Acetyl-CoA-mediated autoacetylation of fatty acid synthase as a metabolic switch of de novo lipogenesis in Drosophila.

De novo lipogenesis is a highly regulated metabolic process, which is known to be activated through transcriptional regulation of lipogenic genes, including fatty acid synthase (FASN). Unexpectedly, we find that the expression of FASN protein remains unchanged during Drosophila larval development from the second to the third instar larval stages (L2 to L3) when lipogenesis is hyperactive. Instead, acetylation of FASN is significantly upregulated in fast-growing larvae. We further show that lysine K813 residue is highly acetylated in developing larvae, and its acetylation is required for elevated FASN activity, body fat accumulation, and normal development. Intriguingly, K813 is autoacetylated by acetyl-CoA (AcCoA) in a dosage-dependent manner independent of acetyltransferases. Mechanistically, the autoacetylation of K813 is mediated by a novel P-loop-like motif (N-xx-G-x-A). Lastly, we find that K813 is deacetylated by Sirt1, which brings FASN activity to baseline level. In summary, this work uncovers a previously unappreciated role of FASN acetylation in developmental lipogenesis and a novel mechanism for protein autoacetylation, through which Drosophila larvae control metabolic homeostasis by linking AcCoA, lysine acetylation, and de novo lipogenesis.

Collagen has a unique SEC24 preference for efficient export from the endoplasmic reticulum.

SEC24 is mainly involved in cargo sorting during COPII vesicle assembly. There are four SEC24 paralogs (A-D) in vertebrates, which are classified into two subgroups (SEC24A/B and SEC24C/D). Pathological mutations in SEC24D cause osteogenesis imperfecta with craniofacial dysplasia in humans. sec24d mutant fish also recapitulate the phenotypes. Consistent with the skeletal phenotypes, the secretion of collagen was severely defective in mutant fish, emphasizing the importance of SEC24D in collagen secretion. However, SEC24D patient-derived fibroblasts show only a mild secretion phenotype, suggesting tissue-specificity in the secretion process. Using Sec24d KO mice and cultured cells, we show that SEC24A and SEC24B also contribute to endoplasmic reticulum (ER) export of procollagen. In contrast, fibronectin 1 requires either SEC24C or SEC24D for ER export. On the basis of our results, we propose that procollagen interacts with multiple SEC24 paralogs for efficient export from the ER, and that this is the basis for tissue-specific phenotypes resulting from SEC24 paralog deficiency.

Performance of Balloon-Assisted Enteroscopy for Non-ERCP Indications in Patients with Surgically Altered Gastrointestinal Anatomy.

BACKGROUND AND AIMS: Surgically altered gastrointestinal (GI) tract anatomy hinders deep enteroscopy. While enteroscopy-assisted endoscopic retrograde cholangiopancreatography (ERCP) in patients with altered GI anatomy has been heavily investigated, the role of non-ERCP balloon-assisted enteroscopy (BAE) has yet to be fully elucidated.Please check and confirm the author names and initials are correct. Also, kindly confirm the details in the metadata are correct.I have checked all you asked and have no correction.  Thank you. METHODS: A multicenter retrospective study of non-ERCP BAEs in patients with surgically altered GI tract anatomy at two tertiary academic hospitals was performed from January 2006 to December 2020. Altered GI tract anatomy was defined by surgical reconstruction affecting the length, angle, or overall trajectory of the endoscope during the intended approach. The main outcome measurements included technical success rate, diagnostic and therapeutic yields, and complication rate.Please check the edit made in the title of the article and correct if necessary.No more correction. Thank you. RESULTS: A total of 68 patients with surgically altered GI tract anatomy underwent 56 antegrade and 24 retrograde non-ERCP BAE procedures. The technical success rate was 86.2% in both, including 83.9% via antegrade approach and 91.7% via retrograde approach. Antegrade approach in Roux-en-Y anatomy was associated with the lowest success rate of 77.8%, whereas retrograde approach in patients with colon resection resulted in the highest rate of 100%. The diagnostic and therapeutic yields of non-ERCP BAE were 79.4% and 82.9%, respectively. The diagnostic yields varied according to the procedural indications. The major complication was luminal perforation in one case (1.3%). CONCLUSIONS: Non-ERCP BAE is effective and safe via both antegrade and retrograde approaches with a high technical success rate and diagnostic and therapeutic yields in patients with surgically altered GI tract anatomy.

Leveraging History to Predict Infrequent Abnormal Transfers in Distributed Workflows.

Scientific computing heavily relies on data shared by the community, especially in distributed data-intensive applications. This research focuses on predicting slow connections that create bottlenecks in distributed workflows. In this study, we analyze network traffic logs collected between January 2021 and August 2022 at the National Energy Research Scientific Computing Center (NERSC). Based on the observed patterns, we define a set of features primarily based on history for identifying low-performing data transfers. Typically, there are far fewer slow connections on well-maintained networks, which creates difficulty in learning to identify these abnormally slow connections from the normal ones. We devise several stratified sampling techniques to address the class-imbalance challenge and study how they affect the machine learning approaches. Our tests show that a relatively simple technique that undersamples the normal cases to balance the number of samples in two classes (normal and slow) is very effective for model training. This model predicts slow connections with an F1 score of 0.926.

Highly Uniform and Low Hysteresis Piezoresistive Pressure Sensors Based on Chemical Grafting of Polypyrrole on Elastomer Template with Uniform Pore Size.

Sensor-to-sensor variability and high hysteresis of composite-based piezoresistive pressure sensors are two critical issues that need to be solved to enable their practical applicability. In this work, a piezoresistive pressure sensor composed of an elastomer template with uniformly sized and arranged pores, and a chemically grafted conductive polymer film on the surface of the pores is presented. Compared to sensors composed of randomly sized pores, which had a coefficient of variation (CV) in relative resistance change of 69.65%, our sensors exhibit much higher uniformity with a CV of 2.43%. This result is corroborated with finite element simulation, which confirms that with increasing pore size variability, the variability in sensor characteristics also increases. Furthermore, our devices exhibit negligible hysteresis (degree of hysteresis: 2%), owing to the strong chemical bonding between the conductive polymer and the elastomer template, which prevents their relative sliding and displacement, and the porosity of the elastomer that enhances elastic behavior. Such features of the sensor render it highly feasible for various practical applications in the near future.

Mutations in SEC24D, encoding a component of the COPII machinery, cause a syndromic form of osteogenesis imperfecta.

As a result of a whole-exome sequencing study, we report three mutant alleles in SEC24D, a gene encoding a component of the COPII complex involved in protein export from the ER: the truncating mutation c.613C>T (p.Gln205(∗)) and the missense mutations c.3044C>T (p.Ser1015Phe, located in a cargo-binding pocket) and c.2933A>C (p.Gln978Pro, located in the gelsolin-like domain). Three individuals from two families affected by a similar skeletal phenotype were each compound heterozygous for two of these mutant alleles, with c.3044C>T being embedded in a 14 Mb founder haplotype shared by all three. The affected individuals were a 7-year-old boy with a phenotype most closely resembling Cole-Carpenter syndrome and two fetuses initially suspected to have a severe type of osteogenesis imperfecta. All three displayed a severely disturbed ossification of the skull and multiple fractures with prenatal onset. The 7-year-old boy had short stature and craniofacial malformations including macrocephaly, midface hypoplasia, micrognathia, frontal bossing, and down-slanting palpebral fissures. Electron and immunofluorescence microscopy of skin fibroblasts of this individual revealed that ER export of procollagen was inefficient and that ER tubules were dilated, faithfully reproducing the cellular phenotype of individuals with cranio-lentico-sutural dysplasia (CLSD). CLSD is caused by SEC23A mutations and displays a largely overlapping craniofacial phenotype, but it is not characterized by generalized bone fragility and presented with cataracts in the original family described. The cellular and morphological phenotypes we report are in concordance with the phenotypes described for the Sec24d-deficient fish mutants vbi (medaka) and bulldog (zebrafish).

Impact of patient audiovisual re-education via a smartphone on the quality of bowel preparation before colonoscopy: a single-blinded randomized study.

BACKGROUND AND AIMS: Education on preparation is essential for successful colonoscopy. This study aimed to evaluate the impact of audiovisual (AV) re-education via a smartphone on bowel preparation quality before colonoscopy. METHODS: A prospective, endoscopist-blinded, randomized, controlled study was performed. Patients who underwent colonoscopy with 3 purgatives, including 4 L of polyethylene glycol (4-L PEG), 2 L of PEG with ascorbic acid (2-L PEG/Asc), and sodium picosulfate with magnesium citrate (SPMC), were enrolled and randomized into the AV re-education via smartphone group (AV group, n = 160) and a control group (n = 160). The primary outcome was the quality of the bowel preparation according to the Boston Bowel Preparation Scale (BBPS). The secondary outcomes included instruction adherence using adherence score (AS) and patient satisfaction with education using a visual analog scale (VAS). RESULTS: A total of 283 patients (AV group, n = 139; control group, n = 144) were analyzed per protocol. The mean BBPS (7.53 vs 6.29, P < .001) and the proportion with adequate preparation were higher in the AV group. The mean BBPS of the AV group was significantly higher than that of the control group for the 2-L PEG/Asc and SPMC preparations, but not for the 4-L PEG preparation. The mean AS and the mean VAS score were all significantly higher in the AV group. Among the 3 purgatives, the mean AS was lowest in the 4-L PEG group (P = .041). CONCLUSIONS: AV re-education via smartphone was easy and convenient, and enhanced preparation quality, patient adherence to instructions, and patient satisfaction.

A variant associated with sagittal nonsyndromic craniosynostosis alters the regulatory function of a non-coding element.

Craniosynostosis presents either as a nonsyndromic congenital anomaly or as a finding in nearly 200 genetic syndromes. Our previous genome-wide association study of sagittal nonsyndromic craniosynostosis identified associations with variants downstream from BMP2 and intronic in BBS9. Because no coding variants in BMP2 were identified, we hypothesized that conserved non-coding regulatory elements may alter BMP2 expression. In order to identify and characterize noncoding regulatory elements near BMP2, two conserved noncoding regions near the associated region on chromosome 20 were tested for regulatory activity with a Renilla luciferase assay. For a 711 base pair noncoding fragment encompassing the most strongly associated variant, rs1884302, the luciferase assay showed that the risk allele (C) of rs1884302 drives higher expression of the reporter than the common allele (T). When this same DNA fragment was tested in zebrafish transgenesis studies, a strikingly different expression pattern of the green fluorescent reporter was observed depending on whether the transgenic fish had the risk (C) or the common (T) allele at rs1884302. The in vitro results suggest that altered BMP2 regulatory function at rs1884302 may contribute to the etiology of sagittal nonsyndromic craniosynostosis. The in vivo results indicate that differences in regulatory activity depend on the presence of a C or T allele at rs1884302.

Clinical outcome after enteroscopy for small bowel angioectasia bleeding: A Korean Associateion for the Study of Intestinal Disease (KASID) multiceter study.

BACKGROUND AND AIMS: Angioectasias are the most common sources of bleeding in the small bowel. They can be treated using balloon-assisted enteroscopy (BAE). This study aimed to identify the rebleeding rate and associated factors after BAE in patients with small bowel angioectasia bleeding. METHODS: We retrospectively analyzed the records of patients with bleeding due to small bowel vascular lesion in a multicenter enteroscopy database including 1108 BAEs. Finally, in rebleeding analysis, we analyzed 66 patients with angioectasia on the basis of the Yano-Yamamoto classification. Patients who had undergone endotherapy (ET) were divided into ET (n = 45) and non-ET (n = 21) groups. Rebleeding was defined as evidence of bleeding at least 30 days after BAE. RESULTS: Fifty-three patients (80.4%) underwent only one-side enteroscopy. The most common ET was argon plasma coagulation (87.2%). During a mean follow-up duration of 24.5 months, ET and non-ET groups had rebleeding rates of 15.6% and 38.1% (P = 0.059), respectively. Median rebleeding time of ET and non-ET groups was 32.5 and 62 months, respectively. Liver cirrhosis (LC), low platelet count (< 105 /µL), and transfusions were the rebleeding-associated factors in the univariate analysis. In the multivariate analysis, the presence of LC (HR 4.064, 95% CI 1.098-15.045; P = 0.036) was the only independent rebleeding-associated risk factor. CONCLUSIONS: ET using BAE did not significantly affect the rebleeding rate in patients with small bowel angioectasia bleeding. An independent rebleeding risk factor was the presence of LC. Regardless of ET, careful long-term follow-up may be needed, especially in LC patients with small bowel angioectasia bleeding.

Long-Term Clinical Outcomes of Rectal Neuroendocrine Tumors According to the Pathologic Status After Initial Endoscopic Resection: A KASID Multicenter Study.

OBJECTIVES: With advances in diagnostic endoscopy, the detection of rectal neuroendocrine tumors (NETs) has increased. However, clinical outcomes, especially after endoscopic treatment, are still unclear. The aim of this study was to determine the long-term clinical outcomes of endoscopically resected rectal NETs according to the pathologic status after initial resection. METHODS: In this large, multicenter, retrospective cohort study, we analyzed the medical records of patients who underwent endoscopic resection of rectal NETs and were followed for ≥24 months at 16 university hospitals. The outcomes of interest were local or distant recurrence and metachronous lesions. RESULTS: On the pathologic assessment of 407 patients, the resection margin status was positive in 76 (18.7%) and indeterminate in 72 (17.7%) patients. Patients whose rectal NETs were diagnosed or suspected as NETs before resection showed a much higher complete resection rate than those whose tumors were resected as polyps and then diagnosed (P<0.001). Fourteen patients received salvage treatment at 1.9±2.8 months after initial treatment. During a median follow-up period of 45.0 months, local recurrence occurred in 3 (0.74%) patients, but there was no recurrence in the lymph nodes or distant organs. Metachronous rectal NETs were diagnosed in 3 (0.74%) patients. According to the pathologic status after initial resection, local recurrence and metachronous lesions occurred in 1 (0.4%) and 2 (0.8%) patients, respectively, in the pathologic tumor-free group, whereas they occurred in 2 (1.4%) and 1 (0.7%) patients, respectively, in the indeterminate group. CONCLUSIONS: Considering the long-term prognosis including that for recurrences or metachronous lesions, endoscopic resection is an efficient and a safe modality for the treatment of rectal NETs. This treatment may result in favorable clinical outcomes in patients with tumors of indeterminate pathology, as well as in pathologic tumor-free cases after initial resection.

Direct Fabrication of Free-Standing MOF Superstructures with Desired Shapes by Micro-Confined Interfacial Synthesis.

Recently, metal-organic frameworks (MOFs) with multifunctional pore chemistry have been intensively investigated for positioning the desired morphology at specific locations onto substrates for manufacturing devices. Herein, we develop a micro-confined interfacial synthesis (MIS) approach for fabrication of a variety of free-standing MOF superstructures with desired shapes. This approach for engineering MOFs provides three key features: 1) in situ synthesis of various free-standing MOF superstructures with controlled compositions, shape, and thickness using a mold membrane; 2) adding magnetic functionality into MOF superstructures by loading with Fe3 O4 nanoparticles; 3) transferring the synthesized MOF superstructural array on to flat or curved surface of various substrates. The MIS route with versatile potential opens the door for a number of new perspectives in various applications.

High-risk metachronous polyps are more frequent in patients with traditional serrated adenomas than in patients with conventional adenomas: a multicenter prospective study.

BACKGROUND AND AIMS: Although the malignant progression of serrated polyps has been clearly documented, the malignant potential of the traditional serrated adenoma (TSA) subtype has not been established. We compared the prevalence of metachronous polyps in surveillance colonoscopies between patients with TSA and those with conventional adenomas (CAs). METHODS: Four hundred twenty patients were diagnosed with TSAs by current diagnostic criteria at 10 tertiary care university hospitals in Korea from January 2003 to December 2005; 186 patients who received surveillance colonoscopy after removal of initial polyps were enrolled. During the same time period, 372 age- and sex-matched patients diagnosed with CAs were used as a control group. RESULTS: TSA patients had a significantly higher recurrence rate of colorectal polyps compared with CA patients (66.1% vs 43.5%, respectively). TSA patients had a greater number (3 vs 2) and larger size (8.6 ± 5.7 vs 6.3 ± 5.2 mm) of recurrent polyps compared with CA patients. TSA patients also had a higher rate of CA (54.8% vs 37.9%), serrated adenoma (14.0% vs. 0.8%), and hyperplastic polyp (33.3% vs. 13.7%) recurrence compared with CA patients. TSA patients had significantly greater odds of having a recurrent high-risk polyp than CA patients (odds ratio, 2.37; 95% confidence interval, 1.55-3.63). CONCLUSIONS: In comparison with patients with CAs, patients with TSAs have a higher metachronous occurrence rate of all polyp subtypes including CAs, serrated adenomas, and hyperplastic polyps. Moreover, the presence of TSAs is an independent predictor of a high-risk polyp occurrence.

Randomized controlled trial of low-volume bowel preparation agents for colonic bowel preparation: 2-L polyethylene glycol with ascorbic acid versus sodium picosulfate with magnesium citrate.

PURPOSE: Both 2-L polyethylene glycol with ascorbic acid (2-L PEG/Asc) and sodium picosulfate with magnesium citrate (SP/MC) are low-volume combined agents for colonic preparation. The aim of the current study was to compare the preparation adequacy and patient tolerability of 2-L PEG/Asc and SP/MC. METHODS: We performed a prospective randomized controlled study in outpatients undergoing daytime colonoscopy at a tertiary academic hospital. We compared preparation adequacy based on the Boston Bowel Preparation Scale (BBPS), polyp and adenoma detection rate (PDR and ADR), compliance, tolerability for ease and palatability, intention to reuse, and patient satisfaction using a questionnaire between 2-L PEG/Asc and three sachets of SP/MC, both given in a split-dose method. RESULTS: A total of 388 patients were evaluated based on intention to treat (ITT) and 356 patients per protocol (PP). No significant differences in preparation adequacy were observed in ITT and PP analyses, based on the BBPS (p > 0.05). The PDR and ADR were greater than 60 and 40% in both groups, respectively (p > 0.05). Compliance levels were higher in the 2-L PEG/Asc group than in the SP/MC group (p < 0.001). Satisfaction (ITT, p = 0.014; PP, p = 0.032) and palatability (ITT and PP, p < 0.001) levels were higher in the SP/MC group than in the 2-L PEG/Asc group, but values for tolerability for ease and intention to reuse were similar in both groups (ITT and PP, p > 0.05). CONCLUSIONS: Both 2-L PEG/Asc and SP/MC had adequate bowel cleansing efficacy to satisfy PDR and ADR as quality indicator and had showed similar tolerability.

Clinical Characteristics and Treatment Outcomes of Cryptogenic Multifocal Ulcerous Stenosing Enteritis in Korea.

BACKGROUND: Cryptogenic multifocal ulcerous stenosing enteritis (CMUSE) is a rare disease that is characterized by multiple, recurring small intestinal ulcers with stenosis of unknown causes. The aim of this study was to investigate the clinical characteristics and the treatment outcomes of patients with CMUSE in Korea. METHODS: We performed a multicenter study to retrospectively analyze clinical data from 20 patients who suffered from CMUSE between 1984 and 2012. Their clinical characteristics and long-term disease courses were investigated. RESULTS: The most common initial symptom of CMUSE was abdominal pain (14/20, 70 %). Small bowel series (13/20, 65 %), double-balloon enteroscopy (12/20, 60 %), CT enterography (12/20, 60 %), and capsule endoscopy (10/20, 50 %) were used to diagnose CMUSE. The strictures of the patients were located in the jejunum (5/20, 25 %), ileum (7/20, 35 %), and both jejunum and ileum (6/20, 30 %). The number of patients in a state of remission, persistent disease, and relapse at the end of follow-up were 13/20 (65 %), 2/20 (10 %), and 5/20 (25 %), respectively. The median relapse-free survival was of 67.1 months. Seventy-five percent relapse-free survivals for female and male patients were 93 and 9 months, respectively (P = 0.031). CONCLUSION: CMUSE is difficult to diagnose and is an easily relapsing disease. Female patients might have a better prognosis than male patients in terms of the relapse-free time.

How to predict adequate bowel preparation before colonoscopy using conventional polyethylene glycol: prospective observational study based on survey.

BACKGROUND AND AIM: The present study investigated the conditions and predictive factors for adequate bowel preparation using 4-L polyethylene glycol (PEG) preparation in clinical practice. METHODS: We conducted a prospective-survey-based observational study. The survey consisted of 14 questions that assessed the preparation method (group 1: split method for morning colonoscopy; group 2: full-volume method for same-day afternoon colonoscopy; group 3: full-volume method for next-day morning colonoscopy), dinner type and timing the day before colonoscopy, elapsed time after PEG consumption, and stool character and defecation frequency immediately before colonoscopy. Preparation status was compared using the Boston bowel preparation scale (BBPS). RESULTS: Total of 465 surveys (391 for group 1, 55 for group 2, 19 for group 3) were conducted. Mean BBPS score was highest in group 1 and lowest in group 3 (P < 0.001). Fasting dinner before colonoscopy group showed a higher mean BBPS than the diet group; eating before 6 p.m. and a low-residue diet showed a higher mean BBPS (P < 0.05). Defecation frequency (>5 times) was related to adequate preparation in the left colon and elapsed time (<5 h) to that in the right colon (P < 0.05). Liquid stool without solid material immediately before colonoscopy was related to adequate preparation (P < 0.001). CONCLUSION: In bowel preparation with 4-L PEG, elapsed time after PEG consumption (<5 h), defecation frequency (>5 times) and liquid stool without solid material immediately before colonoscopy were predictive factors for adequate bowel preparation just before colonoscopy.

Keutel syndrome: report of two novel MGP mutations and discussion of clinical overlap with arylsulfatase E deficiency and relapsing polychondritis.

Keutel syndrome is a rare, autosomal recessive disorder characterized by diffuse cartilage calcification, peripheral pulmonary artery stenosis, midface retrusion, and short distal phalanges. To date, 28 patients from 18 families have been reported, and five mutations in the matrix Gla protein gene (MGP) have been identified. The matrix Gla protein (MGP) is a vitamin K-dependent extracellular protein that functions as a calcification inhibitor through incompletely understood mechanisms. We present the clinical manifestations of three affected siblings from a consanguineous Turkish family, in whom we detected the sixth MGP mutation (c.79G>T, which predicts p.E27X) and a fourth unrelated patient in whom we detected the seventh MGP mutation, a partial deletion of exon 4. Both mutations predict complete loss of MGP function. One of the patients presented initially with a working diagnosis of relapsing polychondritis. Clinical features suggestive of Keutel syndrome were also observed in one additional unrelated patient who was later found to have a deletion of arylsulfatase E, consistent with a diagnosis of X-linked recessive chondrodysplasia punctata. Through a discussion of these cases, we highlight the clinical overlap of Keutel syndrome, X-linked chondrodysplasia punctata, and the inflammatory disease relapsing polychondritis.

Long-term outcome of capsule endoscopy in obscure gastrointestinal bleeding: a nationwide analysis.

BACKGROUND AND STUDY AIMS: The clinical impact of video capsule endoscopy (VCE) in patients with obscure gastrointestinal bleeding (OGIB) remains undetermined. The aim of this study was to evaluate the long-term clinical impact of VCE in patients with OGIB using a nationwide registry. PATIENTS AND METHODS: Data from 305 patients who underwent VCE for OGIB from 13 hospitals in Korea between January 2006 and March 2009 were analyzed. Prospectively collected VCE registry data were reviewed, and follow-up data were collected by chart review and telephone interviews with patients. Multivariate regression analyses using hazard ratios (HR) were performed to determine risk factors for rebleeding. RESULTS: Significant findings were detected in 157 patients (51.5%). After VCE, interventional treatment was performed in 36 patients (11.8%). The overall rebleeding rate was 19.0% during a mean (±SD) follow-up of 38.7±26.4 months. Rebleeding rate did not differ by positive VCE results or application of interventional treatment. Multivariate analysis revealed that angiodysplasia (HR 1.82; 95% confidence interval [CI] 1.04-3.20; P=0.037) and duration of OGIB >3 months (HR 1.64; 95%CI 1.10-2.46; P=0.016) were independent prognostic factors associated with rebleeding. In a subgroup analysis of patients taking anticoagulants, patients who discontinued drugs after VCE showed a lower rebleeding rate than those who did not discontinue this therapy (P=0.019). CONCLUSIONS: VCE did not have a significant impact on the long-term outcome of patients with OGIB. Patients with angiodysplasia on VCE or OGIB>3 months need to be closely followed even after interventional treatment. In patients who are taking anticoagulants, discontinuation of drugs is necessary in order to lower the risk of rebleeding.

Portal hypertensive enteropathy diagnosed by capsule endoscopy in cirrhotic patients: a nationwide multicenter study.

BACKGROUND AND AIM: Due to the limited data on portal hypertensive enteropathy (PHE), the prevalence of and clinical factors related to PHE remain unclear. This study determined the prevalence of PHE using capsule endoscopy (CE) and PHE-related clinical factors. METHODS: This was a retrospective multicenter study using the Capsule Endoscopy Nationwide Database Registry. From 2,879 cases that underwent CE, 45 cirrhosis patients with portal hypertension (PH) were enrolled and divided into PHE (n = 18) and non-PHE (n = 27) groups. From computed tomography (CT) images, six secondary changes due to PH were scored to give a total CT score of 0-6. The main outcome variable was the prevalence of PHE and PHE-related clinical factors. RESULTS: The prevalence of PHE was 40 %. Comparing the PHE and non-PHE groups, the most common findings were angiodysplasias in 55.7 % (vs. 7.4 %, p = 0.001) and varices in 38.9 % (vs. 0 %, p = 0.001). Active bleeding was observed in 16.6 and 3.7 %, respectively, but this difference was not significant. In the univariate analysis, Child-Turcotte-Pugh class C (p = 0.002) and a high CT score (≥3 vs. <3, p = 0.004) were significantly associated with PHE. However, only a high CT score was significant in the multivariate analysis (odds ratio 11.19; 95 % confidence interval, 1.59-infinity; p = 0.040). CONCLUSIONS: The prevalence of PHE was 40 %, and it might be more prevalent in cirrhosis patients with PH who have a high CT score. CE is a useful diagnostic tool for evaluating PHE in cirrhosis patients with PH.

Rescreening colonoscopy practice after a negative index colonoscopy in a clinical setting; cross-sectional study for interval and outcomes of rescreening colonoscopy.

BACKGROUND/AIMS: We evaluated the rescreening colonoscopy practice after negative index colonoscopy (IC) in a real clinical setting. METHODOLOGY: We reviewed the individual records of aged over 40 who had negative IC at a single center between 2003 and 2005. The quality of the IC including bowel preparation (using Boston bowel preparation scale, BBPS), cecal intubation, withdrawal time and the incidence and risk factors for advanced lesions during the rescreening colonoscopy were analyzed. RESULTS: On 1570 negative ICs, 32.6% (n = 512) had rescreen ing colonoscopy until August, 2011. The rescreened group showed significantly lower quality of the IC compared to the group not rescreened (mean BBPS 7.9 vs. 8.2, p = 0.032, mean withdrawal time 5.2 vs. 5.7 minutes, p = 0.003). Rescreening detected polyps in 33.4% (n = 171) and advanced lesions in 3.7% (n = 19, 73.7% male; p = 0.022) including cancers (0.4%, n = 2). Male gender (odds ratio, 2.995; 95% confidence interval, 1.199-7.481) was an independent risk factors for advanced lesions on rescreening. CONCLUSIONS: Advanced lesions were detected in 3.7% of rescreening group after negative IC and male was a risk factor. Following a low-quality IC, a rescreening colonoscopy was performed with short interval in a clinical practice.

MAPK/ERK Signaling Pathway Analysis in Primary Osteoblasts From Patients With Nonsyndromic Sagittal Craniosynostosis.

OBJECTIVE: The MAPK/ERK signaling pathway has been implicated in several craniosynostosis syndromes and represents a plausible target for therapeutic management of craniosynostosis. The causes of sagittal nonsyndromic craniosynostosis (sNSC) have not been well understood and the role that MAPK/ERK signaling cascade plays in this condition warrants an investigation. We hypothesized that MAPK-signaling is misregulated in calvarial osteoblasts derived from patients with sNSC. METHODS: In order to analyze if the MAPK/ERK pathway is perturbed in sNSC, we established primary calvarial osteoblast cell lines from patients undergoing surgery for correction of this congenital anomaly. Appropriate negative and positive control cell lines were used for comparison, and we examined the levels of phosphorylated ERK by immunoblotting. RESULTS: Primary osteoblasts from patients with sNSC showed no difference in ERK1/2 phosphorylation with or without FGF2 stimulation as compared with control osteoblasts. CONCLUSION: Under the described test conditions, we did not observe convincing evidence that MAPK/ERK signaling contributes to the development of sNSC.