bluuebunny/crossref_metadata_2025 huggingface dataset:
Racial Differences in Long‐Term Outcomes after Percutaneous Coronary Intervention with Paclitaxel‐Eluting Coronary Stents
Authors: BATCHELOR WAYNE B. , ELLIS STEPHEN G. , ORMISTON JOHN A. , STONE GREGG W. , JOSHI ANITA A. , WANG HONG , UNDERWOOD PAUL L.
Published: September 2012

Objectives

To assess the influence of race on long‐term outcomes following percutaneous coronary intervention (PCI) with paclitaxel‐eluting stents (PES).

Background

Data on the influence of race on long‐term outcomes following PCI with drug‐eluting stents are limited because of severe underrepresentation of minority populations in randomized trials.

Methods

We compared 5‐year outcomes of 2,301 Whites, 127 Blacks, and 169 Asians treated with PES in the TAXUS IV, V, and ATLAS trials. Outcomes were adjusted using a propensity score logistic regression model with 1:4 matching.

Results

Blacks were more likely than Whites to be female, have a history of hypertension, diabetes mellitus, congestive heart failure, and stroke, but were less likely to have prior coronary artery disease. Compared with Whites, Asians were younger, more likely to be male, have stable angina, and left anterior descending disease, and less likely to have silent ischemia, previous coronary artery bypass surgery, prior coronary artery disease, diabetes mellitus, peripheral vascular disease, and to receive glycoprotein IIb/IIIa inhibitors. Despite higher antiplatelet compliance, the adjusted 5‐year rates of myocardial infarction (15.4% vs. 5.4%, P < 0.001) and stent thrombosis (5.6% vs. 1.1%, P = 0.002) were higher in Blacks than Whites. Despite lower antiplatelet compliance, Asians had no differences in myocardial infarction and stent thrombosis compared with Whites. Mortality and revascularization rates were similar between the three groups.

Conclusions

The long‐term risk of major thrombotic events after PCI with PES was higher in Blacks, but not Asians, compared with Whites. The mechanisms underlying these racial differences warrant further investigation. (J Interven Cardiol 2013;26:49–57)
The effect of crank position and backrest inclination on shoulder load and mechanical efficiency during handcycling
Authors: Arnet U. , van Drongelen S. , Schlüssel M. , Lay V. , van der Woude L. H. V. , Veeger H. E. J.
Published: September 2012

Handbikes come in different models and setups, but only limited knowledge is available on the handbike‐user interface. The aim of this study was to identify optimal handbike setups, assuming that in such a setup mechanical efficiency is high, while shoulder load is low. Thirteen subjects with a spinal cord injury (paraplegia) performed handcycling with different handbike setups at constant power output: four crank positions (two distances, two heights) and four backrest inclinations. The O2‐consumption, kinetics, and kinematics were measured to calculate mechanical efficiency and shoulder load (glenohumeral contact force, net shoulder moments, and rotator cuff force). The analysis showed that more upright backrest positions resulted in lower shoulder load compared with the most reclined position [glenohumeral contact force (260 vs 335 N), supraspinatus (14.4% vs 18.2%), and infraspinatus force (5.4% vs 9.8%)], while there was no difference in efficiency. Except for a reduction in subscapularis force at the distant position, no differences in shoulder load or efficiency were found between crank positions. Recreational handbike users, who want to improve their physical capacity in a shoulder‐friendly way, should set up their handbike with a more upright backrest position and a distant crank placement.
TOWARD AN APPLIED NEUROANTHROPOLOGY OF PSYCHOSIS: THE INTERPLAY OF CULTURE, BRAINS, AND EXPERIENCE
Authors: Myers Neely Anne Laurenzo
Published: September 2012

Psychotic disorders emerge from the interplay between culture, brains, and experience. Understanding psychotic disorders and intervening effectively to prevent them or alleviate their effects requires a rich understanding of all three, which may best be captured by the transdisciplinary methods and theory of an applied neuroanthropology. Neuroanthropology investigates the ways that cultural context interacts with vulnerable people's brains to both encourage and inhibit the neurodevelopmental processes that lead to a psychotic disorder like schizophrenia. Culturally grounded investigations enable us to investigate the ways a person's lived experiences perpetuate neural changes in the brain that may shape the onset and course of psychotic disorders. This article presents an ethnographic case study of a young man diagnosed with a psychotic disorder after spending 80 days in solitary confinement. Building on his narrative, this article explores his development of a psychotic disorder from an ethnographic and neuroscience perspective. Future transdisciplinary, neuroanthropological studies could rigorously investigate issues that his narrative highlights, including the seemingly inhumane use of solitary confinement and the paucity of meaning‐making efforts in biomedical treatment for psychotic disorders. Applied neuroanthropological research on the interplay of culture, brains, and experience in psychotic disorders can contribute to clinical and policy recommendations that improve the lives of people diagnosed with a psychotic disorder around the globe in ways that are locally meaningful for them.
Nurse practice environment, workload, burnout, job outcomes, and quality of care in psychiatric hospitals: a structural equation model approach
Authors: Van Bogaert Peter , Clarke Sean , Willems Riet , Mondelaers Mieke
Published: September 2012

Aim

To study the relationships between nurse practice environment, workload, burnout, job outcomes and nurse‐reported quality of care in psychiatric hospital staff.

Background

Nurses' practice environments in general hospitals have been extensively investigated. Potential variations across practice settings, for instance in psychiatric hospitals, have been much less studied.

Design

A cross‐sectional design with a survey.

Method

A structural equation model previously tested in acute hospitals was evaluated using survey data from a sample of 357 registered nurses, licensed practical nurses, and non‐registered caregivers from two psychiatric hospitals in Belgium between December 2010–April 2011. The model included paths between practice environment dimensions and outcome variables, with burnout in a mediating position. A workload measure was also tested as a potential mediator between the practice environment and outcome variables.

Results

An improved model, slightly modified from the one validated earlier in samples of acute care nurses, was confirmed. This model explained 50% and 38% of the variance in job outcomes and nurse‐reported quality of care respectively. In addition, workload was found to play a mediating role in accounting for job outcomes and significantly improved a model that ultimately explained 60% of the variance in these variables.

Conclusion

In psychiatric hospitals as in general hospitals, nurse–physician relationship and other organizational dimensions such as nursing and hospital management were closely associated with perceptions of workload and with burnout and job satisfaction, turnover intentions, and nurse‐reported quality of care. Mechanisms linking key variables and differences across settings in these relationships merit attention by managers and researchers.
Crystal structure of the MrkD1P receptor binding domain of Klebsiella pneumoniae and identification of the human collagen V binding interface
Authors: Rêgo Ana Toste , Johnson Jeremiah G. , Geibel Sebastian , Enguita Francisco J. , Clegg Steven , Waksman Gabriel
Published: September 2012

Klebsiella species are members of the family enterobacteriaceae, opportunistic pathogens that are among the eight most prevalent infectious agents in hospitals. Among other virulence factors in Klebsiella, type 3 pili exhibit a unique binding pattern in the human kidney via interaction of two MrkD adhesion variants 1C1 and 1P to type IV and/or V collagen. However, very little is known about the nature of this recognition. Here we present the crystal structure of the plasmid born MrkD1P receptor domain (MrkDrd). The structure reveals a jelly‐roll β‐barrel fold comprising 17 β‐strands very similar to the receptor domain of GafD, the tip adhesin from the F17 pilus that recognizes n‐acetyl‐d‐glucosamine (GlcNAc). Analysis of collagen V binding of different MrkD1P mutants revealed that two regions were responsible for its binding: a pocket, that aligns approximately with the GlcNAc binding pocket of GafD involving residues R105 and Y155, and a transversally oriented patch that spans strands β2a, β9b and β6 including residues V49, T52, V91, R102 and I136. Taken together, these data provide structural and functional insights on MrkD1P recognition of host cells, providing a tool for future development of rationally designed drugs with the prospect of blocking Klebsiella adhesion to collagen V.
A Paper-Based Multiplexed Transaminase Test for Low-Cost, Point-of-Care Liver Function Testing
Authors: Pollock Nira R. , Rolland Jason P. , Kumar Shailendra , Beattie Patrick D. , Jain Sidhartha , Noubary Farzad , Wong Vicki L. , Pohlmann Rebecca A. , Ryan Una S. , Whitesides George M.
Published: September 2012

A paper-based, multiplexed microfluidic assay allows rapid, semiquantitative, visual measurement of transaminases in clinical specimens.
Effects of STX209 (Arbaclofen) on Neurobehavioral Function in Children and Adults with Fragile X Syndrome: A Randomized, Controlled, Phase 2 Trial
Authors: Berry-Kravis Elizabeth M. , Hessl David , Rathmell Barbara , Zarevics Peter , Cherubini Maryann , Walton-Bowen Karen , Mu Yi , Nguyen Danh V. , Gonzalez-Heydrich Joseph , Wang Paul P. , Carpenter Randall L. , Bear Mark F. , Hagerman Randi J.
Published: September 2012

Administration of a selective GABA
B
agonist to individuals with fragile X syndrome improves their deficits in social avoidance, a core symptom of the disease.
Childhood Disorders of the Synapse: Challenges and Opportunities
Authors: Hughes Virginia , Sheng Morgan , Zoghbi Huda
Published: September 2012

New research directions are needed to accelerate the development of new treatments for autism and related disorders.
A Multicenter Blinded Analysis Indicates No Association between Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and either Xenotropic Murine Leukemia Virus-Related Virus or Polytropic Murine Leukemia Virus
Authors: Alter Harvey J. , Mikovits Judy A. , Switzer William M. , Ruscetti Francis W. , Lo Shyh-Ching , Klimas Nancy , Komaroff Anthony L. , Montoya Jose G. , Bateman Lucinda , Levine Susan , Peterson Daniel , Levin Bruce , Hanson Maureen R. , Genfi Afia , Bhat Meera , Zheng HaoQiang , Wang Richard , Li Bingjie , Hung Guo-Chiuan , Lee Li Ling , Sameroff Stephen , Heneine Walid , Coffin John , Hornig Mady , Lipkin W. Ian
Published: September 2012

The disabling disorder known as chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) has been linked in two independent studies to infection with xenotropic murine leukemia virus-related virus (XMRV) and polytropic murine leukemia virus (pMLV). Although the associations were not confirmed in subsequent studies by other investigators, patients continue to question the consensus of the scientific community in rejecting the validity of the association. Here we report blinded analysis of peripheral blood from a rigorously characterized, geographically diverse population of 147 patients with CFS/ME and 146 healthy subjects by the investigators describing the original association. This analysis reveals no evidence of either XMRV or pMLV infection.

IMPORTANCE
Chronic fatigue syndrome/myalgic encephalomyelitis has an estimated prevalence of 42/10,000 in the United States, with annual direct medical costs of $7 billion. Here, the original investigators who found XMRV and pMLV (polytropic murine leukemia virus) in blood of subjects with this disorder report that this association is not confirmed in a blinded analysis of samples from rigorously characterized subjects. The increasing frequency with which molecular methods are used for pathogen discovery poses new challenges to public health and support of science. It is imperative that strategies be developed to rapidly and coherently address discoveries so that they can be carried forward for translation to clinical medicine or abandoned to focus resource investment more productively. Our study provides a paradigm for pathogen dediscovery that may be helpful to others working in this field.
Teaching Acupuncture: The Brazilian Medical Residency Programme
Authors: Costi Jéssica Maria , da Silva João Bosco Guerreiro , Min Li Shih , Moré Ari Ojeda Ocampo , Hokama André Luis
Published: September 2012

Acupuncture has had a successful story in Brazil. With its use in the public health system supported by legislation since 1988, its recognition as a medical specialty in 1995 enabled the introduction of an annual board examination and the creation of an official Medical Residency Programme. Since then, medical acupuncture has developed considerably, mostly through its massive spread into the Brazilian public health system. Brazil is the only country outside China that has created a Medical Residency Programme on Acupuncture. The 2-year programme consists of 5760 training hours, beginning with major clinical areas (internal medicine, neurology, orthopaedics and gynaecology) during 24 weeks in the first year. The residents study and practice acupuncture using the traditional Chinese Medicine approach and also the biomedical model. Specialists educated by this programme are therefore expected to have an optimum knowledge of both Western and Eastern medicine. Since it was first created, nine public health institutions have adopted the residency programme on acupuncture so, rather than being an alternative therapy, acupuncture has become an easily accessible and well-accepted conventional medical resource in Brazil.
DIRECT MACROECONOMIC LINKS BETWEEN SELECTED EAST ASIAN ECONOMIES AND THE US? AN EMPIRICAL ANALYSIS
Authors: TAN EU CHYE
Published: September 2012

This paper attempts to establish whether there exists any direct macroeconomic linkages between some East Asian (EA) countries on the one hand and the US on the other hand, based upon quarterly real gross domestic product (GDP) series spanning from the early 1990s. Cointegration, Granger causal relations and contemporaneous correlations of output shocks are explored. Contrary to a priori expectations, the empirical evidence suggests no direct linkages of these economies to the US, with the exception of the Malaysian economy. In the case of Malaysia, only a Granger causal relation from the US is found. All this would allude to the ability of these EA economies save one to grow independently of the US, barring a global economic crisis such as the recent one triggered off by sub-prime loans.
OIL PRICE VOLATILITY AND THE SINGAPORE MACROECONOMY
Authors: NG WEIWEN
Published: September 2012

We construct a realized volatility measure, using prices of daily West Texas Intermediate (WTI) crude oil futures and illustrate the robustness of this oil price volatility–macroeconomy relationship under a multivariate co-integrated vector autoregressive (VAR) model. Empirical results suggest that a spike in oil price volatility leads to investments and aggregate output to decline and inflation to rise over the period from 1983Q2 to 2009Q2. Furthermore, the gradual decline of Singapore's oil intensity signals a weakening relationship between oil price and the macroeconomy that supports our empirical findings.
Mouse model of ischemic acute kidney injury: technical notes and tricks
Authors: Wei Qingqing , Dong Zheng
Published: September 2012

Renal ischemia-reperfusion leads to acute kidney injury (AKI), a major kidney disease associated with an increasing prevalence and high mortality rates. A variety of experimental models, both in vitro and in vivo, have been used to study the pathogenic mechanisms of ischemic AKI and to test renoprotective strategies. Among them, the mouse model of renal clamping is popular, mainly due to the availability of transgenic models and the relatively small animal size for drug testing. However, the mouse model is generally less stable, resulting in notable variations in results. Here, we describe a detailed protocol of the mouse model of bilateral renal ischemia-reperfusion. We share the lessons and experiences gained from our laboratory in the past decade. We further discuss the technical issues that account for the variability of this model and offer relevant solutions, which may help other investigators to establish a well-controlled, reliable animal model of ischemic AKI.
Nonlinear Scattering by Anisotropic Dielectric Periodic Structures
Authors: Shramkova O. V. , Schuchinsky A. G.
Published: September 2012

The combinatorial frequency generation by the periodic stacks of binary layers of anisotropic nonlinear dielectrics is examined. The products of nonlinear scattering are characterised in terms of the three-wave mixing processes. It is shown that the intensity of the scattered waves of combinatorial frequencies is strongly influenced by the constitutive and geometrical parameters of the anisotropic layers, and the frequency ratio and angles of incidence of pump waves. The enhanced efficiency of the frequency conversion at Wolf-Bragg resonances has been demonstrated for the lossless and lossy-layered structures.
Building a Community-Academic Partnership: Implementing a Community-Based Trial of Telephone Cognitive Behavioral Therapy for Rural Latinos
Authors: Aisenberg Eugene , Dwight-Johnson Meagan , O'Brien Mary , Ludman Evette J. , Golinelli Daniela
Published: September 2012

Concerns about the appropriate use of EBP with ethnic minority clients and the ability of community agencies to implement and sustain EBP persist and emphasize the need for community-academic research partnerships that can be used to develop, adapt, and test culturally responsive EBP in community settings. In this paper, we describe the processes of developing a community-academic partnership that implemented and pilot tested an evidence-based telephone cognitive behavioral therapy program. Originally demonstrated to be effective for urban, middle-income, English-speaking primary care patients with major depression, the program was adapted and pilot tested for use with rural, uninsured, low-income, Latino (primarily Spanish-speaking) primary care patients with major depressive disorder in a primary care site in a community health center in rural Eastern Washington. The values of community-based participatory research and community-partnered participatory research informed each phase of this randomized clinical trial and the development of a community-academic partnership. Information regarding this partnership may guide future community practice, research, implementation, and workforce development efforts to address mental health disparities by implementing culturally tailored EBP in underserved communities.
Malignant Transformation of a Mature Cystic Ovarian Teratoma into Thyroid Carcinoma, Mucinous Adenocarcinoma, and Strumal Carcinoid: A Case Report and Literature Review
Authors: Hinshaw Hilary D. , Smith Ashlee L. , Desouki Mohamed Mokhtar , Olawaiye Alexander B.
Published: September 2012

Malignant transformation of a mature cystic teratoma (MCT) is an infrequent, often asymptomatic event. We report the first example of a struma ovarii with a focus of follicular variant of papillary thyroid carcinoma (a), mucinous adenocarcinoma (b), and strumal carcinoid tumor (c)—all three arising in one mature cystic teratoma of the ovary. From our reviews, we found limited data to guide management when these malignant foci occur within an MCT. Consideration should be given to thyroidectomy followed by total-body scanning and serum studies for foci of thyroid carcinoma and adjuvant therapy with thyroidectomy and radioablation if residual disease is identified (a). Additionally, extrapolating from data for mucinous adenocarcinomas, consideration could be given to adjuvant chemotherapy after appropriate staging (b). Strumal carcinoid tumors should be treated as tumors of low malignant potential. Observation is appropriate if after complete staging, no invasive implants are noted (c).
Iterative System Identification and Controller Design with an LMI‐Based Framework: Windsurfer‐Like Approach
Authors: Hiramoto Kazuhiko
Published: September 2012

An LMI‐based method for the integrated system identification and controller design is proposed in the paper. We use the fact that a class of a system identification problem results in an LMI optimization problem. By combining LMIs for the system identification and those to obtain a discrete time controller we propose a framework to integrate two steps for the model‐based control system design, that is, the system identification and the controller synthesis. The framework enables us to obtain a good model for control and a model‐based feedback controller simultaneously in the sense of the closed‐loop performance. An iterative design algorithm similar to so‐called Windsurfer Approach is presented.
On Existence, Uniform Decay Rates, and Blow‐Up for Solutions of a Nonlinear Wave Equation with Dissipative and Source
Authors: Liu Xiaopan
Published: September 2012

This paper studies the blow‐up and existence, and asymptotic behaviors of the solution of a nonlinear hyperbolic equation with dissipative and source terms. By using Galerkin procedure and the perturbed energy method, the local and global existence of solution is established. In addition, by the concave method, the blow‐up of solutions can be obtained.
On Summability of Spectral Expansions Corresponding to the Sturm-Liouville Operator
Authors: Makin Alexander S.
Published: September 2012

We study the completeness property and the basis property of the root function system of the Sturm-Liouville operator defined on the segment [0, 1]. All possible types of two-point boundary conditions are considered.
Rab25 Is a Tumor Suppressor Gene with Antiangiogenic and Anti-Invasive Activities in Esophageal Squamous Cell Carcinoma
Authors: Tong Man , Chan Kwok Wah , Bao Jessie Y.J. , Wong Kai Yau , Chen Jin-Na , Kwan Pak Shing , Tang Kwan Ho , Fu Li , Qin Yan-Ru , Lok Si , Guan Xin-Yuan , Ma Stephanie
Published: September 2012

Esophageal squamous cell carcinoma (ESCC), the major histologic subtype of esophageal cancer, is a devastating disease characterized by distinctly high incidences and mortality rates. However, there remains limited understanding of molecular events leading to development and progression of the disease, which are of paramount importance to defining biomarkers for diagnosis, prognosis, and personalized treatment. By high-throughout transcriptome sequence profiling of nontumor and ESCC clinical samples, we identified a subset of significantly differentially expressed genes involved in integrin signaling. The Rab25 gene implicated in endocytic recycling of integrins was the only gene in this group significantly downregulated, and its downregulation was confirmed as a frequent event in a second larger cohort of ESCC tumor specimens by quantitative real-time PCR and immunohistochemical analyses. Reduced expression of Rab25 correlated with decreased overall survival and was also documented in ESCC cell lines compared with pooled normal tissues. Demethylation treatment and bisulfite genomic sequencing analyses revealed that downregulation of Rab25 expression in both ESCC cell lines and clinical samples was associated with promoter hypermethylation. Functional studies using lentiviral-based overexpression and suppression systems lent direct support of Rab25 to function as an important tumor suppressor with both anti-invasive and -angiogenic abilities, through a deregulated FAK–Raf–MEK1/2–ERK signaling pathway. Further characterization of Rab25 may provide a prognostic biomarker for ESCC outcome prediction and a novel therapeutic target in ESCC treatment. Cancer Res; 72(22); 6024–35. ©2012 AACR.
Clinical Significance of the Genetic Landscape of Pancreatic Cancer and Implications for Identification of Potential Long-term Survivors
Authors: Yachida Shinichi , White Catherine M. , Naito Yoshiki , Zhong Yi , Brosnan Jacqueline A. , Macgregor-Das Anne M. , Morgan Richard A. , Saunders Tyler , Laheru Daniel A. , Herman Joseph M. , Hruban Ralph H. , Klein Alison P. , Jones Siân , Velculescu Victor , Wolfgang Christopher L. , Iacobuzio-Donahue Christine A.
Published: September 2012

Purpose: Genetic alterations of KRAS, CDKN2A, TP53, and SMAD4 are the most frequent events in pancreatic cancer. We determined the extent to which these 4 alterations are coexistent in the same carcinoma, and their impact on patient outcome.

Experimental Design: Pancreatic cancer patients who underwent an autopsy were studied (n = 79). Matched primary and metastasis tissues were evaluated for intragenic mutations in KRAS, CDKN2A, and TP53 and immunolabeled for CDKN2A, TP53, and SMAD4 protein products. The number of altered driver genes in each carcinoma was correlated to clinicopathologic features. Kaplan–Meier estimates were used to determine median disease free and overall survival, and a Cox proportional hazards model used to compare risk factors.

Results: The number of genetically altered driver genes in a carcinoma was variable, with only 29 patients (37%) having an alteration in all 4 genes analyzed. The number of altered driver genes was significantly correlated with disease free survival (P = 0.008), overall survival (P = 0.041), and metastatic burden at autopsy (P = 0.002). On multivariate analysis, the number of driver gene alterations in a pancreatic carcinoma remained independently associated with overall survival (P = 0.046). Carcinomas with only 1 to 2 driver alterations were enriched for those patients with the longest survival (median 23 months, range 1 to 53).

Conclusions: Determinations of the status of the 4 major driver genes in pancreatic cancer, and specifically the extent to which they are coexistent in an individual patients cancer, provides distinct information regarding disease progression and survival that is independent of clinical stage and treatment status. Clin Cancer Res; 18(22); 6339–47. ©2012 AACR.
Targeting Protein Tyrosine Kinase 6 Enhances Apoptosis of Colon Cancer Cells following DNA Damage
Authors: Gierut Jessica J. , Mathur Priya S. , Bie Wenjun , Han Jin , Tyner Angela L.
Published: September 2012

Protein tyrosine kinase 6 (PTK6) is an intracellular tyrosine kinase that has distinct functions in normal epithelia and cancer. It is expressed primarily in nondividing epithelial cells in the normal intestine, where it promotes differentiation. However, after DNA damage, PTK6 is induced in proliferating progenitor cells, where it contributes to apoptosis. We examined links between PTK6 and the tumor suppressor p53 in the isogenic p53+/+ and p53−/− HCT116 colon tumor cell lines. We found that p53 promotes expression of PTK6 in HCT116 cells, and short hairpin RNA-mediated knockdown of PTK6 leads to reduced induction of the cyclin-dependent kinase inhibitor p21. Knockdown of PTK6 enhances apoptosis in HCT116 cells with wild-type p53, following treatment of cells with γ-radiation, doxorubicin, or 5-fluorouracil. No differences in the activation of AKT, ERK1/2, or ERK5, known PTK6-regulated prosurvival signaling proteins, were detected. However, activity of STAT3, a PTK6 substrate, was impaired in cells with knockdown of PTK6 following DNA damage. In contrast to its role in the normal epithelium following DNA damage, PTK6 promotes survival of cancer cells with wild-type p53 by promoting p21 expression and STAT3 activation. Targeting PTK6 in combination with use of chemotherapeutic drugs or radiation may enhance death of colon tumor cells with wild-type p53. Mol Cancer Ther; 11(11); 2311–20. ©2012 AACR.
Dll4-Fc, an Inhibitor of Dll4-Notch Signaling, Suppresses Liver Metastasis of Small Cell Lung Cancer Cells through the Downregulation of the NF-κB Activity
Authors: Kuramoto Takuya , Goto Hisatsugu , Mitsuhashi Atsushi , Tabata Sho , Ogawa Hirohisa , Uehara Hisanori , Saijo Atsuro , Kakiuchi Soji , Maekawa Yoichi , Yasutomo Koji , Hanibuchi Masaki , Akiyama Shin-ichi , Sone Saburo , Nishioka Yasuhiko
Published: September 2012

Notch signaling regulates cell-fate decisions during development and postnatal life. Little is known, however, about the role of Delta-like-4 (Dll4)-Notch signaling between cancer cells, or how this signaling affects cancer metastasis. We, therefore, assessed the role of Dll4-Notch signaling in cancer metastasis. We generated a soluble Dll4 fused to the IgG1 constant region (Dll4-Fc) that acts as a blocker of Dll4-Notch signaling and introduced it into human small cell lung cancer (SCLC) cell lines expressing either high levels (SBC-3 and H1048) or low levels (SBC-5) of Dll4. The effects of Dll4-Fc on metastasis of SCLC were evaluated using a mouse model. Although Dll4-Fc had no effect on the liver metastasis of SBC-5, the number of liver metastasis inoculated with SBC-3 and H1048 cells expressing Dll4-Fc was significantly lower than that injected with control cells. To study the molecular mechanisms of the effects of Dll4-Fc on liver metastasis, a PCR array analysis was conducted. Because the expression of NF-κB target genes was affected by Dll4-Fc, we conducted an electrophoretic mobility shift assay and observed that NF-κB activities, both with and without stimulation by TNF-α, were downregulated in Dll4-Fc–overexpressing SBC-3 and H1048 cells compared with control cells. Moreover, Dll4-Fc attenuates, at least in part, the classical and alternative NF-κB activation pathway by reducing Notch1 signaling. These results suggest that Dll4-Notch signaling in cancer cells plays a critical role in liver metastasis of SCLC by regulating NF-κB signaling. Mol Cancer Ther; 11(12); 2578–87. ©2012 AACR.
Pattern of Uveitis in an Egyptian Population with Multiple Sclerosis: A Hospital-Based Study
Authors: Karara Ahmed M. , Macky Tamer A. , Sharawy Mai H.
Published: September 2012

Purpose: To investigate the prevalence and pattern of uveitis in patients with multiple sclerosis (MS). PatientsandMethods: This is a cross-sectional, observational, descriptive clinical study of patients with MS who had complete ophthalmological examination. Data collected comprised demographics of the patients and complete ocular examination findings. Exclusion criteria were history of ocular surgery, trauma or diagnosis of any other ocular pathology. Results: Seventy-five patients with a mean age of 32.64 years (ranging from 16 to 50) diagnosed with MS of the relapsing-remitting type were included in this study. There were 34 males and 41 females, a ratio of 5:6. The mean duration of the MS disease was 5.6 years. Eight eyes of 7 patients with a mean age of 20 years had intermediate uveitis, of which 5 were males. Out of the 7 patients, 5 had exacerbated MS, and 2 were in remission; 4 had relative afferent pupillary defect. In the 8 eyes with uveitis, 6 had a best spectacle-corrected visual acuity (BSCVA) of 1, 1 had a BSCVA of 0.5 and 1 had a BSCVA of 0.25. Conclusion: Uveitis occurs in about 10% of patients with MS affecting younger males with exacerbated disease. Most inflammations of the uveitic MS patients were in the form of intermediate uveitis that was controlled with medication with no visual threatening complications.
Decoupled Response of Ocean Acidification to Variations in Climate Sensitivity
Authors: Matsumoto Katsumi , McNeil Ben
Published: September 2012

It is now well understood that the global surface ocean, whose pH has been reduced by ~0.1 in response to rising atmospheric CO2 since industrialization, will continue to become more acidic as fossil fuel CO2 emissions escalate. However, it is unclear how uncertainties in climate sensitivity to future CO2 emissions will alter the manifestation of ocean acidification. Using an earth system model of intermediate complexity, this study performs a set of simulations that varies equilibrium climate sensitivity by 1.0°–4.5°C for a given CO2 emissions scenario and finds two unexpected and decoupled responses. First, the greater the climate sensitivity, the larger the surface mixed layer acidification signal but the smaller the subsurface acidification. However, taken throughout the ocean, the highest climate sensitivity will paradoxically cause greater global warming while buffering whole-ocean pH by up to 24% on centennial time scales. Second, this study finds a large decoupling between pH and carbonate ion concentration in surface waters whereby these chemical properties show opposite effects under variable climate sensitivity. For every 1°C increase in climate sensitivity, the surface ocean pH reduction grows by 4%, while surface ocean carbonate ion reduction shrinks by 2%. The chemical and spatial decoupling found here highlights the importance of distinguishing the biological impacts of pH and aragonite saturation and understanding the spatial extent of important calcifying biomes so as to truly understand the long-term impacts of ocean acidification.
Effect of viscosity and electrical conductivity on the morphology and fiber diameter in melt electrospinning of polypropylene
Authors: Nayak Rajkishore , Padhye Rajiv , Kyratzis Ilias Louis , Truong Yen Bach , Arnold Lyndon
Published: September 2012

The feasibility of fabricating polypropylene (PP) nanofibers has been explored by using different additives, such as sodium oleate (SO), poly(ethylene glycol) (PEG) and poly(dimethyl siloxane) (PDMS), during melt electrospinning. PP of high melt flow index (1000) was used with PEG and PDMS for the reduction of the melt viscosity; and it was used with SO for improving the electrical conductivity during melt electrospinning. It was observed that all the additives used in this study helped to reduce the fiber diameter. The most promising additive, SO, was effective in reducing the fiber diameter to the nanometer scale due to the increase in the electrical conductivity. The fiber diameter was decreased by the addition of PEG and PDMS due to the decrease in the melt viscosity. The effect of die shape on the fiber cross-sectional shape was analyzed and an interesting finding is that the die shapes did not have an effect on the cross-sectional shape of the fibers. That is, irrespective of the die shapes (i.e. trilobal, tetralobal, multilobal and circular) used in this study, the cross-sectional shapes of melt electrospun fibers were circular. The distribution of the additives in the fiber was analyzed by energy-dispersive X-ray analysis and was found to be uniform. Tensile tests were performed on single nanofibers with limited success, due to the problems in preparing fiber samples and successfully holding them in the jaws of the testing machine without slippage.
At the End of the Day: Macmillan’s Account of the Cuban Missile Crisis
Authors: Catterall Peter
Published: September 2012

Pre-publicity for the final volume of Harold Macmillan’s memoirs, At the End of the Day, stressed that it would provide the British side of the Cuban missile crisis for the first time. The Churchillian model chosen, changes required by the Cabinet Office and Macmillan’s desire to rebuke those political opponents who claimed that the crisis demonstrated a lack of British influence in Washington, however ensured a focus on his personal relationship with President Kennedy. His larding the text with contemporary observations from his diaries also skewed Macmillan’s account and, in particular, underplayed the significance of British moves at the United Nations in New York to secure a credible United Nations inspection regime and a US guarantee of the inviolability of Cuba. Careful reconstruction of Macmillan’s real-time experience of the Cuban missile crisis demonstrates the limitations of his own account of this event.
Nonlinear dynamic analysis of an axially loaded rotating Timoshenko beam with extensional condition included subjected to general type of force moving along the beam length
Authors: Mamandi Ahmad , Kargarnovin Mohammad H
Published: September 2012

In this paper the non-planar nonlinear dynamic responses of an axially loaded rotating Timoshenko beam subjected to a three-directional force traveling with a constant velocity is studied. On deriving the nonlinear coupled partial differential equations (PDEs) of motion the stretching effect of the beam’s neutral axis due to the pinned-pinned ends’ condition in conjunction with the von Karman strain-displacement relation are considered. The beam’s nonlinear governing coupled PDEs of motion for the bending rotations of warped cross-section, longitudinal and lateral displacements are derived using Hamilton’s principle. To obtain the dynamic responses of the beam, derived PDEs of motion are solved by applying Galerkin’s method. Furthermore, subsequent to the verification of obtained results, a parametric study on the dynamic responses of the beam is conducted by changing the value of the concentrated traveling force-bending moment, load velocity, frequency fluctuation of the load velocity and rotational speed of the beam, respectively. It is observed that the existence of nonlinearity in the governing coupled PDEs of motion due to the beam mid-plane stretching introduces a noticeable effect on the size of the beam’s stiffness.
A retrospective study of 180 anaemic cats: features, aetiologies and survival data
Authors: Korman Rachel M , Hetzel Natasha , Knowles Toby G , Harvey Andrea M , Tasker Séverine
Published: September 2012

The study comprised 180 anaemic cats. Descriptive and survival data were obtained. Cats were classified by aetiology of anaemia development and degenerative, anomalous, metabolic, miscellaneous, neoplastic, infectious, inflammatory, immune-mediated, toxic, traumatic or vascular disease (DAMNITV) classification and anaemia severity. Sixty-four (35.6%) cats had mild [packed cell volume (PCV)/haematocrit (HCT) 20–24.9%], 58 (32.2%) moderate (14–19.9%), 23 (12.8%) severe (11–13.9%) and 35 (19.4%) very severe (<10.9%) anaemia. By aetiology of anaemia development, bone marrow (BM) abnormalities were more common (95, 52.8%) than haemorrhage (37, 20.6%) or haemolysis (19, 10.6%). By DAMNITV classification, infectious diseases were more common (39, 21.7%) than neoplasia (36, 20%), metabolic (21, 11.7%), trauma (15, 8.3%), miscellaneous (14, 7.8%), inflammatory (11, 6.1%), immune-mediated (11, 6.1%), anomalous (8, 4.4%), toxic (2, 1.1%) or vascular disease (1, 0.6%). BM abnormalities were significantly associated with more severe anaemia ( P = 0.003). Most cats (112, 62.2%) survived to discharge whereas 55 (30.6%) were euthanased and 13 (7.2%) died. Survival to discharge was not associated with anaemia severity but was associated significantly with aetiology of anaemia development ( P = 0.046), as cats with haemolysis were more likely to survive to discharge than cats with BM abnormalities. Survival to discharge was also associated significantly with DAMNITV classification ( P = 0.010), with cats with neoplasia being less likely, and cats with immune-mediated disease more likely, to survive to discharge. Cox regression analysis found that survival was not associated with anaemia severity, but was associated with DAMNITV classification ( P = 0.011) and age ( P = 0.082), with cats with immune-mediated disease and younger cats more likely to survive.
Developing a Comprehensive Curriculum for Public Health Advocacy
Authors: Hines Ayelet , Jernigan David H.
Published: September 2012

There is a substantial gap in public health school curricula regarding advocacy. Development of such a curriculum faces three challenges: faculty lack advocacy skills and experience; the public health literature on effective advocacy is limited; and yet a successful curriculum must be scalable to meet the needs of approximately 9,000 public health students graduating each year. To meet these challenges, we propose a 100-hour interactive online curriculum in five sections: campaigning and organizing, policy making and lobbying, campaign communications, new media, and fund-raising. We outline the content for individual modules in each of these sections, describe how the curriculum would build on existing interactive learning and social media technologies, and provide readers the opportunity to “test-drive” excerpts of a module on “grasstops” organizing. Developing advocacy skills and expertise is critical to meeting the challenges of public health today, and we provide a blueprint for how such training might be brought to scale in the field.
Small nucleolar RNA expression profiling identifies potential prognostic markers in peripheral T-cell lymphoma
Authors: Valleron Wilfried , Ysebaert Loic , Berquet Laure , Fataccioli Virginie , Quelen Cathy , Martin Antoine , Parrens Marie , Lamant Laurence , de Leval Laurence , Gisselbrecht Christian , Gaulard Philippe , Brousset Pierre
Published: September 2012

Peripheral T-cell lymphoma (PTCL) is a rare, heterogeneous type of non-Hodgkin lymphoma (NHL) that, in general, is associated with a poor clinical outcome. Therefore, a current major challenge is the discovery of new prognostic tools for this disease. In the present study, a cohort of 122 patients with PTCL was collected from a multicentric T-cell lymphoma consortium (TENOMIC). We analyzed the expression of 80 small nucleolar RNAs (snoRNAs) using high-throughput quantitative PCR. We demonstrate that snoRNA expression analysis may be useful in both the diagnosis of some subtypes of PTCL and the prognostication of both PTCL-not otherwise specified (PTCL-NOS; n = 26) and angio-immunoblastic T-cell lymphoma (AITL; n = 46) patients treated with chemotherapy. Like miRNAs, snoRNAs are globally down-regulated in tumor cells compared with their normal counterparts. In the present study, the snoRNA signature was robust enough to differentiate anaplastic large cell lymphoma (n = 32) from other PTCLs. For PTCL-NOS and AITL, we obtained 2 distinct prognostic signatures with a reduced set of 3 genes. Of particular interest was the prognostic value of HBII-239 snoRNA, which was significantly over-expressed in cases of AITL and PTCL-NOS that had favorable outcomes. Our results suggest that snoRNA expression profiles may have a diagnostic and prognostic significance for PTCL, offering new tools for patient care and follow-up.
Depression, suicidal ideation, and associated factors: a cross-sectional study in rural Haiti
Authors: Wagenaar Bradley H , Hagaman Ashley K , Kaiser Bonnie N , McLean Kristen E , Kohrt Brandon A
Published: September 2012

Background

Since the 2010 earthquake in Haiti, there has been increased international attention to mental health needs throughout the country. The present study represents one of the first epidemiologic studies of depression symptomatology, suicidal ideation, and associated factors in Haiti’s Central Plateau.

Methods

We conducted a cross-sectional, zone-stratified household survey of 408 adults in Haiti’s Central Plateau. Depression symptomatology was assessed with a culturally-adapted Kreyòl version of the Beck Depression Inventory (BDI). Multivariable linear and logistic regression models were built using backward elimination, with the outcomes being continuous BDI scores and endorsing suicidal ideation, respectively.

Results

The mean BDI score was 20.4 (95% confidence interval [CI]: 19.3-21.5), and 6.13% (N = 25) of participants endorsed current suicidal ideation. Factors associated with BDI scores were: continuous age (adjusted beta [aβ]: 0.14, CI: 0.06-0.22), female gender (aβ: 2.1, CI: 0.18-4.0), suicidal ideation (aβ: 11.1, CI: 7.3-14.9), death in family (aβ: 2.7, CI: 0.57-4.9), and prior life-threatening illness (aβ: 2.6, CI: 0.77-4.5). Education was a risk factor for depression among women but not among men, and employment was a risk factor for both genders. Factors associated with endorsing suicidal ideation were: BDI score (ten point change) (adjusted odds ratio [aOR]: 2.5, CI: 1.7-3.6), lack of care if sick (aOR: 5.5, CI: 1.1-28.6), alcohol use (aOR: 3.3, CI: 1.3-8.2), and ever having been to a Vodou priest (aOR: 3.2, CI: 1.1-9.5).

Conclusions

A large proportion of Haiti’s Central Plateau may be experiencing high levels of depression symptomatology and/or current suicidal ideation. Screening could be conducted in biomedical, religious, and Vodou healing contexts. For prevention, poverty reduction and improved healthcare access are key elements. For treatment, general psychiatric services, psychosocial services for the medically ill and their families, and substance abuse interventions should be explored. Paradoxical associations related to education and employment require further exploration.
Engineering Escherichia coli to increase plasmid DNA production in high cell-density cultivations in batch mode
Authors: Borja Gheorghe M , Meza Mora Eugenio , Barrón Blanca , Gosset Guillermo , Ramírez Octavio T , Lara Alvaro R
Published: September 2012

Background

Plasmid DNA (pDNA) is a promising molecule for therapeutic applications. pDNA is produced by Escherichia coli in high cell-density cultivations (HCDC) using fed-batch mode. The typical limitations of such cultivations, including metabolic deviations like aerobic acetate production due to the existence of substrate gradients in large-scale bioreactors, remain as serious challenges for fast and effective pDNA production. We have previously demonstrated that the substitution of the phosphotransferase system by the over-expressed galactose permease for glucose uptake in E. coli (strain VH33) allows efficient growth, while strongly decreases acetate production. In the present work, additional genetic modifications were made to VH33 to further improve pDNA production. Several genes were deleted from strain VH33: the recA, deoR, nupG and endA genes were inactivated independently and in combination. The performance of the mutant strains was evaluated in shake flasks for the production of a 6.1 kb plasmid bearing an antigen gene against mumps. The best producer strain was cultivated in lab-scale bioreactors using 100 g/L of glucose to achieve HCDC in batch mode. For comparison, the widely used commercial strain DH5α, carrying the same plasmid, was also cultivated under the same conditions.

Results

The various mutations tested had different effects on the specific growth rate, glucose uptake rate, and pDNA yields (YP/X). The triple mutant VH33 Δ (recA deoR nupG) accumulated low amounts of acetate and resulted in the best YP/X (4.22 mg/g), whereas YP/X of strain VH33 only reached 1.16 mg/g. When cultivated at high glucose concentrations, the triple mutant strain produced 186 mg/L of pDNA, 40 g/L of biomass and only 2.2 g/L of acetate. In contrast, DH5α produced only 70 mg/L of pDNA and accumulated 9.5 g/L of acetate. Furthermore, the supercoiled fraction of the pDNA produced by the triple mutant was nearly constant throughout the cultivation.

Conclusion

The pDNA concentration obtained with the engineered strain VH33 Δ (recA deoR nupG) is, to the best of our knowledge, the highest reported for a batch cultivation, and its supercoiled fraction remained close to 80%. Strain VH33 Δ (recA deoR nupG) and its cultivation using elevated glucose concentrations represent an attractive technology for fast and efficient pDNA production and a valuable alternative to fed-batch cultivations of commercial strains.