Image segmentation of impacted mesiodens using deep learning.

This study aimed to evaluate the performance of deep learning algorithms for the classification and segmentation of impacted mesiodens in pediatric panoramic radiographs. A total of 850 panoramic radiographs of pediatric patients (aged 3-9 years) was included in this study. The U-Net semantic segmentation algorithm was applied for the detection and segmentation of mesiodens in the upper anterior region. For enhancement of the algorithm, pre-trained ResNet models were applied to the encoding path. The segmentation performance of the algorithm was tested using the Jaccard index and Dice coefficient. The diagnostic accuracy, precision, recall, F1-score and time to diagnosis of the algorithms were compared with those of human expert groups using the test dataset. Cohen's kappa statistics were compared between the model and human groups. The segmentation model exhibited a high Jaccard index and Dice coefficient (>90%). In mesiodens diagnosis, the trained model achieved 91-92% accuracy and a 94-95% F1-score, which were comparable with human expert group results (96%). The diagnostic duration of the deep learning model was 7.5 seconds, which was significantly faster in mesiodens detection compared to human groups. The agreement between the deep learning model and human experts is moderate (Cohen's kappa = 0.767). The proposed deep learning algorithm showed good segmentation performance and approached the performance of human experts in the diagnosis of mesiodens, with a significantly faster diagnosis time.

Novel PAX9 Mutations Causing Isolated Oligodontia.

Hypodontia, i.e., missing one or more teeth, is a relatively common human disease; however, oligodontia, i.e., missing six or more teeth, excluding the third molars, is a rare congenital disorder. Many genes have been shown to cause oligodontia in non-syndromic or syndromic conditions. In this study, we identified two novel PAX9 mutations in two non-syndromic oligodontia families. A mutational analysis identified a silent mutation (NM_006194.4: c.771G>A, p.(Gln257=)) in family 1 and a frameshift mutation caused by a single nucleotide duplication (c.637dup, p.(Asp213Glyfs*104)) in family 2. A minigene splicing assay revealed that the silent mutation resulted in aberrant pre-mRNA splicing instead of normal splicing. The altered splicing products are ones with an exon 4 deletion or using a cryptic 5' splicing site in exon 4. Mutational effects were further investigated using protein expression, luciferase activity assay and immunolocalization. We believe this study will not only expand the mutational spectrum of PAX9 mutations in oligodontia but also strengthen the diagnostic power related to the identified silent mutation.

Masculinity, Rather Than Biological Sex, Is Associated With Psychological Comorbidities in Patients With Irritable Bowel Syndrome.

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.

Perceptions of and Practices for the Management of Constipation: Results of a Korean National Survey.

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<0.05). There were also significant differences in the preference for laxatives depending on the type of hospital. Conclusions: There were discrepancies in the diagnosis and management of CC patients depending on the clinical setting. The utilization rates of the Bristol Stool Form Scale and digital rectal examination by physicians are low in real-world clinical practice. These results imply the need for better and more practical training of physicians in the assessment and management of CC.

Clinical efficacy of Yukgunja-tang combined with a proton pump inhibitor for refractory gastroesophageal reflux disease: study protocol for randomized, double-blind, double-dummy clinical trial.

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 ).

Recessive COL17A1 Mutations and a Dominant LAMB3 Mutation Cause Hypoplastic Amelogenesis Imperfecta.

Hereditary conditions that affect tooth enamel in quantity and/or quality are called amelogenesis imperfecta (AI). AI can occur as an isolated condition or as a symptom of a syndrome. An OMIM search with the term "AI" yielded 79 result entries. Mutations in the same gene cause syndromic or non-syndromic AI, depending on the nature of the mutations. In this study, we recruited two AI families and performed mutational analysis using whole-exome sequencing. The proband of family 1, with hypoplastic pitted AI and mild localized atopic dermatitis, had compound heterozygous COL17A1 mutations (paternal NM_000494.4: c.3598G>T, p.Asp1200Tyr and maternal c.1700G>A, p.Gly567Glu). The proband of family 2, with hypoplastic pitted AI and Jervell and Lange-Nielsen syndrome, had a recurrent LAMB3 mutation (NM_000228.3: c.3463_3475del, p.(Glu1155Thrfs*51)) in addition to compound heterozygous mutations in the KCNQ1 gene.

Criteria for early diagnosis of mandibular third molar agenesis based on the developmental stages of mandibular canine, first and second premolars, and second molar: a retrospective cohort study.

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.

2022 Seoul Consensus on Clinical Practice Guidelines for Functional Constipation.

Chronic constipation is one of the most common digestive diseases encountered in clinical practice. Constipation manifests as a variety of symptoms, such as infrequent bowel movements, hard stools, feeling of incomplete evacuation, straining at defecation, a sense of anorectal blockage during defecation, and use of digital maneuvers to assist defecation. During the diagnosis of chronic constipation, the Bristol Stool Form Scale, colonoscopy, and a digital rectal examination are useful for objective symptom evaluation and differential diagnosis of secondary constipation. Physiological tests for functional constipation have complementary roles and are recommended for patients who have failed to respond to treatment with available laxatives and those who are strongly suspected of having a defecatory disorder. As new evidence on the diagnosis and management of functional constipation emerged, the need to revise the previous guideline was suggested. Therefore, these evidence-based guidelines have proposed recommendations developed using a systematic review and meta-analysis of the treatment options available for functional constipation. The benefits and cautions of new pharmacological agents (such as lubiprostone and linaclotide) and conventional laxatives have been described through a meta-analysis. The guidelines consist of 34 recommendations, including 3 concerning the definition and epidemiology of functional constipation, 9 regarding diagnoses, and 22 regarding managements. Clinicians (including primary physicians, general health professionals, medical students, residents, and other healthcare professionals) and patients can refer to these guidelines to make informed decisions regarding the management of functional constipation.

Ideal Timing of Discontinuation of Antiplatelet Agents Before Gastric Endoscopic Submucosal Dissection for Reducing Delayed Bleeding.

BACKGROUND AND AIMS: This study aimed to evaluate whether the use of antiplatelet agents increases the risk of bleeding after gastric endoscopic submucosal dissection (ESD) and to determine the appropriate time to discontinue antiplatelet agents to minimize complications. METHODS: This retrospective observational study utilized a collected dataset of patients who underwent ESD for gastric adenoma and cancer between January 2010 and December 2020. Patients were classified into three groups according to antiplatelet agent use and discontinuation status. We investigated the risk of post-ESD bleeding with different interruption times and antiplatelet agent types. RESULTS: Of 1879 patients, 1389 were non-users, 190 were in the continuous group, and 203 were in the interrupted group. The rates of overall and delayed bleeding were significantly higher in patients who continued or were interrupted within three days before ESD than in the non-users and interrupted group (6.3% vs. 1.2%, p < 0.001, 6.3% vs. 2.5%, p = 0.01, respectively). Significant differences in delayed bleeding between the continuous and interrupted groups decreased with longer cessation periods. In multivariate analysis, continuous antiplatelet agents were still the strongest risk factor for bleeding (OR 2.81, 95% CI 1.14-6.90). Lower third location and longer procedure times were also independent risk factors for post-ESD bleeding (OR 2.75; 95% CI 1.08-6.97; OR 1.02; 95% CI 1.01-1.02). CONCLUSION: Continuous antiplatelet agent use increases the risk of delayed bleeding after gastric ESD. Therefore, the optimal timing of interruption, rather than the type of antiplatelet agent, should be considered to avoid an additional risk of bleeding and thromboembolism.

FAM20A mutations and transcriptome analyses of dental pulp tissues of enamel renal syndrome.

AIM: Biallelic loss-of-function FAM20A mutations cause amelogenesis imperfecta (AI) type IG, better known as enamel renal syndrome (ERS), characterized by severe enamel hypoplasia, delayed/failed tooth eruption, intrapulpal calcifications, gingival hyperplasia and nephrocalcinosis. FAM20A binds to FAM20C, the Golgi casein kinase (GCK) and potentiates its function to phosphorylate secreted proteins critical for biomineralization. While many FAM20A pathogenic mutations have been reported, the pathogeneses of orodental anomalies in ERS remain to be elucidated. This study aimed to identify disease-causing mutations for patients with ERS phenotypes and to discern the molecular mechanism underlying ERS intrapulpal calcifications. METHODOLOGY: Phenotypic characterization and whole exome analyses were conducted for 8 families and 2 sporadic cases with hypoplastic AI. A minigene assay was performed to investigate the molecular consequences of a FAM20A splice-site variant. RNA sequencing followed by transcription profiling and gene ontology (GO) analyses were carried out for dental pulp tissues of ERS and the control. RESULTS: Biallelic FAM20A mutations were demonstrated for each affected individual, including 7 novel pathogenic variants: c.590-5T>A, c.625T>A (p.Cys209Ser), c.771del (p.Gln258Argfs*28), c.832_835delinsTGTCCGACGGTGTCCGACGGTGTC CA (p.Val278Cysfs*29), c.1232G>A (p.Arg411Gln), c.1297A>G (p.Arg433Gly) and c.1351del (p.Gln451Serfs*4). The c.590-5T>A splice-site mutation caused Exon 3 skipping, which resulted in an in-frame deletion of a unique region of the FAM20A protein, p.(Asp197_Ile214delinsVal). Analyses of differentially expressed genes in ERS pulp tissues demonstrated that genes involved in biomineralization, particularly dentinogenesis, were significantly upregulated, such as DSPP, MMP9, MMP20 and WNT10A. Enrichment analyses indicated overrepresentation of gene sets associated with BMP and SMAD signalling pathways. In contrast, GO terms related to inflammation and axon development were underrepresented. Among BMP signalling genes, BMP agonists GDF7, GDF15, BMP3, BMP8A, BMP8B, BMP4 and BMP6 were upregulated, while BMP antagonists GREM1, BMPER and VWC2 showed decreased expression in ERS dental pulp tissues. CONCLUSIONS: Upregulation of BMP signalling underlies intrapulpal calcifications in ERS. FAM20A plays an essential role in pulp tissue homeostasis and prevention of ectopic mineralization in soft tissues. This critical function probably depends upon MGP (matrix Gla protein), a potent mineralization inhibitor that must be properly phosphorylated by FAM20A-FAM20C kinase complex.

Novel WDR72 Mutations Causing Hypomaturation Amelogenesis Imperfecta.

Amelogenesis imperfecta (AI) is a heterogeneous collection of hereditary enamel defects. The affected enamel can be classified as hypoplastic, hypomaturation, or hypocalcified in form. A better understanding of normal amelogenesis and improvements in our ability to diagnose AI through genetic testing can be realized through more complete knowledge of the genes and disease-causing variants that cause AI. In this study, mutational analysis was performed with whole exome sequencing (WES) to identify genetic etiology underlying the hypomaturation AI condition in affected families. Mutational analyses identified biallelic WDR72 mutations in four hypomaturation AI families. Novel mutations include a homozygous deletion and insertion mutation (NM_182758.4: c.2680_2699delinsACTATAGTT, p.(Ser894Thrfs*15)), compound heterozygous mutations (paternal c.2332dupA, p.(Met778Asnfs*4)) and (maternal c.1287_1289del, p.(Ile430del)) and a homozygous 3694 bp deletion that includes exon 14 (NG_017034.2:g.96472_100165del). A homozygous recurrent mutation variant (c.1467_1468delAT, p.(Val491Aspfs*8)) was also identified. Current ideas on WDR72 structure and function are discussed. These cases expand the mutational spectrum of WDR72 mutations causing hypomaturation AI and improve the possibility of genetic testing to accurately diagnose AI caused by WDR72 defects.

Development of a Single-nucleotide Polymorphism Genotyping Assay for the Rapid Detection of Vancomycin-intermediate Resistance in Staphylococcus aureus Epidemic Lineage ST5.

Background: Vancomycin is a treatment option for patients with severe methicillin-resistant Staphylococcus aureus (MRSA) infection. Unfortunately, reduced susceptibility to vancomycin in S. aureus is becoming increasingly common. We developed a method for the rapid and accurate diagnosis of vancomycin-intermediate resistant S. aureus (VISA). Methods: We performed a microbial genome-wide association study to discriminate between VISA and vancomycin-susceptible S. aureus (VSSA) using 42 whole-genome sequences. A TaqMan single-nucleotide polymorphism (SNP) genotyping assay was developed to detect target SNPs in VISA strains. Results: Four SNPs in the VISA strains resulting in nonsynonymous amino-acid substitutions were associated with reduced susceptibility to vancomycin: SA_RS01235 (G203S), SA_RS09725 (V171A), SA_RS12250 (I48F), and SA_RS12550 (G478A). These four SNPs were mainly detected in the typical hospital-associated sequence type (ST)5 clonal lineage. The TaqMan assay successfully detected all four SNPs using as little as 0.2 ng DNA per reaction. Using 10 VSSA and VISA clinical strains each, we validated that the assay accurately discriminates between VISA and VSSA. Conclusions: The TaqMan SNP genotyping assay targeting four SNPs may be an alternative to current standard methods for the rapid detection of vancomycin-intermediate resistance in S. aureus epidemic lineage ST5.

Efficacy and safety of intragastric balloon for obesity in Korea.

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. CONCLUSION: 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.

Enamel defects in Acp4R110C/R110C mice and human ACP4 mutations.

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 Acp4R110C 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 (Acp4R110C/R110C) mice exhibited a thin layer of aplastic enamel with numerous ectopic mineralized nodules. Acp4R110C/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.

Novel LRP6 Mutations Causing Non-Syndromic Oligodontia.

The process of tooth formation is a series of reciprocal interactions between the ectoderm and mesoderm, and it is believed that many genetic factors are involved in this complex process. More than a dozen genes have been identified in non-syndromic tooth agenesis; however, the genetic etiology underlying tooth agenesis is not fully understood yet. In this study, we identified two novel LRP6 mutations in two non-syndromic oligodontia families. Both probands had 16 and 17 missing teeth in their permanent dentition. Mutational analysis identified a de novo frameshift mutation by a 1-bp insertion in exon 9 (NM_002336.2: c.1870dupA, p.(Met624Asnfs*29)) and a splicing donor site mutation in intron 8 (c.1762+2T>C). An in vitro splicing assay confirmed the deletion of exon 8, and the deletion would result in a frameshift. Due to the premature termination codons introduced by the frameshift, both mutant transcripts would be degraded by nonsense-mediated mRNA decay, resulting in haploinsufficiency.

Benefits of Flavored Lactose-Free Milk for Korean Adults with Lactose Intolerance.

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 ΔH2 peak exceeded 16 ppm above baseline values and with the occurrence of symptoms after WM consumption. The participants who were diagnosed with LI underwent the HBT again with 570 mL of chocolate-flavored LFM (0 g of lactose), followed by the symptom questionnaire survey after 1 week. After excluding 40 participants who did not meet the diagnostic criteria for LI and 2 who were lost to follow-up, a total of 28 lactose-intolerant individuals were enrolled in the study. The ΔH2 values in the first HBT were significantly higher than those in the second HBT (33.3 ± 21.6 ppm vs. 8.6 ± 6.3 ppm, P < .001). Similarly, there was a significant reduction in the total symptom score in the second HBT (4.18 ± 1.51 vs. 0.61 ± 0.98, P < .001). Flavored LFM is well tolerated in South Korean adults diagnosed with LI based on the HBT and symptom questionnaire results. Therefore, LFM may be a viable alternative to WM.

Translated Mutant DSPP mRNA Expression Level Impacts the Severity of Dentin Defects.

Hereditary dentin defects are conventionally classified into three types of dentinogenesis imperfecta (DGI) and two types of dentin dysplasia (DD). Mutations in the dentin sialophosphoprotein (DSPP) gene have been identified to cause DGI type II and III and DD type II; therefore, these are not three different conditions, but rather allelic disorders. In this study, we recruited three families with varying clinical phenotypes from DGI-III to DD-II and performed mutational analysis by candidate gene analysis or whole-exome sequencing. Three novel mutations including a silent mutation (NM_014208.3: c.52-2del, c.135+1G>C, and c.135G>A; p.(Gln45=)) were identified, all of which affected pre-mRNA splicing. Comparison of the splicing assay results revealed that the expression level of the DSPP exon 3 deletion transcript correlated with the severity of the dentin defects. This study did not only expand the mutational spectrum of DSPP gene, but also advanced our understanding of the molecular pathogenesis impacting the severity of hereditary dentin defects.

Association between non-alcoholic fatty liver disease and the risk of dementia: A nationwide cohort study.

BACKGROUND AND AIMS: Little is known about the association between non-alcoholic fatty liver disease (NAFLD) and dementia. Given that hepatic steatosis is linked to abnormal fat metabolism, and fat dysregulation in the brain is related to dementia, we aimed to investigate whether NAFLD is associated with an increased risk of dementia. METHODS: We conducted a nationwide cohort study involving 4 031 948 subjects aged 40-69 years who underwent ≥2 health check-ups provided by the National Health Insurance Service in Korea between January 2004 and December 2007. Based on the hepatic steatosis index (HSI), subjects were categorized into non-NAFLD (HSI <30 at all check-ups) and NAFLD (HSI >36 at one or more check-ups). Dementia defined by ICD-10 codes with prescription data was followed up until December 2017. Cox proportional hazards regression models analysed the dementia risk. RESULTS: At baseline, 31.3% had NAFLD. During the median follow-up of 9.5 years, 138 424 in NAFLD group and 69 982 in non-NAFLD group developed dementia. NAFLD group was associated with a higher risk of dementia than non-NAFLD group on multivariable-adjusted analysis (hazard ratio [HR], 1.05; p < .001), competing risk analysis (HR, 1.08; p < .001) and propensity-score matched analysis (HR, 1.09; p < .001). The association between NAFLD and dementia risk was more prominent among females (HR, 1.16; p < .001). The association was stronger among non-obese NAFLD subjects (BMI <25 kg/m2 , HR, 1.09; p < .001) than obese NAFLD subjects. CONCLUSIONS: This nationwide study found that NAFLD is associated with an increased risk of dementia. The association was prominent among females and non-obese NAFLD subjects.

A Recurrent FAM83H Mutation in an Extended Colombian Family and Variable Craniofacial Phenotypes.

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.