Effect of Liver Fibrosis on Oral and Gut Microbiota in the Japanese General Population Determined by Evaluating the FibroScan-Aspartate Aminotransferase Score.

The association between liver fibrosis and oral or gut microbiota has been studied before. However, epidemiological studies in the general population are limited owing to the difficulty of noninvasive liver-fibrosis assessment. FibroScan-asparate aminotransferase (FAST) scores can be used to accurately and non-invasively evaluate liver fibrosis. This study aimed to determine the association between liver fibrosis and oral or gut microbiota using the FAST score in the general population. After propensity score matching of 1059 participants based on sex, age, body mass index, homeostasis model assessment of insulin resistance, and triglyceride levels, 125 (non-liver-fibrosis group, 100; liver fibrosis group, 25) were included. The diversity of gut microbiota differed significantly between the two groups; however, no significant differences were noted in their oral microbiota. The liver fibrosis group showed an increase in the relative abundance of Fusobacteria strains and a decrease in the relative abundance of Faecalibacterium, with the presence of Fusicatenibacter in the gut microbiota. Feacalibacterium was not identified as an independent factor of liver fibrosis in adjusting the fatty liver index. In the general population, gut microbiota may be more involved in liver fibrosis than oral microbiota.

Association between reactive oxygen species production in neutrophils and liver fibrosis in the general population.

Fibrosis, induced by reactive oxygen species (ROS) production in neutrophils, has harmful effects on the liver and various other organs. However, little is known about the association between liver fibrosis and ROS levels in neutrophils in the general population. This large-scale epidemiological study aimed to determine the association between liver fibrosis and neutrophil-generated ROS levels according to age and sex in the general population. This cross-sectional study included 1,000 participants from a district health promotion project. Participants were grouped based on sex (male; female) and age (young, <65 years; old, ≥65 years). The four groups were as follows: male, young (n = 289); male, old (n = 100); female, young (n = 425); and female, old (n = 186). Liver fibrosis was assessed using the fibrosis 4 (FIB-4) index, aspartate aminotransferase-to-platelet ratio index (APRI), and non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS). Basal and stimulated ROS were considered in the analysis. Multiple linear analyses showed (1) significant positive correlations between all liver fibrosis scores and basal ROS in the young groups, and (2) significant negative correlations between NFS and stimulated ROS in females. Preventing liver fibrosis through neutrophil-related immune system enhancement may avert the development of lifestyle-related diseases and infections.

Greater medial proximal tibial slope is associated with bone marrow lesions in middle-aged women with early knee osteoarthritis.

BACKGROUND: Bone marrow lesion (BML) is an important magnetic resonance finding (MRI) finding that predicts knee osteoarthritis. The purpose of this study was to investigate the influence of proximal tibial morphology on BML, including the spreading root sign (SRS), in women without radiographic knee osteoarthritis (OA). It was hypothesized that varus alignment and a greater posterior tibial slopes (PTS) are associated with BML. MATERIALS AND METHODS: A total of 359 female volunteers without knee OA who were participants in the Iwaki Health Promotion Project in 2017 or 2019 were enrolled. Participants were divided into the non-OA and early knee OA (EKOA) groups based on the Luyten's classification criteria. The presence of pathological cartilage lesions, BMLs, attritions, meniscal lesions and effusions was scored on T2-weighted fat-suppressed magnetic resonance imaging (MRI) according to the Whole-Organ MRI Scoring system. The medial proximal tibial angle (MPTA) and medial and lateral PTS (MPTS and LPTS, respectively) were measured. Regression and receiver operating characteristic (ROC) analyses were performed to reveal the relationship between BMLs and proximal tibial morphological parameters. RESULTS: Of the 359 participants, 54 (15%) were classified as having EKOA. The prevalence of cartilage lesions, BMLs, attritions, meniscal lesions and effusions was higher in the EKOA group than in the non-OA group. The two groups had no significant difference in the proximal tibial parameters. Regression analysis revealed that age and a smaller MPTA were associated with BML in both groups. Attrition (p = 0.029) and the MPTS (p = 0.025) were positively associated with BML in the EKOA group. CONCLUSION: The prevalence of BMLs was higher in women with EKOA and correlated with the varus and greater posterior slopes in those without radiographic knee OA. LEVEL OF EVIDENCE: Level III, retrospective case-control study.

Effusion detected by ultrasonography and overweight may predict the risk of knee osteoarthritis in females with early knee osteoarthritis: a retrospective analysis of Iwaki cohort data.

BACKGROUND: Knee osteoarthritis (OA) has enormous medical and socioeconomic burdens, which early diagnosis and intervention can reduce. We investigated the influence of knee effusion on the progression of knee OA in patients with early knee OA. METHODS: A total of 404 participants without radiographic knee OA were assessed from a 3-year longitudinal analysis. Participants were classified into non-OA and early knee OA groups. The effusion area (mm2) was quantified using ultrasonography. Receiver operating characteristic and logistic regression analyses were performed. RESULTS: At the 3-year follow-up, 114 of 349 knees (32%) had progressed from non-OA and 32 of 55 knees (58%) had progressed from early knee OA to radiographic knee OA. Logistic regression analysis showed that female sex (odds ratio [OR] 3.36, 95% confidence interval [CIs] 2.98-5.42), early knee OA (OR 2.02, 95% CI 1.08-3.75), body mass index (OR 1.11, 95% CI 1.02-1.19), and effusion area (OR 1.01, 95% CI 1.01-1.02) were significantly correlated with knee OA progression. Women who were overweight (body mass index ≥ 25 kg/m2) with more severe effusion had a higher risk of OA progression (area under the curve = 0.691, OR = 6.00) compared to those not overweight (area under the curve = 0.568, OR = 1.91). CONCLUSION: Knee effusion may be an indicator of the progression of early-stage knee OA.

Bone marrow lesion severity was associated with proximal tibial inclination in early knee osteoarthritis.

PURPOSE: This study aimed to investigate the effect of tibial plateau (TP) inclination and serum bone metabolic markers on bone marrow lesion (BML) in the general Japanese population with early knee osteoarthritis (EKOA). METHODS: A total of 441 female volunteers who participated in the Iwaki Health Promotion Project in 2017 were enrolled. Participants without radiographic abnormalities were divided into normal and EKOA groups according to the Luyten's classification criteria for EKOA. The medial proximal tibial angle (MPTA), growth plate-TP angle, and growth plate-medial tibial plateau (MTP) angle were measured on standing anteroposterior radiographs of the knees. BML severity on T2-weighted fat-suppressed magnetic resonance imaging (MRI) was scored using the Whole-Organ MRI Score method. Serum levels of N-telopeptide of type I collagen, tartrate-resistant acid phosphatase-5b (TRACP-5b), bone-specific alkaline phosphatase, procollagen type I N-terminal propeptide, pentosidine, and homocysteine were assessed. Linear regression analysis was conducted to investigate the relationship between proximal tibial inclination, BML, and serum bone metabolic markers. RESULTS: The growth plate was observed in 309 (70%) participants, and 48 (16%) participants had EKOA. The mean MPTA, growth plate-TP angle, and growth plate-MTP angle were 86.1 ± 5.9°, 3.6 ± 1.1°, and 9.9 ± 2.6°, respectively. The MPTA was negatively correlated with the growth plate-TP and growth plate-MTP angles (p = 0.006, p < 0.001). Participants with EKOA who had BML exhibited greater growth plate-MTP angle than those who did not (p = 0.018). Regression analysis revealed that BML severity was positively associated with MPTA (p = 0.036) and a bone formation marker (p = 0.045). CONCLUSION: BML severity was positively associated with proximal tibial inclination and serum TRACP-5b level in participants with EKOA and normal knees, respectively. Assessment of proximal tibial inclination may provide insight into potential BML risk. Residual medial tibial inclination may potentially result in knee pain and symptoms in EKOA. LEVEL OF EVIDENCE: III.

Association of serum creatinine-to-cystatin C ratio with skeletal muscle mass and strength in nonalcoholic fatty liver disease in the Iwaki Health Promotion Project.

We evaluated the feasibility of using serum creatinine-to-cystatin C ratio in the assessments of muscle mass and strength in nonalcoholic fatty liver disease. In a community-based cross-sectional study, skeletal muscle mass and handgrip strength were assessed in 641 Japanese adults. Low skeletal muscle mass index and low handgrip strength were defined as indicated in the sarcopenia diagnostic criteria of the Japan Society of Hepatology. Nonalcoholic fatty liver disease was defined as fatty liver on ultrasonography in the absence of other causes of steatosis. The creatinine-to-cystatin C ratio was useful for identifying the participants with low skeletal muscle mass index, with an area under the receiver-operating characteristic curve of 0.84 [95% confidence interval (CI), 0.77-0.91] in men and 0.72 in women (95% CI, 0.65-0.78), and those with low handgrip strength, with an area under the receiver-operating characteristic curve of 0.96 (95% CI, 0.93-0.99) in men and 0.79 (95% CI, 0.66-0.92) in women. Moreover, the creatinine-to-cystatin C ratio correlated with skeletal muscle mass index (r = 0.511, p<0.001) and handgrip strength (r = 0.657, p<0.001), whereas it did not correlate with exacerbation of hepatic steatosis. In this study, creatinine-to-cystatin C ratio correlated with muscle mass and strength in nonalcoholic fatty liver disease regardless of hepatic steatosis.

Leptin/adiponectin ratio correlates with hepatic steatosis but not arterial stiffness in nonalcoholic fatty liver disease in Japanese population.

BACKGROUND AND AIMS: Cardiovascular disease (CVD) is a leading cause of mortality in nonalcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the relationship of leptin-to-adiponectin (L/A) ratio with hepatic steatosis and arterial stiffness in NAFLD. METHODS: The subjects were 871 Japanese adults who participated in a health survey. Dietary intake, body composition, lipid profile, serum interleukin-6 (IL-6), leptin, and adiponectin were analyzed. NAFLD was defined as fatty liver on ultrasonography in the absence of other causes of steatosis. Arterial stiffness was evaluated by the brachial-ankle pulse wave velocity (baPWV). RESULTS: The subjects with NAFLD had a greater body mass index (BMI) and body fat percentage (BFP); a higher intake of daily energy (kcal) and carbohydrates; and a higher prevalence of hypertension, diabetes, and hyperlipidemia. The subjects with NAFLD had higher serum leptin and lower serum adiponectin concentrations and a higher L/A ratio than subjects without NAFLD. The L/A ratio increased with increasing severity of steatosis. The L/A ratio showed positive correlations with BMI and BFP, and a negative correlation with age. Women had higher L/A ratio and BFP levels than men regardless of the presence or absence of NAFLD. There was a weak positive correlation between baPWV and severity of steatosis. BaPWV was strongly correlated with age, while no relation was found between baPWV and L/A ratio. IL-6 level was correlated with baPVW and age, while the correlation between Il and 6 level and L/A ratio was very weak. The L/A ratio was correlated with triglycerides and the ratio of total cholesterol to high-density lipoprotein-cholesterol. CONCLUSION: L/A ratio and arterial stiffness were associated with the severity of steatosis, whereas there was no correlation between L/A ratio and arterial stiffness in NAFLD. These findings suggest that not only leptin and adiponectin but also other factors might be involved in the pathogenesis for atherosclerosis in NAFLD.

Relationship between gut microbiota composition and sensitization to inhaled allergens.

BACKGROUND: An imbalance in gut microbiota is implicated in several pathological conditions, including allergic diseases. This study investigates the association between gut microbiota composition and sensitization to two inhaled antigens. METHODS: The study comprised 1109 local residents who had participated in the Iwaki Health Promotion Project in 2016. Blood samples were analyzed for levels of antigen-specific IgE against Japanese cedar pollen (JCP) and house dust (HD1). Fecal samples were analyzed for bacterial 16S rRNA (ribosomal ribonucleic acid) using next generation sequencing. The percent composition of gut microbes was compared between patients sensitized and unsensitized group for JCP and HD1 to determine whether the rate of sensitization to inhaled antigens associates with specific bacterial orders composing the gut microbiota. RESULTS: In participants aged 20-49 years, the percent composition of Bacteroidales was significantly higher among participants sensitized to JCP than in those unsensitized. The percent composition of Lactobacillales was significantly higher in participants unsensitized to HD group than in those sensitized to that antigen. In addition, participants with low Bacteroidales and high Bifidobacteriales or Lactobacillales has low sensitization rates to HD compared with high Bacteroidales and low Bifidobacteriales or Lactobacillales. CONCLUSIONS: The presence of bacteria of order Lactobacillales, Bifidobacteriales, and Bacteroidales in the gut microbiota may affect sensitization to inhaled allergens.

ERO1α is a novel endogenous marker of hypoxia in human cancer cell lines.

BACKGROUND: Hypoxia is an important factor that contributes to tumour aggressiveness and correlates with poor prognosis and resistance to conventional therapy. Therefore, identifying hypoxic environments within tumours is extremely useful for understanding cancer biology and developing novel therapeutic strategies. Several studies have suggested that carbonic anhydrase 9 (CA9) is a reliable biomarker of hypoxia and a potential therapeutic target, while pimonidazole has been identified as an exogenous hypoxia marker. However, other studies have suggested that CA9 expression is not directly induced by hypoxia and it is not expressed in all types of tumours. Thus, in this study, we focused on endoplasmic reticulum disulphide oxidase 1α (ERO1α), a protein that localises in the endoplasmic reticulum and is involved in the formation of disulphide bonds in proteins, to determine whether it could serve as a potential tumour-hypoxia biomarker. METHODS: Using quantitative real-time polymerase chain reaction, we analysed the mRNA expression of ERO1α and CA9 in different normal and cancer cell lines. We also determined the protein expression levels of ERO1α and CA9 in these cell lines by western blotting. We then investigated the hypoxia-inducible ERO1α and CA9 expression and localisation in HCT116 and HeLa cells, which express low (CA9-low) and high (CA9-high) levels of CA9, respectively. A comparative analysis was performed using pimonidazole, an exogenous hypoxic marker, as a positive control. The expression and localisation of ERO1α and CA9 in tumour spheres during hypoxia were analysed by a tumour sphere formation assay. Finally, we used a mouse model to investigate the localisation of ERO1α and CA9 in tumour xenografts using several cell lines. RESULTS: We found that ERO1α expression increased under chronic hypoxia. Our results show that ERO1α was hypoxia-induced in all the tested cancer cell lines. Furthermore, in the comparative analysis using CA9 and pimonidazole, ERO1α had a similar localisation to pimonidazole in both CA9-low and CA9-high cell lines. CONCLUSION: ERO1α can serve as a novel endogenous chronic hypoxia marker that is more reliable than CA9 and can be used as a diagnostic biomarker and therapeutic target for cancer.

Comparative analysis of methicillin-resistant Staphylococcus aureus isolated from outpatients of dermatology unit in hospitals and clinics.

Community-onset methicillin-resistant Staphylococcus aureus (CO-MRSA) is a causative agent of intractable skin infections. In general, clinical symptoms of hospital outpatients with skin infections are severer than those of clinic patients. Hence, molecular epidemiological features of the CO-MRSA strains from hospital outpatients are predicted to be different from those of clinic patients. Here, we conducted a comparative analysis for CO-MRSA isolates from outpatients with impetigo in hospitals and clinics located in the same district of Tokyo, Japan. Incidence of MRSA infection was higher in hospital outpatients (21.5%, 20/93 isolates) than in clinic patients (14.5%, 121/845 isolates). The resistance rate to clindamycin, which is a common topical antimicrobial agent in dermatology, in the isolates from hospital outpatients (60.0%) was higher than those from clinic patients (31.4%). Proportion of the staphylococcal cassette chromosome (SCC) mec type II, which is a representative type of hospital-acquired MRSA in Japan, in the isolates from hospital outpatients (65.0%) was significantly higher than those from clinic patients (30.6%) (P < 0.01). Multilocus sequence typing showed that the clonal complex 89-SCCmec type II (CC89-II) clone, which exhibits clindamycin resistance, was the most predominant (55.0%) in the isolates from hospital outpatients. On the other hand, all CC8-IV, CC121-V, and CC89-V clones accounted for 60% in clinic patients were susceptible to clindamycin. Our findings suggested that the clindamycin-resistant CC89-II CO-MRSA clone might be more related to skin infections in hospital outpatients than clinic patients.

Novel Electrocardiographic Criteria for the Diagnosis of Left Ventricular Hypertrophy in the Japanese General Population.

Although there are several diagnostic criteria for left ventricular hypertrophy (LVH), their sensitivity remains low. A recent study reported that the sum of the amplitude of the deepest S wave in any lead (SD) and the S wave in lead V4 (SV4) (SD + SV4) improved sensitivity compared with commonly used criteria. To test whether this new formula improves sensitivity in the Japanese general population, we analyzed 12-lead electrocardiograms for Japanese residents participating in the Iwaki Health Promotion Project (n = 866). Left ventricular mass was calculated by echocardiography, indicating that 156 (18%) of the study population had LVH. In receiver operating characteristic analyses, the sum of the R wave in limb lead Ι (RLΙ) and the S wave in V4 (SV4) (RLΙ + SV4) showed a higher area under the curve (AUC = 0.76) than the Sokolow-Lyon voltage criteria (0.61) and the SD + SV4 criteria (0.63), and almost the same AUC as the Cornell voltage criteria (0.74) and the Cornell product criteria (0.76). The validation study also showed similar results. The cutoff values of RLΙ + SV4 criteria were ≥1.6 mV in men and ≥1.4 mV in women with a sensitivity of 39% and a specificity of 89%, whereas the sensitivity and specificity calculated based on SD + SV4 criteria were 21% and 94%, respectively. Thus, the diagnostic criterion of RLΙ + SV4 seems to be more useful than the previous criteria for diagnosing LVH in the Japanese general population.

Influence of gastric endoscopic submucosal dissection on serum opsonic activity measured by chemiluminescence.

This study aimed to elucidate whether changes in serum opsonic activity measured by lucigenin-dependent chemiluminescence and luminol-dependent chemiluminescence are useful for estimating physical stress during the perioperative period of gastric endoscopic submucosal dissection. Serum opsonic activity in the peripheral blood of 87 patients was examined in the morning of the day of endoscopic submucosal dissection, the next day, and at 4 days after endoscopic submucosal dissection. Peak height and area under the curve for lucigenin-dependent chemiluminescence were 106.1 ± 22.7% and 102.0 ± 24.7% on the day of endoscopic submucosal dissection, which increased significantly to 113.6 ± 29.4% and 111.0 ± 29.1% on the next day (both p<0.01), and 112.4 ± 27.0% and 110.0 ± 28.1% at 4 days after endoscopic submucosal dissection (both p<0.01), respectively. In contrast, significant changes were not observed in peak height and area under the curve for luminol-dependent chemiluminescence during the perioperative period of endoscopic submucosal dissection. This difference suggests that serum opsonic activity during the perioperative period of gastric endoscopic submucosal dissection is associated with the production of substances with lower oxidizing potential. (The study of changes in neutrophil function and physical stress during the perioperative period of endoscopic operation: UMIN000034514).

Endoplasmic reticulum oxidase 1α is critical for collagen secretion from and membrane type 1-matrix metalloproteinase levels in hepatic stellate cells.

Upon liver injury, excessive deposition of collagen from activated hepatic stellate cells (HSCs) is a leading cause of liver fibrosis. An understanding of the mechanism by which collagen biosynthesis is regulated in HSCs will provide important clues for practical anti-fibrotic therapy. Endoplasmic reticulum oxidase 1α (ERO1α) functions as an oxidative enzyme of protein disulfide isomerase, which forms intramolecular disulfide bonds of membrane and secreted proteins. However, the role of ERO1α in HSCs remains unclear. Here, we show that ERO1α is expressed and mainly localized in the endoplasmic reticulum in human HSCs. When HSCs were transfected with ERO1α siRNA or an ERO1α shRNA-expressing plasmid, expression of ERO1α was completely silenced. Silencing of ERO1α expression in HSCs markedly suppressed their proliferation but did not induce apoptosis, which was accompanied by impaired secretion of collagen type 1. Silencing of ERO1α expression induced impaired disulfide bond formation and inhibited autophagy via activation of the Akt/mammalian target of rapamycin signaling pathway, resulting in intracellular accumulation of collagen type 1 in HSCs. Furthermore, silencing of ERO1α expression also promoted proteasome-dependent degradation of membrane type 1-matrix metalloproteinase (MT1-MMP), which stimulates cell proliferation through cleavage of secreted collagens. The inhibition of HSC proliferation was reversed by treatment with MT1-MMP-cleaved collagen type 1. The results suggest that ERO1α plays a crucial role in HSC proliferation via posttranslational modification of collagen and MT1-MMP and, therefore, may be a suitable therapeutic target for managing liver fibrosis.

Vitamin A and insulin are required for the maintenance of hepatic stellate cell quiescence.

Transdifferentiation of vitamin A-storing hepatic stellate cells (HSCs) to vitamin A-depleted myofibroblastic cells leads to liver fibrosis. Vitamin A regulates lipid accumulation and gene transcription, suggesting that vitamin A is involved in the maintenance of HSC quiescence under a physiological condition. However, the precise mechanism remains elusive because there is no appropriate in vitro culture system for quiescent HSCs. Here, we show that treatment of quiescent HSCs with vitamin A partially maintained the accumulation of lipid droplets and expression of quiescent HSC markers (glial fibrillary acidic protein, peroxisome proliferator-activator receptor-γ and CCAAT/enhancer-binding protein-α) and also the expression of myofibroblastic markers (α-smooth muscle actin, heat shock protein 47 and collagen type I). On the other hand, combined treatment with vitamin A and insulin sustained the characteristic of HSC quiescence and completely suppressed the expression of myofibroblastic markers through activation of the JAK2/STAT5 signaling pathway and increased expression of sterol regulatory element binding protein-1. These treated HSCs transdifferentiated to myofibroblastic cells under a culture condition with fetal bovine serum. The results suggest an important role of vitamin A and insulin in the maintenance of HSC quiescence under a physiological condition.

Relationship between self-reported sleep quality and metabolic syndrome in general population.

BACKGROUND: To examine an association between self-reported sleep quality determined by Pittsburgh sleep quality index (PSQI) and metabolic syndrome. METHODS: This study was designed as cross-sectional study. Participants were 1481 adults aged 20 years and above from general population (549 males and 932 females). We assessed the global sleep quality by PSQI. PSQI consists of 7 elements, i.e. subjective sleep quality, sleep latency (prolonged sleep onset time), sleep duration, habitual sleep efficiency (proportion of hours slept to hours spent in bed), sleep disturbance (interruption of sleep), use of sleep medication and daytime dysfunction (trouble staying awake while engaging in social activity). Any participants with score of 6 or more are diagnosed to have sleep disorder. We also assessed the above 7 elements, which consisted of a four-grade system (i.e. 0, 1, 2, 3). Metabolic syndrome consisted of abdominal obesity, hypertension, impaired glucose tolerance and dyslipidemia. Diagnosis of metabolic syndrome was done when the participants have abdominal obesity and meet two or more other components. All analyses were adjusted by age, drinking habit, smoking habit, working hours, exercise habit and depression. RESULTS: Fifty-two male participants (9.5%) and 133 female (14.3%) scored 6 or more points in global PSQI score. The global PSQI score, sleep latency score and sleep disturbance score of participants with metabolic syndrome were higher level than those without the condition (p < 0.001, p = 0.009, p = 0.025 for male and p < 0.001, p < 0.001, p = 0.002 for females, respectively). The odds ratio of metabolic syndrome among participants with PSQI score of 6 or more points were 2.37 (95% confidence interval: 1.23-4.58) for males and 2.71 (1.45-5.07) for females in contrast to those with 5 or less points. The odds ratio of metabolic syndrome with sleep latency score of 2 was 2.65 (1.14-6.15) for male and 3.82 (1.81-8.09) for females in contrast with those of 0. The odds ratio of metabolic syndrome with sleep disturbance score of 1 was 1.76 (1.09-2.86) for males and 2.43 (1.26-4.69) for females in contrast with those of 0. CONCLUSIONS: Global PSQI score and its components (especially, sleep latency and sleep disturbance) were associated with metabolic syndrome.

A Cohort Study of the Influence of the 12-Component Modified Japanese Diet Index on Oral and Gut Microbiota in the Japanese General Population.

The Japanese diet is a healthy dietary pattern, and the oral or gut microbiota have been identified as the main factors underlying the beneficial effects of the Japanese diet. However, epidemiological studies on Japanese dietary patterns calculated from daily eating habits in the general population yielded inconsistent findings. This study aimed to determine the association between the 12-component modified Japanese Diet Index (mJDI12) and the oral and gut microbiota in the general population of a rural area in Japan. After propensity-score matching, 396 participants (198 each in the low and high mJDI12 groups) were picked out. One year after the follow up survey, we reclassified the subjects and compared the low and high mJDI12 groups again. Participants with a high mJDI12 had a higher relative abundance of butyric acid-producing bacteria in their gut microbiota. Moreover, the significantly higher dietary fiber intake in the high mJDI12 group suggested that the high intake of dietary fiber contributed to an increase in butyric acid-producing bacteria in the gut. In contrast, in individuals with a high mJDI12, only Allpprevotella was decreased in the oral microbiota. Thus, the Japanese dietary pattern can have beneficial effects by improving the oral and gut microbiota.

Absence of interstitial lung disease at initial visit may predict a favorable outcome for Japanese patients with systemic sclerosis with anti-topoisomerase I antibody.

Interstitial lung disease (ILD) is recognized a prognostic factor and leading cause of death in patients with systemic sclerosis (SSc). The aim of the present study is to clarify factors at an initial visit that are associated with the deterioration of ILD in SSc patients with anti-topoisomerase I (anti-topo I) antibodies. This was a single-center, retrospective, observational study. Fifty-three consecutive SSc patients with anti-topo I antibodies were included in this study. Of the 53 patients, 43 had ILD at their initial visit, whereas 10 did not. We examined the clinical and immunological factors at an initial visit that were associated with the deterioration of ILD. The deterioration of ILD was defined as the administration of intravenous cyclophosphamide (IVCY) therapy. In this cohort, 45 (85%) patients had ILD at the time of the final observation, and only two who did not have ILD at their initial visit developed ILD during the follow-up period. Until the final observation, 26 (49%) patients received IVCY therapy for the progression of ILD. The age at onset, disease duration, SSc subtype, and skin score were similar between patients with and those without IVCY therapy. Approximately 60% (26 of 43) of patients with ILD at their initial visit received IVCY therapy. On the other hand, none of the 10 patients without ILD at their initial visit received IVCY therapy. Our multivariate analyses using Cox proportional hazards regression model revealed that the presence of ILD at an initial visit was an independent factor associated with the introduction of IVCY therapy (odds ratio, 2.8e+7 [95% confidence interval, 1.8e+17-uncalculated], p = 0.0048). Although anti-topo I antibodies are strongly associated with ILD, it was unlikely for SSc patients with anti-topo I antibodies to receive IVCY therapy when they did not have ILD at an initial visit.

Correction: Kanda et al. Body Compression Corrective Garment and Eating Behavioural Change for Weight Reduction: The Mutsu City Randomised Controlled Trial. Healthcare 2023, 11, 942.

In the original publication [...].

Clinical features of patients with connective tissue disease with anti-human upstream binding factor antibodies: A single-center retrospective study.

Anti-human upstream-binding factor (anti-hUBF) antibodies have been reported predominantly in patients with connective tissue diseases (CTDs); these have also been reported in patients without CTDs such as hepatocellular carcinoma. Because of the low frequency of expression and few case reports, there is no consensus on the clinical significance of these antibodies. Thus, we aimed to examine the clinical features of patients with anti-hUBF antibodies and analyzed 1042 patients with clinically suspected CTDs. The presence of anti-hUBF antibodies was screened using immunoprecipitation assays. Of the 1042 patients, 19 (1.82%) tested positive for anti-hUBF antibodies; among them, 10 (56%) were diagnosed with undifferentiated CTD (UCTD), six with systemic sclerosis (SSc) and three with other diseases. Five of the 10 patients with UCTD were referred to our hospital with suspected SSc. None of the five patients fulfilled the 2013 American College of Rheumatology/European League Against Rheumatism classification criteria, but three scored seven points, a relatively high score. Six anti-hUBF-positive patients with SSc had a significantly lower modified Rodnan skin score (mRSS) than that of anti-hUBF-negative patients with SSc (2 [0-2] vs 7 [0-49], p < 0.01). Compared with anti-topoisomerase I-positive patients, anti-hUBF-positive patients had a significantly lower mRSS (2 [0-2] vs 13 [0-42], p < 0.01) and lower incidence of scleroderma renal crisis (0 of 6 vs 8 of 184, p < 0.01). Compared with anti-centromere-positive patients, anti-hUBF-positive patients had a higher incidence of interstitial lung disease (ILD), but the difference was not statistically significant (4 of 6 vs 19 of 239). In conclusion, anti-hUBF antibodies were predominantly detected in patients with CTDs and UCTD. In patients with CTDs, SSc exhibited a high ratio, displaying a lower mRSS and higher incidence of ILD. In patients with UCTD, careful follow-up is recommended as they may develop CTDs in the future.

Serum hyaluronan levels increase with the total number of osteoarthritic joints and are strongly associated with the presence of knee and finger osteoarthritis.

PURPOSE: Although serum hyaluronan (HA) levels increase in patients with osteoarthritis (OA), the association between OA severity and elevation of serum HA levels is not clear. Our purpose was to investigate the relationship between serum HA levels and OA in various anatomical sites and to detect which joints are strongly correlated with elevated serum HA levels. METHODS: Seven hundred and ten individuals from the general population who participated in the Iwaki Health Promotion Project in 2008 were involved. Kellgren-Lawrence grade 2 or higher in the knee, hip, lumbar spine, finger and wrist was defined as OA. Serum HA levels were determined on the same day. Spearman's correlation coefficients between serum HA levels and total number of joints affected by OA were calculated. Linear regression was analysed with serum HA levels as the independent variable; age, gender, presence of OA and intake of supplements were used as dependent variables. RESULTS: Prevalence of knee OA was 30.7 %, hip 16.8 %, lumbar spine 65.1 %, wrist 9.0 % and finger 22.0 %. Serum HA levels had a positive correlation with the number of involved joints, and the correlation coefficient was 0.410 (p < 0.001). Serum HA was significantly affected by age (ß = 0.382), knee OA (ß = 0.163) and finger OA (ß = 0.164). CONCLUSION: Although this biomarker reflects a systemic condition, higher serum HA levels were associated with total number of OA joints. Knee and finger OA were key joints related to increased serum HA levels. These results are valuable in understanding characteristics of serum HA levels as a biomarker for osteoarthritis.