bluuebunny/crossref_metadata_2025 huggingface dataset:
Lipopolysaccharide-induced phosphorylation of c-Met tyrosine residue 1003 regulates c-Met intracellular trafficking and lung epithelial barrier function
Authors: Zhao Yutong , Zhao Jing , Mialki Rachel K. , Wei Jianxin , Spannhake Ernst W. , Salgia Ravi , Natarajan Viswanathan
Published: April 2013

c-Met, the receptor tyrosine kinase whose natural ligand is hepatocyte growth factor, is known to have a key role in cell motility. We have previously shown that lysophosphatidic acid (LPA) induced a decrease in c-Met activation via serine phosphorylation of c-Met at cell-cell contacts. Here, we demonstrate that lipopolysaccharide (LPS) treatment of human bronchial epithelial cells induced internalization of c-Met via phosphorylation at its tyrosine residue 1003. In addition, it induced epithelial barrier dysfunction as evidenced by a decrease in transepithelial resistance (TER) in a time-dependent manner. Pretreatment with a c-Met inhibitor (PHA-665752) or inhibition of protein kinase C (PKC)-α attenuated the LPS-mediated phosphorylation of c-Met and its internalization. LPS-induced c-Met tyrosine 1003 phosphorylation, activation of PKCα, and c-Met internalization were, however, reversed by pretreatment of cells with LPA, which increased c-Met accumulation at cell-cell contacts. Inhibition of LPS-mediated c-Met tyrosine (Y1003) phosphorylation and internalization by prior treatment with PHA-665752, inhibition of PKCα, or overexpression of c-MetY1003Amutant attenuated LPS-induced reduction of TER. Furthermore, we found that c-Met accumulation at cell-cell contacts contributed to LPA-enhanced epithelial barrier integrity, since downregulation of c-Met by specific small-interfering RNA attenuated LPA-increased TER. The data reveal a novel biological function of c-Met in the regulation of lung epithelial barrier integrity.
Efficient delivery of RNA interference oligonucleotides to polarized airway epithelia in vitro
Authors: Ramachandran Shyam , Krishnamurthy Sateesh , Jacobi Ashley M. , Wohlford-Lenane Christine , Behlke Mark A. , Davidson Beverly L. , McCray Paul B.
Published: April 2013

Polarized and pseudostratified primary airway epithelia present barriers that significantly reduce their transfection efficiency and the efficacy of RNA interference oligonucleotides. This creates an impediment in studies of the airway epithelium, diminishing the utility of loss-of-function as a research tool. Here we outline methods to introduce RNAi oligonucleotides into primary human and porcine airway epithelia grown at an air-liquid interface and difficult-to-transfect transformed epithelial cell lines grown on plastic. At the time of plating, we reverse transfect small-interfering RNA (siRNA), Dicer-substrate siRNA, or microRNA oligonucleotides into cells by use of lipid or peptide transfection reagents. Using this approach we achieve significant knockdown in vitro of hypoxanthine-guanine phosphoribosyltransferase, IL-8, and CFTR expression at the mRNA and protein levels in 1–3 days. We also attain significant reduction of secreted IL-8 in polarized primary pig airway epithelia 3 days posttransfection and inhibition of CFTR-mediated Cl−conductance in polarized air-liquid interface cultures of human airway epithelia 2 wk posttransfection. These results highlight an efficient means to deliver RNA interference reagents to airway epithelial cells and achieve significant knockdown of target gene expression and function. The ability to reliably conduct loss-of-function assays in polarized primary airway epithelia offers benefits to research in studies of epithelial cell homeostasis, candidate gene function, gene-based therapeutics, microRNA biology, and targeting the replication of respiratory viruses.
A Systematic Review of Depression and Anxiety in Patients with Atrial Fibrillation: The Mind-Heart Link
Authors: Patel Dimpi , Mc Conkey Nathaniel D. , Sohaney Ryann , Mc Neil Ashley , Jedrzejczyk Andy , Armaganijan Luciana
Published: April 2013

Atrial fibrillation (AF) is the most commonly seen arrhythmia in clinical practice. At present, few studies have been conducted centering on depression and anxiety in AF patients. Our aim in this systematic review is to use the relevant literature to (1) describe the prevalence of depression and anxiety in AF patients, (2) assess the impact that depression and anxiety have on illness perception in patients with AF, (3) provide evidence to support a hypothetical connection between the pathophysiology of AF and depression and anxiety, (4) evaluate the benefit of treatment of AF on depression and anxiety, and (5) give insight on medically managing a patient with AF and concomitant depression and anxiety.
A Case of Atypical Mucin Balls Wearing Extended Wear of Silicone Hydrogel Lens for Therapeutic Use
Authors: Matsuzaki Yusuke , Toshida Hiroshi , Ohta Toshihiko , Murakami Akira
Published: April 2013

A 25-year-old man visited our hospital showing atopic conjunctivitis and corneal shield ulcer on his left eye. Although eye drops of 0.1% of betamethasone sodium phosphate and 0.1% of hyaluronic acid ophthalmic solution were prescribed, calcific corneal opacities developed. The corrected visual acuity decreased to 6/20 in Snellen chart. After corneal epithelial exfoliation, removal of calcific corneal opacity was scrubbed with MQA soaked in 0.05 M of ethylenediaminetetraacetic acid (EDTA). After washing the eye with 200 mL of physiological saline, a silicon hydrogel lens, PureVision (balafilcon A), was inserted to obtain pain relief for the therapeutic use. At postoperative day 11, mucin balls were found between cornea and contact lens and stained by rose bengal dye. One of them was atypically larger than usual, and the major axis was approximately 1.5 mm. Wearing lens was stopped, and all of mucin balls and corneal staining were disappeared at postoperative day. Little corneal opacity remained, and visual acuity after surgery recovered to 14/20 at five months.
Assessment of Fatty Liver Syndrome and Its Predisposing Factors in a Dairy Herd from Venezuela
Authors: Gonzalez Clara I. , Rosendo Oswaldo
Published: April 2013

The present on-farm research evaluated the occurrence of fatty liver syndrome and its predisposing risk factors for multiparous dairy cows from a commercial herd in Venezuela. Liver biopsy samples were collected at 35 days (d) prepartum (Holstein, ; Holstein × Carora crossbred, ) as well as 1 to 7 d (Holstein, ; Holstein × Carora crossbred, ) and 28 to 35 d (Holstein, ; Holstein × Carora crossbred, ) postpartum in order to analyse hepatic triacylglycerols (TAG, % wet basis) and glycogen concentrations. At postpartum, an occurrence of 72.0% for severe fatty liver along with 73.5% of subclinical ketosis (SCK) was found. The multiple regression model that best explained the association between milk production in the previous lactation (MYP) and TAG at first week postpartum was as follows: TAG, % = −11.2 + 3.16 (prepartum body condition) + 0.0009176 (MYP) (, ). Logistic regression indicated that Holstein × Carora crossbred cows tended to have 27% higher relative risk than Holstein to experience SCK, whereas prepartum liver TAG greater than 3% tended to be associated with a higher relative risk for SCK compared to cows with TAG ≤3%.
The Clinical Efficiency of Positive Airway Pressure Treatment
Authors: Koseoglu Sabri , Ikinciogullari Aykut , Cetin Mehmet Ali , Saygi Uysal Gokce , Kum Rauf Oguzhan , Arli Berna
Published: April 2013

Objectives. The aim of this study was to evaluate the clinical efficiency and compliance of positive airway pressure (PAP) treatment. Materials and Methods. This study was conducted on moderate‐severe obstructive sleep apnea syndrome (OSAS) patients who admitted to Ankara Numune Hospital Sleep Center between 2008 and 2012. Seventy‐five patients with moderate‐severe OSAS who were using PAP treatment regularly were enrolled in the study. Patient′s usage data, Epworth sleepiness scale (ESS) scores, and the differences in complaints of OSAS were recorded. Results. The overall complaints were improved when compared to pretreatment period. Particularly there was improvement in apnea, snoring, excessive daytime sleepiness, fatigue, and sleep quality. Conclusion. PAP is effective in reducing symptoms in people with moderate and severe OSAS. To inform the patients with details and the creation of strategies for close followup are necessary for improving the compliance of the patients. Trial registration number: ACTRN12613000373774.
Assessing Hospital Readmission Risk Factors in Heart Failure Patients Enrolled in a Telemonitoring Program
Authors: Zai Adrian H. , Ronquillo Jeremiah G. , Nieves Regina , Chueh Henry C. , Kvedar Joseph C. , Jethwani Kamal
Published: April 2013

The purpose of this study was to validate a previously developed heart failure readmission predictive algorithm based on psychosocial factors, develop a new model based on patient-reported symptoms from a telemonitoring program, and assess the impact of weight fluctuations and other factors on hospital readmission. Clinical, demographic, and telemonitoring data was collected from 100 patients enrolled in the Partners Connected Cardiac Care Program between July 2008 and November 2011. 38% of study participants were readmitted to the hospital within 30 days. Ten different heart-failure-related symptoms were reported 17,389 times, with the top three contributing approximately 50% of the volume. The psychosocial readmission model yielded an AUC of 0.67, along with sensitivity 0.87, specificity 0.32, positive predictive value 0.44, and negative predictive value 0.8 at a cutoff value of 0.30. In summary, hospital readmission models based on psychosocial characteristics, standardized changes in weight, or patient-reported symptoms can be developed and validated in heart failure patients participating in an institutional telemonitoring program. However, more robust models will need to be developed that use a comprehensive set of factors in order to have a significant impact on population health.
An Unexpected Near Term Pregnancy in a Rudimentary Uterine Horn
Authors: Gonçalves Elisabete , Prata João Pedro , Ferreira Sandra , Abreu Rita , Mesquita Jorge , Carvalho Agostinho , Pinheiro Paula
Published: April 2013

Unicornuate uterus occurs due to a complete or partial nondevelopment of one Mullerian duct; sometimes it is associated with a rudimentary horn, which can communicate or not with uterine cavity or contain functional endometrium. Pregnancy in a rudimentary horn is rare and the outcome almost always unfavorable, usually ending in rupture during the first or second trimester with significant morbidity and mortality. Despite the availability and advances on imagiologic procedures, recognition of this ectopic pregnancy is frequently made at laparotomy after abdominal pain and collapse. The authors describe a case of a primigravida with 34 weeks of gestation admitted with a preeclampsia with severity criteria. A cesarean for fetal malpresentation was done and, unexpectedly, a rudimentary horn pregnancy was found with a live newborn. In the literature, few reports of a horn pregnancy reaching the viability with a live newborn are described, enhancing the clinical importance of this case. A review of literature concerning the epidemics, clinical presentation, and appropriate management of uterine horn pregnancies is made.
Evaluation of Clinical and Immunological Responses: A 2-Year Follow-Up Study in Children with Allergic Rhinitis due to House Dust Mite
Authors: Moed Heleen , Gerth van Wijk Roy , Hendriks Rudi W. , van der Wouden J. C.
Published: April 2013

Background. Allergic rhinitis is a disease with polarization towards Th2and a defect of regulatory T cells. Immunological changes have been reported after immunotherapy treatment. However, there is not much known about the natural course of allergic rhinitis with respect to clinical manifestation and the relation with immunological responses.Objective. To evaluate clinical symptoms of allergic rhinitis, in relation toin vivoallergen-specific skin responses andin vitroallergen-specific effector and regulatory T cells determined at baseline and after two years.Methods. From a large trial, 59 children were randomly selected. The following variables were compared: clinical symptoms, allergen skin tests, specific IgE, T-cell proliferation, IL-5, IL-13, IFN-gamma, IL-10, TGF-beta,CD4+CD25hicells, and Foxp3 expression.Results. Allergic symptoms had decreased after two years. Whereas skin test reactions correlated between years 0 and 2, there was no change in the size of the reaction. Also, proinflammatory reactions did not change after two years, with a positive correlation between years 0 and 2. No relevant changes were observed with respect to regulatory cells.Conclusion. Whereas, comparable to immunotherapy, allergic complaints decrease, the immunological changes of specific T-cell activity (both effector cells and regulator cells) which are observed after immunotherapy, do not change.
Automatic Offline Formulation of Robust Model Predictive Control Based on Linear Matrix Inequalities Method
Authors: Zhang Longge
Published: April 2013

Two automatic robust model predictive control strategies are presented for uncertain polytopic linear plants with input and output constraints. A sequence of nested geometric proportion asymptotically stable ellipsoids and controllers is constructed offline first. Then the feedback controllers are automatically selected with the receding horizon online in the first strategy. Finally, a modified automatic offline robust MPC approach is constructed to improve the closed system's performance. The new proposed strategies not only reduce the conservatism but also decrease the online computation. Numerical examples are given to illustrate their effectiveness.
The Periodic Solutions for Planar -Body Problems
Authors: Hu Xiaohong , Zhu Changrong
Published: April 2013

Based on the works of Perko and Walter, Moeckel and Simo, and Zhang and Zhou, we study the necessary conditions and suffcient conditions for the uniformly rotating planar nested regular polygonal periodic solutions for the -body problems.
Modeling Bistable Composite Laminates for Piezoelectric Morphing Structures
Authors: Murray Darryl V. , Myers Oliver J.
Published: April 2013

A sequential modeling effort for bistable composite laminates for piezoelectric morphing structures is presented. Thin unsymmetric carbon fiber composite laminates are examined for use of morphing structures using piezoelectric actuation. When cooling from the elevated cure temperature to room temperature, these unsymmetric composite laminates will deform. These postcure room temperature deformation shapes can be used as morphing structures. Applying a force to these deformed laminates will cause them to snap through to another shape. This bistability arises from the fabrication process of the thin unsymmetric laminates. The snap through force studied here will be controlled by using piezoelectricity. Macrofiber composite (MFC) actuators are used for piezoelectric actuation. In this research, an analytical modeling method is presented to accurately depict the piezoelectric morphing structures. Sequential numerical modeling of the cure process to account for residual stresses and postcured shapes and piezoelectric morphing structure is done to predict the piezoelectric actuated displacements of the thin unsymmetric composite laminates. Analytical and numerical models are compared to experimental methods and results.
The Technique of Measures of Noncompactness in Banach Algebras and Its Applications to Integral Equations
Authors: Banaś Józef , Dudek Szymon
Published: April 2013

We study the solvability of some nonlinear functional integral equations in the Banach algebra of real functions defined, continuous, and bounded on the real half axis. We apply the technique of measures of noncompactness in order to obtain existence results for equations in question. Additionally, that technique allows us to obtain some characterization of considered integral equations. An example illustrating the obtained results is also included.
SCL-90-R Symptom Profiles and Outcome of Short-Term Psychodynamic Group Therapy
Authors: Jensen Hans Henrik , Mortensen Erik L. , Lotz Martin
Published: April 2013

Background. Psychodynamic group psychotherapy may not be an optimal treatment for anxiety and agoraphobic symptoms. We explore remission of SCL-90-R Global Severity Index (GSI) and target symptoms in 39 sessions of psychodynamic group therapy. Methods. SCL-90-R “target symptom” profile and GSI remission according to Danish norms were identified in 239 patients and evaluated according to reliable and clinical significant change. Results. Four major groups of target symptom cases (depression, interpersonal sensitivity, anxiety, and phobic anxiety) covered 95.7% of the sample. As opposite to phobic anxiety and anxiety patients, patients with interpersonal sensitivity obtained overall the most optimal outcome. The phobic anxiety scale, social network support, and years of school education were independent predictors of GSI remission, and a low anxiety score and absence of phobic anxiety target symptoms were independent predictors of remission of target symptom pathology. Conclusions. The negative results as associated with the SCL-90-R phobic anxiety scale and the phobic anxiety target symptom group are largely in agreement with recent studies. In contrast, whatever the diagnoses, patients with interpersonal sensitivity target symptom may be especially suited for psychodynamic group therapy. The SCL-90-R subscales may allow for a more complex symptom-related differentiation of patients compared with both diagnoses and GSI symptom load.
Temporary Balloon Occlusion of the Common Hepatic Artery for Yttrium-90 Glass Microspheres Administration in a Patient with Hepatocellular Cancer and Renal Insufficiency
Authors: Smith Justin , Murthy Ravi , Lahoti Amit , Odisio Bruno , Avritscher Rony , Chasen Beth , Mahvash Armeen
Published: April 2013

The most severe complication of yttrium-90 therapy is gastrointestinal ulceration caused by extrahepatic dispersion of microspheres. Standard pretreatment planning requires extensive angiographic evaluation of the hepatic circulation and embolization of hepatoenteric collaterals; however, in patients with severe renal insufficiency, this evaluation may lead to acute renal failure. In order to minimize iodinated contrast utilization in a patient with preexisting severe renal insufficiency, the authors describe the use of a balloon catheter for temporary occlusion of the common hepatic artery to induce transient redirection of flow of the hepatoenteric arteries towards the liver, in lieu of conventional coil embolization.
Effects of Single Exposure of Sodium Fluoride on Lipid Peroxidation and Antioxidant Enzymes in Salivary Glands of Rats
Authors: Yamaguti Paula Mochidome , Simões Alyne , Ganzerla Emily , Souza Douglas Nesadal , Nogueira Fernando Neves , Nicolau José
Published: April 2013

Many studies suggest that fluoride exposure can inhibit the activity of various enzymes and can generate free radicals, which interfere with antioxidant defence mechanisms in living systems. To further the understanding of this issue, this present study examined the effects of low-dose fluoride treatment on the activity of enzymatic antioxidant superoxide dismutase (SOD) and catalase (CAT), as well as the levels of lipid peroxidation (LPO) in the parotid (PA) and submandibular (SM) salivary glands of rats. Rats were injected with a single dose of sodium fluoride (NaF) (15 mg F−/kg b.w.) then euthanized at various time intervals up to 24 hours (h) following exposure. NaF exposure did not cause significant differences in SOD or CAT activity or LPO levels in PA glands compared to control. Conversely, SM glands presented increased SOD activity after 3 h and decreased SOD activity after 1, 12, and 24 h, while LPO was increased after 6, 12, and 24 h of the NaF injection. There were no significant differences in the CAT activity in the groups studied. Our results demonstrated that NaF intoxication caused oxidative stress in salivary glands few hours after administration. These changes were more pronounced in SM than in PA gland.
Descemet Stripping Endothelial Keratoplasty in a Patient with Keratoglobus and Chronic Hydrops Secondary to a Spontaneous Descemet Membrane Tear
Authors: Kolomeyer Anton M. , Chu David S.
Published: April 2013

Purpose. To report the use of Descemet stripping endothelial keratoplasty (DSEK) in a patient with keratoglobus and chronic hydrops.Case Report. We describe a case of a 28-year-old man with bilateral keratoglobus and chronic hydrops in the right eye secondary to spontaneous Descemet membrane tear. The patient presented with finger counting (CF) vision, itching, foreign body sensation, and severe photophobia in the right eye. Peripheral corneal thinning with central corneal protrusion and Descemet membrane tear spanning from 4 to 7 o'clock was noted on slit lamp examination. The right eye cornea was 15 mm in the horizontal diameter. After a 5.5-month loss to follow-up, the patient presented with discomfort, photophobia, decreasing vision, and tearing in the right eye. Vision was 20/60 with pinhole. 360-degree peripheral corneal ectasia with mild neovascularization and hydrops was present. Over the next few months, the patient complained of photophobia and intermittent eye pain. His vision deteriorated to CF, he developed corneal scarring with bullae, and a DSEK was performed. Eight months postoperatively, best-corrected vision improved to 20/30, cornea was clear, and the DSEK graft was stable.Conclusions. Nonresolving hydrops secondary to Descemet membrane tear in a patient with keratoglobus may result in permanent endothelial cell damage and scar formation. This may be successfully treated with DSEK.
Regularity Criteria for a Coupled Navier-Stokes and Q-Tensor System
Authors: Fan Jishan , Ozawa Tohru
Published: April 2013

We study a system describing the evolution of a nematic liquid crystal flow. The system couples a forced Navier-Stokes system describing the flow with a parabolic-type system describing the evolution of the nematic crystal director fields (Q-tensors). We prove some regularity criteria for the local strong solutions. However, we do not provide estimates on the rates of increase of high norms.
On Distributed Reduced-Order Observer-Based Protocol for Linear Multiagent Consensus under Switching Topology
Authors: Zhang Yan , Gao Lixin , Tong Changfei
Published: April 2013

We discuss linear multiagent systems consensus problem with distributed reduced-order observer-based protocol under switching topology. We use Jordan decomposition method to prove that the proposed protocols can solve consensus problem under directed fixed topology. By constructing a parameter-dependent common Lyapunov function, we prove that the distributed reduced-order observer-based protocol can also solve the continuous-time multi-agent consensus problem under the undirected switching interconnection topology. Then, we investigate the leader-following consensus problem and propose a reduced-order observer-based protocol for each following agent. By using similar analysis method, we can prove that all following agents can track the leader under a class of directed interaction topologies. Finally, the given simulation example also shows the effectiveness of our obtained result.
A Modified STAP Estimator for Superresolution of Multiple Signals
Authors: Wang Zhongbao , Xie Junhao , Ma Zilong , Quan Taifan
Published: April 2013

A modified space-time adaptive processing (STAP) estimator is described in this paper. The estimator combines the incremental multiparameter (IMP) algorithm and the existing beam-space preprocessing techniques yielding a computationally cheap algorithm for the superresolution of multiple signals. It is a potential technique for the remote sensing of the ocean currents from the broadened first-order Bragg sea echo spectrum of shipborne high-frequency surface wave radar (HFSWR). Some simulation results and real-data analysis are shown to validate the proposed algorithm.
Commutators of Higher Order Riesz Transform Associated with Schrödinger Operators
Authors: Liu Yu , Wang Lijuan , Dong Jianfeng
Published: April 2013

LetL=-Δ+Vbe a Schrödinger operator onℝn(n≥3), whereV≢0is a nonnegative potential belonging to certain reverse Hölder classBsfors≥n/2. In this paper, we prove the boundedness of commutatorsℛbHf=bℛHf-ℛH(bf)generated by the higher order Riesz transformℛH=∇2(-Δ+V)-1, whereb∈BMOθ(ρ), which is larger than the spaceBMO(ℝn). Moreover, we prove thatℛbHis bounded from the Hardy spaceHL1(ℝn)into weakLweak1(ℝn).
Utility of Computed Tomographic Enteroclysis/Enterography for the Assessment of Mucosal Healing in Crohn's Disease
Authors: Hashimoto Shinichi , Shimizu Kensaku , Shibata Hiroaki , Kanayama Satoko , Tanabe Ryo , Onoda Hideko , Matsunaga Naohumi , Sakaida Isao
Published: April 2013

Aim. When determining therapeutic strategy, it is important to diagnose small intestinal lesions in Crohn's disease (CD) precisely and to evaluate mucosal healing as well as clinical remission in CD. The purpose of this study was to compare findings from computed tomographic enteroclysis/enterography (CTE) with those from the mucosal surface and to determine whether the state of mucosal healing can be determined by CTE.Materials and Methods. Of the patients who underwent CTE for CD, 39 patients were examined whose mucosal findings could be confirmed by colonoscopy, capsule endoscopy, balloon endoscopy, or with the resected surgical specimens.Results. According to the CTE findings, patients were determined to be in the active CD group (n=31) or inactive CD group (n=8). The proportion of previous surgery, clinical remission, stenosis, and CDAI score all showed significant difference between groups. Mucosal findings showed an association with ulcer in 93.6% of active group patients but in only 12.5% of inactive group patients (P<0.0001), whereas mucosal healing was found in 62.5% of inactive group patients but in only 3.2% of active group patients (P<0.0001).Conclusion. CTE appeared to be a useful diagnostic method for assessment of mucosal healing in Crohn's disease.
Lifestyle and Dietary Factors in Relation to Risk of Chronic Myeloid Leukemia in the NIH-AARP Diet and Health Study
Authors: Kabat Geoffrey C. , Wu Jennifer W. , Moore Steven C. , Morton Lindsay M. , Park Yikyung , Hollenbeck Albert R. , Rohan Thomas E.
Published: April 2013

Background: Aside from exposure to ionizing radiation and benzene, little is known about lifestyle risk factors for chronic myeloid leukemia (CML) in the general population.

Methods: We examined the relation between lifestyle and dietary risk factors for CML in 493,188 participants (294,271 males and 198,917 females) aged 50 to 71 years who completed a baseline questionnaire in the National Institutes of Health-AARP Diet and Health Study in 1995 to 1996. Over a median of 10.5 years of follow-up, 178 incident cases of CML (139 males and 39 females) were ascertained from state registries. We used Cox proportional hazards models to estimate hazard ratios and 95% confidence intervals for exposures of interest, adjusting for potential confounding variables.

Results: In multivariable analysis of all participants combined, female sex, years of education, and vigorous physical activity (HR for ≥3 times/week vs. <1 time/week 0.70; 95% CI, 0.49–0.99) were inversely associated with risk of CML, whereas smoking intensity (HR for smokers of ≥20 cigarettes per day vs. never smokers: 1.53; 95% CI, 1.03–2.27) and body mass (HR for BMI ≥ 30 vs. <25 kg/m2 1.46; 95% CI, 0.95–2.23) were associated with increased risk. A range of dietary factors was not associated with disease.

Conclusions: This study adds to the sparse information about lifestyle factors, which affect the risk of CML in the general population.

Impact: If these findings are confirmed, it would suggest that CML may be amenable to preventive strategies. Cancer Epidemiol Biomarkers Prev; 22(5); 848–54. ©2013 AACR.
A Novel Antiandrogen, Compound 30, Suppresses Castration-Resistant and MDV3100-Resistant Prostate Cancer Growth In Vitro and In Vivo
Authors: Kuruma Hidetoshi , Matsumoto Hiroaki , Shiota Masaki , Bishop Jennifer , Lamoureux Francois , Thomas Christian , Briere David , Los Gerrit , Gleave Martin , Fanjul Andrea , Zoubeidi Amina
Published: April 2013

Resistance to antiandrogen drugs, like MDV3100, occurs in patients with castration-resistant prostate cancer (CRPC). Thus, preventing or treating antiandrogen resistance is a major clinical challenge. We identified a novel antiandrogen, Compound 30, and compared its efficacy with MDV3100. We found that Compound 30 inhibits androgen receptor (AR) activity in LNCaP cells, C4-2 cells, as well as MDV3100-resistant cell lines. Compared with MDV3100, Compound 30 treatment induces greater reduction in AR, prostate-specific antigen (PSA), and AR transcriptional activity, and prevents AR nuclear translocation in AR-sensitive LNCaP cells. Compound 30 has antiproliferative effects in LNCaP cells, in castrate-resistant C4-2 cells, and those resistant to MDV3100. Compound 30 was equally as effective as MDV3100 in reducing tumor volume and PSA in vivo. More importantly, Compound 30 is effective at inhibiting AR activity in MDV3100-resistant cell lines and significantly prevented tumor growth and PSA increases in mice bearing MDV3100-resistant xenografts. Together, our data show that Compound 30 strongly inhibited AR activity and suppressed castration-resistant LNCaP growth as well as MDV3100-resistant cell growth in vitro and in vivo. These data provide a preclinical proof-of-principle that Compound 30 could be a promising next generation anti-AR agent, especially in the context of antiandrogen-resistant tumors. Mol Cancer Ther; 12(5); 567–76. ©2013 AACR.
Small-Molecule Inhibitors of Acetyltransferase p300 Identified by High-Throughput Screening Are Potent Anticancer Agents
Authors: Yang Heng , Pinello Christie E. , Luo Jian , Li Dawei , Wang Yunfei , Zhao Lisa Y. , Jahn Stephan C. , Saldanha Sanjay Adrian , Planck Jamie , Geary Kyla R. , Ma Haiching , Law Brian K. , Roush William R. , Hodder Peter , Liao Daiqing
Published: April 2013

Acetyltransferase p300 (KAT3B) plays key roles in signaling cascades that support cancer cell survival and sustained proliferation. Thus, p300 represents a potential anticancer therapeutic target. To discover novel anticancer agents that target p300, we conducted a high-throughput screening campaign. A library of 622,079 compounds was assayed for cytotoxicity to the triple-negative breast cancer (TNBC) cell line MDA-MB-231 but not to the human mammary epithelial cells. The resulting compounds were tested in a biochemical assay for inhibiting the enzymatic activity of p300. One compound (L002, NSC764414) displayed an IC50 of 1.98 μmol/L against p300 in vitro, inhibited acetylation of histones and p53, and suppressed STAT3 activation in cell-based assays. L002 could be docked to the active site of the p300 catalytic domain. Biochemical tests of a series of related compounds revealed functional groups that may impact inhibitory potency of L002 against p300. Interestingly, these analogs showed inhibitory activities against the cellular paralog of p300 (CBP), p300/CBP-associated factor, and GCN5, but not to other acetyltransferases (KAT5, KAT6B, and KAT7), histone deacetylases, and histone methyltransferases. Among the NCI-60 panel of cancer cell lines, leukemia and lymphoma cell lines were extremely sensitive to L002, whereas it is toxic to only a limited number of cell lines derived from solid tumors. Notably, breast cancer cell lines, especially those derived from TNBC, were highly susceptible to L002. In vivo, it potently suppressed tumor growth and histone acetylation of MDA-MB-468 xenografts. Thus, these new acetyltransferase inhibitors are potential anticancer therapeutics. Mol Cancer Ther; 12(5); 610–20. ©2013 AACR.
Licochalcone E Present in Licorice Suppresses Lung Metastasis in the 4T1 Mammary Orthotopic Cancer Model
Authors: Kwon Soo Jin , Park So Young , Kwon Gyoo Taik , Lee Ki Won , Kang Young-Hee , Choi Myung-Sook , Yun Jong Won , Jeon Jae-Ho , Jun Jong Gab , Park Jung Han Yoon
Published: April 2013

We investigated whether licochalcone E (LicE), a phenolic constituent of licorice, inhibits mammary tumor growth and metastasis using animal and cell culture models. 4T1 mammary carcinoma cells were injected into the mammary fat pads of syngeneic BALB/c mice. Starting 7 days after the injection, the mice received LicE (7 or 14 mg/kg body weight/day) via oral gavage for 25 days. LicE suppressed solid tumor growth and lung metastasis, but did not exhibit kidney or liver toxicity. In tumor tissues, LicE treatment induced a reduction in the expression of Ki67, cyclins, and cyclin-dependent kinases and stimulated apoptosis with increased expression of Bax and cleaved caspase-3 but decreased expression of Bcl-2. In addition, LicE decreased expression of CD31, vascular endothelial growth factor (VEGF)-A and C, VEGF-receptor 2, lymphatic vessel endothelial receptor-1, CD45, cyclooxygenase-2, inducible nitric oxide synthase, and hypoxia inducible factor-1α in tumor tissues. In lung tissues, LicE reduced the levels of proinflammatory cytokines and angiogenesis/metastasis-related proteins. In mammary cancer cell cultures, LicE (5–20 μmol/L) dose dependently inhibited cell migration and invasion. LicE inhibited secretion of matrix metalloproteinase-9, urokinase-type plasminogen activator and VEGF-A, and stimulated secretion of tissue inhibitor of metalloproteinase-2 in MDA-MB-231 cells. In addition, LicE inhibited tube formation of vascular endothelial cells. We show that LicE administration suppressed tumor growth and lung metastasis in the mouse model in conjunction with LicE inhibition of cell migration, invasion, and tube formation in vitro. Reduced tumor growth and metastasis in LicE-treated mice may be, at least in part, attributed to reduced inflammation and tumor angiogenesis. Cancer Prev Res; 6(6); 603–13. ©2013 AACR.
Clinical Benefit of Eplerenone in Patients With Mild Symptoms of Systolic Heart Failure Already Receiving Optimal Best Practice Background Drug Therapy
Authors: Krum Henry , Shi Harry , Pitt Bertram , McMurray John , Swedberg Karl , van Veldhuisen Dirk J. , Vincent John , Pocock Stuart , Zannad Faiez
Published: April 2013

Background—

In EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure), eplerenone significantly reduced major cardiovascular events versus placebo in 2737 patients with mild symptoms of heart failure and an ejection fraction of <35%, in addition to recommended therapy. However, it is not known whether such benefits were preserved in patients receiving optimal background drug therapy, that is, high doses of angiotensin-converting enzyme inhibitor (ACEi, or angiotensin receptor blocker), β-blocker, or both drug classes.

Methods and Results—

We further analyzed EMPHASIS-HF according to the use and dose of these background drug classes. Patients receiving ≥50% of target dose were considered to be receiving high doses; patients on <50% or no drug comprised the low-dose group. The primary end point of the study (cardiovascular death/heart failure hospitalization), as well as all-cause mortality, was evaluated in this way. The beneficial clinical effects of eplerenone (as observed in the main study) were preserved for the EMPHASIS-HF primary end point in patients receiving higher doses of ACEi or angiotensin receptor blocker, β-blocker, or both (hazard ratio for eplerenone versus placebo, ACEi/angiotensin receptor blocker: high dose, 0.67; low dose, 0.65; β-blockers: high dose, 0.55; low dose, 0.72; both ACEi/angiotensin receptor blocker and β-blocker: high dose, 0.59; low dose, 0.68;
P
value for interaction 0.80, 0.15, and 0.53, respectively), as well as for all-cause mortality. There were no major safety issues, except a borderline increased risk of hypotension with eplerenone in those on high-dose ACEi or ACEi/β-blocker.

Conclusions—

Eplerenone provides substantial benefit on major events (with an acceptable safety profile) in patients with mild symptoms of systolic heart failure, even in those already receiving high doses of standard background therapies.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00232180.
Physical Health Status Measures Predict All-Cause Mortality in Patients With Heart Failure
Authors: Chamberlain Alanna M. , McNallan Sheila M. , Dunlay Shannon M. , Spertus John A. , Redfield Margaret M. , Moser Debra K. , Kane Robert L. , Weston Susan A. , Roger Véronique L.
Published: April 2013

Background—

Physical health status measures have been shown to predict death in heart failure (HF); however, few studies found significant associations after adjustment for confounders, and most were not representative of all HF patients.

Methods and Results—

HF patients from southeastern MN were prospectively enrolled between 10/2007 and 12/2010, completed a 12-item Short Form Health Survey (SF-12) and a 6-minute walk, and were followed through 2011 for death from any cause. Scores ≤25 on the SF-12 physical component indicated low self-reported physical functioning, and the first question of the SF-12 measured self-rated general health. Low functional exercise capacity was defined as ≤300 m walked during a 6-minute walk. Over a mean follow-up of 2.3 years, 86 deaths occurred among the 352 participants. A 1.6-fold (95% confidence interval, 1.0–2.7) and 1.8-fold (95% confidence interval, 1.1–2.9) increased risk of death was observed among patients with low self-reported physical functioning and low functional exercise capacity, respectively. Poor self-rated general health corresponded to a 2.7-fold (95% confidence interval, 1.5–4.9) increased risk of death compared with good to excellent general health. All measures equally discriminated between who would die and who would survive (C-statistics: 0.729, 0.750, and 0.740 for self-reported physical functioning, self-rated general health, and functional exercise capacity, respectively).

Conclusions—

Three physical health status measures, captured by the SF-12 and a 6-minute walk, equally predict death among community HF patients. Therefore, the first question of the SF-12, which is the least burdensome to administer, may be sufficient to identify HF patients at greatest risk of death.
ABCC6 Is a Basolateral Plasma Membrane Protein
Authors: Pomozi Viola , Le Saux Olivier , Brampton Christopher , Apana Ailea , Iliás Attila , Szeri Flóra , Martin Ludovic , Monostory Katalin , Paku Sándor , Sarkadi Balázs , Szakács Gergely , Váradi András
Published: April 2013

Rationale:

ABCC6 plays a crucial role in ectopic calcification; mutations of the gene cause pseudoxanthoma elasticum and general arterial calcification of infancy. To elucidate the role of ABCC6 in cellular physiology and disease, it is crucial to establish the exact subcellular localization of the native ABCC6 protein.

Objective:

In a recent article in
Circulation Research
, ABCC6 was reported to localize to the mitochondria-associated membrane and not the plasma membrane. As the suggested mitochondrial localization is inconsistent with published data and the presumed role of ABCC6, we performed experiments to determine the cellular localization of ABCC6 in its physiological environment.

Methods and Results:

We performed immunofluorescent labeling of frozen mouse and human liver sections, as well as primary hepatocytes. We used several different antibodies recognizing human and mouse ABCC6. Our results unequivocally show that ABCC6 is in the basolateral membrane of hepatocytes and is not associated with the mitochondria, mitochondria-associated membrane, or the endoplasmic reticulum.

Conclusions:

Our findings support the model that ABCC6 is in the basolateral membrane, mediating the sinusoidal efflux of a metabolite from the hepatocytes to systemic circulation.
MiR-378 Controls Cardiac Hypertrophy by Combined Repression of Mitogen-Activated Protein Kinase Pathway Factors
Authors: Ganesan Jayavarshni , Ramanujam Deepak , Sassi Yassine , Ahles Andrea , Jentzsch Claudia , Werfel Stanislas , Leierseder Simon , Loyer Xavier , Giacca Mauro , Zentilin Lorena , Thum Thomas , Laggerbauer Bernhard , Engelhardt Stefan
Published: April 2013

Background—

Several microRNAs (miRs) have been shown to regulate gene expression in the heart, and dysregulation of their expression has been linked to cardiac disease. miR-378 is strongly expressed in the mammalian heart but so far has been studied predominantly in cancer, in which it regulates cell survival and tumor growth.

Methods and Results—

Here, we report tight control of cardiomyocyte hypertrophy through miR-378. In isolated primary cardiomyocytes, miR-378 was found to be both necessary and sufficient to repress cardiomyocyte hypertrophy. Bioinformatic prediction suggested that factors of the mitogen-activated protein kinase (MAPK) pathway are enriched among miR-378 targets. Using mRNA and protein expression analysis along with luciferase assays, we validated 4 key components of the MAPK pathway as targets of miR-378: MAPK1 itself, insulin-like growth factor receptor 1, growth factor receptor-bound protein 2, and kinase suppressor of ras 1. RNA interference with these targets prevented the prohypertrophic effect of antimiR-378, suggesting their functional relation with miR-378. Because miR-378 significantly decreases in cardiac disease, we sought to compensate for its loss through adeno-associated virus–mediated, cardiomyocyte-targeted expression of miR-378 in an in vivo model of cardiac hypertrophy (pressure overload by thoracic aortic constriction). Restoration of miR-378 levels significantly attenuated thoracic aortic constriction–induced cardiac hypertrophy and improved cardiac function.

Conclusions—

Our data identify miR-378 as a regulator of cardiomyocyte hypertrophy, which exerts its activity by suppressing the MAPK signaling pathway on several distinct levels. Restoration of disease-associated loss of miR-378 through cardiomyocyte-targeted adeno-associated virus–miR-378 may prove to be an effective therapeutic strategy in myocardial disease.
Ian Fleming and the Public Profile of the CIA
Authors: Moran Christopher
Published: April 2013

This article represents the first major analysis of the appearance of the U.S. Central Intelligence Agency (CIA) in the James Bond novels of British spy fiction writer Ian Fleming. The article shows that Fleming was remarkably influential during the early Cold War in establishing the public profile of the CIA. The novels, which include manifold references to the agency and its staff, were published at a time when the CIA kept out of the public limelight and when other cultural forms, including Hollywood, refrained from making too much fanfare about intelligence matters. Drawing on recently declassified material, including the papers of fabled CIA Director Allen Dulles, the article demonstrates that the agency took a keen interest in Bond, even drawing inspiration from his adventures and the novels' depictions of technology.
The fate of ethnography : native social science in the English-speaking Caribbean
Authors: Carnegie Charles V.
Published: April 2013

Reviews the research tradition in the social sciences in the post-War Anglophone Caribbean. Painting a general picture of the intellectual climate in the social sciences divisions of the UWI, Carnegie concludes that most studies have dealt with economic and macro-sociological topics. Moreover, there has been a consistent emphasis on the larger nations of the British Caribbean.
What history tells us about the development of Creole in Guadeloupe
Authors: Cérol Marie-Josée
Published: April 2013

Review of the socio-historical context in which Creole developed in Guadeloupe. The author questions the validity of the claim made about the insignificant role of African languages in the development of creole languages. She argues that African languages played a central role in the life of their speakers for a very long period.
Toward a cultural history of America
Authors: Hulme Peter
Published: April 2013

[First paragraph]Caliban and otheressays, by ROBERTO FERNANDEZ RETAMAR. (Translatedby Edward Baker, Foreword by Fredric Jameson.) Minneapolis: Universityof Minnesota Press, 1989. xvi + 139 pp. (Cloth US $35.00, Paper US$14.95)Deconstructing America: representations of the other, by PETER MASON.London: Routledge, 1990. vii + 216 pp. (Cloth £ 30.00)Both these books beiong to a field of study that aims to analyze the ways in which Europe, or more generally the West, has represented to itself in words and images the non-European world. Edward Said's Orientalism inaugurated that field in 1978, immediately constituting a corpus of work through its author's recognition of precedent and analogue, then acting as indispensable touchstone to the subsequent development of the field during the 1980s. Although Said's work deals with the oriënt, however defined, a surprising amount of ideological analysis of colonial representation had already taken place within the Caribbean. Frantz Fanon, Eric Williams, and Aimé Césaire were three notable precursors recognized by Said; and Roberto Fernéndez Retamar's essays, especially those written in the late 1960s and early 1970s, pursued many similar themes within the rather different context of the Cuban Revolution. Four of those essays are now published in English, along with a more recent reflection on the most famous of them, "Caliban."
Caribbean women: changes in the works
Authors: Quiñones-Arocho María Isabel
Published: April 2013

[First paragraph]The women of Azua: work and family in the rural Dominican Republic, by BARBARA FINLAY. New York: Praeger, 1989. xi + 190 pp. (Cloth US$ 35.00)The psychosocial development of Puerto Rican women, edited by CYNTHIA T. GARCIA COLL & MARIA DE LOURDES MATTEI. New York: Praeger, 1989. xiii + 272 pp. (Cloth US$ 45.00)Women and the sexual division oflabour in the Caribbean, edited by KEITH HART. Mona, Jamaica: Consortium Graduate School of Social Sciences, UWI, 1989. 141 pp. (Paper n.p.)The three books under review work have a common theme: the impact of changing gender expectations on Caribbean women. The authors are mainly concerned with recent political and economie changes that might have contributed to either the improvement or deterioration of women's status in these societies. The questions raised by the contributors are strikingly similar: What has been the impact of dependent economie development on women's lives and has this resulted in increased labor participation (a problem explored for rural Dominican women as well as for Jamaican and Barbadian women) or in the migration to metropolitan centers, with its psychosocial consequences (an issue raised for Puerto Rican women living in the United States)? If patriarchal values (often referred to as traditional values) prevail in these societies, then what impact might wage work, migration, or improved education have on those values? Could it be the disintegration of the nuclear family with an increased proportion of female-headed households (Hart), higher rates of mental illness as a result of dysfunctional aceulturation (Garcia Coll and Mattei), or even an improvement of women's status within their families and communities (Finlay)?
Caribbean dance: ‘resistance’, colonial discourse, and subjugated knowledges
Authors: Maurer Bill
Published: April 2013

Review of the literature on African-American dance in the Caribbean. The author focuses on 3 problems. The first is the construction of canons in dance anthropology. The second has to do with the ways in which these canons have dealt with dance in the Caribbean in particular. Finally, the author examines issues 'surrounding the ways anthropology creates its objects of study'.
Plantation development in Berbice from 1753 to 1779: the shift from the interior to the coast
Authors: Kramer Klaas
Published: April 2013

Examination of the factors involved in the shift in plantation development. The author emphasizes the availability of venture capital in the later 18th century; the movements in the prices of commodities in Europe; and the different labour requirements for the production of sugar, cacao, coffee, and cotton.