bluuebunny/crossref_metadata_2025 huggingface dataset:
HAb18G/CD147 Promotes Radioresistance in Hepatocellular Carcinoma Cells: A Potential Role for Integrin β1 Signaling
Authors: Wu Jiao , Li Yong , Dang Ya-Zheng , Gao Hong-Xiang , Jiang Jian-Li , Chen Zhi-Nan
Published: December 2014

Radiotherapy has played a limited role in the treatment of hepatocellular carcinoma (HCC) due to the risk of tumor radioresistance. A previous study in our laboratory confirmed that CD147 interacts with integrin β1 and plays an important role in modulating the malignant properties of HCC cells. In this study, we further evaluated the role of CD147 in the radioresistance of HCC and as a potential target for improving radiosensitivity. Upon irradiation, the colony formation, apoptosis, cell-cycle distribution, migration, and invasion of SMMC-7721, CD147-knockout SMMC-7721, HepG2, and CD147-knockdown HepG2 cells were determined. A nude mouse xenograft model and a metastatic model of HCC were used to detect the role of CD147 in radioresistance in vivo. Deletion of HAb18G/CD147 significantly enhanced the radiosensitivity of SMMC-7721 and HepG2 cells, and knocking out HAb18G/CD147 in SMMC-7721 cells attenuated irradiation-enhanced migration and invasion. The knockout and antibody blockade of CD147 decreased the tumor growth and metastatic potentials of HCC cells under irradiation. CD147-deleted SMMC-7721 cells showed diminished levels of calpain, cleaved talin, active integrin β1, and decreased p-FAK (Tyr397) and p-Akt (Ser473) levels. FAK and PI3K inhibitors, as well as integrin β1 antibodies, increased the radiation-induced apoptosis of SMMC-7721 cells. Our data provide evidence for CD147 as an important determinant of radioresistance via the regulation of integrin β1 signaling. Inhibition of the HAb18G/CD147 integrin interaction may improve the efficiency of radiosensitivity and provide a potential new approach for HCC therapy. Mol Cancer Ther; 14(2); 553–63. ©2014 AACR.
Preclinical Efficacy for AKT Targeting in Clear Cell Carcinoma of the Ovary
Authors: Sasano Tomoyuki , Mabuchi Seiji , Kuroda Hiromasa , Kawano Mahiru , Matsumoto Yuri , Takahashi Ryoko , Hisamatsu Takeshi , Sawada Kenjiro , Hashimoto Kae , Isobe Aki , Testa Joseph R. , Kimura Tadashi
Published: December 2014

The aim of this study was to determine the role of AKT as a therapeutic target in ovarian clear cell carcinoma (CCC), an aggressive, chemoresistant histologic subtype of ovarian cancer. AKT activation was assessed by immunohistochemistry (IHC) using human tissue microarrays of primary ovarian cancers, composed of both CCC and serous adenocarcinoma (SAC). The growth-inhibitory effect of AKT-specific targeting by the small-molecule inhibitor, perifosine, was examined using ovarian CCC cell lines in vitro and in vivo. Finally, the activity of perifosine was examined using in CCC-derived tumors that had acquired resistance to anti-VEGF or chemotherapeutics such as bevacizumab or cisplatin, respectively. Interestingly, AKT was frequently activated both in early-stage and advanced-stage CCCs. Treatment of CCC cells with perifosine attenuated the activity of AKT–mTORC1 signaling, inhibited proliferation, and induced apoptosis. The effect of perifosine was more profound under conditions of high AKT activity compared with low AKT activity. Increased AKT activation and enhanced sensitivity to perifosine were observed in the context of cisplatin-resistant CCC. Treatment with perifosine concurrently with cisplatin significantly enhanced the antitumor effect of cisplatin. Moreover, perifosine showed significant antitumor activity in CCC-derived tumors that had acquired resistance to bevacizumab or cisplatin. Collectively, these data reveal that AKT is frequently activated in ovarian CCCs and is a promising therapeutic target in aggressive forms of ovarian cancer.

Implications: AKT-targeted therapy has value in a first-line setting as well as a second-line treatment for recurrent disease developing after platinum-based chemotherapy or bevacizumab treatment. Mol Cancer Res; 13(4); 795–806. ©2014 AACR.
The Alzheimer's Disease Cooperative Study Prevention Instrument Project: Longitudinal Outcome of Behavioral Measures as Predictors of Cognitive Decline
Authors: Banks Sarah Jane , Raman Rema , He Feng , Salmon David P. , Ferris Steven , Aisen Paul , Cummings Jeffrey
Published: December 2014

Background/Methods: The Alzheimer's Disease Cooperative Study Prevention Instrument Project is a longitudinal study that recruited 644 cognitively healthy older subjects (aged between 75 and 93 years, 58% women) at baseline and evaluated their cognitive change over 4 years. The study was structured like a clinical trial to anticipate a prevention trial and to determine the performance of novel trial instruments in a longitudinal non-interventional trial framework. Behavioral symptoms were assessed at baseline. Results: The existence of participant-reported behavioral symptoms at baseline predicted conversion to Clinical Dementia Rating scale score ≥0.5 over the 4-year period. Conclusions: The results imply that early anxiety and depression may be harbingers of future cognitive decline, and that patients exhibiting such symptoms, even in the absence of co-occurring cognitive symptoms, should be closely followed over time.
In vitro Antimicrobial Activities of 1-Methoxyficifolinol, Licorisoflavan A, and 6,8-Diprenylgenistein against Streptococcus mutans
Authors: Ahn Sug-Joon , Park Soon-Nang , Lee Young Ju , Cho Eun-Jung , Lim Yun Kyong , Li Xue Min , Choi Mi-Hwa , Seo Young-Woo , Kook Joong-Ki
Published: December 2014

The objective of the study was to investigate the antimicrobial effects of purified single compounds from ethanol-extracted licorice root on Streptococcus mutans. The crude licorice root extract (CLE) was obtained from Glycyrrhiza uralensis, which was subjected to column chromatography to separate compounds. Purified compounds were identified by mass spectrometry and nuclear magnetic resonance. Antimicrobial activities of purified compounds from CLE were evaluated by determining the minimum inhibitory concentration and by performing time-kill kinetics. The inhibitory effects of the compounds on biofilm development were evaluated using crystal violet assay and confocal microscopy. Cell toxicity of substances to normal human gingival fibroblast (NHGF) cells was tested using a methyl thiazolyl tetrazolium assay. Chlorhexidine digluconate (CHX) was used in the control group. Three antimicrobial flavonoids, 1-methoxyficifolinol, licorisoflavan A, and 6,8-diprenylgenistein, were isolated from the CLE. We found that the three flavonoids and CHX had bactericidal effects on S. mutans UA159 at the concentration of ≥4 and ≥1 µg/ml, respectively. The purified compounds completely inhibited biofilm development of S. mutans UA159 at concentrations over 4 μg/ml, which was equivalent to 2 μg/ml of CHX. Confocal analysis showed that biofilms were sparsely scattered in the presence of over 4 μg/ml of the purified compounds. However, the three compounds purified from CLE showed less cytotoxic effects on NHGF cells than CHX at these biofilm-inhibitory concentrations. Our results suggest that purified flavonoids from CLE can be useful in developing oral hygiene products, such as gargling solutions and dentifrices for preventing dental caries.
Elevated Plasma Dityrosine in Patients with Hyperlipidemia Compared to Healthy Individuals
Authors: Wu Gui-Rong , Cheserek Maureen , Shi Yong-Hui , Shen Li-Ye , Yu Jing , Le Guo-Wei
Published: December 2014

Background: Dityrosine, the modification of tyrosine residues, may contribute to metabolic disorders. This study was undertaken to investigate plasma dityrosine concentrations in patients with hyperlipidemia and to examine the correlation between dityrosine and lipid profiles. Methods: Fluorescence spectrophotometry was used to measure dityrosine in the plasma of healthy subjects (n = 203) and dyslipidemic subjects, which included patients with mild hyperlipidemia (n = 246) and hyperlipidemia (n = 179). Advanced oxidation protein products (AOPP) and malondialdehyde (MDA) were also assayed in all subjects. Results: Dityrosine levels were higher by 9.3 and 22.9% in mildly hyperlipidemic and hyperlipidemic patients, respectively, compared to controls after adjustment for age, gender, and BMI. AOPP and MDA levels showed similar trends. The levels of dityrosine related positively (p < 0.05) to total cholesterol (r = 0.362), triglycerides (r = 0.449), and low-density lipoprotein cholesterol (r = 0.359). Moreover, plasma dityrosine (r = 0.408), AOPP (r = 0.488), and MDA (r = 0.181) levels were elevated with an increase in the atherosclerosis index in the subjects. Conclusions: These findings suggest that dityrosine formation may be an early event in the pathological process of hyperlipidemia. Dityrosine as a biomarker detected by fluorescence spectrophotometry might be a useful tool to evaluate the plasma redox state in hyperlipidemia.
Chemoprevention of Colorectal Cancer
Authors: Lang Michaela , Gasche Christoph
Published: December 2014

Colorectal cancer has become one of the most prevalent malignant diseases for both men and women. Patients with inflammatory bowel diseases or certain inherited cancer syndromes are at high risk of developing colorectal cancer and have naturally the highest need for cancer prevention. In familial adenomatous polyposis (FAP) and Lynch syndrome, most of the underlying germline mutations can be detected by DNA sequencing, and medical counselling of affected individuals involves both surveillance tests and chemopreventive measures. However, as the mechanisms leading to colorectal cancer differ in these high-risk groups, the molecular action of chemopreventive drugs needs to be adjusted to the certain pathway of carcinogenesis. In the last decades, a number of drugs have been tested, including sulindac, aspirin, celecoxib, and mesalazine, but some of them are still controversially discussed. This review summarizes the advances and current standards of colorectal cancer prevention in patients with inflammatory bowel disease, FAP and Lynch syndrome.
Probiotics and Antibiotics in IBD
Authors: Sokol Harry
Published: December 2014

The involvement of the gut microbiota in the pathogenesis of IBD is supported by many findings and is thus now commonly acknowledged. The imbalance in the composition of the microbiota (dysbiosis) observed in IBD patients is one of the strongest arguments and provides the rationale for a therapeutic manipulation of the gut microbiota. The tools available to achieve this goal include fecal microbiota transplantation, but antibiotics and probiotics have been the most used one until now. Although antibiotics have shown some efficacy in inducing remission in Crohn's disease (CD) and ulcerative colitis (UC), as well as preventing postoperative relapse in CD, they are not currently recommended for the treatment of IBD except for septic complications, notably because of long-term tolerance and ecological issues. Some probiotics have been shown to be as good as 5-aminosalicylic acid to maintain remission in mild-to-moderate UC, but have been disappointing until now in CD in all tested indications. In pouchitis, antibiotics and probiotics have shown efficacy for inducing and maintaining remission, respectively. Targeting the gut microbiota in IBD is an attractive strategy. Current efforts to better understand the host-microbiota interactions in physiological as well as disease settings might lead to the development of rational-based treatments.
IBD: Microbiota Manipulation through Diet and Modified Bacteria
Authors: Simpson Hannah L. , Campbell Barry J. , Rhodes Jonathan M.
Published: December 2014

Background/Aims: Crohn's disease (CD) and ulcerative colitis (UC) are both typified by an altered intestinal microbiota, and gene associations imply various defects in the mucosal barrier and in the innate immune response to bacteria. This review aims to assess how alterations in diet or use of modified bacteria could have therapeutic effects in CD or UC. Methods: A MEDLINE search using the terms ‘prebiotic', ‘genetically modified bacteria', ‘mucosal barrier in association with ulcerative colitis', ‘Crohn's disease‘ or ‘microbiota'. Results: A large body of data from in vitro and animal studies shows promise for therapeutic approaches that target the microbiota. Approaches include dietary supplementation with fermentable fibres (prebiotics) and soluble fibres that block bacterial-epithelial adherence (contrabiotics), enhancement of the mucosal barrier with phosphatidylcholine, and use of genetically modified bacteria that express IL-10 or protease inhibitors. Vitamin D supplementation also shows promise, acting via enhancement of innate immunity. Clinical trials have shown benefit with enterically delivered phosphatidylcholine supplementation in UC and near-significant benefit with vitamin D supplementation in CD. Conclusion: Strategies that target the microbiota or the host defence against it appear to be good prospects for therapy and deserve greater investment.
Endoscopic and Medical Management of Fibrostenotic Crohn's Disease
Authors: Thienpont Clara , Van Assche Gert
Published: December 2014

Crohn's disease (CD) is a disease characterized by acute inflammation at diagnosis which evolves toward a more fistulizing and fibrostenotic disease phenotype over time. This leads to a high risk of bowel resections and ultimately short bowel with diarrhea and malabsorption, which represents a major part of the burden inflicted by CD. Bowel-conserving endoscopic and surgical procedures have therefore been developed. Specific antifibrotic medical therapies are currently lacking. Through-the-scope endoscopic balloon dilation has been described in several cohorts as an alternative to surgical resection or stricturoplasty in selected patients. Efficacy of endoscopic dilation is high, with an immediate success rate of 78% (between 73 and 100%), defined as the ability to pass with the scope through the stricture. However, symptomatic recurrence is frequent, with need for new dilatation in 41% and need for surgery in 42%, with a mean interval of 15 months. Adjunctive techniques such as local steroid or anti-TNF injections or stenting have not been conclusively proven to be of added benefit. We usually reserve endoscopic dilation for patients with short strictures (<5 cm) and nonpenetrating disease, preferably at the ileocolonic anastomosis. Similar to other interventions in endoscopy, endoscopic dilation has an intrinsic risk of complications which can be estimated at 2%. Balloon size and patient selection can serve to increase safety.
Biosimilars: Are They Bioequivalent?
Authors: Gomollón Fernando
Published: December 2014

Biologics have revolutionized several areas of medical therapeutics, and dozens of them are used by millions of patients. Monoclonal antibodies are only one type of biologics, but more than 900 are now in different phases of development. These drugs are complex to make and not cheap. The market is constantly increasing, and several biosimilars (copies of biologics) are being used, while many are still waiting to become available to the public. Biosimilars are more complex than generics, and regulatory agencies have very stringent criteria for approval. In the IBD field, the biosimilar infliximab (Inflectra®, Remsima®) has been recently approved by the EMA, but not by Canadian authorities. The EMA has considered that ‘high similarity' in preclinical studies together with clinical data from two trials in ankylosing spondylitis and rheumatoid arthritis warrant the ‘extrapolation' for all approved indications for original infliximab (Remicade®), specifically Crohn's disease and ulcerative colitis. Canadian authorities have not accepted extrapolation, based on differences in glycosylation (fucosylation) that could be related to properties important in Crohn's disease. Most scientific societies do support the idea of asking for specific clinical trials before approval, although they acknowledge that following EMA, FDA, and WHO guidelines warrant safe products. Practical issues such as interchangeability and substitution remain unsolved, and it is very likely that there will be different solutions at the national level. Pharmacovigilance plans will be key for obtaining reliable data. Biosimilars are not better drugs, but can be clearly cheaper and may facilitate access to new treatments in many populations.
Integrating Omics: The Future of IBD?
Authors: Fiocchi Claudio
Published: December 2014

The complexity of IBD is well recognized as are the putative four major components of its pathogenesis, i.e. environment, genetic makeup, gut microbiota and mucosal immune response. Each of these components is extremely complex on its own, and at present should be more appropriately defined by the terms ‘exposome', ‘genome', ‘microbiome' and ‘immunome', respectively, based on the ‘ome' suffix that refers to a totality of some sort. None of these ‘omes' is apparently capable of causing IBD by itself; it is instead the intricate and reciprocal interaction among them, through the so-called ‘IBD interactome', that results in the emergence of IBD, or more appropriately the ‘IBD integrome'. To deal with and understand such overwhelming biological complexity, new approaches and tools are needed, and these are represented by ‘omics', defined as the study of related sets of biological molecules in a comprehensive fashion, such as genomics, transcriptomics, proteomics, metabolomics, and so on. Numerous bioinformatics-based tools are available to explore and take advantage of the massive amount of information that can be generated by the analysis of the various omes and their interactions, aiming at identifying the molecular interactome underlying any particular status of health and disease. These novel approaches are fully applicable to IBD and allow us to achieve the ultimate goal of developing and applying personalized medicine and far more effective therapies to individual patients with Crohn's disease and ulcerative colitis. For the practicing gastroenterologist, an omics-based delivery of healthcare may be intimidating, but it must be accepted and implemented if he or she is to provide the best possible care to IBD patients.
Colorectal Cancer in Patients with Inflammatory Bowel Disease: The True Impact of the Risk
Authors: Herszényi László , Barabás Loránd , Miheller Pál , Tulassay Zsolt
Published: December 2014

Patients with long-standing inflammatory bowel disease (IBD) have an increased risk of colorectal cancer (CRC). The association between IBD and CRC is well supported, but reported risk estimates vary widely. Although recent evidence from population-based studies reports a decline in risk, CRC accounts for 10-15% of all deaths in IBD. The potential causes of recent epidemiological trends and the real magnitude of risk of CRC in IBD are subjects of debate. The molecular pathway leading to CRC differs from the classic adenoma-to-CRC sequence. Chronic inflammation contributes to the development of low- and high-grade dysplasia which may further convert into CRC. Patients with a young age at onset, long-standing and extensive colitis with severe inflammatory burden, a family history of sporadic CRC, and concomitant primary sclerosing cholangitis are at greatest risk. The CRC risk in patients with colonic Crohn's disease is similar to that of ulcerative colitis. IBD-associated CRC can frequently be detected at late stages and at a younger age. The long-term prognosis of CRC may be poorer in patients with IBD than in those with sporadic CRC. Regular surveillance colonoscopies may permit earlier detection of CRC, with a corresponding improved prognosis. The interval between surveillance colonoscopies is dependent on each patient's personal risk profile.
Up-Regulation of Intrarenal Renin-Agiotensin System Contributes to Renal Damage in High-Salt Induced Hypertension Rats
Authors: Wu Haiyan , Liang Yaoxian , Zheng Yimu , Bai Qiong , Zhuang Zheng , A Lata , Zheng Danxia , Wang Yue
Published: December 2014

Background/Aims: To investigate the change of intrarenal renin-agiotensin system (RAS) and its role in high-salt induced hypertension. Methods: Wistar rats were divided into normal-salt (NS), high-salt diet (HS) and high-salt diet with Losartan group (HS+L), for 6 weeks. Systolic blood pressure (SBP) was monitored. Blood and urine samples were collected every 2 weeks. Angiotensinogen (AGT) was measured by ELISA. AGT mRNA and protein were measured by real-time PCR and immunohistochemistry. Renin activity and angiotensin II (Ang II) were measured by radioimmunoassay. Results: HS versus NS group, SBP increased from 2nd week (P<0.05), urinary protein increased at 6th week (P<0.05). Although plasma renin, AGT and Ang II had no significant changes (P>0.05), renal cortex renin, AGT, and Ang II increased significantly in HS (P<0.05). In HS+L, Losartan failed to reduce SBP (P>0.05) but abolished the increase of proteinuria (P<0.01), renal cortex renin, AGT, Ang II and urinary AGT reduced (P<0.05) while plasma renin, AGT and Ang II enhanced (P<0.05) when compared with HS. Urinary AGT was positively correlated with renal AGT (r=0.592, P <0.01) and Ang II (r=0.726, P <0.01). Conclusion: Inappropriate response of the renal RAS to a high salt diet may contribute to hypertension and renal damage, and urinary AGT could reflect intrarenal RAS activity.
IgA Nephropathy in Czech Patients - Are We Able Reliably Predict the Outcome?
Authors: Maixnerova Dita , Neprasova Michaela , Skibova Jelena , Mokrisova Jana , Rysava Romana , Reiterova Jana , Jancova Eva , Merta Miroslav , Zadrazil Josef , Honsova Eva , Tesar Vladimir
Published: December 2014

Background/Aims: The aim of our study was to retrospectively analyse data of 520 Czech patients with IgA nephropathy (IgAN) and to specify the risk factors affecting renal survival of IgAN patients. Methods: Cox proportional hazards regression model was used to evaluate the effects of different variables on renal survival during a median follow up of six years. McNemar´s test was used to analyse the progression of renal function according to Bartosik´s formula. Results: In our retrospective analysis of 520 Czech IgAN patients Cox proportional hazards regression model with five variables [hypertension, sex, GFR, proteinuria, age] was used. Significant regression coefficient was found for GFR, hypertension and proteinuria. Using stepwise algorithm GFR (OR = 3.09), hypertension (OR = 2.09) and proteinuria (OR = 1.97) were found as the most important factors for renal survival in our group of IgAN patients. Among patients with CKD 3 we found significantly better renal survival in patients with proteinuria < 1g/day compared to patients with higher proteinuria. We did not find the significant difference between predicted progression of renal function due to Bartosik´s formula and real progression of renal parametres assessed by GFR at the end of the follow up in our group of IgAN patients. Conclusion: Our retrospective study of 520 Czech IgAN patients confirmed GFR, hypertension and proteinuria as the most important factors affecting the prognosis of IgAN patients. We validated Toronto Bartosik´s formula to predict prognosis of IgAN patients.
Downregulation of Peptide Transporters PEPT1 and PEPT2 by Oxidative Stress Responsive Kinase OSR1
Authors: Warsi Jamshed , Elvira Bernat , Bissinger Rosi , Shumilina Ekaterina , Hosseinzadeh Zohreh , Lang Florian
Published: December 2014

Background/Aims: OSR1 (oxidative-stress-responsive kinase 1) participates in the regulation of renal tubular ion transport, cell volume and blood pressure. Whether OSR1 contributes to the regulation of organic solute transport remained; however, elusive. The present study thus explored the OSR1 sensitivity of the peptide transporters PEPT1 and PEPT2. Methods: cRNA encoding PEPT1 or PEPT2 were injected into Xenopus oocytes without or with additional injection of cRNA encoding wild-type OSR1, WNK1 insensitive inactive T185AOSR1, constitutively active T185EOSR1, and catalytically inactive D164AOSR1. Electrogenic peptide (glycine-glycine) transport was determined by dual electrode voltage clamp, the abundance of hemagglutinin-tagged PEPT2 (PEPT2-HA) by chemiluminescence. Results: In Xenopus oocytes injected with cRNA encoding PEPT1 or PEPT2, but not in oocytes injected with water, the dipeptide gly-gly (2 mM) generated an appreciable inward current (Igly-gly). Coexpression of OSR1 significantly decreased Igly-gly in both PEPT1 and PEPT2 expressing oocytes. The effect of OSR1 coexpression on Igly-gly in PEPT1 expressing oocytes was mimicked by coexpression of T185EOSR1, but not of D164AOSR1 or T185AOSR1. Kinetic analysis revealed that coexpression of OSR1 decreased maximal Igly-gly. OSR1 further decreased the PEPT2-HA protein abundance in the cell membrane. Conclusion: OSR1 has the capacity to downregulate the peptide transporters PEPT1 and PEPT2 by decreasing the carrier protein abundance in the cell membrane.
Is There Association Between Changes in eGFR Value and the Risk of Permanent Type of Atrial Fibrillation? - Analysis of Valvular and Non-Valvular Atrial Fibrillation Population
Authors: Mlodawska Elzbieta , Tomaszuk-Kazberuk Anna , Lopatowska Paulina , Bachorzewska-Gajewska Hanna , Malyszko Jolanta , Dobrzycki Slawomir , Musial Wlodzimierz Jerzy
Published: December 2014

Background/Aims: There are no data concerning renal function in population with valvular and non-valvular atrial fibrillation (AF). To assess renal function in patients with AF, the association between eGFR and AF perpetuation, in-hospital mortality. Methods: We studied 1523 patients with AF. Patients with chronic kidney disease (CKD) were compared to population with preserved renal function. Results: CKD was more frequently observed in patients with valvular AF(p=0.009). In non-valvular AF patients eGFR <60ml/min./1,73m2 had more often permanent AF(p<0.0001). In patients with CKD CHA2DS2VASc score was 4.1±1.5 and HAS-BLED score was 2.1±1.2 and it was higher as compared to population with preserved renal function (p<0.0001 vs p<0.0001). The odds of permanent AF in patients with non-valvular AF and CKD were increased 1.82 times(OR=1.82,p<0.0001,95%CI:1.46-2.27). The odds of permanent AF in patients with valvular AF and CKD were not significantly increased(OR=1.46,p=0.2,95%CI:0.86-2.5). In non-valvular AF, if eGFR decrease by 10ml/min, odds of permanent AF are increased by 10%(OR=1.1p<0.0001,95%CI1.05- 1.15). In multivariate logistic regression, in non-valvular AF, odds of in-hospital death were higher for patients >75 years old(OR=3.70,p=0.01,95%CI1.33-10.28), with CKD (OR=2.61,p=0.03,95%CI1.09-6.23). The type of AF had no significant influence on in-hospital mortality(OR=0.71,p=0.45,95%CI0.30-1.70). Conclusions: CKD is more often observed in patients with valvular AF. In population with non-valvular AF decreased eGFR is associated with permanent type of AF and with higher CHA2DS2VASc and HAS-BLED score. Among valvular AF patients there are no differences in type of AF between patients with and without CKD. There is the correlation between CKD and AF perpetuation but only in non-valvular population.
Successful Early Rituximab Treatment in a Case of Systemic Lupus Erythematosus with Potentially Fatal Diffuse Alveolar Hemorrhage
Authors: Na Ju Ock , Chang Sung Hae , Seo Ki-Hyeon , Choi Jae Sung , Lee Ho Sung , Lyu Ji Won , Nah Seoung-Su
Published: December 2014

Diffuse alveolar hemorrhage (DAH) is a rare but devastating complication of systemic lupus erythematosus (SLE) with a high early mortality rate. DAH seldom occurs without active organ involvement. Recently, rituximab (RTX), a B cell-targeted therapy, has been reported to be effective for life-threatening autoimmune diseases. We describe a SLE patient who presented with acute respiratory failure due to DAH without other active organ involvement. This condition was dramatically improved with RTX without cyclophosphamide.
Metabolic Control of Microvascular Networks: Oxygen Sensing and Beyond
Authors: Reglin Bettina , Pries Axel R.
Published: December 2014

The metabolic regulation of blood flow is central to guaranteeing an adequate supply of blood to the tissues and microvascular network stability. It is assumed that vascular reactions to local oxygenation match blood supply to tissue demand via negative-feedback regulation. Low oxygen (O2) levels evoke vasodilatation, and thus an increase of blood flow and oxygen supply, by increasing (decreasing) the release of vasodilatory (vasoconstricting) metabolic signal substances with decreasing partial pressure of O2. This review analyses the principles of metabolic vascular control with a focus on the prevailing feedback regulations. We propose the following hypotheses with respect to vessel diameter adaptation. (1) In addition to O2-dependent signaling, metabolic vascular regulation can be effected by signal substances produced independently of local oxygenation (reflecting the presence of cells) due to the dilution effect. (2) Control of resting vessel tone, and thus perfusion reserve, could be explained by a vascular activity/hypoxia memory. (3) Vasodilator but not vasoconstrictor signaling can prevent shunt perfusion via signal conduction upstream to feeding arterioles. (4) For low perfusion heterogeneity in the steady state, metabolic signaling from the vessel wall or a perivascular tissue sleeve is optimal. (5) For amplification of perfusion during transient increases of tissue demand, red blood cell-derived vasodilators or vasoconstrictors diluted in flowing blood may be relevant.
Gliomas in the Sellar Turcica Region: A Retrospective Study Including Adult Cases and Comparison with Craniopharyngioma
Authors: Deng Shuanglin , Li Yunqian , Guan Yi , Xu Songbai , Chen Jingtao , Zhao Gang
Published: December 2014

Purpose: Previous studies of sellar gliomas have been confined to pediatric optic pilocytic gliomas. The present study aimed to analyze the features of sellar gliomas involving both pediatric and adult patients with various pathologies and to compare them with craniopharyngiomas to better differentiate the diagnosis. Methods: Twenty-seven sellar gliomas were retrospectively examined regarding their demographics, pathologies, clinical and imaging presentations, surgeries and postoperative complications. Thirty craniopharyngiomas from the same period and 880 gliomas of the most common pathologies from 2008-2014 were included for comparisons. Results: In total, 55.6% of the sellar gliomas were adult cases. The pathology included pilocytic astrocytoma, ganglioglioma, diffuse astrocytoma, pilomyxoid astrocytoma, oligoastrocytoma, and glioblastoma. Compared with craniopharygiomas, sellar gliomas presented with a significantly lower ratio of visual disturbances, growth hormone deficiencies, lesion cystic changes, and calcification. Sellar gliomas had significantly greater effects on the patients' mentality and anatomical brain stem involvement. Total resections were achieved in 11 patients, which were significantly lower compared with craniopharyngiomas. Conclusions: Sellar gliomas affect both pediatric and adult patients with pathological changes extending beyond pilocytic astrocytomas. They have diverse clinical manifestations and imaging presentations. Differences exist regarding several aspects between sellar gliomas and craniopharyngiomas, which may facilitate a differential diagnosis.
First-Trimester Screening for Gestational Diabetes Mellitus Based on Maternal Characteristics and History
Authors: Syngelaki Argyro , Pastides Alice , Kotecha Reena , Wright Alan , Akolekar Ranjit , Nicolaides Kypros H.
Published: December 2014

Objectives: To develop and validate a prediction model for gestational diabetes mellitus (GDM) at 11-13 weeks' gestation based on maternal characteristics and history and to compare its performance with the method recommended by the National Institute of Health and Care Excellence (NICE) and five other published prediction models. Methods: A predictive logistic regression model for GDM was developed from 1,827 cases (2.4%) who developed GDM and 73,334 unaffected controls. A 5-fold cross-validation study was performed to validate this model and to compare its performance with those of the NICE guidelines and the previously published models. Results: In the logistic regression model, maternal age, weight, height, racial origin, family history of diabetes, use of ovulation drugs, birth weight, and previous history of GDM were found to be significant predictors of GDM. In screening for GDM in the 5-fold cross-validation study, detection rates (DRs) were higher (p < 0.0001) for the proposed model (DR = 83.2%) than for the NICE guidelines (DR = 77.5%) for a false positive rate of approximately 40% (determined by NICE). The area under the receiver operating characteristic curve of the new model was higher (p < 0.0001) than that of the previous five models (0.823 vs. 0.688-786). Conclusions: Early effective screening for GDM can be achieved based on maternal characteristics and history.
Spatial and Time-Course Thermodynamics During Pulmonary Vein Isolation Using the Second-Generation Cryoballoon in a Canine In Vivo Model
Authors: Takami Mitsuru , Misiri Juna , Lehmann H. Immo , Parker Kay D. , Johnson Susan B. , Sarmiento Ray I. , Packer Douglas L.
Published: December 2014

Background—

Thermodynamics in the left atrium–pulmonary vein (PV) junction, phrenic nerve, and esophagus during PV isolation (PVI) using the second-generation cryoballoon are not known.

Methods and Results—

Twenty dogs underwent PVI using second-generation cryoballoon. Ablations were performed for ≤2 deliveries based on PVI without a bonus freeze. Inner balloon, balloon surface, and tissue temperatures were monitored during cryoablation. The tissue thermocouples were placed on the epicardial surface of the left atrium–PV junction, as well as on the phrenic nerve and within the esophagus. A total of 259 cryoballoon and 229 tissue tissue thermocouples profiles during 53 cryoablations of 40 PVs were analyzed. Acutely, PVI was achieved in 36 of 40 PVs (90%). Conductive tissue cooling spread radially from the balloon–left atrium–PV contact point. The lowest tissue temperatures were dependent on the distance of the tissue thermocouples to the balloon surface (
r
=0.85;
P
<0.001). In addition, blood flow leaks around the balloon had a warming effect on the balloon and tissue temperature profiles. Chronic isolation (mean, 48±16 days) was achieved in 27 of 36 PVs (75%). In 8 of 9 acutely isolated but with chronic reconnection PVs, the blood flow leak location was concordant with chronic reconnection gap. Although only 1 esophageal ulcerated lesion was observed, neither phrenic nerve palsy nor severe PV stenosis was seen in any dogs.

Conclusions—

Variance in tissue thermodynamics during cryothermal ablation depends on the distance from balloon and peri-balloon blood flow leaks. This information may be useful for successful PVI without severe complications.
Osteoglycin Prevents Cardiac Dilatation and Dysfunction After Myocardial Infarction Through Infarct Collagen Strengthening
Authors: Van Aelst Lucas N.L. , Voss Sandra , Carai Paolo , Van Leeuwen Rick , Vanhoutte Davy , Sanders-van Wijk Sandra , Eurlings Luc , Swinnen Melissa , Verheyen Fons K. , Verbeken Eric , Nef Holger , Troidl Christian , Cook Stuart A. , Brunner-La Rocca Hans-Peter , Möllmann Helge , Papageorgiou Anna-Pia , Heymans Stephane
Published: December 2014

Rationale:

To maintain cardiac mechanical and structural integrity after an ischemic insult, profound alterations occur within the extracellular matrix. Osteoglycin is a small leucine-rich proteoglycan previously described as a marker of cardiac hypertrophy.

Objective:

To establish whether osteoglycin may play a role in cardiac integrity and function after myocardial infarction (MI).

Methods and Results:

Osteoglycin expression is associated with collagen deposition and scar formation in mouse and human MI. Absence of osteoglycin in mice resulted in significantly increased rupture-related mortality with tissue disruption, intramyocardial bleeding, and increased cardiac dysfunction, despite equal infarct sizes. Surviving osteoglycin null mice had greater infarct expansion in comparison with wild-type mice because of impaired collagen fibrillogenesis and maturation in the infarcts as revealed by electron microscopy and collagen polarization. Absence of osteoglycin did not affect cardiomyocyte hypertrophy in the remodeling remote myocardium. In cultured fibroblasts, osteoglycin knockdown or supplementation did not alter transforming growth factor-β signaling. Adenoviral overexpression of osteoglycin in wild-type mice significantly improved collagen quality, thereby blunting cardiac dilatation and dysfunction after MI. In osteoglycin null mice, adenoviral overexpression of osteoglycin was unable to prevent rupture-related mortality because of insufficiently restoring osteoglycin protein levels in the heart. Finally, circulating osteoglycin levels in patients with heart failure were significantly increased in the patients with a previous history of MI compared with those with nonischemic heart failure and correlated with survival, left ventricular volumes, and other markers of fibrosis.

Conclusions:

Increased osteoglycin expression in the infarct scar promotes proper collagen maturation and protects against cardiac disruption and adverse remodeling after MI. In human heart failure, osteoglycin is a promising biomarker for ischemic heart failure.
Fifteen from one: a revision of the Galaxias olidus Günther, 1866 complex (Teleostei, Galaxiidae) in south-eastern Australia recognises three previously described taxa and describes 12 new species
Authors: RAADIK TARMO A.
Published: December 2014

The systematics of the Galaxias olidus hyper-species complex from freshwater habitats in south-eastern, mainland Australia is revised. Galaxias olidus Günther 1866 is redescribed, Galaxias fuscus Mack 1936 and Galaxias ornatus Castelnau 1873, previously synonymised with G. olidus (sensu lato), are reinstated as valid taxa and redescribed, and 12 taxa are described as new: Galaxias aequipinnis sp. nov., Galaxias arcanus sp. nov., Galaxias brevissimus sp. nov., Galaxias gunaikurnai sp. nov., Galaxias lanceolatus sp. nov., Galaxias longifundus sp. nov., Galaxias mcdowalli sp. nov., Galaxias mungadhan sp. nov., Galaxias oliros sp. nov., Galaxias supremus sp. nov., Galaxias tantangara sp. nov., and Galaxias terenasus sp. nov. These species are morphologically similar and, whilst there is extensive overlap in meristic counts and morphometric characters, each can be diagnosed by unique combinations of characters, including allozyme loci and colour pattern; morphological diagnosis is improved greatly if based on freshly formalin-fixed material. Galaxias schomburgkii Peters 1868, Galaxias bongbong Macleay 1881, Galaxias kayi Ramsay & Ogilby 1886 and Galaxias oconnori Ogilby 1912 are retained as junior synonyms of G. olidus (sensu stricto). The types for Galaxias findlayi Macleay 1882 are lost and no specimens matching its description were collected or examined from the Mt. Kosciuszko region; it is also currently retained as a junior synonym of Galaxias olidus s.s. The species G. terenasus sp. nov. and G. arcanus sp. nov. are the most morphologically specialised in the complex and G. olidus s.s remains the most morphologically variable species. It also remains the most widespread taxon, though its previously known distribution is reduced, particularly in the south-west of its range. Nine species are narrow-range endemics, known from one, or only a few, locations, and these restricted distributions most probably reflect the fragmentation and reduction of former ranges caused by the effects of alien salmonids. Eleven species are of conservation concern, most are considered critically endangered.
Energy Flux into Internal Lee Waves: Sensitivity to Future Climate Changes Using Linear Theory and a Climate Model
Authors: Melet Angélique , Hallberg Robert , Adcroft Alistair , Nikurashin Maxim , Legg Sonya
Published: December 2014

Internal lee waves generated by geostrophic flows over rough topography are thought to be a significant energy sink for eddies and energy source for deep ocean mixing. The sensitivity of the energy flux into lee waves from preindustrial, present, and possible future climate conditions is explored in this study using linear theory. The bottom stratification and geostrophic velocity fields needed for the calculation of the energy flux into lee waves are provided by Geophysical Fluid Dynamics Laboratory’s global coupled ocean–ice–atmosphere model, CM2G. The unresolved mesoscale eddy energy is parameterized as a function of the large-scale available potential energy. Simulations using historical and representative concentration pathway (RCP) scenarios were performed over the 1861–2200 period. The diagnostics herein suggest a decrease of the global energy flux into lee waves on the order of 20% from preindustrial to future climate conditions under the RCP8.5 scenario. In the Southern Ocean, the energy flux into lee waves exhibits a clear annual cycle with maximum values in austral winter. The long-term decrease of the global energy flux into lee waves and the annual cycle of the energy flux in the Southern Ocean are mostly due to changes in bottom velocity.
Isohaline Salinity Budget of the North Atlantic Salinity Maximum
Authors: Bryan Frank , Bachman Scott
Published: December 2014

In this study, the salinity budget of the North Atlantic subtropical salinity maximum region for control volumes bounded by isohaline surfaces is analyzed. The authors provide closed budgets based on output from a high-resolution numerical simulation and partial budgets based on analyses of observational climatologies of hydrography and surface fluxes. With this choice of control volume, advection is eliminated from the instantaneous volume-integrated salt budget, and time-mean advection is eliminated from the budget evaluated from time-averaged data. In this way, the role of irreversible mixing processes in the maintenance and variability of the salinity maximum are more readily revealed. By carrying out the analysis with both near-instantaneous and time-averaged model output, the role of mesoscale eddies in stirring and mixing for this water mass is determined. This study finds that the small-scale mixing acting on enhanced gradients generated by the mesoscale eddies is approximately equal to that acting on the large-scale gradients estimated from climatological-mean conditions. The isohaline salinity budget can be related to water mass transformation rates associated with surface forcing and mixing processes in a straightforward manner. The authors find that the surface net evaporation in the North Atlantic salinity maximum region accounts for a transformation of 7 Sverdrups (Sv; 1 Sv ≡ 106 m3 s−1) of water across the 37-psu isohaline outcrop into the salinity maximum in the simulation, whereas the estimate based on climatological observations is 9 to 10 Sv.
Numerical Simulation of Terrestrial Radiation over a Snow Cover
Authors: Ducharme P. , Houdayer A. , Choquette Y. , Kapfer B. , Martin J. P.
Published: December 2014

The intensity of terrestrial gamma radiation is a function of a number of parameters: emissivity and spatial distribution of the radioactive material in the soil, snow/water cover above ground, soil moisture content, type, and height above ground of the detector. Thus, the conversion of gamma measurements into reliable information must be based on a solid knowledge of the behavior of the gamma detector under different conditions. Such a detector, using a cylindrical NaI(Tl) crystal, was developed to remotely and automatically provide information on snow water equivalent (SWE) and soil moisture content (M). It became rapidly obvious that the behavior of the detector [gamma monitor (GMON)] over an infinite source could not be exactly reproduced in a laboratory. Therefore, a relatively simple model to simulate the behavior of GMON and to establish the relevant data analysis algorithms was conceived. This paper presents the basic assumptions for developing the model, the resulting algorithms, a comparison with field measurements, and some useful information on how GMON reacts to various field conditions.
Safety of Outpatient Airway Dilation for Adult Laryngotracheal Stenosis
Authors: Hsu Yen-Bin , Damrose Edward J.
Published: December 2014

Objectives:

To evaluate the safety of outpatient airway dilation for adult patients with subglottic or tracheal stenosis.

Methods:

The records of patients treated with airway dilation between October 2003 and September 2013 were reviewed. Outcomes of patients who underwent dilation as inpatients versus outpatients were compared. Emergency room visits, readmissions, and 3 or more primary care physician visits within 30 days postoperatively were specifically evaluated. Postoperative hemorrhage, airway edema, recurrent laryngeal nerve paralysis, reintubation, tracheostomy, tracheal rupture, pneumomediastinum, pneumothorax, acute respiratory distress, or death were also reviewed.

Results:

One hundred fourteen dilations performed in 53 patients with airway stenosis were included. Outpatient dilation was performed in 93 (82%); 21 (18%) underwent the procedure in the inpatient setting. Complications were low among both inpatient and outpatient groups (10% vs 1%, P = .09). No complications occurred during the overnight stay of the inpatient group.

Conclusions:

Outpatient airway dilation is a safe and feasible procedure. It can be routinely performed on an ambulatory basis.
Corporate Social Responsibility and Job Choice Intentions
Authors: Dawkins Cedric E. , Jamali Dima , Karam Charlotte , Lin Lianlian , Zhao Jixin
Published: December 2014

A theory of planned behavior (TPB) framework was employed to investigate the impact of corporate social responsibility (CSR) perceptions on the job choice intentions of American, Chinese, and Lebanese college students. Attitudes toward CSR, subjective norm, and perceived behavioral control explained moderate levels of the variance in job choice intention in all three countries. Attitudes toward CSR, which entailed individual evaluations of CSR, were positively related to job choice intentions among Lebanese and American respondents, but not Chinese respondents. Subjective norm, the importance accorded the views of significant others, was most strongly related to job choice intentions among Chinese respondents. Perceived behavioral control, the perceived degree of control over one’s actions and outcomes, had the strongest relationship to job choice intentions among American respondents. The authors concluded that respondents in the three countries did not differ in the extent to which they intend to work for socially responsible firms but tended to derive their intentions in different ways. Implications for tailoring CSR and recruitment efforts across countries are derived based on the findings.
Zinc-Fortified Oral Rehydration Solution Improved Intestinal Permeability and Small Intestinal Mucosal Recovery
Authors: Tran Cuong D. , Hawkes Joanna , Graham Robin D. , Kitchen Julie L. , Symonds Erin L. , Davidson Geoffrey P. , Butler Ross N.
Published: December 2014

A randomized double-blind placebo-controlled study was conducted in children admitted to hospital with gastroenteritis (≥3 loose stools per day). All were treated for 5 days following admission with either zinc (Zn, 3 mg) or without Zn-fortified rice-based oral rehydration solution (ORS). 13C-sucrose breath test (SBT) and intestinal permeability (lactulose/rhamnose or L/R ratio) were performed concurrently prior to commencement of ORS with or without Zn and at day 5 post-admission. There was a significant improvement in the SBT results in both the Zn-fortified group, median (5th-95th percentile) 2.1% (0.4% to 8.3%) versus 4.4% (0.4% to 10.4%), P < .05, and control group, 1.4% (0.1% to 5.4%) versus 4.3% (0.4% to 11.4%), P < .05, between the day of admission and day 5 post-admission. In the Zn-fortified group, there was also a significant improvement in L/R ratio between the day of admission and day 5 post-admission, 53.0 (19.5-90.6) versus 17.7 (13.4-83.2), P < .05. Low levels of Zn improved intestinal permeability but did not enhance short-term recovery following diarrheal illness.