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Nobutaka Hattori,1 Yoshiko Okada,2 Yayoi Kawata,3 Yoshihiko Furusawa,3 Takumi Imai,4 Hisako Yoshida,4 Mihoko Ota,3 Masaki Arai,3 Ayumi Shintani,4 Jovelle Fernandez3 1Department of Neurology, Juntendo University, Tokyo, Japan; 2Japan Parkinson Congress, Tokyo, Japan; 3Japan Medical Office, Takeda Pharmaceutical Company Limited, Tokyo, Japan; 4Department of Medical Statistics, Graduate School of Medicine, Osaka Metropolitan University, Osaka, JapanCorrespondence: Yoshihiko Furusawa, Japan Medical Office, Takeda Pharmaceutical Company Limited, 2 Chome-1-1 Nihonbashihoncho, Chuo City, Tokyo, 103-0023, Japan, Tel +81-3-3278-2111, Fax +81-3-3278-2000, Email yoshihiko.furusawa@takeda.comObjective: The coronavirus disease 2019 (COVID-19) pandemic changed the lives of patients with Parkinson’s disease (PD) and their caregivers. This study aimed to investigate changes in patient behavior and PD symptoms and their effect on caregiver burden resulting from the COVID-19 pandemic in Japan.Methods: This nationwide, observational, cross-sectional survey included patients with self-reported PD and caregivers (members of the Japan Parkinson’s Disease Association). The primary objective was to evaluate changes in behaviors, self-assessed PD symptoms, and caregiver burden from pre–COVID-19 (February 2020) to post–national state of emergency (August 2020 and February 2021).Results: Responses from 1883 patients and 1382 caregivers from 7610 distributed surveys were analyzed. Mean (standard deviation) age of patients and caregivers was 71.6 (8.2) and 68.5 (11.4) years, respectively; 41.6% of patients had a Hoehn and Yahr (HY) scale of 3. Patients (> 40.0%) reported decreased frequency of going out. Most patients (> 70.0%) reported no change in treatment visit frequency, voluntary training, or rehabilitation and nursing care insurance services. Symptoms worsened for approximately 7– 30% of patients; the proportion with HY scale 4– 5 increased from pre–COVID-19 (25.2%) to February 2021 (40.1%). Aggravated symptoms included bradykinesia, walking, gait speed, depressed mood, fatigue, and apathy. Caregivers’ burden increased because of patients’ worsened symptoms and reduced time going out.Conclusion: Control measures during infectious disease epidemics should consider that patients’ symptoms may worsen; therefore, patient and caregiver support is needed to reduce burden of care.Keywords: Parkinson’s disease, COVID-19, questionnaire design, caregiver burden

Jun Ishigooka,1 Tatsuya Hoshino,2 Takumi Imai,3 Hisako Yoshida,3 Midori Ono,2 Mihoko Ota,2 Yoshiya Moriguchi,4 Keita Fujikawa,2 Ayumi Shintani,3 Jovelle L Fernandez2 1Institute of CNS Pharmacology, Tokyo, Japan; 2Japan Medical Office, Takeda Pharmaceutical Company Limited, Tokyo, Japan; 3Department of Medical Statistics, Osaka City University Graduate School of Medicine, Osaka, Japan; 4Medical Affairs, Lundbeck Japan K.K., Tokyo, JapanCorrespondence: Tatsuya HoshinoJapan Medical Office, Takeda Pharmaceutical Company Limited, 1-1, Nihonbashi-Honcho 2-chome, Chuo-ku, Tokyo, 103-8668, JapanTel +81 3 3278 2111Fax +81 3 3278 2925Email tatsuya.hoshino@takeda.comPurpose: A previous international study suggested that perceptions of depression symptoms, social function, and treatment expectations are different between patients/physicians. We aimed to examine whether such differences exist in Japan.Methods: A web-based survey was conducted with patients who reported that they had been diagnosed with depression, and physicians who reported that they had treated patients with depression, in Japan. Questionnaires were designed to quantify patients’ perceptions of symptoms, social function, and treatment expectations. Patients were categorized into three stages of disorder based on their reported current symptoms: severe symptomatic, mild symptomatic, and remission. Physicians were assigned up to three patients, were provided with patient information from the questionnaire completed by those patients, and finally the completed questionnaire forms for each patient. Agreement between the perceptions of the patients and physicians was examined for each stage.Results: Of the 2618 eligible patients, 828 were assigned to 326 eligible physicians. Overall, we found small differences in the perceptions of depression treatment between patients/physicians. Slightly fewer physicians than patients reported physical symptoms (85% vs 91%; p=0.018) in the mild symptomatic stage. Fewer physicians than patients reported cognitive symptoms in the severe (82% vs 87%; p=0.029) and mild (54% vs 66%; p=0.003) symptomatic stages. Social function was deemed to be lower by physicians than by patients, across all stages of disorder (p< 0.001). Regarding treatment expectations, more physicians than patients reported “return to a normal life” in the mild symptomatic (51% vs 35%, p< 0.001) and remission stages (57% vs 36%, p< 0.001), and more patients than physicians reported “reduction of side effects” in the severe (10% vs 4%, p=0.004) and mild (12% vs 5%, p< 0.001) symptomatic disorder stages.Conclusion: These results suggest small differences in patient/physician perceptions of depression treatment in Japan. Discrepancies between patients’/physicians’ perceptions may vary depending on the medical environment.Keywords: depression, perception, patient, physician, web-based survey

Aya Kimura,1 Hiroyuki Yamasaki,1 Haruka Ishii,2 Hisako Yoshida,2 Motoko Shimizu,3 Takashi Mori1 1Department of Anesthesiology, Osaka City University Graduate School of Medicine, Osaka City, Osaka, Japan; 2Department of Medical Statistics, Osaka City University Graduate School of Medicine, Osaka City, Osaka, Japan; 3Department of Anesthesiology, Sumitomo Hospital, Osaka City, Osaka, JapanCorrespondence: Aya KimuraDepartment of Anesthesiology, Osaka City University Graduate School of Medicine, 1-5-7 Asahimachi, Abeno-ku, Osaka City, Osaka, 545-8586, JapanTel +81-6-6645-2186Fax +81-6-6645-2489Email aya1226kimura@gmail.comPurpose: Serotonin (5-HT) is highly associated with pain modulation. The human 5-HT transporter (5-HTT) gene (SLC6A4) features several polymorphisms in its promoter region (5-HTTLPR) that affect the 5-HTT expression. The S allele of 5-HTTLPR induces low 5-HT tone, and it may influence the modulation of chronic pain. Meanwhile, pain occurs in 40– 50% of patients after thoracic surgery, and its mechanism remains under investigation. This study assessed the role of 5-HTTLPR polymorphisms in postthoracotomy pain severity.Patients and Methods: A total of 178 patients undergoing pneumonectomy were enrolled. The genotypes of 5-HTTLPR were divided into two groups: S/S group and S/L or L/L group. Linear mixed-effects models were used to assess the association between 5-HTTLPR genotypes and the numerical rating scale (NRS) score change over time.Results: Among the participants, data were obtained for 162 patients. The genotype distribution was as follows: S/S, 67.3%; S/L or L/L, 32.7%. No significant difference in patient characteristics was found between the genotype groups. There was no significant interaction between the 5-HTTLPR genotypes and the NRS score change over time (p = 0.842).Conclusion: Polymorphisms in 5-HTTLPR were not associated with postthoracotomy pain severity.Keywords: 5-HTTLPR, pain modulation, numerical rating scale

Tatsuya Yoshida,1 Takuya Miura,1 Tomoh Matsumiya,2 Hidemi Yoshida,2 Hajime Morohashi,1 Yoshiyuki Sakamoto,1 Akira Kurose,3 Tadaatsu Imaizumi,2 Kenichi Hakamada1 1Department of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562, Japan; 2Department of Vascular Biology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562, Japan; 3Department of Anatomic Pathology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562, JapanCorrespondence: Kenichi HakamadaDepartment of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, JapanTel +81 172 39 5079Fax +81 172 39 5080Email hakamada@hirosaki-u.ac.jpPurpose: Colorectal cancer (CRC) often recurs after curative resection. Identification of major risk factors for CRC recurrence is important for effective prevention and treatment. In this study, we examined the potential relationship between CRC and TLR3 as this remains unclear.Patients and Methods: Correlations between TLR3 immunostaining and clinicopathological factors and prognosis were examined in 50 samples that were randomly extracted from 264 patients with CRC from January 2010 to December 2011. Chemokines induced by TLR3 agonist stimulation were also examined using TLR3-positive human CRC cell lines. Furthermore, the association between TLR3 and chemokine expression was assessed by analyzing the immunohistochemistry of surgical specimens.Results: Of the 50 patients, 14 (28%) were TLR3-negative. In the comparison of clinicopathological factors between the TLR3-negative and -positive groups, there were more lymph node metastasis-positive cases in the TLR3-negative group, and this difference was significant. Furthermore, there was no difference in overall survival rates between the two groups, but the 5-year recurrence-free survival (RFS) was significantly lower in the TLR3-negative group (46.2%) than in the TLR3-positive group (78.1%). Analysis of 5-year RFS using factors thought to be related to recurrence identified a high tumor budding and a TLR3-negative status as independent risk factors for recurrence. TLR3 activation of CRC cell lines induced expression of C-C motif chemokine ligand 2 (CCL2), C-C motif chemokine ligand 5 (CCL5), and interleukin-8. The expressions of CCL2, CCL5, and IL-8 were observed in the TLR3-positive tumor cells of surgical specimens.Conclusion: Non-expression of TLR3 in CRC cells was associated with lymph node metastasis and was an independent risk factor for recurrence. These results suggest that TLR3 may not only be used as a prognostic factor and a risk factor for recurrence, but further studies on the involvement of TLR3 with tumor growth may provide new therapeutic strategies.Keywords: colorectal cancer, toll-like receptor 3, recurrence, CCL2, CCL5, IL-8

Objective To comprehensively evaluate diagnostic algorithms for myocardial infarction using a high-sensitivity cardiac troponin I (hs-cTnI) assay. Patients and methods We prospectively enrolled patients with suspected myocardial infarction without ST-segment elevation from nine emergency departments in Japan. The diagnostic algorithms evaluated: (i) based on hs-cTnI alone, such as the European Society of Cardiology (ESC) 0/1-h or 0/2-h and High-STEACS pathways; or (ii) used medical history and physical findings, such as the ADAPT, EDACS, HEART, and GRACE pathways. We evaluated the negative predictive value (NPV), sensitivity as safety measures, and proportion of patients classified as low or high-risk as an efficiency measure for a primary outcome of type 1 myocardial infarction or cardiac death within 30 days. Results We included 437 patients, and the hs-cTnI was collected at 0 and 1 hours in 407 patients and at 0 and 2 hours in 394. The primary outcome occurred in 8.1% (33/407) and 6.9% (27/394) of patients, respectively. All the algorithms classified low-risk patients without missing those with the primary outcome, except for the GRACE pathway. The hs-cTnI-based algorithms classified more patients as low-risk: the ESC 0/1-h 45.7%; the ESC 0/2-h 50.5%; the High-STEACS pathway 68.5%, than those using history and physical findings (15–30%). The High-STEACS pathway ruled out more patients (20.5%) by hs-cTnI measurement at 0 hours than the ESC 0/1-h and 0/2-h algorithms (7.4%). Conclusions The hs-cTnI algorithms, especially the High-STEACS pathway, had excellent safety performance for the early diagnosis of myocardial infarction and offered the greatest improvement in efficiency. [ABSTRACT FROM AUTHOR]

Mariko Oe,1 Seigo Sakai,1 Hideto Yoshida,1 Nao Okado,1 Haruna Kaneda,1 Yasunobu Masuda,1 Osamu Urushibata2 1R&D Division, Kewpie Corporation, Sengawa-cho, Chofu-shi, 2Department of Dermatology, Toho University Ohashi Medical Center, Ohashi, Meguro-ku, Tokyo, Japan Background: Hyaluronan (HA) has critical moisturizing property and high water retention capacity especially for human skin. This study aimed to evaluate the effect of oral intake of HA. Methods: The mean molecular weight (MW) of HA is 2 k and 300 k. Sixty Japanese male and female subjects aged 22–59 years who presented with crow’s feet wrinkles were randomly assigned to the HA 2 k or HA 300 k at 120 mg/day or the placebo group. The subjects were administered HA at a rate of 120 mg/day or a placebo for 12 weeks. The skin wrinkles were evaluated by image analysis of skin wrinkle replicas, and their skin condition was evaluated using a questionnaire survey. Results: During the study period, the HA groups showed better level of the whole sulcus ­volume ratio, wrinkle area ratio, and wrinkle volume ratio than the placebo group. After 8 weeks of ingestion, the HA 300 k group showed significantly diminished wrinkles compared with the placebo group. Skin luster and suppleness significantly improved after 12 weeks in all groups compared with the baseline. Conclusion: The results suggest that oral HA (both HA 2 k and HA 300 k) inhibits skin wrinkles and improves skin condition. Keywords: hyaluronic acid, dietary supplement, skin, wrinkle volume, molecular weight

Hiroyuki Yoshida, Akira Yabuno, Keiichi FujiwaraDepartment of Gynecologic Oncology, Saitama Medical University International Medical Center, Hidaka, Saitama, JapanAbstract: Bevacizumab is the first molecular-targeted agent to be used for the treatment of ovarian cancer. Bevacizumab is a humanized monoclonal antibody targeting vascular endothelial growth factor. Two randomized Phase III trials evaluated the combination of bevacizumab plus standard cytotoxic chemotherapy for first-line treatment of advanced ovarian cancer. Additional Phase III trials evaluated bevacizumab combined with cytotoxic chemotherapy in platinum-sensitive and platinum-resistant recurrent ovarian cancer. All these trials reported a statistically significant improvement in progression-free survival but not in overall survival. Furthermore, bevacizumab effectively improved the quality of life with regard to abdominal symptoms in recurrent ovarian cancer patients. Bevacizumab is associated with adverse events not commonly observed with cytotoxic agents used to treat gynecological cancers, such as hypertension, bleeding, thromboembolism, proteinuria, delayed wound healing, and gastrointestinal events. However, most of these events can be adequately managed by gynecologists. The clinical trial results with bevacizumab have supported its recent approval in Europe and the United States as a treatment for ovarian cancer. This review presents the latest evidence for bevacizumab therapy of ovarian cancer and describes selection of patients for personalized treatment.Keywords: anti-angiogenesis, chemotherapy, biomarkers

We report a numerical study of the diffusiophoresis of short polymers using non-equilibrium molecular dynamics simulations. More precisely, we consider polymer chains in a fluid containing a solute that has a concentration gradient and examine the variation of the induced diffusiophoretic velocity of the polymer chains as the interaction between the monomer and the solute is varied. We find that there is a non-monotonic relation between the diffusiophoretic mobility and the strength of the monomer–solute interaction. In addition, we find a weak dependence of the mobility on the length of the polymer chain, which shows clear difference from the diffusiophoresis of a solid particle. Interestingly, the hydrodynamic flow through the polymer is much less screened than for pressure driven flows. [ABSTRACT FROM AUTHOR]

Masato Matsuoka,1 Hideyuki Yoshida,1 Yuichi Kinoshita,2 Tetsuya Nishimura11Department of Ophthalmology, 2Department of Histopathology, Kansai Medical University, Takii Hospital, Osaka, JapanPurpose: Intraocular lymphomas are rare, and they have poor prognosis. Thus, early diagnosis and treatment are needed. A definitive diagnosis of a lymphoma is based on cytological analysis of the intraocular fluids or tissues. We report two cases of intraocular lymphoma diagnosed by the analyses of vitreous and infusion fluid.Patients: Case 1 was a 66-year-old woman who complained of eye floaters and was found to have diffuse vitreous opacification bilaterally. She received corticosteroid therapy, however the vitreous opacification was not resolved, and her visual acuity (VA) remained reduced. She underwent pars plana vitrectomy (PPV), and vitreous and infusion fluid were collected to determine the cause of the reduced VA. The undiluted vitreous obtained from core PPV was submitted for cytokine analysis, and infusion fluid was obtained from the machine cassette after full PPV and used for cytological analysis. Case 2 was a 62-year-old man referred with low vision and was found to have diffuse vitreous opacification in the right eye and dot hemorrhages in both eyes. Four years earlier, he had been diagnosed with diffuse large B-cell lymphoma of the paranasal sinuses and was in remission after chemotherapy. Because metastasis of the lymphoma was suspected, he underwent PPV, and intraocular samples were collected as in Case 1.Results: Atypical lymphoid cells were detected from the infusion fluid in both cases. The ratio of interleukin (IL)-10 to IL-6 was greater than 1.0 in both cases. These results allowed us to make a diagnosis of intraocular lymphoma: primary intraocular lymphoma in Case 1 and metastatic intraocular lymphoma in Case 2.Conclusion: Vitreous and infusion fluid collected during PPV can be used for diagnosing an intraocular lymphoma.Keywords: intraocular lymphoma, cytological analysis, vitreous, pars plana vitrectomy, infusion fluid