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Daiji Nagayama,1,2 Kentaro Fujishiro,3 Kenji Suzuki,3 Kohji Shirai4 1Department of Internal Medicine, Nagayama Clinic, Tochigi, Japan; 2Center of Diabetes, Endocrinology and Metabolism, Toho University, Sakura Medical Center, Chiba, Japan; 3Research and Development Division, Japan Health Promotion Foundation, Tokyo, Japan; 4Internal Medicine, Mihama Hospital, Chiba, JapanCorrespondence: Daiji Nagayama, Nagayama Clinic, 2-12-22, Tenjin-Cho, Oyama-City, Tochigi, 323-0032, Japan, Tel +81-285-22-0219, Fax +81-285-22-0219, Email deverlast96071@gmail.comAbstract: Cardio-ankle vascular index (CAVI) was developed to reflect the stiffness of the arterial tree from the aortic origin to the ankle. This arterial stiffness parameter is useful for assessing the severity of cardiovascular disease (CVD) and its risk. However, compared to pulse wave velocity (PWV), the conventional gold standard of arterial stiffness parameter, there has been a concern regarding CAVI that there are fewer longitudinal studies for CVD. Furthermore, the accuracy of CAVI for atherosclerotic diseases compared to other parameters has not been well validated. This review article aims to summarize recent findings to clarify the predictive ability of CAVI in longitudinal studies. First, several large longitudinal studies have found that not only baseline CAVI but also CAVI changes during the observation period predict cardiovascular events. Second, CAVI may have superior discriminatory power for all-cause mortality and major adverse cardiovascular endpoints compared to PWV. Furthermore, one large longitudinal study found CAVI to be a stronger predictor for renal function decline compared to PWV as well as CAVI0, a variant of CAVI that mathematically excludes BP dependence. Additionally, CAVI shows the properties that allow the elucidation of specific hemodynamics in aortic valve disease or hypovolemia. In conclusion, CAVI may be a modifiable arterial stiffness parameter not only for predicting and preventing atherosclerotic diseases but also for elucidating specific hemodynamic pathophysiology.Keywords: cardio-ankle vascular index, pulse wave velocity, CAVI0, longitudinal study, cardiovascular disease, renal function decline

Keisuke Suzuki, Shiho Suzuki, Tomohiko Shiina, Saro Kobayashi, Koichi Hirata Department of Neurology, Dokkyo Medical University, Mibu, JapanCorrespondence: Keisuke Suzuki, Department of Neurology, Dokkyo Medical University, 880 Kitakobayashi, Shimotsuga, Mibu, Tochigi, 321-0293, Japan, Tel +81-282-86-1111, Fax +81-282-86-5884, Email keisuke@dokkyomed.ac.jpAbstract: Central sensitization (CS) is an increase in the responsiveness of nociceptive neurons in the central nervous system to their normal afferent input. As a result, even minor irritation can induce severe pain, leading to the chronicity and severity of various diseases, such as neurological disorders. CS is associated with migraine, which is a major neurological disorder that inflicts a high disability in daily life. Specifically, CS is thought to be involved in the pathogenesis of cutaneous allodynia as well as chronification of migraine. In this article, we reviewed the association between CS and migraine, including pathophysiological aspects and evidence from clinical studies. We suggest that appropriate screening and management of CS in migraine could further improve the quality of life of migraine patients.Keywords: migraine, central sensitization, cutaneous allodynia, restless legs syndrome

Keita Suzuki,1 Hiromasa Tsujiguchi,1– 3 Akinori Hara,1– 3 Oanh Kim Pham,1 Sakae Miyagi,3,4 Thao Thi Thu Nguyen,5 Haruki Nakamura,1 Fumihiko Suzuki,2,6 Tomoko Kasahara,2 Yukari Shimizu,7 Yohei Yamada,2 Yasuhiro Kambayashi,8 Hirohito Tsuboi,9 Takehiro Sato,3,10 Takayuki Kannon,3,10 Kazuyoshi Hosomichi,3,10 Atsushi Tajima,3,10 Toshinari Takamura,11 Hiroyuki Nakamura1– 3 1Department of Hygiene and Public Health, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan; 2Department of Public Health, Graduate School of Advanced Preventive Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan; 3Kanazawa University Advanced Preventive Medical Sciences Research Center, Kanazawa, Ishikawa, Japan; 4Innovative Clinical Research Center, Kanazawa University, Kanazawa, Ishikawa, Japan; 5Department of Epidemiology, Faculty of Public Health, Haiphong University of Medicine and Pharmacy, Hai Phong, Vietnam; 6Community Medicine Support Dentistry, Ohu University Hospital, Koriyama, Fukushima, Japan; 7Department of Nursing, Faculty of Health Sciences, Komatsu University, Komatsu, Ishikawa, Japan; 8Department of Public Health, Faculty of Veterinary Medicine, Okayama University of Science, Imabari, Ehime, Japan; 9Institute of Medical, Pharmaceutical, and Health Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan; 10Department of Bioinformatics and Genomics, Graduate School of Advanced Preventive Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan; 11Department of Endocrinology and Metabolism, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa, JapanCorrespondence: Keita Suzuki, Department of Hygiene and Public Health, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, 13-1, Takara-machi, Kanazawa, Ishikawa, 920-8640, Japan, Tel +81 76 265 2218, Fax +81 76 234 4233, Email ksuzuk@staff.kanazawa-u.ac.jpBackground: Previous studies examined the association between chronic pain (CP) and serum 25-hydroxyvitamin D (25(OH)D) concentrations; however, the findings obtained were inconsistent. Single nucleotide polymorphisms (SNP) associated with the transcriptional activity of the vitamin D receptor (VDR) gene may influence the association of 25(OH)D levels with CP. We aimed to clarify the association between CP, serum 25(OH)D concentration, and SNPs.Methods: In the Shika study, we performed a cross-sectional analysis of 551 participants older than 40 years who were asked whether they had been having persistent pain lasting for at least 3 months in any part of the body on a self-administered questionnaire. Serum 25(OH)D concentrations were assessed as a biomarker of the vitamin D status using a radioimmunoassay. rs731236, rs7975232, rs1544410, rs2228570, and rs11568820 were identified using peripheral blood samples, and participants were assigned to those with or without the minor allele for each SNP.Results: The prevalence of CP was 37.2%. We observed a tendency for lower 25(OH)D levels in participants with CP than in those without CP in the hetero/minor group of rs11568820, which is a polymorphism within the CDX2-binding site in the 1e promoter region of the VDR gene. Furthermore, a logistic regression analysis revealed that lower serum 25(OH)D concentrations were significantly associated with CP in the hetero/minor group, but not in the major group.Conclusion: These results suggest that sufficient serum 25(OH)D concentration reduces the risk of CP in individuals with the minor allele of the CDX2 polymorphism.Keywords: chronic pain, 25-hydroxyvitamin D, vitamin D receptor gene, promoter, polymorphism, epidemiology

This study aimed to analyse whether initiating nintedanib treatment at a reduced dose could improve the treatment continuation rate while maintaining efficacy in patients with connective tissue disease (CTD)-associated interstitial lung disease. In total, 51 patients (age 61.6 ± 13.2 years; 38 women, 13 men) were retrospectively analysed. The primary endpoint was the cumulative discontinuation rate due to adverse events. Secondary endpoints included changes in drug dosage, efficacy evaluated based on annual changes in forced vital capacity (FVC), and safety assessed based on the frequency of adverse events. Eighteen patients who started treatment at the standard dose of 300 mg (standard dosage group) were compared with 33 patients who started treatment at a reduced dose (reduced dosage group). Systemic sclerosis was the most common CTD (n = 32), followed by idiopathic inflammatory myopathies and, rarely, rheumatoid arthritis. Both groups exhibited comparable cumulative discontinuation rates due to adverse events and similar frequencies of adverse events. No significant differences were observed in maintenance doses between the two groups; however, patients in the reduced dosage group had a lower cumulative dose for up to 52 weeks than those in the standard dosage group. No significant differences were observed in changes in FVC between the two groups. There was no evidence for a difference between the two groups in terms of discontinuation rates, efficacy, and safety. To provide further evidence, future studies using more precise dose-escalation protocols are warranted. [ABSTRACT FROM AUTHOR]

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.

Even though the risk of a negative encounter with a large and potentially dangerous shark species (e.g. white sharks—Carcharodon carcharias) is exceedingly rare, some localities implement indiscriminate shark culls to minimize this risk.Due to the negative ecological impact that these lethal shark control measures can have, the present study aimed to test a novel and eco‐friendly shark barrier system, known as the Shark Exclusion Barrier. The Shark Exclusion Barrier is a shark deterrent technology that is composed of a combination of interconnected and telescoping vertical barrier elements (i.e. the visual stimulus) and electromagnetic stimuli (e.g. electromagnets and Barium Ferrite (BaFe12O19) permanent magnets). Using this system, two separate C. carcharias swim pattern manipulation studies were conducted over the course of two research seasons.In the first season (i.e. 2021), 9, 1‐h trials were conducted where 9–13 different C. carcharias interacted with the barrier.In the second season (i.e. 2023), 35, 2‐h trials were conducted where 6–10 C. carcharias interacted with the barrier.Throughout experimentation, C. carcharias exhibited a significantly greater entrance frequency (p < 0.05) and a significantly reduced pass around frequency (p < 0.05) towards the control region when compared to the Shark Exclusion Barrier region.Furthermore, the barrier exhibited the ability to maintain its structural integrity during swells of ≥2.13 m, breaking waves of ≥1.52 m and a current of ≥1.12 m/s.Due to the promising results, this technology warrants further investigation to determine if it is a plausible alternative to lethal culling measures. [ABSTRACT FROM AUTHOR]

Keita Suzuki,1 Hiromasa Tsujiguchi,1– 3 Sakae Miyagi,3,4 Thao Thi Thu Nguyen,2 Akinori Hara,1– 3 Haruki Nakamura,2 Yukari Shimizu,5 Koichiro Hayashi,1 Yohei Yamada,1 Phat Minh Nguyen,2 Yuichi Tao,2 Takayuki Kannon,3,6 Atsushi Tajima,3,6 Hiroyuki Nakamura1– 3 1Department of Public Health, Graduate School of Advanced Preventive Medical Sciences, Kanazawa University, Kanazawa, Ishikawa 920-8640, Japan; 2Department of Environmental and Preventive Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Ishikawa 920-8640, Japan; 3Kanazawa University Advanced Preventive Medical Sciences Research Center, Kanazawa, Ishikawa 920-8640, Japan; 4Innovative Clinical Research Center, Kanazawa University, Kanazawa, Ishikawa 920-8640, Japan; 5Department of Nursing, Faculty of Health Sciences, Komatsu University, Komatsu, Ishikawa 923-0961, Japan; 6Department of Bioinformatics and Genomics, Graduate School of Advanced Preventive Medical Sciences, Kanazawa University, Kanazawa, Ishikawa 920-8640, JapanCorrespondence: Keita SuzukiDepartment of Public Health, Graduate School of Advanced Preventive Medical Sciences, Kanazawa University, 13-1, Takara-Machi, Kanazawa, Ishikawa 920-8640, JapanTel +81-76-265-2218Fax +81-76-234-4233Email keitasuzuk@stu.kanazawa-u.ac.jpPurpose: Although the explanation for inconsistencies in the reported association between serum 25-hydroxyvitamin D [25(OH)D] levels and chronic pain (CP) has not yet been determined, understanding this discrepancy is necessary for the development of vitamin D supplementation as an effective treatment for CP. The aim of this cross-sectional study was to examine the relationship between 25(OH)D concentrations and CP according to drinking habits in Japanese subjects.Patients and Methods: We distributed invitation letters to 2314 individuals older than 40 years in Shika town, a rural area in Japan, and 724 subjects (386 females; mean age: 63.9 ± 10.4 years) were recruited. CP was defined as persistent pain lasting at least 3 months in any part of the body. Serum concentrations of 25(OH)D, a biomarker of the vitamin D status, were measured using a radioimmunoassay. A serum 25(OH)D level < 20 ng/mL was defined as serum 25(OH)D deficiency. Drinking habits were assessed using a self-administered questionnaire. There were three choices, “rarely drink”, “sometimes” and “everyday”. Respondents who answered “rarely drink” were labelled as non-drinkers and the others as drinkers.Results: The prevalence of CP was 40.6%. A significant interaction between CP and drinking habits on 25(OH)D concentrations was observed (p = 0.098). A one-way analysis of covariance was performed to compare 25(OH)D concentrations between the subjects with and without CP in each drinking group, and the serum 25(OH)D levels of subjects with CP were significantly lower than those without CP among drinkers (p = 0.007). A logistic regression analysis revealed a correlation between serum 25(OH)D deficiency and CP in drinkers after adjustments for several confounding factors (odds ratio: 0.499; 95% confidence interval: 0.268 − 0.927; p = 0.028).Conclusion: The present results suggest that low serum 25(OH)D concentrations are associated with the development of CP in drinkers.Keywords: pain, vitamin D, alcohol, cross-sectional analysis, epidemiology

Kazuyoshi Kawakami,1 Takeru Wakatsuki,2 Azusa Soejima,1 Kazuo Kobayashi,1 Takashi Yokokawa,1 Takeshi Aoyama,1 Kenichi Suzuki,1 Mitsukuni Suenaga,2 Kensei Yamaguchi,2 Ayaka Inoue,3 Yoshiaki Machida,3 Toshihiro Hama1 1Department of Pharmacy, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-Ku, Tokyo 135-8550, Japan; 2Department of Gastroenterological Chemotherapy, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-Ku, Tokyo 135-8550, Japan; 3Section for Practical Education, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Shinagawa-Ku, Tokyo 142-8501, JapanCorrespondence: Kazuyoshi KawakamiThe Japanese Foundation for Cancer Research, Cancer Institute Hospital, Depatment of Pharmacy, 3-8-31 Ariake Koto-ku, Tokyo 135-8550, JapanEmail kazu.kawakami@jfcr.or.jpIntroduction: Regorafenib is an oral multikinase inhibitor for the treatment of metastatic colorectal cancer (mCRC). The clinical factors that may affect adherence to regorafenib remain unclear. The aim of this study was to evaluate adherence to regorafenib with mCRC and to identify factors that might affect adherence to regorafenib.Methods: A total of 108 consecutively enrolled Japanese patients with mCRC received regorafenib. Adherence was measured by pharmacists using pill counts and a self-reported treatment diary for patients at a pharmaceutical outpatient clinic. The median relative dose intensities of regorafenib and the factors adversely affecting adherence were retrospectively surveyed. Logistic regression analysis was then performed using patient socio-demographic factors and clinical factors.Results: A total of 96 patients were included in the analysis. The median adherence rate was 61.7% in the first cycle. The median relative dose intensity was 57.1%. The most common reason for non-adherence was a hand-foot-skin reaction (35.6%). On multivariate analysis, increased non-adherence to regorafenib was significantly associated with sex (female) [odds ratio (OR) = 4.36; 95% confidence interval (CI): 1.43–13.22, p = 0.01].Discussion: Hand-foot-skin reactions and female sex were associated with lower adherence to regorafenib. Since these factors could be associated with lower adherence to regorafenib, it would be useful to consider these factors when assessing adherence.Keywords: adherence, regorafenib, colorectal cancer, hand-foot-skin reactions