bluuebunny/crossref_metadata_2025 huggingface dataset:
On identification in Bayesian disease mapping and ecological–spatial regression models
Authors: MacNab Ying C
Published: May 2012

We discuss identification of structural characteristics of the underlying relative risks ensemble for posterior relative risks inference within Bayesian generalized linear mixed model framework for small-area disease mapping and ecological–spatial regression. We revisit conditionally specified and locally characterized Gaussian Markov random field risks ensemble priors in univariate disease mapping and communicate insight into Gaussian Markov random field variance–covariance characteristics for representing disease risks variability and spatial risks interactions and for structural identification with respect to risks ensemble prior choices. Illustrative examples of identification in Bayesian disease mapping and ecological–spatial regression models are presented for Bayesian hierarchical generalized linear mixed Poisson models and zero-inflated Poisson models.
Similar challenges but different responses: Media coverage of measles vaccination in the UK and China
Authors: Ren Jie , Peters Hans Peter , Allgaier Joachim , Lo Yin-Yueh
Published: May 2012

For several decades scholars have studied media reporting on scientific issues that involve controversy. Most studies so far have focused on the western world. This article tries to broaden the perspective by considering China and comparing it to a western country. A content analysis of newspaper coverage of vaccination issues in the UK and China shows, first, that the government-supported ‘mainstream position’ dominates the Chinese coverage while the British media frequently refer to criticism and controversy. Second, scientific expertise in the British coverage is represented by experts from the health and science sector but by experts from health agencies in the Chinese coverage. These results are discussed with respect to implications for risk communication and scientists’ involvement in public communication.
Modeling and experimental characterization of the stress, strain, and resistance of shape memory alloy actuator wires with controlled power input
Authors: Furst Stephen J , Seelecke Stefan
Published: May 2012

Recently, a novel power controller has been presented that simultaneously controls electric power input and measures resistance of a commercially available Flexinol shape memory alloy wire. This work exploits the new power controller by plotting shape memory alloy stress, strain, and resistance versus Joule heating power instead of input voltage or current. Heating power is directly related to shape memory alloy temperature, whereas standard constant voltage or constant current inputs cause more or less heating as the resistance of the wire changes due to phase transformation. A simple experimental setup consisting of a 50-µm-diameter Flexinol wire mounted in series with the tip of a compliant cantilever beam is used to systematically study the shape memory alloy behavior. Actuator performance is reported for a range of prestress values and actuation frequencies. All the experimental data are compared with simulated behavior that is derived from a free energy–based numerical model for shape memory alloy material. Additionally, a new resistance model based on the simulated wire temperature and phase fractions is introduced and compared to experimental data. Exploiting a multifunctional power controller and an improved understanding of the resistance change during phase transformation will help enable the use of shape memory alloy wires in simultaneous sensing and actuating applications.
CD25 Is a Novel Marker of Hepatic Bile Canaliculus
Authors: Lu Zhong-Hua , -Chen Wei , Ju Chao-Xia , -Den Jun , Kuai Shou-gang , Pei Hao , Huang Li-Hua , Gu Xi-Bing , Ying Yong-Xiang , Hu Xi-Qi , Zhu Teng-Fang , Xing Yi-Ping , Fan Qin-He
Published: May 2012

Objective. Although many antigens have been investigated, the method for the bile canaliculus staining using optical microscopy needs to be improved. The aim of the present study was to assess the expression pattern of a candidate marker, CD25, in normal and diseased liver tissue. Methods. Immunohistochemistry, immunofluorescence, and immune electron microscopy assays were performed with 41 liver sections and 2 different anti-CD25 monoclonal antibodies. A polyclonal antibody against carcinoembryonic antigen (CEA) was also used to stain bile canaliculus as a control. CD25 expression levels in normal and diseased liver tissue were also determined. Results. CD25 was predominantly localized at the bile canaliculus of adult and infantile liver, evidenced by both immunohistochemistry and immunofluorescence assays. The electron microscopy assay showed that there were obvious amorphous electron-dense deposits at the bile canaliculus. In contrast, the CEA-positive area included bile canaliculus as well as basolateral aspects of hepatocytes. CD25 expression levels did not differ significantly among different disease states. Conclusion. This study provides the first evidence that CD25 is a novel marker of bile canaliculus. Characteristics of CD25 expression may shed light on immunohistochemistry and immunofluorescence analysis of bile canaliculus in both basic and clinical hepatic investigations.
Effects of Rosuvastatin With or Without Ezetimibe on Clinical Outcomes in Patients Undergoing Elective Vascular Surgery
Authors: Kouvelos George N. , Arnaoutoglou Eleni M. , Matsagkas Miltiadis I. , Kostara Christina , Gartzonika Constantina , Bairaktari Eleni T. , Milionis Haralampos J.
Published: May 2012

Objective:

Cardiovascular complications represent a major cause of morbidity and mortality in patients undergoing vascular surgery. This was a prospective randomized, open-label study to investigate the effect of lipid-lowering treatment by statin monotherapy or intensified by combining statin with ezetimibe on a  12-month  prognosis after vascular surgery.

Methods:

Patients were randomly assigned to receive rosuvastatin (RSV) 10 mg/d or rosuvastatin 10 mg/d plus ezetemibe (RSV/EZT) 10 mg/d, starting prior to scheduled surgical procedure. The primary end point was the first major cardiovascular event, including death from cardiac causes, nonfatal myocardial infarction, ischemic stroke, and unstable angina.

Results:

A total of 136 patients assigned to RSV and 126 to RSV/EZT completed the study protocol. As many as 6.6% of patients in the RSV group experience a major cardiovascular event within 30 days after surgery versus 5.6% in the RSV/EZT group ( P = .72). From month 1 to 12 of the follow-up period, primary end point was observed (9 taking RSV vs 2 in the RSV/EZT group [ P = .04]). Intensified lipid-lowering therapy with RSV/EZT was associated with a greater decrease in low-density lipoprotein cholesterol levels compared with RSV (75.87 ± 31.64 vs 87.19 ± 31.7, P = .004), while no differential effect on triglyceride, high-density lipoprotein cholesterol or high-sensitivity C-reactive protein levels was noted between groups.

Conclusion:

Our findings indicate that statin therapy intensified by ezetimibe may reduce the incidence of cardiovascular events within the first 12 months after vascular surgery. Nonetheless, whether the use of ezetimibe as an add-on therapy to reduce cardiovascular risk in these patients needs to be tested in larger future studies.
Transverse vibration control of translating visco-elastically connected double-string-like continua
Authors: Foda Mosaad A
Published: May 2012

The aim of this work is to develop a direct and exact approach using the Green's functions to control the steady-state transverse vibration of an axially moving double-string system supported by two rollers (eyelets) at both ends. The two strings are similar and coupled by a viscoelastic layer of a Kelvin–Voigt type. The control is achieved by introducing suitable control forces (using actuators) or passive elements to be located at some chosen locations along the span between the eyelets. A scheme is proposed for evaluating the control forces and their locations to suppress the vibration of the system and correspondingly decrease the generated noise. The variation of the running speed and different end supports are taken into consideration.
Exposure to Airborne Mould in School Environments and Nasal Patency in Children
Authors: Zhang Guicheng , Neumeister-Kemp Heike , Garrett Maria , Kemp Peter , Stick Stephen , Franklin Peter
Published: May 2012

Mould in schools has been associated with increased upper airway obstruction in adults. In this study, we investigated the relationship between school indoor mould spore exposure and nasal patency in children. Airborne mould samples were collected in 32 classrooms from 4 primary schools during both summer and winter using a single-stage Anderson sampler. Nasal patency was measured in 275 children in summer and 200 children in winter using acoustic rhinometry. Various mould species were isolated but the most common species found inside the classrooms were Alternaria, Aspergillus niger, Cladosporium spp. and Penicillium spp. In the univariate analyses, significant negative correlations were found between exposure to various mould species, particularly Alternaria, and rhinometric measures in the children. In multivariate analyses, exposure to Alternaria was associated with both decreased mean nasal cross-sectional area ( p = 0.001) and decreased nasal volume ( p = 0.026). Decreased nasal patency was also associated with exposure to A. niger ( p = 0.034) and Penicillium ( p = 0.043) in the classrooms. The findings of this study suggest that exposure to airborne mould, particularly Alternaria, in school environments may affect the upper airways of children.
Safety and Immediate Effect of Noninvasive Transcranial Pulsed Current Stimulation on Gait and Balance in Parkinson Disease
Authors: Alon Gad , Yungher Don A. , Shulman Lisa M. , Rogers Mark W.
Published: May 2012

Background. Noninvasive electrical stimulation of the brain (ESB) is being investigated as a valued intervention to enhance motor performance. Objective. To ascertain the safety and ability of transcranial pulsed current stimulation (tPCS) to modulate variables of protective stepping and gait of individuals with Parkinson’s disease. Method. Ten patients participated in a pilot study. During the first session, a tPCS delivered current for 20 minutes via a positive electrode placed over the primary motor area (M1). In week 2, participants walked for 20 minutes on a treadmill. In week 3, tPCS and treadmill for 20 minutes were combined. Pre-testing and post-testing of gait and protective stepping were administered, comparing post-intervention (tPCS alone, treadmill alone, tPCS + treadmill) with pre-intervention data. The 3 interventions were compared by calculating the difference between post-intervention and pre-intervention data. A significance level of P < .05 was adopted. Results. Stride length increased from 102.1 ± 24.4 to 111.2 ± 22.1 cm, and gait velocity increased from 0.90 ± 0.23 to 0.985 ± 0.19 m/s after tPCS. Treadmill or treadmill + tPCS did not result in changes in the studied gait parameters. The tPCS session increased gait velocity and stride length significantly compared with treadmill or tPCS + treadmill. Overall, the number of steps needed to recover balance decreased after tPCS and tPCS + treadmill. Conclusion. Noninvasive tPCS over the primary motor cortex had no adverse effects on those with long-standing Parkinson’s disease and may lead to acute improvement of gait and balance recovery.
Support Requirements for Cognitive Readiness in Complex Operations
Authors: Lafond Daniel , DuCharme Michel B. , Gagnon Jean-François , Tremblay Sébastien
Published: May 2012

The authors report two experiments studying the requirements for effective decision making in a complex environment. The focus lies on three components of individual cognitive readiness: situation awareness (SA), problem solving, and decision making. Participants performed a simulated society management task in which they could allocate resources to stabilize a national crisis involving multiple interrelated factors (political, economic, environmental, and social). A striking aspect of this simulation is that even though information about the causes and effects within the system is available, most individuals fail to bring the system to the targeted state because of unintended consequences of their decisions. The experiments test the impact of two cognitive support tools designed to improve anticipation of future outcomes. Results show that supporting short-term anticipation (with perfectly accurate projections) was insufficient to improve effectiveness, but supporting long-term anticipation (with approximate projections) successfully improved performance in this complex environment. We conclude with a review of requirements that training and technological support should address to augment individual cognitive readiness for operations in complex environments and propose an extension to SA theory by conceptualizing a Level 4 SA (long-term projection) that may be particularly important to overcome the “wall of complexity.”
Enhancing Research on Training for Cognitive Readiness
Authors: Kluge Annette , Burkolter Dina
Published: May 2012

In the present article, we aim to provide guidelines on how to conduct research for the enhancement of training for cognitive readiness (CR). After distinguishing between trainable CR skills and stable person-related variables, CR components that are trainable need to be defined in terms of knowledge, skills, and attitudes, and person-related variables need to be selected as prerequisites for training success, as they define the composite construct of CR. Training success in turn needs to include indicators of successful performance in unpredictable environments after training of CR that operationalizes temporal and adaptive transfer. We suggest a basic module for training-of-CR research, which includes a pretest measuring the baseline of the participants’ knowledge, skills, and attitudes; person-related variables as control variables; predictors and moderators of CR training success; and two posttests for the assessment of training performance directly after training and following a retention interval for both temporal and adaptive transfer. For further research, we suggest extending the basic module with research on spacing of practice, performance under stress, and individual differences in cognition and personality. This research will enhance the understanding of the interplay between person- and training-related variables that best predicts the prerequisites for establishing and sustaining competent performance in complex and stressful environments.
Active Commuting to School
Authors: Johnston Craig A. , Moreno Jennette P.
Published: May 2012

Declines in physical activity levels have coincided with increasing rates of obesity in children. This is problematic because physical activity has been shown to attenuate weight gain in children. Active commuting to school is one way of increasing children’s physical activity. However, given the high rates of child pedestrian injury, preventive strategies to reduce these risks are needed. Programs such as the Walking School Bus provide opportunities to not only promote pedestrian safety but increase children’s energy expenditure.
Reduction of residual stresses in laser beam welds by means of defocused laser beams
Authors: Tölle F , Gumenyuk A , Rethmeier M
Published: May 2012

Longitudinal residual stresses in beam welds ranging at the value of the local yield strength can diminish the lifespan of components. To extend the service life of welds special methods of welding residual stress reduction were developed earlier which are however not effective for beam welds in complex component geometries. Application of beam welding sources for post-welding heat treatment of components has become a flexible tool for reducing longitudinal stresses in beam welds. Such heat treatment in a specific transversal distance to the weld by a defocused beam results in huge stress reductions depending on the used process parameters. Experimental results for ferritic and austenitic steels reveal weld stress reductions to up to compressive stresses. For different materials and diverse material thicknesses special process parameter regions have to be used in this procedure. At a transmission component this procedure shows a stress reduction by >300 MPa.
Effect of hardness of martensite and ferrite on void formation in dual phase steel
Authors: Azuma M. , Goutianos S. , Hansen N. , Winther G. , Huang X.
Published: May 2012

The influence of the hardness of martensite and ferrite phases in dual phase steel on void formation has been investigated by in situ tensile loading in a scanning electron microscope. Microstructural observations have shown that most voids form in martensite by evolving four steps: plastic deformation of martensite, crack initiation at the martensite/ferrite interface, crack propagation leading to fracture of martensite particles and void formation by separation of particle fragments. It has been identified that the hardness effect is associated with the following aspects: strain partitioning between martensite and ferrite, strain localisation and critical strain required for void formation. Reducing the hardness difference between martensite and ferrite phases by tempering has been shown to be an effective approach to retard the void formation in martensite and thereby is expected to improve the formability.
Improved properties of Mn series ultralow carbon steel with ultrafine bainitic structure
Authors: Gao G H , Zhang H , Bai B Z
Published: May 2012

In order to reduce the cost of alloying elements, Mn series ultralow carbon bainitic (ULCB) steels have been developed. The different cooling conditions have been used to improve the mechanical properties of Mn series ULCB steels in the present study. The hot rolled ULCB steel plates with 26 mm thickness were water quenched to different finishing quenching temperatures (550, 450 and 350°C) followed by air cooling. Results show that the as rolled ULCB steel plates exhibit high yield strength of 775 MPa and low energy transition temperature of −55°C when the finishing quenching temperature is chosen at 450°C. Low temperature impact toughness was improved through control of the finishing quenching temperature. Microstructure observations show that a fine granular bainite structure is obtained, and the granular bainite structure exhibited shorter crack propagation path than both granular ferrite and lath martensite structures, which contributed to the improved combination of strength and toughness. Furthermore, the formation process of fine granular bainite structure was investigated.
Modelling of shear induced coarsening of dendrites during semisolid processing
Authors: Reisi M , Niroumand B
Published: May 2012

A theoretical model has been developed to investigate the effects of fluid flow on the dendrite coarsening. The accelerated convective solute transport due to convection is considered by incorporating the new apparent diffusivity parameter into the classical coarsening model for stagnant melts. The model predicted that the dendrite arm coarsening followed the [Formula: see text] and [Formula: see text] relationships under laminar and turbulent fluid flow conditions respectively. The model predictions are found to be in good quantitative agreement with experimental data in literature.
Residual stress in pulsed dc microarc oxidation treated AZ31 alloy
Authors: Gu Y H , Chen C-f , Bandopadhyay S , Ning C Y , Guo Y J
Published: May 2012

This paper addresses the residual stress in the microarc oxidation (MAO) coating on AZ31 magnesium alloy. The MAO coating was deposited by pulsed direct current (dc) and examined by scanning electron microscopy and X-ray diffraction for its microstructure and composition. The porosity of the coatings was measured by potentiodynamic polarisation tests and found to be in the range of 3–6%. The residual stresses in the MAO coatings prepared at 300, 500, 1000 and 3000 Hz respectively were found to be between −860 and −1272 MPa. Using a high pulse frequency at 3000 Hz can produce a less porous and less stressed MAO coating, a desirable feature in the biomedical applications of MAO coated AZ31. This finding was further verified by establishing a first principle relation between the residual stress and the porosity via Stoney equation, which enables extrapolation of the experimental data measured.
Deterministic global optimization algorithm based on outer approximation for the parameter estimation of nonlinear dynamic biological systems
Authors: Miró Anton , Pozo Carlos , Guillén-Gosálbez Gonzalo , Egea Jose A , Jiménez Laureano
Published: May 2012

Background

The estimation of parameter values for mathematical models of biological systems is an optimization problem that is particularly challenging due to the nonlinearities involved. One major difficulty is the existence of multiple minima in which standard optimization methods may fall during the search. Deterministic global optimization methods overcome this limitation, ensuring convergence to the global optimum within a desired tolerance. Global optimization techniques are usually classified into stochastic and deterministic. The former typically lead to lower CPU times but offer no guarantee of convergence to the global minimum in a finite number of iterations. In contrast, deterministic methods provide solutions of a given quality (i.e., optimality gap), but tend to lead to large computational burdens.

Results

This work presents a deterministic outer approximation-based algorithm for the global optimization of dynamic problems arising in the parameter estimation of models of biological systems. Our approach, which offers a theoretical guarantee of convergence to global minimum, is based on reformulating the set of ordinary differential equations into an equivalent set of algebraic equations through the use of orthogonal collocation methods, giving rise to a nonconvex nonlinear programming (NLP) problem. This nonconvex NLP is decomposed into two hierarchical levels: a master mixed-integer linear programming problem (MILP) that provides a rigorous lower bound on the optimal solution, and a reduced-space slave NLP that yields an upper bound. The algorithm iterates between these two levels until a termination criterion is satisfied.

Conclusion

The capabilities of our approach were tested in two benchmark problems, in which the performance of our algorithm was compared with that of the commercial global optimization package BARON. The proposed strategy produced near optimal solutions (i.e., within a desired tolerance) in a fraction of the CPU time required by BARON.
An in silico platform for the design of heterologous pathways in nonnative metabolite production
Authors: Chatsurachai Sunisa , Furusawa Chikara , Shimizu Hiroshi
Published: May 2012

Background

Microorganisms are used as cell factories to produce valuable compounds in pharmaceuticals, biofuels, and other industrial processes. Incorporating heterologous metabolic pathways into well-characterized hosts is a major strategy for obtaining these target metabolites and improving productivity. However, selecting appropriate heterologous metabolic pathways for a host microorganism remains difficult owing to the complexity of metabolic networks. Hence, metabolic network design could benefit greatly from the availability of anin silicoplatform for heterologous pathway searching.

Results

We developed an algorithm for finding feasible heterologous pathways by which nonnative target metabolites are produced by host microorganisms, usingEscherichia coli,Corynebacterium glutamicum, andSaccharomyces cerevisiaeas templates. Using this algorithm, we screened heterologous pathways for the production of all possible nonnative target metabolites contained within databases. We then assessed the feasibility of the target productions using flux balance analysis, by which we could identify target metabolites associated with maximum cellular growth rate.

Conclusions

Thisin silicoplatform, designed for targeted searching of heterologous metabolic reactions, provides essential information for cell factory improvement.
A genome-wide study of recombination rate variation in Bartonella henselae
Authors: Guy Lionel , Nystedt Björn , Sun Yu , Näslund Kristina , Berglund Eva C , Andersson Siv GE
Published: May 2012

Background

Rates of recombination vary by three orders of magnitude in bacteria but the reasons for this variation is unclear. We performed a genome-wide study of recombination rate variation among genes in the intracellular bacterium Bartonella henselae, which has among the lowest estimated ratio of recombination relative to mutation in prokaryotes.

Results

The 1.9 Mb genomes of B. henselae strains IC11, UGA10 and Houston-1 genomes showed only minor gene content variation. Nucleotide sequence divergence levels were less than 1% and the relative rate of recombination to mutation was estimated to 1.1 for the genome overall. Four to eight segments per genome presented significantly enhanced divergences, the most pronounced of which were the virB and trw gene clusters for type IV secretion systems that play essential roles in the infection process. Consistently, multiple recombination events were identified inside these gene clusters. High recombination frequencies were also observed for a gene putatively involved in iron metabolism. A phylogenetic study of this gene in 80 strains of Bartonella quintana, B. henselae and B. grahamii indicated different population structures for each species and revealed horizontal gene transfers across Bartonella species with different host preferences.

Conclusions

Our analysis has shown little novel gene acquisition in B. henselae, indicative of a closed pan-genome, but higher recombination frequencies within the population than previously estimated. We propose that the dramatically increased fixation rate for recombination events at gene clusters for type IV secretion systems is driven by selection for sequence variability.
On the stability of set-valued functional equations with the fixed point alternative
Authors: Kenary Hassan Azadi , Rezaei Hamid , Gheisari Yousof , Park Choonkil
Published: May 2012

Using the fixed point method, we prove the Hyers-Ulam stability of a Cauchy-Jensen type additive set-valued functional equation, a Jensen type additive-quadratic set-valued functional equation, a generalized quadratic set-valued functional equation and a Jensen type cubic set-valued functional equation.

Mathematics Subject Classification 2010:47H10; 54C60; 39B52; 47H04; 91B44.
LTP induction within a narrow critical period of immature stages enhances the survival of newly generated neurons in the adult rat dentate gyrus
Authors: Kitamura Takashi , Saitoh Yoshito , Murayama Akiko , Sugiyama Hiroyuki , Inokuchi Kaoru
Published: May 2012

Neurogenesis occurs in the adult hippocampus of various animal species. A substantial fraction of newly generated neurons die before they mature, and the survival rate of new neurons are regulated in an experience-dependent manner. Previous study showed that high-frequency stimulation (HFS) of perforant path fibers to the hippocampal dentate gyrus (DG) induces the long-term potentiation (LTP) in the DG, and enhances the survival of newly generated neurons in the DG. In this study, we addressed whether a time period exists during which the survival of new neurons is maximally sensitive to the HFS. We found that the enhancement of cell survival by HFS was exclusively restricted to the specific narrow period during immature stages of new neurons (7-10 days after birth). Furthermore, the pharmacological blockade of LTP induction suppressed the enhancement of cell survival by the HFS. These results suggest that the LTP induction within a narrow critical period of immature stages enhances the survival of newly generated neurons in rat DG.
A quantitative proteomic analysis of long-term memory
Authors: Rosenegger David , Wright Cynthia , Lukowiak Ken
Published: May 2012

Background

Memory is the ability to store, retain, and later retrieve learned information. Long-term memory (LTM) formation requires: DNA transcription, RNA translation, and the trafficking of newly synthesized proteins. Several components of these processes have already been identified. However, due to the complexity of the memory formation process, there likely remain many yet to be identified proteins involved in memory formation and persistence.

Results

Here we use a quantitative proteomic method to identify novel memory-associated proteins in neural tissue taken from animals that were trained in vivo to form a long-term memory. We identified 8 proteins that were significantly up-regulated, and 13 that were significantly down-regulated in the LTM trained animals as compared to two different control groups. In addition we found 19 proteins unique to the trained animals, and 12 unique proteins found only in the control animals.

Conclusions

These results both confirm the involvement of previously identified memory proteins such as: protein kinase C (PKC), adenylate cyclase (AC), and proteins in the mitogen-activated protein kinase (MAPK) pathway. In addition these results provide novel protein candidates (e.g. UHRF1 binding protein) on which to base future studies.
Suppression of lung cancer in murine model: treated by combination of recombinant human endostsatin adenovirus with low-dose cisplatin
Authors: Bai Rui Z , Wu Yang , Liu Quan , Xie Ke , Wei Yu Q , Wang Yong S , Liu Kang , Luo Yan , Su Jing M , Hu Bing , Liu Ji Y , Li Qiu , Niu Ting , Zhao Zhi W , Yang Li
Published: May 2012

Background

The sustained growth of tumors necessitates neovascularization. As one of the potent endogenous vascular inhibitors, endostatin has been widely used in antiangiogenesis therapy for tumor. Cisplatin is normally administered in chemotherapy for lung cancer but accompanied with serious side effects. In the current study, we investigated a novel chemo-antiangiogenesis therapeutic strategy to both improve toxic effects on lung cancer cells and reduce damages to normal cells in the anti-tumor therapy.

Methods

In vitro, we transduced LLC cells with Ad-hEndo and collected supernatants. Western blotting analysis of the supernatants revealed expression of endostatin. In vivo, to fully investigate the suppression effect on murine lung cancer of the combination therapy, we injected recombinant human endostatin adenovirus intratumorally plus a low dose of cisplatin intraperitoneally routinely. The tumor volume and survival time were observed. Angiogenesis was apparently inhibited within the tumor tissues and on the alginate beads. Assessment of apoptotic cells by the TUNEL assay was conducted in the tumor tissues.

Results

The combination treatment significantly suppressed the tumor growth and prolonged survival time of the murine LLC tumor model. This anti-tumor activity was associated with decreased microvessel density and increased apoptotic index of tumor cells.

Conclusion

According to the results in this study, recombinant human endostatin adenovirus in combination with a low dose of cisplatin demonstrated apparent synergistic anti-tumor activity without marked toxicity. Thus, these observations may provide a rational alternative for lung cancer treatment.
Reduced expression of Toll-like receptor 4 inhibits human breast cancer cells proliferation and inflammatory cytokines secretion
Authors: Yang Huan , Zhou Huiqin , Feng Ping , Zhou Xiaoni , Wen Huiyan , Xie Xiaofang , Shen Haiying , Zhu Xueming
Published: May 2012

Background

Tumor cell expression of Toll-like receptors (TLRs) can promote inflammation and cell survival in the tumor microenvironment. Toll-like receptor 4 (TLR4) signaling in tumor cells can mediate tumor cell immune escape and tumor progression, and it is regarded as one of the mechanisms for chronic inflammation in tumorigenesis and progression. The expression of TLR4 in human breast cancer cell line MDA-MB-231 and its biological function in the development and progression of breast cancer have not been investigated. We sought to characterize the expression of TLR1-TLR10 in the established human breast cancer cell line MDA-MB-231, and to investigate the biological roles of TLR4 in breast cancer cells growth, survival, and its potential as a target for breast cancer therapy.

Methods

TLRs mRNA and protein expressions were detected in human breast cancer cell line MDA-MB-231 by RT-PCR, real-time PCR and flow cytometry (FCM). RNA interference was used to knockdown the expression of TLR4 in MDA-MB-231. MDA-MB-231 transfected with the vector pGenesil-1 and the vector containing a scrambled siRNA were as controls. Recombinant plasmids named TLR4AsiRNA, TLR4BsiRNA and TLR4CsiRNA specific to TLR4 were transfected into human breast cancer cell line MDA-MB-231 with Lipfectamine™2000 reagent. TLR4 mRNA and protein expressions were investigated by RT-PCR, real-time PCR, FCM and immunofluorescence after silence. MTT analysis was performed to detect cell proliferation and FCM was used to detect the secretion of inflammatory cytokines in supernatant of transfected cells.

Results

The human breast cancer cell line MDA-MB-231 was found to express TLR1-TLR10 at both the mRNA and protein levels. TLR4 was found to be the highest expressed TLR in MDA-MB-231. TLR4AsiRNA, TLR4BsiRNA and TLR4CsiRNA were found to significantly inhibit TLR4 expression in MDA-MB-231 at both mRNA and protein levels as compared to vector control(vector transfected cells). TLR4AsiRNA mediated the strongest effect. Knockdown of TLR4 gene in MDA-MB-231 resulted in a dramatic reduction of breast cancer cell viability. The cytokines which were secreted by the TLR4 silenced cells, such as IL-6 and IL-8, also decreased significantly as compared with vector control. No significant difference was observed in siRNA control (Recombinant plasmid named ScrambledsiRNA transfected cells) compared to vector control.

Conclusions

These studies identified the expression levels of multiple TLRs in human breast cancer cell line MDA-MB-231 and demonstrated that knockdown of TLR4 could actively inhibit proliferation and survival of breast cancer cells. Taken together, our results suggest RNAi-directed targeting of TLR4 may be a beneficial strategy for breast cancer therapy.
Drug interactions in the elderly HIV‐infected patient
Authors: Coroiu C , Tollinchi F , Hittinger G , Mokhtari S , Granet P , Faucher‐Zaegel O , Madrid A , Menard A , Mattei JL , Chadapaud S ,   VISAGE study group
Published: May 2012

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Function of Wnt/β-catenin in counteracting Tcf3 repression through the Tcf3–β-catenin interaction
Authors: Wu Chun-I , Hoffman Jackson A. , Shy Brian R. , Ford Erin M. , Fuchs Elaine , Nguyen Hoang , Merrill Bradley J.
Published: May 2012

The canonical Wnt/β-catenin signaling pathway classically functions through the activation of target genes by Tcf/Lef–β-catenin complexes. In contrast to β-catenin-dependent functions described for Tcf1, Tcf4 and Lef1, the known embryonic functions for Tcf3 in mice, frogs and fish are consistent with β-catenin-independent repressor activity. In this study, we genetically define Tcf3–β-catenin functions in mice by generating a Tcf3ΔN knock-in mutation that specifically ablates Tcf3–β-catenin. Mouse embryos homozygous for the knock-in mutation (Tcf3ΔN/ΔN) progress through gastrulation without apparent defects, thus genetically proving that Tcf3 function during gastrulation is independent of β-catenin interaction. Tcf3ΔN/ΔN mice were not viable, and several post-gastrulation defects revealed the first in vivo functions of Tcf3–β-catenin interaction affecting limb development, vascular integrity, neural tube closure and eyelid closure. Interestingly, the etiology of defects indicated an indirect role for Tcf3–β-catenin in the activation of target genes. Tcf3 directly represses transcription of Lef1, which is stimulated by Wnt/β-catenin activity. These genetic data indicate that Tcf3–β-catenin is not necessary to activate target genes directly. Instead, our findings support the existence of a regulatory circuit whereby Wnt/β-catenin counteracts Tcf3 repression of Lef1, which subsequently activates target gene expression via Lef1–β-catenin complexes. We propose that the Tcf/Lef circuit model provides a mechanism downstream of β-catenin stability for controlling the strength of Wnt signaling activity during embryonic development.
Failure of extra-embryonic progenitor maintenance in the absence of dosage compensation
Authors: Mugford Joshua W. , Yee Della , Magnuson Terry
Published: May 2012

Proper regulation of X-linked gene expression, termed dosage compensation, is required for the normal development of mammalian embryos. Through the process of X chromosome inactivation (XCI), somatic cells of mammalian females inactivate one of their two X chromosomes in order to balance X-linked gene dosage with their male counterparts. The process of XCI is dependent upon the long non-coding RNA Xist, which is expressed from and coats the inactivated X chromosome (Xi) in cis. During mouse embryogenesis, imprinted XCI inactivates the paternally inherited X chromosome (Xp) within the extra-embryonic lineages. Consequently, females harboring a paternally derived Xist mutation (X/XXist–) die owing to failure of imprinted XCI and, presumably, poor trophoblast development. Here, we investigate the consequence of two active X chromosomes in the extra-embryonic ectoderm (ExE) of X/XXist– female embryos. At embryonic day (E) 6.5, we find that the X/XXist– ExE lacks the transcriptional regulator CDX2, a factor required to maintain the ExE in a progenitor state. In addition, spongiotrophoblast progenitors are not maintained. Surprisingly, we observe evidence of an Xi in a subpopulation of X/XXist– ExE cells. We demonstrate further that trophectodermal stem cells derived from X/XXist– embryos completely reverse normal imprinted XCI patterns. Taken together, our data suggest that, much like in the cells of the epiblast, the initial imprint that establishes imprinted XCI is probably erased in ExE cells. Conversely, unlike the epiblast, in which XCI is not required for progenitor cell maintenance, we demonstrate that dosage compensation is indispensable for the maintenance of trophoblast progenitors.
Adolescents’ agreement to test for HIV when different testing methods are offered
Authors: Mullins T K , Braverman P K , Dorn L D , Kollar L M , Kahn J A
Published: May 2012

Offering rapid HIV testing improves rates of testing in adults, but little is known about whether offering adolescents a choice of testing methods increases rates of testing. The aims of the study were to determine rates of HIV testing in adolescents when different testing methods were offered and explore factors associated with agreement to be tested for HIV. Participants ( n= 200, sexually experienced 13–22 year olds) were recruited from an urban adolescent clinic, completed a 99-item theory-based survey and were offered their choice of venipuncture, rapid fingerstick or rapid oral fluid HIV testing. Approximately half (49.5%) agreed to HIV testing. Male gender, parental completion of high school, intention to test for HIV if offered by clinician and higher perceived likelihood of current HIV infection were independently associated with agreement to test. Combining new strategies, such as opt-out testing, with routine testing may be needed to improve rates of adolescent HIV testing.
Acute gonococcal Fitz-Hugh–Curtis syndrome: a case report
Authors: Joshi R M , Alkhalegy A A
Published: May 2012

A case of acute Fitz-Hugh–Curtis syndrome in a young woman with purulent peritonitis and acute purulent appendicitis and oophoritis is presented. Open emergency appendectomy was performed and peritoneal pus was drained. Neisseria gonorrhoeae was cultured from the peritoneal pus. The hepatic enzymes were found to be raised. The patient was successfully managed and is asymptomatic after three months follow-up. To our knowledge, this is the first case of Fitz-Hugh–Curtis syndrome reported from Kuwait.
Spontaneous clearance of chronic hepatitis C infection in a patient with a 20-year-old HIV–hepatitis C co-infection and chronic active hepatitis
Authors: Manfredi R , Dentale N , Calza L
Published: May 2012

We report a case of spontaneous clearance of hepatitis C virus (HCV) in a patient co-infected for 20 years with HCV and HIV, and with an chronic active hepatitis C never treated with anti-HCV regimens. We review the literature of eight anecdotal reports describing the spontaneous resolution of chronic HCV infection among HIV-infected patients, and discuss the virological, immunological, pathogenetic and therapeutic implications of this observation.
Human papillomavirus in the oral cavity of children and mode of delivery: a retrospective study
Authors: Mammas I N , Sourvinos G , Giamarelou P , Michael C , Spandidos D A
Published: May 2012

Our study aimed to examine the relationship between the presence of human papillomavirus (HPV) in the oral cavity of children and their mode of delivery. We investigated the presence of HPV infection in oral biopsies from 190 children (mean age: 7 years, range: 2–14 years) using the polymerase chain reaction (PCR) technique. Sixteen of 190 children (8.4%) were HPV-positive, with no significant difference between those delivered vaginally and by Caesarean section (C-section). The majority of the HPV-positive children were infected with type 16, whereas in the younger age group HPV type 11 was detected more frequently in children delivered by normal vaginal delivery (NVD) than by C-section. Our findings demonstrate the presence of HPV in the oral cavity of children delivered by both C-section as well as NVD. Further research on the possible modes of transmission of oral HPV infection will enable us to understand the natural history of HPV infection in childhood.
Are there benefits to starting antiretroviral therapy during primary HIV infection? Conclusions from the Seattle Primary Infection Cohort vary by control group
Authors: Stekler J D , Wellman R , Holte S , Maenza J , Stevens C E , Corey L , Collier A C
Published: May 2012

It is controversial whether starting combination antiretroviral therapy (cART) during primary HIV infection (PHI) is beneficial. Subjects in this observational cohort began cART <30 days (group 1: acute treatment, n = 40), 31–180 days (group 2: early treatment, n = 82) or >180 days (group 3: delayed treatment, n = 35) after HIV infection, and were compared with 27 historical and 60 contemporary controls. Time to HIV-related diagnoses did not differ for group 1 (adjusted hazard ratio [aHR] 1.44, P = 0.3) or group 2 (aHR 1.17, P = 0.5) compared with contemporary controls, but it was delayed for both treated groups (aHR 0.38 for group 1, P = 0.01; and aHR 0.28 for group 2, P < 0.0001) compared with historical controls. Although rates of HIV-related diagnoses were similar in acutely treated subjects and contemporary controls, results were confounded by associations between higher CD4 counts, lower HIV RNA levels and delayed disease progression as reasons for deferring treatment. Randomized trials are needed to address benefits of cART during PHI.
Do not forget to examine the genitals: a case of anal cancer and anogenital intraepithelial neoplasia in an immunocompetent man
Authors: Buba A , Howard M , Stockford G , Farrands P , Richardson D
Published: May 2012

A 46-year-old Caucasian heterosexual male was referred to a dedicated AIN clinic from colorectal multidisciplinary meeting (MDM) with AIN 3 following complete resection of anal squamous cell carcinoma (SCC). On further questioning, he revealed that he also had a lesion on his penis. Histology of the penile lesion demonstrated full thickness penile intraepithelial neoplasia (PIN 3). This case illustrates the importance of thorough genital examination in patients found to have one genital pathology.
Medical ward admissions among HIV-positive patients in Winnipeg, Canada, 2003–10
Authors: Thompson L H , Sochocki M , Friesen T , Bresler K , Keynan Y , Kasper K , Becker M
Published: May 2012

Canadian data regarding the characteristics of HIV-positive patients admitted to hospital as well as the causes and patterns of admissions remain limited. Chart reviews were performed to ascertain admission diagnosis, co-morbidities and CD4 counts among this sub-population, which had an over-representation of Aboriginal persons. Infectious diseases, particularly pneumonia, represent the most common admission diagnosis for HIV-positive persons in Winnipeg. Further, individuals presenting to hospital often have very low CD4 counts, representing significant immune suppression. Earlier HIV diagnosis and treatment in an effort to delay the onset of advanced disease and hospitalization is needed.
Can quantification of congestive heart failure care convince medical doctors to use a care pathway? A process analysis
Authors: Heemskerk Theodora Cornelia Maria , Hugo Marie Antoinette , Mesman Rosalie , Förster Lilian Jane , Götte Marco Jan Wilhelm , te Hoonte Arend Jan
Published: May 2012

The Dutch national health-care policy has two opposing objectives: firstly care has to be cost-effective and secondly the quality of care has to improve. To meet these objectives in the clinical care for congestive heart failure (CHF), the Haga Hospital Heart Centre decided to investigate whether care according to a care pathway would be the solution. The objective of this study was to gain the support of the medical doctors (MDs) for implementation of a CHF care pathway. This was accomplished by providing insight through a process analysis of care as registered in the medical records. The survey was a retrospective process description of the design of the data collection protocol and research process evaluating the current care with international guidelines. The results of the research and the process of data collection facilitated a thorough evaluation of the delivered care. This resulted in an invaluable insight by the MDs into the results and registration of the medical care to CHF patients. In order to reveal the internal urgency of the design and implementation of a care pathway quantification of the care parameters is essential to gain insight into the care processes. With this insight the MDs are more likely to support a care pathway.
Development and implementation of the Rapid Discharge Pathway Version 12 to enable imminently dying patients to die in the place of their choice
Authors: Gambles Maureen , Cannell Lynne , Bolger Maria , Murphy Deborah
Published: May 2012

This study reports on the further development and implementation of a Rapid Discharge Home to Die Care Pathway (RDP Version 12). A rapid discharge pathway (RDP) was originally developed by members of the Hospital Specialist Palliative Care Team at the Royal Liverpool and Broadgreen University Hospitals NHS Trust in response to an identified clinical need to enable imminently dying patients to die in their place of choice when a clinical situation has changed rapidly and there has been an urgent request for a patient to die at home. The initial development and early evaluation, along with an example of the pathway itself, was published in 2004. The current study reports specifically on the subsequent development of the pathway that occurred alongside that of the generic Version 12 of the Liverpool Care Pathway for the Dying Patient published in December 2009. The study outlines the process of development and implementation of the RDP Version 12; patient scenario and a completed example are included to further illustrate the circumstances in which it can be used and the resultant process.