Magnetic Resonance Imaging Patterns Revealing Muscle Pathology and Clinical Features in Idiopathic Inflammatory Myopathies.

OBJECTIVE: Idiopathic inflammatory myopathies (IIMs) are autoimmune disorders significantly impacting skeletal muscles; however, the precise correlation between muscle magnetic resonance imaging (MRI) findings, muscle pathology, disease subtypes, and clinical characteristics remains uncertain. Thus, we investigated the association of muscle MRI findings in IIMs with muscle pathology and clinical features. METHODS: New-onset IIM patients underwent proximal upper and/or lower limb muscle MRI. Patterns of muscle oedema on MRI were categorised into fascial, honeycomb, peripheral, foggy, dense, or coarse dot patterns and compared with inflammatory cell infiltration sites in corresponding muscle biopsies. The incidence of MRI patterns was examined in patient subgroups using myositis-specific antibodies (MSAs) and 2017 EULAR/ACR classification criteria. Univariate and multivariate analyses were conducted to determine the odds ratios (ORs) of MRI findings for clinical characteristics. RESULTS: Fifty-six of 85 patients underwent muscle biopsy. Foggy, honeycomb, and fascial patterns at biopsy sites correlated with inflammatory cell infiltration in the endomysium (OR 11.9, p= 0.005), perimysium (OR 6.0, p= 0.014), and fascia (OR 16.9, p< 0.001), respectively. Honeycomb and foggy patterns were characteristic of patients with anti-TIF1γ or anti-Mi2 antibodies and MSA-negative dermatomyositis, and those with anti-SRP or anti-HMGCR antibodies and MSA-negative polymyositis (PM), respectively. The honeycomb pattern positively correlated with malignancy (OR 6.87, p< 0.001) and Gottron sign (OR 8.05, p= 0.002); the foggy pattern correlated with muscle weakness (OR 11.24, p= 0.005). The dense dot pattern was associated with dysphagia (OR 6.27, p= 0.006) and malignancy (OR 8.49, p= 0.002). CONCLUSION: Muscle MRI holds promise in predicting muscle pathology, disease subtypes, and clinical manifestations of IIMs.

Olfactory Bulbs in Arthritis Model Mouse Persistently Express Interleukin-6 before the Onset of Arthritis: Relationship to Food Intake.

INTRODUCTION: Rheumatoid arthritis (RA) can be comorbid with psychiatric symptoms. Brain abnormalities in RA patients and in arthritis models have been reported. However, it remains unclear when these abnormalities occur and where they are distributed. In this study, we analyzed spatiotemporal changes in gene expression in the brains of mice with collagen-induced arthritis (CIA). METHODS: Mice were divided into three groups: (i) CIA (all mice developed arthritis on day 35): complete Freund's adjuvant (CFA) and type II collagen at initial immunization, and incomplete Freund's adjuvant (IFA) and type II collagen at booster immunization; (ii) C(+/-) (50% mice developed arthritis on day 35): only IFA at booster immunization; and (iii) C(-/-) (no arthritis): only CFA at initial immunization and only IFA at booster immunization. Whole brains were collected at ten stages of arthritis and divided into six sections. Real-time polymerase chain reaction was performed using RNA extracted from the brain, and the expression of proinflammatory cytokines and glial markers was semi-quantified. Arthritis score, body weight, and food and water intakes were recorded and analyzed for correlations with brain gene expression. We also investigated the effect of interleukin-6 (IL-6) injection in the olfactory bulbs (OBs) on the food intake. RESULTS: After booster immunization, a transient increase in Integrin subunit α-M and IL-1ß was observed in multiple areas in CIA. IL-6 is persistently expressed in the OB before the onset of arthritis, which is correlated with body weight loss and decreased food intake. This change in the OB was observed in the C(+/-) but not in the C(-/-) groups. In the C(+/-) group, non-arthritic mice showed the same changes in the OB as the arthritic mice. This elevation in IL-6 levels persisted throughout the chronic phase until day 84. In addition, IL-6 injection into the OB reduced food intake. CONCLUSION: Persistent elevation of IL-6 in the OB from the early stage of arthritis may be an important finding that might explain the neuropsychiatric pathophysiology of RA, including appetite loss, which is present in the early stages of the disease and manifests as a variety of symptoms over time.

Clinical features of newly diagnosed systemic lupus erythematosus after SARS-CoV-2 vaccination.

Systemic lupus erythematosus (SLE) is an autoimmune disease that causes damage to multiple organs. Various factors, including vaccination, have been associated with SLE development. Vaccination for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began in 2020, and there are a few reports on the exacerbation of SLE after SARS-CoV-2 vaccination. The influence of SARS-CoV-2 vaccination on SLE development remains unclear. We present the case of a 53-year-old man who developed peritonitis and was subsequently diagnosed with SLE on Day 9 after receiving a third dose of the messenger ribonucleic acid-1273 SARS-CoV-2 vaccine. This case and previous reports have shown that patients who developed SLE after SARS-CoV-2 vaccination are more likely to develop it within 2 weeks of vaccination, especially when they have a higher rate of immunological abnormalities or a family history of autoimmune diseases. Furthermore, these features suggest that type I interferon is involved in the pathogenesis of SLE after SARS-CoV-2 vaccination.

Inhibitory effect of baricitinib on microglia and STAT3 in a region with a weak blood-brain barrier in a mouse model of rheumatoid arthritis.

OBJECTIVES: In patients with RA, baricitinib not only improves arthritis symptom severity, but also patients' neuropsychological symptoms, such as depression and fatigue. However, the cellular mechanisms through which baricitinib can affect neural activity is unexplored. While the blood-brain barrier (BBB) permeability of this drug remains unclear, Janus kinase inhibitors (JAKi) might reach the area postrema, which is a unique brain region with a weak BBB function. Our recent study demonstrated microglial activation during experimental arthritis in the area postrema. Therefore, we sought to assess the effect of baricitinib on microglia in the area postrema using the CIA mouse model. METHODS: Microglia number and morphology in the area postrema were assessed by immunostaining for ionized calcium-binding adaptor molecule-1 (Iba-1). Data were collected on post-immunization day 35 (early phase) and 84 (late phase), and compared between baricitinib- and vehicle-treated mice. The effect on signal transducers and activators of transcription (STAT3) in the area postrema was also immunohistochemically examined. Behavioural outcomes were assessed by examining feeding behaviours and sucrose preference tests. RESULTS: In the early phase, activated microglial levels in the area postrema were decreased by baricitinib, accompanied by the inhibition of phosphorylated-STAT3 and recovery of food intake and sucrose preference. On the other hand, baricitinib did not affect microglial morphology in the late phase. CONCLUSION: Our results demonstrate that baricitinib can affect brain cells, specifically microglia, in the brain region with a weak BBB and mitigate aberrant behaviours during autoimmune arthritis, pointing to the potential therapeutic effect of JAKi on brain pathologies underpinning RA.

How do central sensitisation features affect symptoms among patients with rheumatoid arthritis? Analysis of pain descriptors and the effect of central sensitivity syndrome on patient and evaluator global assessments.

OBJECTIVES: Central sensitivity syndrome (CSS) comprises various symptoms caused by central sensitisation (CS). Using the central sensitisation inventory (CSI), a screening questionnaire developed for detecting CSS, this syndrome was recently identified in patients with long-standing rheumatoid arthritis (RA). However, the descriptors of CS-related pain and the effects of CSS on symptoms in patients with rheumatoid arthritis (RA) remain unknown. We examined the characteristics of pain and influence of CSS on patient and evaluator global assessment among multiple clinical variables. METHODS: We used the central sensitisation inventory (CSI) and short-form McGill pain questionnaire to evaluate CSS and characteristics of pain in 240 outpatients with RA. Disease activity, fibromyalgia, neuropathic pain, anxiety, depression, pain catastrophising, and health-related quality of life were evaluated. We used multivariate analysis to analyse the characteristics of CS-related pain according to CSI and the effect of CSS on patient global assessment (PGA), evaluator global assessment (EGA), and PGA minus EGA among relevant clinical variables. RESULTS: In patients with RA, the main descriptors of pain according to severity of CSI scores were "sharp" and "stabbing", whereas those of pain according to disease activity were "tender" and "throbbing". CSS was associated with EGA (p=0.000, ß=- 0.199) and PGA minus EGA (p=0.021, ß=0.147), but not with PGA. CONCLUSIONS: In patients with RA, descriptors for CS-related pain differ from those for disease activity-related pain. CSS may have an important impact on EGA and PGA minus EGA. Additionally, CSI may be helpful in identifying why there is discordance between PGA and EGA.

Central sensitisation features are associated with neuropathic pain-like symptoms in patients with longstanding rheumatoid arthritis: a cross-sectional study using the central sensitisation inventory.

OBJECTIVES: Several studies have indicated that arthralgia may be driven by central sensitisation. Central sensitivity syndrome (CSS) is a concept that unifies various symptoms due to central sensitisation. Recently, the central sensitisation inventory (CSI) was developed as a screening questionnaire to detect CSS. Using the CSI, we examined the prevalence, the clinical characteristics of CSS, and the association between CSS and neuropathic pain (NP)-like symptoms among rheumatoid arthritis (RA) patients. METHODS: The CSI was administered to 240 RA outpatients. We evaluated their disease activity and several potentially relevant patient-reported outcomes. We compared the clinical parameters depending on the severity of CSS and examined the effect of the CSI score on NP-like symptoms among the relevant clinical parameters using multivariate analyses. RESULTS: The mean disease duration was 9.58 ± 7.76 years. Eighteen (7.5 %) patients had CSS, which was associated with evaluator global assessment (EGA) (odds ratio (OR) 0.860); fibromyalgia symptom scale (OR 1.46); painDETECT questionnaire score (OR 1.24); hospital anxiety and depression scale-anxiety (OR 1.35); and physical (OR 0.898), mental (OR 0.828), and role-social (OR 0.946) component summary scores on the Short-Form 36-Item Health Survey. CSI score was the factor that contributed most to NP-like symptoms (p=0.000, ß=0.266). CONCLUSIONS: NP-like symptoms might be one of the symptoms of CSS in longstanding RA patients. In longstanding RA patients who have disproportionately greater NP-like symptoms and/or widespread pain compared with degree of inflammation, detecting CSS using CSI might help to understand the pathogenesis of patients.

Sustained microglial activation in the area postrema of collagen-induced arthritis mice.

BACKGROUND: Central nervous system (CNS)-mediated symptoms, such as fatigue, depression, and hyperalgesia, are common complications among patients with rheumatoid arthritis (RA). However, it remains unclear how the peripheral pathology of RA spreads to the brain. Accumulated evidence showing an association between serum cytokine levels and aberrant CNS function suggests that humoral factors participate in this mechanism. In contrast to the well-known early responses of microglia (CNS-resident immune cells) in the area postrema [AP; a brain region lacking a blood-brain barrier (BBB)] to experimental inflammation, microglial alterations in the AP during chronic inflammation like RA remain unclear. Therefore, to determine whether microglia in the AP can react to persistent autoimmune-arthritis conditions, we analyzed these cells in a mouse model of collagen-induced arthritis (CIA). METHODS: Microglial number and morphology were analyzed in the AP of CIA and control mice (administered Freund's adjuvant or saline). Immunostaining for ionized calcium-binding adaptor molecule-1 was performed at various disease phases: "pre-onset" [post-immunization day (PID) 21], "establishment" (PID 35), and "chronic" (PID 56 and 84). Quantitative analyses of microglial number and morphology were performed, with principal component analysis used to classify microglia. Interleukin-1ß (IL-1ß) mRNA expression was analyzed by multiple fluorescent in situ hybridization and real-time polymerase chain reaction. Behavioral changes were assessed by sucrose preference test. RESULTS: Microglia in the AP significantly increased in density and exhibited changes in morphology during the establishment and chronic phases, but not the pre-onset phase. Non-subjective clustering classification of cell morphology (CIA, 1,256 cells; saline, 852 cells) showed that the proportion of highly activated microglia increased in the CIA group during establishment and chronic phases. Moreover, the density of IL-1ß-positive microglia, a hallmark of functional activation, was increased in the AP. Sucrose preferences in CIA mice negatively correlated with IL-1ß expression in brain regions containing the AP. CONCLUSIONS: Our findings demonstrate that microglia in the AP can sustain their activated state during persistent autoimmune arthritis, which suggests that chronic inflammation, such as RA, may affect microglia in brain regions lacking a BBB and have various neural consequences.

Population dynamics in the Japanese Archipelago since the Pleistocene revealed by the complete mitochondrial genome sequences.

The Japanese Archipelago is widely covered with acidic soil made of volcanic ash, an environment which is detrimental to the preservation of ancient biomolecules. More than 10,000 Palaeolithic and Neolithic sites have been discovered nationwide, but few skeletal remains exist and preservation of DNA is poor. Despite these challenging circumstances, we succeeded in obtaining a complete mitogenome (mitochondrial genome) sequence from Palaeolithic human remains. We also obtained those of Neolithic (the hunting-gathering Jomon and the farming Yayoi cultures) remains, and over 2,000 present-day Japanese. The Palaeolithic mitogenome sequence was not found to be a direct ancestor of any of Jomon, Yayoi, and present-day Japanese people. However, it was an ancestral type of haplogroup M, a basal group of the haplogroup M. Therefore, our results indicate continuity in the maternal gene pool from the Palaeolithic to present-day Japanese. We also found that a vast increase of population size happened and has continued since the Yayoi period, characterized with paddy rice farming. It means that the cultural transition, i.e. rice agriculture, had significant impact on the demographic history of Japanese population.

Surgical outcomes after primary Baerveldt glaucoma implant surgery with vitrectomy for neovascular glaucoma.

This study aimed to evaluate the 3-year long-term outcomes of primary Baerveldt glaucoma implant (BGI) surgery for neovascular glaucoma (NVG). We retrospectively evaluated 27 consecutive patients with NVG between November 2013 and November 2017. All the patients were treated with panretinal photocoagulation and pars plana vitrectomy before BGI surgery without anti-vascular endothelial growth factor treatment. The surgical success of the BGI was defined as an IOP of <22 mmHg and <5 mmHg with or without antiglaucoma medication. The outcomes were assessed on the basis of intraocular pressure (IOP), visual acuity, postoperative complications, and cumulative success rate. Except for 2 mortality cases, 25 eyes (92.6%) were followed up for 3 years. The mean IOPs (mmHg)/numbers of glaucoma medications ± standard error of the mean before and 12 and 36 months after BGI surgery were 41.6/4.6 ± 1.9/0.2, 14.8/2.2 ± 0.8/0.4 and 16.9/2.6 ± 1.1/0.3, respectively. In all of the follow-up time points, the postoperative mean IOP and number of glaucoma medications were statistically significantly lower than the preoperative values (analysis of variance, P < 0.001). At 3 years after surgery, the rates of visual acuity improvement (logMAR ≤ -0.3), invariance (-0.3 < logMAR < 0.3), and worsening (logMAR ≥ 0.3) were 56.0% (14/25 eyes), 24.0% (6/25 eyes), and 20.0% (5/25 eyes), respectively. The most common postoperative complications were hyphema (4 eyes, 14.8%) and vitreous hemorrhage (5 eyes, 18.5%), and serious complications such as expulsive hemorrhage, endophthalmitis, and tube/plate exposure did not occur. The cumulative probabilities of surgical success after the operation were 100% at 1 year, 85.2% at 2 years, and 77.4% at 3 years. In conclusion, combined non-valved pars plana tube placement in conjunction with vitrectomy was successful at lowering IOP with relatively low complication rates.

A biomolecular anthropological investigation of William Adams, the first SAMURAI from England.

William Adams (Miura Anjin) was an English navigator who sailed with a Dutch trading fleet to the far East and landed in Japan in 1600. He became a vassal under the Shogun, Tokugawa Ieyasu, was bestowed with a title, lands and swords, and became the first SAMURAI from England. "Miura" comes from the name of the territory given to him and "Anjin" means "pilot". He lived out the rest of his life in Japan and died in Hirado, Nagasaki Prefecture, in 1620, where he was reportedly laid to rest. Shortly after his death, graveyards designated for foreigners were destroyed during a period of Christian repression, but Miura Anjin's bones were supposedly taken, protected, and reburied. Archaeological investigations in 1931 uncovered human skeletal remains and it was proposed that they were those of Miura Anjin. However, this could not be confirmed from the evidence at the time and the remains were reburied. In 2017, excavations found skeletal remains matching the description of those reinterred in 1931. We analyzed these remains from various aspects, including genetic background, dietary habits, and burial style, utilizing modern scientific techniques to investigate whether they do indeed belong to the first English SAMURAI.

Sex differences of dental pathology in early modern samurai and commoners at Kokura in Japan.

So-called "Ohaguro", teeth blackening, in the married females was a general custom regardless of class in the early modern period. As a result, Ohaguro was thought to have enhanced the acid resistance of tooth substance and tightened gingiva and prevented tooth morbidity due to periodontal disease. For investigation into the influence of Ohaguro, the skeletal remains of early modern samurai and commoners at Kokura were examined for differences in the dental pathology based on sex. Though females from archeological sites have significantly more carious teeth and antemortem tooth loss (AMTL) than males in the previous studies, the prevalence of caries and AMTL in males was higher than in females among the early modern samurai and commoners in Kokura. The efficacies of Ohaguro may influence the good dental health of females. On the other hand, as females were considered inferior to males under the feudal system in Japan, males, including children, might tend to consume more nutritious foods compared to females. However, those foods are certainly not better with regard to dental health, since those foods are more highly cariogenic. These factors may have caused higher caries and AMTL prevalence among males compared to females in early modern Kokura.

An Evaluation of Sensor Performance for Harmful Compounds by Using Photo-Induced Electron Transfer from Photosynthetic Membranes to Electrodes.

Rapid, simple, and low-cost screening procedures are necessary for the detection of harmful compounds in the effluent that flows out of point sources such as industrial outfall. The present study investigated the effects on a novel sensor of harmful compounds such as KCN, phenol, and herbicides such as 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU), 2-chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine (atrazine), and 2-N-tert-butyl-4-N-ethyl-6-methylsulfanyl-1,3,5-triazine-2,4-diamine (terbutryn). The sensor employed an electrode system that incorporated the photocurrent of intra-cytoplasmic membranes (so-called chromatophores) prepared from photosynthetic bacteria and linked using carbon paste electrodes. The amperometric curve (photocurrent-time curve) of photo-induced electron transfer from chromatophores of the purple photosynthetic bacterium Rhodobacter sphaeroides to the electrode via an exogenous electron acceptor was composed of two characteristic phases: an abrupt increase in current immediately after illumination (I0), and constant current over time (Ic). Compared with other redox compounds, 2,5-dichloro-1,4-benzoquinone (DCBQ) was the most useful exogenous electron acceptor in this system. Photo-reduction of DCBQ exhibited Michaelis-Menten-like kinetics, and reduction rates were dependent on the amount of DCBQ and the photon flux intensity. The Ic decreased in the presence of KCN at concentrations over 0.05 µM (=µmol·dm(-3)). The I0 decreased following the addition of phenol at concentrations over 20 µM. The Ic was affected by terbutryn at concentrations over 10 µM. In contrast, DCMU and atrazine had no effect on either I0 or Ic. The utility of this electrode system for the detection of harmful compounds is discussed.

Prediction of human thermophysiological responses during shower bathing.

This study develops a model to predict the thermophysiological response of the human body during shower bathing. Despite the needs for the quantitative evaluation of human body response during bathing for thermal comfort and safety, the complicated mechanisms of heat transfer at the skin surface, especially during shower bathing, have disturbed the development of adequate models. In this study, an initial modeling approach is proposed by developing a simple heat transfer model at the skin surface during shower bathing applied to Stolwijk's human thermal model. The main feature of the model is the division of the skin surface into three parts: a dry part, a wet part without water flow, and a wet part with water flow. The area ratio of each part is decided by a simple formula developed from a geometrical approach based on the shape of the Stolwijk's human thermal model. At the same time, the convective heat transfer coefficient between the skin and the flowing water is determined experimentally. The proposed model is validated by a comparison with the results of human subject experiments under controlled and free shower conditions. The model predicts the mean skin temperature during shower fairly well both for controlled and free shower bathing styles.

Mitochondrial DNA analysis of Yayoi period human skeletal remains from the Doigahama site.

We analyzed the mitochondrial DNA extracted from 14 human skeletal remains from the Doigahama site in Japan to clarify the genetic structure of the Doigahama Yayoi population and the relationship between burial style and kinship among individuals. The sequence types obtained in this study were compared with those of the modern Japanese, northern Kyushu Yayoi and ancient Chinese populations. We found that the northern Kyushu Yayoi populations belonged to the groups that include most of the modern Japanese population. In contrast, most of the Doigahama Yayoi population belonged to the group that includes a small number of the modern Japanese population. These results suggest that the Doigahama Yayoi population might have contributed less to the formation of the modern Japanese population than the northern Kyushu Yayoi populations. Moreover, when we examined the kinship between individuals in the Doigahama site, we found that the vicinal burial of adult skeletons indicated a maternal kinship, although that of juvenile skeletons did not. The vicinal burial style might have been influenced by many factors, such as paternal lineages, periods and geographical regions, as well as maternal lineages. In addition, skeletons considered to be those of shamans or leaders had the same sequence types. Their crucial social roles may have been inherited through maternal lineage.

Development of a simple column electrode for sensitive and rapid coulometry.

A simple column electrode, S-CE, with a glassy carbon fibers working electrode stuffed into a Teflon tube was developed. The current-potential curves for the reductions of [Fe(CN)(6)](3-) and Fe(3+) observed at the S-CE were analyzed based on a theory for those at an ordinary column electrode. A quantitative electrolysis was performed at the S-CE rapidly within 20 s. An accurate and precise coulometric determination could be attained at the S-CE even with a fairly dilute solution. For example, coulometric reductions of 5 x 10(-5) and 5 x 10(-6) M Fe(3+) were attained with efficiencies (n = 5) of 99.7 +/- 0.2 and 101.9 +/- 1.1%, respectively.

Lifestyle-determined gender and hierarchical differences in the lead contamination of bones from a feudal town of the Edo period.

We analyzed lead concentrations in bones from both genders of Japanese merchants (including rohnin; masterless samurai) and farmer classes, and compared the findings with those of the samurai class in the Edo period (1603-1867) to clarify gender and hierarchical (or occupational) differences in lead exposure during the Japanese feudal age. Merchant class females had significantly higher lead exposure (90.8 microg Pb/g dry bone; n=20) than males of the same class (39.9 microg Pb/g dry bone; n=31) (p<0.01), indicating a remarkable gender difference in the urban population. In contrast to these high concentrations, males and females of the farmer class living in agricultural (or semi-rural) areas had significantly lower exposure (total mean value; 9.2 mug Pb/g dry bone; n=4) than both genders of the merchant class (p<0.001), and the gender difference was not significant in this class.

Time-dependent self-assembly of 31-epimerically pure and mixed zinc methyl bacteriopheophorbides-d in an aqueous THF solution.

The self-aggregation process of 3(1)-epimerically pure and mixed zinc methyl bacteriopheophorbides-d (ZMBPhes-d) was examined by stopped-flow technique. A 33(v/v)% tetrahydrofuran (THF) - water solution of ZMBPhe-d was rapidly mixed with a 7(v/v)% THF - water solution to form a chlorosome-type aggregate with a red-shifted Qy band around 700 nm. We observed a rapid autocatalytic aggregation in a subsecond time scale. Aggregates of the 3(1)R epimer increased with a change in the Qy absorption maximum from 698 to 705 nm, suggesting that small aggregates formed as intermediate species. In addition, the rate of aggregation was dependent on the stereochemistry at the 3(1)-position of ZMBPhe-d; the 3(1)R epimer self-aggregated more rapidly than the 3(1)S epimer.

Coaggregate of amphiphilic zinc chlorins with synthetic surfactants in an aqueous medium to an artificial supramolecular light-harvesting system.

Aqueous assemblies of zinc chlorins possessing a nonionic (oligo)oxyethylene, a cationic quaternary ammonium or an anionic sulfonate group were prepared in the presence of a synthetic surfactant. The nonionic zinc chlorin formed aggregates when admixed with a nonionic surfactant such as Triton X-100 to give a highly ordered oligomeric J-aggregate similarly as natural bacteriochlorophyll-c or d does in a chlorosome. In addition, the coassemblies of the cationic zinc chlorin with an anionic surfactant and of the anionic zinc chlorin with a cationic surfactant gave large oligomers of these chlorophyllous pigments. The structures of hydrophilic groups in both the zinc chlorin and surfactant molecules controlled their aqueous coassemblies.