BackgroundThe accidents that occurred at the Fukushima Daiichi Nuclear Power Plant after the Great East Japan Earthquake on 11 March 2011 have resulted in long-term, ongoing anxiety among the residents of Fukushima, Japan. Soon after the disaster, Fukushima Prefecture launched the Fukushima Health Management Survey to investigate long-term low-dose radiation exposure caused by the accident. Fukushima Medical University took the lead in planning and implementing this survey. The primary purposes of this survey are to monitor the long-term health of residents, promote their future well-being, and confirm whether long-term low-dose radiation exposure has health effects. This report describes the rationale and implementation of the Fukushima Health Management Survey.MethodsThis cohort study enrolled all people living in Fukushima Prefecture after the earthquake and comprises a basic survey and 4 detailed surveys. The basic survey is to estimate levels of external radiation exposure among all 2.05 million residents. It should be noted that internal radiation levels were estimated by Fukushima Prefecture using whole-body counters. The detailed surveys comprise a thyroid ultrasound examination for all Fukushima children aged 18 years or younger, a comprehensive health check for all residents from the evacuation zones, an assessment of mental health and lifestyles of all residents from the evacuation zones, and recording of all pregnancies and births among all women in the prefecture who were pregnant on 11 March. All data have been entered into a database and will be used to support the residents and analyze the health effects of radiation.ConclusionsThe low response rate (<30%) to the basic survey complicates the estimation of health effects. There have been no cases of malignancy to date among 38 114 children who received thyroid ultrasound examinations. The importance of mental health care was revealed by the mental health and lifestyle survey and the pregnancy and birth survey. This long-term large-scale epidemiologic study is expected to provide valuable data in the investigation of the health effects of low-dose radiation and disaster-related stress.

Chromatin reorganization plays an important role in DNA repair, apoptosis, and cell cycle checkpoints. Among proteins involved in chromatin reorganization, TIP60 histone acetyltransferase has been shown to play a role in DNA repair and apoptosis. However, how TIP60 regulates chromatin reorganization in the response of human cells to DNA damage is largely unknown. Here, we show that ionizing irradiation induces TIP60 acetylation of histone H2AX, a variant form of H2A known to be phosphorylated following DNA damage. Furthermore, TIP60 regulates the ubiquitination of H2AX via the ubiquitin-conjugating enzyme UBC13, which is induced by DNA damage. This ubiquitination of H2AX requires its prior acetylation. We also demonstrate that acetylation-dependent ubiquitination by the TIP60-UBC13 complex leads to the release of H2AX from damaged chromatin. We conclude that the sequential acetylation and ubiquitination of H2AX by TIP60-UBC13 promote enhanced histone dynamics, which in turn stimulate a DNA damage response.Chromatin reorganization by histone modification and mobilization plays a crucial role in DNA metabolism, including replication, transcription, and repair. It appears that histone modification and mobilization can reorganize chromatin to allow DNA repair machinery to access damaged chromosomal DNA (11,29,52,56,57).H2AX is a histone variant that differs from H2A at various amino acid residues along the entire protein and in its Cterminal extensions. H2AX is phosphorylated after the induction of DNA double-strand breaks (DSBs), and the phosphorylated H2AX (␥-H2AX) participates in focus formation at sites of DNA damage. After induction of DSBs, the MRN complex (MRE11, RAD50, and NBS1) binds to broken DNA ends and recruits active ATM, ATR, and/or DNA protein kinase, resulting in the initial phosphorylation of H2AX (32,38,40). MDC1 then associates with ␥-H2AX and recruits additional activated ATM to the sites of DSBs (23,46). This positive feedback loop leads to the expansion of the ␥-H2AX region surrounding DSBs and provides docking sites for many DNA damage and repair proteins, including the MRN complex, 53BP1, and BRCA1 (5, 6, 46). ␥-H2AX plays a role in the accumulation but not in the initial recruitment of repair factors such as the MRN complex, 53BP1, and BRCA1 (10, 63). Therefore, modifications of H2AX other than phosphorylation could play a role in the initial step of the DNA damage response.Until recently, the biological significance of ubiquitination in the DNA damage response has been unclear. H2B ubiquitination regulates the damage checkpoint response (15). H2A is ubiquitinated during the response to UV-induced DNA damage (8). UV-induced DNA damage also causes the ubiquitination of histones H3 and H4, resulting in their release from chromatin (60). Interestingly, ubiquitin-conjugated proteins appear to be accumulated at sites of DSBs, forming nuclear foci like ␥-H2AX (34). These findings raise the possibility that histone ubiquitination is also involved in the reorganization of chromatin in response to D...

: [Background] On 11 March 2011, the Great East Japan Earthquake followed by a gigantic tsunami hit the Pacific coast of Northeast Japan (Tohoku) and damaged Tokyo Electric Power Company's Fukushima Daiichi Nuclear Power Plant, causing a radiation hazard in the entire Fukushima Prefecture. The radiation dose exposed either externally and internally in Fukushima residents have been evaluated to be low so far and it is hardly believed that they may have any direct radiation risk on physical condition. The purpose of this report is, therefore, to describe results of a mental health and lifestyle survey intended to facilitate adequate care for residents who are at a higher risk of developing mental health problems after the complicated accident. [Participants and Methods] The target population of this survey is the residents of evacuation zones including Hirono Town, Naraha Town, Tomioka Town, Kawauchi Village, Okuma Town, Futaba Town, Namie Town, Katsurao Village, Minamisoma City, Tamura City, Yamakiya district of Kawamata Town, and Iitate Village. The targeted population was 210,189 in fiscal year 2011 (FY2011) and 211,615 in fiscal year 2012 (FY2012). Questionnaires have been mailed since January 2012, and subsequently, January 2013, 10 and 22 months after the disaster. Among of them, children 63.4%, adults 40.7% for FY2011, and children 41.0%, adults 29.7% for FY2012 responded to the questionnaires mailed.[Results] Sociodemographic data showed that many evacuee households were separated after the disaster and had to move several times. K6 was used in this survey to estimate general mental health. The proportion (14.6% in FY2011 and 11.9% inFY2012) of adults who scored above the K6 cut -off (≥13) for general mental health was higher than usual, indicating severe mental health problems among evacuees. The proportion (21.6% in FY2011 and 18.3% inFY2012) of adults who scored above the cut -off (≥44) of PTSD checklist (PCL), reflecting traumatic symptoms, was almost equal to that of the workers after the 9.11 World Trade Center attacks. These results also indicate the presence of severe traumatic problems among evacuees. The proportions of children (4 -6Corresponding author : Hirooki Yabe MD, PhD E -mail : hyabe@fmu.ac.jp https://www.jstage.jst.go.jp/browse/fms http://www.fmu.ac.jp/home/lib/F -igaku/ 57 58 H. YABE et al.years old) and children of primary school age (6 -12 years old) who scored above the cut -off (≥16) of Strengths and Difficulties Questionnaire (SDQ) reflecting the mental health status in children, 24.4% and 22.0% in the survey of FY2011, were double the usual state respectively, whereas 16.6% in children of 4 -6 years old and 15.8% in children of 6 -12 years old in FY2012 were 1.5 times. These findings also disclosed the presence of severe mental difficulties in children, with relative improvement year by year. [Conclusion] As revealed by the present mental health survey, the earthquake and tsunami followed by the nuclear accident caused psychological distress among residents in Fukushi...

437 nuclear power plants are in operation at present around the world to meet increasing energy demands. Unfortunately, five major nuclear accidents have occurred in the past--ie, at Kyshtym (Russia [then USSR], 1957), Windscale Piles (UK, 1957), Three Mile Island (USA, 1979), Chernobyl (Ukraine [then USSR], 1986), and Fukushima (Japan, 2011). The effects of these accidents on individuals and societies are diverse and enduring. Accumulated evidence about radiation health effects on atomic bomb survivors and other radiation-exposed people has formed the basis for national and international regulations about radiation protection. However, past experiences suggest that common issues were not necessarily physical health problems directly attributable to radiation exposure, but rather psychological and social effects. Additionally, evacuation and long-term displacement created severe health-care problems for the most vulnerable people, such as hospital inpatients and elderly people.

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The Great East Japan Earthquake and Fukushima Daiichi nuclear disaster in 2011 forced the evacuation of a large number of residents and created changes in the lifestyle of the evacuees. These changes may have affected the evacuees' glucose metabolism, thereby leading to an increase in the incidence of diabetes. This study included Japanese men and women who were living near the Fukushima Daiichi Nuclear Power Plant in Fukushima prefecture before the disaster. Subjects subsequently underwent annual health checkups with a focus on metabolic syndromes, which were conducted under the Health Care Insurers. Using the Comprehensive Health Check survey, we analyzed changes in the glucose metabolism before and after the disaster. A total of 27,486 subjects underwent follow-up examinations after the disaster, with a mean follow-up period of 1.6 years. After the disaster, the prevalence of diabetes increased significantly, and we observed that the incidence of diabetes was significantly greater among evacuees than among nonevacuees. Furthermore, multivariate logistic regression analysis revealed that evacuation was significantly associated with the incidence of diabetes. In conclusion, this is the first study to demonstrate that evacuation is associated with the incidence of diabetes. This information may be used to guide follow-up recommendations for evacuees.

The Fukushima Health Management Survey (including the Basic Survey for external dose estimation and four detailed surveys) was launched after the Fukushima Dai-ichi Nuclear Power Plant accident. The Basic Survey consists of a questionnaire that asks Fukushima Prefecture residents about their behavior in the first four months after the accident; and responses to the questionnaire have been returned from many residents. The individual external doses are estimated by using digitized behavior data and a computer program that included daily gamma ray dose rate maps drawn after the accident. The individual external doses of 421,394 residents for the first four months (excluding radiation workers) had a distribution as follows: 62.0%, <1 mSv; 94.0%, <2 mSv; 99.4%, <3 mSv. The arithmetic mean and maximum for the individual external doses were 0.8 and 25 mSv, respectively. While most dose estimation studies were based on typical scenarios of evacuation and time spent inside/outside, the Basic Survey estimated doses considering individually different personal behaviors. Thus, doses for some individuals who did not follow typical scenarios could be revealed. Even considering such extreme cases, the estimated external doses were generally low and no discernible increased incidence of radiation-related health effects is expected.

Association of breast tumor susceptibility gene products BRCA1 and BRCA2 with the RAD51 recombination protein suggested that cancer could arise through defects in recombination. The identi®cation of NBS1, responsible for Nijmegen breakage syndrome, from the MRE11/RAD50 recombination protein complex also supports this hypothesis. However, our mutation analysis revealed that known members of the RAD52 epistasis group are rarely mutated in human primary cancer. Here we describe the isolation of a novel member of the SNF2 superfamily, characterized with sequence motifs similar to those in DNA and RNA helicases. The gene, designated RAD54B, is signi®cantly homologous to the RAD54 recombination gene. The expression of RAD54B was high in testis and spleen, which are active in meiotic and mitotic recombination. These ®ndings suggest that RAD54B may play an active role in recombination processes in concert with other members of the RAD52 epistasis group. RAD54B maps to human chromosome 8q21.3-q22 in a region associated with cancer-related chromosomal abnormalities. Homozygous mutations at highly conserved positions of RAD54B were observed in human primary lymphoma and colon cancer. These ®ndings suggest that some cancers arise through alterations of the RAD54B function.