Altered prefrontal beta oscillatory activity during removal of information from working memory in obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) is related to working memory impairment. Since patients with OCD have difficulty controlling their obsessive thoughts, removal of irrelevant information might be important in the pathophysiology of OCD. However, little is known about brain activity during the removal of information from working memory in patients with OCD. Our goal was to explore potential deficits in inhibitory function related to working memory processes in patients with OCD. METHODS: Sixteen OCD patients and 20 healthy controls (HCs) were recruited. We compared in prefrontal alpha and beta band activity derived from magnetoencephalography (MEG) between patients with OCD and HCs during multiple phases of information processing associated with working memory, especially in post-trial period of the visuospatial working memory task (the delayed matching-to-sample task), which is presumed to be related to the information removal process of working memory. RESULTS: Prefrontal post-trial beta power change (presumed to occur at high levels during the post-trial period) exhibited significant reductions in patients with OCD compared to HCs. In addition, the post-trial beta power change was negatively correlated with Obsessive-Compulsive Inventory-Revised total scores in patients with OCD. CONCLUSIONS: These findings suggest that impairment in the removal of information from working memory might be a key mechanism underlying the inability of OCD patients to rid themselves of their obsessions.

Added Value of Cone-Beam Computed Tomography for Detecting Hepatocellular Carcinomas and Feeding Arteries during Transcatheter Arterial Chemoembolization Focusing on Radiation Exposure.

Background and Objectives: This study aimed to evaluate the added value of cone-beam computed tomography (CBCT) for detecting hepatocellular carcinomas (HCC) and feeding arteries during transcatheter arterial chemoembolization (TACE). Material and methods: Seventy-six patients underwent TACE and CBCT. We subcategorized patients into groups I (61 patients: possible superselection of tumor/feeding arteries) and II (15 patients: limited superselection of tumor/feeding arteries). We evaluated fluoroscopy time and radiation dose during TACE. Two blinded radiologists independently performed an interval reading based on digital subtraction angiography (DSA) imaging only and DSA combined with CBCT in group I. Result: The mean total fluoroscopy time was 1456.3 ± 605.6 s. The mean dose-area product (DAP), mean DAP of CBCT, and mean ratio of DAP of CBCT to total DAP was 137.1 ± 69.2 Gy cm2, 18.3 ± 7.1 Gy cm2, and 13.3%, respectively. The sensitivity for detecting HCC increased after the additional CBCT reading, from 69.6% to 97.3% and 69.6% to 96.4% for readers 1 and 2, respectively. The sensitivity for detecting feeding arteries increased from 60.3% to 96.6% and 63.8% to 97.4% for readers 1 and 2, respectively. Conclusions: CBCT can increase sensitivity for detecting HCCs and feeding arteries without significantly increasing the radiation exposure.

Nutrient-specific proteomic analysis of the mucin degrading bacterium Akkermansia muciniphila.

Akkermansia muciniphila is a prominent mucin-degrading bacterium that acts as a keystone species in regulating the human gut microbiota. Despite recently increasing research into this bacterium and its relevance to human health, a high-resolution database of its functional proteins remains scarce. Here, we provide a proteomic overview of A. muciniphila grown in different nutrient conditions ranging from defined to complex. Of 2318 protein-coding genes in the genome, we identified 841 (40%) that were expressed at the protein level. Overall, proteins involved in energy production and carbohydrate metabolism indicate that A. muciniphila relies mainly on the Embden-Meyerhof-Parnas pathway, and produces short-chain fatty acids through anaerobic fermentation in a nutrient-specific manner. Moreover, this bacterium possesses a broad repertoire of glycosyl hydrolases, together with putative peptidases and sulfatases, to cleave O-glycosylated mucin. Of them, putative mucin-degrading enzymes (Amuc_1220, Amuc_1120, Amuc_0052, Amuc_0480, and Amuc_0060) are highly abundant in the mucin-supplemented media. Furthermore, A. muciniphila uses mucin-derived monosaccharides as sources of energy and cell wall biogenesis. Our dataset provides nutrient-dependent global proteomes of A. muciniphila ATCC BAA-835 to offer insights into its metabolic functions that shape the composition of the human gut microbiota via mucin degradation.

Excessive osteoclast activation by osteoblast paracrine factor RANKL is a major cause of the abnormal long bone phenotype in Apert syndrome model mice.

The fibroblast growth factor (FGF)/FGF receptor (FGFR) signaling pathway plays important roles in the development and growth of the skeleton. Apert syndrome caused by gain-of-function mutations of FGFR2 results in aberrant phenotypes of the skull, midface, and limbs. Although short limbs are representative features in patients with Apert syndrome, the causative mechanism for this limb defect has not been elucidated. Here we quantitatively confirmed decreases in the bone length, bone mineral density, and bone thickness in the Apert syndrome model of gene knock-in Fgfr2S252W/+ (EIIA-Fgfr2S252W/+ ) mice. Interestingly, despite these bone defects, histological analysis showed that the endochondral ossification process in the mutant mice was similar to that in wild-type mice. Tartrate-resistant acid phosphatase staining revealed that trabecular bone loss in mutant mice was associated with excessive osteoclast activity despite accelerated osteogenic differentiation. We investigated the osteoblast-osteoclast interaction and found that the increase in osteoclast activity was due to an increase in the Rankl level of osteoblasts in mutant mice and not enhanced osteoclastogenesis driven by the activation of FGFR2 signaling in bone marrow-derived macrophages. Consistently, Col1a1-Fgfr2S252W/+ mice, which had osteoblast-specific expression of Fgfr2 S252W, showed significant bone loss with a reduction of the bone length and excessive activity of osteoclasts was observed in the mutant mice. Taken together, the present study demonstrates that the imbalance in osteoblast and osteoclast coupling by abnormally increased Rankl expression in Fgfr2S252W/+ mutant osteoblasts is a major causative mechanism for bone loss and short long bones in Fgfr2S252W/+ mice.

Host-microbial interactions between PTGR2 and Bifidobacterium in the early life gut of atopic dermatitis children.

BACKGROUND: Gut microbiota dysbiosis is linked to the development and responses of the immune system and can play an important role in the onset of allergic diseases including atopic dermatitis (AD). This study investigated the association between host genetics and the gut microbiota in AD. METHODS: A global gene expression profiling of the gut epithelial colonocytes, genetic variations analysis, and the gut microbial composition analysis were performed. RESULTS: This study identified the upregulation of PTGR2 (p = .028), a gene involved in prostaglandin catalysis and inflammatory responses, as a potential risk factor for AD. In subsequent fine mapping analysis using 17 single nucleotide polymorphisms (SNPs) of PTGR2 in 864 Korean subjects (420 AD patients and 444 unaffected controls), several SNPs and haplotypes showed significant associations with AD and its SCORing AD (SCORAD) values (p = .002). To investigate host-microbial interactions, further gut microbiota data and genotypes were obtained from an independent cohort of 176 subjects (91 AD patients and 85 controls). From correlation analysis, a significantly negative association between SNP and Bifidobacterium abundance was observed in AD patients (p = .005). In additional observations of PTGR2-associated downstream molecules, NRF2 (p = .004) and several antioxidant genes (GSTT1, GCLC, GPX1; p < .05) showed significantly reduced expression in AD patients. CONCLUSIONS: Our current findings suggest that the interaction between PTGR2 dysregulated expression and a Bifidobacterium abundance affects a higher risk of AD and a more severe onset.

Gastrointestinal Air Motion Artifact Which Can Be Mistaken for Active Gastrointestinal Bleeding in Multidetector Computed Tomography: Phantom and Clinical Study.

OBJECTIVES: We investigated the computed tomographic characteristics of gastrointestinal air motion artifact (GIAMA), which can be misinterpreted as active gastrointestinal bleeding. METHODS: We simulated GIAMA using 3 types of air-ball phantoms (air-ball in water, air-ball in oil, air-water-ball in oil) and a bovine intestine in oil phantom. We also performed a retrospective clinical review of precontrast abdominal computed tomography images of 76 patients to investigate the frequency, location, shape, and maximum density of hyperdense GIAMA. RESULTS: In phantom studies, air motion artifacts appeared as dark and bright streak artifacts at the borders of a moving air-ball and water or oil. In the clinical study, hyperdense GIAMA was visualized in 60 (79.0%) of 76 patients. The small intestine was most commonly affected (46.4%), and the intramural type had the highest frequency (58.0%). CONCLUSION: Knowing the radiologic features of GIAMA can assists radiologists in identifying active gastrointestinal bleeding sites accurately.

Different upper airway microbiome and their functional genes associated with asthma in young adults and elderly individuals.

BACKGROUND: Microbes in the airway have been shown to be associated with the pathogenesis of asthma. The upper airway microbiome influences the dysbiosis of the lower airway microbiome. However, to date, the influence of upper airway microbiome for adult and elderly asthma has not been fully elucidated. Here, the metagenome of upper airway microbiome of young adults and elderly was analyzed to identify their association with adult asthma. METHODS: Nasopharyngeal swabs were collected from young adult and elderly asthma patients and non-asthmatic subjects. The compositions and functional genes of airway microbiome were analyzed by high-throughput sequencing. RESULTS: The composition of microbiota differed between young adult and elderly, and it was different between asthmatics and non-asthmatics in each age group. Different bacteria were related to FEV1% predicted in each age group. Genes related to lysine degradation, N-glycan biosynthesis, caprolactam degradation, and PPAR signaling pathway, which could be related to the reduction in inflammation and degradation of air pollutants, were higher in non-asthmatics. Genes related to pentose phosphate pathway, lipopolysaccharide biosynthesis, flagella assembly, and bacterial chemotaxis-which may all be related to increased inflammation and colonization of pathogenic bacteria-were higher in young adult asthmatic patients. However, the functional genes of airway microbiome in elderly patients were not significantly different according to asthma morbidity. CONCLUSIONS: These results suggest that the composition and function of upper airway microbiome could influence asthma pathogenesis, and the microbiome could play various roles depending on the age group.

Perturbations of gut microbiome genes in infants with atopic dermatitis according to feeding type.

BACKGROUND: Perturbations of the infant gut microbiota can shape development of the immune system and link to the risk of allergic diseases. OBJECTIVE: We sought to understand the role of the gut microbiome in patients with atopic dermatitis (AD). The metagenome of the infant gut microbiome was analyzed according to feeding types. METHODS: Composition of the gut microbiota was analyzed in fecal samples from 129 infants (6 months old) by using pyrosequencing, including 66 healthy infants and 63 infants with AD. The functional profile of the gut microbiome was analyzed by means of whole-metagenome sequencing (20 control subjects and 20 patients with AD). In addition, the total number of bacteria in the feces was determined by using real-time PCR. RESULTS: The gut microbiome of 6-month-old infants was different based on feeding types, and 2 microbiota groups (Bifidobacterium species-dominated and Escherichia/Veillonella species-dominated groups) were found in breast-fed and mixed-fed infants. Bacterial cell amounts in the feces were lower in infants with AD than in control infants. Although no specific taxa directly correlated with AD in 16S rRNA gene results, whole-metagenome analysis revealed differences in functional genes related to immune development. The reduction in genes for oxidative phosphorylation, phosphatidylinositol 3-kinase-Akt signaling, estrogen signaling, nucleotide-binding domain-like receptor signaling, and antigen processing and presentation induced by reduced colonization of mucin-degrading bacteria (Akkermansia muciniphila, Ruminococcus gnavus, and Lachnospiraceae bacterium 2_1_58FAA) was significantly associated with stunted immune development in the AD group compared with the control group (P < .05). CONCLUSIONS: Alterations in the gut microbiome can be associated with AD because of different bacterial genes that can modulate host immune cell function.

Peptidyl-prolyl cis-trans isomerase NIMA interacting 1 regulates skeletal muscle fusion through structural modification of Smad3 in the linker region.

Myoblast fusion is critical for muscle growth, regeneration, and repair. We previously reported that the enzyme peptidyl-prolyl cis-trans isomerase NIMA interacting 1 (Pin1) is involved in osteoclast fusion. The objective of this study was to investigate the possibility that Pin1 also inhibits myoblast fusion. Here, we show the increased number of nuclei in the Pin1+/- mice muscle fiber compared to that in wild-type mice. Moreover, we show that low dose of the Pin1 inhibitor dipentamethylene thiuram monosulfide treatment caused enhanced fusion in C2C12 cells. The R-Smads are well-known mediators of muscle hypertrophy and hyperplasia as well as being substrates of Pin1. We found that Pin1 is crucial for maintaining the stability of Smad3 (homologues of the Drosophila protein, mothers against decapentaplegic (Mad) and the Caenorhabditis elegans protein Sma). Our results show that serine 204 within Smad3 is the key Pin1-binding site during inhibition of myoblast fusion and that both the transforming growth factor-ß receptor and extracellular signal-regulated kinase (ERK)-mediated phosphorylation are required for the interaction of Pin1 with Smad3. These findings suggest that a precise level of Pin1 activity is essential for regulating myoblast fusion during myogenesis and muscle regeneration.

Interbrain phase synchronization during turn-taking verbal interaction-a hyperscanning study using simultaneous EEG/MEG.

Recently, neurophysiological findings about social interaction have been investigated widely, and hardware has been developed that can measure multiple subjects' brain activities simultaneously. These hyperscanning studies have enabled us to discover new and important evidences of interbrain interactions. Yet, very little is known about verbal interaction without any visual input. Therefore, we conducted a new hyperscanning study based on verbal, interbrain turn-taking interaction using simultaneous EEG/MEG, which measures rapidly changing brain activities. To establish turn-taking verbal interactions between a pair of subjects, we set up two EEG/MEG systems (19 and 146 channels of EEG and MEG, respectively) located ∼100 miles apart. Subjects engaged in verbal communication via condenser microphones and magnetic-compatible earphones, and a network time protocol synchronized the two systems. Ten subjects participated in this experiment and performed verbal interaction and noninteraction tasks separately. We found significant oscillations in EEG alpha and MEG alpha/gamma bands in several brain regions for all subjects. Furthermore, we estimated phase synchronization between two brains using the weighted phase lag index and found statistically significant synchronization in EEG and MEG data. Our novel paradigm and neurophysiological findings may foster a basic understanding of the functional mechanisms involved in human social interactions. Hum Brain Mapp 39:171-188, 2018. © 2017 Wiley Periodicals, Inc.

Comparison of microbial communities in swine manure at various temperatures and storage times.

OBJECTIVE: This study was designed to investigate the effects of temperature and storage time on the evolution of bacterial communities in swine manure. METHODS: Manure was stored at -20°C, 4°C, 20°C, or 37°C and sampled at 7-day intervals over 28 days of storage, for a total of 5 time points. To assess the bacterial species present, 16S ribosomal RNA gene sequences were analyzed using pyrosequencing. RESULTS: After normalization, 113,934 sequence reads were obtained, with an average length of 466.6±4.4 bp. The diversity indices of the communities reduced as temperature and storage time increased, and the slopes of rarefaction curves decreased from the second week in samples stored at -20°C and 4°C. These results indicate that the richness of the bacterial community in the manure reduced as temperature and storage time increased. Firmicutes were the dominant phylum in all samples examined, ranging from 89.3% to 98.8% of total reads, followed by Actinobacteria, which accounted for 0.6% to 7.9%. A change in community composition was observed in samples stored at 37°C during the first 7 days, indicating that temperature plays an important role in determining the microbiota of swine manure. Clostridium, Turicibacter, Streptococcus, and Lactobacillus within Firmicutes, and Corynebacterium within Actinobacteria were the most dominant genera in fresh manure and all stored samples. CONCLUSION: Based on our findings, we propose Clostridium as an indicator genus of swine manure decomposition in an anaerobic environment. The proportions of dominant genera changed in samples stored at 20°C and 37°C during the fourth week. Based on these results, it was concluded that the microbial communities of swine manure change rapidly as storage time and temperature increase.

Direct Delivery of Recombinant Pin1 Protein Rescued Osteoblast Differentiation of Pin1-Deficient Cells.

Pin1 is a peptidyl prolyl cis-trans isomerase that specifically binds to the phosphoserine-proline or phosphothreonine-proline motifs of several proteins. We reported that Pin1 plays a critical role in the fate determination of Smad1/5, Runx2, and ß-catenin that are indispensable nuclear proteins for osteoblast differentiation. Though several chemical inhibitors has been discovered for Pin1, no activator has been reported as of yet. In this study, we directly introduced recombinant Pin1 protein successfully into the cytoplasm via fibroin nanoparticle encapsulated in cationic lipid. This nanoparticle-lipid complex delivered its cargo with a high efficiency and a low cytotoxicity. Direct delivery of Pin1 leads to increased Runx2 and Smad signaling and resulted in recovery of the osteogenic marker genes expression and the deposition of mineral in Pin1-deficient cells. These result indicated that a direct Pin1 protein delivery method could be a potential therapeutics for the osteopenic diseases. J. Cell. Physiol. 232: 2798-2805, 2017. © 2016 Wiley Periodicals, Inc.

Comparison of bacterial communities in leachate from decomposing bovine carcasses.

OBJECTIVE: Burial is associated with environmental effects such as the contamination of ground or surface water with biological materials generated during the decomposition process. Therefore, bacterial communities in leachates originating from the decomposing bovine carcasses were investigated. METHODS: To understand the process of bovine (Hanwoo) carcass decomposition, we simulated burial using a lab-scale reactor with a volume of 5.15 m3. Leachate samples from 3 carcasses were collected using a peristaltic pump once a month for a period of 5 months, and bacterial communities in samples were identified by pyrosequencing of the 16S rRNA gene. RESULTS: We obtained a total of 110,442 reads from the triplicate samples of various sampling time points (total of 15 samples), and found that the phylum Firmicutes was dominant at most sampling times. Differences in the bacterial communities at the various time points were observed among the triplicate samples. The bacterial communities sampled at 4 months showed the most different compositions. The genera Pseudomonas and Psychrobacter in the phylum Proteobacteria were dominant in all of the samples obtained after 3 months. Bacillaceae, Clostridium, and Clostridiales were found to be predominant after 4 months in the leachate from one carcass, whereas Planococcaceae was found to be a dominant in samples obtained at the first and second months from the other two carcasses. The results showed that potentially pathogenic microbes such as Clostridium derived from bovine leachate could dominate the soil environment of a burial site. CONCLUSION: Our results indicated that the composition of bacterial communities in leachates of a decomposing bovine shifted continuously during the experimental period, with significant changes detected after 4 months of burial.

Changes in the Functional Potential of the Gut Microbiome Following Probiotic Supplementation during Helicobacter Pylori Treatment.

BACKGROUND: Probiotic supplementation is utilized to alleviate the side effects associated with antibiotic therapy for Helicobacter pylori infection. Several studies have described the effects of administration of probiotics on the gut microbiota during antibiotic therapy. However, most of these studies have focused on specific bacteria, thereby providing limited information on the functional roles of the altered microbiota. Therefore, we examined the impact of probiotic supplementation on the structure and functional dynamics of the gut microbiota during H. pylori eradication, using whole-metagenomic sequence analysis. METHODS: Subjects were divided into two groups: the antibiotics group, which received only antibiotics, and the probiotics group, which received antibiotics with probiotic supplementation. The structural and functional profiles of gut microbiota was analyzed using metagenomic DNA extracted from the feces during treatment by Illumina MiSeq system. RESULTS: The overall alterations in microbiota, as revealed by whole metagenome sequencing, were similar with results from our previous 16S rRNA gene-based analysis. The proportional shift in functional gene families was greater in the antibiotics group than in the probiotics group. In particular, the proportion of genes related to selenocompound metabolism was reduced in the probiotics group, whereas genes associated with the metabolism of nucleotide sugars were increased. CONCLUSION: The functional alterations of gut microbiota may link to the reduction in intestinal irritation and maintenance of bacterial diversity observed following probiotic supplementation with antibiotic therapy. The potential beneficial roles of altered gut microbiota following probiotic supplementation are expected a reduction in side effects such as intestinal irritation and antibiotics resistance.

The Effect of Probiotics on Gut Microbiota during the Helicobacter pylori Eradication: Randomized Controlled Trial.

BACKGROUND: Helicobacter pylori causes chronic gastritis, gastroduodenal ulcers, and gastric cancer, and has been treated with two antibiotics (amoxicillin and clarithromycin) and proton-pump inhibitors (PPIs). However, antibiotic treatment alters the indigenous gut microbiota to cause side effects. Therefore, the effects of probiotic supplementation on therapy have been studied. Although several studies have covered the probiotics' effects, details about the gut microbiota changes after H. pylori eradication have not been evaluated. Therefore, we analyzed the influences of antibiotics and their combination with probiotics on the composition of the gut microbiota using high-throughput sequencing. METHODS: Subjects were divided into two groups. The antibiotics group was treated with general therapy, and the probiotics group with general therapy and probiotic supplementation. Fecal samples were collected from all subjects during treatments, and the influences on gut microbiota were analyzed by 16S rRNA gene-pyrosequencing. RESULTS: Three phyla, Firmicutes, Bacteroidetes, and Proteobacteria, were predominant in the gut microbiota of all subjects. After treatment, the relative abundances of Firmicutes were reduced, whereas those of Proteobacteria were increased in both groups. However, the changed proportions of the gut microbiota in the antibiotics group were higher than those in the probiotics group. In addition, the increase in the levels of antibiotic-resistant bacteria was higher in the antibiotics group than in the probiotics one. CONCLUSION: Probiotic supplementation can reduce the antibiotic-induced alteration and imbalance of the gut microbiota composition. This effect may restrict the growth of antibiotic-resistant bacteria in the gut and improve the H. pylori eradication success rate.

The Efficacy of Primary Interventional Urethral Realignment for the Treatment of Traumatic Urethral Injuries.

PURPOSE: To evaluate the efficacy of primary interventional urethral realignment (PIUR) in patients with traumatic urethral injuries. MATERIALS AND METHODS: This retrospective study included 13 patients with traumatic urethral injuries who were treated with PIUR between September 2008 and February 2014. All 13 patients were men with the mean age of 56.3 years. Technical success rate of PIUR, time to PIUR, required procedure time, length of hospital stay, duration of urethral catheterization, and complications after PIUR were investigated. RESULTS: PIUR was technically successful in 12 of 13 patients (92.3%). The mean time from trauma to PIUR was 44 hours (range, 1-240 h). The mean procedure time was 20.2 minutes (range, 3-90 min). The median length of hospital stay was 15 days (range, 1-60 d). The mean duration of urethral catheterization after PIUR was 25 days (range, 9-65 d). There were no immediate complications related to PIUR, although 6 of 12 patients developed symptomatic urethral stricture after PIUR. The mean time to stricture development after PIUR was 4.3 months (range, 2-12 mo). Of the 6 patients, 2 were treated with endoscopic internal urethrotomy, and 4 were treated with interventional radiologic urethral balloon dilation. CONCLUSIONS: PIUR can be safe and effective for patients with traumatic urethral injuries. However, symptomatic stricture formation occurred in one-half of the successful realignment procedures.

Sasa quelpaertensis leaf extract regulates microbial dysbiosis by modulating the composition and diversity of the microbiota in dextran sulfate sodium-induced colitis mice.

BACKGROUND: Inflammatory bowel diseases (IBD) are related to a dysfunction of the mucosal immune system and they result from complex interactions between genetics and environmental factors, including lifestyle, diet, and the gut microbiome. Therefore, the effect of Sasa quelpaertensis leaf extract (SQE) on gut microbiota in a dextran sulfate sodium (DSS)-induced colitis mouse model was investigated with pyrosequencing of fecal samples. METHODS: Three groups of animals were examined: i) a control group, ii) a group that was received 2.5% DSS in their drinking water for 7 days, followed by 7 days of untreated water, and then another 7 days of 2.5% DSS in their drinking water, and iii) a group that was presupplemented with SQE (300 mg/kg body weight) by gavage for two weeks prior to the same DSS treatment schedule described in ii. RESULTS: SQE supplementation alleviated disease activity scores and shortened colon length compared to the other two groups. In the DSS group, the proportion of Bacteroidetes increased, whereas that the proportion of Firmicutes was decreased compared to the control group. SQE supplementation recovered the proportions of Firmicutes and Bacteroidetes back to control levels. Moreover, the diversity of microbiota in the SQE supplementation group higher than that of the DSS group. CONCLUSION: SQE was found to protect mice from microbial dysbiosis associated with colitis by modulating the microbial composition and diversity of the microbiota present. These results provide valuable insight into microbiota-food component interactions in IBD.