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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 DsppP19L mouse were characterized by morphological assessment, bSEM, nanohardness testing, histological analysis, in situ hybridization and immunohistochemistry. DsppP19L dentin contained dentinal tubules but grew slowly and was softer and less mineralized than the wild-type. DsppP19L 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 DsppP19L 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.

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.

Although lactose-free dairy products for the clinical management of lactose intolerance (LI) are widely available, scientific evidence on their efficacy is still lacking. This study comparatively analyzed the efficacy of flavored lactose-free milk (LFM) and whole milk (WM) in reducing symptoms in South Korean adults with LI. This prospective study was conducted in adults suspected of LI. All screened participants underwent the hydrogen breath test (HBT) using 570 mL of chocolate-flavored WM (20 g of lactose) and responded to a symptom questionnaire. LI was confirmed when the

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

The eradication rate of clarithromycin-based standard triple therapy (STT) for Helicobacter pylori infection has decreased due to clarithromycin resistance (CR). We evaluated the cost-effectiveness of tailored therapy according to CR test results, and compared the results of STT with those of empirical bismuth quadruple therapy (BQT). The prospectively collected data of 490 H. pylori-positive patients with chronic gastritis or peptic ulcer disease were retrospectively analyzed. Among them, 292 patients underwent CR testing using dual-priming oligonucleotide-based polymerase chain reaction. The tailored group (n = 292) consisted of patients treated with STT for 7 days and BQT for 10 days as per their CR test results. The remaining patients were assigned to the empirical group (n = 198) and received BQT for 10 days without a CR test. The eradication rate, adverse events and medical costs associated with H. pylori eradication therapy were investigated. In the tested patients (tailored group), the CR-positive rate was 32.2% (n = 94/292). The eradication rate according to an intention-to-treat analysis was 87.7% in the tailored group and 91.8% in the empirical group (P = 0.124); the respective rates were 94.4% and 97.9% by per-protocol analysis (P = 0.010). The frequency of adverse events was lower in the empirical group than the tailored group (35.1% vs. 52.7%, P

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.

Aims: Although chronic kidney disease is recognized as an independent risk factor for cerebrovascular disease, its association with hemorrhagic and ischemic stroke remains controversial. Methods: We conducted a retrospective cohort study using the National Health Insurance Service-National Sample Cohort, which is representative of the Korean population. A total of 195,772 Koreans who were not diagnosed with stroke before 2009 were included in this study from 2009 to 2013. The eGFR was divided into six categories (≥ 90, 75–89, 60–74, 45–59, 30–44, ＜30 mL/min/1.73 m 2 ). The Kaplan–Meier plot was illustrated to compare the incidence of stroke. Cox proportional hazard model was used to estimate the hazard ratio (HR) of eGFR for risk of ischemic and hemorrhagic stroke by sex. Results: During an average of 4.36 years of follow-up period, 2,236 and 668 people were diagnosed with newly ischemic and hemorrhagic stroke, respectively. Age-adjusted incidence rate for ischemic stroke among people with eGFR ＜45 mL/min/1.73 m 2 was higher than those with eGFR ≥ 90 mL/min/1.73 m 2 , whereas that for hemorrhagic stroke among people with eGFR ≥ 90 mL/min/1.73 m 2 was higher than those with eGFR ＜45 mL/min/1.73 m 2 . After adjusting for multiple covariates, the adjusted HR for ischemic stroke increased with decreasing eGFR in men ( p for trend ＜0.001), but not in women ( p for trend=0.48). On the other hand, there was no significant relationship between eGFR and risk of hemorrhagic stroke in both men and women. Conclusions: Reduced glomerular filtration rate less than 45 mL/min/1.73 m 2 was associated with an increased risk of ischemic stroke, especially in men.

Background Regular clinic follow‐up is a prerequisite for optimal antiviral therapy and surveillance of hepatocellular carcinoma in patients with chronic hepatitis B (CHB). However, adherence to regular follow‐up stays low in practice. This study investigated whether regular follow‐up is associated with decreased liver cancer mortality in CHB patients. Methods A nationwide population‐based historical cohort study was conducted using customized data from the National Health Insurance Service of Korea. The number of hospital visits every 3‐month interval was counted for 2 years from the date of CHB diagnosis. Patients were classified into three follow‐up groups: regular (four to eight visits), irregular (one to three visits), and no follow‐up. The risk of liver cancer mortality was compared among the groups using Cox proportional hazard regression analysis. Results Of the 414 074 CHB patients, 22.9% had regular follow‐up. In multivariable analysis, regular follow‐up was independently associated with decreased risk of liver cancer mortality compared to no follow‐up (hazard ratio [HR], 0.56; 95% confidence interval [CI], 0.50‐0.63, P 60 years, of low socioeconomic status, disabled, lived in a rural area, had a higher comorbidity rate, or did not have cirrhosis. Conclusions Regular follow‐up at least every 3‐6 months is significantly associated with reduced liver cancer mortality in patients with CHB., Of the 414 074 CHB patients, 22.9% had regular follow‐up. Regular follow‐up was independently associated with decreased risk of liver cancer mortality compared to no follow‐up (hazard ratio [HR], 0.56; 95% confidence interval [CI], 0.50‐0.63, P

BACKGROUND AND AIM This study investigated the usefulness of near-focus narrowband imaging (NF-NBI) for determining gastric tumor margins compared with indigo carmine chromoendoscopy (ICC) before endoscopic submucosal dissection (ESD). METHODS This prospective randomized controlled trial was conducted at seven teaching hospitals in Korea. Patients with gastric adenoma or differentiated adenocarcinoma undergoing ESD were enrolled and randomly assigned to the NF-NBI or ICC group. A marking dot was placed on the most proximal margin of the tumor before ESD. The primary endpoint was delineation accuracy, which was defined as presence of marking dots within 1 mm of the tumor margin under microscopic observation. RESULTS A total of 200 patients in the NF-NBI group and 195 patients in the ICC group were included. The delineation accuracy rate was 84.5% in the NF-NBI group and 81.0% in the ICC group (P = 0.44). However, the distance from the marking dot to the margin of the tumor was significantly shorter in the NF-NBI group than in the ICC group (0.8 ± 0.8 vs 1.2 ± 1.3 mm, P

The emergence of vancomycin-resistant Staphylococcus aureus (VRSA) threatens global health. The mechanism of vancomycin resistance of VRSA without vanA gene acquisition was not fully elucidated. Therefore, we aimed to determine the mechanism of vancomycin resistance of VRSA besides that by vanA gene acquisition. In this study, we obtained vancomycin-resistant strains (V036-V64; MIC = 64 µg /ml) from susceptible strain (V036; MIC = 0.5 µg /ml) by exposure of vancomycin in vitro and examined the phenotypic characteristics and antibiotic susceptibility profiles of the resistant strain (V036-V64). To identify the genetic variations caused vancomycin resistance, we determined the complete genome sequences of V036 and V036-V64 and analyzed for single-nucleotide polymorphisms (SNPs) between two strains. Morphologically, V036-V64 had a twofold thicker cell wall compared with V036. Linezolid, rifampicin, and ceftaroline had similar MIC ranges against V036-V64 and V036, but V036-V64 showed lower susceptibilities to daptomycin and telavancin. We detected eight single-nucleotide polymorphisms differing between V036-V64 and V036: rimM (G16D), ssaA2 (G128A), rpsK (P60R), rpoB (R917C), walK (T492R), d-alanyl-d-alanine carboxypeptidase (L307I), vraT (A152V), and chromosome segregation ATPase (T440I). This study demonstrates that, under selective pressure, by the accumulation of mutations in genes related to cell wall synthesis, vancomycin-susceptible S. aureus can develop thicker cell walls and, hence, develop high vancomycin resistance. Thus, we highlight a novel vanA-negative mechanism for VRSA emergence.

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). Conclusion Probiotic or sulforaphane with triple therapy for H. pylori infection neither increased the eradication rate nor reduced the occurrence of adverse events.

Background The comparative efficacy of bariatric endoscopic procedures has not been completely elucidated. We aimed to comprehensively evaluate the efficacy of bariatric endoscopic procedures. Methods We searched for randomized controlled trials investigating the efficacy of bariatric endoscopic procedures, including the use of an intragastric balloon, duodenal-jejunal bypass liner (DJBL), aspiration therapy, primary obesity surgery endoluminal (POSE) procedure, and botulinum toxin injection to the stomach. Network meta-analyses were performed to determine the percentage of weight loss (%weight loss) and percentage of excess weight loss (%EWL). Results 22 studies with 2141 patients were included in the meta-analysis. Most endoscopic procedures showed superior efficacy in terms of %weight loss compared with the control (mean difference [MD] [95 % confidence interval (CI)]: aspiration therapy 10.4 % [7.0 % to 13.7 %]; fluid-filled balloon 5.3 % [3.4 % to 7.2 %]; POSE 4.9 % [1.7 % to 8.2 %]; and DJBL 4.5 % [1.4 % to 7.7 %]). In terms of %EWL, aspiration therapy, fluid-filled balloon, POSE, and DJBL were superior to the control (MD [95 %CI]: 27.3 % [15.3 % to 39.3 %]; 22.4 % [15.4 % to 29.4 %]; 15.3 % [2.5 % to 28.0 %]; and 13.0 % [4.9 % to 21.2], respectively). The gas-filled balloon and botulinum toxin injection did not show a significant difference in %weight loss or %EWL compared with the control. For the fluid-filled balloon, the %EWL and %weight loss tended to decrease after balloon removal at 6 months after the procedure. Conclusion All bariatric endoscopic procedures, except for gas-filled balloon and botulinum toxin injection to the stomach, showed superior short-term efficacy in terms of %weight loss or %EWL compared with lifestyle modification.

Molar root-incisor malformation (MRIM) or molar-incisor malformation (MIM) is a new type of dental anomaly characterized by dysplastic roots of permanent first molars, occasionally second primary molars, and the crowns of maxillary central incisors. MRIM involving permanent first molars and second primary molars is characterized by normal crowns with short, thin, and narrow roots, whereas MRIM involving permanent maxillary central incisors exhibits constrictions of the crown in the cervical area. In the first case, we extracted the affected first permanent molars at the optimal timing to minimize space deficiencies and induce space closure. In addition, composite resin restorations were performed on the anterior central incisors. In the second case, a mandibular lingual arch was used to stabilize the affected teeth in order to mitigate discomfort by reducing rotational biting forces.

Background Attention should be paid to endoscopy-related complications and safety-related accidents that may occur in the endoscopy unit. This study investigated the current status of complications associated with diagnostic and therapeutic endoscopy in Korea. Methods A questionnaire survey on endoscopy-related complications was conducted in a total of 50 tertiary or general hospitals in Korea. The results were compared to the population-level claims data from the Health Insurance Review & Assessment Service (HIRA), which analyzed endoscopy procedures conducted in 2017 in Korea. Results The incidences of bleeding associated with diagnostic and therapeutic esophagogastroduodenoscopy (EGD) and with diagnostic and therapeutic colonoscopy were 0.224% and 3.155% and 0.198% and 0.356%, respectively, in the 2017 HIRA claims data, compared to 0.012% and 1.857%, and 0.024% and 0.717%, in the 50 hospitals surveyed. The incidences of perforation associated with diagnostic and therapeutic EGD and with diagnostic and therapeutic colonoscopy were 0.023% and 0.613%, and 0.007% and 0.013%, respectively, in the 2017 HIRA claims data compared to 0.001% and 0.325%, and 0.017% and 0.206%, in the 50 hospitals surveyed. In the HIRA claims data, the incidence of bleeding/perforation after diagnostic colonoscopy in clinics, community hospitals, general hospitals, and tertiary hospitals was 0.129%/0.000%, 0.088%/0.004%, 0.262%/0.009%, and 0.479%/0.030% respectively, and the corresponding incidence of bleeding/perforation after therapeutic colonoscopy was 0.258%/0.004%, 0.401%/0.007%, 0.408%/0.024%, and 0.731%/0.055%. Conclusion The incidences of complications associated with diagnostic and therapeutic EGD or colonoscopy tended to increase with the hospital volume in Korea. Trial Registration Clinical Research Information Service Identifier: KCT0001728, Graphical Abstract

Sessile serrated lesions (SSLs) are serrated polyps (SP) with the typical serrated architecture of the crypt lining epithelium. SSL has an important clinical implication because they are recognized as precursor lesion of sporadic colorectal cancer (CRC) through "serrated pathway." SSLs usually appear flat to sessile, and are located in the right colon.A 69-year-old man was referred to a tertiary medical center because of intermittent hematochezia for 2 years.Colonoscopy revealed a large, pedunculated polyp in the rectum. The polyp surface was slightly reddish in color and the elongated stalk was covered with almost normal mucosa. Histopathological examination of the resected specimens revealed the typical features of SSL with low-grade dysplasia.Endoscopic mucosal resection using a detachable snare was performed on the tumor for definite diagnosis and treatment.There was no evidence of immediate or delayed bleeding after endoscopic mucosal resection, and the hemoglobin level normalized after a 1-year follow-up.We report a rare case of a large pedunculated polyp with typical histological features of SSLs in the rectum. Endoscopists should always consider SSLs at any location even with unusual morphological findings.

The revolution in genetics has rapidly increased our knowledge of human and mouse genes that are critical for the formation of dental enamel and helps us understand how enamel evolved. In this graphical review we focus on the roles of 41 genes that are essential for the secretory stage of amelogenesis when characteristic enamel mineral ribbons initiate on dentin and elongate to expand the enamel layer to the future surface of the tooth. Based upon ultrastructural analyses of genetically modified mice, we propose a molecular model explaining how a cell attachment apparatus including collagen 17, α6s4 and αvs6 integrins, laminin 332, and secreted enamel proteins could attach to individual enamel mineral ribbons and mold their cross-sectional dimensions as they simultaneously elongate and orient them in the direction of the retrograde movement of the ameloblast membrane.

Although endoscopic retrograde cholangiopancreatography (ERCP) is a pivotal procedure for the diagnosis and treatment of a variety of pancreatobiliary diseases, it has been known that the risk of procedure-related adverse events (AEs) is significant.We conducted this nationwide cohort study since there have been few reports on the real-world data regarding ERCP-related AEs.Patients who underwent ERCP were identified between 2012 and 2015 using Health Insurance Review and Assessment database generated by the Korea government. Incidence, annual trends, demographics, characteristics according to the types of procedures, and the risk factors of AEs were assessed.A total of 114,757 patients with male gender of 54.2% and the mean age of 65.0 ± 15.2 years were included. The most common indication was choledocholithiasis (49.4%) and the second malignant biliary obstruction (22.8%). Biliary drainage (33.9%) was the most commonly performed procedure, followed by endoscopic sphincterotomy (27.4%), and stone removal (22.0%). The overall incidence of ERCP-related AEs was 4.7% consisting of post-ERCP pancreatitis (PEP; 4.6%), perforation (0.06%), and hemorrhage (0.02%), which gradually increased from 2012 to 2015. According to the type of procedures, ERCP-related AEs developed the most commonly after pancreatic stent insertion (11.4%), followed by diagnostic ERCP (5.9%) and endoscopic sphincterotomy (5.7%). Younger age and diagnostic ERCP turned out to be independent risk factors of PEP.ERCP-related AEs developed the most commonly after pancreatic stent insertion, diagnostic ERCP and endoscopic sphincterotomy. Special caution should be used for young patients receiving diagnostic ERCP due to increased risk of PEP.

Background and aims: The impact of cytomegalovirus (CMV) colitis on long-term outcomes of ulcerative colitis (UC) flares remains controversial. Methods: A total of 257 UC patients with moderate-to-severe flares were observed for a mean follow-up of 41.2 months. CMV colitis was defined as histopathologic confirmation of CMV inclusions obtained from macroscopic endoscopic lesions in patients with UC flares. An independent gastrointestinal pathologist prospectively reviewed all specimens. A poor outcome was defined as any of hospitalization, colectomy or death during the follow-up period. Results: The prevalence of CMV colitis was 14% (36/257) over the 10-year study period (2007–2016). When compared to the controls, patients with CMV colitis were characterized by older age, higher disease activity, endoscopic deep ulcerations and more frequent use of immunosuppressive drugs (all p p Conclusions: True CMV colitis is a poor prognostic indicator among patients with UC flares. An effective strategy for managing recurrent CMV colitis is urgently needed (KCT0003296).

Objectives To identify the molecular genetic etiology of the families with non-syndromic multiple missing permanent teeth (oligodontia). Materials and methods Genomic DNA was isolated and measured, and whole-exome sequencing was performed. The obtained sequencing reads were aligned to the human reference genome and subsequently processed by a series of bioinformatics programs. Finally, short insertions/deletions and single nucleotide variations were annotated with dbSNP build 138. Results The proband of family 1 was missing 14 permanent teeth, and the mutational analysis revealed compound heterozygousWNT10A mutations (c.364A > T and c.511C > T). Two affected individuals in family 2 were missing 20 and 12 permanent teeth, respectively, and compound heterozygous WNT10A mutations (c.364A > T and c.637G > A) were also identified. Conclusions This study reveals compound heterozygousWNT10A missense mutations in two families with non-syndromic oligodontia which will improve the understanding of odontogenesis and the pathogenesis related to WNT10A mutations.

The comparative efficacy of various bariatric procedures has not been completely elucidated. We aimed to evaluate efficacy and safety of various bariatric procedures comprehensively. We searched for randomized controlled trials investigating the efficacy of bariatric surgery. Network meta-analyses were performed to determine the percentage of excess weight loss (%EWL) and remission of diabetes mellitus (DM). Of 45 studies, 33 and 24 provided the data for %EWL and DM remission rates, respectively. Six months after surgery, biliopancreatic diversion with duodenal switch (BPD-DS), Roux-en-Y gastric bypass (RYGB), and sleeve gastrectomy (SG) showed superior efficacy for %EWL compared to the standard-of-care (mean difference [MD], [95% confidence interval [CI]]: BPD-DS, 38.2% [7.3%, 69.1%]; RYGB, 32.1% [3.1%, 61.1%]; SG, 32.5% [5.5%, 59.5%]). However, adjustable gastric banding was not superior to standard-of-care (MD [95% CI] = − 0.2% [− 19.6%, 19.2%]). At 1 year, all bariatric procedures were superior to standard-of-care. At 3 years, RYGB and SG showed superior efficacy when compared to standard-of-care (MD [95% CI]: RYGB, 45.0% [21.8%, 68.2%]; SG, 39.2% [15.2%, 63.3%]). With respect to DM remission 3–5 years after surgery, BPD-DS, RYGB, and SG were superior to standard-of-care. Hernias, obstruction/stricture, bleeding, and ulcers were less common in patients who underwent SG than in those who underwent RYGB. RYGB and SG had excellent long-term outcomes for both the %EWL and DM remission rates. Additionally, SG had a relatively lower risk of adverse events than RYGB.

This study aimed to identify the molecular genetic etiology of an 8-year-old boy with amelogenesis imperfecta in permanent dentition. Bilateral cochlear implants were placed due to sensorineural hearing loss, and there was no other family member with a similar phenotype. Peripheral blood samples were collected with the understanding and written consent of the participating family members. A constitutional chromosome study was performed for the proband. Genomic DNA was isolated, and whole exome sequencing was performed. A series of bioinformatic analyses were performed with the obtained paired-end sequencing reads, and the variants were filtered and annotated with dbSNP147. There was no abnormality in the constitutional chromosome study. Whole exome sequencing analysis with trio samples identified a homozygous mutation (c.506T>C, p. (Leu169Pro)) in the PEX26 gene. We verified “temperature sensitivity (ts)” of patient-derived Pex26-L169P by expression in pex26 CHO mutant ZP167 cells to determine the effect of the L169P mutation on Pex26 function. The L169P mutation causes a mild ts-cellular phenotype representing the decreased peroxisomal import of catalase. This study supports the finding that the recessive mutations in PEX26 are associated with Heimler syndrome and demonstrates the importance of an early and correct diagnosis.

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 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., Lacrimo‐auriculo‐dento‐digital (LADD) syndrome is a rare autosomal dominant genetic disease. Patients affected have malformations of the lacrimal ducts or glands, aplasia or hypoplasia of major salivary glands, dental anomalies, low‐set cup‐shaped ears, hearing loss, and digital anomalies. Here we report a novel mutation in a Korean family with LADD syndrome and a review of previous literature.

Aim To investigate the chemical and mechanical properties of teeth affected by a 1-bp deletion (c.2688delT) in the DSPP gene. Methods and Materials Maxillary first premolars were extracted from the affected individual at age 9 years due to the orthodontic reason for crowding. A sample was imbedded in epoxy resin and sectioned buccolingually, after micro–computerized tomography (μCT) images were taken. Scanning Electron Microscopy (SEM), Energy Dispersive Spectrometry (EDS) and Vickers microhardness testing were also performed. Results μCT reconstruction and analysis showed an irregularly obliterated pulp chamber and an extremely small pulpal volume in the DGI-II sample. The mineral density and microhardness scores were smaller in the dentin of the DGI-II sample compared to the wild-type. Mg content was lower in the dentin of the DGI-II sample compared to the wild-type. Conclusion This study shows that dentin affected by a 1-bp deletion in DSPP has a reduced mineral density, diminished microhardness and reduced Mg content.

This study aimed to analyze the dose of radiation to which the physician is exposed during endoscopic retrograde cholangiopancreatography (ERCP) and to identify predictive factors of radiation exposure during the procedure. Furthermore, we evaluated the patient characteristics and procedural factors associated with prolonged fluoroscopy time (FT). A cross-sectional retrospective analysis of 780 ERCPs performed at a tertiary academic hospital over a 2-year period was conducted. The primary outcome was radiation exposure during ERCP as determined by FT; additionally, the association between variables and radiation exposure was determined. Moreover, we evaluated their correlations with age, sex, body mass index (BMI), diagnosis, duration of procedure, procedure name, and procedure complexity. According to the analysis of the 780 ERCPs performed in 2 years, the mean FT was 5.07 minutes (95% confidence interval [CI], 4.87–5.26). The mean radiation durations were as follows: cholelithiasis, 5.76 minutes (95% CI, 4.75–6.80); malignant biliary obstruction, 6.13 minutes (95% CI, 5.91–6.35); pancreatic disease, 5.28 minutes (95% CI, 4.45–6.28); and benign biliary stricture, 5.32 minutes (95% CI, 5.02–5.94). Significant differences affecting fluoroscopy duration between the 2 endoscopists were not observed in the present study. Multivariate analysis revealed that prolonged fluoroscopy duration was related to specific characteristics, including higher BMI (BMI >27.5 kg/m2) (+4.1 minutes; 95% CI, 2.56–5.63), mechanical lithotripsy (+4.85 minutes; 95% CI, 0.45–9.25), needle-knife use (+4.5 minutes; 95% CI, 2.15–6.86), and malignant biliary obstruction (+2.34 minutes; 95% CI, 0.15–4.53). ERCPs are associated with significantly higher radiation exposure of patients on the specific procedure. Endoscopists should be aware of the determining factors, including patients with obesity, who underwent mechanical lithotripsy, who had malignant biliary obstruction, and who underwent a procedure using a needle knife, that affect FT during ERCP.

Nitrous oxide, the least potent inhalation anesthetic, is widely used for conscious sedation. Recently, it has been reported that the occurrence of anesthetic-induced loss of consciousness decreases the interconnection between brain regions, resulting in brain network changes. However, few studies have investigated these changes in conscious sedation using nitrous oxide. Therefore, the present study aimed to use graph theory to analyze changes in brain networks during nitrous oxide sedation. Participants were 20 healthy volunteers (10 men and 10 women, 20–40 years old) with no history of systemic disease. We acquired electroencephalogram (EEG) recordings of 32 channels during baseline, nitrous oxide inhalation sedation, and recovery. EEG epochs from the baseline and the sedation state (50% nitrous oxide) were extracted and analyzed with the network connection parameters of graph theory. Analysis of 1/f dynamics, revealed a steeper slope while in the sedation state than during the baseline. Network connectivity parameters showed significant differences between the baseline and sedation state, in delta, alpha1, alpha2, and beta2 frequency bands. The most pronounced differences in functional distance during nitrous oxide sedation were observed in the alpha1 and alpha2 frequency bands. Change in 1/f dynamics indicates that changes in brain network systems occur during nitrous oxide administration. Changes in network parameters imply that nitrous oxide interferes with the efficiency of information integration in the frequency bands important for cognitive processes and attention tasks. Alteration of brain network during nitrous oxide administration may be associated to the sedative mechanism of nitrous oxide.

Autoimmune pancreatitis (AIP) is a distinct subtype of pancreatitis, which is classified into type 1 and 2 based on the clinicopathological features. According to the international consensus diagnostic criteria, pancreas resection or core biopsy specimens are recommended to make an accurate histological evaluation. However, the usefulness of endoscopic ultrasonography (EUS) guided fine needle aspiration (FNA) for histological evaluation has also been reported. Furthermore, the simultaneous presentation of type 2 AIP and Crohn's disease (CD) is very rare, especially in the Asian population. Therefore, we herein report a case of type 2 AIP with CD, which was diagnosed using EUS guided FNA with a 22-gauge needle.

OBJECTIVE: Amelogenesis imperfecta (AI) is a rare hereditary disorder affecting the quality and quantity of the tooth enamel. The purpose of this study was to identify the genetic etiology of hypoplastic AI families based on the candidate gene approach. Materials and methods We recruited three Turkish families with hypoplastic AI and performed a candidate gene screening based on the characteristic clinical feature to find the pathogenic genetic etiology. RESULTS: The candidate gene sequencing of the LAMB3 gene for family 1 revealed a heterozygous nonsense mutation in the last exon [c.3431C > A, p.(Ser1144*)]. FAM20A gene sequencing for families 2 and 3 identified a homozygous deletion [c.34_35delCT, p.(Leu12Alafs*67)] and a homozygous deletion-insertion (c.1109 + 3_1109 + 7delinsTGGTC) mutation, respectively. CONCLUSION: The candidate gene approach can be successfully used to identify the genetic etiology of the AI in some cases with characteristic clinical features. CLINICAL RELEVANCE: Identification of the genetic etiology of the AI will help both the family members and dentist understand the nature of the disorder. Characteristic clinical feature can suggest possible genetic causes.

Endoscopic submucosal dissection (ESD) is widely used for large superficial gastrointestinal tumors. Epigastric pain is a frequent complication of ESD. However, little is known about its incidence and associated factors. This study evaluated pain incidence and characteristics of patients with pain after gastric ESD. We retrospectively analyzed a prospectively collected registry of clinical, endoscopic, and pathologic results of patients who underwent ESD for gastric adenoma or cancer from January 2010 to December 2015. A Visual Analogue Scale (VAS) was used to assess pain immediately after, and 2, 12, and 24 h after ESD. The primary outcome was the use of painkillers (VAS score > 4). Analyzed data included age, sex, pathology, specimen and tumor size, procedure time, and tumor location. Of 1226 patients, 461 (36.4%) needed a painkiller at least once after ESD (pain group). Compared with the no pain group, the pain group had more females, less alcohol consumption, larger tumor and specimen size, and more antral lesions. In multivariate analysis, female sex (OR 1.559, 95% CI 1.217–1.996, p

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, clar ithromycin 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 ex amined 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. CY P2C19 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 signifi cantly 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.

Long-term antiviral therapy decreases the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB), however, it cannot eliminate the risk. We investigated the incidence of HCC at different stages of liver cirrhosis (LC) and identified clinical predictors for HCC development during antiviral therapy.The data from 356 treatment-naïve patients aged 40 to 69 years without a history of HCC who had received entecavir for ≥6 months were collected retrospectively. The incidence of HCC was evaluated in patients with CHB only, with LC without varices (stage 1), with varices (stage 2), and with ascites (stage 3).The median follow-up period was 3.6 years. In total, 45 patients (12.6%) developed HCC. The annual incidence rates of HCC in patients with CHB only or LC in stages 1, 2, and 3 were 0.4%, 2.6%, 9.8%, and 6.7%, respectively. In multivariate analyzes, LC at stage 2 (hazard ratio [HR] 17.16, 95% confidence interval [C.I.] 3.93-75.01, p .001), alcohol consumption (HR 3.84, 95% C.I. 1.99-7.39, p .001), and older age (HR 1.06, 95% C.I. 1.01-1.11, p = .010) were significantly associated with HCC development. The risk decreased in those who stopped drinking after 2 years of abstinence (p = .0314).LC with significant portal hypertension (varices or ascites), alcohol consumption, and older age at the time of starting antiviral therapy are independent predictors for future HCC development.

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.

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.

Objective This study aimed to suggest criteria for the early diagnosis of agenesis of the maxillary second premolars (U5) based on the developmental stages of the maxillary canines (U3), first premolars (U4), and second molars (U7). Design Overall, 303 control patients and 72 patients with agenesis who met the inclusion criteria were analyzed among 5136 patients aged 5–11 years for whom panoramic radiographs were obtained at Seoul National University Dental Hospital from June 2008 to December 2009. All developmental stages of U3, U4, U5, and U7 in both groups were evaluated and categorized into the stages proposed by Demirjian et al. To confirm the delayed dental development in the agenesis group, the Wilcoxon rank sum test was used. For verifying the tooth with the most similar developmental pattern to U5, the Kendall tau Rank Correlation and Bootstrap methods were used. Moreover, survival analysis and leave-one-out-cross-validation were performed to identify the earliest developmental stages of U3, U4, and U7 at which agenesis of U5 can be confirmed. Results The developmental stage of U4 in the agenesis group was significantly delayed compared with that in the control group at ages 5–10. All of the stages of U3, U4, and U7 showed high correlation coefficients with U5. Conclusion U5 agenesis can be confirmed with high prediction accuracy when at least two of the three conditions are satisfied: U3, U4, and U7 in Demirjian stages E, D, and C, respectively.

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 (Ambn lacZ/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. Ambn lacZ/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 Ambn lacZ/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 Ambn lacZ/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.

Background and aim We conducted a nationwide validation study of diagnostic algorithms to identify cases of inflammatory bowel disease (IBD) within the Korea National Health Insurance System (NHIS) database. Method Using the NHIS dataset, we developed 44 algorithms combining the International Classification of Diseases (ICD)-10 codes, codes for Rare and Intractable Diseases (RID) registration and claims data for health care encounters, and pharmaceutical prescriptions for IBD-specific drugs. For each algorithm, we compared the case identification results from electronic medical records data with the gold standard (chart-based diagnosis). A multiple sampling test verified the validation results from the entire study population. Results A random nationwide sample of 1697 patients (848 potential cases and 849 negative control cases) from 17 hospitals were included for validation. A combination of the ICD-10 code, ≥ 1 claims for health care encounters, and ≥ 1 prescription claims (reference algorithm) achieved excellent performance (sensitivity, 93.1% [95% confidence interval 91-94.7]; specificity, 98.1% [96.9-98.8]; positive predictive value, 97.5% [96.1-98.5]; negative predictive value, 94.5% [92.8-95.8]) with the lowest error rate (4.2% [3.3-5.3]). The multiple sampling test confirmed that the reference algorithm achieves the best performance regarding IBD diagnosis. Algorithms including the RID registration codes exhibited poorer performance compared with that of the reference algorithm, particularly for the diagnosis of patients affiliated with secondary hospitals. The performance of the reference algorithm showed no statistical difference depending on the hospital volume or IBD type, with P-value Conclusions We strongly recommend the reference algorithm as a uniform standard operational definition for future studies using the NHIS database.

The aim of the present study was to describe the characteristics of infections with Staphylococcus aureus with reduced vancomycin susceptibility (SARVS) including vancomycin-intermediate S. aureus (VISA) in South Korea, using data from the national sentinel surveillance system during 2014–2016. A total of 66 patients infected or colonized with SA-RVS were reported using the sentinel surveillance system. Among them, VISA was confirmed in 14 isolates (21.2%) and no vancomycin-resistant S. aureus (VRSA) was detected. Most of patients had any kind of indwelling devices (81.8%, 54/66) and underwent surgical procedures in the previous 6 months (84.8%, 56/66). Patients who admitted to an intensive care unit (ICU) in the previous 3 months were 68.2% (45/66). Furthermore, patients who used vancomycin or had MRSA in the previous 1 month were 54.5% (36/66) and 59.1% (39/66), respectively. Upon review of the medical records, 54.5% (36/66) of patients were classified as having SA-RVSassociated infection and 30-day mortality was 19.4% (7/36). Our findings revealed that there was no VRSA in South Korea. SA-RVS including VISA existed particularly in patients who had indwelling devices, history of surgical procedure, and history of ICU admission.

Introduction: We explored the long-term evolution of direct healthcare costs for inflammatory bowel diseases (IBD) using a population-level database in a country with an escalating burden of IBD. Methods: We searched the database of the Korean National Health Insurance Claims, which covers more than 97% of the South Korean population. An IBD diagnosis was defined as the combination of a billing code for Crohn’s disease (CD: K50.xx) or ulcerative colitis (UC: K51.xx) and at least one claim for IBD-specific drugs. Between 2006 and 2015, a total of 59,447 patients (CD: 17,677; UC: 41,770) were included. Results: The total and mean cost per capita increased significantly over time. In the last year of the study (2015), the cost for anti-tumor necrosis factor (TNF) therapy accounted for 68.8% (CD) and 48.8% (UC) of the total cost. Age at diagnosis (p = .03), while costs associated with UC remained stable. Only medication costs increased significantly during the follow-up period for CD. Conclusions: Over the past 10 years, the increased usage of anti-TNF agents has been the key driver of IBD-related healthcare costs. Long-term cost-cutting strategies for patients with CD are warranted.

WOS: 000458956100004 PubMed ID: 30506946 Amelogenesis imperfecta (AI) is a collection of isolated (non-syndromic) inherited diseases affecting dental enamel formation or a clinical phenotype in syndromic conditions. We characterized three consanguineous AI families with generalized irregular hypoplastic enamel with rapid attrition that perfectly segregated with homozygous defects in a novel gene: RELT that is a member of the tumor necrosis factor receptor superfamily (TNFRSF). RNAscope in situ hybridization of wild-type mouse molars and incisors showed specific Relt mRNA expression by secretory stage ameloblasts and by odontoblasts. Relt(-/-) mice generated by CRISPR/Cas9 exhibited incisor and molar enamel malformations. Relt(-/-) enamel had a rough surface and underwent rapid attrition. Normally unmineralized spaces in the deep enamel near the dentino-enamel junction (DEJ) were as highly mineralized as the adjacent enamel, which likely altered the mechanical properties of the DEJ. Phylogenetic analyses showed the existence of selective pressure on RELT gene outside of tooth development, indicating that the human condition may be syndromic, which possibly explains the history of small stature and severe childhood infections in two of the probands. Knowing a TNFRSF member is critical during the secretory stage of enamel formation advances our understanding of amelogenesis and improves our ability to diagnose human conditions featuring enamel malformations. National Institute of Dental and Craniofacial Research [DE015846DE016276]; National Research Foundation of Korea [NRF-2017R1A2A2A05069281NRF-2018R1A5A2024418] National Institute of Dental and Craniofacial Research, Grant/Award Number: DE015846DE016276; National Research Foundation of Korea, Grant/Award Number: NRF-2017R1A2A2A05069281NRF-2018R1A5A2024418

Amelogenesis imperfecta (AI) is a heterogeneous group of rare genetic disorders affecting tooth enamel formation. Here we report an identification of a novel de novo missense mutation [c.817_818delinsAT, p.(Ala273Met)] in the SP6 gene, causing non-syndromic autosomal dominant AI. This is the second paper on amelogenesis imperfecta caused by SP6 mutation. Interestingly the identified mutation in this study is a 2-bp variant at the same nucleotide positions as the first report, but with AT instead of AA insertion. Clinical phenotype was much more severe compared to the previous report, and western blot showed an extremely decreased level of mutant protein compared to the wild-type, even though the mRNA level was similar.

Background/Aims: The benefit of oral antiviral therapy in preventing hepatocellular carcinoma (HCC) in the general population is not well understood. We used a novel prediction method to estimate the risk of HCC in the Korean population based on various treatment guidelines. Methods: The 5-year risk of HCC following antiviral therapy was calculated using an HCC risk prediction model. A virtual cohort that represented Koreans (>40 years old) with chronic hepatitis B virus (HBV) infection was established using the fifth National Health and Nutrition Examination Survey. The antiviral indications tested were the Korean National Health Insurance (NHI) and European Association for the Study of the Liver (EASL) guidelines as well as a new extended indication (serum HBV DNA >2,000 IU/mL regardless of serum aminotransferase level). Results: A total of 993,872 subjects were infected with HBV in the general Korean population. Over a 5-year period, 2,725 HCC cases were predicted per 100,000 persons (0.55%/yr). When the cohort was treated based on the Korean NHI, the EASL, and the newly extended indications, HCC risks decreased to 2,531 (-7.1%), 2,089 (-23.3%), and 1,122 (-58.8%) cases per 100,000 persons, respectively (p

Evaluation of pulp vitality is an important diagnostic procedure in dentistry. Conventional techniques for measurement of pulp vitality, including thermal stimulation, electrical stimulation, or direct dentin stimulation, are frequently associated with false positive or false negative results. Recently, oxygen saturation from pulse oximetry has been utilized in the evaluation of pulp vitality. Perfusion index (PI) data calculated from photoplethysmography have been widely used to evaluate peripheral perfusion. The combination of oxygen saturation and PI may aid in the accurate measurement of pulp vitality. We aimed to investigate the baseline values of oxygen saturation and PI using pulse oximetry in adult volunteers.Fifteen adult volunteers with viable incisors were tested. To measure PI, a fabricated oxygen sensor was applied to an incisor without a pulp lesion while oxygen saturation was simultaneously measured in the finger. Oxygen saturation and PI were continuously measured with customized software. The normal reference values of oxygen saturation and PI were obtained by analyzing the recorded data.Pulse oximetry showed relatively stable, objective, and accurate oxygen saturation results. The tooth oxygen saturation ranged from 97% to 100%. The PI ranged from 0.3% to 0.5%, and PI and oxygen saturation showed relatively consistent values across subjects.Although there are some limitations to our study, these results may prove useful for detecting teeth with impaired vitality and non-invasively differentiating between necrotic and vital pulp.

Aplasia of lacrimal and salivary glands (ALSG) is a rare autosomal dominant inherited disease, characterized by aplasia, atresia, or hypoplasia of the lacrimal and salivary systems with variable expressivity. The purpose of this study was to identify genetic etiology of an ALSG family. We recruited a Turkish family with ALSG and performed a mutational analysis, based on the candidate gene approach, to clarify the molecular genetic etiology. The candidate gene sequencing of the FGF10 gene identified a novel heterozygous nonsense mutation (c.237G > A, p.Trp79*) in the exon 1. The identified novel mutation would result in a haploinsufficiency of the FGF10, because of nonsense-mediated mRNA decay caused by a premature stop codon. This report further confirms that ALSG is caused by the haploinsufficiency of functional FGF10. Identification of the genetic etiology of the ALSG will help both the family members and dentist understand the nature of the disorder. Therefore, it will positively motivate oral health care to avoid further destruction of the tooth due to the lack of salivary production.

Chronic hepatitis C virus (HCV) infection is a major cause of liver cirrhosis and hepatocellular carcinoma. Combination therapy of pegylated interferon-alpha (PEG-IFN-α) and ribavirin (RBV) is a current standard treatment for chronic HCV infection in Korea, which has considerable adverse effects. Acute pancreatitis is a rare complication of PEG-IFN-α administration. We report a case of a 62-year-old female who experienced acute pancreatitis after 4 weeks of PEG-IFN-α-2a and RBV combination therapy for chronic HCV infection. The main cause of the acute pancreatitis in this case was probably PEG-IFN-α rather than RBV for several reasons. A few cases have been reported in which acute pancreatitis occurred during treatment with PEG-IFN-α-2b. This is the first report of acute pancreatitis associated with PEG-IFN-α-2a in Korea.

Objective The objective of this study was to evaluate the variation in the condition referred to as molar root-incisor malformation (MRIM) and elucidate the distribution of affected teeth. This study further aimed to identify associated environmental stressors. Study Design Individuals were identified through retrospective review of dental radiographs and through referral to the investigators. Histologic evaluation included examination of mineralized and decalcified sections of affected first permanent molar teeth. Results Thirty cases of MRIM were identified, with all having affected first permanent molars with dysplastic root formation. The primary second molars were affected in 57% of the cases, with permanent anterior teeth being involved in 40% of the cases. A variety of medical conditions were associated with MRIM, the most common being neurologic. Several affected individuals reported no significant past medical history or environmental stressors. Conclusions The etiology of MRIM remains unclear, and this unique developmental defect of the first permanent molar roots appears to occur in populations throughout the world. Clinicians identifying the MRIM phenotype should carefully evaluate the permanent incisors for associated developmental defects that could result in pulpal necrosis.