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Atsushi Kimura,1 Kohei Yamaguchi,2 Haruka Tohara,2 Yusuke Sato,3 Naoko Sawada,3 Yasuhide Nakagawa,3 Yukako Matsuda,4,5 Motoharu Inoue,5 Yuji Wada,6 Kazuhiro Tamaki3,4 1College of Risk Management, Nihon University, Tokyo, Japan; 2Department of Dysphagia Rehabilitation, Tokyo Medical and Dental University, Tokyo, Japan; 3Geriatric Health Services Facility Nanohana, Medical Corporation Kanjinkai, Tokyo, Japan; 4Nanohana Dentistry Clinic, Medical Corporation Kanjinkai, Tokyo, Japan; 5Department of Dysphagia Rehabilitation, Nihon University of Dentistry, Tokyo, Japan; 6College of Gastronomy Management, Ritsumeikan University, Shiga, JapanCorrespondence: Atsushi Kimura, College of Risk Management, Nihon University, Setagaya-ku, Tokyo, 1548513, Japan, Tel +81 3 6453 1600, Fax +81 3 6453 1630, Email kimura.atsushi@nihon-u.ac.jp Kazuhiro Tamaki, Geriatric Health Services Facility Nanohana, Medical Corporation Kanjinkai, Nishitama-Gun, Tokyo, 1901212, Japan, Tel +81 42 568 5111, Fax +81 42 568 5127, Email tamakikazuhiro@g.kanjinkai.netPurpose: Past research has shown that exposure to the image of a slim person reduces food consumption among young adults. However, it remains unknown whether this paradigm could be adapted and applied to increase food intake among older adults with dementia by exposing them to the image of a higher-weight person to mitigate weight loss and malnutrition. The present study explored whether weight-related visual cues affect the amount of food consumed by older adults with dementia.Participants and Methods: In the experiment, twenty-one elderly people with dementia living in a nursing home were visually exposed to one of four conditions (a cartoon image of a normal-weight chef, a higher-weight chef, a flower or no image) during real-life daily lunch situations over the course of four weeks, during which each condition was presented for one week.Results: Results demonstrate that participants finished their meals more frequently when they were exposed to the image of the higher-weight chef than when they were not exposed to any images.Conclusion: These results suggest that exposure to a cartoon chef character representing a stereotyped social group related to body weight activates the stereotype and increases stereotype-consistent behavior in older adults with dementia. The present findings will contribute to understanding the effect of visual information on eating behavior and to designing eating environments which facilitate sufficient nutrition intake among older adults with dementia.Keywords: nudge, body weight, dementia, food consumption, dining environment

Background: A useful biomarker for the efficacy of immune checkpoint inhibitors (ICIs) in advanced renal cell carcinoma (RCC) has not yet been established. This study aims to investigate whether inflammatory markers are associated with the efficacy of nivolumab plus ipilimumab therapy before and during treatment., Methods: Data from patients with advanced clear cell RCC who received a combination treatment of nivolumab plus ipilimumab were retrospectively analyzed. The neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and C-reactive protein (CRP) levels were assessed at baseline and 3, 6, and 9 weeks after treatment initiation. The correlation between these inflammatory markers and the patient's prognosis was investigated., Results: Eighty-four patients were identified. The multivariate analysis identified NLR at week 3, CRP at week 6, and NLR and CRP at week 9 as the consistent predictor associated with poor overall survival (OS) at each time point. The survival analysis and receiver operating characteristic (ROC) curve analysis revealed that an NLR of ≥ 2.4 at week 3, CRP of ≥ 1.4 mg/dL at week 6, and NLR of ≥ 4.8 and CRP of ≥ 1.0 mg/dL at week 9 were associated with worse OS (hazard ratios (HR) = 5.70, P = 0.008, HR = 3.23, P = 0.004, HR = 7.38, P < 0.001 and HR = 3.55, P = 0.002)., Conclusions: Both NLR and CRP were considered useful biomarkers for understanding the prognosis during nivolumab plus ipilimumab therapy. Furthermore, an NLR of ≥ 4.8 and CRP of ≥ 1.0 mg/dL at week 9 are helpful in reconsidering treatment continuation., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Background: Liquid modification is a widely established strategy of treatment for patients with dysphagia. The modification of liquid particularly by thickening or carbonation is a common approach to promote safe swallowing., Objective: This study sought to investigate how carbonated and/or thickened water modulates swallowing behaviours during swallowing in healthy young individuals., Methods: Thirty-one healthy volunteers (9 men, 22 women; mean age ± standard deviation [SD], 25.7 ± 6.2 years) were instructed to swallow 20 mL of water, carbonated water and carbonated juice with and without added thickening agent. Electromyograms (EMGs) of the suprahyoid (S-hyo) muscles were recorded to evaluate swallowing behaviours. Obtained S-hyo EMG bursts was analysed using the following outcome parameters: onset latency, the time between swallowing que to onset of EMG burst; rising time and falling time, defined as the time between onset and peak, and between peak and offset, respectively; duration, defined as the time between onset and offset of EMG burst; and area integral value under the waveform., Results: Effects of thickening demonstrated the extended onset latency, EMG burst duration including falling time and the larger area of EMG in thickened liquid compared to thin liquid, but there was not much difference between thin and thickened carbonated liquids. Carbonation significantly decreased the duration including falling time for thickened but not for thin liquids., Conclusion: Patients with dysphagia can benefit from use of carbonated or thickened water while the effects on swallowing physiology may differ between carbonation and thickening., (© 2024 John Wiley & Sons Ltd.)

To ascertain the involvement of insulin receptors (IRs) in colorectal carcinogenesis, we investigated the association of height, body mass index (BMI), and physical activity with colorectal cancer (CRC) and two subtypes of CRC according to the expression level of IR. We utilized data from a large-scale, population-based prospective cohort study of 18,158 middle-aged and elderly subjects in Akita and Okinawa, Japan. In the statistical analysis, we used the Cox proportional hazards model and estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of CRC and its subtypes as defined by immunohistochemistry of IRβ, a transmembrane subunit of IR. In the IRβ-defined subtypes, height showed no apparent association with the risk of IRβ-positive CRC. In contrast, a multivariable HR of IRβ-positive CRC was 1.77 (95% CI = 1.04-3.03) with a BMI of ≥30.0 kg/m 2 (i.e., obesity), compared to a BMI of <25.0 kg/m 2 . Further, an increase in physical activity was significantly associated with decreased risk of IRβ-positive CRC (multivariable HR per 5 METs-hour/day = 0.93, 95% CI = 0.88-0.99). Meanwhile, we found no significant association between any exposure and IRβ-negative CRC. Likewise, heterogeneity between the two subtypes of CRC was not statistically significant. These findings imply that obesity and physical activity exert promoting and suppressing effects on the development of CRC expressing IRs, respectively., (© 2024 UICC.)

This 5-year longitudinal study investigated the relationship between depressive symptoms and fracture risk in a large Japanese cohort. Depressive symptoms were a significant risk factor for hip fractures in women., Purpose: A relationship between depressive symptoms and fractures has not been clearly demonstrated. We aimed to investigate the relationship between depressive symptoms and 5-year fracture risk in the Japan Public Health Center-based Prospective Study for the Next Generation., Methods: From 2011 to 2016, 114,092 participants were enrolled, and a follow-up survey was conducted 5 years later. We analyzed 30,552 men and 38,063 women aged 40-74 years who had no past fractures at baseline. Presence of depressive symptoms was defined as a modified 11-item Center for Epidemiological Studies Depression Scale score of 8 or higher, a history of depression, or use of antidepressants. Subjects were asked to report vertebral, upper limb, and/or hip fractures, except for traffic or work accidents, that occurred during the follow-up period. The adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for fracture were analyzed via logistic regression analysis to evaluate the relationship between depressive symptoms and fracture., Results: Women with depressive symptoms demonstrated a high AOR for hip fractures (AOR: 2.78, 95% CI: 1.30 - 5.92); this result was consistent in post menopause women. In men, this association was not found for any age group or any type of fracture., Conclusions: Depressive symptoms in women may increase the risk of hip fractures. Further studies are required to explore this relationship in more detail., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Purpose: To evaluate the usefulness of robotic subxiphoid-optical thymectomy (RST)., Methods: Thirty-seven procedures (thymoma, n = 19; thymic carcinoma, n = 1; myasthenia gravis, n = 3; and others, n = 14) performed between October 2020 and December 2023 were included. The right and left 6th intercostal midclavicular lines and subxiphoid, with an assistant port placed in the right third intercostal anterior axillary line, were adapted. Postoperative pain was assessed using a numerical rating scale (NRS)., Results: A good view of the surgical field is obtained. The median console time was 113 min and the time to roll-in was 30 min. The body mass index (BMI) was 21.6. One patient with thymic carcinoma required combined resection of the left phrenic nerve and left brachiocephalic vein without conversion to thoracotomy, and 1 patient had post-pericardiotomy syndrome with bilateral pleural effusion. There was a correlation between the prolonged time to roll-in and BMI (ρ = 0.439; p = 0.007). Pain was controlled with oral medication on postoperative day 1 and significantly decreased at discharge and at the first outpatient visit without epidural anesthesia (median NRS scores: 4, 1, and 1, respectively)., Conclusion: RST is a safe procedure that provides surgeons with a sufficient view of the anterior mediastinum and causes minimal postoperative pain., (© 2024. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Previous studies have investigated the association between reproductive factors and lung cancer risk; however, findings have been inconsistent. In order to assess this association among Asian women, a total of 308,949 female participants from 11 prospective cohorts and four Asian countries (Japan, Korea, China, and Singapore) were included. Cox proportional hazards regression models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CIs). A total of 3,119 primary lung cancer cases and 2247 lung cancer deaths were identified with a mean follow-up of 16.4 years. Parous women had a lower risk of lung cancer incidence and mortality as compared with nulliparous women, with HRs of 0.82 (95% CI = 0.70-0.96) and 0.78 (95% CI = 0.65-0.94). The protective association of parity and lung cancer incidence was greater among ever-smokers (HR = 0.66, 95% CI = 0.49-0.87) than in never-smokers (HR = 0.90, 95% CI = 0.74-1.09) (P-interaction = 0.029). Compared with age at first delivery ≤20 years, older age at first delivery (21-25, ≥26 years) was associated with a lower risk of lung cancer incidence and mortality. Women who ever used hormone replacements had a higher likelihood of developing non-small cell lung cancer (HR = 1.31, 95% CI = 1.02-1.68), compared to those who never used hormone replacements. Future studies are needed to assess the underlying mechanisms, the relationships within these female reproductive factors, and the potential changes in smoking habits over time., (© 2024 UICC.)

Background: In recent years, platform switching implant treatment has been increasing, which is believed to minimize bone loss around the implant after placement. However, there have been no reports on the relationship between keratinized mucosa width (KMW) and bone loss and soft tissue recession in platform switching implants., Objective: We evaluated the effect of the KMW on the amount of bone loss and soft tissue recession around a platform switching implant retrospectively using multivariate analysis., Materials and Methods: This one-year retrospective study included 91 implants in 48 patients. Age, sex, a history of periodontitis, implant location, oral hygiene status, and the KMW were included as explanatory variables to evaluate bone loss (BL) and buccal gingival height (GH). Generalized estimating equations (GEEs) were used to evaluate the effect of the KMW on platform switching peri-implant tissues., Results: The mean bone loss on the mesial (ΔBLm), distal (ΔBLd), and buccal (ΔBLb) sides of the implant were 0.16 ± 0.27 mm, 0.19 ± 0.34 mm, and 0.24 ± 0.50 mm, respectively, at 1 year after superstructure placement. The mean amount of change of GH (ΔGH) on the buccal side was 0.30 ± 0.47 mm. After correcting for confounders using GEEs, the results suggested that KMW <1.5 mm was a significant factor (P < 0.001) for bone loss over time in ΔBLm, ΔBLd, and ΔBLb. In addition, for soft tissues on the buccal side, KMW <1.5 mm was a significant factor for ΔGH reduction over time (P < 0.001)., Conclusions: Keratinized mucosa width ≥1.5 mm was associated with a higher probability less hard and soft tissue recession around the platform switching implant after 1 year from superstructure placement., (© 2024 The Authors. Clinical Implant Dentistry and Related Research published by Wiley Periodicals LLC.)

Purpose of Review: To highlight the recent progression in surgical treatments for central retinal vein occlusion (CRVO) and central retinal artery occlusion (CRAO)., Recent Findings: Anti-VEGF treatment, accepted as a primary treatment for CRVO, is unable to effectively treat all types of the diseases. Regarding CRAO, there are not any accepted therapies available. There have however been recent innovations in surgery, such as utilizing robotics-assisted tools in cannulation procedures for central retinal artery occlusion, or micro-cystotomy for refractory macular edema resulting from ischemic CRVO., Summary: Refractory macular edema due to CRVO can be treated with aspiration of the fluid found inside the large cysts often seen in edema. The success rate of micro-cystotomy has been reported at 78% in eyes with refractory macular edema. Recent studies have shown that cannulation with tissue plasminogen activator (tPA) is effective for eyes with CRAO due to thrombus.Recent cannulation or micro-cystotomy procedures can be enhanced with the use of robotic tools which allow us to perform this difficult procedure more easily. Newly developed technology, and consequent developments in surgical procedures, will allow us to deal with unmet needs for retinal vessel occlusive diseases., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To investigate the incidence of intraocular inflammation (IOI) and its risk factors following intravitreal injections of brolucizumab for neovascular age-related macular degeneration in Japan., Methods: A total of 1,351 Japanese consecutive patients with neovascular age-related macular degeneration who were treated with brolucizumab from May 2020 to May 2022 at 14 institutions were examined. The variables analyzed were the number of brolucizumab injections, time to onset of IOI, and risk factors., Results: Intraocular inflammation developed in 152 eyes (11.3%). Retinal vasculitis and/or retinal occlusion occurred in 53 eyes (3.9%). Ninety-four patients received bilaterally, bilateral IOI occurred in five patients (5.3%). Sixteen eyes (1.2%) had irreversible visual acuity loss and nine eyes (0.67%) had visual loss of three lines or more due to retinal vasculitis and/or retinal occlusion. The cumulative IOI incidence was 4.5%, 10.3%, and 12.2% at 30, 180, and 365 days (1-year), respectively. History of IOI (including retinal vasculitis) and/or retinal occlusion (odds ratio [OR], 5.41; P = 0.0075) and female sex (OR, 1.99; P = 0.0004) were significantly associated with IOI onset., Conclusion: The 1-year cumulative incidence of IOI in Japanese neovascular age-related macular degeneration patients treated with brolucizumab was 12.2%. History of IOI (including retinal vasculitis) and/or retinal occlusion and female sex were significant risk factors.

Aim: This study investigated the ways in which nurses caring for COVID-19 patients during the pandemic's early stages recognized professional growth through their experiences and continued working for several years, as well as the key experiences for identifying professional growth, external factors, and career intentions., Methods: We used a qualitative research method called the Trajectory Equifinality Model (TEM). The participants were nine nurses caring for COVID-19 patients during the pandemic's early stages and had already recognized professional growth through a series of experiences. We constructed a TEM diagram based on two interviews per participant (in February-March, and July-August 2022)., Results: The process by which the participants recognized professional growth through a series of experiences was divided into Phases 1-4. The participants experienced adversity in Phases 1 and 3, and the following professional growth in Phases 2 and 4: gaining confidence as a nurse performing tasks of great social significance by acquiring the ability to fulfill my roles and realizing I could use the skills I had acquired by providing nursing care to COVID-19 patients in other situations, respectively. The key experiences for identifying professional growth as well as the inhibiting and facilitating factors of the process differed depending on the phase. The participants' career intention was wanting to continue to be involved in nursing by utilizing the skills and experience I have accumulated., Conclusion: Managers and directors of nursing should provide appropriate support in each phase to help nurses recognize their professional growth during emerging epidemics., (© 2023 Japan Academy of Nursing Science.)

Miharu Inoue,1 Jiro Takeuchi,2 Mio Sakuma,2 Tsukasa Nakamura,3 Takeshi Morimoto2 1Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital, Nagoya, Japan; 2Department of Clinical Epidemiology, Hyogo Medical University, Nishinomiya, Japan; 3Department of Infectious Diseases, Shimane Prefectural Central Hospital, Izumo, JapanCorrespondence: Takeshi Morimoto, Department of Clinical Epidemiology, Hyogo Medical University, 1-1 Mukogawa, Nishinomiya, Hyogo, 663-8501, Japan, Tel +81-798-45-6879, Fax +81-798-45-6920, Email morimoto@kuhp.kyoto-u.ac.jpPurpose: Low total protein (TP) is associated with mortality among patients with specific diseases, but its association was uncertain among general patients. We evaluated the effects of low TP on in-hospital mortality among general inpatients.Patients and Methods: We used data from the Japan Adverse Drug Events study series. We enrolled adult inpatients (≥ 16 years) admitted to a tertiary care hospital between September 1 and November 30, 2013. We excluded patients with multiple myeloma, pregnant women, and bone marrow graft donors. Patient data were extracted from electronic medical records. All patients were stratified into those with and without malignancy and divided into the low and normal TP groups. Low TP was defined as < 6.5 g/dL. We compared the in-hospital mortality of the low and normal TP groups stratified by the presence of malignancy.Results: Among the 2235 enrolled patients (mean age, 67.8 years), the TP value was lower in 516 patients with malignancy than in 1719 patients without malignancy (6.6 g/dL vs 6.8 g/dL, P = 0.0002). Among patients without or with malignancy, 27% (462/1719) and 35% (183/516) were in the low TP group, respectively. Mortality was higher in the low TP group among patients without malignancy (23.2% vs 10.2%, P < 0.0001). Likewise, among patients with malignancy, mortality was higher in the low TP group (34.7% vs 11.3%, P = 0.0029). The adjusted hazard ratio of the low TP group was 1.75 (95% confidence interval, 1.04– 2.96) in patients without malignancy and 2.45 (95% confidence interval, 1.12– 5.37) in patients with malignancy, but the interaction was not significant (P = 0.23).Conclusion: Low TP values were associated with higher in-hospital mortality among general inpatients, and this association was observed among patients with and those without malignancy. Routinely measured TP should be utilized to risk stratification on admission.Keywords: admission, general patients, historical cohort study, mortality, total protein

Background: Colorectal Cancer (CRC) has been molecularly classified into several subtypes according to tumor, stromal, and immune components. Here, we investigated whether the preventive effect of vitamin D on CRC varies with subtypes defined by Vitamin D receptor (VDR) expression in tumors and their surrounding stroma, along with the association of somatic mutations in CRC., Methods: In a population-based prospective study of 22,743 Japanese participants, VDR expression levels in tumors and their surrounding stroma were defined in 507 cases of newly diagnosed CRC using immunohistochemistry. Hazard ratios of CRC and its subtypes according to dietary vitamin D intake were estimated using multivariable Cox proportional hazards models., Results: Dietary vitamin D intake was not associated with CRC or its subtypes defined by VDR expression in tumors. However, an inverse association was observed for CRC with high VDR expression in the stroma (the highest tertile vs the lowest tertile: 0.46 [0.23-0.94], P trend  = 0.03), but not for CRC with low VDR expression in the stroma (P heterogeneity  = 0.02). Furthermore, CRC with high VDR expression in the stroma had more somatic TP53 and BRAF mutations and fewer APC mutations than those with low VDR expression in the stroma., Conclusions: This study provides the first evidence that the preventive effect of vitamin D on CRC depends on VDR expression in the stroma rather than in the tumors. CRC with high VDR expression in the stroma is likely to develop through a part of the serrated polyp pathway, which tends to occur with BRAF but not with APC mutations., (© 2024. Japanese Society of Gastroenterology.)

Background: We previously showed that total tumor resection enhances metastatic growth in a syngeneic metastatic mouse model of neuroblastoma. In this study, we further investigated which surgical factors contributed most to metastatic growth., Methods: Tumor cells derived from MYCN transgenic mice were subcutaneously injected into wild-type mice. Mice were randomly assigned to receive partial resection (PR group), subcutaneous implantation of a sponge (Sp group), or observation (Obs group). The lymph node metastasis volume and the frequency of lung metastasis were compared 14 days after assignment by measuring C-reactive protein (CRP) and interleukin-6 (IL-6) levels., Results: The lymph node metastasis volume in the Sp group was larger than in the Obs group (148.4 [standard deviation {SD}: 209.5] vs. 10.2 [SD 12.8] mm 3 ). The frequency of lung metastasis was greater in the Sp group than in the PR group (11.9 [SD 12.2] vs. 6.6 [SD 4.0] counts/slide). The CRP level in the Sp group was higher than in the PR group (2.3 [SD 0.5] vs. 1.5 [SD 0.4] μg/mL), and the IL-6 level in the Sp group was higher than in the PR or Obs groups (28.4 [SD 34.5] vs. 12.4 [SD 19.0] vs. 5.4 [SD 8.1] pg/mL)., Conclusion: Metastatic growth may be enhanced by systemic inflammation., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Inflation is the leading theory of the first instant of the universe. Inflation, which postulates that the universe underwent a period of rapid expansion an instant after its birth, provides convincing explanation for cosmological observations. Recent advancements in detector technology have opened opportunities to explore primordial gravitational waves generated by the inflation through “B-mode” (divergent-free) polarization pattern embedded in the cosmic microwave background anisotropies. If detected, these signals would provide strong evidence for inflation, point to the correct model for inflation, and open a window to physics at ultra-high energies. LiteBIRD is a satellite mission with a goal of detecting degree-and-larger-angular-scale B-mode polarization. LiteBIRD will observe at the second Lagrange point with a 400 mm diameter telescope and 2622 detectors. It will survey the entire sky with 15 frequency bands from 40 to 400 GHz to measure and subtract foregrounds. The US LiteBIRD team is proposing to deliver sub-Kelvin instruments that include detectors and readout electronics. A lenslet-coupled sinuous antenna array will cover low-frequency bands (40–235 GHz) with four frequency arrangements of trichroic pixels. An orthomode-transducer-coupled corrugated horn array will cover high-frequency bands (280–402 GHz) with three types of single frequency detectors. The detectors will be made with transition edge sensor (TES) bolometers cooled to a 100 milli-Kelvin base temperature by an adiabatic demagnetization refrigerator. The TES bolometers will be read out using digital frequency multiplexing with Superconducting QUantum Interference Device (SQUID) amplifiers. Up to 78 bolometers will be multiplexed with a single SQUID amplifier. We report on the sub-Kelvin instrument design and ongoing developments for the LiteBIRD mission.

The high-frequency telescope for LiteBIRD is designed with refractive and reflective optics. In order to improve sensitivity, this paper suggests the new optical configurations of the HFT which have approximately 7 times larger focal planes than that of the original design. The sensitivities of both the designs are compared, and the requirement of anti-reflection (AR) coating on the lens for the refractive option is derived. We also present the simulation result of a sub-wavelength AR structure on both surfaces of silicon, which shows a band-averaged reflection of 1.1–3.2% at 101–448 GHz.

Mastication is controlled by central pattern generator in the brainstem and can be modulated by volition. The aim of this study was to investigate the effect of chewing well on swallowing. Twenty-six healthy participants were instructed to eat 8, 12, and/or 16 g of steamed rice with barium sulphate under the following two conditions: chewing freely task (CF; chewing naturally in their usual manner) and chewing well task (CW; chewing the food with a request to "chew well"). We evaluated bolus transport and swallowing movement using videofluoroscopy and electromyography of the masseter, suprahyoid and thyrohyoid muscles. The chewing time and pharyngeal transit time (PTT) at the first swallow showed high reproducibility in both CF and CW. PTT for CW was significantly shorter and longer than CF in 12 and 16 g, respectively. In 12 g, CW increased the pharyngeal bolus velocity and decreased thyrohyoid EMG activity during swallowing compared with CF. In 16 g, the difference between CW and CF in the estimated swallowed bolus volume was positively correlated with that in upper esophageal sphincter transit duration. We speculate that CW modulates PTT during swallowing depending on the mouthful volume., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: To evaluate the association between trypsin-like protease (TLP) activity in the oral cavity as an indicator of periodontal health status and kidney function in Japanese workers., Materials and Methods: This cross-sectional study included 1117 Japanese workers (mean age = 43.8 years). Tongue-swab TLP activity was quantified as a* value (the redness intensity of the matrix disc of the TLP activity assessment kit; a larger value indicates more intense enzymatic activity in the samples and poorer periodontal health status). Kidney function was assessed using the estimated glomerular filtration rate (eGFR; a lower value indicates poorer kidney function). We performed ordinal logistic regression analyses to assess the association of the a* value with three eGFR categories: ≥90, 60-89 and <60 mL/min/1.73 m 2 ., Results: The prevalence for each eGFR category was as follows: ≥90 (31.6%), 60-89 (63.8%) and <60 mL/min/1.73 m 2 (4.6%). After adjusting for potential confounders, the a* value was found to be significantly associated with reduced kidney function. The multivariable-adjusted odds ratio (95% confidence interval) for reduced kidney function was 1.12 (1.02-1.22) per unit increase in the a* value., Conclusions: Higher TLP activity was associated with reduced kidney function in Japanese workers., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Lingual pressure (LP) generation is cooperatively controlled not only by the intrinsic tongue (I-ton) muscles but also by hyoid muscle activation. However, the measurement of endurance and fatigue properties of I-ton muscles is difficult due to the instability of electrodes., Objective: The purpose of this study was to apply suction electrodes to measure electromyograms (EMGs) of I-ton muscle and to evaluate integrated EMG amplitude (iEMG) and mean power frequency (MPF) of EMG in the I-ton and hyoid muscles performing continuous LP., Methods: Twenty healthy adult volunteers (10 males, 10 females, mean age 28.8 years) were instructed to perform 10-s LP generation tasks at 25%, 50%, 75% and 100% of maximum LP in randomised order with visual feedback. During each task, EMGs of the I-ton, suprahyoid (S-hyo), infrahyoid (I-hyo) and masseter (Mass) muscles were simultaneously recorded. The iEMG and MPF of EMG burst during 10-s LP tasks were compared. The recording period was divided into three substages to analyse temporal changes with the Friedman test., Results: During the 10-s task, the iEMG significantly increased as the LP strength increased (p < .001). There was no time-dependent change in the I-ton iEMG; however, the MPF of the I-ton EMG burst decreased in all tasks (p < .05). The S-hyo and I-hyo iEMGs gradually increased, especially with strong LP (p < .01)., Conclusion: While I-ton muscles may easily fatigue during 10-s LP generation, S-hyo and I-hyo muscles may help compensate for the weakened I-ton muscle activity by increasing their activity to maintain LP., (© 2023 John Wiley & Sons Ltd.)

Fibroblast growth factor 21 (FGF21) is expressed in several organs, including the liver, adipose tissue, and cardiovascular system, and plays an important role in cross-talk with other organs by binding to specific FGF receptors and their co-receptors. FGF21 represents a potential target for the treatment of obesity, type 2 diabetes mellitus, and non-alcoholic steatohepatitis (NASH). The production of FGF21 in skeletal muscle was recently suggested to be beneficial for metabolic health through its autocrine and paracrine effects. However, the regulatory mechanisms of FGF21 in skeletal muscle remain unclear. In the present study, we showed that berberine regulated FGF21 production in C2C12 myotubes in a dose-dependent manner. We also examined the effects of A-674563, a selective Akt1 inhibitor, on the berberine-mediated regulation of FGF21 expression in C2C12 myotubes. Berberine significantly increased the secretion of FGF21 in C2C12 myotubes, while A-674563 attenuated this effect. Moreover, a pre-treatment with A-674563 effectively suppressed berberine-induced increases in Bmal1 expression in C2C12 myotubes, indicating that the up-regulation of Bmal1 after the berberine treatment was dependent on Akt1. Additionally, berberine-induced increases in FGF21 secretion were significantly attenuated in C2C12 cells transfected with Bmal1 siRNA, indicating the contribution of the core clock transcription factor BMAL1 to Akt-regulated FGF21 in response to berberine. Collectively, these results indicate that berberine regulates the expression of FGF21 through the Akt1 pathway in C2C12 myotubes. Moreover, the core clock gene Bmal1 may participate in the control of the myokine FGF21. Berberine stimulated Akt1-dependent FGF21 expression in C2C12 myotubes. The up-regulation of FGF21 through the modulation of PI3K/AKT1/BMAL1 in response to berberine may be involved in the regulation of cellular function (such as Glut1 expression) by acting in an autocrine and/or paracrine manner in skeletal muscle., (© 2023. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.)

Glyoxalase I (GLO I), a major enzyme involved in the detoxification of the anaerobic glycolytic byproduct methylglyoxal, is highly expressed in various tumors, and is regarded as a promising target for cancer therapy. We recently reported that piceatannol potently inhibits human GLO I and induces the death of GLO I-dependent cancer cells. Pyruvate kinase M2 (PKM2) is also a potential therapeutic target for cancer treatment, so we evaluated the combined anticancer efficacy of piceatannol plus low-dose shikonin, a potent and specific plant-derived PKM2 inhibitor, in two GLO I-dependent cancer cell lines, HL-60 human myeloid leukemia cells and NCI-H522 human non-small-cell lung cancer cells. Combined treatment with piceatannol and low-dose shikonin for 48 h synergistically reduced cell viability, enhanced apoptosis rate, and increased extracellular methylglyoxal accumulation compared to single-agent treatment, but did not alter PKM1, PKM2, or GLO I protein expression. Taken together, these results indicate that concomitant use of low-dose shikonin potentiates piceatannol-induced apoptosis of GLO I-dependent cancer cells by augmenting methylglyoxal accumulation., (© 2023 The Authors. Genes to Cells published by Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.)

Background: In recent years, an increasing number of epidemiological studies have suggested a role of polyphenols in the prevention of chronic diseases. Prospective cohort studies have typically measured polyphenol concentrations in a single blood sample and the reproducibility of plasma polyphenol measurements is largely unknown., Objective: We evaluated the reproducibility of 35 plasma polyphenols collected at an interval of 1-year. We also examined correlations of these polyphenols with food group intakes calculated from weighed food records (WFR) and food frequency questionnaire (FFQ)., Methods: The study included 227 middle-aged participants from the JPHC-NEXT Protocol Area in Japan. We measured 35 polyphenols in plasma collected at two points 1-year apart. Food group intakes were calculated from 12-day WFR and FFQ. For the reproducibility analysis, the intraclass correlation coefficient (ICC) of 35 polyphenol concentrations were examined between the two points. Pearson's partial correlations was used to assess the correlation between polyphenols and food groups., Results: Moderate- to high ICCs were observed for tea-originated polyphenols such as gallic acid, quercetin, epigallocatechin, and kaempferol - and coffee-derived polyphenols, such as caffeic acid, and ferulic acid. For the dietary analyses, moderate correlations were observed for non-alcoholic beverages intake and epigallocatechin, epicatechin, catechin, and gallic acid. For green tea, higher correlations were observed with these polyphenols., Conclusion: Plasma concentrations of tea and coffee-related polyphenols, except for catechin, had good reproducibility over a 1-year period. The correlations between intake of non-alcoholic beverages, particularly green tea, and tea polyphenols, indicated moderate- to high correlations., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Mutsuko Kato, Michie Namba, Sachika Shimoyama, Mayumi Inoue, Chihiro Ouchi, Takehiro Shimizu Department of Ophthalmology, Japan Red Cross Okayama Hospital, Okayama, JapanCorrespondence: Mutsuko KatoDepartment of Ophthalmology, Japan Red Cross Okayama Hospital, 2-1-1 Aoe, Kita-ward, Okayama, 700-8607, JapanTel +81 86 222 8811Fax +81 86 222 8841Email mutsukato@okayama-med.jrc.or.jpPurpose: To report our modified simple technique for optic capture and the clinical results of intrascleral IOL fixation preserving the lens capsule, without vitrectomy, in cases of cataract with insufficient zonular support to stabilize the intraocular lens (IOL).Patients and Methods: In 37 eyes of 25 patients with phacodonesis and two or more risk factors for progressive zonular insufficiency, we inserted a CTR to support the capsule and zonules during cataract surgery and IOL fixation; an optic was inserted into the lens capsule, and a haptic was fixed in the scleral tunnel without vitrectomy. In all cases, anterior or total vitrectomy was not needed.Results: The postoperative mean (± standard deviation) tilt and decentration of the implanted IOL did not change from 6 to 12 months (6.77 ± 3.15° to 6.33 ± 3.38° and 0.60 ± 0.30 to 0.61 ± 0.35 mm, respectively). We encountered no late IOL dislocation and no retinal complications, including retinal breaks or cystoid macular oedema, postoperatively (follow-up = 21.1 ± 5.2 months).Conclusion: Our modified techniques preclude the need for vitrectomy. If the lens capsule can be preserved using a CTR, our modified technique can be used to stabilize IOL.Keywords: insufficient zonular support, phacodonesis, lens capsule, capsular tension ring, intrascleral IOL fixation

Background: The population of people living with dementia (PLwD) continues to grow in Japan where advance care planning (ACP) for PLwD is relatively new. Our aim was to evaluate the feasibility and cultural acceptability of a dementia-specific ACP communication skills toolkit for Japanese primary care clinicians., Methods: We delivered 13 training sessions in primary care clinics across central Japan and conducted a post-training survey to assess whether the toolkit increased confidence in dementia-specific ACP communication skills and the acceptability of the toolkit with the following four statements: (1) The language in the sessions was clear, (2) The sessions took an appropriate amount of time to complete, (3) The design of the sessions was an effective educational method, and (4) The sessions were culturally appropriate for communication with Japanese patients with dementia and their family members. We asked participants to respond using a 5-point Likert scale from strongly agree to strongly disagree., Results: All participants were Japanese and included 80 physicians (mean age 39.8 years), 33 nurses (mean age 45.7 years), and 58 other participants (mean age 42.9 years), who were 30.0%, 87.9%, and 55.2% female, respectively. Most participants practiced in rural settings. In pre- post-comparisons, participant confidence increased in determining capacity, understanding dementia prognosis, goals of care, eliciting surrogates, recommending self-care practices to families, and leading family meetings (all p < 0.001). Most participants strongly agreed or agreed that the toolkit was an effective method (96.9%), took an appropriate amount of time (94.5%), contained clear language (89.8%), and was culturally appropriate (73.6%)., Conclusions: Dementia-specific ACP communication skills toolkit can be delivered in Japan. Japanese primary care clinicians generally felt the dementia-specific ACP toolkit increased their confidence in ACP communication skills and was acceptable. The language, time, and design were well received, though further work is needed to improve the cultural appropriateness of the toolkit., (© 2024 The Author(s). Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society.)

This study aimed to compare fat accumulation in young and aged mice raised on a high-fat diet and to characterize the obesity-reducing effects of a Kampo medicine, bofutsushosan (BTS; fangfengtongshengsan in Chinese). Aged mice fed a high-fat diet containing 2% BTS extract for 28 days exhibited a significant reduction in weight gain and accumulation of visceral and subcutaneous fat, which were greater degree of reduction than those of the young mice. When the treatment period was extended to two months, the serum aspartate aminotransferase and alanine aminotransferase levels and the accumulation of fat droplets in the hepatocytes decreased. The mRNA expression of mitochondrial uncoupling protein 1 (UCP1) in the brown adipose tissue was significantly reduced in the aged mice compared to the young mice but increased by 2% in the BTS-treated aged mice. Additionally, the effect of BTS extract on oleic acid-albumin-induced triglyceride accumulation in hepatoblastoma-derived HepG2 cells was significantly inhibited in a concentration-dependent manner. Evaluation of the single crude drug extracts revealed that Forsythia Fruit, Schizonepeta Spike, and Rhubarb were the active components in BTS extract. These results suggest that BTS extract is effective against visceral, subcutaneous, and ectopic fats in the liver, which tend to accumulate with aging. Thus, BTS extract is useful in preventing and ameliorating the development of obesity and metabolic syndrome., (© 2024. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.)

Sleep-related breathing disorder (SRBD) causes hypertension, and obesity has been highly associated with SRBD, which has become a serious health problem in young and middle-aged Japanese males. However, the relation between SRBD and hypertension considering the effects of obesity remains unknown. In this cross-sectional study, we examined the relationship between SRBD and hypertension, with consideration for the effects of obesity, in Japanese occupational population. Using 3% oxygen desaturation index (3%ODI) obtained by simplified polysomnography (PSG), participants were classified into low (0 ≤ 3%ODI < 5), medium (5 ≤ 3%ODI < 15), and high (15 ≤ 3%ODI) 3%ODI groups. We excluded employees who had not undergone medical examination with simplified PSG in the same year from 2012 to 2018. Logistic regression analysis was performed to calculate odds ratios for having hypertension according to 3%ODI levels. In total, 2532 employees were included. Among them, 25% and 4% were categorized into the medium and high 3%ODI groups, respectively. The odds ratio for hypertension increased significantly with higher 3%ODI levels after adjustment for age, sex, alcohol drinking status and smoking status (p for trend < 0.0001). However, further adjustment for obesity status (body mass index ≥ 25 kg/m 2 ) attenuated the associations. When we performed the stratified analysis by obesity status, the odds ratio for hypertension increased significantly with higher 3%ODI only for non-obese individuals, with significant interaction (p for interaction = 0.014). Higher 3%ODI was significantly associated with higher prevalence of hypertension especially in non-obese participants, suggesting the importance of vigilance for the presence of SRBD even in non-obese individuals. We investigated the association between SRBD and hypertension considering the effects of obesity, which would suggest the need to keep in mind the presence of SRBD even in non-obese individuals., (© 2024. The Author(s).)

Purpose: To determine the methylation level of the miR-124 promoter in non-neoplastic rectal mucosa of patients with pediatric-onset ulcerative colitis (UC) to predict UC-associated colorectal cancer (UC-CRC)., Methods: Between 2005 and 2017, non-neoplastic rectal tissue specimens were collected from 86 patients with UC, including 13 patients with UC-CRC; cancer tissues were obtained from the latter group. The methylation status of the miR-124 promoter was quantified using bisulfite pyrosequencing and compared between pediatric- and adult-onset UC patients., Results: Patients with pediatric-onset UC experienced a significantly shorter disease duration than those with adult-onset UC. The levels of miR-124 promoter methylation in non-neoplastic rectal mucosa were positively correlated with the age at the diagnosis and duration of UC. The rate of increase in miR-124 methylation was accelerated in patients with pediatric-onset UC compared to those with adult-onset UC. Furthermore, the miR-124 methylation levels in non-neoplastic rectal mucosa were significantly higher in patients with UC-CRC than in those with UC alone (P = 0.02). A receiver operating characteristic analysis revealed that miR-124 methylation in non-neoplastic tissue discriminated between patients with pediatric-onset UC with or without CRC., Conclusion: miR-124 methylation in non-neoplastic rectal mucosa may be a useful biomarker for identifying patients with pediatric-onset UC who face the highest risk of developing UC-CRC., (© 2023. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)