Resilience after a nuclear accident: readiness in using mobile phone applications to measure radiation and health indicators in various groups (SHAMISEN SINGS project).

An anonymous web-based survey was developed to check different aspects (SHAMISEN SINGS project): stakeholder awareness and perceptions of available mobile applications (apps) for measuring ionising radiation doses and health/well-being indicators; whether they would be ready to use them in the post-accidental recovery; and what are their preferred methodologies to acquire information etc. The results show that participation of the citizens would be most beneficial during post-accident recovery, providing individual measurements of external ionizing dose and health/well-being parameters, with possible follow-up. Also, participants indicated different preferences for sources to gain knowledge on ionising radiation and for the functions that an ideal app should have. The level of awareness and readiness to use apps to measure ionising radiation dose depended on two main aspects: individual differences (age & gender) and whether people were from countries affected by the previous major accidents. We concluded that stakeholders could have benefits from the data management plan: (1) it potentiates resilience at individual and community level; (2) citizens' measurements contribute to environmental monitoring and public health screening; (3) linkages between different types of data (environmental exposure, individual behavioural diaries, and measurements of health indicators) allow to perform more rigorous epidemiological studies.

Flowchart for selecting an appropriate surgical airway in neurologically impaired pediatric intubated patients: a case series

Abstract Objective: Medical advances have resulted in increased survival rates of neurologically impaired children who may require mechanical ventilation and subsequent tracheostomy as a surgical airway. However, at present, there is no definite consensus regarding the timing and methods for placement of a surgical airway in a neurologically impaired intubated child who needs to be cared for over a long-term period. We therefore created a flowchart for the selection of a surgical airway for Neurologically Impaired Pediatric Patients (NIPPs). Methods: The flowchart includes information on the patients' backgrounds, such as intubation period, prognosis related to reversibility, and history of aspiration pneumonia. To evaluate the importance of the flowchart, first we conducted a survey of pediatricians regarding selection of a surgical airway, and we also evaluated the appropriateness of the flowchart among pediatricians and caregivers through questionnaire surveys which include satisfaction with the decision-making process, and postoperative course after discharge. Results: A total of 21 NIPPs with intubation underwent surgery and a total of 24 participants (14 pediatricians and 10 caregivers) completed the survey. The answers regarding the importance of the flowchart showed that eleven pediatricians had experience selecting of surgical airways, nine of whom had had experiences in which they had to make a difficult decision. The answers regarding the appropriateness of the flowchart revealed that all pediatricians and caregivers were satisfied with the decision-making process and postoperative course after discharge using the flowchart. Conclusions: The present study demonstrated the effectiveness of our flowchart for selecting an appropriate surgical airway in NIPP. By referring to our flowchart, pediatricians and caregivers are likely to be able to select an appropriate surgical airway, leading to increased satisfaction with the decision-making process and postoperative course. Level of Evidence: 4.

Flowchart for selecting an appropriate surgical airway in neurologically impaired pediatric intubated patients: a case series.

OBJECTIVE: Medical advances have resulted in increased survival rates of neurologically impaired children who may require mechanical ventilation and subsequent tracheostomy as a surgical airway. However, at present, there is no definite consensus regarding the timing and methods for placement of a surgical airway in a neurologically impaired intubated child who needs to be cared for over a long-term period. We therefore created a flowchart for the selection of a surgical airway for Neurologically Impaired Pediatric Patients (NIPPs). METHODS: The flowchart includes information on the patients' backgrounds, such as intubation period, prognosis related to reversibility, and history of aspiration pneumonia. To evaluate the importance of the flowchart, first we conducted a survey of pediatricians regarding selection of a surgical airway, and we also evaluated the appropriateness of the flowchart among pediatricians and caregivers through questionnaire surveys which include satisfaction with the decision-making process, and postoperative course after discharge. RESULTS: A total of 21 NIPPs with intubation underwent surgery and a total of 24 participants (14 pediatricians and 10 caregivers) completed the survey. The answers regarding the importance of the flowchart showed that eleven pediatricians had experience selecting of surgical airways, nine of whom had had experiences in which they had to make a difficult decision. The answers regarding the appropriateness of the flowchart revealed that all pediatricians and caregivers were satisfied with the decision-making process and postoperative course after discharge using the flowchart. CONCLUSIONS: The present study demonstrated the effectiveness of our flowchart for selecting an appropriate surgical airway in NIPP. By referring to our flowchart, pediatricians and caregivers are likely to be able to select an appropriate surgical airway, leading to increased satisfaction with the decision-making process and postoperative course.

ER-851, a Novel Selective Inhibitor of AXL, Overcomes Resistance to Antimitotic Drugs.

Innate and adaptive resistance to cancer therapies, such as chemotherapies, molecularly targeted therapies, and immune-modulating therapies, is a major issue in clinical practice. Subpopulations of tumor cells expressing the receptor tyrosine kinase AXL become enriched after treatment with antimitotic drugs, causing tumor relapse. Elevated AXL expression is closely associated with drug resistance in clinical samples, suggesting that AXL plays a pivotal role in drug resistance. Although several molecules with AXL inhibitory activity have been developed, none have sufficient activity and selectivity to be clinically effective when administered in combination with a cancer therapy. Here, we report a novel small molecule, ER-851, which is a potent and highly selective AXL inhibitor. To investigate resistance mechanisms and identify driving molecules, we conducted a comprehensive gene expression analysis of chemoresistant tumor cells in mouse xenograft models of genetically engineered human lung cancer and human triple-negative breast cancer. Consistent with the effect of AXL knockdown, cotreatment of ER-851 and antimitotic drugs produced an antitumor effect and prolonged relapse-free survival in the mouse xenograft model of human triple-negative breast cancer. Importantly, when orally administered to BALB/c mice, this compound did not induce retinal toxicity, a known side effect of chronic MER inhibition. Together, these data strongly suggest that AXL is a therapeutic target for overcoming drug resistance and that ER-851 is a promising candidate therapeutic agent for use against AXL-expressing antimitotic-resistant tumors.

Skin rash associated with combined cytotoxic chemotherapy and immunotherapy for cancer: A retrospective single-center case series.

In recent years, the development of combination therapies with immune checkpoint inhibitors (ICIs) and cytotoxic anticancer drugs has radically changed the management of diverse malignancies and significantly improved patient outcomes. Several clinical trials have shown that skin rash caused by combination therapy with ICIs and cytotoxic drugs may be more frequent and severe than that developing after administration of ICIs alone or cytotoxic drug monotherapy. However, most reports provide little information on severity, treatment, post-diagnosis course, and recurrence of rashes on drug rechallenges. We aimed to describe the experience of skin rashes developing within 2 weeks from the first administration of combination therapy with ICIs and cytotoxic drugs in 11 patients visiting our dermatology department. This study included seven men and four women, and the patients' median age was 52 years. The primary disease was non-small-cell lung cancer in eight patients, cervical cancer in two patients, and esophageal cancer in one patient. Nine patients had a maculopapular rash and two patients developed erythema multiforme-like eruptions. The skin rash was often accompanied by extracutaneous symptoms, such as fever (n = 9), mucositis (n = 4), and liver dysfunction (n = 2). In all cases, the symptoms improved with topical steroid therapy alone, with no patients exhibiting severe symptoms requiring systemic steroids or immunosuppressive agents. In addition, when the causative drugs were re-administered after recovery from the rash, only two patients relapsed with accompanying systemic symptoms, and all patients except one were able to continue treatment using the same drug regimen. Although it was suggested that the rash caused by the combination therapy of ICIs and cytotoxic drugs may be more prominent than that caused by each agent alone, comprehensive judgment, including histopathological examination, may indicate the feasibility of continuing the treatment regimen for cancer.

Effects of External Radiation Exposure on Perinatal Outcomes in Pregnant Women After the Fukushima Daiichi Nuclear Power Plant Accident: the Fukushima Health Management Survey.

BACKGROUND: This study aimed to investigate the effects of maternal exposure to external radiation on perinatal outcomes among women who experienced the Fukushima Daiichi Nuclear Disaster (FDND) using the Fukushima Health Management Survey (FHMS). METHODS: Data from the Pregnancy and Birth Survey and Basic Survey in the FHMS were combined to analyze external maternal radiation exposure following the FDND, and the relationship between radiation dose and perinatal outcomes was analyzed using binomial logistic regression analysis. Missing dose data were supplemented using multiple imputation. RESULTS: A total of 6,875 individuals responded to the survey. Congenital anomalies occurred in 2.9% of patients, low birth weight (LBW) in 7.6%, small for gestation age (SGA; <10th percentile) in 8.9%, and preterm birth in 4.1%. The median maternal external radiation dose was 0.5 mSv (maximum, 5.2 mSv). Doses were classified as follows: <1 mSv (reference), 1 to <2 mSv, and ≥2 mSv. For congenital anomalies, the crude odds ratio for 1 to <2 mSv was 0.81 (95% confidence interval [CI], 0.56-1.17) (no participants with congenital anomaly were exposed to ≥2 mSv). At 1 to <2 mSv and ≥2 mSv, the respective adjusted odds ratios were 0.91 (95% CI, 0.71-1.18) and 1.21 (95% CI, 0.53-2.79) for LBW, 1.14 (95% CI, 0.92-1.42) and 0.84 (95% CI, 0.30-2.37) for SGA, and 0.91 (95% CI, 0.65-1.29) and 1.05 (95% CI, 0.22-4.87) for preterm birth. CONCLUSION: External radiation dose due to the FDND was not associated with congenital anomalies, LBW, SGA, or preterm birth.

A Reactive Metabolite of Clozapine Induces Hematopoietic Toxicity in HL-60 Cells Undergoing Granulocytic Differentiation through Its Effect on Glutathione Metabolism.

Clozapine is an atypical antipsychotic with several advantages over conventional antipsychotics, in addition to its well-known efficacy in treatment-resistant schizophrenia. However, the high risk of agranulocytosis associated with clozapine therapy limits its clinical application. Clozapine bioactivation to an unstable protein-reactive metabolite, identified as a nitrenium intermediate, has been implicated in cytotoxicity toward neutrophils. Clozapine affects myeloid precursor cells rather than neutrophils; however, the impact of its reactive metabolite on myeloid precursor cells undergoing granulocytic differentiation remains unclear. Herein, we used hydrogen peroxide (H2O2) to generate the reactive metabolite and compared reactive metabolite-induced cytotoxicity between HL-60 cells undergoing granulocytic differentiation and differentiated HL-60 cells. In addition, we examined the role of oxidative stress in this type of cytotoxicity. The reactive metabolite of clozapine induced rapid cytotoxicity in HL-60 cells undergoing granulocytic differentiation, but not in differentiated HL-60 cells, with the metabolite exhibiting more potent cytotoxicity than clozapine. No cytotoxicity was observed following incubation with olanzapine, a structural analog of clozapine, even after exposure of the drug to H2O2. The reactive metabolite of clozapine decreased the levels of reduced glutathione, while addition of reduced glutathione attenuated the reactive metabolite-induced cytotoxicity. These findings indicate that glutathione metabolism plays a role in the hematopoietic toxicity induced by the reactive metabolite of clozapine. Oxidative stress may potentially increase susceptibility to the hematopoietic toxicity induced by the reactive metabolite of clozapine.

Factors Associated With Smoking Relapse Among Women in Japan From Pregnancy to Early Parenthood.

OBJECTIVE: To identify factors, including mental health, associated with smoking relapse among women in Japan from pregnancy to early parenthood. DESIGN: Secondary analysis of data from an ongoing cross-sectional study conducted between 2013 and 2016. SETTING: We mailed questionnaires to all women who received a maternal and child health handbook from a municipality in Fukushima Prefecture or who underwent a maternal health checkup and gave birth in Fukushima Prefecture. PARTICIPANTS: Of the 28,562 women who responded to the questionnaire, 6,747 who previously smoked and quit around the time they registered their pregnancies were included in the analysis. METHODS: Participants were divided into groups according to smoking relapse status: a nonrelapse group, which included those who maintained smoking cessation, and a relapse group, which included those who quit smoking but later relapsed. We further classified the latter group into those who quit smoking before or after pregnancy registration. We used a logistic regression model with forced entry to calculate adjusted odds ratios. RESULTS: Of the 6,747 participants who previously smoked, 881 (13.1%) relapsed. Regardless of the timing of smoking cessation, younger age and living in a specific region of Fukushima Prefecture were associated with smoking relapse. Relapse was associated with symptoms of depression in participants who quit smoking before registration and with multiparity in participants who quit smoking after registration of their pregnancies. CONCLUSIONS: Support for women at risk of smoking relapse after pregnancy requires consideration of regional characteristics and incorporation of family and mental health support with a focus on younger women.

Differences in Data Trustworthiness and Risk Perception between Bar Graphs and Pictograms.

We investigated whether differences in presentation style affect risk perception, understanding, preference, and trust toward data. One hundred and sixty Fukushima Medical University students were shown the lifetime probability of breast cancer incidence for a 50-year-old woman, presented in both a pictogram and a horizontal bar graph format. Participants rated each of the following on a five-point scale by looking at each figure: risk perception, perceived truth of data, and comparative risk perception. The perceived truth of data was high for pictograms, especially among men and among those defined as having lower health literacy. Women correctly perceived the risk of breast cancer as higher than that of dying in a car accident when the data were presented on a pictogram. There was no difference in risk perception, perceived truth of data, or comparative risk perception arising from being shown the bar graphs and the pictograms in a particular order. There was a 50/50 split on which type of graph was perceived as easier to understand, but the preference was for the pictogram format. It is important to devise a visual method of health communication that considers the purpose of the information and characteristics of the target audience.

Tailoring Digital Tools to Address the Radiation and Health Information Needs of Returnees after a Nuclear Accident.

Digital tools are increasingly used for health promotion, but their utility during recovery from a nuclear disaster has yet to be established. This study analysed differences in knowledge, attitude, and practice (KAP) toward digital tools for radiation protection and health promotion, and preferences for specific application functions, among cohorts living within and outside areas affected by the Fukushima Daiichi nuclear power station (FDNPS) accident. A needs assessment was conducted by internet survey, and responses from those affected (N = 86) and not affected (N = 253) were compared and quantified by an adjusted odds ratio (aOR), using logistic regression analyses. KAP toward the radiation-related application in the affected group had an aOR of 1.95 (95% confidence interval (CI) = 1.12-3.38) for knowledge, and 5.71 (CI = 2.55-12.8) for practice. Conversely, toward the health-related application, the aOR of the affected group was 0.50 (CI = 0.29-0.86). The preference in the affected group was significantly lower for two application functions related to radiation measurement and two health-related functions (one about the effects of radiation in general and another about personal health advice in general): aOR range 0.43-0.50. Development of specific applications incorporating the findings from this survey was intended to foster a locally appropriate eHealth environment during recovery from the FDNPS accident.

User-Guided Design of a Digital Tool for Health Promotion and Radiation Protection: Results from an Internet Needs Survey.

BACKGROUND: Digital tools can be powerful and effective in connecting people with life-saving and health-promoting support when facing a health crisis. To develop a digital application for radiation protection and health promotion for evacuees returning home after the Fukushima nuclear accident, we conducted a needs assessment survey and explored the association of people's eHealth literacy (eHL) level with their digital tool knowledge, attitudes, and practice (KAP). METHODS: From 339 responses to an online survey, data from 264 lay persons were analyzed. The KAP items were those used in a prior EU project, and eHL levels were assessed with a Japanese version of the eHealth Literacy Scale. RESULTS: Multivariable analyses showed significant associations between eHL and the digital tool KAP for radiation protection (knowledge: adjusted odds ratio (aOR) = 1.10; attitude: 1.06; practice: 1.10) and for health promotion (knowledge: aOR = 1.13; attitude: 1.06; practice: 1.16). CONCLUSIONS: People with a higher eHL had a more positive KAP. For those with a lower eHL, we are formulating easy-to-understand explanations to promote the utilization of the digital tool and enthusiasm for future community-oriented digital tools.

Survey of chemotherapy-induced nausea and vomiting in patients with urothelial carcinoma.

Chemotherapy-induced nausea and vomiting (CINV) can cause anorexia, weight loss and deterioration of patient quality of life. It is one of the most unpleasant adverse effects of chemotherapy treatment regimens. For the optimal treatment of gastrointestinal symptoms during urothelial carcinoma chemotherapy, the present study investigated the association between gastrointestinal symptoms and therapeutic effects of gemcitabine plus platinum [cisplatin (GC) or carboplatin (GCa)] therapies. The incidence and frequency of nausea/vomiting with GC split therapy (gemcitabine, 1,000 mg/m2 on days 1 and 8; split-dose cisplatin, 35 mg/m2 on days 1 and 8; 21-day schedule) and GCa therapy [gemcitabine, 750-1,000 mg/m2 on days 1, 8 and 15; carboplatin, area under the blood concentration-time curve=5 mg min/ml (Calvert formula) on day 2; 28-day schedule] were lower compared with those of GC therapy (gemcitabine, 1,000 mg/m2 on days 1, 8 and 15; single-dose cisplatin 70 mg/m2 on day 2; 28-day schedule). However, no differences in therapeutic outcomes were observed among therapies. GCa therapy, regardless of renal function, and GC split therapy demonstrated significant increases compared with GC therapy in alleviating gastrointestinal symptoms associated with cancer chemotherapy in patients with urothelial carcinoma. Overall, these results suggested that split-dose cisplatin administration or the use of carboplatin instead of cisplatin may be useful in patients who experience CINV without compromising treatment effectiveness.

Discovery of 5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine derivatives as novel selective Axl inhibitors.

Axl and Mer are members of the TAM (Tyro3-Axl-Mer) family of receptor tyrosine kinases. Previously, we reported that enzyme-mediated inhibition of Mer by an Axl/Mer dual inhibitor led to retinal toxicity in mice, whereas selective Axl inhibition by compound 1 did not. On the other hand, compound 1 showed low membrane permeability. Here, we designed and synthesized a novel series of 5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine derivatives and evaluated their Axl and Mer inhibitory activities, leading to identification of ER-001259851-000 as a potent and selective Axl inhibitor with drug-likeness and a promising pharmacokinetic profile in mice.

Discovery of a potent and selective Axl inhibitor in preclinical model.

Axl and Mer are a members of the TAM (Tyro3-Axl-Mer) family of receptor tyrosine kinases, which, when activated, can promote tumor cell survival, proliferation, migration, invasion, angiogenesis, and tumor-host interactions. Chronic inhibition of Mer leads to retinal toxicity in mice. Therefore, successful development of an Axl targeting agent requires ensuring that it is safe for prolonged treatment. Here, to clarify whether enzyme inhibition of Mer by a small molecule leads to retinal toxicity in mice, we designed and synthesized Axl/Mer inhibitors and Axl-selective inhibitors. We identified an Axl/Mer dual inhibitor 28a, which showed retinal toxicity at a dose of 100 mg/kg in mice. Subsequent derivatization of a pyridine derivative led to the discovery of a pyrimidine derivative, 33g, which selectively inhibited the activity of Axl over Mer without retinal toxicity at a dose of 100 mg/kg in mice. Additionally, the compound displayed in vivo anti-tumor effects without influencing body weight in a Ba/F3-Axl isogenic subcutaneous model.

Protocol for a multicentre, prospective, cohort study to investigate patient satisfaction and quality of life after immediate breast reconstruction in Japan: the SAQLA study.

INTRODUCTION: The aim of breast reconstruction (BR) is to improve patients' health-related quality of life (HRQOL). Therefore, measuring patient-reported outcomes (PROs) would clarify the value and impact of BR on a patient's life and thus would provide evidence-based information to help decision-making. The Satisfaction and Quality of Life After Immediate Breast Reconstruction study aimed to investigate satisfaction and HRQOL in Japanese patients with breast cancer who undergo immediate breast reconstruction (IBR). METHODS AND ANALYSIS: This ongoing prospective, observational multicentre study will assess 406 patients who had unilateral breast cancer and underwent mastectomy and IBR, and were recruited from April 2018 to July 2019. All participants were recruited from seven hospitals: Okayama University Hospital, Iwate Medical University Hospital, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Showa University Hospital, University of Tsukuba Hospital, Osaka University Hospital and Yokohama City University Medical Center. The patients will be followed up for 36 months postoperatively. The primary endpoint of this study will be the time-dependent changes in BREAST-Q satisfaction with breast subscale scores for 12 months after reconstructive surgery, which will be collected via an electronic PRO system. ETHICS AND DISSEMINATION: This study will be performed in accordance with the Ethical Guidelines for Medical and Health Research Involving Human Subjects published by Japan's Ministry of Education, Science and Technology and the Ministry of Health, Labour and Welfare, the modified Act on the Protection of Personal Information and the Declaration of Helsinki. This study protocol was approved by the institutional ethics committee at the Okayama University Graduate School of Medicine, Dentistry, on 2 February 2018 (1801-039) and all other participating sites. The findings of this trial will be submitted to an international peer-reviewed journal. TRIAL REGISTRATION NUMBER: UMIN000032177.

Implementing a flexible endoscopic evaluation of swallowing at elderly care facilities to reveal characteristics of elderly subjects who screened positive for a swallowing disorder.

OBJECTIVES: The risk of aspiration pneumonia has been reported to increase with age, especially in elderly residents of nursing homes. However, the characteristics of those with swallowing impairments at elderly care facilities have not yet been evaluated using reliable instrumental examinations. The aims of the current study were to investigate the frequency of swallowing impairment and determine the characteristics of the elderly with swallowing disorders residing at care facilities. METHODS: To reveal the characteristics of the elderly with swallowing disorders, questionnaires for dysphagia screening and flexible endoscopic evaluation of swallowing (FEES) were used. Regarding the dysphagia screening, two types of questionnaires were sent to 451 elderly persons aged 65 years and older who were living in facilities for the elderly in Japan. FEES was performed to assess swallowing impairment at each facility for those who were found to be positive for dysphagia by the questionnaires. The frequency of swallowing impairment and the characteristics of elderly subjects with swallowing disorders were investigated. RESULTS: Among 413 subjects who completed both questionnaires, 229 were screened positive for dysphagia, 160 of whom underwent FEES. Swallowing impairment was observed in 93 subjects. The subjects with swallowing impairment had a significantly high prevalence of fever, sputum, and/or history of aspiration pneumonia. Their oral intake ability and activities of daily living were significantly low. CONCLUSION: We demonstrated the frequency of swallowing disorders and the characteristics of elderly subjects with swallowing disorders living in care facilities using FEES. Our results suggest the importance of screening all elderly care facility residents for dysphagia.

Free flap reconstruction of Achilles tendon and overlying skin defect using ALT and TFL fabricated chimeric flap.

A 33-year-old man developed a left Achilles tendon rupture and skin necrosis. We reconstructed the defect using an anterolateral thigh flap and a tensor fasciae lata muscle flap in a chimeric fashion. he was able to stand on a toe of the operated foot without help 6 months postoperatively.

[Effect of Non-alcoholic Beverage Intake in Children on Alcoholic Beverage Drinking and Smoking].

　The early intake of alcohol and/or nicotine in childhood or adolescence is one of risk factors for alcohol and/or nicotine dependence in adult. Recently, non-alcoholic beverages with less than 0.00% alcohol are on sale for adults as substitutes for alcoholic beverages without strict legal limitations. However, it is unclear whether non-alcoholic beverages could be a risk factor in drinking and smoking in childhood or adolescence. The purpose of the present survey is to clarify the effect of non-alcoholic beverage intake in children on alcoholic beverage drinking and smoking. We examined as follows: the experience of alcoholic or non-alcoholic beverage intake, and of smoking in elementary school pupils and/or their family members, and interest in or motivation for drinking and smoking in the pupils. As a result, the percentage of alcoholic or non-alcoholic beverage intake, and of smoking in the pupils were 16.8% or 21.9%, and 0.3%, respectively. The number of family members took the alcoholic or non-alcoholic beverage was larger in the pupils took it compared to the pupils did not take it. In the pupils who experienced the non-alcoholic beverage intake, interest in or motivation for drinking alcoholic beverages and/or smoking is higher than in those who did not. These findings indicate that non-alcoholic beverage intake is related to drinking and smoking. We will introduce drug abuse prevention education on the risk of drug dependence among childhood or adolescents based on the findings of this survey.

Effect of Radiological Countermeasures on Subjective Well-Being and Radiation Anxiety after the 2011 Disaster: The Fukushima Health Management Survey.

After the Fukushima Daiichi Nuclear Power Station accident in 2011, concerns about radiation exposure and decline in subjective well-being have been reported. To tackle these problems, various countermeasures in relation to radiation have been implemented. In this study, we comprehensively evaluated the effects of radiological countermeasures on subjective well-being (e.g., satisfaction with life (SWL) and emotional well-being) and radiation anxiety, through a questionnaire survey targeting Fukushima residents (N = 1023). Propensity scores matching was applied to evaluate significant effects of radiological countermeasures on subjective well-being and radiation anxiety. Among the radiological countermeasures, thyroid examination, whole body counter, and air dose monitoring showed the highest proportions of participation, utilization, and useful evaluation, suggesting a high degree of public attention focused on these countermeasures. The basic survey was associated with significant increases in SWL and self-rated health (SH). Thyroid examination was significantly associated with not only a reduction in radiation anxiety but also an increase of emotional stress, suggesting the importance of careful design of system and detailed communication. Food inspection was associated with deterioration in SH. Those who utilized explanatory meetings showed increases in sadness, worry, and radiation anxiety, indicating that additional attention is required of the experts and authorities involved in explanatory meetings.

Berberine Induces Apoptotic Cell Death via Activation of Caspase-3 and -8 in HL-60 Human Leukemia Cells: Nuclear Localization and Structure-Activity Relationships.

Berberine (BBR), an isoquinoline alkaloid, is a well-known bioactive compound contained in medicinal plants used in traditional and folk medicines. In this study, we investigated the subcellular localization and the apoptotic mechanisms of BBR were elucidated. First, we confirmed the incorporation of BBR into the cell visually. BBR showed antiproliferative activity and promptly localized to the nucleus from 5[Formula: see text]min to 15[Formula: see text]min after BBR treatment in HL-60 human promyelocytic leukemia cells. Next, we examined the antiproliferative activity of BBR (1) and its biosynthetically related compounds (2-7) in HL-60 cells. BBR exerted strongest antiproliferative activity among 1-7 and the results of structures and activity relation suggested that a methylenedioxyl group in ring A, an [Formula: see text]-alkyl group at C-9 position, and the frame of isoquinoline may be necessary for antiproliferative activity. Moreover, BBR showed the most potent antiproliferative activity in HL-60 cells among human cancer and normal cell lines tested. Next, we examined the effect of BBR on molecular events known as apoptosis induction. In HL-60 cells, BBR induced chromatin condensation and DNA fragmentation, and triggered the activation of PARP, caspase-3 and caspase-8 without the activation of caspase-9. BBR-induced DNA fragmentation was abolished by pretreatment with inhibitors against caspase-3 and caspase-8, but not against caspase-9. ERK and p38 were promptly phosphorylated after 15 min of BBR treatment, and this was correlated with time of localization to the nucleus of BBR. These results demonstrated that BBR translocated into nucleus immediately after treatments and induced apoptotic cell death by activation of caspase-3 and caspase-8.