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1. Investigation of the preference of marlin Kajikia audax sashimi with different lipid contents through sensory evaluation

Author: Kanako Hashimoto, Tokifusa Kawashima, Yuko Murata, Shintaro Imamura, Takuya Seko, and Kenji Ishihara
Subjects: sensory evaluation, preference, marlin, sashimi, lipid content, Nutrition. Foods and food supply, TX341-641, Food processing and manufacture, TP368-456
Abstract: Identifying the sensory properties of fish consumers is important for providing their preferred seafood. Odor, flavor, texture, and appearance affected the sensory preference for fish. Moreover, several compounds are involved in sensory preference. This study focused on lipids that affect preference for seafood and examined the lipid content preference in marlin Kajikia audax sashimi. First, lipid contents and fatty acid compositions of different individual sizes and body parts of marlin were compared. Next, the preference for overall, taste, texture, odor, aftertaste, and lipid content in marlin sashimi taken from different parts of the body with different amounts of lipids was investigated using the paired preference method. Then the relationship of lipid content preference with other preferences were also evaluated using the Chi-square test. The crude lipid of big-sized marlin (51.1–55.1 kg) was 9.5%−13.2%, and the crude lipid of small-sized marlin (23.5–30.0 kg) was 0.8%−1.2%. The dorsal parts of big-sized marlin had lipid contents in the anterior parts higher than those in the posterior parts (p < 0.05). Whereas no differences were observed in the fatty acid composition of different body parts. The lipid content preference for the anterior dorsal part (high lipid part) was higher than that for the posterior dorsal part (lower lipid part) (p < 0.05). However, no difference in overall preference was observed. Additionally, the relationship between lipid content preference and other preference were indicated that the high lipid content parts preferred group significantly preferred the high lipid content parts at overall and taste evaluation (p < 0.01). On the other hand, the low lipid content parts preferred groups showed opposite evaluation. Therefore, the lipid content was associated with the preference for marlin sashimi and be classified into two groups: one prefers high lipid sashimi and the other prefers low lipid sashimi.
Published: 2024
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2. Blood flow alterations in cavernous sinus dural arteriovenous fistula: Optical coherence tomography angiography findings

Author: Masahiro Akada, Yuki Muraoka, Satoshi Morooka, Kenji Ishihara, Takahiro Kogo, Natsuki Akaike, Kazumasa Nakanishi, Yukihiro Yamao, Masayuki Hata, and Akitaka Tsujikawa
Subjects: Cavernous sinus dural arteriovenous fistula, anterior segment blood flow, Optical coherence tomography angiography, Elevated intraocular pressure, Endovascular treatment, Ophthalmology, RE1-994
Abstract: Purpose: This case report details the diagnostic process for a patient with an initial diagnosis of scleritis who was unresponsive to typical treatment modalities, culminating in the identification of a cavernous sinus dural arteriovenous fistula (CS-DAVF). The case highlights the role of anterior segment optical coherence tomography angiography (OCTA) in the diagnosis of this vascular anomaly and in monitoring the response to treatment. Observations: A 45-year-old man with persistently elevated intraocular pressure (IOP) and ocular congestion in the left eye was unresponsive to treatment for scleritis. The persistent ocular symptoms and new-onset tinnitus prompted further investigation. Anterior segment OCTA revealed vascular anomalies, and magnetic resonance imaging confirmed a CS-DAVF. The patient underwent endovascular treatment for the CS-DAVF. This intervention led to a significant reduction in IOP in the left eye and the resolution of ocular congestion. Conclusions and importance: This case highlights the diagnostic complexities of ophthalmic symptoms that mimic those of other conditions. Furthermore, it demonstrates the essential role of anterior segment OCTA in the accurate diagnosis and effective management of CS-DAVF and highlights the need for comprehensive diagnostic approaches in ophthalmology.
Published: 2024
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3. Quantification of dilated deep capillaries in diabetic retinopathy on optical coherence tomography angiography

Author: Noriko Terada, Tomoaki Murakami, Kenji Ishihara, Keiichi Nishikawa, Kentaro Kawai, and Akitaka Tsujikawa
Subjects: Medicine, Science
Abstract: Abstract Morphological changes in capillaries are one of major clinical signs in diabetic retinopathy (DR). In this study, we quantified the dilated deep capillaries on optical coherence tomography angiography (OCTA) images. Central 3 × 3 mm en face images were obtained using a swept source OCTA device in 105 eyes of 99 patients with DR. Capillaries with a greater diameter in the deep layers were defined as the dilated deep capillaries, using stepwise image processing. The relative areas of automatically selected capillaries with a great diameter were calculated as the index of the dilated deep capillaries. Most eyes with DR had string-like or dot-like dilated deep capillaries in the OCTA images, which appeared to be dilated capillary segments or microaneurysms histologically. They were distributed more densely in the parafovea than in the central sector, while there were no differences between individual quadrants. The index of the dilated deep capillaries was higher in eyes with DR than in nondiabetic eyes. The index in the central subfield was modestly associated with visual acuity, diabetic macular edema, and proliferative diabetic retinopathy. The quantitative dilated deep capillaries are designated as a biomarker of vision-threatening DR.
Published: 2023
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4. Vitreous hemorrhage in retinal vein occlusion without visible traction from the posterior vitreous membrane: An optical coherence tomography angiography case report study

Author: Yuki Akiyama, Yuki Muraoka, Takahiro Kogo, Naomi Nishigori, Masaharu Ishikura, Kenji Ishihara, Tomoaki Murakami, Sotaro Ooto, and Akitaka Tsujikawa
Subjects: Science (General), Q1-390, Social sciences (General), H1-99
Abstract: Background: We report an unusual case of retinal vein occlusion (RVO) associated with vitreous hemorrhage (VH) without visible traction from the posterior vitreous membrane (PVM) at the bleeding point, challenging our current understanding of VH pathophysiology. Case presentation: A 52-year-old man presented with VH in the right eye. A detailed examination using optical coherence tomography angiography (OCTA) and ultra-widefield fluorescein angiography revealed branch RVO with non-perfused areas (NPAs) extending peripherally and neovascularization elsewhere (NVE). OCTA showed NVE infiltrating the vitreous cavity, leading to substantial bleeding without visible PVM traction at the bleeding point. The NVE was successfully removed following vitrectomy, and visual acuity improved from 20/20 to 20/13 preoperatively, along with a postoperative improvement in floaters. Conclusions: This unique case of RVO suggests the possibility of VH occurring independent of PVM contractions at the bleeding point, challenging the traditional understanding of VH. This finding underscores the potential role of OCTA in diagnosing and managing retinal vascular diseases, underscoring the need for further investigations into the underlying mechanisms, with potential implications for personalized therapeutic strategies.
Published: 2024
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5. Japan-epiretinal membrane (J-ERM) registry: A prospective cohort study protocol investigating the surgical outcome of epiretinal membrane.

Author: Yuki Kanzaki, Ryo Matoba, Kenji Ishihara, Tetsuro Morita, Yuki Muraoka, Shuhei Kimura, Takashi Koto, Ryo Kawasaki, Takayuki Baba, Fumiki Okamoto, Makoto Inoue, Taiji Sakamoto, Akitaka Tsujikawa, and Yuki Morizane
Subjects: Medicine, Science
Abstract: BackgroundEpiretinal membrane (ERM) causes visual impairment such as reduction in visual acuity and metamorphopsia due to retinal traction. With the improvement of optical coherence tomography (OCT) and microincision vitrectomy surgery (MIVS), the surgery of ERM has significantly advanced. However, there have been no large-scale studies on the following: (1) how to evaluate visual impairment in ERM, (2) the relationship between OCT findings and visual function, (3) when is the optimal timing of surgery, and (4) the relationship between the surgical instruments as well as techniques and prognosis. The purpose of this study was to obtain evidence regarding these ERM surgeries.Methods and designThis is a prospective, multicenter cohort study of ERM surgery in Japan from March 1, 2023, to March 31, 2027 (UMIN000048472, R-3468-2). Patients who underwent ERM surgery during the study period and agreed to participate in this study will be included. The goal is to have a total of 5,000 eyes surgically treated for ERM. The following data will be collected: age, gender, medical history, subjective symptoms, visual function before and 6 and 12 months after surgery, clinical findings, OCT data, surgical technique, instruments used in surgery, and complications.DiscussionThe results of this study will support the surgical decisions and procedures in ERM practices.
Published: 2024
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6. Evaluation of Foveal Cone and Müller Cells in Epiretinal Membrane using Adaptive Optics OCT

Author: Masaharu Ishikura, MD, Yuki Muraoka, MD, PhD, Shin Kadomoto, MD, PhD, Naomi Nishigori, MD, Takahiro Kogo, MD, Shogo Numa, MD, PhD, Eri Nakano, MD, PhD, Masayuki Hata, MD, PhD, Kenji Ishihara, MD, PhD, Sotaro Ooto, MD, PhD, and Akitaka Tsujikawa, MD, PhD
Subjects: Epiretinal membrane, Adaptive optics, Adaptive optics optical coherence tomography, Müller cell, Ellipsoid zone, Ophthalmology, RE1-994
Abstract: Objective: To investigate cellular-level morphological alterations in the retinal neuroglia in eyes with epiretinal membrane (ERM). Design: Prospective cross-sectional, observational study (November 2020–May 2022). Subjects and Controls: We included 41 eyes with unilateral idiopathic ERM and 33 healthy eyes of healthy volunteers. Methods: We examined the foveal microstructures in all eyes using adaptive optics OCT (AO-OCT) with axial and lateral resolutions of 3.4 and 3.0 μm, respectively. Adaptive optics OCT images were acquired for a 2.5° (728 μm) area at the foveal center. Main Outcome Measures: Foveal microstructures on AO-OCT images, best-corrected visual acuity (BCVA) in logarithm of the minimum angle of resolution units, and associations between these parameters. Results: Adaptive optics OCT imaging of healthy eyes and eyes with ERM revealed sharp hyperreflective lines of the external limiting membrane (ELM), accompanied by hyporeflective gaps, individual nuclei of the foveal cone photoreceptors, and Müller cell bodies. The arrangement of Müller cell bodies was more vertical in eyes with ERM than in normal eyes. Epiretinal membranes adhered to foveal Müller cells via the internal limiting membrane (ILM), exerting vertical traction that pulled the foveal cones anteriorly. Adaptive optics OCT also enabled visualization of outer segment (OS) discs. Hyperreflective changes in the OS discs were observed beneath the vertically thickened ellipsoid zone (EZ) in 15 eyes (36.6%) with ERM. For eyes with ERM, multiple regression analysis showed that the length from ILM to the inner border of the outer nuclear layer and the EZ thickness were significantly associated with BCVA (β = 5.3 × 10-4 and 82.7 × 10-4, respectively), with associated 95% confidence intervals of 1.3 × 10-4 to 9.3 × 10-4 (P = 0.011) and 39.0 × 10-4 to 126.5 × 10-4 (P
Published: 2024
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7. Effects of dietary n-3/n-6 fatty acid content on post-operative adhesions in myocardial infarction mice

Author: Yumi Chiba, Ikumi Nakamura, Kenji Ishihara, Takuya Seko, and Tomoaki Ishigami
Subjects: fatty acid, n-3/n-6, diet, myocardial infarcted mouse, adhesion, Nutrition. Foods and food supply, TX341-641
Abstract: Summary: Background and aim: Adhesions after thoracic surgery led to more difficult sternal re-entry and surgical dissection, blunted visibility of mediastinal tissues, potential injury to cardiovascular structures, an increased risk of surgical bleeding, and more time-consuming procedures.Recent molecular and cell biology studies have shown that n-3 unsaturated fatty acids exert pleiotropic effects on vascular endothelial cells, inflammatory cells, and platelets, suppress lesion formation and plaque instability, prevent recurrence of vascular events and cardiac death in patients with ischemic heart disease. Since around 2010′, attention has been focused on the n-3 fatty acids and DHA of edible “seaweed oil” extracted from algae. However, no previous studies have reported how dietary containing marine algae oil and nutritional oral taking habits affect post-operative adhesions.The purpose of this study was to investigate the effects of diets with different n-3/n-6 fatty acid content on adhesions in thoracic cavity. Methods: Four-week-old mice were randomly divided into three groups and housed in separate cages. The groups of animals were continuously provided with three different diets for 1 month (the Control group (n=4), DHA-containing “marine algae oil” diet; the DHA group (n=4), the HF group (n=5)). MI model mice were induced by a trained animal surgical expert. After operation, evaluated items were 1) body weight, 2) echocardiography for cardiac function, and 3) adhesions. Evaluations of 1) and 2) were performed before MI preparation, 1 day, and 7 days after MI, and assessment of 3) was evaluated the adhesion at 7 days after MI. Results: The results were 1) there were no significant differences in body weight among the three groups, 2) cardiac function in the HF group tended to deteriorate, and on post-operative day 7, the DHA group tended to deteriorate less than the Control group and 3) adhesions tended to be worse in the HF group and mild in the DHA group. Conclusion: Adhesions tended to be the worst in the HF group and mild in the DHA group. The results in this study indicated that the type of diet affects adhesion levels following MI.
Published: 2023
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8. UVA induces retinal photoreceptor cell death via receptor interacting protein 3 kinase mediated necroptosis

Author: Zhen Yu, Victor S. M. C. Correa, Nikolaos E. Efstathiou, Henar Albertos-Arranz, Xiaohong Chen, Kenji Ishihara, Yasuhiro Iesato, Toshio Narimatsu, Dimitrios Ntentakis, and Demetrios G. Vavvas
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282, Cytology, QH573-671
Abstract: Abstract Ultraviolet light A (UVA) is the only UV light that reaches the retina and can cause indirect damage to DNA via absorption of photons by non-DNA chromophores. Previous studies demonstrate that UVA generates reactive oxygen species (ROS) and leads to programmed cell death. Programmed cell death (PCD) has been implicated in numerous ophthalmologic diseases. Here, we investigated receptor interacting protein 1 and 3 (RIPK1 and RIPK3) kinases, key signaling molecules of PCD, in UVA-induced photoreceptor injury using in vitro and ex vivo models. UVA irradiation activated RIPK3 but not RIPK1 and mediated necroptosis through MLKL that lie downstream of RIPK3 and induced apoptosis through increased oxidative stress. Moreover, RIPK3 but not RIPK1 inhibition suppresses UVA-induced cell death along with the downregulation of MLKL and attenuates the levels of oxidative stress and DNA fragmentation. In conclusion, these results identify RIPK3, not RIPK1, as a critical regulator of UVA-induced necroptosis cell death in photoreceptors and highlight RIPK3 potential as a neuroprotective target.
Published: 2022
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9. Pigmentary lesions in eyes with rhegmatogenous retinal detachment with flap tears: a retrospective observational study

Author: Midori Ideyama, Yuki Muraoka, Kentaro Kawai, Masaharu Ishikura, Shin Kadomoto, Naomi Nishigori, Takanori Kameda, Kenji Ishihara, Manabu Miyata, Masahiro Miyake, Tomoaki Murakami, Sotaro Ooto, and Akitaka Tsujikawa
Subjects: Medicine, Science
Abstract: Abstract We included 97 patients with unilateral rhegmatogenous retinal detachment (RRD) with posterior vitreous detachment who underwent vitrectomy, and examined pigmentary lesion (PL) characteristics around the sites of original tears using pre- and postoperative ultra-widefield scanning light ophthalmoscopy, green light fundus autofluorescence (FAF) imaging, and intraoperative digital video. If PL did not involve RRD, we used OCT to preoperatively assess any pathologic changes to the lesion. A total of 116 retinal tears (mean count, 1.2 ± 0.5; range, 1–4 per eye) were observed in the detached retina. Overall, 102 (88%), 63 (54%), 14 (12%), and 25 (22%) tears were accompanied by lattice degeneration (LD) or PL, both LD and PL, only LD, and only PL, respectively. In green FAF images, LD showed normal to mild-hyper fluorescence, whereas all PL showed hypofluorescence. On OCT, PL were located at the RPE level, while choroid abnormalities were unclear. In the retinal areas of 22 eyes, which were not affected by RRD, we observed PL without retinal tears; some were accompanied by vitreous traction and tractional retinal detachment. Pre-, intra-, and post-operative assessments of original flap tears suggested that PL might be a risk factor for RRD, developing alongside or separately from LD.
Published: 2022
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10. Clinically Significant Nonperfusion Areas on Widefield OCT Angiography in Diabetic Retinopathy

Author: Kentaro Kawai, MD, Tomoaki Murakami, MD, PhD, Yuki Mori, MD, Kenji Ishihara, MD, PhD, Yoko Dodo, MD, PhD, Noriko Terada, MD, Keiichi Nishikawa, MD, Kazuya Morino, MD, and Akitaka Tsujikawa, MD, PhD
Subjects: Diabetic retinopathy, Nonperfusion areas, Neovascularization, Semiautomatic quantification, Widefield OCT angiography, Ophthalmology, RE1-994
Abstract: Purpose: To investigate the distribution of clinically significant nonperfusion areas (NPAs) on widefield OCT angiography (OCTA) images in patients with diabetes. Design: Prospective, cross-sectional, observational study. Participants: One hundred and forty-four eyes of 114 patients with diabetes. Methods: Nominal 20 × 23 mm OCTA images were obtained using a swept-source OCTA device (Xephilio OCT-S1), followed by the creation of en face images 20-mm (1614 pixels) in diameter centering on the fovea. The nonperfusion squares (NPSs) were defined as the 10 × 10 pixel squares without retinal vessels, and the ratio of eyes with the NPSs to all eyes in each square was referred to as the NPS ratio. The areas with probabilistic differences (APD) for proliferative diabetic retinopathy (PDR) and nonproliferative diabetic retinopathy (NPDR) (APD[PDR] and APD[NPDR]) were defined as sets of squares with higher NPS ratios in eyes with PDR and NPDR, respectively. The P ratio (NPSs within APD[PDR] but not APD[NPDR]/all NPSs) was also calculated. Main Outcome Measures: The probabilistic distribution of the NPSs and the association with diabetic retinopathy (DR) severity. Results: The NPSs developed randomly in eyes with mild and moderate NPDR and were more prevalent in the extramacular areas and the temporal quadrant in eyes with severe NPDR and PDR. The APD(PDR) was distributed mainly in the extramacular areas, sparing the areas around the vascular arcades and radially peripapillary capillaries. The APD(PDR) contained retinal neovascularization more frequently than the non-APD(PDR) (P = 0.023). The P ratio was higher in eyes with PDR than in those with NPDR (P < 0.001). The multivariate analysis designated the P ratio (odds ratio, 8.293 × 107; 95% confidence interval, 6.529 × 102–1.053 × 1013; P = 0.002) and the total NPSs (odds ratio, 1.002; 95% confidence interval, 1.001–1.003; P < 0.001) as independent risk factors of PDR. Most eyes with NPDR and 4-2-1 rule findings of DR severity had higher P ratios but not necessarily greater NPS numbers. Conclusions: The APD(PDR) is uniquely distributed on widefield OCTA images, and the NPA location patterns are associated with DR severity, independent of the entire area of NPAs. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.
Published: 2023
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11. The intercapillary space spectrum as a marker of diabetic retinopathy severity on optical coherence tomography angiography

Author: Noriko Terada, Tomoaki Murakami, Akihito Uji, Kenji Ishihara, Yoko Dodo, Keiichi Nishikawa, Kazuya Morino, and Akitaka Tsujikawa
Subjects: Medicine, Science
Abstract: Abstract Microcirculatory disturbance plays a pivotal role in the pathogenesis in diabetic retinopathy (DR). We retrospectively quantified the total counts and morphological features of intercapillary spaces, i.e., intercapillary areas and nonperfusion areas (NPAs), on swept-source optical coherence tomography angiography (SS-OCTA) images and to evaluate their associations with DR severity grades. We acquired 3 × 3 mm OCTA images in 75 eyes of 62 diabetic patients and 22 eyes of 22 nondiabetic subjects. In the en-face superficial images within the central 2 mm, the areas enclosed by retinal vessels were automatically detected. Their total numbers decreased in some eyes with no apparent retinopathy and most eyes with DR, which allowed us to discriminate diabetic subjects from nondiabetic subjects [area under the receiver operating characteristic curve (AUC) = 0.907]. The areas and area/perimeter ratios continuously increased in DR, indicating a continuum between healthy intercapillary areas and NPAs. The number of intercapillary spaces with a high area/perimeter ratio increased according to DR severity, which showed modest performance in discriminating moderate NPDR or higher grades (AUC = 0.868). These quantified parameters of intercapillary spaces can feasibly be used for the early detection of microcirculatory impairment and the diagnosis of referable DR.
Published: 2022
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12. Receptor interacting protein 3 kinase, not 1 kinase, through MLKL-mediated necroptosis is involved in UVA-induced corneal endothelium cell death

Author: Zhen Yu, Nikolaos E. Efstathiou, Victor S. M. C. Correa, Xiaohong Chen, Kenji Ishihara, Yasuhiro Iesato, Toshio Narimatsu, Dimitrios Ntentakis, Yanyun Chen, and Demetrios G. Vavvas
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282, Cytology, QH573-671
Abstract: Abstract Ultraviolet (UV) is one of the most energetic radiations in the solar spectrum that can result in various tissue injury disorders. Previous studies demonstrated that UVA, which represents 95% of incident photovoltaic radiation, induces corneal endothelial cells (CECs) death. Programmed cell death (PCD) has been implicated in numerous ophthalmologic diseases. Here, we investigated receptor-interacting protein 3 kinase (RIPK3), a key signaling molecule of PCD, in UVA-induced injury using a short-term corneal endothelium (CE) culture model. UVA irradiation activated RIPK3 and mediated necroptosis both in mouse CE and primary human CECs (pHCECs). UVA irradiation was associated with upregulation of key necroptotic molecules (DAI, TRIF, and MLKL) that lie downstream of RIPK3. Moreover, RIPK3 inhibition or silencing in primary corneal endothelial cells suppresses UVA-induced cell death, along with downregulation of MLKL in pHCECs. In addition, genetic inhibition or knockout of RIPK3 in mice (RIPK3K51A and RIPK3−/− mice) similarly attenuates cell death and the levels of necroptosis in ex vivo UVA irradiation experiments. In conclusion, these results identify RIPK3, not RIPK1, as a critical regulator of UVA-induced cell death in CE and indicate its potential as a future protective target.
Published: 2021
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13. Pathological Neurovascular Unit Mapping onto Multimodal Imaging in Diabetic Macular Edema

Author: Tomoaki Murakami, Kenji Ishihara, Noriko Terada, Keiichi Nishikawa, Kentaro Kawai, and Akitaka Tsujikawa
Subjects: center-involving diabetic macular edema, clinically significant macular edema, diabetic macular edema, diabetic retinopathy, disorganization of retinal inner layers, fluorescein angiography, Medicine (General), R5-920
Abstract: Diabetic retinopathy is a form of diabetic microangiopathy, and vascular hyperpermeability in the macula leads to retinal thickening and concomitant reduction of visual acuity in diabetic macular edema (DME). In this review, we discuss multimodal fundus imaging, comparing the pathogenesis and interventions. Clinicians diagnose DME using two major criteria, clinically significant macular edema by fundus examination and center-involving diabetic macular edema using optical coherence tomography (OCT), to determine the appropriate treatment. In addition to fundus photography, fluorescein angiography (FA) is a classical modality to evaluate morphological and functional changes in retinal capillaries, e.g., microaneurysms, capillary nonperfusion, and fluorescein leakage. Recently, optical coherence tomography angiography (OCTA) has allowed us to evaluate the three-dimensional structure of the retinal vasculature and newly demonstrated that lamellar capillary nonperfusion in the deep layer is associated with retinal edema. The clinical application of OCT has accelerated our understanding of various neuronal damages in DME. Retinal thickness measured by OCT enables us to quantitatively assess therapeutic effects. Sectional OCT images depict the deformation of neural tissues, e.g., cystoid macular edema, serous retinal detachment, and sponge-like retinal swelling. The disorganization of retinal inner layers (DRIL) and foveal photoreceptor damage, biomarkers of neurodegeneration, are associated with visual impairment. Fundus autofluorescence derives from the retinal pigment epithelium (RPE) and its qualitative and quantitative changes suggest that the RPE damage contributes to the neuronal changes in DME. These clinical findings on multimodal imaging help to elucidate the pathology in the neurovascular units and lead to the next generation of clinical and translational research in DME.
Published: 2023
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14. Children’s death survey using death certificates in the Chiba prefecture

Author: Shumari Urabe, Kenji Ishihara, Fumiko Chiba, Rutsuko Yamaguchi, Yuki Shiko, Yohei Kawasaki, and Hirotaro Iwase
Subjects: Child Death Review, Cause of death, Death certificate, Death Investigation, Public Health, Criminal law and procedure, K5000-5582
Abstract: In recent years, Child Death Review (CDR) has attracted attention in Japan. It is necessary to consider not only hospital deaths but also out-of-hospital deaths. However, recommending preventive measures may be difficult because statistics on Japanese child mortality are limited. We examined cause of death (COD) and its application in preventive medicine based on death certificates (DCs) in the Chiba Prefecture. Death documents (DDs) and death slips (DSs) were created for individuals aged under 20 years who died between January 2012 and December 2016. They were based on DCs submitted to the Chiba Prefecture. We examined the trend of COD, occurrence of extrinsic mortality, and characteristics of doctors and compared CODs mentioned in DCs with autopsy results. For 1149 cases, the descriptions of DSs and DDs matched. Half of the extrinsic and undetermined deaths, which were examined by police doctors, occurred out-of-hospital. The autopsy rate was 13.5%. The COD mentioned in DCs did not match the autopsy results for 26 out of 69 autopsies performed at our institute. Approximately 70% of sudden infant death syndromes were diagnosed without autopsy. Low autopsy rate, incorrect writings, and errors during the death diagnosis cannot be ignored while conducting CDR. As more than half of the preventable deaths occurred out-of-hospital and there is no system to collect detailed information on them, the Japanese CDR system may not be reliable. It is necessary to improve the death investigation system by promoting autopsies for children and constructing a comprehensive database.
Published: 2021
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15. Pathologic basis of the preferential thinning of thecorpus callosum in adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP)

Author: Michiaki Kinoshita, Kiyomitsu Oyanagi, Yasufumi Kondo, Keisuke Ishizawa, Kenji Ishihara, Mari Yoshida, Teruhiko Inoue, Yoshio Mitsuyama, Kunihiro Yoshida, Mitsunori Yamada, Yoshiki Sekijima, and Shu-ichi Ikeda
Subjects: ALSP, Corpus callosum, CSF1R, HDLS, Lesion staging, Microglia, Neurology. Diseases of the nervous system, RC346-429
Abstract: Background: Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is an early onset dementia characterized by axonal loss in the cerebral white matter with swollen axons (spheroids). It had been reported that the preferential thinning and “focal lesions” of the corpus callosum were observed on T2-weighted MRI in ALSP patients. The present study aimed to reveal the pathologic basis of them in relation to brain lesion staging (I ~ IV: Oyanagi et al. 2017). Methods: Seven autopsied brains of ALSP and five controls were neuropathologically examined. Results: Even at Stage I, corpus callosum body showed evident atrophy, and the atrophy advanced with stage progression. Spheroid size and density were maximal at Stage II in both centrum semiovale and corpus callosum body, but spheroids were larger in corpus callosum body than in centrum semiovale. Microglia in the body at Stage II had a larger cytoplasm than those in centrum semiovale. But spheroids and microglia in the “focal lesions” were identical with those of centrum semiovale. Conclusion: Preferential thinning of corpus callosum was considered to be formed in relation to peculiar morphological alteration of microglia there in ALSP. Instead, “focal lesions” were formed in connection with the lesions in centrum semiovale.
Published: 2021
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16. Detection of Balenine in Mouse Plasma after Administration of Opah-Derived Balenine by HPLC with PITC Pre-Column Derivatization

Author: Yasutaka Shigemura, Yu Iwasaki, Yoshio Sato, Tomomi Kato, Takuya Seko, and Kenji Ishihara
Subjects: balenine, opah, carnosine, anserine, phenyl isothiocyanate, pre-column derivatization, Chemical technology, TP1-1185
Abstract: We examined the absorption of balenine (Bal) in mouse blood after the administration of a high-purity Bal prepared from opah muscle. Using HPLC with phenyl isothiocyanate pre-column derivatization, we successfully isolated imidazole peptides and their constituents. We detected Bal and 3-methylhistidine (3-Me-His) in mouse blood 1 h after the administration of opah-derived Bal. The concentrations of Bal and 3-Me-His significantly increased to 128.27 and 69.09 nmol/mL in plasma, respectively, but were undetectable in control and carnosine (Car)-administrated mice. In contrast, β-alanine and histidine did not increase in mouse plasma 1 h after the administration of Car and opah-derived Bal. The present study is the first report on the absorption of food-derived Bal in mouse blood and serves as a pilot study for future clinical trials.
Published: 2022
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17. Clinical relevance of reduced decorrelation signals in the diabetic inner choroid on optical coherence tomography angiography

Author: Yoko Dodo, Kiyoshi Suzuma, Kenji Ishihara, Shin Yoshitake, Masahiro Fujimoto, Tatsuya Yoshitake, Yuko Miwa, and Tomoaki Murakami
Subjects: Medicine, Science
Abstract: Abstract Diabetes induces lesions of the retinal and choroidal capillaries, which promote the pathogenesis of diabetic retinopathy (DR). The decorrelation signals in optical coherence tomography angiography (OCTA) represent the blood flow and vascular structure, and three-dimensional OCTA images enable individual capillary layers to be evaluated separately. The current study documented that en-face OCTA images revealed spots of flow void in the choriocapillaris layer in eyes with DR. Quantitative investigation demonstrated that non-flow areas within the central subfield (CSF) increased in eyes with more severe DR grades. The non-flow areas in the choriocapillaris layer were also associated with poorer visual acuity (VA) in all 108 eyes. A modest correlation was noted between the areas of flow void and poorer VA in 69 eyes without DME, whereas the non-flow areas were not related to VA or to CSF thickness measured by OCT in 39 eyes with DME. In 12 eyes with ischemic maculopathy, the choriocapillaris layer beneath the disrupted ellipsoid zone of the photoreceptor (EZ) had greater areas of flow void than did the area beneath an intact EZ. These data suggested that disrupted choroidal circulation has clinical relevance and contributes to the pathogenesis of DR.
Published: 2017
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18. Relation between macular morphology and treatment frequency during twelve months with ranibizumab for diabetic macular edema.

Author: Yuki Mori, Tomoaki Murakami, Kiyoshi Suzuma, Kenji Ishihara, Shin Yoshitake, Masahiro Fujimoto, Yoko Dodo, Tatsuya Yoshitake, Yuko Miwa, and Akitaka Tsujikawa
Subjects: Medicine, Science
Abstract: To investigate whether baseline optical coherence tomography (OCT) parameters can predict the treatment frequency of intravitreal ranibizumab (IVR) injections during the first year in patients with diabetic macular edema (DME) treated with pro re nata (PRN) IVR injections.We retrospectively reviewed 68 eyes of 63 patients with center-involved DME who received IVR injections for 12 months or longer according to three monthly IVR injections followed by the PRN dosing. We measured the mean retinal thicknesses in the individual subfields of the Early Treatment Diabetic Retinopathy Study grid and evaluated the qualitative and quantitative parameters on OCT sectional images. We investigated the relationship between these OCT parameters at baseline and the number of IVR injections during the 12-month follow-up.Three loading doses were administered to 10 eyes; four to seven annualized IVR injections were administered to 34 eyes. The number of eyes that received IVR injections decreased gradually until month 6 and was almost constant from months 7 to 11. No relationships were seen between the treatment frequency and baseline systemic factors and the ophthalmic examination findings. Univariate analyses showed that the number of IVR injections during the first year was associated with the mean retinal thickness in the individual subfields and the transverse length of the disrupted external limiting membrane (ELM) and ellipsoid zone of the photoreceptors. Multivariate analysis showed a significant association with the thickness in the inferior subfield alone. The treatment frequency during the 12-month follow-up was not correlated with improved visual acuity but was associated with the decrease in the central subfield thickness and disrupted ELM.The retinal thickness in the inferior subfield predicts the treatment frequency during the first year in eyes with DME treated with PRN IVR injections.
Published: 2017
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19. Oral Administration of Fucoxanthin Increases Plasma Fucoxanthinol Concentration and Antioxidative Ability and Improves Meat Color in Broiler Chicks

Author: Keisuke Sasaki, Kenji Ishihara, Makoto Yamazaki, Kazuki Nakashima, Hiroyuki Abe, Chiaki Oyamada, Michiyo Motoyama, and Mitsuru Mitsumoto
Subjects: antioxidative status, broiler chicks, feed additive, fucoxanthin, meat color, Animal culture, SF1-1100
Abstract: Effects of the oral administration of fucoxanthin (FX), a major carotenoid of algae, on plasma fucoxanthinol (FX-OH) concentration, plasma antioxidative status, and meat color and lipid stability during chilling storage in broiler chicks were investigated. One-week-old male broiler chicks were divided into control and FX treatment groups. For the FX treatement group, FX was given into the crop of each bird at a volume of 10mg per day per bird for 2 weeks. After 2 weeks of treatment, the plasma, liver, and superficial pectoral muscle were harvested. FX was not detected in either the plasma or liver of control and FX-treated birds, although FX-OH was detected in both the plasma and liver of the FX-treated group. Plasma antioxidative activity against a peroxyl radical derived from 2,2′-azobis-(2-amidinopropane) dihydrochloride was observed in FX-treated chicks but not in control chicks. FX treatment did not affect the L* and a* values nor the lipid peroxide content of superficial pectoral muscle during 6 days of chilling storage. However, FX treatment increased the b* value of superficial pectoral muscle compared to the control group (P
Published: 2010
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20. Is Lesion of Exner’s Area Linked to Progressive Agraphia in Amyotrophic Lateral Sclerosis with Dementia? An Autopsy Case Report

Author: Kenji Ishihara, Hiroo Ichikawa, Yoshio Suzuki, Jun’ichi Shiota, Imaharu Nakano, and Mitsuru Kawamura
Subjects: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Agraphia, as a neuropsychological symptom of ALS, especially ALS with dementia (ALS-D), has recently attracted more attention. However, the brain lesion responsible has not been identified. Here we present an autopsy case of ALS-D of a patient with obvious agraphia, without aphasia, that also presented cerebrospinal degeneration with TDP-43-pathology compatible with ALS-D. Of the pre-motor frontal lobe cortices, degeneration and immuno-histochemical pathology were most obvious in the caudal area of the left middle frontal gyrus, or Exner’s area. Assuring this area plays a pivotal role in the kanji and kana formation used in writing the Japanese language, this case of ALS-D showed both agraphia and Exner's area stressed pathological lesions. It may thus be the first case to indicate an intimate relationship between the neuropsychological symptoms and an associated lesion for ALS-D.
Published: 2010
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21. Analysis of the Mechanism for the Development of Allergic Skin Inflammation and the Application for Its Treatment: Establishment of a Modified Allergic Dermatitis Model in Mouse Ear Lobes by Application of 12-O-Tetradecanoyl Phorbol 13-Acetate: Putative Involvement of Thymic Stromal Lymphopoietin and Roles of Histamine

Author: Noriyasu Hirasawa, Yuhsuke Ohsawa, Kenji Ishihara, Toshio Seyama, JangJa Hong, and Kazuo Ohuchi
Subjects: Therapeutics. Pharmacology, RM1-950
Abstract: Abstract.: We established a novel allergic dermatitis model in mouse ear lobes in which antigen-nonspecific inflammation was induced by painting 12-O-tetradecanoylphorbol 13-acetate (TPA) between sensitization and challenge with picryl chloride (PiCl). This model has an advantage for analyzing atopic dermatitis-like inflammation within a short period. Analysis of the time course changes in the PiCl-induced swelling showed that the allergic inflammation was shifted from a delayed-type response to a biphasic response consisting of a weak immediate-phase response and a late-phase response by painting with TPA. The application of TPA increased the PiCl-induced infiltration of eosinophils and mast cells at the inflammatory site and shifted the cytokine milieu from Th1 to Th2. The expression of the Th2-inducing cytokine thymic stromal lymphopoietin (TSLP) mRNA was also increased by TPA. These findings suggested that the induction of antigen-nonspecific inflammation by TPA before the antigen challenge enhanced the Th2 response and modified the PiCl-induced delayed type-hypersensitivity. Using this model, we clarified that histamine plays significant roles in the early-phase swelling via H1 receptors and the late-phase swelling via H3/H4 receptors. Thus, we suggested the usefulness of the combined treatment with an H1 antagonist and an H4 antagonist for the suppression of atopic dermatitis. Keywords:: allergic dermatitis, histamine, picryl chloride, 12-O-tetradecanoylphorbol 13-acetate, thymic stromal lymphopoietin, allergic inflammation
Published: 2009
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22. Writing Errors and Anosognosia in Amyotrophic Lateral Sclerosis with Dementia

Author: Hiroo Ichikawa, Shinichi Koyama, Hideki Ohno, Kenji Ishihara, Kiyomi Nagumo, and Mitsuru Kawamura
Subjects: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Amyotrophic lateral sclerosis (ALS) with dementia (ALS-D) is known to exhibit characteristics of frontotemporal dementia. However, in clinical situations, it is often difficult to evaluate their cognitive functions because of impaired voluntary speech and physical disabilities. In order to identify characteristic and diagnostic cognitive symptoms of relatively advanced ALS-D patients, we retrospectively reviewed the clinical features of seven cases of clinically definitive ALS who had dementia, impaired voluntary speech, and physical disability. Their medical records showed that six out of seven patients made writing errors, and all of the patients demonstrated anosognosia. The writing errors consisted of paragraphia such as substitution, omission, or syntactic errors with individual differences in error types. Dissociation between kana and kanji were also observed. Anosognosia was evaluated by a self-rating scale with which the patients and the medical staff evaluated the patient's physical ability; the results indicated a large discrepancy between the evaluation by the patients and the medical staff. We emphasize that aphasic writing errors have been underestimated, particularly in ALS-D patients with impaired voluntary speech. We also reported that anosognosia was the most important and quantifiable symptom in ALS-D. The relationship between writing errors and anosognosia should be investigated further.
Published: 2008
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23. A Case of Frontotemporal Lobar Degeneration with Progressive Dysarthria

Author: Nami Ihori, Shigeo Araki, Kenji Ishihara, and Mitsuru Kawamura
Subjects: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: We investigated the evolution of the neurological and neuropsychological characteristics in a right-handed woman who was 53-years-old at the onset and who showed personality changes and behavioral disorders accompanied by progressive dysarthria. She had hypernasality and a slow rate of speech with distorted consonants and vowels, which progressed as motor disturbances affecting her speech apparatus increased; finally, she became mute two years post onset. Her dysarthria due to bilateral voluntary facio-velo-linguo-pharyngeal paralysis accompanied with automatic-voluntary dissociation fit the description of anterior opercular syndrome. She showed personality changes and behavioral abnormalities from the initial stage of the disease, as is generally observed in frontotemporal degeneration (FTD), and her magnetic resonance image showed progressive atrophy in the frontotemporal lobes; thus, she was clinically diagnosed with FTLD. This patient’s symptoms suggest that FTLD, including bilateral anterior operculum degeneration, causes progressive pseudobulbar paretic dysarthria accompanied by clinical symptoms of FTD, which raises the possibility of a new clinical subtype in the FTLD spectrum.
Published: 2006
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24. Effects of salicylate derivatives on localization of p.H723R allele product of SLC26A4

Author: Michio Murakoshi, Yuhi Koike, Shin Koyama, Shinichi Usami, Kazusaku Kamiya, Katsuhisa Ikeda, Yoichi Haga, Kohei Tsumoto, Hiroyuki Nakamura, Noriyasu Hirasawa, Kenji Ishihara, and Hiroshi Wada
Subjects: Misfolding, Hearing Loss, Sensorineural, Membrane Transport Proteins, General Medicine, Salicylate derivative, Salicylates, Hereditary hearing loss, HEK293 Cells, Otorhinolaryngology, Sulfate Transporters, Mutation, Pendrin, Humans, Surgery, Alleles
Abstract: 金沢大学理工研究域フロンティア工学系, ObjectivePendrin is a transmembrane protein encoded by the SLC26A4 gene that functions in maintaining ion concentrations in the endolymph of the inner ear, most likely by acting as a chloride/bicarbonate transporter. Variants in the SLC26A4 gene are responsible for sensorineural hearing loss. Although pendrin localizes to the plasma membrane, we previously identified that 8 missense allele products of SLC26A4 were retained in the intracellular region and lost their anion exchange function. We also found that 10 mM salicylate induced the translocation of 4 out of 8 allele products from the intracellular region to the plasma membrane and restored their anion exchanger activity. However, since 10 mM salicylate exhibits cytotoxicity, the use of chemical compounds with less cell toxicity is needed. In the present study, therefore, salicylate derivatives were used as the chemical compounds and their effects on the p.H723R allele products of SLC26A4 were investigated.MethodsHEK293 cells were transfected with the cDNA of p.H723R. Cell proliferation, viability and toxicity assays were performed to investigate the response and health of cells in culture after treatment with four types of salicylate derivatives, i.e., 2-hydroxybenzyl alcohol, 2,3-dihydroxybenzoic acid, 2’-hydroxyacetophenone and methyl salicylate. The effects of these salicylate derivatives on the localization of the p.H723R were investigated by immunofluorescence microscopy.ResultsThe application of 10 mM salicylate showed an increase in cell toxicity and decrease in cell viability, leading to a significant decrease in cell proliferation. In contrast, the application of 1 mM salicylate derivatives did not show any significant increase in cell toxicity and decrease in cell viability, corresponding to a logarithmic increase in cell concentration with an increase in culture time. Immunofluorescence experiments showed that the p.H723R retained in the endoplasmic reticulum (ER). Among the salicylate derivatives applied, 2-hydroxybenzyl alcohol induced the translocation of p.H723R from the ER to the plasma membrane 3 h after its application.ConclusionThe results obtained showed that 2-hydroxybenzyl alcohol restored the localization of the p.H723R allele products of SLC26A4 from the ER to the plasma membrane at a concentration of 1 mM by 3 h after its administration with less cytotoxicity than 10 mM salicylate., Embargo Period 12 months
Published: 2022

25. Atypical Symptoms and Brain Imaging Findings in Dementia

Author: Kenji Ishihara
Subjects: Microbiology (medical), Immunology, Immunology and Allergy
Published: 2022

26. Whipple’s disease with normal duodenal histology diagnosed by ileal biopsy using balloon endoscopy

Author: Hideki Mori, Chiaki Yakabi, Kiwamu Yonahara, Kazunao Hamahiga, Miyu Yoshimura, Masaki Sakihara, Kenji Ishihara, Kinya Azama, Takayuki Chinen, and Osamu Zaha
Subjects: Gastroenterology, General Medicine
Published: 2022

27. Factors predicting the treatment frequency of ranibizumab injections during the second year in diabetic macular edema

Author: Keiichi Nishikawa, Tomoaki Murakami, Kenji Ishihara, Yoko Dodo, Noriko Terada, Kazuya Morino, and Akitaka Tsujikawa
Subjects: Ophthalmology, Diabetic Retinopathy, Treatment Outcome, Ranibizumab, Intravitreal Injections, Diabetes Mellitus, Visual Acuity, Humans, Angiogenesis Inhibitors, General Medicine, Macular Edema, Tomography, Optical Coherence, Retrospective Studies
Abstract: To investigate the predictors of annual treatment frequency in the second year of pro re nata (PRN) intravitreal ranibizumab (IVR) injections for diabetic macular edema (DME).A retrospective study.We reviewed 65 eyes of 60 patients with center-involved DME who received PRN IVR injections after 3 monthly loading doses. The central subfield thickness (CST) and qualitative findings were assessed on the spectral domain optical coherence tomography (SD-OCT) images. We then investigated whether the parameters at the baseline or at the 12-month visit were associated with treatment frequency in the second year.The number of ranibizumab injections decreased from 6 (4-8) during the first year to 2 (0-3) during the second year (P.001). The injection numbers during the first year (ρ = 0.259, P = .037) but not during the second year (ρ = 0.152, P = .226) were modestly related to the logarithm of the minimum angle of resolution (logMAR) improvement at 24 months. Multivariate analyses revealed that the CST (β = 0.336, P = .005) and hyperreflective walls in the foveal cystoid spaces (β = 0.273, P = .020) at baseline were associated with the number of IVR injections during the second year. The treatment frequency during the second year was also related to the CST (β = 0.266, P = .012), hyperreflective walls (β = 0.394, P = .002), and cumulative doses of ranibizumab injections (β = 0.294, P = .006) at the 12-month visit.The cumulative doses of ranibizumab injections, CST, and hyperreflective walls in the foveal cystoid spaces at the 12-month visit are designated predictors of the treatment frequency of ranibizumab injections during the second year in DME.
Published: 2022

28. Empagliflozin in Patients with Chronic Kidney Disease

Author: Herrington, William G, Staplin, Natalie, Wanner, Christoph, Green, Jennifer B, Hauske, Sibylle J, Emberson, Jonathan R, Preiss, David, Judge, Parminder, Mayne, Kaitlin J, Ng, Sarah Y A, Sammons, Emily, Zhu, Doreen, Hill, Michael, Stevens, Will, Wallendszus, Karl, Brenner, Susanne, Cheung, Alfred K, Liu, Zhi-Hong, Li, Jing, Hooi, Lai Seong, Liu, Wen, Kadowaki, Takashi, Nangaku, Masaomi, Levin, Adeera, Cherney, David, Maggioni, Aldo P, Pontremoli, Roberto, Deo, Rajat, Goto, Shinya, Rossello, Xavier, Tuttle, Katherine R, Steubl, Dominik, Petrini, Michaela, Massey, Dan, Eilbracht, Jens, Brueckmann, Martina, Landray, Martin J, Baigent, Colin, Haynes, Richard, The EMPA-KIDNEY Collaborative Group: Colin Baigent, Martin J Landray, Christoph Wanner, William G Herrington, Richard Haynes, Jennifer B Green, Sibylle J Hauske, Martina Brueckmann, Mark Hopley, Maximillian von-Eynatten, Jyothis George, Susanne Brenner, Alfred K Cheung, David Preiss, Zhi-Hong Liu, Jing Li, Laiseong Hooi, Wen Liu, Takashi Kadowaki, Masaomi Nangaku, Adeera Levin, David Cherney, Roberto Pontremoli, Aldo P Maggioni, Natalie Staplin, Jonathan Emberson, Stefan Hantel, Shinya Goto, Rajat Deo, Katherine R Tuttle, Michael Hill, Parminder Judge, Kaitlin J Mayne, Sarah Y A Ng, Xavier Rossello, Emily Sammons, Doreen Zhu, Peter Sandercock, Rudolf Bilous, Charles Herzog, Paul Whelton, Janet Wittes, Derrick Bennett, Patricia Achiri, Chrissie Ambrose, Cristina Badin, Jill Barton, Richard Brown, Andy Burke, Sebastian Butler, Rejive Dayanandan, Pia Donaldson, Robert Dykas, Lucy Fletcher, Kate Frederick, Hannah Kingston, Mo Gray, Emily Harding, Akiko Hashimoto, Lyn Howie, Susan Hurley, Ryonfa Lee, Nik Luker, Kevin Murphy, Mariko Nakahara, John Nolan, Michelle Nunn, Sorcha Mulligan, Akiko Omata, Sandra Pickworth, YanRu Qiao, Shraddha Shah, Karen Taylor, Alison Timadjer, Monique Willett, Liz Wincott, Qin Yan, Hui Yu, Louise Bowman, Fang Chen, Robert Clarke, Michelle Goonasekera, Waseem Karsan, Marion Mafham, Christina Reith, Mohammed Zayed, Ritva Ellison, Rowan Moys, Will Stevens, Kevin Verdel, Karl Wallendszus, Chris Bowler, Anna Brewer, Andy Measor, Guanguo Cui, Charles Daniels, Angela Field, Bob Goodenough, Ashley Lawson, Youcef Mostefai, Dheeptha Radhakrishnan, Samee Syed, Shuang Xia, Ruth Adewuyi-Dalton, Thomas Arnold, Anne-Marie Beneat, Anoushka Bhatt, Chloe Bird, Andrew Breach, Laura Brown, Mark Caple, Tatyana Chavagnon, Karen Chung, Sarah Clark, Luminita Condurache, Katarzyna Eichstadt, Marta Espino Obrero, Scarlett Forest, Helen French, Nick Goodwin, Andrew Gordon, Joanne Gordon, Cat Guest, Tina Harding, Michal Hozak, Matthew Lacey, David MacLean, Louise Messinger, Stewart Moffat, Martin Radley, Claire Shenton, Sarah Tipper, Jon Tyler, Lesley Weaving, James Wheeler, Elissa Williams, Tim Williams, Hamish Woodhouse, Angela Chamberlain, Jo Chambers, Joanne Davies, Denise Donaldson, Pati Faria-Shayler, Denise Fleming-Brown, Jennifer Ingell, Carol Knott, Anna Liew, Helen Lochhead, Juliette Meek, Isabel Rodriguez-Bachiller, Andrea Wilson, Patrick Zettergren, Rach AitSadi, Ian Barton, Alex Baxter, Yonghong Bu, Lukasz Danel, Sonja Grotjahn, Rijo Kurien, Michael Lay, Archie Maskill, Aleksandra Murawska, Rachel Raff, Allen Young, Rebecca Sardell, Vladimir Cejka, Marcela Fajardo-Moser, Christian Hartner, Doris Poehler, Janina Renner, Franziska Scheidemantel, Miya Bryant, Anita Hepditch, Cassandra Johnson, Erin Latore, Yolanda Miller, Lauren Price, Merilee Whalen, Ashleigh Wheeler, Jenny Ingell, Yu An, Yinghua Chen, Peiling Chen, Hao Dai, Hong Du, Fang Feng, Qing Guo, Libo Hou, Wuhanbilige Hundei, Binbin Jin, Yan Li, Jiamin Liu, Xia Song, Yanping Wang, Yanwu Yu, Ning Zhang, Lingshan Zhao, Hui Zhong, Cheng Beng Goh, Ye Mun Low, Soon Yi Sor, Farah Hanis Zulkipli, Sarojini Sivanandam, Natsuki Arai, Ai Fukasawa, Mizue Furukawa, Keisuke Habuki, Shoko Hayashi, Wakako Isari, Saki Kanegae, Maria Kawai, Reiki Kobayashi, Takako Kuramae, Chika Kuribayashi, Sawako Maeno, Satoshi Masumoto, Tomoko Morisaki, Minoru Oda, Kazue Sawada, Kenta Sugamori, Ayana Tatsuzawa, Aiko Tomita, Kazuyuki Yuasa, Hiroko Inazawa, Amanda Axler, Kerri Gallo, Ester Baldini, Barbara Bartolomei Mecatti, Francesca Bianchini, Martina Ceseri, Laura Cipressa, Gianna Fabbri, Andrea Lorimer, Donata Lucci, Sharang Ghavampour, Anja Knoppe, Hans Schmidt-Gurtler, Hubert Dumann, Sybille Merscher, Margret Patecki, Georg Rainer Schlieper, Anke Torp, Bianca Weber, Maja Zietz, Bernd Hohenstein, Urs Benck, Diliana Draganova, Thomas Weinreich, Lothar Wolf, Jasmine Gaidu, Hanna Reiner, Mandy Visnjic, Daniel Steffl, Marie Breitenfeldt, Annette Kraemer-Guth, Christine Braun, Simone Hagge, Michael Schomig, Stephan Matthias, Dominik Stoffler, Beate Schumacher, Thomas Sitter, Louise Fuessl, Julia Krappe, Jerome Loutan, Volker Vielhauer, Luciano Andriaccio, Magdalena Maurer, Bernhard Winkelmann, Martin Dursch, Linda Seifert, Linda Tenbusch, Julia Weinmann-Menke, Simone Boedecker, Wiebke Kaluza-Schilling, Daniel Kraus, Carina Krieger, Margit Schmude, Anne Schreiber, Ewelina Eckrich, Diethelm Tschope, Abdulwahab Arbi, Young Lee-Barkey, Bernd Stratmann, Natalie Prib, Sina Rolfsmeier, Irina Schneider, Lars Rump, Johannes Stegbauer, Christine Pötz, Mara Schemmelmann, Claudia Schmidt, Michael Koch, Sendogan Aker, Annika Küpper, Manuela Martin, Thiemo Pfab, Christian Albert, Michael Haase, Barbara Zander, Claudia Schneider-Danwitz, Wolfgang Seeger, Wolf-Adam Seeger, Britta Zemann, Christoph Stellbrink, Kristin Marx, Ekaterina Stellbrink, Britta Brettschneider, Stephanie Watson, Marion Iselt, Gerhard Klausmann, Inga-Nadine Kummer, Auguste Kutschat, Simone Streitenberger, Matthias Girndt, Silke Markau, Ina Girakossyan, Claudia Hanf, Joachim Beige, Ralph Wendt, Ulrike Schmidt, Andreas Schneider, Roland Veelken, Claudia Donhauser, Luis Becker, Nexhat Miftari, Ricarda Wolfling, Sarah Morlok, Christian Hugo, Alexander Paliege, Jens Passauer, Julian Stumpf, Annegret Fleischer, Kerstin Haaser, Bernhard Kraemer, Jan Jochims, Bernd Kruger, Claudia Foellinger, Anastassiya Reisler, Frank Strutz, Stefan Haack, Ursula Hohenstatt, Martin Busch, Konstantin Herfurth, Gunter Wolf, Rainer Paul, Hermann Haller, Jessica Kaufeld, Jan Menne, Elisabeth Bahlmann-Kroll, Angela Bergner, Horst Weihprecht, Aydin Er, Florian Sonntag, Elif Turan, Michael Wittmann, Franziska Klauser, Eva Voigt, Volker Schettler, Egbert Schulz, Madlen Rohnstock, Elke Schettler, Bernd Schroppel, Rene van Erp, Martin Kachele, Ulla Ludwig, Lena Schulte-Kemna, Waltraud Kmietschak, Elke Preiss, Martina Ruocco, Gunnar Heine, Martin Brzoska, Sebastian Gabel, Christina Büttner, Asma Sabarai, Bernhard Banas, Tobias Bergler, Yvonne Ehrl, Franz Putz, Antonia Schuster, Stefanie Kuhn, Torsten Schramm, Stefan Degenhardt, Gerhard Schmidt, Lea Weiland, Ulrike Giebeln-Hudnell, Jan Kielstein, Gabriele Eden, Brigitte Fuchs, Gina Morig, Manuela Winkler, Harald Darius, Charalampos Kriatselis, Carl-Philipp Roesch, Astrid Maselli, Dominik Alscher, Markus Ketteler, Moritz Schanz, Severin Schricker, Bianka Rettenmaier, Andrea Schwab, Pablo Pergola, Irene Leal, Melissa Cagle, Anna Romo, Anthony Torres, Sucharit Joshi, Kulli Barrett, Alexis Africano, Vicki Dodds, Dorleena Gowen, Ashlee Morris, Juan Fernandez, Guillermo Jimenez, Ricardo Viera, Kendaling Bruce, Ryan Barrios, Maylin Garcia, Kerelyn Garcia, Iradis Leal, David Tietjen, David Bains, Carlo Castillo, Genielle Brewer, Justin Davis, Natalie Freking, Brittany Golson, Sally Ham, Jesslyn Roesch, Pusadee Suchinda, Shameem Beigh, Usah Lilavivat, Joyce Bilton, Kim Bocchicchia, Jeffrey Turner, Neera Dahl, Aldo Peixoto, Yasemin Kavak, Lauren Liberti, Hari Nair, Nicolas Page, Stephanie Rosenberg, Kathryn Simmons, Tamara Isakova, Rebecca Frazier, Rupal Mehta, Anand Srivastava, Patrick Fox, Jonathan Hecktman, Alexander Hodakowski, Carlos Martinez, Rachel Phillips, Alexis Stevenson, Reem Mustafa, Kyle Jansson, Cassandra Kimber, Jason Stubbs, Ahmad Tuffaha, Sri Yarlagadda, Debbie Griffin, Elisabeth Laundy, Zhuo Tang, Radica Alicic, Ann Cooper, Lisa Davis, Ashwini Gore, Rebecca Goldfaden, Leslie Harvill, Lisa Hichkad, Barry Johns, Thomas Jones, Kayla Merritt, Jennifer Sheldon, Jennifer Stanfield, Lindsay Alexander, Kaitlyn Preston, Lindsey Wood, Rajesh Pradhan, Roger DeRaad, Kelli McIntosh, Louis Raymond, Michael Shepperd, Susan McLaughlin, Mary Seifert, Andrew Shepherd, Joseph Aiello, William Durham, Laurie Loudermilk, John Manley, Sabrina Burnette, Stephanie Evans, Tara Johnson, Lance Sloan, Judy Ann Acosta, Stacy Gillham, Katia Sloan, SueAnn Squyres, Michael Rocco, Amret Hawfield, Ben Bagwell, Lauren Richmond, Joseph Soufer, Subha Clarke, Amanda Aliu, Kristine Calabrese, Amanda Davis, Veronica Poma, Tracy Spinola, James Magee, Ricardo Silva, Rushab Choksi, Lorraine Dajani, John Evans, Anil George, Prasanth Krish, Gerard Martins, Mae Sheikh-Ali, David Sutton, Freda Driver, Abraham Hanburry, Laura Hume, Amber Hurst, Matthew Taddeo, Marla Turner, Veronica Yousif, Srinivasan Beddhu, Laith Al-Rabadi, Nikita Abraham, Amalia Caamano, Judy Carle, Victoria Gonce, Kaitlyn Staylor, Na Zhou, Shweta Bansal, Manoj Bhattarai, Kumar Sharma, Subrata Debnath, Aliseiya Garza, Chakradhar Velagapudi, Sergio Rovner, Javier Almeida, Pablo Casares, Verlaine Stewart-Ray, Rene Almaraz, Renata Dayrell, Ana Moncada, Ricardo Pulido, Roxana Rodriquez, Wasim Deeb, Kathryn DeGoursey, Rodel Gloria, Trevor Greene, Robert Miller, Edward Pereira, Miguel Roura, Debbie Domingo, Sasha Dorestin, William Hodge, Cathy Jackson, Deborah Lund, Katrina Taylor, Kenneth Boren, Brittany Cleveland, Sandra Gaiser, Mandeep Sahani, Logan Aldrich, Exodus Edmerson, Edmond Limon, Cole Valletta, Patricia Vasquez, Christopher Provenzano, Navkiranjot Brar, Heather Henderson, Bellovich Keith, Qur Khai, Quresh Khairullah, Gail Makos, Joel Topf, Sherry Gasko, Rosemarie Henschel, Kaitlin Knapp, Teresa Kozlowski, Paula LaFleur, Ashwathy Varughese, Hui Xue, Patricia Wu, Olga Arechiga, Shan Darbeau, Michael Fechter, Stephanie Martinez, Lenita Hanson, Nyla Cooper, Arelis Madera, Jay Cadorna, Rita Sheridan, Helen Sparks, Bradley Eilerman, Susanne Bodine, Wael Eid, Rebecca Flora, Amber Avery, Cashmere Hardy, Mihaela Biscoveanu, Steven Nagelberg, Tracey Cummins, Frederic Rahbari-Oskoui, Anju Oommen, Zohreh Forghani, Stacie Hitchcock, Darya Hosein, Diane Watkins, Minesh Patel, Anthony Lambert, Elizabeth Newman, Autumn Wood, Tammy Ross, Stephany Topping, Jeffrey Mulhern, Lorna Murphy, Ann Vasseur, Gregory Greenwood, Alexander Hadley, Denise Laurienti, Christopher Marshall, Nicholas McLean, Scott Satko, Brandy Caudill, Jacob Maris, Janice Rogers, Cindy Vanhoy, George Thomas, Georges Nakhoul, John O'Toole, Jonathan Taliercio, Leslie Cooperman, Marina Markovic, Barbara Tucky, Devasmita Dev, Alia Hasan, Hima Yalamanchili, Namita Jain, Lesley McNeil, Eric Wines, Jean Park, Adline Ghazi, Mia Hamm, Tejas Patel, Amy Mottl, Emily Chang, Vimal Derebail, Emmie Cole, Anne Froment, Sara Kelley, Jordan Osmond Foster, Vahid Mahabadi, Golriz Jafari, Anita Kamarzarian, Wendy Arriaga, Daisy Arteaga, Rosario Machicado, Genesis Naverrete, Prashant Kumar, Imran Nazeer, Karina Urquia, Tammi Glider, Vickie Jones, Savannah Rucker, Jennifer Wiley, Rahul Pandey, Jesus Arroyo, Harish Pariani, Mohammad Ahmad, Shahin Mozaffari, Erika Perez, Matthew Budoff, Sion Roy, Divya Birudaraju, Ahmed Ghanem, Sajad Hamal, Stephen Aronoff, Elisa Joye Petr, Richard Sachson, Jaime Wiebel, Sana Akram, Laurie Jones, Curtis Knight, Maurie Tarlac, Shahbaz Ahmed, Harold Szerlip, Akinwande Akinfolarin, Ankit Mehta, Shana Camp, Cindy Castro, Zanaida Cooper, Jessica Terry, Ahmed Awad, Bhavya Kothapalli, Ryan Lustig, Serine Alfaress, Hyder Jasim, Mary Parrigon, Dennis Karounos, Sadiq Ahmed, Maggie Berry, Ruth Oremus, Carlos Hernandez-Cassis, Elias Ugwu, Nazia Junejo, Nancy Suazo, Mark Segal, Amir Kazory, Sherry Brown, Tristan Daniels, Sofia Dayi, Renee Hogan, Kathy McCray, Jennifer Stickley, Mahboob Rahman, Mirela Dobre, Lavinia Negrea, Aparna Padiyar, Nishigandha Pradhan, Arash Rashidi, Nagaraju Sarabu, Vicki Donley, Tricia Young, Godson Oguchi, Judepatricks Onyema, Kahla Damianik, Jack Dienes, Judith Plummer-Morgan, Marilyn Roman, Mauver Skipper, Stacey-Ann Villaruel, Krystle Williams, Danny Sugimoto, Jeffrey Dugas, Ismeal Ahmed, Jamie Bhairoo, Dolores Rijos, Huzaifa Salim, Madita Gavrila, Kathryn Lafferty, Ria Rabara, Sally Ruse, Maria Weetman, James Bushnell, Albert Power, Alison Jenkins, Stefanie Jones, Amanda Scott, Cath Byrne, Mark Jesky, Alison Cowley, Emma McHaffie, Holly Waterfall, Jo Taylor, Laura Bough, Thomas Phillips, Barbara Winter-Goodwin, Sui Phin Kon, Iain MacDougall, Eirini Lioudaki, Sapna Shah, Claire Sharpe, Francisco Aguilar, Abegail Hernandez Pena, Conception Pugay, Amelia Te, Hugh Finn, Wasim Hanif, Samiul Mostafa, Alice Aitken, Katharine Draxlbauer, Evelina Grobovaite, Jennifer Kearney, Theresa McCarthy, Giorgio Gentile, Duncan Browne, Palanichamy Chellamuthu, Tabinda 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Cipressa, Laura, Fabbri, Gianna, Lorimer, Andrea, Lucci, Donata, Ghavampour, Sharang, Knoppe, Anja, Schmidt-Gurtler, Han, Dumann, Hubert, Merscher, Sybille, Patecki, Margret, Rainer Schlieper, Georg, Torp, Anke, Weber, Bianca, Zietz, Maja, Hohenstein, Bernd, Benck, Ur, Draganova, Diliana, Weinreich, Thoma, Wolf, Lothar, Gaidu, Jasmine, Reiner, Hanna, Visnjic, Mandy, Steffl, Daniel, Breitenfeldt, Marie, Kraemer-Guth, Annette, Braun, Christine, Hagge, Simone, Schomig, Michael, Matthias, Stephan, Stoffler, Dominik, Schumacher, Beate, Sitter, Thoma, Fuessl, Louise, Krappe, Julia, Loutan, Jerome, Vielhauer, Volker, Andriaccio, Luciano, Maurer, Magdalena, Winkelmann, Bernhard, Dursch, Martin, Seifert, Linda, Tenbusch, Linda, Weinmann-Menke, Julia, Boedecker, Simone, Kaluza-Schilling, Wiebke, Kraus, Daniel, Krieger, Carina, Schmude, Margit, Schreiber, Anne, Eckrich, Ewelina, Tschope, Diethelm, Arbi, Abdulwahab, Lee-Barkey, Young, Stratmann, Bernd, Prib, Natalie, Rolfsmeier, Sina, Schneider, 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Herfurth, Konstantin, Wolf, Gunter, Paul, Rainer, Haller, Hermann, Kaufeld, Jessica, Menne, Jan, Bahlmann-Kroll, Elisabeth, Bergner, Angela, Weihprecht, Horst, Er, Aydin, Sonntag, Florian, Turan, Elif, Wittmann, Michael, Klauser, Franziska, Voigt, Eva, Schettler, Volker, Schulz, Egbert, Rohnstock, Madlen, Schettler, Elke, Schroppel, Bernd, van Erp, Rene, Kachele, Martin, Ludwig, Ulla, Schulte-Kemna, Lena, Kmietschak, Waltraud, Preiss, Elke, Ruocco, Martina, Heine, Gunnar, Brzoska, Martin, Gabel, Sebastian, Büttner, Christina, Sabarai, Asma, Banas, Bernhard, Bergler, Tobia, Ehrl, Yvonne, Putz, Franz, Schuster, Antonia, Kuhn, Stefanie, Schramm, Torsten, Degenhardt, Stefan, Schmidt, Gerhard, Weiland, Lea, Giebeln-Hudnell, Ulrike, Kielstein, Jan, Eden, Gabriele, Fuchs, Brigitte, Morig, Gina, Winkler, Manuela, Darius, Harald, Kriatselis, Charalampo, Roesch, Carl-Philipp, Maselli, Astrid, Alscher, Dominik, Ketteler, Marku, Schanz, Moritz, Schricker, Severin, Rettenmaier, Bianka, Schwab, Andrea, Pergola, Pablo, Leal, Irene, Cagle, Melissa, Romo, Anna, Torres, Anthony, Joshi, Sucharit, Barrett, Kulli, Africano, Alexi, Dodds, Vicki, Gowen, Dorleena, Morris, Ashlee, Fernandez, Juan, Jimenez, Guillermo, Viera, Ricardo, Bruce, Kendaling, Barrios, Ryan, Garcia, Maylin, Garcia, Kerelyn, Leal, Iradi, Tietjen, David, Bains, David, Castillo, Carlo, Brewer, Genielle, Davis, Justin, Freking, Natalie, Golson, Brittany, Ham, Sally, Roesch, Jesslyn, Suchinda, Pusadee, Beigh, Shameem, Lilavivat, Usah, Bilton, Joyce, Bocchicchia, Kim, Turner, Jeffrey, Dahl, Neera, Peixoto, Aldo, Kavak, Yasemin, Liberti, Lauren, Nair, Hari, Page, Nicola, Rosenberg, Stephanie, Simmons, Kathryn, Isakova, Tamara, Frazier, Rebecca, Mehta, Rupal, Srivastava, Anand, Fox, Patrick, Hecktman, Jonathan, Hodakowski, Alexander, Martinez, Carlo, Phillips, Rachel, Stevenson, Alexi, Mustafa, Reem, Jansson, Kyle, Kimber, Cassandra, Stubbs, Jason, Tuffaha, Ahmad, Yarlagadda, Sri, Griffin, Debbie, Laundy, Elisabeth, Tang, Zhuo, Alicic, Radica, Cooper, Ann, Davis, Lisa, Gore, Ashwini, Goldfaden, Rebecca, Harvill, Leslie, Hichkad, Lisa, Johns, Barry, Jones, Thoma, Merritt, Kayla, Sheldon, Jennifer, Stanfield, Jennifer, Alexander, Lindsay, Preston, Kaitlyn, Wood, Lindsey, Pradhan, Rajesh, Deraad, Roger, Mcintosh, Kelli, Raymond, Loui, Shepperd, Michael, Mclaughlin, Susan, Seifert, Mary, Shepherd, Andrew, Aiello, Joseph, Durham, William, Loudermilk, Laurie, Manley, John, Burnette, Sabrina, Evans, Stephanie, Johnson, Tara, Sloan, Lance, Ann Acosta, Judy, Gillham, Stacy, Sloan, Katia, Squyres, Sueann, Rocco, Michael, Hawfield, Amret, Bagwell, Ben, Richmond, Lauren, Soufer, Joseph, Clarke, Subha, Aliu, Amanda, Calabrese, Kristine, Davis, Amanda, Poma, Veronica, Spinola, Tracy, Magee, Jame, Silva, Ricardo, Choksi, Rushab, Dajani, Lorraine, Evans, John, George, Anil, Krish, Prasanth, Martins, Gerard, Sheikh-Ali, Mae, Sutton, David, Driver, Freda, Hanburry, Abraham, Hume, Laura, Hurst, Amber, Taddeo, Matthew, Turner, Marla, Yousif, Veronica, Beddhu, Srinivasan, Al-Rabadi, Laith, Abraham, Nikita, Caamano, Amalia, Carle, Judy, Gonce, Victoria, Staylor, Kaitlyn, Zhou, Na, Bansal, Shweta, Bhattarai, Manoj, Sharma, Kumar, Debnath, Subrata, Garza, Aliseiya, Velagapudi, Chakradhar, Rovner, Sergio, Almeida, Javier, Casares, Pablo, Stewart-Ray, Verlaine, Almaraz, Rene, Dayrell, Renata, Moncada, Ana, Pulido, Ricardo, Rodriquez, Roxana, Deeb, Wasim, Degoursey, Kathryn, Gloria, Rodel, Greene, Trevor, Miller, Robert, Pereira, Edward, Roura, Miguel, Domingo, Debbie, Dorestin, Sasha, Hodge, William, Jackson, Cathy, Lund, Deborah, Taylor, Katrina, Boren, Kenneth, Cleveland, Brittany, Gaiser, Sandra, Sahani, Mandeep, Aldrich, Logan, Edmerson, Exodu, Limon, Edmond, Valletta, Cole, Vasquez, Patricia, Provenzano, Christopher, Brar, Navkiranjot, Henderson, Heather, Keith, Bellovich, Khai, Qur, Khairullah, Quresh, Makos, Gail, Topf, Joel, Gasko, Sherry, Henschel, Rosemarie, Knapp, Kaitlin, Kozlowski, Teresa, Lafleur, Paula, Varughese, Ashwathy, Xue, Hui, Wu, Patricia, Arechiga, Olga, Darbeau, Shan, Fechter, Michael, Martinez, Stephanie, Hanson, Lenita, Cooper, Nyla, Madera, Areli, Cadorna, Jay, Sheridan, Rita, Sparks, Helen, Eilerman, Bradley, Bodine, Susanne, Eid, Wael, Flora, Rebecca, Avery, Amber, Hardy, Cashmere, Biscoveanu, Mihaela, Nagelberg, Steven, Cummins, Tracey, Rahbari-Oskoui, Frederic, Oommen, Anju, Forghani, Zohreh, Hitchcock, Stacie, Hosein, Darya, Watkins, Diane, Patel, Minesh, Lambert, Anthony, Newman, Elizabeth, Wood, Autumn, Ross, Tammy, Topping, Stephany, Mulhern, Jeffrey, Murphy, Lorna, Vasseur, Ann, Greenwood, Gregory, Hadley, Alexander, Laurienti, Denise, Marshall, Christopher, Mclean, Nichola, Satko, Scott, Caudill, Brandy, Maris, Jacob, Rogers, Janice, Vanhoy, Cindy, Thomas, George, Nakhoul, George, O'Toole, John, Taliercio, Jonathan, Cooperman, Leslie, Markovic, Marina, Tucky, Barbara, Dev, Devasmita, Hasan, Alia, Yalamanchili, Hima, Jain, Namita, Mcneil, Lesley, Wines, Eric, Park, Jean, Ghazi, Adline, Hamm, Mia, Patel, Teja, Mottl, Amy, Chang, Emily, Derebail, Vimal, Cole, Emmie, Froment, Anne, Kelley, Sara, Osmond Foster, Jordan, Mahabadi, Vahid, Jafari, Golriz, Kamarzarian, Anita, Arriaga, Wendy, Arteaga, Daisy, Machicado, Rosario, Naverrete, Genesi, Kumar, Prashant, Nazeer, Imran, Urquia, Karina, Glider, Tammi, Jones, Vickie, Rucker, Savannah, Wiley, Jennifer, Pandey, Rahul, Arroyo, Jesu, Pariani, Harish, Ahmad, Mohammad, Mozaffari, Shahin, Perez, Erika, Budoff, Matthew, Roy, Sion, Birudaraju, Divya, Ghanem, Ahmed, Hamal, Sajad, Aronoff, Stephen, Joye Petr, Elisa, Sachson, Richard, Wiebel, Jaime, Akram, Sana, Jones, Laurie, Knight, Curti, Tarlac, Maurie, Ahmed, Shahbaz, Szerlip, Harold, Akinfolarin, Akinwande, Mehta, Ankit, Camp, Shana, Castro, Cindy, Cooper, Zanaida, Terry, Jessica, Awad, Ahmed, Kothapalli, Bhavya, Lustig, Ryan, Alfaress, Serine, Jasim, Hyder, Parrigon, Mary, Karounos, Denni, Ahmed, Sadiq, Berry, Maggie, Oremus, Ruth, Hernandez-Cassis, Carlo, Ugwu, Elia, Junejo, Nazia, Suazo, Nancy, Segal, Mark, Kazory, Amir, Brown, Sherry, Daniels, Tristan, Dayi, Sofia, Hogan, Renee, Mccray, Kathy, Stickley, Jennifer, Rahman, Mahboob, Dobre, Mirela, Negrea, Lavinia, Padiyar, Aparna, Pradhan, Nishigandha, Rashidi, Arash, Sarabu, Nagaraju, Donley, Vicki, Young, Tricia, Oguchi, Godson, Onyema, Judepatrick, Damianik, Kahla, Dienes, Jack, Plummer-Morgan, Judith, Roman, Marilyn, Skipper, Mauver, Villaruel, Stacey-Ann, Williams, Krystle, Sugimoto, Danny, Dugas, Jeffrey, Ahmed, Ismeal, Bhairoo, Jamie, Rijos, Dolore, Salim, Huzaifa, Gavrila, Madita, Lafferty, Kathryn, Rabara, Ria, Ruse, Sally, Weetman, Maria, Bushnell, Jame, Power, Albert, Jenkins, Alison, Jones, Stefanie, Scott, Amanda, Byrne, Cath, Jesky, Mark, Cowley, Alison, Mchaffie, Emma, Waterfall, Holly, Taylor, Jo, Bough, Laura, Phillips, Thoma, Winter-Goodwin, Barbara, Phin Kon, Sui, Macdougall, Iain, Lioudaki, Eirini, Shah, Sapna, Sharpe, Claire, Aguilar, Francisco, Hernandez Pena, Abegail, Pugay, Conception, Te, Amelia, Finn, Hugh, Hanif, Wasim, Mostafa, Samiul, Aitken, Alice, Draxlbauer, Katharine, Grobovaite, Evelina, Kearney, Jennifer, Mccarthy, Theresa, Gentile, Giorgio, Browne, Duncan, Chellamuthu, Palanichamy, Dugal, Tabinda, Chant, Terri, Jones, Laura, Laity, Emily, Miners, Megan, Muir, Jame, Swanson, Elizabeth, Frankel, Andrew, Tomlinson, Jame, Alegata, Marlon, Almasarwah, Rashid, Apostolidi, Anthoula, Vourvou, Maria, Walters, Thoma, Taal, Maarten, Dukka, Hari, Kolhe, Nitin, Mcdonald, Carly, White, Kelly, Ugni, Shiva, Gunda, Smita, Oluyombo, Rotimi, Brindle, Vicki, Coutts, Ping, Fuller, Tracy, Nadar, Evelyn, Ramadoss, Suresh, Motherwell, Nichola, Pajak, Susannah, Tonks, Louise, Bhandari, Sunil, Bodington, Richard, Hazara, Adil, Fellowes, Dominic, Wong, Christopher, Goldsmith, Christopher, Barnes, Sherald, Bennett, Ann, Burston, Claire, Hope, Samantha, Hunt, Nicola, Kurian, Lini, Fish, Richard, Farrugia, Daniela, Lee, Judy, Sadler, Emma, Turner, Hannah, Hill, Christopher, Brown, Henry, Masengu, Agne, Maxwell, Peter, Bleakley, Nina, Murtagh, Hugh, Petchey, William, Yiu, Vivian, Kellett, Joanne, Williams, Angharad, Clarke, Helen, Carnall, Victoria, Benyon, Sarah, Blake, Caroline, Estcourt, Stephanie, Piper, Jane, Morgan, Neal, Hutchinson, Carolyn, Mckinley, Teresa, Woodman, Alastair, Graham, Judi, Leonard, Niall, Smyth, John, Adell, Vicki, Hagan, Samantha, Caplin, Ben, Oomatia, Amin, Damian, Eleanor, Sobande, Toluleyi, Doulton, Tim, Delaney, Michael, Montasser, Mahmoud, Hansen, Jenny, Loader, David, Moon, Angela, Morris, France, Sinha, Smeeta, Chukwu, Chukwuma, Hudson, Amy, Campbell, Diane, Kershaw, Melanie, Whittaker, Stephanie, Irtiza-Ali, Ayesha, Ghalli, Farid, Nosseir, Heba, Leslie, Allison, Trivedi, Kate, Fraser, Donald, Alhadj Ali, Mohammad, Griffin, Sian, Latif, Farah, Witczak, Justyna, Wonnacott, Alexa, Jeffers, Lynda, Webley, Yvette, Phelan, Paul, Miller-Hodges, Eve, Geddes, Ailsa, Glenwright, Margaret, Hunter, Amy, Pickett, Thoma, Moriarty, Jim, Hill, Linda, Tyler, Amanda, Ayub, Waqar, Evans, Gail, Hewins, Sue, Hewitt, Davina, Read, Kerry, Bell, Samira, Cosgrove, Leanne, Craik, Rachel, Murray, Shona, Bhandary, Nitin, Coles, Holly, Easow, Rashmi, Joseph, Maya, Khwaja, Arif, Jackson, Yvonne, Mbuyisa, Angeline, Sellars, Rachel, Chitalia, Nihil, Mohandas, Cynthia, Gherman, Anca, Kamundi, Charlotte, Olufuwa, Olumide, Mccafferty, Kieran, Adeleke, Adedolapo, Healy, Cara, Jeyarajah, Damini, Kinsella-Perks, Edward, Smith, Richard, Camilleri, Brian, Buckman, Carol, Finch, Jenny, Rivers, Vanessa, Connor, Andrew, Carr, Sheila, Shainberg, Lisa, Lewington, Andrew, Baker, Richard, Dorey, Suzannah, Tobin, Kay, Wheatley, Rosalyn, Banerjee, Debasish, Hull, Richard, Abat, Sharirose, Paul, Riny, Karim, Mahzuz, Htet, Zay, Tufail, Saad, Varma, Ravi, Convery, Karen, Fottrell-Gould, Deirdre, Hudig, Lisa, Tropman, Emily, Abdul-Samad, Thahir, Grace, Anne, Phipps, Marie, Suckling, Rebecca, Somalanka, Subash, Sood, Bhrigu, Swift, Pauline, Acheampong, Sarah, Ansu, Kwame, Augustin, Martia, Sampson, Anna, Vinall, Lynn, Wren, Kim, Wanninayake, Shamila, Wooding, Nichola, Edwards, Heather, Owen, Lydia, Bolton, Stephanie, Carson, Marion, Matthews, Michael, Brunskill, Nigel, Jesus-Silva, Jorge, Howson, Alex, Quashie-Akponeware, Mary, Tindall, Hilary, Nethaji, Chidambaram, Eldon, Helen, Patel, Rajan, Mark, Patrick, Rankin, Alastair, Sullivan, Michael, Forsyth, Kirsty, Mcdougall, Rowan, Dasgupta, Tanaji, Davies, Louisa, Ryder, Maggie, Grimmer, Philip, Macdonald, Clare, Webster, Mary, Newcastle, Newcastle, Ellam, Timothy, Wong, Edwin, Meshykhi, Christine, Webster, Andrea, Wilson, Peter, Vilar, Enric, Berdeprado, Jocelyn, Doctolero, Eunice, Wilkinson, Lily, Mccarroll, Frank, Ammar, Hesham, Kuan, Ying, Moran, Conor, Shivashankar, Girish, Campbell, Ryan, Glowski, Deborah, Mcdermott, Paula, Ali, Amar, Patel, Zuber, Bond, Christine, Whalley, Gillian, Zhang, Haitao, Yang, Liu, Zhang, Lihua, Kan, Tingting, Zhu, Ling, Zhao, Jinghong, Hou, Weiping, Wu, Jing, Cheng, Hong, Bian, Weijing, Zhao, Zhirui, Shao, Fengmin, Cao, Huixia, Jiao, Xiaojing, Niu, Peiyuan, Niu, Jianying, Chen, Yu, Zhang, Lihong, Zhu, Shenglang, Lin, Haiyan, Yao, Shaopeng, Chen, Jiehui, Jiang, Ying, Hu, Ying, Xiao, Huaying, Yang, Fuye, Zhang, Xinzhou, Guo, Baochun, Jin, Qiu, Liu, Lixia, Xiao, Xiangcheng, Xie, Yanyun, Meng, Ting, Xu, Chuanwen, Huang, Jie, Xu, Yanmei, Kong, Weixin, Wang, Xiaoliang, Liu, Qianpan, Wang, Xueying, Gao, Ming, Hu, Xiumei, Lu, Ying, Wang, Li, Peng, Kun, Wang, Wei, Gong, Qiuhong, Cai, Jianfang, Li, Xiaojue, Liu, Xuejiao, Zhou, Shuhan, Liu, Hong, Weng, Yao, Tang, Shuai, Yao, Yao, Zhao, Shi, Cheng, Chen, Wei, Wei, Li, Na, Aqashiah Mazlan, Sadanah, Zubaidah Bahtar, Alia, Katiman, Elliyyin, Othman, Noraini, Mushahar, Lily, Mazlan, Nurdiana, Sharafina Safiee, Nur, Ramasamy, Sarasa, Seng Wong, Hin, Ahmad Rosdi, Hajar, Zhao Zhi Tan, Esther, Fan Tay, Ju, Seng Teng, Kok, Yahaya, Hasnah, Jiun Liu, Wen, Wee Ee, Lik, Kay Leong Khoo, Kenneth, Mohd Yusoff, Yuana, Safhan Mohamad Nor, Fariz, Kamil Ahmad, Mohd, Ramli Seman, Mohd, Hui Hong Tan, Clare, Lui Sian Ngu, Laura, Yoke May Chan, Jaime, Peji, Javelin, Loong Loh, Chek, Yan Lee, Yee, Ramanaidu, Sridhar, Mean Thong, Kah, Hong Wong, Yik, Junus, Suria, Hua Ching, Chen, Faisal Asmee, Mohammad, Ruziana Ku Md Razi, Ku, Leong Low, Chun, Sze Bing Sim, Christopher, Duan Tham, Zhang, Kamila Abdullah, Noor, Meng Chen, Tai, Chieh Chan, Yong, Chang, Eason, Yean Kang, Huan, Quan Lee, Kai, Ann Lee, Sue, Kheng Lee, Aik, Vinathan, Jeevika, Abdul Cader, Rizna, Mustafar, Ruslinda, Kamaruzaman, Lydia, Mohd, Rozita, Ismail, Rahimah, Men Leong, Chong, Koon Low, Chee, Wei Wong, Liang, Adnan, Norlezah, Ibrahim, Sabariah, Zaimi Abdul Wahab, Mohamad, Bavanandan, Sunita, Shen Lim, Yik, Hazlina Wan Mohamad, Wan, Munirah Jaafar, Siti, Ashykeen Mohd Fauzi, Nur, Sudin, Aziee, Kun Lim, Soo, Chung Gan, Chye, Hing, Albert, Ahmad Faizal Alaidin Razali, Wan, Fong Liew, Yew, Bao Tyng Chan, Chelsia, Chih Cheng, Mei, Chen Ong, Yu, Meng Ong, Loke, Amalina Mohamed Affandi, Farah, Rahmat, Korina, Chai Peng, Ban, Amat, Masayu, Hadafi Ahmad, Nuzaimin, Yee Mah, Doo, Loon Tye, Yi, Azhari, Zaid, Nabilah Mohamad Zaini, Siti, Aidil Musa, Mohd, Ahmad Miswan, Norazinizah, Ramli, Rafizanur, Aziah Ahmad, Nor, Leong Goh, Bak, Izah Ahmad, Nurul, Huda Ibrahim, Fairol, Jian Ng, Tze, Shanmuganathan, Malini, Lian Tay, Li, Harun, Zaiha, Ramli, Salmi, 'Ain Yusof, Nurul, Abd Rahman, Rossenizal, Iqbal Abdul Hafidz, Muhammad, Hidayati Mohd Sharif, Nur, Yasmoon Awang, Irda, Nakashima, Eitaro, Imamine, Rui, Minatoguchi, Makiko, Miura, Yukari, Nakaoka, Miduki, Suzuki, Yoshiki, Yoshikawa, Hitomi, Shin, Koki, Fujita, Kanae, Iwasa, Misuzu, Sasajima, Haruka, Sato, Airi, Hamamoto, Yoshiyuki, Fujita, Yuki, Haraguchi, Takuya, Hyo, Takanori, Izumi, Kiyohiro, Komiya, Toshiyuki, Kubota, Sodai, Kurose, Takeshi, Kuwata, Hitoshi, Nakatani, Susumu, Oishi, Kaori, Okamoto, Saki, Okamura, Kaori, Takeoka, Jun, Tanaka, Nagaaki, Tanigaki, Katsuya, Toda, Naohiro, Watanabe, Koin, Komori, Hiromi, Kumuji, Rika, Takesada, Asako, Tanaka, Aya, Maruyama, Shoichi, Hasegawa, Tomonori, Ishiguro, Akiko, Ishimoto, Takuji, Ito, Kazuhiro, Kamimura, Yutaka, Kato, Noritoshi, Kato, Sawako, Kojima, Hiroshi, Kosugi, Tomoki, Maeda, Kayaho, Mizuno, Masasi, Saito, Shoji, Sato, Hitomi, Sato, Yuka, Suzuki, Yasuhiro, Tanaka, Akihito, Yasuda, Yoshinari, Hasegawa, Fujiko, Hayashi, Maiko, Higashi, Shizuka, Shimamura, Kaho, Sumi, Momoko, Tajima, Kazuki, Unekawa, Chimaki, Wakayama, Kana, Wakita, Yukiko, Otani, Takatoshi, Imai, Ayako, Kawashima, Sayaka, Kogure, Eri, Sato, Tomoe, Takezawa, Misato, Yoshida, Shinya, Araki, Hideo, Katsuda, Yuko, Konishi, Masahiro, Matsunaga, Takahiro, Oe, Masashi, Ogane, Kunihiro, Sakai, Masato, Takahashi, Tomoko, Yamano, Takahiro, Yokoyama, Takuya, Ito, Hitomi, Katayama, Masayo, Kuroda, Emi, Ikeda, Toru, Kojo, Takuma, Yoshidome, Etsuo, Mizumachi, Rieko, Yamamoto, Akane, Yamasaki, Narihisa, Yamasaki, Yoshihiko, Wada, Jun, Eguchi, Jun, Higuchi, Chigusa, Katayama, Akihiro, Kinomura, Masaru, Kitagawa, Masashi, Kitamura, Shinji, Miyamoto, Satoshi, Morinaga, Hiroshi, Nakatsuka, Atsuko, Nojima, Ichiro, Shikata, Kenichi, Sugiyama, Hitoshi, Tanabe, Katsuyuki, Tsuji, Kenji, Uchida, Haruhito, Watanabe, Mayu, Hashimoto, Chie, Kato, Takahiro, Yamamoto, Sayaka, Wada, Takehiko, Fukagawa, Masafumi, Hamano, Naoto, Koizumi, Masahiro, Komaba, Hirotaka, Nakagawa, Yosuke, Iwamoto, Michiyo, Masutani, Kosuke, Katanosaka, Akane, Kiyota, Mayu, Uchi, Hikari, Ueda, Yuka, Yamamoto, Sonoka, Nagasu, Hajime, Itano, Seiji, Iwakura, Tsukasa, Kadoya, Hiroyuki, Kanda, Eiichiro, Kashihara, Naoki, Kidokoro, Kengo, Kondo, Megumi, Sasaki, Tamaki, Satoh, Minoru, Tokuyama, Atsuyuki, Umeno, Reina, Wada, Yoshihisa, Yamamoto, Toshiya, Yamanouchi, Yu, Abe, Masumi, Inukai, Yoko, Ogawa, Wataru, Asahara, Shunichiro, Fujii, Hideki, Goto, Shunsuke, Hirota, Yushi, Hosooka, Tetsuya, Kono, Keiji, Nishi, Shinichi, Okada, Yuko, Sakaguchi, Kazuhiko, Sugawara, Kenji, Takahashi, Michiko, Takai, Tomoko, Tamori, Yoshikazu, Watanabe, Kentaro, Kitajima, Miyu, Nishi, Misaki, Wada, Junko, Ito, Yasuhiko, Kamiya, Hideki, Asai, Akimasa, Asai, Nao, Asano, Saeko, Banno, Shogo, Ejima, Yohei, Hase, Hanako, Hayami, Tomohide, Himeno, Tatsuhito, Ishikawa, Takahiro, Ito, Mayumi, Iwagaitsu, Shiho, Kasagi, Rina, Kato, Yoshiro, Kato, Makoto, Kato, Koichi, Katsuno, Takayuki, Kawai, Miyuka, Kinashi, Hiroshi, Kondo, Masaki, Koshino, Masako, Matsuoka, Naoya, Morishita, Yoshiaki, Motegi, Mikio, Nakamura, Jiro, Shimoda, Hiromi, Sugiyama, Hirokazu, Tsunekawa, Shin, Yamaguchi, Makoto, Takahashi, Kazuyo, Watada, Hirotaka, Funayama, Takashi, Furukawa, Yasuhiko, Gohda, Tomohito, Goto, Hiromasa, Kaga, Hideyoshi, Kanaguchi, Yasuhiko, Kanazawa, Akio, Kaneko, Kayo, Kano, Toshiki, Kihara, Masao, Kimura, Shogo, Kobayashi, Takashi, Maiguma, Masayuki, Makita, Yuko, Mano, Satoshi, Mita, Tomoya, Miyatsuka, Takeshi, Murakoshi, Maki, Muto, Masahiro, Nakata, Masami, Nakata, Junichiro, Nishida, Yuya, Nohara, Nao, Ogihara, Takeshi, Sato, Daisuke, Sato, Junko, Sato, Hiroaki, Suzuki, Yusuke, Suzuki, Ruka, Suzuki, Hitoshi, Takagi, Miyuki, Tamura, Yoshifumi, Uchida, Toyoyoshi, Ueda, Seiji, Asawa, Miki, Miyaji, Minako, Nagashima, Eri, Shibata, Yoshie, Yanagisawa, Eri, Yamauchi, Toshimasa, Hirakawa, Yosuke, Nishi, Hiroshi, Shojima, Nobuhiro, Horikawa, Satoko, Nakayama, Yukiko, Yamada, Naoko, Omori, Yuki, Yano, Shintaro, Ioka, Miyabi, Kuwabara, Nahoko, Nagano, Remi, Nozawa, Megumi, Osawa, Yumi, Maegawa, Hiroshi, Kume, Shinji, Araki, Shinichi, Miyazawa, Itsuko, Morino, Katsutaro, Kawai, Ikuko, Sobata, Masumi, Takaoka, Motoko, Iwaita, Yasushi, Udagawa, Takashi, Inamori, Ami, Kawase, Aya, Yamanaka, Aya, Shimano, Hitoshi, Fujita, Akiko, Iwasaki, Hitoshi, Kai, Hirayasu, Osaki, Yoshinori, Saito, Chie, Sekiya, Motohiro, Tsunoda, Ryoya, Yamagata, Kunihiro, Nakamura, Rikako, Yamada, Aiko, Ohsugi, Mitsuru, Awazawa, Motoharu, Bouchi, Ryotaro, Hashimoto, Shota, Hashimoto, Makiko, Hisatake, Tomoko, Ihana, Noriko, Ishizuka, Koko, Izumi, Kazuo, Kajio, Hiroshi, Kobayashi, Michi, Kodani, Noriko, Maruyama, Koji, Matsumoto, Michihiro, Matsushita, Maya, Nakamura, Tomoka, Sugiyama, Takehiro, Tanabe, Akiyo, Terakawa, Aiko, Ueki, Kojiro, Orimo, Yuko, Ozawa, Takako, Takahira, Eriko, Yamasaki, Yoshimitsu, Haneda, Masakazu, Tomita, Tadahiro, Akimoto, Saori, Fujimoto, Akihiro, Ishihara, Kenji, Murakami, Chiho, Nishiyama, Akiyo, Toyonaga, Yukiko, Uozumi, Kana, Yamaji, Yukihiro, Shigehara, Tetsuya, Okajyo, Jun, Shimizu, Yukihiro, Iwasaki, Shingo, Fukao, Yuki, Furusho, Megumi, Nunokawa, Shintaro, Katagiri, Hideki, Izumi, Tomohito, Kaneko, Keizo, Kodama, Shinjiro, Miyazaki, Mariko, Munakata, Yuichiro, Nagasawa, Tasuku, Oe, Yuji, Sugawara, Hiroto, Takahashi, Kei, Hirata, Kazushige, Inomata, Keiko, Otomo, Shoko, Uchida, Taeko, Yamashita, Chigusa, Kiyosue, Arihiro, Tamura, Ryota, Dube, Francoi, Bolduc, Marilene, Talbot, Marie-Christine, Cham, Leslie, Lai, Vesta, Tse, Josephine, Jolly, Shivinder, Duck, Tabbatha, Lyle, Scott, Epp, Rachel, Galloway, Camille, Haskett, Susan, Matvienko, Elizabeta, Paulsen, Liam, Moist, Louise, Lozon, Zabrina, Ramsey, Tina, Whitmore, Brittany, Al-Zeer, Bader, Macleod, Paula, O'Sullivan, Aoife, Sheriff, Zainab, Tholl, Sam, Pandey, Amritanshu, Armstrong, Samantha, Gebeyehu, Bethelihem, Toth, Patrick, Goldenberg, Ronald, Jahangiriesmaili, Mahsa, Sanguila, Shariff, Suresh, Neethi, Talsania, Tanvi, Zalunardo, Nadia, Agharazii, Mohsen, Roussel, Marie-Pier, Saillant, Annie, Samson, France, Bajaj, Harpreet, Bhavsar, Miken, Dhall, Parul, Dhillon, Gagandeep, Grewal, Bhupinder, Nimbkar, Taniya, Madore, Francoi, Marcotte, Guylaine, Steen, Oren, Bullen, Mathura, Raguwaran, Shayani, Valleteau, Andre, Langlois, Marie-France, Brown, Christine, Steele, Andrew, Garrity, Melissa, Ghate, Taneera, Robinson, Holly, Tolibas, Michael, Tailor, Chetna, Elliott, Lauren, McClary-Wright, Christine, Boreky, Fadia, Fikry, Sameh, Ali, Ayesha, Barot, Chintankumar, Basily, Wagdy, Saram, Thisun, Varad, Vinay, Khandwala, Hasnain, Aguilera, Alex, Alvarez, Patricia, Gill, Balwinder, Huda, Nazihah, Navivala, Aamir, Pinto, Daniel, Bevilacqua, Micheli, Fung, Elaine, Hernandez, Geraldine, Mann, Puneet, Saini, Jaskiran, Rabasa-Lhoret, Remi, Bovan, Danijela, Devaux, Marie, Barnini, Cecilia, Leoncini, Giovanna, Manco, Luca, Nobili, Giulia, Piemontese, Matteo, Aucella, Filippo, Grifa, Rachele, Totaro, Francesco, La Manna, Gaetano, Capelli, Irene, Cianciolo, Giuseppe, Lerario, Sarah, Zappulo, Fulvia, Rosati, Alberto, Fani, Filippo, Spatoliatore, Giuseppe, Gesualdo, Loreto, Pesce, Francesco, Russo, Maria, Zippo, Maria, Cafiero, Cesira, Motta, Daria, Bianco, Simona, Bilucaglia, Donatella, Messa, Piergiorgio, Pavone, Laura, Tripodi, Federica, Vettoretti, Simone, Fioretto, Paola, Carraro, Gianni, Farnia, Filippo, Postal, Anna, D'Amelio, Alessandro, Cardone, Antonio, Piccinni, Giovanni, Aloisi, Annalisa, Scolari, Francesco, Alberici, Federico, Guerini, Alice, Saccà, Chiara, Salviani, Chiara, Zani, Roberta, DE NICOLA, Luca, Garofalo, Carlo, Elena Liberti, Maria, Minutolo, Roberto, Pennino, Luigi, Polese, Lucio, Mené, Paolo, Barberi, Simona, Falcone, Clorinda, Russo, Francesco, Caroppo, Maurizio, Santorelli, Gennaro, Rivera, Rodolfo, Santoro, Domenico, Giuffrida, Alfio, Zirino, Fortunata, Calvi, Cristina, Estienne, Luca, Gambaro, Giovanni, Gangemi, Concetta, Ortalda, Vittorio, Pessolano, Giuseppina, Grandaliano, Giuseppe, Baccaro, Rocco, Ferraro, Pietro, Mangiacapra, Roberto, Melandri, Marco, Foligno, Nadia, Quartagno, Rita, Vezzoli, Giuseppe, Brioni, Elena, and Group, EMPA-KIDNEY Collaborative
Subjects: chronic renal disease, empagliflozin, empa-kidney, General Medicine
Abstract: Background The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY trial was designed to assess the effects of treatment with empagliflozin in a broad range of such patients. Methods We enrolled patients with chronic kidney disease who had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m2 of body-surface area, or who had an eGFR of at least 45 but less than 90 ml per minute per 1.73 m2 with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in eGFR to Results A total of 6609 patients underwent randomization. During a median of 2.0 years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; 95% confidence interval [CI], 0.64 to 0.82; PConclusions Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo. (Funded by Boehringer Ingelheim and others; EMPA-KIDNEY ClinicalTrials.gov number, NCT03594110. opens in new tab; EudraCT number, 2017-002971-24. opens in new tab.)
Published: 2023

29. Influence of Lateral Stress Ratio on N-Value and Cyclic Strength of Sands Containing Fines

Author: Kenji HARADA, Kenji ISHIHARA, and Hiroshi YABE
Subjects: Mechanics of Materials, Mechanical Engineering, General Materials Science, Condensed Matter Physics
Published: 2022

30. Trends and Characteristics in Health Care-related Deaths Investigated through Medico-legal Autopsies after System Changes in Japan

Author: Rutsuko, Yamaguchi, Yohsuke, Makino, Go, Inokuchi, Kenji, Ishihara, Suguru, Torimitsu, Fumiko, Chiba, Yumi, Hoshioka, Syumari, Urabe, Yukiko, Oya, Ayumi, Motomura, Daisuke, Yajima, and Hirotaro, Iwase
Subjects: Japan, Cause of Death, Autopsy, Delivery of Health Care, Retrospective Studies
Abstract: In Japan, a new cause-of-death investigation system and related new laws were enacted in the mid-2010s. These laws provided for an autopsy system for non-criminal unnatural deaths and a medical accident investigation system outside the criminal justice process for health care-related deaths. We retrospectively explored changes in the number and characteristics of medico-legal autopsy cases of health care-related deaths in Chiba Prefecture, Japan, and examined trends over time during these reforms. We found that the percentage of forensic autopsies based on the Code of Criminal Procedure for health care-related deaths had decreased significantly. The number of autopsies of accidental and unintentional deaths in nursing homes, which are not covered by the newly established medical accident investigation system, has been increasing, reflecting the ageing of society. The trend toward decriminalisation of health care-related deaths was expected to contribute more to medical safety if the scope was expanded and a system for disclosure of autopsy information was established.
Published: 2022

31. Clinically Significant Nonperfusion Areas on Widefield OCT Angiography in Diabetic Retinopathy

Author: Kentaro Kawai, Tomoaki Murakami, Yuki Mori, Kenji Ishihara, Yoko Dodo, Noriko Terada, Keiichi Nishikawa, Kazuya Morino, and Akitaka Tsujikawa
Subjects: Widefield OCT angiography, Diabetic retinopathy, Semiautomatic quantification, General Medicine, Nonperfusion areas, Neovascularization
Abstract: [Purpose] To investigate the distribution of clinically significant nonperfusion areas (NPAs) on widefield OCT angiography (OCTA) images in patients with diabetes. [Design] Prospective, cross-sectional, observational study. [Participants] One hundred and forty-four eyes of 114 patients with diabetes. [Methods] Nominal 20 × 23 mm OCTA images were obtained using a swept-source OCTA device (Xephilio OCT-S1), followed by the creation of en face images 20-mm (1614 pixels) in diameter centering on the fovea. The nonperfusion squares (NPSs) were defined as the 10 × 10 pixel squares without retinal vessels, and the ratio of eyes with the NPSs to all eyes in each square was referred to as the NPS ratio. The areas with probabilistic differences (APD) for proliferative diabetic retinopathy (PDR) and nonproliferative diabetic retinopathy (NPDR) (APD[PDR] and APD[NPDR]) were defined as sets of squares with higher NPS ratios in eyes with PDR and NPDR, respectively. The P ratio (NPSs within APD[PDR] but not APD[NPDR]/all NPSs) was also calculated. [Main Outcome Measures] The probabilistic distribution of the NPSs and the association with diabetic retinopathy (DR) severity. [Results] The NPSs developed randomly in eyes with mild and moderate NPDR and were more prevalent in the extramacular areas and the temporal quadrant in eyes with severe NPDR and PDR. The APD(PDR) was distributed mainly in the extramacular areas, sparing the areas around the vascular arcades and radially peripapillary capillaries. The APD(PDR) contained retinal neovascularization more frequently than the non-APD(PDR) (P = 0.023). The P ratio was higher in eyes with PDR than in those with NPDR (P < 0.001). The multivariate analysis designated the P ratio (odds ratio, 8.293 × 107; 95% confidence interval, 6.529 × 102–1.053 × 1013; P = 0.002) and the total NPSs (odds ratio, 1.002; 95% confidence interval, 1.001–1.003; P < 0.001) as independent risk factors of PDR. Most eyes with NPDR and 4-2-1 rule findings of DR severity had higher P ratios but not necessarily greater NPS numbers. [Conclusions] The APD(PDR) is uniquely distributed on widefield OCTA images, and the NPA location patterns are associated with DR severity, independent of the entire area of NPAs. [Financial Disclosure(s)] Proprietary or commercial disclosure may be found after the references.
Published: 2022

32. Symptomatology and Neuropathology of patients presenting with focal cortical signs

Author: Kenji Ishihara, Toshiya Fukui, Mitsuru Kawamura, Jun‐ichi Shiota, and Imaharu Nakano
Subjects: Neurology (clinical), General Medicine, Pathology and Forensic Medicine
Abstract: Here, we describe two patients who presented with focal cortical signs and underwent neuropathological examination. Case 1 was a 73-year-old woman with progressive speech disorder and abnormal behavior. She showed agraphia of the frontal lobe type, featured by the omission of kana letters when writing, other than pyramidal tract signs, pseudobulbar palsy, and frontal lobe dementia. Neuropathological examination, including TAR DNA-binding protein 43 (TDP-43) immunohistochemistry, revealed bilateral frontal and anterior temporal lobe lesions accentuated in the precentral gyrus and posterior part of the middle frontal gyrus. Both upper and lower motor neurons showed pathological changes compatible with amyotrophic lateral sclerosis. Case 2 was a 62-year-old man with progressive speech disorder and hand clumsiness. He had a motor speech disorder, compatible with apraxia of speech, and limb apraxia of the limb-kinetic and ideomotor type. Neuropathological examination revealed degeneration in the left frontal lobe, including the precentral gyrus, anterior temporal, and parietal lobe cortices. Moreover, numerous argyrophilic neuronal intracytoplasmic inclusions (Pick body) and ballooned neurons were observed in these lesions and the limbic system. The pathological diagnosis was Pick disease involving the peri-Rolandic area and parietal lobe. In these two cases, the distribution of neuropathological changes in the cerebral cortices correlated with the clinical symptoms observed.
Published: 2022

33. Synergistic effect of dietary glycerol galactoside and porphyran from nori on cecal immunoglobulin A levels in mice

Author: Hiromi Kunitake, Toshihiko Muraoka, Chiaki Oyamada, Kenji Ishihara, and Takuya Seko
Subjects: Marketing, Immunoglobulin A, biology, General Chemical Engineering, Porphyran, Galactoside, Industrial and Manufacturing Engineering, chemistry.chemical_compound, chemistry, Biochemistry, Glycerol, biology.protein, Food Science, Biotechnology
Published: 2021

34. A case suspected of Alzheimer type dementia showing multimodal (face and voice) person recognition disorder from face and voice

Author: Toshiomi Asahi, Nobuyoshi Takahashi, Sayaka Kaneko, and Kenji Ishihara
Subjects: medicine.medical_specialty, Precuneus, Audiology, Hippocampus, Alzheimer Disease, Memory, medicine, Humans, Dementia, Semantic memory, Cognitive Dysfunction, Aged, 80 and over, Tomography, Emission-Computed, Single-Photon, Psychological Tests, Recall, business.industry, Recognition, Psychology, Inferior parietal lobule, Frontotemporal lobar degeneration, medicine.disease, Magnetic Resonance Imaging, Temporal Lobe, Prosopagnosia, medicine.anatomical_structure, Face, Voice, Female, Neurology (clinical), Alzheimer's disease, business, Cognitive load
Abstract: A 90-year-old woman presented with a multimodal (face and voice) person recognition disorder. Although she had moderate general cognitive impairment, her visual cognitive capacity, other than face recognition, was well preserved. She could identify the faces and voices of family members but could not recall the names and voices of relatives whom she met infrequently, famous individuals, or the medical staff. She could remember the first names and some information about prominent individuals when supplied with their surnames. Therefore, we thought that her person-specific semantic memory was intact but she was unable to access it through their faces and voices. MRI revealed predominantly right-sided bilateral anterior temporal lobe and hippocampal atrophy. SPECT images showed decreased blood flow in the bilateral anterior temporal lobes and inferior parietal lobule (heavily and predominantly right-sided), right posterior cingulate gyrus, and precuneus. Progressive person recognition disorder or prosopagnosia has been considered a right temporal variant of frontotemporal lobar degeneration because abnormal behaviors and psychiatric symptoms frequently coexist. However, no such symptoms were observed in this case, therefore we suspected dementia of the Alzheimer type.
Published: 2021

35. Neuroprotective effects and mechanisms of action of nicotinamide mononucleotide (NMN) in a photoreceptor degenerative model of retinal detachment

Author: Xiaohong Chen, J.B. Lee, Lin Lu, Paulo Rodolfo Tagliari Barbisan, Kenji Ishihara, David A. Sinclair, Yasuhiro Iesato, Takashi Ueta, Zhen Yu, Konstantina A. Togka, João A. Amorim, Demetrios G. Vavvas, and Giannis A. Moustafa
Subjects: Lipopolysaccharides, Aging, nicotinamide mononucleotide, Stimulation, Apoptosis, Nicotinamide adenine dinucleotide, medicine.disease_cause, Neuroprotection, Cell Line, Protein Carbonylation, chemistry.chemical_compound, Mice, SIRT1, Sirtuin 1, NAD+, Glial Fibrillary Acidic Protein, medicine, In Situ Nick-End Labeling, Animals, Outer nuclear layer, Nicotinamide mononucleotide, photoreceptor degeneration, TUNEL assay, CD11b Antigen, Chemistry, Macrophages, Retinal Degeneration, Retinal Detachment, Membrane Proteins, Cell Biology, NAD, Cell biology, Oxidative Stress, medicine.anatomical_structure, Neuroprotective Agents, neuroprotection, NAD+ kinase, Oxidative stress, Heme Oxygenase-1, Priority Research Paper, Photoreceptor Cells, Vertebrate
Abstract: Currently, no pharmacotherapy has been proven effective in treating photoreceptor degeneration in patients. Discovering readily available and safe neuroprotectants is therefore highly sought after. Here, we investigated nicotinamide mononucleotide (NMN), a precursor of nicotinamide adenine dinucleotide (NAD+), in a retinal detachment (RD) induced photoreceptor degeneration. NMN administration after RD resulted in a significant reduction of TUNEL+ photoreceptors, CD11b+ macrophages, and GFAP labeled glial activation; a normalization of protein carbonyl content (PCC), and a preservation of the outer nuclear layer (ONL) thickness. NMN administration significantly increased NAD+ levels, SIRT1 protein expression, and heme oxygenase-1 (HO-1) expression. Delayed NMN administration still exerted protective effects after RD. Mechanistic in vitro studies using 661W cells revealed a SIRT1/HO-1 signaling as a downstream effector of NMN-mediated protection under oxidative stress and LPS stimulation. In conclusion, NMN administration exerts neuroprotective effects on photoreceptors after RD and oxidative injury, suggesting a therapeutic avenue to treating photoreceptor degeneration.
Published: 2020

36. Pigmentary lesions in eyes with rhegmatogenous retinal detachment: A retrospective observational study

Author: Ideyama Midori, Yuki Muraoka, Kentaro Kawai, Masaharu Ishikura, Shin Kadomoto, Naomi Nishigori, Takanori Kameda, Kenji Ishihara, Manabu Miyata, Masahiro Miyake, Tomoaki Murakami, Sotaro Ooto, and Akitaka Tsujikawa
Subjects: genetic structures, sense organs, eye diseases
Abstract: We included 97 patients with unilateral rhegmatogenous retinal detachment (RRD) with posterior vitreous detachment who underwent vitrectomy, and examined pigmentary lesion (PL) characteristics around the sites of original tears using pre- and postoperative ultra-widefield scanning light ophthalmoscopy, green light fundus autofluorescence (FAF) imaging, and intraoperative digital video. If PL did not involve RRD, we used OCT to preoperatively assess any pathologic changes to the lesion. A total of 116 retinal tears (mean count, 1.2 ± 0.5; range, 1–4 per eye) were observed in the detached retina. Overall, 102 (88%), 63 (54%), 14 (12%), and 25 (22%) tears were accompanied by lattice degeneration (LD) or PL, both LD and PL, only LD, and only PL, respectively. In green FAF images, LD showed normal to mild-hyper fluorescence, whereas all PL showed hypofluorescence. On OCT, PL were located at the RPE level, while choroid abnormalities were unclear. In the retinal areas of 22 eyes, which were not affected by RRD, we observed PL without retinal tears; some were accompanied by vitreous traction and tractional retinal detachment. Pre-, intra-, and post-operative assessments of original flap tears suggested that PL might be a risk factor for RRD, developing alongside or separately from LD.
Published: 2022

37. Use of In Situ Sounding Tests for Evaluating Soil Liquefaction Triggering

Author: Yoshimichi Tsukamoto and Kenji Ishihara
Published: 2022

38. Evaluating Post-liquefaction Settlement and Lateral Deformation

Author: Yoshimichi Tsukamoto and Kenji Ishihara
Published: 2022

39. Analysis on Triggering of Soil Liquefaction Including Effects of Imperfect Saturation

Author: Yoshimichi Tsukamoto and Kenji Ishihara
Published: 2022

40. Characterising Undrained Monotonic Behaviour of Saturated Sand

Author: Yoshimichi Tsukamoto and Kenji Ishihara
Published: 2022

41. Use of In Situ Sounding Tests for Evaluating Stability of Soil Deposits Subject to Liquefaction

Author: Yoshimichi Tsukamoto and Kenji Ishihara
Published: 2022

42. Characterising Undrained Behaviour of Imperfectly Saturated and Unsaturated Sands

Author: Yoshimichi Tsukamoto and Kenji Ishihara
Published: 2022

43. Development of the Earthquake Geotechnical Engineering (EGE) in ISSMGE

Author: Kenji Ishihara
Published: 2022

44. Liquefaction Resistance of Saturated Sand

Author: Yoshimichi Tsukamoto and Kenji Ishihara
Published: 2022

45. Novel Regenerative Braking Control of Electric Power-Assisted Wheelchair for Safety Downhill Road Driving.

Author: Hirokazu Seki, Kenji Ishihara, and Susumu Tadakuma
Published: 2009
Full Text: View/download PDF

46. Reform of the death investigation system in Japan

Author: Kenji Ishihara and Hirotaro Iwase
Subjects: Successor cardinal, Government, Medicolegal autopsy, Health Policy, media_common.quotation_subject, World War II, Medical examiner, History, 19th Century, Forensic Medicine, History, 20th Century, History, 18th Century, Administration (probate law), Issues, ethics and legal aspects, Promotion (rank), Japan, Law, Political science, Humans, Autopsy, media_common, Cause of death
Abstract: The autopsy rate in Japan is lower than that in other countries, and most death investigations have historically been conducted by police officers through external inspection. Although medicolegal autopsy was not performed during the samurai administration, the European death investigation system was adopted in the second half of the 19th century and judicial autopsy began in universities’ forensic medicine departments. After World War II, the medical examiner system was introduced under US influence, but it was only adopted in certain areas. Further reforms were introduced in the 21st century—in 2012, two laws relating to death investigation were enacted: The Act on Promotion of Death Investigation (Promotion Act), which provided foundational principles and included measures for investigating the causes of death and identification of bodies, and the Act on the Investigation of Cause of Death and on Identification of Bodies Handled by the Police, which recommended a procedure for death investigation, including a new autopsy system. The Death Investigation Promotion Program was to meant to be decided by the government in 2014. However, the relevant Act expired after it ran out of time. Later, in 2019, the Basic Act for Promotion of Death Investigation, the successor to the Promotion Act, was passed. This Act is significant because it sets the basic foundational principle and imposes plans created by the government. However, it remains unclear how these measures can be implemented, so further discussion and financial investment are now required.
Published: 2020

47. ANALYSIS OF BUILDING STOCK CHANGE IN MAJOR CITIES BASED ON THE CITY PLANNING BASIC SURVEYS BY CREATING TIME-SERIES PANEL DATA OF BUILDINGS

Author: Yukio Komatsu and Kenji Ishihara
Subjects: Urban planning, Regional science, General Medicine, Business, Stock (geology), Panel data
Published: 2020

48. CHANGE OF BUILDING ATTRIBUTES AND THEIR GEOGRAPHICAL DISTRIBUTION IN TOKYO WARDS

Author: Yukio Komatsu and Kenji Ishihara
Subjects: Geography, Public land, business.industry, Environmental resource management, Distribution (economics), General Medicine, business
Published: 2020

49. RIP1 kinase mediates angiogenesis by modulating macrophages in experimental neovascularization

Author: Jong Jer Lee, Yusuke Murakami, Kunihiro Azuma, Eleftherios I. Paschalis, Makoto Aihara, Shoji Notomi, Daniel E. Maidana, Tetsuya Toyono, Kenji Ishihara, Joan W. Miller, Demetrios G. Vavvas, Takashi Ueta, Eiichi Hasegawa, and Nikolaos Efstathiou
Subjects: Medical Sciences, Indoles, Angiogenesis, AMD, necrosis, Neovascularization, Mice, 0302 clinical medicine, Macrophage, Cells, Cultured, Caspase, 0303 health sciences, Multidisciplinary, Neovascularization, Pathologic, biology, Kinase, Chemistry, GTPase-Activating Proteins, Imidazoles, Biological Sciences, Drug Combinations, PNAS Plus, Caspases, Receptor-Interacting Protein Serine-Threonine Kinases, 030220 oncology & carcinogenesis, Models, Animal, Fibroblast Growth Factor 2, Proteoglycans, Collagen, medicine.symptom, Oligopeptides, RIPK, Recombinant Fusion Proteins, Necroptosis, Inflammation, 03 medical and health sciences, Human Umbilical Vein Endothelial Cells, In Situ Nick-End Labeling, medicine, Animals, Humans, Corneal Neovascularization, RNA, Messenger, Kinase activity, 030304 developmental biology, Lasers, Macrophages, medicine.disease, Enzyme Activation, Mice, Inbred C57BL, Receptors, Vascular Endothelial Growth Factor, Corneal neovascularization, 030221 ophthalmology & optometry, Cancer research, biology.protein, Laminin, immune, neovascular, Biomarkers, Corneal Injuries
Abstract: Significance Pathological angiogenesis has been implicated in diverse pathologies. Infiltrating macrophages, especially those activated to M2-like phenotype, are critically important for angiogenesis. Although the role of RIP1 kinase in the regulation of apoptosis, necroptosis, and inflammation has been well-established, its role in angiogenesis remains elusive, despite being abundantly expressed in angiogenesis-related infiltrating macrophages. This study demonstrates that RIP1 kinase inhibition attenuates angiogenesis in multiple mouse models of pathological angiogenesis in vivo and suggests a therapeutic role of RIP1 kinase inhibition in pathological angiogenesis. Mechanistically, the inhibitory effect on angiogenesis depends on RIP kinase inhibition-mediated caspase activation in infiltrating macrophages through suppression of M2-like polarization, and subsequent attenuation of pathological angiogenesis., Inflammation plays an important role in pathological angiogenesis. Receptor-interacting protein 1 (RIP1) is highly expressed in inflammatory cells and is known to play an important role in the regulation of apoptosis, necroptosis, and inflammation; however, a comprehensive description of its role in angiogenesis remains elusive. Here, we show that RIP1 is abundantly expressed in infiltrating macrophages during angiogenesis, and genetic or pharmacological inhibition of RIP1 kinase activity using kinase-inactive RIP1K45A/K45A mice or necrostatin-1 attenuates angiogenesis in laser-induced choroidal neovascularization, Matrigel plug angiogenesis, and alkali injury-induced corneal neovascularization in mice. The inhibitory effect on angiogenesis is mediated by caspase activation through a kinase-independent function of RIP1 and RIP3. Mechanistically, infiltrating macrophages are the key target of RIP1 kinase inhibition to attenuate pathological angiogenesis. Inhibition of RIP1 kinase activity is associated with caspase activation in infiltrating macrophages and decreased expression of proangiogenic M2-like markers but not M1-like markers. Similarly, in vitro, catalytic inhibition of RIP1 down-regulates the expression of M2-like markers in interleukin-4–activated bone marrow-derived macrophages, and this effect is blocked by simultaneous caspase inhibition. Collectively, these results demonstrate a nonnecrotic function of RIP1 kinase activity and suggest that RIP1-mediated modulation of macrophage activation may be a therapeutic target of pathological angiogenesis.
Published: 2019

50. Detection of Balenine in Mouse Plasma after Administration of Opah-Derived Balenine by HPLC with PITC Pre-Column Derivatization

Author: Yasutaka Shigemura, Yu Iwasaki, Yoshio Sato, Tomomi Kato, Takuya Seko, and Kenji Ishihara
Subjects: Health (social science), Plant Science, respiratory system, balenine, opah, carnosine, anserine, phenyl isothiocyanate, pre-column derivatization, Health Professions (miscellaneous), Microbiology, respiratory tract diseases, Food Science
Abstract: We examined the absorption of balenine (Bal) in mouse blood after the administration of a high-purity Bal prepared from opah muscle. Using HPLC with phenyl isothiocyanate pre-column derivatization, we successfully isolated imidazole peptides and their constituents. We detected Bal and 3-methylhistidine (3-Me-His) in mouse blood 1 h after the administration of opah-derived Bal. The concentrations of Bal and 3-Me-His significantly increased to 128.27 and 69.09 nmol/mL in plasma, respectively, but were undetectable in control and carnosine (Car)-administrated mice. In contrast, β-alanine and histidine did not increase in mouse plasma 1 h after the administration of Car and opah-derived Bal. The present study is the first report on the absorption of food-derived Bal in mouse blood and serves as a pilot study for future clinical trials.
Published: 2021

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