Video capsule endoscopy in overt and occult obscure gastrointestinal bleeding: Insights from a single-center, observational study in Japan.

Objective: This study aimed to evaluate the use of video capsule endoscopy (VCE) in patients with obscure gastrointestinal bleeding (OGIB), compare cases of overt and occult OGIB, assess the rates of balloon-assisted enteroscopy (BAE) interventions and rebleeding, and identify predictive markers of positive VCE findings. Methods: Medical records of 430 patients who underwent VCE for OGIB between 2004 and 2022 were analyzed. Occult OGIB was defined as IDA or positive fecal occult blood, whereas overt OGIB was defined as clinically imperceptible bleeding. We retrospectively analyzed demographics, VCE findings based on Saurin classification (P0, P1, and P2), outcome of BAE interventions, and rebleeding rates. Results: A total of 253 patients with overt OGIB and 177 with occult OGIB were included. P1 findings were predominant in both groups, with a similar distribution. The percentage of patients receiving conservative therapy was higher in P1 than in P2 for both overt and occult OGIB. BAE was more frequently performed in P2 than in P1 VCE (83.0% vs. 35.3% in overt OGIB, 84.4% vs. 24.4% in occult OGIB). The percentage of positive findings and intervention in total BAE performed patients were comparable in P1 and P2 of overt OGIB, whereas these percentages in P2 were more than P1 of occult OGIB. Conclusion: VCE effectively identified OGIB lesions requiring intervention, particularly occult OGIB lesions, potentially reducing unnecessary BAE. Rebleeding rates varied according to the VCE findings, emphasizing the importance of follow-up in high-risk patients.

2023 Fukushima Medical University International Symposium on the Fukushima Health Management Survey, "Thinking Together about Health, Life, and our Future in Fukushima".

In response to the release of radioactive materials and evacuation of residents after the Tokyo Electric Power Company's Fukushima Daiichi Nuclear Power Plant accident, caused by the Great East Japan Earthquake, the Fukushima Health Management Survey (FHMS) began in June of 2011. This survey aims to provide long-term follow-up of the physical and mental health of Fukushima residents and to maintain and improve their health for the future. Every year since 2019, Fukushima Medical University (FMU) has organized the FHMS International Symposium to share survey results with people in Fukushima Prefecture and beyond. The fifth annual symposium convened at FMU's Ekimae Campus on Saturday, 4 March 2023, with the theme, "Thinking Together about Health, Life and our Future in Fukushima."

2022 Fukushima Medical University International Symposium on the Fukushima Health Management Survey Build Back Better, Together. "Science for Society: Advancing Fukushima's Well-Being".

The Fukushima Medical University (FMU) International Symposium on the Fukushima Health Management Survey (FHMS) convened for the fourth time in March 2022 to share FHMS findings within Fukushima and beyond. Dr. TAKENOSHITA Seiichi, FMU President, underscored Fukushima's restoration journey, while Governor UCHIBORI Masao committed to partnering with FMU for residents' welfare.The Introduction by Dr. KAMIYA Kenji highlighted FHMS results for more than 460,000 participants, of whom 99.8% were exposed to radiation doses below 5 mSv post-accident. Thyroid examinations detected tumors, but no dose-response relationship was found. The Comprehensive Health Check showed increased lifestyle-related diseases among evacuees, with improvements in some health markers. Mental health issues initially prevalent after the accident decreased over time, and perinatal outcomes were consistent with national data.Session 1 focused on radiation effects in Fukushima. The UNSCEAR 2020 Report indicated significantly reduced radiation exposure estimates and negligible cancer risks. Studies from Hiroshima, Nagasaki, and Chernobyl found no radiation-induced genetic effects.Session 2 explored post-disaster well-being, emphasizing the evolution of psychological responses. Practices like Psychological First Aid (PFA) and emotional resilience promotion were highlighted. Katsurao Village's post-evacuation health measures addressed lifestyle diseases, but faced challenges. The WHO framework for mental health and psychosocial support in nuclear emergencies emphasized the importance of mental health care throughout all disaster phases.The symposium facilitated valuable insights, underlining comprehensive health strategies and the significance of long-term studies for Fukushima's recovery and health management.

Rev1 overexpression accelerates N-methyl-N-nitrosourea (MNU)-induced thymic lymphoma by increasing mutagenesis.

Rev1 has two important functions in the translesion synthesis pathway, including dCMP transferase activity, and acts as a scaffolding protein for other polymerases involved in translesion synthesis. However, the role of Rev1 in mutagenesis and tumorigenesis in vivo remains unclear. We previously generated Rev1-overexpressing (Rev1-Tg) mice and reported that they exhibited a significantly increased incidence of intestinal adenoma and thymic lymphoma (TL) after N-methyl-N-nitrosourea (MNU) treatment. In this study, we investigated mutagenesis of MNU-induced TL tumorigenesis in wild-type (WT) and Rev1-Tg mice using diverse approaches, including whole-exome sequencing (WES). In Rev1-Tg TLs, the mutation frequency was higher than that in WT TL in most cases. However, no difference in the number of nonsynonymous mutations in the Catalogue of Somatic Mutations in Cancer (COSMIC) genes was observed, and mutations involved in Notch1 and MAPK signaling were similarly detected in both TLs. Mutational signature analysis of WT and Rev1-Tg TLs revealed cosine similarity with COSMIC mutational SBS5 (aging-related) and SBS11 (alkylation-related). Interestingly, the total number of mutations, but not the genotypes of WT and Rev1-Tg, was positively correlated with the relative contribution of SBS5 in individual TLs, suggesting that genetic instability could be accelerated in Rev1-Tg TLs. Finally, we demonstrated that preleukemic cells could be detected earlier in Rev1-Tg mice than in WT mice, following MNU treatment. In conclusion, Rev1 overexpression accelerates mutagenesis and increases the incidence of MNU-induced TL by shortening the latency period, which may be associated with more frequent DNA damage-induced genetic instability.

Effects of Overweight on Risk of Thyroid Nodules in Children and Adolescents: The Fukushima Health Management Survey.

CONTEXT: Examining how overweight/obesity impacts thyroid nodule development in children and adolescents by sex and age can speculate on the mechanism. OBJECTIVE: We examined whether overweight in children and adolescents are associated with thyroid nodule development by sex and age. DESIGN: Approximately 300,000 participants who underwent thyroid ultrasonography in the Fukushima Health Management Survey after a nuclear accident were enrolled. Those without nodules in the initial two examinations (1-3 and 4-5 years postaccident) were prospectively assessed for nodule development in the third examination (6-7 years postaccident) relative to baseline overweight status, with an average follow-up of 4.2 years. SETTING: A population-based prospective cohort study. PARTICIPANTS: The first and second thyroid examinations involved 299,939 and 237,691 participants, respectively, excluding those with thyroid nodules. After the third examination, 184,519 participants were finalized for analysis. MAIN OUTCOME MEASURES: Multivariable-adjusted odds ratios of new detected thyroid nodules for overweight participants compared with normal-weight participants. RESULTS: New thyroid nodules were detected in 660 participants. Being overweight was positively associated with thyroid nodules. The adjusted odds ratio (95% confidence interval) of thyroid nodules for overweight participants compared with other participants was 1.27 (1.04-1.57). Additionally, the multivariable-adjusted odds ratios for males and females with overweight were 1.21 and 1.32, respectively, and those for different age groups (0-9, 10-14, and 15-19 years) ranged from 1.17 to 1.75. CONCLUSIONS: Being overweight was associated with thyroid nodules in children and adolescents, mostly adolescent females, regardless of their proximity to the nuclear power plant.

Prevalence of thyroid diffuse goiter and its association with body mass index and the presence of cysts and nodules in children and adolescents: the Fukushima Health Management Survey.

The main cause of diffuse thyroid goiter is autoimmune chronic thyroiditis, otherwise known as Hashimoto's thyroiditis. Thyroid hormones play pivotal roles in growth and development during childhood. However, the prevalence of diffuse goiter and the relationships between diffuse goiter, thyroid volume, cysts and nodules, and anthropometric measurements in children are not well known. Among 789,459 participants who participated in thyroid ultrasound examinations, 320,206 participants (male: 161,728; female: 158,478) aged 1-23 years were analyzed. Logistic regression analyses were conducted to calculate the odds ratios of the standard deviation score of body mass index (BMI-SDS), the SDS of bilateral width multiplied thickness area (BWTAR-SDS) as a provisional determination of thyroid volume, and the presence of nodules or cysts for positive diffuse goiter compared with negative diffuse goiter after correction for sex and age. The prevalence of diffuse goiter increased in a female-dominant manner with aging. Compared with the absence of diffuse goiter, the age- and sex-adjusted odds ratios (95% confidence intervals) for BMI-SDS (1 SD), BWTAR-SDS (1 SD), cysts, and nodules were 1.24 (1.21-1.27), 3.21 (3.13-3.29), 0.53 (0.50-0.58), and 1.38 (1.17-1.64), respectively. The odds ratios of nodules for positive diffuse goiter were 4.18 (1.08-16.08), 1.76 (1.01-3.07), 1.80 (1.32-2.45), and 1.34 (1.08-1.67) in the age groups 1-7, 8-11, 12-15, and 16-23 years, respectively. The age-dependent increase in the prevalence of diffuse goiter was independently associated with increased BMI and positive prevalence of nodules in young individuals.

Nuclear DNA damage-triggered ATM-dependent AMPK activation regulates the mitochondrial radiation response.

PURPOSE: AMP-activated protein kinase (AMPK) acts as a cellular energy sensor and is essential for controlling mitochondrial homeostasis. Here, we investigated the regulatory mechanisms involved in AMPK activation to elucidate how networks of intracellular signaling pathways respond to stress conditions. MATERIALS AND METHODS: Inhibitors of ATM, DNA-PK, and AKT were tested in normal TIG-3 and MRC-5 human fibroblasts to determine which upstream kinases are responsible for AMPK activation. SV40 transformed-human ATM-deficient fibroblasts (AT5BIVA) and their ATM-complemented cells (i.e., AT5BIVA/ATMwt) were also used. Protein expression associated with AMPK signaling was examined by immunostaining and/or Western blotting. RESULTS: Radiation-induced nuclear DNA damage activates ATM-dependent AMPK signaling pathways that regulate mitochondrial quality control. In contrast, hypoxia and glucose starvation caused ATP depletion and activated AMPK via a pathway independent of ATM. DNA-PK and AKT are not involved in AMPK-mediated mitochondrial signaling pathways. CONCLUSION: Activation of the AMPK signaling pathway differs depending on the stimulus. Radiation activates AMPK through two pathways: depletion of ATP-mediated LKB1 signaling and nuclear DNA damage-induced ATM signaling. Nuclear DNA damage signaling to mitochondria therefore plays a pivotal role in determining the cell fates of irradiated cells.

Relationship between the Residual Cesium Body Contents and Individual Behaviors among Evacuees from Municipalities near the Fukushima Daiichi Nuclear Power Plant.

ABSTRACT: To support estimations of early individual internal doses to residents who suffered from the 2011 accident at the Fukushima Daiichi Nuclear Power Plant (FDNPP), we have sought to use whole-body counter (WBC) measurement results of subjects who lived in municipalities neighboring the FDNPP at the time of the accident. These WBC measurements started several months after the accident; the targeted radionuclides were 134Cs and 137Cs. Our previous study had analyzed the relationship between the residual Cs contents of individuals and evacuation behaviors in the period immediately after the accident for residents of Namie-town, one of the most radiologically affected municipalities. Those results suggested that the first major release event at the FDNPP on 12 March 2011 caused significant exposure, particularly to those who delayed evacuation on that day. The present study expanded its scope to include subjects from four towns neighboring the FDNPP (Namie, Futaba, Okuma, and Tomioka) to gather additional evidence of the exposure that took place on 12 March 2011. Additionally, we investigated the relationship between individual cesium doses and subjects' destinations following the largest release event on 15 March 2011. The study population was 1,145 adults. We first divided the subjects into two evacuation groups depending on the distance from the FDNPP and their evacuation whereabouts (25-km boundary) as of 15:00 on 12 March 2011: the G1 group (≥25 km) and the G2 group (<25 km). We further divided these two subject groups into seven subgroups based on the subjects' destinations as of 0:00 on 16 March 2011. Our four main findings are as follows. (1) The 137Cs detection rate was significantly different between the G1 and G2 groups of Namie-town and Futaba-town but not for those of Okuma-town and Tomioka-town. This result corresponds to the plume passage (flowing toward the northwest to the north) in the afternoon of 12 March 2011 and supports our previous study. (2) The upper-percentile committed effective doses (CEDs) of the G2 groups were higher than those of the G1 groups for all four towns, although the between-group difference varied with the town. The highest CEDs were found in the G2 group of Futaba-town, and the lowest CEDs were in the Namie-town G1 group: 0.16 mSv and 0.04 mSv at the 90th percentile, respectively. The CEDs for both the G1 and G2 groups were relatively high for Okuma-town and Tomioka-town compared to those of the G1 group of Namie-town, although the former subjects were expected to be less exposed on 12 March 2011 and then evacuated to remote places, as did the residents of the other towns. (3) The CEDs of the G1 subgroup that evacuated outside Fukushima Prefecture were extremely low, suggesting that these subjects were little exposed on both 12 and 15 March 2011. However, the CEDs of the same G1 subgroup were rather higher than those of the corresponding G2 subgroup for Futaba-town and Okuma-town. We thus speculate that the WBC measurements were likely to have been affected by the contamination occurring in the second-round temporary re-entry (except for the Namie-town residents). (4) The analyses of the Namie-town evacuees indicated that the area including the middle and northern parts of Fukushima Prefecture was relatively more affected by the major release event on 15 March 2011. In conclusion, the early cesium intake due to the FDNPP accident remained detectable in the WBC measurements of certain present subjects; however, further analyses of the available data are necessary for a full understanding of the WBC measurement results.

Influence of post-disaster evacuation on childhood obesity and liver dysfunction: The Fukushima Health Management Survey.

BACKGROUND: After the Great East Japan Earthquake and subsequent Fukushima Daiichi Nuclear Power Plant accident in 2011, the Fukushima Prefectural Government launched a long-term health management survey for the population of Fukushima. Results of the Comprehensive Health Check (CHC) showed that some children aged 6-15 years, who resided in the evacuation area at the time of the disaster, had obesity, hyperlipidemia, liver dysfunction, and/or renal dysfunction from as early as 2011. The aim of the present study was to determine the long-term trend of obesity and hepatic enzyme abnormalities in Fukushima children. METHODS: We evaluated the changes in body mass index standard deviation score (BMI-SDS), aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transpeptidase from 2011 to 2018. RESULTS: Obesity (BMI-SDS ≥ 2) was significantly associated with hepatobiliary enzyme abnormalities. The mean BMI-SDS was significantly higher in 2011 after the disaster, but then soon showed a gradual decrease. The frequency of obesity did not increase significantly after the disaster. There were no significant differences in the prevalence of hepatobiliary enzyme abnormalities in the children aged 6-15 years of either sex from 2011 to 2018. CONCLUSIONS: In the present study, we found that the increase in the mean BMI-SDS after the disaster was temporary, suggesting that the frequency of obesity and liver dysfunction might not have been significantly influenced by the disaster.

Relationship between evacuation after the Great East Japan Earthquake and new-onset hyperuricemia: A 7-year prospective longitudinal study of the Fukushima Health Management Survey.

INTRODUCTION: On March 11, 2011, the Great East Japan Earthquake occurred in Japan, with a nuclear accident subsequently occurring at the Fukushima Daiichi Nuclear Power Plant. The disaster forced many evacuees to change particular aspects of their lifestyles. However, the effect of evacuation on the new-onset of hyperuricemia have not been sufficiently elucidated. This study assessed the association between evacuation and new-onset hyperuricemia after the earthquake based on the Fukushima Health Management Survey from a lifestyle and socio-psychological perspective. MATERIALS AND METHODS: This is a 7-year prospective longitudinal study included 18,140 residents (6,961 men and 11,179 women) with non-hyperuricemia who underwent both the Comprehensive Health Check and the Mental Health and Lifestyle Survey in fiscal year 2011. Associations between new-onset hyperuricemia and lifestyle- and disaster-related factors, including evacuation, were estimated using a Cox proportional hazards regression model analysis. Hyperuricemia was defined as uric acid levels > 7.0 mg/dL for men and > 6.0 mg/dL for women. RESULTS: During a median follow-up of 4.3 years, 2,996 participants (1,608 men, 23.1%, 1,388 women, 12.4%) newly developed hyperuricemia. Significant associations were observed between evacuation and onset of hyperuricemia in women (adjusted hazard ratio 1.18, 95% confidence interval, 1.05-1.32, p = 0.007), but not in men (adjusted hazard ratio 1.11, 95% confidence interval, 0.99-1.24, p = 0.067). DISCUSSION: Evacuation after a natural disaster is an independent risk factor for the new-onset of hyperuricemia in women. The possibility of hyperuricemia developing in response to natural disasters should be considered.

Newly discovered genomic mutation patterns in radiation-induced small intestinal tumors of ApcMin/+ mice.

Among the small intestinal tumors that occur in irradiated mice of the established mouse model B6/B6-Chr18MSM-F1 ApcMin/+, loss of heterozygosity analysis can be utilized to estimate whether a deletion in the wild-type allele containing the Adenomatous polyposis coli (Apc) region (hereafter referred to as Deletion), a duplication in the mutant allele with a nonsense mutation at codon 850 of Apc (Duplication), or no aberration (Unidentified) has occurred. Previous research has revealed that the number of Unidentified tumors tends to increase with the radiation dose. In the present study, we investigated the molecular mechanisms underlying the development of an Unidentified tumor type in response to radiation exposure. The mRNA expression levels of Apc were significantly lower in Unidentified tumors than in normal tissues. We focused on epigenetic suppression as the mechanism underlying this decreased expression; however, hypermethylation of the Apc promoter region was not observed. To investigate whether deletions occur that cannot be captured by loss of heterozygosity analysis, we analyzed chromosome 18 using a customized array comparative genomic hybridization approach designed to detect copy-number changes in chromosome 18. However, the copy number of the Apc region was not altered in Unidentified tumors. Finally, gene mutation analysis of the Apc region using next-generation sequencing suggested the existence of a small deletion (approximately 3.5 kbp) in an Unidentified tumor from a mouse in the irradiated group. Furthermore, nonsense and frameshift mutations in Apc were found in approximately 30% of the Unidentified tumors analyzed. These results suggest that radiation-induced Unidentified tumors arise mainly due to decreased Apc expression of an unknown regulatory mechanism that does not depend on promoter hypermethylation, and that some tumors may result from nonsense mutations which are as-yet undefined point mutations.

Blood data trends of children in Fukushima after the Great East Japan Earthquake: Fukushima health management survey.

BACKGROUND: After the Great East Japan Earthquake on March 11, 2011 and the subsequent accident at the Tokyo Electric Power Company-operated Daiichi Nuclear Power Plant, the Fukushima Prefecture government initiated the Fukushima Health Management Survey (FHMS) to assess the long-term health effects of the disaster on Fukushima residents. The blood tests of children aged ≤15 years between 2011 and 2012 did not reveal any changes regarding peripheral blood data; however, long-term monitoring is still necessary. Therefore, this study aimed to investigate the long-term health status of children aged ≤15 years who had evacuated the Fukushima Prefecture. METHODS: From 2011 to 2018, 71,250 evacuees aged 15 years or younger participated in the FMHS and were subjected to blood tests. By analyzing the data of the comprehensive health check survey managed by the FHMS, we examined the changes in hemoglobin (Hb) levels, white blood cell (WBC) counts, including fractions, and platelet (PLT) counts among children from 2011 to 2018. RESULTS: Minor fluctuations in Hb levels, PLT counts, and WBC counts were observed during the study period, but the central 95% intervals of distribution of the laboratory values were generally within previously reported reference intervals. In particular, there was no increase in the proportions of patients with anemia, polycythemia, or deviating WBC counts. CONCLUSION: From 2011 to 2018, there was no increase in the percentages of children with anemia, polycythemia, or deviating WBC counts among the Fukushima Prefecture evacuees.

Eight-Year Trends in the Effect of the Great East Japan Earthquake on Obstetrics Outcomes: A Study from the Fukushima Health Management Survey.

Information regarding the longitudinal effects of natural/environmental disasters on obstetrics outcomes is limited. This study aimed to analyze the longitudinal changes in obstetrics outcomes over 8 years after the Great East Japan Earthquake and the Fukushima power plant accident. We used data from the first 8 years of the Pregnancy and Birth Survey by the Fukushima prefectural government, launched in 2011. We compared data on obstetrics outcomes by year and divided Fukushima Prefecture into six districts based on administrative districts. Longitudinal changes in the occurrence of preterm birth before 37 gestational weeks, low birth weight, and anomalies in newborns were accessed using the Mantel-Haenszel test for trends in all six districts. Overall, 57,537 participants were included. In 8 years, maternal age, conception rate after sterility treatment, and cesarean section delivery incidence increased. Although significant differences were observed in preterm birth and low birth weight occurrence among districts, there was no significant trend in the occurrence of preterm birth, low birth weight, and anomalies in newborns in all six districts of Fukushima Prefecture. The Great East Japan Earthquake and Fukushima power plant accident were associated with increased cesarean section delivery incidence but had no significant adverse effects on obstetrics outcomes.

Confounding factors and biases involved in regional differences in the detection rate of thyroid cancer in the second-round Thyroid Ultrasound Examination: the Fukushima Health Management Survey.

In response to concerns about health due to radiation exposure, the Fukushima Prefecture launched the Thyroid Ultrasound Examination program for residents aged 0-18 years at the time of the earthquake. Herein, we considered the confounding factors involved in the regional differences in the development of thyroid cancer. In this study, the 242 065 individuals who participated in both first- and second-round surveys were classified into four groups by address according to their air radiation dose. The number of participants diagnosed as malignant or suspicious for malignancy by cytological examination were 17, 38, 10 and 4 with detection rates of 53.8, 27.8, 21.7 and 14.5 per 100 000 participants in Regions 1, 2, 3 and 4, respectively. Sex (P = 0.0400), age at the time of the primary examination (P < 0.0001) and interval between the first- and second-round surveys (P < 0.0001) were significantly different among the four regions, and these were suspected to be confounding factors affecting regional differences in malignant nodule detection rates. In addition, significant regional differences were observed in the participation rate in the confirmatory examination (P = 0.0037) and the fine needle aspiration cytology implementation rate (P = 0.0037), which could be potential biases. No significant regional differences in the detection of malignant nodules were found in the multivariate logistic regression analysis after adjusting for the survey interval alone or for sex, age and survey interval. The confounding factors and biases identified in this study that may have important impacts on thyroid cancer detection rate should be fully considered in future studies.

Impact of Lifestyle and Psychosocial Factors on the Incidence of Hepatobiliary Enzyme Abnormalities After the Great East Japan Earthquake: Seven-Year Follow-up of the Fukushima Health Management Survey.

OBJECTIVE: Residents who lived near the Fukushima Power Plant accident were forced to change their lifestyle after the 2011 accident. This study aimed to elucidate the association of resident lifestyle and psychological factors with onset of hepatobiliary enzyme abnormalities (HEA) after the accident. METHODS: This longitudinal study included 15705 residents who underwent a comprehensive health check, as well as a mental health and lifestyle survey between June 2011 and March 2012. Follow-up surveys were conducted between June, 2012 and March 2018. Risk factors for new HEA onset were evaluated using the Cox proportional hazards model, moreover, population attributable risks for new HEA onset were calculated. RESULTS: HEA developed in 29.7% of subjects. In addition to metabolic factors such as overweight, hyperglycemia, and hyperlipidemia; there were differences in alcohol intake, evacuation, unemployment, educational background, and psychological distress between subjects with and without HEA onset. After we adjusted for potential confounding factors, an association of being overweight, hypertension, and dyslipidemia, as well as alcohol consumption, evacuation, and psychological distress with increased risk of HEA onset was realized. Among these identified risk factors, evacuation accounted for the greatest share. CONCLUSIONS: Metabolic characteristics and disaster-related lifestyle aspects, including mental status, were risk factors for HAE onset after the Fukushima Power Plant accident.

Ultrasonography-based reference values for the cross-sectional area of the thyroid gland in children and adolescents: The Fukushima Health Management Survey.

We previously described the thyroid volume, which was calculated by measuring the thyroid width, thickness, and longitudinal length using ultrasonography, in children and adolescents. We have proposed a simplified method for quantitatively assessing the thyroid size, to overcome the inaccuracy and challenges in measuring the longitudinal length of the thyroid. Based on measurements of 317,847 (girls: 156,913, boys: 160,934) children and adolescents, we calculated sex-specific means and standard deviations of thyroid width and thickness, and of the cross-sectional area computed by multiplying them, for every age and 0.1 m2 of body surface area, after ensuring normal distribution with Box-Cox transformation. Multivariate regression analysis revealed that female sex, age, and body surface area were independently associated with areas of each thyroid lobe. Our novel method may be useful in quantitatively assessing the thyroid size, and appropriately diagnosing pathological conditions, such as hypoplasia, atrophy, and enlargement of the thyroid gland, in children and adolescents.

Longitudinal Trends in Blood Pressure Associated with The Changes in Living Environment Caused by the Great East Japan Earthquake: The Fukushima Health Management Survey.

The Great East Japan Earthquake occurred on 11 March 2011, forcing Fukushima Prefecture residents to change their living environment. Such sudden changes possibly have long-term effects on cardiovascular-related diseases. We therefore sought to identify temporal relationships between living environment changes and blood pressure levels over three years following the earthquake. Participants included 14,941 men and 21,533 women aged 16 years or older who answered self-administered questionnaires, including questions on living environment changes at baseline (2012). Blood pressure levels were measured each year from 2012 to 2015. Linear mixed-effects models were used to analyze associations between living environment changes and blood pressure levels. Men with changes in living environment (i.e., those living in shelters or in temporary housing, rental apartments, relatives' houses, or others) showed significantly higher diastolic blood pressure levels than those who lived in their home at baseline (77.3 mmHg vs. 77.8 mmHg; p < 0.001). The time-dependent effect of diastolic blood pressure levels associated with living environment was not statistically significant, indicating a sustained difference in diastolic blood pressure associated with living environment changes at baseline after three years. The effect of living environment changes on diastolic blood pressure increment was also evident in men without antihypertensive medication use during the study period and in men who were current drinkers at baseline. There were no associations between living environment changes and diastolic blood pressure levels among women. Sudden changes in living environment due to the disaster had an impact on the long-term effects of higher diastolic blood pressure among middle-aged men.

Comparison between external and internal doses to the thyroid after the Fukushima Daiichi Nuclear Power Plant accident.

To analyze the association between radiation dose and thyroid cancer after the 2011 Fukushima Daiichi Nuclear Power Plant (FDNPP) accident, external doses have often been used because of the difficulty to estimate internal thyroid doses individually due to the lack of human data. However, no evaluation has been made as to whether external dose is a good surrogate marker for internal thyroid dose individually. This study aimed at analyzing the relationship between external doses and internal thyroid doses estimated by recently developed methodology. For four municipalities affected by the accident, 200 individuals aged under 20 at the time of the accident per municipality were randomly selected, and their external and internal thyroid doses and their ratios were estimated individually. In a separate analysis, median and arithmetic mean values for external thyroid doses estimated for persons of 16 municipalities that included the above four were compared with those for previously estimated internal thyroid doses. The ratios of the median of internal thyroid dose to that of external thyroid dose in these 16 municipalities ranged from 0.56 to 13.8 for 15-year-old children and 0.91 to 21.1 for 1-year-old children. No consistent relationship between external and internal thyroid doses was found in all 16 municipalities. Thus, thyroid doses from both external and internal exposures should be used to analyze the association between radiation dose and thyroid cancer detection rates for persons who lived in Fukushima Prefecture at the time of the FDNPP accident. (240).

Morphology dynamics in intestinal crypt during postnatal development affect age-dependent susceptibility to radiation-induced intestinal tumorigenesis in ApcMin/+ mice: possible mechanisms of radiation tumorigenesis.

Age at exposure is a major modifier of radiation-induced carcinogenesis. We used mouse models to elucidate the mechanism underlying age-related susceptibility to radiation-induced tumorigenesis. Radiation exposure in infants was effective at inducing tumors in B6/B6-Chr18MSM-F1 ApcMin/+ mice. Loss of heterozygosity analysis revealed that interstitial deletion may be considered a radiation signature in this model and tumor number containing a deletion correlated with the susceptibility to radiation-induced tumorigenesis as a function of age. Furthermore, in Lgr5-eGFP-ires-CreERT2; Apcflox/flox mice, deletions of both floxed Apc alleles in Lgr5-positive stem cells in infants resulted in the formation of more tumors than in adults. These results suggest that tumorigenicity of Apc-deficient stem cells varies with age and is higher in infant mice. Three-dimensional immunostaining analyses indicated that the crypt architecture in the intestine of infants was immature and different from that in adults concerning crypt size and the number of stem cells and Paneth cells per crypt. Interestingly, the frequency of crypt fission correlated with the susceptibility to radiation-induced tumorigenesis as a function of age. During crypt fission, the percentage of crypts with lysozyme-positive mature Paneth cells was lower in infants than that in adults, whereas no difference in the behavior of stem cells or Paneth cells was observed regardless of age. These data suggest that morphological dynamics in intestinal crypts affect age-dependent susceptibility to radiation-induced tumorigenesis; oncogenic mutations in infant stem cells resulting from radiation exposure may acquire an increased proliferative potential for tumor induction compared with that in adults.

Effects of oxygen on the response of mitochondria to X-irradiation and reactive oxygen species-mediated fibroblast activation.

PURPOSE: In living organisms, sensitivity to radiation increases in the presence of oxygen (O2) compared with that under anoxic or hypoxic conditions. Here, we investigated whether O2 concentration affected the response of mitochondria to X-rays radiation, which is associated with tumor microenvironment formation via fibroblast activation in radiation-related tumors. MATERIALS AND METHODS: O2 concentrations were controlled at <5% (internal environmental oxygen condition) or anoxic levels during culture of normal human diploid lung fibroblasts TIG-3 and MRC-5. Protein expression associated with the response of mitochondria to radiation was assessed using immunostaining or western blotting. RESULTS: Induction of DNA damage (marker: γ-H2A histone family member X) and mitochondrial signaling (AMP-activated protein kinase), suppression of mitochondrial metabolic activity, and generation of reactive oxygen species occurred with radiation in cells cultured under 5% and 20% O2 conditions. However, reducing O2 concentration mitigated the effects of radiation on cell growth, mitochondrial damage (parkin), induction of antioxidant responses (nuclear factor E2-related factor 2), and fibroblast activation (α-smooth muscle actin). Radiation did not affect the markers used in this study in the absence of O2. CONCLUSION: O2 concentration affected the response of mitochondria to radiation and reactive oxygen species-mediated fibroblast activation. Higher O2 concentrations enhanced the effects of radiation on mitochondria in human fibroblasts. In vitro studies may overestimate in vivo radiation effects due to high O2 concentrations.