IntroductionMembrane phospholipid abnormalities are considered a pathophysiological background for schizophrenia. The aim of the study was to explore in detail the fatty acid (FA) composition in patients with antipsychotic-free schizophrenia and its association with clinical symptoms and cognitive function.Materials and methodsErythrocyte membrane FAs were measured in 29 antipsychotic-free patients with schizophrenia (male/female = 11/18; mean [standard deviation] age=26.7 [7.9] years) and age and sex-matched 32 healthy volunteers. Clinical symptoms and cognitive function were assessed using the Positive and Negative Syndrome Scale (PANSS), Brief Assessment of Cognition in Schizophrenia (BACS), and the Schizophrenia Cognition Rating Scale (SCoRS).ResultsEicosapentaenoic acid levels were lower in the schizophrenia group than in the healthy control group. In contrast, arachidonic acid and nervonic acid levels were higher in the schizophrenia group than in the control group. Nervonic acid levels were significantly associated with depression scores as measured by the PANSS. No FA levels were correlated with BACS score; however, oleic acid levels were significantly related to cognitive dysfunction, as measured by the SCoRS.ConclusionThese findings suggest that depressive symptoms along with cognitive dysfunction in daily living in schizophrenia may be linked to the FA composition abnormalities. Further studies will be needed to examine potential longitudinal FA changes during the course of schizophrenia as well as disease specificity.

IntroductionAbnormalities in membrane phospholipids are considered one of the pathophysiological backgrounds for schizophrenia. This study, explores the fatty acid composition of erythrocyte membranes and its association with clinical characteristics in two groups: individuals with an at-risk mental state (ARMS) and patients experiencing their first-episode of schizophrenia (FES). Materials and methodsThis study measured erythrocyte membrane fatty acids in 72 antipsychotic-free individuals with ARMS, 18 antipsychotic-free patients with FES, and 39 healthy volunteers. Clinical symptoms and cognitive and social functions were assessed using the Positive and Negative Syndrome Scale (PANSS), Brief Assessment of Cognition in Schizophrenia (BACS), Schizophrenia Cognition Rating Scale (SCoRS), and Social and Occupational Functioning Assessment Scale (SOFAS). ResultsEicosapentaenoic and docosapentaenoic acid levels were lower in the ARMS and FES groups than in the healthy control group. In contrast, nervonic acid (NA) levels were markedly higher in the ARMS and FES groups than in the controls, while only the FES group showed higher levels of arachidonic acid. Oleic acid and NA levels were significantly associated with PANSS scores in both the FES and ARMS groups, particularly for the negative and general subscores. However, the patient groups had no significant associations between the fatty acid composition and the BACS, SCoRS, and SOFAS scores. Furthermore, the baseline fatty acid composition did not differ between the ARMS individuals who later developed psychosis (N = 6) and those who were followed for more than 2 years without developing psychosis onset (N = 30). DiscussionThe findings suggest that abnormal fatty acid compositions may be shared in the early stages of schizophrenia and the clinical high-risk state for psychosis and may serve as vulnerability markers of psychopathology.

Background and Aims: Although culture conditions were recognized as key points, an optimal culture medium formulation, which closely resembles natural human oviduct fluid (HOF), has not been obtained yet. Our aim is to make an ideal embryo culture medium close to HOF components, and to evaluate the quality of this medium with embryo quality and clinical outcomes in assisted reproductive technology (ART) by a prospective randomized controlled trial (RCT). Method: Study I: HOF was collected laparoscopically from patients (n = 28) with normal pelvic findings. According to HOF analysis results, the new medium ‘OVIT’ was designed. Study II: Embryos (2 pronuclei (2PN) = 9,633) were assigned from 1,435 patients. The blastulation rate (BR), good BR (gBR), utilized (transferred/cryo-preserved) BR (uBR), pregnancy rate (PR), and miscarriage rate (MR) were compared between the OVIT and control groups by RCT. Study III: The neonatal healthiness who were concepted by ART using OVIT and /or control medium was compared between two groups. Results: The novel medium ‘OVIT’ was produced according to 31 HOF components. The concentrations of essential amino acids (e-AAs) were lower in OVIT than in current media, yet the opposite was true for non-e-AA concentrations. gBR and uBR were higher in the OVIT group than in the control group. In the older female group, gBT and uBR were significantly higher in the OVIT group. The neonatal conditions of those who were born by ART using OVIT and/or control medium were similar. Conclusion: HOF components and AA concentrations were analysed, and the results indicated numerous differences between OVIT and current media. This medium provides a better culture condition and improves embryo quality. This study has found novel perspectives for older patients having difficulties in producing embryos of good quality and indicated the superior quality of OVIT compared with the quality of traditional media.

AbstractPurposeOur aim is to make an ideal embryo culture medium close to human oviduct fluid (HOF) components, and to evaluate the quality of this medium with embryo quality and clinical outcomes in assisted reproductive technology (ART) by a prospective randomized controlled trial (RCT).MethodsStudy I: HOF was collected laparoscopically from patients (n = 28) with normal pelvic findings. According to HOF analysis results, the new medium “HiGROW OVIT®” (OVIT) was designed. Study II: Embryos (2 pronuclei (2PN) = 9633) were assigned from 1435 patients. The blastulation rate (BR), good BR (gBR), utilized (transferred/cryo‐preserved) BR (uBR), pregnancy rate (PR), and miscarriage rate (MR) were compared between the OVIT and control groups by RCT.ResultsThe novel medium ‘OVIT’ was produced according to 31 HOF components. The concentrations of essential amino acids (e‐AAs) were lower in OVIT than in current media, yet the opposite was true for ne‐AA concentrations. gBR and uBR were higher in the OVIT group than in the control group. In the older female group, gBT and uBR were significantly higher in the OVIT group.ConclusionsThe novel medium ‘OVIT’ was produced according to HOF data. The OVIT had significantly better embryo quality and clinical outcomes than the current media.

Accumulating evidence implicates oxidative stress as a potential pathophysiological mechanism of schizophrenia. Accordingly, we synthesized new chemicals using apocynin and tandospirone as lead compounds (A-2, A-3 and A-4). These novel compounds decreased reactive oxygen species (ROS) concentrations in vitro and reversed decreases in glutathione levels in the medial prefrontal cortex of rats transiently exposed to MK-801, an N-methyl-d-aspartate receptor antagonist, in the neonatal period. To determine whether A-2, A-3 and A-4 show behavioral effects associated with antipsychotic properties, the effects of these compounds on methamphetamine (MAP)-induced locomotor and vertical activity were examined in the model rats. A-2 and A-3, administered for 14 days around the puberty period, ameliorated MAP-induced hyperlocomotion in MK-801-treated rats in the post-puberty period, while A-4 suppressed MAP-induced vertical activity. These findings indicate that apocynin-tandospirone derivatives present anti-dopaminergic effects and may alleviate psychotic symptoms of schizophrenia.

Antipsychotic medications based on the dopamine hypothesis possess limited effects for negative symptoms and cognitive impairments of schizophrenia. Growing body of evidence suggests that redox dysregulation contributes to the pathophysiology of the illness. We synthesized new chemicals using apocynin and tandospirone as leading compounds, and tested their antioxidant properties. The new compounds (A-1, A-2, A-3, and A-4), olanzapine (OLA), and clozapine (CLZ) were examined in terms of the ⋅OH radical decreasing activity and the effects on intracellular reactive oxygen species (ROS) formation induced by X-irradiation in human lymphoma U937 cells. The effects of these drugs, given around the period of puberty (postnatal days; PD 49 to 62), on glutathione (GSH) levels, as well as the number of parvalbumin (PV)-positive γ-aminobutyric acid (GABA) interneurons were evaluated in the medial prefrontal cortex (mPFC) of rats transiently exposed to MK-801 in the neonatal period. A-2, A-3, A-4, OLA, and CLZ decreased intracellular ⋅OH and OCl−. The novel compounds reversed the decrease in GSH concentrations and reduction of PV-positive neurons in the mPFC in the model rats. CLZ only decreased GSH levels while OLA did not show a significant effect on either measure. These findings suggest that the new compounds derived from apocynin and tandospirone elicit antioxidant properties, and may provide a novel therapeutic approach for the treatment of schizophrenia and its spectrum disorders.

Sequential and single step media are the most widely used for embryo cultures in IVF. There is no medium which designed from human oviductal fluid. Almost all media that available to use at present are derived and arranged from previous somatic cell culture media. In 2017, the medium (HiGROW OVIT; Fuso Pharma, Japan) composed of amino acid concentrations by the data of human oviductal fluid became available to use in Japan, which contained different concentrations of amino acids from previous media. In this study, we examine the clinical availability of the new media in terms of utilization of embryos and giving birth to healthy baby in IVF. prospective randomized trial. Human oviductal fluid was aspirated laparoscopically from 28 women aged 26–39 years with no major intrapelvic abnormality to formulate new embryo culture medium. Liquid chromatography with tandem quadruple mass spectrometry and ion chromatography were used to analyze 31 components of the oviductal fluid sample. We conducted an RCT to evaluate the medium using 3,418 embryos obtained from 674 cycles of patients who underwent IVF or intracytoplasmic sperm injection (ICSI) between September 2017 and March 2019. Before fertilization, the oocytes were divided into two groups: cultures using the new medium composed of human oviductal amino acid (OVIT); and cultures using current medium (Medium A). The embryo grade during culture period to the blastocyst stage and clinical outcome after embryo transfer were compared between the OVIT group and the Medium A group. Between the two groups, patient characteristics were not significantly different. The number of embryos in the OVIT group on day 3 which showed "8-cell 2-grade" by Veeck's criterion, was larger (18.6% (318/1,709)) than in the Medium A group (14.1% (241/1,709)); P<0.01. The OVIT group showed significantly higher rates of blastocyst development (62.4% (1,024/1,641)) than the Medium A group (58.5% (961/1,643)); P<0.05). The number of embryos which were elected for ET or cryopreserved was larger in the OVIT group (44.4% (759/1,709)) compared with the Medium A group (37.2% (636/1,709)); P<0.01. Furthermore, in the OVIT group had higher implantation rates (28.1% (124/442)) after ET than that in the Medium A group (25.5% (94/368); the difference was not statistically different. Birth weight of the OVIT group was 3,179.2±473.3 grams (n=39) and the Medium A group was 3,087.1±409.1 grams (n=28). The ratio of male to female was 20/19 in the OVIT group (n=39), and 10/16 in the Medium A group (n=26). One trismus nascentium child was confirmed in the OVIT group and one congenital ear fistula child was confirmed in the Medium A group. Medium composed of human oviductal amino acids enhances embryonic ability more than the current single step medium, and it may make a contribution to clinical success in IVF treatment.

We present the result of a multi-longitude campaign on the photometric study of the dwarf nova ASASSN-18fk during its superoutburst in 2018. It was observed with 18 telescopes at 15 sites during ~70 nights within a three-month interval. Observations covered the main outburst, six rebrightenings and 50-d decline to a near-quiescent state. We identify ASASSN-18fk as WZ Sge-type dwarf nova with multiple rebrightenings and show the evolution of the 0.06-d superhump period over all stages of the superoutburst. A strong 22-min brightness modulation that superimposed on superhumps is found during rebrightenings and decline. Some evidence of this modulation in a form of a sideband signal is detected during the very onset of the outburst. We interpret the 22-min modulation as a spin period of the white dwarf and suggest that ASASSN-18fk is a good candidate for a superhumping intermediate polar.

Olfactory impairment has been reported in patients with schizophrenia and individuals with a high risk of psychosis, but its neural basis is largely unknown. We used magnetic resonance imaging to investigate the morphology of the olfactory sulcus (an indicator of olfactory system development) and its relation to olfactory function in 38 persons with an at-risk mental state (ARMS), 62 patients with schizophrenia, and 61 healthy controls. Odor detection and identification were examined with a T & T olfactometer. Compared with the controls, the olfactory sulcus was significantly shallower and odor identification was inferior among the ARMS and schizophrenia subjects. Across all subjects, but not within each group, the olfactory sulcus depth was significantly related to better identification of odors. Our results support the concept that olfactory sulcus morphology reflects the neurodevelopmental process of the olfactory system.

Continuous failures to achieve a pregnancy despite effective embryo transfers is extremely distressing for couples. In consequence, many adjuvant therapies to IVF have been proposed to achieve an “ideal” immune environment. We here focus on Intralipid® therapy (IL) reported to have immunosuppressive properties on NK cells.94 patients exhibited an immune profile of endometrial over-immune activation and an history of repeated implantation failures despite multiple embryos transfers (RIF). They received a slow perfusion of Intralipid®. We here report the live birth rate following the procedure at the next embryo transfer. To get new insight on its mechanism of action, a second immune profiling had been performed under Intralipid® before the embryo transfer.The live birth rate of the RIF cohort treated with Intralipid® reached 54% (51/94) at the next embryo transfer. In patients successfully pregnant under Intralipid® who benefitted of a test of sensibility before the embryo transfer, we observed a significant decrease of the three biomarkers used to diagnose the over-immune endometrial activation (CD56 cells; IL-18/TWEAK, IL-14/FN-14).Double blind placebo versus Intralipid® studies should be conducted. Intralipid® may be an option to explore in RIF patients who exhibit an over-immune activation of uNK cells.

Odor identification deficits are well documented in patients with schizophrenia, but it remains unclear whether individuals at clinical high-risk for psychosis exhibit similar changes and whether their olfactory function is related to social/cognitive functions and symptomatology. In this study, we investigated odor detection sensitivity and identification ability in 32 individuals with at-risk mental state (ARMS), 59 schizophrenia patients, and 169 healthy controls using a T&T olfactometer. The ARMS and schizophrenia subjects were administered the Brief Assessment of Cognition in Schizophrenia (BACS), the Schizophrenia Cognition Rating Scale (SCoRS), and the Social and Occupational Functioning Assessment Scale (SOFAS) to assess their cognitive and social functions, and the Positive and Negative Syndrome Scale (PANSS) for clinical symptoms. Both the ARMS and schizophrenia subjects had lower odor identification ability when compared with healthy controls, while no significant difference was found in the odor detection sensitivity. The lower odor identification ability in the ARMS group correlated with the severity of negative symptoms and weakly correlated with lower performance on the BACS verbal fluency test. The olfactory measures of schizophrenia patients did not correlate with illness duration, medication, symptom severity, and social and cognitive functions. For the ARMS and schizophrenia groups, the olfactory measures did not correlate with the SOFAS and SCoRS scores. These findings suggest that high-risk subjects for psychosis already show odor identification deficits similar to those observed in schizophrenia patients, which probably reflect a biological trait related to vulnerability to psychosis.

The antimetastatic effect of peptidoheteroglycan（FA-1a）and╱or 5-FU was examined in an experimental model of lung metastases induced by Lewis lung carcinoma in mice. Injection of FA-1a i. p. after removal of the implanted primary tumor inhibited the development of lung metastases. Combination treatment with FA-1a and 5-FU inhibited significantly the lung metastases. Lung metastases were inhibited by i. v. injection of FA-1a︱activated adherent peritoneal exudate cells（PEC）, and these cells showed the direct cytocidal action on tumor cells. FA-1a depressed aniline hydroxylase and aminopyrine demethylase activities of the hepatic microsomal drug-metabolizing system in tumor-bearing mice. Moreover, the concentration of 5-FU in the tissues（lung, liver, kidney, spleen, and blood）was increased significantly by coadministration of FA-1a. These findings raise the possibility that FA-1a may have clinical value in the prevention of cancer metastasis.

We purified a peptidoheteroglycan (FA-1a) from Chlorella pyrenoidosa and investigated its effects on the third component of complement (C3) and peritoneal macrophages activation. In crossed immunoelectrophoresis, human serum C3 was converted by FA-la and ATSO (positive control), and appeared as the third peak (converted C3). After oral administration (p.o.) of FA-la to mice, the binding of C3 cleavage product (C3b) to peritoneal macrophages and the proportion of C3 positive cells were increased as shown by the immunotluorescent antibody technique. These activated macrophages enhanced phagocytosis of polystyrene latex beads. This is the first report showing that p.o. of FA-la prepared from Chlorella pyrenoidosa is capable of activating C3 and macrophages. The present results indicate that FA-la may open new perspectives in immuno-chemotherapy.

Navigator error is estimated to cause about 79% of all ship collisions in Japan. It is highly possible that there are many navigators' errors not leading to serious ship collisions. To understand navigator errors, an experimental study on navigator erroneous behavior in navigational watch-keeping was conducted. By use of a cognition and activity model for watch-keeping task, which is developed based on Endsley's situation awareness model, we analyzed navigators' skills to focus attention on a ship with collision hazard. Two types of errors that may cause ship collisions were identified, and their causing factors were discussed. One of identified errors was delay of perception, and this error meant that navigators detected a ship with collision hazard late. Another error was oversight, and this error meant that navigators did not pay attention to proper ship.

Aims While olfaction is a sense closely associated with the limbic system and emotions, the relation between emotional status and olfactory functioning has not been well documented. This study aimed to examine the possible effect of anxiety on olfaction in healthy subjects. Methods We investigated the effect of state and trait anxiety on the detection and recognition thresholds for five different odors in 124 healthy subjects (62 men and 62 women, mean age = 27.2 years) using a T&T olfactometer. Results While the influences of age, socioeconomic status, IQ , and smoking history on olfaction were not significant, women had a lower recognition threshold for the odor of sweet fruit and a higher detection threshold for that of rotten food as compared with men. Both state and trait anxiety ratings were significantly associated with reduced olfactory ability, especially for identification of rose odor. Conclusions These findings suggest that emotional status affects olfactory functioning in healthy subjects. Our findings may also partly explain the mild olfactory impairment reported in clinical conditions, such as anxiety disorders.