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Yoichi Tanaka,1,2 Ren Fujii,2,3 Hayato Shigetoh,2,4 Gosuke Sato,2 Shu Morioka2 1Department of Occupational Therapy, School of Rehabilitation, Hyogo Medical University, Hyogo, Japan; 2Neuro Rehabilitation Research Center, Kio University, Nara, Japan; 3Musashigaoka Clinical Research Center, Musashigaoka Hospital, Kumamoto, Japan; 4Department of Physical Therapy, Faculty of Health Science, Kyoto Tachibana University, Kyoto, JapanCorrespondence: Yoichi Tanaka, Department of Occupational Therapy, School of Rehabilitation, Hyogo Medical University, 1-3-6 Minatojima Chuo-ku, Kobe, Hyogo, Japan, Tel +81 78-304-3180, Email yi-tanaka@hyo-med.ac.jpPurpose: This study aimed to juxtapose the circadian rhythm of pain with the conventional 7-day assessment and ascertain the feasibility of condensing the evaluation of the circadian rhythm of pain into a 3-day timeframe.Patients and Methods: Seventy-three patients with pain persisting for a minimum of 3 months and a numerical rating scale (NRS) score of ≥ 2 were recruited from three medical centers. The circadian patterns of pain were appraised over a 7-day period by quantifying the intensity of pain at six temporal junctures each day using a 10-cm visual analog scale (VAS). Cluster analysis was performed using six standardized variables derived from the VAS score of each participant at six designated time points to identify cohorts with analogous circadian rhythms of pain. The clusters were discerned for the 7- and 3-day assessments (Tuesday–Thursday, Friday–Sunday, and Sunday–Tuesday), according to the research objectives. Cohen’s kappa coefficient was calculated to gauge the intra-observer variability to assess the consistency between the outcomes of the cluster analysis for the 7-day assessment and each of the 3-day assessments.Results: The highest Cohen’s kappa coefficient was observed for the 3-day evaluation spanning from Friday to Sunday, indicating a substantial concordance with the results of the 7-day assessment.Conclusion: Our results suggest that it may be prudent to consider implementing a condensed 3-day evaluation of the circadian rhythm of pain that is tailored to individual characteristics. This approach will allow a better understanding of the diurnal rhythms of chronic pain in patients and implement more targeted and specific pain management strategies. Furthermore, it will contribute to increased patient satisfaction through early intervention.Keywords: pain, chronic pain, physical activity, circadian rhythm

Yukihito Kato,1,&ast; Takashi Kojima,1,2 Akeno Tamaoki,3 Yoshiki Tanaka,1,&ast; Naoki Yamamoto,4,5,&ast; Kazuo Ichikawa1 1Chukyo Eye Clinic, Nagoya, Aichi, Japan; 2Nagoya Eye Clinic, Nagoya, Aichi, Japan; 3Department of Ophthalmology, Japan Community Health Care Organization Chukyo Hospital, Nagoya, Aichi, Japan; 4Center for Society-Academia Collaboration, Research Promotion Headquarters, Fujita Health University, Toyoake, Aichi, Japan; 5International Center for Cell and Gene Therapy, Research Promotion Headquarters, Fujita Health University, Toyoake, Aichi, Japan&ast;These authors contributed equally to this workCorrespondence: Kazuo Ichikawa, Chukyo Eye Clinic, 12-22, Sanbonmatsu-cho, Atsuta-ku, Nagoya-city, Aichi, Japan, Tel +81 52 884 7976, Fax +81 52 884 7977, Email ichikawa@chukyogroup.jpPurpose: This study aimed to evaluate the efficacy of a majority decision algorithm that integrates intraoperative aberrometry (IA) and two intraocular lens (IOL) frequency formulas. The primary objective was to compare the accuracy of three formulas (IA; Sanders, Retzlaff, and Kraff/Theoretical (SRK/T); and Barrett Universal II (BUII)), in achieving emmetropia in eyes implanted with TFNT lenses (Alcon).Patients and Methods: A total of 145 eyes of 145 patients were included in the evaluation. Preoperative data were obtained from IOLMaster 700, while intraoperative data were collected from ORA SYSTEMTM. Visual acuity ≥ 0.8 at the 3-month post-surgery mark was confirmed. We assessed refractive prediction error (RPE), which is the difference between predicted refraction (PR) and postoperative subjective refraction. This evaluation aimed to identify the optimal IOL power with the implemented algorithm.Results: Among the 145 eyes evaluated, 55.9%, 78.7%, and 97.2% achieved postoperative subjective refraction within ± 0.13 Diopters (D), ± 0.25 D, and ± 0.50 D, respectively. The percentages of eyes within ± 0.25 D of PR varied by formula type, with values of 57%, 57%, and 54% for IA, BUII, and SRK/T, respectively. For eyes with short to medium axial length (AL< 26.00 mm), the percentages within ± 0.25 D of RPE were 52%, 58%, and 58% for IA, SRK/T, and BUII, respectively. In contrast, for eyes with long axial length (≥ 26.00 mm) the percentages were 68%, 52%, and 45% for IA, BUII, and SRK/T, respectively.Conclusion: The proposed majority decision algorithm incorporating IA and two IOL frequency formulas was effective in reducing postoperative refractive error. IA was particularly beneficial for eyes with long axial length. These findings suggest the algorithm has potential to optimize IOL power selection to improve quality of life of patients and clinical practice outcomes.Keywords: multifocal intraocular lens, cataract, intraocular lens power calculation, axial length, optimum visual acuity

Yoshiya Tanaka,1 Mark C Genovese,2,3 Hironori Matsushima4 1The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health Japan, Kitakyushu, Japan; 2Division of Immunology and Rheumatology, Stanford University, Stanford, CA, USA; 3Gilead Sciences, Inc, Foster City, CA, USA; 4Gilead Sciences, Inc, Tokyo, JapanCorrespondence: Yoshiya Tanaka, The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health Japan, 1-1 Iseigaoka, Yahata-nishi, Kitakyushu, 807-8555, Japan, Tel +81-93-603-1611, Fax +81-93-691-7580, Email tanaka@med.uoeh-u.ac.jpAbstract: Filgotinib is an orally administered, preferential Janus kinase (JAK) inhibitor indicated for the treatment of moderate-to-severe rheumatoid arthritis (RA). The short-term safety, efficacy, and patient-reported outcomes (PROs) with filgotinib from Phase 2b/3 clinical trials (DARWIN 1 and 2; FINCH 1, 2, and 3) are described in patients who inadequately responded to methotrexate (MTX) and biologic disease-modifying antirheumatic drugs or who were naïve to MTX. This article reviews the safety and efficacy from the long-term extension (LTE) trials, DARWIN 3 (N=739) and FINCH 4 (N=2731), and PROs across the filgotinib development program in RA. Overall, in the DARWIN clinical trials (conducted from 2013– 2023), patients received their LTE treatment for ≤ 8 years, while in the FINCH trials (ongoing from 2016– 2025), patients received filgotinib treatment for ≤ 6 years in the LTE. The longer-term safety profile and consistent, sustained efficacy (American College of Rheumatology 20/50/70, Clinical Disease Activity Index, and Disease Activity Scale in 28 joints with C-reactive protein response rates) of filgotinib were largely similar to those observed in the shorter-term parent trials ≤ 52 weeks. PRO results from the parent trials showed improvements in patients’ quality of life with filgotinib treatment, which compared to or exceeded improvements seen with placebo and active comparators (adalimumab, MTX). Filgotinib has a higher specificity for JAK1 compared with other therapeutic treatments, leading to reduced inhibition of JAK2/3–dependent pathways, potentially providing a distinct safety profile. Filgotinib is approved in Europe and Japan for treatment of people with moderate-to-severe RA, though it has not been approved by the US Food and Drug Administration, due to concerns around the benefit/risk profile of the filgotinib 200-mg dosage and the potential impact on semen parameters.Keywords: Janus kinase inhibitors, selectivity, JAKi, disease-modifying antirheumatic drug, DMARD, RA

Yohei Tanaka,1 Richard Parker,2 Amaryllis Aganahi2 1Clinica Tanaka Plastic, Reconstructive Surgery and Anti-Aging Center, Matsumoto, Nagano, Japan; 2RATIONALE, Kyneton, VIC, AustraliaCorrespondence: Yohei Tanaka, Clinica Tanaka Plastic, Reconstructive Surgery and Anti-aging Center, M-1 Bld 1F, 3-4-3, Ote, Matsumoto, Nagano, 390-0874, Japan, Tel +81-263-36-0016, Fax +81-263-36-0016, Email info@clinicatanaka.jpBackground: Clinical, optical and histological research confirms that solar skin damage continues to pose a threat to human skin health globally despite widespread sunscreen usage and sun awareness campaigns. Despite this, very few studies examine the critical changes in gene expression and DNA repair activity following recommended topical solar protection and repair strategies to ameliorate the harmful effects of ultraviolet, visible light and near-infrared radiation.Purpose: To investigate alterations in gene expression following topical solar protection and solar repair strategies.Methods: Using epidermal keratinocytes and dermal fibroblasts derived from a 3-dimensional reconstructed human skin model, gene expression was assessed via the Genemarkers Standard Skin Panel using 112 genes deploying two analytical techniques: DNA microarray and quantitative real-time PCR exploration. Tissues were inoculated with products then collected after 24 hours following application of solar protection formulations and 16 hours following solar repair formulations (The Essential Six, RATIONALE, Victoria, Australia).Results: A DNA microarray revealed 67 genes that were significantly up-regulated or down-regulated following the treatment. The quantitative real-time PCR revealed that, in comparison to the control, the genes encoding Intercellular Adhesion Molecule 1 (ICAM1), Metallothionein 1A (MT1A), Prostaglandin-Endoperoxide Synthase 1 (PTGS2), Late Cornified Envelope 3D (LCE3D), Peroxisome Proliferator Activated Receptor (PPARD), and Granulocyte/Macrophage Colony Stimulating Factor 2 (GM-CSF2) have been up-regulated following usage of the solar protection regime, 1.87, 861.16, 4.34, 1.91, 1.06, and 3.6, respectively. ICAM1, MT1A, PTGS2, LCE3D, PPARD, and GM-CSF2 were up-regulated following use of the solar repair regime, 3.78, 2.98, 14.89, 5.09, 2.42, and 13.51, respectively.Conclusion: This study demonstrates that a specific solar protection and repair regime upregulated genes involved in photoprotection and repair mechanisms in a 3-dimensional (3D) reconstructed human-like skin model.Keywords: gene expression, anti-photoageing, anti-photoimmunosuppression, antioxidant, photoprotection, DNA repair

Yasutomo Tanaka,1,2 Masatoshi Hanada,1,2 Chika Kitagawa,3 Kazuaki Suyama,4 Ryota Shiroishi,5 Naoto Rikitomi,3 Toru Tsuda,6 Yoshiaki Utsunomiya,5 Takako Tanaka,1 Kazuya Shingai,1 Yorihide Yanagita,7 Ryo Kozu1,2 1Department of Physical Therapy Science, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; 2Department of Rehabilitation Medicine, Nagasaki University Hospital, Nagasaki, Japan; 3Nagasaki Pulmonary Rehabilitation Clinic, Nagasaki, Japan; 4Tagami Hospital, Nagasaki, Japan; 5Utsunomiya Medical Clinic, Fukuoka, Japan; 6Kirigaoka Tsuda Hospital, Fukuoka, Japan; 7Department of Physical Therapy, School of Health Science, Toyohashi Sozo University, Aichi, JapanCorrespondence: Ryo Kozu, Department of Physical Therapy Science, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8520, Japan, Tel/Fax +81 95 819 7963, Email ryokozu@nagasaki-u.ac.jpPurpose: Assessment for frailty is important as it enables timely intervention to prevent or delay poor prognosis in chronic obstructive pulmonary disease (COPD). The aims of this study, in a sample of outpatients with COPD, were to (i) assess the prevalence of physical frailty using the Japanese version of the Cardiovascular Health Study (J-CHS) criteria and the Short Physical Performance Battery (SPPB) and the degree of agreement between the findings of the two assessments and (ii) identify factors associated with the disparity in the results obtained with these instruments.Patients and Methods: This was a multicenter cross-sectional study of individuals with stable COPD enrolled in four institutions. Frailty was assessed using the J-CHS criteria and the SPPB. Weighted Cohen’s kappa (k) statistic was performed to investigate the magnitude of agreement between the instruments. We divided participants into two groups depending on whether there was agreement or non-agreement between the results of the two frailty assessments. The two groups were then compared with respect to their clinical data.Results: A total of 103 participants (81 male) were included in the analysis. The median age and FEV1 (%predicted) were 77 years and 62%, respectively. The prevalence of frailty and pre-frail was 21% and 56% with the J-CHS criteria and 10% and 17% with the SPPB. The degree of agreement was fair (k = 0.36 [95% CI: 0.22– 0.50], P< 0.001). There were no significant differences in the clinical characteristics between the agreement group (n = 44) and the non-agreement group (n = 59).Conclusion: We showed that the degree of agreement was fair with the J-CHS criteria detecting a higher prevalence than the SPPB. Our findings suggest that the J-CHS criteria may be useful in people with COPD with the aim of providing interventions to reverse frailty in the early stages.Keywords: cardiovascular health study, Short Physical Performance Battery, chronic lung disease, physical function

Tetsuya Hasegawa, Misaki Hirato, Chieko Kobashi, Aya Yamaguchi, Rina Takagi, Yoshiaki Tanaka, Toshikatsu Kaburaki, Akihiro Kakehashi Department of Ophthalmology, Saitama Medical Center Jichi Medical University, Saitama-shi, Saitama-ken, JapanCorrespondence: Akihiro KakehashiDepartment of Ophthalmology, Saitama Medical Center Jichi Medical University, Saitama-shi, Saitama-ken, JapanTel +81 48 647 2111Fax +81 48 648 5166Email kakeaki@omiya.jichi.ac.jpPurpose: To evaluate the foveal avascular zone (FAZ) and retinal structure in familial exudative vitreoretinopathy (FEVR).Patients and Methods: Eighteen eyes with stage 1 or 2 FEVR and 20 control eyes were evaluated. The central retinal thickness (CRT), foveal inner retinal thickness (IRT), surface retinal vessel density (SRVD), and deep retinal vessel density (DRVD) were measured using optical coherence tomography. The FAZ area was calculated using ImageJ software. The equivalent spherical value (SE) and axial length (AL) were measured.Results: The CRT (232.5± 3.086 vs 211± 12.6325 μm; p=0.003) and foveal IRT (15.83± 13.95 vs 0.9± 4.02 μm; p=0.002) were thicker in the FEVR group than in the control group. The surface FAZ area (0.265± 0.08 vs 0.364± 0.09 mm2; p=0.004) and the deep FAZ area (0.364± 0.1 vs 0.484± 0.11 mm2; p=0.03) were smaller in the FEVR group than in the control group. The SRVD values did not differ among the sectors, but the DRVD was higher in the FEVR group except for the inferior sector (superior, p=0.027; inferior, p=0.88; temporal, p=0.035; nasal, p=0.027). The SE and AL did not differ between the two groups. There were no correlations between the surface and deep layer FAZ area and age, CRT, SE, and AL. The surface, deep FAZ area, and foveal IRT were correlated negatively (surface, r = − 0.47, p=0.033; deep layer FAZ area, r = − 0.46, p=0.037).Conclusion: Eyes with FEVR have a smaller FAZ because the vascular structure in the inner retina remained in the fovea.Keywords: familial exudative vitreoretinopathy, optical coherence tomography angiography, foveal avascular zone

Tadashi Yamashita,1 Ramon Emilio Daniel Roces,2 Cecilia Ladines-Llave,2 Maria Teresa Reyes Tuliao,3 Mary Wanjira Kamau,4 Chika Yamada,5,6 Yuko Tanaka,7 Kyoko Shimazawa,1 Saori Iwamoto,1 Hiroya Matsuo6 1Kobe City College of Nursing, Kobe, Japan; 2Hospital of Muntinlupa, Muntinlupa, Philippines; 3City Health Office, City Government of Muntinlupa, Muntinlupa, Philippines; 4School of Nursing Sciences, University of Nairobi, Nairobi, Kenya; 5Department of Environment Coexistence, Center for Southeast Asian Studies, Kyoto University, Kyoto, Japan; 6Department of Public Health, Graduate School of Health Sciences, Kobe University, Kobe, Japan; 7Department of School Health Sciences, Institute of Biomedical Sciences, Tokushima University, Tokushima, JapanCorrespondence: Tadashi YamashitaKobe City College of Nursing, 3-4 Gakuennishi-Machi, Nishi-Ku, Kobe, 651-2103, JapanTel/Fax +81-78-794-8079Email tadashi_y_kobe@yahoo.co.jpPurpose: The World Health Organization advocates that all pregnant women in areas where anemia is prevalent receive supplements of iron and folic acid. However, owing to a myriad of factors, the uptake of iron and folic acid supplementation (IFAS) is still low in many countries. Therefore, this study was conducted to assess the prevalence of IFAS and its associated factors among pregnant women.Patients and Methods: A cross-sectional study was conducted at a hospital in Muntinlupa, Philippines, between March and August 2019 among 280 pregnant women. A systematic random sampling technique was used to select participants. Data were collected using interviewer-administered questionnaires. Multivariable logistic regression analyses were employed to identify factors associated with the prevalence of IFAS among pregnant women.Results: Among 280 pregnant women, a majority (85.6%, n= 238) took IFAS during pregnancy. Among the respondents, 128 (45.9%) women had knowledge about signs and symptoms of anemia, 126 (45.3%) had knowledge of the benefits associated with IFAS, and 42 (15.4%) had knowledge about side effects associated with IFAS. The main sources of information about IFAS were health care providers (41.8%), followed by community health workers (CHWs) (14.6%). Maternal knowledge concerning IFAS benefits (OR =  2.50, CI =  1.04– 5.97, p=0.04) was positively associated with the prevalence of IFAS.Conclusion: Maternal knowledge about the benefits of taking IFAS was significantly associated with the prevalence of IFAS among pregnant women in Muntinlupa, Philippines. There is a pressing need to improve health education on the benefits of IFAS among pregnant women to increase its prevalence. This emphasizes the necessity of increased involvement of health care providers and CHWs to increase women’s knowledge of IFAS benefits and support them through pregnancy.Keywords: anemia, pregnancy, health education, health care providers, community health workers

Yoshiya Tanaka,1 Kana Hoshino-Negishi,2 Yoshikazu Kuboi,2 Fumitoshi Tago,3 Nobuyuki Yasuda,2 Toshio Imai2 1First Department of Internal Medicine, University of Occupational and Environmental Health, Fukuoka, Japan; 2 KAN Research Institute Inc, Hyogo, Japan; 3Eisai Co. Ltd., Tokyo, JapanCorrespondence: Yoshiya TanakaFirst Department of Internal Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahata-Nishi, Kitakyushu, Fukuoka 807-8555, JapanTel +81-93-603-1611Fax +81-93-691-9334Email tanaka@med.uoeh-u.ac.jpAbstract: Rheumatoid arthritis (RA) is an autoimmune disorder that affects joints and is characterized by synovial hyperplasia and bone erosion associated with neovascularization and infiltration of proinflammatory cells. The introduction of biological disease-modifying anti-rheumatic drugs has dramatically changed the treatment of RA over the last 20 years. However, fewer than 50% of RA patients enter remission, and 10– 15% are treatment refractory. There is currently no cure for RA. Fractalkine (FKN, also known as CX3CL1) is a cell membrane-bound chemokine that can be induced on activated vascular endothelial cells. FKN has dual functions as a cell adhesion molecule and a chemoattractant. FKN binds specifically to the chemokine receptor CX3CR1, which is selectively expressed on subsets of immune cells such as patrolling monocytes and killer lymphocytes. The FKN–CX3CR1 axis is thought to play important roles in the initiation of the inflammatory cascade and can contribute to exacerbation of tissue injury in inflammatory diseases. Accordingly, studies in animal models have shown that inhibition of the FKN–CX3CR1 axis not only improves rheumatic diseases but also reduces associated complications, such as pulmonary fibrosis and cardiovascular disease. Recently, a humanized anti-FKN monoclonal antibody, E6011, showed promising efficacy with a dose-dependent clinical response and favorable safety profile in a Phase 2 clinical trial in patients with RA (NCT02960438). Taken together, the preclinical and clinical results suggest that E6011 may represent a new therapeutic approach for rheumatic diseases by suppressing a major contributor to inflammation and mitigating concomitant cardiovascular and fibrotic diseases. In this review, we describe the role of the FKN–CX3CR1 axis in rheumatic diseases and the therapeutic potential of anti-FKN monoclonal antibodies to fulfill unmet clinical needs.Keywords: fractalkine, CX3CR1, humanized anti-fractalkine monoclonal antibody (E6011), CD16+ monocyte, rheumatic diseases

Akihiro Shiroshita,1,2 Hiroshi Shiba,3 Yu Tanaka,4 Akihiro Nishi,5 Kenya Sato,6 Chigusa Shirakawa,7 Yuki Kataoka7,8 1Department of Respiratory Medicine, Ichinomiyanishi Hospital, Ichinomiya, Japan; 2Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; 3Post Graduate Education Center, Kameda Medical Center, Kamogawa, Japan; 4Department of Pulmonology, Kameda Medical Center, Kamogawa, Japan; 5General Medicine, Awa Regional Medical Center, Tateyama, Japan; 6Department of Thoracic Medicine, Saiseikai Yokohamashi Tobu Hospital, Yokohama, Japan; 7Department of Respiratory Medicine, Hyogo Prefectural Amagasaki General Medical Center, Amagasaki, Japan; 8Hospital Care Research Unit, Hyogo Prefectural Amagasaki General Medical Center, Amagasaki, JapanCorrespondence: Akihiro ShiroshitaDepartment of Respiratory Medicine, Ichinomiyanishi Hospital, 1 Kaimeihira, Ichinomiya, Aichi 494-0001, JapanTel +81-80-3807-4960Fax +586-48-0077Email akihirokun8@gmail.comPurpose: To date, no consensus exists on the effects of systemic steroid use on pneumonic chronic obstructive pulmonary disease (COPD) exacerbation owing to trial design issues in previous trials involving these conditions. This multicenter study aimed to evaluate more precisely the effectiveness of the use of systemic steroids in treating pneumonic COPD exacerbation in a larger sample by adjusting for confounding factors.Patients and Methods: This multicenter, retrospective, observational study was conducted across five acute general hospitals in Japan. We analyzed the association between parenteral/oral steroid therapy and time to clinical stability in pneumonic COPD exacerbation. We used a validated algorithm derived from the 10th revision of the International Classification of Diseases and Related Health Problems (ICD-10) to include patients with pneumonic COPD exacerbation. We excluded patients with other hypoxia causes (asthma exacerbation, pneumothorax, heart failure) and complicated pneumonia (obstructive pneumonia, empyema), those who required tracheal intubation/vasopressors, and those who were clinically stable on day of admission. The primary outcome was the time to clinical stability. Multiple imputation was used for missing data. Propensity scores within each imputed dataset were calculated using potential confounding factors. The Fine and Gray model was used within each dataset to account for the competing risk of death and hospital discharge without clinical stability, and we combined the results.Results: Altogether, 1237 patients were included. Systemic steroid therapy was administered to 658 patients (53%). The pooled estimated subdistribution hazard ratio of time to clinical stability in steroid vs non-steroid users was 0.89 (95% confidence interval, 0.78 to 1.0).Conclusion: This study revealed that systemic steroid therapy may not improve the time to clinical stability in patients with pneumonic COPD exacerbation of mild to moderate severity. Further randomized controlled trials including more severe patients will be needed to evaluate the effectiveness of systemic steroid therapy accurately.Keywords: COPD, pneumonia, steroid, outcomes, mortality

Xiaolan Wen,1,2 Yanling Wu,1,2 Annoor Awadasseid,1,3 Yoshimasa Tanaka,4 Wen Zhang1 1Laboratory of Chemical Biology and Molecular Drug Design, College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, People’s Republic of China; 2Laboratory of Molecular Immunology, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou 310051, People’s Republic of China; 3Center for Natural Products Research, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, 610041, People’s Republic of China; 4Laboratory of Bioinformatics and Molecular Medicine, Center for Medical Innovation, Nagasaki University, Nagasaki, 852-8588, JapanCorrespondence: Yanling WuLaboratory of Molecular Immunology, Zhejiang Provincial Center for Disease Control and Prevention, 3399 Binsheng Road, Binjiang District, Hangzhou, Zhejiang 310051, People’s Republic of ChinaTel +86 138 6715 2930Email ylwu@cdc.zj.cnWen ZhangLaboratory of Chemical Biology and Molecular Drug Design, College of Pharmaceutical Science, Zhejiang University of Technology, 18 Chaowang Road, Xiacheng District, Hangzhou, Zhejiang 310014, People’s Republic of ChinaTel +86 136 1671 0236Email wzhang63@zjut.edu.cnAbstract: Wnt/β-catenin-mediated signaling is a key pathway regulating tissue growth and development, and tumorigenesis, and has received increasing attention in recent years. In addition to participating in healthy tissue and organ development, ectopic activation of the pathway can cause a variety of tumors and other pathologies. The pathway plays a critical role in many processes such as proliferation, differentiation, apoptosis, migration, invasion, epithelial–mesenchymal transition and cancer cell stemness. The importance of the Wnt signal is self-evident. This review describes the underlying mechanism of Wnt signaling pathway and highlights the latest findings on the relationship between Wnt signaling pathway and tumorigenesis. In addition, the potential relationship between miRNAs and Wnt signaling is presented. Furthermore, we discuss the intrinsic link between Wnt signaling and cancer cell stemness, which shed light on the malignant progression of tumor cells. Finally, cancer treatment strategies based on the canonical Wnt signaling pathway are summarized, hoping to help clinical development.Keywords: Wnt/β-catenin, tumor, miRNAs, cancer stem cell, target, therapeutic strategy

Ayana Goto, Nobuhisa Matsuhashi, Takao Takahashi, Toshiyuki Tanahashi, Satoshi Matsui, Hisashi Imai, Yoshihiro Tanaka, Kazuya Yamaguchi, Kazuhiro Yoshida Department of Surgical Oncology, Gifu University School of Medicine, Gifu City 501-1194, JapanCorrespondence: Nobuhisa MatsuhashiDepartment of Surgical Oncology, Gifu University School of Medicine, 1-1 Yanagido, Gifu City 501-1194, JapanTel +81-58-230-6233Fax +81-58-230-1074Email nobuhisa517@hotmail.comIntroduction: The abdominal desmoid tumor shows invasive development and high local recurrence rate. The primary treatment method is complete removal of the tumor because of the high recurrence rate; however, the problem for the surgeon is the reconstruction of the abdominal wall after resection of the abdominal desmoid tumor.Case Presentation: A 63-year-old man underwent open drainage and ileostomy for the perforation of ileocecal tumor. After 3 months, he underwent right hemicolectomy and ileostomy closure. Pathological examination revealed no malignancy, and the ileocecal tumor showed the presence of abscess. He noticed a palpable mass in the left abdomen. Enhanced abdominal computed tomography (CT) revealed a large abdominal incisional hernia and an enhanced mass of 40 mm in the left rectus muscle. Needle biopsy was performed and the diagnosis was desmoid tumor. He underwent resection of the desmoid tumor and repair of hernia. We performed wide local resection, with a 2-cm surgical margin. The hernia was repaired by simple closure, and the defect in the left abdomen was repaired with reconstruction using the fascia lata patch through plastic surgery.Conclusion: We encountered a case of abdominal wall desmoid tumor combined with a large abdominal incisional hernia. We selected the use of autologous fascia based on the risk of recurrence. The patient has not shown recurrence of incisional hernia or desmoid tumor 22 months after surgery. The use of fascia lata patch can be considered as a satisfactory alternative for such reconstruction cases.Keywords: abdominal desmoid tumor, incisional hernia, abdominal wall reconstruction, autologous fascia

Naoko Katsurada,1 Motoko Tachihara,1 Yukihisa Hatakeyama,1 Kiyoko Koyama,1 Masako Yumura,1 Tatsunori Kiriu,1 Ryota Dokuni,1 Daisuke Hazama,1 Shuntaro Tokunaga,1 Daisuke Tamura,1 Kyosuke Nakata,1 Masatsugu Yamamoto,1 Hiroshi Kamiryo,1 Kazuyuki Kobayashi,1 Yugo Tanaka,2 Yoshimasa Maniwa,2 Yoshihiro Nishimura1 1Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan; 2Division of General Theocratic Surgery, Kobe University Graduate School of Medicine, Kobe, JapanCorrespondence: Motoko TachiharaDivision of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, JapanTel +81-78-382-5660Fax +81-78-382-5661Email mt0318@med.kobe-u.ac.jpPurpose: Adjuvant chemotherapy with cisplatin (CDDP) plus vinorelbine is the standard regimen for the treatment of non-small cell lung cancer (NSCLC). However, CDDP elicits severe toxic effects, including emesis, neurotoxicity, and renal damage; carboplatin (CBDCA) may be a feasible alternative for CDDP-unfit patients. CBDCA plus paclitaxel (PTX) adjuvant chemotherapy showed a survival benefit for patients with stage IB tumors > 4 cm in size, while CBDCA plus nanoparticle albumin-bound (nab)-PTX showed greater efficacy and lower neurotoxicity than CBDCA plus PTX in advanced NSCLC. Here, we investigated the feasibility of using CBDCA plus nab-PTX as adjuvant chemotherapy for NSCLC.Patients and Methods: Patients with completely resected stage II or III NSCLC, with an Eastern Cooperative Oncology Group performance status of 0– 1 and adequate kidney function, received four cycles of postoperative adjuvant chemotherapy with CBDCA (AUC=5 mg/mL/min, on day 1) and nab-PTX (100 mg/m2, on days 1, 8, and 15) administered every 4 weeks within 8 weeks after surgery. The study was designed as a prospective, single-center, Phase II study. The primary endpoint was the completion rate of chemotherapy; secondary endpoints were two-year relapse-free survival (RFS) and safety. The expected completion rate was 80%, with a 50% lower limit.Results: Of 21 enrolled patients, 18 (85.7%) were CDDP-unfit owing to age (≥ 75 years old [n=11, 52.4%]) or mild renal impairment (n=7, 33.3%). Nineteen of the 21 enrolled patients were assigned to the intervention. The most common grade 3 or 4 adverse events were neutropenia (n=15, 78.9%) and anemia (n=3, 15.8%). The completion rate for the four cycles was 63.2% (95% CI, 38.4– 83.7). Two-year RFS was 56.8% (95% CI, 29.7– 76.9).Conclusion: The completion rate for CBDCA plus nab-PTX as adjuvant chemotherapy for CDDP-unfit NSCLC patients did not reach treatment feasibility. Further dose modifications may be required in future studies.Keywords: nab-paclitaxel, carboplatin, adjuvant chemotherapy, non-small cell cancer

The current understanding of light hypernuclei, which are sub-atomic nuclei with strangeness, is being challenged and studied in detail by several European research groups and collaborations. In recent years, studies of hypernuclei using high-energy heavy ion beams have reported unexpected results on the three-body hypernuclear state 3ΛH, named the hypertriton. For some time, reports of a shorter lifetime and larger binding energy than what was previously accepted have created a puzzling situation for its theoretical description; this is known as the "hypertriton puzzle". With the inclusion of the most recent experimental measurements, the current status of the hypertriton puzzle is evolving. Additionally, the possible neutral bound state of a Λ hyperon with two neutrons, nnΛ, has raised questions about our understanding of the formation of light hypernuclei either in bound or resonance states. These results have initiated several ongoing experimental programs all over the world to study these three-body hypernuclear states precisely. We are studying these light hypernuclear states by employing heavy ion beams at 2AGeV on a fixed carbon target with the WASA detector system and the Fragment Separator (FRS) at GSI. The WASA-FRS experimental campaign was performed during the first quarter of 2022, and this paper presents a short overview of the campaign and how it seeks to tackle the hypertriton and nnΛ puzzles. Data analysis is ongoing, and several preliminary results will be reported.

Yohei TanakaClinica Tanaka Plastic, Reconstructive Surgery and Anti-aging Center, Matsumoto, Nagano, JapanBackground: Despite the knowledge that the vast majority of skin aging is caused by the sun, and the widespread prevalence of sunscreen usage, solar skin damage continues to occur due to the combined biological impact of ultraviolet, visible light and near-infrared radiation. Sunscreens have only proven effective at filtering ultraviolet light. They do not attenuate visible light or near-infrared.Objective: To evaluate the effectiveness of a novel, solar-specific skincare approach embracing both comprehensive daily solar protection from ultraviolet through to near-infrared radiation and nightly solar repair.Participants: Eighteen Japanese patients were enrolled in this study. Topical skincare products (The Essential Six, RATIONALE, Victoria, Australia), comprising solar protection preparations to be used in the morning and topical solar repair at night, were applied to the patients’ skin for 12 months. Patients refrained from using any other skincare formulations and did not undergo any form of medical esthetic treatment during the study.Measurements: Digital facial skin and three-dimensional volumetric assessment were performed pre- and post-treatment, and patient assessments were recorded after 6 and 12 months post-treatment.Results: Improvements in skin texture and luminosity as recorded via digital photography, significant amelioration of skin redness and pigmentation in facial surface analysis, and volumetric reduction in three-dimensional volumetric assessment were observed compared to the pre-treatment for all patients. Eighty-nine percent, and 94% of patients self-reported their approval of treatment outcomes after 6 and 12 months post-treatment, respectively. Minor complications, characterized by slight pain and itching were observed in 3 patients. These minor complications resolved spontaneously.Conclusion: The results of this study indicate that the solar-specific skincare formulations focused on the daily comprehensive prevention of negative solar effects and nightly repair of photodamage provide a safe and highly effective pathway to skin preservation and rejuvenation.Keywords: long-term objective assessment, rejuvenation, solar protection, solar repair, sunscreen, volumetric measurement

Machiko Shimmura-Tomita, Hiroko Takano, Nozomi Kinoshita, Fumihiko Toyoda, Yoshiaki Tanaka, Rina Takagi, Mina Kobayashi, Akihiro Kakehashi Department of Ophthalmology, Saitama Medical Center, Jichi Medical University, Saitama, Japan Purpose: To determine risk factors and clinical signs for severe Acanthamoeba keratitis (AK) by comparing severe cases with mild cases with good prognosis.Patients and methods: We reviewed medical records of ten cases of AK (five males and five females) referred to our hospital and classified cases into two groups. One eye that required therapeutic keratoplasty and three eyes with a poor visual acuity (

Yoshiaki Tanaka,1 Fumihiko Toyoda,1 Machiko Shimmura-Tomita,1 Nozomi Kinoshita,1 Hiroko Takano,1 Yoh Dobashi,2 Shigeki Yamada,2 Hiroto Obata,3 Akihiro Kakehashi1 1Department of Ophthalmology, Saitama Medical Center, Jichi Medical University, Saitama, Japan; 2Department of Pathology, Saitama Medical Center, Jichi Medical University, Saitama, Japan; 3Department of Ophthalmology, Saitama Medical Center, Saitama Medical University, Kawagoe, Japan Purpose: The aim of this case series was to clarify the clinicopathological features of epiretinal membranes (ERMs) that developed in eyes after silicone oil (SO) tamponade to treat rhegmatogenous retinal detachments (RRDs). Patients and methods: In the Department of Ophthalmology, Saitama Medical Center, Jichi Medical University, patients with idiopathic ERMs (23 eyes) and ERMs in eyes filled with SO (SO ERMs) after vitreous surgery to treat RRDs (nine eyes) were enrolled from July 2012 to March 2014. ERM tissues obtained intraoperatively were examined histopathologically. Besides the main outcome measure of the pathological findings of the ERM tissues, other outcome measures included the preoperative findings on optical coherence tomography (OCT) images and the surgical findings. Results: Eight (89%) of nine eyes with SO ERMs had bilayered membranes composed of a firm layer on the retinal side with glial cells and extracellular matrix and a fragile sponge-like layer on the vitreous side. The sponge-like layer was composed of emulsified SO surrounded by macrophages. Quantitative analysis showed that the areas with cluster of differentiation 68 (CD68)-positive macrophages identified by immunohistochemistry in eyes with SO ERMs were significantly (P

Taku Naiki,1 Keitaro Iida,1 Toshiki Etani,1 Takashi Nagai,2 Yutaro Tanaka,1 Yosuke Sugiyama,3 Ryosuke Ando,1 Shuzo Hamamoto,1 Rika Banno,4 Daisuke Nagata,4 Noriyasu Kawai,1 Takahiro Yasui1 1Department of Nephro-Urology, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan; 2Department of Urology, Anjo Kosei Hospital, Anjo, Japan; 3Department of Pharmacy, Nagoya City University Hospital, Nagoya, Japan; 4Department of Urology, Konan Kosei Hospital, Konan, Japan Background: The objective of this study was to evaluate the efficacy of a combination of gemcitabine and docetaxel (GD) as a second-line treatment for elderly patients with metastatic urothelial carcinoma (mUC).Patients and methods: A total of 122 patients with mUC who were previously treated with platinum-based chemotherapy received second-line GD therapy from July 2010 to June 2016. This consisted of 800 mg/m2 gemcitabine and 40 mg/m2 docetaxel on days 1 and 8 in each 21-day cycle. Using pooled cumulative data, we divided patients into the following three groups based on age:

Yuya Watanabe,1–4,* Yosuke Yamada,2,4,* Keiichi Yokoyama,2,5,6,* Tsukasa Yoshida,2,4,7 Yasuko Yoshinaka,5,6 Mie Yoshimoto,8 Yoko Tanaka,9 Aya Itoi,10 Emi Yamagata,11 Naoyuki Ebine,1 Kazuko Ishikawa-Takata,12 Misaka Kimura2,3 1Faculty of Health and Sports Science, Doshisha University, Kyotanabe, Japan; 2Laboratory of Applied Health Sciences, Kyoto Prefectural University of Medicine, Kyoto, Japan; 3Department of Health and Sports Sciences, Kyoto Gakuen University, Kameoka, Japan; 4Section of Healthy Longevity Research, National Institute of Health and Nutrition, National Institutes of Biomedical Innovation, Health and Nutrition, Tokyo, Japan; 5Specified Non-profit Corporation Genki-up AGE Project, Kameoka, Japan; 6Department of Business Administration, Kyoto Gakuen University, Kyoto, Japan; 7Senior Citizen’s Welfare Section, Kameoka City Government, Kameoka, Japan; 8Corporation of Japan Dental Hygienists’ Association, Kyoto, Japan; 9Kyoto Dietetic Association, Kyoto, Japan; 10Department of Health, Sports and Nutrition, Faculty of Health and Welfare, Kobe Women’s University, Kobe, Japan; 11Faculty of Nursing, Doshisha Women’s College of Liberal Arts, Kyotanabe, Japan; 12Department of Nutrition and Metabolism, National Institute of Health and Nutrition, National Institutes of Biomedical Innovation, Health and Nutrition, Tokyo, Japan *These authors contributed equally to this work Objective: The number of long-term care (LTC) users and the associated expenditures in Japan are increasing dramatically. The national government recommends LTC prevention through activation of communities. However, there is no clear evidence of the effect of population-based comprehensive geriatric intervention program (CGIP) for restraints of LTC users and the associated expenditures in the future. The aims of the current paper are to describe the study protocol and progress of a cluster randomized controlled trial (RCT) with a CGIP in Kameoka City. Methods: The cluster RCT involved random allocation of regions as intervention (n=4,859) and nonintervention (n=7,195). Participants were elderly persons aged ≥65 years without LTC certification who had responded to a mailing survey. The residents living in intervention regions were invited to a physical check-up, and 1,463 people participated (30.3%). These individuals were invited to the CGIP, and 526 accepted. The CGIP comprised instructions on: 1) low-load resistance training using bodyweight, ankle weights, and elastic bands; 2) increasing daily physical activity; 3) oral motor exercise and care; and 4) a well-balanced diet based on a program from Ministry of Health, Labour and Welfare. We allocated the intervention regions randomly into home-based self-care program alone (HB group, 5 regions, n=275) and home-based program+weekly class-style session (CS group, 5 regions, n=251). We evaluated the effects of the CGIP at 12 weeks and at 12 or 15 months on physical function, and are conducting follow-up data collection for an indefinite period regarding LTC certification, medical costs, and mortality. Results and discussion: The study was launched with good response rates in each phase. Participants of both groups significantly increased their step counts by ~1,000 per day from the baseline during the CGIP. This RCT will provide valuable information and evidence about effectiveness of a community-based CGIP. Keywords: frailty, sarcopenia, long-term care, ActiveGuide, low-load resistance training, oral care, nutritional intervention, Shokuiku, physical function, physical activity monitor

Mitsuru Yashiro,1 Masaki Ohya,1 Toru Mima,1 Yumi Ueda,2 Yuri Nakashima,1 Kazuki Kawakami,1 Yohei Ishizawa,2 Shuto Yamamoto,1 Sou Kobayashi,1 Takurou Yano,1 Yusuke Tanaka,1 Kouji Okuda,1 Tomohiro Sonou,1 Tomohiro Shoshihara,1 Yuko Iwashita,1 Yu Iwashita,1 Kouichi Tatsuta,1 Ryo Matoba,2 Shigeo Negi,1 Takashi Shigematsu1 1Department of Nephrology, Wakayama Medical University, Wakayama, Japan; 2DNA Chip Research Inc., Minato, Japan Background: FGF23 plays an important role in calcium–phosphorus metabolism. Other roles of FGF23 have recently been reported, such as commitment to myocardium enlargement and immunological roles in the spleen. In this study, we aimed to identify the roles of FGF23 in the kidneys other than calcium–phosphorus metabolism. Methods: DNA microarrays and bioinformatics tools were used to analyze gene expression in mIMCD3 mouse renal tubule cells following treatment with FGF23, erythropoietin and/or an inhibitor of ERK. Results: Three protein-coding genes were upregulated and 12 were downregulated in response to FGF23. Following bioinformatics analysis of these genes, PPARγ and STAT3 were identified as candidate transcript factors for mediating their upregulation, and STAT1 as a candidate for mediating their downregulation. Because STAT1 and STAT3 also mediate erythropoietin signaling, we investigated whether FGF23 and erythropoietin might show interactive effects in these cells. Of the 15 genes regulated by FGF23, 11 were upregulated by erythropoietin; 10 of these were downregulated following cotreatment with FGF23. Inhibition of ERK, an intracellular mediator of FGF23, reversed the effects of FGF23. However, FGF23 did not influence STAT1 phosphorylation, suggesting that it impinges on erythropoietin signaling through other mechanisms. Conclusion: Our results suggest cross talk between erythropoietin and FGF23 signaling in the regulation of renal epithelial cells. Keywords: FGF23, STAT1, PPARγ, DNA microarray, bioinformatics analysis, nonprotein-coding gene

Koji Masuda, Yoshihiro Tanaka, Masayuki Kanehisa, Taiga Ninomiya, Ayako Inoue, Haruka Higuma, Chiwa Kawashima, Mari Nakanishi, Kana Okamoto, Jotaro Akiyoshi Department of Neuropsychiatry, Oita University Faculty of Medicine, Hasama-Machi, Oita, Japan Background: In Japan, the effects of reduced water, such as hydrogen-rich electrolyzed reduced water and natural reduced water, like Hita Tenryosui water®, have been examined. The purpose of the present study was to identify the role of natural reduced water in anxiety and blood biochemical analysis.Materials and methods: Natural reduced water and distilled water were administered to rats for 180 consecutive days, and their effect on anxiety-like behavior and depression was examined by using elevated plus maze, light/dark, forced swimming, and conditioned fear tests. Before and after administration of natural reduced or distilled water, we performed blood and urine analyses.Results: Natural reduced water exhibited anxiolytic-like effects in the conditioned fear and elevated plus maze tests. The mean levels of urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) in the natural reduced water were significantly lower than the distilled water group. Natural reduced water group also showed decrease in blood–urea nitrogen levels compared with the distilled water group.Conclusion: These results indicate that natural reduced water may decrease anxiety-related behaviors and prevent heightened oxidative stress. Keywords: urea nitrogen, depression, Hita Tenryosui, conditioned fear, elevated plus maze, 8-OHdG

Yoichi Tanaka,1,2 Yuki Nishi,1 Yuki Nishi,1 Michihiro Osumi,3 Shu Morioka1,3 1Department of Neurorehabilitation, Graduate School of Health Sciences, Kio University, 2Department of Rehabilitation, Nara Prefecture General Rehabilitation Center, 3Department of Neurorehabilitation Research Center, Kio University, Nara, Japan Abstract: Pain is a subjective emotional experience that is influenced by psychosociological factors such as social skills, which are defined as problem-solving abilities in social interactions. This study aimed to reveal the relationships among pain, social skills, and other psychosociological factors by using structural equation modeling. A total of 101 healthy volunteers (41 men and 60 women; mean age: 36.6±12.7 years) participated in this study. To evoke participants’ sense of inner pain, we showed them images of painful scenes on a PC screen and asked them to evaluate the pain intensity by using the visual analog scale (VAS). We examined the correlation between social skills and VAS, constructed a hypothetical model based on results from previous studies and the current correlational analysis results, and verified the model’s fit using structural equation modeling. We found significant positive correlations between VAS and total social skills values, as well as between VAS and the “start of relationships” subscales. Structural equation modeling revealed that the values for “start of relationships” had a direct effect on VAS values (path coefficient =0.32, p

Tadashi Yamashita,1 Maria Teresa Reyes Tuliao,2 Magdalena Concel Meana,2 Sherri Ann Suplido,3 Cecilia L Llave,4 Yuko Tanaka,5 Hiroya Matsuo6 1Kobe City College of Nursing, Kobe, Japan; 2Health Department of Muntinlupa, Muntinlupa, Philippines; 3Department of Obstetrics and Gynecology, Philippine General Hospital, Manila, Philippines; 4College of Medicine (CM), University of the Philippine (UP), Manila, Philippines; 5Department of School of Health Sciences, Faculty of Medicine, Tokushima University Graduate School, Tokushima, Japan; 6Department of International Health, Kobe University Graduate School of Health Sciences, Kobe, Japan Background: A low ratio of utilization of healthcare services in postpartum women may contribute to maternal deaths during the postpartum period. The maternal mortality ratio is high in the Philippines. The aim of this study was to examine the current utilization of healthcare services and the effects on the health of women in the Philippines who delivered at home. Methods: This was a cross-sectional analytical study, based on a self-administrated questionnaire, conducted from March 2015 to February 2016 in Muntinlupa, Philippines. Sixty-three postpartum women who delivered at home or at a facility were enrolled for this study. A questionnaire containing questions regarding characteristics, utilization of healthcare services, and abnormal symptoms during postpartum period was administered. To analyze the questionnaire data, the sample was divided into delivery at home and delivery at a facility. Chi-square test, Fisher’s exact test, and Mann–Whitney U test were used. Results: There were significant differences in the type of birth attendant, area of residence, monthly income, and maternal and child health book usage between women who delivered at home and those who delivered at a facility (P

Mizuho Nishio,1 Kazuaki Nakane,2 Yutaka Tanaka3 1Clinical PET Center, Institute of Biomedical Research and Innovation, Hyogo, Japan; 2Department of Molecular Pathology, Osaka University Graduate School of Medicine and Health Science, Osaka, Japan; 3Department of Radiology, Chibune General Hospital, Osaka, Japan Background: Homology is a mathematical concept that can be used to quantify degree of contact. Recently, image processing with the homology method has been proposed. In this study, we used the homology method and computed tomography images to quantify emphysema.Methods: This study included 112 patients who had undergone computed tomography and pulmonary function test. Low-attenuation lung regions were evaluated by the homology method, and homology-based emphysema quantification (b0, b1, nb0, nb1, and R) was performed. For comparison, the percentage of low-attenuation lung area (LAA%) was also obtained. Relationships between emphysema quantification and pulmonary function test results were evaluated by Pearson’s correlation coefficients. In addition to the correlation, the patients were divided into the following three groups based on guidelines of the Global initiative for chronic Obstructive Lung Disease: Group A, nonsmokers; Group B, smokers without COPD, mild COPD, and moderate COPD; Group C, severe COPD and very severe COPD. The homology-based emphysema quantification and LAA% were compared among these groups.Results: For forced expiratory volume in 1 second/forced vital capacity, the correlation coefficients were as follows: LAA%, -0.603; b0, -0.460; b1, -0.500; nb0, -0.449; nb1, -0.524; and R, -0.574. For forced expiratory volume in 1 second, the coefficients were as follows: LAA%, -0.461; b0, -0.173; b1, -0.314; nb0, -0.191; nb1, -0.329; and R, -0.409. Between Groups A and B, difference in nb0 was significant (P-value = 0.00858), and those in the other types of quantification were not significant.Conclusion: Feasibility of the homology-based emphysema quantification was validated. The homology-based emphysema quantification was useful for the assessment of emphysema severity. Keywords: homology, emphysema, COPD, low-attenuation lung region

Yohei Tanaka,1,2 Jun Nakayama2 1Department of Plastic Surgery, Clinica Tanaka Plastic, Reconstructive Surgery and Anti-aging Center, 2Department of Molecular Pathology, Shinshu University Graduate School of Medicine, Matsumoto, Nagano, Japan Background and objective: Humans are increasingly exposed to near-infrared (NIR) radiation from both natural (eg, solar) and artificial (eg, electrical appliances) sources. Although the biological effects of sun and ultraviolet (UV) exposure have been extensively investigated, the biological effect of NIR radiation is still unclear. We previously reported that NIR as well as UV induces photoaging and standard UV-blocking materials, such as sunglasses, do not sufficiently block NIR. The objective of this study was to investigate changes in gene expression in three-dimensional reconstructed corneal epithelial tissue culture exposed to broad-spectrum NIR irradiation to simulate solar NIR radiation that reaches human tissues.Materials and methods: DNA microarray and quantitative real-time polymerase chain reaction analysis were used to assess gene expression levels in a three-dimensional reconstructed corneal epithelial model composed of normal human corneal epithelial cells exposed to water-filtered broad-spectrum NIR irradiation with a contact cooling (20°C). The water-filter allowed 1,000–1,800 nm wavelengths and excluded 1,400–1,500 nm wavelengths.Results: A DNA microarray with >62,000 different probes showed 25 and 150 genes that were up- or downregulated by at least fourfold and twofold, respectively, after NIR irradiation. In particular, epidermal growth factor receptor (EGFR) was upregulated by 19.4-fold relative to control cells. Quantitative real-time polymerase chain reaction analysis revealed that two variants of EGFR in human corneal epithelial tissue were also significantly upregulated after five rounds of 10 J/cm2 irradiation (P

Ayumi Ota, Yoshiaki Tanaka, Fumihiko Toyoda, Machiko Shimmura, Nozomi Kinoshita, Hiroko Takano, Akihiro Kakehashi Department of Ophthalmology, Jichi Medical University, Saitama Medical Center, Omiya-ku, Saitama, Japan Purpose: To clarify the relationship between variations in posterior vitreous detachments (PVDs) and visual prognoses in idiopathic epiretinal membranes (ERMs).Methods: In this retrospective, observational, and consecutive case series, we observed variations in PVDs in 37 patients (mean age, 65.7±11.0 years) with ERMs and followed them for 2 years. Three PVD types were found biomicroscopically: no PVD, complete PVD with collapse (C-PVD with collapse), and partial PVD without shrinkage, with persistent vitreous attachment to the macula through the premacular hole of the posterior hyaloid membrane (P-PVD without shrinkage [M]). The best-corrected visual acuity (BCVA) was measured and converted to the logarithm of the minimum angle of resolution (logMAR) BCVA at the first visit and 2 years later.Results: No PVD was observed in 16 of the 37 eyes (mean age, 61.3±11.3 years), C-PVD with collapse in 11 of the 37 eyes (mean age, 69.1±9.9 years), and P-PVD without shrinkage (M) in 10 of the 37 eyes (mean age, 69.3±10.9 years). The logMAR BCVA at the first visit was the worst in the P-PVD without shrinkage (M) group (0.22±0.35) compared with the no-PVD group (−0.019±0.07; P

Jusen Tsuru,1 Yoshihiro Tanaka,1 Yoshinobu Ishitobi,1 Yoshihiro Maruyama,1 Ayako Inoue,1 Aimi Kawano,1 Rie Ikeda,1 Tomoko Ando,1 Harumi Oshita,2 Saeko Aizawa,1 Koji Masuda,1 Haruka Higuma,1 Masayuki Kanehisa,1 Taiga Ninomiya,1 Jotaro Akiyoshi1 1Department of Neuropsychiatry, 2Department of Applied Linguistics, Faculty of Medicine, Oita University, Oita, Japan Background: Decreased expression of brain-derived neurotrophic factor (BDNF) is implicated in enhanced stress responses. The BDNF Val66Met polymorphism is associated with psychological changes; for example, carriers of the Met allele exhibit increased harm avoidance as well as a higher prevalence of depression and anxiety disorder.Methods: To analyze the effects of BDNF Val66Met on stress responses, we tested 226 university students (88 women and 138 men) using a social stress procedure (Trier Social Stress Test [TSST]) and an electrical stimulation stress test. Stress indices were derived from repeated measurements of salivary α-amylase, salivary cortisol, heart rate, and psychological testing during the stress tests. All subjects were genotyped for the Val66Met polymorphism (G196A).Results: A significant three-way interaction (time [3 levels] × BDNF [Val/Val, Val/Met, Met/Met]; P

Yoshihiro Tanaka, Yoshihiro Maruyama, Yoshinobu Ishitobi, Aimi Kawano, Tomoko Ando, Rie Ikeda, Ayako Inoue, Junko Imanaga, Shizuko Okamoto, Masayuki Kanehisa, Taiga Ninomiya, Jusen Tsuru, Jotaro Akiyoshi Department of Neuropsychiatry, Faculty of Medicine, Oita University, Hasama-Machi, Oita, Japan Background: Bipolar disorder (BP) is often associated with a change in hypothalamus–pituitary–adrenal axis function change due to chronic stress. Salivary α-amylase (sAA) levels increase in response to psychosocial stress and thus function as a marker of sympathoadrenal medullary system activity. However, sAA has been studied less often than salivary cortisol in BP patients. Method: We measured Profile of Mood States and State-Trait Anxiety Inventory scores, heart rate variability, and salivary cortisol levels during electrical stimulation stress in 25 BP patients and 22 healthy volunteers. Results: Tension–anxiety, depression–dejection, anger–hostility, fatigue, and confusion scores in BP patients significantly increased compared with those of the healthy controls. In contrast, the vigor scores of BP patients significantly decreased compared with those of the healthy controls. Significant difference in the sAA levels was observed between BP patients and healthy controls. sAA of female patients was significantly higher than that of female healthy controls, and sAA in male patients tended to be higher than that of male healthy controls. No difference in salivary cortisol was observed between BP patients and the healthy controls. Only three time points were measured before and after the electrical stimulation stress. Furthermore, sAA secretion by BP patients increased before and after electrical stimulation. Conclusion: These preliminary results suggest that sAA may be a useful biological marker for BP patients. Keywords: HPA axis, bipolar disorder, α-amylase, cortisol, SAM activity

Yohei Tanaka,1–3 Yuichiro Tsunemi,2 Makoto Kawashima,2 Naoto Tatewaki,3 Hiroshi Nishida31Clinica Tanaka Plastic, Reconstructive Surgery and Anti-aging Center, Nagano, 2Department of Dermatology, Tokyo Women's Medical University, Tokyo, 3Department of Applied Life Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata, JapanBackground: Near-infrared has been shown to penetrate deeper than optical light sources independent of skin color, allowing safer treatment for the Asian skin type. Many studies have indicated the efficacy of various types of devices, but have not included a sufficiently objective evaluation. In this study, we used three-dimensional imaging for objective evaluation of facial skin tightening using a water-filtered near-infrared device.Methods: Twenty Japanese patients were treated with the water-filtered near-infrared (1,000–1,800 nm) device using a contact-cooling and nonfreezing gel stored in a freezer. Three-dimensional imaging was performed, and quantitative volume measurements were taken to evaluate the change in post-treatment volume. The patients then provided their subjective assessments.Results: Objective assessments of the treated cheek volume evaluated by a three-dimensional color schematic representation with quantitative volume measurements showed significant improvement 3 months after treatment. The mean volume reduction at the last post-treatment visit was 2.554 ± 0.999 mL. The post-treatment volume was significantly reduced compared with the pretreatment volume in all patients (P < 0.0001). Eighty-five percent of patients reported satisfaction with the improvement of skin laxity, and 80% of patients reported satisfaction with improvement of rhytids, such as the nasolabial folds. Side effects, such as epidermal burns and scar formation, were not observed throughout the study.Conclusion: The advantages of this water-filtered near-infrared treatment are its high efficacy for skin tightening, associated with a minimal level of discomfort and minimal side effects. Together, these characteristics facilitate our ability to administer repeated treatments and provide alternative or adjunctive treatment for patients, with improved results. This study provides a qualitative and quantitative volumetric assessment, establishing the ability of this technology to reduce volume through noninvasive skin tightening.Keywords: objective evaluation, quantitative volume measurement, skin laxity, three-dimensional imaging, rhytids

Yohei Tanaka1,2, Kiyoshi Matsuo1, Shunsuke Yuzuriha11Department of Plastic and Reconstructive Surgery, Shinshu University School of Medicine, Matsumoto, Japan; 2Clinica Tanaka Plastic and Reconstructive Surgery and Anti-aging Center, Matsumoto, JapanBackground: We reported previously that near-infrared (NIR) irradiation provides long-lasting stimulation of elastin, and is efficient for skin rejuvenation. Many studies have indicated the efficacy of various types of laser, but did not include sufficiently objective evaluation. Therefore, we evaluated the efficacy of NIR laser treatment not only subjectively but also objectively.Methods: Fifty Japanese patients were treated with a NIR 1064-nm neodymium: YAG laser. Objective computer assessments were performed by Canfield VISIA Complexion Analysis for improvement of dilated pores, skin texture, and wrinkles. The volunteers then provided subjective assessments. Histological evaluations of elastin were performed by Victoria blue staining up to 90 days post-treatment in four Japanese volunteers.Results: Mean pretreatment percentiles of dilated pores, skin texture, and wrinkles were 51.08 ± 24.82, 54.7 ± 26.33, and 58.02 ± 28.61, respectively. Mean post-treatment percentiles of dilated pores, skin texture, and wrinkles were 53.58 ± 23.89, 58.58 ± 24.44, and 62.2 ± 25.39, respectively. All objective computer assessments evaluated by percentiles in dilated pores, skin texture, and wrinkles showed significant improvement after NIR laser treatment. Ninety-six percent, 100%, and 98% of volunteers reported satisfaction with the improvement of dilated pores, skin texture, and wrinkles, respectively. NIR laser treatment appeared to increase the amount of elastin at day 30, which then decreased slightly but was still elevated at day 90 compared with nonirradiated controls on day 0. Thickening of the epidermis was detected on day 30, and epidermal smoothness persisted for up to 90 days. No treatment-related adverse events were observed.Conclusions: NIR irradiation increased elastin in the dermis, and achieved skin rejuvenation. The results indicated that NIR irradiation provides safe and effective long-term stimulation of elastin, which is beneficial for improving dilated pores, skin texture, and wrinkles.Keywords: near-infrared laser, elastin, skin rejuvenation, objective assessment