1.Development of a new alternative method to inhalation exposure: intratracheal instillation studies using molecular dispersion.
Toshiki MORIMOTO ; Chinatsu NISHIDA ; Hiroto IZUMI ; Taisuke TOMONAGA ; Kazuma SATO ; Yasuyuki HIGASHI ; Ke-Yong WANG ; Takuma KOJIMA ; Kazuo SAKURAI ; Akihiro MORIYAMA ; Jun-Ichi TAKESHITA ; Kei YAMASAKI ; Hidenori HIGASHI ; Kazuhiro YATERA ; Yasuo MORIMOTO
Environmental Health and Preventive Medicine 2025;30():69-69
BACKGROUND:
Organic chemicals have been known to cause allergic diseases such as bronchial asthma and hypersensitivity pneumonitis; however, the possibility that they do not cause irreversible pulmonary fibrosis has not been considered. Polyacrylic acid (PAA), an organic chemical, has caused irreversible progressive pulmonary fibrosis in exposed workers, indicating its potential to induce pulmonary inflammation and fibrosis. Although intratracheal instillation studies are commonly used for evaluating lung pathology, traditional methods face challenges with chemical substances, particularly nanoparticles, which tend to aggregate in suspension and prevent uniform pulmonary distribution. Such aggregation alters the qualitative and quantitative responses to lung injury, limiting accurate assessment of lung pathology. To overcome this limitation, we developed a 'molecular dispersion method' that uses pH modification to negative charges to PAA particles, maintaining their dispersion. Using this method, we investigated the effects of PAA on pulmonary inflammation and fibrosis in a rat model.
METHODS:
F344 rats were intratracheally instilled with PAA using molecular dispersion (0.1 mg/rat, 1.0 mg/rat), PAA without molecular dispersion (1.0 mg/rat), and normal saline (control group). Rats were sacrificed at 3 days, 1 week, 1 month, 3 months, and 6 months after exposure to examine inflammatory and fibrotic responses.
RESULTS:
PAA caused persistent increases in neutrophil influx in the bronchoalveolar lavage fluid (BALF) from 3 days to 1 month following instillation. In histopathological findings, the group with molecular dispersion had almost no inflammatory masses in the lung tissue compared to the group without molecular dispersion, and exhibited relatively uniform dispersion.
CONCLUSION
Intratracheal instillation of dispersed PAA induced neutrophil inflammation and fibrosis in the rat lung, suggesting that PAA might have pulmonary inflammogenicity and fibrogenicity. Intrapulmonary dispersion of PAA particles following intratracheal instillation studies using the molecular dispersion method was similar to that following inhalation studies.
Animals
;
Rats, Inbred F344
;
Acrylic Resins/adverse effects*
;
Rats
;
Inhalation Exposure/adverse effects*
;
Male
;
Pulmonary Fibrosis/pathology*
;
Pneumonia/pathology*
;
Lung/pathology*
;
Bronchoalveolar Lavage Fluid/cytology*
2.Revision of quality indicators for cervical cancer and trend analysis of existing indicators in Japan
Tamaki KAKUWA ; Ryoko RIKITAKE ; Satoru NAGASE ; Mikio MIKAMI ; Tsukasa BABA ; Masanori KANEUCHI ; Hideki TOKUNAGA ; Manabu SEINO ; Toshinari MURAMATSU ; Wataru YAMAGAMI ; Kazuhiro TAKEHARA ; Hitoshi NIIKURA ; Yasuyuki HIRASHIMA ; Kiyoshi YOSHINO ; Yuichi ICHINOSE ; Akira KAWATA ; Takahiro HIGASHI
Journal of Gynecologic Oncology 2025;36(5):e78-
Objective:
Cervical cancer rates in Japan (16.0/100,000) exceed the global average rate (11.3/100,000, according to the High/Very-High Human Development Index in 2020). This necessitates the evaluation of care quality and the quality indicators (QIs) for cervical cancer that were developed in 2013 to serve this purpose. This study updated these indicators using current evidence and consensus while longitudinally examining trends in practice patterns.
Methods:
The revision involved reviewing existing QIs and patterns of care indicators and incorporating new indicators using the modified Delphi method. Adherence to these indicators was assessed using a linked hospital-based cancer registry-based diagnostic procedure combination database covering approximately 70% of patients with cancer in Japan. The longitudinal trends of the existing indicators were evaluated using the linear probability model.
Results:
Seven new indicators were added to the existing twelve. Two of the new indicators mainly focused on early-stage surgical intervention, while one focused on advanced-stage bevacizumab combination therapy, with adherence rates of 81.7%, 0.8%, and 45.9%.Longitudinal analyses revealed significant improvements with the use of cisplatin in concurrent chemoradiotherapy for advanced-stage cervical cancer (+1%/year), oral anticancer agents as maintenance therapy after primary treatment for early-stage cervical cancer (−0.8%/ year), and hysterectomy for adenocarcinoma in situ in patients above 44 years old (−2%/year).
Conclusion
The QIs for cervical cancer in Japan have been revised based on 2022 evidence.The existing and new indicators should be continually evaluated to correspond to the latest knowledge. This will facilitate the standardization and promotion of bottom-up improvements in cervical cancer care.
3.Study design and baseline characteristics of a population-based prospective cohort study of dementia in Japan: the Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD).
Toshiharu NINOMIYA ; Shigeyuki NAKAJI ; Tetsuya MAEDA ; Masahito YAMADA ; Masaru MIMURA ; Kenji NAKASHIMA ; Takaaki MORI ; Minoru TAKEBAYASHI ; Tomoyuki OHARA ; Jun HATA ; Yoshihiro KOKUBO ; Kazuhiro UCHIDA ; Yasuyuki TAKI ; Shuzo KUMAGAI ; Koji YONEMOTO ; Hisako YOSHIDA ; Kaori MUTO ; Yukihide MOMOZAWA ; Masato AKIYAMA ; Michiaki KUBO ; Manabu IKEDA ; Shigenobu KANBA ; Yutaka KIYOHARA
Environmental Health and Preventive Medicine 2020;25(1):64-64
BACKGROUND:
The burden of dementia is growing rapidly and has become a medical and social problem in Japan. Prospective cohort studies have been considered an effective methodology to clarify the risk factors and the etiology of dementia. We aimed to perform a large-scale dementia cohort study to elucidate environmental and genetic risk factors for dementia, as well as their interaction.
METHODS:
The Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD) is a multisite, population-based prospective cohort study of dementia, which was designed to enroll approximately 10,000 community-dwelling residents aged 65 years or older from 8 sites in Japan and to follow them up prospectively for at least 5 years. Baseline exposure data, including lifestyles, medical information, diets, physical activities, blood pressure, cognitive function, blood test, brain magnetic resonance imaging (MRI), and DNA samples, were collected with a pre-specified protocol and standardized measurement methods. The primary outcome was the development of dementia and its subtypes. The diagnosis of dementia was adjudicated by an endpoint adjudication committee using standard criteria and clinical information according to the Diagnostic and Statistical Manual of Mental Disorders, 3rd Revised Edition. For brain MRI, three-dimensional acquisition of T1-weighted images was performed. Individual participant data were pooled for data analyses.
RESULTS:
The baseline survey was conducted from 2016 to 2018. The follow-up surveys are ongoing. A total of 11,410 individuals aged 65 years or older participated in the study. The mean age was 74.4 years, and 41.9% were male. The prevalence of dementia at baseline was 8.5% in overall participants. However, it was 16.4% among three sites where additional home visit and/or nursing home visit surveys were performed. Approximately two-thirds of dementia cases at baseline were Alzheimer's disease.
CONCLUSIONS
The prospective cohort data from the JPSC-AD will provide valuable insights regarding the risk factors and etiology of dementia as well as for the development of predictive models and diagnostic markers for the future onset of dementia. The findings of this study will improve our understanding of dementia and provide helpful information to establish effective preventive strategies for dementia in Japan.
Aged
;
Alzheimer Disease/genetics*
;
Dementia/genetics*
;
Environment
;
Female
;
Humans
;
Incidence
;
Japan/epidemiology*
;
Male
;
Middle Aged
;
Prevalence
;
Prospective Studies
;
Risk Factors
4.Quality indicators for cervical cancer care in Japan.
Tomone WATANABE ; Mikio MIKAMI ; Hidetaka KATABUCHI ; Shingo KATO ; Masanori KANEUCHI ; Masahiro TAKAHASHI ; Hidekatsu NAKAI ; Satoru NAGASE ; Hitoshi NIIKURA ; Masaki MANDAI ; Yasuyuki HIRASHIMA ; Hiroyuki YANAI ; Wataru YAMAGAMI ; Satoru KAMITANI ; Takahiro HIGASHI
Journal of Gynecologic Oncology 2018;29(6):e83-
OBJECTIVE: We aimed to propose a set of quality indicators (QIs) based on the clinical guidelines for cervical cancer treatment published by The Japan Society of Gynecologic Oncology, and to assess adherence to standard-of-care as an index of the quality of care for cervical cancer in Japan. METHODS: A panel of clinical experts devised the QIs using a modified Delphi method. Adherence to each QI was evaluated using data from a hospital-based cancer registry of patients diagnosed in 2013, and linked with insurance claims data, between October 1, 2012, and December 31, 2014. All patients who received first-line treatment at the participating facility were included. The QI scores were communicated to participating hospitals, and additional data about the reasons for non-adherence were collected. RESULTS: In total, 297 hospitals participated, and the care provided to 15,163 cervical cancer patients was examined using 10 measurable QIs. The adherence rate ranged from 50.0% for ‘cystoscope or proctoscope for stage IVA’ to 98.8% for ‘chemotherapy using platinum for stage IVB’. Despite the variation in care, hospitals reported clinically valid reasons for more than half of the non-adherent cases. Clinically valid reasons accounted for 75%, 90.9%, 73.4%, 44.5%, and 88.1% of presented non-adherent cases respectively. CONCLUSION: Our study revealed variations in pattern of care as well as an adherence to standards-of-care across Japan. Further assessment of the causes of variation and non-adherence can help identify areas where improvements are needed in patient care.
Guideline Adherence
;
Humans
;
Insurance
;
Japan*
;
Methods
;
Patient Care
;
Platinum
;
Proctoscopes
;
Qi
;
Standard of Care
;
Uterine Cervical Neoplasms*

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