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β-Hydroxy-β-methylbutyrate (HMB) is an intermediate in the metabolism of the branched-chain amino acid leucine. HMB has several demonstrated effects on skeletal muscle function, some of which are contradictory. In addition, the effect of exogenous HMB intake on the levels of intermediate metabolites is not known. Therefore, we investigated changes in HMB metabolites after oral HMB administration in mice. First, ICR mice were treated with either distilled water or HMB (0.215 g/10 mL/kg). Sampling was performed at 0, 1, 6, 12, and 24 h after administration. Next, ICR mice were given distilled water or HMB (0.215 g/10 mL/kg/d) for 10 d. Mice given HMB shown a significant increase in liver β-methylcrotonyl-CoA and increased β-hydroxybutyrate in plasma and the gastrocnemius muscle 1 h after HMB administration. Mice administered HMB for 10 d showed significantly decreased food intake and body weight; however, the relative weight of the gastrocnemius muscle was significantly increased. These results may be attributed to an increase in β-hydroxybutyrate resulting from exogenous HMB, since β-hydroxybutyrate inhibits food intake and suppresses skeletal muscle catabolism. In conclusion, β-hydroxybutyrate, a metabolite of HMB, was found to play an important role in the function of HMB., Highlights • β-Hydroxybutyrate levels in plasma and gastrocnemius were enhanced by HMB. • HMB increases in tissues and plasma returned to original levels within 6 h. • HMB treatment for 10 d suppressed food intake and decreased body weight. • Gastrocnemius weight was increased despite deceased body weight in HMB-treated mice.

During follicular development, a few dominant follicles develop to large antral dominant follicles, whereas the remaining follicles undergo atretic degeneration. Because vascularization on the follicular surface is a morphological feature of dominant follicles, we previously classified these follicles as vascularized follicles (VFs) and non-VFs (NVFs). In NVFs, progesterone producing genes were expressed similarly to that in VFs; however, the progesterone concentration in follicular fluid was low in large NVFs. Therefore, we estimated that progesterone is converted to cortisol, which induces the loss of follicular functions. In this study, we comparative analyzed the expression of genes for progesterone converting enzymes (Cytochrome (CYP)11B1, CYP21A2, Hydroxysteroid (HSD)11B2) and cortisol receptor (NR3C1) in VF and NVF granulosa cells. In NVFs, expression of cortisol producing genes (CYP11B1 and CYP21A2) was higher than in VFs. Expression of the gene for the cortisol metabolizing enzyme HSD11B2 in NVFs was significantly lower than in VFs. In NVFs, accompanied by increasing cortisol concentration in follicular fluid, apoptosis of granulosa and cumulus cells was observed. Cultivation with FSH and metyrapone (a CYP11B1 inhibitor) of NVF cumulus–oocyte complexes inhibited apoptosis of cumulus cells and induced cumulus cell proliferation and oocyte maturation. Cortisol-induced CYP11B1 and CYP21A2 expression, whereas FSH-induced HSD11B2 mRNA expression in VF granulosa cells in the presence of cortisol. Furthermore, an addition of 18β-glycyrrhetinic acid (18-GA; a HSD17B2 inhibitor) to cortisol and FSH-containing medium increased apoptosis of VF granulosa cells. These results suggested that cortisol is a stimulatory factor that induces follicular atresia; furthermore, inhibition of cortisol production by FSH might increase the number of healthy preovulatory follicles in pigs.

Background Central pontine myelinolysis (CPM) is a non-inflammatory demyelinating lesion of the pons. CPM and extrapontine demyelination (EPM) are together termed osmotic demyelination syndrome (ODS), a known and serious complication of acute correction of hyponatremia. Conversely, hyperglycemic hyperosmolarity syndrome (HHS) develops in patients with type 2 diabetes who still have some insulin secretory ability due to infection, non-compliance with treatment, drugs, and coexisting diseases, and is often accompanied by ketosis. HHS represents a life-threatening endocrine emergency (mortality rate, 10–50%) associated with marked hyperglycemia and severe dehydration. HHS may develop ODS, and some cases have been associated with hypernatremia. Case presentation The patient was an 87-year-old woman with hyperglycemia, dehydration, malnutrition, and potential thrombus formation during long-term bed rest. HHS was suspected to have developed due to progression of hyperglycemia and dehydration caused by pneumonia. Furthermore, ketoacidosis developed from ketosis and prerenal renal failure associated with circulating hypovolemia shock, which was also associated with disseminated intravascular coagulation. Treatment was started with continuous intravenous injection of fast-acting insulin and low-sodium replacement fluid. In addition, ceftriaxone sodium hydrate, heparin sodium, thrombomodulin α, human serum albumin, and dopamine hydrochloride were administered. Blood glucose, serum sodium, serum osmolality, and general condition (including vital, infection/inflammatory findings, and disseminated intravascular coagulation) improved promptly, but improvements in disturbance of consciousness were poor. Diffusion-weighted imaging of the brain 72 h after starting treatment showed no obvious abnormalities, but high-intensity signals in the midline of the pons became apparent 30 days later, leading to definitive diagnosis of CPM. Conclusions Fluctuation of osmotic pressure by treatment from hyperosmolarity due to hyperglycemia and hypernatremia in the presence of risk factors such as malnutrition, severe illness, and metabolic disorders may be a cause of CPM onset. When treating HHS with risk factors, the possibility of progression to ODS needs to be kept in mind.

We encountered type 1 diabetic sisters with different islet-associated antibodies and pancreatic β-cell injury rates. The younger sister had different disease susceptibility human leukocyte antigen (HLA) haplotypes (DRB1*0901-DQB1*0303/DRB1*0802-DQB1*0302) on both chromosomes, while the older sister showed a disease susceptibility HLA haplotype (DRB1*0901-DQB1*0303/-) on one chromosome. Furthermore, the younger sister was positive for anti-glutamic acid decarboxylase antibody (GADA), anti-insulinoma-associated protein-2 antibody (IA-2A), and zinc transporter 8 antibody (ZnT8A), and showed depleted endogenous insulin secretory ability at the time of diagnosis. On the other hand, the older sister was positive only for GADA and ZnT8A, and the ability to secrete endogenous insulin was relatively retained at onset. From our cases and existing reports, we verified that: 1) having a HLA haplotype for disease susceptibility on both chromosomes; 2) having HLA-DQ8 and HLA-A24, -DQA1*03 and -DR9; 3) having more islet autoantibodies including IA-2A and ZnT8A may be involved in accelerating the progression of type 1 diabetes by enhancing the damage to pancreatic β-cells.

Introduction Japan is assumed to have serious health and social problems due to Internet overuse, but little is known about the actual conditions. This study was conducted to investigate the prevalence of problematic Internet use (PIU) and associated Internet use in adolescents in Japan. Methods A nationwide survey of adolescent Internet use was conducted in 2012 and 2013. The participants were 100,050 students from randomly selected junior and senior high schools nationwide who gave valid responses to a self-reported questionnaire. The questionnaire included questions on Internet use and the Japanese version of the Young's Diagnostic Questionnaire (YDQ) as well as other questions related to lifestyle habits. Internet users were classified by gender according to three categories on the basis of their YDQ scores: adaptive use, maladaptive use, and PIU. Results The estimated prevalence of PIU was 6.2% in males, 9.8% in females, and 7.9% in total; it closely correlated with female gender, school grades, and number of Internet hours. The following common and gender-specific applications that conferred a risk of PIU were identified: downloading (both genders), online gaming (males), social networking services, blogs, and bulletin boards (females). Conclusions A cross-sectional survey using YDQ of a large number of high school students yielded a PIU prevalence of 7.9% in Japan. This study showed that problems associated with Internet overuse have already become serious; therefore, planning and implementation of prevention and control measures is urgently required., Highlights • A nationwide representative survey on Internet use disorder (IUD) in Japan • Number of subjects: > 100,000 junior and senior high school students • Estimated prevalence of IUD: males (6.2%), females (9.8%), and in total (7.9%) • IUD correlated with female gender, school grades, and number of Internet hours • Common and gender-specific applications conferring risk for IUD were identified.

OBJECTIVE This study aimed to clarify the prevalence of anger and impulsivity and its associated factors through a nationwide survey of junior and senior high school adolescent students in Japan. METHODS A self-administered questionnaire covering (1) personal data, (2) lifestyle, (3) mental health status, and (4) feelings of anger and impulsivity was distributed to junior and senior high school students in Japan. Among the total of 10,955 junior high schools and 5,115 senior high schools nationwide, 130 and 110 were randomly selected, respectively. Of those, 92 junior and 80 senior high schools participated in the survey. The survey period was from December 2008 to the end of January 2009. A total of 95,680 questionnaires were collected. After excluding invalid responses, the remaining 94,777 responses (response rate: 62.3%) were analyzed. RESULTS From the questions regarding anger and impulsivity, 8.7% (95% CI, 8.5%-8.9%) and 7.5% (95% CI, 7.3%-7.7%) of the participants were considered to have experienced intense anger and impulsivity, respectively. Logistic regression analysis indicated that the odds ratios for experiencing intense feelings of anger were significantly higher (all P values < .05) among students who smoked, consumed alcohol, skipped breakfast, did not wish to go to university, had short sleep duration, had decreased positive feelings, had increased depressive feelings, or used mobile phones for longer hours. The odds ratios for experiencing intense impulsivity were significantly higher among students who smoked, consumed alcohol, skipped breakfast, did not participate in club activities, had short sleep duration, had decreased positive feelings, had increased depressive feelings, or used mobile phones for longer hours. CONCLUSIONS The results suggest that healthy lifestyle habits, good sleep habits, and improved mental health are important for preventing intense feelings of anger and impulsivity among adolescents.

Gene amplified in squamous cell carcinoma (SCC) 1 (GASC1), also known as KDM4C/JMJD2C, encodes a histone demethylase that specifically demethylates lysine residues (H3K9, H3K36, and H1.4K26) and plays a crucial role in the regulation of gene expression as well as in heterochromatin formation. GASC1 is located at human chromosome 9p23-24, where frequent genomic amplification is observed in human esophageal cancer, and its aberrant expression is detected in a variety of human cancers, such as breast, colon, and prostate. Therefore, it is highly likely that GASC1 contributes to the genesis and/or development of cancer. However, there is a lack of direct evidence of GASC1 having an oncogenic function. In this study, we aimed to clarify the role of GASC1 in the skin SCC carcinogenesis. For this purpose, we generated Gasc1-heterozygous mice (Gasc1+/-) with reduced expression of Gasc1. On the basis of our results, Gasc1+/- mice displayed a significantly lower incidence and multiplicity of both benign and malignant tumors induced by the two-stage skin carcinogenesis protocol than wild-type mice. In addition, the volume of carcinoma was significantly lower in Gasc1+/- mice. Consistent with these observations, knocking down of Gasc1 resulted in reduced cell viability of SCC cells in vitro. Our findings clearly demonstrated that GASC1 has an oncogenic role in skin carcinogenesis.

Background and Aim No nationally representative survey of irritable bowel syndrome (IBS) among adolescents has ever been performed in Japan. In the present study, we aimed to clarify the prevalence of IBS among Japanese adolescents and the factors associated with it. Methods The items related to the diagnostic criteria for IBS based on the Rome III Diagnostic Criteria for Functional Gastrointestinal Disorders were included in a cross-sectional nationwide survey of “alcohol consumption and smoking habits among junior and senior high school students.” The participating schools were sampled from among all junior and senior high schools in Japan using the cluster-sampling method, and self-administered questionnaires were sent to the selected schools by mail. Among 99 416 questionnaires that were collected, data from 98 411 valid responses were analyzed. Results The results showed that the prevalence of IBS was 18.6%. Although no sex difference was observed in the overall prevalence of IBS, the prevalence of diarrhea-predominant IBS was higher among boys than among girls, and the prevalence of constipation-predominant IBS was higher among girls than among boys. The prevalence of IBS increased with progression of the school grade, and there were the significant relationships between IBS and sleep-phase delay and insomnia symptoms. IBS was also significantly associated with poor mental health status. Conclusion These results indicate that IBS is common among junior and senior high school students, and associated with lifestyle and mental health.

The MYC transcription factor plays a crucial role in the regulation of cell cycle progression, apoptosis, angiogenesis, and cellular transformation. Due to its oncogenic activities and overexpression in a majority of human cancers, it is an interesting target for novel drug therapies. MYC binding to the E-box (5'-CACGTGT-3') sequence at gene promoters contributes to more than 4000 MYC-dependent transcripts. Owing to its importance in MYC regulation, we designed a novel sequence-specific DNA-binding pyrrole-imidazole (PI) polyamide, Myc-5, that recognizes the E-box consensus sequence. Bioinformatics analysis revealed that the Myc-5 binding sequence appeared in 5'- MYC binding E-box sequences at the eIF4G1, CCND1, and CDK4 gene promoters. Furthermore, ChIP coupled with detection by quantitative PCR indicated that Myc-5 has the ability to inhibit MYC binding at the target gene promoters and thus cause downregulation at the mRNA level and protein expression of its target genes in human Burkitt's lymphoma model cell line, P493.6, carrying an inducible MYC repression system and the K562 (human chronic myelogenous leukemia) cell line. Single i.v. injection of Myc-5 at 7.5 mg/kg dose caused significant tumor growth inhibition in a MYC-dependent tumor xenograft model without evidence of toxicity. We report here a compelling rationale for the identification of a PI polyamide that inhibits a part of E-box-mediated MYC downstream gene expression and is a model for showing that phenotype-associated MYC downstream gene targets consequently inhibit MYC-dependent tumor growth.

The purpose of this study was to examine the associations of sleep complaints, such as insomnia and snoring, with metabolic syndrome. Data from a national study conducted on residents from randomly selected districts in Japan in 2007 were used. The survey included: (i) information on physical status, (ii) dietary intake, and (iii) a questionnaire on lifestyle characteristics. Data on physical status and lifestyle characteristics available for 3936 adults (1592 men and 2344 women) were analyzed. Multiple logistic regression analysis yielded statistically significant associations. Adjusted odds ratios calculated with reference to metabolic syndrome were 1.23 (95% CI: 1.03–1.48, P = 0.02) for insomnia and 1.89 (95% CI: 1.56–2.30, P < 0.01) for snoring. For insomnia, the adjusted odds ratio in relation to hypertension was 1.28 (95% CI: 1.08–1.52, P < 0.01), and for snoring, the adjusted odds ratios in relation to abdominal obesity and dyslipidemia were 1.90 (95% CI: 1.6–2.26, P < 0.01) and 1.50 (95% CI: 1.27–1.77, P < 0.01), respectively. Metabolic syndrome was found to be closely associated with insomnia and snoring. Such associations should be taken into consideration when developing measures against metabolic syndrome and sleep problems.

The United States uses two forms of multilateralism to increase levels of foreign public support for military action: diplomatic multilateralism and operational multilateralism. Diplomatic multilateralism is typically done by obtaining a United Nations Security Council resolution authorizing military action. The use of multinational forces, the so-called coalition of the willing and many flags program, is an example of operational multilateralism. While scholars have empirical evidence that diplomatic multilateralism generates foreign domestic support for the use of force, there is no equivalent study for operational multilateralism. We do not know if or how much the two types of multilateralism would differ in inducing foreign domestic support for military action. This article, by using Japan as a field of survey experiment, answers these questions.

We conducted an epidemiological study to examine the associations between sleep environments and sleep habits in Japanese adolescents. The targets were students attending junior and senior high schools throughout Japan. Sample schools were selected by cluster sampling. Self-reported anonymous questionnaires were then sent to the schools for all students to complete. A total of 99 416 adolescents responded, with an overall response rate of 64.0%. A total of 96 861 questionnaires were subjected to analysis. Associations between sleep environments (type of bed, lighting during sleep, sharing a bedroom) and sleep duration, bedtimes, wake-up times, sleep quality, or symptoms of insomnia were examined. In total, 65.5% of the adolescents surveyed slept on a bed, and 33.0% slept on a futon laid on the floor or tatami. In total, 66.6% slept with the light off, 31.0% slept with a dim light on, and 2.0% slept with the light on. Of those surveyed, 69.3% had their own bedrooms, 17.1% shared a bedroom with one other person, 8.0% shared a bedroom with three people, and 5.0% shared a bedroom with four people or more. The factors with high odds ratios with regard to insomnia were use of a futon laid on the floor or tatami, sleeping with the light on, and not sharing a bedroom. Sleep environments are associated with insomnia. Type of bed, lighting, and sharing a bedroom should be considered as factors that affect the sleep of adolescents.

The aim of the present study was to clarify the prevalence of excessive daytime sleepiness and its associated factors among pregnant women in Japan. Of the 940 randomly selected survey locations identified by the Japan Association of Obstetricians and Gynecologists, 344 obstetric institutions participated in the survey. The study was conducted on women with confirmed pregnancies who had had a second or subsequent consultation at one of these institutions. The survey items included age, highest educational achievement, trimester of pregnancy, number of pregnancies, employment status, smoking, alcohol consumption, restless sleep, difficulty initiating sleep, difficulty maintaining sleep, early morning awakening, sleep duration, napping, snoring or breathlessness, and restless leg syndrome. The Epworth Sleepiness Scale was used to assess the level ofexcessive daytime sleepiness. We calculated the prevalenceofexcessive daytime sleepiness and then examined its associated factors using χ2 test and multiple logistic regression analysis. The prevalence of excessive daytime sleepiness among pregnant women was 6.2%. The results of multiple logistic regression analysis indicated that the adjusted odds ratio with regard to excessive daytime sleepiness was significantly higher among younger women and thosein anearlier trimesterofpregnancy. The odds ratio with regard toexcessive daytime sleepiness was also significantly higher for women in their first pregnancy, full-time workers, and current alcohol consumers. Women indicating the presence of sleep-related issues, including restless sleep, difficulty maintaining sleep, napping, snoring or breathlessness, and symptoms of restless leg syndrome, reported significantly higher levels of excessive daytime sleepiness.

Existing research emphasizes how United Nations Security Council (UNSC) approval helps convey information to domestic audiences that military action is conducted with good intentions, for desirable consequences and in a legitimate manner. This information transmission mechanism can also increase support for UNSC-endorsed military action in countries unlikely to provide major contributions to military actions. There is some cross-national evidence supporting the information transmission mechanism in the United States. Examining the causal mechanisms underlying foreign public support for US military action through a survey experiment with approximately 2,000 respondents in Japan shows that foreign public support varies depending on whether the military action has UNSC approval. The process of presenting draft resolutions to the UNSC also affects public support.

The main objective of our study was to clarify the prevalence of disorders of arousal (confusional arousals, sleepwalking, sleep terrors) and sleep-related bruxism (teeth grinding) and their associated factors among Japanese adolescents.Our study was designed as a cross-sectional sampling survey. The targets were students attending junior and senior high schools throughout Japan. The questionnaire asked for personal data and information on lifestyle, depressive state, and sleep status including the frequency of experiencing disorders of arousal and sleep-related bruxism.A total of 99,416 adolescents responded. The overall response rate was 63.7%, and 98,411 questionnaires were subjected to analysis. The prevalence of disorders of arousal was 7.1% (95% confidence interval [CI], 6.9-7.3%) among boys and 7.7% (95% CI, 7.5-7.9%) among girls. The prevalence of sleep-related bruxism was 2.3% (95% CI, 2.2-2.4%) among boys and 3.0% (95% CI, 2.8-3.2%) among girls. The factors associated with disorders of arousal were the grade in school, smoking habit, alcohol consumption, naptime (min), breakfast habit, participation in club activities, sleep duration, difficulty initiating sleep, nocturnal awakening, early morning awakening, subjective sleep assessment, snoring, decrease in positive feelings, and depression (all p.001). The factors associated with sleep-related bruxism were gender, smoking habit, nocturnal awakening, snoring, early morning awakening, decrease in positive feelings, and depressive feelings (all p.001).If disorders of arousal or sleep-related bruxism are observed in an adolescent, his or her smoking habit, alcohol consumption, sleep status, and depressive state should be considered.

Early drinking is considered to result in making tolerant of alcohol consumption and a higher prevalence of alcohol related disorders in the later. We focused generational impacts on drinking rate among high school students based on multiple nationwide data. The surveys were nationwide, cross-sectional random sampling surveys given every 4 years from the Japanese Youth Tobacco and Alcohol Surveys, 1996 to 2008. Participants were male 53,925 high school students from 7th grade to 11th grade. We divided to the three follow-up groups every 4 years from 1996 to 2004 for male junior high school students in 7th grades and the end periods were 4 years later in 11th grades. Outcome measures in this study were life time drinking, current drinking within 30 days and weekly drinking. All drinking rates decreased each at 7th and at 11th grade. The increments in these drinking rates from 7th grade to 11th grade in males decreased gradually in recent follow-up groups. Generational impacts should be considered by using follow-up groups to study drinking behaviors among students.

Backgrounds: Smoking in childhood has become an important public health concern. Previous studies have reported on secular trends in childhood smoking rates and compared with smoking rates at fixed ages. They also described secular trends regarding the prevalence of smoking at fixed ages. The variations in smoking rate of young children and adolescents by follow-up groups have not been studied by follow-up groups at a national level. Objective: We looked at trends and generational impacts on smoking rate by using follow-up groups of male Japanese high school students to quantitatively assess differences in trends, based on multiple nationwide data from the Japanese Youth Tobacco and Drinking Surveys gathered every 4 years between 1996 and 2008. Methods: The surveys were nationwide, cross-sectional random sampling surveys given every 4 years from 1996 to 2008, using the single-stage cluster sampling methodology. The cluster unit of the sampling was school. The survey targeted junior and senior high school students from schools selected through Japan using the National School Directory. Students enrolled in the sampled schools were subjects of the study. Participants were 53,925 high school students from 7th grade to 11th grade in 1996, 2000, 2004 and 2008. We divided the three follow-up groups every 4 years from 1996 to 2004 for male junior high school students in 7th grades, age 13. The end periods were 4 years later when they had become 11th graders, age 17, from 2000 to 2008. Main outcome measures in this study were life time smoking, current smoking within 30 days and daily smoking at 7th or 11th grade and the trend of the smoking rates between 7th to 11th grades. Results: Life time smoking rate, current smoking rate and daily smoking rate in Japanese high school students decreased at 7th grade from 1996 to 2004. They also decreased at 11th grade from 2000 to 2008. However, the slopes differed among their follow-up groups. The increments in their smoking rates from 7th grade to 11th grade in male high school students were smaller in recent follow-up groups both in 2000 and in 2004 than in follow-up groups in 1996. Then, those increments in follow-up groups between in 2000 and in 2004 were similar in lifetime smoking rate and current smoking rate. Conclusions: We have shown that monitoring trends by follow-up group are important in studying smoking for public health. Values of smoking rates from a young age to adolescence by follow-up group should be examined. Values of smoking rate and regular changes in smoking rate are important because smoking rate changes dynamically during adolescence. Not only trends in smoking rates at fixed ages, but also generational impacts should be considered by using follow-up groups to study smoking behaviors among students. We need to continue careful monitoring of follow-up group smoking prevalence. When long-term health promotions are planned or assessed, policy makers need to look at changes in follow-up groups.

Aims There are no legal regulations in Japan governing minors’ consumption of alcohol-flavoured non-alcoholic beverages (AFNAB); therefore, we examined if their consumption could lead to increased alcohol use among adolescents in Japan. Methods This cross-sectional study used a nonclinical, nationally representative sample of 38,494 junior (19,662 boys) and 61,556 senior (31,925 boys) high school students recruited in 2012. We measured AFNAB consumption rates and the order that adolescents first consumed AFNAB and alcohol. Results The AFNAB consumption was strongly associated with alcohol use in high school students. Among all age groups, alcohol was more commonly consumed before AFNAB for both males and females. Conclusions Consumption of AFNAB is more prevalent among minors than alcohol consumption and it has a strong association with alcohol consumption. However, concerns that AFNAB use would lead to increased alcohol use were not supported because AFNAB consumption usually started after adolescents began consuming alcohol. Short Summary Consumption of AFNAB is more prevalent among high school students than alcohol consumption and it has a strong association with alcohol consumption. However, concerns that AFNAB use would lead to increased alcohol use were not supported because AFNAB consumption usually started after adolescents began consuming alcohol.

安城更生病院 (以下，当院) は以前より教育に力を注ぎ，医療人を目指す学生から専門職業人に至るまで，積極的に実習・研修・見学を受け入れてきた。今回の調査は，当院において平成18年度から平成20年度に受け入れた実習・研修および見学の実績を把握するために調査した。 当院における実習・研修および見学の受け入れ人数は，平成18年度1,047名・平成19年度1,107名・平成20年度1,309名と年々増加傾向にあった。そして，ほぼ全ての職種 (15職種) で実習・研修および見学を受け入れていることが明らかとなった。中でも，医療に興味を持つ中高生が増加している点は，我々にとって希望の光であった。加えて，教育プログラムのあるもので，実習・研修の増加が認められた。これらのことは，実習・研修生がどこで何を学ぶかを明確に，実習・研修先を選んでいることを示唆するものである。 一方で当院は研修のプログラム管理・評価およびフィードバックが充分なされていないことが明らかとなった。 今後，より魅力ある質の高い教育に貢献するために，プログラム管理・評価・フィードバックへの関わりが課題である。

安城更生病院 (以下，当院) では多職種で構成された教育研修委員会を立ち上げ，今年で5年目を迎えた。この委員会は，新人オリエンテーション・生涯教育を担当している。今回の調査はこれまでにこの委員会が実施した新人オリエンテーションの実績を振り返るとともに今後の課題を検証することとした。 当院の新人オリエンテーションの主目的は彼らが社会人として生きるための基礎知識を学ぶことである。そこで新人オリエンテーションの評価を行なうために参加者に対して各プログラムの研修時間と受講者の満足度との関係を調査した。その結果，オリエンテーションのコンセプトとして挙げている “病院の基本理念・方針の周知” において印象に残った受講者が少ないことが明らかとなった。一方で院内見学・感染対策の手洗い指導・接遇と応対など参加型の研修が受講者の印象に残っていることが分かった。加えて，講義型の医療事故防止プログラムは研修時間を延長しても受講者の満足度向上にはつながらなかった。これらのことは講義型の研修は受講者にとって実践をイメージできないために研修の満足度を低下させている可能性が示唆された。今後は，更に充実したオリエンテーションになるよう各コンテンツの企画段階から教育研修委員会が介入し，新入職員が気持ちよく社会人としてスタートできるようサポートしていきたい。

We have designed and synthesized new types of pyrrole (P)-imidazole (I) polyamide conjugates 1 and 2 possessing a suberoylanilide hydroxamic acid (SAHA) moiety that is a strong inhibitor of histone deacetylase (HDAC). SAHA conjugate 2 was designed to target the promoter region of the p16 tumor suppressor gene. The DNA binding affinity of SAHA conjugate 2 to its target sequence was examined using surface plasmon resonance. HDAC inhibition activity of conjugates 1 and 2 was evaluated using a colorimetric assay. The results demonstrated that even though it possesses the relatively large SAHA moiety, conjugate 2 has high DNA sequence-specific binding properties and moderate HDAC inhibitory activity in vitro. SAHA conjugate 2 was found to cause morphological changes in HeLa cells and to induce selective Histone H3 lysine 9 acetylation.

Expressed sequence tag (EST) analyses were performed with the aim of identifying enzyme genes in the liver of the Bleeker’s squid Loligo bleekeri. Of the 768 ESTs identified and sequenced, 669 were grouped into 324 clusters. Of these clusters, 123 comprising 245 ESTs were found to be homologous to genes reported to date. Among these, 43 clusters were annotated as enzymes according to the Enzyme Commission (EC) numbering system. Two EC groups, oxidoreductases and hydrolases, possessed a large number of ESTs. A cluster homologous to the glutathione peroxidase, an enzyme in the oxidoreductase group, contained 16 ESTs, which accounted for 2.4% of the total ESTs sequenced. There are three serine proteases, three cathepsins, two triacylgricerol lipases, and two chitinases among the clusters homologous to the enzymes in the hydrolase group. Since the squid liver functions in the digestive process, these enzymes would be involved in food digestion. Our data provide information on the various types of enzymes expressed in the squid liver and may provide a useful basis for further characterization of these enzymes.

UNLABELLED We sought to establish a causal relationship between oxidative stress and porphyria in patients and carriers. We reported changes in urinary porphyrin concentrations related to 8-hydroxy-2'-deoxyguanosine. METHODS We measured urinary 8-hydroxy-2'-deoxyguanosine concentration in porphyria patients and carriers with multifactorial inheritance as a possible marker of attack. The porphyria types included 10 patients with porphyria cutanea tarda, 5 with variegate porphyria, 8 with hereditary coproporphyria, 7 with congenital erythropoietic porphyria, 5 with erythropoietic protoporphyria, 5 with acute intermittent porphyria, 7 erythropoietic protoporphyria carriers, and 7 acute intermittent porphyria carriers. RESULTS Urinary porphyrin concentrations in these patients were significantly higher than those in healthy subjects (p

ALS patients usually use augmentative and alternative communication tools to communicate with other people, but the assessment tools, including the selection of an input switch, are very difficult to operate. In this study, we developed a novel device to measure the physical ability of patients to operate the input switch with a push lever. The study focused on the amount of pushing and the power required to operate the input switch, and the effectiveness was verified.

The synthesis of sialylated glycosides using saccharide primers and cells was investigated. α · and β · Saccharide primers were chemically synthesized and introduced into B16 melanoma cells to prime oligosaccharide synthesis. Incorporation of α‐ and β‐dodecyl lactosides into B16 cells resulted in the sialylation of the galactose residue to give GM3‐type oligosaccharides. The β‐dodecyl galactoside primer was sialylated but the α‐dodecyl galactoside primer was not. Both the α‐ and β‐dodecyl glucoside primers were not elongated. In the glycosylation of primers by cells, this research confirmed that sialyl transferases tolerate acceptor modifications and are permissive to primer elongation regardless of the α‐ or β‐linkage to the aglycon unit. However, the presence of the terminal galactose residue that is β‐linked to the adjacent saccharide or aglycon unit is essential for sialylation by cellular enzymes to occur.

Sleep disturbance such as insomnia is one of common complaint among adults in developed countries. Insomnia induces sleepiness and drowsiness, resulting in a reduction of working efficiency in the daytime. Drivers in the transportation system and machine operators could cause serious industrial accidents if they have sleep disturbances. Recent studies reported that approximately 20% of Japanese population had sleep disturbances. Here we provide a general account of sleep disturbance about Japanese population.

During in vitro maturation of porcine cumulus cell-oocyte complexes and in vitro luteinization of porcine granulosa cells, FSH induces the expression of the protease TNFα-converting enzyme/A disintegrin and metalloproteinase domain 17 (TACE/ADAM17) and the epidermal growth factor (EGF)-like factors, which activate the EGF receptor (EGFR)-MAPK3/1 pathway in both cumulus and granulosa cells. FSH is known to activate not only protein kinase A and p38MAPK pathways in both cell types but also activates protein kinase C (PKC). Because PKC-induced association of cellular-Sarcoma (c-Src) and TACE/ADAM17 is required for TACE/ADAM17 enzyme activation in some cancer cells, we hypothesized that PKC and c-Src impact TACE/ADAM17-mediated activation of EGFR signaling pathway in porcine granulosa and cumulus cells. When granulosa cells or cumulus cell-oocyte complexes were cultured with FSH, PKC activity and c-Src phosphorylation increased and were associated with increased TACE/ADAM17 enzyme activity. The PKC inhibitor calphostin C (CalC) and the c-Src inhibitor (4 amino 5 (4 chlorophenyl) 7 (t butyl)pyrazolo[3,4 d]pyrimidine [PP2]) suppressed TACE/ADAM17 enzyme activity, whereas these inhibitors did not affect Tace/Adam17 mRNA expression. Immunoprecipitation analysis showed that FSH mediated the association of c-Src with TACE/ADAM17 via a PKC-dependent mechanism. Either CalC or PP2 suppressed EGFR downstream signaling pathway (MAPK3/1) in these ovarian cell types and reduced cumulus expansion, meiotic maturation of oocytes, and progesterone production. The negative effects were overcome by the addition of amphiregulin. Collectively, these results indicate that activation of TACE/ADAM17 via a PKC-induced c-Src-dependent manner mediates proteolytic activation of the EGF-like factors that are involved in the induction of granulosa cell differentiation, cumulus expansion, and meiotic maturation of porcine oocytes in vitro.

In this study, we attempted to clarify the associations between various sleep disturbance symptoms and the frequency and amount of alcohol use among Japanese adolescents. This study was designed as a cross-sectional sampling survey. A self-administered questionnaire survey was administered to students enrolled in randomly selected junior and senior high schools throughout Japan. A total of 99,416 adolescents responded, and 98,867 questionnaires were subjected to analysis. The prevalence rates of sleep disturbance in the 30 days preceding the day of the survey were as follows: subjectively insufficient sleep (SIS) (boys: 37.6%, girls: 38.7%); short sleep duration (SSD) with less than 6 h of sleep (boys: 28.0%, girls: 33.0%); difficulty initiating sleep (DIS) (boys: 12.5%, girls: 14.1%); difficulty maintaining sleep (DMS) (boys: 10.1%, girls: 10.9%); and early morning awakening (EMA) (boys: 5.1%, girls: 5.0%). Adolescents reporting one or more symptoms of DIS, DMS, and EMA were classified as having insomnia, and its prevalence was 21.5%. The prevalence of each symptom of sleep disturbance increased significantly with the number of days on which alcohol was consumed in the previous 30 days and the amount of alcohol consumed per drinking session (p < 0.01). Multiple logistic regression analyses showed that the adjusted odds ratio (AOR) for each symptom of sleep disturbance, except SIS and EMA, tended to increase with the number of days on which alcohol was consumed and the amount of alcohol consumed per drinking session. The prevalence of sleep disturbance is particularly high among adolescents drinking alcohol. The risk of having each symptom of sleep disturbance, except SIS and EMA, increases with the number of days on which alcohol was consumed and the amount of alcohol consumed per drinking session. These findings reconfirm the need to eliminate underage drinking to ensure good sleep among adolescents.

The in vitro maturation (IVM) technique is beneficial for producing animal offspring, but the blastocyst rate is low after IVM. In this technique, cumulus-oocyte complexes (COCs) are collected from medium size follicles. The follicles are ultimately selected as large dominant follicles or atretic follicles; therefore it is possible that the COCs collected using IVM are contaminated by follicles that will develop into large follicles and induce atresia. In the dominant follicles, estradiol-17beta and progesterone induce the differentiation of follicular somatic cells which exhibit the ability to respond to ovulation during follicular development. Thus, we hypothesized that changes in the hormonal condition of healthy follicles are essential for oocyte maturation during IVM. In this study, we performed a comparative analysis of the steroid hormone concentrations in non-vascularized follicles (NVFs) and vascularized follicles (VFs). The estradiol-17beta concentration increased in medium VFs, whereas the level was low in NVFs of the same size. The progesterone concentration increased with large follicular size in VFs, but the level remained low in follicles of any size among NVFs. To improve the oocyte quality derived from NVFs, NVF COCs were cultured with FSH alone or FSH under theVF hormonal conditions. Cultivation under the VF hormonal conditions dramatically improved the proliferation and survival of cumulus cells, meiotic maturation of oocytes, cumulus expansion, and blastocyst rate following in vitro fertilization. Thus, the cultivation of NVF COCs under VF hormonal conditions improves the developmental potential to the blastocyst stage by NVF oocytes.

OBJECTIVES The aim of study was to determine the associations of work hours and actual availability of weekly rest days with the onset of lifestyle-related diseases such as obesity, hypertension, hypertriglyceridemia, low levels of high-density lipoprotein (HDL) cholesterol and hyperglycemia. METHODS For this longitudinal study, we used data from checkups conducted in 1999 and 2006 for 30,194 men who worked for a local public institution in Japan. We calculated the cumulative incidence rates of onset of obesity, hypertension, hyperglycemia, hypertriglyceridemia and low HDL cholesterol over this 7-year period and performed a χ2 test to determine the association between the above diseases and work conditions (work hours and actual availability of weekly rest days) at the time of the baseline survey. We then performed multiple logistic regression analysis of the diseases that showed significant associations. RESULTS The adjusted odds ratio for the onset of hypertriglyceridemia in subjects who worked ≥9 hours was high (1.11 [95% CI: 1.02-1.22], p=0.02) in comparison with those who worked

Sleep has been a great interest in modern developed countries, epidemiological studies have been carried out extensively. In 2006, average sleep duration of the Japanese men, has been reported 7 hours 49 minutes (9 minutes shorter than 20 years ago) and women has been reported 7 hours 35 minutes (7 minutes shorter than 20 years ago). Sleep habits is affected by gender, age and also social factors and lifestyle. Thus, sleep-related problems have become an important public health issue in the society in developed countries. It is important to progress the preventive health promotion activities and results that are based on the development of future epidemiological studies of sleep.

Mucocele of the appendix (MA) is an uncommon disease. Preoperative differential diagnosis of MA and a peritoneal inclusion cyst (PIC) from gynecologic diseases is still a challenge. We herein report a very rare case with MA and PIC. As far as we know, this is the first report of a case having MA and PIC found simultaneously at surgery. A 31-year-old woman complained of lower abdominal pain and high fever. Based on her symptoms and laboratory tests, pelvic inflammatory disease (PID) was considered to be the most probable diagnosis. She underwent antibiotics therapy and her conditions subsided. However, ascites reappeared in a month, and ultrasound and MRI demonstrated a right ovarian cyst and a suspected right hydrosalpinx. Laparotomy revealed large PIC and MA with normal bilateral adnexa. Patients with an adnexal mass or symptoms suggesting PID should be examined carefully considering such conditions in a daily gynecologic practice.