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Linear independence results for certain gap series with monomial orders and Lambert series
Get PDF弘前大学博士（理学
Polygonum tinctorium extract suppresses the virulence of methicillin-resistant Staphylococcus aureus by disrupting its extracellular vesicles
Get PDFEthnopharmacological relevance: Methicillin-resistant S. aureus (MRSA) is a significant global health concern, causing both hospital- and community acquired infections. The extracellular vesicles released by S. aureus (SaEVs) contain essential factors related to the bacterial survival and pathogenicity. Polygonum tinctorium is traditionally used as a natural dye (indigo) and for treating various infectious diseases caused by microorganisms. However, the effect of P. tinctorium extract (Indigo Ex) and its mechanism on SaEVs is unknown.
Aim of the study: We investigated the effect and mechanism of Indigo Ex on SaEVs, which could be used in controlling S. aureus, especially MRSA infection.
Materials and methods: Indigo Ex was prepared from pesticide-free P. tinctorium, which was dried, powdered, and extracted with d-limonene. SaEVs were isolated and purified from MRSA culture supernatant by step-gradient ultracentrifugation. The effect of Indigo Ex on SaEVs morphology was observed by both transmission and scanning electron microscopy after incubating the Indigo Ex and SaEVs under shaking conditions. The cytotoxicity of Indigo Ex was performed using mouse macrophage cell line, RAW 264.7. In addition, the ability of Indigo Ex-treated SaEVs to stimulate the immune response and cytotoxicity in RAW 264.7 cells were evaluated by ELISA and WST-1 assay, respectively.
Results: SaEV particles were disrupted when treated with undiluted Indigo Ex in a time-dependent manner. For the cytotoxicity of Indigo Ex on RAW 264.7 cells, over 50% of the cell viability decreased when diluted Indigo Ex 1000-fold and no cytotoxic effect was observed at a 25,000-fold dilution of Indigo Ex. Interestingly, the Indigo Ex-treated SaEVs showed less cytotoxic effect than SaEVs alone. Similarly, SaEVs treated with Indigo Ex reduced stimulation of pro-inflammatory cytokines (TNF-α and IL-6) and anti inflammatory cytokine (IL-10) in RAW 264.7 cells compared to untreated SaEVs. Our results indicate that Indigo Ex disrupted SaEV particles, resulting in reduced virulence and stimulation of immune response.
Conclusions: This study reveals that the low concentration of Indigo Ex can suppresses the virulence of SaEVs without causing cytotoxicity to the host cells. Therefore, Indigo Ex may have the potential to be used to control S. aureus infection.弘前大学博士（医学）Publication: Journal of Ethnopharmacology Volume 337, Part 3, 30 January 2025, 118933
Publisher: Elsevier
© 2024 The Authors. Published by Elsevier B.V
Feasibility and safety of platinum-doublet therapy in patients with small-cell lung cancer in the third-line setting: A multi-institutional retrospective study
Get PDFSmall-cell lung cancer (SCLC) is a highly malignant tumor, and no standard third-line therapy has been established. The present study retrospectively analyzed the efficacy and safety of platinum‑based regimens in patients with third-line SCLC who received third-line chemotherapy. The association of regimen type with overall survival (OS) or time to treatment failure (TTF) was evaluated using the Cox hazard proportional method, including well known covariates affecting the prognosis of SCLC. TTF and OS analyses were conducted using the Kaplan-Meier method. The data cutoff date was June 30, 2020. As a result, from January 2015 to August 2019, 111 patients were diagnosed with SCLC, and 37 received third-line chemotherapy. Subsequently, 15 patients received a platinum-doublet regimen, and 22 patients received a single-agent regimen. Only the type of regimen was significantly associated with TTF in univariate analysis (odds ratio, 0.44; 95% confidence interval, 0.20-0.95; P=0.03). There were no significant factors associated with OS. The median TTF of patients receiving a platinum-doublet regimen and those receiving a single-agent regimen were 3.9 and 2.3 months, respectively (P=0.03). The overall response rates of the platinum-doublet and single-agent regimens were 20.0 and 4.5%, respectively. Similarly, the disease control rates were 73.3 and 36.4% for platinum-doublet and single-agent regimens, respectively. There was a tendency for adverse events (AEs) with any grade to occur more often in platinum-based regimens compared with in single-agent regimens. Severe AEs of grade 3 or higher were observed more often in the platinum-based regimen, especially in myelosuppression. In conclusion, the present study demonstrated the feasibility and safety of platinum-doublet regimens in patients with SCLC in a third-line setting (Registration no. 2020-048. Date of registration, June 5, 2020).弘前大学博士（医学）Authors: Takashi Fukushima, Tomonori Makiguchi, Yusuke Tanaka, Kei Chubachi, Mina Ishidoya, Sachio Suzuki, Hisashi Tanaka, Kageaki Taima, Yukihiro Hasegawa, Koichi Okudera, Sadatomo Tasaka
Published online on: September 1, 2022
Article Number: 368
Copyright: © Fukushima et al. This is an open access article distributed under the terms of Creative Commons Attribution License
Examination of factors that lead to the transition of community-dwelling older adults to a state requiring support and care
Get PDF弘前大学博士（保健学）学位論文のもととなる研究成果としての筆頭著者原著
論文題目：Examination of factors that lead to the transition of community-dwelling older adults to a state requiring support and care : A longitudinal study on factors influencing locomotive syndrome
掲載学術誌（巻号）：弘前医学 Vol. 75, No. 2-4 , 129-141（2025）
HDL: http://hdl.handle.net/10129/000200077
Long-term safety and efficacy of subcutaneous implantable cardioverter-defibrillator compared with transvenous implantable cardioverter-defibrillator in propensity score-matched patients from Japan
No full textBackground
Subcutaneous implantable cardioverter-defibrillator (S-ICD) has been reported to be non-inferior to transvenous ICD (TV-ICD) in terms of device-related complications and inappropriate shock (IAS). We aimed to evaluate the long-term clinical outcomes of S-ICD compared with TV-ICD in Japanese patients.
Methods
We studied 315 consecutive patients (TV-ICD, 167; S-ICD, 148) who underwent ICD implantation. A propensity score matching analysis was performed to select patient subgroups for comparison (104 patients in each group). Clinical outcomes, including appropriate and inappropriate ICD therapy, procedure- and lead-related complications, and mortality, were compared between the two groups.
Results
During follow-up (median, 1458 [interquartile range, 1353–1572] days), the cumulative incidence of appropriate shock therapy was 9.6% and 8.7% in the S-ICD and TV-ICD groups, respectively (p = 0.94). Although the S-ICD group tended to have a higher IAS than the TV-ICD group (5.8% vs. 1.9%), the difference was not significant (p = 0.19). Conversely, the cumulative incidence of procedural and lead-related complications was significantly lower in the S-ICD group (2.9% vs. 9.6%, p = 0.02). Notably, lead-related complications were more common in the TV-ICD group (p = 0.05). There was no difference in all-cause mortality between the two groups (p = 0.75), and heart failure exacerbation was the most common cause of death in both groups.
Conclusions
In propensity score-matched Japanese patients with S-ICD, the cumulative incidence of appropriate shock and mortality was comparable to those with TV-ICD. There was no significant difference in the rate of IAS. Notably, patients with S-ICD had fewer lead-related complications than those with TV-ICD.弘前大学博士（医学）Author(s); Yuki Konno MD | Shingo Sasaki MD, PhD | Yuji Ishida MD, PhD | Yuichi Toyama MD, PhD | Kimitaka Nishizaki MD, PhD | Takahiko Kinjo MD, PhD | Taihei Itoh MD, PhD | Masaomi Kimura MD, PhD | Kazufumi Kato MD | Toshihiro Iwasaki MD | Hitoshi Umezaki MD | Shun Hirosawa MD | Hirofumi Tomita MD, PhD
Associations Between Workday/Leisure Day Lifestyle Behavior and Cardiovascular Disease Risk Factors Among Night Shift Workers Using the Isotemporal Substitution Model
No full textBackground/Objectives:
Night shift workers (NSWs) are at a high risk of cardiovascular disease (CVD). However, the association between CVD risk factors and lifestyle behavior (sedentary behavior [SB], physical activity [PA], and sleep) is unclear among NSWs. NSWs lead different lifestyles on workdays and leisure days. This study aimed to investigate the association between lifestyle behavior times and CVD risk factors among NSWs during workdays and leisure days using an isotemporal substitution model.
Methods:
This cross-sectional study included 66 male NSWs. Time spent on lifestyle behaviors was obtained using a tri-axial accelerometer and classified into SB, light-intensity PA, moderate-to-vigorous PA (MVPA), and sleep. Lifestyle behavior times were divided into workdays and leisure days. CVD risk factors were determined based on periodic health checkups. An isotemporal substitution model was used to estimate the effect of replacing one lifestyle behavior with another on CVD risk factors.
Results:
The lifestyle behavior times differed between workdays and leisure days. On workdays, reallocating 30 min of SB to light-intensity PA was significantly associated with a lower waist circumference. In addition, reallocating sleep to SB or MVPA was significantly associated with higher triglyceride levels. On leisure days, reallocating SB or sleep time to MVPA was significantly associated with lower aspartate aminotransferase levels.
Conclusions:
Given the difference in the associations between lifestyle behavior times and CVD risk factors among NSWs between workdays and leisure days, NSWs should be mindful of the time spent on SB, PA, and sleep on workdays and leisure days to achieve healthier outcomes.弘前大学博士（医学）Author: Umeda, Yoko ; Kinoshita, Keita ; Sugimura, Yoshikuni ; Yang, Yichi ; Kyi Mar Wai ; Li, Yitao ; Ihara, Kazushig
Moderate cryptoxanthin intake correlates with maintenance of a proper PINT index in a general Japanese population
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Small fibre neuropathy (SFN) is an early manifestation of diabetic polyneuropathy. Although oxidative stress, inflammation and change of intestinal bacterial population are assumed to be their pathogenesis, the effects of dietary nutrition have not been evaluated. The relationship between dietary nutrition intake and pain sensation was evaluated in the Japanese population.
Methods
We conducted the Iwaki project, a population-based study recruiting 1,028 individuals, in 2018. The relationships between the pain threshold from intraepidermal electrical stimulation (PINT) and the amount of dietary nutrition evaluated by a brief-type self-administered diet history questionnaire were examined. The odds ratio was further explored after categorizing subjects based on low ( 159.2 μg/day).
Results
Univariate linear regression analyses showed significant correlations between PINT and cryptoxanthin intake even after adjustments for other nutritional intakes (ß = 0.107, p < 0.01). Multivariate logistic regression analysis revealed low and high cryptoxanthin intake as significant risk factors for abnormal PINT (≥ 0.20 mA). Multivariate linear regression analyses showed significant correlations between PINT and cryptoxanthin intake levels after adjustment for other clinically PINT-related factors (ß = 0.09, p < 0.01).
Conclusions
Adequate intake of cryptoxanthin is recommended to maintain the pain threshold in the Japanese population.弘前大学博士（医学）Author(s): Ryuzaki, Masaki ; Mizukami, Hiroki ; Takeuchi, Yuki ; Osonoi, Sho ; Sasaki, Takanori ; Wang, Zhenchao ; Kushibiki, Hanae ; Yamada, Takahiro ; Yamazakia, Keisuke ; Ogasawara, Saori ; Tarusawa, Takefusa ; Mikami, Tatsuya ; Hakamada, Kenichi ; Nakaji, Shigeyuk
The potential effectiveness of tolvaptan in critically ill patients including cardiac and noncardiac populations: a retrospective observational study
Get PDFPurpose: We investigated the potential diuretic effectiveness of the selective arginine vasopressin 2 receptor antagonist tolvaptan in critically ill patients including cardiac and noncardiac populations.
Methods: This was a single-center retrospective observational study. We analyzed the data of our hospital's critically ill adult patients (n=473) including noncardiac as well as cardiac populations who had an ICU stay ≥4 days in 2019–2020 and who did not undergo renal transplantation or permanent renal replacement therapy before their ICU admission. Adjusting for several confounders (the patients' disease severity, comorbidities including cardiac disease, and diuretics used), we estimated the predictors for the patients whose daily urine volume had increased by up to twofold or more compared to the minimal value (the primary endpoint) by applying a multivariable logistic regression model. We also investigated tolvaptan's effect on time-course changes in the serum creatine (sCr) level (the secondary endpoint) by using a generalized estimating equation model.
Results: Tolvaptan use was significantly correlated with increased urine volume (odds ratio [OR] 1.86, 95%CI: 1.13–3.06, p=0.015) but was not significantly associated with time-course changes in the sCr level: beta estimator [95%CI], 0.07 [−0.01 to 0.15], p=0.08.
Conclusion: Tolvaptan independently increased the urine volume, apparently without worsening the renal function in critically ill patients including cardiac and noncardiac populations.弘前大学博士（医学）Yamazaki, Y., Niwa, H., Ishiyama, E. et al. The potential effectiveness of tolvaptan in critically ill patients including cardiac and noncardiac populations: a retrospective observational study. Naunyn-Schmiedeberg's Arch Pharmacol 398, 5427–5436 (2025). https://doi.org/10.1007/s00210-024-03618-