Impacts of workplace verbal aggression classified via text mining on workers' mental health.

BACKGROUND: Exposure to workplace aggression adversely affects workers' health; however, little is known regarding the impact of specific types of verbal content. AIMS: We aimed to examine the relationship between exposure to several types of aggressive words at work and the victim's depressive symptoms and sleep disturbance using text mining. METHODS: We conducted a longitudinal survey with 800 workers in wholesale and retail companies; of which, 500 responded to the follow-up survey. The Centre for Epidemiologic Studies-Depression Scale and Pittsburgh Sleep Quality Index were filled out by the participants, and their responses were analysed by logistic regression to evaluate the risk of depression or sleep problems. We collected exact aggressive words encountered at work over the past year as a dependent variable and classified it into four types using text mining, such as words criticizing one's performance. RESULTS: The follow-up rate was 63%. Exposure to words threatening one's life showed a significant relationship with the risk of depression (odds ratio [OR] = 13.94, 95% confidence interval [CI] = 1.76-110.56). The exposure to words criticizing one's job performance is significantly related to the risk of sleep disturbance (OR = 5.56, 95% CI = 2.08-14.88). CONCLUSIONS: These findings suggest that different contents of verbal aggression can have different impacts on workers' health. This indicates that not only overtly threatening and abusive language but also words related to one's performance can be a risk factor for workers, depending on how they are delivered. To mitigate the adverse effects, promoting effective communication and cultivating psychological detachment from work may be beneficial.

Reduced Autophagy in Aged Trigeminal Neurons Causes Amyloid ß Diffusion.

The relationship between oral health and the development of Alzheimer's disease (AD) in the elderly is not yet well understood. In this regard, the association between aging or neurodegeneration of the trigeminal nervous system and the accumulation of amyloid-ß(1-42) (Aß42) oligomers in the pathogenesis of AD is unknown. We focused on selective autophagy in the trigeminal mesencephalic nucleus (Vmes) and the diffusion of Aß42 oligomers with respect to aging of the trigeminal nervous system and whether the degeneration of Vmes neurons affects the diffusion of Aß42 oligomers. We used female 2- to 8-mo-old transgenic 3xTg-AD mice and AppNL-G-F knock-in mice and immunohistochemically examined aging-related changes in selective autophagy and Aß42 oligomer processing in the Vmes, which exhibits high amyloid-ß (Aß) expression. We induced degeneration of Vmes neurons by extracting the maxillary molars and examined the changes in Aß42 oligomer kinetics. Autophagosome-like membranes, which stained positive for Aß, HO-1, and LC3B, were observed in Vmes neurons of 3xTg-AD mice, while there was weak immunoreactivity of the membranes for intraneuronal Aß in AppNL-G-F mice. By contrast, there was strong immunopositivity for extracellular Aß42 oligomers with the formation of Aß42 oligomer clusters in AppNL-G-F mice. The expression of Rubicon, which indicates age-related deterioration of autophagy, increased the diffusion of Aß42 oligomer with the age of Vmes neurons. Tooth extraction increased the extracellular immunopositivity for Aß42 oligomers in AppNL-G-F mice. These results suggest that autophagy maintains homeostasis in Vmes neurons and that deterioration of autophagy due to aging or neurodegeneration leads to the diffusion of Aß42 oligomers into the extracellular space and possibly the development of AD.

Development of Rat Caries-Induced Pulpitis Model for Vital Pulp Therapy.

Rodent animal models for vital pulp therapy are commonly used in dental research because their tooth anatomy and cellular processes are similar to the anatomy and processes in humans. However, most studies have been conducted using uninfected sound teeth, which makes it difficult to adequately assess the inflammatory shift after vital pulp therapy. In the present study, we aimed to establish a caries-induced pulpitis model based on the conventional rat caries model and then evaluate inflammatory changes during the wound-healing process after pulp capping in a model of reversible pulpitis induced by carious infection. To establish the caries-induced pulpitis model, the pulpal inflammatory status was investigated at different stages of caries progression by immunostaining targeted to specific inflammatory biomarkers. Immunohistochemical staining revealed that both Toll-like receptor 2 and proliferating cell nuclear antigen were expressed in moderate and severe caries-stimulated pulp, indicating that an immune reaction occurred at both stages of caries progression. M2 macrophages were predominant in moderate caries-stimulated pulp, whereas M1 macrophages were predominant in the severe caries-stimulated pulp. Pulp capping in teeth with moderate caries (i.e., teeth with reversible pulpitis) led to complete tertiary dentin formation within 28 d after treatment. Impaired wound healing was observed in teeth with severe caries (i.e., teeth with irreversible pulpitis). During the wound-healing process in reversible pulpitis after pulp capping, M2 macrophages were predominant at all time points; their proliferative capacity was upregulated in the early stage of wound healing compared with healthy pulp. In conclusion, we successfully established a caries-induced pulpitis model for studies of vital pulp therapy. M2 macrophages have an important role in the early stages of the wound-healing process in reversible pulpitis.

Novel Functional Peptide for Next-Generation Vital Pulp Therapy.

Although vital pulp therapy should be performed by promoting the wound-healing capacity of dental pulp, existing pulp-capping materials were not developed with a focus on the pulpal repair process. In previous investigations of wound healing in dental pulp, we found that organic dentin matrix components (DMCs) were degraded by matrix metalloproteinase-20, and DMC degradation products containing protein S100A7 (S100A7) and protein S100A8 (S100A8) promoted the pulpal wound-healing process. However, the direct use of recombinant proteins as pulp-capping materials may cause clinical problems or lead to high medical costs. Thus, we hypothesized that functional peptides derived from recombinant proteins could solve the problems associated with direct use of such proteins. In this study, we identified functional peptides derived from the protein S100 family and investigated their effects on dental pulp tissue. We first performed amino acid sequence alignments of protein S100 family members from several mammalian sources, then identified candidate peptides. Next, we used a peptide array method that involved human dental pulp stem cells (hDPSCs) to evaluate the mineralization-inducing ability of each peptide. Our results supported the selection of 4 candidate functional peptides derived from proteins S100A8 and S100A9. Direct pulp-capping experiments in a rat model demonstrated that 1 S100A8-derived peptide induced greater tertiary dentin formation compared with the other peptides. To investigate the mechanism underlying this induction effect, we performed liquid chromatography-tandem mass spectrometry analysis using hDPSCs and the S100A8-derived peptide; the results suggested that this peptide promotes tertiary dentin formation by inhibiting inflammatory responses. In addition, this peptide was located in a hairpin region on the surface of S100A8 and could function by direct interaction with other molecules. In summary, this study demonstrated that a S100A8-derived functional peptide promoted wound healing in dental pulp; our findings provide insights for the development of next-generation biological vital pulp therapies.

Characteristics of gut microbiome, organic acid profiles and viral antibody indexes of healthy Japanese with live Lacticaseibacillus detected in stool.

To estimate the health-promoting effects of Lacticaseibacillus paracasei (previously Lactobacillus casei) strain Shirota (LcS) that reached the lower gastrointestinal tract alive, we investigated the characteristics of gut microbiome, organic acid profiles, defecatory symptoms and serum viral antibody indexes of healthy Japanese adults between the group in whom live LcS was detected or not from stool. The ß-diversity index of the gut microbiome constituted a significant difference between the live-LcS-detected-group (LLD) and the live-LcS-not-detected-group (LLnD). In the LLD, the Bifidobacteriaceae, Lactobacillaceae, and Coriobacteriaceae counts were significantly higher, and the succinate concentration was significantly lower than that in the LLnD. The serum herpes simplex virus (HSV) immunoglobulin (Ig)M antibody index in the LLD tended to be lower than that of the LLnD in HSV IgG-positive subjects. Of the LLD, those in the fermented milk products containing LcS (FML)-high-frequency-group (FML-HF) and those in the FML-low-frequency-group (FML-LF) had different gut microbiome and organic acid profiles. However, the pattern of differences between FML-HF and FML-LF was dissimilar those between LLD and LLnD. In contrast, among subjects with FML-LF, those in the group with LLD in stool (LF-LLD) and those in the LLnD in stool (LF-LLnD) showed a similar pattern of differences in their gut microbiome and organic acid profiles as those in the LLnD and LLD. The LLD and LF-LLD commonly had lower caloric and carbohydrate intakes from the diet than their respective control groups. In this study, we found that the presence of live LcS in stool is associated with a healthy gut environment and inhibition of the reactivation of latently infected viruses in the host. However, these health-promoting effects on the host were not related to the frequency of FML intake. Furthermore, dysbiosis of the gut microbiome and diet including caloric intake was related to the viability of ingested LcS in the gut.

Large-scale prospective genome-wide association study of oxaliplatin in stage II/III colon cancer and neuropathy.

BACKGROUND: The severity of oxaliplatin (L-OHP)-induced peripheral sensory neuropathy (PSN) exhibits substantial interpatient variability, and some patients suffer from long-term, persisting PSN. To identify single-nucleotide polymorphisms (SNPs) predicting L-OHP-induced PSN using a genome-wide association study (GWAS) approach. PATIENTS AND METHODS: A large prospective GWAS including 1379 patients with stage II/III colon cancer who received L-OHP-based adjuvant chemotherapy (mFOLFOX6/CAPOX) under the phase II (JOIN/JFMC41) or the phase III (ACHIVE/JFMC47) trial. Firstly, GWAS comparison of worst grade PSN (grade 0/1 versus 2/3) was carried out. Next, to minimize the impact of ambiguity in PSN grading, extreme PSN phenotypes were selected and analyzed by GWAS. SNPs that could predict time to recovery from PSN were also evaluated. In addition, SNPs associated with L-OHP-induced allergic reactions (AR) and time to disease recurrence were explored. RESULTS: No SNPs exceeded the genome-wide significance (P < 5.0 × 10-8) in either GWAS comparison of worst grade PSN, extreme PSN phenotypes, or time to recovery from PSN. An association study focusing on AR or time to disease recurrence also failed to reveal any significant SNPs. CONCLUSION: Our results highlight the challenges of utilizing SNPs for predicting susceptibility to L-OHP-induced PSN in daily clinical practice.

Observation of Coulomb-Assisted Nuclear Bound State of Ξ

In an emulsion-counter hybrid experiment performed at J-PARC, a Ξ^{-} absorption event was observed which decayed into twin single-Λ hypernuclei. Kinematic calculations enabled a unique identification of the reaction process as Ξ^{-}+^{14}N→_{Λ}^{10}Be+_{Λ}^{5}He. For the binding energy of the Ξ^{-} hyperon in the Ξ^{-}-^{14}N system a value of 1.27±0.21 MeV was deduced. The energy level of Ξ^{-} is likely a nuclear 1p state which indicates a weak ΞN-ΛΛ coupling.

Neck Location on the Outer Convexity is a Predictor of Incomplete Occlusion in Treatment with the Pipeline Embolization Device: Clinical and Angiographic Outcomes.

BACKGROUND AND PURPOSE: With the increasing use of the Pipeline Embolization Device for the treatment of aneurysms, predictors of clinical and angiographic outcomes are needed. This study aimed to identify predictors of incomplete occlusion at last angiographic follow-up. MATERIALS AND METHODS: In our retrospective, single-center cohort study, 105 ICA aneurysms in 89 subjects were treated with Pipeline Embolization Devices. Patients were followed per standardized protocol. Clinical and angiographic outcomes were analyzed. We introduced a new morphologic classification based on the included angle of the parent artery against the neck location: outer convexity type (included angle, <160°), inner convexity type (included angle, >200°), and lateral wall type (160° ≤ included angle ≤200°). This classification reflects the metal coverage rate and flow dynamics. RESULTS: Imaging data were acquired in 95.3% of aneurysms persistent at 6 months. Complete occlusion was achieved in 70.5%, and incomplete occlusion, in 29.5% at last follow-up. Multivariable regression analysis revealed that 60 years of age or older (OR, 5.70; P = .001), aneurysms with the branching artery from the dome (OR, 10.56; P = .002), fusiform aneurysms (OR, 10.2; P = .009), and outer convexity-type saccular aneurysms (versus inner convexity type: OR, 30.3; P < .001; versus lateral wall type: OR, 9.71; P = .001) were independently associated with a higher rate of incomplete occlusion at the last follow-up. No permanent neurologic deficits or rupture were observed in the follow-up period. CONCLUSIONS: The aneurysm neck located on the outer convexity is a new, incomplete occlusion predictor, joining older age, fusiform aneurysms, and aneurysms with the branching artery from the dome. No permanent neurologic deficits or rupture was observed in the follow-up, even with incomplete occlusion.

Two-Neutron Halo is Unveiled in

We report the measurement of reaction cross sections (σ_{R}^{ex}) of ^{27,29}F with a carbon target at RIKEN. The unexpectedly large σ_{R}^{ex} and derived matter radius identify ^{29}F as the heaviest two-neutron Borromean halo to date. The halo is attributed to neutrons occupying the 2p_{3/2} orbital, thereby vanishing the shell closure associated with the neutron number N=20. The results are explained by state-of-the-art shell model calculations. Coupled-cluster computations based on effective field theories of the strong nuclear force describe the matter radius of ^{27}F but are challenged for ^{29}F.

Alteration in faecal bile acids, gut microbial composition and diversity after laparoscopic sleeve gastrectomy.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is a well established treatment for severe obesity and type 2 diabetes. Although the gut microbiota is linked to the efficacy of LSG, the underlying mechanisms remain elusive. The effect of LSG for morbid obesity on the gut microbiota and bile acids was assessed here. METHODS: Severely obese subjects who were candidates for LSG were included and followed until 6 months after surgery. The composition and abundance of the microbiota and bile acids in faeces were assessed by 16S ribosomal RNA sequencing, quantitative PCR and liquid chromatography-mass spectrometry. RESULTS: In total, 28 patients with a mean(s.d.) BMI of 44·2(6·6) kg/m2 were enrolled. These patients had achieved excess weight loss of 53·2(19·0) per cent and showed improvement in metabolic diseases by 6 months after LSG, accompanied by an alteration in the faecal microbial community. The increase in α-diversity and abundance of specific taxa, such as Rikenellaceae and Christensenellaceae, was strongly associated with reduced faecal bile acid levels. These changes had a significant positive association with excess weight loss and metabolic alterations. However, the total number of faecal bacteria was lower in patients before (mean(s.d.) 10·26(0·36) log10 cells per g faeces) and after (10·39(0·29) log10 cells per g faeces) operation than in healthy subjects (10·83(0·27) log10 cells per g faeces). CONCLUSION: LSG is associated with a reduction in faecal bile acids and greater abundance of specific bacterial taxa and α-diversity that may contribute to the metabolic changes.

ANTECEDENTES: La gastrectomía vertical laparoscópica (laparoscopic sleeve gastrectomy, LSG) es un tratamiento bien establecido para la obesidad grave y la diabetes tipo 2. Aunque la microbiota intestinal se ha vinculado con la eficacia de LSG, los mecanismos subyacentes siguen siendo poco conocidos. En este estudio se evaluó el efecto de LSG en la obesidad mórbida sobre la microbiota del intestino y de los ácidos biliares (bile acids, BA). MÉTODOS: Tras la aprobación del Comité ético y la obtención del consentimiento informado, los sujetos con obesidad grave que eran candidatos para LSG fueron incluidos en el estudio y seguidos durante 6 meses después de la operación. Se evaluaron la composición y abundancia de la microbiota y BA en las heces mediante secuenciación del gen 16S rRNA, PCR cuantitativa y cromatografía líquida-espectrometría de masas. RESULTADOS: En total, 28 pacientes con una mediana (rango) del IMC de 43,9 kg/m2 (35,0-61,9) fueron reclutados y a los 6 meses tras una LSG, consiguieron una pérdida del exceso de peso de 47,3% (20,7-95,1) y mejoría de las enfermedades metabólicas acompañada de una alteración en la comunidad microbiana fecal. El aumento en la diversidad α y abundancia de especies taxonómicas específicas como Rikenellaceae y Christensenellaceae, se asociaba fuertemente con niveles fecales reducidos de BA. Estos cambios se asociaban de manera positiva y significativa con la pérdida del exceso de peso y las alteraciones metabólicas. Sin embargo, el número total de bacterias fecales en los pacientes fue inferior al de los sujetos sanos (10,84 log10 células/g heces (9,46-11,35)) antes de la operación (10,26 log10 células/g heces (9,44-10,91)) y después de la misma (10,42 log10 células/g heces (9,57-10,96)). CONCLUSIÓN: LSG se asoció con menos BA fecal y mayor abundancia de especies bacterianas específicas y diversidad α lo que puede contribuir a los cambios metabólicos.

Correction: Synergistic anti-AML effects of the LSD1 inhibitor T-3775440 and the NEDD8-activating enzyme inhibitor pevonedistat via transdifferentiation and DNA rereplication.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The CODATwins Project: The Current Status and Recent Findings of COllaborative Project of Development of Anthropometrical Measures in Twins.

The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural-geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.

Gut microbiota development of preterm infants hospitalised in intensive care units.

Gut microbiome development affects infant health and postnatal physiology. The gut microbe assemblages of preterm infants have been reported to be different from that of healthy term infants. However, the patterns of ecosystem development and inter-individual differences remain poorly understood. We investigated hospitalised preterm infant gut microbiota development using 16S rRNA gene amplicons and the metabolic profiles of 268 stool samples obtained from 17 intensive care and 42 term infants to elucidate the dynamics and equilibria of the developing microbiota. Infant gut microbiota were predominated by Gram-positive cocci, Enterobacteriaceae or Bifidobacteriaceae, which showed sequential transitions to Bifidobacteriaceae-dominated microbiota. In neonatal intensive care unit preterm infants (NICU preterm infants), Staphylococcaceae abundance was higher immediately after birth than in healthy term infants, and Bifidobacteriaceae colonisation tended to be delayed. No specific NICU-cared infant enterotype-like cluster was observed, suggesting that the constrained environment only affected the pace of transition, but not infant gut microbiota equilibrium. Moreover, infants with Bifidobacteriaceae-dominated microbiota showed higher acetate concentrations and lower pH, which have been associated with host health. Our data provides an in-depth understanding of gut microbiota development in NICU preterm infants and complements earlier studies. Understanding the patterns and inter-individual differences of the preterm infant gut ecosystem is the first step towards controlling the risk of diseases in premature infants by targeting intestinal microbiota.

Subcapsular beaded appearance of the kidney on contrast-enhanced CT: indicative of dilated subcapsular lymphatics?

AIM: To assess the renal subcapsular beaded appearance (RSBA) seen on contrast-enhanced multidetector-row computed tomography (CT). MATERIALS AND METHODS: In total, 2,020 consecutive MDCT examinations with both non-contrast-enhanced and contrast-enhanced procedures were assessed retrospectively to identify interconnecting lobular structures in the renal subcapsular area that created a beaded appearance on contrast-enhanced CT. Positive cases were investigated for CT attenuation on unenhanced CT and were then compared with fat-suppressed heavily T2-weighted magnetic resonance imaging (MRI) and follow-up CT if available. The degree of RSBA occupying the renal periphery was evaluated using a three-grade system (Grade I: <25%, Grade II: 25-75%, Grade III: >75% of surface involvement). Only Grades II and III were defined as a positive RSBA. Possible associated findings such as hypertension, chronic kidney disease (CKD), renal atrophy, and liver cirrhosis were also evaluated. RESULTS: The RSBA was positive in 33 (1.63%) of patients and was more commonly found in patients in their seventies (39.4%) with male predominance (male:female ratio, 7:3; p=0.005). Of 33 positive cases, five showed low CT attenuation predominance, 25 showed iso-attenuation, and three showed high attenuation on unenhanced CT. In five positive cases, T2-weighted MRI showed markedly high signal intensity, suggesting prominent capsular lymphatic structures. The RSBA was associated with hypertension (p=0.001) and CKD (p=0.011). CONCLUSION: The MRI findings suggested that the RSBA probably reflects dilated subcapsular lymphatics. Knowledge of this CT finding is clinically important because it might be misinterpreted as other pathological findings.

Impact of different timing of consuming sweet snack on postprandial glucose excursions in healthy women.

AIMS: Our aim was to evaluate the acute effect of eating sweet snacks at different times of day on glycaemic parameters in young women without diabetes. METHODS: In this randomized controlled three-treatment crossover study, 17 women [(means ± SD) age: 21.2 ± 0.8 years, BMI: 20.7 ± 2.5 kg/m2, HbA1c: 36 ± 2 mmol/mol (5.1 ± 0.2%)] wore flash (continuous) glucose monitoring systems for 7 days. Each participant consumed identical test meals on days 4, 5 and 6, but consumed sweet snacks (baked cake: 498 kcal; 53.6 g of carbohydrate, 8.0 g of protein, 28.0 g of fat) at 12:30 (post-lunch), 15:30 (mid-afternoon) and 19:30 (post-dinner), respectively, on each of those days. Daily glycaemic parameters on those 3 days of snacking at different times of day were compared within-participant. RESULTS: The mean amplitude of glycaemic excursions (3.54 ± 0.32 vs. 2.73 ± 0.20 mmol/L; P < 0.05), standard deviation of glucose (1.20 ± 0.11 vs. 0.92 ± 0.07 mmol/L; P < 0.05), incremental area under the curve (IAUC) for glucose at 12:00-07:00 (986 ± 89 vs. 716 ± 88 mmol/L × min; P < 0.05) and IAUC at 07:00-10:00 the next day (141 ± 17 vs. 104 ± 12 mmol/L × min; P < 0.05) when the snack was eaten post-dinner were all significantly higher than with mid-afternoon snacking. CONCLUSION: Eating sweet snacks post-dinner should be avoided because it worsens glucose excursions as well as postprandial glucose levels after both dinner and the following day's breakfast in young healthy (non-diabetic) women.

Consuming snacks mid-afternoon compared with just after lunch improves mean amplitude of glycaemic excursions in patients with type 2 diabetes: A randomized crossover clinical trial.

AIMS: Our aim was to explore the acute effects of consuming snacks at different times on glucose excursions in patients with type 2 diabetes (T2D). METHODS: Seventeen patients with T2D [means±SD: age 67.4±9.4-years; BMI 23.5±3.1kg/m2; HbA1c 55±6mmol/mol (7.2±1.0%)] were randomly assigned in this crossover study. Each participant wore a continuous glucose monitoring device for 4 days and consumed identical test meals on the second and third days, comprising breakfast at 0700h, lunch at 1200h and dinner at 1900h. Half the participants consumed 75kcal biscuits at 1230h (just after lunch) on the second day and at 1530h (mid-afternoon) on the third day, while the other half consumed snacks at the same times, but vice versa. Each patient's glucose parameters were compared against baseline for the 2days of snacking at different times of day. RESULTS: Consuming snacks in the mid-afternoon led to significantly lower mean amplitudes of glycaemic excursions (mean±SEM: 5.19±0.48 vs. 6.90±0.69mmol/L, P<0.01; standard deviation: 1.75±0.17 vs. 2.16±0.21mmol/L, P<0.01) and incremental areas under the curve for glucose after dinner (479±76 vs. 663±104mmol/L per min, P<0.01) compared with snacking just after lunch, whereas mean glucose levels did not differ over the 2days. CONCLUSION: These results suggest that consuming snacks well separated from lunch may be an effective way to suppress postprandial glucose levels and glycaemic excursions.

Evaluation of the fat plane of the pancreatic groove using multidetector CT.

AIM: To assess the pancreatic groove fat plane in the normal population and compare this with the fat plane in patients with groove pancreatitis or carcinoma using multidetector computed tomography (CT). MATERIAL AND METHODS: The pancreatic groove fat plane was evaluated retrospectively in 460 normal subjects (normal group), and in 25 patients with groove pancreatitis or carcinoma (pathology group) using 5 mm- and 1 mm-thick slices of unenhanced axial multidetector CT images. Two investigators independently assessed the degree of pancreatic groove fat plane visualisation using a four-point scale (grade 1: visualisation of 0-25%, grade 2: 26-50%, grade 3: 51-75%, grade 4: 76-100%). Pancreatic parenchymal condition, age, sex, body mass index, diabetes mellitus, and dyslipidaemia were also evaluated. RESULTS: The interobserver agreement for the visualisation grades was almost perfect (k-value = 0.95). In the normal group, grade 4 visualisation of the pancreatic groove fat plane was more common in those aged >80 years (78.6%) compared with younger age groups. Pancreatic atrophy and fatty infiltration significantly improved fat plane visualisation. In the pathology group, grade 4 visualisation of the pancreatic groove fat plane was not seen in either groove carcinoma or pancreatitis. A cut-off point of ≤50% visualisation of the pancreatic groove fat plane showed 95% sensitivity and 82% specificity for detecting possible abnormalities in older patients (>60 years). The clinical factors investigated were not significantly related to pancreatic groove fat plane visualisation. CONCLUSION: Pancreatic groove fat plane visualisation could be a good predictor for detecting groove abnormalities.

Incidence of overwork-related mental disorders and suicide in Japan.

BACKGROUND: Mental disorders and suicide resulting from overwork or work-related stress have become major occupational health issues worldwide, particularly in Asian countries. However, no studies have reported incidence rates of mental disorders and suicide by sex, age group and industry, using a national database containing all cases involving compensation in Asian countries. AIMS: The present study examined incidence rates of occupational mental disorders and suicide by sex, age group and industry using a database containing all cases involving compensation for mental disorders and suicide in Japan over a 5-year period. METHODS: Cases involving compensation for mental disorders and suicide in Japan between January 2010 and March 2015 were analysed. Incidence rates over the 5-year study period were calculated by sex, age group and industry. RESULTS: In total, 1990 cases involving compensation for mental disorders and suicide (619 women and 1371 men) between January 2010 and March 2015 were analysed. The incidence rate involving compensation was higher in employees aged between 30 and 39 years. In men, incidence rates were higher in 'accommodation/eating/drinking services', 'information/communication' and 'scientific research, professional and technical services'. In these industries, incidence rates were particularly high for those aged 29 years or younger. CONCLUSIONS: Our findings highlight the importance of promoting mental health support for younger employees and increasing awareness of their working conditions. Differences in incidence rates by sex, age and industry should be taken into consideration in the development of a national policy and industry- and age-specific preventive measures for overwork-related mental disorders and suicide.

Synergistic anti-AML effects of the LSD1 inhibitor T-3775440 and the NEDD8-activating enzyme inhibitor pevonedistat via transdifferentiation and DNA rereplication.

Lysine-specific demethylase 1A (LSD1, KDM1A) specifically demethylates di- and monomethylated histones H3K4 and K9, resulting in context-dependent transcriptional repression or activation. We previously identified an irreversible LSD1 inhibitor T-3775440, which exerts antileukemic activities in a subset of acute myeloid leukemia (AML) cell lines by inducing cell transdifferentiation. The NEDD8-activating enzyme inhibitor pevonedistat (MLN4924, TAK-924) is an investigational drug with antiproliferative activities in AML, and is also reported to induce cell differentiation. We therefore tested the combination of these two agents in AML models. The combination treatment resulted in synergistic growth inhibition of AML cells, accompanied by enhanced transdifferentiation of an erythroid leukemia lineage into granulomonocytic-like lineage cells. In addition, pevonedistat-induced rereplication stress during the S phase was greatly augmented by concomitant treatment with T-3775440, as reflected by the increased induction of apoptosis. We further demonstrated that the combination treatment was markedly effective in subcutaneous tumor xenograft models as well as in a disseminated model of AML, leading to tumor eradication or prolonged survival in T-3775440/pevonedistat cotreated mice. Our findings indicate the therapeutic potential of the combination of LSD1 inhibitors and pevonedistat for the treatment of AML.

Prognostic significance of the prognostic nutritional index in esophageal cancer patients undergoing neoadjuvant chemotherapy.

Nutritional status is one of the most important issues faced by cancer patients. Several studies have shown that a low preoperative nutritional status is associated with a worse prognosis in patients with various types of cancer, including esophageal cancer (EC). Recently, neoadjuvant chemotherapy (NAC) and/or radiotherapy have been accepted as the standard treatment for resectable advanced EC. However, NAC has the potential to deteriorate the nutritional status of a patient. This study aimed to evaluate the prognostic significance of the nutritional status for EC patients who underwent NAC. We retrospectively reviewed 66 squamous cell EC patients who underwent NAC consisting of docetaxel, cisplatin, and 5-fluorouracil followed by subtotal esophagectomy at Nara Medical University Hospital between January 2009 and August 2015. To assess the patients' nutritional status, the prognostic nutritional index (PNI) before commencing NAC and prior to the operation was calculated as 10 × serum albumin (g/dl) + 0.005 × total lymphocyte count in the peripheral blood (per mm3). The cutoff value of the PNI was set at 45. A multivariable analysis was performed to identify prognostic factors for overall survival (OS) and relapse-free survival (RFS). The mean pre-NAC and preoperative PNI were 50.2 ± 5.7 and 48.1 ± 4.7, respectively (P = 0.005). The PNI decreased following NAC in 44 (66.7%) patients. Before initiating NAC, 9 (13.6%) patients had a low PNI, and 12 (18.2%) patients had a low PNI prior to the operation. The pre-NAC PNI and preoperative PNI were significantly associated with the OS (P = 0.013 and P = 0.004, respectively) and RFS (P = 0.036 and P = 0.005, respectively) rates. The multivariable analysis identified the preoperative PNI as an independent prognostic factor for poor OS and RFS, although the pre-NAC PNI was not an independent predictor. Our results suggest that the preoperative PNI is a useful marker for predicting the long-term outcomes of EC patients undergoing NAC and subsequent subtotal esophagectomy. Therefore, patients with a low preoperative nutritional status may be at a higher risk of EC recurrence.