Language confidence and job satisfaction among foreign-born nurses in Japan: mediating effect of workplace discrimination and moderating effect of immigration duration.

AIM: This study explored the relationship between language confidence and job satisfaction, the mediating role of workplace discrimination, and the moderating role of immigration duration among foreign-born nurses in Japan. INTRODUCTION: Job satisfaction is an important factor in preventing migrant nurses' turnover intentions; however, the relationships among language confidence, immigration duration, workplace discrimination, and job satisfaction among foreign-born nurses remain unclear. METHODS: A cross-sectional study was conducted. Data were collected between June and August 2022 through an online survey of nurses who were born outside of Japan but were currently working as registered nurses in Japan. PROCESS v4.0 Macro for SPSS 28.0 was applied to analyze the effect of language confidence on job satisfaction, the mediator effect of workplace discrimination (model 4), and the moderator effect of immigration duration (model 15). RESULTS: Data from 187 participants were analyzed. The results showed that 1) foreign-born nurses' language confidence was negatively correlated with workplace discrimination and positively correlated with job satisfaction; 2) workplace discrimination played a partially mediating role between language confidence and job satisfaction; and 3) immigration duration positively moderated the relationship between language confidence and job satisfaction. CONCLUSION: Foreign-born nurses with stronger confidence in their proficiency in Japanese perceived less workplace discrimination and higher job satisfaction. Workplace discrimination acted as a mediator in the relationship between language confidence and job satisfaction, and this relationship was strengthened with longer migration periods. Managers and policymakers should implement policies and strategies to combat workplace discrimination and provide tailored support to improve foreign-born nurses' job satisfaction, which may contribute to their retention in Japan.

Relationship Between Resilience and Perceived Control After Acute Coronary Syndrome: A Prospective Study.

BACKGROUND: Patients with acute coronary syndrome report poor health-related quality of life and decreased levels of perceived control. Perceived control is a person's belief that they can cope with negative events. Resilience is an adaptation that gives people the capacity to recover from difficult situations, and higher levels of resilience may impact recovery after an acute event. OBJECTIVE: The aim of this study was to analyze the relationship between resilience, perceived control, and health outcomes of patients hospitalized with acute coronary syndrome within 6 months of discharge. METHODS: Data were collected prospectively from adult patients hospitalized with acute coronary syndrome in 3 university hospitals in the Tokyo Metropolitan area, Japan. All data were collected between December 2015 and December 2019. The Sukemune-Hiew Resilience Test (part 1) was used to measure resilience, which includes 3 domains of social support, self-efficacy, and sociality. The Control Attitudes Scale-Revised was used to measure perceived control. Linear regression and path analysis were used to statistically analyze the relationship among variables. RESULTS: Higher resilience, especially self-efficacy, was associated with higher perceived control during admission. Higher resilience, especially social support, during admission was associated with perceived control at 6 months after adjusting for income and education. Higher resilience during admission was associated with better perceived control at 3 months, which was associated with better health outcomes at 6 months. Higher income and lower depression were related to higher resilience. CONCLUSIONS: Nurses should make sure patients with depression, low income, and low social support are connected with appropriate treatment and social support resources.

The Impact of Collaborative Online International Learning on Intercultural Sensitivity Among Nursing Students in the United States and Japan.

ABSTRACT: Collaborative online international learning (COIL) is a curricular approach that allows students to collaborate across cultures using various communication technologies. Little is known about the influence of COIL on intercultural sensitivity, a key competency for nursing students to better serve increasingly diverse patient populations. We implemented COIL in undergraduate nursing courses in the United States and Japan and examined its impact on intercultural sensitivity using the Intercultural Sensitivity Scale (ISS) as a pretest and posttest. The results of a paired t -test indicated ISS total scores significantly increased after COIL, supporting its use in nursing education courses.

A Case Report of Collaborative Online International Learning in Nursing and Health Studies Between the United States and Japan.

ABSTRACT: Collaborative online international learning (COIL) is an innovative and cost-effective pedagogy to develop cross-cultural awareness through digital technology across shared multicultural learning environments. We implemented our first COIL virtual exchange for undergraduate students at universities in the United States and Japan. We used Padlet for asynchronous discussions to build rapport among students at each institution and Zoom for synchronous discussions to deliver oral presentations. Feedback from students indicate an overall increase in intercultural competence and cultural sensitivity. COIL can provide meaningful, affordable, and feasible health education that enhances cultural understanding through virtual exchange.

Effectiveness of ethinylestradiol/drospirenone for premenstrual symptoms in Japanese patients with dysmenorrhea: Open-label pilot study.

AIM: A combined oral contraceptive containing ethinylestradiol 20 µg plus drospirenone 3 mg (EE20 + DRSP) in a 24/4 regimen has been shown to alleviate the symptoms of premenstrual syndrome and premenstrual dysphoric disorder. This study was conducted to evaluate the efficacy of EE20 + DRSP in Japanese patients with premenstrual symptoms. MATERIAL AND METHODS: A multicenter, prospective, open-label, single-arm, phase IV study was performed in Japanese women with dysmenorrhea and premenstrual symptoms. They were treated with EE20 + DRSP to alleviate the symptoms of dysmenorrhea for six treatment cycles. Premenstrual symptoms were evaluated using a Premenstrual Symptoms Questionnaire at baseline and after three and six cycles of EE20 + DRSP. The degree of dysmenorrhea was also evaluated using a visual analog scale at baseline and after one, three, and six cycles of EE20 + DRSP. RESULTS: Forty-eight patients were treated with EE20 + DRSP. Most of the premenstrual symptoms were alleviated significantly by three and six cycles of EE20 + DRSP treatment. EE20 + DRSP treatment significantly improved the severity of premenstrual symptoms. We also confirmed the effectiveness of EE20 + DRSP for the treatment for dysmenorrhea. CONCLUSION: This study showed that EE20 + DRSP could be a useful treatment strategy for premenstrual symptoms in Japanese women.

Curcumin targets the AKT-mTOR pathway for uterine leiomyosarcoma tumor growth suppression.

BACKGROUND: Uterine leiomyosarcomas generally do not respond well to standard chemotherapy. We previously demonstrated that curcumin, the active ingredient derived from the herb Curcuma longa, inhibits uterine leiomyosarcoma cells in vitro via the inhibition of the AKT-mammalian target of rapamycin (mTOR) pathway. As a preclinical investigation, we performed an in vivo study using female nude mice to confirm the therapeutic potential of curcumin against uterine leiomyosarcoma. METHODS: Human leiomyosarcoma cells, SK-UT-1, were inoculated in female nude mice to establish subcutaneous tumors. Either vehicle control or 250 mg/kg curcumin was administered intraperitoneally every day for 14 consecutive days, and the mice were then killed. The tumors were measured every 2-3 days. The tumors were processed for immunohistochemical analyses to detect total AKT, phosphorylated AKT, total mTOR, phosphorylated mTOR, and phosphorylated S6. To detect apoptosis, the tumors were stained for cleaved PARP and TUNEL. Ki-67 immunohistochemistry was performed to determine cell viability of the tumors. RESULTS: Compared with the control, curcumin reduced uterine leiomyosarcoma tumor volume and mass significantly with a concordant decrease in mTOR and S6 phosphorylation. However, AKT phosphorylation was not significantly altered. Cleaved PARP and TUNEL staining increased significantly with curcumin administration, indicating the induction of apoptosis. There was no difference in Ki-67 staining between the two groups. CONCLUSION: Curcumin inhibited uterine leiomyosarcoma tumor growth in vivo by targeting the AKT-mTOR pathway for inhibition.

Comparison of global nursing education and necessary supports for nurse educators between Japan and four English-speaking countries: An international cross-sectional study.

AIM: This study aimed to compare characteristics of nurse educators, factors related to teaching global nursing, contents of global education and support and the level of burden of global education and factors related to the burden between nurse educators among top nursing universities in Japan and four English-speaking countries. BACKGROUND: Intercultural sensitivity is the active desire to motivate oneself to understand, appreciate and accept different cultures. Nurse educators need to be culturally sensitive to teach cultural care to nursing students. DESIGN: This is a cross-sectional exploratory international comparative study using an online survey. METHODS: Participants were nurse educators with a nurse license in the top 20 in Japan and the top 10 universitiesin the United States, Canada, United Kingdom and Australia (hereafter "English-speaking countries"), respectively. The questions in Google form selected participants by the inclusion criteria. Intercultural sensitivity was measured by the Intercultural Sensitivity Scale. Chi-square test, Fisher's exact test, t-test, Mann-Whitney U test and Spearman's correlation coefficients were used for the analyses. Data were collected from October 2023 to January 2024. RESULTS: A total of 144 in Japan (response rate=29.0 %) and 106 educators in English-speaking countries (response rate=2.4 %) were included in the analysis. Nurse educators in Japan had less work experience in foreign countries, had fewer opportunities to take part in cross-cultural interactions and had significantly lower intercultural sensitivity. In both groups, those who had more experience in foreign countries with higher intercultural sensitivity taught global nursing. While in Japan nurse educators who had higher proficiency in non-native languages and those who had more frequently taken part in cross-cultural interactions taught global nursing, in English-speaking countries full-time workers who had attended international academic conferences taught. In Japan, global nursing was a more optional course and the number of contents taught was lower. While participants in Japan had international seminars at universities as support for global nursing education, those in English-speaking countries had faculty members with different cultural backgrounds. Participants in Japan felt more burden for global nursing education. In Japan, more proficient non-native language, more frequent cross-cultural interaction and higher intercultural sensitivities were associated with a lower burden, while teaching other than in their native language, contents taught and performance evaluation were associated with a higher burden in English-speaking countries. CONCLUSIONS: Higher intercultural sensitivity, performance evaluation and proficiency in non-native language may be important for nurse educators to teach global nursing and support is necessary to enhance them.

Anxiety among Japanese nursing researchers before and after dispatch for COVID-19 pandemic support: Effects of anxiety-enhancing and buffering factors.

AIM: We investigated the levels of anxiety and the factors influencing it among Japanese nursing researchers before and after engaging in dispatch support activities during the COVID-19 pandemic. This study also tested the relationships between pre- and post-relief anxiety and their enhancing and buffering factors. METHODS: A web-based survey was conducted with 9832 members from the Japan Academy of Nursing Science, covering 15 items related to participant attributes such as age and disaster relief qualifications, factors affecting anxiety about support activities such as the content and duration of one activity, and the level of anxiety before and after activities. After performing multiple regression analyses on the effects of the attributes and the factors influencing anxiety before and after support activities, path analysis was conducted on the adopted independent variables to examine their influence on anxiety before and after support activities. RESULTS: Of the 886 participants, 82.3% were affiliated with educational institutions and 94.8% had no qualifications in disaster relief. Most of the support involved vaccination and activities at health centers. The relationship between pre- and post-relief activities and factors influencing anxiety constituted a high goodness-of-fit, with health center assistance being both a direct and indirect reinforcer of post-relief anxiety. CONCLUSIONS: Participants expressed anxiety enhanced by activities at the health center both before and after support activities in the wake of the COVID-19 pandemic. Intervention research should examine anxiety-buffering and -enhancing factors, and a support system to respond to rapidly increasing medical needs is necessary.

Comparing factors related to perceived control and preventive behaviors from COVID-19 between Japanese and American nursing students: A cross-sectional study.

AIM: Higher levels of perceived control are important to maintain health. The difference in factors related to perceived control and preventive behaviors during the COVID-19 pandemic between Japanese and American nursing students remains unknown. This study aimed to compare factors related to perceived control and infection preventive behaviors between the two countries. METHODS: This cross-sectional study included nursing students attending four universities in Japan and one in the United States. Using Google Forms, the participants answered a survey comprising sociodemographic data, the Perceived Control and Self-Efficacy Scale, the Perceived Health Competence Scale, and a preventive behavior questionnaire. The data were collected from November 2020 to May 2021. Linear and logistic regressions were used to analyze the factors related to perceived control and preventive behaviors, respectively. RESULTS: Data from 878 students were analyzed. University/campus emerged as a strong predictor for perceived control and preventive behaviors in both countries, with a positive correlation between perceived control and preventive behaviors. Older age, less frequent alcohol consumption, higher perceived health competence, less frequent work in Japan; and chronic conditions in the United States were associated with frequent preventive behaviors. Younger age was correlated with higher perceived control in Japan, while religion and increased workload were potential factors for American students. CONCLUSION: Individual factors were pivotal in Japan, whereas interpersonal factors were more likely related to perceived control in the United States. Additionally, in both countries, policy or organizational factors significantly influenced students' preventive behaviors.

Curcumin induces cross-regulation between autophagy and apoptosis in uterine leiomyosarcoma cells.

OBJECTIVE: Uterine leiomyosarcoma (LMS) has an unfavorable response to standard chemotherapy. A natural occurring compound, curcumin, has been shown to have inhibitory effects on cancers. We previously demonstrated that curcumin reduced uterine LMS cell proliferation by targeting the AKT-mTOR pathway and activating apoptosis. To further explore the anticancer effect of curcumin, we investigated the efficacy of curcumin on autophagy in LMS cells. METHODS: Cell proliferation in human uterine LMS cell lines, SKN and SK-UT-1, was assessed after exposure to rapamycin or curcumin. Autophagy was detected by Western blotting for light chain 3 and sequestosome 1 (SQSTM1/p62) expression. Apoptosis was confirmed by Western blotting for cleaved poly (ADP-ribose) polymerase (PARP). RESULTS: Both rapamycin and curcumin potently inhibited SKN and SK-UT-1 cell proliferation in a dose-dependent manner. Curcumin induced autophagy and apoptosis in SKN and SK-UT-1 cells, whereas rapamycin, a specific mTOR inhibitor, did not. Curcumin increased extracellular signal-regulated kinase 1/2 activity in both SKN and SK-UT-1 cells, whereas PD98059, an MEK1 inhibitor, inhibited both the extracellular signal-regulated kinase 1/2 pathway and curcumin-induced autophagy. CONCLUSIONS: These experimental findings suggest that curcumin is a potent inhibitor of cell proliferation in uterine LMS and provide new insights about ongoing signaling events leading to the possible development of a new therapeutic agent.

Epigallocatechin-3-gallate potentiates curcumin's ability to suppress uterine leiomyosarcoma cell growth and induce apoptosis.

BACKGROUND: Uterine leiomyosarcoma (LMS) has an unfavorable response to standard chemotherapeutic regimens. Two natural occurring compounds, curcumin and epigallocatechin gallate (EGCG), are reported to have anti-cancer activity. We previously reported that curcumin reduced uterine LMS cell proliferation by targeting the AKT-mTOR pathway. However, challenges remain in overcoming curcumin's low bioavailability. METHODS: The human LMS cell line SKN was used. The effect of EGCG, curcumin or their combination on cell growth was detected by MTS assay. Their effect on AKT, mTOR, and S6 was detected by Western blotting. The induction of apoptosis was determined by Western blotting using cleaved-PARP specific antibody, caspase-3 activity and TUNEL assay. Intracellular curcumin level was determined by a spectrophotometric method. Antibody against EGCG cell surface receptor, 67-kDa laminin receptor (67LR), was used to investigate the role of the receptor in curcumin's increased potency by EGCG. RESULTS: In this study, we showed that the combination of EGCG and curcumin significantly reduced SKN cell proliferation more than either drug alone. The combination inhibited AKT, mTOR, and S6 phosphorylation, and induced apoptosis at a much lower curcumin concentration than previously reported. EGCG enhanced the incorporation of curcumin. 67LR antibody partially rescued cell proliferation suppression by the combination treatment, but was not involved in the EGCG-enhanced intracellular incorporation of curcumin. CONCLUSIONS: EGCG significantly lowered the concentration of curcumin required to inhibit the AKT-mTOR pathway, reduce cell proliferation and induce apoptosis in uterine LMS cells by enhancing intracellular incorporation of curcumin, but the process was independent of 67LR.

The antidiabetic drug metformin inhibits uterine leiomyoma cell proliferation via an AMP-activated protein kinase signaling pathway.

Uterine leiomyomas are the most common gynecological benign tumors and greatly affect reproductive health and wellbeing. Metformin is the most widely used antidiabetic drug in the world, and there is increasing evidence of a potential efficacy of this agent as an anticancer drug. In order to understand metformin's anti-tumorigenic potential better, in this study, we investigated the inhibitory effect of metformin and expression of key targets of metformin cell signaling in leiomyoma cells. Cell proliferation was assessed after exposure to metformin. Apoptosis was assessed by western blotting for cleaved-PARP and TUNEL staining. The expressions of phosphorylated AMPK and phosphorylated S6 were determined by western blotting. Metformin potently inhibited ELT-3 cell proliferation in a dose-dependent manner. Western blotting analysis demonstrated that metformin induced phosphorylation of AMPK and the inhibitory effect was attenuated with AMPK inhibitor, compound C. In parallel, treatment with metformin decreased phosphorylation of S6 protein. These experimental findings show that metformin is a potent inhibitor of cell proliferation in leiomyoma cells. This effect is mediated by AMPK activation and subsequent inhibition of the mTOR pathway. Thus, this study provides a possible mechanism of the action of metformin in the inhibition of leiomyoma cell growth.

Enhancing intercultural sensitivity in Japanese nursing students through international online nursing courses: A quasi-experimental study.

BACKGROUND: Globalization has highlighted the importance of being competent in communicating with people of various cultural backgrounds. PURPOSE: To evaluate the effect of international courses for nursing students through online education in terms of intercultural sensitivity and perceived English proficiency. DESIGN: A one-group pretest-posttest quasi-experimental design with an online self-reported questionnaire was conducted. PARTICIPANTS AND SETTINGS: Participants were second-, third-, and fourth-year nursing students at a medical university in Tokyo in the spring term of 2021. METHOD: Measurements were performed before and after the international nursing courses, which consisted of 1) nursing communication English, taught by native English instructors to second- and third-year students; and 2) international health nursing, taught by overseas-experienced faculty members to fourth-year students. Furthermore, there is an elective Collaborative Online International Learning course, where students discuss, collaborate, and complete common assignments with students from a university in the United States. Intercultural sensitivity was measured using the Japanese version of the Intercultural Sensitivity Scale. The pre- and post-test intercultural sensitivity were compared using a paired t-test. Content analysis was employed to analyze the open-ended questions. RESULTS: A total of 104 students' data were analyzed. Students' intercultural sensitivity mean improved significantly from 79.88 ± 8.47 (pre) to 83.04 ± 8.63 (post). Participants in the elective course (n = 7) showed significantly higher intercultural sensitivity levels than non-participants. The self-evaluated English proficiency of second- and third-year students who took English courses significantly improved after the courses. Themes extracted by elective course participants revealed students' perceptions toward learning about diverse cultures, resilience, and intercultural communication skills, which they can utilize for nursing practice in the future. CONCLUSION: Taking international nursing courses can increase nursing students' intercultural sensitivity. Universities are encouraged to provide international nursing courses to help enhance their cultural sensitivity and competency for their future nursing careers.

Cross-sectional study of factors related to COVID-19 vaccination uptake among university healthcare students.

Introduction: Healthcare students are more likely to become infected than other university students as they may encounter patients with COVID-19 during clinical training. Vaccination uptake is essential to prevent infection. This study explored factors related to COVID-19 vaccination uptake among healthcare students. Methods: This cross-sectional study conducted online surveys of undergraduate and graduate nursing and healthcare graduate students from four medical universities in the Tokyo Metropolitan Area of Japan. Data were collected from June to August 2022, when the fourth vaccination program was initiated. Results: Data from 1,169 students were analyzed (response rate = 37.3%). The mean age was 25.1 ± 7.6 years, and most were female (82.3%). Academic majors included nursing (68.0%), medicine (16.3%), dentistry (9.3%), and others (6.4%). Thirty students (2.6%) were not vaccinated, one student (0.1%) had received one vaccination, 997 (85.3%) had received three, and 27 (2.3%) had received four. The major reason for not being vaccinated was insufficient confirmation of its safety (n = 25). Students who had received at least one vaccination (n = 1,139), 965 (84.7%) reported experiencing adverse side effects, the most frequent being pain at the injection site (76.2%), followed by fever (68.3%). In the logistic regression, a greater number of vaccinations (3-4 times) was associated with older age (odds ratio, OR = 1.53), working (OR = 1.67), and more frequent infection-preventive behaviors (OR = 1.05). Significantly fewer students were vaccinated at University B than at University A (OR = 0.46). Additionally, those majoring in subjects other than nursing (OR = 0.28), and students from non-Asian countries (OR = 0.30) were less likely to be vaccinated. Discussion: It is necessary to pay attention to and encourage the vaccination of students who engage in low levels of preventive behavior, students who are young, international, or unemployed, and those in non-healthcare professional majors.

Factors related to mental health effect among nursing students in Japan and the United States during the coronavirus pandemic: A cross-sectional study.

In the context of mental health, university students have been considered a vulnerable population. However, limited studies have underscored the association between preventive health behaviour levels and mental health effects among nursing students. The current cross-sectional study provides a comparative analysis of the impact of mental health factors on nursing students in Japan and the United States (US) in the context of the coronavirus disease 2019 (COVID-19) pandemic. The study consisted of 878 participants, comprising both undergraduate and graduate nursing students from four universities in Japan, and one from the US. Hierarchical logistic regression was used to analyse the participant data in this study. In contrast to the American students, the Japanese students demonstrated significantly lower levels of perceived control and significantly higher levels of preventive health behaviours. Furthermore, Japanese students exhibited significantly higher levels of stress and/or symptoms of depression induced by the social distancing orders compared to the American students (z = -4.218, P < 0.001). However, no difference was observed after adjusting for perceived control, individual factors, socio-economic factors, and preventive behaviours. During the pandemic, risk factors that can worsen mental health among the nursing students included younger age [odds ratio (95%CI) = 0.62 (0.48-0.81)], women [OR = 2.17 (1.02-4.61)], higher preventive health behaviour [OR = 1.05 (1.02-1.08)], lower perceived control [OR = 0.97 (0.94-0.99)], and lower perceived health competence [OR = 0.93 (0.90-0.96)]. Thus, this study recommends establishing training programmes that enhance perceived control and perceived health competence while encouraging preventive behaviour to support the mental health of nursing students, particularly young female students.

Healthcare graduate students' perceived control and preventive behavior for COVID-19 in Japan and the United States: A cross-sectional study.

Background: Both individual and policy level perceived control are known to be positively related to preventive behavior, and both may differ among healthcare graduate students with different cultural backgrounds. This study compared the preventive health behavior and perceived control among domestic and international healthcare graduate students in Japan and the United States during the COVID-19 pandemic, and analyzed factors associated with preventive health behavior and perceived control. Methods: The study used a self-administered online survey, conducted at two universities in Japan and one university in the United States. The survey included sociodemographic data and scales of preventive health behaviors, perceived control (policy level), and perceived health competence (individual level). Association among variables were analyzed using structural equation modeling. Results: A total of 610 students (485 domestic and 125 international) in Japan and 231 students (220 domestic and 11 international) in the United States completed the survey. Participants' average age was 31.3 years, and 67.0% were female. Model fit of structural equation modeling was good (χ2 = 9.419, P = 0.151, comparative fit index = 0.995, RMSEA = 0.026). Japanese students had better preventive health behavior than American (ß = -0.407, P < 0.001) and international students in both countries (ß = -0.112, P < 0.001). However, Japanese students had significantly lower perceived control than American students (ß = 0.346, P < 0.001) and international students in both countries (ß = 0.188, P < 0.001). Overall higher perceived control (ß = 0.175, P < 0.001) and being female (ß = 0.141, P < 0.001) were significantly associated with better preventive behavior. Although higher perceived control was related to higher perceived health competence (ß = 0.295, P < 0.001), perceived health competence was not associated with preventive behavior (ß = 0.025, P = 0.470). Religion was not associated with perceived control or preventive behavior. Conclusion: Nationality was identified as the main factor associated with both perceived control and preventive behavior. Policy level perceived control was more strongly associated with preventive health behavior than individual level perceived health competence. Further investigations in the contribution of specific cultural dimensions associated with perceived control and preventive behaviors are recommended.

Pathological variants in genes associated with disorders of sex development and central causes of hypogonadism in a whole-genome reference panel of 8380 Japanese individuals.

Disorders of sex development (DSD) comprises a congenital condition in which chromosomal, gonadal, or anatomical sex development is atypical. In this study, we screened for pathogenic variants in 32 genes associated with DSDs and central causes of hypogonadism (CHG) in a whole-genome reference panel including 8380 Japanese individuals constructed by Tohoku Medical Megabank Organization. Candidate pathogenic (P) or likely pathogenic (LP) variants were extracted from the ClinVar, InterVar, and Human Gene Mutation databases. Ninety-one candidate pathological variants were found in 25 genes; 28 novel candidate variants were identified. Nearly 1 in 40 (either ClinVar or InterVar P or LP) to 157 (both ClinVar and InterVar P or LP) individuals were found to be carriers of recessive DSD and CHG alleles. In these data, genes implicated in gonadal dysfunction did not show loss-of-function variants, with a relatively high tendency of intolerance for haploinsufficiency based on pLI and Episcore, both of which can be used for estimating haploinsufficiency. We report the types and frequencies of causative variants for DSD and CHG in the general Japanese population. This study furthers our understanding of the genetic causes and helps to refine genetic counseling of DSD and CHG.

A new microdeletion syndrome of 5q31.3 characterized by severe developmental delays, distinctive facial features, and delayed myelination.

Chromosomal deletion including 5q31 is rare and only a few patients have been reported to date. We report here the first two patients with a submicroscopic deletion of 5q31.3 identified by microarray-based comparative genomic hybridization. The common clinical features of both patients were marked hypotonia,feeding difficulty in infancy, severe developmental delay, and epileptic/nonepileptic encephalopathy associated with delayed myelination. Both patients also shared characteristic facial features,including narrow forehead, low-set and dysmorphic ears, bilateral ptosis, anteverted nares, long philtrum, tented upper vermilion,edematous cheeks, and high arched palate. The deleted region contains clustered PCDHs, including PCDHA [corrected]. and PCDHG, which are highly expressed in the brain where they function to guide neurons during brain development, neuronal differentiation, and synaptogenesis. The common deletion also contains neuregulin 2(NRG2), a major gene for neurodevelopment. We suggest that 5q31.3 deletion is responsible for severe brain developmental delay and distinctive facial features, and that the common findings in these two patients should be recognized as a new microdeletion syndrome. We need further investigations to determine which genes are really responsible for patients' characteristic features

Curcumin disrupts uterine leiomyosarcoma cells through AKT-mTOR pathway inhibition.

OBJECTIVE: Uterine leiomyosarcoma generally has an unfavorable response to standard chemotherapy. The loss of PTEN which results in constitutive AKT-mTOR activation causes an increase in leiomyosarcoma formation in mice. The active ingredient derived from the herb Curcuma longa, curcumin, shows antitumor properties in a variety of cancer cell lines by altering a number of oncogenic pathways. To explore the possibility of curcumin as an alternative to standard chemotherapy, we decided to investigate curcumin's antitumor effect on uterine leiomyosarcoma cells. METHODS: Human leiomyosarcoma cell lines, SKN and SK-UT-1, were cultured for in vitro experiments. Rapamycin or curcumin was added in different doses and their effect on cell growth was detected by MTS assay. The influence of rapamycin or curcumin on AKT, mTOR, p70S6 and S6 phosphorylation and protein expression was detected by Western Blotting. The ability of rapamycin or curcumin to induce apoptosis was determined by Western blotting using cleaved-PARP specific antibody, Caspase-3 activity assay and TUNEL assay. RESULTS: Both rapamycin and curcumin significantly reduced SKN cell proliferation. Curcumin inhibited mTOR, p70S6 and S6 phosphorylation similar with rapamycin. Cleaved PARP, caspase-3 activity and DNA fragmentation increased proportional with curcumin concentration. At a high concentration, curcumin significantly induced apoptosis in SKN cells, but not rapamycin. CONCLUSIONS: Curcumin inhibited uterine leiomyosarcoma cells' growth by targeting the AKT-mTOR pathway for inhibition. However, rapamycin, a specific mTOR inhibitor, did not induce apoptosis in SKN cells unlike curcumin that also has a pro-apoptotic potential in SKN cells.

Inhibitory effect of curcumin on uterine leiomyoma cell proliferation.

OBJECTIVE: Uterine leiomyomas are the most common gynaecological benign tumour and greatly affect reproductive health and wellbeing. They are the predominant indication for hysterectomy in premenopausal women. Curcumin, a well-known component of turmeric, has been reported to prevent various diseases such as cancer, diabetes and obesity. Previous study reported that curcumin represses the proliferation of several tumour cells. However, there has not been a precise characterisation of the curcumin-induced inhibition of uterine leiomyoma cells. In this study, we investigated the inhibitory effect of curcumin on leiomyoma cells proliferation. STUDY DESIGN: Eker rat-derived uterine leiomyoma cell lines (ELT-3 cells) were used. Cell proliferation was assessed by counting the number of cells and MTS assay. The activation of peroxisome proliferator-activated receptor-gamma (PPARγ) was evaluated by luciferase assay. RESULTS: We found that curcumin significantly inhibited ELT-3 cell proliferation. PPARγ was expressed in ELT-3 cells and curcumin acted as a PPARγ ligand. This inhibitory effect of curcumin was attenuated by the treatment of cells with PPARγ antagonist. CONCLUSION: These experimental findings in vitro show that the inhibitory effect of curcumin on ELT-3 cell proliferation occurs through the activation of PPARγ. Curcumin may be useful as an alternative therapy for uterine leiomyoma.