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"J Korean Neurosurg Soc"[jour]
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Thyrotropin-producing pituitary tumor is relatively rare. In particular, concurrent cases associated with Graves' disease are extremely rare and only nine cases have been reported so far. We describe a case of...
http://ift.tt/2imiyIF
A traumatic non-anastomotic pseudoaneurysm is a rare complication of an axillofemoral bypass graft. Fewer than 20 cases have been reported in the literature. Our case is unusual in that we report a double loca...
http://ift.tt/2iGWsEa
Although open injuries involving the brachial plexus are relatively uncommon, they can lead to permanent disability and even be life threatening if accompanied by vascular damage. We present a case report of a...
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Prepancreatic postduodenal portal vein is extremely rare, with only 13 cases reported in the literature.
http://ift.tt/2iGWko9
Hepatocellular carcinoma has a poor prognosis; few patients can undergo surgical curative treatment according to Barcelona Clinic Liver Cancer guidelines. Progress in surgical techniques has led to operations ...
http://ift.tt/2j3ePQp
Previous international consensus statements provided general policies for the management of Helicobacter pylori infection. However, there are geographic differences in the prevalence and antimicrobial resistance of H. pylori, and in the availability of medications and endoscopy. Thus, nationwide or regional consensus statements are needed to improve control of H. pylori infection and gastric cancer.
This consensus statement for management of H. pylori in Taiwan has three major sections: (1) optimal diagnosis and indications; (2) current treatment strategies; and (3) screening-to-treat and surveillance for control of gastric cancer. The literature review emphasized recent data for development of draft statements and determination of levels of evidence. Twenty-five Taiwan experts conducted a consensus conference, by a modified Delphi process, to modify the draft statements. Consensus, defined as an agreement of least 80% of the experts, and recommendation grade were determined by anonymous voting.
There were 24 consensus statements. Section 1 has seven statements on recommendations for the diagnosis and indications for treatment of H. pylori infection. Section 2 has 10 statements that provide an updated treatment algorithm for first-line, second-line, and third-line regimens. Section 3 has seven statements regarding H. pylori eradication for reducing the risk of gastric cancer, with a cost-benefit analysis. After H. pylori eradication, the consensus highlights the use of endoscopic surveillance and/or chemoprevention to further reduce the burden of gastric cancer.
This consensus statement has updated recommendations for improving the clinical management of H. pylori infection in areas such as Taiwan, which have high prevalence of H. pylori infection and gastric cancer.
Previous international consensus statements provided general policies for the management of Helicobacter pylori infection. However, there are geographic differences in the prevalence and antimicrobial resistance of H. pylori, and in the availability of medications and endoscopy. Thus, nationwide or regional consensus statements are needed to improve control of H. pylori infection and gastric cancer.
This consensus statement for management of H. pylori in Taiwan has three major sections: (1) optimal diagnosis and indications; (2) current treatment strategies; and (3) screening-to-treat and surveillance for control of gastric cancer. The literature review emphasized recent data for development of draft statements and determination of levels of evidence. Twenty-five Taiwan experts conducted a consensus conference, by a modified Delphi process, to modify the draft statements. Consensus, defined as an agreement of least 80% of the experts, and recommendation grade were determined by anonymous voting.
There were 24 consensus statements. Section 1 has seven statements on recommendations for the diagnosis and indications for treatment of H. pylori infection. Section 2 has 10 statements that provide an updated treatment algorithm for first-line, second-line, and third-line regimens. Section 3 has seven statements regarding H. pylori eradication for reducing the risk of gastric cancer, with a cost-benefit analysis. After H. pylori eradication, the consensus highlights the use of endoscopic surveillance and/or chemoprevention to further reduce the burden of gastric cancer.
This consensus statement has updated recommendations for improving the clinical management of H. pylori infection in areas such as Taiwan, which have high prevalence of H. pylori infection and gastric cancer.
A 31-year-old gentleman who had undergone an emergent esophagectomy and reconstruction with a colon interposition graft, presented with a long-standing cologastric stricture. He had undergone multiple attempts at endoscopic dilation over multiple decades with little symptomatic relief. He underwent a resection and reconstruction of the anastomosis entirely through an abdominal approach. He did well from surgery and experienced complete symptomatic relief immediately. Complications of colon interposition grafts can occasionally be treated using an abdominal incision only.
The rising use of endovascular techniques utilizing femoral artery access may increase the frequency with which surgeons face the challenge of hernia repair in reoperative groins—which may or may not include a vascular graft. We present a case where a vascular graft contributed to an acute presentation and complicated dissection, and review the literature. A 67-year-old man who had undergone prior endovascular aneurysm repair via open bilateral femoral artery access and concomitant prosthetic femorofemoral bypass, presented with an incarcerated, scrotal inguinal hernia. The graft with its associated fibrosis contributed to the incarceration by compressing the inguinal ring. Repair was undertaken via an open, anterior approach with tension-free, Lichtenstein herniorraphy after releasing graft-associated fibrosis. Repair of groin hernias in this complex setting requires careful surgical planning, preparation for potential vascular reconstruction and meticulous technique to avoid bowel injury in the face of a vascular conduit and mesh.
We report a rare case of a 46-year-old woman 2 weeks after a cesarean section with Pfannenstiel incision, who presented at the Emergency Department with a significant abdominal pain accompanied by two episodes of vomiting. After that a clinical examination and an abdominal computed tomography scan were completed, a visceral herniation through Pfannenstiel incision was suspected. The indication of surgical exploration was clear. Finally, the laparotomy revealed a linea arcuata hernia with a hernia of the small intestine. After a reduction of the hernia sac, the defect was repaired and no mesh was placed. An antibiotic treatment with co-amoxicillin for 1 week during the recovery was prescribed. The patient recovered uneventfully and could be discharged by postoperative day 7.
Publication date: Available online 7 January 2017
Source:Acta Biomaterialia
Author(s): Chuanxiong Nie, Ye Yang, Chong Cheng, Lang Ma, Jie Deng, Lingren Wang, Changsheng Zhao
The design of self-sterilizing surfaces with favorable biocompatibility is acknowledged as an effective approach to deal with the bacterial infections of biomedical devices. In this study, we report an intriguing protocol for the large-scale fabrication of self-sterilizing and biocompatible surface film coatings by using polymer shielded silver nanoparticle loaded oxidized carbon nanotube (AgNPs@oCNT) nano-dispersions. To achieve the antibacterial coatings, the bioinspired positively charged and negatively charged AgNPs@oCNTs were alternately deposited onto substrates by spray-coating assisted layer-by-layer assembly. Then the bacterial inhibitory zones, optical density value monitoring, bacterial killing efficiency and adhesion were investigated; and all the results revealed that the AgNPs@oCNTs thin film coatings exhibited robust and long-term antibacterial activity against both Gram negative and Gram positive bacteria. Moreover, due to the shielding effects of polymer layers, the coatings showed extraordinary blood compatibility and limited toxicity against human umbilical vein endothelial cells. It is believed that the proposed large-scale fabrication of bactericidal, blood and cell compatible AgNPs@oCNT based thin film coatings will have great potential to forward novel operational pathogenic inhibition strategies to avoid undesired bacterial contaminations of biomedical implants or biological devices.Statement of SignificanceBacterial infection of medical devices has been considered to be a world-wide clinical threat towards patients' health. In this study, a bioinspired and biocompatible antibacterial coating was prepared via the spray-assisted layer-by-layer (LbL) assembly. The silver nanopartilces loaded oxidized carbon nanotube (AgNPs@oCNT), which were coated by functional polymers (chitosan and synthetic heparin mimicking polymers), were prepared via mussel inspired chemistry; and the spray-assisted assembly process allowed the fast construction on devices. Owing to the antibacterial efficiency of the loaded AgNPs, the coating showed robust bacterial killing activity and resistance towards bacterial adhesion. Moreover, since that the AgNPs were shielded by the polymers, the coating exhibited no clear toxicity at blood or cellular level. Benefiting from the universal and large-scale fabrication advancements of the spray assisted LbL coating; it is believed that the proposed strategy can be applied in designing many other kinds of self-sterilizing biomedical implants and devices.
Publication date: Available online 8 January 2017
Source:Auris Nasus Larynx
Author(s): Pona Park, Joo Hyun Park, Ji Soo Kim, Ja-Won Koo
ObjectiveTo evaluate the lateralization value of video head-impulse test (vHIT) for the diagnosis of vestibulopathy and to analyze cases showing dissociated results with caloric test.MethodsIn total, 19 healthy volunteers and 92 dizzy patients who underwent both a caloric test and a vHIT were enrolled. Patients were divided into two groups depending on their fluctuating pattern of vertigo. The vestibulo-ocular reflex (VOR) gain and gain asymmetry (GA) of a vHIT as well as unilateral weakness (UW) and the sum of the slow-phase velocities (SPVs) of warm and cold irrigation of the same side were compared. A cutoff value of VOR gain of a vHIT was also calculated using a receiver-operating characteristic curve.ResultsA VOR gain in an affected ear and GA of a vHIT showed a statistically significant correlation with UW in a caloric test. The cutoff value of a vHIT was determined to be 0.875, derived under the assumption that UW of a caloric test ≤25% is normal. However, the parameters of the two tests were dissociated in 18%.ConclusionA VOR gain of vHIT is a valuable objective parameter with a lateralization value determining vestibular hypofunction. However, considering substantial dissociation between a vHIT and a caloric test, these tests can be complementary tools for the lateralization of vestibular impairment for the comprehensive evaluation of patients' VOR.
http://ift.tt/2iT4NlU
Perforator-Pedicled Propeller(PPP) Flap has been widely accepted for reconstruction of soft tissue defects as it requires a simple operative technique and has a consistent vascular pedicle1. However, according to a systematic review and meta-analysis2, the donor site was only self-closing in 69.7 percent (154 of 221), and covered by a skin graft in 30.3 percent of the cases (67 of 221). Besides, for patients with dead space infection of the defects, the regular PPP flap is difficult to achieve satisfactory results.
http://ift.tt/2i89Tw0
Publication date: Available online 7 January 2017
Source:Egyptian Journal of Ear, Nose, Throat and Allied Sciences
Author(s): Eng Haw Lim, Irfan Mohamad, Ramiza Ramza Ramli, Bhavaraju Venkata Murali Krishna
Metastatic disease of colorectal carcinoma can be present at the time of initial diagnosis or develop along the course of the disease. The liver is the most common site of distant metastasis of colorectal carcinoma. Other sites that are frequently involved include lung, peritoneum and bone. Head and neck involvement is extremely rare. We report a case of a middle-aged lady who was treated for colorectal carcinoma presented with infratemporal fossa metastasis 3years after the diagnosis of rectal carcinoma.
http://ift.tt/2iSmG6m
Publication date: Available online 7 January 2017
Source:Egyptian Journal of Ear, Nose, Throat and Allied Sciences
Author(s): N. Maithrea, Sandie Ewe, K.C. Pua, Irfan Mohamad
Neuroendocrine tumours (NETs) can arise in most organs of the body but are most frequently recorded in the gastrointestinal tract or lungs. They are rarely found in the head and neck region. The commonest site in the head and neck region is in the larynx. NETS in the larynx are almost invariably primary in origin. We describe a case of a middle-aged gentleman, a chronic smoker who was diagnosed with primary large cell neuroendocrine carcinoma of larynx with cervical nodal metastases. Large cell neuroendocrine carcinoma of larynx is a rare subset of NETs with a markedly more aggressive clinical course. He was initially treated with radiotherapy, and subsequently underwent total laryngectomy, total glossectomy. Right radical neck dissection and reconstruction with pectoralis major myocutaneous flap.
http://ift.tt/2j76yf4
Publication date: Available online 7 January 2017
Source:Egyptian Journal of Ear, Nose, Throat and Allied Sciences
Author(s): Eng Haw Lim, Irfan Mohamad, Ramiza Ramza Ramli, Bhavaraju Venkata Murali Krishna
Metastatic disease of colorectal carcinoma can be present at the time of initial diagnosis or develop along the course of the disease. The liver is the most common site of distant metastasis of colorectal carcinoma. Other sites that are frequently involved include lung, peritoneum and bone. Head and neck involvement is extremely rare. We report a case of a middle-aged lady who was treated for colorectal carcinoma presented with infratemporal fossa metastasis 3years after the diagnosis of rectal carcinoma.
http://ift.tt/2iSmG6m
Publication date: Available online 7 January 2017
Source:Egyptian Journal of Ear, Nose, Throat and Allied Sciences
Author(s): N. Maithrea, Sandie Ewe, K.C. Pua, Irfan Mohamad
Neuroendocrine tumours (NETs) can arise in most organs of the body but are most frequently recorded in the gastrointestinal tract or lungs. They are rarely found in the head and neck region. The commonest site in the head and neck region is in the larynx. NETS in the larynx are almost invariably primary in origin. We describe a case of a middle-aged gentleman, a chronic smoker who was diagnosed with primary large cell neuroendocrine carcinoma of larynx with cervical nodal metastases. Large cell neuroendocrine carcinoma of larynx is a rare subset of NETs with a markedly more aggressive clinical course. He was initially treated with radiotherapy, and subsequently underwent total laryngectomy, total glossectomy. Right radical neck dissection and reconstruction with pectoralis major myocutaneous flap.
http://ift.tt/2j76yf4
To evaluate the lateralization value of video head-impulse test (vHIT) for the diagnosis of vestibulopathy and to analyze cases showing dissociated results with caloric test.
http://ift.tt/2i7ShjK
The aim of this study is to evaluate whether adding the item of "apple body type" to the STOP-BANG questionnaire enhances diagnostic performance of the questionnaire for detecting obstructive sleep apnea (OSA).
http://ift.tt/2iszSfm
To evaluate the lateralization value of video head-impulse test (vHIT) for the diagnosis of vestibulopathy and to analyze cases showing dissociated results with caloric test.
http://ift.tt/2i7ShjK
Publication date: Available online 8 January 2017
Source:Sensors and Actuators B: Chemical
Author(s): Jiaqing Guo, Yanping Lin, Hao Huang, Shichao Zhang, Tingting Huang, Wen Weng
A facile one-pot solvothermal strategy was used to prepare fluorescent carbon nitride nanoparticles (CNNPs) using tartaric acid and urea as carbon and nitrogen sources at relatively low temperatures. The obtained CNNPs were characterized by multiple analytical techniques. The CNNPs with fluorescence (FL) quantum yield up to 17.9% exhibited excellent selectivity and sensitivity of fluorescence quenching for free chlorine. The quenching rate was quick, and the linear response range of free chlorine was from 0 to 30μM. The limit of detection (LOD) was as low as 13nM, which was much lower than that of the most widely used N,N-diethyl-p-phenylenediamine (DPD) colorimetric method. This sensing system exhibits many advantages, such as short response time (less than 1min), excellent selectivity, high sensitivity, and wide linear response range. The results show that this method has promising potential applications in the detection of free chlorine in real water samples.
http://ift.tt/2iXnSpL
| Related Articles |
Stent-Assisted Coiling May Prevent the Recurrence of Very Small Ruptured Intracranial Aneurysms: A Multicenter Study.
World Neurosurg. 2017 Jan 03;:
Authors: Zhang Y, Yang M, Zhang H, Zhang X, Li Y, Jiang C, Liu J, Yang X
Abstract
OBJECTIVE: To evaluate the safety and efficacy of endovascular treatments, including stent-assisted coiling, of very small (≤3 mm), ruptured intracranial aneurysms.
METHODS: Ninety-three endovascularly treated patients with very small ruptured aneurysms were recruited from four high-volume centers between September 2010 and February 2014. Factors influencing procedural complications and outcomes were analyzed.
RESULTS: Fifty-one (54.8%) aneurysms were treated by stent-assisted coiling, 41 (44.1%) by coiling alone, and 1 (1.1%) by balloon-assisted coiling. Intraprocedural or postprocedural complications occurred in 13 patients (14.0%): coil migration in one , intraprocedural rupture in one, hydrocephalus in six and ischemic event in one. No tested factor was able to predict procedural complications. Angiographic follow-up of 67 aneurysms (72%) revealed recurrence in five patients (7.5%). One recurrent case was treated initially by stent-assisted coiling and the remaining four by coiling alone (p=0.044). Multivariate regression analysis showed that coiling alone was significantly associated with aneurysm recurrence (odds ratio, 13.8; 95% confidence interval, 1.1-175.3; p=0.043).
CONCLUSIONS: Endovascular treatment of very small ruptured aneurysms was safe and effective and was not associated with a high rate of intraprocedural rupture. Treatment using stents significantly lowered the recurrence rate without additional risks.
PMID: 28062369 [PubMed - as supplied by publisher]
Publication date: 1 March 2017
Source:European Journal of Pharmaceutical Sciences, Volume 99
Author(s): Camila Martins Kawakami, Leandro Nériton Cândido Máximo, Bianca Bueno Fontanezi, Roberto Santana da Silva, Lorena Rigo Gaspar
The aim of the present study was to investigate the photochemical behavior of DHHB and its photostabilizing effect on avobenzone (AVO) in different sunscreen formulations. The formulations were subjected to photostability studies by HPLC and spectrophotometry. In vitro phototoxicity was assessed using 3T3 fibroblast cultures. The mechanism of interaction between DHHB and AVO was investigated by steady state and time-resolved fluorescence spectroscopy. All formulations provided ultra-protection against UVA radiation. HPLC results demonstrated that DHHB did not present a photostabilizing effect on AVO. Fluorescence spectroscopy showed that AVO and DHHB interact by a static quenching mechanism and DHHB did not affect the AVO excited state lifetime. In addition, the energy transfer by Förster mechanism (FRET), which is the most often mechanism responsible for singlet-singlet quenching, is unlikely in this work. These results suggest why DHHB did not work as a photostabilizer on AVO singlet excited state. Phototoxicity results demonstrated that combinations containing DHHB (C2) did not show a phototoxic potential. Finally, although DHHB was considered to be photostable for all formulations studied (F2 and F3) it did not increase the photostability of AVO (F3). Thus, we suggested that formulations containing DHHB (F2) should be considered more advantageous than formulations containing AVO and AVO/DHHB (F1 and F3 respectively).
Publication date: 1 March 2017
Source:European Journal of Pharmaceutical Sciences, Volume 99
Author(s): Antonio J. Ruiz-Alcaraz, María Tristán-Manzano, Antonio Guirado, Jesús Gálvez, María Martínez-Esparza, Pilar García-Peñarrubia
Inflammation is part of a complex biological response directed by the immune system to fight pathogens and maintain homeostasis. Dysregulation of the inflammatory process leads to development of chronic inflammatory or autoimmune diseases. Several cell types, such as macrophages, and cytokines such as interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) are involved in the regulation of inflammation. The important role played by these cytokines as mediators of the inflammatory process and the side effects of current therapies have promoted the search of new therapeutic alternatives. Quinoxalines are important compounds allowing a wide range of chemical modifications in order to provide an extensive repertoire of biological activities. We have previously shown that a series of 4-alkoxy-6,9-dichloro[1,2,4]triazolo[4,3-a]quinoxalines exhibit potent anti-inflammatory activity, inhibiting the production of TNF-α and IL-6. Our aim here was to study the mechanism thereby this series of compounds act upon different intracellular signaling pathways to uncover their potential molecular targets. By using immunoblotting assays, we found that these compounds inhibit ERK 1/2 and JNK/c-Jun cascades, and reduce c-Fos expression, while activate the anti-inflammatory PI3K/Akt route. These results provide further information on their effect upon the intracellular signal transduction mechanisms leading to inhibition of TNF-α and IL-6 secretion. Our results may be of great interest for the pharmaceutical industry, and could be used as a starting point for the development of new and more potent anti-inflammatory drugs derived from the quinoxaline core.
Publication date: 1 March 2017
Source:European Journal of Pharmaceutical Sciences, Volume 99
Author(s): Cristiane R.D. Hoffmeister, Cinira Fandaruff, Maíra A. da Costa, Lucio M. Cabral, Luciana R. Pitta, Stanley E.R. Bilatto, Livia D. Prado, Daniel S. Corrêa, Leandro Tasso, Marcos Antônio S. Silva, Helvécio V.A. Rocha
Efavirenz (EFV), a non-nucleoside reverse transcriptase inhibitor (NNRTI), is part of first-line therapy for the treatment of human immunodeficiency virus type 1 infection (HIV-1/AIDS). This drug shows relatively low oral absorption and bioavailability, as well as high intra- and inter-subject variability. Several studies have shown that treatment failure and adverse effects are associated with low and high EFV plasma concentrations, respectively. Some studies suggest different EFV formulations to minimize inter-patient variability and improve its solubility and dissolution; however, all of these formulations are complex, using for instance, cyclodextrins, dendrimers and polymeric nanoparticles, rendering them inviable industrially. The aim of this work was to prepare simple and low-cost suspensions of EFV for improvement of solubility and dissolution rate by using colloid mill, spray or freeze-drying, and characterization of the powders obtained. The results demonstrated an increase in the dissolution rate of EFV, using 0.2% of sodium lauryl sulfate (SLS) and 0.2% of hydroxypropylcellulose (HPC) or hydroxypropylmetilcellulose (HPMC) in both freeze and spray dried powders. The pharmacokinetic studies demonstrated improved pharmacokinetic parameters for the formulation containing SLS and HPC. The powders obtained, which present enhanced dissolution properties, can be incorporated in a solid dosage form for treatment of AIDS in paediatric patients with promising results.
Children with sensorineural hearing loss have risk of surgically induced vestibular dysfunction post cochlear implantation due to instrumentation. It is clinically important to estimate the risk of vestibular loss post cochlear implant so the patient can be made fully aware of these risks when considering cochlear implantation. The aim of the study was to identify compensated vestibular dysfunction post cochlear implantation. Vestibular function was evaluated both pre and post CI using monothermal warm air caloric testing. Recordings were made using head band camera on SYNAPSYS Ulmer VNG software. 'Monothermal caloric asymmetry' (MCA) was depicted as 'unilateral weakness' based on the slow phase velocity of nystagmus. MCA of >15% was taken as evidence of canal paresis. The incidence of compensated vestibular dysfunction post CI surgery was found to be 16.66%. The results were statistically significant (p value 0.02) and indicated worsening of canal paresis indicative of vestibular dysfunction. Children for cochlear implantation should undergo evaluation of their vestibular system pre and post surgery. Caution should be exercised before planning bilateral cochlear implantation in the same sitting.
Publication date: Available online 8 January 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Simone Conci, Andrea Ruzzenente, Marco Sandri, Francesca Bertuzzo, Tommaso Campagnaro, Fabio Bagante, Paola Capelli, Mirko D'Onofrio, Marco Piccino, Adriano E. Dorna, Corrado Pedrazzani, Calogero Iacono, Alfredo Guglielmi
BackgroundWe compared the prognostic performance of the International Union Against Cancer/American Joint Committee on Cancer (UICC/AJCC) 7th edition pN stage, number of metastatic LNs (MLNs), LN ratio (LNR), and log odds of MLNs (LODDS) in patients with perihilar cholangiocarcinoma (PCC) undergoing curative surgery in order to identify the best LN staging method.MethodsNinety-nine patients who underwent surgery with curative intent for PCC in a single tertiary hepatobiliary referral center were included in the study. Two approaches were used to evaluate and compare the predictive power of the different LN staging methods: one based on the estimation of variable importance with prediction error rate and the other based on the calculation of the receiver operating characteristic (ROC) curve.ResultsLN dissection was performed in 92 (92.9%) patients; 49 were UICC/AJCC pN0 (49.5%), 33 pN1 (33.3%), and 10 pN2 (10.1%). The median number of LNs retrieved was 8. The prediction error rate ranged from 42.7% for LODDS to 47.1% for UICC/AJCC pN stage. Moreover, LODDS was the variable with the highest area under the ROC curve (AUC) for prediction of 3-year survival (AUC = 0.71), followed by LNR (AUC = 0.60), number of MLNs (AUC = 0.59), and UICC/AJCC pN stage (AUC = 0.54).ConclusionsThe number of MLNs, LNR, and LODDS appear to better predict survival than the UICC/AJCC pN stage in patients undergoing curative surgery for PCC. Moreover, LODDS seems to be the most accurate and predictive LN staging method.
http://ift.tt/2iWEQVc
Angiopoietin pathway gene expression associated with poor breast cancer survival.
Breast Cancer Res Treat. 2017 Jan 06;:
Authors: Ramanathan R, Olex AL, Dozmorov M, Bear HD, Fernandez LJ, Takabe K
Abstract
PURPOSE: Angiogenesis is one of the hallmarks of cancer and is essential for cancer progression and metastasis. However, clinical trials with vascular endothelial growth factor (VEGF) pathway inhibitors have failed to show overall survival benefit in breast cancer. Targeted therapy against the angiopoietin pathway, a downstream angiogenesis cascade, could be effective in breast cancer. This study investigates the association of angiopoietin pathway gene expression with breast cancer survival using a "big data" approach employing RNA sequencing data from The Cancer Genome Atlas (TCGA).
METHODS: A total of 888 patients with adequate gene expression, disease-free survival (DFS), and overall survival (OS) data were selected for analysis. DFS and OS were calculated for patients with high and low expression of angiopoietin and VEGF pathway genes using TCGA data. Gene-specific thresholds to dichotomize patients into high and low expression were determined and survival plots were generated.
RESULTS: The TCGA cohort was representative of national breast cancer patients with respect to stage, pathology, and survival. High Ang2 gene expression was associated with not only decreased DFS (p = 0.05), but also decreased OS (p < 0.05). High co-expression of Ang2 and its receptor Tie2 was associated with both decreased DFS and OS (p < 0.05). There was strong correlation between angiopoietin and VEGF pathway genes. While high expression of VEGFA alone was not associated with survival, high co-expression with Ang2 was associated with decreased OS.
CONCLUSIONS: This study validates TCGA as a representative database providing genomic data and survival outcomes in breast cancer. Our TCGA data support the angiopoietin pathway as a key mediator in the pathologic angiogenic switch in breast cancer.
PMID: 28062977 [PubMed - as supplied by publisher]
Publication date: 15 March 2017
Source:Behavioural Brain Research, Volume 321
Author(s): Caterina Palleria, Antonio Leo, Francesco Andreozzi, Rita Citraro, Michelangelo Iannone, Rosangela Spiga, Giorgio Sesti, Andrew Constanti, Giovambattista De Sarro, Franco Arturi, Emilio Russo
Diabetes has been identified as a risk factor for cognitive dysfunctions. Glucagone like peptide 1 (GLP-1) receptor agonists have neuroprotective effects in preclinical animal models. We evaluated the effects of GLP-1 receptor agonist, liraglutide (LIR), on cognitive decline associated with diabetes. Furthermore, we studied LIR effects against hippocampal neurodegeneration induced by streptozotocin (STZ), a well-validated animal model of diabetes and neurodegeneration associated with cognitive decline. Diabetes and/or cognitive decline were induced in Wistar rats by intraperitoneal or intracerebroventricular injection of STZ and then rats were treated with LIR (300μg/kg daily subcutaneously) for 6 weeks. Rats underwent behavioral tests: Morris water maze, passive avoidance, forced swimming (FST), open field, elevated plus maze, rotarod tests. Furthermore, LIR effects on hippocampal neurodegeneration and mTOR pathway (AKT, AMPK, ERK and p70S6K) were assessed. LIR improved learning and memory only in STZ-treated animals. Anxiolytic effects were observed in all LIR-treated groups but pro-depressant effects in CTRL rats were observed. At a cellular/molecular level, intracerebroventricular STZ induced hippocampal neurodegeneration accompanied by decreased phosphorylation of AMPK, AKT, ERK and p70S6K. LIR reduced hippocampal neuronal death and prevented the decreased phosphorylation of AKT and p70S6K; AMPK was hyper-phosphorylated in comparison to CTRL group, while LIR had no effects on ERK. LIR reduced animal endurance in the rotarod test and this effect might be also linked to a reduction in locomotor activity during only the last two minutes of the FST. LIR had protective effects on cognitive functions in addition to its effects on blood glucose levels. LIR effects in the brain also comprised anxiolytic and pro-depressant actions (although influenced by reduced endurance). Finally, LIR protected from diabetes-dependent hippocampal neurodegeneration likely through an effect on mTOR pathway.
This study tested the effect of enamel salivary exposure time prior to an acid challenge (30 min, 1, 2, or 12 h) and type of intraoral appliance (palatal or mandibular) on initial erosion.
After initial surface hardness evaluation, enamel blocks (n = 340) were randomly divided into groups and volunteers (n = 20). The control group was not exposed to saliva previously to the erosive challenge. The volunteers wore palatal and mandibular appliances simultaneously. After salivary exposure, the blocks were subjected to acid exposure by immersion in hydrochloric acid (0.01 M, pH 2.3) for 30 s. Then, the enamel surface hardness was evaluated. Data were analyzed using ANOVA, Kruskal–Wallis and Tukey's test (p < 0.05).
No difference was observed on percent surface hardness change (% SHC) in the enamel blocks between the types of intraoral appliances. Exposure to saliva for 30 min and 1 h promoted similar enamel resistance to the erosive attack, which was similar to the control group for both appliances. Blocks exposed to saliva for 2 h showed less hardness loss when compared to 30 min. Keeping the blocks in saliva during 12-h overnight resulted in similar percentage of enamel hardness loss compared to 2 h.
A 2-hour in situ exposure to saliva is adequate to promote partial protection against initial erosive lesions, independently of the type of intraoral appliance used.
This finding will help researchers in the development of erosion studies, which will provide information for dentists to offer a better treatment for erosion.
The photocatalytic removal of nitrate with simultaneous hydrogen generation was demonstrated using zero-valent nano-copper-modified titania (P25) as photocatalyst in the presence of UV-A-Vis radiation. Glycerol, a by-product in biodiesel production, was chosen as a hole scavenger. Under the adopted experimental conditions, a nitrate removal efficiency up to 100% and a simultaneous hydrogen production up to 14 μmol/L of H2 were achieved (catalyst load = 150 mg/L, initial concentration of nitrate = 50 mg/L, initial concentration of glycerol = 0.8 mol/L). The reaction rates were independent of the starting glycerol concentration. This process allows accomplishing nitrate removal, with the additional benefit of producing hydrogen under artificial UV-A radiation. A kinetic model was also developed and it may represent a benchmark for a detailed understanding of the process kinetics. A set of acute and chronic bioassays (Vibrio fischeri, Raphidocelis subcapitata, and Daphnia magna) was performed to evaluate the potential ecotoxicity of the nitrate/by-product mixture formed during the photocatalytic process. The ecotoxicological assessment indicated an ecotoxic effect of oxidation intermediates and by-products produced during the process.
Within the context of global climate changes, it is expected that low-lying coastal freshwater ecosystems will face seawater intrusion with concomitant increase in salinity levels. Increased salinity may provoke disruption of competitive relationships among freshwater species. However, species may be capable of acclimating to salinity, which, in turn, may influence the resilience of ecosystems. Accordingly, this work aimed at assessing the effects of multigenerational exposure to low levels of salinity in the competitive outcome of two species of green microalgae: Raphidocelis subcapitata and Chlorella vulgaris. To attain this, three specific objectives were delineated: (1) compare the toxicity of natural seawater (SW) and NaCl (as a surrogate of SW) to the two microalgae, (2) determine the capacity of the two microalgae species to acclimate to low salinity levels, and (3) assess the influence of exposure to low salinity levels in the competitive outcome of the two microalgae. Results revealed SW to be slightly less toxic than NaCl for the two microalgae. The EC25,72 h for growth rate was 4.63 and 10.3 mS cm−1 for R. subcapitata and 6.94 and 15.4 mS cm−1 for C. vulgaris, respectively for NaCl and SW. Both algae were capable of acclimating to low levels of salinity, but C. vulgaris seemed to acclimate faster than R. subcapitata. When exposed in competition, under control conditions, the growth rates of C. vulgaris were lower than those of R. subcapitata. However, C. vulgaris was capable of acquiring competitive advantage equaling or surpassing the growth rate of R. subcapitata with the addition of NaCl or SW, respectively. The multigenerational exposure to low levels of salinity influenced the competitive outcome of the two algae both under control and salinity exposure. These results suggest that long-term exposure to low salinity stress can cause shifts in structure of algae communities and, therefore, should not be neglected since algae are at the basis of food web constituting important energetic resources to higher trophic levels.
Adsorption of copper ions onto chitosan films was studied, and the matrix effect was evaluated using a synthetic solution and a real effluent from closed copper mine. Chitosan films were prepared by casting technique and characterized. The adsorption study was carried out by equilibrium isotherms, thermodynamics, and kinetics. The thermodynamic parameters indicated that the copper adsorption onto chitosan film was favorable, spontaneous, and exothermic, suggesting an increased randomness at the solid/solution interface. The matrix effect was evaluated in kinetic assays, where a synthetic solution and a real system were carried out at different stirring rates. The highest values of adsorption capacity reached in all stirring rates were about 20% lower in the real effluent, and this reduction in the competitiveness was due to the presence of other ions in the matrix of the real effluent. The maximum adsorption capacity of copper ions onto chitosan films for the synthetic solution was of 450 mg g−1, and the removal percentage was in the range from 78 to 96%, and these values for the real effluent were of 360 mg g−1 and removal ranging from 62 to 76%. The mapping done of ions present in the water adsorbed of the mine in the films showed that the same was homogeneously distributed in the films' surfaces.
Activated carbon (AC)/CoFe2O4 nanocomposites, MAC-1 and MAC-2, were prepared by a simple pyrolytic method using a mixture of iron(III)/cobalt(II) benzoates and iron(III)/cobalt(II) oxalates, respectively, and were used as efficient adsorbents for the removal of amoxicillin (AMX) and paracetamol (PCT) of aqueous effluents. The synthesized nanocomposites were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), vibrating sample magnetometry (VSM), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX) and transmission electron microscopy (TEM). The sizes of cobalt ferrite nanoparticles formed from benzoates of iron(III)/cobalt(II) and oxalates of iron(III)/cobalt(II) precursors were in the ranges of 5–80 and 6–27 nm, respectively. The saturation magnetization (M s), remanence (M r) and coercivity (H c) of the MAC-2 nanocomposites were found to be 3.07 emu g−1, 1.36 emu g−1 and 762.49 Oe; for MAC-1, they were 0.2989 emu g−1, 0.0466 emu g−1 and 456.82 Oe. The adsorption kinetics and isotherm studies were investigated, and the results showed that the as-prepared nanocomposites MAC-1 and MAC-2 could be utilized as an efficient, magnetically separable adsorbent for environmental cleanup. The maximum sorption capacities obtained were 280.9 and 444.2 mg g−1 of AMX for MAC-1 and MAC-2, respectively, and 215.1 and 399.9 mg g−1 of PCT using MAC-1 and MAC-2, respectively. Both adsorbents were successfully used for simulated hospital effluents, removing at least 93.00 and 96.77% for MAC-1 and MAC-2, respectively, of a mixture of nine pharmaceuticals with high concentrations of sugars, organic components and saline concentrations.
Particulate matter (PM10) associated with the fractions of organic macromolecules, including humic acid (HA), kerogen + black carbon (KB), and black carbon (BC), was determined during summer and winter at urban and suburban sites in a coastal city of southeast China. The organic macromolecules were characterized by elemental analysis (EA), scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR), and their sources were identified by using stable carbon/nitrogen isotope (δ13C/δ15N) and the Hybrid Single Particle Lagrangian Integrated Trajectory (HYSPLIT) Model. The results showed that HA, kerogen (K), and BC accounted for the range of 3.89 to 4.55 % in PM10, while they were the dominant fractions of total organic carbon (TOC), ranging from 64.70 to 84.99 %. SEM analysis indicated that BC particles were porous/nonporous and consisted of spherical and non-spherical (i.e., cylindrical and elongate) structures. The FTIR spectra of HA, KB, and BC exhibited similar functional groups, but the difference of various sites and seasons was observed. HA in PM10 contained a higher fraction of aliphatic structures, such as long-chain fatty and carbohydrates with a carboxylic extremity. The C/N ratio, SEM, and δ13C/δ15N values provided reliable indicators of the sources of HA, K, and BC in PM10. The results suggested that HA and K majorly originated from terrestrial plants, and BC came from the mixture of combustion of terrestrial plants, fossil fuel, and charcoal. The air masses in winter originated from Mongolia (4 %), the northern area of China (48 %), and northern adjacent cities (48 %), suggesting the influence of anthropogenic sources through long-range transport, while the air masses for the summer period came from South China Sea (34 %) and Western Pacific Sea (66 %), representing clean marine air masses with low concentrations of organic macromolecules.
Publication date: Available online 7 January 2017
Source:Radiotherapy and Oncology
Author(s): Christian Graeff
Background and purposeMoving targets could be conformally treated with actively scanned carbon ion beams using 4D-optimization. As this heavily exploits 4D-CTs, an important question is whether the conformity also upholds in the context of interfractional changes, i.e. variable positioning, anatomy and breathing patterns.Materials and methodsIn 4 lung cancer patients, 6 weekly 4D-CTs were available. 4D-CTs and their phases were non-rigidly registered to propagate contours and 4D-doses. On the first 4D-CT, a 4D-optimized plan delivering a uniform dose to each motion phase (total dose 9.4Gy(RBE)) was simulated, as well as an ITV plan for comparison. On the five following 4D-CTs, 4D-dose was forward calculated and evaluated for target coverage and conformity. Variable uniform (3–7mm) and range margins (2mm/%) were investigated.ResultsFor all patients, target coverage (V95>95% accumulated over 5 fractions) could be achieved, but with variable margin size weakly depending on motion amplitude and range changes. The same margins were also necessary for ITV plans, which lead to lower conformity and higher integral doses.Conclusion4D-optimization appears feasible also under interfractional changes and maintains a dosimetric advantage over less conformal ITV irradiations. Further studies are needed to identify patients benefiting most from the technically more complex 4D-optimization.
http://ift.tt/2iRHrNG
Publication date: Available online 7 January 2017
Source:Radiotherapy and Oncology
Author(s): Ahsan S. Farooqi, Emma B. Holliday, Pamela K. Allen, Xiong Wei, James D. Cox, Ritsuko Komaki
PurposeProphylactic cranial irradiation (PCI) can improve overall survival (OS) and suppress brain metastases (BM) in patients with limited-stage small cell lung cancer (LS-SCLC) after complete response to primary therapy. However, PCI can be toxic. We sought to identify characteristics of patients who may not benefit from PCI.MethodsWe identified 658 patients who received chemoradiotherapy at MD Anderson in 1986–2012; 364 received PCI and 294 did not. Median follow-up time was 21.2months (range 1.2–240.8months). Cox proportional hazards regression, competing-risk regression, and Kaplan–Meier analyses were used to identify factors influencing OS and BM.ResultsPCI reduced risks of death [HR 0.73, 95% CI 0.61–0.88, P=0.001] and BM [HR 0.54, 95% CI 0.39–0.76, P<0.001]. Having tumors ⩾5cm increased the risk of BM [HR 1.77, 95% CI 1.22–2.55, P=0.002] but not death [HR 1.16, 95% CI 0.96–1.40, P=0.114]. Among patients ⩾70years with ⩾5-cm tumors, PCI did not improve OS [2-year rates 39.4% vs 40.9%, P=0.739].ConclusionsPCI remains standard therapy after complete response to chemoradiotherapy for LS-SCLC. However, older patients may be at risk from comorbidity or extracranial disease. Further work is warranted to identify patients who may not benefit from PCI.
http://ift.tt/2iQS8lt
Publication date: Available online 7 January 2017
Source:Journal of the American Academy of Dermatology
Author(s): Thuzar M. Shin, Jeremy R. Etzkorn, Joseph F. Sobanko, David J. Margolis, Joel M. Gelfand, Emily Y. Chu, Rosalie Elenitsas, Waqas R. Shaikh, Christopher J. Miller
BackgroundSubclinical spread of in situ melanoma occurs at a wide frequency, ranging from 12% to 71%.ObjectiveTo identify clinical factors associated with subclinical spread of in situ melanoma.MethodsWe used a retrospective, cross-sectional study of 674 consecutive in situ melanomas to examine 627 patients treated with Mohs surgery and melanoma antigen recognized by T cells 1 immunostaining. The presence of subclinical spread was correlated with clinical characteristics. Univariate and multivariate logistic regression analyses were performed to generate odds ratios (ORs) and 95% confidence intervals (CIs).ResultsBoth univariate and multivariate analyses demonstrated significantly increased odds for subclinical spread of in situ melanomas when they were located on the head or neck, at acral sites, or on the pretibial leg (OR 1.97, 95% CI 1.41-3.40); in persons with a history of prior treatment (OR 2.77, 95% CI 1.74-4.420); melanomas of preoperative size >1 cm (OR 1.74, 95% CI 1.23-2.46, P = .002); or in persons ≥60 years old (OR 1.47, 95% CI 1.01-2.13, P = .042). A count prediction model demonstrated that the risk for subclinical spread increased with the number of clinical risk factors.LimitationWe used a single-site, retrospective study design.ConclusionClarifying the risk factors for subclinical spread might help to refine triage of in situ melanomas to the appropriate surgical techniques for margin assessment prior to reconstruction.
http://ift.tt/2jgrMGG
Publication date: Available online 7 January 2017
Source:Journal of the American Academy of Dermatology
Author(s): Chun-Ying Wu, Yun-Ting Chang, Chao-Keui Juan, Jeng-Jer Shieh, Yu-Pu Lin, Han-Nan Liu, Jaw-Town Lin, Yi-Ju Chen
BackgroundA link between rosacea and inflammatory bowel disease (IBD) has been proposed with unknown mechanisms. Epidemiologic evidence of this association needs to be examined.MethodsIn this nationwide cohort study, a total of 89,356 patients with rosacea and 178,712 matched patients without rosacea between 1997 and 2013 were identified in the Taiwanese National Health Insurance Research Database. Cumulative incidences of IBD were compared between these 2 cohorts. Frailty Cox proportional hazard model was used and subgroup analyses were conducted to examine the risk factors for IBD.ResultsThe 15-year cumulative incidences of IBD were 0.036% (95% confidence interval [CI] 0.00%-1.57%) and 0.019% (95% CI 0.00%-0.83%) in rosacea and nonrosacea cohorts, respectively (P = .05). Rosacea (adjusted hazard ratio 1.94, 95% CI 1.04-3.63, P = .04) and male gender (adjusted hazard ratio 3.52, 95% CI 2.03-6.11, P < .01) were independently associated with IBD, after adjustment for major comorbidities. Multivariate subgroup analyses revealed consistent results. The incidence rates of IBD decreased with increasing antibiotic use in patients with rosacea, but without statistical significance.LimitationInformation related to lifestyle, diet, alcohol, and smoking was not included in the database.ConclusionPatients with rosacea may have an increased risk of IBD.
http://ift.tt/2i5PRSK
Publication date: Available online 7 January 2017
Source:Annals of Diagnostic Pathology
Author(s): Georgia Karpathiou, Celine Chauleur, Thomas Corsini, Melany Venet, Cyril Habougit, Freschia Honeyman, Fabien Forest, Michel Peoc'h
BackgroundSeromucinous ovarian tumors are rare and not adequately described in the literature and this is especially true for seromucinous carcinomas.Aim of the studyTo describe histological and clinical features of these tumors in comparison with the rest of ovarian epithelial tumors.Materials and MethodsTwo hundred and forty one (241) ovarian tumors, borderline (n=92) or malignant (n=149), treated surgically without neoadjuvant chemotherapy, were examined.ResultsSeromucinous borderline (SMBT) and malignant tumors (SMC) comprised 7.8% (n=7) and 4% (n=6) of all borderline tumors and carcinomas, respectively, studied. Mean age of diagnosis was 63.2 and 68.3 years and mean size was 6.4 cm and 12 cm for SMBT and SMC, respectively. Seromucinous tumors were associated with endometriosis in 23.1% of the cases and they were bilateral in 30.8%. Microscopically, variety in cellular composition, papillary architecture and development into thick walled, occasionally muscular, cysts were the main findings. Medullary/paraovarian/tubal or deeply cortical localization was also characteristic. Stage predicted overall and progression-free survival (p<0.0001 and p=0.03, respectively). Five-year survival was 62% for patients with high grade serous carcinoma, 55% for seromucinous carcinoma, 100% for endometrioid carcinoma, 75% for clear cell carcinoma, and 80% for patients with mucinous carcinoma. Differences were not however statistically significant.ConclusionSeromucinous tumors have unique features that support their classification as a different entity. Their localization and their often thick fibrous or/and muscular wall provides further evidence for an histogenesis from the secondary müllerian system or vestigial structures.
http://ift.tt/2ir73zL
Splenic irradiation for splenomegaly: A systematic review.
Cancer Treat Rev. 2016 Dec 22;53:47-52
Authors: Zaorsky NG, Williams GR, Barta SK, Esnaola NF, Kropf PL, Hayes SB, Meyer JE
Abstract
Splenic irradiation (SI) is a palliative treatment option for symptomatic splenomegaly (i.e. for pain, early satiety, pancytopenia from sequestration) secondary to hematologic malignancies and disorders. The purpose of the current article is to review the literature on SI for hematologic malignancies and disorders, including: (1) patient selection and optimal technique; (2) efficacy of SI; and (3) toxicities of SI. PICOS/PRISMA methods are used to select 27 articles including 766 courses of SI for 486 patients from 1960 to 2016. The most common cancers treated included chronic lymphocytic leukemia and myeloproliferative disorders; the most common regimen was 10Gy in 1Gy fractions over two weeks, and 27% of patients received retreatment. A partial or complete response (for symptoms, lab abnormalities) was obtained in 85-90% of treated patients, and 30% were retreated within 6-12months. There was no correlation between biologically equivalent dose of radiation therapy and response duration, pain relief, spleen reduction, or cytopenia improvement (r(2) all <0.4); therefore, lower doses (e.g. 5Gy in 5 fractions) may be as effective as higher doses. Grade 3-4 toxicity (typically leukopenia, infection) was noted in 22% of courses, with grade 5 toxicity in 0.7% of courses. All grade 5 toxicities were due to either thrombocytopenia with hemorrhage or leukopenia with sepsis (or a combination of both); they were sequelae of cancer and not directly caused by SI. In summary, SI is generally a safe and efficacious method for treating patients with symptomatic splenomegaly.
PMID: 28063304 [PubMed - as supplied by publisher]
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The future of MRI in radiation therapy belongs to integrated MRI-linac systems, not the standalone MRI-Sim.
Med Phys. 2017 Jan 07;:
Authors: Feygelman V, Lohr F, Orton CG
Abstract
The use of MRI in radiotherapy planning and simulation is increasing rapidly and is beginning to be integrated into the external beam radiation therapy (EBRT) treatment process. Some have suggested that integrated MRI-linac systems, not the standalone MRI-Sim, represents the future of MRI in radiotherapy, and this is the claim debated in this month's Point/Counterpoint. This article is protected by copyright. All rights reserved.
PMID: 28063171 [PubMed - as supplied by publisher]
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Mutated Chromatin Regulatory Factors as Tumor Drivers in Cancer.
Cancer Res. 2017 Jan 06;:
Authors: Koschmann C, Nunez FJ, Mendez F, Brosnan-Cashman JA, Meeker AK, Lowenstein PR, Castro MG
Abstract
Genes encoding proteins that regulate chromatin structure and DNA modifications [i.e., chromatin regulatory factors (CRF)] and genes encoding histone proteins harbor recurrent mutations in most human cancers. These mutations lead to modifications in tumor chromatin and DNA structure and an altered epigenetic state that contribute to tumorigenesis. Mutated CRFs have now been identified in most types of cancer and are increasingly regarded as novel therapeutic targets. In this review, we discuss DNA alterations in CRFs and how these influence tumor chromatin structure and function, which in turn leads to tumorigenesis. We also discuss the clinical implications and review concepts of targeted treatments for these mutations. Continued research on CRF mutations will be critical for our future understanding of cancer biology and the development and implementation of novel cancer therapies. Cancer Res; 77(2); 1-7. ©2017 AACR.
PMID: 28062403 [PubMed - as supplied by publisher]
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Glucose transporter 4 promotes head and neck squamous cell carcinoma metastasis through the TRIM24-DDX58 axis.
J Hematol Oncol. 2017 Jan 07;10(1):11
Authors: Chang YC, Chi LH, Chang WM, Su CY, Lin YF, Chen CL, Chen MH, Chang PM, Wu AT, Hsiao M
Abstract
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) represents a unique and major health concern worldwide. Significant increases in glucose uptake and aerobic glycolysis have been observed in HNSCC cells. Glucose transporters (GLUTs) represent a major hub in the glycolysis pathway, with GLUT4 having the highest glucose affinity. However, GLUT4's role in HNSCC has not been fully appreciated.
METHODS: An in silico analysis was performed in HNSCC cohorts to identify the most significant glucose transporter associated with HNSCC patient prognosis. An immunohistochemical analysis of a tissue microarray with samples from 90 HNSCC patients was used to determine the association of GLUT4 with prognosis. Complementary functional expression and knockdown studies of GLUT4 were performed to investigate whether GLUT4 plays a role in HNSCC cell migration and invasion in vitro and in vivo. The detailed molecular mechanism of the function of GLUT4 in inducing HNSCC cell metastasis was determined.
RESULTS: Our clinicopathologic analysis showed that increased GLUT4 expression in oral squamous cell carcinoma patients was significantly associated with a poor overall survival (OS, P = 0.035) and recurrence-free survival (RFS, P = 0.001). Furthermore, the ectopic overexpression of GLUT4 in cell lines with low endogenous GLUT4 expression resulted in a significant increase in migratory ability both in vitro and in vivo, whereas the reverse phenotype was observed in GLUT4-silenced cells. Utilizing a GLUT4 overexpression model, we performed gene expression microarray and Ingenuity Pathway Analysis (IPA) to determine that the transcription factor tripartite motif-containing 24 (TRIM24) was the main downstream regulator of GLUT4. In addition, DDX58 was confirmed to be the downstream target of TRIM24, whose downregulation is essential for the migratory phenotype induced by GLUT4-TRIM24 activation in HNSCC cells.
CONCLUSIONS: Here, we identified altered glucose metabolism in the progression of HNSCC and showed that it could be partially attributed to the novel link between GLUT4 and TRIM24. This novel signaling axis may be used for the prognosis and therapeutic treatment of HNSCC in the future.
PMID: 28061796 [PubMed - in process]
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Raoultella spp.-clinical significance, infections and susceptibility to antibiotics.
Folia Microbiol (Praha). 2017 Jan 06;:
Authors: Sękowska A
Abstract
The genus Raoultella belongs to the family of Enterobacteriaceae. Raoultella spp. are Gram-negative, aerobic, non-motile rods. This genus can be distinguished from the genus Klebsiella, in that genus use histamine as the only source of carbon in the medium. Also, Raoultella grow at 4 °C and do not produce gas from lactose at 44.5 °C. Raoultella sp. is known to inhabit natural environments (water, soil, plants). The reservoir of Raoultella is the gastrointestinal tract and upper respiratory tract. Raoultella spp. are opportunistic bacteria, which usually cause infections of the biliary tract, pneumonia and bacteraemia in oncologic and with lower immunity patients. Raoultella planticola and Raoultella ornithinolytica are the most frequently encountered human pathogens among the genus Raoultella. In this review, the current knowledge on Raoultella infections is summarized.
PMID: 28063019 [PubMed - as supplied by publisher]
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Widespread Virus Replication in Alveoli Drives Acute Respiratory Distress Syndrome in Aerosolized H5N1 Influenza Infection of Macaques.
J Immunol. 2017 Jan 06;:
Authors: Wonderlich ER, Swan ZD, Bissel SJ, Hartman AL, Carney JP, O'Malley KJ, Obadan AO, Santos J, Walker R, Sturgeon TJ, Frye LJ, Maiello P, Scanga CA, Bowling JD, Bouwer AL, Duangkhae PA, Wiley CA, Flynn JL, Wang J, Cole KS, Perez DR, Reed DS, Barratt-Boyes SM
Abstract
Human infections with highly pathogenic avian influenza A (H5N1) virus are frequently fatal but the mechanisms of disease remain ill-defined. H5N1 infection is associated with intense production of proinflammatory cytokines, but whether this cytokine storm is the main cause of fatality or is a consequence of extensive virus replication that itself drives disease remains controversial. Conventional intratracheal inoculation of a liquid suspension of H5N1 influenza virus in nonhuman primates likely results in efficient clearance of virus within the upper respiratory tract and rarely produces severe disease. We reasoned that small particle aerosols of virus would penetrate the lower respiratory tract and blanket alveoli where target cells reside. We show that inhalation of aerosolized H5N1 influenza virus in cynomolgus macaques results in fulminant pneumonia that rapidly progresses to acute respiratory distress syndrome with a fatal outcome reminiscent of human disease. Molecular imaging revealed intense lung inflammation coincident with massive increases in proinflammatory proteins and IFN-α in distal airways. Aerosolized H5N1 exposure decimated alveolar macrophages, which were widely infected and caused marked influx of interstitial macrophages and neutrophils. Extensive infection of alveolar epithelial cells caused apoptosis and leakage of albumin into airways, reflecting loss of epithelial barrier function. These data establish inhalation of aerosolized virus as a critical source of exposure for fatal human infection and reveal that direct viral effects in alveoli mediate H5N1 disease. This new nonhuman primate model will advance vaccine and therapeutic approaches to prevent and treat human disease caused by highly pathogenic avian influenza viruses.
PMID: 28062701 [PubMed - as supplied by publisher]
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Experimental infection of mandarin duck with highly pathogenic avian influenza A (H5N8 and H5N1) viruses.
Vet Microbiol. 2017 Jan;198:59-63
Authors: Kang HM, Lee EK, Song BM, Heo GB, Jung J, Jang I, Bae YC, Jung SC, Lee YJ
Abstract
A highly pathogenic avian influenza (HPAI) H5N8 virus was first detected in poultry and wild birds in South Korea in January 2014. Here, we determined the pathogenicity and transmissibility of three different clades of H5 viruses in mandarin ducks to examine the potential for wild bird infection. H5N8 (clade 2.3.4.4) replicated more efficiently in the upper and lower respiratory tract of mandarin ducks than two previously identified H5N1 virus clades (clades 2.2 and 2.3.2.1). However, none of the mandarin ducks infected with H5N8 and H5N1 viruses showed severe clinical signs or mortality, and gross lesions were only observed in a few tissues. Viral replication and shedding were greater in H5N8-infected ducks than in H5N1-infected ducks. Recovery of all viruses from control duck in contact with infected ducks indicated that the highly pathogenic H5 viruses spread horizontally through contact. Taken together, these results suggest that H5N8 viruses spread efficiently in mandarin ducks. Further studies of pathogenicity in wild birds are required to examine possible long-distance dissemination via migration routes.
PMID: 28062008 [PubMed - in process]
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Baro-otolagia Secondary to Cholesteatoma.
Aerosp Med Hum Perform. 2017 Jan 01;88(1):65-67
Authors: Govindaraju R, Adaikappan M, Rajagopalan R
Abstract
BACKGROUND: Baro-otalgia is a common complaint among passengers in an aircraft, in particular those who had a recent upper respiratory tract infection. The underlying pathophysiology is secondary to unequal aeration of the middle ear cleft with the surrounding atmosphere and it can be explained using Boyle's Law. We describe an unusual presentation of baro-otalgia in a pilot secondary to cholesteatoma obstructing the aditus despite normal middle ear pressure equalization provided by a grommet in the ear.
CASE REPORT: A 26-yr-old pilot with a presenting complaint of conductive hearing loss was diagnosed and treated for congenital cholesteatoma. His hearing improved, but 4 yr later he developed ear pain during the cruising phase of flight at an altitude of 9144 m (30,000 ft) above sea level. This pain persisted until descent to 4876 m (16,000 ft). Despite insertion of a middle ear ventilating tube, he remained symptomatic, requiring further investigation. This led to the diagnosis of recurrent cholesteatoma obstructing the aditus to the mastoid cavity. Upon surgical removal of the cholesteatoma, symptoms resolved.
DISCUSSION: We hypothesize that the recurrent cholesteatoma caused obstruction to normal aeration of the mastoid air cells during the changing atmospheric air pressure, thus producing pain. This is akin to sinus barotrauma instead of the usual pathophysiology underlying barotitis.Govindaraju R, Adaikappan M, Rajagopalan R. Baro-otolagia secondary to cholesteatoma. Aerosp Med Hum Perform. 2017; 88(1):65-67.
PMID: 28061926 [PubMed - in process]
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Therapeutic value of nerve growth factor in promoting neural stem cell survival and differentiation and protecting against neuronal hearing loss.
Mol Cell Biochem. 2017 Jan 07;:
Authors: Han Z, Wang CP, Cong N, Gu YY, Ma R, Chi FL
Abstract
Nerve growth factor (NGF) is a neurotrophic factor that modulates survival and differentiation of neural stem cells (NSCs). We investigated the function of NGF in promoting growth and neuronal differentiation of NSCs isolated from mouse cochlear tissue, as well as its protective properties against gentamicin (GMC) ototoxicity. NSCs were isolated from the cochlea of mice and cultured in vitro. Effect of NGF on survival, neurosphere formation, and differentiation of the NSCs, as well as neurite outgrowth and neural excitability in the subsequent in vitro neuronal network, was examined. Mechanotransduction capacity of intact cochlea and auditory brainstem response (ABR) threshold in mice were also measured following GMC treatment to evaluate protection using NGF against GMC-induced neuronal hearing loss. NGF improved survival, neurosphere formation, and neuronal differentiation of mouse cochlear NSCs in vitro, as well as promoted neurite outgrowth and neural excitability in the NSC-differentiated neuronal culture. In addition, NGF protected mechanotransduction capacity and restored ABR threshold in gentamicin ototoxicity mouse model. Our study supports a potential therapeutic value of NGF in promoting proliferation and differentiation of NSCs into functional neurons in vitro, supporting its protective role in the treatment of neuronal hearing loss.
PMID: 28063006 [PubMed - as supplied by publisher]
A PSMA-targeted theranostic agent for photodynamic therapy.
J Photochem Photobiol B. 2016 Dec 18;167:111-116
Authors: Chen Y, Chatterjee S, Lisok A, Minn I, Pullambhatla M, Wharram B, Wang Y, Jin J, Bhujwalla ZM, Nimmagadda S, Mease RC, Pomper MG
Abstract
Prostate-specific membrane antigen (PSMA) is over-expressed in the epithelium of prostate cancer and in the neovasculature of many non-prostate solid tumors. PSMA has been increasingly used as a target for cancer imaging and therapy. Here we describe a low-molecular-weight theranostic photosensitizer, YC-9, for PSMA-targeted optical imaging and photodynamic therapy (PDT). YC-9 was synthesized by conjugating IRDye700DX N-hydroxysuccinimide (NHS) ester with a PSMA targeting Lys-Glu urea through a lysine-suberate linker in suitable yield. Optical imaging in vivo demonstrated PSMA-specific tumor uptake of YC-9 with rapid clearance from non-target tissues. PSMA-specific cell kill was demonstrated with YC-9in vitro through PDT in PSMA(+) PC3-PIP and PSMA(-) PC3-flu cells. In vivo PDT in mice bearing PSMA(+) PC3-PIP tumors at 4h post-injection of YC-9 (A total of four PDT sessions were performed, 48h apart) resulted in significant tumor growth delay, while tumors in control groups continued to grow. PDT with YC-9 significantly increased the median survival of the PSMA(+) PC3-PIP tumor mice (56.5days) compared to control groups [23.5-30.0days, including untreated, light alone, YC-9 alone (without light) and non-targeted IRDye700DX PDT treatment groups], without noticeable toxicity at the doses used. This study proves in principle that YC-9 is a promising therapeutic agent for targeted PDT of PSMA-expressing tissues, such as prostate tumors, and may also be useful against non-prostate tumors by virtue of neovascular PSMA expression.
PMID: 28063300 [PubMed - as supplied by publisher]
Solitary fibrous tumor of the lung: a case report.
Surg Case Rep. 2017 Dec;3(1):10
Authors: Ichiki Y, Kakizoe K, Hamatsu T, Matsuyama A, Suehiro T, Tanaka F, Hisaoka M, Sugimachi K
Abstract
Solitary fibrous tumors (SFTs) are relatively rare neoplasms that commonly occur in the pleura. The pathological feature of SFTs is a proliferation of spindle-shaped cells in interlacing or storiform fascicles. SFTs appear to derived from pluripotential submesothelial cells, but not the covering mesothelium. SFTs distinctively show diffuse staining for CD34 but lack staining for smooth muscle markers. We herein report a relatively rare case of a 68-year-old male patient without symptoms, who underwent resection for what was considered to be SFT.
PMID: 28063145 [PubMed - in process]
A population-based analysis of germline BAP1 mutations in melanoma.
Hum Mol Genet. 2017 Jan 05;:
Authors: O'Shea SJ, Robles-Espinoza CD, McLellan L, Harrigan J, Jacq X, Hewinson J, Iyer V, Merchant W, Elliott F, Harland M, Timothy Bishop D, Newton-Bishop J, Adams DJ
Abstract
Germline mutation of the BRCA1 associated protein-1 (BAP1) gene has been linked to uveal melanoma, mesothelioma, meningioma, renal cell carcinoma and basal cell carcinoma. Germline variants have also been found in familial cutaneous melanoma pedigrees, but their contribution to sporadic melanoma has not been fully assessed. We sequenced BAP1 in 1,977 melanoma cases and 754 controls and used deubiquitinase assays, a pedigree analysis, and a histopathological review to assess the consequences of the mutations found. Sequencing revealed 30 BAP1 variants in total, of which 27 were rare (ExAc allele frequency <0.002). Of the 27 rare variants, 22 were present in cases (18 missense, one splice acceptor, one frameshift and two near splice regions) and 5 in controls (all missense). A missense change (S98R) in a case that completely abolished BAP1 deubiquitinase activity was identified. Analysis of cancers in the pedigree of the proband carrying the S98R variant and in two other pedigrees carrying clear loss-of-function alleles showed the presence of BAP1-associated cancers such as renal cell carcinoma, mesothelioma and meningioma, but not uveal melanoma. Two of these three probands carrying BAP1 loss-of-function variants also had melanomas with histopathological features suggestive of a germline BAP1 mutation. The remaining cases with germline mutations, which were predominantly missense mutations, were associated with less typical pedigrees and tumours lacking a characteristic BAP1-associated histopathological appearances, but may still represent less penetrant variants. Germline BAP1 alleles defined as loss-of-function or predicted to be deleterious/damaging are rare in melanoma.
PMID: 28062663 [PubMed - as supplied by publisher]
Somatic mutation profiling of hobnail variant of papillary thyroid carcinoma.
Endocr Relat Cancer. 2017 Jan 06;:
Authors: Morandi L, Righi A, Maletta F, Rucci P, Pagni F, Gallo M, Rossi S, Caporali L, Sapino A, Lloyd R, Asioli S
Abstract
Hobnail variant of papillary thyroid carcinoma (HPTC) represents a recently described, aggressive and rare group of thyroid tumors with poorly understood pathogenesis. Molecular data about this group of cancers are few and a more detailed molecular characterization of these tumors is needed. The main objective of the study is to define a comprehensive molecular typing of HPTC. Eighteen patients affected by HPTC, including eighteen primary tumors and four lymph node metastases, were screened for NRAS, KRAS, HRAS, BRAF, TP53, PIK3CA, hTERT, PTEN, CDKN2A, EGFR, AKT1, CTNNB1, and NOTCH1 gene mutations. Sequencing is conducted on the MiSEQ system and molecular data are compared with clinical-pathologic data and follow up. The patients include 14 women and 4 men. Ages range from 23 to 87 years. All 18 primary tumors of HPTC showed ≥30% hobnail features. BRAF and TP53 mutations are by far the most common genetic alterations in primary HPTC (72.2% and 55.6% respectively), followed by hTERT (44.4%), PIK3CA (27.8%), CTNNB1 (16.7%), EGFR (11.1%), AKT1 (5.5%) and NOTCH1 (5.5%). The mutational pattern in primary tumors and metastasis was usually maintained. Univariate Cox regression analyses with bootstrap procedure indicated a significantly increased mortality risk in patients harboring BRAF mutation and BRAF mutation associated with TP53 and/or PIK3CA mutations. The detection of these multiple mutations appears to allow the identification of a subset of more aggressive tumors within the group and to bear information that should be useful for prognostic stratification of these patients including the planning of adjuvant therapy.
PMID: 28062544 [PubMed - as supplied by publisher]
Double-hit lymphomas: clinical, morphological, immunohistochemical and cytogenetic study in a series of Brazilian patients with high-grade non-Hodgkin lymphoma.
Diagn Pathol. 2017 Jan 07;12(1):3
Authors: Oliveira CC, Maciel-Guerra H, Kucko L, Hirama EJ, Brilhante AD, Quevedo FC, da Cunha IW, Soares FA, Niero-Melo L, Dos Reis PP, Domingues MA
Abstract
BACKGROUND: Double-hit lymphomas (DHL) are rare high-grade neoplasms characterized by two translocations: one involving the gene MYC and another involving genes BCL2 or BCL6, whose diagnosis depends on cytogenetic examination. This research studied DHL and morphological and/or immunophenotypic factors associated with the detection of these translocations in a group of high-grade non-Hodgkin lymphoma cases.
METHOD: Clinical and morphological reviews of 120 cases diagnosed with diffuse large B-cell lymphoma and Burkitt lymphoma were conducted. Immunohistochemistry (CD20, CD79a, PAX5, CD10, Bcl6, Bcl2, MUM1, TDT and Myc) and fluorescence in situ hybridization for detection of MYC, BCL2 and BCL6 gene translocations were performed in a tissue microarray platform.
RESULTS: Three cases of DHL were detected: two with translocations of MYC and BCL2 and one with translocations of MYC and BCL6, all leading to death in less than six months. Among 90 cytogenetically evaluable biopsies, associations were determined between immunohistochemistry and fluorescence in situ hybridization for MYC (p = 0.036) and BCL2 (p = 0.001). However, these showed only regular agreement, indicated by Kappa values of 0.23 [0.0;0.49] and 0.35 [0.13;0.56], respectively. "Starry sky" morphology was strongly associated with MYC positivity (p = 0.01). The detection of three cases of DHL, all resulting in death, confirms the rarity and aggressiveness of this neoplasm.
CONCLUSIONS: The "starry sky" morphological pattern and immunohistochemical expression of Myc and Bcl2 represent possible selection factors for additional cytogenetic diagnostic testing.
PMID: 28061782 [PubMed - in process]
