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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Telomere (TL) is a biomarker of biological aging, and its shortening is associated with major risk factors for cardiovascular diseases (CVD). This study aimed to identify whether TL is associated with arterial stiffness as reflected by brachial–ankle pulse wave velocity (baPWV). This population-based cross-sectional study involved 1065 individuals in the Iwaki area, Japan. Total TL length and TL G-tail length were measured by hybridization protection assay. The baPWV was measured on the right and left sides using a non-invasive vascular screening device. The associations between TL and baPWV were assessed by multivariate linear regression. Compared with the shortest total TL tertile, the longest total TL group showed a significant decrease in baPWV (lowest vs. highest tertile: adjusted beta: −41.24, 95% confidence interval (CI): −76.81, −5.68). The mean baPWV decreased with a longer TL (TL G-tail length: p trend < 0.001, total TL: p trend < 0.001). TL G-tail and total TL lengths were inversely associated with baPWV, implicating TL shortening in the development of CVD. This study provides evidence of the factors influencing CVD risks at a very early stage when individuals can still take necessary precautions before CVD gives rise to a symptomatic health outcome.

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]

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]

Affordable and accessible behaviour-based interventions that do not overwhelm or demoralise overweight/obese individuals are needed. Combining clothing with behaviour change techniques might be an option. This is because clothing is a social norm, and clothing and motivation for weight loss are associated with the common desire to look better. Therefore, we conducted a single-blind randomised controlled trial to examine the effect of an intervention that combined behaviour change techniques, including simplified goal setting and self-monitoring, with a body compression corrective garment (BCCG), which exerts continuous but minimal tactile pressure on the hips and abdomen. We enrolled healthy community-dwelling adults with a body mass index ≥ 25 kg/m2 and assigned 35 and 34 participants to the intervention and control groups, respectively. The reduction in body weight was 1.3 kg more in the intervention group than in the control group after the 12-week intervention period (p < 0.05, repeated-measures mixed model). In addition, eating behaviour and body appreciation showed significant improvement in the intervention group compared with the control group. Our newly developed intervention improved eating behaviour and body appreciation and reduced the body weight of overweight/obese participants. Wearing a BCCG seems to facilitate behavioural changes and lead to weight loss. [ABSTRACT FROM AUTHOR]

The influx of intestinal bacteria-derived lipopolysaccharide (LPS) into the blood has attracted attention as a cause of diseases. The aim of this study is investigating the associations between the influx of LPS, dietary factors, gut microbiota, and health status in the general adult population. Food/nutrient intake, gut microbiota, health status and plasma LPS-binding protein (LBP; LPS exposure indicator) were measured in 896 residents (58.1% female, mean age 54.7 years) of the rural Iwaki district of Japan, and each correlation was analyzed. As the results, plasma LBP concentration correlated with physical (right/left arms' muscle mass [β = −0.02, −0.03]), renal (plasma renin activity [β = 0.27], urine albumin creatinine ratio [β = 0.50]), adrenal cortical (cortisol [β = 0.14]), and thyroid function (free thyroxine [β = 0.05]), iron metabolism (serum iron [β = −0.14]), and markers of lifestyle-related diseases (all Qs < 0.20). Plasma LBP concentration were mainly negatively correlated with vegetables/their nutrients intake (all βs ≤ −0.004, Qs < 0.20). Plasma LBP concentration was positively correlated with the proportion of Prevotella (β = 0.32), Megamonas (β = 0.56), and Streptococcus (β = 0.65); and negatively correlated with Roseburia (β = −0.57) (all Qs < 0.20). Dietary factors correlated with plasma LBP concentration correlated with positively (all βs ≥ 0.07) or negatively (all βs ≤ −0.07) the proportion of these bacteria (all Qs < 0.20). Our results suggested that plasma LBP concentration in the Japanese general adult population was associated with various health issues, and that dietary habit was associated with plasma LBP concentration in relation to the intestinal bacteria. [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]

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]

Water-soluble dietary fiber is primarily a substrate for degradation of short chain fatty acids (SCFAs), particularly butyric acid, by gut microbiota. SCFAs have beneficial effects on the whole body. However, epidemiological studies on the association between water-soluble dietary fiber from daily food intake and butyric acid-producing bacteria are inconsistent. The purpose of this study was to determine the association between levels of water-soluble dietary fiber from daily food intake and gut microbiota, particularly butyric acid producers, in middle-aged and older adults in a rural area in Japan. We examined the effects of water-soluble dietary fiber intake on gut microbiota after adjusting for confounding factors. After propensity score matching, 520 subjects (260 in the low-intake group and 260 in the high-intake group) were selected. One year later after a follow-up survey, we re-classified the participants and again compared low- and high-intake groups. As a result, people with a high intake had a higher relative abundance of butyric acid-producing bacteria. It was also revealed that butyric acid-producing bacteria remained high in the group that maintained high intake the next year. We concluded that continuous intake of water-soluble dietary fiber from daily food is necessary to maintain sufficient amounts of butyric acid-producing bacteria. [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]

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.

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]

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]

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]

Bullous pemphigoid (BP) is a cutaneous autoimmune blistering disorder. Recently, it has been reported that dipeptidyl peptidase-4 inhibitors (DPP4i) is associated with the development of BP (DPP4i-BP). Patients with DPP4i-BP have autoantibodies (autoAbs) preferentially targeting full-length BP180, but not the BP180NC16a domain. In this report, we described a case of anti-BP230 antibody (Ab)-positive BP receiving DPP4i. A 78-year-old male with a medical history of type 2 diabetes receiving vildagliptin at 100 mg daily for 38 months was referred to our hospital with itching blisters on his body and extremities. Skin biopsy showed subepidermal bulla with eosinophil infiltration. Direct immunofluorescence staining revealed a linear staining pattern with complement C3 and IgG at the subepidermal basement membrane zone. By laboratory testing, autoAbs against BP180NC16a and full-length BP180 were negative by enzyme-linked immunosorbent assay (ELISA); however, anti-BP230 Abs were positive by ELISA (index: 123.91). His HLA genotype was DQB1*04:01 and 05:01. Based on these results, we diagnosed the patient with anti-BP230 Abs-positive BP associated with DPP4i. To the best of our knowledge, this is the first case of DPP4i-BP with only anti-BP230 Abs. Further accumulation of DPP4i-BP cases is needed to clarify the relationship between overall features of DPP4i-BP and anti-BP230 Abs. [ABSTRACT FROM AUTHOR]

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]

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 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]

Little is known about the relationship between polyunsaturated fatty acids (PUFAs) and reactive oxygen species (ROS) in the general population. Therefore this study aimed to describe the association of PUFAs with ROS according to age and sex in the general population and to determine whether PUFA levels are indicators of ROS. This cross-sectional study included 895 participants recruited from a 2015 community health project. Participants were divided into 6 groups based on sex and age (less than 45 years old (young), aged 45–64 years (middle-aged), and 65 years or older (old)) as follows: male, young (n = 136); middle-aged (n = 133); old (n = 82); female, young (n = 159); middle-aged (n = 228); and old (n = 157). The PUFAs measured were arachidonic acid (AA), dihomo gamma linolenic acid (DGLA), AA/DGLA ratio, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). ROS considered in the analysis were basal ROS and stimulated ROS levels. Multiple linear analyses showed: (1) significant correlations between PUFA levels, especially DGLA and AA/DGLA ratio, and neutrophil function in the young and middle-aged groups; (2) no significant correlations in old age groups for either sex. Because PUFAs have associated with the ROS production, recommendation for controlled PUFA intake from a young age should be considered. [ABSTRACT FROM AUTHOR]

This study aimed (1) to assess serum trace elements concentrations and hematological parameters, (2) to evaluate the sex differences in the associations between serum trace elements levels and hematological parameters, and (3) to identify the associations between serum trace elements concentrations and risk of anemia among Japanese community dwellers. This is a community-based cross-sectional study that utilized the data of the 2014 Iwaki Health Promotion Project. Participants were 1176 community dwellers (>18 years) residing in the Iwaki District, Aomori Prefecture, Japan. We assessed the data of serum trace elements concentrations of cadmium (Cd), cobalt (Co), copper (Cu), selenium (Se), zinc (Zn), and iron (Fe) as well as the hematological parameters of red blood cells (RBC) counts, hemoglobin, packed cells volume (PCV), mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH). Serum concentrations of Zn (871.5 μg/L vs. 900.1 μg/L) and Fe (946.8 μg/L vs. 1096.1 μg/L) were significantly lower in females than in males, while serum concentrations of Co (0.4 μg/L vs. 0.3 μg/L) and Cu (1062.4 μg/L vs. 965.3 μg/L) were significantly higher in females. By multivariate linear regression, serum Se concentration was significantly, positively associated with PCV (β = 1.04; 95% confidence interval (CI): 0.17, 1.92; p = 0.016) among the study participants. Serum Zn also had positive associations with hemoglobin (β = 0.42; 95% CI: 0.07, 0.77; p = 0.020), PCV (β = 1.79; 95% CI: 0.78, 2.81; p < 0.001), and RBCs count (β = 15.56; 95% CI: 7.31, 31.69; p = 0.002). On the other hand, serum Co concentration was negatively associated with the hematological parameters, particularly in females. Moreover, serum Zn concentration had a decreased risk of anemia (lowest vs. highest quartiles: odds ratio (OR) = 0.42; 95% CI: 0.23, 0.76; p = 0.005) while higher Co concentrations had an increased risk of anemia (lowest vs. highest quartiles: OR = 1.95; 95% CI: 1.04, 3.67; p = 0.037). However, no significant association was found between serum Cu level and hematological parameters. There were substantial sex differences in serum trace elements, implying that trace elements metabolism differed between males and females. Zn can play a protective role in the development of anemia. Surprisingly, increased Co concentration increased the risk of anemia among our study population, which called for further studies to confirm and to consider for speciation analysis. [ABSTRACT FROM AUTHOR]

High visceral fat area (VFA) is a stronger predictor of cardiovascular disease and overall mortality than body mass index or waist circumference. VFA may be decreased by proper dietary habits. Although previous epidemiologic studies demonstrated an association between nutritional components or foodstuffs and VFA, only the associations of a few nutrients, such as dietary fiber and calcium, are reported. We performed a comprehensive 2-year longitudinal study in more than 624 healthy people and analyzed 33 micronutrients to investigate nutrients that contribute to changes in visceral fat. Our analyses revealed that "macronutrients" and "micronutrients" were "mutual confounders". Therefore, when evaluating the association between VFA and micronutrients, associations were adjusted by macronutrients. The ingestion of 7 nutrients: soluble dietary fiber, manganese, potassium, magnesium, vitamin K, folic acid, and pantothenic acid, which are abundant components in vegetable diets, was significantly inversely correlated with a change in VFA. Additionally, a change in the ingestion of one nutrient, monounsaturated fat, was significantly positively correlated with a change in VFA. These associations were independent of body mass index and waist circumference. Thus, a predominantly vegetable diet may decrease VFA. In addition, adjusting the intake of macronutrients might help to clarify the association of micronutrients with VFA. [ABSTRACT FROM AUTHOR]

Although decreased calcium absorption, decreased bone formation, alcohol drinking, and smoking have been considered as causes of osteopenia in men, the cause is unknown in half of the cases. Many reports highlighted the association between Helicobacter pylori infection and osteoporosis, mainly in East Asia and Japan. To identify relevant factors of osteoporosis in men, we examined estrogen and calcium intakes and other lifestyle factors together with gastric mucosal atrophy caused by Helicobacter pylori infection. This study is a cross-sectional study design of 268 healthy men who underwent general medical examinations. Multivariate analysis was performed, with age, body mass index, smoking habit, drinking habit, exercise habit, estradiol level, calcium intake, and Helicobacter pylori infection and its associated gastric mucosal atrophy as the independent variables and the presence of osteopenia as the dependent variable. The adjusted odds ratio was 0.74 (95% Confidence Interval [0.29, 1.90], p =.531) and 1.31 (95% Confidence Interval [0.54, 3.21], p =.552), when Helicobacter pylori infection was positive without and with gastric mucosal atrophy, respectively. Helicobacter pylori infection and gastric mucosal atrophy were not significant factors. Low body mass index, smoking habit, and low calcium intake were significantly associated with decreased bone density. In conclusion, Helicobacter pylori infection was not a significant risk, whereas low body mass index, current smoking, and lower calcium intake had a significant influence on the development of osteopenia in men. [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]

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]