic disc from the papillo-macular bundle, as suggested by a shallow cpRNFL peak angle.

Reproduction is regulated by gonadotropins secreted from gonadotrophs. The production and secretion of gonadotropins are mainly regulated by gonadotropin-releasing hormone (GnRH). Agonists or antagonists that influence GnRH action on gonadotrophs are important to regulate reproduction; however, these factors have not been fully characterized due to the lack of simple and easy-to-use techniques to detect gonadotropin secretion from gonadotropin-producing cells. In the present study, we found that Gaussia luciferase (Gluc), which was expressed in LβT2 cells, can be secreted like a luteinizing-hormone (LH) upon stimulation with GnRH. The Gluc secreted into the medium was easily monitored as luminescence signals. The detection range of the GnRH-induced Gluc activity was comparable to that of the enzyme-linked immunosorbent assay for LH. In addition, when the Gluc was expressed in AtT20 cells, which produce adrenocorticotropic hormone (ACTH), the Gluc activity in the medium increased in parallel with the ACTH secretion upon stimulation with corticotropin-releasing hormone. Thus, the Gluc assay in the present study can be easily used for high-throughput screening of factors that influence LH or ACTH secretion from LβT2 or AtT20 cells, respectively.

Purpose We previously reported that the retinal deformation due to myopia was represented by the peripapillary retinal arteries angle (PRAA). In this study, we investigated the relationship between the PRAA and biomechanical properties measured with Corvis ST (CST) tonometry. Methods Thirty-four normative eyes of 34 subjects who underwent CST measurement were enrolled. The PRAA was calculated from a fundus photograph. Variables related to the PRAA were identified from age, axial length, spherical equivalent refractive error, and 10 CST parameters using model selection with the second-order bias-corrected Akaike information criterion index. Results The PRAA was best described with axial length (coefficient = -5.66, P < 0.0001), maximum deflection amplitude (mm; coefficient = 130.5, P = 0.0004), and deflection amplitude ratio (DA ratio) 2 mm (coefficient = -25.8, P = 0.0032), where mm was the amount of the maximum corneal apex movement and DA ratio 2 mm was the ratio between the deformation amplitudes at the apex and 2 mm away from the apex. The optimal model was significantly better than the model only with axial length (P = 0.0014, analysis of variance). Conclusions The PRAA was significantly better described with the CST parameters compared to the axial length model only; eyes with small PRAA (larger myopic retinal deformation) showed narrow and shallow maximum corneal deflection. Translational Relevance The Corvis ST parameters, which represents corneal biomechanical characteristics, were associated with myopic retinal deformation.

Cesium tungsten bronzes (Cs0.32WO3) have attracted much attention as a near-infrared absorbing material. We report the successful synthesis of highly crystalline and high purity Cs0.32WO3 nanoparticles through a spray pyrolysis route. Careful analyses disclosed the presence of cationic defects, that is, a tungsten deficiency and insufficient Cs doping in the Cs0.32WO3 nanoparticles. These cationic defects can be controlled by facile heat treatment in a mildly reducing atmosphere. In particular, we clarify that the tungsten deficiency is a key factor among the cationic defects to obtain high near-infrared absorption properties. Furthermore, this study clearly demonstrates the precise tunability of the optical properties by means of the lattice constants of the Cs0.32WO3 crystal. The realized range of lattice constants is significantly wider than those previously reported. These findings should contribute to the engineering of Cs0.32WO3 structure and properties.

Fluoroalkyl alcohols are effectivity oxidized to the corresponding fluoroalkyl carbonyl compounds by reaction with sodium hypochlorite pentahydrate in acetonitrile in the presence of acid and nitroxyl radical catalysts. Although the reaction proceeded slower under a nitroxyl radical catalyst- free condition, the desired carbonyl compounds were obtained in high yields. For the reaction with fluoroalkyl allylic alcohols, the corresponding α,β-epoxyketone hydrates were obtained in high yields.

The reaction of cyclopropylmethanols bearing aromatic substituents on their cyclopropane rings with diethylaminosulfur trifluoride (DAST) effectively caused ring-opening fluorination to produce homoallylic fluorides. This reaction proceeded via a carbocation intermediate. DAST reacted with cyclopropanecarbaldehydes having electron donating aromatic substituents to cause ring-opening fluorinations with the addition of two fluorine atoms to afford 1,4-difluorobut-1-enes.

With the introduction of simultaneous PET/MRI scanners, concurrent acquisition of PET and MRI data is feasible, allowing for improved patient convenience and decreased radiation dose. Although PET/MRI has been used in many settings, not all cancers benefit from the combined modality. With the availability of somatostatin receptor-targeted PET tracers such as 68Ga-DOTA-TOC and 68Ga-DOTA-TATE, imaging of NET patients has refocused on targeted imaging, particularly with the development of peptide receptor radiotherapy. Nonetheless, there are many patients who continue to benefit from dedicated MR imaging, such as those with liver-predominant disease. In these patients, SSR PET/MRI is an important option for optimal imaging. Both diffusion-weighted imaging and hepatobiliary phase imaging provide improved lesion detection compared to conventional MRI and CT, and the results can effect therapeutic decisions. Additionally, the use of motion correction techniques can be used to leverage the additional PET data acquired in dedicated liver PET/MRI to remove respiratory artifacts.

Human G2A is activated by various stimuli such as lysophosphatidylcholine (LPC), 9-hydroxyoctadecadienoic acid (9-HODE), and protons. The receptor is coupled to multiple intracellular signaling pathways, including the Gs-protein/cAMP/CRE, G12/13-protein/Rho/SRE, and Gq-protein/phospholipase C/NFAT pathways. In the present study, we examined whether zebrafish G2A homologs (zG2A-a and zG2A-b) could respond to these stimuli and activate multiple intracellular signaling pathways. We also examined whether histidine residue and basic amino acid residue in the N-terminus of the homologs also play roles similar to those played by human G2A residues if the homologs sense protons. We found that the zG2A-a showed the high CRE, SRE, and NFAT activities, however, zG2A-b showed only the high SRE activity under a pH of 8.0. Extracellular acidification from pH 7.4 to 6.3 ameliorated these activities in zG2A-a-expressing cells. On the other hand, acidification ameliorated the SRE activity but not the CRE and NFAT activities in zG2A-b-expressing cells. LPC or 9-HODE did not modify any activity of either homolog. The substitution of histidine residue at the 174(th) position from the N-terminus of zG2A-a to asparagine residue attenuated proton-induced CRE and NFAT activities but not SRE activity. The substitution of arginine residue at the 32nd position from the N-terminus of zG2A-a to the alanine residue also attenuated its high and the proton-induced CRE and NFAT activities. On the contrary, the substitution did not attenuate SRE activity. The substitution of the arginine residue at the 10th position from the N-terminus of zG2A-b to the alanine residue also did not attenuate its high or the proton-induced SRE activity. These results indicate that zebrafish G2A homologs were activated by protons but not by LPC and 9-HODE, and the activation mechanisms of the homologs were similar to those of human G2A.

Being delivered as a low birthweight (LBW) infant is a risk factor for elevated blood pressure and future problems with cardiovascular and cerebellar diseases. Although premature babies are reported to have low numbers of nephrons, some unclear questions remain about the mechanisms underlying elevated blood pressure in full-term LBW infants. We previously reported that glucocorticoids increased miR-449a expression, and increased miR-449a expression suppressed Crhr1 expression and caused negative glucocorticoid feedback. Therefore, we conducted this study to clarify the involvement of pituitary miR-449a in the increase in blood pressure caused by higher glucocorticoids in LBW rats. We generated a fetal low-carbohydrate and calorie-restricted model rat (60% of standard chow), and some individuals showed postnatal growth failure caused by growth hormone receptor expression. Using this model, we examined how a high-fat diet (lard-based 45kcal% fat)-induced mismatch between prenatal and postnatal environments could elevate blood pressure after growth. Although LBW rats fed standard chow had slightly higher blood pressure than control rats, their blood pressure was significantly higher than controls when exposed to a high-fat diet. Observation of glomeruli subjected to periodic acid methenamine silver (PAM) staining showed no difference in number or size. Aortic and cardiac angiotensin II receptor expression was altered with compensatory responses. Blood aldosterone levels were not different between control and LBW rats, but blood corticosterone levels were significantly higher in the latter with high-fat diet exposure. Administration of metyrapone, a steroid synthesis inhibitor, reduced blood pressure to levels comparable to controls. We showed that high-fat diet exposure causes impairment of the pituitary glucocorticoid negative feedback via miR-449a. These results clarify that LBW rats have increased blood pressure due to high glucocorticoid levels when they are exposed to a high-fat diet. These findings suggest a new therapeutic target for hypertension of LBW individuals.

Background Oxidative stress is a major factor responsible for minimal-change nephrotic syndrome (MCNS), which occurs most commonly in children. However, the influence of oxidative stress localized to mitochondria remains unclear. We examined the effect of a mitochondrion-targeting antioxidant, MitoTEMPO, in rats with puromycin aminonucleoside (PAN)-induced MCNS to clarify the degree to which mitochondrial oxidative stress affects MCNS. Materials and methods Thirty Wistar rats were divided into three groups: normal saline group (n = 7), PAN group (n = 12), and PAN + MitoTEMPO group (n = 11). Rats in the PAN and PAN + MitoTEMPO groups received PAN on day 1, and those in the PAN + MitoTEMPO group received MitoTEMPO on days 0 to 9. Whole-day urine samples were collected on days 3 and 9, and samples of glomeruli and blood were taken for measurement of lipid peroxidation products. We also estimated the mitochondrial damage score in podocytes in all 3 groups using electron microscopy. Results Urinary protein excretion on day 9 and the levels of lipid peroxidation products in urine, glomeruli, and blood were significantly lower in the PAN + MitoTEMPO group than in the PAN group (p = 0.0019, p = 0.011, p = 0.039, p = 0.030). The mitochondrial damage score in podocytes was significantly lower in the PAN + MitoTEMPO group than in the PAN group (p

Brain microvascular endothelial cells derived from human induced pluripotent stem cells (hiPS-BMECs) have been proposed as a new blood-brain barrier model, but their transport function has not been fully clarified. Therefore, in this study, we investigated the gene expression and function of transporters in hiPS-BMECs by means of quantitative reverse transcription-PCR, in vitro transcellular transport studies, and uptake experiments. mRNAs encoding ABC and SLC transporters, such as BCRP, MCT1, CAT1, and GLAST, were highly expressed in hiPS-BMECs. Transcellular transport studies showed that prazosin, [14C]l-lactate, [3H]l-arginine, and [3H]l-glutamate (substrates of BCRP, MCT1, CAT1, and GLAST, respectively) were transported asymmetrically across the hiPS-BMEC monolayer. Substrates of LAT1, OCTN2, CAT1, GLAST, MCT1, and proton-coupled organic cation (H+/OC) antiporter were taken up by hiPS-BMECs in a time-, temperature-, and concentration-dependent manner, and the uptakes were markedly decreased by inhibitors of the corresponding transporter. These results indicate that hiPS-BMECs express multiple nutrient and drug transporters.

Background: Resolution of inflammation is an active process essential for tissue homeostasis. Resolvin E series are potent pro-resolving mediators of inflammation derived from the omega-3 fatty acid eicosapentaenoic acid (EPA). Resolvin E3 (RvE3) is a novel lipid mediator recently identified as a member of the Resolvin E series. Aims and Objects: We determined the impact of RvE3 on allergic airway inflammation using a murine model of asthma. Methods: Allergic airway inflammation was induced in BALB/c mice by House dust mite (HDM) sensitization and challenge (Day0-2,14-17). RvE3 was administrated intraperitoneally after the last HDM challenge(Day17,18). Leukocytes from the bronchoalveolar lavage fluid (BALF) were enumerated, and the lung tissue was used for pathological analysis and assessment of expression of cytokine in the lung. Lung resistance was measured and reported as the percent increase from baseline. Results: RvE3 treatment significantly reduced airway eosinophil recruitment, levels of Th2 cytokine (IL-5 and IL-13), and lung resistance to inhaled methacholine. RvE3 treatment improved airway hyper-responsiveness and airway inflammation. Conclusion: These findings provide evidence for RvE3 as a pivotal counterregulatory signal in allergic inflammation.

Acetylation of α-tubulin is a well-studied posttranscriptional modification, which is mostly catalyzed by α-tubulin N-acetyltransferase (ATAT1). ATAT1 possibly affects various cellular functions related with microtubules, such as intracellular transport, cell motility, cilia formation, and neuronal signaling. Here, we analyzed the subcellular localization of immunolabeled ATAT1 in human fibroblast KD cells through the cell cycle using confocal laser scanning microscopy. ATAT1 dramatically changed its localization through the cell cycle, depending on the mitotic phase. In interphase, immunolabeled ATAT1 was observed in centrioles, nuclei, and basal bodies if the cells projected primary cilia. ATAT1 was intensely detected as clusters in the nuclei in the G1–G2 phase. In telophase, ATAT1 colocalized with chromatids and spindle poles, and ultimately migrated to the daughter nucleus, newly synthesized centrioles, and midbody. The nucleolus is a core region of ribosomal RNA transcription, and the midbody is associated with severing and depolymerizing of microtubules in the stembody. The specific distributions of ATAT1 through the cell cycle suggest multiple functions of ATAT1, which could include acetylation of microtubules, RNA transcription activity, severing microtubules, and completion of cytokinesis.

In contrast to many anuran amphibians, water is not reabsorbed from the urinary bladder in aquatic Xenopus , thereby helping to prevent excessive water influx. However, little is known about the molecular mechanisms for this process. In the present study, we have identified urinary bladder-type aquaporin, AQP-x2, in Xenopus laevis by cDNA cloning. The predicted amino acid sequence contained six putative transmembrane domains and the two conserved Asn-Pro-Ala motifs, characteristic of AQPs. The sequence also contained a putative N -glycosylation site and phosphorylation motifs for protein kinase A and protein kinase C. The oocyte swelling assay showed that AQP-x2 facilitated water permeability. Reverse transcription-PCR analysis indicated that AQP-x2 mRNA was expressed in the urinary bladder and lung, and faintly in the kidney. Immunomicroscopical study further localized AQP-x2 protein to the cytoplasm of granular cells in the luminal epithelium of the urinary bladder whilst AQP3 was observed along the basolateral side of these cells. In vitro stimulation of the urinary bladder with 10 −8 M vasotocin (AVT), 10 −8 M hydrin 1, or 10 −8 M hydrin 2 had no clear effect on the subcellular distribution of AQP-x2. When the AVT concentration was increased to 10 −6 M, however, AQP-x2 was partially transferred to the apical plasma membrane. The treatment with hydrin 1 or hydrin 2 at the same concentration failed to induce the translocation to the apical membrane. On the other hand, AQP3 remained along the basolateral side even after the treatment with vasotocin or hydrins. The results suggest that the poor responsiveness of AQP-x2 to neurohypophyseal peptides may be a main cause for the little water permeability of the urinary bladder of X. laevis .

Background Rotavirus gastroenteritis is severe and often results in dehydration and pre-renal azotemia. In addition, some patients with acute obstructive uropathy due to ammonium acid urate stones, developing approximately 6–7 days after the onset of rotavirus gastroenteritis, have been reported, mainly in Japan. The pathophysiological mechanism responsible for stone formation has not been clarified. In the present study, we investigated the clinical characteristics of these patients, and analyzed the pathophysiology underlying the formation of urinary stones. Methods A total of 164 patients were enrolled. All had acute gastroenteritis due to rotavirus infection and were treated at Osaka Medical College Hospital and affiliated hospitals between January 2009 and May 2011. All were younger than 15 years of age, and their laboratory data, including urinalysis, were available. Results Among the enrolled patients, 30 (20 boys and 10 girls aged 0.2–10 years; median, 1.5 years; interquartile range, 1–3 years) had crystals in their urine. Most of the patients were admitted approximately 2 days after onset of gastroenteritis and had hyperuricemia and aciduria. The crystals consisted mainly of uric acid, and rarely of ammonium acid urate. Conclusion In order for ammonium acid urate stones to form in patients with acute obstructive uropathy associated with rotavirus gastroenteritis, prolonged continuous acidosis with hyperuricemia, might be necessary. Therefore, normalization of metabolic acidosis is important in order to prevent the onset of obstructive uropathy associated with rotavirus gastroenteritis.

To evaluate a simultaneous PET/MRI approach to imaging patients with neuroendocrine tumor using a combination of (68)Ga-DOTA-TOC as a PET contrast agent and gadoxetate disodium as a hepatobiliary MRI contrast agent.Ten patients with neuroendocrine tumor with known or suspected hepatic disease were imaged using a (68)Ga-DOTA-TOC PET/CT immediately followed by a 3.0T time-of-flight PET/MRI, using a combined whole body and liver specific imaging. The presence of lesions and DOTA-TOC avidity were assessed on CT, PET from PET/CT, diffusion weighted imaging, hepatobiliary phase imaging (HBP), and PET from PET/MRI. Maximum standardized uptake values (SUVmax) in hepatic lesions and nodal metastases were compared between PET/CT and PET/MRI, as were detection rates using each imaging approach.A total of 101 hepatic lesions were identified, 47 of which were DOTA-TOC avid and able to be individually measured on both PET/CT and PET/MRI. HBP imaging had a higher sensitivity for detection of hepatic lesions compared to CT or PET (99% vs. 46% and 64%, respectively; p values0.001). There was a strong correlation between SUVmax of liver lesions obtained with PET/CT compared to PET/MR imaging (Pearson's correlation = 0.91). For nodal disease, CT had a higher sensitivity compared to whole body MRI (p = 0.015), although PET acquired from PET/MRI detected slightly more lesions compared to PET from PET/CT.A simultaneous PET/MRI using both (68)Ga-DOTA-TOC and gadoxetate disodium was successful in whole body staging of patients with neuroendocrine tumor. HBP imaging had an increased detection rate for hepatic metastases.

Mammalian ovarian G-protein-coupled receptor 1 (OGR1) is activated by some metals in addition to extracellular protons and coupling to multiple intracellular signaling pathways. In the present study, we examined whether zebrafish OGR1, zebrafish GPR4, and human GPR4 (zOGR1, zGPR4, and hGPR4, respectively) could sense the metals and activate the intracellular signaling pathways. On one hand, we found that only manganese and cobalt of the tested metals stimulated SRE-promoter activities in zOGR1-overexpressed HEK293T cells. On the other hand, none of the metals tested stimulated the promoter activities in zGPR4- and hGPR4-overexpressed cells. The OGR1 mutant (H4F), which is lost to activation by extracellular protons, did not stimulate metal-induced SRE-promoter activities. These results suggest that zOGR1, but not GPR4, is also a metal-sensing G-protein-coupled receptor in addition to a proton-sensing G-protein-coupled receptor, although not all metals that activate hOGR1 activated zOGR1.

We investigated the detailed time course of conjunctival hyperemia induced by ripasudil 0.4%, a novel Rho-kinase inhibitor anti-glaucoma eye drop, in healthy subjects.We recruited 51 healthy subjects and administered ripasudil 0.4% in their right eye. We evaluated conjunctival hyperemia using slit lamp photography and measured the intraocular pressure (IOP) using the Icare PRO Rebound Tonometer at baseline and after 5, 15, 30, 60, 90, and 120 min. The conjunctival hyperemia score was graded by three independent observers on a scale of 0 (none) to 3 (severe). Additionally, we analyzed the "percent coverage" of conjunctival hyperemia by using an automated hyperemia analysis software program; this program provides the pixel coverage of the conjunctival vessels in the region of interest. Dunnett and Steel multiple comparison tests were used, as appropriate, for the subsequent analyses.The conjunctival hyperemia score and percent coverage increased rapidly after the instillation of ripasudil 0.4%, peaking at 15 min (score: 1.83 ± 0.29 [mean ± SD]) and 5 min (11.6% ± 4.7%), respectively, and then gradually decreasing until 120 min (0.45 ± 0.22 and 4.7% ± 1.8%, respectively), when they reached a level that was not significantly different from the baseline values. The IOP decreased significantly compared to the baseline at 30, 60, and 90 min, based on the Dunnett test.Conjunctival hyperemia induced by ripasudil 0.4% peaks rapidly to moderate severity, but subsides relatively quickly.

The electronic properties of the perovskite oxide SrCu3Fe4O12 subjected to pressure in a diamond anvil cell were investigated by 57Fe Mossbauer spectroscopy and electrical resistance measurements. ...

Effect of the basic property of reactants (tertiary amine catalysts, a substrate amine, and acid neutralizers) on catalytic dehydrocondensation between a carboxylic acid and an amine by using 2-chloro-4,6- dimethoxy-1,3,5-triazine (CDMT) was studied. The reaction yield was affected by the acid-base equilibrium among reactants. In dichloromethane, a representative aprotic solvent, a strongly basic catalyst gave amides in higher yields than weakly basic catalysts, regardless of the basicity of the acid neutralizer, which is called the proton capture agent (PCA). In contrast, in protic solvents, such as methanol or aqueous methanol, weakly basic catalysts gave amides in somewhat better yields than the strongly basic catalysts. In general, PCAs with weakly basic properties are favorable, because those with strongly basic properties tend to give byproducts arising from the reaction between CDMT and the substrate amine. © 2013 The Pharmaceutical Society of Japan.

In 2014, Niigata University and the Institute of Applied Energy developed a point-concentration receiver-evaluation system using a silicon carbide (SiC) honeycomb and a three-dimensional simulation method. The system includes several improvements over its forerunner, including the ability to increase/decrease the power-on aperture (POA), air-mass flow-rate (AMF) and the height of the focal surface. This paper will focus on the results of tests using an improved receiver evaluation system, at a focal height of 1600 mm. Maximum outlet air temperature reached as high as 800 K, but exerted no untoward effects on the system. Also, receiver efficiency rated between 45 % and 70 %, according to POA. A numerical, 3D method of analysis was created at the same time, in order to analyze temperature and flow-distribution, in detail. This simulation, based on the dual-cell approach, reproduced the thermal non-equilibrium between the solid and fluid domain of the receiver material. The most interesting feature of this s...

The intersite charge transfer at room temperature was found to occur by applying pressure in the A-site-ordered double-perovskite-structure oxide LaCu3Fe4O12. The pressure-induced charge transfer b...

Shunsuke Nakakura1, Hitoshi Tabuchi1, Yukio Baba2, Futoshi Maruiwa2, Nobuko Ando2, Takashi Kanamoto3, Yoshiaki Kiuchi31Department of Ophthalmology, Saneikai Tsukazaki Hospital, Himeji, Hyogo Prefecture, Japan; 2Department of Ophthalmology, Baba Eye Clinic, Hiroshima, Japan, 3Department of Ophthalmology and Visual Sciences, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima City, JapanObjective: To compare the safety and effectiveness of fixed-combination regimes (latanoprost–timolol and brinzolamide 1% compared to dorzolamide 1%/timolol and latanoprost) in open-angle glaucoma patients after switching from a combination of three topical antiglaucoma eye drops.Methods: We conducted an open, randomized 12-week multicenter prospective study. We randomly allocated 39 patients who had been treated with three antiglaucoma eye drops (prostaglandin F2α analogues plus beta-blockers and carbonic anhydrase inhibitors) into two groups. Group A (n = 20) were treated with latanoprost–timolol and brinzolamide 1% therapy and Group B (n = 16) were treated with dorzolamide 1%/timolol and latanoprost. Thirty-six patients completed all 12 weeks of this study. The major clinical parameters measured were intraocular pressure (IOP), conjunctive hyperemia, superficial punctate keratopathy and hyperpigmentation of eyelid at baseline, 4, and 12 weeks. Additionally noted were adverse events and patient preferences, measured using a questionnaire at study initiation and at 12 weeks.Results: At baseline, IOPs were (Group A: 14.1 ± 2.9 mmHg, B: 14.5 ± 2.9 mmHg; P = 0.658), (Group A: 13.8 ± 2.6 mmHg, B: 14.3 ± 2.8 mmHg; P = 0.715) at 4 weeks, and (Group A: 14.1 ± 2.7 mmHg, B: 14.2 ± 2.7 mmHg; P = 0.538) at 12 weeks. Among the groups, there was no significant difference at any time point after baseline (P = 0.923, 0.951, respectively). All adverse events were not remarkably different after therapy. In regards to patient preference before and after switching therapy, 10 patients (50%) in Group A and 10 patients (63%) in Group B preferred using fixed-combination eye drop therapy.Conclusions: Effectiveness and safety were maintained in both groups after switching therapy. Overall, patients generally preferred using a fixed-combination therapy.Keywords: glaucoma, latanoprost–timolol, dorzolamide–timolol, brinzolamide, fixed combination, intraocular pressure

Purpose To report clinical results of switching to latanoprost therapy in patients with deepening of the upper eyelid sulcus caused by travoprost and bimatoprost. Methods Prospective, clinical, observational case reports. Four patients presented with eyelid changes giving the eye a sunken eye appearance; two were being treated with travoprost and two with bimatoprost. Both patients on bimatoprost and one of the patients on travoprost therapy were switched to latanoprost while the eyelid sign was evident. The other patient discontinued the travoprost therapy for 4 months and switched to latanoprost therapy 1 month later, i.e., 5 months after discontinuing travaprost therapy. The physical changes in the eyelids were documented by photography and the intraocular pressure by Goldmann applanation tonometry. Results Three patients had a resolution of the sunken eye appearance 2 to 3 months after switching to latanoprost. The one patient who switched to latanoprost after recovery of the sunken eye had no recurrence during a 6 months follow-up period. There were no significant changes in the intraocular pressure in any of the subjects. Conclusions A deepening of the upper eyelid sulcus is a complication of prostaglandin F2α analogs. However, this side effect may be less common with latanoprost and eyes with this side effect caused by travoprost or bimatoprost may tolerate latanoprost therapy.

Juvenile hormone esterases (JHEs) function in juvenile hormone (JH) degradation. In the silkworm, Bombyx mori, we have characterized authentic JHE (Bmjhe) and five other carboxyl/cholinesterase (CCE) genes (Bmcce-1 to -5) with GQSAG, a motif sequence of JHE. But none of the genes appeared to function in vivo as a JHE, except for Bmjhe. Recently it was reported that the GQSAG motif might be dispensable, and that the Thr-316 residue has functional significance for JHE activity. On the basis of these findings, we identified two novel JHE candidates, Bmcce-6 and Bmcce-7, that lack GQSAG but possess Thr-316. In the CCE phylogenetic tree, BmCCE-6 was close to the lepidopteran JHE cluster, while BmCCE-7 constituted the same cluster as pheromone-degrading esterases. The developmental expression profiles were different among Bmjhe, Bmcce-6, and Bmcce-7. None of the proteins hydrolyzed JH in vitro. Our results suggest that only one CCE (BmJHE) functions as JHE in the silkworm.