A pilot study to assess the origin of the spectral power increases of heart rate variability associated with transient changes in the R-R interval.

Spectral analysis of heart rate variability (HRV) is used to assess cardiovascular autonomic function. In the power density spectrum calculated from a time series of the R-R interval (RRI), three main components are distinguished: very-low-frequency (VLF; 0.003-0.04 Hz), low-frequency (LF; 0.04-0.15 Hz), and high-frequency (HF; 0.15-0.4 Hz) components. However, the physiological correlates of these frequency components have yet to be determined. In this study, we conducted spectral analysis of data segments of various lengths (5, 30, 100, and 200 s) of the RRI time series during active standing. Because of the trade-off relationship between time and frequency resolution, the analysis of the RRI data segment shorter than 30 s was needed to identify the temporal relationships between individual transient increases in RRI and the resulting spectral power changes. In contrast, the segment of 200 s was needed to properly evaluate the magnitude of the increase in the VLF power. The results showed that a transient increase in the RRI was tightly associated with simultaneous increases in the powers of the VLF, LF, and HF components. We further found that the simultaneous power increases in these three components were caused by the arterial baroreceptor reflex responding to rapid blood pressure rise.

Scale Development for "Great Research Mentors" and Its Relationship to Mentees' Psychological Burnout in Young Physician Researchers.

Fostering the research skills of young physician scientists is essential to increase the level of medical research in Japan. We aimed to clarify the mentor characteristics associated with a decreased risk of mentees' psychological burnout. A task team comprising medical doctors, researchers, nurses, and other healthcare professionals developed 35 items related to the characteristics of research mentors. In 2015, we recruited 258 physician researchers who were awarded a new Grant-in-Aid for Young Scientists between 2014-2015 and asked them to score 35 items on a five-point Likert scale. We developed a large research mentor scale using factor analysis and investigated which characteristics (i.e., domains) of the developed scale would be associated with a decreased level of psychological burnout measured by the Copenhagen Burnout Inventory. Maximum likelihood factor analysis with varimax rotation found three domains with 16 items. The three domains were labeled "Building a good trust relationship" (6 items, Cronbach's alpha = 0.889), "Mentorship in research" (6 items, alpha = 0.853), and "Established and authorized mentor" (3 items, alpha = 0.882). Multivariate linear regression models demonstrated that "Mentorship in research" was inversely associated with personal burnout (PBO) (beta = -6.25, p = 0.014) and work-related burnout (WBO) (beta = -4.76, p = 0.029); and "Building a good trust relationship" was inversely associated with client-related burnout (CBO) (beta = -4.91, p = 0.014). A great research mentor may be encouraged to have mentorship in research and a trusting relationship with mentees for mental health support.

Temporal relationships among changes in the RR-interval and the powers of the low- and high-frequency components of heart rate variability in normal subjects.

Spectral analysis of heart rate variability (HRV) is widely used as a non-invasive method to assess the cardiovascular autonomic function. Of the two main frequency components of HRV, namely low-frequency (LF, 0.04-0.15 Hz) and high-frequency (HF, 0.15-0.4 Hz) components, it is generally accepted that the HF power reflects modulation of heart rate which is mediated by cardiac parasympathetic (vagal) nerve activity. In contrast, the origin and functional correlates of the LF component are still controversial. Although several lines of evidence have indicated a close correlation between LF power and the baroreflex modulation of autonomic outflows, the detailed mechanisms underlying the genesis of the LF component remain unclarified. In this study, we conducted an ultra-short-term (UST) spectral analysis of R-R interval (RRI) time series using Fast Fourier Transform (FFT) with 5- and 25-s windows to clarify the temporal relationships among transient changes in the RRI and, LF and HF powers in healthy subjects. We found that during active standing, transient RRI increases occurred sporadically. The UST spectral analysis revealed that this RRI increase was associated with a simultaneous increase in HF power which was closely linked to the prominent LF power increase. These results indicate that during active standing, increases in LF and HF powers occur simultaneously, and they may reflect enhanced cardiac vagal activity which generates transient bradycardia.

Plasma acrolein level in rheumatoid arthritis increases independently of the disease characteristics.

OBJECTIVE: This study aimed to clarify whether plasma acrolein level actually increases in rheumatoid arthritis (RA) patients, and to elucidate whether any relationship exists between the levels and the RA background variables. METHODS: Plasma levels of protein-conjugated acrolein (PC-Acro) in 84 patients (RA group) and 298 normal individuals (Control group) were measured by enzyme-linked immunosorbent assay procedures. The data were statistically analyzed with Wilcoxon rank-sum test, multiple logistic regression analyses and Spearman's rank correlation coefficient. RESULTS: The RA group showed significantly higher PC-Acro levels than the Control group (median [interquartile range]: 80.5 [63.2-105.2] and 65.9 [58.9-78.1] nmol/ml, respectively). Of background factors giving influence to PC-Acro level in the combination of the two groups, 'diagnosis of RA positive' indicated strong correlation to high PC-Acro level (odds ratio: 2.96; 95% confidence interval: 1.54-5.71). These increases of PC-Acro in the RA patients did not correlate to their disease duration and/or inflammatory variables: PC-Acro level could elevate even in early RA patients showing negative inflammatory findings. CONCLUSION: Plasma levels of PC-Acro increased with RA, but the levels did not correlate with RA background variables. This report provides the basis for further studies of early diagnosis of RA as well as its pathogenesis.

Continuous Work Support Checklist for Female Healthcare Workers: Scale Development and Validation.

Healthcare jobs are very popular among women, however in Japan, women readily quit working because of gender-role responsibilities. This study aimed to develop a workplace support checklist for women to continue to work. In 2017, we investigated 780 (female 74.8%) faculty members and healthcare professionals of one medical university in Japan. We asked them to score the extent to which they considered 35 items identified by a task team, to be related to continuous work support for female workers in healthcare. We carried out an exploratory factor analysis and extracted four domains with 16 items in all: "Support for child rearing and home care" (five items), "Information dissemination" (five items), "Active promotion of women workers to higher positions" (three items), and "Consulting and counseling service" (three items), with Cronbach's alpha values ranging from 0.88 to 0.92. We found that the first three factors were generally associated with reasonably relevant characteristics of being female, in their 30s, married, and members of faculty. We also found that women with "Intention to leave" the workplace underscored the importance of "Support for child rearing and home care" and "Consulting and counseling service". These results suggest that the checklist is reliable and valid.

An increase in the deoxygenated hemoglobin concentration induced by a working memory task during the refractory period in the hemodynamic response in the human cerebral cortex.

In activated brain regions, the deoxygenated hemoglobin (deoxy-Hb) concentration decreases despite an increase in oxygen consumption. This is attributed to the fact that the cerebral blood flow (CBF) induced by neuronal activation exceeds the accompanying increase in the cerebral metabolic rate of oxygen (CMRO2). The discrepancy between large CBF and disproportionately small CMRO2 responses provides the basis for detecting the hemodynamic correlates of neuronal activities by functional magnetic resonance imaging (fMRI). However, this implies that if the supply of oxygen is made smaller than the oxygen consumed by the suppression of stimulus-induced CBF, the polarity of signals would be reversed. We used near-infrared spectroscopy (NIRS) to search for a condition wherein a marked decrease in the stimulus-evoked oxygenated Hb (oxy-Hb) concentration change was accompanied by an increase in the deoxy-Hb concentration in the human brain. We found that when a specific brain region was activated by two working memory (WM) task blocks in rapid succession, the local change in the deoxy-Hb concentration evoked by the second task block was reversed to an increase due to the refractory effect in the hemodynamic response. The result suggests that the polarity of the blood oxygenation level-dependent (BOLD) signal could change during repetitive neuronal activation, and thus caution must be taken in the interpretation of the BOLD signal under such situations.

[Scale Development on Perception of Academic Harassment among Medical University Faculties].

OBJECTIVES: In academia, harassment may often occur and remain unrevealed in Japan, which discourages young researchers from pursuing their career. It is necessary to estimate and improve the perception of "academic harassment" among university faculties. Therefore, in this study, we aim to develop a scale of perception of academic harassment. METHODS: Prior to a quantitative survey, a task team consisting of medical doctors, researchers, nurses, hospital workers, and managers in general affairs division identified 36 items related to academic harassment. In February 2016, we sent a self-administered questionnaire to 1,126 academic faculty members who worked in a medical university located in Tokyo, Japan. We instructed them to score the extent to which they consider each item as related to academic harassment based on a Likert scale. We carried out maximum likelihood factor analyses with promax rotation and computed Cronbach's alpha to develop a scale and investigate the reliability of the scale. RESULTS: In total, 377 returned the questionnaires (response rate, 33.5%; male, 73.8%). In factor analyses, we removed 17 items owing to low factor loadings, and four factors were eventually extracted. The first factor was termed "Harassment in organization (7 items)" because it included conditions of forcing a particular person to work on chores or lectures for students that may prevent one's academic research outputs. The second factor was termed "Violence and denying personal character (4 items)". The third factor was termed "Research misconduct (5 items)" including conditions of excluding a particular person from the coauthor list of research outputs or pressuring a person to fabricate, falsify, or plagiarize research outputs. The fourth factor was termed "Research interference (3 items)" including a condition of interference with conference attendance. Cronbach's alpha values of these four factors ranged from 0.83 to 0.91, suggesting that the scale had high reliability. The means of these factors did not differ according to gender but were higher in participants aged 50 or older than in younger participants. CONCLUSIONS: The results suggest that the scale of perception on academic harassment consisting of four factors with 19 items is valid and reliable to some extent.

[Association between Job Stress and Number of Physical Symptoms among Female Nurses of Medical-university-affiliated Hospitals].

OBJECTIVES: To clarify the association between job stress and the number of physical symptoms among newly certified female nurses. METHODS: In this cross-sectional self-administered survey, we investigated 313 female nurses working at three medical-university-affiliated hospitals in February 2016. We investigated working conditions including numbers of working and on-call hours, work-life balance, Job Content Questionnaire (JCQ) scores, and 16 physical symptoms perceived more often than once a week. RESULTS: Among the 313 participants (mean age, 31.9), 57% were aged 21-29 years and 70% were single. Of the 16 physical symptoms investigated, fatigability was the most frequent complaint (66.1%), followed by lower back pain (44.7%). Univariate analysis showed that significant factors related to physical symptoms are job demands (p<0.001) and social support (p<0.001) in JCQ, binary index of supports (p<0.001), and total working hours per day (p =0.025). Multivariable-adjusted logistic regression analyses demonstrated that the likelihood of reporting a greater number (n≥3) of physical symptoms increased by 7% [95% confidence interval (CI), 2-13%] with a one-unit increase in job demand degree, and decreased by 16% (95% CI, 10-22%) in social support degree. When binary JCQ indexes were assessed, the high-support group [odds ratio (OR) 0.36; 95% CI, 0.23-0.59] was protectively associated with a greater number of physical symptoms while long working hours was significantly associated with a higher risk (OR 18%, 95% CI, 1-38%). CONCLUSIONS: Reporting a greater number of physical symptoms may be a good indicator of job stress perceived by a nurse in a university hospital setting.

Temperature-dependent variation in alternative migratory tactics and its implications for fitness and population dynamics in a salmonid fish.

Temperature-driven life-history modifications by adaptation occur in ectotherms, and therefore, life-history modifications by adaptation need to be taken into consideration when predicting population responses to the climate change. Partial migration is a common form of life-history diversity in which a population contains both migratory and resident behaviours. Salmonid fish exhibit a wide range of life-history diversity and, in particular, partial migration. We evaluated the effect of temperature-driven life-history modifications on population dynamics in partially migratory masu salmon (Oncorhynchus masou) by field observations and theoretical models. Field observations revealed that spatial patterns of alternative migratory tactics were associated with temperature gradients. The occurrence of resident males increased, whereas the proportion of migrant males and the proportion of delayed migrants including both sexes decreased with increasing temperature and, thereby, with improved early growth conditions. The expected fitness for each migratory tactic was computed in a life-history model with early growth conditions as a function. Individual fitness was maximized by adopting resident tactics under favourable early growth conditions, early migrant tactics under intermediate early growth conditions and delayed migrant tactics under unfavourable early growth conditions. The results suggest that individuals exhibited a status-dependent conditional strategy, that is, the adoption of alternative migratory tactics is influenced by the status of individuals to make the best of a situation. A simulation model suggests that increased residency by males to increased temperature leads to a substantial decrease in the number of migrants. Moreover, the decrease in the number of delayed (older) migrants with increasing temperature magnified fluctuations in abundance. Our findings indicate the importance of temperature-driven life-history modifications for predicting dynamics of natural populations under climate warming.

Oxidation of aromatic N-heterocyclic compounds to N-oxides by Verticillium sp. GF39 cells.

Verticillium sp. GF39, catalyzing the oxidation of 1-methylisoquinoline to 1-methylisoquinoline N-oxide, was found to be the highest N-oxide producer. Under the optimized reaction conditions, the whole cells of Verticillium sp. GF39 formed 5 mM 1-methylisoquinoline N-oxide from 1-methylisoquinoline with a molar conversion yield of 100% after a 10-h incubation at 20°C. The whole cells also acted on pyridine, 2-methylpyridine, quinoline and isoquinoline and formed the corresponding N-oxides.

Enantioselective synthesis of (S)-2-cyano-2-methylpentanoic acid by nitrilase.

The nitrilase gene of Rhodococcus rhodochrous J1 was expressed in Escherichia coli using the expression vector, pKK223-3. The recombinant E. coli JM109 cells hydrolyzed enantioselectively 2-methyl-2-propylmalononitrile to form (S)-2-cyano-2-methylpentanoic acid (CMPA) with 96 % e.e. Under optimized conditions, 80 g (S)-CMPA l(-1) was produced with a molar yield of 97 % at 30 °C after a 24 h without any by-products.

A NADPH-dependent (S)-imine reductase (SIR) from Streptomyces sp. GF3546 for asymmetric synthesis of optically active amines: purification, characterization, gene cloning, and expression.

A NADPH-dependent (S)-imine reductase (SIR) was purified to be homogeneous from the cell-free extract of Streptomyces sp. GF3546. SIR appeared to be a homodimer protein with subunits of 30.5 kDa based on SDS-polyacrylamide gel electrophoresis and HPLC gel filtration. It also catalyzed the (S)-enantioselective reduction of not only 2-methyl-1-pyrroline (2-MPN) but also 1-methyl-3,4-dihydroisoquinoline and 6,7-dimethoxy-1-methyl-3,4-dihydroisoquinoline. Specific activities for their imines were 130, 44, and 2.6 nmol min(-1) mg(-1), and their optical purities were 92.7 % ee, 96.4 % ee, and >99 % ee, respectively. Using a NADPH-regenerating system, 10 mM 2-MPN was converted to amine with 100 % conversion and 92 % ee after 24 h. The amino acid sequence analysis revealed that SIR showed about 60 % identity to 6-phosphogluconate dehydrogenase. However, it showed only 37 % identity with Streptomyces sp. GF3587 (R)-imine reductase. Expression of SIR in Escherichia coli was achieved, and specific activity of the cell-free extract was about two times higher than that of the cell-free extract of Streptomyces sp. GF3546.

Regioselective synthesis of 1,3,5-adamantanetriol from 1,3-adamantanediol using Kitasatospora cells.

Washed cells (62 mg) of Kitasatospora sp. GF12 in 4 ml buffer (pH 7) catalyzed the regioselective hydroxylation of 60 mM 1,3-adamantanediol [1,3-ad(OH)(2)] to 30.9 mM 1,3,5-adamantanetriol [1,3,5-ad(OH)(3)] over 120 h at 24 °C. Glycerol at 400 mM was added to the reaction mixture to recycle the intracellular NADH/NADPH. Whole cells of GF12, also catalyzed the hydroxylation of 10 mM 1-adamantanol (1-adOH), to 3.6 mM 1,3,5-ad(OH)(3).

Purification and characterization of a novel (R)-imine reductase from Streptomyces sp. GF3587.

The (R)-imine reductase (RIR) of Streptomyces sp. GF3587 was purified and characterized. It was found to be a NADPH-dependent enzyme, and was found to be a homodimer consisting of 32 kDa subunits. Enzymatic reduction of 10 mM 2-methyl-1-pyrroline (2-MPN) resulted in the formation of 9.8 mM (R)-2-methylpyrrolidine ((R)-2-MP) with 99% e.e. The enzyme showed not only reduction activity for 2-MPN at neutral pH (6.5-8.0), but also oxidation activity for (R)-2-MP under alkaline pH (10-11.5) conditions. It appeared to be a sulfhydryl enzyme based on the sensitivity to sulfhydryl specific inhibitors. It was very specific to 2-MPN as substrate.

Asymmetric synthesis of chiral cyclic amine from cyclic imine by bacterial whole-cell catalyst of enantioselective imine reductase.

Streptomyces sp. GF3587 and 3546 were found to be imine-reducing strains with high R- and S-selectivity by screening using 2-methyl-1-pyrroline (2-MPN). Their whole-cell catalysts produced 91 mM R-2-methylpyrrolidine (R-2-MP) with 99.2%e.e. and 27.5 mM S-2-MP (92.3%e.e.) from 2-MPN at 91-92% conversion in the presence of glucose, respectively.

Bioconversion of 1-adamantanol to 1,3-adamantanediol using Streptomyces sp. SA8 oxidation system.

To efficiently produce 1,3-adamantanediol (1,3-ad(OH)(2)) from 1-adamantanol (1-adOH), our stocks of culture strains and soil microorganisms were surveyed for hydroxylation activity towards 1-adOH. Among them, the soil actinomycete SA8 showing the highest hydroxylation activity was identified as Streptomyces sp. based on 16S ribosomal DNA sequence analysis. The reaction products were purified by silica gel column chromatography, and from NMR and MS analyses, they were identified as 1,3-ad(OH)(2) and 1,4-ad(OH)(2). Streptomyces sp. SA8 produced 5.9 g l(-1) 1,3-ad(OH)(2)from 6.2 g l(-1) 1-adOH in culture broth after 120 h at 25 degrees C. Using resting cells, 2.3 g l(-1) 1,3-ad(OH)(2) was produced after 96 h of incubation at a 69% conversion rate. In both cases, 1,4-ad(OH)(2) was formed as a byproduct at a rate of about 15%. Strain SA8 also hydroxylated 2-adamantanol and 2-methyl-2-adamantanol.

Regioselective carboxylation of catechol by 3,4-dihydroxybenzoate decarboxylase of Enterobacter cloacae P.

3,4-Dihydroxybenzoate decarboxylase in Enterobacter cloacae P241 was induced by adding 3,4-dihydroxybenzoic acid, 3-hydroxybenzoic acid, 3,4,5-trihydroxybenzoic acid or 4-acetamidobenzoic acid to the culture medium. After stabilizing the enzyme activity by adding 5 mM dithiothreitol and 20 mM Na(2)S(2)O(3) to a cell-free extract, catechol at 50 mM was carboxylated in the presence of 3 M KHCO(3) to 3,4-dihydroxybenzoic acid with a molar conversion ratio of 28% after 14 h at 30 degrees C.

Bioconversion of 2,6-dimethylpyridine to 6-methylpicolinic acid by Exophiala dermatitidis (Kano) de Hoog DA5501 cells grown on n-dodecane.

Alkane-assimilating microorganisms were isolated from enrichment cultures using n-octane, n-dodecane, n-hexadecane, or pristane (2,6,10,14-tetramethylpentadecane) as a sole carbon source to find microbial catalysts oxidizing methyl groups of 2,6-dimethylpyridine. The cells of Exophiala dermatitidis (Kano) de Hoog DA5501, an n-dodecane-assimilating fungus, oxidized a single methyl group of 2,6-dimethylpyridine to produce 6-methylpicolinic acid (6-methylpyridine-2-carboxylic acid) without the formation of dipicolinic acid (pyridine-2,6-dicarboxylic acid); 67 mM 6-methylpicolinic acid (9.2 g/l) accumulated with a molar conversion yield of 89% by 54-h incubation. The fungus cells also oxidized the methyl group of 2,6-dimethylpyrazine and 2,4,6-trimethylpyridine regioselectively.