bluuebunny/crossref_metadata_2025 huggingface dataset:
1,25‐DihydroxyvitaminD3and its analogues increase catalase at themRNA, protein and activity level in a canine transitional carcinoma cell line
Authors: Middleton R. P. , Nelson R. , Li Q. , Blanton A. , Labuda J. A. , Vitt J. , Inpanbutr N.
Published: November 2013

Antioxidant enzymes, such as catalase, superoxide dismutases (SOD),MnSODand Cu/ZnSOD, protect cells by scavenging reactive oxygen species (ROS). Numerous studies have reported the anti‐cancer effects of 1,25‐dihydroxyvitaminD3(calcitriol) and its related analogues, seocalcitol and analogue V. In this study, canine bladder transitional cell carcinoma (cbTCC) cells were used to determine effects of calcitriol and its related analogues on antioxidant enzyme gene expression, protein expression and activity. CatalasemRNAwas increased in response to calcitriol (10−7 M), and seocalcitol (10−7and 10−9 M).MnSOD mRNAwas decreased in response to calcitriol at 10−7 M. Catalase was significantly increased in response to calcitriol (10−7and 10−9 M), and seocalcitol (10−9 M). Catalase enzymatic activity increased in response to calcitriol, seocalcitol and analogue V (10−9 M). In addition, global gene expression analysis identified the involvement of mitogen‐activated protein kinase (MAPK) signalling incbTCC's response to calcitriol and seocalcitol treatment.
Experimental Investigation on the Performance of a Formic Acid Electrolyte-Direct Methanol Fuel Cell
Authors: Ouellette David , Cruickshank Cynthia Ann , Matida Edgar
Published: November 2013

The performance of a new methanol fuel cell that utilizes a liquid formic acid electrolyte, named the formic acid electrolyte-direct methanol fuel cell (FAE-DMFC) is experimentally investigated. This fuel cell type has the capability of recycling/washing away methanol, without the need of methanol-electrolyte separation. Three fuel cell configurations were examined: a flowing electrolyte and two circulating electrolyte configurations. From these three configurations, the flowing electrolyte and the circulating electrolyte, with the electrolyte outlet routed to the anode inlet, provided the most stable power output, where minimal decay in performance and less than 3% and 5.6% variation in power output were observed in the respective configurations. The flowing electrolyte configuration also yielded the greatest power output by as much as 34%. Furthermore, for the flowing electrolyte configuration, several key operating conditions were experimentally tested to determine the optimal operating points. It was found that an inlet concentration of 2.2 M methanol and 6.5 M formic acid, as along with a cell temperature of 52.8 °C provided the best performance. Since this fuel cell has a low optimal operating temperature, this fuel cell has potential applications for handheld portable devices.
Characterization of a Novel Polymeric Trileaflet Heart Valve Prosthesis
Authors: Corbett Scott C. , Verma Neil , Zadeh Parnian Boloori , Coskun Ahmet U. , N.-Hashemi Hamid
Published: November 2013

While heart valve prostheses have been used successfully since 1960, 10-year survival rates still range from 37–58% [1]. The underlying problem with bioprostheses is a limited life from structural changes such as calcification and leaflet wear, leading to valve failure [2]. Biological tissue fixation and methods used to mount the tissue to a supporting stent can be blamed for this shortcoming. The underlying problem with mechanical heart valves is the presence of a centrally located leaflet, or occluder. It propagates high velocity jets, turbulence and areas of stagnation: the disturbances which necessitate anticoagulation [3]. A polyurethane valve has the potential to improve upon the shortcomings of existing valves and ultimately improve patient survival.
Induction of Cardiomyocyte Differentiation From Mouse Embryonic Stem Cells in a Confined Microfluidic Environment
Authors: Wan Chen-rei , Chung Seok , Sudo Ryo , Kamm Roger D.
Published: November 2013

Embryonic stem cell derived cardiomyocytes are deemed an attractive treatment option for myocardial infarction. Their clinical efficacy, however, has not been unequivocally demonstrated. There is a need for better understanding and characterization of the cardiogenesis process. A microfluidic platform in vitro is used to dissect and better understand the differentiation process. Through this study, we find that while embryoid bodies (EBs) flatten out in a well plate system, differentiated EBs self-assemble into complex 3D structures. The beating regions of EBs are also different. Most beating areas are observed in a ring pattern on 2D well plates around the center, self-assembled beating large 3D aggregates are found in microfluidic devices. Furthermore, inspired by the natural mechanical environment of the heart, we applied uniaxial cyclic mechanical stretch to EBs. Results suggest that prolonged mechanical stimulation acts as a negative regulator of cardiogenesis. From this study, we conclude that the culture environments can influence differentiation of embryonic stem cells into cardiomycytes, and that the use of microfluidic systems can provide new insights into the differentiation process.
Volumetric Flow at the Supraceliac and Infrarenal Levels in Patients With Abdominal Aortic Aneurysm: Waveforms and Allometric Scaling Relationships
Authors: Les Andrea S. , Yeung Janice J. , Young Phillip M. , Herfkens Robert J. , Dalman Ronald L. , Taylor Charles A.
Published: November 2013

Hemodynamic forces are thought to play a critical role in abdominal aortic aneurysm (AAA) formation and growth, as well as in the migration and failure of aortic stent grafts. Computational simulation of blood flow enables the study of such hemodynamic forces; however, these simulations require accurate geometries and boundary conditions, usually in the form of flow and pressure data at specific locations. Although hundreds of computed tomography (CT) and magnetic resonance (MR) imaging studies of AAA geometry are performed daily in the clinical setting, flow information is difficult to obtain: It is not possible to reliably measure flow using CT, and while phase-contrast MRI (PC-MRI) can measure velocities, it is rarely used clinically for AAA patients. As a result, many AAA blood flow simulations use highly resolved patient-specific geometries, but may utilize literature-derived flows for inlet boundary conditions from a single, unrelated, sometimes healthy person of dissimilar body mass.
Osteogenesis Imperfecta: Molecular and Mesoscale Disease Mechanisms
Authors: Gautieri Alfonso , Uzel Sebastien , Vesentini Simone , Redaelli Alberto , Buehler Markus J.
Published: November 2013

Osteogenesis Imperfecta (OI) is a genetic disorder in collagen characterized by mechanically weakened tendon and fragile bones that affects more than 1 in 10,000 individuals. Even though many studies have attempted to associate specific mutation types with phenotypic severity, the mechanisms by which a single point mutation influences the mechanical behavior of tissues at multiple length-scales remain unknown. Here we show by a hierarchy of full atomistic and mesoscale simulation that OI mutations severely compromise the mechanical properties of collagenous tissues at multiple scales, from single molecules to collagen fibrils.
Simulation of Passive Left Ventricle Filling
Authors: Doyle Matthew G. , Tavoularis Stavros , Bourgault Yves
Published: November 2013

The overall objective of this research is to develop a model of the mechanics of the left ventricle (LV) of a canine heart, including blood flow, myocardium motion, and the interaction between the two. The focus of this part of the research is on calculating initial conditions for simulations of the cardiac cycle, by performing both solid-only and fluid-structure interaction (FSI) simulations of passive LV filling. Passive refers to the state at which the muscle fibers in the LV wall are fully relaxed. During these simulations, the LV is pressurized to a value of the end-diastolic pressure, which is within the physiological range. This allows us to use the resulting deformed geometry and stress state as starting conditions for cardiac cycle simulations.
Pathological Biomechanics of Cerebrospinal Fluid Pressure in Syringomyelia: Fluid Structure Interaction of an In Vitro Coaxial Elastic Tube System
Authors: Martin Bryn A. , Labuda Richard , Royston Thomas J. , Oshinski John N. , Iskandar Bermans , Loth Francis
Published: November 2013

Full explanation for the formation and pathogenesis of syringomyelia (SM), a neurological pathology characterized by the formation of a cystic cavity (syrinx) in the center of the spinal cord (SC), has not yet been given. The SM pathology forms a coaxial elastic tube system with the inner tube formed by the spinal cord having a syrinx and the outer tube formed by the spinal column (dura and vertebrae). It has been assumed that abnormal cerebrospinal fluid (CSF) pressure caused by subarachnoid space (SAS) flow blockage (stenosis) is the underlying cause of syrinx formation and subsequent pain in the patient, but paucity in detailed in vivo pressure data have made theoretical explanation for the syrinx difficult. In order to understand this complex pressure environment, four in vitro models representative of various conditions associated with SM were examined. Overall, interaction of the syrinx and stenosis resulted in a diastolic valve mechanism which could have the effect of syrinx enlargement. In all experiments, the blockage was shown to increase and dissociate SAS pressure, while longitudinal pressure in the syrinx remained largely unchanged. These results provide data for validation of computational models and existing SM theories.
Dynamics of Cytokine Capture Within Hemoadsorption Beads Used to Treat Sepsis
Authors: Kimmel Jeremy D. , DiLeo Morgan V. , Valenti Isabella E. , Gibson Gregory A. , Watkins Simon C. , Federspiel William J.
Published: November 2013

Sepsis is a serious medical condition characterized by systemic inflammation caused by infection, and affects more than 750,000 individuals per year in the US, with a mortality rate of approximately 30% [1]. The pathophysiology of sepsis is complex and not entirely understood, but is believed to be related to the dysfunction of multiple interdependent humoral mediator pathways, including redundant release of inflammatory cytokines [2]. Removal of both pro- and anti-inflammatory cytokines from the circulating blood is believed to be a promising therapy for severe sepsis [3]. We are developing an extracorporeal hemoadsorption device to remove cytokines from the blood using a novel, biocompatible, sorbent bead technology. A simple model was developed to characterize cytokine adsorption within hemoadsorption beads [4]. Despite rapid clearance of cytokines with hemoadsorption in an ex vivo murine sepsis model [5], our model analysis predicted that only the outer 20μm of each sorbent bead (avg diam = 450μm) adsorbed cytokine. In this work, we used in vitro column capture experiments and confocal laser scanning microscopy (CLSM) to examine cytokine adsorption dynamics within hemoadsorption beads.
Comparison of Three Types of Dynamic Boundary Conditions
Authors: Clipp Rachel B. , Steele Brooke N.
Published: November 2013

Computational models can be used to predict the blood pressure and blood flow in a region of interest within the vascular system. A computational model includes a region of interest geometry and boundary conditions. The outlet boundary conditions not only need to reflect the downstream network of vessels, but also the dynamic nature of the downstream network. An example of this is the pulmonary vasculature, which has arterioles that dilate and constrict during the respiratory process altering the resistance/impedance of the downstream network [1]. In order to accurately model a system with a dynamic change, such as the pulmonary system, a dynamic boundary condition should be utilized.
A Pore Resistance Model and the Effect of Electrical Conductivity on Electroporation
Authors: Li Jianbo , Lin Hao
Published: November 2013

Electroporation is an elegant means to gain access to the cytoplasm, and to deliver molecules into the cell while simultaneously maintaining viability and functionality. In this technique, electric pulses are applied to transiently permeabilize the cell membrane. Biologically active agents, such as DNA, RNA, and amino acids, can then enter the cell to perform tasks such as gene and cancer therapy. Despite wide applications, electroporation faces significant challenges to achieve simultaneous high delivery efficiency and cell viability. Addressing such challenges requires the development of good fundamental understanding and a quantitative prediction capability, and the current work is a step toward this goal.
Grizzly Bears (Ursus Arctos Horribilis) and Black Bears (Ursus Americanus) Prevent Trabecular Bone Loss During Disuse (Hibernation)
Authors: McGee-Lawrence Meghan E. , Wojda Samantha J. , Barlow Lindsay N. , Castillo Alesha B. , Kennedy Oran , Auger Janene , Black Hal L. , Nelson O. Lynne , Robbins Charles T. , Donahue Seth W.
Published: November 2013

Reduced skeletal loading causes cortical and trabecular bone loss in humans and other animals, but trabecular bone responds to disuse more rapidly and shows greater losses than cortical bone for a given period of inactivity [1–2]. Manifestations of disuse on trabecular bone include unbalanced bone remodeling, decreased bone mineral density, and compromised bone architecture [3].
Parametric Hexahedral Patient-Specific Mesh Generation From Coronary Angiography Using PyFormex
Authors: De Santis Gianluca , Mortier Peter , De Beule Matthieu , Taeymans Yves , Segers Patrick , Verdonck Pascal , Verhegghe Benedict
Published: November 2013

To date patient-specific analysis (both CFD and FEA) is limited by the complex pre-processing procedure needed for generating a patient-specific mesh [1,2]. Following the classical approach, CT / MRI images undergo first reconstruction/segmentation, leading to STL surfaces, and finally a mesh is generated. This multi-step procedure suffers from operator-dependence, is time consuming, does not allow a parametric mesh generation and requires several dedicated softwares. A novel approach is proposed for 3D angiographic coronary data, which allows generating structured parametric patient-specific mesh using a single open-source software, limiting the operator-dependence and the pre-processing time.
Determination of Lesion Size as Function of HIFU Sonication Time Using MRI Monitored HIFU Ablations
Authors: Dasgupta Subhashish , Wansapura Janaka , Hariharan Prasanna , Pratt Ron , Witte David , Myers Matthew R. , Banerjee Rupak K.
Published: November 2013

The purpose of this study is to determine the dependence of the size of the thermal lesion on sonication time in an ex-vivo porcine liver sample during simulated High Intensity Focused Ultrasound (HIFU) tissue ablation. MRI guided HIFU ablations were performed on a freshly excised porcine liver sample at 70 W acoustic power. The size of the lesion (ablated zone) was measured at sonication times, 20 s, 30 s and 40 s. Numerical calculations were performed to validate the experimental lesion size. Also, a histology study of the ablated liver sample was performed to confirm cell necrosis within the ablated zones. It was found that the HIFU induced lesion size is strongly dependant on sonication time and lesion size almost doubles (increases from 0.368 to 0.715 cm2) as sonication time increases from 20s to 40s. The area of lesions, determined experimentally, agreed within 5% with results of numerical calculations.
The Effect of the Posterior Location of the Dilator on the Iris Concavity
Authors: Amini Rouzbeh , Whitcomb Julie E. , Al-Qaisi Muhammad K. , Akkin Taner , Barocas Victor H.
Published: November 2013

Aqueous humor (AH) constantly flows in the anterior eye to provide avascular tissues, notably the lens and cornea, with oxygen and nutrients. If AH outflow is impeded, the normal intraocular pressure could reach to dangerous levels. In angle closure, the abnormal shape and position of the iris is directly related to the blockage of the outflow. In particular, when the peripheral iris moves forward, it may narrow or close the angle between the iris and cornea, where most of AH leaves the anterior eye.
Tension Bands Placed on the Thigh and Shank Produce Changes in the Knee Flexion Moment and Gait Asymmetry
Authors: Dowling Ariel V. , Fenner Nathan , Andriacchi Thomas P.
Published: November 2013

Decreased symmetry in walking mechanics is common to many conditions associated with falling, such as muscle weakness, poor balance or flexibility, dizziness or vertigo, confusion, and vision problems [1]. Falls and the risk of falls have a substantial impact on the quality of life with aging. More than one in three adults over 65 years experience falls each year, and in half of these cases the falls are recurrent [2,3]. As patients with asymmetric gait are at a greater risk of falling during activities of daily living such as walking [1], conducting experiments on methods to correct gait asymmetries on this cohort can be potentially dangerous. However, experiments conducted with healthy patients that have an induced gait asymmetry during walking would minimize the risk to the unhealthy population while still allowing the researcher to test a subject with a gait asymmetry.
A Kinematic Model Coupling Cytoskeletal Dynamics With JNK Activation in Response to Matrix Stretching
Authors: Kaunas Roland , Huang Zuyi , Hahn Juergen
Published: November 2013

Mechanical stretch regulates many cell functions, including proliferation, apoptosis, migration and morphology that occur in response to stretch-induced changes in intracellular signaling and gene expression. We have previously reported that the temporal pattern of stretch-induced JNK activation is highly dependent on the spatiotemporal pattern of stretch that is applied. Specifically, cyclic uniaxial stretch causes a transient activation of JNK that subsides as their actin stress fibers (SFs) become oriented perpendicular to the direction of stretch, while cyclic equibiaxial stretch causes a sustained activation of JNK and does not induce SF orientation (1).
Nonlinear Osmotic Properties of the Cell Nucleus
Authors: Finan John D. , Chalut Kevin J. , Wax Adam , Guilak Farshid
Published: November 2013

Osmotic stress affects biological function in articular chondrocytes and plays an important role in mechanotransduction in articular cartilage. One potential pathway for osmotic sensitivity in chondrocytes is direct deformation of the nucleus by osmotic stress [1,2]. However, the mechanism of this phenomenon is currently unclear. The nucleus is not contained within a semi-permeable lipid bilayer as are most osmotically sensitive organelles. It is conceivable that fixed charges in chromatin might attract dissolved ions and render it osmotically sensitive. However, this model cannot account for the abolition of the osmotic sensitivity of the nucleus by permeabilization of the cell membrane [3]. The goal of this study was to characterize the osmotic sensitivity of the chondrocyte nucleus and determine the underlying mechanism.
Inflammatory Response of Endothelial Cells to Wall Shear Stress in Three Dimensional Stenotic Models
Authors: Rouleau Leonie , Rossi Joanna , Tardif Jean-Claude , Mongrain Rosaire , Leask Richard L.
Published: November 2013

Endothelial cells (ECs) are believed to respond differentially to hemodynamic forces in the vascular tree. Once atherosclerotic plaque has formed in a vessel, the obstruction creates complex spatial gradients in wall shear stress (WSS). In vitro models have used mostly unrealistic and simplified geometries, which cannot reproduce accurately physiological conditions. The objective of this study was to expose ECs to the complex WSS pattern created by an asymmetric stenosis. Endothelial cells were grown and exposed for different times to physiological steady flows in straight dynamic controls and in idealized asymmetric stenosis models. Cell morphology was noticeably different in the regions with spatial WSS gradients, being more randomly oriented and of cobblestone shape. Inflammatory molecule expression was also altered by exposure to shear and endothelial nitric oxide synthase (eNOS) was upregulated by its presence. A regional response in terms of inflammation was observed through confocal microscopy. This work provides a more realistic model to study endothelial cell response to spatial and temporal WSS gradients that are present in vivo and is an important advancement towards a better understanding of the mechanisms involved in coronary artery disease.
Effect of hydrogen plasma irradiation of catalyst films on growth of carbon nanotubes filled with iron nanowires
Authors: Sato Hideki , Kubonaka Nobuo , Nagata Atsushi , Fujiwara Yuji
Published: November 2013

Carbon nanotubes filled with iron (Fe-filled CNTs) show shape anisotropy on account of the high aspect ratio of magnetic nanowires, and are promising candidates for various applications, such as magnetic recording media, probes for scanning force microscopy, and medical treatment for cancer. The ability to appropriately control the magnetic properties of CNTs for those applications is desirable. In this study, the authors investigated magnetic properties of Fe-filled CNTs synthesized by thermal chemical vapor deposition for the purpose of tuning their coercivity. Here, the authors implemented hydrogen plasma irradiation of catalyst film that was previously deposited on a substrate as a catalyst layer. This treatment activates the catalyst film and thus enhances the growth of the Fe-filled CNTs. It was confirmed that the H2 plasma irradiation enhances the growth of the CNTs in terms of increasing their length and diameter compared to CNTs without irradiation. On the other hand, the coercivity of Fe-filled CNTs dropped to approximately half of those without H2 plasma irradiation. This is probably due to a decrease in the aspect ratio of the Fe nanowires, which results from the increase in their diameter. Furthermore, the crystal structure of the Fe nanowires may affect the coercivity.
Evaluation of the dosimetric properties of a synthetic single crystal diamond detector in high energy clinical proton beams
Authors: Mandapaka A. K. , Ghebremedhin A. , Patyal B. , Marinelli Marco , Prestopino G. , Verona C. , Verona‐Rinati G.
Published: November 2013

Purpose:

To investigate the dosimetric properties of a synthetic single crystal diamond Schottky diode for accurate relative dose measurements in large and small field high‐energy clinical proton beams.

Methods:

The dosimetric properties of a synthetic single crystal diamond detector were assessed by comparison with a reference Markus parallel plate ionization chamber, an Exradin A16 microionization chamber, and Exradin T1a ion chamber. The diamond detector was operated at zero bias voltage at all times. Comparative dose distribution measurements were performed by means of Fractional depth dose curves and lateral beam profiles in clinical proton beams of energies 155 and 250 MeV for a 14 cm square cerrobend aperture and 126 MeV for 3, 2, and 1 cm diameter circular brass collimators. ICRU Report No. 78 recommended beam parameters were used to compare fractional depth dose curves and beam profiles obtained using the diamond detector and the reference ionization chamber. Warm‐up/stability of the detector response and linearity with dose were evaluated in a 250 MeV proton beam and dose rate dependence was evaluated in a 126 MeV proton beam. Stem effect and the azimuthal angle dependence of the diode response were also evaluated.

Results:

A maximum deviation in diamond detector signal from the average reading of less than 0.5% was found during the warm‐up irradiation procedure. The detector response showed a good linear behavior as a function of dose with observed deviations below 0.5% over a dose range from 50 to 500 cGy. The detector response was dose rate independent, with deviations below 0.5% in the investigated dose rates ranging from 85 to 300 cGy/min. Stem effect and azimuthal angle dependence of the diode signal were within 0.5%. Fractional depth dose curves and lateral beam profiles obtained with the diamond detector were in good agreement with those measured using reference dosimeters.

Conclusions:

The observed dosimetric properties of the synthetic single crystal diamond detector indicate that its behavior is proton energy independent and dose rate independent in the investigated energy and dose rate range and it is suitable for accurate relative dosimetric measurements in large as well as in small field high energy clinical proton beams.
Phonetic processing of non-native speech in semantic vs non-semantic tasks
Authors: Gustafson Erin , Engstler Caroline , Goldrick Matthew
Published: November 2013

Research with speakers with acquired production difficulties has suggested phonetic processing is more difficult in tasks that require semantic processing. The current research examined whether similar effects are found in bilingual phonetic processing. English–French bilinguals' productions in picture naming (which requires semantic processing) were compared to those elicited by repetition (which does not require semantic processing). Picture naming elicited slower, more accented speech than repetition. These results provide additional support for theories integrating cognitive and phonetic processes in speech production and suggest that bilingual speech research must take cognitive factors into account when assessing the structure of non-native sound systems.
A Brain-Machine Interface Enables Bimanual Arm Movements in Monkeys
Authors: Ifft Peter J. , Shokur Solaiman , Li Zheng , Lebedev Mikhail A. , Nicolelis Miguel A. L.
Published: November 2013

Large-scale recordings from monkey cortex enabled simultaneous control of two avatar arms through a brain-machine interface.
Smaller, Softer, Safer, Smarter Robots
Authors: Wood Robert , Walsh Conor
Published: November 2013

Advances in robotics aim to extend physician capabilities.
Silencing the Sounds of Hypertrophic Cardiomyopathy
Authors: Voora Deepak
Published: November 2013

An RNA interference strategy of allele specific silencing in the heart identifies a potential new therapy for patients with hypertrophic cardiomyopathy.
Graph Theory Modeling for Diagnosing Presymptomatic Alzheimer's Disease
Authors: Bytautiene Egle
Published: November 2013

Graph theory modeling of brain MRI images reveals early, presymptomatic signs of Alzheimer's disease.
Targeting ER Stress in Parkinson's Disease
Authors: Gregg Christopher
Published: November 2013

α-Synuclein–mediated toxicity in Parkinson’s disease involves nitrosative stress, endoplasmic reticulum (ER) stress, and impaired ER function, which can be rescued in vitro with a small molecule.
A Chance of a Cure for HIV
Authors: Sheth Anandi N.
Published: November 2013

In an HIV-infected infant who received antiretroviral therapy from 30 hours until 18 months of age, HIV virus was undetectable months after therapy was stopped.
Annexin A6-Balanced Late Endosomal Cholesterol Controls Influenza A Replication and Propagation
Authors: Musiol Agnes , Gran Sandra , Ehrhardt Christina , Ludwig Stephan , Grewal Thomas , Gerke Volker , Rescher Ursula
Published: November 2013

Influenza is caused by influenza A virus (IAV), an enveloped, negative-stranded RNA virus that derives its envelope lipids from the host cell plasma membrane. Here, we examined the functional role of cellular cholesterol in the IAV infection cycle. We show that shifting of cellular cholesterol pools via the Ca
2+
-regulated membrane-binding protein annexin A6 (AnxA6) affects the infectivity of progeny virus particles. Elevated levels of cellular AnxA6, which decrease plasma membrane and increase late endosomal cholesterol levels, impaired IAV replication and propagation, whereas RNA interference-mediated AnxA6 ablation increased viral progeny titers. Pharmacological accumulation of late endosomal cholesterol also diminished IAV virus propagation. Decreased IAV replication caused by upregulated AnxA6 expression could be restored either by exogenous replenishment of host cell cholesterol or by ectopic expression of the late endosomal cholesterol transporter Niemann-Pick C1 (NPC1). Virus released from AnxA6-overexpressing cells displayed significantly reduced cholesterol levels. Our results show that IAV replication depends on maintenance of the cellular cholesterol balance and identify AnxA6 as a critical factor in linking IAV to cellular cholesterol homeostasis.

IMPORTANCE
Influenza A virus (IAV) is a major public health concern, and yet, major host-pathogen interactions regulating IAV replication still remain poorly understood. It is known that host cell cholesterol is a critical factor in the influenza virus life cycle. The viral envelope is derived from the host cell membrane during the process of budding and, hence, equips the virus with a special lipid-protein mixture which is high in cholesterol. However, the influence of host cell cholesterol homeostasis on IAV infection is largely unknown. We show that IAV infection success critically depends on host cell cholesterol distribution. Cholesterol sequestration in the endosomal compartment impairs progeny titer and infectivity and is associated with reduced cholesterol content in the viral envelope.
Transcriptomic Analysis of the Host Response to Giardia duodenalis Infection Reveals Redundant Mechanisms for Parasite Control
Authors: Tako Ernest A. , Hassimi Maryam F. , Li Erqiu , Singer Steven M.
Published: November 2013

The immune system has numerous mechanisms that it can use to combat pathogens and eliminate infections. Nevertheless, studies of immune responses often focus on single pathways required for protective responses. We applied microarray analysis of RNA in order to investigate the types of immune responses produced against infection with the intestinal pathogenGiardia duodenalis. Infection withG. duodenalisis one of the most common causes of diarrheal disease in the world. While several potential antiparasitic effector mechanisms, including complement lysis, nitric oxide (NO), and α-defensin peptides, have been shown to inhibit parasite growth or killGiardia in vitro, studiesin vivohave thus far shown clear roles only for antibody and mast cell responses in parasite control. A total of 96 transcripts were identified as being upregulated or repressed more than 2-fold in the small intestine 10 days following infection. Microarray data were validated using quantitative PCR. The most abundant category of transcripts was antibody genes, while the most highly induced transcripts were all mast cell proteases. Among the other induced transcripts was matrix metalloprotease 7 (Mmp7), the protease responsible for production of mature α-defensins in mice. While infections in Mmp7-deficient mice showed only a small increase in parasite numbers, combined genetic deletion of Mmp7 and inducible nitric oxide synthase (iNOS, Nos2) or pharmacological blockade of iNOS in Mmp7-deficient mice resulted in significant increases in parasite loads following infection. Thus, α-defensins and NO are redundant mechanisms for control ofGiardiainfectionsin vivo.

IMPORTANCEThe immune system has multiple weapons which it uses to help control infections. Many infections result in activation of several of these response mechanisms, but it is not always clear which responses actually contribute to control of the pathogen and which are bystander effects. This study used the intestinal parasiteGiardia duodenalisto examine the redundancy in immune responses during infections in mice. Our results showed that at least four distinct mechanisms are activated following infections. Furthermore, by blocking two pathways at the same time, we showed that both mechanisms contribute to control of the infection, whereas blocking single responses showed no or minimal effect in these cases.
Long-Lasting T Cell-Independent IgG Responses Require MyD88-Mediated Pathways and Are Maintained by High Levels of Virus Persistence
Authors: Raval Forum M. , Mishra Rabinarayan , Garcea Robert L. , Welsh Raymond M. , Szomolanyi-Tsuda Eva
Published: November 2013

Many viruses induce acute T cell-independent (TI) B cell responses due to their repetitive epitopes and the induction of innate cytokines. Nevertheless, T cell help is thought necessary for the development of long-lasting antiviral antibody responses in the form of long-lived plasma cells and memory B cells. We found that T cell-deficient (T cell receptor β and δ chain [TCRβδ] knockout [KO]) mice persistently infected with polyomavirus (PyV) had long-lasting antiviral serum IgG, and we questioned whether they could generate TI B cell memory. TCRβδ KO mice did not form germinal centers after PyV infection, lacked long-lived IgG-secreting plasma cells in bone marrow, and did not have detectable memory B cell responses. Mice deficient in CD4+T cells had a lower persisting virus load than TCRβδ KO mice, and these mice had short-lived antiviral IgG responses, suggesting that a high virus load is required to activate naive B cells continuously, and maintain the long-lasting serum IgG levels. Developing B cells in bone marrow encounter high levels of viral antigens, which can cross-link both their B cell receptor (BCR) and Toll-like receptors (TLRs), and this dual engagement may lead to a loss of their tolerance. Consistent with this hypothesis, antiviral serum IgG levels were greatly diminished in TCRβδ KO/MyD88−/−mice. We conclude that high persisting antigen levels and innate signaling can lead to the maintenance of long-lasting IgG responses even in the absence of T cell help.

IMPORTANCELifelong control of persistent virus infections is essential for host survival. Several members of the polyomavirus family are prevalent in humans, persisting at low levels in most people without clinical manifestations, but causing rare morbidity/mortality in the severely immune compromised. Studying the multiple mechanisms that control viral persistence in a mouse model, we previously found that murine polyomavirus (PyV) induces protective T cell-independent (TI) antiviral IgG. TI antibody (Ab) responses are usually short-lived, but T cell-deficient PyV-infected mice can live for many months. This study investigates how protective IgG is maintained under these circumstances and shows that these mice lack both forms of B cell memory, but they still have sustained antiviral IgG responses if they have high levels of persisting virus and intact MyD88-mediated pathways. These requirements may ensure life-saving protection against pathogens even in the absence of T cells, but they prevent the continuous generation of TI IgG against harmless antigens.
Concurrent necrotising otitis externa and adenocarcinoma of the temporal bone: a diagnostic challenge
Authors: Foden Neil , Burgess Christopher , Damato Stephen , Ramsden James
Published: November 2013

We present a case of an 81-year-old man who was diagnosed with a necrotising (malignant) otitis externa (NOE). Initial biopsies from the external auditory canal showed scanty squamous epithelium but no evidence of malignancy. Despite an initial improvement on intravenous antibiotics and subsequent discharge from hospital, the patient returned with worsening otalgia. Following readmission to the hospital, intravenous antibiotics were restarted. Despite this, the patient developed a lower motor neurone palsy of cranial nerve VII on the ipsilateral side of the pain. He was taken to the theatre for an exploration of the left mastoid with further biopsies. Adenocarcinoma was diagnosed histologically and the patient was started on palliative radiotherapy. This case adds to the known literature on metastatic disease in the temporal bone and highlights the need to exclude malignancy in cases of NOE.
Postlumbar puncture arachnoiditis mimicking epidural abscess
Authors: Gürbüz Mehmet Sabri , Erdoğan Barıs , Yüksel Mehmet Onur , Somay Hakan
Published: November 2013

Lumbar spinal arachnoiditis occurring after diagnostic lumbar puncture is a very rare condition. Arachnoiditis may also present with fever and elevated infection markers and may mimic epidural abscess, which is one of the well known infectious complications of lumbar puncture. We report the case of a 56-year-old man with lumbar spinal arachnoiditis occurring after diagnostic lumbar puncture who was operated on under a misdiagnosis of epidural abscess. In the intraoperative and postoperative microbiological and histopathological examination, no epidural abscess was detected. To our knowledge, this is the first case of a patient with postlumbar puncture arachnoiditis operated on under a misdiagnosis of epidural abscess reported in the literature. The authors suggest that arachnoiditis may mimic epidural abscess due to its clinical and radiological features and should be considered in the differential diagnosis of complications of lumbar puncture.
Non-atherosclerotic multiple coronary artery aneurysms
Authors: Bajaj Rishi , Mamidala Suresh , Bajaj Prabhjot , Kumar Deepti
Published: November 2013

A 52-year-old man underwent two-dimensional echocardiogram which showed moderate to severe aortic regurgitation (AR) and dilated ascending aorta. CT angiography (CTA) showed dilated ascending aorta (5 cm) and transoesophageal echocardiogram revealed bicuspid aortic valve. He underwent cardiac catheterisation which revealed triple vessel aneurysmal disease of the left anterior descending, left circumflex and right coronary artery. The patient underwent aortic graft placement for ascending aortic aneurysm and aortic valve replacement with a Saint Jude valve for severe AR. There was no history or stigmata of Kawasaki disease and workup for coronary artery aneurysm including vasculitis and connective tissue disorders was negative. Histopathology did not reveal evidence of active aortitis or dissection. His aneurysms are being observed by a yearly coronary CTA. We present a rare case of multiple coronary artery aneurysms associated with bicuspid aortic valve and ascending aortic aneurysm.
Imaging diagnosis of upper motor neuron compromising in a patient with Chiari 1 malformation
Authors: Nunes Renato Hoffmann , Littig Ingrid Aguiar , Rocha Antônio José da , Valerio Berenice Cataldo Oliveira
Published: November 2013

We report a case of a typical MRI from a patient with bulbar-onset sporadic amyotrophic lateral sclerosis associated with Chiari type 1 malformation. Our report reinforces the conventional neuroimaging appearance associated with each condition and the associated abnormalities on a clinical and advanced imaging techniques basis. The MRI signal intensity was useful for detecting upper motor neuron degeneration based on corticospinal tract signal intensity, while diffusion tensor imaging parameters were limited to this purpose. Our description reinforces the relevance of the T1 magnetisation transfer sequence to demonstrate corticospinal tract degeneration and corroborate an amyotrophic lateral sclerosis diagnosis in an individual participant, when there is a potential concurrent ‘amyotrophic lateral sclerosis mimic syndrome’. To our knowledge, this is the first description of the non-conventional MR techniques applicability to distinguish the impact of amyotrophic lateral sclerosis from Chiari 1 malformation.
Shunt in scrotum: unusual complication in operated cases of hydrocephalus
Authors: Panda Shasanka Shekhar , Singh Amit , Bajpai Minu , Sharma Nitin
Published: November 2013

Shunt surgeries in patients with hydrocephalus are associated with morbidity and mortality. The most common problems are shunt obstruction and malfunction. We described a case of shunt migration into the scrotal sac masquerading as scrotal swelling. Shunt repositioning along with posterior wall repair and herniotomy was performed.
Emergency department malnutrition screening and support model improves outcomes in a pilot randomised controlled trial
Authors: Vivanti A , Isenring E , Baumann S , Powrie D , O'Neill M , Clark D , Courtice S , Campbell K , Ferguson M
Published: November 2013

Objective

To trial malnutrition screening in older adults presenting to an emergency department (ED) and compare two service delivery models of nutritional support on nutritional status, quality of life, falls and unplanned hospital admissions.

Design

Participants (>60 years) presenting to ED screened at malnutrition risk were randomly allocated to either the control group (receiving regular treatment from community hospital interface programme nursing staff) or intervention group (receiving dietetic assessment, nutrition intervention and follow-up in addition to regular community hospital interface programme support). Outcome measures including body weight, quality of life, depression, falls history and days of hospital admissions were collected at baseline and 12 weeks.

Results

Of 703 patients screened, 84 (12%) were identified at malnutrition risk. 24 consented to the intervention study, with 88% (21/24) confirmed to be malnourished. Clinically important but not statistically significant differences were found over the 12-week trial; the intervention group (n=9) gained 0.8 kg (±3.7) while the control group (n=10) lost −1.1 kg (±4.6). The intervention group also had better quality of life, less depression and shorter hospital admissions.

Conclusions

Malnutrition screening appears feasible in ED. This pilot suggests a model of care providing nutrition support to older adults identified at nutritional risk may lead to improved patient outcomes but further research in a larger sample is required to confirm these findings.
Prevention of exercise-related injuries and adverse events in patients with type 2 diabetes
Authors: Mendes Romeu , Sousa Nelson , Reis Victor Machado , Themudo-Barata José Luís
Published: November 2013

Physical activity is widely recommended as an essential non-pharmacological therapeutic strategy to the prevention and control of type 2 diabetes and cardiovascular risk. Microvascular and macrovascular complications associated with the natural progression of the disease and typical age and anthropometric profile of individuals with type 2 diabetes may expose these patients to an increased risk of injury and acute adverse events during exercise. These injuries and adverse events can lead to fear of new injury and consequent physical inactivity. Preventative measures are essential to reduce risk, increase safety and avoid the occurrence of exercise-related injuries in people with type 2 diabetes. This population can exercise safely if certain precautions are taken and if exercise is adapted to complications and contraindications of each individual. Conditions such as diabetic foot, diabetic retinopathy, diabetic nephropathy, diabetic autonomic neuropathy, cardiovascular risk factors, musculoskeletal disorders, hypoglycaemia, hyperglycaemia, dehydration and interactions between medication and exercise should be taken into consideration when prescribing exercise.
Mutualistic and antagonistic networks involving the rare silky prairie-clover (Dalea villosa var. villosa) and its co-flowering plants and insect visitors
Authors: Bizecki Robson Diana
Published: November 2013

In Canada, silky prairie-clover (Dalea villosa var. villosa (Nutt.) Spreng) is a nationally rare plant, growing only in sand dunes in Saskatchewan and Manitoba. Previous research indicates that this species is incapable of self-pollination, making it dependent on insect pollinators for successful reproduction. The insect visitor community to D. villosa in Spruce Woods Provincial Park (SWPP), Manitoba, was documented and compared with that of 13 co-flowering plants that share some of its insect visitors. In total, 29 insect taxa were observed feeding on nectar or pollen from D. villosa. Hymenoptera were the most frequent visitors, comprising 60.7% of the taxa and making 93.5% of all visits. The visitation rate per stem to D. villosa (0.0042 stems·min–1) was the second highest of all of the plants with which it was compared. The insect visitor diversity was 4.0 (Simpson’s reciprocal index), and the constancy index was 0.72. The high visitation rate, diversity, and constancy to this species may be due to a lack of competition for pollinators. Over half of the insect visitor taxa (54%) and visits (68%) were by omnivorous insects, as opposed to herbivorous ones. This means that there is interconnectivity between a mutualistic network involving D. villosa and several antagonistic networks.
An enhanced multi-objective optimization approach for risk allocation in public–private partnership projects: a case study of Malaysia
Authors: Alireza Valipour , Mohammadreza Yadollahi , Zin Rosli Mohamad , Yahaya Nordin , Noor Norhazilan Md.
Published: November 2013

The decision making for risk allocation problems in public–private partnership (PPP) projects is a vital process that directly affects the timeliness, cost, and quality of the project. Fair risk allocation is a vital factor to achieve success in the implementation of these projects. It is essential for private and public sectors to apply efficient risk allocation approaches to experience a more effective process of agreement arbitration and to reduce the appearance of dispute during the concession period. The aim of this study is to develop an optimization approach to enhance risk allocation process in PPP projects. The shared risks in projects are identified through comprehensive literature review and questionnaire survey obtained from Malaysian professionals involved in PPP projects. Objective functions are then developed to minimize the total time and cost of the project and maximize the quality while satisfying risk threshold constraints. The combinatorial nature of the risk allocation problem describes a multi-objective situation that can be simulated as a knapsack problem (KP). The formulation of the KP is described and solved applying genetic algorithm (GA). Due to the flexibility of GA, the results are Pareto Optimal solutions that describe the combinations of risk percentages for shared risks in PPP projects.
Recruitment and survival rate variability in fish populations: density-dependent regulation or further evidence of environmental determinants?
Authors: Lobón-Cerviá Javier
Published: November 2013

Recently, Minto et al. (2008) , based on a fishery data set including marine, estuarine, and freshwater fishes, described higher variability in the survival rates of juveniles at low rather than at high parental density in an inversely density-dependent fashion and suggested density-dependent mechanisms underpinning those patterns. This study, based on a long-term study of brown trout (Salmo trutta; a species and habitat not included in the Minto et al. (2008) analysis), documents that survival rates in these stream-living populations exhibit a pattern that matches exactly those reported by Minto et al. (2008) . Nevertheless, hypothesis testing rejected the occurrence of stock–recruitment relationships and the operation of density-dependent recruitment regulation. The patterns elucidated for these brown trout populations can be entirely explained by the operation of two single environmental factors, namely, stream discharge in March determining annual survival rates across streams and sites and site-specific depth determining site-specific survival rates. It is open to question that exactly the same patterns can be generated by two sets of opposing factors, density-dependent (i.e., Minto et al. 2008 ) and environmental factors (i.e., this study). The consistency of this pattern suggests that survival rates and recruitment are probably determined by environmental factors across fish populations and habitats.