1.Cross-sectional biomonitoring of urinary deoxynivalenol, T-2 and HT-2 toxins, and zearalenone in Japanese adults.
Toshiki TAJIMA ; Tomohiko ISOBE ; Isao SAITO ; Takaaki KONDO ; Koji SUZUKI ; Ryosuke FUJII ; Yoshiki TSUBOI ; Yoshiko SUGITA-KONISHI ; Jun UEYAMA
Environmental Health and Preventive Medicine 2025;30():19-19
BACKGROUND:
Among the more than 300 mycotoxins that are known to have toxic effects on animals and humans, Fusarium toxins deoxynivalenol (DON), T-2 and HT-2 toxins (T2/HT2), and zearalenone (ZEN) are frequently detected in domestic agricultural products. This study aimed to assess DON, T2/HT2, and ZEN exposure in Japanese adults by measuring urinary mycotoxins, observing their distributions, and making comparisons with data from other countries.
METHODS:
A total of 201 individuals participated in the study. Twenty-four-hour urine samples were collected from young adults (34 men and 35 women) in the Tokai region (urban area) and spot urine samples were collected from middle-aged and elderly adults (64 men and 68 women) in the Donan area of Hokkaido Prefecture (rural area). Urinary DON, T2/HT2, and ZEN levels were measured using a validated liquid chromatography-tandem mass spectrometry method.
RESULTS:
For DON, T2/HT2, and ZEN, the detection frequencies above the limit of detection (LOD) level (0.15, 0.13, and 0.01 µg/L, respectively) in all the samples were 53%, 26%, and 71%, respectively. The median concentrations (95th percentile) of urinary DON, HT2, and ZEN were 0.19 (3.93),
Humans
;
Zearalenone/urine*
;
Japan
;
Male
;
Female
;
Trichothecenes/urine*
;
T-2 Toxin/urine*
;
Biological Monitoring
;
Adult
;
Middle Aged
;
Aged
;
Cross-Sectional Studies
;
Young Adult
;
Mycotoxins/urine*
;
Environmental Exposure/analysis*
;
East Asian People
2.Peripheral blood mitochondrial DNA copy number as a predictor of steatotic liver disease development: insights from epidemiological and experimental studies.
Genki MIZUNO ; Atsushi TESHIGAWARA ; Hiroya YAMADA ; Eiji MUNETSUNA ; Yoshiki TSUBOI ; Yuji HATTORI ; Mirai YAMAZAKI ; Yoshitaka ANDO ; Itsuki KAGEYAMA ; Takuya WAKASUGI ; Naohiro ICHINO ; Keisuke OSAKABE ; Keiko SUGIMOTO ; Ryosuke FUJII ; Hiroaki ISHIKAWA ; Nobutaka OHGAMI ; Koji OHASHI ; Koji SUZUKI
Environmental Health and Preventive Medicine 2025;30():42-42
BACKGROUND:
Mitochondria, which harbor their own genome (mtDNA), have attracted attention due to the potential of mtDNA copy number (mtDNA-CN) as an indicator of mitochondrial dysfunction. Although mtDNA-CN has been proposed as a simple and accessible biomarker for metabolic disorders such as metabolic dysfunction-associated steatotic liver disease, the underlying mechanisms and the causal relationship remain insufficiently elucidated. In this investigation, we combined longitudinal epidemiological data, animal studies, and in vitro assays to elucidate the potential causal relationship between reduced mtDNA-CN and the development of steatotic liver disease (SLD).
METHODS:
We conducted a longitudinal study using data from a health examination cohort initiated in 1981 in Yakumo, Hokkaido, Japan. Data from examinations performed in 2015 and 2022 were analyzed, focusing on 76 subjects without SLD at baseline (2015) to assess the association between baseline mtDNA-CN and subsequent risk of SLD development. In addition, 28-day-old SD rats were fed ad libitum on a 45% high-fat diet and dissected at 2 and 8 weeks of age. Blood and liver mtDNA-CN were measured and compared at each feeding period. Additionally, in vitro experiments were performed using HepG2 cells treated with mitochondrial function inhibitors to induce mtDNA-CN depletion and to examine its impact on intracellular lipid accumulation.
RESULTS:
Epidemiological analysis showed that the subjects with low mtDNA-CN had a significantly higher odds ratio for developing SLD compared to high (odds ratio [95% confidence interval]: 4.93 [1.08-22.50]). Analysis of the animal model showed that 8 weeks of high-fat diet led to the development of fatty liver and a significant decrease in mtDNA-CN. A further 2 weeks of high-fat diet consumption resulted in a significant decrease in hepatic mtDNA-CN, despite the absence of fatty liver development, and a similar trend was observed for blood. Complementary in vitro experiments revealed that pharmacologically induced mitochondrial dysfunction led to a significant reduction in mtDNA-CN and was associated with increases in intracellular lipid accumulation in HepG2 cells.
CONCLUSIONS
Our findings suggest that reduced mtDNA-CN may contribute causally to SLD development and could serve as a convenient, noninvasive biomarker for early detection and risk assessment.
Animals
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DNA, Mitochondrial/genetics*
;
Humans
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Male
;
DNA Copy Number Variations
;
Female
;
Fatty Liver/blood*
;
Rats
;
Middle Aged
;
Longitudinal Studies
;
Rats, Sprague-Dawley
;
Adult
;
Japan/epidemiology*
;
Aged
;
Biomarkers/blood*
;
Hep G2 Cells
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Diet, High-Fat/adverse effects*
3.Associations of serum carotene levels and decline for the ability of attention: a longitudinal study in the Japanese general population.
Hiroshi OKUMIYAMA ; Yoshiki TSUBOI ; Ryosuke FUJII ; Akihiko IWAHARA ; Takeshi HATTA ; Shuntaro SATO ; Hiroya YAMADA ; Koji SUZUKI
Environmental Health and Preventive Medicine 2025;30():58-58
BACKGROUND:
Although serum carotene may contribute to dementia prevention, there is a lack of longitudinal evidence for early cognitive decline before dementia symptoms. The aim of this study was to examine whether serum carotene levels were associated with annually evaluated cognitive trajectories among the Japanese general population.
METHODS:
Among 581 baseline participants, 199 individuals (83 males; mean age [min, max], 62.7 [39, 90] years) who underwent cognitive assessments more than twice after baseline were analyzed. "Attention" levels were assessed using one- and three-target Digit Cancellation Tests (D-CAT1 and D-CAT3). "General cognitive ability" was assessed by the short version of Mini-Mental State Examination (SMMSE). Serum carotenes (α-carotene, β-carotene and lycopene) were measured by high-performance liquid chromatography. After the measurements, we calculated total carotene levels by summing up the levels of all measured carotene. Carotene levels were categorized into three groups for analysis (low: 0%-25%, middle: 25%-75%, and high: 75%-100%). A linear mixed model was used to estimate the slope of the D-CAT score trajectory and to compare it between three categories.
RESULTS:
Compared with the middle carotene group, decline of attention was faster in the D-CAT1 for low β-carotene (β = -3.48, p = 0.035), lycopene (β = -3.10, p = 0.062), and total carotene (β = -4.75, p = 0.003), but not for α-carotene (β = -2.60, p = 0.111). For the D-CAT3, decline of attention was faster in the group of low lycopene (β = -3.17, p = 0.002) and total carotene (β = -2.17, p = 0.037) compared with the middle carotene group, while no clear association for α-carotene (β = -0.67, p = 0.521) and β-carotene (β = -0.64, p = 0.639). There were no clear associations between serum carotene and the SMMSE score.
CONCLUSIONS
These findings suggest low levels of serum lycopene are associated with a decline of attention in the setting of the general population.
Humans
;
Male
;
Carotenoids/blood*
;
Female
;
Longitudinal Studies
;
Middle Aged
;
Japan
;
Aged
;
Adult
;
Aged, 80 and over
;
Attention
;
Lycopene
;
East Asian People
4.Prognosis of biopsy-confirmed metabolic dysfunction- associated steatotic liver disease: A sub-analysis of the CLIONE study
Michihiro IWAKI ; Hideki FUJII ; Hideki HAYASHI ; Hidenori TOYODA ; Satoshi OEDA ; Hideyuki HYOGO ; Miwa KAWANAKA ; Asahiro MORISHITA ; Kensuke MUNEKAGE ; Kazuhito KAWATA ; Tsubasa TSUTSUMI ; Koji SAWADA ; Tatsuji MAESHIRO ; Hiroshi TOBITA ; Yuichi YOSHIDA ; Masafumi NAITO ; Asuka ARAKI ; Shingo ARAKAKI ; Takumi KAWAGUCHI ; Hidenao NORITAKE ; Masafumi ONO ; Tsutomu MASAKI ; Satoshi YASUDA ; Eiichi TOMITA ; Masato YONEDA ; Akihiro TOKUSHIGE ; Yoshihiro KAMADA ; Hirokazu TAKAHASHI ; Shinichiro UEDA ; Shinichi AISHIMA ; Yoshio SUMIDA ; Atsushi NAKAJIMA ; Takeshi OKANOUE ;
Clinical and Molecular Hepatology 2024;30(2):225-234
Background/Aims:
Metabolic dysfunction-associated steatotic liver disease (MASLD) was recently proposed as an alternative disease concept to nonalcoholic fatty liver disease (NAFLD). We aimed to investigate the prognosis of patients with biopsy-confirmed MASLD using data from a multicenter study.
Methods:
This was a sub-analysis of the Clinical Outcome Nonalcoholic Fatty Liver Disease (CLIONE) study that included 1,398 patients with NAFLD. Liver biopsy specimens were pathologically diagnosed and histologically scored using the NASH Clinical Research Network system, the FLIP algorithm, and the SAF score. Patients who met at least one cardiometabolic criterion were diagnosed with MASLD.
Results:
Approximately 99% of cases (n=1,381) were classified as MASLD. Patients with no cardiometabolic risk (n=17) had a significantly lower BMI than patients with MASLD (20.9 kg/m2 vs. 28.0 kg/m2, P<0.001), in addition to significantly lower levels of inflammation, ballooning, NAFLD activity score, and fibrosis stage based on liver histology. These 17 patients had a median follow-up of 5.9 years, equivalent to 115 person-years, with no deaths, liver-related events, cardiovascular events, or extrahepatic cancers. The results showed that the prognosis for pure MASLD was similar to that for the original CLIONE cohort, with 47 deaths and one patient who underwent orthotopic liver transplantation. The leading cause of death was extrahepatic cancer (n=10), while the leading causes of liver-related death were liver failure (n=9), hepatocellular carcinoma (n=8), and cholangiocarcinoma (n=4).
Conclusions
Approximately 99% of NAFLD cases were considered MASLD based on the 2023 liver disease nomenclature. The NAFLD-only group, which is not encompassed by MASLD, had a relatively mild histopathologic severity and a favorable prognosis. Consequently, the prognosis of MASLD is similar to that previously reported for NAFLD.
5.Trend and characteristics of minimally invasive surgery for patients with endometrial cancer in Japan
Hiroshi YOSHIDA ; Hiroko MACHIDA ; Koji MATSUO ; Yoshito TERAI ; Takuma FUJII ; Masaki MANDAI ; Kei KAWANA ; Hiroaki KOBAYASHI ; Mikio MIKAMI ; Satoru NAGASE
Journal of Gynecologic Oncology 2023;34(3):e56-
Objective:
Owing to the potential benefits of minimally invasive hysterectomy for endometrial cancer, the practice pattern has recently shifted in Japan. This study examined the trends in minimally invasive surgery (MIS) in patients with endometrial cancer in Japan.
Methods:
This retrospective observational study examined the Japan Society of Obstetrics and Gynecology Tumor Registry database between 2015–2019. This study examined the time-specific proportion change and predictors of MIS use in initial endometrial cancer treatment in Japan, and compared it with the use of abdominal surgery. Additionally, the association between hospital surgical treatment volume and MIS use was examined.
Results:
A total of 14,059 patients (26.5%) underwent minimally invasive hysterectomy, and 39,070 patients (73.5%) underwent abdominal hysterectomy in the study period. Patients who underwent MIS were more likely to be treated at high-volume centers, younger, central, or western Japan residents, registered in recent years, and had a tumor with stage I disease, type 1 histology, and less myometrial invasion (all adjusted p<0.05). The proportion of MIS treatments increased from 19.1% in 2015 to 34.3% in 2019 (p<0.001). On multivariable analysis, treatment at high-volume centers was a contributing factor for MIS (adjusted odds ratio=3.85; 95% confidence interval=3.44–4.30). MIS at high-volume centers increased significantly from 24.8% to 41.0% (p<0.001) during the study period, whereas MIS at low-volume centers remained at median 8.8%.
Conclusion
MIS has increased significantly in recent years, accounting for nearly 34% of surgical management of endometrial cancer in Japan. High-volume treatment centers take the lead in performing MIS.
6.Implementation of an online-based JICA Knowledge Co-Creation Program on capacity development among African community health professionals
Koji KANDA ; Toshihiro ITOH ; Tomoko FUJII ; Sachiko SHIOKAWA ; Takahiko YOSHIDA
Journal of International Health 2022;37(4):211-221
Introduction Asahikawa Medical University has been conducting a JICA Knowledge Co-Creation Program (KCCP) “Health Administration for Community Health Officers in Africa” in Japan since 2008. Due to the COVID-19 pandemic, the KCCP in 2020 was a hybrid of distance learning and following on-site training in Japan, which the latter was canceled thereafter. This paper reports on how this hybrid program was organized and implemented.Methods: Preparation The program was held in January-February 2021, with eight official participants from five countries and nine observers from two countries. The participants were required to engage in self-learning by PowerPoint materials with lecturers’ audio descriptions and zoom-based interactive meetings. The PowerPoint materials were freely accessible at our Google Drive account. There were 10 zoom sessions during the program.Results: Implementation At the beginning, all the lecture materials were converted to mp4 clips and uploaded to a Youtube channel due to the difficulties downloading heavy files with limited internet connection. A total of 24 videos were created with an average length of 58 minutes in each. Zoom-based interactive meetings were held regularly in the morning in the African continent. Almost all of the sessions were productive, but the participants were sometimes interrupted due to a weak network environment or their regular work assignments. Most provided contents were well understood.Discussion Despite some technical and environmental difficulties, the new-style, web-based training course facilitated the participation of observers as well as regular participants, providing more opportunities for interaction and discussion among trainees than a previous old-fashioned, on-site program. Improvement of the training environment particularly for participants is necessary to produce better training outcomes in the future, such as renting a hotel room and securing virtual connections.
7.A Case in which Kampo Medicine was Effective for Pain Management after Tonsillectomy where NSAIDs and Acetaminophen were Difficult to Use
Kazuhiro HIRASAWA ; Shingo ONO ; Shota FUJII ; Yujin CHIBA ; Koji OTSUKA ; Kiyoaki TSUKAHARA
Kampo Medicine 2022;73(1):87-90
Tonsillectomy is an operation generally carried out in otolaryngology. Postoperatively, the pain is very strong and it is often difficult to eat for several days. This time, we experienced a case after tonsillectomy in which rikkosan was effective for pain management. The patient was a 23-year-old woman. With a diagnosis of habitual tonsillitis, we performed her tonsillectomy. Postoperative pain was strong, however, it was difficult to use both non-steroidal anti-inflammatory drug and acetaminophen due to the history of drug eruption. Pain was alleviated immediately after taking rikkosan Subsequently we managed pain by using rikkosan as needed. Following a good postoperative course, she was discharged 6 days after surgery.
8.Oxidized human serum albumin as a possible correlation factor for atherosclerosis in a rural Japanese population: the results of the Yakumo Study.
Ryosuke FUJII ; Jun UEYAMA ; Arisa AOI ; Naohiro ICHINO ; Keisuke OSAKABE ; Keiko SUGIMOTO ; Koji SUZUKI ; Nobuyuki HAMAJIMA ; Kenji WAKAI ; Takaaki KONDO
Environmental Health and Preventive Medicine 2018;23(1):1-1
BACKGROUND:
The effect of the redox state of human serum albumin (HSA) on the antioxidant properties of the entire body has been a focus of recent research. The usefulness of HSA redox state as a biomarker for reducing oxidative stress has been investigated in clinical settings; however, evidence for its significance as a health index in non-clinical settings is yet to be established. This study aimed to examine the associations between HSA redox state and the atherosclerotic indices of carotid intima-media thickness (IMT) and plaque formation in a rural Japanese population.
METHODS:
We conducted a cross-sectional study as part of a health check-up program in the rural area of Hokkaido, Japan, at the end of August 2013. A total of 281 residents (124 men and 157 women) were included in the final analysis. Lifestyle-related data were obtained through a self-reported questionnaire, and ultrasound examinations were performed to measure IMT and determine plaque formation. The high-performance liquid chromatography postcolumn bromocresol green method was used to separate HSA into human nonmercaptalbumin and human mercaptalbumin (HMA).
RESULTS:
We found a significant negative relationship between the fraction of HMA [f(HMA)] and IMT (standardized β = - 0.132, p = 0.03). Moreover, f(HMA) was significantly associated with plaque formation (p < 0.01) with an odds ratio of 0.89 (95% confidence interval, 0.81-0.97) for every 10% increment in f(HMA).
CONCLUSIONS
We found that the HSA redox state, as determined by f(HMA), was associated with atherosclerotic indices in Japanese subjects. These results suggest that the HSA redox state indicates the risk of developing atherosclerosis.
Adult
;
Aged
;
Aged, 80 and over
;
Atherosclerosis
;
epidemiology
;
etiology
;
Biomarkers
;
Carotid Intima-Media Thickness
;
statistics & numerical data
;
Cross-Sectional Studies
;
Female
;
Humans
;
Japan
;
epidemiology
;
Male
;
Middle Aged
;
Oxidation-Reduction
;
Risk Factors
;
Serum Albumin
;
metabolism
;
Serum Albumin, Human
;
metabolism
9.Six Cases of Infected Abdominal Aortic Aneurysm
Masahiro Inagaki ; Toshiya Tokui ; Yasumi Maze ; Koji Hirano ; Taro Fujii
Japanese Journal of Cardiovascular Surgery 2017;46(1):17-20
Infected abdominal aortic aneurysm (IAAA) are rare, but life-threatening. This time we experienced six cases of infected abdominal aortic aneurysm. We measured the soothing of bacteremia by two weeks of antibiotic treatment before operation, if not in a state of impending rupture or rupture. The in situ prosthetic graft replacement surgery was the first choice. In five cases, we replaced by an in situ dacron graft with Rifampicin. However, one case that was by pondylitis caused by Helicobacter cinaedi was treated by extra-anatomical bypass. There was no post-operative infectious complication. In addition, surgery/hospital death was 0%.
10.Hyperbaric Oxygen Treatment of Carbon Monoxide Poisoning in the Past 5 Years
Kenji NAKAMAE ; Yoshiyuki HYODO ; Yoshikazu NARA ; Hirotaka INOUE ; Masayuki OKIJIMA ; Masahiro OGAWA ; Koji KONDO ; Yuki FUJII ; Atsuya SAKAIDE ; Kazuyoshi NISHIYAMA ; Ryota TANI ; Izumi OTA ; Osamu KAWAGUCHI
Journal of the Japanese Association of Rural Medicine 2016;65(1):1-8
Hyperbaric oxygen (HBO) therapy for acute carbon monoxide (CO) poisoning is performed after oxygen therapy and breathing therapy. The usefulness of HBO therapy in emergency treatment has been reported. In this study, we examined the effectiveness of HBO for CO poisoning that was performed at our hospital over the past 5 years. Subjects were 23 patients who had HBO therapy for CO poisoning in the period January 2008-November 2013. The male to female ratio of the cases was 14:9 and the mean age was 54.6±20.8 years. The cause was suicide in 39.1% of cases and accident in 60.9%. The mean number of treatments was 5.4±6.8. The atmosphere absolute was 2ATA:2.8ATA=12:11. The ratio of direct conveyance of the patient to our hospital to indirect conveyance of the patient from another hospital was 15:8. The effectiveness of HBO therapy at the time of discharge was 73.9%. However, delayed neuropsychiatric sequelae (DNS) was detected in 3 of the 23 cases of CO poisoning. No correlations were found between elapsed time after CO inhalation and various blood parameters. However, time to start of therapy is important for DNS, and our results suggest that early treatment at a hospital with a hyperbaric chamber is necessary.


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