Presenteeism and sleep duration on workdays and days off.

BACKGROUND: Presenteeism refers to being present at work but experiencing reduced productivity due to health problems, and has been known to be related to sleep loss. Workers commonly sleep longer on days off than on workdays, and presenteeism may be reduced with extended sleep on days off. AIMS: This study aimed to determine the association between sleep duration both on workdays and days off and presenteeism. METHODS: The participants were 1967 workers who engaged in work for 5 days and rested for 2 days weekly. Sleep duration was classified into less than 6 hours (short; S), 6-8 hours (medium; M), and 9 hours or longer (long; L), for workdays and days off, respectively. Presenteeism was assessed using the World Health Organization Health and Work Performance Questionnaire. RESULTS: On both workdays and days off, compared to medium sleep duration, short sleep duration was significantly associated with increased odds of presenteeism. The odds of presenteeism were significantly increased for S-S (odds ratio [OR] 2.17, 95% confidence interval [CI]1.40-3.37), S-M (OR 1.59, 95% CI 1.14-2.22), S-L (OR 2.71, 95% CI 1.05-7.00), and M-S (OR 6.82, 95% CI 2.71-17.17) combined sleep duration for workdays and days off, respectively, compared to an M-M (reference). CONCLUSIONS: Sleep loss on workdays cannot be compensated for with longer sleep on days off. This study suggests that sufficient sleep duration on both workdays and days off is important for reducing presenteeism.

Genome Sequence Resources for Four Phytopathogenic Fungi from the Colletotrichum orbiculare Species Complex.

Colletotrichum orbiculare species complex fungi are hemibiotrophic plant pathogens that cause anthracnose of field crops and weeds. Members of this group have genomes that are remarkably expanded relative to other Colletotrichum fungi and compartmentalized into AT-rich, gene-poor and GC-rich, gene-rich regions. Here, we present an updated version of the C. orbiculare genome, as well as draft genomes of three other members from the C. orbiculare species complex: the alfalfa pathogen C. trifolii, the prickly mallow pathogen C. sidae, and the burweed pathogen C. spinosum. The data reported here will be important for comparative genomics analyses to identify factors that play a role in the evolution and maintenance of the expanded, compartmentalized genomes of these fungi, which may contribute to their pathogenicity.

Surgical starting time in the morning versus the afternoon: propensity score matched analysis of operative outcomes following laparoscopic colectomy for colorectal cancer.

BACKGROUND: The number of colorectal cancer cases is increasing, and so the number of laparoscopic colectomy procedures being performed is also increasing, leading to an increased workload for surgeons. However, operating for prolonged time periods may cause surgeons to lose their concentration and develop fatigue. We hypothesized that there is a time-of-day variation in outcome for patients with colorectal cancer who undergo laparoscopic colectomy. The present study aimed to compare the operative outcome between laparoscopic colectomy for colorectal cancer performed in the morning versus the afternoon. METHODS: This was a single-center, retrospective study. All 1961 consecutive patients who underwent laparoscopic surgery for colorectal cancer between 2007 and 2017 were included; 1006 of these patients underwent morning surgery, while 955 underwent afternoon surgery. These patients were analyzed using propensity score matching, giving 791 patients in each group. The short- and long-term outcomes in both groups were compared. RESULTS: Before propensity score matching, the morning group had a larger mean tumor size than the afternoon group (30 cm vs 35 cm; P = 0.0035). After matching, the two groups did not significantly differ in any patient characteristics. Compared with the afternoon group, the morning group had a significantly lesser incidence of intra-operative organ injury (0.25% vs 1.13%; P = 0.027), and a significantly greater incidence of post-operative abdominal abscess (2.03% vs 0.75% P = 0.028). The incidences of other complications and morbidities were similar in both groups. The median operative time in the morning group (201 min) was significantly longer than that in the afternoon group (193 min; P = 0.0124). The two groups did not differ in 5-year overall survival rates and 5-year disease-free rates within any disease stage. CONCLUSIONS: Surgical start times are correlated with surgical outcomes. Our data will help to ensure the safest possible surgeries.

Proposal of a new mechanism for the directional propagation of the action potential using a mimicking system.

A nerve conduction model is constructed by using some liquid-membrane cells that mimic the function of the K+ and Na+ channels. By imitating two types of Na+ channels (ligand-gated Na+ channels and voltage-gated Na+ channels), a new mechanism for the directional propagation of the action potential along the axon toward the axon terminal is proposed. When the nerve cell is excited by an external (outer) stimulus, it can be presumed that the ligand-gated channels work as power sources at the synapse to propagate the change in the membrane potential, and then the voltage-gated channels locally assist the propagation at each site of the axon (nodes of Ranvier).

Effect of temperature on diapause termination and post-diapause development in Eotetranychus smithi (Acari: Tetranychidae).

Previous studies on the spider mite Eotetranychus smithi Pritchard & Baker have shown that diapause in eggs is induced by low temperature alone and that females developed at ≤ 17.5 °C laid diapause eggs, regardless of the photoperiod. In this study, diapause eggs were kept at 5 °C and a photoperiod of 16L:8D for 0-120 days and then maintained at 25 °C to know the effect of chilling on diapause termination. Diapause eggs mostly hatched when they were maintained at 25 °C after chilling for 30-90 days at 5 °C, which suggests that diapause termination is favored by low temperatures. To clarify the hatching conditions after diapause termination, diapause eggs kept at 5 °C for 45 days were subsequently maintained at various constant temperatures (from 15 to 25 °C) under a long-day photoperiod (16L:8D). The hatchability at all temperatures tested was high (> 90%) and did not significantly differ among the high temperatures. Duration of embryonic development was shorter with increasing warming temperature after chilling. The lower thermal threshold (t) and thermal constant (k) for post-diapause egg development were 10.5 °C and 76.9 degree-days, respectively. Females, which developed from diapause eggs that were chilled at 5 °C for 45 days and then maintained at 15 °C, laid only non-diapause eggs, which indicates that they were prevented from re-entering diapause even under diapause-inducing conditions (15 °C). Thus, temperature is the main factor to control diapause termination and post-diapause development, which has also been found for other spider mites that enter diapause at the egg stage.

Impact of constant versus fluctuating temperatures on the development and life history parameters of Tetranychus urticae (Acari: Tetranychidae).

The impact of daily temperature fluctuations on arthropod life history parameters is inadequately studied compared with the ample amount of research that has been conducted on the effects of constant temperatures. Fluctuating temperatures are likely to be more realistic, as they are ecologically more similar to what these arthropods experience in nature. Here, we compared the impact of 11 constant temperatures that ranged from 10 to 35 °C with fluctuating temperatures with the same corresponding mean temperature and an amplitude of 10 °C between high (12 h) and low (12 h) temperatures on the development and life history parameters of Tetranychus urticae under continuous light conditions. No eggs hatched at constant 10 °C, whereas 81.5% of eggs successfully completed development at fluctuating 10 °C (15/5 °C). Egg-to-female adult development was faster under fluctuating temperatures from 12.5 to 27.5 °C than under constant temperatures, whereas the opposite trend was observed at >30 °C. The lower thermal thresholds (T) were 11.63 and 8.63 °C, and thermal constants (K) were 127.81 and 150.69 degree-days for egg-to-female adults at constant and fluctuating temperatures, respectively. The numbers of oviposition days were significantly higher at fluctuating 15 °C than at the corresponding constant temperature, whereas the opposite trend was observed from 20 to 30 °C. The intrinsic rate of increase (r) was higher at fluctuating than at constant 15 °C. The net reproductive rate (R 0) was also higher at fluctuating than at constant 15 and 35 °C, but showed an opposite trend at 20 and 25 °C. We conclude that fluctuating temperatures should be considered to accurately predict spider mite population dynamics in nature.

Oxytocin's neurochemical effects in the medial prefrontal cortex underlie recovery of task-specific brain activity in autism: a randomized controlled trial.

The neuropeptide oxytocin may be an effective therapeutic strategy for the currently untreatable social and communication deficits associated with autism. Our recent paper reported that oxytocin mitigated autistic behavioral deficits through the restoration of activity in the ventromedial prefrontal cortex (vmPFC), as demonstrated with functional magnetic resonance imaging (fMRI) during a socio-communication task. However, it is unknown whether oxytocin exhibited effects at the neuronal level, which was outside of the specific task examined. In the same randomized, double-blind, placebo-controlled, within-subject cross-over clinical trial in which a single dose of intranasal oxytocin (24 IU) was administered to 40 men with high-functioning autism spectrum disorder (UMIN000002241/000004393), we measured N-acetylaspartate (NAA) levels, a marker for neuronal energy demand, in the vmPFC using (1)H-magnetic resonance spectroscopy ((1)H-MRS). The differences in the NAA levels between the oxytocin and placebo sessions were associated with oxytocin-induced fMRI signal changes in the vmPFC. The oxytocin-induced increases in the fMRI signal could be predicted by the NAA differences between the oxytocin and placebo sessions (P=0.002), an effect that remained after controlling for variability in the time between the fMRI and (1)H-MRS scans (P=0.006) and the order of administration of oxytocin and placebo (P=0.001). Furthermore, path analysis showed that the NAA differences in the vmPFC triggered increases in the task-dependent fMRI signals in the vmPFC, which consequently led to improvements in the socio-communication difficulties associated with autism. The present study suggests that the beneficial effects of oxytocin are not limited to the autistic behavior elicited by our psychological task, but may generalize to other autistic behavioral problems associated with the vmPFC.

Exosomal microRNA in serum is a novel biomarker of recurrence in human colorectal cancer.

BACKGROUND: Functional microRNAs (miRNAs) in exosomes have been recognised as potential stable biomarkers in cancers. The aim of this study is to identify specific miRNAs in exosome as serum biomarkers for the early detection of recurrence in human colorectal cancer (CRC). METHODS: Serum samples were sequentially obtained from six patients with and without recurrent CRC. The miRNAs were purified from exosomes, and miRNA microarray analysis was performed. The miRNA expression profiles and copy number aberrations were explored using microarray and array CGH analyses in 124 CRC tissues. Then, we validated exosomal miRNAs in 2 serum sample sets (90 and 209 CRC patients) by quantitative real-time RT-PCR. RESULTS: Exosomal miR-17-92a cluster expression level in serum was correlated with the recurrence of CRC. Exosomal miR-19a expression levels in serum were significantly increased in patients with CRC as compared with healthy individuals with gene amplification. The CRC patients with high exosomal miR-19a expression showed poorer prognoses than the low expression group (P<0.001). CONCLUSIONS: Abundant expression of exosomal miR-19a in serum was identified as a prognostic biomarker for recurrence in CRC patients.

Field-induced quantum criticality and universal temperature dependence of the magnetization of a spin-1/2 heisenberg chain.

High-precision dc magnetization measurements have been made on Cu(C4H4N2) (NO3)2 in magnetic fields up to 14.7 T, slightly above the saturation field Hs=13.97 T, in the temperature range from 0.08 to 15 K. The magnetization curve and differential susceptibility at the lowest temperature show excellent agreement with exact theoretical results for the spin-1/2 Heisenberg antiferromagnet in one dimension. A broad peak is observed in magnetization measured as a function of temperature, signaling a crossover to a low-temperature Tomonaga-Luttinger-liquid regime. With an increasing field, the peak moves gradually to lower temperatures, compressing the regime, and, at Hs, the magnetization exhibits a strong upturn. This quantum critical behavior of the magnetization and that of the specific heat withstand quantitative tests against theory, demonstrating that the material is a practically perfect one-dimensional spin-1/2 Heisenberg antiferromagnet.

A novel and selective sodium-glucose cotransporter-2 inhibitor, tofogliflozin, improves glycaemic control and lowers body weight in patients with type 2 diabetes mellitus.

AIM: To assess the efficacy, safety and tolerability of different doses of tofogliflozin, a novel, highly selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes mellitus (T2DM). METHODS: In a 12-week, multicentre, multinational, randomized, double-blind, parallel-group, placebo-controlled, dose-finding study, patients with inadequate glycaemic control from diet and exercise alone, or from diet and exercise plus a stable dose of metformin, were randomized to one of five doses of tofogliflozin (2.5, 5, 10, 20, or 40 mg) or placebo. The primary efficacy endpoint was absolute change at week 12 from baseline in glycated haemoglobin (HbA1c), minus the change in the placebo group. RESULTS: Statistically significant dose-dependent reductions in HbA1c were shown in all treated groups except the 2.5-mg dose group, with a maximum reduction of 0.56% (placebo-subtracted) at the 40-mg dose, along with increased urinary glucose excretion. Metformin treatment had no substantial influence on tofogliflozin efficacy. Dose-dependent reductions in fasting plasma glucose and body weight were observed, and glucose intolerance was improved, with a trend towards blood pressure reduction. Slight increases were observed for mean ketone bodies with no abnormal change in ketone body ratio. No deaths or treatment-related serious adverse events were reported. The incidence of adverse events was similar in the placebo (37.9%) to that in the tofogliflozin group (35.9-46.3%). Withdrawal because of adverse events was rare (≤2 patients per treatment group), with similar rates of withdrawal in the placebo and tofogliflozin groups. CONCLUSIONS: A once-daily dose of tofogliflozin for 12 weeks was an effective, safe and well-tolerated treatment for T2DM.

Amplification of PVT-1 is involved in poor prognosis via apoptosis inhibition in colorectal cancers.

BACKGROUND: We previously conducted gene expression microarray analyses to identify novel indicators for colorectal cancer (CRC) metastasis and prognosis from which we identified PVT-1 as a candidate gene. PVT-1, which encodes a long noncoding RNA, mapped to chromosome 8q24 whose copy-number amplification is one of the most frequent events in a wide variety of malignant diseases. However, PVT-1 molecular mechanism of action remains unclear. METHODS: We conducted cell proliferation and invasion assays using colorectal cancer cell lines transfected with PVT-1siRNA or negative control siRNA. Gene expression microarray analyses on these cell lines were also carried out to investigate the molecular function of PVT-1. Further, we investigated the impact of PVT-1 expression on the prognosis of 164 colorectal cancer patients by qRT-PCR. RESULTS: CRC cells transfected with PVT-1 siRNA exhibited significant loss of their proliferation and invasion capabilities. In these cells, the TGF-ß signalling pathway and apoptotic signals were significantly activated. In addition, univariate and multivariate analysis revealed that PVT-1 expression level was an independent risk factor for overall survival of colorectal cancer patients. CONCLUSION: PVT-1, which maps to 8q24, generates antiapoptotic activity in CRC, and abnormal expression of PVT-1 was a prognostic indicator for CRC patients.

Pressure-dependent magnetization and magnetoresistivity studies on tetragonal FeS (mackinawite): revealing its intrinsic metallic character.

The transport and magnetic properties of the tetragonal Fe[Formula: see text]S were investigated using magnetoresistivity and magnetization within [Formula: see text] K, [Formula: see text] 70 kOe and [Formula: see text] 3.0 GPa. In addition, room-temperature x-ray diffraction and photoelectron spectroscopy were also applied. In contrast to previously reported nonmetallic character, Fe[Formula: see text]S is intrinsically metallic but due to a presence of a weak localization such metallic character is not exhibited below room temperature. An applied pressure reduces strongly this additional resistive contribution and as such enhances the temperature range of the metallic character which, for ∼3 GPa, is evident down to 75 K. The absence of superconductivity as well as the mechanism behind the weak localization will be discussed.

Paired related homoeobox 1, a new EMT inducer, is involved in metastasis and poor prognosis in colorectal cancer.

BACKGROUND: Paired related homoeobox 1 (PRRX1) has been identified as a new epithelial-mesenchymal transition (EMT) inducer in breast cancer. However, the function of PRRX1 in colorectal cancer (CRC) has not been elucidated. METHODS: We utilised ectopic PRRX1-expressing cell lines to analyse the function of PRRX1 in CRC. The clinical significance of PRRX1 was also examined on three independent CRC case sets. RESULTS: PRRX1 induced EMT and the stem-like phenotype in CRC cells. In contrast to studies of breast cancer, abundant expression of PRRX1 was significantly associated with metastasis and poor prognosis in CRC. CONCLUSION: PRRX1 is an indicator of metastasis and poor prognosis in CRC cases. Further investigation is required to uncover the signalling network regulating PRRX1.

Low-temperature low-field phases of the pyrochlore quantum magnet Tb2Ti2O7.

By means of ac magnetic-susceptibility measurements, we find evidence for a new magnetic phase of Tb2Ti2O7 below about 140 mK in zero magnetic field. In magnetic fields parallel to [111], this phase is characterized by frequency- and amplitude-dependent susceptibility and extremely slow spin dynamics. In the zero-temperature limit, it extends to about 67 mT (the internal field H(int)≃52 mT), at which it makes transition to another phase. The field dependence of the susceptibility of this second phase, which extends to about 0.60 T (H(int)≃0.54 T) in the zero-temperature limit, indicates the presence of a weak magnetization plateau below about 50 mK, as has been predicted by a single-tetrahedron four-spin model, suggesting that the second phase is a quantum kagome ice.

Msx2 deficiency in mice causes pleiotropic defects in bone growth and ectodermal organ formation.

The composite structure of the mammalian skull, which forms predominantly via intramembranous ossification, requires precise pre- and post-natal growth regulation of individual calvarial elements. Disturbances of this process frequently cause severe clinical manifestations in humans. Enhanced DNA binding by a mutant MSX2 homeodomain results in a gain of function and produces craniosynostosis in humans. Here we show that Msx2-deficient mice have defects of skull ossification and persistent calvarial foramen. This phenotype results from defective proliferation of osteoprogenitors at the osteogenic front during calvarial morphogenesis, and closely resembles that associated with human MSX2 haploinsufficiency in parietal foramina (PFM). Msx2-/- mice also have defects in endochondral bone formation. In the axial and appendicular skeleton, post-natal deficits in Pth/Pthrp receptor (Pthr) signalling and in expression of marker genes for bone differentiation indicate that Msx2 is required for both chondrogenesis and osteogenesis. Consistent with phenotypes associated with PFM, Msx2-mutant mice also display defective tooth, hair follicle and mammary gland development, and seizures, the latter accompanied by abnormal development of the cerebellum. Most Msx2-mutant phenotypes, including calvarial defects, are enhanced by genetic combination with Msx1 loss of function, indicating that Msx gene dosage can modify expression of the PFM phenotype. Our results provide a developmental basis for PFM and demonstrate that Msx2 is essential at multiple sites during organogenesis.

Wilson ratio of a Tomonaga-Luttinger liquid in a spin-1/2 Heisenberg ladder.

Using micromechanical force magnetometry, we have measured the magnetization of the strong-leg spin-1/2 ladder compound (C(7)H(10)N)(2)CuBr(2) at temperatures down to 45 mK. Low-temperature magnetic susceptibility as a function of field exhibits a maximum near the critical field H(c) at which the magnon gap vanishes, as expected for a gapped one-dimensional antiferromagnet. Above H(c) a clear minimum appears in the magnetization as a function of temperature, as predicted by theory. In this field region, the susceptibility in conjunction with our specific-heat data yields the Wilson ratio R(W). The result supports the relation R(W)=4K, where K is the Tomonaga-Luttinger-liquid parameter.

Successive phase transitions and extended spin-excitation continuum in the S=1/2 triangular-lattice antiferromagnet Ba3CoSb2O9.

Using magnetic, thermal, and neutron measurements on single-crystal samples, we show that Ba3CoSb2O9 is a spin-1/2 triangular-lattice antiferromagnet with the c axis as the magnetic easy axis and two magnetic phase transitions bracketing an intermediate up-up-down phase in magnetic field applied along the c axis. A pronounced extensive neutron-scattering continuum above spin-wave excitations, observed below T(N), implies that the system is in close proximity to one of two spin-liquid states that have been predicted for a 2D triangular lattice.

Pharmacotherapeutic determinants for QTc interval prolongation in Japanese patients with mood disorder.

An increased incidence of sudden death has been observed among patients treated with antidepressants. A prolonged QTc interval is a known prognostic factor for fatal arrhythmia, and several studies have shown that the use of antidepressants can cause a prolonged QTc interval. However, few studies, especially in Japan, have compared the effects of multiple drugs on QTc interval or examined dose relationships in a clinical setting.We compared the effects of antidepressants on QT interval, corrected to QTc by Bazett's formula, in 729 Japanese patients who were diagnosed with mood disorder.Using stepwise multiple linear regression analysis, we found that the use of tricyclic antidepressants (P<0.01) and concomitant use of antipsychotics (P<0.05), as well as advanced age and being female (known factors for prolonged QTc interval; both P<0.01), significantly prolonged the QTc interval. Analysis of individual antidepressants also revealed that the use of clomipramine (P<0.01) and amitriptyline (P<0.05) significantly prolonged the QTc interval.Our results reveal that tricyclic antidepressants, especially clomipramine and amitriptyline, confer a risk of prolonged QTc interval in a dose-dependent manner. The selective serotonin reuptake inhibitors investigated (fluvoxamine, paroxetine, sertraline) were not indicated as risk factors for QTc prolongation.

Recognition of pathogen-derived sphingolipids in Arabidopsis.

In plants, many invading microbial pathogens are recognized by cell-surface pattern recognition receptors, which induce defense responses. Here, we show that the ceramide Phytophthora infestans-ceramide D (Pi-Cer D) from the plant pathogenic oomycete P. infestans triggers defense responses in Arabidopsis. Pi-Cer D is cleaved by an Arabidopsis apoplastic ceramidase, NEUTRAL CERAMIDASE 2 (NCER2), and the resulting 9-methyl-branched sphingoid base is recognized by a plasma membrane lectin receptor-like kinase, RESISTANT TO DFPM-INHIBITION OF ABSCISIC ACID SIGNALING 2 (RDA2). 9-Methyl-branched sphingoid base is specific to microbes and induces plant immune responses by physically interacting with RDA2. Loss of RDA2 or NCER2 function compromised Arabidopsis resistance against an oomycete pathogen. Thus, we elucidated the recognition mechanisms of pathogen-derived lipid molecules in plants.

Pebbles and sand on asteroid (162173) Ryugu: In situ observation and particles returned to Earth.

The Hayabusa2 spacecraft investigated the C-type (carbonaceous) asteroid (162173) Ryugu. The mission performed two landing operations to collect samples of surface and subsurface material, the latter exposed by an artificial impact. We present images of the second touchdown site, finding that ejecta from the impact crater was present at the sample location. Surface pebbles at both landing sites show morphological variations ranging from rugged to smooth, similar to Ryugu's boulders, and shapes from quasi-spherical to flattened. The samples were returned to Earth on 6 December 2020. We describe the morphology of >5 grams of returned pebbles and sand. Their diverse color, shape, and structure are consistent with the observed materials of Ryugu; we conclude that they are a representative sample of the asteroid.