Evolutionary insights into strategy shifts for the safe and effective accumulation of ascorbate in plants.

Plants accumulate high concentrations of ascorbate, commonly in their leaves, as a redox buffer. While ascorbate levels have increased during plant evolution, the mechanisms behind this phenomenon are unclear. Moreover, has the increase in ascorbate concentration been achieved without imposing any detrimental effects on the plants? In this review, we focus on potential transitions in two regulatory mechanisms related to ascorbate biosynthesis and the availability of cellular dehydroascorbate (DHA) during plant evolution. The first transition might be that the trigger for the transcriptional induction of VTC2, which encodes the rate-limiting enzyme in ascorbate biosynthesis, has shifted from oxidative stress (in green algae) to light/photosynthesis (in land plants), probably enabling the continuous accumulation of ascorbate under illumination. This could serve as a preventive system against the unpredictable occurrence of oxidative stress. The second transition might be that DHA-degrading enzymes, which protect cells from the highly reactive DHA in green algae and mosses, have been lost in ferns or flowering plants. Instead, flowering plants may have increased glutathione concentrations to reinforce the DHA reduction capacity, possibly allowing ascorbate accumulation and avoiding the toxicity of DHA. These potential transitions may have contributed to strategies for plants' safe and effective accumulation of ascorbate.

Visual Assessment of Therapeutic Relationships in Psychiatric Patients: A Pilot Study Using the Pictorial Representation of Illness and Self Measure.

BACKGROUND: Although the therapeutic relationship (or 'alliance') is well known to be a key component of psychiatric treatment, there has been no simple way to objectively measure the patient-therapist relationship. Here, we measured the psychological distance between patients and their therapists by using the Pictorial Representation of Illness and Self Measure (PRISM). PATIENTS AND METHODS: We analyzed the patient-therapist relationship of 112 patients from two hospitals in Japan (54 males, 57 females, 1 unknown; age 46.20 ± 15.03 years [mean ± SD]) who completed the PRISM and self report questionnaires (LSNS-6, K6, and BASIS-32) about their social network, psychological distress, and outcomes of mental health treatment. RESULTS: PRISM measurements were available for all patients who consented to participate. In the comparison by disease category, schizophrenia recorded the closest distance to the psychiatrist in charge, followed by bipolar disorder, depression, and neurotic disorder. Regarding the distance to the psychiatrist in charge, PRISM showed a weak negative correlation (r = -0.23, p < 0.05) with age, indicating that with increasing age, the therapeutic rela tionship was more important to the patients. CONCLUSION: Our findings indicate the possibility of implementing PRISM to assess the impact of the therapeutic relationship in patients with a wide range of psychiatric disorders, and they suggest that PRISM holds great potential for clinical application.

The D-mannose/L-galactose pathway plays a predominant role in ascorbate biosynthesis in the liverwort Marchantia polymorpha but is not regulated by light and oxidative stress.

Ascorbate plays an indispensable role in plants, functioning as both an antioxidant and a cellular redox buffer. It is widely acknowledged that the ascorbate biosynthesis in the photosynthetic tissues of land plants is governed by light-mediated regulation of the D-mannose/L-galactose (D-Man/L-Gal) pathway. At the core of this light-dependent regulation lies the VTC2 gene, encoding the rate-limiting enzyme GDP-L-Gal phosphorylase. The VTC2 expression is regulated by signals via the photosynthetic electron transport system. In this study, we directed our attention to the liverwort Marchantia polymorpha, representing one of the basal land plants, enabling us to conduct an in-depth analysis of its ascorbate biosynthesis. The M. polymorpha genome harbors a solitary gene for each enzyme involved in the D-Man/L-Gal pathway, including VTC2, along with three lactonase orthologs, which may be involved in the alternative ascorbate biosynthesis pathway. Through supplementation experiments with potential precursors, we observed that only L-Gal exhibited effectiveness in ascorbate biosynthesis. Furthermore, the generation of VTC2-deficient mutants through genome editing unveiled the inability of thallus regeneration in the absence of L-Gal supplementation, thereby revealing the importance of the D-Man/L-Gal pathway in ascorbate biosynthesis within M.  polymorpha. Interestingly, gene expression analyses unveiled a distinct characteristic of M. polymorpha, where none of the genes associated with the D-Man/L-Gal pathway, including VTC2, showed upregulation in response to light, unlike other known land plants. This study sheds light on the exceptional nature of M. polymorpha as a land plant that has evolved distinctive mechanisms concerning ascorbate biosynthesis and its regulation.

AJM300 (carotegrast methyl), an oral antagonist of α4-integrin, as induction therapy for patients with moderately active ulcerative colitis: a multicentre, randomised, double-blind, placebo-controlled, phase 3 study.

BACKGROUND: AJM300 is an oral, small-molecule α4-integrin antagonist. We assessed the efficacy and safety of AJM300 in patients with moderately active ulcerative colitis. METHODS: This multicentre, randomised, double-blind, placebo-controlled, phase 3 study consisted of two phases: a treatment phase and an open-label re-treatment phase. The study was done at 82 hospitals and clinics in Japan. Patients with a Mayo Clinic score of 6-10, endoscopic subscore of 2 or more, rectal bleeding subscore of 1 or more, and an inadequate response or intolerance to mesalazine were enrolled. Patients were randomly allocated (1:1) via a website to either AJM300 (960 mg) or placebo by the minimisation method, which was adjusted centrally by dynamic assignment against the Mayo Clinic score (≥6 to ≤7, ≥8 to ≤10 points), any use of corticosteroid, anti-TNFα antibody, or immunosuppressants during the disease-active period (yes vs no), duration of induction therapy until randomisation (<4 weeks vs ≥4 weeks) as the minimisation factors. Patients, investigators, site staff, assessors, and the sponsor were masked to treatment assignments. The study drug was administered orally, three times daily, for 8 weeks, and continued for up to 24 weeks if endoscopic remission was not achieved or rectal bleeding did not stop. The primary endpoint was the proportion of patients with a clinical response at week 8, and was analysed in the full analysis set. Clinical response was defined as a reduction in Mayo Clinic score of 30% or more and 3 or more, a reduction in rectal bleeding score of 1 or more or rectal bleeding subscore of 1 or less, and an endoscopic subscore of 1 or less at week 8. The study is registered with ClinicalTrials.gov, NCT03531892, and is closed to recruitment. FINDINGS: Between June 6, 2018, and July 22, 2020, 203 patients were randomly assigned to AJM300 (n=102) or placebo (n=101). At week 8, 46 (45%) patients in the AJM300 group and 21 (21%) patients in the placebo group had a clinical response (odds ratio 3·30, 95% CI 1·73-6·29; p=0·00028). During the 8-week treatment and 16-week extension treatment periods, adverse events occurred in 39 (39%) of 101 patients in the placebo group and 39 (38%) of 102 patients in the AJM300 group. We found no difference in the incidence of adverse events between groups or after repeated administration of AJM300. The most common adverse event was nasopharyngitis (11 [11%] of 101 patients in the placebo group and ten [10%] of 102 patients in the AJM300 group). The most common treatment-related adverse event was also nasopharyngitis (four [4%] of 101 patients in the placebo group and three [3%] of 102 patients in the AJM300 group). Most adverse events were mild-to-moderate in severity. No deaths were reported. A serious adverse event was reported in the AJM300 group (one patient with anal abscess), but this was judged to be unrelated to study drug. INTERPRETATION: AJM300 was well tolerated and induced a clinical response in patients with moderately active ulcerative colitis who had an inadequate response or intolerance to mesalazine. AJM300 could be a novel induction therapy for the treatment of patients with moderately active ulcerative colitis. FUNDING: EA Pharma and Kissei Pharmaceutical. TRANSLATION: For the Japanese translation of the abstract see Supplementary Materials section.

Effect of feeding Bacillus subtilis on rumen fermentation, blood metabolites, nutrient digestibility, and energy and nitrogen balances in non-lactating crossbred cows.

The purpose of this study was to investigate the effects of feeding Bacillus subtilis on rumen fermentation, blood metabolites, nutrient digestibility, and energy and nitrogen balances in non-lactating crossbred (Holstein-Friesian × Bos indicus) cows. Four cows were assigned to the control and B. subtilis diets in a crossover design, and respiratory and metabolic experiments were conducted. For the B. subtilis diet, B. subtilis DSM15544 spores were added at the rate of 1.0 × 1010  CFU/head/day to the control diet. At 4 hr after feeding, cows fed the B. subtilis diet had increased levels of i-butyric acid in the rumen fluid and tended to have lower concentrations of plasma non-esterified fatty acids when compared with cows fed the control diet. This suggests that feeding B. subtilis could improve energy efficiency. However, there was no effect on energy retention in this study. Although there were no effects on nutrient digestibility, nitrogen balance, or methane production, heat production was significantly higher in cows fed the B. subtilis diet than in those fed the control diet.

Screening for psychotrauma related symptoms: Japanese translation and pilot testing of the Global Psychotrauma Screen.

Background: The impact of traumatic experiences or adverse life experiences has been shown to potentially affect a wide range of mental health outcomes. However, there was no brief instrument to screen for a range of psychological problems in different domains after a potentially traumatic event, and for risk factors and protective factors. Objective: The aim of this study is to examine the internal consistency and concurrent validity of the Japanese version of the Global Psychotrauma Screen (GPS) in a traumatized sample in Japan. Method: A total sample (n = 58) with varying levels of potential posttrauma symptoms due to domestic violence or other events were recruited into this study. Self-rating measures of posttraumatic stress disorder (PTSD), depression, anxiety, and alcohol problems were conducted to investigate the concurrent validity. Results: The results show that a range of posttrauma symptoms assessed by the GPS were highly endorsed by this traumatized sample in all domains except for self-harm, derealization, and depersonalization. The GPS sum score was highly correlated (r > 0.79) with other measures of PTSD, depression, and anxiety symptoms. Also, the subdomain scores showed acceptable correlations with corresponding domain measures. Participants who had been sexually assaulted or had unwanted sexual experiences, and participants who had been physically assaulted during childhood, had higher scores on the total GPS and on subdomains of PTSD, as well as symptoms associated with Complex PTSD. Conclusions: This study provides an initial indication that the GPS may be a useful screening tool for trauma survivors and elucidates that the consequences of trauma are not limited to PTSD.

Antecedentes: Se ha demostrado que el impacto de las experiencias traumáticas o de las experiencias vitales adversas tiene el potencial de comprometer la salud mental dentro de un amplio rango de consecuencias. Sin embargo, no existía ningún instrumento breve para tamizar una variedad de problemas psicológicos, en diferentes dominios, después de un evento potencialmente traumático, ni para los factores de riesgo, ni para los factores protectores.Objetivo: El objetivo de este estudio es el de examinar la consistencia interna y la validez concurrente de la versión japonesa del Mapeo Global de Psicotrauma (GPS, por sus siglas en ingles) en una muestra de personas traumatizadas en Japón.Método: Para este estudio, se reclutó una muestra total (n=58) con distintos niveles de síntomas postraumáticos potenciales secundarios a violencia domestica u otros eventos. Para investigar la validez concurrente, se realizaron mediciones auto reportadas para el trastorno de estrés postraumático (TEPT), la depresión, la ansiedad y para problemas asociados al consumo de alcohol.Resultados: Los resultados muestran que un espectro de síntomas postraumáticos, evaluados mediante el GPS, se encontraba altamente vinculado a esta muestra de personas traumatizadas en todos los dominios, a excepción de las autolesiones, la desrealización, y la despersonalización. El puntaje final del GPS se encontraba altamente correlacionado (r > 0,79) con otras mediciones del TEPT, la depresión y los síntomas ansiosos. Además, los puntajes de los subdominios del GPS mostraron una correlación aceptable con las medidas de dominios correspondientes. Los participantes que habían sido agredidos sexualmente o habían tenido experiencias sexuales no deseadas, y los participantes que habían sido agredidos físicamente durante su infancia mostraban puntajes más altos en el GPS total y en los subdominios del TEPT, así como para los síntomas asociados al TEPT complejo.Conclusiones: Este estudio proporciona un primer indicio de que el GPS podría ser una herramienta de tamizaje útil para sobrevivientes al trauma, y esclarece que las consecuencias del trauma no se limitan al TEPT.

Workplace Violence and Its Effects on Burnout and Secondary Traumatic Stress among Mental Healthcare Nurses in Japan.

Workplace violence (WPV) in healthcare settings has drawn attention for over 20 years, yet few studies have investigated the association between WPV and psychological consequences. Here, we used a cross-sectional design to investigate (1) the 12-month prevalence of workplace violence (WPV), (2) the characteristics of WPV, and (3) the relationship between WPV and burnout/secondary traumatic stress among 599 mental healthcare nurses (including assistant nurses) from eight hospitals. Over 40% of the respondents had experienced WPV within the past 12 months. A multivariate logistic regression analysis indicated that occupation and burnout were each significantly related to WPV. Secondary traumatic stress was not related to WPV. Our results suggest that WPV may be a long-lasting and/or cumulative stressor rather than a brief, extreme horror experience and may reflect specific characteristics of psychological effects in psychiatric wards. A longitudinal study measuring the severity and frequency of WPV, work- and non-work-related stressors, risk factors, and protective factors is needed, as is the development of a program that helps reduce the psychological burden of mental healthcare nurses due to WPV.

Concerns and Side Effects of Azathioprine During Adalimumab Induction and Maintenance Therapy for Japanese Patients With Crohn's Disease: A Subanalysis of a Prospective Randomised Clinical Trial [DIAMOND Study].

BACKGROUND: Combining a thiopurine with the human anti-tumour necrosis factor-α monoclonal antibody adalimumab for Crohn's disease [CD] treatment is controversial with regard to efficacy and safety. By conducting a subanalysis of a multicentre, randomised, prospective, open-label trial [the DIAMOND study, UMIN registration number 000005146], we studied the risk of discontinuation of thiopurine in combination with adalimumab. METHODS: In the preceding DIAMOND study, we analysed the: [i] timing and reasons for dropout in the monotherapy group and combination group; [ii] risk factors for dropout in the combination group. RESULTS: There was no significant difference in the dropout rate up to Week 52 between the monotherapy group and combination group [p = 0.325]. The main reason for study dropout was active CD in the monotherapy group, whereas it was adverse effects in the combination group [Fisher's exact test, p <0.001]. Kaplan-Meier analyses revealed significantly earlier dropout in the combination group [log-rank test, p = 0.001]. Multivariable analysis revealed low body weight to be a risk for dropout due to adverse effects in the combination group. CONCLUSIONS: Combination of azathioprine with adalimumab resulted in dropout in the early stage of the study due to side effects of azathioprine, in comparison with late dropout due to active CD in the adalimumab monotherapy group.

Cardiac Arrest Induced by Carotid Sinus Reflex Activation During Flow-Diverter Stent Deployment.

BACKGROUND: A 60-year-old female with multiple carotid aneurysms underwent endovascular treatment with a Pipeline Flex embolization device (PED) under local anesthesia via femoral puncture. CASE DESCRIPTION: Cardiac arrest occurred when the delivery systems were pushed to promote adequate opening and apposition of the PED against the vessel wall and was recovered to sinus rhythm in approximately 30 seconds by pulling down the microcatheter. The carotid sinus reflex was suspected as the cause of this temporary asystole. Delivery of the PED was accompanied by application of forward pressure on the delivery system. This resulted in buckling of the delivery systems in the neck and likely excessive pressure on the carotid sinus. The procedure was continued and successfully completed with care not to excessively push the system and with the additional use of atropine. CONCLUSIONS: Although it was a rare complication, the phenomenon and its mechanisms were known in the carotid artery stenting procedure. To the best of our knowledge, this is the first report of cardiac arrest induced by a carotid sinus reflex during PED deployment. It is important for an operator of PED deployment to recognize its possibility. Vital signs should be closely checked during PED deployment, particularly while pushing the catheter.

Effect of a concomitant elemental diet with maintenance anti-tumor necrosis factor-α antibody therapy in patients with Crohn's disease: A multicenter, prospective cohort study.

BACKGROUND AND AIM: The aim of this study was to clarify the additional effect of a concomitant elemental diet (ED) for patients with Crohn's disease on maintenance anti-tumor necrosis factor-α antibody (anti-TNF). METHODS: Crohn's disease patients who received anti-TNF induction therapy were enrolled. Patients who achieved clinical response (defined as delta Crohn's disease activity index [CDAI] > 70 and CDAI < 200) at 10-14 weeks after the start of infliximab or adalimumab were included. Eligible patients took a tolerability test of ED (900 kcal/day) for 3 days. Then, patients who preferred concomitant ED and whose ED tolerance was confirmed were allocated to the ED group and given Elental 900 kcal/day or more. Other patients were allocated to the non-ED group. The primary endpoint was the cumulative remission rate at 2 years after baseline. Clinical relapse was defined as CDAI > 200 and/or need for additional treatment. Adherence to the ED was confirmed at each visit. RESULTS: Seventy-two patients were included. Thirty-seven were allocated to the ED group, and 35 were allocated to the non-ED group. The cumulative remission rate at 2 years was not significantly different between the two groups (60.9% vs 56.7%, P = 0.98). Adherence to the ED in the ED group was relatively low, and only 11 patients were maintained on an ED of 900 kcal/day. CONCLUSIONS: The addition of ED for Crohn's disease patients who responded to initial anti-TNF induction therapy was not found to improve outcomes. The efficacy of concomitant ED in other clinical settings, such as loss of response, needs to be clarified in the future (UMIN000009789).

Burnout, Psychological Symptoms, and Secondary Traumatic Stress Among Midwives Working on Perinatal Wards: A Cross-Cultural Study Between Japan and Switzerland.

The aim of this study was to explore cross-cultural differences in symptoms of burnout, anxiety, depression, general psychological distress, and secondary traumatic stress between Asian (Japan) and European (Switzerland) midwives. One hundred seventy midwives participated in the study. There were significant differences in age group [χ2(3) = 24.2, p < 0.01], marital or relationship status [χ2(2) = 28.4, p < 0.01], and years of experience [χ2(2) = 17.8, p < 0.01] between the two countries. The Japanese staff were younger, more often unmarried, and had less experience than the Swiss staff. The mean score of depersonalization was significantly higher in Switzerland (4.8 ± 3.8) than in Japan (3.2 ± 3.7; |z| = 2.71, p < 0.01). The mean score of general psychological distress in the Swiss sample (12.8 ± 6.5) was significantly higher than that in the Japanese sample (10.3 ± 6.2; |z| = 2.04, p = 0.04). In addition, the mean score of secondary traumatic stress was higher in the Swiss sample (31.8 ± 9.7) than in the Japanese sample (24.1 ± 8.6; |z| = 4.56, p < 0.01). These results may reflect cultural differences such as working conditions or family environment between Japan and Switzerland.

Reduced Expression of APUM24, Encoding a Novel rRNA Processing Factor, Induces Sugar-Dependent Nucleolar Stress and Altered Sugar Responses in Arabidopsis thaliana.

Ribosome biogenesis is one of the most energy-consuming events in the cell and must therefore be coordinated with changes in cellular energy status. Here, we show that the sugar-inducible gene ARABIDOPSIS PUMILIO PROTEIN24 (APUM24) encodes a Pumilio homology domain-containing protein involved in pre-rRNA processing in Arabidopsis thaliana Null mutation of APUM24 resulted in aborted embryos due to abnormal gametogenesis and embryogenesis, whereas reduced expression of APUM24 caused several phenotypes characteristic of ribosome biogenesis or function-related mutants. APUM24 interacted with other pre-rRNA processing factors and a putative endonuclease for the removal of the internal transcribed spacer 2 (ITS2) of pre-rRNA in the nucleolus. The APUM24-containing complex also interacted with ITS2, and reduced APUM24 expression caused the overaccumulation of processing intermediates containing ITS2. Thus, APUM24 likely functions as an ITS2 removal-associated factor. Most importantly, the apum24 knockdown mutant was hypersensitive to highly concentrated sugar, and the mutant showed sugar-dependent overaccumulation of processing intermediates and nucleolar stress (changes in nucleolar size). Furthermore, reduced APUM24 expression diminished sugar-induced promotion of leaf and root growth. Hence, a breakdown in the coordinated expression of ribosome biogenesis-related genes with energy status may induce nucleolar stress and disturb proper sugar responses in Arabidopsis.

Chest High-resolution Computed Tomography Findings in 601 Patients with Inflammatory Bowel Diseases.

RATIONALE AND OBJECTIVES: Pulmonary involvement in inflammatory bowel disease may reflect the common embryonic origin of the gastrointestinal tract and the bronchial tree. No studies have compared pulmonary high-resolution computed tomography (HRCT) findings between ulcerative colitis (UC) and Crohn disease (CD). This study aimed to assess the relationship between pulmonary HRCT findings and inflammatory bowel disease activity and to compare HRCT findings between UC and CD. MATERIALS AND METHODS: We retrospectively identified 601 consecutive patients (350 with UC and 251 with CD) who had undergone chest HRCT examinations at our institutions between April 2004 and April 2016. Parenchymal abnormalities, enlarged lymph nodes, and pleural effusion were evaluated on HRCT. RESULTS: One hundred sixty-seven patients (94 men, 73 women; aged 12-86 years, mean: 47.2 years) with UC and 93 patients (61 men, 32 women; aged 12-71 years, mean: 37.9 years) with CD had abnormal findings on chest HRCT. The HRCT findings of UC and CD mainly consisted of centrilobular nodules (in 49.1% and 45.2% of cases, respectively) and bronchial wall thickening (in 31.7% and 54.8%, respectively). There was no relationship between HRCT findings and disease activity. Bronchial wall thickening was significantly more frequent in patients with CD than in those with UC (P < .001). CONCLUSION: The main chest HRCT findings in UC and CD are centrilobular nodules and bronchial wall thickening. There are differences in HRCT findings between UC and CD.

Clinical and Pharmacokinetic Factors Associated With Adalimumab-Induced Mucosal Healing in Patients With Crohn's Disease.

BACKGROUND & AIMS: We previously reported results from a prospective randomized controlled trial comparing the efficacy of adalimumab monotherapy versus combination with azathioprine for patients with Crohn's disease (CD) who were naive to biologics and thiopurines. We performed a subanalysis of data from this study to evaluate factors associated with endoscopic response and mucosal healing in study participants. METHODS: We compared simple endoscopic scores for CD between patients with moderate to severe active CD randomly assigned groups that received adalimumab monotherapy (n = 85) or adalimumab in combination with azathioprine (n = 91), from June 2011 to June 2014 in Japan. We evaluated associations of simple endoscopic scores for CD with clinical factors and trough levels of adalimumab. Ultimately, 135 patients at Week 26 and 139 patients at Week 52 from 44 referral sites were analyzed for the present investigation. RESULTS: The odds for endoscopic response were significantly higher in the combination group than in the monotherapy group at Week 26 (odds ratio [OR], 2.12; 95% confidence interval [CI], 1.04-4.32) but not at Week 52 (OR, 1.50; 95% CI, 0.77-2.94). The odds of mucosal healing did not differ significantly between groups at Weeks 26 or 52. Simple endoscopic scores for CD at Week 0 was significantly associated with mucosal healing at Week 26 (OR, 0.80; 95% CI, 0.72-0.90) and at Week 52 (OR, 0.91; 95% CI, 0.84-0.99). Higher adalimumab trough level at Week 26 associated with mucosal healing at Week 52 (OR, 1.34; 95% CI, 1.14-1.58; P for trend = .001) and was significantly higher in patients with endoscopic response than in patients without endoscopic response at Weeks 26 and 52 (P < .001). CONCLUSIONS: In a post hoc analysis of data from a randomized controlled trial of patients with moderate to severe CD, we found that adalimumab in combination with azathioprine increased trough levels of adalimumab. Higher trough levels of adalimumab associated with endoscopic response and mucosal healing at Weeks 26 and 52. UMIN registration No: 000005146.

The relationship of sleep complaints risk factors with sleep phase, quality, and quantity in Japanese workers.

Numerous studies have determined that lifestyle factors (smoking, drinking, snacking, etc.) and the bedroom environment can influence sleep. We developed a new sleep scale-the 3-Dimensional Sleep Scale (3DSS)-which measures three elements of sleep: phase, quality, and quantity. The purpose of this study is to determine which risk factors of sleep complaints are associated with these sleep elements. Data were obtained from 366 Japanese day workers (302 men and 64 women). Sleep condition was assessed with the 3DSS, and we also assessed various habits within 2 h of going to bed, including smoking, drinking, snacking, caffeine intake, mobile phone use, and working. We also asked about bedroom environmental conditions (noise, lighting, and temperature and humidity). Multivariate logistic regression analysis using the backward selection method (likelihood ratio) was used, with 3DSS scores as the outcome (i.e., over or under the cutoff). The results showed that smoking was associated with significantly greater odds ratio [2.71 (1.65-4.44)] of disordered sleep phase, while lighting as well as temperature and humidity led to greater odds [3.67 (1.55-8.68), 1.93 (1.20-3.11)] of poor sleep quality. Finally, only noise was significantly related to greater odds [1.98 (1.13-3.46)] of low sleep quantity. These findings indicated the various risk factors of sleep complaints could be associated with different sleep elements. This might help in the effective treatment of sleep complaints.

Induction of plant disease resistance upon treatment with yeast cell wall extract.

It has been reported that treatment with yeast cell wall extract (YCWE) induces PDF1 and PR-1 gene expression; these transcripts are important markers of plant disease resistance, though the detailed signaling mechanisms that induce these defense responses are still unknown. In this report, we found that YCWE treatment triggered rice cell suspension cultures to accumulate phenylalanine (Phe), cis-12-oxo-phytodienoic acid (OPDA), 12-hydroxyjasmonoyle isoleucine (12OHJA-Ile), and azelaic acid (AzA). YCWE treatment also reduced endogenous triacylglycerol (TG) content. The addition of 13C-uniform-labeled oleic, linoleic and linolenic acids to the rice cell suspension cultures gave rise to 13C-uniform-labeled AzA. It was also found that YCWE treatment for Arabidopsis thaliana resulted in accumulations of OPDA, AzA, Phe, and camalexin together with enhanced resistance against Botrytis cinerea infection. This suggested that YCWE treatment upon plants may activate JA and AzA signaling systems to induce plant disease resistance.

Discovery of nitrate-CPK-NLP signalling in central nutrient-growth networks.

Nutrient signalling integrates and coordinates gene expression, metabolism and growth. However, its primary molecular mechanisms remain incompletely understood in plants and animals. Here we report unique Ca2+ signalling triggered by nitrate with live imaging of an ultrasensitive biosensor in Arabidopsis leaves and roots. A nitrate-sensitized and targeted functional genomic screen identifies subgroup III Ca2+-sensor protein kinases (CPKs) as master regulators that orchestrate primary nitrate responses. A chemical switch with the engineered mutant CPK10(M141G) circumvents embryo lethality and enables conditional analyses of cpk10 cpk30 cpk32 triple mutants to define comprehensive nitrate-associated regulatory and developmental programs. Nitrate-coupled CPK signalling phosphorylates conserved NIN-LIKE PROTEIN (NLP) transcription factors to specify the reprogramming of gene sets for downstream transcription factors, transporters, nitrogen assimilation, carbon/nitrogen metabolism, redox, signalling, hormones and proliferation. Conditional cpk10 cpk30 cpk32 and nlp7 mutants similarly impair nitrate-stimulated system-wide shoot growth and root establishment. The nutrient-coupled Ca2+ signalling network integrates transcriptome and cellular metabolism with shoot-root coordination and developmental plasticity in shaping organ biomass and architecture.

A case of an intractable duodenal ulcer associated with a pancreatic arteriovenous malformation.

A 62-year-old man with epigastralgia was referred to our hospital for the evaluation of an intractable duodenal ulcer, which did not improve following proton pump inhibitor treatment. An upper gastrointestinal endoscopy revealed that the base of the ulcer was gray-white in color with conspicuous fibrosis tissue, unlike the appearance of common ulcers. A contrast-enhanced abdominal CT scan and angiography revealed tortuous and dilated vascular structures in the pancreatic head. This was diagnosed as a pancreatic arteriovenous malformation. We suggest that the intractable duodenal ulcer was caused by the pancreatic arteriovenous malformation. Therefore, we performed a pancreaticoduodenectomy. Pancreatic arteriovenous malformations should be considered as one of the causes of treatment-resistant duodenal ulcers.

Direct transcriptional activation of BT genes by NLP transcription factors is a key component of the nitrate response in Arabidopsis.

Nitrate modulates growth and development, functioning as a nutrient signal in plants. Although many changes in physiological processes in response to nitrate have been well characterized as nitrate responses, the molecular mechanisms underlying the nitrate response are not yet fully understood. Here, we show that NLP transcription factors, which are key regulators of the nitrate response, directly activate the nitrate-inducible expression of BT1 and BT2 encoding putative scaffold proteins with a plant-specific domain structure in Arabidopsis. Interestingly, the 35S promoter-driven expression of BT2 partially rescued growth inhibition caused by reductions in NLP activity in Arabidopsis. Furthermore, simultaneous disruption of BT1 and BT2 affected nitrate-dependent lateral root development. These results suggest that direct activation of BT1 and BT2 by NLP transcriptional activators is a key component of the molecular mechanism underlying the nitrate response in Arabidopsis.

Two cases of adenocarcinoma occurring in sporadic fundic gland polyps observed by magnifying endoscopy with narrow band imaging.

Gastric fundic gland polyps (FGPs) are common non-adenomatous gastric polyps arising from normal fundic mucosa without Helicobacter pylori (H. pylori) infection. Although systemic FGPs associated with familial adenomatous polyposis (FAP) often have dysplasia, there are few reports of dysplasia occurring in sporadic FGPs, especially when detected by magnifying endoscopy with narrow band imaging (ME-NBI). We experienced two cases of adenocarcinoma occurring in sporadic FGPs, and their ME-NBI findings were very useful for differentiating FGP with cancer from non-dysplastic FGP. A 68-year-old man and a 63-year-old woman were referred to our institution for medical checkup. H. pylori was negative in both patients. Endoscopic examination revealed a small reddish polypoid lesion on the anterior wall of the upper gastric body and several FGPs. ME-NBI showed an irregular microvascular architecture composed of closed loop- or open loop-type vascular components, plus an irregular microsurface structure composed of oval-type surface components which was different from that of FGPs. FAP was denied because of the absence of colon polyps and no familial history of FAP. Pathological diagnosis was adenocarcinoma occurring in sporadic FGP.