Search

Background : Delayed post-polypectomy bleeding (DPPB) is a serious complication of polypectomy that is poorly understood. The aim of this study was to evaluate the effectiveness of endoscopic hemostasis in managing DPPB and to identify associated risk factors. Methods : We retrospectively analyzed 289 patients who experienced DPPB (≥ 24 hours after polypectomy) and underwent endoscopic hemostasis at five university hospitals between 2005 and 2018. Patient characteristics, polyp size, technical factors, rebleeding, complications, and length of hospitalization were assessed. Results : Endoscopic hemostasis was successful in all 289 cases of DPPB. The techniques and devices employed included epinephrine injection (24.9%), argon plasma coagulation (18.0%), hemostatic forceps (10.7%), and hemoclips (87.9%). Rebleeding occurred in 15 cases (5.2%) after initial endoscopic hemostasis. The incidence of rebleeding was significantly associated with polyp size (< 10 mm: 2.8%, 10 mm-19 mm: 5.6%, ≥ 20 mm: 13.5%, P = 0.030) and sedation status (yes: 1.8%, no: 7.3%, P = 0.040). However, hemostasis method, bleeding characteristics, and polyp location were not significantly linked to rebleeding. Multivariate analysis revealed that polyp size (odds ratio, 5.02; 95% confidence interval, 1.25-20.13; P = 0.023) was significantly associated with rebleeding after endoscopic hemostasis for DPPB. In all 15 cases of rebleeding, a second endoscopic hemostasis was successfully performed without the need for embolization or surgical intervention. No perforations occurred during the first or second endoscopic hemostatic procedures. Conclusion : Polyp size and sedation status were associated with rebleeding after endoscopic hemostasis for DPPB. As an intervention for DPPB, endoscopic hemostasis appears safe and effective.

Recent clinical outcomes of multi-regimen chemotherapy in patients with cholangiocarcinoma (CCC) have shown benefits in terms of overall survival. However, repeated endoscopic biliary drainage (EBD) and serious adverse events negatively affect prolongation of the survival period. The aim of this study was to investigate the prevalence of massive hemobilia and the outcomes of its management with fully covered self-expandable metal stents (FC-SEMSs) in patients with hilum-involving CCC receiving multi-regimen chemotherapy. The methods and effects of FC-SEMS placement were retrospectively investigated following the occurrence of massive hemobilia during EBD. A total of 356 patients with CCC received multi-regimen chemotherapy. Among them, 181 patients had hilar invasion, and seven patients (3.9%) developed massive hemobilia during repeated EBD using removable stents. In all cases, the tumor encased the right hepatic artery. In six patients (85.7%), hemostasis was immediately and completely achieved by inserting one or two FC-SEMSs proximal to the hilar invasion area. Therefore, if the tumor encases the right hepatic artery, massive hemobilia is likely to occur during multi-regimen chemotherapy. Thus, prompt placement of a FC-SEMS would be an effective treatment option for massive hemobilia in patients with hilum-involving CCC.

Abstract We study the (ambi-)twistor model for spinning particles interacting via electromagnetic field, as a toy model for studying classical dynamics of gravitating bodies including effects of both spins to all orders. We compute the momentum kick and spin kick up to one-loop order and show precisely how they are encoded in the classical eikonal. The all-orders-in-spin effects are encoded as a dynamical implementation of the Newman-Janis shift, and we find that the expansion in both spins can be resummed to simple expressions in special kinematic configurations, at least up to one-loop order. We confirm that the classical eikonal can be understood as the generator of canonical transformations that map the in-states of a scattering process to the out-states. We also remark that cut contributions for converting worldline propagators from time-symmetric to retarded amount to the iterated action of the leading eikonal at one-loop order.

Background/Aims: Although guidelines exist regarding the evaluation and management of patients with chronic constipation (CC), little is known about real-world clinical practice patterns. This study aimed to evaluate the various practices used to manage CC patients in various clinical settings in South Korea. Methods : A nationwide web-based survey was conducted, randomly selecting gastroenterologists and non-gastroenterologists. The 25-item questionnaire included physicians’ perceptions and practices regarding the available options for diagnosing and managing CC patients in Korea. Results : The study participants comprised 193 physicians (86 gastroenterologists, 44.6%) involved in the clinical management of CC patients. The mean clinical experience was 12 years. Only 21 of 193 respondents (10.9%) used the Rome criteria when diagnosing CC. The Bristol Stool Form Scale was used by 29% of the respondents (56/193), while the digital rectal examination was performed by 11.9% of the respondents (23/193). Laboratory testing and colonoscopies were performed more frequently by gastroenterologists than by non-gastroenterologists (both p=0.001). Physiologic testing was used more frequently by gastroenterologists (p=0.046), physicians at teaching hospitals, and physicians with clinical experience ≤10 years (both p

Abstract Background Yukgunja-tang (YGJ) is an herbal prescription used to treat the symptoms of gastroesophageal reflux disease (GERD). Although many preclinical and clinical studies on YGJ have been conducted on GERD, there is a lack of evidence from blinded studies to exclude placebo effects. Therefore, this protocol proposes a clinical trial that is single-centered, randomized, double-blinded, double-dummy to objectively evaluate the efficacy and safety of co-administered YGJ and rabeprazole (RPZ) in patients with GERD previously treated with proton pump inhibitors (PPIs) and still experiencing symptoms. Methods A total of 86 participants with refractory GERD (rGERD) will be randomized in a 1:1 ratio to the treatment [YGJ and RPZ (10 mg/d)] and control groups [double-dose RPZ (20 mg/d)] for 4 weeks of treatment (weeks 0–4) followed by 4 weeks of follow-up (weeks 4–8). The Frequency Scale for the Symptoms of GERD will be analyzed for the primary endpoint. Reflux Disease Questionnaire, Reflux Symptom Score, GERD-Health Related Quality of Life, Overall Treatment Evaluation, Spleen Qi Deficiency Questionnaire, Damum Questionnaire, and dyspepsia Visual Analogue Scale will be used to evaluate treatment effects on GERD related symptoms and quality of life and to compare treatment effects by subgroups. Safety tests will be analyzed by investigating adverse events. Discussion This clinical trial will be the first rigorous double-blind, double-dummy, placebo-controlled study to precisely evaluate the efficacy and safety of the combination of YGJ and PPIs in the treatment of rGERD. The results of this study will provide a reliable clinical basis for selecting botanical drug treatments for patients with rGERD. Trial registration Clinical Research Information Service (registration number: KCT0008600, July 13, 2023, https://cris.nih.go.kr ).

Abstract Background Permanent first molars with severe dental caries, developmental defects, or involved in oral pathologies are at risk of poor prognosis in children. Accordingly, using the third molar to replace the first molar can be a good treatment option when third molar agenesis is predicted early. Thus, this retrospective cohort study aimed to develop criteria for early detection of mandibular third molar (L8) agenesis based on the developmental stages of mandibular canine (L3), first premolar (L4), second premolar (L5), and second molar (L7). Method Overall, 1,044 and 919 panoramic radiographs of 343 males and 317 females, respectively, taken between the ages of 6 and 12 years were included. All developmental stages of L3, L4, L5, L7, and L8 were analyzed based on the dental age, as suggested by Demirjian et al. The independent t-test was used to assess age differences between males and females. The rank correlation coefficients were examined using Kendall’s tau with bootstrap analysis and Bonferroni’s correction to confirm the teeth showing developmental stages most similar to those of L8s. Finally, a survival analysis was performed to determine the criteria for the early diagnosis of mandibular third molar agenesis. Results Some age differences were found in dental developmental stages between males and females. Correlation coefficients between all stages of L3, L4, L5, and L7 and L8 were high. In particular, the correlation coefficient between L7 and L8 was the highest, whereas that between L3 and L8 was the lowest. Conclusion If at least two of the following criteria (F stage of L3, F stage of L4, F stage of L5, and E stage of L7) are met in the absence of L8 crypt, agenesis of L8 can be confirmed.

Abstract The spin supplementary conditions are constraints on spin degrees of freedom in classical relativity which restricts physical degrees of freedom to rotations. It is argued that the equivalent constraints in quantum field theory are the projection conditions on polarisation tensors, which remove timelike/longitudinal polarisations from the physical spectrum. The claim is supported by three examples of massive spinning particles coupled to electromagnetism: Dirac and Proca fields in quantum field theory, and 𝒩 = 1 worldline QFT for classical worldline theory. This suggests a resolution to the apparent discrepancy between effective field theory description of massive higher-spin fields [1, 2] and post-Newtonian effective field theory of spinning classical particles [3], where the former admits more unfixed parameters compared to the latter; the additional parameters are fixed by projection conditions and therefore are not tunable parameters.

Abstract We present the derivation of the third subleading order (N3LO) spin-orbit interaction at the state of the art of post-Newtonian (PN) gravity via the EFT of spinning objects. The present sector contains the largest and most elaborate collection of Feynman graphs ever tackled to date in sectors with spin, and in all PN sectors up to third subleading order. Our computations are carried out via advanced multi-loop methods. Their most demanding aspect is the imperative transition to a generic dimension across the whole derivation, due to the emergence of dimensional-regularization poles across all loop orders as of the N3LO sectors. At this high order of sectors with spin, it is also critical to extend the formal procedure for the reduction of higher-order time derivatives of spin variables beyond linear order for the first time. This gives rise to a new unique contribution at the present sector. The full interaction potential in Lagrangian form and the general Hamiltonian are provided here for the first time. The consequent gravitational-wave (GW) gauge-invariant observables are also derived, including relations among the binding energy, angular momentum, and emitted frequency. Complete agreement is found between our results, and the binding energy of GW sources, and also with the extrapolated scattering angle in the scattering problem, derived via traditional GR. In contrast with the latter derivation, our framework is free-standing and generic, and has provided theory and results, which have been critical to establish the state of the art, and to push the precision frontier for the measurement of GWs.

Background/Aims Intragastric balloon (IGB) is the only available endoscopic bariatric and metabolic therapy in Korea. End-ball (Endalis) has the longest history of clinical use among the IGBs available in Korea. However, little clinical data on this system have been reported. In this study, we aimed to evaluate the efficacy and safety of End-ball in Korea. Methods We performed a retrospective cohort study of patients who underwent IGB insertion (End-ball) from 2013 to 2019. Demographic and anthropometric data were collected. The efficacy and safety of IGB treatment were analyzed. Results In total, 80 patients were included. Mean age was 33.7 years and 83.8% were female. Initial body mass index was 34.48±4.69 kg/m2. Body mass index reduction was 3.72±2.63 kg/m2 at the time of IGB removal. Percent of total body weight loss (%TBWL) was 10.76%±6.76%. Percentage excess body weight loss was 43.67%±27.59%. Most adverse events were minor, and 71.4% of participants showed nausea, vomiting, or abdominal pain. Conclusions IGB treatment showed good efficacy and safety profile in Korean patients with obesity. In terms of %TBWL and percentage excess body weight loss, the efficacy was similar to that in the Western population.

Abstract We derive the third subleading (N3LO) corrections of the quadratic-in-spin sectors via the EFT of spinning objects in post-Newtonian (PN) gravity. These corrections consist of contributions from 4 sectors for generic compact binaries, that enter at the fifth PN order. One of these contributions is due to a new tidal interaction, that is unique to the sectors with spin, and complements the first tidal interaction that also enters at this PN order in the simple point-mass sector. The evaluation of Feynman graphs is carried out in a generic dimension via advanced multi-loop methods, and gives rise to dimensional-regularization poles in conjunction with logarithms. At these higher-spin sectors the reduction of generalized Lagrangians entails redefinitions of the position beyond linear order. We provide here the most general Lagrangians and Hamiltonians. We then specify the latter to simplified configurations, and derive the consequent gauge-invariant relations among the binding energy, angular momentum, and frequency. We end with a derivation of all the scattering angles that correspond to an extension of our Hamiltonians to the scattering problem in the simplified aligned-spins configuration, as a guide to scattering-amplitudes studies.

Abstract Effects of massive object’s spin on massive-massless 2 → 2 classical scattering is studied. Focus is set on the less-considered dimensionless expansion parameter λ/b, where λ is the massless particle’s wavelength and b is the impact parameter. Corrections in λ/b start to appear from O $$ \mathcal{O} $$ (G 2), with leading correction terms tied to the gravitational Faraday effect, which is a special case of the Lense-Thirring effect. We compute the eikonal phase up to O $$ \mathcal{O} $$ (G 2) and extract spin effect on the scattering angle and time delay up to 14th order in spin. The gravitational Faraday effect at linear order in spin [1] is reproduced by λ/b correction terms, which we compute to higher orders in spin. We find that the equivalence principle, or universality, holds up to NLO for general spinning bodies, i.e. away from geometric optics limit. Furthermore, in the black hole limit, we confirm the absence of particular spin structure observed [2–8], along with the associated shift symmetry [7], and argue that it holds to arbitrary spin order at O $$ \mathcal{O} $$ (G 2) in the massless probe limit.

Abstract Human ACP4 (OMIM*606362) encodes a transmembrane protein that belongs to histidine acid phosphatase (ACP) family. Recessive mutations in ACP4 cause non-syndromic hypoplastic amelogenesis imperfecta (AI1J, OMIM#617297). While ACP activity has long been detected in developing teeth, its functions during tooth development and the pathogenesis of ACP4-associated AI remain largely unknown. Here, we characterized 2 AI1J families and identified a novel ACP4 disease-causing mutation: c.774_775del, p.Gly260Aspfs*29. To investigate the role of ACP4 during amelogenesis, we generated and characterized Acp4 R110C mice that carry the p.(Arg110Cys) loss-of-function mutation. Mouse Acp4 expression was the strongest at secretory stage ameloblasts, and the protein localized primarily at Tomes’ processes. While Acp4 heterozygous (Acp4 +/R110C) mice showed no phenotypes, incisors and molars of homozygous (Acp4 R110C/R110C) mice exhibited a thin layer of aplastic enamel with numerous ectopic mineralized nodules. Acp4 R110C/R110C ameloblasts appeared normal initially but underwent pathology at mid-way of secretory stage. Ultrastructurally, sporadic enamel ribbons grew on mineralized dentin but failed to elongate, and aberrant needle-like crystals formed instead. Globs of organic matrix accumulated by the distal membranes of defective Tomes’ processes. These results demonstrated a critical role for ACP4 in appositional growth of dental enamel probably by processing and regulating enamel matrix proteins around mineralization front apparatus.

Abstract From the S-matrix of spinning particles, we extract the 2 PM conservative potential for binary spinning black holes up to quartic order in spin operators. An important ingredient is the exponentiated gravitational Compton amplitude in the classical spin-limit for all graviton helicity sectors. The validity of the resulting Hamiltonian is verified by matching to known lower spin order results, as well as direct computation of the 2PM impulse and spin kicks from the eikonal phase and that from the test black hole scattering based on Mathisson-Papapetrou-Dixon equations.

Background/Aims: Biliary complications including biliary strictures and bile leaks are the most common complications that occur after liver transplantation (LT). Endoscopic treatment with endoscopic retrograde cholangiography (ERC) is considered the first-line treatment, and percutaneous transhepatic cholangiography (PTC) can serve as an alternative or rescue therapy. However, nationwide clinical data on the frequency of ERC and PTC following LT have not yet been investigated. Methods: Using the nationwide claims database, we investigated patients who underwent LT between 2012 and 2014 in Korea and followed them until 2015. We analyzed the prevalence and characteristics of patients and biliary procedures, including ERC and PTC implemented after LT. Results: A total of 3,481 patients underwent LT during the 3-year study period. Among them, 3.0% of patients underwent biliary intervention postoperatively during the same hospitalization period, and 21.4% of patients received biliary intervention later on after initially being discharged from the hospital following LT. A total of 16.9% and 12.1% of patients underwent ERC and PTC after LT, respectively. The median period from LT to the first biliary intervention was 7.8 months (interquartile range, 3.5 to 14.6 months), and these patients underwent an average of 3.2±2.8 biliary procedures during the follow-up period. Patients undergoing living donor LT were more than twice as likely to undergo biliary procedures as those undergoing deceased donor LT (25.5% vs 12.1%). Conclusions: Approximately one-fourth of patients in Korea who underwent LT subsequently underwent ERC or PTC. Compared with deceased donor LT patients, those undergoing living donor LT underwent more biliary interventions and were more difficult to treat.

Background/Aims This study aimed to determine the current status of facilities, equipment, and personnel for endoscopic sedation from endoscopy units of representative hospitals in South Korea. Methods A questionnaire survey was conducted on 50 qualified endoscopy units accredited by the Korean Society of Gastrointestinal Endoscopy. Results All included endoscopy units had regulations and educational programs regarding sedation training for endoscopists and nursing personnel. There present one assisting nurse during endoscopy in 35 units (70%) and at least two nurses in 12 units (24.0%). All endoscopy units had examination rooms equipped with oxygen supply and suction systems. Endoscopist-directed sedation was performed in 48 units (96.0%). Propofol-based sedation was the most used sedation method. All units had a separate recovery bay. The daily number of patients per bed was greater than 10 in 17 units (34.0%). In 26 (52.0%) units, a single nurse cared for ≥10 patients per day. All the units fulfilled the discharge criteria. Conclusions This study presents data regarding endoscopic sedation clinical practice in 50 endoscopy units in South Korea. This study presents the current status of endoscopic sedation clinical practice in 50 qualified endoscopy units accredited by the KSGE, which provide excellent quality management.

Abstract Non-syndromic inherited defects of tooth dentin are caused by two classes of dominant negative/gain-of-function mutations in dentin sialophosphoprotein (DSPP): 5′ mutations affecting an N-terminal targeting sequence and 3′ mutations that shift translation into the − 1 reading frame. DSPP defects cause an overlapping spectrum of phenotypes classified as dentin dysplasia type II and dentinogenesis imperfecta types II and III. Using CRISPR/Cas9, we generated a Dspp −1fs mouse model by introducing a FLAG-tag followed by a single nucleotide deletion that translated 493 extraneous amino acids before termination. Developing incisors and/or molars from this mouse and a Dspp P19L mouse were characterized by morphological assessment, bSEM, nanohardness testing, histological analysis, in situ hybridization and immunohistochemistry. Dspp P19L dentin contained dentinal tubules but grew slowly and was softer and less mineralized than the wild-type. Dspp P19L incisor enamel was softer than normal, while molar enamel showed reduced rod/interrod definition. Dspp −1fs dentin formation was analogous to reparative dentin: it lacked dentinal tubules, contained cellular debris, and was significantly softer and thinner than Dspp +/+ and Dspp P19L dentin. The Dspp −1fs incisor enamel appeared normal and was comparable to the wild-type in hardness. We conclude that 5′ and 3′ Dspp mutations cause dental malformations through different pathological mechanisms and can be regarded as distinct disorders.

Abstract Oligodontia is the congenital absence of six or more teeth and comprises the more severe forms of tooth agenesis. Many genes have been implicated in the etiology of tooth agenesis, which is highly variable in its clinical presentation. The purpose of this study was to identify associations between genetic mutations and clinical features of oligodontia patients. An online systematic search of papers published from January 1992 to June 2021 identified 381 oligodontia cases meeting the eligibility criteria of causative gene mutation, phenotype description, and radiographic records. Additionally, ten families with oligodontia were recruited and their genetic etiologies were determined by whole-exome sequence analyses. We identified a novel mutation in WNT10A (c.99_105dup) and eight previously reported mutations in WNT10A (c.433 G > A; c.682 T > A; c.318 C > G; c.511.C > T; c.321 C > A), EDAR (c.581 C > T), and LRP6 (c.1003 C > T, c.2747 G > T). Collectively, 20 different causative genes were implicated among those 393 cases with oligodontia. For each causative gene, the mean number of missing teeth per case and the frequency of teeth missing at each position were calculated. Genotype–phenotype correlation analysis indicated that molars agenesis is more likely linked to PAX9 mutations, mandibular first premolar agenesis is least associated with PAX9 mutations. Mandibular incisors and maxillary lateral incisor agenesis are most closely linked to EDA mutations.

We obtain for the first time all quadratic-in-spin interactions in spinning binaries at the third subleading order in post-Newtonian (PN) gravity, and provide their observable binding energies and their gauge-invariant relations to the angular momentum. Our results are valid for generic compact objects, orbits, and spin orientations, and enter at the fifth PN order for maximally-rotating objects, thus pushing the state of the art. This is accomplished through an extension of the effective field theory of spinning gravitating objects, and of its computational application. We also discover a new finite-size effect which is unique to spinning objects, with a new “Spin Love number” as its characteristic coefficient, that is a new probe for gravity and QCD.

Background/Aims The aim of this in vivo animal study was to evaluate the effectiveness and safety of dedicated cold snare (DCS) compared with those of traditional snare (TS) for cold snare polypectomy (CSP). Methods A total of 36 diminutive (5 mm) and 36 small (9 mm) pseudolesions were made by electrocoagulation in the colons of mini-pigs. Results For the diminutive lesions, there were no significant differences in technical success rate, procedure time, or complete resection rate between the DCS and TS groups; the rate of uneven resection margin in the DCS group was significantly lower than that of the TS group. For small lesions, technical success rate and complete resection rate were significantly higher in the DCS group than in the TS group (100% [18/18] vs. 55.6% [10/18], p=0.003; 94.4% [17/18] vs. 40% [4/10], p=0.006). In addition, the procedure duration was significantly shorter, and the rate of uneven resection margin was significantly lower in the DCS group (28.5 sec vs. 66.0 sec, p=0.006; 11.1% [2/18] vs. 100% [10/10], p

Background: Previous studies have suggested the potential association between renal diseases and gallstone. The extent of proteinuria is recognized as a marker for the severity of chronic kidney disease. However, little data is available to identify the risk of incident gallstone according to the level of proteinuria. Methods: Using a data of 207,356 Koreans registered in National Health Insurance Database, we evaluated the risk of gallstone according to the levels of urine dipstick proteinuria through an average follow-up of 4.36 years. Study subjects were divided into 3 groups by urine dipstick proteinuria (negative: 0, mild: 1+ and heavy: 2+ or greater). Multivariate Cox-proportional hazard model was used to assess the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident cholelithiasis according to urine dipstick proteinuria. Results: The group with higher urine dipstick proteinuria had worse metabolic, renal, and hepatic profiles than those without proteinuria, which were similarly observed in the group with incident cholelithiasis. The heavy proteinuria group had the greatest incidence of cholelithiasis (2.39%), followed by mild (1.54%) and negative proteinuria groups (1.39%). Analysis for multivariate Cox-proportional hazard model indicated that the heavy proteinuria group had higher risk of cholelithiasis than other groups (negative: reference, mild proteinuria: HR 0.97 [95% CI, 0.74–1.26], and heavy proteinuria: HR 1.46 [95% CI, 1.09–1.96]). Conclusion: Urine dipstick proteinuria of 2+ or greater was significantly associated with increased risk for incident gallstone.

Background: Malignant biliary obstruction (MBO) is usually caused by biliary tract cancer or pancreatic cancer. This study was performed to summarize the current situation regarding palliative endoscopic retrograde biliary drainage (ERBD) for MBO in Korea and to determine its clinical significance by analyzing representative nationwide data. Methods: Patients that underwent palliative ERBD for MBO between 2012 and 2015 were identified using the Health Insurance Review and Assessment database, which covers the entire Korean population. We assessed clinical characteristics and complications and compared the clinical impacts of initial metal and plastic stenting in these patients. Results: A total of 9,728 subjects (mean age, 65 ± 11.4 years; male, 61.4%) were identified and analyzed. The most common diagnosis was malignant neoplasm of liver and intrahepatic bile ducts (32.1%) and this was followed by extrahepatic or Ampulla of Vater cancer and pancreatic cancer. Initial plastic stent(s) placement was performed in 52.9% of the study subjects, and metal stent(s) placement was performed in 23.3%. The number of sessions of endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic biliary drainage (PTBD) was significantly higher in patients that underwent initial plastic stenting than in patients that underwent metal stenting (2.2 ± 1.7 vs 1.8 ± 1.4, P < 0.0001), but rates of post-ERCP pancreatitis, hospital days, and time to second ERCP or PTBD were not significantly different. Conclusion: This nationwide assessment study suggests that initial metal stenting is associated with fewer sessions of total ERCP or PTBD following the initial procedure, despite the preference for initial plastic stenting in Korea.

Abstract In this paper, we demonstrate that at leading order in post Minkowskian (PM) expansion, the stress-energy tensor of Kerr-Newman black hole can be recovered to all orders in spin from three sets of minimal coupling: the electric and gravitational minimal coupling for higher-spin particles, and the “minimal coupling” for massive spin-2 decay. These couplings are uniquely defined from kinematic consideration alone. This is shown by extracting the classical piece of the one-loop stress-energy tensor form factor, which we provide a basis that is valid to all orders in spin. The 1 PM stress tensor, and the metric in the harmonic gauge, is then recovered from the classical spin limit of the form factor.

Abstract In this paper we compute the spin-dependent terms of the gravitational potential for general spinning bodies at the leading Newton’s constant G and to all orders in spin. We utilize the on-shell approach, which extracts the classical potential directly from the scattering amplitude. For spinning particles, extra care is required due to the fact that the spin space of each particle is independent. Once the appropriate matching procedures are applied, taking the classical-spin limit we obtain the potential for general spinning bodies. When the Wilson coefficients are set to unity, we successfully reproduced the potential for the Kerr black hole. Interestingly, for finite spins, we find that the finite-spin deviations from Kerr Wilson coefficients cancel with that in the matching procedure, reproducing the Kerr potential without the need for taking the classical-spin limit. Finally, we find that when cast into the chiral basis, the spin-dependence of minimal coupling exhibits factorization, allowing us to take the classical-spin limit straight forwardly.

Background/Aims The eradication failure rate of standard triple therapy (proton pump inhibitor, clarithromycin, and amoxicillin) for Helicobacter pylori infection has increased owing to antibiotic resistance in Korea. We assessed whether Saccharomyces boulardii probiotic or broccoli sprout extract sulforaphane supplementation could increase the H. pylori eradication rate and/or reduce antibiotic-associated adverse events. Methods A total of 217 patients with H. pylori-positive chronic gastritis or peptic ulcer disease were recruited. Clarithromycin resistance was assessed in all patients by testing for A2142G and A2143G point mutations in H. pylori 23S rRNA using a dual-priming polymerase chain reaction (PCR) oligonucleotide. Thirty-four patients (17.3%) were clarithromycin-resistant and were excluded from the study. Finally, 183 patients with infections not resistant to clarithromycin were randomly assigned to triple therapy only (group A, n = 61), triple therapy plus probiotics (group B, n = 61), or triple therapy plus sulforaphane (group C, n = 61) groups. CYP2C19 polymorphisms were examined at position G681A of exon 5 and G636A of exon 4 by PCR with restriction fragment length polymorphism (PCR-RFLP) analysis. H. pylori eradication was assessed by 13C-urea breath test 4 weeks after treatment completion. Results The eradication rates were similar among the groups both in the intention-to-treat (A = 85.2%, B = 89.6%, and C = 81.6%) and per-protocol (A = 89.2%, B = 86.8%, and C = 96.3%) analyses. The frequencies of overall adverse events in the groups also did not differ (A vs. B: p = 0.574; A vs. C: p = 1.000). Conclusions Probiotic or sulforaphane with triple therapy for H. pylori infection neither increased the eradication rate nor reduced the occurrence of adverse events.

Abstract Building upon recent progress in applying on-shell amplitude techniques to classical observables in general relativity, we propose a closed-form formula for the conservative Hamiltonian of a spinning binary system at the 1st post-Minkowskian (1PM) order. It is applicable for general compact spinning bodies with arbitrary spin multipole moments. The formula is linear in gravitational constant by definition, but exact to all orders in momentum and spin expansions. At each spin order, our formula implies that the spin-dependence and momentum dependence factorize almost completely. We expand our formula in momentum and compare the terms with 1PM parts of the post-Newtonian computations in the literature. Up to canonical transformations, our results agree perfectly with all previous ones. We also compare our formula for black hole to that derived from a spinning test-body near a Kerr black hole via the effective one-body mapping, and find perfect agreement.

Background/Aims The eradication rate of the first-line triple therapy (a proton pump inhibitor, clarithromycin, and amoxicillin) for Helicobacter pylori infection has gradually decreased in Korea. We evaluated whether clinical parameters, clarithromycin resistance, and CYP2C19 genotype can affect the eradication failure. Methods A total of 203 patients with H. pylori-positive chronic gastritis were consecutively enrolled. They received clarithromycin-based triple therapy for 7 days. A clarithromycin resistance test was performed by detection of A2142G and A2143G point mutations in H. pylori 23S rRNA. The CYP2C19 genotype was examined for polymorphism G681A of exon 5 and G636A of exon 4 by polymerase chain reaction with restriction fragment length polymorphism. Eradication was assessed by a 13C-urea breath test 4 weeks after treatment. Results Of 203 patients, 190 completed the study. The eradication rate was 64.0% according to intention-to-treat analysis and 68.4% by per-protocol analysis. CYP2C19 genotypes were identified as follows: 75 poor metabolizers, 75 intermediate metabolizers, and 40 rapid metabolizers. Nonetheless, this polymorphism was not significantly associated with eradication failure (p = 0.682). Clarithromycin resistance was detected in 33/190 patients (17.4%), and their eradication rate was zero. Clarithromycin resistance (odds ratio [OR], 19.13; 95% confidence interval [CI], 9.35 to 35.09) and female gender (OR, 1.73; 95% CI, 1.15 to 4.25) were significantly associated with eradication failure. The other clinical parameters such as age, cigarette smoking, alcohol intake, the body mass index, hypertension, and diabetes were not significantly associated with eradication. Conclusions Clarithromycin resistance and female gender are factors affecting H. pylori eradication failure in patients with chronic gastritis.

The Korean Society of Gastrointestinal Endoscopy introduced the Accredited Endoscopy Unit Program to enhance endoscopy unit quality through systematic quality management in 2012. It was gradually expanded from training hospitals to institutions with 100+ beds, and the criteria for certification were applied according to the actual conditions of each institution. On the basis of the continuous communication with the institutions and feedback, the Accredited Endoscopy Unit Program certification criteria were revised in 2019 and introduced as follows: (1) the qualification criteria for endoscopy doctors and nurses; (2) facilities and equipment; (3) endoscopic examination process; (4) performance; (5) disinfection and infection control; and (6) endoscopic sedation. The assessment items consist of essential and recommended items. All essential items must be met for accreditation to be awarded. The assessment criteria for each evaluation area were revised as follows: (1) upgrading assessment criteria; (2) qualification of endoscopists and reinforcement of quality control education; (3) detailed standards for safety, disinfection, endoscopic sedation, and management instructions; and (4) presentation of new performance measurement of endoscopy and colonoscopy.

Abstract In this paper, we explore the physics of electromagnetically and gravitationally coupled massive higher spin states from the on-shell point of view. Starting with the three-point amplitude, we focus on the simplest amplitude characterized by matching to minimal coupling in the UV. In the IR, for charged states this leads to g = 2 for arbitrary spin, and the leading deformation corresponds to the anomalous magnetic dipole moment. We proceed to construct the (gravitational) Compton amplitude for generic spins via consistent factorization. We find that in gravitation couplings, the leading deformation leads to inconsistent factorization. This implies that for systems with Gauge2 = Gravity relations, such as perturbative string theory, all charged states must have g = 2. It is then natural to ask for generic spin, what is the theory that yields such minimal coupling. By matching to the one body effective action, we verify that for large spins the answer is Kerr black holes. This identification is then an on-shell avatar of the no- hair theorem. Finally using this identification as well as the newly constructed Compton amplitudes, we proceed to compute the spin-dependent pieces for the classical potential at 2PM order up to degree four in spin operator of either black holes.

Background/Aims: The primary aims of this study were to evaluate the content quality of YouTube videos on exercises to help relieve constipation and to assess whether the video source, exercise types, and popularity affected their quality. Methods: Eight gastroenterologists independently evaluated the exercises presented in the constipation YouTube videos for seven items: image quality, usefulness in relieving constipation (quality 1), usefulness for general physical health (quality 2), difficulty in following, activity intensity, fun, and overall quality. Raters were asked open-ended questions to evaluate the strengths and weaknesses of the videos. Five-point ordinal scales were used to score each item aforementioned, with the exception of image quality and overall quality that used a six-point Likert scale. Results : The 20 videos had a mean length of 268 seconds and a mean viewership of 32,694. The most common video source was commercial (n=10), and the most common type of physical activity was yoga (n=11). The median values of image quality, quality 1, quality 2, difficulty in following, activity intensity, fun, and overall quality were 3, 2, 2, 2, 2, 2, and 2, respectively. Yoga videos had significantly higher median quality 1 values (3) compared with massage videos (2, adjusted p=0.006) and others videos (2, adjusted p

Amelogenesis imperfecta (AI) is a collection of rare genetic disorders affecting the quantity and/or quality of the tooth enamel. AI can be classified into three major types according to the clinical phenotype: hypoplastic, hypocalcified, and hypomatured. Among them, the hypocalcified type shows the weakest physical properties, leaving rough and discolored enamel surfaces after tooth eruption. To date, mutations in the FAM83H gene are responsible for the autosomal-dominant hypocalcified AI. In this study, we recruited a four-generation Colombian family with hypocalcified AI and identified a recurrent nonsense mutation in the FAM83H gene (NM_198488.5:c.1289C>A, p.(Ser430 *)) by candidate gene sequencing. Cephalometric analyses revealed the anterior open bite that occurred in the proband is not correlated with the AI in this family.

Amelogenesis imperfecta (AI) is a heterogeneous group of rare genetic disorders affecting amelogenesis during dental development. Therefore, the molecular genetic etiology of AI can provide information about the nature and progress of the disease. To confirm the genetic etiology of AI in a Korean family with an autosomal dominant inheritance, pedigree and mutational analyses were performed. DNA was isolated from the participating family members and whole-exome sequencing was performed with the DNA sample of the father of the proband. The identified mutation was confirmed by Sanger sequencing. The mutational analysis revealed a novel nonsense mutation in the FAM83H gene (NM_198488.5: c.1363C > T, p.(Gln455*)), confirming autosomal dominant hypocalcified AI. Full-mouth restorative treatments of the affected children were performed after the completion of the deciduous dentition. Early diagnosis of AI can be useful for understanding the nature of the disease and for managing the condition and treatment planning.

Abstract Background Lacrimo‐auriculo‐dento‐digital (LADD) syndrome is a rare autosomal dominant disorder caused by mutations in one of the three genes: fibroblast growth factor receptor 2 (FGFR2), FGFR3, or FGF10. Affected patients have hypoplasia/aplasia of lacrimal ducts/glands, hypoplasia/aplasia of salivary glands, dental anomalies, ear anomalies, hearing loss, and digital anomalies. Case Presentation Proband was an 11‐year‐old male with xerostomia, xerophthalmia, and a referring diagnosis of Sjogren syndrome. He presented with microdontia, hypodontia, low‐set/cupped ear auricles, and hearing loss in the left ear. Methods Whole exome sequencing (WES) was performed on proband. Variations and segregation within the family were verified using Sanger sequencing. Results Molecular studies revealed a novel heterozygous missense mutation in exon 11 of FGFR2: c.1547C>T (p.Ala516Val), compatible with LADD syndrome. Conclusion To the best of our knowledge, this is the first report of a family with LADD syndrome in Korea. The combination of xerostomia and xerophthalmia, seen in patients with LADD syndrome, may be misdiagnosed as Sjogren syndrome. WES may be a useful clinical tool in ascertaining the affected gene in patients with suspected genetic disorders. Here, a literature review and summary of 23 case reports/series of LADD syndrome are presented, which may help to identify patients with this condition.

Abstract Background Matrix metallopeptidase 20 (MMP20) is an evolutionarily conserved protease that is essential for processing enamel matrix proteins during dental enamel formation. MMP20 mutations cause human autosomal recessive pigmented hypomaturation‐type amelogenesis imperfecta (AI2A2; OMIM #612529). MMP20 is expressed in both odontoblasts and ameloblasts, but its function during dentinogenesis is unclear. Methods We characterized 10 AI kindreds with MMP20 defects, characterized human third molars and/or Mmp20−/− mice by histology, Backscattered Scanning Electron Microscopy (bSEM), µCT, and nanohardness testing. Results We identified six novel MMP20 disease‐causing mutations. Four pathogenic variants were associated with exons encoding the MMP20 hemopexin‐like (PEX) domain, suggesting a necessary regulatory function. Mutant human enamel hardness was softest (13% of normal) midway between the dentinoenamel junction (DEJ) and the enamel surface. bSEM and µCT analyses of the third molars revealed reduced mineral density in both enamel and dentin. Dentin close to the DEJ showed an average hardness number 62%–69% of control. Characterization of Mmp20−/− mouse dentin revealed a significant reduction in dentin thickness and mineral density and a transient increase in predentin thickness, indicating disturbances in dentin matrix secretion and mineralization. Conclusion These results expand the spectrum of MMP20 disease‐causing mutations and provide the first evidence for MMP20 function during dentin formation.

The pathophysiology of functional gastrointestinal disorders (FGIDs) is still unclear and various complex mechanisms have been suggested to be involved. In many cases, improvement of symptoms and quality of life (QoL) in patients with FGIDs is difficult to achieve with the single-targeted treatments alone and clinical application of these treatments can be challenging owing to the side effects. Herbal preparations as complementary and alternative medicine can control multiple treatment targets of FGIDs simultaneously and relatively safely. To date, many herbal ingredients and combination preparations have been proposed across different countries and together with a variety of traditional medicine. Among the herbal therapies that are comparatively considered to have an evidence base are iberogast (STW-5) and peppermint oil, which have been mainly studied and used in Europe, and rikkunshito and motilitone (DA-9701), which are extracted from natural substances in traditional medicine, are the focus of this review. These herbal medications have multi-target pharmacology similar to the etiology of FGIDs, such as altered intestinal sensory and motor function, inflammation, neurohormonal abnormality, and have displayed comparable efficacy and safety in controlled trials. To achieve the treatment goal of refractory FGIDs, extensive and high quality studies on the pharmacological mechanisms and clinical effects of these herbal medications as well as efforts to develop new promising herbal compounds are required.

There have been many advances in endoscopic imaging technologies. Magnifying endoscopy with narrow-band imaging is an innovative optical technology that enables the precise discrimination of structural changes on the mucosal surface. Several studies have demonstrated its usefulness and superiority for tumor detection and differential diagnosis in the stomach as compared with conventional endoscopy. Furthermore, magnifying endoscopy with narrow-band imaging has the potential to predict the invasion depth and tumor margins during gastric endoscopic submucosal dissection. Classifications of the findings of magnifying endoscopy with narrow-band imaging based on microvascular and pit patterns have been proposed and have shown excellent correlations with invasion depth confirmed by microscopy. In terms of tumor margin prediction, magnifying endoscopy with narrow-band imaging offers superior delineation of gastric tumor margins compared with traditional chromoendoscopy with indigo carmine. The limitations of narrow-band imaging, such as the need for considerable training, long procedure time, and lack of studies about its usefulness in undifferentiated cancer, should be resolved to confirm its value as a complementary method to endoscopic submucosal dissection. However, the role of magnifying endoscopy with narrow-band imaging is expected to increase steadily with the increasing use of endoscopic submucosal dissection for the treatment of gastric tumors.

Recently, a new type of dental anomaly, a molar–incisor malformation or molar root–incisor malformation (MRIM), was recognized. The disease phenotype is now relatively well characterized; however, its etiology and disease-mechanism need to be elucidated. The affected teeth do not respond well to conventional treatment because of severe malformation and an unusual root structure. In this study, we present the treatment of MRIM cases with the extraction of severely aberrant permanent first molars (PFMs) and suggest that the PFM extractions are performed when it is clear that third molars will develop. The purpose of this report was primarily to present amendments to the guidelines for the treatment of patients with MRIM.

Diverticular bleeding of the small bowel is rare and occurs primarily in adults aged more than 60 years. In younger adults, Meckel’s diverticulum, a true diverticulum that congenitally occurs in the distal ileum, is the most common cause of diverticular bleeding of the small bowel. Unlike Meckel’s diverticula, other kinds of small bowel diverticula are not congenital and their incidence is related to age. Furthermore, congenital true diverticular bleeding of the jejunum in adults is very rare. We report the case of a 24-year-old man with subepithelial tumor-like lesion accompanied with obscure overt gastrointestinal bleeding. This lesion was initially suspected to be a subepithelial tumor based on radiologic tests and capsule endoscopy. He was finally diagnosed with a congenital true diverticulum in the jejunum with the appearance of a Meckel’s diverticulum after surgical resection.

Abstract Background Mannose-binding lectin (MBL) acts in the innate immune response to Helicobacter pylori. Interleukin 8 (IL-8) is a potent cytokine produced by gastric epithelial cells in response to H. pylori. We aimed to investigate whether polymorphisms in MBL2 and IL-8 influence susceptibility to H. pylori infection, and the associations of these polymorphisms with the risk of gastroduodenal diseases in a Korean population. Methods We consecutively enrolled 176 H. pylori-negative control subjects, 221 subjects with H. pylori-positive non-atrophic gastritis, 52 mild atrophic gastritis (AG), 61 severe AG, 175 duodenal ulcer, and 283 gastric cancer (GC). Allele-specific PCR-RFLP was conducted for polymorphisms in MBL2 exon 1 (codon 52, 54, and 57) and IL-8 -251 T > A. IL-8 levels in gastric mucosal tissues and serum MBL levels were measured by enzyme-linked immunosorbent assay. Results MBL2 exon 1 polymorphic variants were found only in codon 54, and the allele frequencies did not differ significantly between the control and disease groups. Although serum MBL levels in codon 54 A/A mutants were markedly low, it did not influence susceptibility to H. pylori infection or the risk of gastroduodenal diseases. IL-8 levels were significantly different between T/T wild type, T/A heterozygote, and A/A mutant genotypes. IL-8 -251 A allele carriers (A/A + T/A) showed increased IL-8 levels, and were significantly associated with the risk of severe AG and GC. Conclusions We suggest that a combination of H. pylori infection and the IL-8 -251 T > A polymorphism might increase the risk of severe AG and GC in a Korean population.

Propofol (2,6-diisopropylphenol) is a hypnotic drug with a very rapid onset and offset of action. It has increasingly been used in gastrointestinal endoscopy. Administration of propofol by nurses or endoscopists is commonly referred to as non-anesthesiologist-administered propofol (NAAP). There have been a lot of studies on the safety of NAAP compared with those by anesthesiologists. Safety results of those studies are summarized in this review.

Abstract Background ENAM mutations cause autosomal dominant or recessive amelogenesis imperfecta (AI) and show a dose effect: enamel malformations are more severe or only penetrant when both ENAM alleles are defective. Methods Whole exome sequences of recruited AI probands were initially screened for mutations in known AI candidate genes. Sanger sequencing was used to confirm sequence variations and their segregation with the disease phenotype. The co‐occurrence of ENAM and LAMA3 mutations in one family raised the possibility of digenic inheritance. Enamel formed in Enam+/+Ambn+/+, Enam+/−, Ambn+/−, and Enam+/−Ambn+/− mice was characterized by dissection and backscattered scanning electron microscopy (bSEM). Results ENAM mutations segregating with AI in five families were identified. Two novel ENAM frameshift mutations were identified. A single‐nucleotide duplication (c.395dupA/p.Pro133Alafs*13) replaced amino acids 133‐1142 with a 12 amino acid (ATTKAAFEAAIT*) sequence, and a single‐nucleotide deletion (c.2763delT/p.Asp921Glufs*32) replaced amino acids 921‐1142 with 31 amino acids (ESSPQQASYQAKETAQRRGKAKTLLEMMCPR*). Three families were heterozygous for a previously reported single‐nucleotide ENAM deletion (c.588+1delG/p.Asn197Ilefs*81). One of these families also harbored a heterozygous LAMA3 mutation (c.1559G>A/p.Cys520Tyr) that cosegregated with both the AI phenotype and the ENAM mutation. In mice, Ambn+/− maxillary incisors were normal. Ambn+/− molars were also normal, except for minor surface roughness. Ambn+/− mandibular incisors were sometimes chalky and showed minor chipping. Enam+/− incisor enamel was thinner than normal with ectopic mineral deposited laterally. Enam+/− molars were sometimes chalky and rough surfaced. Enam+/−Ambn+/− enamel was thin and rough, in part due to ectopic mineralization, but also underwent accelerated attrition. Conclusion Novel ENAM mutations causing AI were identified, raising to 22 the number of ENAM variations known to cause AI. The severity of the enamel phenotype in Enam+/−Ambn+/− double heterozygous mice is caused by composite digenic effects. Digenic inheritance should be explored as a cause of AI in humans.

Abstract Background Ameloblastin (AMBN) is a secreted matrix protein that is critical for the formation of dental enamel and is enamel‐specific with respect to its essential functions. Biallelic AMBN defects cause non‐syndromic autosomal recessive amelogenesis imperfecta. Homozygous Ambn mutant mice expressing an internally truncated AMBN protein deposit only a soft mineral crust on the surface of dentin. Methods We characterized a family with hypoplastic amelogenesis imperfecta caused by AMBN compound heterozygous mutations (c.1061T>C; p.Leu354Pro/ c.1340C>T; p.Pro447Leu). We generated and characterized Ambn knockout/NLS‐lacZ (AmbnlacZ/lacZ) knockin mice. Results No AMBN protein was detected using immunohistochemistry in null mice. ß‐galactosidase activity was specific for ameloblasts in incisors and molars, and islands of cells along developing molar roots. AmbnlacZ/lacZ 7‐week incisors and unerupted (D14) first molars showed extreme enamel surface roughness. No abnormalities were observed in dentin mineralization or in nondental tissues. Ameloblasts in the AmbnlacZ/lacZ mice were unable to initiate appositional growth and started to degenerate and deposit ectopic mineral. No layer of initial enamel ribbons formed in the AmbnlacZ/lacZ mice, but pockets of amelogenin accumulated on the dentin surface along the ameloblast distal membrane and within the enamel organ epithelia (EOE). NLS‐lacZ signal was positive in the epididymis and nasal epithelium, but negative in ovary, oviduct, uterus, prostate, seminal vesicles, testis, submandibular salivary gland, kidney, liver, bladder, and bone, even after 15 hr of incubation with X‐gal. Conclusions Ameloblastin is critical for the initiation of enamel ribbon formation, and its absence results in pathological mineralization within the enamel organ epithelia.

Abstract Background Truncation FAM83H mutations cause human autosomal dominant hypocalcified amelogenesis imperfecta (ADHCAI), an inherited disorder characterized by severe hardness defects in dental enamel. No enamel defects were observed in Fam83h null mice suggesting that Fam83h truncation mice would better replicate human mutations. Methods We generated and characterized a mouse model (Fam83hTr/Tr) expressing a truncated FAM83H protein (amino acids 1–296), which recapitulated the ADHCAI‐causing human FAM83H p.Tyr297* mutation. Results Day 14 and 7‐week Fam83hTr/Tr molars exhibited rough enamel surfaces and slender cusps resulting from hypoplastic enamel defects. The lateral third of the Fam83hTr/Tr incisor enamel layer was thinner, with surface roughness and altered enamel rod orientation, suggesting disturbed enamel matrix secretion. Regular electron density in mandibular incisor enamel indicated normal enamel maturation. Only mildly increased posteruption attrition of Fam83hTr/Tr molar enamel was observed at 7‐weeks. Histologically, the Fam83hTr/Tr enamel organ, including ameloblasts, and enamel matrices at sequential stages of amelogenesis exhibited comparable morphology without overt abnormalities, except irregular and less evident ameloblast Tomes' processes in specific areas. Conclusions Considering Fam83h−/− mice showed no enamel phenotype, while Fam83hTr/Tr (p.Tyr297*) mice displayed obvious enamel malformations, we conclude that FAM83H truncation mutations causing ADHCAI in humans disturb amelogenesis through a neomorphic mechanism, rather than haploinsufficiency.

Amelogenesis imperfecta (AI) is a collection of rare genetic conditions affecting tooth enamel. The affected enamel can be of insufficient quantity and/or altered quality, impacting structural content, surface integrity and coloration. Heterozygous mutations in ENAM result in hypoplastic AI without other syndromic phenotypes, with variable expressivity and reduced penetrance, unlike other AI-associated genes. In this study, we recruited a Caucasian family with hypoplastic AI. Mutational analysis (using whole exome sequencing) revealed a splicing donor site mutation (NM_031889.3: c. −61 + 1G > A). Mutational effects caused by this variant were investigated with a minigene splicing assay and in vitro expression analysis. The mutation resulted in a retention of intron 1 and exon 2 (a normally skipped exon), and this elongated 5′ UTR sequence attenuated the translation from the mutant mRNA. Structure and translation predictions raised the possibility that the long complex structures—especially a hairpin structure located right before the translation initiation codon of the mutant mRNA—caused reduced protein expression. However, there could be additional contributing factors, including additional uORFs. For the first time, we determined that a mutation altered the ENAM 5′ UTR, but maintained the normal coding amino acid sequence, causing hypoplastic AI.

The data in this article is related to the research article entitled “Notch2 signaling promotes osteoclast resorption via activation of PYK2” (Jin et al., 2016 [1]). To block Notch signaling activation, we used several gamma-secretase inhibitors (GSIs) and evaluate the inhibitory potential of GSIs on osteoclastogenesis. We measured the effect of GSIs on osteoclastogenesis and normal spreading of osteoclasts by using the mouse bone marrow-derived macrophages (BMMs) which may contributes to insight of physiological relevant of in vivo. This data article suggests valuable approach to GSIs treatment doses and potential of those in the osteoclast differentiation and spreading. Keywords: Osteoclast, Notch, GSI, Differentiation, Spreading

Nano-sized extracellular vesicles (EVs), including exosomes, microvesicles, and other types of vesicles, are released by most mammalian cells and bacteria. We here ask whether feces contain EVs of mammalian and/or bacterial origin, and whether these EVs induce systemic inflammation. Fecal extracellular vesicles (fEVs) were isolated from mice and humans. The presence of EVs from Gram-negative and Gram-positive bacteria was detected by enzyme-linked immunosorbent assay using anti-lipid A and anti-lipoteichoic acid antibodies, whereas Western blot using anti-beta-actin antibody was employed to detect host-derived EVs in the fEVs. Further, fEVs were administered into mice by intraperitoneal injection, and inflammatory responses were investigated in the peritoneum, blood, and lungs. The role of TLR2 and TLR4 were studied using knockout mice. Significant quantities of EVs were present in feces from mice as well as humans, and derived from Gram-negative and Gram-positive bacteria, as well as the host. Bacteria-free fEVs introduced into the peritoneum induced local and systemic inflammation (including in the lungs), but fEVs from germ-free animals had weaker effects. This pronounced local and systemic inflammatory responses seemed to be induced by EVs from both Gram-negative and Gram-positive bacteria, and was attenuated in mice lacking TLR2 or TLR4. Our findings show that fEVs cause sepsis-like systemic inflammation, when introduced intraperitoneally, a process regulated by TLR2 and TLR4.

Background/AimsEmerging data indicate that polymorphic sequence variations in the tumor necrosis factor alpha (TNF-α) gene may affect its production, and be associated with the risk of inflammatory bowel disease (IBD). PRKCDBP is a putative tumor suppressor gene and a transcriptional target of TNF-α. The aim of this case-control study is to explore the possible association of single nucleotide polymorphisms (SNPs) in PRKCDBP with the development of IBD in Koreans.MethodsGenotyping analysis of four SNPs of PRKCDBP [rs35301211 (G210A), rs11544766 (G237C), rs12294600 (C797T), and rs1051992 (T507C)] was performed on 170 ulcerative colitis (UC),131 Crohn's disease (CD) patients, and 100 unrelated healthy controls using polymerase chain reaction and restriction fragment length polymorphism.ResultsHeterozygous configuration of three SNPs (G210A, G237C, and C797T) was very rare in both patients and healthy controls. However, allele frequencies of the T507C SNP showed a significant difference between UC patients and controls (P=0.037). The CC genotype of the T507C SNP was identified in 46.6% (61 of 131) of CD and 49.4% (84 of 170) of UC patients, but only in 33.0% (33 of 100) of healthy controls. Furthermore, CC homozygosity was more prevalent than TC heterozygosity in both CD and UC patients versus controls (P=0.016; gender-adjusted odds ratio [aOR], 2.16; 95% confidence interval [CI], 1.16-4.04 and P=0.009; aOR, 2.09; 95% CI, 1.193.64; respectively)ConclusionsOur results suggest that the T507C SNP in PRKCDBP, a TNF-α-inducible gene, might be associated with susceptibility to IBD (particularly UC) development in Koreans.

Amelogenesis imperfecta is a group of rare inherited disorders that affect tooth enamel formation, quantitatively and/or qualitatively. The aim of this study was to identify the genetic etiologies of two families presenting with hypomaturation amelogenesis imperfecta. DNA was isolated from peripheral blood samples obtained from participating family members. Whole exome sequencing was performed using DNA samples from the two probands. Sequencing data was aligned to the NCBI human reference genome (NCBI build 37.2, hg19) and sequence variations were annotated with the dbSNP build 138. Mutations in MMP20 were identified in both probands. A homozygous missense mutation (c.678T>A; p.His226Gln) was identified in the consanguineous Family 1. Compound heterozygous MMP20 mutations (c.540T>A, p.Tyr180* and c.389C>T, p.Thr130Ile) were identified in the non-consanguineous Family 2. Affected persons in Family 1 showed hypomaturation AI with dark brown discoloration, which is similar to the clinical phenotype in a previous report with the same mutation. However, the dentition of the Family 2 proband exhibited slight yellowish discoloration with reduced transparency. Functional analysis showed that the p.Thr130Ile mutant protein had reduced activity of MMP20, while there was no functional MMP20 in the Family 1 proband. These results expand the mutational spectrum of the MMP20 and broaden our understanding of genotype-phenotype correlations in amelogenesis imperfecta.

Background/Aims: Irritable bowel syndrome (IBS) generally shows sex differences, and psychiatric comorbidities play an important role in its pathogenesis. We aim to measure the levels of gender roles and investigate their relationship with psychiatric factors in patients with IBS versus healthy controls. Methods: Patients diagnosed with IBS by Rome III and whose colonoscopy findings were normal were enrolled at multiple sites in Korea. The participants completed the Korean Sex Role Inventory-Short Form (KSRI-SF) to assess masculinity and femininity, the stress questionnaire, the Hospital Anxiety Depression Scale (HADS), and the 36-item Short Form Health Survey questionnaire to assess the quality of life (QOL). Results: In total, 102 patients with IBS (male:female = 35:67; mean age 42.6 ± 16.7 years) and 55 controls (male:female = 20:35; mean age 42.4 ± 11.1 years) were recruited. IBS patients had higher stress (9.69 ± 8.23 vs 4.56 ± 8.31, P < 0.001) and HADS scores (16.12 ± 7.17 vs 10.22 ± 5.74, P < 0.001) than the control group, but showed no significant difference in KSRI-SF scores. No significant differences in HADS and KSRI-SF scores were found between males and females. However, IBS patients whose symptoms worsened due to stress and patients with anxiety or depression had significantly lower masculinity. QOL was poorer in IBS patients than in controls. In stepwise multivariate analyses, the anxiety score, depression score, and the degree of daily life disturbance, not masculinity, were associated with the QOL of IBS patients. Conclusions: IBS patients had higher stress, more psychiatric comorbidities, and lower QOL than controls. Low masculinity, rather than sex, was associated with stress and psychological comorbidities, which deteriorated the QOL in IBS patients. [ABSTRACT FROM AUTHOR]