Can sleep disturbance influence changes in mental health status? Longitudinal research evidence from ageing studies in England and Japan.

BACKGROUND: Little is known about the role of sleep disturbance in relation to changes in depressive states. We used data obtained from the participants aged 65 and over in the English Longitudinal Study of Ageing (ELSA, waves four and five, N = 3108) and the Japan Gerontological Evaluation Study (JAGES, 2010 and 2013 sweeps, N = 7527) to examine whether sleep disturbance is longitudinally associated with older adults' patterns of depressive states. METHODS: We created four patterns of depressive states (non-case, recovered, onset, repeatedly depressive) by combining responses to the measures (scoring four or more on seven items from the Center for Epidemiological Studies Depression Scale for the ELSA participants and scoring five or more for the Geriatric Depression Scale-15 for the JAGES participants) obtained at the baseline and follow-up. Sleep disturbance was assessed through responses to three questions on sleep problems. Age, sex, partnership status, household equivalised income, alcohol and cigarette use, and physical function were treated as confounders in this study. Additionally, information on sleep medication was available in JAGES and was included in the statistical models. RESULTS: More ELSA participants were non-depressive cases and reported no sleep disturbances compared with the JAGES participants. Findings from multinomial logistic regression analysis showed that more sleep disturbance was associated with the onset group in ELSA (RRR = 2.37, 95% CI = 1.44-3.90) and JAGES (RRR = 2.41, 95% CI = 1.79-3.25) as well as the recovery (RRR = 3.42, 95% CI = 1.98-5.90, RRR = 2.71, 95% CI = 1.95-3.75) and repeatedly depressed group (RRR = 7.24, 95% CI = 3.91-13.40, RRR = 5.16, 95% CI = 3.82-6.98). CONCLUSIONS: Findings suggest that the association between sleep disturbance and depression in older adults is complex.

Calreticulin mutant mice develop essential thrombocythemia that is ameliorated by the JAK inhibitor ruxolitinib.

Mutations of calreticulin (CALR) are detected in 25-30% of patients with essential thrombocythemia (ET) or primary myelofibrosis and cause frameshifts that result in proteins with a novel C-terminal. We demonstrate that CALR mutations activated signal transducer and activator of transcription 5 (STAT5) in 293T cells in the presence of thrombopoietin receptor (MPL). Human megakaryocytic CMK11-5 cells and erythroleukemic F-36P-MPL cells with knocked-in CALR mutations showed increased growth and acquisition of cytokine-independent growth, respectively, accompanied by STAT5 phosphorylation. Transgenic mice expressing a human CALR mutation with a 52 bp deletion (CALRdel52-transgenic mice (TG)) developed ET, with an increase in platelet count, but not hemoglobin level or white blood cell count, in association with an increase in bone marrow (BM) mature megakaryocytes. CALRdel52 BM cells did not drive away wild-type (WT) BM cells in in vivo competitive serial transplantation assays, suggesting that the self-renewal capacity of CALRdel52 hematopoietic stem cells (HSCs) was comparable to that of WT HSCs. Therapy with the Janus kinase (JAK) inhibitor ruxolitinib ameliorated the thrombocytosis in TG mice and attenuated the increase in number of BM megakaryocytes and HSCs. Taken together, our study provides a model showing that the C-terminal of mutant CALR activated JAK-STAT signaling specifically downstream of MPL and may have a central role in CALR-induced myeloproliferative neoplasms.

TET2 is essential for survival and hematopoietic stem cell homeostasis.

Ten-Eleven-Translocation 2 (TET2) is an enzyme that catalyzes the conversion of 5-methylcytosine into 5-hydroxymethylcytosine (5-hmC) and thereby alters the epigenetic state of DNA; somatic loss-of-function mutations of TET2 are frequently observed in patients with diverse myeloid malignancies. To study the function of TET2 in vivo, we analyzed Ayu17-449 (TET2(trap)) mice, in which a gene trap insertion in intron 2 of TET2 reduces TET2 mRNA levels to about 20% of that found in wild-type (WT) mice. TET2(trap/trap) mice were born at Mendelian frequency but died at a high rate by postnatal day 3, indicating the essential role of TET2 for survival. Loss of TET2 results in an increase in the number of hematopoietic stem cells (HSCs)/progenitors in the fetal liver, and TET2(trap/trap) HSCs exhibit an increased self-renewal ability in vivo. In competitive transplantation assays, TET2(trap/trap) HSCs possess a competitive growth advantage over WT HSCs. These data indicate that TET2 has a critical role in survival and HSC homeostasis.

Decolorization and mineralization of Oolong tea polyphenols in colored soft drink wastewater by photo Fenton reaction.

The decolorization and the mineralization of the colored soft drink wastewater including Oolong tea polyphenols by the photo Fenton reaction have been investigated. The decolorization of the colored soft drink wastewater including Oolong tea polyphenols by the photo Fenton reaction could be divided into 3 phases. Just after H2O2 was added to the solution, the color of the solution immediately increased from absorbance of 0.247 to 0.711 at the wavelength of 400 nm, which was defined as the 1st phase. Subsequently the significant decolorization by the photo Fenton reaction occurred at the 2nd phase. Finally, complete decolorization (the color attributed to the color of Fe3+) could be achieved in 180 min at the 3rd phase. The instantaneous and considerable color increase at the 1st phase could be attributed to the formation of intermediate colored compounds like quinones and soluble iron complexes produced by the Fenton reaction. About 95% mineralization of model colored soft drink wastewater with 229 mg L(-1) initial TOC concentration was achieved after 165 min.

Absence of gain-of-function JAK1 and JAK3 mutations in adult T cell leukemia/lymphoma.

Janus kinase 1 (JAK1) and JAK3 plays a critical role in lymphocyte proliferation and differentiation. Somatic JAK1 mutations are found in 18% of adult precursor T acute lymphoblastic leukemias and somatic JAK3 mutations are found in 3.3% of cutaneous T cell lymphomas. Some of the mutations are confirmed as a gain-of-function mutation and are assumed to be involved in leukemogenesis. Adult T cell leukemia/lymphoma (ATLL) is a type of T cell neoplasm, and activation of JAK/STAT pathways is sometimes observed in them. We investigated JAK1 and JAK3 mutations in 20 ATLL patients. No JAK1 mutations were found, and five types of single nucleotide polymorphisms were observed in 12 cases, whose frequencies almost match those in Asian populations. As for JAK3, a synonymous mutation was found in one case. JAK1 and JAK3 mutations are unlikely involved in the leukemogenesis of ATLL.

Terahertz imaging applied to cancer diagnosis.

We report on terahertz (THz) time-domain spectroscopy imaging of 10 microm thick histological sections. The sections are prepared according to standard pathological procedures and deposited on a quartz window for measurements in reflection geometry. Simultaneous acquisition of visible images enables registration of THz images and thus the use of digital pathology tools to investigate the links between the underlying cellular structure and specific THz information. An analytic model taking into account the polarization of the THz beam, its incidence angle, the beam shift between the reference and sample pulses as well as multiple reflections within the sample is employed to determine the frequency-dependent complex refractive index. Spectral images are produced through segmentation of the extracted refractive index data using clustering methods. Comparisons of visible and THz images demonstrate spectral differences not only between tumor and healthy tissues but also within tumors. Further visualization using principal component analysis suggests different mechanisms as to the origin of image contrast.

Independent histological risk factors for lymph node metastasis of superficial esophageal squamous cell carcinoma; implication of claudin-5 immunohistochemistry for expanding the indications of endoscopic resection.

Endoscopic resection is curative for superficial esophageal squamous cell carcinoma (ESCC) limited to the lamina propria. Endoscopic resection is not recommended for superficial ESCC invading muscularis mucosa or submucosa, however, because of the high frequency of lymph node metastasis (LNM) in such patients. Methods to more accurately predict LNM by analysis of endoscopically resected specimens are needed. Patients with superficial ESCC who underwent surgery without prior chemoradiotherapy (n= 110) were retrospectively examined to determine whether LNM correlated with immunohistochemical parameters and conventional histological parameters, including depth of invasion and vascular permeation. Cancer cell expression of claudins-1, 5, and 7, E-cadherin, beta-catenin, and matrix metalloproteinase 7 was evaluated. Univariate analysis revealed that LNM correlated with claudin-5 expression, but not any other immunohistochemical parameter examined. Multivariate analysis revealed three independent risk factors for LNM: aberrant claudin-5 expression in cancer cells (odds ratio; OR [95% confidence interval]= 4.61[1.44-14.77]), depth of submucosal invasion greater than 200 microm (3.55 [1.02-13.17]), and positive lymphatic permeation (3.34 [1.22-9.15]). LNM was found in one of 29 (3.4%) patients with none of these three risk factors, and in 32 of 81 (39.5%) patients with one or more of these risk factors. In superficial ESCC, routine analysis of claudin-5 expression in cancer cells together with depth of invasion and lymphatic permeation may be useful for predicting LNM and thereby reducing the number of patients undergoing additional surgery after successful endoscopic resection.

Work-family conflicts and health behaviors among British, Finnish, and Japanese employees.

BACKGROUND: Work-family conflicts are associated with poor health. However, work-family conflicts and health behaviors have been little studied. PURPOSE: This study examined the associations of conflicts between paid work and family life with unhealthy behaviors among British, Finnish, and Japanese employees. METHOD: Data were derived from postal questionnaire surveys among 40 to 60 years old employees from three cohorts, the British Whitehall II Study (n = 3,397), the Finnish Helsinki Health Study (n = 4,958), and the Japanese Civil Servants Study (n = 2,901). Outcomes were current smoking, heavy drinking, physical inactivity, and unhealthy food habits. Work-family conflicts were measured with eight items. Age, marital status, and occupational class were adjusted for in logistic regression analyses. RESULTS: Work-family conflicts had few and inconsistent associations with unhealthy behaviors in all three cohorts. In the Finnish cohort, strong work-family conflicts were associated with current smoking among men. Women with strong conflicts had more often unhealthy food habits and were more often heavy drinkers than women with weaker conflicts. Likewise, British women with strong work-family conflicts were more often heavy drinkers. CONCLUSION: Although work-family conflicts were fairly prevalent in the examined cohorts, these conflicts had but few associations with the studied key health behaviors.

Cytoplasmic localization and efflux of endogenous D-aspartate in pheochromocytoma 12 cells.

In our previous reports [Z. Long, H. Homma, J.-A. Lee, T. Fukushima, T. Santa, T. Iwatsubo, R. Yamada, K. Imai, FEBS Lett. 434 (1998) 231-235; Z. Long, M. Sekine, M. Adachi, T. Furuchi, K. Imai, N. Nimura, H. Homma, Arch. Biochem. Biophys. 404 (2002) 92-97], we demonstrated for the first time that D-aspartate (D-Asp) is actually synthesized in cultured mammalian cells such as PC12, MPT1, and GH3 cells. After its synthesis, this unique amino acid is spontaneously and continuously released into the extracellular space during cell culture. In the current study, we characterized two different types of D-Asp efflux in PC12 cells. One is a spontaneous and continuous form of release of cytoplasmic origin that does not involve exocytotic efflux of vesicular origin. Endogenous D-Asp is predominantly localized to the cytoplasm of cells, and this form of D-Asp release presents a striking contrast to exocytotic, quantal discharge of vesicular dopamine. The other form of efflux is also of cytoplasmic origin and occurs through volume-sensitive organic anion channels that are opened upon hyposmotic stimuli. Interestingly, this latter form of efflux is potentiated by acetylcholine stimulation.

Associations of lifestyle factors with quality of life (QOL) in Japanese children: a 3-year follow-up of the Toyama Birth Cohort Study.

PURPOSE: To examine the associations between lifestyle factors and quality of life (QOL) among Japanese children. METHODS: Participants were 7794 children (3869 boys and 3925 girls) aged 9-10. They completed a questionnaire regarding lifestyles at baseline survey and were followed up for 3 years. In the follow-up survey, QOL was evaluated using a Japanese version of the COOP charts. Children rated their QOL as one of five response categories. Subjects rated as 'very well' or 'pretty good' were considered to have good QOL, and the remainder was assumed to have poor QOL. Logistic regression analysis was performed to evaluate the relationship between lifestyles or changes in lifestyles and QOL. In the multivariate analysis model, age, sex, body mass index (BMI), and lifestyle factors were simultaneously entered. RESULTS: During the follow-up period, children became more sedentary. Compared to children participating in physical activity 'very often' at baseline, those who exercised 'almost never' were more likely to have poor QOL [OR (95% CI): 1.92 (1.26-2.93)]. Children who developed or maintained undesirable lifestyles had high OR for poor QOL. Compared to children taking breakfast 'often' during the follow-up period, those changing from 'often' to 'seldom' or those taking breakfast 'seldom' were more likely to have poor QOL [1.61 (1.24-2.07), 2.05 (1.03-4.09), respectively]. When compared with children maintaining their participation in physical activity 'often', those who changed from 'often' to 'seldom' and those who kept 'seldom' were more likely to have poor QOL [2.10 (1.84-2.39), 2.21 (1.88-2.59), respectively]. CONCLUSIONS: This study shows that unfavourable lifestyles in childhood are associated with poor QOL in early adolescence. Early intervention could be worth considering to keeping desirable lifestyles during childhood.

Ectopic expression of Arabidopsis CYCD2 and CYCD3 in tobacco has distinct effects on the structural organization of the shoot apical meristem.

Transgenic tobacco lines expressing Arath-CYCD2 or Arath-CYCD3 genes under a cauliflower mosaic virus 35S promoter are modified in the timing of their development, but not in the phenotype of their vegetative organs. They display an increased rate of leaf initiation, which is shown to be associated with distinct changes in the structural organization of their shoot apical meristem (SAM). Constitutive expression of Arath-CYCD2 leads to a progressive modification of the SAM structural organization with predominant periclinal divisions in the L3 layer and to the loss of the classical cytophysiological zonation, the central zone being reduced to the central cells of the L1 and L2 layers. These changes reveal a particular sensitivity of the corpus cells (L3) to Arath-CYCD2 over-expression and suggest a role for CYCD2 in controlling the planes of cell division in these cells. The SAM structural modifications in the Arath-CYCD3 over-expressing lines are less drastic; only an increased cell number together with a reduced cell size, particularly in the L1 layer, characterizes the peripheral zones. This could be related to the shortening of the G1-phase duration that renders cell growth incomplete between successive mitoses. Cell proliferation continues beyond the SAM in the developing internodes and confers a delayed senescence to Arath-CYCD3 over-expressing juvenile tissues. In addition, the ploidy levels of mature stem tissues in both types of transgenic lines are unaffected, suggesting that the studied G1 to S cell-cycle genes have no effect on the extent of endoreduplication in tobacco stem tissues.

Distributions of iron, manganese, copper and zinc in various composts and amended soils.

A detailed observation was conducted on Fe, Mn, Cu and Zn in the composts derived from seafood processing by-product, garbage, swine manure and sewage sludge, respectively, as well as in amended farmlands. All elements were at lower levels of total contents but a higher percentage of water-soluble and exchangeable forms in composted seafood processing by-product and composted garbage than in composted swine manure and composted sewage sludge. Total contents increased in the order: composted seafood processing by-product approximately composted garbage < composted swine manure < composted sewage sludge. The applications of composted seafood processing by-product and composted garbage have neither caused Fe, Mn, Cu and Zn accumulation nor changed their distribution in soils; while the application of composted swine manure has largely increased Cu and Zn contents in soils, mainly in organic matter-bound form, and that of composted sewage sludge increased Mn, Cu and Zn in soils mainly in carbonate-bond and Fe-Mn oxides-bound ones. Fe is an exception, its total contents in soils decreased with the applications of composts except for composted garbage. Also, the rainfall and irrigation were another two main factors that affected available elements in soils.

New halogenated marine prostanoids with cytotoxic activity from the Okinawan soft coral Clavularia viridis.

Five new halogenated prostanoids 1-4 and 6 were isolated from the Okinawan soft coral Clavularia viridis. The gross structure of 1 was elucidated mainly on the basis of NMR spectral data. The relative and absolute configurations were determined by analysis of NOESY and CD data, chemical conversion, and the modified Mosher's method. The structures of 2-4 and 6 were deduced by comparison of their spectral data with those of 1. Compound 1 demonstrated cytotoxic activity.

The relationship between new stroke onset and serum thiocyanate as an indicator to cigarette smoking.

The case subjects were 67 stroke patients (27 males and 40 females, mean age 65.7+/-7.1), who suffered from stroke attack and had participated in annual medical check-up between 1987 and 1988 at Oyabe Public Health Center. The controls, which were adjusted for sex, age and blood pressure level with the case subjects, were selected from participants attending their annual medical check-up in 1987-1988. The serum thiocyanate level of case subjects were significantly higher than that of controls (p<0.05). The usefulness of measurement of serum thiocyanate level as an indicator of smoking status was assessed by using multiple logistic regression analysis adjusting for body mass index, mean blood pressure, and serum cholesterol was found. An odds ratio of 3.00 (95% confidence interval: 1.06-8.48, p<0.05) in cerebral infarction. It is considered that serum thiocyanate may be useful as an indicator of smoking status to assess the relationship with stroke onset, especially for cerebral infarction.

Mutational analysis of BRCA1 and BRCA2 and clinicopathologic analysis of ovarian cancer in 82 ovarian cancer families: two common founder mutations of BRCA1 in Japanese population.

We analyzed genetic alterations in BRCA1 and BRCA2 genes among 82 ovarian cancer families in Japan. The clinical characteristics of BRCA-associated ovarian cancer patients were compared with cases carrying no mutations as well as with population controls. Using a direct sequencing method, 45 of the 82 ovarian cancer families were found to carry BRCA1 or BRCA2 germ-line mutations (40 with BRCA1 and 5 with BRCA2). In 24 independent mutations of BRCA1, 5 recurrent mutations were found and 2 of them, the L63X and Q934X mutations, were detected in seven and eight independent families, respectively. In addition, 16 mutations of BRCA1 and 3 mutations of BRCA2 have never been described previously. In consideration of clinicopathological features, there was a significantly higher proportion of tumors with serous adenocarcinoma and of cases of advanced stages in the BRCA1 or BRCA2 cases than in those of the controls. On the other hand, there were no differences of mean age at diagnosis between patients with BRCA1 or BRCA2 mutation and those of the controls. Our results indicate that the features of BRCA-associated ovarian cancer in Japan appear to be similar to those in Western countries, and the L63X and Q934X mutations of BRCA1 appear to be common founder mutations unique to the Japanese population.