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Shiro Ono, Kiyomi Yoshimoto, Masaki Matsubara, Nobushiro Nishimura, Hiromasa Kawashima, Ryo Yoneima, Noritaka Yada, Kenji Nishio Department of General Medicine, Nara Medical University, Kashihara, Nara, JapanCorrespondence: Shiro Ono, Department of General Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8522, Japan, Tel +81-744-29-8905, Fax +81-744-24-5739, Email shiroono0207@naramed-u.ac.jpPurpose: This study aims to investigate the characteristics of Epstein–Barr virus associated-hemophagocytic lymphohistiocytosis (EBV-HLH) and HLH caused by a severe form of infectious mononucleosis (IM-HLH) compared to IM by EBV, and thus also to assist in early diagnosis and providing appropriate treatment.Methods: Data for this analysis were collected from patients at the Department of General Medicine, Nara Medical University, between April 1, 2012, and August 1, 2020. EBV infection was diagnosed using clinical presentation and laboratory tests. HLH diagnosis followed the HLH-2004 protocol, supplemented by plasma EBV DNA detection. A range of clinical and laboratory parameters were collected, including age, sex, clinical outcomes, blood cell counts, hemoglobin, platelets, and various serum values. Plasma EBV DNA levels and flow cytometric analysis (FCM) of bone marrow were performed for HLH cases.Results: Among 1850 hospitalized patients, 14 cases were identified, including 2 HLH cases and 12 IM cases. Comparative analysis revealed distinctive features of HLH, including lower lymphocyte and platelet counts and higher levels of ferritin, soluble interleukin 2 receptor (sIL-2R), and D dimer compared to IM. Notably, one HLH case responded well to corticosteroid monotherapy, while the other case did not, resulting in a fatal outcome. Detection of a cluster of CD5-CD7 lymphocytes in bone marrow is a hallmark of EBV-HLH and useful to distinguish from IM-HLH.Conclusion: This study underscores the importance of early differentiation among EBV-HLH, IM-HLH, and IM in adults to guide appropriate treatment strategies. While specific laboratory markers help distinguish HLH from IM, a more detailed analysis of FCM is crucial for precise diagnosis of HLH cases and tailored therapeutic interventions.Keywords: hemophagocytic lymphohistiocytosis, Epstein–Barr virus infection, Epstein–Barr virus–associated hemophagocytic lymphohistiocytosis, diagnosis of EBV-HLH, flow cytometric analysis of bone marrow

Seigo Miyoshi,1 Hitoshi Katayama,1 Minoru Matsubara,2 Takahide Kato,1 Naohiko Hamaguchi,1 Osamu Yamaguchi1 1Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan; 2Department of Internal Medicine, Sumitomo Besshi Hospital, Niihama, Ehime 792-8543, JapanCorrespondence: Seigo MiyoshiDepartment of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791-0295, JapanTel +81-89-960-5303Fax +81-89-960-5306Email seigom@m.ehime-u.ac.jpBackground and Objective: Spirometry is sometimes difficult to perform in elderly patients and patients with cognitive impairment. Forced oscillometry (FOT) is a simple, noninvasive technique used for measuring respiratory impedance. The aim of this study was to develop regression equations to estimate vital capacity (VC), forced vital capacity (FVC), and forced expiratory volume in 1 s (FEV1.0) on the basis of FOT indices and to evaluate the accuracy of these equations in patients with asthma, chronic obstructive pulmonary disease (COPD), and interstitial lung disease (ILD).Materials and Methods: We retrospectively included data on 683 consecutive patients with asthma (388), COPD (128), or ILD (167) in this study. We generated regression equations for VC, FVC, and FEV1.0 by multivariate linear regression analysis and used them to estimate the corresponding values. We determined whether the estimated data reflected spirometric indices.Results: Actual and estimated VC, FVC, and FEV1.0 values showed significant correlations (all r > 0.8 and P < 0.001) in all groups. Biases between the actual data and estimated data for VC, FVC, and FEV1.0 in the asthma group were − 0.073 L, − 0.069 L, and 0.017 L, respectively. The corresponding values were − 0.064 L, 0.027 L, and 0.069 L, respectively, in the COPD group and − 0.040 L, − 0.071 L, and − 0.002 L, respectively, in the ILD group. The estimated data in the present study did not completely correspond to the actual data. In addition, sensitivity for an FEV1.0/FVC ratio of < 0.7 and the diagnostic accuracy for the classification of COPD grade using estimated data were low.Conclusion: These results suggest that our method is not highly accurate. Further studies are needed to generate more accurate regression equations for estimating spirometric indices based on FOT measurements.Keywords: forced expiratory volume in 1 second, forced oscillation technique, forced vital capacity, spirometry, vital capacity

Mariko Matsubara,1,2 Haruka Tohara,1 Koji Hara,1 Hiromichi Shinozaki,1 Yasuhiro Yamazaki,1 Chiaki Susa,1 Ayako Nakane,1 Yoko Wakasugi,1 Shunsuke Minakuchi1 1Gerodontology and Oral Rehabilitation, Department of Gerontology and Gerodontology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, 2Department of Oral Surgery, Ichigao Carillon Hospital, Kanagawa, Japan Purpose: This study was aimed to examine the effectiveness of a high-speed jaw-opening exercise, which targets the contraction of fast-twitch muscle fibers, in improving swallowing function.Subjects and methods: Twenty-one subjects (mean age 74.0±5.7 years) with dysphagia-related symptoms, such as coughing or choking during eating, performed the exercise. None of the included subjects had neurological symptoms or history of surgery that could cause significant dysphagia. All subjects took regular meals, and maintained independent activities of daily life. The exercise schedule consisted of 3 sets of 20 repetitions each of rapid and maximum jaw-opening movement with a 10-second interval between sets. The exercise was performed twice daily for 4 weeks.Results: Following the intervention, there was a significant increase in the vertical position of the hyoid bone at rest. Furthermore, during swallowing, the elevation of the hyoid bone and the velocity of its movement and esophageal sphincter opening increased significantly while the duration of the hyoid elevation and the pharyngeal transit time reduced significantly.Conclusions: Our results demonstrated that high-speed jaw-opening exercise resulted in increased elevation velocity of the hyoid bone during swallowing, indicating its role in effectively strengthening the fast-twitch muscle fibers of suprahyoid muscles. Furthermore, since the rest position of the hyoid bone appeared to have improved, this exercise may be especially useful in elderly individuals with a lower position of the hyoid bone at rest and those with decreased elevation of the hyoid bone during swallowing, which are known to be associated with an increased risk of aspiration. Keywords: deglutition disorders, jaw, exercise, rehabilitation, fast-twitch muscle fibers, high speed

Shoichiro Yamamoto,1 Seigo Miyoshi,1 Hitoshi Katayama,1 Mikio Okazaki,2 Hisayuki Shigematsu,2 Yoshifumi Sano,2 Minoru Matsubara,3 Naohiko Hamaguchi,1 Takafumi Okura,1 Jitsuo Higaki1 1Department of Cardiology, Pulmonology, Hypertension, and Nephrology, 2Department of Cardiovascular and Thoracic Surgery, Ehime University Graduate School of Medicine, Toon, 3Department of Internal Medicine, Sumitomo Besshi Hospital, Niihama, Japan Purpose: Spirometry is sometimes difficult to perform in elderly patients and in those with severe respiratory distress. The forced-oscillation technique (FOT) is a simple and noninvasive method of measuring respiratory impedance. The aim of this study was to determine if FOT data reflect spirometric indices.Patients and methods: Patients underwent both FOT and spirometry procedures prior to inclusion in development (n=1,089) and validation (n=552) studies. Multivariate linear regression analysis was performed to identify FOT parameters predictive of vital capacity (VC), forced VC (FVC), and forced expiratory volume in 1 second (FEV1). A regression equation was used to calculate estimated VC, FVC, and FEV1. We then determined whether the estimated data reflected spirometric indices. Agreement between actual and estimated spirometry data was assessed by Bland–Altman analysis.Results: Significant correlations were observed between actual and estimated VC, FVC, and FEV1 values (all r>0.8 and P0.8 and P

Atsushi Kuga,1 Toshinaga Tsuji,2 Shinji Hayashi,2 Mako Matsubara,3 Shinji Fujikoshi,4 Hirofumi Tokuoka,1 Aki Yoshikawa,5 Rodrigo Escobar,6 Kazuhide Tanaka,7 Takaharu Azekawa8 1Bio Medicine, Medicines Development Unit Japan, Eli Lilly Japan K.K., Kobe, Japan; 2Medical Affairs Department, Shionogi & Co. Ltd, Osaka, Japan; 3Pharmacovigilance Department, Shionogi & Co. Ltd, Osaka, Japan; 4Statistical Science, Medicines Development Unit Japan, Eli Lilly Japan K.K., Kobe, Japan; 5Scientific Communications, Medicines Development Unit Japan, Eli Lilly Japan K.K. Kobe, Japan; 6Bio-Medicines, Eli Lilly and Company, Indianapolis, IN, USA; 7Hitsuji Clinic, Kusatsu, Japan; 8Shioiri Mental Clinic, Yokosuka, Japan Objective: The objective of this study was to assess the effectiveness of duloxetine monotherapy, in comparison with selective serotonin reuptake inhibitor (SSRI) monotherapy, in the treatment of painful physical symptoms (PPS) in Japanese patients with major depressive disorder (MDD) in real-world clinical settings.Methods: This was a multicenter, 12-week prospective, observational study. This study enrolled MDD patients with at least moderate PPS, defined as a Brief Pain Inventory-Short Form (BPI-SF) average pain score (item 5) ≥3. Patients were treated with duloxetine or SSRIs (escitalopram, sertraline, paroxetine, or fluvoxamine) for 12 weeks, and PPS were assessed by BPI-SF average pain score. The primary outcome was early improvement in the BPI-SF average pain score at 4 weeks post-baseline. Results: A total of 523 patients were evaluated for treatment effectiveness (duloxetine N=273, SSRIs N=250). The difference in BPI-SF average pain score between the two groups was not statistically significant at 4 weeks post-baseline, the primary endpoint (least-squares mean change from baseline [95% confidence interval]: duloxetine,−2.8 [−3.1, −2.6]; SSRIs, −2.5 [−2.8, −2.3]; P=0.166). There was a numerical advantage for duloxetine in improvement from 4 to 12 weeks post-baseline, and the difference was statistically significant at 8 weeks post-baseline (least-squares mean change from baseline [95% confidence interval]: duloxetine, −3.6 [−3.9, −3.3]; SSRIs, −3.1 [−3.4, −2.8]; P=0.023). The 30% and 50% responder rates were significantly higher in patients treated with duloxetine at 4 and 8 weeks post-baseline. There were no serious adverse events experienced by duloxetine-treated patients. The rate of discontinuations due to adverse events was similar for duloxetine and the SSRIs (1.0% and 0.8% of patients, respectively).Conclusion: In this observational study, BPI-SF improvement was not significantly different at 4 weeks, the primary endpoint; however, patients treated with duloxetine tended to show better improvement in PPS compared to those treated with SSRIs. Keywords: depression, duloxetine, observational study, pain, SSRI

Hiromichi Shinozaki, Haruka Tohara, Mariko Matsubara, Nobuhiro Inokuchi, Yasuhiro Yamazaki, Ayako Nakane, Yoko Wakasugi, Shunsuke Minakuchi Department of Gerodontology, Tokyo Medical and Dental University, Tokyo, Japan Purpose: This study aimed to examine the relationship between jaw opening force and hyoid bone dynamics and resting position in elderly individuals based on gender. Subjects and methods: Subjects were 36 healthy elderly individuals aged ≥65 years without dysphagia (16 men and 20 women; mean age 75.5 years, range 65–88 years). Videofluorographic images during the swallowing of 10 mL of 40% (w/v) barium sulfate were obtained and the degrees of anterior, superior, and hypotenuse displacements of the hyoid bone and maximum/resting hyoid position were evaluated. Jaw opening force was measured three times using a jaw opening force sthenometer; the mean of these three measurements was used for analysis. Results: In men, there was a positive correlation between jaw opening force and resting hyoid position and negative correlations among all the degrees of anterior, superior, and hypotenuse displacements of the hyoid bone. In women, there was no statistically significant correlation between jaw opening force and any of the measurement items. There was no statistically significant correlation between jaw opening force and maximum hyoid position in either men or women. Conclusion: Our findings suggest that low jaw opening force leads to low resting hyoid position only in elderly men, and a lower hyoid position in healthy elderly men results in a larger total amount of hyoid displacement during swallowing. Moreover, a maximum hyoid position in healthy individuals of either gender does not differ depending on their jaw opening force. Keywords: aging, deglutition disorders, dysphasia, gender differences

Aki Kondo,1 Mari Goto,2 Tatsuya Mimura,1 Masao Matsubara1 1Department of Ophthalmology, Tokyo Women’s Medical University Medical Center East, 2Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan Purpose: Silent information regulator T1 (SIRT1), a member of the sirtuin family, has a preventive role in various ocular diseases. We evaluated the relations between the aqueous humor level of SIRT1 and age, sex, systemic diseases, the severity of lens opacity, and other factors. Setting: This study was conducted at a university teaching hospital in Tokyo, Japan. Design: This study was designed based on the consecutive case series. Methods: Aqueous humor samples were obtained from 29 eyes of the 21 consecutive patients undergoing surgery for age-related cataract (ARC). SIRT1 levels were determined by enzyme-linked immunosorbent assay. Results: Aqueous humor levels of SIRT1 showed a positive correlation with visual acuity (logarithm of the minimum angle of resolution) and with the severity of nuclear cataract (r=0.32 and 0.30, respectively, P

Shoko Kure,1 Wei-Xia Peng,1 Mitsuhiro Kudo,1 Miyuki Matsubara,2 Takashi Tsunoda,3 Zenya Naito1,21Department of Integrated Diagnostic Pathology, Nippon Medical School, 2Department of Pathology, Nippon Medical School Hospital, 3Department of Orthopedics, Nippon Medical School Department of Orthopedics, Nippon Medical School, Tokyo, JapanAbstract: Liposarcoma is categorized as a soft tissue sarcoma that most commonly appears in the lower extremities during adulthood, but rarely in the feet. We present a rare case of a primary myxoid liposarcoma in the foot of a 63-year-old man that was diagnosed by fine needle aspiration cytology (FNAC). The patient presented to our hospital with a 10-year history of a slow-growing mass on the left lateral ankle. On physical examination, the 60 mm ×60 mm mass, was found to be soft and elastic, causing poor mobility without pain. Magnetic resonance imaging of the mass revealed high signal intensity on T1-weighted images and heterogeneously high signal intensity on T2-weighted images without fat suppression. As a result of the physical examination and imaging, the mass was suspected to be a lipoma or ganglion cyst. However, the FNAC procedure revealed atypical small, round, short spindle cells, or foamy cells with a myxoid background, suggesting myxoid liposarcoma. Histology using an open biopsy showed a proliferation of atypical spindle and asteroid cells with a few foamy lipoblasts in a capillary-rich and myxoid background. The atypical lipoblasts were slightly positive for S-100. These findings were consistent with myxoid liposarcoma. The patient was treated with a resection of the mass. Liposarcoma is considered to be the second most common soft-tissue sarcoma. It usually involves the lower extremities, particularly the thigh, and is very rare in the adult foot. Our case was a rare occurrence of myxoid liposarcoma of the foot diagnosed preoperatively using FNAC.Keywords: myxoid liposarcoma, foot, fine needle aspiration cytology (FNAC), adult

Sakurako Takeda,1,2 Tatsuya Mimura,1 Masao Matsubara1,2 1Department of Ophthalmology, Tokyo Women’s Medical University Medical Center East, Tokyo, Japan; 2Department of Ophthalmology, Nippori Clinic, Medical Center East, Tokyo Women’s Medical University, Tokyo, Japan Purpose: We aimed to evaluate the effect on the intraocular pressure (IOP) of a dorzolamide/timolol (1%/0.5%) fixed combination (DTFC) ophthalmic agent for 3 years.Participants: A total of 19 consecutive patients who had previously been treated with monotherapy or any combination of a beta-blocker, carbonic anhydrase inhibitor, or prostaglandin analog, for primary open-angle glaucoma (POAG) (n=5) or normal tension glaucoma (N=14) were enrolled.Methods: Patients were switched to DTFC from their prior glaucoma therapy. The IOP was measured at intervals of 4–6 weeks for 3 years. Treatment failure was defined as an increase of IOP by ≥10% from baseline after switching to DTFC.Results: The average IOP decreased significantly from 14.1±2.9 mmHg at baseline to 12.2±2.2, 11.8±2.4, 12.1±2.5, 11.6±1.8, and 12.1±2.7 mmHg at 3, 6, 12, 24, and 36 months, respectively, after switching therapy (all P

Sakurako Takeda,1,2 Tatsuya Mimura,1 Masao Matsubara1,2 1Department of Ophthalmology, Tokyo Women’s Medical University Medical Center East, Tokyo, Japan; 2Department of Ophthalmology, Nippori Clinic, Medical Center East, Tokyo Women’s Medical University, Tokyo, Japan Purpose: To evaluate the effect of treatment for 3 years with a dorzolamide/timolol (1%/0.5%) fixed combination (DTFC) on visual field progression in patients with open-angle glaucoma.Participants: A total of 14 consecutive patients were enrolled who had been previously treated with monotherapy or any combination of a beta blocker, carbonic anhydrase inhibitor, and/or prostaglandin analog for primary open-angle glaucoma (POAG; n=4) or normal-tension glaucoma (NTG; n=10).Methods: Patients were switched to DTFC from their prior glaucoma therapy. The IOP was measured at intervals of 4–6 weeks, and the visual fields were examined at least twice a year for 3 years. The annual change of mean deviation (MD slope) was used to quantify visual field loss. Results: The mean MD value was –5.9±5.0 dB at baseline; it was –5.6±4.8 dB at 12 months, –5.9±5.0 dB at 24 months, and –5.6±5.1 dB at 36 months after switching. The mean MD slope was –0.2±0.8 dB/year before switching and 0.3±1.3 dB/year from baseline to 1 year, –0.3±1.1 dB/year from 1–2 years, and 0.3±0.9 dB/year from 2–3 years after switching. The mean MD slope from baseline to 36 months was correlated with the IOP reduction rate at 36 months after switching. Visual field progression was associated with the IOP reduction rate at 12 months after switching.Conclusion: Switching to DTFC from prior glaucoma therapy improved the MD slope for at least 3 years. Reduction of the IOP after switching to DTFC was effective for delaying visual field progression. Although our study was not nonrandomized and was small in scale, the findings suggest that DTFC might have a beneficial effect on the visual fields in patients with open-angle glaucoma. Keywords: dorzolamide/timolol (1%/0.5%) fixed combination, switch, visual field, MD slope

Kohji Hoshina,1 Yuichi Tagami,2 Osamu Mimura,3 Hiroshi Edagawa,4 Masao Matsubara,5 Teiichi Nakayama6 1Hoshina Eye Clinic, Nishinomiya, Japan; 2Department of Ophthalmology, Kobe Century Memorial Hospital, Kobe, Japan; 3Department of Ophthalmology, Hyogo College of Medicine, Nishinomiya, Japan; 4Edagawa Eye Clinic, Tokyo, Japan; 5Department of Ophthalmology, Tokyo Women's Medical University Medical Center East, Tokyo, Japan; 6Ritsumeikan University, Kyoto, Japan Background: It seemed that visual functions might have some effects on the performance of baseball players. We measured static, kinetic, and dynamic visual acuity (SVA, KVA, and DVA, respectively) of Japanese professional baseball players to ascertain whether there would be any difference in SVA, KVA, and DVA among player groups stratified according to their performance level. Methods: The subjects were 102 male professional baseball players with a mean age of 26 years who were members of a Japanese professional baseball club from 2000 to 2009. They were stratified into three groups according to their performance level: A (players who were on the roster of the top-level team all the time throughout the study period), B (players who were on the roster of the top-level team sometimes but not all the time), and C (players who were never on the roster of the top-level team). They were interviewed for the use of corrective visual aids, and examined for SVA, KVA, and DVA. The measurements of these parameters were compared among groups A, B, and C. We also investigated and analyzed the association of KVA or DVA with player position (pitchers or fielders) and with hand dominance for batting. KVA was compared between the pitchers and the fielders because they each require different playing skills. DVA was compared between the right-handed and the left-handed batters. Results: There was no statistically significant difference among groups A, B, and C. There was a statistically significant difference in KVA between the pitchers and the fielders (t-test; P < 0.05) There was no statistically significant difference in DVA between the right-handed and the left-handed batters. Conclusions: There was no significant difference in the examined visual functions among player groups with different performance levels. Keywords: static visual acuity, kinetic visual acuity, dynamic visual acuity, Japanese professional baseball players

Escherichia coli, as a model microorganism, was treated in phosphate-buffered saline under high hydrostatic pressure between 100 and 300 MPa, and the inactivation dynamics was investigated from the viewpoint of predictive microbiology. Inactivation data were curve fitted by typical predictive models: logistic, Gompertz and Weibull functions. Weibull function described the inactivation curve the best. Two parameters of Weibull function were calculated for each holding pressure and their dependence on holding pressure was obtained by interpolation. With the interpolated parameters, inactivation curves were simulated and compared with the experimental data sets.

The Montreal Neurological Institute's CBIG collection and patient registry has gathered nearly 4000 participants with neurological conditions and healthy controls since 2016, using the LORIS open-source database to integrate patient and sample data for global research projects on neurological diseases. The biobank aims to collect de-identified biological material, clinical, imaging, and genetic information to advance understanding of neurological disorders under Open Science principles. The C-BIG Repository seeks to enhance material and data collection and sharing, with a long-term goal of expanding participant recruitment worldwide to accelerate research on neurological disorders. A study on ANXA11-linked ALS investigated protein composition and spatial distribution of aggregates in post-mortem brain tissue, revealing insights into the significance of CTF accumulation in the brain of FTLD-MND. [Extracted from the article]