4-Hydroxy­phenyl 4-fluoro­benzoate

In the title compound, C13H9FO3, the dihedral angle between the two benzene rings is 59.86 (4)°. In the crystal, inter­molecular O—H⋯H hydrogen bonds lead to molecular chains propagating in [010]

Copy number variation at leptin receptor gene locus associated with metabolic traits and the risk of type 2 diabetes mellitus

<p>Abstract</p> <p>Background</p> <p>Recent efforts have been made to link complex human traits and disease susceptibility to DNA copy numbers. The leptin receptor (LEPR) has been implicated in obesity and diabetes. Mutations and genetic variations of <it>LEPR </it>gene have been discovered in rodents and humans. However, the association of DNA copy number variations at the <it>LEPR </it>gene locus with human complex diseases has not been reported. In an attempt to study DNA copy number variations associated with metabolic traits and type 2 diabetes mellitus (T2DM), we targeted the <it>LEPR </it>gene locus in DNA copy number analyses.</p> <p>Results</p> <p>We identified DNA copy number variations at the <it>LEPR </it>gene locus among a Korean population using genome-wide SNP chip data, and then quantified copy numbers of the E2 DNA sequence in the first two exons overlapped between <it>LEPR </it>and <it>LEPROT </it>genes by the quantitative multiplex PCR of short fluorescent fragment (QMPSF) method. Among the non-diabetic subjects (n = 1,067), lower E2 DNA copy numbers were associated with higher fasting glucose levels in men (<it>p </it>= 1.24 × 10^-7) and women (<it>p </it>= 9.45 × 10^-5), as well as higher total cholesterol levels in men (<it>p </it>= 9.96 × 10^-7). In addition, the significant association between lower E2 DNA copy numbers and lower level of postprandial 2hr insulin was evident only in non-diabetic women, whereas some obesity-related phenotypes and total cholesterol level exhibited significant associations only in non-diabetic men. Logistic regression analysis indicated that lower E2 DNA copy numbers were associated with T2DM (odds ratio, 1.92; 95% CI, 1.26~2.96; p < 0.003) in our nested case-control study. Interestingly, the E2 DNA copy number exhibited a negative correlation with LEPR gene expression, but a positive correlation with LEPROT gene expression.</p> <p>Conclusions</p> <p>This work suggests that a structural variation at the <it>LEPR </it>gene locus is functionally associated with complex metabolic traits and the risk of T2DM.</p

Efficacy of early immunomodulator therapy on the outcomes of Crohn’s disease

BACKGROUND: The natural course of Crohn’s disease (CD), with continuing relapses and remissions, leads to irreversible intestinal damage. Early adoption of immunomodulator therapy has been proposed in order to address this; however, it is still uncertain whether early immunomodulator therapy could affect the natural course of the disease in real practice. We evaluated the efficacy of such therapy on the prognosis of newly diagnosed patients with CD. METHODS: This retrospective study included 168 patients who were newly diagnosed with CD and who started treatment at Severance Hospital, Seoul, Korea between January 2006 and March 2013. The short- and long-term outcomes were compared between patients treated with early immunomodulator therapy and those treated with conventional therapy. RESULTS: A Kaplan-Meier analysis identified that administration of immunomodulators within 6 months after diagnosis of CD was superior to conventional therapy in terms of clinical remission and corticosteroid-free remission rates (P=0.043 and P=0.035). However, P=0.827). Patients with a baseline elevated CRP level were more likely to relapse (P<0.005). Drug-related adverse events were more frequent in the early immunomodulator therapy group than in the conventional therapy group P=0.029). CONCLUSIONS: Early immunomodulator therapy was more effective than conventional therapy in inducing remission, but not in preventing relapse. Baseline high CRP level was a significant indicator of relapse

Fatal Biliary-Systemic Air Embolism during Endoscopic Retrograde Cholangiopancreatography: A Case with Multifocal Liver Abscesses and Choledochoduodenostomy

We report a rare case of a massive fatal embolism that occurred in the middle of endoscopic retrograde cholangiopancreatography (ERCP) and retrospectively examine the significant causes of the event. The patient was a 50-year old female with an uncertain history of previous abdominal surgery for multiple biliary stones 20 years prior. The patient presented with acute right upper quadrant pain. An abdominal computed tomographic (CT) scan revealed the presence of multiple stones in the common bile duct (CBD) and intra-hepatic duct (IHD) with biliary obstruction, multifocal liver abscesses, and air-biliarygram. Emergency ERCP showed a wide and straight opening of choledochoduodenostomy, which may have been created during a previous surgery, and multiple filling defects in the CBD. With the use of a forward endoscope, mud stones were extracted through the opening of the choledochoduodenostomy. Cardiac arrest suddenly developed during the procedure, and despite immediate resuscitation, the patient died due to a massive systemic air embolism. We reviewed previously reported fatal cases and accessed factors facilitating air embolisms in this case

Collagen Immobilization on Ultra-thin Nanofiber Membrane to Promote In Vitro Endothelial Monolayer Formation

The endothelialization on the poly (epsilon-caprolactone) nanofiber has been limited due to its low hydrophilicity. The aim of this study was to immobilize collagen on an ultra-thin poly (epsilon-caprolactone) nanofiber membrane without altering the nanofiber structure and maintaining the endothelial cell homeostasis on it. We immobilized collagen on the poly (epsilon-caprolactone) nanofiber using hydrolysis by NaOH treatment and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/sulfo-N-hydroxysulfosuccinimide reaction as a cost-effective and stable approach. NaOH was first applied to render the poly (epsilon-caprolactone) nanofiber hydrophilic. Subsequently, collagen was immobilized on the surface of the poly (epsilon-caprolactone) nanofibers using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/sulfo-N-hydroxysulfosuccinimide. Scanning electron microscopy, Fourier transform infrared spectroscopy, transmission electron microscopy, and fluorescence microscopy were used to verify stable collagen immobilization on the surface of the poly (epsilon-caprolactone) nanofibers and the maintenance of the original structure of poly (epsilon-caprolactone) nanofibers. Furthermore, human endothelial cells were cultured on the collagen-immobilized poly (epsilon-caprolactone) nanofiber membrane and expressed tight junction proteins with the increase in transendothelial electrical resistance, which demonstrated the maintenance of the endothelial cell homeostasis on the collagen-immobilized-poly (epsilon-caprolactone) nanofiber membrane. Thus, we expected that this process would be promising for maintaining cell homeostasis on the ultra-thin poly (epsilon-caprolactone) nanofiber scaffolds.11Ysciescopu

The pioneer factor PBX1 is a novel driver of metastatic progression in ERalpha-positive breast cancer

Over 30% of ERalpha breast cancer patients develop relapses and progress to metastatic disease despite treatment with endocrine therapies. The pioneer factor PBX1 translates epigenetic cues and mediates estrogen induced ERalpha binding. Here we demonstrate that PBX1 plays a central role in regulating the ERalpha transcriptional response to epidermal growth factor (EGF) signaling. PBX1 regulates a subset of EGF-ERalpha genes highly expressed in aggressive breast tumours. Retrospective stratification of luminal patients using PBX1 protein levels in primary cancer further demonstrates that elevated PBX1 protein levels correlate with earlier metastatic progression. In agreement, PBX1 protein levels are significantly upregulated during metastatic progression in ERalpha-positive breast cancer patients. Finally we reveal that PBX1 upregulation in aggressive tumours is partly mediated by genomic amplification of the PBX1 locus. Correspondingly, ERalpha positive breast cancer patients carrying PBX1 amplification are characterized by poor survival. Notably, we demonstrate that PBX1 amplification can be identified in tumor derived-circulating free DNA of ERalpha positive metastatic patients. Metastatic patients with PBX1 amplification are also characterized by shorter relapse-free survival. Our data identifies PBX1 amplification as a functional hallmark of aggressive ERalpha-positive breast cancers. Mechanistically, PBX1 amplification impinges on several critical pathways associated with aggressive ERalpha positive breast cancer

Bowel Obstruction Caused by an Intramural Duodenal Hematoma: A Case Report of Endoscopic Incision and Drainage

Complications associated with an intramural hematoma of the bowel, is a relatively unusual condition. Most intramural hematomas resolve spontaneously with conservative treatment and the patient prognosis is good. However, if the symptoms are not resolved or the condition persists, surgical intervention may be necessary. Here we describe internal incision and drainage by endoscopy for the treatment of an intramural hematoma of the duodenum. A 63-yr-old woman was admitted to the hospital with hematemesis. The esophagogastroduodenoscopy (EGD) showed active ulcer bleeding at the distal portion of duodenal bulb. A total of 10 mL of 0.2% epinephrine and 2 mL of fibrin glue were injected locally. The patient developed diffuse abdominal pain and projectile vomiting three days after the endoscopic treatment. An abdominal computed tomography revealed a very large hematoma at the lateral duodenal wall, approximately 10×5 cm in diameter. Follow-up EGD was performed showing complete luminal obstruction at the second portion of the duodenum caused by an intramural hematoma. The patient's condition was not improved with conservative treatment. Therefore, 21 days after admission, endoscopic treatment of the hematoma was attempted. Puncture and incision were performed with an electrical needle knife. Two days after the procedure, the patient was tolerating a soft diet without complaints of abdominal pain or vomiting. The hematoma resolved completely on the follow-up studies