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Background: For psychotic disorders (i.e. schizophrenia), pharmacotherapy plays a key role in controlling acute and long-term symptoms. To find the optimal individual dose and dosage strategy, specialised tools are used. Three tools have been proven useful to personalise drug treatments: therapeutic drug monitoring (TDM) of drug levels, pharmacogenetic testing (PG), and molecular neuroimaging., Methods: In these Guidelines, we provide an in-depth review of pharmacokinetics, pharmacodynamics, and pharmacogenetics for 45 antipsychotics. Over 30 international experts in psychiatry selected studies that have measured drug concentrations in the blood (TDM), gene polymorphisms of enzymes involved in drug metabolism, or receptor/transporter occupancies in the brain (positron emission tomography (PET))., Results: Study results strongly support the use of TDM and the cytochrome P450 (CYP) genotyping and/or phenotyping to guide drug therapies. Evidence-based target ranges are available for titrating drug doses that are often supported by PET findings., Conclusion: All three tools discussed in these Guidelines are essential for drug treatment. TDM goes well beyond typical indications such as unclear compliance and polypharmacy. Despite its enormous potential to optimise treatment effects, minimise side effects and ultimately reduce the global burden of diseases, personalised drug treatment has not yet become the standard of care in psychiatry.

Purpose: To investigate the incidence and prognostic factors of ocular sequelae in Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) cases arising between 2016 and 2018 in Japan, and compare the findings with those presented in the previous 2005-2007 survey., Design: Retrospective, national trend survey., Methods: Dermatologic case report forms (CRFs) (d-CRFs) were sent to 257 institutions that treated at least 1 SJS/TEN case, and 508 CRFs were collected from 160 institutions. Ophthalmologic CRFs (o-CRFs) regarding patient demographic data, onset date, ocular findings (first appearance, day of worst severity, and final follow-up), topical treatment (betamethasone), outcome (survival or death), and ocular sequelae (visual disturbance, eye dryness) were sent to the ophthalmologists in those 160 institutions. The results of this survey were then compared with that of the previous 2005-2007 survey., Results: A total of 240 cases (SJS/TEN: 132/108) were included. The incidence of ocular sequelae incidence was 14.0%, a significant decrease from the 39.2% in the previous survey (SJS/TEN: 87/48). In 197 (82.1%) of the cases, systemic treatment was initiated within 3 days after admission, an increase compared to the previous survey (ie, treatment initiated in 82 [60.7%] of 135 cases). Of the 85 cases with an Acute Ocular Severity Score of 2 and 3, 62 (72.9%) received corticosteroid pulse therapy and 73 (85.9%) received 0.1% betamethasone therapy; an increase compared to the 60.0% and 70.8%, respectively, in the previous survey. Ocular-sequelae-associated risk factors included Acute Ocular Severity Score (P < .001) and specific year in the survey (P < .001)., Conclusions: The ophthalmologic prognosis of SJS/TEN has dramatically improved via early diagnosis, rapid assessment of acute ocular severity, and early treatment., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: A high-risk patent foramen ovale (PFO) could be the cause of cryptogenic stroke, and an atrial septal aneurysm (ASA) increases the risk of stroke recurrence in cryptogenic stroke patients with a patent foramen ovale (PFO). Factors related to stroke recurrence according to PFO characteristics have not been fully evaluated., Methods: Data from a multicenter, observational registry of ischemic stroke patients undergoing transesophageal echocardiography were used for this study. Patients were classified into three groups: high-risk PFO, PFO with large shunt (≥20 microbubbles) or ASA; right-to-left shunt (RLS), RLS including PFO with <20 microbubbles or without ASA, or pulmonary arteriovenous fistula; and negative RLS. Cox proportional hazards regression analysis was used to explore the factors related to stroke recurrence in these three groups., Results: In total, 586 patients (185 females; 65.5±13.2 years) were analyzed. In cryptogenic stroke (329 patients) with median follow-up of 4.2 (interquartile range, 1.0-6.1) years, 55 patients had stroke recurrence. The negative RLS, RLS, and high-risk PFO groups included 179, 90, and 60 patients, in which stroke recurrence occurred in 5.3%, 2.5%, and 4.6% per person-year, respectively. In patients with high-risk PFO, the National Institutes of Health stroke scale score (hazard ratio [HR] 1.257 [1.034-1.530]) and periventricular hyperintensity (HR 3.369 [1.103-10.294]) were predictors of stroke recurrence on multivariable Cox hazards analysis, but no factors were related to stroke recurrence in the RLS and negative RLS groups., Conclusion: Periventricular hyperintensity was shown to predict recurrent stroke in patients with a high-risk PFO., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yuji Ueno reports financial support was provided by Bristol-Myers Squibb. Yuji Ueno reports a relationship with Ohara Pharmaceutical Co Ltd that includes: speaking and lecture fees. Nobukazu Miyamoto reports a relationship with Ohara Pharmaceutical Co Ltd that includes: speaking and lecture fees. Kazuo Yamashiro reports a relationship with Nestle Japan Ltd Tokyo Commercial Office that includes: funding grants. Takao Urabe reports a relationship with Daiichi Sankyo Inc that includes: speaking and lecture fees. Takao Urabe reports a relationship with Boehringer Ingelheim Ltd that includes: speaking and lecture fees. Takao Urabe reports a relationship with Otsuka Pharmaceutical Co Ltd that includes: speaking and lecture fees. Takao Urabe reports a relationship with Bayshore Pharmaceuticals LLC that includes: speaking and lecture fees. Takao Urabe reports a relationship with AstraZeneca that includes: speaking and lecture fees. Takao Urabe reports a relationship with Otsuka Pharmaceutical Co Ltd that includes: funding grants. Takao Urabe reports a relationship with AbbVie Ltd. that includes: funding grants. Nobutaka Hattori reports a relationship with Asahi Kasei Medical Co Ltd that includes: funding grants. Nobutaka Hattori reports a relationship with Shin Nippon Biomedical Laboratories Ltd that includes: funding grants. Nobutaka Hattori reports a relationship with FP Pharmaceutical Corporation that includes: funding grants. Nobutaka Hattori reports a relationship with Eisai Co Ltd that includes: funding grants. Nobutaka Hattori reports a relationship with CellSource that includes: funding grants. Nobutaka Hattori reports a relationship with MJFF that includes: funding grants. Nobutaka Hattori reports a relationship with Mds Pharma Services that includes: funding grants. Nobutaka Hattori reports a relationship with Meiji Seika Pharma Co Ltd that includes: speaking and lecture fees. Nobutaka Hattori reports a relationship with Sumitomo Pharma Co Ltd that includes: speaking and lecture fees. Nobutaka Hattori reports a relationship with Ono Pharmaceutical Co Ltd that includes: funding grants. Nobutaka Hattori reports a relationship with Otsuka Pharmaceutical Co Ltd that includes: speaking and lecture fees. Nobutaka Hattori reports a relationship with Takeda Pharmaceutical Co Ltd Tokyo Headquarters that includes: speaking and lecture fees. Nobutaka Hattori reports a relationship with Kyowa Kirin Co Ltd that includes: speaking and lecture fees. Nobutaka Hattori reports a relationship with FP Pharmaceutical Corporation that includes: speaking and lecture fees. Nobutaka Hattori reports a relationship with Eisai Co Ltd that includes: speaking and lecture fees. Nobutaka Hattori reports a relationship with Nihon Medi-Physics Co Ltd that includes: speaking and lecture fees. Nobutaka Hattori reports a relationship with Novartis Pharma that includes: speaking and lecture fees. Nobutaka Hattori reports a relationship with Biogen Japan Ltd that includes: speaking and lecture fees. Nobutaka Hattori reports a relationship with Abbvie GK that includes: speaking and lecture fees. Nobutaka Hattori reports a relationship with Teijin Pharma Limited that includes: speaking and lecture fees. Nobutaka Hattori reports a relationship with Alexion Pharmaceuticals Inc that includes: speaking and lecture fees. Nobutaka Hattori reports a relationship with Daiichi Sankyo Inc that includes: speaking and lecture fees. Nobutaka Hattori reports a relationship with Sumitomo Pharma Co Ltd that includes: funding grants. Nobutaka Hattori reports a relationship with Otsuka Pharmaceutical Co Ltd that includes: funding grants. Nobutaka Hattori reports a relationship with Takeda Pharmaceutical Co Ltd Tokyo Headquarters that includes: funding grants. Nobutaka Hattori reports a relationship with Kyowa Kirin Co Ltd that includes: funding grants. Nobutaka Hattori reports a relationship with SUNWELS that includes: funding grants. Nobutaka Hattori reports a relationship with Eisai Co Ltd that includes: funding grants. Nobutaka Hattori reports a relationship with Nihon Medi-Physics Co Ltd that includes: funding grants. Nobutaka Hattori reports a relationship with Abbott Japan Co Ltd that includes: funding grants. Nobutaka Hattori reports a relationship with Abbvie GK that includes: funding grants. Nobutaka Hattori reports a relationship with Medtronic that includes: funding grants. Nobutaka Hattori reports a relationship with Boston Scientific Japan that includes: funding grants. Nobutaka Hattori reports a relationship with Ono Pharmaceutical Co Ltd that includes: funding grants. Nobutaka Hattori reports a relationship with Mitsubishi Tanabe Pharma Corporation that includes: funding grants. Nobutaka Hattori reports a relationship with Kowa Co Ltd Tokyo Office that includes: funding grants. Nobutaka Hattori reports a relationship with PARKINSON Laboratories Co., Ltd that includes: funding grants. Nobutaka Hattori reports a relationship with Ohara Pharmaceutical Co Ltd that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: We compared quantitative susceptibility mapping (QSM) with wave-CAIPI 9 × (QSM&#95;WC9 ×) with reference standard QSM with GRAPPA 2 × (QSM&#95;G2 ×) in two MR scanners. We also compared detectability of microbleeds in both QSMs to demonstrate clinical feasibility of both QSMs., Materials and Methods: This prospective study was approved by the institutional review board and written informed consent was obtained from each subject. Healthy subjects were recruited to evaluate intra-scanner reproducibility, inter-scanner consistency, and inter-sequence consistency of QSM&#95;G2 × and QSM&#95;WC9 × at 2 MR scanners. Susceptibility values measured with volume of interests (VOIs) were evaluated. Patients who were requested for susceptibility weighted imaging were also recruited in this study to measure microbleeds on QSM&#95;G2 × and QSM&#95;WC9 × . The number of microbleeds was compared between two QSMs., Results: Total 55 healthy subjects (male 34, female 21, 38.3 years [23-79]) were included in this study. We investigated reproducibility and consistency of QSM&#95;WC9 × by comparing reference standard QSM&#95;G2 × in two MR scanners in this study, and high correlation (ρ, 0.93-0.97) and high intraclass correlation coefficient (ICC) (0.97-0.99) were obtained. Sixty patients (male 30, female 30; age, 55.4 years [21-85]) were finally enrolled in this prospective study. The ICC of the detected number of microbleeds between QSM&#95;G2 × and QSM&#95;WC9 × was 0.99 (0.98-0.99)., Conclusion: QSM&#95;WC9 × and reference standard QSM&#95;G2 × in two MR scanners showed good reproducibility and consistency in estimating magnetic susceptibilities. QSM&#95;WC9 × and QSM&#95;G2 × were also comparable in terms of microbleeds detection with good agreement of raters and high ICC., (© 2024. The Author(s).)

Synaptic phenotypes in living patients with psychiatric disorders are poorly characterized. Excitatory glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) is a fundamental component for neurotransmission. We recently developed a positron emission tomography (PET) tracer for AMPAR, [ 11 C]K-2, the first technology to visualize and quantify AMPARs density in living human brain. In this study, we characterized patients with major psychiatric disorders with [ 11 C]K-2. One hundred forty-nine patients with psychiatric disorders (schizophrenia, n = 42; bipolar disorder, n = 37; depression, n = 35; and autism spectrum disorder, n = 35) and 70 healthy participants underwent a PET scan with [ 11 C]K-2 for measurement of AMPAR density. We detected brain regions that showed correlation between AMPAR density and symptomatology scores in each of four disorders. We also found brain areas with significant differences in AMPAR density between patients with each psychiatric disorder and healthy participants. Some of these areas were observed across diseases, indicating that these are commonly affected areas throughout psychiatric disorders. Schizophrenia, bipolar disorder, depression, and autism spectrum disorder are uniquely characterized by AMPAR distribution patterns. Our approach to psychiatric disorders using [ 11 C]K-2 can elucidate the biological mechanisms across diseases and pave the way to develop novel diagnostics and therapeutics based on the synapse physiology., (© 2024. The Author(s).)

The main objective of this research was to demonstrate food aversion learning in rats with unrestricted access to food and water, using wheel running as the unconditioned stimulus. Experiment 1 showed that the target-running paired training group consumed a statistically smaller amount of the target food (tteok rice cakes) compared to the target/running unpaired control group, but the decrease in consumption over days in the paired group was not fully supported by a statistical test. Experiment 2a improved the methodology by familiarizing rats with tteok before training, which resulted in both a statistically significant group effect and a statistically significant daily decrease in tteok consumption. Experiment 2b demonstrated that tteok aversion could be reacquired after an extinction phase. These experiments indicate that running-based tteok aversion in non-deprived rats is a valid example of Pavlovian conditioning and suggest that wheel running can cause similar effects in unrestricted rats as observed in food- or water-restricted rats. Additionally, daily measurements of kaolin clay ingestion suggested that wheel running induced nausea in the rats of these experiments., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aim: Mental health issues in adolescence contribute to various disease burdens later in life and are associated with violence, crime, and suicide. Activities such as sleep, diet, exercise, and time spent using electronic devices are related to declining mental health. However, few studies have examined the association between commuting times to school and mental health. This study tested the hypothesis that high school students' long commuting times are associated with poor mental health., Method: A cross-sectional study was conducted between October and December 2022 among 2067 students at two private high schools. Survey items included participant information (sex, grade, school), commuting time, mental health status (Patient Health Questionnaire 9 [PHQ-9]: depressive symptoms, and Generalized Anxiety Disorder 7 [GAD-7]: anxiety symptoms), lifestyle factors, and sleep-related factors., Results: Data from 1899 high school students were analyzed. The prevalence of depressive and anxiety symptoms was 17.3% and 19.0%, respectively. A commuting time of ≥1 h was significantly associated with depressive symptoms (adjusted odds ratio: 1.60 [95% confidence interval]: 1.14-2.24) and anxiety symptoms (adjusted odds ratio: 1.51 [95% confidence interval]: 1.09-2.10). Sex, grade, use of ≥8 h/day of electronic devices, and chronotype were significantly associated with depressive symptoms, while sex, grade, use of ≥8 h/day of electronic devices, and insomnia were significantly associated with anxiety symptoms., Conclusion: It is suggested that long commuting times are associated with poor mental health in high school students. Parents and schools should consider commuting time when advising students on school selection to maintain their mental health., (© 2024 The Author(s). Psychiatry and Clinical Neurosciences © 2024 Japanese Society of Psychiatry and Neurology.)

Histiocytoid Sweet's syndrome (HSS) is a variant of Sweet's syndrome (SS) that clinically resembles SS but differs histologically by infiltrates, predominantly composed of immature cells of the myeloid lineage. Medications such as proteasome inhibitors have been reported to cause HSS but there has been little discussion on the underlying mechanism. Here we report two cases of HSS associated with a proteasome inhibitor. Both patients were on ixazomib for the treatment of multiple myeloma and presented with acute erythematous plaques on the upper half of the body. Pathological findings were consistent with HSS. Similarities between proteasome inhibitor-induced HSS and Nakajo-Nishimura syndrome, an inherited inflammatory disease, can be identified both clinically and histologically, suggesting a potential explanation of the mechanism behind proteasome inhibitor-associated HSS., (© 2024 Japanese Dermatological Association.)

Physical inactivity as well as breakfast skipping is known as risk factor for various metabolic diseases, such as obesity and type 2 diabetes. We have previously reported that a breakfast skipping model, in which the timing of feeding is delayed, induces abnormal lipid metabolism by altering the circadian rhythm of lipid metabolism-related genes in rats. The purpose of this study was to elucidate the synergistic effect of physical inactivity and breakfast skipping on lipid metabolism. We adopted sciatic neurectomized rats as physically inactive models, because we confirmed that the rats mildly decreased their spontaneous locomotor activity compared to sham-operated rats. And then the physically inactive model rats were fed a mild high-fat diet during zeitgeber time (ZT) 12-0 in the control group and ZT16-0 in the breakfast skipping group for 11 days. Body weight gain and total food intake were similar in both groups. Breakfast skipping induced a significant visceral fat accumulation, which was not observed in our previous breakfast skipping or physically inactive studies. The mRNA levels of clock and lipogenesis-related genes were altered by breakfast skipping in the liver and epididymal adipose tissue, and serum insulin level was altered by breakfast skipping. These results suggest that physical inactivity and breakfast skipping synergistically induces drastic visceral fat accumulation due to the alteration of circadian clock and lipid metabolism in the liver and adipose tissue. Therefore, regular feeding timing plays an important role in the health of a sedentary modern society., (© 2024. The Author(s).)

Mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) gastric cancer (GC) exhibits an immune-active tumor microenvironment (TME) compared to MMR proficient (pMMR)/microsatellite stable/Epstein-Barr virus-negative [EBV (-)] GC. The tumor cell-intrinsic cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway has been considered a key regulator of immune cell activation in the TME. However, its significance in regulating the immune-active TME in dMMR/MSI-H GC remains unclear. Here, we demonstrated that tumor cell-intrinsic cGAS-STING was highly expressed in dMMR GC compared to pMMR/EBV (-) GC. The expression of tumor cell-intrinsic STING was significantly and positively associated with the number of CD8 + tumor-infiltrating lymphocytes in GC. Analysis of TCGA datasets revealed that the expression of interferon-stimulated genes and STING downstream T-cell attracting chemokines was significantly higher in MSI-H GC compared to other subtypes of GC with EBV (-). These results suggest that tumor cell-intrinsic STING signaling plays a key role in activating immune cells in the dMMR/MSI-H GC TME and might serve as a novel biomarker predicting the efficacy of immunotherapy for GC treatment., (© 2024. The Author(s).)

Rationale and Objectives: Gadolinium deposition in the dentate nucleus (DN) has been evaluated by T1-weighted imaging (T1WI) and T1 (R1) mapping, but not MR fingerprinting (MRF). This study investigated associations between T1 and T2 values of DN and gadolinium-based contrast agents (GBCAs) using 2-dimensional MRF., Materials and Methods: This study included 101 patients. Region of interest analysis was performed for T1 and T2 values of DN on MRF (T1-MRF, T2-MRF) and T1-weighted images (T1WI ratio). T1 and T2 ratios compared to normal cerebellar white matter (T1-MRF ratio, T2-MRF ratio) were calculated. The type of previous GBCA was confirmed in 79 patients, and linear regressions were performed between T1, T2 values and number of GBCAs., Results: Good correlations were observed between T1-MRF and T1WI ratio (ρ = -0.69, P < 0.001) and between T1-MRF ratio and T1WI ratio (ρ = -0.76, P < 0.001). Mild correlations were observed between T2-MRF and T1WI ratio (ρ = -0.32, P < 0.001) and between T2-MRF ratio and T1WI ratio (ρ = -0.44, P < 0.001). The number of linear-type GBCAs was associated with T1-MRF (β = -0.62, P < 0.001) and T1-MRF ratio (β = -0.54, P < 0.001) in univariate linear regression analyses, and with T1-MRF (β = -0.61, P < 0.001) and T1-MRF ratio (β = -0.53, P < 0.001) in multivariate analysis. The number of linear-type GBCAs was associated with T2-MRF (β = -0.30, P < 0.001) and T2-MRF ratio (β = -0.29, P < 0.001) in univariate analyses, and with T2-MRF (β = -0.31, P < 0.001) and T2-MRF ratio (β = -0.32, P < 0.001) in multivariate analyses. No associations were observed between number of macrocyclic GBCAs and T1-MRF (ratio) or T2-MRF (ratio)., Conclusion: The number of linear-type GBCA administrations was associated with lower T1 and T2 values (ratios) in DN., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yasutaka Fushimi reports financial support was provided by JSPS Kakenhi JP21K15623, JP22K07746. Yuta Urushibata reports a relationship with Siemens Healthcare K. K., Japan. that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

HER2, a member of the human epidermal growth factor receptor(HER)family, exhibits gene amplification, protein overexpression, or both in 13-27% of gastric cancer(GC)cases. Through the activation of downstream Akt and ERK pathways, HER2 promotes the survival and proliferation of gastric cancer cells. The impact of HER2 signaling on the tumor microenvironment(TME)in GC remains unclear, and the heterogeneity of HER2 overexpression in GC tissues is considered a contributing factor. In this study, we focused on differences in the TME between HER2-positive and HER2-negative areas in HER2-positive GC and found that HER2 signaling, particularly the HER2-Akt cascade, may suppress stimulator of interferon genes (STING)expression and reduce CD8+ T cell infiltration in tumor cells. Overall, our findings suggest the potential for a novel therapeutic approach to activate the anti-tumor immune response in HER2-positive GC.

Background: Hay fever (HF) presents with various symptoms, including allergic conjunctivitis and rhinitis, and requires cross-organ treatment. This study assessed the impact of the coronavirus disease 2019 (COVID-19) pandemic on HF treatment trends., Methods: This retrospective cohort study utilized data from the JMDC database collected between January 2018 and May 2021. Patients with HF were identified based on the relevant International Classification of Diseases 10th Revision diagnosis codes and the prescription of HF-related medications. The treatment approaches were compared during the cedar and cypress pollen allergy season (January to May in Japan) before and during the COVID-19 pandemic (2018 and 2019, and 2020 and 2021, respectively)., Results: This study included 2,598,178 patients with HF. The numbers of prescribed HF-related claims in 2018, 2019, 2020, and 2021 were 3,332,854, 3,534,198, 2,774,380, and 2,786,681 times, respectively. Oral second-generation antihistamine prescriptions decreased by >10% from 2019 to 2020, with a <10% change in the subsequent year. Anti-allergic eye drop prescriptions also decreased by >10% from 2019 to 2020 but increased by >10% from 2020 to 2021. Compared with 2018, 2019, and 2020, the number of claims in the rhinitis symptoms dominant group was significantly decreased in 2021 (p < 0.001, all). In contrast, the number of claims in the eye symptoms dominant group and the rhinitis and eye symptoms dominant group increased in 2021 compared with that in 2018, 2019, and 2020 (p < 0.001, all)., Conclusion: Changes in HF treatment and related outcomes could be attributed to lifestyle modifications resulting from the COVID-19 pandemic. Measures, such as limiting outdoor activities and adopting mask-wearing practices may have influenced HF symptoms, preventive behaviors, and the overall approach to treating HF., (© 2024 The Author(s). Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.)

Repetitive transcranial magnetic stimulation (rTMS) to the left dorsolateral prefrontal cortex (DLPFC) is an established treatment for medication-resistant depression. Several targeting methods for the left DLPFC have been proposed including identification with resting-state functional magnetic resonance imaging (rs-fMRI) neuronavigation, stimulus coordinates based on structural MRI, or electroencephalography (EEG) F3 site by Beam F3 method. To date, neuroanatomical and neurofunctional differences among those approaches have not been investigated on healthy subjects, which are structurally and functionally unaffected by psychiatric disorders. This study aimed to compare the mean location, its dispersion, and its functional connectivity with the subgenual cingulate cortex (SGC), which is known to be associated with the therapeutic outcome in depression, of various approaches to target the DLPFC in healthy subjects. Fifty-seven healthy subjects underwent MRI scans to identify the stimulation site based on their resting-state functional connectivity and were measured their head size for targeting with Beam F3 method. In addition, we included two fixed stimulus coordinates over the DLPFC in the analysis, as recommended in previous studies. From the results, the rs-fMRI method had, as expected, more dispersed target sites across subjects and the greatest anticorrelation with the SGC, reflecting the known fact that personalized neuronavigation yields the greatest antidepressant effect. In contrast, the targets located by the other methods were relatively close together with less dispersion, and did not differ in anticorrelation with the SGC, implying their limitation of the therapeutic efficacy and possible interchangeability of them., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Atopic dermatitis (AD), a complex and heterogeneous chronic inflammatory skin disorder, manifests in a spectrum of clinical subtypes. The application of genomics has elucidated the role of genetic variations in predisposing individuals to AD. Transcriptomics, analyzing gene expression alterations, sheds light on the molecular underpinnings of AD. Proteomics explores the involvement of proteins in AD pathophysiology, while epigenomics examines the impact of environmental factors on gene expression. Lipidomics, which investigates lipid profiles, enhances our understanding of skin barrier functionalities and their perturbations in AD. This review synthesizes insights from these omics approaches, highlighting their collective importance in unraveling the intricate pathogenesis of AD. The review culminates by projecting future trajectories in AD research, particularly the promise of multi-omics in forging personalized medicine and novel therapeutic interventions. Such an integrated multi-omics strategy is poised to transform AD comprehension and management, steering towards more precise and efficacious treatment modalities., (© 2024 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: There is limited data on the impact of COVID-19 epidemic on the number of orthopaedic surgeries in Japan., Methods: We conducted a nationwide hospital survey asking for the monthly number of orthopaedic surgeries performed at each facility from January 2019 to June 2021. Those facilities that had performed at least 100 surgeries in 2019 were included for analyses. The facilities were further grouped by prefecture and by hospital characteristics. A brief health economic evaluation was also performed. Risk ratios were compared using univariate analyses with P < 0.05 considered statistically significant., Results: Questionnaire was sent to 1988 hospitals with 1671 hospitals (84%) responding. The survey data indicated a total number of orthopaedic surgeries decreased in 2020 compared to 2019 (1,061,541 vs 1,119,955 P < 0.01), and also for the first six months of 2021 compared to the same period in 2019 (530,388 vs 550,378 P < 0.01). In 2020, over 50% of all facilities in nearly all of the prefectures saw a decline in surgical procedures. The risk of incurring more than a 25% decease in the number of surgeries was significantly higher in 2020 for class I designated medical institutions compared to those that were not designated for any types of infectious diseases among the institutions with a tertiary emergency medical center in 2020 (crude risk ratio 2.9: 95% CI 1.2-7.4, p = 0.02) and in 2021 (crude risk ratio 4.7: 95% CI 1 0.9-12.1, p < 0.01). The estimated total nationwide decrease of revenue were in the range of approximately ¥29.2 to ¥116.8 billion per year for orthopaedic surgeries alone., Conclusion: There was a statistically significant decrease in the number of orthopaedic surgeries in Japan. The magnitude of the decline varied by prefectures and hospital characteristics, with the greater impact imposed on medical institutions with higher classification functions. The estimated immediate health economic impact was sizable., Competing Interests: Declaration of competing interest No benefits in any form have been or will be received from a commercial party related directly or indirectly to the subject of this manuscript. The first author reports personal speaker fees from Johnson & Johnson K·K., Pfizer Japan, 3 M Japan, Stryker Japan, Taisho Toyama Pharmaceutical, MSD K.K., Hisamitsu Pharmaceutical, Kaken Pharmaceutical, Astellas Pharma, Smith＆Nephew, Daiichi Sankyo Company, outside the submitted work., (Copyright © 2023 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Aim: Although the antidepressant effect of ketamine on treatment-resistant depression (TRD) has been frequently reported in North American and European countries, evidence is scarce among the Asian population. We aimed to evaluate the efficacy and safety of intravenous ketamine in Japanese patients with TRD., Methods: In this double-blind randomized placebo-controlled trial, 34 Japanese patients with TRD were randomized to receive either intravenous ketamine (0.5 mg/kg) or placebo, administered over 40 min, twice a week, for 2 weeks. The primary outcome was the change in the Montgomery Åsberg Depression Rating Scale (MADRS) total score from baseline to post-treatment. Secondary outcomes included changes in other depressive symptomatology scores and remission, response, and partial response rates. We also examined the association between baseline clinical demographic characteristics and changes in the MADRS total score., Results: Intention-to-treat analysis indicated no significant difference in the decrease in MADRS total score between the groups (-8.1 ± 10.0 vs -2.5 ± 5.2, t[32] = 2.02, P = 0.052), whereas per-protocol analysis showed a significant reduction in the ketamine group compared to the placebo group (-9.1 ± 10.2 vs -2.7 ± 5.3, t[29] = 2.22, P = 0.034). No significant group differences were observed in other outcomes. Adverse events were more frequent in the ketamine group than in the placebo group, and no serious adverse events were reported. A higher baseline MADRS total score and body mass index were associated with a greater reduction in the MADRS total score., Conclusion: Intravenous ketamine outperformed placebo in Japanese patients with TRD who completed the study, suggesting that ketamine could alleviate depressive symptoms of TRD across diverse ethnic populations., (© 2024 The Author(s). Psychiatry and Clinical Neurosciences © 2024 Japanese Society of Psychiatry and Neurology.)