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Introduction: Palmoplantar pustulosis (PPP) is a pruritic, painful, chronic dermatitis that greatly impacts functioning and quality of life and can be difficult to treat. Approved treatment options for PPP are limited, and many patients do not fully respond to current treatments., Methods: This was a randomized, double-blind, placebo-controlled, phase 2 study in Japanese patients with moderate to severe PPP and inadequate response to topical treatment. Patients were randomized 1:1 to receive apremilast 30 mg twice daily or placebo for 16 weeks followed by an extension phase where all patients received apremilast through week 32. PPP Area and Severity Index (PPPASI), modified PPPASI (which evaluates pustules and vesicles separately), and Palmoplantar Severity Index (PPSI) total scores and subscores (erythema, pustules/vesicles, and desquamation/scales) were evaluated over 32 weeks of apremilast treatment. Achievement of ≥ 50% improvement in PPPASI (PPPASI-50) was evaluated at week 16 among baseline demographic and clinical characteristic subgroups., Results: At week 16, improvements in total score and subscores for PPPASI, modified PPASI, and PPSI, as well as rates of PPPASI-50 were at least moderately greater with apremilast than placebo. Mean PPPASI total score decreased by - 68.3% from baseline to week 32 with continued apremilast treatment. At week 32, mean change from baseline in PPPASI/modified PPPASI subscores ranged from - 58.5% to - 77.0% with apremilast. At week 32, PPSI total score for physician and patient assessments decreased by - 51.3% and - 40.0%, respectively, with continued apremilast treatment. PPPASI-50 response at week 16 was greater with apremilast versus placebo in most demographic and baseline characteristic subgroups., Conclusions: Improvements in all PPPASI and PPSI total scores and subscores observed with apremilast over 16 weeks were maintained through 32 weeks in patients with moderate to severe PPP and inadequate response to topical treatment. Rates of PPPASI-50 response at week 16 were mostly consistent across patient subgroups., Clinicaltrials: GOV: NCT04057937., (© 2024. The Author(s).)

Background: Although major guidelines recommend the routine introduction of angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs) and beta-blockers for patients with ST-segment elevation myocardial infarction (STEMI), evidence regarding the target blood pressure (BP) or pulse rate (PR) at hospital discharge is sparse. This retrospective study aimed to compare the clinical outcomes in patients with STEMI between those with good BP and PR control and those with poor BP or PR control., Methods: We included 748 patients with STEMI who received both ACE inhibitors/ARBs and beta-blockers at hospital discharge, and divided them into a good control group (systolic BP ≤140 mmHg and PR ≤80 bpm, n = 564) and a poor control group (systolic BP >140 mmHg or PR >80 bpm, n = 184). The primary endpoint was major cardiovascular events (MACE) defined as the composite of all-cause death, non-fatal myocardial infarction, and re-admission for heart failure., Results: During the median follow-up duration of 568 days, a total of 119 MACE were observed. The Kaplan-Meier curves showed that MACE were more frequently observed in the poor control group (p = 0.009). In the multivariate Cox hazard analysis, the good control group was inversely associated with MACE (HR 0.656, 95 % CI: 0.444-0.968, p = 0.034) after controlling for multiple confounding factors., Conclusions: The good control of systolic BP and PR at discharge was inversely associated with long-term adverse events in STEMI patients treated with both ACE inhibitors/ARBs and beta blockers. This study suggests the importance of titration of ACE inhibitors/ARBs and beta-blockers for better clinical outcomes in patients with STEMI., Competing Interests: Declaration of competing interest Dr. Sakakura has received speaking honoraria from Abbott Vascular, Boston Scientific, Medtronic Cardiovascular, Terumo, OrbusNeich, Japan Lifeline, Kaneka, and NIPRO. Dr. Jinnouchi has received speaking honoraria from Abbott Vascular. Prof. Fujita has served as a consultant for Mehergen Group Holdings, Inc., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The trigeminal spinal subnucleus caudalis (Sp5C), also known as the medullary dorsal horn, receives orofacial somatosensory inputs, particularly nociceptive inputs, from the trigeminal nerve. In the Sp5C, excitatory and inhibitory neurons, glutamatergic and GABAergic/glycinergic neurons, respectively, form the local circuits. The axons of the glutamatergic neurons in lamina I ascend toward the thalamic and parabrachial nuclei, and this projection is the main pathway of orofacial nociception. Additionally, the axons of the higher brain regions, including the locus coeruleus, dorsal raphe, and cerebral cortex, are sent to the Sp5C., Highlight: Among these descending projections, this review focuses on the functional profiles of the corticotrigeminal projections to the Sp5C, along with their anatomical aspects. The primary and secondary somatosensory and insular cortices are of particular interest., Conclusion: Corticotrigeminal projections from the somatosensory cortex to the Sp5C play a suppressive role in nociceptive information processing, whereas recent studies have demonstrated a facilitative role of the insular cortex in nociceptive information processing at the Sp5C level., 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. Published by Elsevier B.V.)

Conditioned taste aversion (CTA) is an essential ability for animals to consume food safely and is regulated by neuromodulatory systems including the dopamine, noradrenaline, serotonin, and acetylcholine systems. However, because few studies focused on a comprehensive understanding of whole-brain activities, how these neuromodulators contribute to the process of CTA remains an open issue. 18 F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) can visualize activated regions within the whole brain simultaneously and noninvasively. This study aimed to understand the mechanisms of CTA, especially focusing on the retrieval process after CTA acquisition by FDG-PET imaging. CTA was established in rats who received an intraoral application of saccharin solution (IOAS) on the first day (Day 1), a LiCl i.p. injection after an IOAS on Day 2, and an IOAS on Day 3 (CTA group). The subtraction images of Day 3 of the SHAM group, which received a 0.9 % NaCl (saline) injection instead of a LiCl on Day 2, from those of Day 3 of the CTA group revealed increases in FDG signals in multiple brain regions including the substantia nigra, ventral tegmental area, locus coeruleus, dorsal raphe, and nucleus basalis magnocellularis, in addition to the hippocampus and nociception-related regions, including the parabrachial nucleus and solitary nucleus. On the other hand, the visceral pain induced by the LiCl injection increased FDG signals in the primary and secondary somatosensory and insular cortices in addition to the parabrachial nucleus and solitary nucleus. These results suggest that the retrieval process of CTA induces brain regions producing neuromodulators and pain-related brainstem., 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 © 2023 Elsevier B.V. All rights reserved.)

Purpose: Few studies have reported changes in the accumulation patterns of physical activity over a year after stroke. This study characterized the longitudinal changes in physical activity levels and their accumulation patterns for a 1-year follow-up period in stroke survivors., Materials and Methods: In this single-center, prospective, longitudinal observational study, 47 stroke survivors were assessed at rehabilitation discharge and at 6 and 12 months post-discharge. Physical activity was evaluated, and measures included the number of steps, walking duration, total number of bouts per day, and intensity (light, moderate-to-vigorous) and spread (short, medium, and long bouts)., Results: There were no significant main or interaction effects of time on any physical activity variables. Light physical activity accounted for 90% of all walking bouts and 70% of walking duration. Regarding moderate-to-vigorous physical activity (MVPA), 85% of walking bouts and 35% of walking duration were accumulated in short and medium bouts. The number of long-bout MVPA was three per day., Conclusions: Physical activity levels and accumulation patterns were highly stable throughout the 12-month follow-up period. Accumulating light physical activity and intermittent MVPA is important for maintaining physical activity levels in stroke survivors. These findings will promote a better understanding of disability and rehabilitation practice.IMPLICATIONS FOR REHABILITATIONPhysical activity levels and accumulation patterns were highly stable throughout the 12-month follow-up period.The accumulation of moderate-to-vigorous physical activity in long bouts might be challenging for stroke survivors.Accumulating light physical activity and intermittent moderate-to-vigorous physical activity may be acceptable for stroke survivors.

Objectives: Despite the involvement of B cells in the pathogenesis of immune-mediated diseases (IMDs), biological mechanisms underlying their function are scarcely understood. To overcome this gap, here we constructed and investigated a large-scale repertoire catalogue of five B cell subsets of patients with IMDs., Methods: We mapped B cell receptor regions from RNA sequencing data of sorted B cell subsets. Our dataset consisted of 595 donors under IMDs and health. We characterised the repertoire features from various aspects, including their association with immune cell transcriptomes and clinical features and their response to belimumab treatment., Results: Heavy-chain complementarity-determining region 3 (CDR-H3) length among naïve B cells was shortened among autoimmune diseases. Strong negative correlation between interferon signature strength and CDR-H3 length was observed in naïve B cells and suggested the role for interferon in premature B cell development. VDJ gene usage was skewed especially in plasmablasts and unswitched-memory B cells of patients with systemic lupus erythematosus (SLE). We developed a scoring system to quantify this skewing, and it positively correlated with peripheral helper T cell transcriptomic signatures and negatively correlated with the amount of somatic hyper mutations in plasmablasts, suggesting the association of extrafollicular pathway. Further, this skewing led to high usage of IGHV4-34 gene with 9G4 idiotypes in unswitched-memory B cells, which showed a prominent positive correlation with disease activity in SLE. Gene usage skewing in unswitched-memory B cells was ameliorated after belimumab treatment., Conclusions: Our multimodal repertoire analysis enabled us the system-level understanding of B cell abnormality in diseases., Competing Interests: Competing interests: MO, YN, TI, and TO belonged to the Social Cooperation Program, Department of functional genomics and immunological diseases, supported by Chugai Pharmaceutical. NB is an employee of Chugai Pharmaceutical. KF receives consulting honoraria and research support from Chugai Pharmaceutical., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Insulin plays roles in brain functions such as neural development and plasticity and is reported to be involved in dementia and depression. However, little information is available on the insulin-mediated modulation of electrophysiological activities, especially in the cerebral cortex. This study examined how insulin modulates the neural activities of inhibitory neurons and inhibitory postsynaptic currents (IPSCs) in rat insular cortex (IC; either sex) by multiple whole-cell patch-clamp recordings. We demonstrated that insulin increased the repetitive spike firing rate with a decrease in the threshold potential without changing the resting membrane potentials and input resistance of fast-spiking GABAergic neurons (FSNs). Next, we found a dose-dependent enhancement of unitary IPSCs (uIPSCs) by insulin in the connections from FSNs to pyramidal neurons (PNs). The insulin-induced enhancement of uIPSCs accompanied decreases in the paired-pulse ratio, suggesting that insulin increases GABA release from presynaptic terminals. The finding of miniature IPSC recordings of the increased frequency without changing the amplitude supports this hypothesis. Insulin had little effect on uIPSCs under the coapplication of S961, an insulin receptor antagonist, or lavendustin A, an inhibitor of tyrosine kinase. The PI3-K inhibitor wortmannin or the PKB/Akt inhibitors, deguelin and Akt inhibitor VIII, blocked the insulin-induced enhancement of uIPSCs. Intracellular application of Akt inhibitor VIII to presynaptic FSNs also blocked insulin-induced enhancement of uIPSCs. In contrast, uIPSCs were enhanced by insulin in combination with the MAPK inhibitor PD98059. These results suggest that insulin facilitates the inhibition of PNs by increases in FSN firing frequency and IPSCs from FSNs to PNs. (250 words)., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest associated with this manuscript., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Palmoplantar pustulosis (PPP) is a pruritic, painful, recurrent, and chronic dermatitis with limited therapeutic options., Objective: To evaluate the efficacy and safety of apremilast for the treatment of Japanese patients with PPP and inadequate response to topical treatment., Methods: This phase 2, randomized, double-blind, placebo-controlled study enrolled patients with Palmoplantar Pustulosis Area and Severity Index (PPPASI) total score ≥ 12 and moderate or severe pustules/vesicles on the palm or sole (PPPASI pustule/vesicle severity score ≥ 2) at screening and baseline with an inadequate response to topical treatment. Patients were randomized (1:1) to apremilast 30 mg twice daily or placebo for 16 weeks, followed by a 16-week extension phase during which all patients received apremilast. The primary endpoint was achievement of PPPASI-50 response (≥ 50% improvement from baseline in PPPASI). Key secondary endpoints included change from baseline in PPPASI total score, Palmoplantar Pustulosis Severity Index (PPSI), and patient's visual analog scale (VAS) for PPP symptoms (pruritus and discomfort/pain)., Results: A total of 90 patients were randomized (apremilast: 46; placebo: 44). A significantly greater proportion of patients achieved PPPASI-50 at week 16 with apremilast versus placebo (P = 0.0003). Patients receiving apremilast showed greater improvement in PPPASI at week 16 versus placebo (nominal P = 0.0013), as well as PPSI and patient-reported pruritus and discomfort/pain (nominal P ≤ 0.001 for all). Improvements were sustained through week 32 with apremilast treatment. The most common treatment-emergent adverse events included diarrhea, abdominal discomfort, headache, and nausea., Conclusions: Apremilast treatment demonstrated greater improvements in disease severity and patient-reported symptoms versus placebo at week 16 in Japanese patients with PPP with sustained improvements through week 32. No new safety signals were observed., Clinicaltrials: GOV: NCT04057937., (© 2023. The Author(s).)

Background: Epidemiological studies reported that acute myocardial infarction (AMI) occurs more often in winter season or days with low temperatures. However, most of these studies did not distinguish ST-elevation myocardial infarction (STEMI) from AMI. The purpose of this study was to investigate the relationship between temperature and the occurrence of STEMI., Methods: We reviewed all daily temperature in Saitama City between January 2015 and December 2021 (2557 days) and divided them into days in which our institution received STEMI (days with STEMI) and days in which our institution did not receive STEMI (days without STEMI)., Results: The daily maximum temperature was significantly lower in days with STEMI than in days without STEMI [20.0 °C (68.0 °F) versus 21.2 °C (70.2 °F), p = 0.001]. The maximum temperature was significantly lower in days with STEMI than in days without STEMI in the elderly [19.9 °C (67.8 °F) versus 21.1 °C (70.0 °F), p = 0.003], whereas this trend was weaker in the non-elderly [20.2 °C (68.4 °F) versus 20.9 °C (69.6 °F), p = 0.171]. Furthermore, the maximum temperature was significantly lower in days with STEMI than in days without STEMI in male [20.0 °C (68.0 °F) versus 21.1 °C (70.0 °F), p = 0.002], whereas this trend was weaker in females [20.0 °C (68.0 °F) versus 20.9 °C (69.6 °F), p = 0.169]., Conclusions: The daily temperatures were significantly lower in days with STEMI than in days without STEMI, and this relationship was pronounced in elderly or male patients., Competing Interests: Declaration of competing interest Dr. Sakakura has received speaking honoraria from Abbott Vascular, Boston Scientific, Medtronic Cardiovascular, Terumo, OrbusNeich, Japan Lifeline, Kaneka, and NIPRO. Dr. Jinnouchi has received speaking honoraria from Abbott Vascular. Prof. Fujita has served as a consultant for Mehergen Group Holdings, Inc., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objectives: Little is known about the immunology underlying variable treatment response in rheumatoid arthritis (RA). We performed large-scale transcriptome analyses of peripheral blood immune cell subsets to identify immune cells that predict treatment resistance., Methods: We isolated 18 peripheral blood immune cell subsets of 55 patients with RA requiring addition of new treatment and 39 healthy controls, and performed RNA sequencing. Transcriptome changes in RA and treatment effects were systematically characterised. Association between immune cell gene modules and treatment resistance was evaluated. We validated predictive value of identified parameters for treatment resistance using quantitative PCR (qPCR) and mass cytometric analysis cohorts. We also characterised the identified population by synovial single cell RNA-sequencing analysis., Results: Immune cells of patients with RA were characterised by enhanced interferon and IL6-JAK-STAT3 signalling that demonstrate partial normalisation after treatment. A gene expression module of plasmacytoid dendritic cells (pDC) reflecting the expansion of dendritic cell precursors (pre-DC) exhibited strongest association with treatment resistance. Type I interferon signalling was negatively correlated to pre-DC gene expression. qPCR and mass cytometric analysis in independent cohorts validated that the pre-DC associated gene expression and the proportion of pre-DC were significantly higher before treatment in treatment-resistant patients. A cluster of synovial DCs showed both features of pre-DC and pro-inflammatory conventional DC2s., Conclusions: An increase in pre-DC in peripheral blood predicted RA treatment resistance. Pre-DC could have pathophysiological relevance to RA treatment response., Competing Interests: Competing interests: YN, MOt, YTa and TO belong to the Social Cooperation Programme, Department of Functional Genomics and Immunological Diseases, supported by Chugai Pharmaceutical. KK receives speaking fees from Chugai Pharmaceutical. HK receives speaking fees and research budget from Chugai Pharmaceutical. KF receives consulting honoraria and research support from Chugai Pharmaceutical. SY, YN, SS, KK and HS receives speaking fees from Bristol-Myers Squibb. HK receives consulting fees and speaking fees from Bristol-Myers Squibb. KF receives speaking fees and research support from Bristol-Myers Squibb., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Inhibitory synaptic currents from fast-spiking neurons (FSNs), a typical gamma-aminobutyric acid (GABA)ergic interneuron in the cerebral cortex, to pyramidal neurons are facilitated by insulin. FSNs frequently show electrical synapses to FSNs, however, the effect of insulin on these electrical synapses is unknown. The aim of this study was to evaluate effects of insulin on electrical synaptic potentials between FSNs., Methods: Electrical synaptic potentials via gap junctions between FSNs were recorded to examine how insulin modulates these potentials in the rat insular cortex (IC)., Results: Bath application of insulin (10 nM), which increases the spike firing rate of pyramidal neurons and unitary inhibitory postsynaptic currents recorded from FSN to pyramidal neuron connections, slightly but significantly increased electrical synaptic currents. The mean ratio of electrical synapses, the coupling coefficient that is obtained by postsynaptic voltage responses divided by presynaptic voltage amplitude, was 8.3 ± 1.1% in control and 9.2 ± 1.1% (n = 14) during 10 nM insulin application. Input resistance and voltage responses to large hyperpolarizing currents (-140 pA) were not changed by insulin., Conclusion: These results suggest that insulin facilitates spike synchronization by increasing electrical synaptic currents via gap junctions of GABAergic FSNs in the IC.

Objective: Idiopathic inflammatory myopathies (IIM) demonstrate characteristic clinical phenotypes depending on the myositis-specific antibody (MSAs) present. We aimed to identify common or MSA-specific immunological pathways in different immune cell types from peripheral blood by transcriptome analysis., Methods: We recruited 33 patients with IIM who were separated into the following groups: 15 patients with active disease at onset and 18 with inactive disease under treatment. All patients were positive for MSAs: anti-melanoma differentiation-associated gene 5 (MDA5) antibody (Ab) in 10 patients, anti-Mi-2 Ab in 7, and anti-aminoacyl-transfer RNA synthetase (ARS) Ab in 16. The patients were compared with 33 healthy controls. Twenty-four immune cell types sorted from peripheral blood were analyzed by flow cytometry, RNA sequencing, and differentially expressed gene analysis combined with pathway analysis., Results: The frequencies of memory B cell types were significantly decreased in active patients, and the frequency of plasmablasts was prominently increased in active patients with anti-MDA5 Ab in comparison with healthy controls. The expression of type I interferon (IFN)-stimulated genes of all immune cell types was increased in the active, but not inactive, patients. Endoplasmic reticulum stress-related genes in all IIM memory B cells and oxidative phosphorylation-related genes in inactive IIM double negative B cells were also increased, suggesting prominent B cell activation in IIM. Furthermore, active patients with anti-MDA5 Ab, anti-Mi-2 Ab, or anti-ARS Ab were distinguished by IFN-stimulated and oxidative phosphorylation-related gene expression in plasmablasts., Conclusion: Unique gene expression patterns in patients with IIM with different disease activity levels and MSA types suggest different pathophysiologies. Especially, B cells may contribute to common and MSA-specific immunological pathways in IIM., (© 2023 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: Human Leukocyte Antigen (HLA) alleles regulate susceptibility to rheumatoid arthritis (RA) and immune-mediated diseases. This study aims to elucidate the impact of HLA alleles to T cell subsets., Methods: We performed genome-wide and HLA allele association analysis for T cell receptor (TCR) beta chain repertoire in 13 purified T cell subsets from the ImmuNexUT database, consisting of 407 donors with ten immune-mediated diseases and healthy controls., Results: HLA class II alleles were associated with TRBV gene usage and the public clones of CD4 T cells, while HLA class I alleles were associated with CD8 T cells. RA-risk and immune-mediated diseases-risk HLA alleles were associated with TRBV gene usage of naive and effector CD4 T cell subsets and public clones accumulating in Th17. Clonal diversity was independent of HLA alleles and was correlated with transcriptome changes that reflect TCR signaling., Conclusion: This study revealed in vivo evidence that both HLA alleles and environmental factors shape naive and effector TCR repertoires in RA and immune-mediated diseases patients., Competing Interests: Declaration of competing interest Y.N., M. Ota, and T.O. belong to the Social Cooperation Program, Department of Functional Genomics and Immunological Diseases, supported by Chugai Pharmaceutical. K.F.s receives consulting honoraria and research support from Chugai Pharmaceutical. All the other authors declared no conflicts of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Mobile applications are increasingly used in healthcare. We have developed a smartphone healthcare application, CALO mama Plus , that can register daily diet, exercise, mood, and sleep quality, calculate dietary intake, and provide advice using artificial intelligence technology. This 3-month randomized controlled trial tested the hypothesis that CALO mama Plus could promote body weight reduction in Japanese adults with overweight or obesity. We recruited office workers as participants. The key eligibility criteria were an age of 20-65 years and a body mass index of 23-40 kg/m 2 . The primary outcome was body weight change over 3 months. We enrolled 141 participants and randomly assigned them to the intervention ( n = 72) and control ( n = 69) groups. The intervention group used CALO mama Plus , and the control group did not receive any intervention. The change in body weight was -2.4 ± 4.0 kg and -0.7 ± 3.3 kg in the intervention and control groups, respectively. An analysis of covariance adjusted for related variables showed a significant between-group difference in body weight change (-1.60 kg; 95% confidence interval -2.83 to -0.38; p = 0.011). The present study suggests that CALO mama Plus effectively promotes weight loss.

The situation around primary percutaneous coronary intervention (PCI) has dramatically changed since coronavirus disease 2019 (COVID-19) pandemic. The impact of COVID-19 pandemic on clinical outcomes as well as door-to-balloon time (DTBT), which is known as one of the indicators of early reperfusion, has not been fully investigated in patients with ST-elevation acute myocardial infarction (STEMI). The purpose of this study was to compare DTBT and in-hospital outcomes in patients with STEMI between before versus after COVID-19 pandemic. The primary interest was DTBT and the incidence of in-hospital outcomes including in-hospital death. We included 330 patients with STEMI who underwent primary PCI, and divided them into the pre COVID-19 group (n = 209) and the post COVID-19 group (n = 121). DTBT was significantly longer in the post COVID-19 group than in the pre COVID-19 group (p < 0.001), whereas the incidence of in-hospital death was comparable between the 2 groups (p = 0.238). In the multivariate logistic regression analysis, chest CT before primary PCI (OR 4.64, 95% CI 2.58-8.34, p < 0.001) was significantly associated with long DTBT, whereas chest CT before primary PCI (OR 0.76, 95% CI 0.29-1.97, p = 0.570) was not associated with in-hospital death after controlling confounding factors. In conclusion, although DTBT was significantly longer after COVID-19 pandemic than before COVID-19 pandemic, in-hospital outcomes were comparable between before versus after COVID-19 pandemic. This study suggests the validity of the screening tests including chest CT for COVID-19 in patients with STEMI who undergo primary PCI., (© 2022. The Author(s) under exclusive licence to Japanese Association of Cardiovascular Intervention and Therapeutics.)

Background: Behçet's syndrome (BS) is an immune-mediated disease characterized by recurrent oral ulcers, genital ulcers, uveitis, and skin symptoms. HLA-B51, as well as other genetic polymorphisms, has been reported to be associated with BS; however, the pathogenesis of BS and its relationship to genetic risk factors still remain unclear. To address these points, we performed immunophenotyping and transcriptome analysis of immune cells from BS patients and healthy donors., Methods: ImmuNexUT is a comprehensive database consisting of RNA sequencing data and eQTL database of immune cell subsets from patients with immune-mediated diseases and healthy donors, and flow cytometry data and transcriptome data from 23 BS patients and 28 healthy donors from the ImmuNexUT study were utilized for this study. Differential gene expression analysis and weighted gene co-expression network analysis (WGCNA) were performed to identify genes associated with BS and clinical features of BS. eQTL database was used to assess the relationship between genetic risk factors of BS with those genes., Results: The frequency of Th17 cells was increased in BS patients, and transcriptome analysis of Th17 cells suggested the activation of the NFκB pathway in Th17 cells of BS patients. Next, WGCNA was used to group genes into modules with similar expression patterns in each subset. Modules of antigen-presenting cells were associated with BS, and pathway analysis suggested the activation of antigen-presenting cells of BS patients. Further examination of genes in BS-associated modules indicated that the expression of YBX3, a member of a plasmacytoid dendritic cell (pDC) gene module associated with BS, is influenced by a BS risk polymorphism, rs2617170, in pDCs, suggesting that YBX3 may be a key molecule connecting genetic risk factors of BS with disease pathogenesis. Furthermore, pathway analysis of modules associated with HLA-B51 indicated that the association of IL-17-associated pathways in memory CD8 + T cells with HLA-B51; therefore, IL-17-producing CD8 + T cells, Tc17 cells, may play a critical role in BS., Conclusions: Various cells including CD4 + T cells, CD8 + T cells, and antigen-presenting cells are important in the pathogenesis of BS. Tc17 cells and YBX3 may be potential therapeutic targets in BS., (© 2022. The Author(s).)

Synovitis-Acne-Pustulosis-Hyperostosis-Osteitis (SAPHO) syndrome is a rare inflammatory osteoarticular disorder, which encompassed many diseases, including pustulotic arthro-osteitis (PAO). Musculoskeletal manifestations, including osteitis, synovitis, and hyperostosis, are the hallmarks of the SAPHO syndrome and affect a variety of regions of the body. Recent survey indicated that more than 80% of cases of SAPHO syndrome in Japan were PAO, originally proposed by Sonozaki et al. in 1981, whereas severe acne was the most commonly reported skin ailment amongst participants with SAPHO syndrome in Israel. Prevalence of SAPHO syndrome remains unavailable, whereas the prevalence of palmoplantar pustulosis (PPP) was reported to be 0.12% in Japan, and 10-30% of patients with PPP had PAO. SAPHO syndrome and PAO are predominantly found in patients in the third through fifth decades of life, and a female predominance is seen in both groups. The diagnosis is typically made by a rheumatologist or dermatologist. Identification of a variety of the clinical, radiological, and laboratory features outlined, as well as diagnostic criteria, are used to make the diagnosis. Goals of treatment seek to maximize health-related quality of life, preventing structural changes and destruction, and normalizing physical function and social participation. Finally, we review the non-pharmacological and pharmacological managements., (© Japan College of Rheumatology 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Patients with psoriasis report impaired health-related quality of life (HRQoL; Dermatology Life Quality Index score ≥ 2) even after achieving clear or almost-clear skin with biologic treatment., Objective: To assess the effectiveness of brodalumab in HRQoL improvement and the factors associated with incomplete HRQoL improvement in Japanese patients with psoriasis., Methods: As a part of the single-arm, open-label, multicenter, prospective ProLOGUE study (Japan Registry of Clinical Trials identifier: jRCTs031180037), patients were treated with 210 mg of subcutaneous brodalumab in daily clinical practice until week 48. The absolute Psoriasis Area and Severity Index scores and patient-reported outcomes were assessed at baseline and weeks 12 and 48., Results: Seventy-three patients (male, 82.2%; median age, 54.0 years) were enrolled. The Dermatology Life Quality Index and European Quality of Life 5-Dimension 5-Level Utility Index scores significantly improved from baseline to weeks 12 and 48. At week 48, all 13 patients with a Dermatology Life Quality Index score of ≥2 and an absolute Psoriasis Area and Severity Index score of 0 to ≤2 reported itching., Limitations: Unclear generalizability of the results to other biologics., Conclusion: Treatment with brodalumab improved HRQoL in patients with psoriasis. Itching may contribute to incomplete HRQoL improvement in patients who have achieved clear or almost-clear skin., Competing Interests: Dr Miyagi reports financial support from Kyowa Kirin during the conduct of the study; is a consultant or advisor for AbbVie and Janssen Pharmaceuticals; has received funding or grants from AbbVie, Eisai, and Taiho Pharmaceutical; has received speaking and lecture fees from AbbVie, Janssen Pharmaceuticals, Maruho, Novartis Pharma, Boehringer Ingelheim, Eisai, Eli Lily Japan, CSL Behring, Taiho Pharmaceutical, Ono Pharmaceutical, Otsuka Pharmaceutical, and LEO Pharma; and has received travel reimbursement from AbbVie, Janssen Pharmaceuticals, Maruho, Novartis Pharma, Taiho Pharmaceutical, and Ono Pharmaceutical outside the submitted work. Dr Kanai is an employee of Kyowa Kirin. Dr Murotani reports financial support from Kyowa Kirin during the conduct of the study. Dr Okubo reports financial support from Kyowa Kirin during the conduct of the study; is a consultant or advisor for AbbVie, Amgen, Boehringer Ingelheim, Kyowa Kirin, Sun Pharma, UCB Pharma, Taiho Pharmaceutical, Eli Lilly Japan, Novartis Pharma, Maruho, LEO Pharma, and Janssen Pharmaceuticals; has received funding or grants from AbbVie, Eisai, Kaken Pharmaceutical, Kyowa Kirin, GlaxoSmithKline Shiseido, Sun Pharma, JIMRO, Taiho Pharmaceutical, Torii Pharmaceutical, Eli Lilly Japan, Novartis Pharma, Maruho, LEO Pharma, and Janssen Pharmaceuticals; and has received speaking and lecture fees from AbbVie, Amgen, Boehringer Ingelheim, Eisai, Kyowa Kirin, Sanofi, Sun Pharma, UCB Pharma, JIMRO, Taiho Pharmaceutical, Mitsubishi Tanabe Pharma, Torii Pharmaceutical, Eli Lilly Japan, Novartis Pharma, Maruho, LEO Pharma, Celgene, and Janssen Pharmaceuticals outside the submitted work. Dr Honna reports financial support from Kyowa Kirin during the conduct of the study; has received funding or grants from Kyowa Kirin and Eli Lilly Japan; and has received speaking and lecture fees from Kyowa Kirin, Novartis Pharma, Maruho, Eisai, Janssen Pharmaceuticals, Taiho Pharmaceutical, Mitsubishi Tanabe Pharma, AbbVie, Torii Pharmaceutical, Eli Lilly Japan, Sun Pharma, and Celgene outside the submitted work. Dr Kobayashi reports statistical analysis support and writing assistance from Kyowa Kirin during the conduct of the study and has received speaking and lecture fees from Janssen Pharmaceuticals and Taiho Pharmaceutical outside the submitted work. Dr Seishima reports financial support from Kyowa Kirin during the conduct of the study; has received funding or grants from Taiho Pharmaceutical, Novartis Pharma, Sanofi, Maruho, Mitsubishi Tanabe Pharma, Kyowa Kirin, Sun Pharma, Kaken Pharmaceutical, Japan Blood Products Organisation, Eisai, and Torii Pharmaceutical; has received speaking and lecture fees from Taiho Pharmaceutical, Novartis Pharma, Sanofi, Maruho, Eli Lilly Japan, Mitsubishi Tanabe Pharma, Kyowa Kirin, Sun Pharma, Kaken Pharmaceutical, LEO Pharma, Celgene, Janssen Pharmaceuticals, Eisai, AbbVie, Torii Pharmaceutical, and JIMRO; and has received travel reimbursement from Taiho Pharmaceutical, Novartis Pharma, Sanofi, Maruho, Eli Lilly Japan, Mitsubishi Tanabe Pharma, Kyowa Kirin, Sun Pharma, Kaken Pharmaceutical, Japan Blood Products Organisation, LEO Pharma, Celgene, Janssen Pharmaceuticals, Pola Pharma, Eisai, AbbVie, Torii Pharmaceutical, and JIMRO outside the submitted work. Dr Mizutani reports financial support, article publishing charges, statistical analysis support, and writing assistance from Kyowa Kirin during the conduct of the study and has received speaking and lecture fees from Taiho Pharmaceutical, Novartis Pharma, Sanofi, Maruho, Eli Lilly Japan, Mitsubishi Tanabe Pharma, Sun Pharma, Kaken Pharmaceutical, Japan Blood Products Organisation, and Kyowa Kirin outside the submitted work. Author Kitabayashi is an employee of Kyowa Kirin and owns stock in the company. Dr Imafuku reports financial support from Kyowa Kirin during the conduct of the study; has received speaking and lecture fees from Astellas Pharma, AbbVie, Eli Lilly Japan, Otsuka Pharmaceutical, Kaken Pharmaceutical, Sato Pharmaceutical, Sanofi, Sun Pharma, GlaxoSmithKline, Celgene, Daiichi Sankyo, Takeda Pharmaceutical, Taiho Pharmaceutical, Mitsubishi Tanabe Pharma, Tsumura, Torii Pharmaceutical, Nippon Zoki Pharmaceutical, Novartis Pharma, Pfizer, Bristol Myers Squibb, Maruho LEO Pharma, Janssen Pharmaceuticals, and UCB Japan; has received funding or grants from AbbVie, Eisai, Sato Pharmaceutical, Sun Pharma, Taiho Pharmaceutical, Mitsubishi Tanabe Pharma, Tsumura, Maruho, and LEO Pharma; and is a consultant or advisor for Bristol, Meiji Seika Pharma, and LEO Pharma outside the submitted work., (© 2022 by the American Academy of Dermatology, Inc. Published by Elsevier Inc.)

It is plausible that the coronavirus disease pandemic and related changes in work and life patterns affected dietary patterns, but existing studies have limitations owing to a cross-sectional design. Using longitudinal data, we examined dietary changes in people due to the pandemic and work and life patterns. We conducted an online survey on changes in work and life patterns during the pandemic from April 30, 2020, to May 8, 2020, among users of a health app called CALO mama provided in Japan. We retrieved and linked the dietary data for 5929 participants from January 1, 2020, to May 13, 2020. Generalized linear mixed models were used to estimate the frequencies of food intake associated with the pandemic and work and life patterns. During the state of emergency, the frequency of intake of vegetables, beans, seaweeds, fish, meats, dairy products, and snacks increased, whereas alcohol intake decreased. Working from home was associated with increased intake of vegetables, fruits, dairy products, and snacks but decreased intake of seaweeds, meats, and alcohol. Time spent on childcare was associated with decreased intake of vegetables and fruits but increased intake of meats. Probable depressive symptoms were negatively associated with the frequency of food intake other than snacks and alcohol. We conclude that diet quality improved during the pandemic in general, but attention must be paid to overconsumption of snacks and negative factors such as increased burden of childcare and depression for healthy eating., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The disparity of overall diet quality by personal educational attainment has been a public issue. However, it remains unknown which food groups contribute to the disparity. This cross-sectional study assesses which food groups explain associations between education and overall diet quality in Japanese women., Methods: A total of 3,788 middle-aged (mean age, 47.7 years) and 2,188 older women (mean age, 74.4 years), who lived in 47 prefectures in Japan, provided data on their education (low, middle, and high) and dietary intakes from a diet history questionnaire. A diet quality score (possible score 0-70) was calculated based on seven food components. Mean diet quality scores, with adjustment for lifestyle and neighborhood variables, were estimated by education using a general linear model, and Dunnett's multiple comparison was conducted. Additionally, mean scores of each food component were estimated by education and compared using the same manner., Results: After adjustment for lifestyle and neighborhood variables, mean diet quality score of high or middle education was higher than low education for both generations. Middle-aged women with high and middle education had higher scores of 'milk', 'snacks, confection, and beverages', 'fruits', and 'vegetable dishes' than those with low education. Older women with high and middle education had higher scores of 'sodium from seasonings' and 'fruits' than those with low education., Conclusions: This study suggests that positive associations between education and diet quality are explained by different food groups in middle-aged and older Japanese women, which are independent of lifestyle and neighborhood variables.

Background: Plaque psoriasis significantly affects patients' health-related quality of life. To aid treatment decisions, not only objective assessment by physicians but also subjective assessment by patients is important., Objective: To assess the significance of Dermatology Life Quality Index (DLQI) evaluation at the time of biologics introduction in clinical practice in Japanese patients with plaque psoriasis., Methods: This was a single-arm, open-label, multicenter study. At baseline, Psoriasis Area and Severity Index (PASI) and DLQI scores were measured and stratified based on DLQI scores ≥6/≤5 and PASI scores ≤10/>10. Other patient-reported outcomes assessed included EQ-5D-5L, itch numerical rating scale (NRS), skin pain NRS, Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-8 (PHQ-8), Sleep Problem Index-II (SPI-II), and Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9)., Results: Of the 73 enrolled patients, 23 had PASI scores ≤10. Those with PASI/DLQI scores >10/≥6 had a significantly higher median PASI score than those with PASI/DLQI scores >10/≤5 (p = 0.0125). Regardless of PASI scores (>10/≤10), median itch NRS and GAD-7 scores were significantly higher in patients with DLQI scores ≥6 than in those with DLQI scores ≤5 (itch NRS, p = 0.0361 and p = 0.0086, respectively; GAD-7, p = 0.0167 and p = 0.0273, respectively). Patients with PASI/DLQI scores ≤10/≥6 had significantly higher skin pain NRS (p = 0.0292) and PHQ-8 (p = 0.0255) scores and significantly lower median SPI-II scores (p = 0.0137) and TSQM-9 Effectiveness domain scores (p = 0.0178) than those with PASI/DLQI scores ≤10/≤5., Conclusion: DLQI may be useful for assessing patients' concerns that cannot be identified by PASI alone while initiating biologics or switching from other biologics in clinical practice., Competing Interests: Declaration of Competing Interest S. Imafuku and T. Kakuma have received grants and meeting travel fees related to the submitted work from Kyowa Kirin. K. Murotani, K. Ito, C. Ohata, F. Yamazaki, T. Miyagi, H. Takahashi, Y. Okubo, H. Saeki, M. Honma, Y. Tada, T. Mabuchi, M. Higashiyama, S. Kobayashi, Y. Hashimoto, and M. Seishima have received grants related to the submitted work from Kyowa Kirin. Y. Kanai and T. Nomura are employees of Kyowa Kirin., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Depression in elderly people is a major global concern around the world. Epidemiological evidence of the association of beverages with depressive symptoms has received research attention; however, epidemiological studies on the association of coffee and green tea consumption with depressive symptoms among the elderly population are limited. The objective of this study is to cross-sectionally examine the association of depressive symptoms with the intake of coffee, green tea, and caffeine and to verify the antidepressant effect of caffeine., Methods: The subjects were 1,992 women aged 65-94 years. Intakes of coffee, green tea, and caffeine, as well as depressive symptoms, were assessed with a validated brief dietary history questionnaire (BDHQ) and the Center for Epidemiologic Studies Depression Scale (CES-D), respectively. Multiple logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for depressive symptoms with adjustments for potential confounders., Results: Coffee intake was associated with a lower prevalence of depressive symptoms, the ORs of which for the 4th versus the 1st quartiles of intake was 0.64 (95% CI, 0.46-0.88, P for trend = 0.01) in a fully adjusted model. Caffeine intake was marginally associated with depressive symptoms, but the association was not statistically significant (OR 0.75; 95% CI, 0.55-1.02, P for trend = 0.058)., Conclusion: The result suggests that the inverse association of coffee intake with depressive symptoms might be associated with not only caffeine intake but also some other substances in coffee or factors related to coffee intake. Because of the cross-sectional design of the present study, longitudinal studies are required to confirm the present finding.

Objective: It has been hypothesized that fruit and vegetable intake is inversely associated with non-alcoholic fatty liver (NAFLD). However, some studies have speculated that fruit intake might be positively associated with NAFLD owing to the fructose content of the fruit. This might cause consumers to hesitate consuming fruit. The aim of this study was to assess the association between fruit and vegetable consumption and NAFLD., Methods: This was a cross-sectional study of 977 men and 1467 women, 40 to 69 y of age without current liver disease other than NAFLD and who did not report excess alcohol intake (i.e., ≥30 g/d in men and ≥20 g/d in women). Dietary intake was assessed using a validated diet history questionnaire. NAFLD was diagnosed from abdominal ultrasonography results. The association between quartiles of fruit or vegetable consumption and NAFLD prevalence was assessed using logistic regression analysis, with lowest category as reference., Results: The prevalence of NAFLD was 34.9% in men and 11.7% in women. Adjusted for age and lifestyle factors, fruit intake was inversely associated with NAFLD in both sexes. However, these associations disappeared after further adjustment for body mass index. Consumption of total vegetables was not associated with NAFLD. In women, a linear inverse association was demonstrated between green and yellow vegetable intake and NAFLD in the final model (P trend  = 0.04), but odds ratios for any intake category did not reach significance., Conclusions: No obesity-independent association was found between fruit or vegetable intake and NAFLD. According to the findings of this study, Japanese do not need to restrict fruit consumption to limit fructose intake as a means of preventing NAFLD., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Although the importance of capacity building for public health nutrition (PHN) has been increasing globally, reports on the current status of training programs for PHN in East-Asia including Japan are limited. The aim of this study was to compare the current status of education and research activities in the field of PHN in Japan with those in South Korea, Taiwan, and mainland China., Methods: Necessary information was collected by internet search and telephone inquiry. Collection focused on the number of departments in colleges and universities with PHN as a compulsory subject in the 2016 academic year, and the number of articles and information related to these articles published in the journal Public Health Nutrition between 2007 and 2016., Results: The number of departments with PHN as a compulsory subject was the highest in Japan ( n  = 137), followed by mainland China ( n  = 32), Taiwan ( n  = 18) and South Korea ( n  = 7). Using the classification list of education in each country and region, the majority of these departments were classified as home economics, natural science, health and welfare, and medical science in Japan, South Korea, Taiwan, and mainland China, respectively. Regarding publications, most of the articles were written in colleges and universities not having PHN as a compulsory subject in Japan, South Korea, and Taiwan. The number of articles per department among departments with compulsory PHN education was lowest in Japan ( n  = 0.3) compared to Taiwan, mainland China, and South Korea ( n  = 1.2, 2.7, and 3.7, respectively)., Conclusions: Japan has a much higher number of departments with PHN as a compulsory subject than neighboring East Asian states and relatively low research activities in the field of PHN. This suggests that current university education may not lead to active PHN research in Japan. Further studies are warranted to explore the reasons for this., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s). 2019.)

Objective: Epidemiologic evidence on the associations between dietary glycemic index (GI) and glycemic load (GL) and depressive symptoms is not only limited, particularly in Asian populations where dietary GI and GL are typically higher than in Western countries, but also inconclusive. This cross-sectional study examined these associations in Japanese women., Methods: Subjects were 3963 young (age 18-years) and 3826 middle-aged (mean age 47.8 years) Japanese women. Dietary GI and GL were assessed using a validated diet history questionnaire. Depression symptoms were defined as present when subjects had a Center for Epidemiologic Studies Depression score ≥16., Results: The prevalence of depressive symptoms was 50.2% for young women and 27.3% for middle-aged women. The mean (SD) values of energy-adjusted dietary GI and GL (GI for glucose = 100) were, respectively, 64.9 (4.3) and 142.0 (27.4) for young women and 65.0 (4.1) and 142.2 (29.5) for middle-aged women. After adjustment for potential confounding factors, higher dietary GI was associated with a lower prevalence of depressive symptoms. Adjusted OR (95% CI) for depressive symptoms in the highest compared to lowest quintiles of dietary GI was 0.66 (0.52, 0.82) for young women (P for trend = 0.001) and 0.75 (0.60, 0.96) for middle-aged women (P for trend = 0.046). Conversely, there was no association between dietary GL and depressive symptoms in either age group., Conclusions: Dietary GI, but not GL, was inversely associated with depressive symptoms in a group of young and middle-aged Japanese women with relatively high dietary GI and GL.

Objective: Epidemiologic evidence on the potential effects of dietary acid load on frailty is lacking. This cross-sectional study examined the association between dietary acid load and frailty., Methods: This study was based on self-reported data obtained from 2176 Japanese women aged 65-94 years. Dietary acid load was characterized as potential renal acid load (PRAL) and net endogenous acid production (NEAP), based on information on nutrient intake, obtained from a validated brief diet history questionnaire. Frailty score (0-5) was defined as the sum of slowness/weakness (two points), exhaustion (one point), low physical activity (one point), and unintentional weight loss (one point). A score of ≥3 was classified as indicating frailty., Results: The prevalence of frailty was 17.9%. After adjustment for potential confounding factors, higher PRAL and NEAP were associated with a higher prevalence of frailty. Adjusted OR (95% CI) for frailty in the highest compared to the lowest quintiles was 1.59 (1.08, 2.34) for PRAL (P for trend = 0.048) and 1.42 (0.98, 2.06) for NEAP (P for trend = 0.03). PRAL and NEAP also showed positive associations with the prevalence of slowness/weakness and low physical activity (all P for trend ≤0.03). PRAL (but not NEAP) was positively associated with the prevalence of exhaustion (P for trend = 0.04). There was no association for unintentional weight loss., Conclusions: Dietary acid load was positively associated with the prevalence of frailty, particularly slowness/weakness and low physical activity, in elderly Japanese women.

Background: The intake of tryptophan, the precursor of serotonin, is assumed to affect serotonin availability and depression onset. Nevertheless, a definitive relationship between dietary tryptophan intake and depressive symptoms has not been established. We examined the association between tryptophan intake and depressive symptoms screened in a group of 4272 first-year female dietetic students and 3651 their mothers., Methods: Dietary tryptophan intake during the preceding month was assessed with a validated, self-administered diet history questionnaire. Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale (CES-D) using two cutoff scores: CES-D score ≥ 16 and CES-D score ≥ 19 (the optimal cutoff score for Japanese people). The multivariate adjusted prevalence ratio (PR) and 95% confidence interval (CI) for depressive symptoms were calculated using Poisson regression analysis., Results: The prevalence of depressive symptoms (CES-D score ≥ 16) was 50.0% for young women and 26.5% for middle-aged women. The adjusted PR (95% CI) for depressive symptoms in the highest versus lowest quintile of tryptophan intake was 0.84 (0.75, 0.93) in young women (P for trend < 0.0001) and 0.83 (0.64, 1.01) in middle-aged women (P for trend < 0.0001). These associations were stable even when depressive symptoms were defined as a CES-D score ≥ 19., Limitations: This is a cross-sectional study. Depressive symptoms were assessed using a self-reported questionnaire., Conclusions: This cross-sectional study showed that a higher tryptophan intake was independently associated with a lower prevalence of depressive symptoms in young Japanese women., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Importance: Palmoplantar pustulosis (PPP) is a recalcitrant skin disease with no biologics currently approved for treatment. The involvement of interleukin 23 (IL-23) and cytokines of the type 17 helper T cell lineage in the pathogenesis of PPP has been recently postulated., Objective: To evaluate the efficacy and safety of guselkumab, an anti-IL-23 monoclonal antibody, in Japanese patients with PPP., Design, Setting, and Participants: This double-blind, randomized, placebo-controlled, parallel-group, 24-week trial was conducted between May 14, 2013, and September 27, 2014, at 11 centers in Japan. Participants were patients with moderate to severe PPP that did not respond adequately to conventional treatments., Interventions: Patients were randomized 1:1 to receive guselkumab, 200 mg, by subcutaneous injection or matching placebo at weeks 0 and 4., Main Outcomes and Measures: Changes in total scores of skin-related outcomes from baseline at the end of week 16 (primary clinical cutoff) and through week 24 were measured. Serum biomarker analyses were performed at baseline, week 4, and week 16, and safety was monitored through week 24., Results: Of 49 randomized patients (35 [71%] women; median [range] age, 52 [28-77] years), 41 completed the study at week 24. Mean (SD) PPP severity index total scores (primary end point) improved significantly from baseline in guselkumab-treated patients (-3.3 [2.43]) vs placebo (-1.8 [2.09]) (least squares mean difference, -1.5; 95% CI, -2.9 to -0.2; P = .03). At week 16, PPP area and severity index scores (least squares mean difference, -5.65; 95% CI, -9.80 to -1.50; P = .009) and proportion of patients achieving 50% reduction in these scores (difference in proportion, 39.2; 95% CI, 14.0-64.3; P = .009) improved significantly. A numerically higher proportion of patients had a physician's global assessment score of 1 or less in the guselkumab group vs placebo. Improvement in efficacy scores was maintained through week 24 in the guselkumab group. Significant reductions from baseline in serum IL-17A and IL-17F cytokine levels were observed at weeks 4 and 16. Frequency of treatment-emergent adverse events was comparable between the guselkumab group (19 of 25 patients [76%]) and the placebo group (18 of 24 patients [75%]). Frequent adverse effects included nasopharyngitis (14 patients [29%]), headache (3 patients [6%]), contact dermatitis (3 patients [6%]), and injection site erythema (3 patients [6%]). No major safety concerns emerged during the study., Conclusions and Relevance: Targeting IL-23 and its associated immune cascade with guselkumab may be a safe and useful therapeutic option for treatment of PPP., Trial Registration: clinicaltrials.gov Identifier: NCT01845987.

Objective: The aim of this study was to investigate the potential links between dietary non-enzymatic antioxidant capacity (NEAC) in overall diet and separately from foods and beverages and markers of DNA damage., Methods: The participants were 513 employees, 20 to 65 y of age. Urinary levels of 8-hydroxydeoxyguanosine (8-OHdG) and 7-methylguanine (m 7 Gua) were measured using column-switching high-performance liquid chromatography. Dietary NEAC was determined from databases of NEAC measurements obtained by different assays: ferric reducing-antioxidant power (FRAP), oxygen radical absorbance capacity (ORAC), and total radical-trapping antioxidant parameter (TRAP). Dietary NEAC for each participant was calculated by multiplying the estimated NEAC values with the consumed amount and summing up those values, which was ascertained by a validated brief self-administered diet history questionnaire. Multiple-regression analyses were performed to assess the associations between dietary NEAC and 8-OHdG and m 7 Gua, with adjustment for potential confounders., Results: No statistically significant associations were found between overall dietary NEAC or NEAC from either foods or beverages and urinary 8-OHdG levels, after adjustment for potential confounders (overall: FRAP, P trend  = 0.40; ORAC, P = 0.27; TRAP, P = 0.45). Likewise, no association was found between overall dietary NEAC and m 7 Gua levels (FRAP, P trend  = 0.30; ORAC, P = 0.65; TRAP, P = 0.41). However, we did identify significant inverse association between NEAC from foods, as estimated by TRAP, and m 7 Gua levels (P trend  = 0.049)., Conclusion: Overall, dietary NEAC was not associated with 8-OHdG or m 7 Gua levels. In contrast, dietary NEAC from foods but not beverages may be inversely associated with DNA damage caused by methylation., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background & Aims: Prevention of non-alcoholic fatty liver disease (NAFLD) through lifestyle modification is an important public health issue. Carbohydrate intake from soft drinks has received particular interest. Owing to differences in dietary habits, however, major contributors to the intake of dietary carbohydrates, such as rice, bread, and noodles, might have more influence on NAFLD prevalence in East Asian countries than consumption of soft drinks. We examined the relationship of the intake of rice, bread, and noodles, as well as overall carbohydrate intake, with NAFLD prevalence in middle-aged Japanese., Methods: This is a cross-sectional study of 977 men and 1467 women aged 40-69 y. Dietary information was obtained using a validated self-administered diet history questionnaire. Diagnosis of NAFLD was based on the following criteria: presence of steatosis on abdominal ultrasound, alcohol intake <20 g/day in women and <30 g/day in men, and exclusion of other liver diseases. Logistic regression was performed as multivariate analysis., Results: The presence of NAFLD was 34.9% (n = 341) in men and 11.7% (n = 171) in women. Carbohydrate intake was positively associated with NAFLD prevalence in women (p for trend = 0.008). There was also a positive association between rice intake and NAFLD prevalence in women; the multi-adjusted odds ratio for the highest versus the lowest quartiles of rice intake was 1.87 (95% CI: 1.03, 3.41; p for trend = 0.006). These associations were not observed in men. No association was observed between bread and noodle intake and the prevalence of NAFLD in either sex., Conclusions: Consumption of carbohydrates and rice was positively associated with NAFLD prevalence in middle-aged Japanese women., (Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Living status (e.g., living with family or alone) may affect dietary habits. We compared nutritional adequacy according to living status and the frequency of eating out-of-home foods in young Japanese women., Methods: Female dietetic students (aged 18-20 years; n = 4,017) participated in a cross-sectional multicenter study, which was conducted in 85 dietetic schools in 35 of 47 prefectures in Japan. Habitual dietary intake was assessed with a validated diet history questionnaire. Nutritional adequacy was determined based on the Dietary Reference Intakes for Japanese, 2015, for two goals: preventing non-communicable chronic disease (a tentative dietary goal for preventing lifestyle-related diseases [DG] that tracks five nutrients) and avoiding insufficient intake of mainly vitamins and minerals (estimated average requirement [EAR] that tracks 14 nutrients)., Results: Women living with their family were less likely to meet DG nutrient levels, but more likely to meet EAR nutrient levels compared with those living alone. In contrast, women living alone had more inadequate nutrients with EAR and fewer nutrients with not-meeting DG than those living with families. A higher frequency of eating out-of-home was significantly associated with a higher prevalence of not-meeting DG nutrient levels only in the women living with their family., Conclusions: The prevalence of nutritional adequacy varied based on living status. In addition, women living with their family and those with a high frequency of eating out-of-home foods had the highest prevalence of not-meeting DG. Effective ways of improving dietary quality among young Japanese women differ by living status., (Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Studies in many Western countries have consistently shown that monetary diet cost is positively associated with diet quality, but this may not necessarily be the case in Japan. This cross-sectional study examined the nutritional correlates of monetary diet cost among 3963 young (all 18 years old), 3800 middle-aged (mean age 48 years) and 2211 older (mean age 74 years) Japanese women. Dietary intakes were assessed using a comprehensive self-administered diet history questionnaire for young and middle-aged women and a brief self-administered diet history questionnaire for older women. Monetary diet cost was estimated using retail food prices. Total vegetables, fish and shellfish, green and black tea, white rice, meat, fruit and alcoholic beverages contributed most (79-89 %) to inter-individual variation in monetary diet cost. Multiple regression analyses showed that monetary diet cost was negatively associated with carbohydrate intake, but positively with intakes of all other nutrients examined (including not only dietary fibre and key vitamins and minerals but also saturated fat and Na) in all generations. For food group intakes, irrespective of age, monetary diet cost was associated inversely with white rice and bread but positively with pulses, potatoes, fruit, total vegetables, fruit and vegetable juice, green and black tea, fish and shellfish, and meat. In conclusion, in all three generations of Japanese women and contrary to Western populations, monetary diet cost was positively associated with not only healthy dietary components (including fruits, vegetables, fish and shellfish, dietary fibre, and key vitamins and minerals), but also less healthy components (including saturated fat and Na).

Background: The intake of protein and antioxidants has been inversely associated with frailty, individually. However, to our knowledge, no study has evaluated these associations in considering antioxidants or protein intakes as respective confounders. Further, the cooperative effect of dietary protein and antioxidants on frailty has not been investigated. Therefore, we examined the association of high protein and high dietary total antioxidant capacity (TAC) with frailty under the adjustment for dietary TAC or protein intake, respectively. The association between the combination of high dietary protein and high dietary TAC and frailty was also investigated., Methods: A total of 2108 grandmothers or acquaintances of dietetic students aged 65 years and older participated in this cross-sectional multicenter study conducted in 85 dietetic schools in Japan. Dietary variables, including protein intake, and dietary TAC were estimated from a validated brief-type self-administered diet history questionnaire. Frailty was defined as a score of three or more points obtained from the following four components: slowness and weakness (two points), exhaustion, low physical activity, and unintentional weight loss., Results: Median (interquartile range) age of the present subjects was 74 (71-78) years. Multivariate adjusted ORs (95% CIs) for frailty in the highest compared to the lowest tertile were 0.66 (0.49, 0.87) for total protein intake (P for trend = 0.003) and 0.51 (0.37, 0.69) for dietary TAC (P for trend <0.0001) after adjustment for dietary TAC or total protein intake, respectively. The OR of frailty for the group with both the highest tertiles of total protein intake and dietary TAC was markedly lower (multivariate adjusted OR [95% CIs]: 0.27 [0.16, 0.44]; P <0.0001) compared to the group with the lowest tertile of protein intake and the lowest tertile of dietary TAC., Conclusions: Both protein intake and dietary TAC were independently inversely associated with frailty among old Japanese women. Further, a diet with the combination of high dietary protein and high dietary TAC was strongly inversely associated with the prevalence of frailty in this population. To select food combinations that allow for an increase of both protein and antioxidants in diet according to the local food culture and dietary habits may be an effective strategy for frailty prevention.

Several previous studies have shown that a diet score based on the Japanese food guide Spinning Top (the original score) is associated with both favourable and unfavourable dietary intake patterns. We developed a food-based diet quality score (the modified score) and examined associations with nutrient intakes. Subjects were 3963 young (all aged 18 years), 3800 middle-aged (mean age 47·7 (sd 3·9) years) and 2211 older (mean age 74·4 (sd 5·2) years) Japanese women. Dietary intakes were assessed using comprehensive (for the young and middle-aged) and brief-type (for the older) diet history questionnaires. The original score was calculated based on intakes of grains, vegetables, fish/meat, milk, fruits, and snacks/alcoholic beverages. The modified score was similarly calculated, but included Na from seasonings and without applying the upper cut-off values for dietary components where increased consumption is advocated for Japanese women (grains, vegetables, fish/meat, milk, and fruits). The original score was positively associated with intakes of carbohydrate, dietary fibre, and all the vitamins and minerals examined including Na and inversely with intakes of fats and alcohol in young and middle-aged women. In older women, the original score was inversely associated with intakes of all nutrients except for carbohydrate and vitamin C. However, the modified score was associated positively with intakes of protein, carbohydrate, dietary fibre, K, Ca, Mg, Fe, vitamins A, C and E, and folate and inversely with intakes of fats, alcohol and Na in all generations. In conclusion, the modified diet score was positively associated with favourable nutrient intake patterns in Japanese women.

This study investigated the age effects on the control of dynamic balance during step adjustments under temporal constraints. Fifteen young adults and 14 older adults avoided a virtual white planar obstacle by lengthening or shortening their steps under free or constrained conditions. In the anterior-posterior direction, older adults demonstrated significantly decreased center of mass velocity at the swing foot contact under temporal constraints. Additionally, the distances between the 'extrapolated center of mass' position and base of support at the swing foot contact were greater in older adults than young adults. In the mediolateral direction, center of mass displacement was significantly increased in older adults compared with young adults. Consequently, older adults showed a significantly increased step width at the swing foot contact in the constraint condition. Overall, these data suggest that older adults demonstrate a conservative strategy to maintain anterior-posterior stability. By contrast, although older adults are able to modulate their step width to maintain mediolateral dynamic balance, age-related changes in mediolateral balance control under temporal constraints may increase the risk of falls in the lateral direction during obstacle negotiation., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: We sought to identify clinical features at diagnosis that can distinguish isolated polymyalgia rheumatica (PMR) without giant cell arteritis (GCA) from PMR with GCA, and clinical features at diagnosis of isolated PMR that can predict subsequent relapse and corticosteroid discontinuation., Methods: A retrospective study of 115 patients with isolated PMR and 29 patients with GCA was performed. A comparison between isolated PMR patients, GCA patients (with or without PMR), and PMR with GCA patients was performed. Predictors of relapse and corticosteroid discontinuation were identified using a logistic regression in the patients with isolated PMR., Results: Matrix metalloproteinase-3 (MMP-3) level was significantly different among the patient groups. MMP-3: 230.5 ± 201.5 ng/mL in isolated PMR, 80.5 ± 47.5 ng/mL in GCA (p < 0.01), and 96.8 ± 54.8 ng/mL in PMR with GCA (p = 0.03). In the patients with isolated PMR, female gender (odds ratio [OR], 2.73; 95% confidence interval [CI], 1.16-6.41; p < 0.05) and creatinine (Cr) < 50 μmol/L (OR, 2.48; 95% CI, 1.02-5.99; p < 0.05) were significant prognostic factors that predicted relapse., Conclusion: A low level of MMP-3 is an excellent positive predictor for PMR with GCA. Among patients with isolated PMR, female gender and Cr < 50 μmol/L were significant prognostic factors that predicted relapse.

We examined the cohabitational effect of the grandparents on dietary intakes among young Japanese women and their mothers, using data from a cross-sectional multicenter study conducted in 35 of 47 prefectures in Japan. Among a total of 2032 three-generation families, 1336 female dietetic students (18-20 years), 1336 of their mothers (36-59 years), and 1560 of their paternal or maternal grandmothers (59-94 years) were included. Intake of foods and nutrients was assessed with self-administered diet history questionnaires. The prevalence of students and their mothers living with the grandparents (GP) was 36%. Students living with GP had a higher intake of fruits, vegetables, total dietary fiber, β-carotene, vitamin C and potassium and lower intake of meats than those living without GP. For mothers, fish and shellfish and vitamin C intakes were higher and meat intake was lower among participants living with GP. The median correlation coefficients of food and nutrient intakes in the students-grandmothers living together was higher than in those living apart for both paternal grandmothers (PGM) and maternal grandmothers (MGM) (all P <0.01). The median values of mothers-PGM living together were also significantly higher than in those living apart (P <0.01). However, the values of mothers-MGM did not significantly differ between those living with and without MGM. These results may suggest that family members who live together tend to share similar dietary habits. Further, the mother's dietary habits might affect those of their children even after they live apart., (Copyright © 2015 Elsevier Ltd. All rights reserved.)