Human-mouse comparison of the multistage nature of radiation carcinogenesis in a mathematical model.

Mouse models are vital for assessing risk from environmental carcinogens, including ionizing radiation, yet the interspecies difference in the dose response precludes direct application of experimental evidence to humans. Herein, we take a mathematical approach to delineate the mechanism underlying the human-mouse difference in radiation-related cancer risk. We used a multistage carcinogenesis model assuming a mutational action of radiation to analyze previous data on cancer mortality in the Japanese atomic bomb survivors and in lifespan mouse experiments. Theoretically, the model predicted that exposure will chronologically shift the age-related increase in cancer risk forward by a period corresponding to the time in which the spontaneous mutational process generates the same mutational burden as that the exposure generates. This model appropriately fitted both human and mouse data and suggested a linear dose response for the time shift. The effect per dose decreased with increasing age at exposure similarly between humans and mice on a per-lifespan basis (0.72- and 0.71-fold, respectively, for every tenth lifetime). The time shift per dose was larger by two orders of magnitude in humans (7.8 and 0.046 years per Gy for humans and mice, respectively, when exposed at ~35% of their lifetime). The difference was mostly explained by the two orders of magnitude difference in spontaneous somatic mutation rates between the species plus the species-independent radiation-induced mutation rate. Thus, the findings delineate the mechanism underlying the interspecies difference in radiation-associated cancer mortality and may lead to the use of experimental evidence for risk prediction in humans.

Temporal changes in cumulative mortality risks of cancer, by occupation, in the working population of Japan from 1995 to 2020: a benchmark for radiation risk comparison.

The purpose of this study was to provide benchmark data for discussing the tolerability of cancer risk associated with occupational radiation exposure. It focused on differences in cancer mortality risk by occupation among Japan's working population and examined baseline cancer mortality risks and its variations from 1995 through 2020. Data were collected every five years from national vital statistics sources. By focusing on the same types of cancer among radiation induced effects, cumulative mortality risks were calculated for colorectal, lung, and breast cancer (females only) for those aged 15-74. The average cumulative mortality risk for the working population in Japan has decreased by 30%-60% over the past 25 years. Service workers and male managers were at an average risk, among all workers, while clerical workers and transportation and manufacturing workers had about half the average risk. The risks were higher for professionals and female managers, about 1.5-2 times the average for professionals and up to 5 times the average for female managers. The decrease in the average cancer mortality risk in the working population as a baseline suggests that risk tolerance in society might have changed over time. Since differences in mortality by occupation were confirmed, the usefulness of occupational data as a benchmark needs further investigation, as high-risk/low-risk occupations vary by country and region. The results of this study contribute to put radiation risks into perspective with the background risk of cancer.

Comparison of lifetime mortality risk, incidence risk, and DALYs of baseline cancer rates among countries as a benchmark for radiation-related cancer risk.

Statistical benchmark data are necessary when considering the basis for radiation protection criteria based on calculated risks. We herein focused on baseline mortality and incidence cancer rates as benchmark data collected from 33 countries. Furthermore, we calculated the lifetime mortality and incidence risks and disability-adjusted life years (DALYs) for all solid cancers, colon cancer, lung cancer, breast cancer, thyroid cancer, and leukemia using the baseline cancer rates and compared them among the countries. The results showed that the lifetime mortality and incidence risks and DALYs for all solid cancers differed among the countries by a factor of 2-4 for males and 2-3 for females; these were low in less-developed countries. Our study proposed that health risk based on baseline cancer rates should be the benchmark for comparing radiation cancer risks.

Evaluation of the lifetime brain/central nervous system cancer risk associated with childhood head CT scanning in Japan.

The use of computed tomography (CT) scanning has increased worldwide over the decades, and Japan is one of the leading countries in annual frequency of diagnostic CT. Although benefits of CT scan are undisputable, concerns have been raised about potential health effects of ionizing radiation exposure from CT, particularly among children who are likely more susceptible to radiation than adults. Our study aims to evaluate the cumulated lifetime risk of the brain/central nervous system (CNS) cancer due to head CT examinations performed on Japanese children at age 0 to 10 years in 2012, 2015 and 2018. The frequency and dose distribution of head CT examinations were estimated based on information from recent national statistics and nationwide surveys. The lifetime risk attributable to exposure was calculated by applying risk models based on the study of Japanese atomic-bomb survivors. In contrast to the overall increasing trend, the frequency of childhood CT, especially at age < 5, was decreasing, reflecting a growing awareness for efforts to reduce childhood CT exposure over the past decade. In 2018, 138 532 head CT examinations were performed at age 0 to 10, which would consequently induce a lifetime excess of 22 cases (1 per 6300 scans) of brain/CNS cancers, accounting for 5% of the total cases. More excess cases were estimated among men than among women, and excess cases could emerge at relatively young ages. These results would have useful implications as scientific basis for future large-scale epidemiological studies and also as quantitative evidence to justify the benefits of CT vs risks in Japan.

Clinical indications for the use of computed tomography in children who underwent frequent computed tomography: a near-13-year follow-up retrospective study at a single institution in Japan.

Recent studies suggest a causal link of childhood leukemia and brain tumor with repeated computed tomography (CT) scans. The reasons why frequent CT scans are taken in a specific child remain unclear. The present study aimed to clarify the medical reasons why frequent CT examinations in children, and the characteristics of the diseases of those children that required multiple CT scans. A long-term follow-up retrospective study was conducted over a 12.75-year period at a single institution. Radiological reports were investigated that contained the indications for the CT scans. The clinical indications were classified for the examination of children under 16 years of age who underwent more than three CT scans into trauma, tumor, inflammation, and others. This study showed that 8.5% of CT examinations were done three times or more. The numbers of patients by indication were 23.3% for trauma, 5.3% for hydrocephalus, and 2.3% for appendicitis. The frequencies of trauma and inflammation decreased rapidly with an increasing number of CT scans. In particular, hydrocephalus brought high frequency more than ten scans. Regarding the frequencies of clinical indications by age groups, there was a significant difference (p<0.05). The near-13-year follow-up study indicated the main clinical indications for frequent CT scans in children were trauma and hydrocephalus. Multiple follow-up CT scans in children with hydrocephalus would be traded off against the resultant increase in brain tumor risk associated with CT exposure.

Report of the Japan Health Physics Society ad hoc working group for the Plutonium intake accident.

This paper describes an overview of the radiation protection response to the Plutonium intake accident that occurred at the Plutonium Fuel Facility of the Oarai Research and Development Center of the Japan Atomic Energy Agency on 6 June 2017. In the hood of the analyzing room at the Plutonium Fuel Facility five workers were checking a storage container of fast reactor nuclear fuel material. Around 11:15 a.m., vinyl bags inside the fuel material container containing Plutonium and enriched uranium burst during the inspection work. All the workers heard the bang, which caused misty dust leakage from the container. This event caused significant both skin and nasal α-contamination for three workers and just skin α-contamination for one worker. Decontamination was conducted in the shower room. Then the five workers were transferred to the Nuclear Fuel Cycle Engineering Laboratory to evaluate inhalation intake of Plutonium etc in the lungs. The maximum values of 2.2 × 104 Bq for 239Pu and 2.2 × 102 Bq for 241Am were estimated by the lung monitor. Based on these results, injection of a chelate agent was conducted for prompt excretion of Plutonium etc. The next morning, the five workers were transferred to the National Institute of Radiological Sciences for treatment including decontamination of their skin and measurement by a lung monitor. At that time no obvious energy peak was confirmed for Plutonium. The Japan Health Physics Society launched an ad-hoc working group for Plutonium intake accident around the middle of June to survey issues and to extract lessons for radiological protection. The authors, who are the members of the ad-hoc working group, here report the activity of the working group.

Internal doses from radionuclides and their health effects following the Fukushima accident.

This paper presents an overview of current internal dose estimates from the Fukushima accident, potential population specific uncertainties in these estimates are investigated, along with the relative effects of internal and external exposures. Thyroid doses were largely due to 131I, but variations in thyroid weight and fractional uptake and retention times of 131I in the thyroid contribute to uncertainties in thyroid dose estimates. Lower values for these parameters in the Japanese population, as compared to international reference assumptions, would lead to underestimation of doses on the basis of reference thyroid weights and overestimation of doses using reference thyroid uptake and retention times. Any overall bias in thyroidal doses due to population specific factors is the net result of the balance between these effects. Internal doses to other organs are largely due to 134Cs and 137Cs and their whole body distribution, population specific differences in these dose estimates are driven by average body mass, due to the inverse relationship between this and retention times. Potential differences in dose estimates and any inferred risks, due to local population specific factors, may be less than a factor of two for children and male adults, but the potential difference may be slightly underestimated for female adults. Recent micro-dosimetric studies have confirmed the existing perception that risk from internal exposures to 137Cs, 134Cs, and 131I should be nearly equivalent to that from external exposure to gamma rays at the same absorbed dose. Epidemiological studies provide comparisons between external and internal exposures to 131I in children and suggest that effects of internal exposure are similar to those of external exposure. Effective dose has been formulated to harmonise internal and external exposure risks for radiation protection purposes. On the basis of this review, the use of effective dose in this context does not seem to be unreasonable.

Dose and dose-rate effects of ionizing radiation: a discussion in the light of radiological protection.

The biological effects on humans of low-dose and low-dose-rate exposures to ionizing radiation have always been of major interest. The most recent concept as suggested by the International Commission on Radiological Protection (ICRP) is to extrapolate existing epidemiological data at high doses and dose rates down to low doses and low dose rates relevant to radiological protection, using the so-called dose and dose-rate effectiveness factor (DDREF). The present paper summarizes what was presented and discussed by experts from ICRP and Japan at a dedicated workshop on this topic held in May 2015 in Kyoto, Japan. This paper describes the historical development of the DDREF concept in light of emerging scientific evidence on dose and dose-rate effects, summarizes the conclusions recently drawn by a number of international organizations (e.g., BEIR VII, ICRP, SSK, UNSCEAR, and WHO), mentions current scientific efforts to obtain more data on low-dose and low-dose-rate effects at molecular, cellular, animal and human levels, and discusses future options that could be useful to improve and optimize the DDREF concept for the purpose of radiological protection.

Radiological protection issues arising during and after the Fukushima nuclear reactor accident.

Following the Fukushima accident, the International Commission on Radiological Protection (ICRP) convened a task group to compile lessons learned from the nuclear reactor accident at the Fukushima Daiichi nuclear power plant in Japan, with respect to the ICRP system of radiological protection. In this memorandum the members of the task group express their personal views on issues arising during and after the accident, without explicit endorsement of or approval by the ICRP. While the affected people were largely protected against radiation exposure and no one incurred a lethal dose of radiation (or a dose sufficiently large to cause radiation sickness), many radiological protection questions were raised. The following issues were identified: inferring radiation risks (and the misunderstanding of nominal risk coefficients); attributing radiation effects from low dose exposures; quantifying radiation exposure; assessing the importance of internal exposures; managing emergency crises; protecting rescuers and volunteers; responding with medical aid; justifying necessary but disruptive protective actions; transiting from an emergency to an existing situation; rehabilitating evacuated areas; restricting individual doses of members of the public; caring for infants and children; categorising public exposures due to an accident; considering pregnant women and their foetuses and embryos; monitoring public protection; dealing with 'contamination' of territories, rubble and residues and consumer products; recognising the importance of psychological consequences; and fostering the sharing of information. Relevant ICRP Recommendations were scrutinised, lessons were collected and suggestions were compiled. It was concluded that the radiological protection community has an ethical duty to learn from the lessons of Fukushima and resolve any identified challenges. Before another large accident occurs, it should be ensured that inter alia: radiation risk coefficients of potential health effects are properly interpreted; the limitations of epidemiological studies for attributing radiation effects following low exposures are understood; any confusion on protection quantities and units is resolved; the potential hazard from the intake of radionuclides into the body is elucidated; rescuers and volunteers are protected with an ad hoc system; clear recommendations on crisis management and medical care and on recovery and rehabilitation are available; recommendations on public protection levels (including infant, children and pregnant women and their expected offspring) and associated issues are consistent and understandable; updated recommendations on public monitoring policy are available; acceptable (or tolerable) 'contamination' levels are clearly stated and defined; strategies for mitigating the serious psychological consequences arising from radiological accidents are sought; and, last but not least, failures in fostering information sharing on radiological protection policy after an accident need to be addressed with recommendations to minimise such lapses in communication.

Effect of standard skin care treatments on skin barrier function in X-irradiated hairless mice.

Objective: The effectiveness of skin care to radiation dermatitis (RD) on patients who received radiotherapy for cancer has not been clarified. The purpose of this study was to investigate the effect of moisturizers and skin washing on skin barrier function possibly leading to the development of RD using X-ray irradiated hairless mice. Methods: Nine-week-old hairless mice were irradiated with 10 â€‹Gy of X-rays, and the skin care group had moisturizers applied or skin washing with soap from the day of irradiation during observations. The condition of the skin was observed to evaluate RD. Skin barrier function was evaluated by measuring skin temperature and transepidermal water loss (TEWL) once every two days until 25 days after X-ray irradiation. Results: RD was not observed in all groups until 25 days after X-ray irradiation. Skin temperature tended to increase in all groups regardless of irradiation or skin care. However, unlike the control group, the measured value of TEWL in the no skin care group tended to increase in the days after the X-ray irradiation. On the other hand, TEWL was increased in the skin care group compared with the no skin care group a few days after X-ray irradiation. While TEWL was constant in the moisturizer group, the skin washing groups showed an increasing tendency of TEWL and it reached a peak at 13 days after X-ray irradiation. Conclusions: These results suggested that the decrease in skin barrier function was caused by X-ray irradiation and also that skin washing could contribute to the deterioration of skin barrier function after X-ray irradiation.

Quantitative Analysis of the Clinical Reasons Influencing the Frequency of Pediatric Head CT Examinations: A Single-Center Observation Study.

Epidemiological studies on radiation exposure from pediatric CT scans have attracted attention in terms of radiological protection. These studies have not taken into account the reasons why CT examinations were performed. It is presumed that there are clinical reasons that justify more frequent CT examinations in children. The purpose of this study was to characterize the clinical reasons why relatively high numbers of head CT examinations (NHCT) are frequently performed and to conduct a statistical analysis to determine the factors governing the NHCT. Patient information, the date of examination, and medical conditions for examination data stored on the radiology information system were used to investigate the reasons for undergoing CT examinations. The target facility was National Children's Hospital; data were obtained from March 2002 to April 2017, and the age of the study population was less than 16 years old. Quantitative analysis of the factors associated with frequent examinations was conducted by Poisson regression analysis. Among all patients who had a CT scan, 76.6% had head CT examinations, and 43.4% of children were under 1 year old at the time of the initial examination. There were marked differences in the number of examinations depending on the disease. The average NHCT was higher for children younger than 5 days of age. Among children less than 1 year of age with surgery, there was a marked difference between hydrocephalus, with a mean = 15.5 (95% CI 14.3,16.8), and trauma, with a mean = 8.3 (95% CI 7.2,9.4). In conclusion, this study revealed that NHCT was significantly higher in children who had undergone surgery than in those who had not been to the hospital. The clinical reasons behind patients with higher NHCT should be considered in investigating a causal relationship between CT exposure and brain tumors.

Age-related change in mammographic breast density of women without history of breast cancer over a 10-year retrospective study.

Background: Women with higher breast density are at higher risk of developing breast cancer. Breast density is known to affect sensitivity to mammography and to decrease with age. However, the age change and associated factors involved are still unknown. This study aimed to investigate changes in breast density and the associated factors over a 10-year period. Materials and Methods: The study included 221 women who had undergone eight or more mammograms for 10 years (2011-2020), were between 25 and 65 years of age, and had no abnormalities as of 2011. Breast density on mammographic images was classified into four categories: fatty, scattered, heterogeneously dense, and extremely dense. Breast density was determined using an image classification program with a Microsoft Lobe's machine-learning model. The temporal changes in breast density over a 10-year period were classified into three categories: no change, decrease, and increase. An ordinal logistic analysis was performed with the three groups of temporal changes in breast density categories as the objective variable and the four items of breast density at the start, BMI, age, and changes in BMI as explanatory variables. Results: As of 2011, the mean age of the 221 patients was 47 ± 7.3 years, and breast density category 3 scattered was the most common (67.0%). The 10-year change in breast density was 64.7% unchanged, 25.3% decreased, and 10% increased. BMI was increased by 64.7% of women. Breast density decreased in 76.6% of the category at the start: extremely dense breast density at the start was correlated with body mass index (BMI). The results of the ordinal logistic analysis indicated that contributing factors to breast density classification were higher breast density at the start (odds ratio = 0.044; 95% CI [0.025-0.076]), higher BMI at the start (odds ratio = 0.76; 95% CI [0.70-0.83]), increased BMI (odds ratio = 0.57; 95% CI [0.36-0.92]), and age in the 40s at the start (odds ratio = 0.49; 95% CI [0.24-0.99]). No statistically significant differences were found for medical history. Conclusion: Breast density decreased in approximately 25% of women over a 10-year period. Women with decreased breast density tended to have higher breast density or higher BMI at the start. This effect was more pronounced among women in their 40s at the start. Women with these conditions may experience changes in breast density over time. The present study would be useful to consider effective screening mammography based on breast density.

Molecular and cellular basis of the dose-rate-dependent adverse effects of radiation exposure in animal models. Part I: Mammary gland and digestive tract.

While epidemiological data are available for the dose and dose-rate effectiveness factor (DDREF) for human populations, animal models have contributed significantly to providing quantitative data with mechanistic insights. The aim of the current review is to compile both the in vitro experiments with reference to the dose-rate effects of DNA damage and repair, and the animal studies, specific to rodents, with reference to the dose-rate effects of cancer development. In particular, the review focuses especially on the results pertaining to underlying biological mechanisms and discusses their possible involvement in the process of radiation-induced carcinogenesis. Because the concept of adverse outcome pathway (AOP) together with the key events has been considered as a clue to estimate radiation risks at low doses and low dose-rates, the review scrutinized the dose-rate dependency of the key events related to carcinogenesis, which enables us to unify the underlying critical mechanisms to establish a connection between animal experimental studies with human epidemiological studies.

Molecular and cellular basis of the dose-rate-dependent adverse effects of radiation exposure in animal models. Part II: Hematopoietic system, lung and liver.

While epidemiological data have greatly contributed to the estimation of the dose and dose-rate effectiveness factor (DDREF) for human populations, studies using animal models have made significant contributions to provide quantitative data with mechanistic insights. The current article aims at compiling the animal studies, specific to rodents, with reference to the dose-rate effects of cancer development. This review focuses specifically on the results that explain the biological mechanisms underlying dose-rate effects and their potential involvement in radiation-induced carcinogenic processes. Since the adverse outcome pathway (AOP) concept together with the key events holds promise for improving the estimation of radiation risk at low doses and low dose-rates, the review intends to scrutinize dose-rate dependency of the key events in animal models and to consider novel key events involved in the dose-rate effects, which enables identification of important underlying mechanisms for linking animal experimental and human epidemiological studies in a unified manner.

Relationship between haematological data and radiation doses of TEPCO workers before and after the FDNNP accident.

We evaluated the correlation between radiation dose and the medical examination data of Tokyo Electric Power Company Holdings, Inc (TEPCO) employees working during the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident in 2011. This study included 2164 male TEPCO workers who received periodic medical examinations from March 2006 to January 2013. First, we conducted log-linear regression analyses using the haematological data of 585 emergency workers and confounding factors to examine the effect of internal radiation exposure in March 2011. Since external radiation exposure was a major influence, we then evaluated the correlation between both internal and external radiation dose and the haematological data of 1801 emergency workers and confounding factors before and after the accident. Among 585 workers, internal radiation exposure in March 2011 alone was mainly due to thyroid doses (0.1-10 Gy) but not to bone marrow (BM) doses (0.01-1 mGy). Compared to before and after the accident, we found that the levels of monocytes, eosinophils (Eos) and basophils increased slightly, whereas the frequency of smoking and alcohol consumption decreased substantially. External dose exposure was positively correlated with haemoglobin (Hb), red blood cell and Eos but negatively correlated with age, haematocrit and frequency of alcohol consumption. Among these variables, Hb exhibited the strongest correlation with external dose. Regarding the correlation with Hb, although there is a possibility that confounding factors other than exposure were not evaluated, our findings on emergency workers can serve as a reference for the evaluation of health conditions during the emergency period of future nuclear-related accidents.

Change in waist circumference and lifestyle habit factors as a predictor of metabolic risk among middle-aged and elderly Japanese people: population-based retrospective 10-year follow-up study from 2008 to 2017.

BACKGROUND: Waist circumference (WC) increases more than body mass index (BMI) over time. This study investigated the change in WC among middle-aged and elderly Japanese people for 10 years, and its relationship with lifestyle and lipid metabolism factor. METHODS: Health checkup data and lifestyle habits of a retrospective cohort of 745 people aged 40-65 years who underwent health checkups at least three times between 2008 and 2017 were analyzed. Information of Lifestyle habits about smoking history, regular exercise, alcohol intake skipping breakfast was collected using a self-administered questionnaire. Participants who were taking medications for diabetes, hyperlipidemia, or hypertension were excluded from analyses. Longitudinal associations between the change in WC and lifestyle habit factors with adjustments for sex, age, and WC at the start of health checkups were assessed using generalized linear models. RESULTS: Regardless of lifestyle, body weight (BW) decreased 0.8 kg (p < 0.001) for women, 0.9 kg (p = 0.003) for men, WC increased 0.8 cm (p = 0.007) for women, 0.2 cm (p = 0.657) for men. In addition, serum triglycerides and high- and low-density lipoprotein levels estimated 10 years later revealed that increased WC ratios also exacerbated the respective blood sample data. CONCLUSION: Both men and women showed an increase in WC regardless of BW changes, and the increase in WC worsened lipid metabolism. For the middle-aged and elderly, whose WC increases over time, it will be more important to take notice of their WC than BW or BMI for effective health checkups.

Field size effects on DNA damage and proliferation in normal human cell populations irradiated with X-ray microbeams.

To clarify the health risks of internal radiation exposure, it is important to investigate the radiological effects of local exposure at cell levels from radioactive materials taken up by organs. Focusing on the response of cell populations post-irradiation, X-ray microbeams are very effective at reproducing the effects of local exposure within an internal exposure in vitro. The present study aims to clarify the effects of local exposure by investigating the response of normal human cell (MRC-5) populations irradiated with X-ray microbeams of different beam sizes to DNA damage. The populations of MRC-5 were locally irradiated with X-ray microbeams of 1 Gy at 0.02-1.89 mm2 field sizes, and analyzed whether the number of 53BP1 foci as DSB (DNA double strand break) per cell changed with the field size. We found that even at the same dose, the number of DSB per cell increased depending on the X-irradiated field size on the cell population. This result indicated that DNA damage repair of X-irradiated cells might be enhanced in small size fields surrounded by non-irradiated cells. This study suggests that X-irradiated cells received some signal (a rescue signal) from surrounding non-irradiated cells may be involved in the response of cell populations post-irradiation.

Days Spent at Home near the End of Life in Japanese Elderly Patients with Lung Cancer: Post hoc Analysis of A Prospective Study.

OBJECTIVE: Days spent at home (DASH) near the end of life is considered an important patient-centered goal and outcome because many patients want to stay at home toward the end of life. This study aimed to estimate the individual DASH near the end of life and identify its early predictors, including muscle mass and physical function, among elderly patients with advanced non-small-cell lung cancer (NSCLC). METHODS: We conducted a post hoc analysis of the prospective observational study (UMIN000009768) that recruited patients aged ≥ 70 years who were scheduled to undergo first-line chemotherapy because of advanced NSCLC. We measured the muscle mass by bioelectrical impedance analysis at baseline. DASH was calculated as 30 days minus the number of days spent in hospitals, palliative care facilities, or nursing homes during the last 30 days of life. We performed linear regression analyses to evaluate the predictors of DASH. RESULTS: Altogether, 16 women and 28 men with a median overall survival of 15.5 months (range: 2.9-58.9) were included. The median DASH in the last 30 days of life was 8 days (range: 0-30, interquartile range: 0-23). Men had longer DASH than women by 7.3 days. Patients who had good trunk muscle mass index and hand-grip strength had significantly longer DASH than those who did not (4.7 days per kg/m2 increase [P = 0.017] and 0.4 days per kg increase [P = 0.032], respectively). CONCLUSIONS: Most elderly patients with advanced NSCLC had a limited DASH near the end of life. The risk factors for reduced DASH were women, reduced muscle mass, and poor physical function at the time of diagnosis of advanced NSCLC. Our findings would encourage early discussions about end-of-life care for patients with advanced cancers with risk factors for short DASH at the time of diagnosis, and thus, improve the quality of end-of-life care.

The Trends of Medical Care Expenditure with Adjustment of Lifestyle Habits and Medication; 10-Year Retrospective Follow-Up Study.

In Japan, the prevention of lifestyle-related diseases is the most important issue for the optimization of medical expenditure. This study aimed to analyze the impact of lifestyle and medication status on medical expenditure. Health checkup data and medical expenditure records of a retrospective cohort of 1463 people aged between 40 and 65 years old who underwent specific health checks at least three times between 2008 and 2017 were analyzed. Regression analysis was performed with medical expenditure as the dependent variable and age, gender, waist ratio, medication status, and lifestyle habits as independent variables using a Tobit model. Focusing on the factors that increase medical expenditure, the regression coefficients of age, medication status, weight gain of 10 kg or more since the age of 20, and walking more than 1 h per day were 0.048 (95% CI 0.04 to 0.06), 1.020 (95% CI 0.88 to 1.16), 0.210 (95% CI 0.06 to 0.36), and -0.208 (95% CI -0.35 to -0.07), respectively. The estimate of 5-year cumulative medical expenditure showed that those with walking habits without medication had the lowest medical expenditure. The result of this study suggests that walking more than 1 h a day may lower health expenditure in the general population.

Cellular kinetics of hematopoietic cells with Sfpi1 deletion are present at different frequencies in bone-marrow and spleen in X-irradiated mice.

PURPOSE: Several past studies using a mouse model of radiation-induced AML (rAML) have shown that hemizygous deletion of the Sfpi1 gene (HDSG) is an initiating event for the development of rAML. In this study, we examined the difference in frequency of HDSG in hematopoietic stem cells (HSCs) Rich hematopoietic Cell population (HRCs) from bone marrow (BM) and spleen of C3H mice irradiated with 3 Gy X-rays. MATERIALS AND METHODS: 8-weeks old male C3H mice were irradiated 3Gy of whole body X-ray (1 Gy/min) and mice were sacrificed at 1, 4, 8, and 26 weeks. Then, HSPCs were isolated from BM of femur and spleen, the frequency of HRCs with Sfpi1 gene deletion was analyzed by fluorescence in situ hybridization (FISH). RESULTS AND CONCLUSIONS: The frequency of HRCs with HDSG in both BM and spleen was increased 1 week after X-irradiation. Then, the frequency of HRCs with HDSG in BM showed a gradual decrease from 4 to 26 weeks, whereas HRCs with HDSG in spleen remained high, even at 26 weeks after X-irradiation. HDSG is less likely to be eliminated, particularly in the spleen, after X-irradiation. The spleen as well as BM of the femur may be major sites of rAML development.