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.

Development of advanced photon calibrator for Kamioka gravitational wave detector (KAGRA).

The Kamioka Gravitational wave detector (KAGRA) cryogenic gravitational-wave observatory has commenced joint observations with the worldwide gravitational wave detector network. Precise calibration of the detector response is essential for accurately estimating parameters of gravitational wave sources. A photon calibrator is a crucial calibration tool used in laser interferometer gravitational-wave observatory, Virgo, and KAGRA, and it was utilized in joint observation 3 with GEO600 in Germany in April 2020. In this paper, KAGRA implemented three key enhancements: a high-power laser, a power stabilization system, and remote beam position control. KAGRA employs a 20 W laser divided into two beams that are injected onto the mirror surface. By utilizing a high-power laser, the response of the detector at kHz frequencies can be calibrated. To independently control the power of each laser beam, an optical follower servo was installed for power stabilization. The optical path of the photon calibrator's beam positions was controlled using pico-motors, allowing for the characterization of the detector's rotation response. Additionally, a telephoto camera and quadrant photodetectors were installed to monitor beam positions, and beam position control was implemented to optimize the mirror response. In this paper, we discuss the statistical errors associated with the measurement of relative power noise. We also address systematic errors related to the power calibration model of the photon calibrator and the simulation of elastic deformation effects using finite element analysis. Ultimately, we have successfully reduced the total systematic error from the photon calibrator to 2.0%.

Metformin suppresses progression of muscle aging via activation of the AMP kinase-mediated pathways in Drosophila adults.

OBJECTIVE: Metformin, a medicine used for the treatment of type 2 diabetes, was previously reported to suppress age-dependent hyperproliferation of intestinal stem cells in Drosophila. Here, we aimed to investigate its anti-aging effects on other tissues, such as adult muscle and elucidate the mechanisms underlying the anti-ageing effect. MATERIALS AND METHODS: To evaluate the anti-muscle ageing effect of Metformin, we visualized ubiquitinated protein aggregates accumulated in adult muscle as the flies age by immunostaining and measured the total pixel size of the aggregates. We altered gene expression in the muscle by induction of dsRNA against the relevant mRNAs or mRNAs encoding the constitutively active mutant proteins using the Gal4/UAS system. We determined the mRNA levels by quantitative Real Time-Polymerase Chain Reaction (QRT-PCR). RESULTS: Continuous metformin feeding significantly extended the lifespan of Drosophila adults. Furthermore, the feeding suppressed the aging-dependent accumulation of ubiquitinated aggregates in adult muscle. To delineate the mechanism through which metformin influences the muscle aging phenotype, we induced the constitutively active AMPK specifically in the muscles and found that the activation of the AMPK-mediated pathway was sufficient for the anti-aging effect of Metformin. Furthermore, the AMPK-mediated downregulation of Tor-mediated pathways, subsequent induction of an eIF-4E inhibitor were involved in the effect. These genetic data suggested that the metformin effect is related to the partial suppression of protein synthesis in ribosomes. Furthermore, metformin stimulated autophagy induction in adult muscles. CONCLUSIONS: Our results suggest that metformin can be regarded as an anti-aging compound in Drosophila muscle. The stimulation of autophagy was also involved in the anti-aging effect, which delayed the progression of muscle aging in Drosophila adults.

Effects of age and gender on spatiotemporal and kinematic gait parameters in older adults.

PURPOSE: Gait changes are more prominently observed in older adults than in young adults, especially in kinematics of lower extremities and trunk. These changes can result in incidental falls during gait, possibly leading to inability to perform activities of daily living independently. This study aimed to investigate the effect of gender and age on gait changes, such as spatiotemporal parameters and peak joint angles in lower extremities and trunk during gait. METHODS: A total of 387 participants (223 women) were included. The Microsoft Kinect V2 sensor was used to obtain the coordinate data of lower extremities and trunk during gait. The coordinate data obtained were processed using the software. Walking speed, stride length, stride time and cadence were calculated as spatiotemporal variables of walking. Forward trunk tilt angle (FTT), hip flexion and extension, and knee flexion and extension were measured as peak angles during one-gait cycle. Participants were categorized into five groups according to age by five years. Multivariate analysis of variance was performed to compare the spatiotemporal and kinematical data among groups. RESULTS: Significant differences among age groups were noted in terms of the walking speed and stride length. Significant differences were also observed in the FTT and hip extension angle. CONCLUSIONS: Increased gait changes, increased peak FTT and decreased peak hip extension angle were observed with an increase of age. These altered symptoms may contribute to the screening of older adults at risk of declined physical function at an early stage.

Eccrine sweat glands' maximum ion reabsorption rates during passive heating in older adults (50-84 years).

PURPOSE: We examined whether eccrine sweat glands ion reabsorption rate declined with age in 35 adults aged 50-84 years. Aerobic fitness (VO2max) and salivary aldosterone were measured to see if they modulated ion reabsorption rates. METHODS: During a passive heating protocol (lower leg 42 °C water submersion) the maximum ion reabsorption rates from the chest, forearm and thigh were measured, alongside other thermophysiological responses. The maximum ion reabsorption rate was defined as the inflection point in the slope of the relation between galvanic skin conductance and sweat rate. RESULTS: The maximum ion reabsorption rate at the forearm, chest and thigh (0.29 ± 0.16, 0.33 ± 0.15, 0.18 ± 0.16 mg/cm2/min, respectively) were weakly correlated with age (r ≤ - 0.232, P ≥ 0.05) and salivary aldosterone concentrations (r ≤ - 0.180, P ≥ 0.179). A moderate positive correlation was observed between maximum ion reabsorption rate at the thigh and VO2max (r = 0.384, P = 0.015). Salivary aldosterone concentration moderately declined with age (r = - 0.342, P = 0.021). Whole body sweat rate and pilocarpine-induced sudomotor responses to iontophoresis increased with VO2max (r ≥ 0.323, P ≤ 0.027) but only moderate (r = - 0.326, P = 0.032) or no relations (r ≤ - 0.113, P ≥ 0.256) were observed with age. CONCLUSION: The eccrine sweat glands' maximum ion reabsorption rate is not affected by age, spanning 50-84 years. Aldosterone concentration in an aged cohort does not appear to modulate the ion reabsorption rate. We provide further support for maintaining cardiorespiratory fitness to attenuate any decline in sudomotor function.

A genetically defined signature of responsiveness to erlotinib in early-stage pancreatic cancer patients: Results from the CONKO-005 trial.

BACKGROUND: high recurrence rates of up to 75% within 2 years in pancreatic ductal adenocarcinoma (PDAC) patients resected for cure indicate a high medical need for clinical prediction tools and patient specific treatment approaches. Addition of the EGFR inhibitor erlotinib to adjuvant chemotherapy failed to improve outcome but its efficacy in some patients warrants predictors of responsiveness. PATIENTS AND METHODS: we analysed tumour samples from 293 R0-resected patients from the randomized, multicentre phase III CONKO-005 trial (gemcitabine ± erlotinib) with targeted sequencing, copy number, and RNA expression analyses. FINDINGS: a total of 1086 mutations and 4157 copy-number aberrations (CNAs) with a mean of 17.9 /tumour were identified. Main pathways affected by genetic aberrations were the MAPK-pathway (99%), cell cycle control (92%), TGFß signalling (77%), chromatin remodelling (71%), and the PI3K/AKT pathway (65%). Based on genetic signatures extracted with non-negative matrix factorization we could define five patient clusters, which differed in mutation patterns, gene expression profiles, and survival. In multivariable Cox regression analysis, SMAD4 aberrations were identified as a negative prognostic marker in the gemcitabine arm, an effect that was counteracted when treated with erlotinib (DFS: HR=1.59, p = 0.016, and OS: HR = 1.67, p = 0.014). Integration of differential gene expression analysis established SMAD4 alterations with low MAPK9 expression (n = 91) as a predictive biomarker for longer DFS (HR=0.49; test for interaction, p = 0.02) and OS (HR = 0.32; test for interaction, p = 0.001). INTERPRETATION: this study identified five biologically distinct patient clusters with different actionable lesions and unravelled a previously unappreciated association of SMAD4 alteration status with erlotinib effectiveness. Confirmatory studies and mechanistic experiments are warranted to challenge the hypothesis that SMAD4 status might guide addition of erlotinib treatment in early-stage PDAC patients.

Search for η

We measured missing mass spectrum of the ^{12}C(γ,p) reaction for the first time in coincidence with potential decay products from η^{'} bound nuclei. We tagged an (η+p) pair associated with the η^{'}N→ηN process in a nucleus. After applying kinematical selections to reduce backgrounds, no signal events were observed in the bound-state region. An upper limit of the signal cross section in the opening angle cosθ_{lab}^{ηp}<-0.9 was obtained to be 2.2 nb/sr at the 90% confidence level. It is compared with theoretical cross sections, whose normalization ambiguity is suppressed by measuring a quasifree η^{'} production rate. Our results indicate a small branching fraction of the η^{'}N→ηN process and/or a shallow η^{'}-nucleus potential.

Regional pancreatoduodenectomy versus standard pancreatoduodenectomy with portal vein resection for pancreatic ductal adenocarcinoma with portal vein invasion.

BACKGROUND: Pancreatoduodenectomy (PD) with portal vein resection (PVR) is a standard operation for pancreatic ductal adenocarcinoma (PDAC) with portal vein (PV) invasion, but positive margin rates remain high. It was hypothesized that regional pancreatoduodenectomy (RPD), in which soft tissue around the PV is resected en bloc, could enhance oncological clearance and survival. METHODS: This retrospective study included consecutive patients who underwent PD with PVR between January 2005 and December 2016 in a single high-volume centre. In standard PD (SPD) with PVR, the PV was skeletonized and the surrounding soft tissue dissected. In RPD, the retropancreatic segment of the PV was resected en bloc with its surrounding soft tissue. The extent of lymphadenectomy was similar between the procedures. RESULTS: A total of 268 patients were included (177 SPD, 91 RPD). Tumours were more often resectable in patients undergoing SPD (60·5 per cent versus 38 per cent in those having RPD; P = 0·014), and consequently they received neoadjuvant therapy less often (7·9 versus 25 per cent respectively; P < 0·001). R0 resection was achieved in 73 patients (80 per cent) in the RPD group, compared with 117 (66·1 per cent) of those in the SPD group (P = 0·016), although perioperative outcomes were comparable between the groups. Median recurrence-free (RFS) and overall (OS) survival were 17 and 32 months respectively in patients who had RPD, compared with 11 and 21 months in those who had SPD (RFS: P = 0·003; OS: P = 0·004). CONCLUSION: RPD is as safe and feasible as SPD, and may increase the survival of patients with PDAC with PV invasion.

ANTECEDENTES: La duodenopancreatectomía (pancreaticoduodenectomy, PD) con resección de la vena porta (portal vein resection, PVR) es una operación estándar para el adenocarcinoma ductal pancreático (pancreatic ductal adenocarcinoma, PDAC) con invasión de la vena porta (portal vein, PV); sin embargo, las tasas de margen positivo siguen siendo altas. Nuestra hipótesis fue que la duodenopancreatectomía regional (regional pancreaticoduodenectomy, RPD) en la que el tejido blando alrededor de la PV se reseca en bloque podría mejorar el resultado oncológico y la supervivencia. MÉTODOS: Este estudio retrospectivo incluyó pacientes consecutivos que se sometieron a PD con PVR entre enero de 2005 y diciembre de 2016 en un solo centro de alto volumen. En la PD estándar (SPD) con PVR, la PV se esqueletizó disecando el tejido blando circundante. En la RPD, el segmento retropancreático de la PV se resecó en bloque con el tejido blando circundante. La extensión de la linfadenectomía fue similar en ambos procedimientos. RESULTADOS: Se incluyeron un total de 268 pacientes (177 sometidos a SPD y 91 a RPD). Los pacientes sometidos a SPD presentaron con mayor frecuencia tumores resecables (35 (38%) versus 107 (61%), P = 0,014)) y recibieron con mayor frecuencia terapia neoadyuvante (23 (25%) versus 14 (8%), P < 0,001)) que los pacientes sometidos a RPD. La resección R0 se logró en 73 (80%) pacientes pertenecientes al grupo RPD, en comparación con 117 (66%) pacientes sometidos a SPD (P = 0.011), aunque los resultados perioperatorios fueron comparables entre los grupos. La mediana de supervivencia libre de recidiva (recurrence-free survival, RFS) y de supervivencia global (overall survival, OS) fueron 17 meses y 31 meses, respectivamente, en pacientes sometidos a RPD, en comparación con 11 meses y 21 meses en pacientes sometidos a SPD, (P = 0,003 para RFS y P = 0,004 para la OS). CONCLUSIÓN: La RPD es tan segura y factible como la SPD y puede aumentar la supervivencia de pacientes con PDAC con invasión de la PV.

Mechanism of palmitic acid-induced deterioration of in vitro development of porcine oocytes and granulosa cells.

The concentration of fatty acids in follicular fluid reflect the physical condition of donors, and palmitic acid (PA) is a major component of follicular fluid. The present study examined the effect of PA on in vitro oocyte growth and investigated the molecular backgrounds of the PA induced-low quality oocytes. Oocyte-granulosa cell complexes (OGCs) were collected from early antral follicles of gilts. The OGCs were cultured for 14 days in a medium containing 0.5 mM PA or vehicle (BSA). PA was found to reduce granulosa cell (GCs) proliferation (0.73 fold) and viability (93.9% vs. 85.8%) and increase lipid content in oocytes and GCs. Oocytes developed in the presence of PA had low developmental ability to the blastocyst stage. In addition, PA affected developmental and epigenetic markers of histone modifications in oocytes; levels of H4K12 acetylation and H3K9 demethylation. PA affected cellular proliferation, apoptosis and endoplasmic reticulum stress markers along with reducing the phosphor-AKT/AKT levels and increasing the expression levels of caspase-3 and CHOP in GCs. Incubation of OGCs with PA increased ceramide content in the GC, and addition of ceramide to the culture medium inhibited GC proliferation. In conclusion, it is suggested that high PA content in the medium reduces viability and proliferation through ceramide accumulation, and PA impaires the developmental ability of oocytes grown in vitro. In addition, high-fat conditions induce changes in the histone modifications of oocytes grown in vitro.

Possible underestimation of blood loss during laparoscopic hepatectomy.

Background: Previous studies have documented potential advantages of laparoscopic hepatectomy in decreasing blood loss compared with open surgery. This study aimed to compare intraoperative blood loss estimated using four different methods in open versus laparoscopic hepatectomy. Methods: Patients undergoing liver resection between 2014 and 2017 were evaluated prospectively, differentiating between the laparoscopic and open approach. Groups were compared using univariable and multivariable analyses. Intraoperative blood loss was estimated using three formulas based on the postoperative decreases in haematocrit, haemoglobin or red blood cell volume, and using the conventional method of the sum of suction fluid amounts and gauze weight. In addition, blood loss per hepatic transection area was calculated to compare groups. Results: Some 125 patients who underwent hepatectomy were selected, including 56 open hepatectomies and 69 laparoscopic liver resections. Intraoperative blood loss per hepatic transection area estimated by the conventional method was significantly less in the laparoscopic than the open group (3·6 (range 0·2-50·0) versus 6·6 (1·2-82·5) ml/cm2 respectively; P < 0·001). In contrast, there were no significant differences between groups in blood loss estimated based on the decrease in haematocrit (12·9 (0-65·2) versus 8·1 (0-123·7) ml/cm2; P = 0·818), haemoglobin or red blood cell volume. Blood loss estimation using three formulas showed significant linear correlations with the blood loss estimated by the conventional method in the open group (r s = 0·758 to 0·762), but not in the laparoscopic group (r s = -0·019 to 0·031). Conclusion: The conventional method of calculating blood loss in laparoscopic hepatectomy can underestimate losses.

Sesamin suppresses aging phenotypes in adult muscular and nervous systems and intestines in a Drosophila senescence-accelerated model.

OBJECTIVE: Sesamin is a major lignan constituent of sesame and possesses various health-promoting effects. Previous studies have demonstrated that sesamin extends the lifespan of Drosophila and Caenorhabditis elegans and corrects oxidative damage-related tissue dysfunction in mammals. To understand its anti-aging effects, we aimed to determine whether sesamin restores tissue function hampered by oxidative damage and suppresses several aging-related phenotypes using Drosophila senescence-accelerated models. MATERIALS AND METHODS: We elucidated the anti-aging effects of sesamin on several aging-related phenotypes in the muscle, brain and midgut using the senescence-accelerated models (Sod1n1 mutant and Sod1-depleted flies) by immunostaining experiments. We determined the expression levels of several anti-oxidative and DNA repair genes using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). We also identified the metabolite of sesamin in Drosophila by LC-MS/MS. RESULTS: We confirmed that sesamin (0.35 and 2 mg/ml) extended the lifespan of the fly models. As observed in mammals, it can be absorbed and metabolized by Drosophila adults. The sesamin feeding suppressed the age-dependent impairment of locomotor activity and inhibited the accumulation of reactive oxygen species (ROS) in their bodies. Sesamin delayed the age-dependent accumulation of damaged proteins in the muscle, partially suppressed the loss of dopaminergic neurons in adult brains displaying ROS accumulation, and suppressed the accumulation of DNA damage and hyperproliferation of intestinal stem cells. Four antioxidative genes and two DNA repair genes were simultaneously upregulated in sesamin-fed adults.  CONCLUSIONS: These observations represent the first direct evidence of the anti-aging effects of sesamin at the individual level. We propose that sesamin exerts anti-aging effects in the muscles, brain and midgut by inducing antioxidative and DNA repair genes, resulting in extended lifespan in flies.

The influence of local skin temperature on the sweat glands maximum ion reabsorption rate.

PURPOSE: Changes in mean skin temperature (Tsk) have been shown to modify the maximum rate of sweat ion reabsorption. This study aims to extend this knowledge by investigating if modifications could also be caused by local Tsk. METHODS: The influence of local Tsk on the sweat gland maximum ion reabsorption rates was investigated in ten healthy volunteers (three female and seven male; 20.8 ± 1.2 years, 60.4 ± 7.7 kg, 169.4 ± 10.4 cm) during passive heating (water-perfused suit and lower leg water immersion). In two separate trials, in a randomized order, one forearm was always manipulated to 33 °C (Neutral), whilst the other was manipulated to either 30 °C (Cool) or 36 °C (Warm) using water-perfused patches. Oesophageal temperature (Tes), forearm Tsk, sweat rate (SR), galvanic skin conductance (GSC) and salivary aldosterone concentrations were measured. The sweat gland maximum ion reabsorption rates were identified using the ∆SR threshold for an increasing ∆GSC. RESULTS: Thermal [Tes and body temperature (Tb)] and non-thermal responses (aldosterone) were similar across all conditions (p > 0.05). A temperature-dependent response for the sweat gland maximum ion reabsorption rates was evident between 30 °C (0.18 ± 0.10 mg/cm2/min) and 36 °C (0.28 ± 0.14 mg/cm2/min, d = 0.88, p < 0.05), but not for 33 °C (0.22 ± 0.12 mg/cm2/min), d = 0.44 and d = 0.36, p > 0.05. CONCLUSION: The data indicate that small variations in local Tsk may not affect the sweat gland maximum ion reabsorption rates but when the local Tsk increases by > 6 °C, ion reabsorption rates also increase.

RNA-seq analysis of diet-driven obesity and anti-obesity effects of quercetin glucoside or epigallocatechin gallate in Drosophila adults.

OBJECTIVE: High-fat diet (HFD) feeding stimulates fat accumulation in mammals and Drosophila. In the present study, we examined whether simultaneous feeding of familiar anti-obesity drugs, quercetin glycosides (QG) and epigallocatechin gallate (EGCG), to Drosophila has the same suppressive effect on fat accumulation as previously reported in rats and mice. To understand the underlying molecular mechanisms of HFD diet-induced obesity and the suppression effect of the drugs, we performed transcriptome analyses. MATERIALS AND METHODS: We induced extra fat accumulation by feeding Drosophila fly food containing 20% coconut oil and quantified the triglyceride accumulated in flies. The effects of anti-obesity drugs were also evaluated. We isolated total RNA from each sample and performed RNA-seq analyses and quantitive Real Time-Polymerase Chain Reaction (qRT-PCR) to investigate altered gene expression. RESULTS: The mRNA levels of several genes involved in lipid metabolism, glycolysis/gluconeogenesis, and anti-oxidative stress changed in HFD-fed adults. Moreover, the levels altered in those fed an HFD with QG or EGCG. The qRT-PCR further confirmed the RNA-seq data, suggesting that the expression of five essential genes for lipid metabolism changed in HFD-fed flies and altered in the flies treated with anti-obesity drugs. The most remarkable alteration was observed in the dHSL gene encoding a lipase involved in lipid-storage after HFD feeding and HFD with QG or EGCG. These alterations are consistent with HFD-induced fat accumulation as well as the anti-obesity effects of the drugs in mammals, suggesting that the genes play an important role in anti-obesity effects. CONCLUSIONS: These are the first reports to date of entire profiles of altered gene expression under the conditions of diet-induced obesity and its suppression by anti-obesity drugs in Drosophila.

Sex and racial/ethnic differences in the association between childhood attention-deficit/hyperactivity disorder symptom subtypes and body mass index in the transition from adolescence to adulthood in the United States.

BACKGROUND: While attention-deficit/hyperactivity disorder (ADHD) has been associated with higher body mass index (BMI), little research has focused on how this association differs by sex or race/ethnicity. OBJECTIVE: To investigate the association between ADHD and BMI by sex and race/ethnicity (ie, European [EA], African [AA], and Hispanic American [HA]). METHODS: Data came from the National Longitudinal Survey of Adolescent to Adult Health Waves II to IV (n = 13 332, age: 12-34 years). On the basis of self-reported childhood ADHD symptoms between the ages of 5 and 12 years, participants were categorized into: ADHD predominantly hyperactive/impulsive (ADHD-HI); ADHD predominantly inattentive (ADHD-I); ADHD combined (ADHD-C; a combination of ADHD-HI and ADHD-I symptoms); and non-ADHD. RESULTS: The patterns of ADHD-BMI associations in the transition period between adolescence and young adulthood differed by sex and race/ethnicity. Compared with non-ADHD, ADHD-HI was associated with higher BMI among EA males and females, while ADHD-I was associated with higher BMI among EA females. ADHD-C was associated with higher BMI for HA females. We found no evidence of an association among AA males and females and HA males. CONCLUSION: These study results suggest that the association between ADHD subtypes and BMI might differ across population subgroups in the United States.

Adverse childhood experiences, exposure to a natural disaster and posttraumatic stress disorder among survivors of the 2011 Great East Japan earthquake and tsunami.

AIMS: To investigate whether adverse childhood experiences (ACEs) modify the impact of exposure to a natural disaster (the 2011 Great East Japan earthquake and tsunami) on the occurrence of posttraumatic stress disorder (PTSD) among older people. METHODS: Data were collected as part of the Japan Gerontological Evaluation Study (JAGES), which is an on-going epidemiological survey investigating social determinants of health among older people across Japan. Information on PTSD symptoms based on the Screening Questionnaire for Disaster Mental Health, traumatic exposure to the earthquake (i.e., house damage and loss of relatives/friends during the earthquake/tsunami) and ACEs was obtained from 580 participants aged 65 or older living in Iwanuma City, Miyagi Prefecture, which suffered severe damage as a result of the earthquake and the subsequent tsunami in March 2011. Associations were examined using Poisson regression analysis with a robust variance estimator after adjusting for covariates. RESULTS: The prevalence of PTSD was 9.7% in this population; compared to those with no traumatic experience, the prevalence of PTSD was approximately two times higher among those who experienced the loss of close friends/relatives (PR = 1.84, 95% CI = 1.11-3.03, p = 0.018), or whose house was damaged (PR = 2.15, 95% CI = 1.07-4.34, p = 0.032). ACE was not significantly associated with PTSD. Stratified analyses by the presence of ACE showed that damage due to the earthquake/tsunami was associated with PTSD only among those without ACEs; more specifically, among non-ACE respondents the PR of PTSD associated with house damage was 6.67 (95% CI = 1.66-26.80), while for the loss of a relative or a close friend it was 3.56 (95% CI = 1.18-10.75). In contrast, no statistically significant associations were observed among those with ACEs. CONCLUSION: Following the Great East Japan earthquake/tsunami in 2011 a higher risk of developing PTSD symptoms was observed in 2013 especially among older individuals without ACEs. This suggests that ACEs might affect how individuals respond to subsequent traumatic events later in life.

General thoughts of death and mortality: findings from the Komo-Ise cohort, Japan.

AIMS: Death ideation (thinking about/wishing for one's own death, thinking that one would be better off dead) is linked to an increased mortality risk. However, comparatively little is known about more general thoughts of death (GTOD) where no wish to die or life value is expressed. This study examined whether GTOD predicted mortality in a community-based cohort of older adults. METHODS: Data came from the Komo-Ise cohort study in Gunma prefecture, Japan. The analytic sample comprised 8208 individuals (average age 61.3 (range 47-77)) who were asked in wave 2 of the study in 2000 if they had 'Thought about death more than usual, either your own, someone else's or death in general?' in the past 2 weeks. Death data were obtained from the municipal resident registration file. Cox proportional hazards regression analysis was used to examine associations. RESULTS: During the follow-up period (2000-2008), there were 672 deaths. In a model adjusted for baseline covariates, GTOD were significantly associated with all-cause mortality (hazards ratio 1.66, 95% confidence interval 1.20-2.29). Stratified analyses showed an association between GTOD and mortality in men, older subjects (⩾70 years), married individuals and those with higher social support. CONCLUSIONS: GTOD are associated with an increased mortality risk among older citizens in Japan. Research is now needed to determine the factors underlying this association and assess the clinical relevance of screening for GTOD in older individuals.

Strain-triggered mechanical feedback in self-organizing optic-cup morphogenesis.

Organogenesis is a self-organizing process of multiple cells in three-dimensional (3D) space, where macroscopic tissue deformations are robustly regulated by multicellular autonomy. It is clear that this robust regulation requires cells to sense and modulate 3D tissue formation across different scales, but its underlying mechanisms are still unclear. To address this question, we developed a versatile computational model of 3D multicellular dynamics at single-cell resolution and combined it with the 3D culture system of pluripotent stem cell-derived optic-cup organoid. The complementary approach enabled quantitative prediction of morphogenesis and its corresponding verification and elucidated that the macroscopic 3D tissue deformation is fed back to individual cellular force generations via mechanosensing. We hereby conclude that mechanical force plays a key role as a feedback regulator to establish the robustness of organogenesis.

Cerebrospinal fluid orexin-A levels in systemic lupus erythematosus patients presenting with excessive daytime sleepiness.

Objective Involvement of the hypothalamus is rare in patients with systemic lupus erythematosus (SLE). In this study, we measured cerebrospinal fluid (CSF) orexin-A levels in SLE patients with hypothalamic lesions to investigate whether the orexin system plays a role in SLE patients with hypothalamic lesions who present with excessive daytime sleepiness (EDS). Methods Orexin-A levels were measured in CSF from four patients with SLE who presented with hypothalamic lesions detected by MRI. Three patients underwent repeated CSF testing. All patients met the updated American College of Rheumatology revised criteria for SLE. Results Tests for serum anti-aquaporin-4 antibodies, CSF myelin basic protein and CSF oligoclonal bands were negative in all patients. All patients presented with EDS. Low to intermediate CSF orexin-A levels (92-180 pg/ml) were observed in three patients in the acute stage, two of whom (patients 1 and 2) underwent repeated testing and showed increased CSF orexin-A levels, reduced abnormal hypothalamic lesion intensities detected by MRI and EDS dissipation at follow-up. In contrast, CSF orexin-A levels were normal in one patient (patient 4) while in the acute stage and at follow-up, despite improvements in EDS and MRI findings. Patient 4 showed markedly increased CSF interleukin-6 levels (1130 pg/ml) and a slightly involved hypothalamus than the other patients. Conclusions Our findings suggest that the orexinergic system has a role in EDS in SLE patients with hypothalamic lesions. Furthermore, cytokine-mediated tissue damage might cause EDS without orexinergic involvement.