De novo Inflammatory Bowel Disease in Kidney Transplant Recipients: A Single-Center Case Series Study.

Introduction: Gastrointestinal complications are common after solid organ transplantation. New-onset inflammatory bowel disease (IBD) after transplantation (de novo) is a major differential diagnosis of diarrhea after liver transplantation (LT) because of its high incidence in the field. However, the incidence of IBD after kidney transplantation (KT) remains unknown. Methods: This case series comprised six de novo IBD patients who had undergone KT at our hospital from April 1998 to December 2020. In this period, 232 KT recipients were identified. Participants were analyzed based on their colonoscopy diagnoses. Detailed clinical information regarding both KT- and IBD-related symptoms or outcomes was obtained, and we calculated the incidence of de novo IBD from the date of KT. Results: Of the 232 recipients in the median observation period of 6.1 (interquartile range: 2.6, 10.8) years, six recipients (one with Crohn's disease and five with ulcerative colitis) were diagnosed with de novo IBD. The incidence of de novo IBD after KT was 355.8/100,000 person-years (95% confidence interval, 159.8-791.9 per 100,000 person-years). Bloody stools and diarrhea did not always occur, with bloody stools occurring in three and diarrhea in 2 patients at the time of diagnosis. No recipient developed graft failure or extraintestinal complications (e.g., IBD-related nephritis or arthritis). Conclusion: Despite a small sample size, this study's results indicate that the incidence of de novo IBD after KT may be similar to that after LT and higher than that in the general population. Larger studies are required to validate these preliminary findings.

Expression of mRNAs Encoding Hypothalamic Small Proteins, Neurosecretory Protein GL and Neurosecretory Protein GM, in the Japanese Quail, Coturnix japonica.

Neurosecretory protein GL (NPGL) and neurosecretory protein GM (NPGM) are novel neuropeptides that have been discovered in the hypothalamic infundibulum of chickens. NPGL and NPGM play important roles in lipid metabolism in juvenile chickens. The physiological functions of NPGL and NPGM in sexually mature birds remain unknown. The Japanese quail (Coturnix japonica) seems to be an appropriate model for analyzing NPGL and NPGM during sexual maturity. However, studies on NPGL or NPGM have yet to be reported in the Japanese quail. In the present study, we identified cDNAs encoding precursor proteins of NPGL and NPGM in the quail hypothalamus. In situ hybridization revealed that NPGL mRNA-expressing cells in the hypothalamus were localized in the infundibular nucleus and median eminence, and NPGM mRNA-expressing cells were only found in the mammillary nucleus. Immunohistochemistry revealed that NPGM-like immunoreactive cells were distributed in the mammillary nucleus, whereas NPGL-like immunoreactive cells were not detected in the hypothalamus. Real-time PCR analysis indicated that the expression of NPGL mRNA was higher in the hypothalamus of females than in that of males, and NPGM mRNA expression showed no sex differences. NPGL and NPGM mRNA expression in males was upregulated after 24 h of food deprivation. In females, only NPGM mRNA expression was increased by fasting. These results suggest that the physiological functions of NPGL and NPGM are different in quail, and these factors are involved in sex differences in energy metabolism.

Chirality-Induced Selectivity of Phonon Angular Momenta in Chiral Quartz Crystals.

A generation, propagation, and transfer of phonon angular momenta are examined on thermal transport in chiral insulative and diamagnetic crystals of α-quartz. We found that thermally driven phonons carry chirality-dependent angular momenta in the quartz crystals and they could be extracted from the quartz as a spin signal. Namely, chirality-induced selectivity of phonon angular momenta is realized in the chiral quartz. We argue that chiral phonons available in chiral materials could be a key element in triggering or enhancing chirality-induced spin selectivity with robust spin polarization and long-range spin transport found in various chiral materials.

Antidepressants available in Japan for older people with major depressive disorder: A systematic review and meta-analysis.

AIM: To update the major depressive disorder (MDD) treatment guidelines of the Japanese Society of Mood Disorders, we conducted a systematic review and pairwise meta-analysis of double-blind, randomized, placebo-controlled trials of available antidepressants in Japan for older adults with MDD. METHODS: Outcome measures included response rate (primary), improvement in depressive symptom scale score, remission rate, all-cause discontinuation, discontinuation due to adverse events, and at least one adverse event. A random-effects model was used to calculate the risk ratio (RR) and standardized mean difference (SMD) with a 95% confidence interval (95% CI). RESULTS: Nine double-blind, randomized, placebo-controlled trials (n = 2145) were identified. No study has been conducted in Japan. Our meta-analysis included the following antidepressants: duloxetine, escitalopram, imipramine, sertraline, venlafaxine, and vortioxetine. Antidepressants have significantly higher response rates than placebo (RR [95% CI] = 1.38 [1.04, 1.83], p = 0.02). Antidepressants outperformed placebo in terms of improving depressive symptom scale score (SMD [95% CI] = -0.62 [-0.92, -0.33], p < 0.0001). However, antidepressants were associated with a higher discontinuation rate due to adverse events (RR [95% CI] = 1.94 [1.30, 2.88], p = 0.001) and a higher incidence of at least one adverse event (RR [95% CI] = 1.11 [1.02, 1.21], p = 0.02) compared to placebo. The groups did not differ significantly in terms of remission rate or all-cause discontinuation. CONCLUSIONS: Our meta-analysis concluded that treatment with antidepressants available in Japan is only weakly recommended for moderate to severe MDD in older adults.

Goal Attainment Scaling for Depression: Validation of the Japanese GAS-D Tool in Patients with Major Depressive Disorder.

Purpose: Goal attainment scaling (GAS) has been proposed as a person-centric, semi-quantitative measure that assimilates achievement of individually set goals into a single standardized "goal attainment score" that can be compared at the population level. We aimed to examine the reliability and validity of the Japanese version of the GAS for depression (GAS-D) tool in assessing goal attainment in people living with major depressive disorder (MDD). Patients and Methods: This was a prespecified analysis of a prospective, 24-week, multicenter, observational cohort study of employed Japanese outpatients with MDD initiating treatment with vortioxetine according to the Japanese label (JRCT1031210200). Participants were assessed using the Japanese version of the GAS-D and other clinical rating scales at baseline and Weeks 8, 12 and 24. Results: Goal attainment was significantly associated with symptom severity as assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS) scale, confirming convergent validity. In particular, GAS-D scores were significantly related to MADRS total score at Weeks 12 and 24, indicating that improvements in overall symptom severity with vortioxetine treatment were likely to be reflected in the achievement of individualized treatment goals. With an intraclass correlation coefficient of 0.67 (95% CI 0.45-0.82), the GAS-D also showed moderate test-retest reliability between Weeks 8 and 12 while proving independent of demographic characteristics. Conclusion: The results of this open-label study support the use of the GAS-D as a valid and sensitive outcome measure in the assessment of treatment response in MDD.

Comparison of brexpiprazole, aripiprazole, and placebo for Japanese major depressive disorder: A systematic review and network meta-analysis.

AIM: This systematic review and frequentist network meta-analysis used random-effects models is conducted to determine whether there are differences in the efficacy, acceptability, tolerability, and safety profiles of brexpiprazole (BRE) and aripiprazole (ARI) for Japanese with major depressive disorder (MDD) who were inadequately responsive to antidepressants. METHODS: Outcome measures were scores on the Montgomery Åsberg Depression Rating Scale (primary), the Clinical Global Impression severity scale, and social functioning scale; the non-response rate; the non-remission rate; all-cause discontinuation; discontinuation due to adverse events (DAE); at least one adverse event (1AE); serious adverse event, akathisia; tremor; weight gain. RESULTS: A literature search identified three double-blind, randomized, placebo-controlled trials. These comprised one BRE study (with a 1 mg/day [BRE1] and a 2 mg/day [BRE2]) and two ARI studies (with a 3 mg/day arm and a flexible-dose arm[within the dosage range approved in Japan]) (n = 1736). Both BRE and ARI demonstrated better efficacy than the placebo. BRE but not ARI had a higher DAE than the placebo. ARI but not BRE had a higher 1AE than the placebo. BRE and ARI had a higher risk of akathisia and weight gain than the placebo. There were no significant differences between BRE and ARI for any of the outcomes. Although BRE1 had good efficacy, it carried risk of weight gain. Although BRE2 also had efficacy, it carried risks of DAE, akathisia, and weight gain. However, the risk of akathisia in BRE2 was reduced by an initial dose of 0.5 mg/day rather than 1.0 mg/day. CONCLUSIONS: Overall BRE showed similar utility to ARI and a good risk-benefit balance.

Adjunctive brexpiprazole 1 mg and 2 mg daily for Japanese patients with major depressive disorder following inadequate response to antidepressants: a phase 2/3, randomized, double-blind (BLESS) study.

AIMS: Inadequate antidepressant response interrupts effective treatment of major depressive disorder (MDD). The BLESS study evaluates the dosage, efficacy, and safety of brexpiprazole adjunctive therapy in Japanese patients with inadequate antidepressant therapy (ADT) response. METHODS: This placebo-controlled, randomized, multicenter, parallel-group phase 2/3 study randomized Japanese MDD patients (Hamilton Rating Scale for Depression 17-item total score ≥ 14; historical inadequate response to 1-3 ADTs) with inadequate response to 8-week single-blind, prospective SSRI/SNRI treatment to 6-week adjunctive treatment with brexpiprazole 1 mg, 2 mg, or placebo. The primary endpoint was change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score from baseline. Secondary endpoints included MADRS response, remission rate, and Clinical Global Impression-Improvement score. Safety was comprehensively evaluated, especially regarding antipsychotic adverse events (AEs). RESULTS: Of 1194 screened patients, 740 were randomized and 736 (1 mg, n = 248; 2 mg, n = 245; placebo, n = 243) had ≥1 baseline/post-baseline MADRS total score. The LSM (SE) change from baseline in MADRS total score at Week 6 by MMRM analysis was -8.5 (0.47) with brexpiprazole 1 mg, -8.2 (0.47) with brexpiprazole 2 mg, and -6.7 (0.47) with placebo (placebo-adjusted LSM difference [95% CI]: 1 mg, -1.7 [-3.0, -0.4]; P = 0.0089; 2 mg, -1.4 [-2.7, -0.1]; P = 0.0312). Secondary efficacy results supported the primary endpoint. Brexpiprazole was generally well tolerated. CONCLUSION: Brexpiprazole 1 mg daily was an appropriate starting dose and both 1 mg and 2 mg daily were effective and well tolerated as adjunctive therapy for Japanese MDD patients not adequately responsive to ADT.

Impact of genetic polymorphism on personalized diet and exercise program for steatotic liver disease.

AIMS: The effects of genetic polymorphism on a personalized diet and exercise program for steatotic liver disease (SLD) are still unclear. METHODS: Participants of this retrospective cohort study were 203 Japanese patients with SLD diagnosed by abdominal ultrasonography. All of them were introduced the personalized diet and exercise treatment. A diet of 25-30 kcal/kg multiplied by ideal body weight (BW) daily and aerobic and resistance exercise (exercise intensity of 4-5 metabolic equivalents daily, respectively) were performed for 6 days. Treatment efficacy was evaluated in terms of the rate of decrease of liver function tests, glycolipid metabolism markers, physical findings, image findings, and cardiovascular disease (CVD) risk score at 6 months compared with baseline. Furthermore, the impact of genetic polymorphism was also investigated. RESULTS: At 6 months compared with baseline, liver function tests (AST, ALT, γGTP), glycolipid metabolism markers (hemoglobin A1c, triglycerides [TG], low-density lipoprotein cholesterol), physical findings (BW, body mass index), image finding (liver stiffness measurement), and CVD risk score (Suita score) improved significantly. There was no significant difference in treatment efficacy, except for the rates of decrease of TG, according to genotype PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs6834314. The rates of decrease of TG with TM6SF2 CT were significantly higher than those with CC or TT, and the rates of TG with HSD17B13 AA were significantly higher than those with AG by multiple comparisons. CONCLUSION: Personalized diet and exercise program for SLD improved liver function tests, physical findings, glycolipid metabolism markers, and CVD risk score. Genetic polymorphism might partially affect treatment efficacy. Further studies should be performed to develop an individualized program for SLD, considering genetic polymorphism.

Real-world predictors of divorce among outpatients with bipolar disorder: sex differences and clinical implications.

BACKGROUND: Bipolar disorder is a mental illness characterized by recurring episodes of mania and depression and is known to cause social impairment. Additionally, it has been revealed that bipolar disorder increases the risk of divorce and loss of family member support, which can worsen the prognosis. However, there is limited evidence regarding the predictive factors of divorce among patients with bipolar disorder in real-world settings. METHODS: This study utilized an observational approach and involved psychiatrists from 176 member clinics of the Japanese Association of Neuro-Psychiatric Clinics. They were requested to conduct a retrospective review of medical records and complete a questionnaire focused on patients diagnosed with bipolar disorder. The data collection period for baseline patient characteristics spanned from September to October 2017. Next, we investigated the incidence of divorce over a 2-year period, ranging from baseline to September to October 2019. RESULTS: A total of 1071 outpatients with bipolar disorder were included in the analysis, and 2.8% (30/1071) experienced divorce during the first 2 years of observation. The incidence of divorce in this population was considerably higher than that in the general Japanese population. Binomial logistic regression analysis confirmed that a younger baseline age and lower BMI values were statistically significant predictors of divorce occurrence for all study participants. The predictors of divorce were then examined separately by sex. The results revealed that for men, a younger age at baseline and having bipolar I disorder compared to bipolar II disorder were statistically significant predictors of divorce. In contrast, for women, having a lower BMI and using anxiolytics emerged as statistically significant predictors of divorce. CONCLUSIONS: In this study, a younger baseline age and lower BMI values were statistically significant predictors of divorce in patients with bipolar disorder. Notably, the predictors of divorce varied significantly between men and women. These findings provide important insights from a family perspective regarding social support for individuals with bipolar disorder in real-world clinical settings.

Neurosecretory Protein GM-Expressing Neurons Participate in Lipid Storage and Inflammation in Newly Developed Cre Driver Male Mice.

Obesity induces inflammation in the hypothalamus and adipose tissue, resulting in metabolic disorders. A novel hypothalamic neuropeptide, neurosecretory protein GM (NPGM), was previously identified in the hypothalamus of vertebrates. While NPGM plays an important role in lipid metabolism in chicks, its metabolic regulatory effects in mammals remain unclear. In this study, a novel Cre driver line, NPGM-Cre, was generated for cell-specific manipulation. Cre-dependent overexpression of Npgm led to fat accumulation without increased food consumption in male NPGM-Cre mice. Chemogenetic activation of NPGM neurons in the hypothalamus acutely promoted feeding behavior and chronically resulted in a transient increase in body mass gain. Furthermore, the ablated NPGM neurons exhibited a tendency to be glucose intolerant, with infiltration of proinflammatory macrophages into the adipose tissue. These results suggest that NPGM neurons may regulate lipid storage and inflammatory responses, thereby maintaining glucose homeostasis.

Persistent Homology Analysis of the Microstructure of Laser-Powder-Bed-Fused Al-12Si Alloy.

The laser powder bed fusion (L-PBF) process provides the cellular microstructure (primary α phase surrounded by a eutectic Si network) inside hypo-eutectic Al-Si alloys. The microstructure changes to the particle-dispersed microstructure with heat treatments at around 500 °C. The microstructural change leads to a significant reduction in the tensile strength. However, the microstructural descriptors representing the cellular and particle-dispersed microstructures have not been established, resulting in difficulty in terms of discussion regarding the structure-property relationship. In this study, an attempt was made to analyze the microstructure in L-PBF-built and subsequently heat-treated Al-12Si (mass%) alloys using the persistent homology, which can analyze the spatial distributions and connections of secondary phases. The zero-dimensional persistent homology revealed that the spacing between adjacent Si particles was independent of Si particle size in the as-built alloy, whereas fewer Si particles existed near large Si particles in the heat-treated alloy. Furthermore, the first principal component of a one-dimensional persistent homology diagram would represent the microstructural characteristics from cellular to particle-dispersed morphology. These microstructural descriptors were strongly correlated with the tensile and yield strengths. This study provides a new insight into the microstructural indices describing unique microstructures in L-PBF-built alloys.

Assessing Reliability and Validity of the Oxford Depression Questionnaire (ODQ) in a Japanese Clinical Population.

Purpose: Originally developed in English, the Oxford Depression Questionnaire (ODQ) is a patient-reported scale specifically developed for assessing emotional blunting in people with major depressive disorder (MDD). We aimed to examine the reliability and validity of the Japanese version of the ODQ. Patients and methods: This was a prespecified analysis of a prospective, 24-week, multicenter, observational cohort study of employed Japanese outpatients with MDD initiating treatment with vortioxetine according to the Japanese label (JRCT1031210200). Participants were assessed using the Japanese version of the ODQ and other clinical rating scales at baseline and Weeks 8, 12 and 24. Results: One hundred and sixteen patients initiated vortioxetine and had ≥1 post-baseline visit. Directionally, the associations between ODQ scores and other clinical measures were as expected and demonstrated good concurrent validity. Factor analysis shows that the scale has a good fit for three factors. The Cronbach's α coefficient was 0.912, and the scale also showed good test-retest reliability with intraclass correlation coefficients for the ODQ total score and domains ranging between 0.69 and 0.82. ODQ scores had strong positive correlations with symptom severity assessed using the Montgomery and Åsberg Depression Rating Scale and were moderately correlated with work productivity, overall functioning, and quality of life scales. Conclusion: Data from this prospective analysis confirm that the Japanese version of the ODQ retains the good validity and reliability of the original English scale and is suitable for use in prospective studies wanting to capture treatment effects on emotional blunting in MDD.

Optimal dose for the efficacy of asenapine in patients with schizophrenia: Real-world data.

AIMS: A meta-analysis of short-term studies revealed no significant differences between the doses of asenapine, 10 and 20 mg/day, in the acute treatment of schizophrenia. However, it should be noted that many patients from clinical practice were excluded, and the dose-response to asenapine in a real-world setting is still unclear. Additionally, the dose-response in the maintenance phase is not clear. This study aimed to evaluate the differences in the efficacy of different asenapine doses in patients with maintenance phase of schizophrenia in a real-world setting. METHODS: This study conducted post-marketing surveillance of asenapine in clinical settings in Japan. It followed patients diagnosed with schizophrenia who received asenapine for the first time for a maximum of 52 weeks. These patients were divided into two categories based on their average daily asenapine dosage: ≤10 mg/day and >10 mg/day. Asenapine efficacy was assessed by adjusting for patient demographics using multivariate logistic regression analysis, employing the Clinical Global Impression-Global Improvement (CGI-I) scale, which has seven categories. RESULTS: A total of 2774 patients were included in the analysis. Of these, 1689 and 1085 patients were treated with asenapine ≤10 mg/day and >10 mg/day, respectively. The CGI-I improvement rate was significantly higher in the asenapine >10 group (p = 0.012) after adjusting for patient background factors. CONCLUSION: These results suggest that asenapine doses >10 mg/day may be more effective than 10 mg/day in the treatment of schizophrenia; however, further studies are needed to confirm these findings.

Acute kidney injury is an unfavorable prognostic factor in acute liver failure and is associated with tumor necrosis factor-alpha.

Acute kidney injury (AKI) is a common complication of acute liver failure (ALF); but its pathogenesis is unknown. ALF was divided into 2 subgroups; ALF with hepatic coma, which corresponds to ALF in the US and Europe, and ALF without hepatic coma. AKI has been shown to worsen the prognosis of ALF patients with hepatic coma; however, its prognostic significance in ALF without hepatic coma remains unknown. A single-center retrospective study of 174 patients with ALF was performed. AKI was defined according to KDIGO criteria. AKI developed in 29 (66.0%) of 44 ALF patients with hepatic coma and 27 (38.5%) of 130 ALF patients without hepatic coma. Systemic inflammatory response syndrome (SIRS) was found to be significantly associated with AKI incidence in ALF patients (P < .001). Tumor necrosis factor-alpha (TNF-α) was found to be significantly associated with the presence and severity of AKI (P = .0039 and P = .0140, respectively). On multivariate analysis, TNF-α was an independent risk factor linked with AKI (P = .0103). Even in the absence of hepatic coma, the transplant-free survival rate of ALF was significantly associated with the presence and severity of AKI. Even when hepatic coma is absent, AKI complicated in ALF is strongly associated with TNF-α and worsens the transplant-free survival rate. Before the onset of hepatic coma, plasma exchange, or extracorporeal blood purification to remove inflammatory cytokines should be considered in ALF patients.

Characteristics of persistent depression in the long-term: Randomized controlled trial and two-year observational study.

Major depressive disorder is a chronic condition that can recur and relapse. It would be clinically useful to know the patient background to predict the chronicity of depressive symptoms, and the change in diagnosis of bipolar disorder. This study included 197 patients enrolled in a six-week randomized controlled trial with a two-year follow-up. We conducted multiple logistic regression analyses to identify the clinical and sociodemographic characteristics associated with persistent depressive disorder (PDD), relapse, and changes in bipolar disorder diagnosis. The significantly correlated factors were residual symptoms, including insight, work and activity, and general somatic symptoms at week six. We could not identify any factors that contributed to relapse or change in the diagnosis of bipolar disorder. We found that the specific residual symptoms of acute treatment affected long-term treatment outcomes for depression. Attention should be paid to the residual symptoms of depression in the early stages of treatment, and measures should be considered to improve them. There are several limitations to this study, including the fact that PDD may exist among patients who discontinued treatment, treatment was not standardized during the study period, and adherence was confirmed verbally.

Usefulness of mirtazapine and SSRIs in late-life depression: post hoc analysis of the GUNDAM study.

OBJECTIVE: Mirtazapine and SSRIs are widely prescribed as first-line agents for late-life depression. However, evidence for these drugs is mostly based on non-elderly patients. Therefore, we reanalyzed a randomized controlled trial of mirtazapine versus SSRIs for depression in a sub-population of late-life patients. METHODS: A randomized controlled trial was conducted with 141 patients, of whom 41 were elderly, and 100 were non-elderly. This study compared SSRIs and mirtazapine in late-life depression, examined late-onset and early adult-onset separately and compared elderly and non-elderly patients for each drug. Treatment effects and adverse events were assessed using the Hamilton Depression Rating Scale and the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale, respectively. RESULTS: In late-life depression, mirtazapine showed faster HAM-D total score improvement (3.3 points difference, p = 0.021) and higher improvement in insomnia (1.7 points difference, p = 0.001) and appetite (1.2 points difference, p = 0.020). Similar findings were observed for late-onset depression with the HAM-D total score (4.3 points difference, p = 0.007) and appetite (0.9 points difference, p = 0.004), favoring mirtazapine. Depressive symptoms were generally less improved in late-life depression than in non-late-life depression. Regarding the effect of mirtazapine on appetite, late-life depression showed greater improvement (0.7 points difference, p = 0.008). Nausea and micturition disturbances were more common with SSRIs in late-life depression than in non-late-life depression. In contrast, somnolence was less common in late-life depression with mirtazapine. CONCLUSION: The potential usefulness of mirtazapine in elderly patients was demonstrated. The results also showed differences in the treatment response to SSRIs and mirtazapine between elderly and non-elderly patients.

Newer antidepressant for Japanese adults with major depressive disorder: A systematic review and meta-analysis.

INTRODUCTION: The question remains to be elucidated: "Is treatment with antidepressants at doses approved in Japan effective for Japanese patients with MDD?" It is crucial to confirm this in order to provide appropriate treatments for Japanese patients with major depressive disorder (MDD). Therefore, we conducted a systematic review and random-effects pairwise meta-analysis including these nine double-blind, randomized, placebo-controlled trials. METHODS: We calculated the standardized mean difference (SMD) and risk ratio (RR) with a 95% confidence interval (95% CI). RESULTS: Pooled newer antidepressants outperformed placebo regarding improvement of depressive symptom scale scores [SMD (95% CI) = -0.20 (-0.27, -0.12), p < 0.00001], response to treatment [RR (95% CI) = 1.23 (1.13, 1.32), p < 0.00001], and remission rate [RR (95% CI) = 1.30 (1.16, 1.45), p < 0.00001]. Although all-cause discontinuation was not significantly different between the treatment groups, the pooled antidepressant group showed a higher discontinuation rate due to adverse event [RR (95% CI) = 1.60 (1.13, 2.26), p = 0.007] and a higher incidence of at least one adverse event than the placebo group [RR (95% CI) = 1.13 (1.08, 1.18), p < 0.00001]. DISCUSSION: We concluded that newer antidepressants are effective for Japanese adults with MDD although the clinicians must monitor the health conditions of these individuals.

Feasibility of a wrist-worn wearable device for estimating mental health status in patients with mental illness.

Object: Real-world data from wearable devices has the potential to understand mental health status in everyday life. We aimed to investigate the feasibility of estimating mental health status using a wrist-worn wearable device (Fitbit Sense) that measures movement using a 3D accelerometer and optical pulse photoplethysmography (PPG). Methods: Participants were 110 patients with mental illnesses from different diagnostic groups. The study was undertaken between 1 October 2020 and 31 March 2021. Participants wore a Fitbit Sense on their wrist and also completed the State-Trait Anxiety Inventory (STAI), Positive and Negative Affect Schedule (PANAS), and EuroQol 5 dimensions 5-level (EQ-5D-5L) during the study period. To determine heart rate (HR) variability (HRV), we calculated the sdnn (standard deviation of the normal-to-normal interval), coefficient of variation of R-R intervals, and mean HR separately for each sleep stage and the daytime. The association between mental health status and HR and HRV was analyzed. Results: The following significant correlations were found in the wake after sleep onset stage within 3 days of mental health status assessment: sdnn, HR and STAI scores, HR and PANAS scores, HR and EQ-5D-5L scores. The association between mental health status and HR and HRV was stronger the closer the temporal distance between mental health status assessment and HR measurement. Conclusion: A wrist-worn wearable device that measures PPG signals was feasible for use with patients with mental illness. Resting state HR and HRV could be used as an objective assessment of mental health status within a few days of measurement.

Lysophosphatidylglucoside/GPR55 signaling promotes foam cell formation in human M2c macrophages.

Atherosclerosis is a major cause of cerebral and cardiovascular diseases. Intravascular plaques, a well-known pathological finding of atherosclerosis, have a necrotic core composed of macrophages and dead cells. Intraplaque macrophages, which are classified into various subtypes, play key roles in maintenance of normal cellular microenvironment. Excessive uptake of oxidized low-density lipoprotein causes conversion of macrophages to foam cells, and consequent progression/exacerbation of atherosclerosis. G-protein-coupled receptor 55 (GPR55) signaling has been reported to associate with atherosclerosis progression. We demonstrated recently that lysophosphatidylglucoside (lysoPtdGlc) is a specific ligand of GPR55, although in general physiological ligands of GPR55 are poorly understood. Phosphatidylglucoside is expressed on human monocytes and can be converted to lysoPtdGlc. In the present study, we examined possible involvement of lysoPtdGlc/GPR55 signaling in foam cell formation. In monocyte-derived M2c macrophages, lysoPtdGlc/GPR55 signaling inhibited translocation of ATP binding cassette subfamily A member 1 to plasma membrane, and cholesterol efflux. Such inhibitory effect was reversed by GPR55 antagonist ML193. LysoPtdGlc/GPR55 signaling in M2c macrophages was involved in excessive lipid accumulation, thereby promoting foam cell formation. Our findings suggest that lysoPtdGlc/GPR55 signaling is a potential therapeutic target for inhibition of atherosclerosis progression.