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Background and HypothesisDynamics of the distributed sets of functionally synchronized brain regions, known as large-scale networks, are essential for the emotional state and cognitive processes. However, few studies were performed to elucidate the aberrant dynamics across the large-scale networks across multiple psychiatric disorders. In this paper, we aimed to investigate dynamic aspects of the aberrancy of the causal connections among the large-scale networks of the multiple psychiatric disorders.Study DesignWe applied dynamic causal modeling (DCM) to the large-sample multi-site dataset with 739 participants from 4 imaging sites including 4 different groups, healthy controls, schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BD), to compare the causal relationships among the large-scale networks, including visual network, somatomotor network (SMN), dorsal attention network (DAN), salience network (SAN), limbic network (LIN), frontoparietal network, and default mode network.Study ResultsDCM showed that the decreased self-inhibitory connection of LIN was the common aberrant connection pattern across psychiatry disorders. Furthermore, increased causal connections from LIN to multiple networks, aberrant self-inhibitory connections of DAN and SMN, and increased self-inhibitory connection of SAN were disorder-specific patterns for SCZ, MDD, and BD, respectively.ConclusionsDCM revealed that LIN was the core abnormal network common to psychiatric disorders. Furthermore, DCM showed disorder-specific abnormal patterns of causal connections across the 7 networks. Our findings suggested that aberrant dynamics among the large-scale networks could be a key biomarker for these transdiagnostic psychiatric disorders.

Subcortical brain structures are the hubs for various psycho-behavioral functions. There is no mega-analysis to simultaneously investigate subcortical volumetric alterations in schizophrenia, bipolar disorder, major depressive disorder, and autism spectrum disorder. Nor are there any neuroimaging data-driven clinical criteria overcoming limitations of the current diagnostic system, which would reflect cognitive/social functioning. We conducted a large-scale multisite study of subcortical volumetric and lateralization alterations in these disorders using T1-weighted images of 5,604 subjects (3,078 controls and 2,526 patients). We found schizophrenia-specific and cross-disorder shared alterations. Moreover, we clustered the 5,604 subjects based on subcortical volumes, and explored whether data-driven clustering results can explain cognitive/social functioning in the subcohorts. We showed a four-biotype classification, namely extremely and moderately smaller limbic regions, larger basal ganglia, and normal volumes, for predicting cognitive/social functioning. Our results will contribute to the future creation of novel biological data-driven psychiatry diagnostic criteria, expected to support appropriate treatment selection.

Carbonyl stress is a condition featuring increased rich reactive carbonyl compounds, which facilitate the formation of advanced glycation end products including pentosidine. We previously reported the relationship between enhanced carbonyl stress and disrupted white matter integrity in schizophrenia, although which microstructural component is disrupted remained unclear. In this study, 32 patients with schizophrenia (SCZ) and 45 age-and gender-matched healthy volunteers (HC) were recruited. We obtained blood samples for carbonyl stress markers (plasma pentosidine and serum pyridoxal) and multi-modal magnetic resonance imaging measures of white mater microstructures including apparent axonal density (intra-cellular volume fraction (ICVF)) and orientation (orientation dispersion index (ODI)), myelin content (calibrated T1-weigted/T2-weighted image ratio), and inflammation (free water (FW)). In SCZ, the plasma pentosidine level was significantly increased. Group comparison revealed that mean white matter values were decreased for ICVF, increased for FW, and not different for the myelin component. We found a significant negative correlation between the plasma pentosidine level and mean ICVF values in SCZ, and a significant negative correlation between the serum pyridoxal level and mean ODI value in HC, regardless of age. Our results suggest an association between enhanced carbonyl stress and axonal abnormality in SCZ.

Introduction: The incidences of allergic diseases such as allergic rhinitis, atopic dermatitis, asthma, and food allergies are rising in developed countries. Mast cells play critical roles in various biologic processes related to allergic diseases, including expressing the high-affinity receptor for immunoglobulin (Ig) E on their surface. The interaction of multivalent antigens with surface-bound IgE causes the secretion of granule-stored mediators, as well as the de novo synthesis of cytokines. These mediators and cytokines precede the development of allergic diseases. In Osaka Prefecture, Japan, certain locally cultivated crops have received ‘Naniwa-yasai’, a designation that certifies the significance of traditional vegetables in supporting Osaka’s agriculture and cuisine for over a century. In this study, we investigated the anti-allergic effects of four traditional vegetables from Osaka.Results: The anti-allergic activity of extracts made from Tanabe radish, Moriguchi radish, bunching onion (Allium fistulosum), and mizu eggplant were examined. Various concentrations of each extract were added to RBL-2H3 mast cells prior to stimulation with the calcium ionophore A23187. β-hexosaminidase release was markedly and dose dependently decreased in mast cells following the addition of A. fistulosum, demonstrating its anti-allergic activity. None of the other vegetables had an anti-allergic effect on RBL-2H3 cells.Conclusion: An Osakan traditional vegetable, bunching onion (Allium fistulosum), exhibited anti-allergic activity, and should be explored further as a possible treatment for allergic diseases.Keywords: mast cell, anti-allergy, traditional vegetables, bunching onion (Allium fistulosum)

Inducing adequate therapeutic seizures during electroconvulsive therapy (ECT) is sometimes difficult due to a high seizure threshold, even at the maximum stimulus charge. Previous studies have demonstrated that seizure threshold is lower in patients treated with right unilateral ultrabrief pulse (RUL-UBP) ECT than in those treated with bilateral or brief pulse (BL-BP) ECT. Therefore, switching to RUL-UBP ECT may be beneficial for patients in whom seizure induction is difficult with conventional ECT. In the present report, we discuss the case of a patient suffering from catatonic schizophrenia in whom BL-BP ECT failed to induce seizures at the maximum charge. However, RUL-UBP ECT successfully elicited therapeutic seizures and enabled the patient to achieve complete remission. This case illustrates that, along with other augmentation strategies, RUL-UBP ECT represents an alternative for seizure induction in clinical practice.

Regioselective C–H oxidation of aliphatic molecules with synthetic catalysts is challenging. We incorporated substrate-recognition sites into a ruthenium porphyrin–heteroaromatic N-oxide catalytic system in order to characterise its regioselectivity for the oxidation of alkanes. This substrate-recognition catalytic reaction exhibits high regioselectivity and high reaction efficiency.

Purpose Upper airway stenosis is one of the most formidable situations in medicine and is frequently encountered in the ENT clinic. We introduce here our method of emergency endonasal endotracheal intubation under videoendoscopic observation. Methods Transnasal endoscopic observation was done, and the region of airway stenosis was detected. Then, the endotracheal tube was prepared and the endoscope was inserted into the tube. The endoscope with tube was inserted up to the larynx. Immediately after the administration of lidocaine to the larynx, the endoscope with tube was inserted to the endolarynx and then to the trachea. The endotracheal tube was tightly held in the nostril, and the endoscope was removed. Results We have encountered four cases this year. The primary disease developing airway stenosis was acute epiglottitis due to pharyngeal and deep neck abscesses in three cases and laryngeal edema due to Ludwig's angina. All patients underwent uneventful intubation, and dyspnea was immediately ceased. Conclusion In cases showing severe suffocation, the clinician should perform airway maintenance even in an outpatient setting apart from a more monitored setting like the operation room. This technique resembles the usual nasal endoscopic laryngeal observation and is done even in the usual ENT office and/or emergency room. The supine position tends to worsen airway stenosis in patients with upper airway stenosis; however, this technique can be performed in a sitting or semi-sitting position. This method is less invasive for patients and also reduces the risk to the medical staff, especially in this COVID-19 era.

We investigated the effects of geranium essential oil (GEO) on anaphylaxis. GEO can exert antioxidant and anti-inflammatory effects, but its roles in allergic reactions are incompletely understood. Here, we used mouse cells to show that GEO inhibited the degranulation of cultured mast cells (CMCs). Citronellol is the major component of GEO and inhibited CMC degranulation. The l-enantiomer of citronellol more effectively suppressed CMC degranulation than did d-citronellol. We also examined whether citronellol could inhibit the immunoglobulin (Ig) E-induced production of tumor necrosis factor (TNF)-α. Treatment with various concentrations of citronellol before CMC activation with IgE significantly inhibited the induction of TNF-α in a dose-dependent manner. Mechanistically, citronellol suppressed the phosphorylation of mitogen-activated protein kinase (ERK), which is critical for ERK activation and the production of inflammatory cytokines in mast cells. These findings suggest that citronellol may represent a candidate compound for the effective treatment of allergic diseases.

[Image: see text] Based on the idea that compounds designed to exhibit high affinity for heme would block hemozoin formation, a critical heme-detoxification process for malarial parasites, we synthesized a series of compounds with two π-conjugated moieties at terminal amino groups of triamine. These compounds exhibited moderate to high antimalarial activities in vitro toward both chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum. In a P. berghei-infected mouse model, 3a and 12a showed potent antimalarial activities compared to artesunate, as well as a prolonged duration of antimalarial effect. We found a good correlation between protective activity against hemin degradation and antimalarial activity. Compounds 8b and 3a strongly inhibited hemozoin formation catalyzed by heme detoxification protein.

Naturally occurring autoantibodies have natural physiologic functions related to normal cell processes. However, the repertoire of naturally occurring autoantibodies against neuronal antigens in CSF is unclear. The purpose of this study was to identify naturally occurring autoantibodies against neuronal antigens in CSF from patients with various neurologic diseases by proteomics-based analysis. The CSF samples were collected from 77 patients with various neurologic disorders. The antigen source for 2-dimensional immunoblotting was the SH-SY5Y human neuroblastoma cell line. There were 8 spots recognized in CSF from more than one-fourth of the 77 patients including all patient groups and these spots were recognized in intravenous immunoglobulin preparations. These antigen spots were identified as heat shock 105-kDa/110-kDa protein 1, isoform CRA_b, 78-kDa glucose-regulated protein, heat shock cognate 71-kDa protein, tubulin beta chain, vimentin (2 spots), and 60-kDa heat shock protein, mitochondrial; we could not identify the protein name corresponding to 1 of the 8 spots. In summary, there were 6 proteins identified that were main target antigens that reacted with naturally occurring autoantibodies in CSF from patients with varied neurologic disorders; the functions of autoantibodies against the identified antigens are unknown and may be clarified with further studies. Biological significance Naturally occurring autoantibodies may have important functions in tissue homeostasis. In this study, we identified 6 common target antigens that reacted with autoantibodies in cerebrospinal fluid (CSF) from patients, independent of disease type. These findings may clarify the importance of naturally occurring autoantibodies in CSF and the use of these antibodies potentially may be a novel therapy for various neurologic disorders.

Background: The incidence of allergic diseases such as allergic rhinitis, atopic dermatitis, asthma, and food allergies has increased in several countries. Mast cells have critical roles in various biologic processes related to allergic diseases. Mast cells express the high-affinity receptor for immunoglobulin (Ig) E on their surface. The interaction of multivalent antigens with surface-bound IgE causes the secretion of granule-stored mediators, as well as the de novosynthesis of cytokines. Those mediators and cytokines proceed the allergic diseases. We investigated the effects of water-soluble, low-molecular-weight -(1, 3–1, 6) D-glucan isolated from Aureobasidium pullulans 1A1 strain black yeast (LMW--glucan) on mast cell-mediated anaphylactic reactions. We reported that LMW--glucan dose-dependently inhibited the degranulation of mast cells. Furthermore, we found that orally administered LMW--glucan inhibited the IgE-mediated passive cutaneous anaphylaxis (PCA) reaction in mice. Here, we examined if LMW--glucan had effects on Japanese cedar pollinosis. Findings: In a clinical study, a randomized, single-blind, placebo-controlled, parallel group study in 65 subjects (aged 2262) was performed. This study was undertaken 3 weeks before and until the end of the cedar pollen season. During the study, all subjects consumed one bottle of placebo or LMW--glucan daily and all subjects were required to record allergic symptoms in a diary. The LMW--glucan group had a significantly lower prevalence of sneezing, nose-blowing, tears, and hindrance to the activities of daily living than the placebo group. Conclusions: These results suggested that LMW--glucan could be an effective treatment for allergic diseases

The aim of the present study was to investigate the biological activity of 20 essential oils (EOs) derived from herbal plants and citrus fruits. The in vitro anti-allergic and anti-inflammatory activities of these oils were investigated, and the EO which was found to have the strongest activity of the 20 EOs examined, was investigated further to identify its components and bioactive compounds. The in vitro anti-allergic activity was determined by measuring the release of β-hexosaminidase from rat basophilic leukemia (RBL-2H3) cells treated with the calcium ionophore, A23187. The in vitro anti-inflammatory activity was determined by measuring the production of tumor necrosis factor-α (TNF-α) in RAW264.7 murine macrophages treated with lipopolysaccharide. Among the EOs examined, lemongrass [Cymbopogon citratus (DC.) Stapf] elicited the strongest anti-allergic and anti-inflammatory effects. A principal component of this EO is citral (3,7-dimethyl-2,6-octadien-1-al) (74.5%), a mixture of the stereoisomers, geranial (trans-citral, 40.16%) and neral (cis-citral, 34.24%), as determined by chromatography-mass spectrometry analysis. The activities of citral and geranial are similar to those of lemongrass EO. These compounds elicited significant in vivo anti-allergic and anti-inflammatory effects, suppressing an immunoglobulin E (IgE)-induced passive cutaneous anaphylactic reaction in mice and a 12-O-tetradecanoylphorbol-13-acetate-induced inflammatory mouse ear edema, respectively. Our data demonstrate that lemongrass EO and its constituents, citral and geranial, may be a therapeutic candidate for allergic and inflammatory diseases.

To research the potential ability of marine-derived actinomycetes to act as biocatalysts, 8 Micromonospora strains and 5 Streptomyces strains were screened. Two recommended media (227 and 1076 media) and 2 modified media (1076-25% and P-1076-25% media) for liquid culture of these marine-derived actinomycetes were tested. As a result, 2 Micromonospora strains (Micromonospora sp. NBRC107096 and 107097) cultured with the 1076-25% medium and 2 Streptomyces strains (Streptomyces tateyamensis NBRC105048 and Streptomyces sp. NBRC105896) cultured with P-1076-25% medium showed a good growth. The stereoselective reduction of α-keto esters using these 4 actinomycetes was tested. As a result, it was found that these strains had a reducing activity toward various α-keto esters. The introduction of L-glutamate or sucrose as an additive remarkably increased the conversion ratios in the reduction of substrates by the Micromonospora strain. Furthermore, in the presence of L-alanine, Streptomyces tateyamensis NBRC105048 reduced ethyl pyruvate, ethyl 2-oxobutanoate, ethyl 2-oxopentanoate, ethyl 2-oxohexanoate, and ethyl 3-methyl-2-oxobutyrate to the corresponding α-hydroxy ester with a high conversion ratio and with excellent enantiomeric excess. Thus, we found that these marine-derived actinomycetes have great potential to be used as biocatalysts for stereoselective reduction of carbonyl compounds.

Loss-of-function mutations of flavin-containing monooxygenase 3 (FMO3), the enzyme responsible for trimethylamine N-oxygenation, cause the inherited disorder trimethylaminuria, or fish odor syndrome. The aim of this study was to further investigate the inter-individual variations of FMO3 activity in a Japanese cohort that we had studied previously. The subjects were 640 Japanese volunteers with self-reported trimethylaminuria; genomic DNA was sequenced in those that had 10-70% FMO3 metabolic capacity in urine tests. A heterozygote for the novel single nucleotide substitution p.Ile441Thr (proband 1) and a heterozygote for the novel single nucleotide substitution p.Ser195Leu (proband 2) were identified. The biological parents of probands 1 and 2 were heterozygous and had >90% trimethylamine N-oxygenation metabolic capacity. In addition, single nucleotide substitutions p.Val58Ile, p.Pro70Leu, and p.Gly421Val in FMO3 were found in probands 3-7. In the course of DNA sequencing, another FMO3 variant, p.Thr488Ala, was found in two unrelated heterozygous subjects. Variant FMO3 proteins recombinantly expressed in Escherichia coli membranes exhibited decreased activity toward typical FMO3 substrates. Although the allele frequencies of these six novel variants were low (

We investigated the effects of water-soluble low-molecular-weight β-(1,3-1,6) D-glucan isolated from Aureobasidium pullulans 1A1 strain black yeast (LMW-β-glucan) on mast cell-mediated anaphylactic reactions. Although it is known that LMW-β-glucan has anti-tumor, anti-metastatic and anti-stress effects, the roles of LMW-β-glucan in immediate-type allergic reactions have not been fully investigated. We examined whether LMW-β-glucan could inhibit mast cell degranulation and passive cutaneous anaphylaxis (PCA). LMW-β-glucan dose-dependently inhibited the degranulation of both rat basophilic leukemia (RBL-2H3) and cultured mast cells (CMCs) activated by calcium ionophore A23187 or IgE. However, LMW-β-glucan had no cytotoxicity towards RBL-2H3 cells and CMCs. Furthermore, orally administered LMW-β-glucan inhibited the IgE-induced PCA reaction in mice. These results show LMW-β-glucan to be a possible compound for the effective therapeutic treatment of allergic diseases.

We suppose that there are two independent normal populations, π1: N(μ1, σ2) and π2: N(μ2, a 2σ2), where μ1, μ2, σ2 are unknown but a (0

This paper describes a method of estimating the amount of swelling in rollers under working conditions, such as high load pressures, high rotation speeds, high temperatures, and slippage occurring between paired rollers. Three kinds of swelling test system were considered. “Rotation tests” refer to swelling tests inside the actual environment of the machine. A pair of rollers rotates under conditions of load pressure, high temperature and slippage (difference in rotation speed). “Static tests” are similar to the traditional swelling test where the roller is free from speed, slip and load. “Quasi-static tests” is similar to Static tests but load pressure can be applied. The Experiments were efficiently conducted with these three systems by using DOE (design of experiments). As a result, rotation speed, slippage and load pressure (within the usual range in ATM) had small effects, whereas, environmental temperature, total contact time, application quantity and application frequency had large effects on roller radius. Accelerated test method was examined and finally, the maximum amount of swelling in the roller under the actual conditions inside the machines can be predicted using the regression curve analyzed from 3 experimental points by the “static test”, and the method provides a swelling test that is completed within one day.

To investigate interhemispheric transfer of language information in left-handed participants, event-related potentials were recorded during a semantic matching task. The stimuli were prime and target word pairs sequentially presented to either the left (LVF) or the right (RVF) visual field. A posterior slow negative shift (SNp) preceding target presentation was measured as an index of storage of language information and an N400 attenuation elicited for targets was used to analyze the priming effect. The SNp developed over both hemispheres for RVF primes, whereas for LVF primes it declined over the left hemisphere. The N400 attenuation was larger in the right hemisphere than in the left hemisphere. The lateralized pattern of the SNp development and the N400 attenuation, which contrasts with the previous finding in right handers (Kato & Okita, 2008), suggests that the transfer of language information from the dominant hemisphere to the nondominant hemisphere is reduced.

Heading Aims: We evaluated tubal disorders, including peritubal adhesions, as risk factors for repeat ectopic pregnancy (REP) after laparoscopic linear salpingotomy (LS) or salpingectomy for tubal pregnancy. Methods: This was a retrospective clinical study in a university hospital. Results: Of 43 women monitored for at least 6 months after LS, 28 (65%) subsequently conceived. In 24 (86%) of these women the pregnancy was intrauterine, and four (14%) had REP. Of 40 women with a unilateral tube monitored for at least 6 months after salpingectomy, 24 (60%) conceived. In 17 (71%) of these women the pregnancy was intrauterine, and seven (29%) had REP. There was no significant difference between groups in postoperative pregnancy or REP rates. There was no significant difference in the mean adhesion score by revised American Fertility Society stage points (re-AFS) at operation and the site of subsequent pregnancy in either the LS or the salpingectomy group, although the mean re-AFS score was significantly higher in women who had REP (3.1) than in those whose subsequent pregnancy was intrauterine (0.4). Conclusions: There was no significant difference in postoperative pregnancy or REP rates following previous LS or salpingectomy. The re-AFS score appeared to be an accurate predictor of the prognosis of subsequent pregnancies.

Background/purpose: The use of soft adhesives in the manufacture of pressure-sensitive adhesive tapes has recently increased. The dermal peeling force of adhesive tapes with soft adhesives was studied. Methods: Four kinds of adhesive tapes with adhesives of different softness were made, by adding varying amounts of isopropyl myristate as a softener. The tapes were applied on the flexor side of the forearm of six healthy male volunteers. The dermal peeling force, the amount of stripped corneocytes, the level of pain when the tapes were removed and the degree of penetration of adhesives into the sulcus cutis (skin furrows) were evaluated at 1 and 24 h after application of the tapes. Furthermore, a skin model panel (a sulcus cutis and crista cutis model panel) and a crista cutis model panel were constructed from a general stainless-steel panel, and the peeling force of the tapes against the model panels was measured. Results and conclusion: As the softness of adhesives increased, the peeling force against a general stainless-steel panel with a flat surface decreased, although the peeling force against human skin did not significantly change. The amount of stripped corneocytes on the removed tapes and the level of pain when the tapes were removed decreased with the increase in softness of the adhesives. These results suggest that adhesive tapes with soft adhesives that contain isopropyl myristate as a softener are suitable for the skin. Furthermore, the degree of penetration of adhesive into the sulcus cutis increased as the softness of adhesives increased. Upon evaluation of the peeling force against the model panels, as the softness of adhesives increased, there was a slight decrease in the peeling force against the skin model panel, while there was a remarkable decrease in the peeling force against the crista cutis model panel. These results suggest that the lack of change in the dermal peeling force as the softness of adhesives increased was caused by penetration of soft adhesive into the sulcus cutis, and that the decrease in the amount of stripped corneocytes was caused by a decrease in the peeling force against the crista cutis, which consists of corneocytes mainly removed by the tapes.

Rubber rollers and conveyor belts transport flexible sheet-type media. With high-speed belt transporting systems such as mail sorters, demand for an increase in speed may cause the belt to come off. Therefore, we have examined the effects of belt transport speed and other factors that may cause belt mistracking for a basic belt conveyor system, consisting of one flat belt and two crown-face rollers. Experiments were conducted and we have formulated an experimental expression of the amount of belt mistracking using the roller misalignment parameters. As for transport speed, a speed increase did not enlarge belt mistracking. This tendency was explained by applying the cornering force of automotive engineering. In parallel, simulation was conducted using commercial motion system analysis software. The qualitative tendencies of the belt mistracking from simulation and experiment were in good agreement and factorial effects were clarified for ten parameters. Quantitatively, when axial load on rollers and other parameters were made equal, the belt mistracking according to simulation was generally in agreement with the experimental value.