Differing Effects of Body Size on Circulating Lipid Concentrations and Hemoglobin A1c Levels in Young and Middle-Aged Japanese Women.

The condition of being underweight is a social problem in Japan among women. However, there is a lack of evidence for dietary guidance for underweight women because there has been no comparison of lipids or HbA1c among underweight, normal weight, and overweight women in different age groups. We analyzed the effect of body size and age on the serum lipid and hemoglobin A1c levels in Japanese women in a cross-sectional study. A total of 26,118 women aged >20-65 years underwent physical examinations between 2012 and 2022. Seventeen percent of women aged >20-29 years were underweight, and 8% of those aged 50-65 years were underweight. Total cholesterol and non-HDL-C concentrations increased with age, but the difference between underweight and overweight individuals was lowest among women aged 50-65 years. On the other hand, the differences in HDL-C, TG, and HbA1c levels between underweight and overweight subjects were greatest in the 50-65 age group, but the differences between underweight and normal weight subjects were much smaller. Considering that, unlike HDL-C, TG, and HbA1c, TC and non-HDL-C increase to levels comparable to overweight levels in underweight women in aged 50-65 years, educating people about a diet that lowers non-HDL-C is necessary even in young underweight women.

Young Japanese Underweight Women with "Cinderella Weight" Are Prone to Malnutrition, including Vitamin Deficiencies.

Undernutrition among young women at "Cinderella weight" is socially important in Japan. To determine the nutritional status of Cinderella-weight women, we conducted an exploratory cross-sectional study on the health examination results of employees aged 20 to 39 (n = 1457 and 643 for women and men, respectively). The percentage of underweight women was found to be much higher than that of men (16.8% vs. 4.5%, respectively). In underweight women (n = 245), handgrip strength (22.82 ± 5.55 vs. 25.73 ± 5.81 kg, p < 0.001), cholesterol level (177.8 ± 25.2 vs. 194.7 ± 31.2 mg/dL, p < 0.05), and lymphocyte count (1883 ± 503 vs. 2148 ± 765/µL, p < 0.001) were significantly lower than in overweight women (n = 116). Then, the BMI < 17.5 group (n = 44) was referred to the outpatient nutrition evaluation clinic. Lower prealbumin, cholesterol, and lymphocyte levels were also observed in 34%, 59%, and 32% of the patients, respectively. Regarding dietary characteristics, 32% of the underweight women in this study skipped breakfast, and 50% had low dietary diversity scores. Lower total energy intake, carbohydrate and fiber intake, and Ca and Fe intake were also observed in 90% of the patients. Deficiencies in vitamin B1, B12, D, and folate were diagnosed in 4.6%, 25%, 14%, and 98% of the patients, respectively. Thus, young underweight women may be prone to malnutrition.

Cryptochrome deficiency enhances transcription but reduces protein levels of pineal Aanat

Cryptochrome (Cry) 1 and 2 are essential for circadian rhythm generation, not only in the suprachiasmatic nucleus, the site of the mammalian master circadian clock, but also in peripheral organs throughout the body. CRY is also known as a repressor of arylalkylamine-N-acetyltransferase (Aanat) transcription; therefore, Cry deficiency is expected to induce constantly high pineal melatonin content. Nevertheless, we previously found that the content was consistently low in melatonin-proficient Cry1 and Cry2 double-deficient mice (Cry1−/−/Cry2−/−) on C3H background. This study aims to clarify the mechanism underlying this discrepancy. In the Cry1−/−/Cry2−/− pineal, expression levels of Aanat and clock gene Per1 were consistently high with no circadian fluctuation on the first day in constant darkness, demonstrating that CRY acts in vivo as a repressor of the pineal circadian clock and AANAT. In contrast, the enzyme activity and protein levels of AANAT remained low throughout the day, supporting our previous observation of continuously low melatonin. Thus, effects of Cry deficiency on the responses of ß-adrenergic receptors were examined in cultured pineal glands. Isoproterenol, a ß-adrenergic stimulant, significantly increased melatonin content, although the increase was smaller in Cry1−/−/Cry2−/− than in WT mice, during both the day and night. However, the increase in cAMP in response to forskolin was similar in both genotypes, indicating that CRY deficiency does not affect the pathway downstream of the ß-adrenergic receptor. These results suggest that a lack of circadian adrenergic input due to CRY deficiency decreases ß-receptor activity and cAMP levels, resulting in consistently low AANAT levels despite abundant Aanat mRNA.

Spatiotemporal profiles of arginine vasopressin transcription in cultured suprachiasmatic nucleus.

Arginine vasopressin (AVP), a major neuropeptide in the suprachiasmatic nucleus (SCN), is postulated to mediate the output of the circadian oscillation. Mice carrying a reporter gene of AVP transcription (AVP(ELuc)) were produced by knocking-in a cDNA of Emerald-luciferase (ELuc) in the translational initiation site. Homozygous mice did not survive beyond postnatal day 7. Using the heterozygous (AVP(ELuc/+)) mice, a bioluminescence reporter system was developed that enabled to monitor AVP transcription through AVP-ELuc measurement in real time for more than 10 cycles in the cultured brain slice. AVP(ELuc/+) mice showed circadian behaviour rhythms and light responsiveness indistinguishable from those of the wild-type. Robust circadian rhythms in AVP-ELuc were detected in the cultured SCN slice at a single cell as well as tissue levels. The circadian rhythm of the whole SCN slice was stable, with the peak at the mid-light phase of a light-dark cycle, while that of a single cell was more variable. By comparison, rhythmicity in the paraventricular nucleus and supraoptic nucleus in the hypothalamus was unstable and damped rapidly. Spatiotemporal profiles of AVP expression at the pixel level revealed significant circadian rhythms in the entire area of AVP-positive cells in the SCN, and at least two clusters that showed different circadian oscillations. Contour analysis of bioluminescence intensity in a cell-like region demonstrated the radiation area was almost identical to the cell size. This newly developed reporter system for AVP gene expression is a useful tool for the study of circadian rhythms.

Glucocorticoids Reset the Nasal Circadian Clock in Mice.

The symptoms of allergic rhinitis show marked day-night changes that are likely to be under the control of the circadian clock, but the mechanism of this control is poorly understood. Because most peripheral tissues have endogenous circadian clocks, we examined the circadian rhythm of the clock gene product PERIOD2 (PER2) in the nasal mucosa of male mice using a luciferase reporter and demonstrated for the first time the phase-dependent effects of dexamethasone (DEX) on nasal PER2 rhythm in vivo and ex vivo. The phase shifts in PER2 rhythm caused by DEX were observed around the peak phase of serum glucocorticoids, suggesting that the circadian rhythm of endogenous glucocorticoids regulates the peripheral clock of the mouse nasal mucosa. From the viewpoint of circadian physiology, the best time to administer intranasal steroid treatment for allergic rhinitis would be when no phase shift is caused by DEX: in the early evening in diurnal humans.

Monitoring circadian time in rat plasma using a secreted Cypridina luciferase reporter.

A firefly luciferase reporter enabled us to monitor promoter activity in vivo as well as ex vivo; however, this requires a sufficient supply of the substrate luciferin and specific monitoring devices. To overcome these disadvantages, we developed transgenic rats carrying a secreted enzyme Cypridina luciferase (CLuc) reporter under the promoter of clock gene Per2 (Per2-CLuc). Per2-CLuc activity in serially sampled blood from freely moving rats exhibited robust circadian rhythms with a peak at early morning. The Per2-CLuc bioluminescence could be quantified even with approximately 100pl of plasma. Plasma Per2-CLuc rhythms were phase reversed, and the level was reduced by restricting food access for 2h during the light phase, suggesting that the plasma Per2-CLuc rhythms reflect the phase of peripheral clocks entrained to feeding cues as well as fuel metabolism. Fasting for 2days did not alter the circadian Per2-CLuc rhythms in rats, suggesting that feeding per se did not affect the circadian Per2-CLuc rhythms. Tissue-specific Per2-CLuc rhythms were observed in culture medium of peripheral tissues. The Per2-CLuc reporter is a powerful tool to access gene expression in vivo as well as ex vivo with ordinary laboratory equipment.

De novo synthesis of PERIOD initiates circadian oscillation in cultured mouse suprachiasmatic nucleus after prolonged inhibition of protein synthesis by cycloheximide.

The circadian oscillation is known to stop with prolonged inhibition of protein synthesis and to restart from a particular phase after the removal of inhibition. In order to know the underlying molecular mechanisms, the mouse suprachiasmatic nucleus was cultured and treated with a protein synthesis inhibitor, cycloheximide (CHX), for various durations. Circadian rhythms in Bmal1 expression and PER2 protein were monitored by means of bioluminescence reporters. Bmal1-LUC and PER2::LUC bioluminescence decreased to basal levels after CHX application. CHX washout restarted the circadian rhythms from a fixed phase when CHX treatment exceeded 18 h. mRNA of Per1, Per2 and Rev-erbα increased and reached high plateau levels in 18 h after CHX application, which continued for 48 h; whereas Bmal1 mRNA increased for the first 18 h but then decreased to the basal level. Immunoblot analysis showed a decreased PER2::LUC level at 24 h after CHX application, indicating that the transcription of Pers and Rev-erbα was disinhibited by CHX. CHX washout increased PER2::LUC bioluminescence and protein level in a few hours. High Per mRNA levels induced the rapid increases of their proteins, which might trigger the restarting of circadian oscillation. These findings indicate that the circadian oscillation is stopped by disinhibition of Per1 and Per2 transcriptions, and restarted upon the recovery of the PER mediated auto-feedback loop. De novo synthesis of PER protein is a key factor to initiate the circadian oscillation after prolonged inhibition of protein synthesis.

Emergence of the neural network for reading in five-year-old beginning readers of different levels of pre-literacy abilities: an fMRI study.

The present study traced the emergence of the neural circuits for reading in five-year-old children of diverse pre-literacy ability. In the fall and winter of kindergarten, children performed a one-back task with letter versus false font stimuli during fMRI scanning. At the start of kindergarten, children with on-track pre-literacy skills (OT) recruited bilateral temporo-parietal regions for the letter > false font comparison. In contrast, children at-risk for reading difficulty (AR) showed no differential activation in this region. Following 3 months of kindergarten and, for AR children, supplemental reading instruction, OT children showed left-lateralized activation in the temporo-parietal region, whereas AR children showed bilateral activation and recruitment of frontal regions including the anterior cingulate cortex. These data suggest that typical reading development is associated with initial recruitment and subsequent disengagement of right hemisphere homologous regions while atypical reading development may be associated with compensatory recruitment of frontal regions.

The role of awareness in semantic and syntactic processing: an ERP attentional blink study.

An important question in the study of language is to what degree semantic and syntactic processes are automatic or controlled. This study employed an attentional blink (AB) paradigm to manipulate awareness in the processing of target words in order to assess automaticity in semantic and syntactic processing. In the semantic block, targets occurring both within and outside the AB period elicited an N400. However, N400 amplitude was significantly reduced during the AB period, and missed targets did not elicit an N400. In the syntactic block, ERPs to targets occurring outside the AB period revealed a late negative syntactic incongruency effect, whereas ERPs to targets occurring within the AB period showed no effect of incongruency. The semantic results support the argument that the N400 primarily indexes a controlled, postlexical process. Syntactic findings suggest that the ERP response to some syntactic violations depends on awareness and availability of attentional resources.

An ERP study of syntactic processing in English and nonsense sentences.

The timecourse of the interaction between syntactic and semantic information during sentence processing in monolingual native English speakers was investigated using event-related potentials (ERPs). To examine the effects of semantic information on syntactic processing, the results for normal English sentences were compared to those for semantically impoverished nonsense (Jabberwocky) sentences. Within each sentence type condition, half of the sentences contained a syntactic violation. Violations elicited a larger amplitude N1 and more negative ERPs around 200 ms after the onset of the critical word relative to the grammatical condition. Although these effects were observed in both sentence types, they were anteriorly distributed for English sentences only. Moreover, the P600 elicited by the syntactic violation was attenuated in processing Jabberwocky as compared to English sentences. These results suggest that semantic and syntactic information are integrated during the earlier stages of syntactic processing indexed by the anterior negativities, and that these interactions continue in the later stages of processing indexed by the P600.

Factors relating to organizational commitment of older male employees in Japan.

Recently, an increasing number of employers have provided employment opportunities for older adults. Yet, few studies pay attention to older employees' perceptions of their employment. Using a Japanese national sample of 995 male employees aged 55 to 64, this study examined whether the existing research on organizational commitment applies to older employees, whether measures that are unique to older employees have significant relationships to their organizational commitment, and whether the effects of these factors differ by retirement status. The results of hierarchical multiple regression analyses showed significant relationships between employee organizational commitment and employment security, personal relationships in workplaces and job characteristics. Negative ageism and employer-sponsored programs for older employees also had significant relationships to organizational commitment. The effects of salary, job autonomy, job demands, and employer-sponsored programs differed by retirement status. While the study was consistent with the existing research, it also suggested the importance of measures that are unique to older employees.

Possible contribution of apoptosis-inducing factor (AIF) and reactive oxygen species (ROS) to UVB-induced caspase-independent cell death in the T cell line Jurkat.

We analyzed the mechanism of UVB-induced cell death using the Jurkat T cell line. Apoptosis was assessed by measuring phosphatidylserine (PS) externalization, caspase activity, the decrease in mitochondrial membrane potential (Delta Psi m), nucleosomal DNA fragmentation, and morphological changes such as chromatin condensation. The mitochondrio-nuclear translocation of apoptosis-inducing factor (AIF) was evaluated by confocal laser microscopy. The cell death pattern of UVB-irradiated cells was similar to the Fas-induced cell death pattern. However, zVAD-fmk inhibited the nucleosomal fragmentation of DNA but not the externalization of PS, decrease in Delta Psi m, or mitochondrio-nuclear translocation of AIF. N-acetyl L-cysteine significantly inhibited the translocation of AIF induced by UVB. These results suggested that caspase-dependent and -independent pathways were involved in UVB-induced cell death in Jurkat cells, and the mitochondrio-nuclear translocation of AIF was associated with the latter pathway. In addition, reactive oxygen species generated by UVB might be involved in inducing the mitochondrio-nuclear translocation of AIF.

Licensing and training requirements for direct care workers in Japan: what can the United States and Japan learn from each other?

Shortages of direct care workers have been of concern both in the United States and in Japan. This article compares issues surrounding long-term care provisions in the two countries and introduces Japan's unique licensure and certificate system for direct care workers. Japan has established three levels of direct care worker certificates and a direct care licensure, which can be potentially used as a career ladder. Studies show that this system has resulted in different work conditions and benefits between different certificate and licensure levels but had a limited impact on hourly wage and task differentiation. Implications for the United States are also discussed.

Functional evaluation of ex vivo expanded cord blood lymphocytes: possible use for adoptive cellular immunotherapy.

OBJECTIVE: To examine the possibility of adoptive cellular immunotherapy such as donor lymphocyte infusion using ex vivo expanded cord blood (CBL) lymphocytes, the potential expansion ability of CBL lymphocytes and the function of expanded CBL lymphocytes were evaluated. MATERIALS AND METHODS: Mononuclear cell fractions derived from CBL or peripheral blood (PBL) were placed in anti-CD3 monoclonal antibody-coated flasks and cultured in the presence of recombinant human interleukin-2 for 4 days. Cells then were transferred to noncoated flasks and cultured for another 2 weeks. On day 14, polyclonality, cell surface markers, killer activity, and intracellular cytokine profiles were evaluated. RESULTS: Cells were polyclonally expanded. The differences in cumulative fold expansion on day 14 between CBL [1174 +/- 637 (292-1939), n = 6] and PBL [1247 +/- 568 (517-2328), n = 9] were not significant (p = 0.95). Phenotypic patterns of both expanded CBL and PBL were similar. CD4/CD8 ratio of expanded CBL appeared to remain greater than 1 on day 8. In contrast, that of expanded PBL became less than 1. In both cases, approximately 20% of cells had the CD3(+)CD8(+)CD56(+) phenotype. At an effector to target ratio (E/T) of 40:1, the natural killer activity of expanded CBL (64.5% +/- 10.8%, n = 9) was significantly higher than that of expanded PBL (48.3% +/- 16.8%, n = 9) (p < 0.01, Mann-Whitney U-test). However, there was no significant difference in lymphokine-activated killer activity between expanded CBL (45.3% +/- 25.2%, n = 7) and expanded PBL (67.2% +/- 12.3%, n = 7). Interferon-gamma-producing cells were dominant in both cases. CONCLUSIONS: It was feasible to achieve approximately 1000-fold expansion of CBL, and the phenotype and function of expanded CBLs were essentially equivalent to those of expanded PBL. This suggested that ex vivo expanded CBL may be applied to adoptive cellular immunotherapy such as donor lymphocyte infusion.

Profile of home care aides, nursing home aides, and hospital aides: historical changes and data recommendations.

PURPOSE: To examine demographic characteristics and work conditions of home care aides, nursing home aides, and hospital aides in the late 1980s and late 1990s. DESIGN AND METHODS: This study replicated a previous study which examined the Current Population Survey (CPS) March supplement from 1987 to 1989. The present study examined CPS data from 1997 to 1999 both to obtain a profile of aides in the late 1990s and to compare 1990's work conditions and demographic characteristics with those of aides in the late 1980s. RESULTS: Whereas demographic characteristics and work conditions of hospital and nursing home aides show little change over the decade, home care aides today are generally younger, more educated, more likely to hold full-time positions, and more likely to have health benefits than their counterparts 10 years ago. Yet work conditions are still poorer for home care aides than for the other types of aides. IMPLICATIONS: Work conditions need further improvement, particularly for home care aides. More accurate data to describe paraprofessional care workers are also necessary to address the serious worker shortage problems.