Genetics of chilling response at early growth stage in rice: a recessive gene for tolerance and importance of acclimation.

Low-temperature adaptation in rice is mediated by the ability of a genotype to tolerate chilling temperatures. A genetic locus on chromosome 11 was analysed for chilling tolerance at the plumule stage in rice. The tolerant allele of A58, a japonica landrace in Japan, was inherited as a recessive gene (ctp-1A58), whereas the susceptible alleles from wild rice (Ctp-1W107) and modern variety (Ctp-1HY) were the dominant genes. Another recessive tolerant allele (ctp-1Silewah) was found in a tropical japonica variety (Silewah). Fine-mapping revealed that a candidate gene for the ctp-1 locus encoded a protein similar to the nucleotide-binding domain and leucine-rich repeat (NLR) protein, in which frameshift mutation by a 73 bp-deletion might confer chilling tolerance in ctp-1A58. Analysis of near-isogenic lines demonstrated that ctp-1A58 imparted tolerance effects only at severe chilling temperatures of 0.5 °C and 2 °C, both at plumule and seedling stages. Chilling acclimation treatments at a wide range of temperatures (8 °C-16 °C) for 72 h concealed the susceptible phenotype of Ctp-1W107 and Ctp-1HY. Furthermore, short-term acclimation treatment of 12 h at 8 °C was enough to be fully acclimated. These results suggest that the NLR gene induces a susceptible response upon exposure to severe chilling stress, however, another interacting gene(s) for acclimation response could suppress the maladaptive phenotype caused by the Ctp-1 allele. This study provides new insights for the adaptation and breeding of rice in a low-temperature environment.

Using patient storytelling to improve medical students' empathy in Japan: a pre-post study.

BACKGROUND: Empathy for patients is now internationally accepted as one of the competencies of physicians for patient-centered medical practice and an essential component of medical education. Recently, "patient storytelling" has attracted attention in empathy education for medical students to understand patients' experiences, feelings, and perspectives. This study aimed to quantitatively evaluate how patient storytelling enhanced undergraduate medical students' empathy in Japan to the extent that they sustained it for six months. METHODS: Participants were 159 fourth-year undergraduate medical students in Tokyo in academic years 2018 and 2019. The questionnaire surveys were conducted three times: at the beginning of the class, immediately after the class, and six months after the class. The Japanese version of the Jefferson Scale of Empathy-Student Version was used in this study. Gender, age, and clinical orientation were also obtained through the self-reported questionnaire. We invited a male patient storyteller who was diagnosed with chronic kidney disease to the classes on "Professionalism." The title of his storytelling was "The Power of Medical Professionals' Words." RESULTS: JSE-S scores improved significantly immediately after listening to patient storytelling. The scores remained improved six months after the class. Interest of specialty was significantly positively associated with an immediate change in JSE-S scores. However, gender had no significant association with changes in JSE-S scores either immediately or six months after education. CONCLUSIONS: Our findings may suggest that patient storytelling would be useful to cultivate empathy among undergraduate medical students. It is to be expected that more medical schools will use patient storytelling to educate medical students in humanistic and communication education.

Readability assessment of vaccine information: A systematic review for addressing vaccine hesitancy.

OBJECTIVE: Vaccine hesitancy is a problem attracting growing attention and concern. Communication can be an effective tool to counteract vaccine hesitancy and promote optimal vaccine uptake. Readability has been recognized as one of the more important aspects of health communication for achieving good health literacy. We reviewed studies of readability assessment in the area of vaccine communication. METHODS: We conducted a systematic literature search in September 2020, using four online databases (Medline, CINAHL, PsycArticles, and PsycINFO). We included studies that assessed the readability level of online and offline vaccine information materials. RESULTS: We found 12 articles that were appropriate for inclusion. Ten of the studies were published after 2016. The readability levels of the majority of the materials assessed were found to be difficult and higher than 8th-grade level. CONCLUSION: Readability assessments of vaccine information are scarce. The limited evidence shows that the readability level of vaccine information supplied by health care providers is more difficult to read than recommended. More studies on the readability of vaccine information are recommended. PRACTICE IMPLICATIONS: Difficulty reading vaccine information may influence attitudes toward acceptance of or hesitancy to take vaccines. It is recommended that health care professionals use guidelines and tools to create easy-to-read vaccine information.

Factors related to self-care drug treatment and medication adherence of elderly people in Japan.

Objectives: The number of home-dwelling elderly people who need drug treatment is increasing with the aging of the population. Elderly people are often suffering from various chronic diseases requiring treatment with multiple drugs, which makes self-care at home difficult. This study focused on medication adherence and aimed to identify the current state of self-care for drug treatment in home-dwelling elderly people and the factors that relate to self-care and medication. Study design: Cross-sectional study. Methods: Medication adherence was measured on a 12-item medication adherence scale for home-dwelling elderly people aged 65 and over who were taking medications. The present condition of medication self-care for home-dwelling elderly people was clarified in terms of medication adherence. Next, we clarified the relationship between medication adherence and other factors such as demographic and clinical characteristics, communication with doctors, and health literacy. Results: The average age was 73.7 (47.2% male). Functional health literacy and communicative health literacy were significantly associated with a high level of medication adherence. There was also a significant association between medication adherence and good communication with doctors. Conclusions: Medication adherence among home-dwelling elderly people was found to be related to the ability to obtain, understand, and communicate information, in addition to the basic literacy skills of health literacy. We also found that good communication with doctors was closely related to medication adherence. Our findings suggest that it is necessary to be consciously involved in promoting health literacy and communication when supporting self-care for medical treatment of home-dwelling elderly people in the future.

Development of a Japanese version of the Advance Care Planning Engagement Survey: Examination of its reliability and validity.

OBJECTIVES: The importance of supporting advance care planning (ACP) by healthcare professionals is recognized worldwide, and assessing the outcomes, such as people's understanding and readiness for ACP, using an appropriate instrument is essential. We, therefore, developed a Japanese version of the Advance Care Planning Engagement Survey (ACP Engagement Survey; 15 items, 9 items, and 4 items), an international scale for assessing the progress of the ACP, and examined its validity and reliability. METHODS: The ACP Engagement Survey was translated into Japanese, back-translated, and culturally adapted, and the final version was reviewed by the author of the original version. Data on basic demographic information and ACP-related experiences were simultaneously collected as external criteria in an online survey of older adults with chronic diseases. The Cronbach's alpha was calculated to assess its internal consistency, and a retest was performed three days later to calculate the intra-class correlation coefficients (ICCs). RESULTS: A total of 200 respondents (mean age 70; 9.5% female) were included in the analysis. None of the items showed a ceiling effect, but several items did exhibit a floor effect. The factor structure was the same 2-factor structure as the original version, and both factors exhibited a high cumulative contribution rate. The Cronbach's alphas were 0.94 (15-item version), 0.91 (9-item version), and 0.95 (4-item version), and ICCs were of 0.88 (15-item version), 0.9 (9-item version), and 0.84 (4-item version). SIGNIFICANCE OF RESULTS: The Japanese version of the ACP Engagement Survey was confirmed to have very good reliability regarding both internal consistency and test-retest reliability. Together with the result of the item analysis, we can conclude that the Japanese version of the ACP Engagement Survey is sufficiently reliable to be utilized in interventional studies, and it has acceptable content validity, construct validity, and criterion-related validity.

Examining Long-Term Effects of Human Papillomavirus Vaccine Recommendation Messages: A 4-Month Follow-Up Survey of a Randomized Controlled Study in Japan.

We previously conducted a randomized controlled study to examine persuasive messages recommending HPV vaccination to mothers with daughters in Japan. That study showed that the three types of intervention message used (statistical information only, a patient's narrative in addition to statistical information, and a mother's narrative in addition to statistical information) all significantly improved mothers' intention to have their daughter(s) receive the HPV vaccine, in comparison with mothers who received no messaging. The present study is a follow-up survey to assess the long-term effect of the intervention. Four months after the initial study, in January 2018, participants in the previous study were contacted and queried about their current intention to have their daughter(s) receive the HPV vaccine. Statistical analysis was conducted using the paired t-test and analysis of variance. A total of 978 mothers participated in the current survey. Vaccination intention 4 months after intervention had decreased to a level that did not differ significantly from the level prior to intervention in all three intervention conditions. The amount of change in vaccination intention 4 months after intervention did not differ significantly among the three intervention groups (p = 0.871). A single exposure to messaging was insufficient to produce a persistent intervention effect.

Dual-process theories to counter the anti-vaccination movement.

Vaccine hesitancy is a problem attracting growing attention and concern. In this paper, we discuss why anti-vaccination messages are influential and which pro-vaccine messages can be effective to address vaccine hesitancy from the perspective of dual-process theories of cognitive functioning. The functioning of the human brain can be characterized by two different types of cognitive functioning: intuitive System 1, which is evolutionarily old, fast, and automatic; and analytical System 2, which is evolutionarily recent, slow, and deliberative. Anti-vaccination messages that inspire fear activate System 1, and vaccine recommendation messages that use statistics activate System 2. System 1 has a greater influence on judgment than System 2. The processing of System 1 is called "trajectory." Even if adequate knowledge about the effectiveness and safety of vaccination is input to System 2, vaccine hesitancy cannot be easily erased once it is generated by System 1. We suggest that vaccine recommendation messages should target System 1 in addition to System 2, to counter anti-vaccination messages and address vaccine hesitancy.

Online Japanese-Language Information on Lifestyle Factors Associated With Reduced Fertility: Content Analysis.

BACKGROUND: Approximately one-third of Japanese couples currently worry or previously worried about infertility. To develop strategies for the primary prevention of infertility as a population approach, it is important for the general population to be knowledgeable about fertility and infertility. The internet may contribute to the dissemination of information regarding infertility and fertility. However, few studies have examined online information about fertility. OBJECTIVE: This study aimed to quantitatively examine online Japanese-language information about lifestyle factors associated with reduced fertility. METHODS: We conducted online searches, using the 10 search terms with the highest numbers of searches that people hoping to conceive are likely to input in two major search engines in Japan (Google Japan and Yahoo! Japan). From the 2200 retrieved websites, 1181 duplicates and 500 websites unrelated to our objective were excluded, resulting in a final dataset of 519 websites. Coding guidelines were developed for the following lifestyle factors associated with reduced fertility: sexually transmitted diseases, psychological stress, cigarette smoking, alcohol use, nutrition and diet, physical activity and exercise, underweight, overweight and obesity, and environmental pollutants. RESULTS: In terms of the website author's professional expertise, 69.6 % of the coding instances for the selected lifestyle factors were mentioned by hospitals, clinics, or the media, whereas only 1.7% were mentioned by laypersons. Psychological stress (20.1%) and sexually transmitted diseases (18.8%) were the most frequently mentioned lifestyle factors associated with reduced fertility. In contrast, cigarette smoking, alcohol use, nutrition and diet, physical activity and exercise, underweight, overweight and obesity, and environmental pollutants were mentioned relatively infrequently. The association between reduced fertility and sexually transmitted diseases was mentioned significantly more frequently by hospitals and clinics than by the media (P<.001). The association between reduced fertility and nutrition and diet was mentioned significantly more frequently by the media than by hospitals and clinics (P=.008). With regard to the sex of the target audience for the information, female-specific references to psychological stress, sexually transmitted diseases, nutrition and diet, underweight, physical activity and exercise, and overweight and obesity were significantly more frequent than were male-specific references to these lifestyle factors (psychological stress: P=.002, sexually transmitted diseases: P<.001, nutrition and diet: P<.001, underweight: P<.001, physical activity and exercise: P<.001, overweight and obesity: P<.001). CONCLUSIONS: Of the lifestyle factors known to be related to reduced fertility, cigarette smoking, alcohol use, and male-specific lifestyle factors are mentioned relatively infrequently in online information sources in Japan, and these factors should be discussed more in information published on websites.

Influence of high versus low readability level of written health information on self-efficacy: A randomized controlled study of the processing fluency effect.

We investigated the relationship of processing fluency of written information about exercise to participants' perceived interest, safety, self-efficacy, outcome expectation, and behavioral intention regarding the exercise. We randomly assigned 400 men and women aged 40-69 years to control or intervention conditions. Perceived self-efficacy of performing the exercise in the intervention group (i.e. easy to read) was significantly higher than that in the control group (i.e. difficult to read) (p = 0.04). Easy-to-read written health information may be important not only for making written health information comprehensible but also for increasing readers' self-efficacy for adopting health-related behaviors.

The association between health literacy levels and patient-reported outcomes in Japanese type 2 diabetic patients.

OBJECTIVES: The aim of this study is to empirically examine a full pathway model of health literacy, and health and well-being outcomes among patients with type 2 diabetes. METHODS: A three-wave longitudinal survey was administered to 148 patients with diabetes. Covariance structure analysis was conducted to create a path diagram, with health literacy and burden of medical expenses included as independent variables and with psychosocial factors, behaviors, and health and well-being outcomes included as dependent variables. RESULTS: The model fit indices showed a comparative fit index of 0.985 at baseline, 0.959 after 3 months, and 0.948 after 6 months, with a root mean square error of approximation of 0.040 at baseline, 0.079 after 3 months, and 0.085 after 6 months. There were 14 significant paths across the three time points between health literacy and understanding of diabetes care, self-efficacy, communication with doctors, and medication adherence. CONCLUSION: The model fitness index showed an adequate result. Health literacy was significantly positively associated with understanding of diabetes care, self-efficacy, communication with doctors, and medication adherence. Health literacy had a direct positive influence on medication adherence and possibly an indirect positive influence on exercise/diet via self-efficacy. The results were generally consistent across the three time points, suggesting good reliability of the models. Improving health literacy may lead to better self-management of diabetes and favorable health outcomes.

Reliability and validity of a 12-item medication adherence scale for patients with chronic disease in Japan.

BACKGROUND: To improve and support medication adherence among patients with chronic diseases, especially for long-term medication, it is important to consider both their relationship with healthcare providers and their lifestyle. We tested the reliability and validity of a modified 12-item Medication Adherence Scale. METHODS: We revised a 14-item measure of medication adherence, created in 2009, to a more concise and clear 12-item version, and we verified the reliability and validity of the 12-item scale. We included 328 patients with chronic diseases participating in the Chronic Disease Self-Management Program in Japan from 2011 to 2014. Confirmatory factor analysis was used to assess whether the four factors assessed were the same as the previous 14-item Medication Adherence Scale. Cronbach's coefficient alpha was used to assess internal consistency reliability, and the relationships between patient demographic characteristics and medication adherence were compared with previous studies. RESULTS: The 12 items were categorized into the four factors "medication compliance", "collaboration with healthcare providers", "willingness to access and use information about medication", and "acceptance to take medication and how taking medication fits patient's lifestyle". Confirmatory factor analysis showed χ2/df = 2.6, CFI = 0.94, and RMSEA = 0.069. Cronbach's alpha for the 12-item scale was 0.78. Cronbach's alpha for the four subscales was 0.74, 0.81, 0.67, and 0.45. Higher medication adherence was significantly associated with being a female patient, living with someone else, and age 40-49 years versus age 20-29 years. These relationships were the same as in previous studies. CONCLUSIONS: We modified our original 14-item scale to a 12-item Medication Adherence Scale for patients with chronic diseases, which considers their relationship with healthcare providers and lifestyle. Refinement might be needed because of the relatively low reliability of subscales. However, the modified scale is expected to contribute to more effective self-management of medication and to improving medication adherence, particularly among patients with chronic diseases who require long-term medication not only in Japan but also in other countries.

A Succinate Ether Derivative of Tocotrienol Enhances Dickkopf-1 Gene Expression through Epigenetic Alterations in Malignant Mesothelioma Cells.

BACKGROUND: Wnt signaling plays an essential role in tumor cell growth, including the development of malignant mesothelioma (MM). Epigenetic silencing of negative Wnt regulators leading to constitutive Wnt signaling has been observed in various cancers and warrants further attention. We have reported that a succinate ether derivative of α-tocotrienol (T3E) has potent cytotoxic effects in MM cells. Thus, in this study, we investigated whether the anti-MM effect of T3E could be mediated via the epigenetic alteration of the Wnt antagonist gene, Dickkopf-1 (DKK1). METHODS: WST-1 and cell analyzers were employed to analyze the effects of T3E on cell viability and apoptosis of human MM cell lines (H2452, H28). Real-time PCR and Western blot were performed to evaluate the expression at mRNA and protein levels. Methylation status and epigenetic modifications of DKK1's promoter regions after T3E treatment in MM cells were studied using methylation-specific PCR and Chromatin immunoprecipitation. Small interfering RNA-mediated knockdown -(siRNA), and specific inhibitors, were used to validate DKK1 as a target of T3E. RESULTS: T3E markedly impaired MM cell viability, increased the expression of phosphorylated-JNK and DKK1 and suppressed cyclin D, a downstream target gene of Wnt signaling. Knockdown of DKK1 expression by siRNA or a specific JNK inhibitor confirmed the contribution of DKK1 and JNK to T3E-induced cytotoxicity in MM cells. On the other hand, cytoskeleton-associated protein 4 (CKAP4) expression, which promotes cell proliferation as a Wnt-independent DKK1 receptor was inhibited by T3E. Silencing CKAP4 by -siRNA did not appear to directly affect MM cell viability, thereby indicating that expression of both DKK1 and CKAP4 is required. Furthermore, T3E-mediated inhibition of both DNA methyltransferases (DNMT1, 3A, and 3B) and histone deacetylases (HDAC1, 2, 3, and 8) in MM cells leads to increased DKK1 expression, thereby promoting tumor growth inhibition. MM cells treated with Zebularine (a DNMT inhibitor) and sodium butyrate (an HDAC inhibitor) exhibited cytotoxic effects, which may explain the inhibitory action of T3E on MM cells. In addition, an enhanced expression of DKK1 in MM cells following T3E treatment is positively correlated with the methylation status of its promoter; T3E decreased DNA methylation and increased histone acetylation. Moreover, T3E specifically increased histone H3 lysine 4 (H3K4) methylation activity, whereas no effects were observed on histone H3K9 and H3K27. CONCLUSIONS: Targeting the epigenetic induction of DKK1 may lead to effective treatment of MM, and T3E has great potential to induce anti-MM activity.

COMPARISON OF COSMIC-RAY ENVIRONMENTS ON EARTH, MOON, MARS AND IN SPACECRAFT USING PHITS.

Estimation of cosmic-ray doses is of great importance not only in aircrew and astronaut dosimetry but also in evaluation of background radiation exposure to public. We therefore calculated the cosmic-ray doses on Earth, Moon and Mars as well as inside spacecraft, using Particle and Heavy Ion Transport code System PHITS. The same cosmic-ray models and dose conversion coefficients were employed in the calculation to properly compare between the simulation results for different environments. It is quantitatively confirmed that the thickness of physical shielding including the atmosphere and soil of the planets is the most important parameter to determine the cosmic-ray doses and their dominant contributors. The comparison also suggests that higher solar activity significantly reduces the astronaut doses particularly for the interplanetary missions. The information obtained from this study is useful in the designs of the future space missions as well as accelerator-based experiments dedicated to cosmic-ray research.

Factors associated with deaths in 'Elderly Housing with Care Services' in Japan: a cross-sectional study.

BACKGROUND: Although the Japanese government has expanded its 'Elderly Housing with Care Services' (EHCS) to ensure sufficient places of death for the elderly, resident deaths have occurred in less than 30% of the facilities. Our purpose was to identify the factors associated with residents' deaths in the EHCS, especially within the areas that are expected to have a large increase in the number of deaths. METHODS: Our cross-sectional study involved all EHCS (N = 412) in Japan's Tokyo, Kanagawa prefecture and used self-administered questionnaire data that the EHCS directors completed. In addition, we accessed the national statistics related to the municipal characteristics of the cities where the EHCS were located. These sources provided information about health care provision for the residents as well as facility/resident/regional characteristics that could potentially be associated with residents' deaths in the EHCS. Based on this information, a sequential multiple logistic regression analysis was performed. First, we included in-facility health care provision (presence of nursing staff) and facility/residents/regional characteristics in Model 1. Next, visiting nurse agency's care provision was included in Model 2. Finally, we included community hospitals or clinical care provision in Model 3. RESULTS: One hundred and fifty-four facilities answered the questionnaire (response rate: 37.4%). A total of 114 facilities were analysed. In-facility residents' deaths occurred in more than half (54.4%) of the facilities. After adjusting for all variables (Model 3), end-of-life (EOL) care provision from community hospitals or clinics, the number of years since establishment and the number of residents were significantly associated with residents' deaths. In Model 2, visiting nurse's EOL care provision was significantly associated with residents' death. CONCLUSION: Our results suggest that in order to accommodate residents' deaths, the government or the facility's directors should promote the cooperation between EHCS facilities and community hospitals or clinics for in-residents' EOL care. Furthermore, as the results suggest that community nurses contribute to the occurrences of death by collaborating with the physician, promoting cooperation with visiting nurse agencies may be also needed.

Cytotoxicity Induced by a Redox-silent Analog of Tocotrienol in Human Mesothelioma H2452 Cell Line via Suppression of Cap-dependent Protein Translation.

De novo synthesis of proteins is regulated by cap-dependent protein translation. Aberrant activation of the translation is a hallmark of many cancer types including malignant mesothelioma (MM). We previously reported that a redox-silent analog of α-tocotrienol, 6-O-carboxypropyl-α-tocotrienol (T3E) induces potent cytotoxicity against human MM cells. However, the detailed mechanism of cytotoxicity of T3E remains unclear. In this study, we investigated if T3E induced potent cytotoxicity aganist MM cells. T3E reduced the formation of the cap-dependent translation complex and induced inactivation of oncogene from rat sarcoma virus (RAS). These events were associated with T3E cytotoxicity in MM cells. Furthermore, atorvastatin, an inhibitor of RAS function, had similar effects on MM cells. Moreover, 4EGI-1, a specific inhibitor of the cap-dependent translation complex, induced severe cytotoxicity in MM cells. Overall, T3E had a cytotoxic effect on MM cells via disruption of the activated cap-dependent translation complex through inactivation of RAS.