Publications by authors named "Kazuhito Yokoyama"

120 Publications

Serum perfluoroalkyl substances and breast cancer risk in Japanese women: A case-control study.

Sci Total Environ 2021 Jul 29;800:149316. Epub 2021 Jul 29.

Division of Epidemiology, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.

Background: Perfluoroalkyl substances (PFASs) may contribute to causing breast cancer; however, associations between exposure to PFASs and risk of breast cancer are controversial.

Objectives: In the present study, we newly distinguished branched isomers of PFASs from their linear isomers and aimed to investigate the association between serum PFAS concentrations and breast cancer risk in Japanese women.

Methods: We used a case-control design to study 405 eligible matched pairs attending four hospitals in Nagano Prefecture, Japan from May 2001 to September 2005. We used in-port arylation gas-chromatography mass spectrometry with negative chemical ionization to measure serum concentrations of 20 PFAS congeners. We calculated multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of breast cancer and its hormone-receptor subtypes by quartiles or tertiles of serum PFASs.

Results: After multivariable adjustment for breast cancer risk factors, we found that serum concentrations of 20 PFAS congeners were significantly inversely associated with risk of breast cancer. Comparing the extreme quartiles of linear isomers of perfluorooctane sulfonate or perfluorooctanoic acid, ORs were 0.15 (95% CI: 0.07, 0.33 P for trend <0.0001) and 0.21 95% CI: 0.10, 0.44 P for trend <0.0001). Among postmenopausal women, whereas we found the linear isomer of perfluorotridecanoic acid to be inversely associated with breast cancer risk, a medium degree of exposure to the branched isomer of perfluorotridecanoic acid was associated with a marginally increased risk of breast cancer (OR [95% CI] = 1.74 [0.98, 3.09]).

Discussion: In our case-control study, we found overall no association between serum PFAS concentrations and increased risk of breast cancer. Many inverse associations between serum PFAS concentrations and breast cancer risk were found.
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http://dx.doi.org/10.1016/j.scitotenv.2021.149316DOI Listing
July 2021

Prenatal blood levels of some toxic metals and the risk of spontaneous abortion.

J Environ Health Sci Eng 2021 Jun 26;19(1):357-363. Epub 2021 Feb 26.

Department of Epidemiology and Environmental Health, Juntendo University Faculty of Medicine, Tokyo, Japan.

High-level toxic metal exposure has become rare in the recent years. Although, it has not known whether relatively lower exposure may adversely affect human reproductive system. Spontaneous abortion (SA) is a serious reproductive problem, which, in many cases, the cause(s) is not clearly understood. To assess the relationship between prenatal blood level of metals and SA risk, we compared blood concentration of some heavy metals in samples taken from mothers recruited in Tehran Environment and Neurodevelopmental Defects (TEND) study conducted on apparently healthy pregnant women in Tehran, Iran who subsequently experienced spontaneous abortion with mothers who their pregnancy ended to live births. During early gestation, 206 women were enrolled to the survey and followed up till fetal abortion or baby deliveries occur. Blood metal concentrations were measured using an inductively coupled plasma mass spectrometer. The mean blood levels of lead, antimony, and nickel were higher in SA than ongoing pregnancy; however, this difference was not statistically significant. When adjusted for covariates, the logistic regression analysis showed significant association between maternal age and the risk of SA in all models. Among toxic metals only antimony had a noticeable positive relation with the risk of SA (OR: 1.65, 95% CI:1.08-2.52, value: 0.02). Pearson's correlation coefficient showed significant ( < 0.05) positive correlations among prenatal blood metals levels, except for nickel. Although the present study failed to provide strong evidence for the effects of toxic metals on the occurrence of SA at the relatively low-levels, these metals should be avoided in women who plan pregnancy and/or during the early stages of gestation to prevent the chance of adverse effects.
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http://dx.doi.org/10.1007/s40201-020-00608-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172701PMC
June 2021

Investigation of clinical target volume segmentation for whole breast irradiation using three-dimensional convolutional neural networks with gradient-weighted class activation mapping.

Radiol Phys Technol 2021 Sep 16;14(3):238-247. Epub 2021 Jun 16.

Department of Epidemiology and Environmental Health, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.

This study aims to implement three-dimensional convolutional neural networks (3D-CNN) for clinical target volume (CTV) segmentation for whole breast irradiation and investigate the focus of 3D-CNNs during decision-making using gradient-weighted class activation mapping (Grad-CAM). A 3D-UNet CNN was adopted to conduct automatic segmentation of the CTV for breast cancer. The 3D-UNet was trained using three datasets of left-, right-, and both left- and right-sided breast cancer patients. Segmentation accuracy was evaluated using the Dice similarity coefficient (DSC). Grad-CAM was applied to trained CNNs. The DSCs for the datasets of the left-, right-, and both left- and right-sided breasts were on an average 0.88, 0.89, and 0.85, respectively. The Grad-CAM heatmaps showed that the 3D-UNet used for segmentation determined the CTV region from the target-side breast tissue and by referring to the opposite-side breast. Although the size of the dataset was limited, DSC ≥ 0.85 was achieved for the segmentation of breast CTV using the 3D-UNet. Grad-CAM indicates the applicable scope and limitations of using a CNN by indicating the focus of such networks during decision-making.
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http://dx.doi.org/10.1007/s12194-021-00620-8DOI Listing
September 2021

Analysis of lead distribution in avian organs by LA-ICP-MS: Study of experimentally lead-exposed ducks and kites.

Environ Pollut 2021 Aug 5;283:117086. Epub 2021 Apr 5.

Laboratory of Toxicology, Faculty of Veterinary Medicine, Hokkaido University, Kita 18 Nishi 9, Kita-ku, Sapporo, Hokkaido, 060-0818, Japan.

Lead poisoning of wild birds by ingestion of lead ammunition occurs worldwide. Histopathological changes in organs of lead-intoxicated birds are widely known, and lead concentration of each organ is measurable using mass spectrometry. However, detailed lead localization at the suborgan level has remained elusive in lead-exposed birds. Here we investigated the detailed lead localization in organs of experimentally lead-exposed ducks and kites by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). In both the ducks and kites, lead accumulated diffusely in the liver, renal cortex, and brain. Lead accumulation was restricted to the red pulp in the spleen. With regard to species differences in lead distribution patterns, it is noteworthy that intensive lead accumulation was observed in the arterial walls only in the kites. In addition, the distribution of copper in the brain was altered in the lead-exposed ducks. Thus, the present study shows suborgan lead distribution in lead-exposed birds and its differences between avian species for the first time. These findings will provide fundamental information to understand the cellular processes of lead poisoning and the mechanisms of species differences in susceptibility to lead exposure.
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http://dx.doi.org/10.1016/j.envpol.2021.117086DOI Listing
August 2021

An Investigation of the Wild Rat Crown Incisor as an Indicator of Lead (Pb) Exposure Using Inductively Couple Plasma Mass Spectrometry (ICP-MS) and Laser Ablation ICP-MS.

Int J Environ Res Public Health 2021 01 18;18(2). Epub 2021 Jan 18.

Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Kita 18 Nishi 9, Kita-ku, Sapporo 060-0818, Japan.

Lead (Pb) is a metal toxicant of great public health concern. The present study investigated the applicability of the rat incisor in Pb exposure screening. The levels of lead in teeth (Pb-T) in the crown and root of incisors in laboratory Pb-exposed Sprague Dawley rats were quantified using inductively coupled plasma mass spectrometry (ICP-MS). The crown accumulated much Pb-T than the root of the Sprague Dawley rat incisor. The levels of lead in blood (Pb-B) were positively correlated with the Pb-T in the crown and root incisors of the Sprague Dawley rats. As an application of the Pb-T crown results in experimental rats, we subsequently analyzed the Pb-T in the crown incisors of Pb-exposed wild rats () sampled from residential sites within varying distances from an abandoned lead-zinc mine. The Pb-T accumulation in the crown of incisors of rats decreased with increased distance away from the Pb-Zn mine. Furthermore, the Pb-T was strongly correlated ( = 0.85) with the Pb levels in the blood. Laser ablation ICP-MS Pb-T mappings revealed a homogenous distribution of Pb in the incisor with an increased intensity of Pb-T localized in the tip of the incisor crown bearing an enamel surface in both Sprague Dawley and rats. These findings suggest that Pb-T in the crown incisor may be reflective of the rat's environmental habitat, thus a possible indicator of Pb exposure.
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http://dx.doi.org/10.3390/ijerph18020767DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830958PMC
January 2021

Tehran environmental and neurodevelopmental disorders (TEND) cohort study: Phase I, feasibility assessment.

J Environ Health Sci Eng 2020 Dec 9;18(2):733-742. Epub 2020 Sep 9.

Department of Research Methodology and Data Analysis, Institute for Environmental Research, Tehran University of Medical Sciences, Tehran, Iran.

Purpose: To advance knowledge about childhood neurodevelopmental disorders and study their environmental determinants, we conducted a study in Tehran, Iran to assess the feasibility of prospective birth cohort study.

Methods: We evaluated participation of pregnant women, feasibility of sampling biological material, and health care services availability in Tehran in four steps: (1) first trimester of pregnancy; (2) third trimester of pregnancy; (3) at delivery; and (4) two to three months after delivery. We collected related data through questionnaires, also various biological samples were obtained from mothers (blood, urine, milk and nails-hands and feet) and newborns (umbilical cord blood, meconium, and urine samples) from February 2016 to October 2017.

Results: overall 838 eligible pregnant women were approached. The participation rate was 206(25%) in our study and about 185(90%) of subjects were recruited in hospitals. Out of 206 participants in the first trimester, blood, urine, hand nail, and foot nail samples were collected from 206(100%),193(93%), 205(99%), and 205(99%), respectively. These values dropped to 65(54%), 83(69%), 84(70%), and 84(70%) for the remaining participants 120(58%) in the third trimester, respectively. Also, we gathered milk samples from 125(60%) of mothers at two to three months after delivery.

Conclusion: Our findings suggest that hospitals were better places for recruitment of subjects in a birth cohort in Tehran. We further concluded that birth cohort study recruitment can be improved by choosing appropriate gestational ages. Obtaining the newborn's urine, meconium, and umbilical cord blood were challenging procedures and require good collaboration between hospital staff and researchers.
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http://dx.doi.org/10.1007/s40201-020-00499-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721759PMC
December 2020

Hair Metal Levels and Childhood Weight Gain.

Iran J Public Health 2020 Aug;49(8):1510-1519

Maternal, Fetal, and Neonatal Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Background: Exposure to toxic metals remains a public health problem with lifelong impacts on childhood growth and development. We aimed to investigate metals effects on preschool children's anthropometric variables.

Methods: The study was conducted in Tehran, Iran, from Jul 2013 to Mar 2016. We measured scalp hair metal concentrations (lead, cadmium, arsenic, zinc, manganese, and cobalt), using inductively coupled plasma mass spectrometry, in 207 preschool children's (36 to 72 months old).

Results: A significant negative correlation between children's hair lead levels and children's weight was found (r= -0.178, ). Linear regression analysis confirmed the relationship when adjusted for the confounders, including children's age, sex, height, family income, and maternal education (β= -0.191; t= -3.426, < 0.01). The ANOVA analysis showed a significant (<0.01) difference between hair lead level and children's weight-for-age percentiles. Totally and separately, in almost all weight percentiles, hair lead levels were higher in girls than boys.

Conclusion: The present study on Iranian children showed the current levels of lead exposure might negatively influence on children growth, with higher risk for girls than boys.
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http://dx.doi.org/10.18502/ijph.v49i8.3895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554378PMC
August 2020

Single-dose toxicity study by intra-arterial injection of BSH entrapped water-in-oil-in-water emulsion for boron neutron capture therapy to hepatocellular carcinoma.

Appl Radiat Isot 2020 Sep 13;163:109202. Epub 2020 May 13.

Institute of Engineering Innovation, School of Engineering, The University of Tokyo, Tokyo, 113-8656, Japan; Cooperative Unit of Medicine & Engineering, The University of Tokyo Hospital, Tokyo, 113-8655, Japan.

We developed a mixing medical device by attaching Shirasu porous glass Millipore membrane to prepare water-in-oil-in-water (WOW) emulsion in a shorter time to be applied as B-entrapped WOW emulsion for hepatocellular carcinoma (HCC) treatment. Single-dose toxicity studies by intra-arterial injection of BSH-entrapped WOW were performed in rabbits and pig, and no side effects were observed. We hope to proceed to the preclinical and clinical studies for further evaluation of B compound as multidisciplinary treatments for HCC.
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http://dx.doi.org/10.1016/j.apradiso.2020.109202DOI Listing
September 2020

Comorbidity status in hospitalized elderly in Japan: Analysis from National Database of Health Insurance Claims and Specific Health Checkups.

Sci Rep 2019 12 27;9(1):20237. Epub 2019 Dec 27.

Medical Technology Innovation Center, Juntendo University, Tokyo, Japan.

The detailed comorbidity status of hospitalized elderly patients throughout Japan has remained largely unknown; therefore, our goal was to rigorously explore this situation and its implications as of the 2015 fiscal year (from April 2015 to March 2016). This study was based on a health insurance claims database, covering all insured policy holders in Japan aged ≥60 years (male: n = 2,135,049, female: 1,969,019) as of the 2015 fiscal year. Comorbidity status was identified by applying principal factor analysis to the database. The factors identified in male patients were [1] myocardial infarction, hypertension, dyslipidemia, and diabetes mellitus; [2] congestive heart failure (CHF), cardiac arrhythmia, and renal failure; [3] Parkinson's disease, dementia, cerebrovascular disease, and pneumonia; [4] cancer and digestive disorders; and [5] rheumatoid arthritis and hip fracture. However, in female patients, the results obtained for the quaternary and quinary factors were the opposite of those obtained in male patients. In superelderly patients, dementia, cerebrovascular disease, and pneumonia appeared as the tertiary factor, and hip fracture and osteoporosis appeared as the quaternary factor. The comorbidities in the elderly patients suggest the importance of coronary heart disease and its related metabolic disorders; in superelderly patients, fracture and osteoporosis appeared as factors, in addition to dementia and pneumonia.
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http://dx.doi.org/10.1038/s41598-019-56534-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934653PMC
December 2019

Effects of pain neuroscience education in hospitalized patients with high tibial osteotomy: a quasi-experimental study using propensity score matching.

BMC Musculoskelet Disord 2019 Nov 7;20(1):516. Epub 2019 Nov 7.

Faculty of Sports and Health Science, Fukuoka University, Fukuoka, Japan.

Background: Pain neuroscience education (PNE) has been shown to reduce pain or psychological symptoms in patients with chronic pain and preoperative knee osteoarthritis; however, the evidence of its effectiveness in hospitalized patients who have undergone high tibial osteotomy (HTO) is unknown. This study was performed to determine whether the implementation of a newly developed hospital-time PNE provided by physical therapists to patients after HTO can result in meaningful improvements.

Methods: In total, 119 patients aged ≥45 years with knee osteoarthritis who were scheduled to undergo HTO were analyzed. Patients with a low Pain Catastrophizing Scale (PCS) score of < 21 were excluded. The patients were classified into two groups: those who underwent a combination of PNE and rehabilitation (intervention group, n = 67) and those who underwent rehabilitation only (control group, n = 52). The patients were pseudo-randomized by their baseline demographic factors using a propensity score-matching method. The PNE was based on a psychosocial model and began 1 week postoperatively in a group setting; five 1-h weekly sessions were conducted. The primary outcome was the walking pain score as measured by a numerical rating scale. The secondary outcomes were the pain catastrophizing scores as measured by the PCS, self-efficacy as measured by the Pain Self-Efficacy Questionnaire, and physical function. Measurements were taken at baseline (before surgery) and before discharge from the hospital (5 weeks postoperatively) to identify any intervention effects.

Results: After propensity score matching, 52 pairs of patients were extracted. In the intervention group, 46 (88.5%) patients completed the PNE. In total, 44 patients in the intervention group and 52 patients in the control group were analyzed. Five weeks following surgery, the rehabilitation itself had also significantly decreased catastrophizing, and the difference between the two groups had only a small effect size (d = 0.44).

Conclusions: These findings provide preliminary evidence that physical therapist-delivered PNE during hospitalization may help to at least slightly reduce pain catastrophizing in patients with catastrophizing prior to knee arthroplasty.

Trial Registration: This trial was retrospectively registered with ClinicalTrials.gov (UMIN000037114) on 19 June 2019.
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http://dx.doi.org/10.1186/s12891-019-2913-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6839222PMC
November 2019

Bioimaging of Pb and STIM1 in mice liver, kidney and brain using Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS) and immunohistochemistry.

Chemosphere 2020 Jan 12;238:124581. Epub 2019 Aug 12.

Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18 Nishi 9, Kita-ku, Sapporo, 060-0818, Japan. Electronic address:

Lead (Pb) pollution is one of the most serious environmental problems and has attracted worldwide attention. Pb causes hematological, central nervous system, as well as renal toxicity, and so on. Although many investigations about Pb in blood to evaluate pollution status and toxic effects have been reported, there are open question about biological behavior of Pb. In order to reveal any toxicological mechanisms or influences, we focused on the local distribution of Pb in mice organs. Lead acetate (100 mg/L and 1000 mg/L) in drinking water were given to the BALB/c mice (male, seven weeks of age, N = 24) for three weeks. Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS) analysis revealed a homogenous distribution of Pb in the liver and inhomogeneous distribution in the kidney and brain. The hippocampus, thalamus, and hypothalamus had higher concentrations than other areas such as the white matter. Surprisingly, in the kidney, Pb tended to accumulate in the medulla rather than the cortex, strongly suggesting that high sensitivity areas and high accumulation areas differ. Moreover, distribution of stromal interacting protein 1 (STIM1) which is candidate gene of Pb pathway to the cells was homogenous in the liver and kidney whereas inhomogeneous in the brain. In contrast to our hypothesis, interestingly, Pb exposure under the current condition did not induce mRNA expressions for any candidate channel or transporter genes. Thus, further study should be conducted to elucidate the local distribution of Pb and other toxic metals, and pathway that Pb takes to the cells.
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http://dx.doi.org/10.1016/j.chemosphere.2019.124581DOI Listing
January 2020

National burden of the pharmaceutical cost of wet compresses and its cost predictors: nationwide cross-sectional study in Japan.

Health Econ Rev 2019 Jun 29;9(1):20. Epub 2019 Jun 29.

Department of Epidemiology and Environmental Health, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.

Background: Although a high number of wet compresses are prescribed daily in medical institutions in Japan, our understanding of the national burden of the cost of wet compresses and the details regarding their prescription is far from complete. We investigated the national burden of the annual pharmaceutical cost of wet compresses prescribed in Japan and estimated the predictors of this cost using nationwide health insurance claims data.

Methods: We extracted the records on wet compress products from summary table files obtained from the second version of the "NDB Open Data Japan" website and calculated the annual pharmaceutical cost of wet compresses by patients' 5-year age group, sex, and prefecture. We also conducted an ecological study treating each prefecture as an individual unit and multiple linear regression analyses using the age-standardized cost of wet compresses per resident as a dependent variable.

Results: The annual pharmaceutical cost of wet compresses prescribed in Japan in fiscal year 2015 was 149.0 billion Japanese yen (1.18 billion euros; 1.33 billion USD). Multiple linear regression analyses showed that the number of orthopedists and rehabilitation physicians per 100,000 residents were significantly positively associated with the annual pharmaceutical cost of wet compresses per resident (P = 0.042 and P = 0.008, respectively).

Conclusions: The annual pharmaceutical cost of wet compresses prescribed in Japan has a considerable impact on the nation's limited healthcare resources. The number of orthopedists and rehabilitation physicians per 100,000 residents may be independent predictors of the wet compress cost in Japan.
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http://dx.doi.org/10.1186/s13561-019-0238-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6734351PMC
June 2019

Cardiac arrest induced by the intentional ingestion of boric acid and mirtazapine treated by percutaneous cardiopulmonary bypass: a case report.

J Med Case Rep 2019 May 16;13(1):147. Epub 2019 May 16.

Department of Acute Critical Care Medicine, Shizuoka Hospital, Juntendo University, 1129 Nagaoka, Izunokuni City, Shizuoka, 410-2295, Japan.

Background: Mirtazapine has a good tolerability and safety profile that demonstrates several benefits over other antidepressants and it is associated with few fatalities. Boric acid is an odorless white powder that is generally not recognized as a poisonous substance. We report a case of cardiac arrest induced by the intentional ingestion of mirtazapine, boric acid, and sennosides, by a patient who required percutaneous cardiopulmonary bypass.

Case Presentation: Our patient was a 49-year-old Japanese woman with a history of depression; she was found in an unconscious state after ingesting boric acid (unknown amount), mirtazapine (1950 mg), and sennosides (780 mg). On arrival, she was in a deep coma with marked hypotension induced by atrial fibrillation, tachycardia, and diffuse hypokinetic cardiac motion. She had systemic diffuse erythema. Her serum concentrations of boric acid and mirtazapine on arrival were 560.49 mg/L and 1270 ng/mL, respectively. She experienced repeated cardiac arrest, and was therefore treated with tracheal intubation, mechanical ventilation, percutaneous cardiopulmonary bypass, and continuous hemodialysis filtration. Stable circulation and respiration and a normal kidney function were finally obtained and she was transferred to a local medical facility in a persistent unconscious state.

Conclusions: This is the first case of a return of spontaneous circulation after cardiac arrest induced by the intentional ingestion of boric acid and mirtazapine, requiring percutaneous cardiopulmonary bypass for survival. To maintain cerebral perfusion during percutaneous cardiopulmonary bypass, even in a prolonged state of cardiac arrest induced by overdose, is medically, ethically, and economically challenging.
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http://dx.doi.org/10.1186/s13256-019-2079-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521468PMC
May 2019

For making a declaration of countermeasures against the falling birth rate from the Japanese Society for Hygiene: summary of discussion in the working group on academic research strategy against an aging society with low birth rate.

Environ Health Prev Med 2019 Mar 5;24(1):14. Epub 2019 Mar 5.

Department of Hygiene, Kawasaki Medical School, Okayama, Japan.

In 1952, the Japanese Society for Hygiene had once passed a resolution at its 22nd symposium on population control, recommending the suppression of population growth based on the idea of cultivating a healthier population in the area of eugenics. Over half a century has now passed since this recommendation; Japan is witnessing an aging of the population (it is estimated that over 65-year-olds made up 27.7% of the population in 2017) and a decline in the birth rate (total fertility rate 1.43 births per woman in 2017) at a rate that is unparalleled in the world; Japan is faced with a "super-aging" society with low birth rate. In 2017, the Society passed a resolution to encourage all scientists to engage in academic researches to address the issue of the declining birth rate that Japan is currently facing. In this commentary, the Society hereby declares that the entire text of the 1952 proposal is revoked and the ideas relating to eugenics is rejected. Since the Society has set up a working group on the issue in 2016, there have been three symposiums, and working group committee members began publishing a series of articles in the Society's Japanese language journal. This commentary primarily provides an overview of the findings from the published articles, which will form the scientific basis for the Society's declaration. The areas we covered here included the following: (1) improving the social and work environment to balance between the personal and professional life; (2) proactive education on reproductive health; (3) children's health begins with nutritional management in women of reproductive age; (4) workplace environment and occupational health; (5) workplace measures to counter the declining birth rate; (6) research into the effect of environmental chemicals on sexual maturity, reproductive function, and the children of next generation; and (7) comprehensive research into the relationship among contemporary society, parental stress, and healthy child-rearing. Based on the seven topics, we will set out a declaration to address Japan's aging society with low birth rate.
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http://dx.doi.org/10.1186/s12199-019-0768-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6402135PMC
March 2019

Risk factors for occupational accidents in agricultural enterprises in Japan.

Ind Health 2019 Sep 13;57(5):627-636. Epub 2019 Feb 13.

Department of Epidemiology and Environmental Health, Juntendo University Faculty of Medicine, Japan.

In Japan, the agricultural working environment has undergone significant changes from self-employment to enterprises and employees. As the structure of the agricultural industry changes, there has been a growing interest in occupational health and safety because agriculture is a hazardous industry. However, the public is not aware of the actual situation regarding occupational accidents in agricultural enterprises because most Japanese farmers are not necessarily required to report occupational accidents. The aim of this study is to explore the risk factors regarding occupational accidents for Japanese agricultural employees. We conducted a cross-sectional study among 1,606 employees at 101 agricultural enterprises in Japan. Information on occupational accidents, personal characteristics, and working conditions was collected by questionnaires. A total of 337 valid responses were obtained. Of these respondents, 104 (30.9%) experienced occupational accidents. Multiple logistic regression analysis revealed that permanent employment (OR 3.67, 95% CI, 1.84-7.33), pesticide use (OR 2.61, 95% CI, 1.52-4.47), and long working hours (OR 1.76, 95% CI, 1.15-2.68) were associated with the risk of occupational accidents. This study revealed the risk factors for occupational accidents for Japanese agricultural employees. It is suggested that work-hour restrictions for permanent employees might contribute to reducing occupational accidents.
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http://dx.doi.org/10.2486/indhealth.2017-0218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6783292PMC
September 2019

Harmonizing work with diseases treatment and prevention.

Ind Health 2019;57(1):1-2

Guest editor, University of Occupational and Environmental Health, Japan.

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http://dx.doi.org/10.2486/indhealth.57_100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6363586PMC
July 2019

Hospital-based screening to detect patients with cadmium nephropathy in cadmium-polluted areas in Japan.

Environ Health Prev Med 2019 Jan 26;24(1). Epub 2019 Jan 26.

Department of Internal Medicine, Akita Rosai Hospital, Japan Organization of Occupational Health and Safe, Akita, 018-5604, Japan.

Background: In health examinations for local inhabitants in cadmium-polluted areas, only healthy people are investigated, suggesting that patients with severe cadmium nephropathy or itai-itai disease may be overlooked. Therefore, we performed hospital-based screening to detect patients with cadmium nephropathy in two core medical institutes in cadmium-polluted areas in Akita prefecture, Japan.

Methods: Subjects for this screening were selected from patients aged 60 years or older with elevated serum creatinine levels and no definite renal diseases. We enrolled 35 subjects from a hospital in Odate city and 22 from a clinic in Kosaka town. Urinary ß-microglobulin and blood and urinary cadmium levels were measured.

Results: The criteria for renal tubular dysfunction and the over-accumulation of cadmium were set as a urinary ß-microglobulin level higher than 10,000 μg/g cr. and a blood cadmium level higher than 6 μg/L or urinary cadmium level higher than 10 μg/g cr., respectively. Subjects who fulfilled both criteria were diagnosed with cadmium nephropathy. Six out of 57 patients (10.5% of all subjects) had cadmium nephropathy.

Conclusions: This hospital-based screening is a very effective strategy for detecting patients with cadmium nephropathy in cadmium-polluted areas, playing a complementary role in health examinations for local inhabitants.

Registration Number: No. 6, date of registration: 6 June, 2010 (Akita Rosai Hospital), and No. 1117, date of registration: 26 December, 2013 (Akita University).
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http://dx.doi.org/10.1186/s12199-019-0762-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6347770PMC
January 2019

Characterization and imaging of lead distribution in bones of lead-exposed birds by ICP-MS and LA-ICP-MS.

Chemosphere 2018 Dec 31;212:994-1001. Epub 2018 Aug 31.

Laboratory of Toxicology, Department of Environmental Veterinary Sciences, School of Veterinary Medicine, Hokkaido University, Sapporo, Kita18, Nishi9, Kita-ku, Sapporo, Hokkaido 060-0818, Japan. Electronic address:

Lead (Pb) poisoning in raptors and water birds is a serious problem in many countries. However, only a small fraction of Pb poisoning has been detected in birds. Bone specimens may be useful indices of Pb exposure because bones contain ∼90% of the total Pb body burden. The original purpose of this study was to comprehensively analyze Pb accumulation in various bone types using inductively coupled plasma-mass spectrometry (ICP-MS). Since our results showed that Pb accumulation differed greatly depending on bone type, a secondary objective was defined, aiming to investigate the fine Pb distribution and its relation to bone structure and bone marrow by using laser ablation (LA)-ICP-MS. Our findings suggested that bone samples (1) consisting of trabecular tissue and (2) those that contain bone marrow could accumulate high levels of Pb following acute exposure. The shorter turnover time of trabecular bone can cause a rapid accumulation of Pb, and bone marrow may have an important role for internal exposure of Pb to bone tissue. Pb is accumulated in bones via blood flow, and bone marrow receives blood from outside the bones. In conclusion, bone samples provide valuable information on Pb exposure and could be useful to investigate and understand mortalities related to suspected Pb poisoning.
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http://dx.doi.org/10.1016/j.chemosphere.2018.08.149DOI Listing
December 2018

[Socioeconomic Factors and Policies Regarding Declining Birth Rates in Japan].

Nihon Eiseigaku Zasshi 2018 ;73(3):305-312

Department of Epidemiology and Environmental Health, School of Medicine, Juntendo University.

The factors contributing to the declining birthrate in Japan include the declining marriage rate, an increase in the average age of those getting married, economic burden, childcare burden, later child-bearing, and infertility. There is a gender difference in role division, with 70% of unmarried people live with their parents and continue to work while leaving the household chores to their mothers. The loss of these housekeeping services and the increase in the number of irregular workers are factors contributing to the declining marriage rate and the increase in the average age of those getting married. The expansion of the family support policy in Japan from the male breadwinner model to the earner-career model may have been delayed, but it is expected to provide economic benefits as well as actual childcare service benefits in order to reduce the economic and physical burden of childcare for married couples. It is also necessary to provide education in reproductive health to both men and women in schools and workplaces regarding late child-bearing and infertility. Furthermore, it is necessary to evaluate the cost-effectiveness analysis of improvements in fertility and disclose the relevant information in addition to sharing information on medical technology related to pregnancy/childbirth and treatment of diseases. It is urgent to prepare society for natural and healthy pregnancies/childbirths during optimal child-bearing years.
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http://dx.doi.org/10.1265/jjh.73.305DOI Listing
October 2018

Results of a nationwide epidemiologic survey of autosomal recessive congenital ichthyosis and ichthyosis syndromes in Japan.

J Am Acad Dermatol 2019 Nov 26;81(5):1086-1092.e1. Epub 2018 Sep 26.

Department of Dermatology and Allergology, Juntendo University Graduate School of Medicine, Tokyo, Japan.

Background: Autosomal recessive congenital ichthyosis (ARCI) and ichthyosis syndrome (IS) are rare genetic skin disorders.

Objective: To estimate the number of patients with ARCI and IS in Japan and clarify the clinicoepidemiologic features of these diseases.

Methods: We performed a nationwide survey of patients treated for ARCI or IS during January 2005-December 2009. We developed diagnostic criteria and conducted a primary survey in a stratified random sample of Japanese hospitals to quantify the number of outpatients and inpatients with ARCI or IS. We performed a secondary survey of clinicoepidemiologic features in positive cases.

Results: The estimated number of patients receiving treatment for ARCI and IS during 2005-2009 was 220 (95% confidence interval [CI] 180-260). The estimated disease distribution was as follows: 95 (95% CI 80-110) patients with nonbullous congenital ichthyosiform erythroderma, 30 (95% CI 20-40) with lamellar ichthyosis, 15 (95% CI 10-20) with harlequin ichthyosis, and 85 (95% CI 50-120) with IS.

Limitations: Patients with a mild case of the disease might not have visited a dermatology department, potentially causing underestimation of affected patients.

Conclusion: We report the estimated number of patients with ARCI and IS in Japan and sex differences in the age distribution.
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http://dx.doi.org/10.1016/j.jaad.2018.07.056DOI Listing
November 2019

Changes in thallium distribution in the scalp hair after an intoxication incident.

Forensic Sci Int 2018 Oct 5;291:230-233. Epub 2018 Sep 5.

Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. Electronic address:

In cases of criminal thallium poisoning, forensic investigation is required to identify the amount and time of thallium exposure. Usually, blood and urine thallium levels are respectively used as biomarkers. Additionally, hair has the unique potential to reveal retrospective information. Although several studies have attempted to clarify how thallium is distributed in hair after thallium poisoning, none have evaluated the time course of changing thallium distribution. We investigated changes in the distribution of thallium in hair at different time points after exposure in five criminal thallotoxicosis patients. Scalp hair samples were collected twice, at 2.6 and 4.2-4.5months after an exposure incident by police. Results of our segmented analysis, a considerable amount of thallium was detected in almost all hair sample segments. The thallium exposure date estimated from both hair sample collections matched the actual exposure date. We found that determination of thallium amounts in hair samples divided into consecutive segments provides valuable information about exposure period even if a considerable time passes after exposure. Moreover, when estimating the amount of thallium exposure from a scalp hair sample, it is necessary to pay sufficient attention to individual differences in its decrease from hair.
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http://dx.doi.org/10.1016/j.forsciint.2018.08.019DOI Listing
October 2018

Changes in thallium distribution in the scalp hair after an intoxication incident.

Forensic Sci Int 2018 Oct 5;291:230-233. Epub 2018 Sep 5.

Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. Electronic address:

In cases of criminal thallium poisoning, forensic investigation is required to identify the amount and time of thallium exposure. Usually, blood and urine thallium levels are respectively used as biomarkers. Additionally, hair has the unique potential to reveal retrospective information. Although several studies have attempted to clarify how thallium is distributed in hair after thallium poisoning, none have evaluated the time course of changing thallium distribution. We investigated changes in the distribution of thallium in hair at different time points after exposure in five criminal thallotoxicosis patients. Scalp hair samples were collected twice, at 2.6 and 4.2-4.5months after an exposure incident by police. Results of our segmented analysis, a considerable amount of thallium was detected in almost all hair sample segments. The thallium exposure date estimated from both hair sample collections matched the actual exposure date. We found that determination of thallium amounts in hair samples divided into consecutive segments provides valuable information about exposure period even if a considerable time passes after exposure. Moreover, when estimating the amount of thallium exposure from a scalp hair sample, it is necessary to pay sufficient attention to individual differences in its decrease from hair.
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http://dx.doi.org/10.1016/j.forsciint.2018.08.019DOI Listing
October 2018

[Effects of Trace Environmental Chemicals on Child Health-Lead as an Example].

Nihon Eiseigaku Zasshi 2018 ;73(2):210-214

Department of Epidemiology and Environmental Health, Juntendo University Graduate School of Medicine.

The low birthrate and aging population of Japan are entering a serious phase. As measures against the declining birthrate, improvement of the environment is promoted to support childbirth and child-rearing, but even if the birthrate increases in the future, it will take time before the effect is observed as an increase in the population. As the number of children and young people is decreasing, in order to maintain a wealthy and sustainable society, we should create an environment wherein each child can grow healthily and demonstrate sufficient abilities in participating in society. The authors have been studying the influence of exposure to environmental chemical substances on the development of children. Lead is especially considered to impair neurological development even at low concentrations of exposure. In this paper, using lead as an example, we discuss risk assessment and countermeasures for the health effects of trace chemical substances on a society with a declining birthrate. Substances that show neurotoxicity increase social costs even at low concentrations of exposure. To preserve and promote social vitality in Japan despite the declining birthrate and aging population, it is essential that measures are taken on the basis of scientifically reasonable cost/benefit assessment. For this purpose, we think that it is necessary to analyze costs and benefits in addition to the risk assessment of low concentrations of chemical substances.
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http://dx.doi.org/10.1265/jjh.73.210DOI Listing
August 2018

[Solutions against Declining Birthrates Confronting Japan's Aging Society by Supporting Female Workers in Harmonizing Work with Their Health and Social Issues: Fertility, Chronic Illness, and Raising Children].

Nihon Eiseigaku Zasshi 2018 ;73(2):200-209

Department of Public Health, Juntendo University Faculty of Medicine.

Japan is currently facing serious social problems related to low birth rates and aging. We propose two possible solutions from the perspective of occupational health. First, companies should establish support systems to help working women with pregnancy and childbirth. Such systems would require the cooperation and understanding of coworkers, including men, and the introduction of flexible work schedules that are also designed to allow workers to care for family members with disabilities. Additionally, with regard to the protection and promotion of the fertility of working women, occupational health staff members should provide education to working women regarding appropriate lifestyle choices in areas such as diet, prevention of work-related health problems, and mental health before and after childbirth. Moreover, workers undergoing assisted reproductive technology procedures should be supported as they experience physical, mental, and economic burdens associated with this process. Second, companies should guarantee the right of workers to take a sick leave and then return to work so they can balance work and the need to treat chronic conditions. Occupational staff members should follow up employees who return to work, by offering, for example, mental health care to cancer survivors. They should also play important roles in preventing the exacerbation of disease and empowering workers to continue their visits to medical institutions. Collaborative study bridges between companies and medical institutions are necessary for the promotion of these harmonization schemes.
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http://dx.doi.org/10.1265/jjh.73.200DOI Listing
August 2018

Employment sustainability after return to work among Japanese stroke survivors.

Int Arch Occup Environ Health 2018 08 25;91(6):717-724. Epub 2018 May 25.

Department of Public Health, Tokyo Women's Medical University, Tokyo, 162-8666, Japan.

Purpose: Few studies have investigated the work continuance rate among stroke survivors who return to work (RTW). The objective of this study was to investigate work sustainability after RTW and the causes of recurrent sickness absence (RSA) among Japanese stroke survivors.

Methods: Data on stroke survivors were collected from an occupational health register. The inclusion criteria were as follows: employees who were aged 15-60 years old and returned to work after an episode of sick leave due to a clinically certified stroke that was diagnosed during the period from 1 January 2000 through 31 December 2011.

Results: 284 employees returned to work after their first episode of stroke-induced sick leave. The work continuance rate for all subjects was 78.8 and 59.0% at one and 5 years after the subjects' RTW, respectively. After returning to work, the subjects worked for a mean of 7.0 years. Of 284 employees who returned to work, 86 (30.3%) experienced RSA. The RSA were caused by recurrent strokes in 57.0% (49/86) of cases, mental disorders in 20.9% (18/86) of cases, and fractures (often due to accidents involving steps at train stations or the subject's home) in 10.5% (9/86) of cases. 21 employees resigned after returning to work. The resignation rates at 1 and 5 years were 4.9 and 7.6%, respectively. According to the multivariate analysis including all variables, the subjects in the ≥ 50 year group were at greater risk of work discontinuation than the ≤ 49 year (reference) age group (HR: 2.26, 95% CI 1.39-3.68).

Conclusions: Occupational health professionals need to provide better RTW support to stroke survivors and should pay particularly close attention to preventing recurrent strokes, mental disorders, and fractures.
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http://dx.doi.org/10.1007/s00420-018-1319-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6060773PMC
August 2018

Prenatal mercury exposure and birth weight.

Reprod Toxicol 2018 03 31;76:78-83. Epub 2018 Jan 31.

Department of Epidemiology and Environmental Health, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. Electronic address:

Adverse effects of prenatal mercury exposure on pregnancy outcomes remain a public health concern. We assessed the relationship between prenatal mercury exposure and newborn anthropometric characteristics in 334 mother-child pairs from the early stages of pregnancy to delivery in Tokyo, Japan, between December 2010 and October 2012. We found a negative correlation between blood mercury levels during the first and second trimesters of gestation and birth weight (r = -0.134 and -0.119, respectively; p < 0.05). Multiple linear regression analysis confirmed the relationship between first-trimester maternal blood mercury levels and birth weight when adjusted for independent variables (β = -0.170, t = -2.762; p = 0.006). Mean mercury levels in umbilical cord blood were twice as high as maternal blood levels (10.15 ± 7.74 and 4.97 ± 3.25 μg/L, respectively; r = 0.974, p < 0.001). Our findings suggest that pregnant women and women of reproductive age should avoid mercury exposure, even at low levels, because of its potentially adverse effects on fetal development.
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http://dx.doi.org/10.1016/j.reprotox.2018.01.002DOI Listing
March 2018

Information exchange using a prescribed form and involvement of occupational health nurses promotes occupational physicians to collaborate with attending physicians for supporting workers with illness in Japan.

Ind Health 2019 Feb 19;57(1):10-21. Epub 2017 Dec 19.

Department of Public Health, Tokyo Women's Medical University, Japan.

The maintenance of a balance between work and disease treatment is an important issue in Japan. This study explored factors that affect collaboration between occupational physicians (OPs) and attending physicians (APs). A questionnaire was mailed to 1,102 OPs. The questionnaire assessed the demographic characteristics of OPs; their opinions and behaviors related to collaboration, including the exchange of medical information with APs; and the occupational health service system at their establishments. In total, 275 OPs completed the questionnaire (25.0% response rate). Over 80% of respondents believed OPs should collaborate with APs. After adjusting for company size, collaboration ≥10 times/yr (with regard to both returning to work following sick leave and annual health check-ups for employees) was significantly associated with environmental factors, such as the presence of occupational health nurses (odds ratio (OR): 5.56 and 5.01, respectively, p<0.05) and the use of prescribed forms for information exchange (OR: 4.21 and 3.63, respectively, p<0.05) but not with the demographic characteristics of the OPs (p>0.05). The majority of OPs believed that collaboration with APs is important for supporting workers with illnesses. Support systems including prescribed forms of information exchange and occupational health nurses, play pivotal roles in promoting this collaboration.
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http://dx.doi.org/10.2486/indhealth.2017-0133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6363580PMC
February 2019

Discrepancies Between the Supports Needed for Discharge of Patients With Terminal Cancer to Family Caregivers and What Supports Were Actually Provided in Japan: Assessment of Palliative Care Unit Nurses.

Am J Hosp Palliat Care 2018 Apr 26;35(4):704-711. Epub 2017 Nov 26.

4 Yokohama Municipal Citizen's Hospital, Hodogaya-ku, Yokohama, Japan.

Objectives: Even if patients with terminal cancer hope to spend the rest of their lives at home, they are often unable to leave the hospital early due to their family caregivers' anxiety. This study aimed to investigate in Japan the discrepancies between the supports needed by and actually provided by palliative care unit nurses (PCUNs) to the family caregivers for discharge of patients with terminal cancer.

Methods: In this cross-sectional study, self-administered questionnaires including 6-point Likert-type scales assessing the reasons for difficulties in transition to home-based care were distributed to 1227 PCUNs. Using paired t tests, the differences between the scores on perceived importance and actual supports to family caregivers were examined. The supports actually provided were classified by factor analysis. The relationships between the PCUNs' characteristics and mean scores on the supports in each category were examined using multiple regression analysis.

Results: A total of 1023 (83.4%) completed questionnaires were returned. Scores on the actually provided supports for discharge to family caregivers were consistently and significantly lower than the corresponding scores on perceived importance for all 57 items ( P < .001). Factor analysis revealed that the supports actually provided to the family caregivers had a 4-factor structure. Multiple regression analyses revealed that gaining experience in palliative care, receiving necessary training, cooperating with palliative care staff, and cooperating with local service providers were significantly associated with higher levels of actual supply of supports to family caregivers.

Conclusion: Our findings suggest that PCUNs need to be encouraged to provide further support to family caregivers for the discharge of patients with terminal cancer.
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http://dx.doi.org/10.1177/1049909117741586DOI Listing
April 2018

Leisure-time physical activity in youth as a predictor of adult leisure physical activity among Japanese workers: a cross-sectional study.

Environ Health Prev Med 2017 Apr 7;22(1):37. Epub 2017 Apr 7.

Department of Epidemiology and Environmental Health, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.

Background: Workers in Japan are not sufficiently active; however, it remains unclear how their leisure-time physical activity habits may be developed. This cross-sectional study investigated the relationship of age- and intensity-specific leisure-time physical activity in youth to adulthood leisure-time physical activity habits among Japanese workers.

Methods: In 2012, 968 workers (333 males and 635 females) from three companies and six hospitals in the Tokai region of Japan agreed to complete and submit a self-administered questionnaire. Intensity-specific leisure-time physical activity at ages 12 and 20 years was assessed retrospectively, and workers' current participation in regular leisure-time physical activity was assessed as an outcome measure. Multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression analysis.

Results: Mean ages for males and females were 40 and 37 years, respectively. Strenuous leisure-time physical activity at age 12 years was significantly positively associated with adulthood participation in leisure-time physical activity among male workers [adjusted OR (95% CI) = 2.29 (1.02, 5.14)]. Additionally, both strenuous and moderate physical activity at age 20 years was significantly positively associated with participation in regular leisure-time physical activity in adulthood among males and females.

Conclusions: Our results suggest that some leisure-time physical activity in youth may predict adult workers' participation in regular leisure-time physical activity in Japan. Encouragement of leisure-time physical activity in youth could therefore be an effective measure to develop adult leisure-time physical activity habits among workers.
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http://dx.doi.org/10.1186/s12199-017-0648-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5664430PMC
April 2017
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