The Raf/MEK/extracellular signal-regulated kinase 1/2 pathway can mediate growth inhibitory and differentiation signaling via androgen receptor downregulation in prostate cancer cells.

Upregulated ERK1/2 activity is correlated with androgen receptor (AR) downregulation in certain prostate cancer (PCa) that exhibits androgen deprivation-induced neuroendocrine differentiation, but its functional relevance requires elucidation. We found that sustained ERK1/2 activation using active Raf or MEK1/2 mutants is sufficient to induce AR downregulation at mRNA and protein levels in LNCaP. Downregulation of AR protein, but not mRNA, was blocked by proteasome inhibitors, MG132 and bortezomib, indicating that the pathway regulation is mediated at multiple points. Ectopic expression of a constitutively active AR inhibited Raf/MEK/ERK-mediated regulation of the differentiation markers, neuron-specific enolase and neutral endopeptidase, and the cyclin-dependent kinase inhibitors, p16(INK4A) and p21(CIP1), but not Rb phosphorylation and E2F1 expression, indicating that AR has a specific role in the pathway-mediated differentiation and growth inhibitory signaling. However, despite the sufficient role of Raf/MEK/ERK, its inhibition using U0126 or ERK1/2 knockdown could not block androgen deprivation-induced AR downregulation in an LNCaP neuroendocrine differentiation model, suggesting that additional signaling pathways are involved in the regulation. We additionally report that sustained Raf/MEK/ERK activity can downregulate full length as well as hormone binding domain-deficient AR isoforms in androgen-refractory C4-2 and CWR22Rv1, but not in LAPC4 and MDA-PCa-2b. Our study demonstrates a novel role of the Raf/MEK/ERK pathway in regulating AR expression in certain PCa types and provides an insight into PCa responses to its aberrant activation

Analysis of Content Legibility for Smartphones of Websites of the Korean Urological Association and Other Urological Societies in Korea

Purpose: We performed an analysis of the smartphone legibility of the websites of the Korean Urological Association (KUA) and other urological societies. Materials and Methods: This study was conducted on the websites of the KUA and nine other urological societies. Each website was accessed via iPhone Safari and Android Chrome, respectively, to evaluate the establishment and readability of the mobile web pages. The provision of Really Simple Syndication (RSS) feeds by the websites and whether the websites had Twitter and Facebook accounts were evaluated. In addition, a validation test on the web standards was performed by using the World Wide Web Consortium (W3C???) Markup Validation Service, and subsequently the numbers of errors and warnings that occurred were analyzed. Results: When accessed via Safari, two websites were legible, four were somewhat legible, and four were somewhat illegible. When accessed via Chrome, two websites were legible, six were somewhat legible, and two were somewhat illegible. One website provided an RSS feed and two websites managed members via separate Twitter accounts. No website supported mobile web pages. The result of the W3C??? Markup Validation test on 10 websites showed a mean error rate of 221.6 (range, 13-1,477) and a mean warning rate of 127.13 (range, 0-655). Conclusions: The smartphone legibility level of the websites of urological societies was relatively low. Improved smartphone legibility and web standard compliance of the websites of urological societies are required to keep up with the popularity of smartphones

Paradoxical Air Embolism during Percutaneous Nephrolithotomy: A Case Report

Air embolism is a rare complication of percutaneous nephrolithotomy. Patent foramen ovale, which is necessary in fetal circulation, is a potential route for emboli arising from the venous system to enter the systemic arterial circulation, resulting in paradoxical air embolism syndrome. A case of paradoxical air embolism during percutaneous nephrolithotomy is presented. To our knowledge, this is the first report of paradoxical air embolism associated with patent foramen ovale during percutaneous nephrolithotomy

Comparative Genomic Analysis of the 2016 Vibrio cholerae Outbreak in South Korea

In August 2016, South Korea experienced a cholera outbreak that caused acute watery diarrhea in three patients. This outbreak was the first time in 15 years that an outbreak was not linked to an overseas source. To identify the cause and to study the epidemiological implications of this outbreak, we sequenced the whole genome of Vibrio cholerae isolates; three from each patient and one from a seawater sample. Herein we present comparative genomic data which reveals that the genome sequences of these four isolates are very similar. Interestingly, these isolates form a monophyletic Glade with V. cholerae strains that caused an outbreak in the Philippines in 2011. The V. cholerae strains responsible for the Korean and Philippines outbreaks have almost identical genomes in which two unique genomic islands are shared, and they both lack SXT elements. Furthermore, we confirm that seawater is the likely source of this outbreak, which suggests the necessity for future routine surveillance of South Korea's seashore.

Imaging the P‐Wave Velocity Structure of Arctic Subsea Permafrost Using Laplace‐Domain Full‐Waveform Inversion

Climate change in the Arctic has recently become a major scientific issue, and detailed information on the degradation of subsea permafrost on continental shelves in the Arctic is critical for understanding the major cause and effects of global warming, especially the release of greenhouse gases. The subsea permafrost at shallow depths beneath the Arctic continental shelves has significantly higher P‐wave velocities than the surrounding sediments. The distribution of subsea permafrost on Arctic continental shelves has been studied since the 1970s using seismic refraction methods. With seismic refraction data, the seismic velocity and the depth of the upper boundary of subsea permafrost can be determined. However, it is difficult to identify the lower boundary and the internal shape of permafrost. Here, we present two‐dimensional P‐wave velocity models of the continental shelf in the Beaufort Sea by applying the Laplace‐domain full‐waveform inversion method to acquired multichannel seismic reflection data. With the inverted P‐wave velocity model, we identify anomalous high seismic velocities that originated from the subsea permafrost. Information on the two‐dimensional distribution of subsea permafrost on the Arctic continental shelf area, including the upper and lower bounds of subsea permafrost, are presented. Also, the two‐dimensional P‐wave velocity model allows us to estimate the thawing pattern and the shape of subsea permafrost structures. Our proposed P‐wave velocity models were verified by comparison with the previous distribution map of subsea permafrost from seismic refraction analyses, geothermal modeling, and well‐log data

Oral intake of Lactobacillus rhamnosus M21 enhances the survival rate of mice lethally infected with influenza virus

BackgroundInfluenza viruses cause acute respiratory disease. Because of the high genetic variability of viruses, effective vaccines and antiviral agents are limited. Considering the fact that the site of influenza virus entry is the mucosa of the upper respiratory tract, probiotics that can enhance mucosal immunity as well as systemic immunity could be an important source of treatment against influenza infection.MethodsMice were fed with Lactobacillus rhamnosus M21 or skim milk and were challenged with influenza virus. The resulting survival rate, lung inflammation, and changes in the cytokine and secretory immunoglobulin A (sIgA) levels were examined.ResultsBecause of infection (influenza virus), all the mice in the control group and 60% of the mice in the L. rhamnosus M21 group died; however, the remaining 40% of the mice fed with L. rhamnosus M21 survived the infection. Pneumonia was severe in the control group but moderate in the group treated with L. rhamnosus M21. Although there were no significant changes in the proinflammatory cytokines in the lung lysates of mice collected from both groups, levels of interferon-γ and interleukin-2, which are representative cytokines of type I helper T cells, were significantly increased in the L. rhamnosus M21-treated group. An increase in sIgA as well as the diminution of inflammatory cells in bronchoalveolar lavage fluid was also observed in the L. rhamnosus M21-treated group.ConclusionThese results demonstrate that orally administered L. rhamnosus M21 activates humoral as well as cellular immune responses, conferring increased resistance to the host against influenza virus infection

Influence of Combined Methionine Synthase (MTR 2756A > G) and Methylenetetrahydrofolate Reductase (MTHFR 677C > T) Polymorphisms to Plasma Homocysteine Levels in Korean Patients with Ischemic Stroke

PURPOSE: Methionine synthase (MTR) and 5,10-methylenetetrahydrofolate reductase (MTHFR) are the main regulatory enzymes for homocysteine metabolism. The present case- control study was conducted to determine whether there is an association between the MTR 2756A > G or MTHFR 677C > T polymorphism and plasma homocysteine concentration in Korean subjects with ischemic stroke. MATERIALS AND METHODS: DNA samples of 237 patients who had an ischemic stroke and 223 age and sex-matched controls were studied. MTR 2756A > G and MTHFR 677C > T genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Frequencies of mutant alleles for MTR and MTHFR polymorphisms were not significantly different between the controls and cases. The patient group, however, had significantly higher homocysteine concentrations of the MTR 2756AA and MTHFR 677TT genotypes than the control group (p=0.04 for MTR, p=0.01 for MTHFR). The combined MTR 2756AA and MTHFR 677TT genotype (p= 0.04) and the homocysteine concentrations of the patient group were also higher than those of the controls. In addition, the genotype distribution was significant in the MTHFR 677TT genotype (p=0.008) and combined MTR 2756AA and MTHFR 677TT genotype (p=0.03), which divided the groups into the top 20% and bottom 20% based on their homocysteine levels. CONCLUSION: The results of the present study demonstrate that the MTR 2756A > G and MTHFR 677C > T polymorphisms interact with elevated total homocysteine (tHcy) levels, leading to an increased risk of ischemic stroke.ope

Hepatoid adenocarcinoma of the stomach: an unusual case of elevated alpha-fetoprotein with prior treatment for hepatocellular carcinoma

Hepatoid adenocarcinoma (HAC) is a rare type of extrahepatic carcinoma whose morphology is similar to that of hepatocellular carcinoma (HCC). Metachronous HCC and HAC in the same patient is extremely rare. The case of a 68-year-old man with chronic hepatitis B infection who had both HCC and HAC of the stomach is reported herein. Nine years previously this patient had been diagnosed with HCC and received a right lobectomy. HCC that recurred at the caudate lobe at 6 months after the operation was successfully treated with transarterial chemoembolization. The patient was followed up regularly thereafter without evidence of tumor recurrence for 9 years. In July 2010 his serum alpha-fetoprotein (AFP) level elevated from 6.5 ng/mL to 625.4 ng/mL, and he developed a probable single metastatic lymph node around the hepatic artery without intrahepatic lesions. Subsequent evaluation with upper endoscopy revealed a 4-cm ulcerative lesion on the antrum of the stomach. Subtotal gastrectomy was performed with lymph-node dissection. Histologic examination revealed a special type of extrahepatic AFP-producing adenocarcinoma-HAC with lymph-node metastasis-which indicates that HAC can be a cause of elevated AFP even in patients with HCC. HAC should be considered if a patient with stable HCC exhibits unusual elevation of AFP

Analgesic effect of highly reversible ω-conotoxin FVIA on N type Ca2+ channels

<p>Abstract</p> <p>Background</p> <p>N-type Ca²⁺channels (Ca_v2.2) play an important role in the transmission of pain signals to the central nervous system. ω-Conotoxin (CTx)-MVIIA, also called ziconotide (Prialt^®), effectively alleviates pain, without causing addiction, by blocking the pores of these channels. Unfortunately, CTx-MVIIA has a narrow therapeutic window and produces serious side effects due to the poor reversibility of its binding to the channel. It would thus be desirable to identify new analgesic blockers with binding characteristics that lead to fewer adverse side effects.</p> <p>Results</p> <p>Here we identify a new CTx, FVIA, from the Korean <it>Conus Fulmen </it>and describe its effects on pain responses and blood pressure. The inhibitory effect of CTx-FVIA on N-type Ca²⁺channel currents was dose-dependent and similar to that of CTx-MVIIA. However, the two conopeptides exhibited markedly different degrees of reversibility after block. CTx-FVIA effectively and dose-dependently reduced nociceptive behavior in the formalin test and in neuropathic pain models, and reduced mechanical and thermal allodynia in the tail nerve injury rat model. CTx-FVIA (10 ng) also showed significant analgesic effects on writhing in mouse neurotransmitter- and cytokine-induced pain models, though it had no effect on acute thermal pain and interferon-γ induced pain. Interestingly, although both CTx-FVIA and CTx-MVIIA depressed arterial blood pressure immediately after administration, pressure recovered faster and to a greater degree after CTx-FVIA administration.</p> <p>Conclusions</p> <p>The analgesic potency of CTx-FVIA and its greater reversibility could represent advantages over CTx-MVIIA for the treatment of refractory pain and contribute to the design of an analgesic with high potency and low side effects.</p