Purpose: Neuroinflammation is considered an important pathway associated with several diseases that result in cognitive decline. 18F-THK5351 positron emission tomography (PET) signals might indicate the presence of neuroinflammation, as well as Alzheimer’s disease-type tau aggregates. β-amyloid (Aβ)-negative (Aβ–) amnestic mild cognitive impairment (aMCI) may be associated with non-Alzheimer’s disease pathophysiology. Accordingly, we investigated associations between 18F-THK5351 PET positivity and cognitive decline among Aβ– aMCI patients. Materials and Methods: The present study included 25 amyloid PET negative aMCI patients who underwent a minimum of two follow-up neuropsychological evaluations, including clinical dementia rating-sum of boxes (CDR-SOB). The patients were classified into two groups: 18F-THK5351-positive and -negative groups. The present study used a linear mixed effects model to estimate the effects of 18F-THK5351 PET positivity on cognitive prognosis among Aβ– aMCI patients. Results: Among the 25 Aβ– aMCI patients, 10 (40.0%) were 18F-THK5351 positive. The patients in the 18F-THK5351-positive group were older than those in the 18F-THK5351-negative group (77.4±2.2 years vs. 70.0±5.5 years; p<0.001). There was no difference between the two groups with regard to the proportion of apolipoprotein E ε4 carriers. Interestingly, however, the CDR-SOB scores of the 18F-THK5351-positive group deteriorated at a faster rate than those of the 18F-THK5351-negative group (B=0.003, p=0.033). Conclusion The results of the present study suggest that increased 18F-THK5351 uptake might be a useful predictor of poor prognosis among Aβ– aMCI patients, which might be associated with increased neuroinflammation (ClinicalTrials.gov NCT02656498).

Sumoylation, the conjugation of a small ubiquitin-like modifier (SUMO) protein to a target, has diverse cellular effects. However, the functional roles of the SUMO modification during myogenesis have not been fully elucidated. Here, we report that basal sumoylation of histone deacetylase 1 (HDAC1) enhances the deacetylation of MyoD in undifferentiated myoblasts, whereas further sumoylation of HDAC1 contributes to switching its binding partners from MyoD to Rb to induce myocyte differentiation. Differentiation in C2C12 skeletal myoblasts induced new immunoblot bands above HDAC1 that were gradually enhanced during differentiation. Using SUMO inhibitors and sumoylation assays, we showed that the upper band was caused by sumoylation of HDAC1 during differentiation. Basal deacetylase activity was not altered in the SUMO modification-resistant mutant HDAC1 K444/476R (HDAC1 2R). Either differentiation or transfection of SUMO1 increased HDAC1 activity that was attenuated in HDAC1 2R. Furthermore, HDAC1 2R failed to deacetylate MyoD. Binding of HDAC1 to MyoD was attenuated by K444/476R. Binding of HDAC1 to MyoD was gradually reduced after 2 days of differentiation. Transfection of SUMO1 induced dissociation of HDAC1 from MyoD but potentiated its binding to Rb. SUMO1 transfection further attenuated HDAC1-induced inhibition of muscle creatine kinase luciferase activity that was reversed in HDAC1 2R. HDAC1 2R failed to inhibit myogenesis and muscle gene expression. In conclusion, HDAC1 sumoylation plays a dual role in MyoD signaling: enhancement of HDAC1 deacetylation of MyoD in the basally sumoylated state of undifferentiated myoblasts and dissociation of HDAC1 from MyoD during myogenesis.
Creatine Kinase, MM Form ; Gene Expression ; Histone Deacetylase 1 ; Histone Deacetylases ; Histones ; Luciferases ; Muscle Cells ; Muscle Development ; Myoblasts ; Myoblasts, Skeletal ; Sumoylation ; Transfection

BACKGROUND/AIMS: α-Synucleinopathy in the brain is the neuropathological hallmark of Parkinson’s disease (PD). However, the functional impact of α-synucleinopathy in the enteric nervous system remains unknown. We aim to evaluate the association between gastrointestinal (GI) dysfunction and α-synuclein (αSYN) pathology in the stomach and colon of PD patients and controls, as well as to investigate the association between the αSYN pathology in GI tract and future PD risk. METHODS: A total of 35 PD patients and 52 neurologically intact subjects were enrolled in this study. Endoscopic biopsies were performed, and then immunohistochemical staining for αSYN was performed. All subjects completed the validated Rome III questionnaire for the assessment of GI symptoms. The association between GI symptoms and the αSYN pathology in GI mucosa was evaluated. Incident PD cases were assessed during a median follow-up of 46 months. RESULTS: The proportion of self-reported constipation and functional constipation through the Rome III questionnaire was significantly higher in PD patients than in controls (P < 0.001 and P = 0.015). However, no significant association was found between the αSYN pathology in the stomach and colon mucosa and constipation, as well as other GI symptoms including dyspepsia symptoms and abdominal discomfort or pain, regardless of the presence or absence of clinical PD (P > 0.05). No incident PD cases were diagnosed during study period. CONCLUSIONS: Our present study suggests that the deposition of αSYN in the mucosal enteric nervous system may not be reflected by functional impairment of the affected segment of the gut.
Biopsy ; Brain ; Colon ; Constipation ; Dyspepsia ; Enteric Nervous System ; Follow-Up Studies ; Gastrointestinal Tract ; Humans ; Mucous Membrane ; Parkinson Disease ; Pathology ; Stomach

BACKGROUND: We observed several cases of rare vascular anomalies within the femoral triangle during varicose vein operations. METHODS: From among 2,093 patients who underwent stripping operations of the great saphenous vein between January 2002 and June 2016, 14 cases of rare vascular anomalies were enrolled in this study. RESULTS: Twelve cases of femoral artery and vein transposition (0.57%), 1 case of separate entrance of the great saphenous vein trunk and its tributaries (0.05%), and 1 case of separate entrance with femoral artery and vein transposition (0.05%) were observed. The preoperative diagnosis rate was 71% (10 of 14) using duplex ultrasound. In all cases of femoral artery and vein transposition, the saphenofemoral junction was located at the lateral or posterolateral side of the superficial femoral artery, corresponding to complete or incomplete transposition, respectively. Among the 12 cases of femoral artery and vein transposition, 5 cases were complete transposition and 7 cases were incomplete transposition. In 2 cases of separate entrance of the great saphenous vein trunk and its tributaries, the separated tributaries formed a common trunk before connecting to the femoral vein. CONCLUSION: The anatomy of the saphenofemoral junction may infrequently be altered in some individuals. Detailed preoperative sonographic examinations and meticulous groin dissection during the operation are necessary to prepare for unexpected anatomical variations.
Diagnosis ; Femoral Artery ; Femoral Vein ; Groin ; Humans ; Saphenous Vein ; Ultrasonography ; Varicose Veins* ; Veins

A 39-year-old woman arrived at our emergency department, complaining of severe pain and swelling of her left leg. She had slipped down stairs and injured on her left leg about 3 months ago. Computed tomography angiography showed left distal superficial femoral artery’s pseudoaneurysm with arteriovenous fistula and thrombotic occlusion of left common iliac vein. We decided to do endovascular intervention due to severe venous hypertension and chronic inflammation around the fistula. The femoral arteriovenous fistula was closed via stent-graft (7 mm×5, 9 mm×5 cm) deployment. The occluded left iliac vein was reopened by nitinol metal stenting (12 mm×4 cm, 14 mm×4 cm). The authors report a very rare case of femoral arteriovenous fistula combined with iliac vein thrombosis developed after a blunt trauma.
Adult ; Aneurysm, False ; Angiography ; Arteriovenous Fistula* ; Emergency Service, Hospital ; Female ; Fistula ; Humans ; Hypertension ; Iliac Vein* ; Inflammation ; Leg ; Stents ; Thrombosis*

BACKGROUND AND OBJECTIVES: Marfan syndrome (MFS) is a connective tissue disorder with autosomal dominant inheritance and a highly variable clinical spectrum. However, there are limited data available on the clinical features of Korean patients with MFS. The aim of the present study was to describe the clinical characteristics and outcomes of Korean patients with MFS. SUBJECTS AND METHODS: We included all patients who were diagnosed with MFS between January 1995 and May 2015 at a single tertiary medical center. Patients with an MFS-related disorder including MASS phenotype (myopia, mitral valve prolapse, borderline and non-progressive aortic root dilatation, skeletal findings, and striae), mitral valve prolapse syndrome, and ectopia lentis syndrome were excluded. A total of 343 Korean patients aged ≥15 years who satisfied the revised Ghent nosology were included. RESULTS: The mean patient age at diagnosis was 35.9±12.6 years and 172 (50.1%) patients were male. Median follow-up duration was 52.8 months. A total of 303 patients (88.6%) had aortic root dilatation with Z score ≥2 or aortic root dissection. Ectopia lentis was relatively less common (163 patients, 55.1%) and systemic score ≥7 was found in 217 patients (73.8%). Among 219 probands, a family history of MFS was present in 97 patients (44.5%) and sporadic cases in 121 patients (55.5%). Among the 157 probands who underwent genetic analysis, 141 (89.8%) had an FBN1 mutation associated with aortic root aneurysm/dissection. Aortic dissection (AD) or intramural hematoma (IMH) was identified in 110 patients (32.1%). Among the 221 patients without AD or IMH, descending aortic aneurysms were identified in 19 patients (8.6%). Two hundred thirteen patients (62%) underwent cardiovascular surgery of any type. Eight patients died during follow-up. CONCLUSION: We described the clinical characteristics and outcomes of Korean MFS patients. Cardiovascular manifestations were commonly detected and FBN1 mutation was present in approximately 90% of patients. In contrast, ectopia lentis was identified in approximately half of patients. Our findings will be informative for the evaluation of patients with MFS.
Aortic Aneurysm ; Asian Continental Ancestry Group ; Connective Tissue ; Demography ; Diagnosis ; Dilatation ; Ectopia Lentis ; Follow-Up Studies ; Hematoma ; Humans ; Korea* ; Male ; Marfan Syndrome* ; Mitral Valve Prolapse ; Phenotype ; Wills

BACKGROUND/AIMS: Accurately diagnosing inflammatory bowel disease (IBD) remains a challenge, but is crucial for providing proper management for affected patients. The aim of the present study was to evaluate the frequency of change in diagnosis in Korean patients who were referred to our institution with a diagnosis of IBD. METHODS: We enrolled 1,444 patients diagnosed with ulcerative colitis (UC) and 1,452 diagnosed with Crohn's disease (CD), who had been referred to the Asan Medical Center between January 2010 and December 2014. These patients were assessed and subsequently classified as having UC, CD, indeterminate colitis, possible IBD, or non-IBD. RESULTS: During a median follow-up of 15.9 months, 400 of the 2,896 patients (13.8%) analyzed in this study experienced a change in diagnosis. A change in diagnosis from UC to CD, or vice-versa, was made in 24 of 1,444 patients (1.7%) and 23 of 1,452 patients (1.6%), respectively. A change to a non-IBD diagnosis was the most common modification; 7.5% (108 of 1444) and 12.7% (184 of 1452) of the patients with a referral diagnosis of UC and CD, respectively, were reclassified as having non-IBD. Among the 292 patients who were ultimately determined not to have IBD, 135 (55 UC and 80 CD cases) had received IBD-related medication. CONCLUSIONS: There are diagnostic uncertainties and difficulties in relation to IBD. Therefore, precise assessment and systematic follow-up are essential in the management of this condition.
Chungcheongnam-do ; Cohort Studies* ; Colitis ; Colitis, Ulcerative ; Crohn Disease ; Diagnosis* ; Follow-Up Studies ; Humans ; Inflammatory Bowel Diseases* ; Korea* ; Referral and Consultation

PURPOSE: Despite technical simplicity and the low cost of brachial-ankle pulse wave velocity (BA-PWV), its use has been hampered by a lack of data supporting its usefulness and reliability. The aim of this study was to evaluate the usefulness of BA-PWV to measure aortic stiffness in comparison to using cardiovascular magnetic resonance (CMR). MATERIALS AND METHODS: A total of 124 participants without cardiovascular risk factors volunteered for this study. BA-PWV was measured using a vascular testing device. On the same day, using CMR, cross-sectional areas for distensibility and average blood flow were measured at four aortic levels: the ascending, upper thoracic descending, lower thoracic descending, and abdominal aorta. RESULTS: Compared to PWV measured by CMR, BA-PWV values were significantly higher and the differences therein were similar in all age groups (all p<0.001). There was a significant correlation between BA-PWV and PWV by CMR (r=0.697, p<0.001). Both BA-PWV and PWV by CMR were significantly and positively associated with age (r=0.652 and 0.724, p<0.001). The reciprocal of aortic distensibility also demonstrated a statistically significant positive correlation with BA-PWV (r=0.583 to 0.673, all p<0.001). CONCLUSION: BA-PWV was well correlated with central aortic PWV and distensibility, as measured by CMR, regardless of age and sex.
Adult ; Ankle Brachial Index/*methods ; Ankle Joint ; Aorta/anatomy & histology/*physiology ; *Blood Flow Velocity ; Cardiovascular Diseases ; Female ; Heart/physiopathology ; Humans ; *Magnetic Resonance Imaging, Cine ; Male ; Pulse Wave Analysis/*methods ; Regional Blood Flow ; Reproducibility of Results ; Risk Factors ; *Vascular Stiffness

BACKGROUND/AIMS: Chicken skin mucosa (CSM), surrounding colorectal adenoma, is an endoscopic finding with pale yellow-speckled mucosa; however, its clinical significance is unknown. This study aimed to evaluate the prevalence and clinical characteristics of CSM, and the association between colorectal carcinogenesis and CSM. METHODS: This cross-sectional study was performed in 733 consecutive patients who underwent endoscopic polypectomy for colorectal adenoma after the screening of colonoscopy at the Asan Health Promotion Center between June 2009 and December 2011. The colonoscopic and pathological findings of colorectal adenoma including number, size, location, dysplasia, morphology, and clinical parameters were reviewed. RESULTS: The prevalence of CSM was 30.7% (225 of 733 patients), and most CSM-related adenomas were located in the distal colon (93.3%). Histological analysis revealed lipid-laden macrophages in the lamina propria of the mucosa. Multivariate analyses showed that CSM was significantly associated with advanced pathology, including villous adenoma and high-grade dysplasia (odds ratio [OR], 2.078; 95% confidence interval [CI], 1.191-3.627; P=0.010), multiple adenomas (i.e., > or =2 adenomas; OR, 1.692; 95% CI, 1.143-2.507; P=0.009), and a protruding morphology (OR, 1.493; 95% CI, 1.027-2.170; P=0.036). There were no significant differences in polyp size or clinical parameters between patients with and without CSM. CONCLUSIONS: CSM-related adenoma was mainly found in the distal colon, and was associated with advanced pathology and multiple adenomas. CSM could be a potential predictive marker of the carcinogenetic progression of distally located colorectal adenomas.
Adenoma* ; Adenoma, Villous ; Carcinogenesis ; Chickens* ; Chungcheongnam-do ; Colon* ; Colonoscopy ; Cross-Sectional Studies ; Health Promotion ; Humans ; Macrophages ; Mass Screening ; Mucous Membrane* ; Multivariate Analysis ; Pathology ; Polyps ; Prevalence ; Skin*

A new CT-based diagnostic method of protrusio acetabuli (PA) was introduced. However, prevalence of PA by this method and correlation between PA and other manifestations of Marfan syndrome (MFS) is unknown in Korean MFS patients. This study aimed to investigate the prevalence of PA diagnosed by a CT-based method in Korean patients with MFS, the association of PA with other manifestations of MFS, and the contribution of PA to MFS diagnosis. We retrospectively reviewed the records of 146 MFS patients with the presence of a causative FBN1 mutation and 146 age- and sex-matched controls from a single tertiary care center. All MFS patients underwent a complete assessment of criteria based on the revised Ghent nosology. PA was assessed quantitatively using a CT-based circle-wall distance (CWD) method. PA was diagnosed in 77.4% of patients in the MFS group and in 11.0% of the control group. CWD was significantly different between the two groups (1.50 mm vs. -0.64 mm, P<0.001). The presence of PA did not correlate with the presence of ectopia lentis, aortic root diameter, or history of aortic dissection. The presence of PA did not have a significant impact on the final diagnosis of MFS. Even though the presence of PA does not related to the cardinal clinical features of MFS or influence MFS diagnosis, its presence may be helpful for the suspicion of MFS when aortic dissection or aneurysm is found on CT angiography of the aorta because of the high frequency of PA in MFS patients.
Acetabulum/*abnormalities/radiography ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Aortic Aneurysm/*epidemiology/radiography ; Comorbidity ; Female ; Humans ; Male ; Marfan Syndrome/*epidemiology/*radiography ; Middle Aged ; Prevalence ; Reproducibility of Results ; Republic of Korea/epidemiology ; Risk Factors ; Sensitivity and Specificity ; Tomography, X-Ray Computed/*methods/*statistics & numerical data ; Young Adult