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• The loss of FcγRIIB exacerbated skin and lung fibrosis in bleomycin-induced fibrosis model. • FcγRIIB regulated leukocytes infiltration and cytokine and chemokine production. • Modulating FcγRIIB signaling has potential as a therapeutic approach for systemic sclerosis. Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by excessive fibrosis. FcγRIIB is a low-affinity receptor for the Fc fragment of IgG. FcγRIIB is expressed on the surface of various leukocyte subsets and signals negative feedback pathways to down-regulate B-cell antigen receptor signaling. The aim of the present study was to investigate the role of FcγRIIB in the development of a murine bleomycin-induced scleroderma model. The experimental fibrosis model was generated by the intradermal injection of bleomycin into wild-type (WT) and FcγRIIB-deficient (FcγRIIB-/-) mice. We histologically assessed skin and lung fibrosis as well as inflammatory cell infiltration. Cytokine and chemokine expression levels were measured with RT-PCR. The severity of fibrosis in the skin and lung was significantly worse in FcγRIIB-/- mice than in WT mice. In the skin of bleomycin-treated mice, the numbers of CD8+ T cells, F4/80+ macrophages, MPO+ neutrophils, NK1.1+NK cells, and B220+ B cells were significantly higher in FcγRIIB-/- mice than in WT mice. The expression of TNF-α and IL-1β was significantly higher in FcγRIIB-/- mice than in WT mice as was the expression of ICAM-1, CXCL2, and CCL3 in the affected skin. An adoptive transfer of splenic leukocytes from FcγRIIB-/- mice into WT mice showed exacerbated skin and lung fibrosis compared to WT mice without an adoptive transfer. These results indicate that FcγRIIB plays an inhibitory role in skin and lung fibrosis. Moreover, modulating FcγRIIB signaling has potential as a therapeutic approach for SSc. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Recently, we identified novel avian and amphibian hypothalamic neuropeptides that inhibited gonadotropin release and stimulated growth hormone release. They were characterized by a similar structure including the C-terminal LPLRF-NH2 motif. To clarify that the expression of these novel hypothalamic neuropeptides is a conserved property in vertebrates, we characterized a cDNA encoding a similar novel peptide, having LPLRF-NH2 from the goldfish brain, by a combination of 3′ and 5′ rapid amplification of cDNA ends (RACE). The deduced peptide precursor consisted of 197 amino acid residues, encoding three putative peptide sequences that included -LPXRF (where X is L or Q) at their C-termini. Mass spectrometric analyses revealed that a tridecapeptide (SGTGLSATLPQRF-NH2 ) was derived from the precursor in the brain as an endogenous ligand. Southern blotting analysis of reverse-transcriptase-mediated PCR products demonstrated a specific expression of the goldfish peptide gene in the diencephalon. In situ hybridization revealed the cellular localization of goldfish peptide mRNA in the nucleus posterioris periventricularis in the hypothalamus. Immunoreactive cell bodies were also restricted to the the nucleus posterioris periventricularis and the nervus terminalis and immunoreactive fibers were distributed in several brain regions including the nucleus lateralis tuberis pars posterioris and pituitary. Thus, the goldfish hypothalamus expresses a novel neuropeptide containing the C-terminal -LPQRF-NH2 sequence, which may possess multiple regulatory functions and act, at least partly, on the pituitary to regulate pituitary hormone release. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic, inflammatory cutaneous disease. FcγRIIB is a low-affinity receptor for the IgG Fc fragment that provides a negative feedback pathway to down-regulate B-cell antigen receptor signaling. The aim of this study was to investigate the role of FcγRIIB in the development of murine imiquimod (IMQ)-induced, psoriasis-like skin inflammation. The experimental psoriasis-like skin inflammation was induced by the topical application of IMQ to the ears of FcγRIIB deficient (FcγRIIB-/-) and wild-type (WT) mice. After 6 days, epidermal thickness and inflammatory cell infiltration of the skin were histopathologically assessed and cytokine and chemokine expression levels were measured with RT-PCR. Skin inflammation was significantly worse in FcγRIIB-/- mice than WT mice. In the skin, the numbers of Gr-1+ neutrophils, CD11c+ dendritic cells, and Foxp3+ T cells were significantly higher in FcγRIIB-/- mice than WT mice. In the spleen, the numbers of CD25+Foxp3+ T cells and CD19+IL-10+ B cells were also significantly higher in FcγRIIB-/-mice than WT mice. The mRNA expression of Il-6 , Il-17a , and Il-23a was significantly enhanced in FcγRIIB-/- mice. An adoptive transfer of splenic leukocytes from FcγRIIB-/- mice into WT mice also exacerbated skin inflammation compared to WT mice that received splenic leukocytes from WT mice. Intravenous immunoglobulin significantly reduced skin inflammation in WT mice, but this improvement was not observed in FcγRIIB-/- mice. These results indicate that FcγRIIB likely plays a suppressive role in IMQ-induced, psoriasis-like skin inflammation. Furthermore, signal modulation via FcγRIIB is a potential therapeutic target for psoriasis. • The loss of FcγRIIB exacerbated skin inflammation in imiquimod-induced psoriasis-like skin inflammation. • FcγRIIB regulated leukocyte infiltration and cytokine production. • Modulating FcγRIIB signaling is a potential therapeutic approach for psoriasis. [ABSTRACT FROM AUTHOR]

Many factors are associated with the development and progression of metabolic dysfunction-associated steatotic liver disease (MASLD); however, genetics and gut microbiota are representative factors. Recent studies have highlighted the link between host genes and the gut microbiota. Although there have been many studies on the separate effects of single nucleotide polymorphisms (SNPs) and gut bacteria on MASLD, few epidemiological studies have examined how SNPs and gut bacteria interact in the development and progression of MASLD. This study aimed to investigate the association between PNPLA3 rs738409, a representative MASLD-related SNP, and gut bacteria in MASLD using a cross-sectional study of the general population. The 526 participants (318 normal and 208 MASLD groups) were grouped into the PNPLA3 rs738409 SNP, CC, CG, and GG genotypes, and the differences in the gut microbiota were investigated in each group. The PNPLA3 rs738409 CC and CG genotypes were associated with decreased Blautia and Ruminococcaceae in the MASLD group. They were negatively correlated with controlled attenuation parameter levels, body mass index, serum blood glucose, and triglycerides. In contrast, there was no association between the normal and MASLD groups and the gut bacteria in the PNPLA3 rs738409, the GG genotype group. This finding implies that dietary interventions and probiotics may be more effective in preventing and treating MASLD in individuals with the PNPLA3 rs738409 CC and CG genotypes. In contrast, their efficacy may be limited in those with the GG genotype. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 70-year-old patient experiencing severe nail toxicity associated with pembrolizumab, an immune checkpoint inhibitor used in cancer treatment. Topics discussed include the rarity of such adverse effects, the potential influence of prior treatments, and the challenges in managing extensive nail bed ulceration and loss of nails caused by pembrolizumab.

This study aimed to evaluate long‐term changes in nailfold videocapillaroscopy (NVC) findings in dermatomyositis patients with antinuclear matrix protein 2 (NXP‐2) antibody (Ab). All four patients with anti‐NXP‐2 Ab presented irregularly enlarged and reduced capillaries and hemorrhages at the initial assessment. After disease stabilization, irregularly enlarged capillaries and hemorrhages disappeared within the mean observation period of 6 months. These early improvements were not observed in patients with anti‐TIF1 Ab. The results of this study show that long‐term changes in NVC findings should be assessed using myositis‐specific Ab information. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The relationship between serum adiponectin concentration (S-Adipo) and various diseases, such as type 2 diabetes (T2D) is conflicting. We hypothesized that the extent of kidney damage in patients with T2D may be responsible for this inconsistency and, thus, examined association between S-Adipo and T2D after consideration for the extent of kidney damage present. Of the 1816 participants in the population-based Iwaki study of Japanese people, 1751 participants with a complete dataset were included. Multivariate logistic regression analyses revealed that low S-Adipo was independently associated with T2D (<0.001), as was high urinary albumin to creatinine ratio (uACR) (<0.001). Principal components analysis showed that the relative value of S-Adipo to uACR (adiponectin relative excess) was significantly associated with T2D (odds ratio: 0.49, p < 0.001). Receiver operating curve analyses revealed that an index of adiponectin relative excess the ratio of S-Adipo to uACR was superior to S-Adipo per se as a marker of T2D (area under the curve: 0.746 vs. 0.579, p < 0.001). This finding indicates that the relationship between S-Adipo and T2D should be evaluated according to the extent of kidney damage present and may warrant similar analyses of the relationships between S-Adipo and other medicalconditions, such as cardiovascular disease. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: We evaluated the clinical characteristics of metabolic dysfunction-associated fatty liver disease (MAFLD) to evaluate the usefulness of the MAFLD diagnostic criteria in a resident health survey. Methods: In 1056 participants of a health survey, we compared obesity, diabetes, metabolic dysregulation, FibroScan-aspartate aminotransferase (FAST) score, dietary habits, and gut microbiota between healthy individuals and participants with MAFLD and Nonalcoholic fatty liver disease (NAFLD). Results: The proportion of participants with MAFLD in the fatty liver was higher than that with NAFLD (88.1% vs. 75.5%, respectively). Of 36 participants with a FAST score > 0.35, 29 (80.6%) participants had MAFLD and 23 (63.9%) participants had NAFLD. Of 29 patients with liver fibrosis, 26 (89.7%) participants had obesity and metabolic dysregulation. In the evaluation of diet, the total energy, protein, dietary fiber, and salt intake were significantly higher in participants with MAFLD than those in participants without fatty liver. In the microbiota analysis, the results of the linear discriminant analysis effect size analysis revealed nine bacterial genera that were significantly different in participants with MAFLD in comparison with participants without fatty liver. Of these genera, the relative abundance of Blautia was especially low in participants with MAFLD. Conclusion: In a resident health survey, participants with MAFLD had a higher proportion of fatty liver than those with NAFLD. MAFLD criteria could help in improved screening of participants with liver fibrosis. Therefore, the MAFLD criteria could be a useful diagnostic tool for aggressively identifying participants with a high risk of fatty liver. Additionally, Blautia might be involved in the development of MAFLD. [ABSTRACT FROM AUTHOR]

Relationships between the neutrophil–lymphocyte ratio (NLR) and/or the platelet-lymphocyte ratio (PLR) and neuroinflammatory diseases have been reported. Depression is also associated with neuroinflammation. Here, we determined the association between the NLR, PLR, and depressive symptoms. This cross-sectional study is a secondary analysis of the data of the Iwaki Health Promotion Project 2017. We analyzed the characteristics and laboratory data of 1,015 Japanese subjects (597 females, 408 males) including their NLR and PLR values. We assigned the subjects with a Center for Epidemiologic Studies Depression Scale (CES-D) score ≥ 16 to the depressive symptoms group. We performed a multivariate logistic regression analysis to determine whether the NLR and/or PLR were associated with depressive symptoms (CES-D ≥ 16). Two hundred subjects (19.7%; 122 [20.4%] females, 78 [19.1%] males) were assigned to the depressive symptoms group. There were significant differences between the non-depressive symptoms and depressive symptoms groups in the NLR [median (25th to 75th percentile): 1.54 (1.24, 1.97) vs. 1.76 (1.32, 2.37), P = 0.005] and the PLR [median (25th to 75th percentile): 123.7 (102.0, 153.9) vs. 136.8 (107.0, 166.5), P = 0.047] in males, but not in females. The multivariate logistic regression analysis demonstrated that the NLR was significantly associated with depressive symptoms in males (adjusted odds ratio: per 1 increase, 1.570; 95% confidence interval: 1.120–2.220; P = 0.009). In conclusion, our findings indicate that higher NLR may be associated with depressive symptoms in males. [ABSTRACT FROM AUTHOR]

Relationships between the neutrophil–lymphocyte ratio (NLR) and/or the platelet-lymphocyte ratio (PLR) and neuroinflammatory diseases have been reported. Depression is also associated with neuroinflammation. Here, we determined the association between the NLR, PLR, and depressive symptoms. This cross-sectional study is a secondary analysis of the data of the Iwaki Health Promotion Project 2017. We analyzed the characteristics and laboratory data of 1,015 Japanese subjects (597 females, 408 males) including their NLR and PLR values. We assigned the subjects with a Center for Epidemiologic Studies Depression Scale (CES-D) score ≥ 16 to the depressive symptoms group. We performed a multivariate logistic regression analysis to determine whether the NLR and/or PLR were associated with depressive symptoms (CES-D ≥ 16). Two hundred subjects (19.7%; 122 [20.4%] females, 78 [19.1%] males) were assigned to the depressive symptoms group. There were significant differences between the non-depressive symptoms and depressive symptoms groups in the NLR [median (25th to 75th percentile): 1.54 (1.24, 1.97) vs. 1.76 (1.32, 2.37), P = 0.005] and the PLR [median (25th to 75th percentile): 123.7 (102.0, 153.9) vs. 136.8 (107.0, 166.5), P = 0.047] in males, but not in females. The multivariate logistic regression analysis demonstrated that the NLR was significantly associated with depressive symptoms in males (adjusted odds ratio: per 1 increase, 1.570; 95% confidence interval: 1.120–2.220; P = 0.009). In conclusion, our findings indicate that higher NLR may be associated with depressive symptoms in males. [ABSTRACT FROM AUTHOR]

Upon food digestion, the gut microbiota plays a pivotal role in energy metabolism, thus affecting the development of type 2 diabetes (DM). We aimed to examine the influence of the composition of selected nutrients consumed on the association between the gut microbiota and DM. This cross-sectional study of a general population was conducted on 1019 Japanese volunteers. Compared with non-diabetic subjects, diabetic subjects had larger proportions of the genera Bifidobacterium and Streptococcus but smaller proportions of the genera Roseburia and Blautia in their gut microbiotas. The genera Streptococcus and Roseburia were positively correlated with the amounts of energy (p = 0.027) and carbohydrate and fiber (p = 0.007 and p = 0.010, respectively) consumed, respectively. In contrast, the genera Bifidobacterium and Blautia were not correlated with any of the selected nutrients consumed. Cluster analyses of these four genera revealed that the Blautia-dominant cluster was most negatively associated with DM, whereas the Bifidobacterium-dominant cluster was positively associated with DM (vs. the Blautia-dominant cluster; odds ratio 3.97, 95% confidence interval 1.68–9.35). These results indicate the possible involvement of nutrient factors in the association between the gut microbiota and DM. Furthermore, independent of nutrient factors, having a Bifidobacterium-dominant gut microbiota may be a risk factor for DM compared to having a Blautia-dominant gut microbiota in a general Japanese population. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Iron is an essential trace metal for most organisms. However, excess iron causes oxidative stress through production of highly toxic hydroxyl radicals via the Fenton/Haber-Weiss reaction. Iron storage in the body is reported to be associated with fat accumulation and type 2 diabetes mellitus. We investigated the role of iron in adiposity by using KKAy mice and obese and diabetic model mice. Eight-week-old KKAy mice were divided into two groups and treated with deferoxamine (DFO), an iron chelator agent, or a vehicle for 2 wk. DFO treatment diminished fat iron concentration and serum ferritin levels in KKAy mice. Fat weight and adipocyte size were reduced significantly in DFO-treated mice compared with vehicle-treated mice. Macrophage infiltration into fat was also decreased in DFO-treated mice compared with vehicle-treated mice. Superoxide production and NADPH oxidase activity in fat, as well as urinary 8-hydroxy-2′-deoxyguanosine excretion, were decreased in KKAy mice after DFO treatment while p22phox expression in adipose tissue was diminished in such mice. Ferritin expression in the fat of DFO-treated KKAy mice was decreased. In addition, F4/80-positive cells also presented through both p22phox and ferritin expression. The mRNA expression levels of inflammatory cytokines were also reduced in fat tissue of DFO-treated mice. These findings suggest that reduction of iron levels ameliorates adipocyte hypertrophy via suppression of oxidative stress, inflammatory cytokines, and macrophage infiltration, thereby breaking a vicious cycle in obesity. [ABSTRACT FROM AUTHOR]

The aim of this work was to investigate the effect of age on the association between daily gait speed (DGS) and abdominal obesity defined by visceral fat area (VFA). A cross-sectional study was performed using data from an annual community-based health check-up. A total of 699 participants aged 20–88 years were enrolled in this analysis. DGS was assessed using tri-axial accelerometers worn for ≥ 7 days with at least 10 measuring hours each day. VFA was measured using a visceral fat meter. Since DGS differed significantly with age, the participants were divided into two groups: younger adults (YA), aged 20–49 years, and older adults (OA), aged 50–88 years. The association between DGS and VFA differed significantly with age (r = 0.099 for YA and r = − 0.080 for OA; test for difference between correlation coefficients, P = 0.023). In OA, the adjusted odds ratio of abdominal obesity (VFA ≥ 100 cm2) was 0.40 (95% confidence interval 0.18, 0.88, P = 0.022) for the highest DGS quartile (DGS ≥ 1.37 m/s) compared to that for the lowest quartile (DGS < 1.11 m/s), whereas no significant association was found in YA. These data could aid in raising awareness of the self-management of obesity via DGS monitoring, especially in OA. [ABSTRACT FROM AUTHOR]

Endoscopic sub-mucosal dissection (ESD) is considered as a low-invasive treatment for early-stage colorectal cancer, but the degree of invasiveness has not been well investigated. The aim of this study was to evaluate the physical stress due to colorectal ESD based on changes in serum opsonic activity (SOA). SOA was examined by measuring reactive oxygen species (ROS) produced by neutrophils using lucigenin-dependent chemiluminescence (LgCL) and luminol-dependent chemiluminescence (LmCL). Sixty-nine patients were enrolled into the study and examined SOA in the morning of the day of ESD, the next day, and at four days after ESD. The peak height (PH) and area under the curve (AUC) of LgCL showed no significant difference between the day and the next day, whereas the PH and AUC for LgCL were significantly higher four days after ESD than on the day of ESD (p <.05). In contrast, the PH and AUC of LmCL showed no significant changes during the ESD perioperative period. This difference suggests that SOA changes during the colorectal ESD perioperative period involved minor increases in the production of lower-toxicity ROS. This finding supports the position that ESD is a technique that does not generate a great deal of physical stress. On the other hand, a significant increase in SOA at four days after colorectal ESD suggests that care is needed with postoperative management even after the patient has started to eat meals again. [ABSTRACT FROM AUTHOR]

Background: The oral microbiome, which consists of various habitats, has been shown to be influenced by smoking. However, differences in the tongue microbiomes of current and former smokers, as well as their resultant functional consequences, have rarely been investigated in East Asian populations. Methods: We used 16S rRNA amplicon sequencing of tongue-coating samples obtained from East Asian subjects who were current, former, or never smokers to identify differences in their tongue microbiomes and related metagenomic functions. Two sets of participants from 2016 to 2017 (n = 657 and n = 187, respectively) were analyzed separately. Results: We found significant differences between the overall microbiome compositions of current versus never smokers (p = 0.0015), but not between former versus never smokers (p = 0.43) based on the weighted UniFrac distance. Twenty-nine of 43 investigated genera showed significantly different expression levels in current versus never smokers. Neisseria and Capnocytophaga were less abundant, and Streptococcus and Megasphaera were more abundant in current smokers. Moreover, the abundances of metagenomic pathways, including those related to nitrate reduction and the tricarboxylic acid cycle, were significantly different between current and never smokers. Conclusions: The tongue microbiomes and related metagenomic pathways of current smokers differ from those of never smokers among East Asians. [ABSTRACT FROM AUTHOR]

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. 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. 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. The presence of bacteria of order Lactobacillales, Bifidobacteriales, and Bacteroidales in the gut microbiota may affect sensitization to inhaled allergens. Image 1 [ABSTRACT FROM AUTHOR]

Owing to increasing medical expenses, researchers have attempted to detect clinical signs and preventive measures of diseases using electronic health record (EHR). In particular, time-series EHRs collected by periodic medical check-up enable us to clarify the relevance among check-up results and individual environmental factors such as lifestyle. However, usually such time-series data have many missing observations and some results are strongly correlated to each other. These problems make the analysis difficult and there exists strong demand to detect clinical findings beyond them. We focus on blood test values in medical check-up results and apply a time-series analysis methodology using a state space model. It can infer the internal medical states emerged in blood test values and handle missing observations. The estimated models enable us to predict one's blood test values under specified condition and predict the effect of intervention, such as changes of body composition and lifestyle. We use time-series data of EHRs periodically collected in the Hirosaki cohort study in Japan and elucidate the effect of 17 environmental factors to 38 blood test values in elderly people. Using the estimated model, we then simulate and compare time-transitions of participant's blood test values under several lifestyle scenarios. It visualizes the impact of lifestyle changes for the prevention of diseases. Finally, we exemplify that prediction errors under participant's actual lifestyle can be partially explained by genetic variations, and some of their effects have not been investigated by traditional association studies. [ABSTRACT FROM AUTHOR]

Since activation of the sympathetic nervous system is associated with both impaired insulin secretion and insulin resistance, or namely with diabetes, evaluation of such activation in ordinary clinical settings may be important. Therefore, we evaluated the relationships between urinary concentrations of the catecholamine metabolites, urinary normetanephrine (U-NM) and urinary metanephrine (U-M), and glucose metabolism in a general population. From 1,148 participants in the 2016 population-based Iwaki study of Japanese, enrolled were 733 individuals (gender (M/F): 320/413; age: 52.1±15.1), who were not on medication affecting serum catecholamines, not diabetic, and had complete data-set and blood glucose levels appropriate for the evaluation of insulin secretion and resistance, using homeostasis model assessment (HOMA-β and HOMA-R, respectively). Univariate linear regression analyses revealed significant correlations between both U-NM and U-M, and HOMA-β, but adjustment for multiple factors correlated with HOMA indices abolished these (β = -0.031, p = 0.499, and β = -0.055, p = 0.135, respectively). However, the correlation between U-NM and HOMA-R observed using univariate linear regression analysis (β = 0.132, p<0.001) remained significant even after these adjustments (β = 0.107, p = 0.007), whereas U-M did not correlate with HOMA-R. Furthermore, use of the optimal cut-off value of U-NM for the prediction of insulin resistance (HOMA-R >1.6) determined by ROC analysis (0.2577 mg/gCr) showed that individuals at risk had an odds ratio of 2.65 (confidence interval: 1.42–4.97) after adjustment for the same factors used above. Higher U-NM concentrations within the physiologic range are a significant risk factor for increased insulin resistance in a general Japanese population. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract 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-SCC mec 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. [ABSTRACT FROM AUTHOR]

Background: Depression is a seriously disabling public health problem with very high world-wide prevalence. This study examined cross-sectional association between depression and both inflammatory markers and laboratory data involved in metabolic disturbance among Japanese subjects.Methods: This cross-sectional study is a secondly analysis for the data of the Iwaki Health Promotion Project 2014 (1167 subjects). Plasma inflammatory markers and laboratory metabolic data involved were used. Center for Epidemiologic Studies Depression Scale (CES-D) was used to assess the prevalence and severity of depressive symptoms. Participants with CES-D scores ≥ 16 were assigned to the 'Depression' group (Group D). Differences between group Non-depression (ND) and D were estimated using χ2 test or Fisher's exact test for categorical variables and Student's t-test or Mann-Whitney test for continuous variables. Multivariate logistic regression analysis was also used to identify characteristics, co-morbidities, conditions and laboratory data associated with depression after adjusting for possible confounding factors.Results: There were significant differences in sex, age, blood pressure, interleukin (IL)-6, fasting blood sugar (FBS), hemoglobin A1c (HbA1c), and cortisol level using univariate analysis between the two groups. However, multivariate logistic regression analysis indicated that lower age, lower C-peptide, and higher leptin were associated with the depression.Conclusion: This study showed that higher plasma leptin and lower C-peptide levels were significantly associated with depressive symptoms. No significant association was found between plasma inflammatory markers and depressive symptoms after adjusting for possible confounding factors. [ABSTRACT FROM AUTHOR]

Differences between the non-depressive symptoms and depressive symptoms groups were examined by Fisher's exact test for categorical variables and Mann-Whitney test for continuous variables. Publisher Correction: Higher neutrophil-lymphocyte ratio is associated with depressive symptoms in Japanese general male population Correction to: I Scientific Reports i https://doi.org/10.1038/s41598-022-13562-x, published online 03 June 2022 The original version of this Article contained errors in Table 1, where the column ' I P i -value' was incomplete for "Females". [Extracted from the article]

Correction to: I Scientific Reports i https://doi.org/10.1038/s41598-022-13562-x, published online 03 June 2022 The original version of this Article contained errors in Table 1, where the column ' I P i -value' was incomplete for "Females". Differences between the non-depressive symptoms and depressive symptoms groups were examined by Fisher's exact test for categorical variables and Mann-Whitney test for continuous variables. Publisher Correction: Higher neutrophil-lymphocyte ratio is associated with depressive symptoms in Japanese general male population. [Extracted from the article]

The gut microbiota composition was investigated by applying the quantitative real-time polymerase chain reaction (q-PCR) method targeting the V3-V4 region of the prokaryotic 16S rRNA genes, as previously described [23]." The gut microbiota composition was investigated by conducting a next-generation sequencing analysis targeting the V3-V4 region of the prokaryotic 16S rRNA genes, as previously described [23]. Interrelations between Gut Microbiota Composition, Nutrient Intake and Diabetes Status in an Adult Japanese Population. [Extracted from the article]

ATP-binding cassette transporter family A member 12 (ABCA12) is a keratinocyte transmembrane lipid transporter that plays a critical role in preserving the skin permeability barrier. Biallelic loss of function of the ABCA12 gene is causative of some forms of recessive congenital ichthyosis, an intractable disease marked by dry, thickened and scaly skin on the whole body. Genetic diagnosis is essential, although the results may occasionally be inconclusive, because some patients with low ABCA12 expression have one mutant allele and one apparently intact allele. Aside from aberrant splicing or deletion mutations, one possible explanation for such discrepancy is loss of promoter function. This study aims to elucidate the promoter region of ABCA12 and to locate the essential elements therein, thus providing the necessary information for genetic diagnostic screening of congenital ichthyosis. Close examination of the 2980-bp upstream regions of the ABCA12 gene revealed that a palindromic motif (tgagtca) at -2084 to -2078 is essential for the promoter function, and a short fragment of -2200/-1934 alone has potent promoter activity. Identification of the key promoter element of ABCA12 in this study may provide relevant information for genetic diagnosis of recessive congenital ichthyosis. [ABSTRACT FROM AUTHOR]

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 (β = 0.382), knee OA (β = 0.163) and finger OA (β = 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. [ABSTRACT FROM AUTHOR]

The third variable region (V3) of the human immunodeficiency virus type 1 (HIV-1) envelope gp120 subunit participates in determination of viral infection coreceptor tropism and host humoral immune responses. Positive charge of the V3 plays a key role in determining viral coreceptor tropism. Here, we examined by bioinformatics, experimental, and protein modelling approaches whether the net positive charge of V3 sequence regulates viral sensitivity to humoral immunity. We chose HIV-1 CRF01şAE strain as a model virus to address the question. Diversity analyses using CRF01şAE V3 sequences from 37 countries during 1984 and 2005 (n = 1361) revealed that reduction in the V3's net positive charge makes V3 less variable due to limited positive selection. Consistently, neutralization assay using CRF01şAE V3 recombinant viruses (n = 30) showed that the reduction in the V3's net positive charge rendered HIV-1 less sensitive to neutralization by the blood anti-V3 antibodies. The especially neutralization resistant V3 sequences were the particular subset of the CCR5-tropic V3 sequences with net positive charges of +2 to +4. Molecular dynamics simulation of the gp120 monomers showed that the V3's net positive charge regulates the V3 configuration. This and reported gp120 structural data predict a less-exposed V3 with a reduced net positive charge in the native gp120 trimer context. Taken together, these data suggest a key role of the V3's net positive charge in the immunological escape and coreceptor tropism evolution of HIV-1 CRF01şAE in vivo. The findings have molecular implications for the adaptive evolution and vaccine design of HIV-1. [ABSTRACT FROM AUTHOR]

Abstract: Employing retrograde transsynaptic transport of rabies virus, we investigated the organization of basal ganglia inputs to hindlimb, proximal and distal forelimb, and orofacial representations of the macaque primary motor cortex (MI). Four days after rabies injections into these MI regions, neuronal labeling occurred in the striatum and the subthalamic nucleus (STN) through the cortico-basal ganglia loop circuits. In the striatum, two distinct sets of the labeling were observed: one in the dorsal putamen, and the other in the ventral striatum (ventromedial putamen and nucleus accumbens). The dorsal striatal labeling was somatotopically arranged and its distribution pattern was in good accordance with that of the corticostriatal inputs, such that the hindlimb, orofacial, or forelimb area was located in the dorsal, ventral, or intermediate zone of the putamen, respectively. The distribution pattern of the ventral striatal labeling was essentially the same in all cases. In the STN, the somatotopic arrangement of labeled neurons was in register with that of corticosubthalamic inputs. The present results suggest that the cortico-basal ganglia motor circuits involving the dorsal putamen and the STN may constitute separate closed loops based on the somatotopy, while the ventral striatum provides common multisynaptic projections to all body-part representations in the MI. [Copyright &y& Elsevier]

• It remains uncertain whether both inflammatory markers and fractional exhaled nitric oxide (FeNO) are associated with depression. • This cross-sectional study showed that a lower FeNO level was significantly associated with the development of depressive symptoms after adjusting for possible confounding factors. • On the other hand, no significant association was found between interleukin (IL)-6 and depressive symptoms or between high-sensitivity C-reactive protein (hs-CRP) and depressive symptoms. We examined cross-sectional associations between depression and both inflammatory markers and fractional exhaled nitric oxide (FeNO). This cross-sectional study is a secondary analysis of the data of the Iwaki Health Promotion Project 2016 (1,148 subjects). We analyzed the subjects' characteristics and laboratory data including plasma interleukin (IL)-6, high-sensitivity C-reactive protein (hs-CRP), and FeNO. The subjects with Center for Epidemiologic Studies Depression Scale scores ≥16 were assigned to the depression group. We performed a multivariate logistic regression analysis to determine whether inflammatory markers and FeNO were associated with depression. We assessed 1,099 subjects (430 males, 669 females). The depression group was 237 subjects (21.5%) [84 males (19.5%), 153 females (22.9%)]. The non-depression group was 862 subjects (346 males and 516 females). There were no significant differences in IL-6, hs-CRP, or FeNO between both groups. However, the multivariate logistic regression analysis indicated that lower FeNO was significantly associated with depression in males after adjusting for possible confounding factors (age, BMI, comorbidities, high-sensitivity troponin T, FEV 1 %, asthma, antidepressant use, smoker and alcohol drinker) (per 1 bpm increase, OR: 0.982; 95%CI: 0.967–0.998; p = 0.032). Our findings indicate that lower FeNO may be associated with depression in males. [ABSTRACT FROM AUTHOR]

Since type 2 diabetes (DM) is a life-style related disease, life-style should be considered when association between genetic factors and DM are examined. However, most studies did not examine genetic associations in consideration with lifestyle. Glucagon-like peptide-1 (GLP-1) receptor (GLP1R) mediates the insulinotropic action of GLP-1 in β-cells. We here examined the association while taking into consideration of interactions between the gene polymorphism and various nutrient factors. Participants from the population-based Iwaki study of Japanese subjects held in 2014–2017 with information on nutritional intake evaluated by self-administered dietary history questionnaire, and GLP1R genotype (rs3765467: A/G), were included (n = 1,560). Although not significant, insulin secretion indices assessed by homeostasis model assessment of β-cell function (HOMA-β) in subjects with the GG genotype tended to be lower than in those with the AA+AG genotypes in most groups stratified into tertiles based on daily nutrient consumptions (high, middle, and low). Stratification also showed that the GG genotype was a significant risk for decreased insulin secretion (HOMA-β ≤ 30) even after adjustment for multiple factors (age, body mass index, alcohol consumption), but only in the highest tertiles of energy, protein and carbohydrate consumption in men [odds ratios (95% confidence interval) 3.95 (1.03–15.1), 15.83 (1.58–158.9), and 4.23 (1.10–11.2), respectively]. A polymorphism of the GLP1R gene was associated with decreased insulin secretion in a nutrient consumption-dependent manner in Japanese men, indicating an interaction between GLP1R and nutritional factors in the pathophysiology of DM. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is associated with a high risk of type 2 diabetes (DM), therefore, early diagnosis of NAFLD is important to prevent incident DM. FIB-4 index, a biomarker, often used to evaluate severity of NAFLD, may be useful to evaluate risk for incident DM in ordinary clinical setting. Here, we determined the association of FIB-4 index with changes in indices representing glucose metabolism with aging in a non-diabetic population. From among the participants of the population-based Iwaki study of Japanese people conducted during 2014–2017, 1,268 non-diabetic individuals with complete data sets (age: 51.4 ± 15.9 years; men/women: 485/773) were enrolled in a cross-sectional study. In addition, of the participants, 439 who attended consecutive appointments between 2014 and 2017 were enrolled in a longitudinal study that aimed to evaluate the changes in insulin secretion and resistance with aging (age: 53.1 ± 13.7 years; men/women: 178/261). The cross-sectional study showed significant correlations of FIB-4 index with homeostasis model of assessment (HOMA) indices, even after adjustment for multiple factors (HOMA-β: β = − 0.254, p < 0.001; HOMA-R: β = − 0.247, p < 0.001). The longitudinal study showed a significant association between FIB-4 index and the change in HOMA-β (p < 0.001) but not HOMA-R (p = 0.639) during the 3-year study period. Use of the optimal cut-off value of the FIB-4 index for the prediction of decreased insulin secretion (HOMA-β < 30), determined using receiver operating characteristic analysis (1.592), showed that individuals at risk had a hazard ratio of 2.22 (confidence interval 1.17−4.06) for decreased insulin secretion, after adjustment for confounders. FIB-4 index may represent a useful predictor of a subsequent decrease in insulin secretion, at least in a non-diabetic Japanese population. [ABSTRACT FROM AUTHOR]

• Leptin-to-adiponectin (L/A) ratio correlated with hepatic steatosis in NAFLD. • Arterial stiffness correlated strongly with age, and weakly with hepatic steatosis. • Arterial stiffness was not correlated with L/A ratio in NAFLD. • Interleukin-6 correlated with arterial stiffness, and very weakly with L/A ratio. • L/A ratio correlated with triglycerides and the ratio of total cholesterol to HDL-cholesterol. 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. 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). 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]