bluuebunny/crossref_metadata_2025 huggingface dataset:
Catheter Ablation of Focal Atrial Tachycardia from the Aortic Cusp: The Role of Electroanatomic Mapping and Intracardiac Echocardiography
Authors: MLČOCHOVÁ HANKA , WICHTERLE DAN , PEICHL PETR , KAUTZNER JOSEF
Published: December 2010

Catheter ablation of periatrioventricular (peri‐AV) nodal atrial tachycardias (AT) from the noncoronary aortic cusp (NCC) can be challenging due to the close proximity of the AV node In such cases, intracardiac echocardiography (ICE) together with three‐dimensional mapping system can be helpful in guiding the ablation catheter and in assessing the anatomic relationship of the aorta to the surrounding structures. We report two patients with AT originating near the AV node who underwent successful catheter ablation from the NCC. ICE proved useful in positioning the ablation catheter within the aortic cusps. Electroanatomic mapping enabled tagging the earliest activation site and renavigation back.

(PACE 2013; 36:e19–e22)
Examining the effect of the injury definition on risk factor analysis in circus artists
Authors: Hamilton G. M. , Meeuwisse W. H. , Emery C. A. , Shrier I.
Published: December 2010

A secondary data analysis of a prospective cohort study was conducted to explore how different definitions of injury affect the results of risk factor analyses. Modern circus artists (n=1281) were followed for 828 547 performances over a period of 49 months (2004–2008). A univariate risk factor analysis (age, sex, nationality, artist role) estimating incidence rate ratios (IRR) with 95% confidence intervals (95% CI) was conducted using three injury definitions: (1) medical attention injuries, (2) time‐loss injuries resulting in ≥1 missed performances (TL‐1) and (3) time‐loss injuries resulting in >15 missed performances (TL‐15). Results of the risk factor analysis were dependent on the injury definition. Sex (females to male; IRR=1.13, 95% CI; 1.02–1.25) and age over 30 (<20 years to >30 years; IRR=1.37, 95% CI; 1.07–1.79) were risk factors for medical attention injuries only. Risk of injury for Europeans compared with North Americans was higher for TL‐1 and TL‐15 injuries compared with medical attention injuries. Finally, non‐sudden load artists (low‐impact acts) were less likely than sudden load artists (high‐impact acts) to have TL‐1 injuries, but the risk of medical attention injuries was similar. The choice of injury definition can have effects on the magnitude and direction of risk factor analyses.
Changes in kinematics and trunk electromyography during a 2000 m race simulation in elite female rowers
Authors: Pollock C. L. , Jones I. C. , Jenkyn T. R. , Ivanova T. D. , Garland S. J.
Published: December 2010

Achieving excellence in rowing requires optimization of technique to maximize efficiency and force production. Investigation of the kinematics of the trunk, upper and lower extremity, together with muscle activity of the trunk, provides an insight into the motor control strategies utilized over a typical race. Nine elite female rowers performed a 2000 m race simulation. Kinematic data of the trunk and extremities, together with electromyography (EMG) activity of spinal and pelvic extensor and flexor muscles, were compared at 250 and 1500 m. At 1500 m, there was greater dissociation in the timing of leg extension and arm flexion and delayed trunk extension. Also at 1500 m, the spine demonstrated a delayed peak extension angular velocity of the T4–T7 and L3–S1 spinal segments in the early drive along with delayed and increased peak extension angular velocity of T10–L1 and L1–L3 spinal segments during the late drive. Trunk muscle fatigue was not evident; however, the abdominals demonstrated larger EMG burst areas at 1500 m. Alterations in trunk kinematics suggest that the trunk acts as a less stiff lever on which to transfer the forces of the legs to the arms and handle. Increased abdominal activity may reflect increased demand to control the trunk, given the altered coordination between the legs, trunk and arms.
Electron Tomography of RabA4b‐ and PI‐4Kβ1‐Labeled Trans Golgi Network Compartments in Arabidopsis
Authors: Kang Byung‐Ho , Nielsen Erik , Preuss Mary Lai , Mastronarde David , Staehelin L. Andrew
Published: December 2010

The trans Golgi network (TGN) of plant cells sorts and packages Golgi products into secretory (SV) and clathrin‐coated (CCV) vesicles. We have analyzed of TGN cisternae in Arabidopsis root meristem cells by cell fractionation and electron microscopy/tomography to establish reliable criteria for identifying TGN cisternae in plant cells, and to define their functional attributes. Transformation of a trans Golgi cisterna into a Golgi‐associated TGN cisterna begins with cisternal peeling, the formation of SV buds outside the plane of the cisterna and a 30–35% reduction in cisternal membrane area. Free TGN compartments are defined as cisternae that have detached from the Golgi to become independent organelles. Golgi‐associated and free TGN compartments, but not trans Golgi cisternae, bind anti‐RabA4b and anti‐phosphatidylinositol‐4 kinase (PI‐4K) antibodies. RabA4b and PI‐4Kβ1 localize to budding SVs in the TGN and to SVs en route to the cell surface. SV and CCV release occurs simultaneously via cisternal fragmentation, which typically yields ∼30 vesicles and one to four residual cisternal fragments. Early endosomal markers, VHA‐a1‐green fluorescent protein (GFP) and SYP61‐cyan fluorescent protein (CFP), colocalized with RabA4b in TGN cisternae, suggesting that the secretory and endocytic pathways converge at the TGN. pi4k1/pi4k2 knockout mutant plants produce SVs with highly variable sizes indicating that PI‐4Kβ1/2 regulates SV size.
Effect of Methoxychlor on Ca2+ Handling and Viability in OC2 Human Oral Cancer Cells
Authors: Tseng Li‐Ling , Shu Su‐Shung , Kuo Chun‐Chi , Chou Chiang‐Ting , Hsieh Yao‐Dung , Chu Sau‐Tung , Chi Chao‐Chuan , Liang Wei‐Zhe , Ho Chin‐Man , Jan Chung‐Ren
Published: December 2010

Abstract:  The effect of the insecticide methoxychlor on the physiology of oral cells is unknown. This study aimed to explore the effect of methoxychlor on cytosolic Ca2+ concentrations ([Ca2+]i) in human oral cancer cells (OC2) by using the Ca2+‐sensitive fluorescent dye fura‐2. Methoxychlor at 5–20 μM increased [Ca2+]i in a concentration‐dependent manner. The signal was reduced by 70% by removing extracellular Ca2+. Methoxychlor‐induced Ca2+ entry was not affected by nifedipine, econazole, SK&F96365 and protein kinase C modulators but was inhibited by the phospholipase A2 inhibitor aristolochic acid. In Ca2+‐free medium, treatment with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin or 2,5‐di‐tert‐butylhydroquinone (BHQ) inhibited or abolished methoxychlor‐induced [Ca2+]i rise. Incubation with methoxychlor also inhibited thapsigargin‐ or BHQ‐induced [Ca2+]i rise. Inhibition of phospholipase C with U73122 did not alter methoxychlor‐induced [Ca2+]i rise. At 5–20 μM, methoxychlor killed cells in a concentration‐dependent manner. The cytotoxic effect of methoxychlor was not reversed by chelating cytosolic Ca2+ with 1,2‐bis(2‐aminophenoxy)ethane‐N,N,N’,N’‐tetraacetic acid/AM (BAPTA/AM). Annexin V‐FITC data suggest that methoxychlor (10 and 20 μM) evoked apoptosis in a concentration‐dependent manner. Together, in human OC2, methoxychlor induced a [Ca2+]i rise probably by inducing phospholipase C‐independent Ca2+ release from the endoplasmic reticulum and Ca2+ entry via phospholipase A2‐sensitive channels. Methoxychlor induced cell death that may involve apoptosis.
Plasma osteoprotegerin levels are decreased in smoker chronic periodontitis patients
Authors: Özçaka Ö , Nalbantsoy A , Köse T , Buduneli N
Published: December 2010

Background:  The aim of this study was to evaluate plasma levels of soluble receptor activator of nuclear factor‐kappa B ligand (sRANKL) and osteoprotegerin (OPG) in smoker versus non‐smoker chronic periodontitis patients.

Methods: Plasma samples were obtained from 13 smoker and 31 non‐smoker systemically healthy chronic periodontitis patients, as well as 13 smoker and 29 non‐smoker systemically and periodontally healthy subjects. Before commencing any periodontal intervention, venous blood samples were obtained and whole‐mouth clinical periodontal measurements were recorded. sRANKL and OPG concentrations in plasma samples were determined by enzyme‐linked immunosorbent assay (ELISA) technique. Data were tested statistically by student’s t test, Wilcoxon matched pairs test, and Spearman’s correlation analysis.

Results:  All clinical periodontal measurements were significantly higher in chronic periodontitis groups than the healthy controls (p < 0.05). Smoker and non‐smoker chronic periodontitis patients exhibited similar values in all clinical periodontal measurements and plasma sRANKL, OPG concentrations (p > 0.05). Smoker chronic periodontitis patients exhibited significantly lower (p = 0.007) plasma OPG concentrations and higher sRANKL/OPG ratio (p = 0.01) than smoker healthy controls.

Conclusions:  Within the limits of this study, periodontal inflammation in smoker chronic periodontitis patients seems to lower plasma osteoprotegerin levels and thereby increase the RANKL/OPG ratio, and possibly play a role in the increased susceptibility for alveolar bone destruction in smoker subjects.
Patterns of soft drink consumption and primary tooth extractions in Queensland children
Authors: Slater PJ , Gkolia PP , Johnson HL , Thomas AR
Published: December 2010

Background:  The authors examined the association of patterns of soft drink consumption and primary tooth extractions in Queensland children aged 12 years or less.

Methods:  Data were gathered through the Child Health Surveys conducted by Queensland Health in 2003 and 2008. The analysis allowed for various demographic characteristics using logistic regression analysis.

Results:  The data in both surveys showed an increased risk of tooth extraction in children who had a greater frequency and amount of soft drink consumption, and those that consumed soft drink between meals. In 2008, the percentage of children that had soft drink daily or several times a week had decreased, with an increase in those that never had soft drink.

Conclusions:  To reduce the risk of primary tooth extraction due to decay, this paper recommends the continuing moderation of soft drink consumption frequency and the consumption of soft drinks with, rather than between, meals.
Intrusion of an overerupted mandibular molar using mini‐screws and mini‐implants: a case report
Authors: Arslan A , Ozdemir D Nalbantgil , Gursoy‐Mert H , Malkondu O , Sencift K
Published: December 2010

Overeruption of mandibular molars due to the loss of antagonist teeth causes occlusal functional disturbances. To restore proper occlusion, intrusion of the overerupted molars becomes essential before multidisciplinary reconstructive dental approaches can be initiated. Treatment protocols involving prosthodontic reduction, surgical impaction, and conventional orthodontic intrusion have been introduced. Orthodontic intrusion seems to be a favourable procedure which requires calibrated anchorage support. This case illustrates the management of a complex dental and functional problem with an interdisciplinary approach through the use of orthodontic, periodontal, restorative and implant therapy. In order to intrude the overerupted molar, a partial orthodontic appliance was used in conjunction with mini‐implants and mini‐screws. The results showed that the biological responses of the teeth and the surrounding bony structures to the intrusion appeared normal and acceptable. Periodontal health and vitality of the teeth were maintained throughout the treatment and even after one‐year follow‐up.
Treatment of periodontal disease for glycaemic control in people with diabetes
Authors: Simpson TC , Needleman I , Wild SH , Moles DR , Mills EJ
Published: December 2010

Background:  Glycaemic control is a key issue in the care of people with diabetes mellitus (DM). Some studies have suggested a bidirectional relationship between glycaemic control and periodontal disease.

Objectives:  To investigate the relationship between periodontal therapy and glycaemic control in people with diabetes and to identify the appropriate future strategy for this question.

Search strategy:  A comprehensive approach was adopted employing handsearching; searching of electronic databases including the Cochrane Oral Health Group’s Trials Register, CENTRAL, MEDLINE, EMBASE, CINAHL, ZETOC, ISI Web of Knowledge and LILACS; contact with appropriate non‐English language healthcare professionals; authors and organizations. The final date for searching for studies was 24 March 2010.

Selection criteria:  This review studied randomized controlled trials of people with Type 1 or 2 diabetes mellitus (DM) with a diagnosis of periodontitis. Suitable interventions included mechanical periodontal therapy with or without adjunctives and oral hygiene education.

Data collection and analysis:  The titles and abstracts of 690 papers were examined by two review authors independently. Ultimately, seven studies were included and 19 excluded after full text scrutiny. All trials were assessed for risk of bias.

Main results:  Three studies had results pooled into a meta‐analysis. The effect for the mean percentage difference in HbA1c for scaling/root planing and oral hygiene (+/− antibiotic therapy) versus no treatment/usual treatment after 3–4 months was −0.40% (95% confidence interval (CI) fixed effect −0.78% to −0.01%), representing a statistically significant reduction in HbA1c (P = 0.04) for scaling/root planing.

One study was assessed as being at low risk of bias with the other two at moderate to high risk of bias. A subgroup analysis examined studies without adjunctive antibiotics −0.80% (one study: 95% CI −1.73% to 0.13%; P = 0.09), with adjunctive antibiotics in the test group −0.36% (one study: 95% CI −0.83% to 0.11%; P = 0.14), and with antibiotics in both test and control groups after 3/4 months −0.15% (one study: 95% CI −1.04% to 0.74%; P = 0.74).

Authors’ conclusions:  There is some evidence of improvement in metabolic control in people with diabetes, after treating periodontal disease. There are few studies available and individually these lacked the power to detect a significant effect. Most of the participants in the study had poorly controlled Type 2 DM with little data from randomized trials on the effects on people with Type 1 DM.
Shelf Space Management When Demand Depends on the Inventory Level
Authors: Baron Opher , Berman Oded , Perry David
Published: December 2010

Two factors that their influence on the demand has been investigated in many papers are (i) the shelf space allocated to a product and to its complement or supplement products and (ii) the instantaneous inventory level seen by customers. Here we analyze the joint shelf space allocation and inventory decisions for multiple items with demand that depends on both factors. The traditional approach to solve inventory models with a state‐dependent demand rate uses a time domain approach. However, this approach often does not lead to closed‐form expressions for the profit rate with both dependencies. We analyze the problem in the inventory domain via level crossing theory. This approach leads to closed‐form expressions for a large set of demand rate functions exhibiting both dependencies. These closed‐form expressions substantially simplify the search for optimal solutions; thus we use them to solve the joint inventory control and shelf space allocation problem. We consider examples with two products to investigate the significance of capturing both demand dependencies. We show that in some settings it is important to capture both dependencies. We consider two heuristics, each one of them ignores one of the two dependencies. Using these heuristics it seems that ignoring the dependency on the shelf space might be less harmful than ignoring the dependency on the inventory level, which, based on computational results, can lead to profit losses of more than 6%. We demonstrate that retailers should use their operational control, e.g., reorder point, to promote higher demand products.
Non‐neuronal release of ACh plays a key role in secretory response to luminal propionate in rat colon
Authors: Yajima Takaji , Inoue Ryo , Matsumoto Megumi , Yajima Masako
Published: December 2010

Non‐technical summaryACh is the best characterized neurotransmitter that is synthesized in cholinergic neurons in the brain and gut wall. In the gut, acetylcholine is released from the nerve endings in response to luminal stimuli and regulates the movement of gut contents via stimulating muscle contraction and epithelial ion secretion. We show that acetylcholine is synthesized in colonic epithelial cells and released on the serosal side by luminal chemical stimulation of the short chain fatty acid propionate and causes chloride secretion. These results suggest that non‐neuronal release of acetylcholine in response to luminal stimuli plays a role in colonic chloride secretion.
Neurogliaform cells and other interneurons of stratum lacunosum‐moleculare gate entorhinal–hippocampal dialogue
Authors: Capogna Marco
Published: December 2010

The stratum lacunosum‐moleculare of the hippocampus is an area of integration that receives inputs from extrinsic excitatory fibres including those from the entorhinal cortex, and is under the control of several neuromodulators. A critical aspect is the presence in this hippocampal layer of specific interneurons that are likely to influence the strength and the temporal structure of entorhinal–CA1 hippocampal dynamics. I review here recent data on the physiological role of these interneurons. Special focus is devoted to one interneuron type, the so‐called neurogliaform cell, because recent studies have defined its unusual mode of cell‐to‐cell communication. Neurogliaform cells mediate feedforward inhibition of CA1 pyramidal cells, form a network of cells connected via chemical and electrical synapses, and evoke slow inhibitory synaptic currents mediated by GABAA and GABAB receptors. The modulation of entorhinal input by neurogliaform cells and their contribution to network theta rhythm are also discussed. I hope that novel information on neurogliaform cells will contribute to the ever‐growing appreciation of GABAergic cell type diversity, and will inspire neuroscientists interested not only in synaptic physiology but also in the brain's spatial representation system.
Systems biology and integrative physiological modelling
Authors: Hester Robert L. , Iliescu Radu , Summers Richard , Coleman Thomas G.
Published: December 2010

Over the last 10 years, ‘Systems Biology’ has focused on the integration of biology and medicine with information technology and computation. The current challenge is to use the discoveries of the last 20 years, such as genomics and proteomics, to develop targeted therapeutical strategies. These strategies are the result of understanding the aetiologies of complex diseases. Scientists predict the data will make personalized medicine rapidly available. However, the data need to be considered as a highly complex system comprising multiple inputs and feedback mechanisms. Translational medicine requires the functional and conceptual linkage of genetics to proteins, proteins to cells, cells to organs, organs to systems and systems to the organism. To help understand the complex integration of these systems, a mathematical model of the entire human body, which accurately links the functioning of all organs and systems together, could provide a framework for the development and testing of new hypotheses that will be important in clinical outcomes. There are several efforts to develop a ‘Human Physiome’, with the strengths and weaknesses of each being presented here. The development of a ‘Human Model’, with verification, documentation and validation of the underlying and integrative responses, is essential to provide a usable environment. Future development of a ‘Human Model’ requires integrative physiologists working in collaboration with other scientists, who have expertise in all areas of human biology, to develop the most accurate and usable human model.
An Analytical Complete Model of Tilting-Pad Journal Bearing Considering Pivot Stiffness and Damping
Authors: Yan Zhiyong , Lu Yi , Zheng Tiesheng
Published: December 2010

Considering the freedom of pad tilting and pad translation along preload orientation, an analytical complete model, as well as mathematical method, which contains 2n+2 degrees of freedom, is presented for calculating the dynamical characteristics of tilting-pad journal bearing. Based on the motion relationship of shaft and pad, the local coordinate system, the generalized displacement, and the generalized force vector are chosen. The concise transformation of generalized displacement, generalized force, and its Jacobian matrix between the local and global coordinate systems are built up in matrix form. A fast algorithm using the Newton–Raphson method for calculating the equilibrium position of journal and pads is proposed. The eight reduced stiffness and damping coefficients can be obtained assuming that the journal and all pads are subject to harmonic vibration. Numerical results show that the reduced damping coefficients and the threshold speed can be effectively enhanced by giving suitable pad pivot stiffness and damping simultaneously, and this analytical method can be applied to analyze dynamical behavior of the tilting-pad journal bearing rotor system.
On the Suitability of Econometric Demand Models in Design for Market Systems
Authors: Frischknecht Bart D. , Whitefoot Katie , Papalambros Panos Y.
Published: December 2010

A goal of design for market systems research is to predict demand for differentiated products so that counterfactual experiments can be performed based on design changes. We review conventional methods and propose an additional method to evaluate the suitability of econometric demand models estimated from revealed preference data for use in product design studies. We evaluate one demand model form from literature and two newly constructed forms for new vehicle demand along existing metrics of fit and predictive validity as well as a newly developed metric of proportional substitution sensitivity. We show that a model that includes horizontally differentiated preferences for size performs better under metrics of fit and predictive validity but that no model relaxes the IIA property satisfactorily to avoid exploitation by design optimization. We conduct design studies separately, applying each demand model form assuming the automotive market is in Bertrand–Nash price equilibrium. Results illustrate that the influence of the demand model form on the optimum in terms of design variables and expected firm profit is significant.
ATM-Dependent and -Independent Dynamics of the Nuclear Phosphoproteome After DNA Damage
Authors: Bensimon Ariel , Schmidt Alexander , Ziv Yael , Elkon Ran , Wang Shih-Ya , Chen David J. , Aebersold Ruedi , Shiloh Yosef
Published: December 2010

Quantitative phosphoproteomics suggests that kinases other than ATM participate in the initial phase of the cellular response to DNA double-strand breaks.
mTORC2 Akt-ing at the Ribosome
Authors: VanHook Annalisa M.
Published: December 2010

mTORC2-mediated phosphorylation of Akt occurs during translation.
Artemisone Uptake in
Plasmodium falciparum
-Infected Erythrocytes
Authors: Pooley Sophie , Fatih Farrah A. , Krishna Sanjeev , Gerisch Michael , Haynes Richard K. , Wong Ho-Ning , Staines Henry M.
Published: December 2010

Artemisone is one of the most promising artemisinin derivatives in clinical trials. Previous studies with radiolabeled artemisinin and dihydroartemisinin have measured uptake in
Plasmodium falciparum
-infected erythrocytes. Uptake is much greater in infected than in uninfected erythrocytes, but the relative contributions of transport, binding, and metabolism to this process still await definition. In this study, we characterized mechanisms by which [
14
C]artemisone is taken up into uninfected and
P. falciparum
-infected human erythrocytes
in vitro
. Radiolabeled artemisone rapidly enters uninfected erythrocytes without much exceeding extracellular concentrations. Unlabeled artemisone does not compete in this process. Radiolabeled artemisone is concentrated greatly by a time- and temperature-dependent mechanism in infected erythrocytes. This uptake is abrogated by unlabeled artemisone. In addition, the uptake of artemisone into three subcellular fractions, and its distribution into these fractions, is examined as a function of parasite maturation. These data are relevant to an understanding of the mechanisms of action of this important class of drugs.
Ex VivoActivity of Histone Deacetylase Inhibitors against Multidrug-Resistant Clinical Isolates ofPlasmodium falciparumandP. vivax
Authors: Marfurt Jutta , Chalfein Ferryanto , Prayoga Pak , Wabiser Frans , Kenangalem Enny , Piera Kim A. , Fairlie David P. , Tjitra Emiliana , Anstey Nicholas M. , Andrews Kathy T. , Price Ric N.
Published: December 2010

Histone acetylation plays an important role in regulating gene transcription and silencing inPlasmodium falciparum. Histone deacetylase (HDAC) inhibitors, particularly those of the hydroxamate class, have been shown to have potentin vitroactivity against drug-resistant and -sensitive laboratory strains ofP. falciparum, raising their potential as a new class of antimalarial compounds. In the current study, stage-specificex vivosusceptibility profiles of representative hydroxamate-based HDAC inhibitors suberoylanilide hydroxamic acid (SAHA), 2-ASA-9, and 2-ASA-14 (2-ASA-9 and 2-ASA-14 are 2-aminosuberic acid-based HDAC inhibitors) were assessed in multidrug-resistant clinical isolates ofP. falciparum(n= 24) andP. vivax(n= 25) from Papua, Indonesia, using a modified schizont maturation assay. Submicromolar concentrations of SAHA, 2-ASA-9, and 2-ASA-14 inhibited the growth of bothP. falciparum(median 50% inhibitory concentrations [IC50s] of 310, 533, and 266 nM) andP. vivax(median IC50s of 170, 503, and 278 nM). Inverse correlation patterns between HDAC inhibitors and chloroquine forP. falciparumand mefloquine forP. vivaxindicate species-specific susceptibility profiles for HDAC inhibitors. These HDAC inhibitors were also found to be potentex vivoagainstP.vivaxschizont maturation, comparable to that inP. falciparum, suggesting that HDAC inhibitors may be promising candidates for antimalarial therapy in geographical locations where both species are endemic. Further studies optimizing the selectivity andin vivoefficacy of HDAC inhibitors inPlasmodiumspp. and defining drug interaction with common antimalarial compounds are warranted to investigate the role of HDAC inhibitors in antimalarial therapy.
Antialarmin Effect of Tick Saliva during the Transmission of Lyme Disease
Authors: Marchal Claire , Schramm Frederic , Kern Aurélie , Luft Benjamin J. , Yang Xiaohua , Schuijt Tim , Hovius Joppe , Jaulhac Benoît , Boulanger Nathalie
Published: December 2010

Tick saliva has potent immunomodulatory properties. In arthropod-borne diseases, this effect is largely used by microorganisms to increase their pathogenicity and to evade host immune responses. We show that in Lyme borreliosis, tick salivary gland extract and a tick saliva protein, Salp15, inhibitin vitrokeratinocyte inflammation induced byBorrelia burgdorferisensu stricto or by the major outer surface lipoprotein ofBorrelia, OspC. Chemokines (interleukin-8 [IL-8] and monocyte chemoattractant protein 1 [MCP-1]) and several antimicrobial peptides (defensins, cathelicidin, psoriasin, and RNase 7) were downregulated. Interestingly, antimicrobial peptides (AMPs) transiently inhibited bacterial motility but did not kill the organisms when testedin vitro. We conclude that tick saliva affects the chemotactic properties of chemokines and AMPs on immune cells and has an antialarmin effect on human primary keratinocytes. Alarmins are mediators that mobilize and activate antigen-presenting cells. Inhibition of cutaneous innate immunity and of the migration of immune cells to the site of the tick bite ensures a favorable environment forBorrelia.The bacterium can then multiply locally and, subsequently, disseminate to the target organs, including joints, heart, and the central nervous system.
Complete Genome Sequence of
Mycoplasma bovis
Type Strain PG45 (ATCC 25523)
Authors: Wise Kim S. , Calcutt Michael J. , Foecking Mark F. , Röske Kerstin , Madupu Ramana , Methé Barbara A.
Published: December 2010

This complete and fully assembled genome sequence of
Mycoplasma bovis
type strain PG45 is the first available for this species and offers a framework for comparison with additional pathogenic isolates. The single circular chromosome of 1,003,404 bp reveals multiple gene sets and mechanisms involved in variable expression of surface antigens and the incursion of numerous and assorted mobile elements, despite its reduced size.
Making an informed choice: vetting new employees
Authors: Miller Julie
Published: December 2010

Bringing a new employee into your practice team is a huge undertaking and one that must not be taken lightly, as you risk making a mistake that could take considerable time, effort and money to resolve. In this article, Julie Miller explains why it is essential to invest time in recruiting and selecting the right individual to join you and the rest of your team.
Common conditions of reindeer
Authors: Foster Aiden
Published: December 2010

Reindeer are highly adapted to the extreme climates of northern latitudes and, therefore, when imported to countries such as the UK, are usually expected to live in substantially different conditions to those in which they evolved. This can make them susceptible to a variety of diseases and pathogens, which prospective owners and their vets need to be aware of, especially if reindeer are to share accommodation with other species such as sheep and cattle. The extensive experience and published literature from North America and Scandinavian countries, where reindeer are managed as semidomesticated herds accustomed to seasonal migration, can help to inform the growing knowledge base in the UK. This article discusses some of the common problems affecting reindeer in this country.
Diagnosis and treatment of penetrating injuries of the hoof in horses
Authors: O'Neill Henry , O'Meara Bryan
Published: December 2010

Penetration of the foot by a foreign object (eg, a nail or screw) is commonly seen in horses. Animals will present with varying degrees of lameness, depending on the location, depth and duration of the penetration. Wounds to any part of the sole within the limits of the white line have the potential to involve sensitive structures, but those penetrating the middle third of the sole may contact vital tendinous, synovial or osseous structures. The prognosis depends on a number of variables including the structures affected, the severity of the lesion and the delay in the onset of treatment. The first aid administered to a patient at the initial visit can have a serious impact on the outcome but also has financial implications. This article describes the diagnosis and treatment of superficial and deep penetrating injuries of the hoof in horses.
Polycyclic aromatic hydrocarbon-induced oxidative stress and lipid peroxidation in relation to immunological alteration
Authors: Jeng Hueiwang Anna , Pan Chih-Hong , Diawara Norou , Chang-Chien Guo-Ping , Lin Wen-Yi , Huang Chia-Tsuan , Ho Chi-Kung , Wu Ming-Tsang
Published: December 2010

Objectives

We evaluated the association between exposure to polycyclic aromatic hydrocarbons (PAHs) and immunological measurements using blood samples from coke oven workers exposed to high and low PAH levels.

Methods

A population-based cross-sectional study was conducted from 2008–2009 with coke oven workers and steel-rolling workers as the exposed and control groups, respectively. Questionnaires on basic demographic information were administered. Personal breathing zone and urine samples were collected to quantify personal PAH intake and biological response doses. Immunological and cytokine parameters in serum were analysed. Urinary malondialdehyde (MDA) and 8-hydroxydeoxyguanosine (8-OHdG) were analysed to determine oxidative stress induced by PAHs in relation to altered humoural immunological status.

Results

Mean levels of serum immunoglobulin A (IgA) and TNF-α were significantly increased in coke oven workers compared to steel-rolling workers who had no or minimal PAH exposure (p=0.0033 and p<0.0001, respectively). There were no significant differences in mean levels of IL-4 and IL-10 between coke oven workers and steel-rolling workers. Moderate activation of lipid peroxidation and oxidative damage as determined by plasma MDA and 8-OHdG levels were detected simultaneously with significant alterations in IgA and IgE levels. Multiple regression analyses demonstrated that PAHs with high molecular weights >252 (dibenzo(a,h)anthracene, benzo(a)pyrene, benzo(a)anthracene and/or indeno(1,2,3-cd)pyrene) correlated with IgA and IgE levels.

Conclusions

This study showed that coke oven workers with chronic exposure to PAHs may develop immunological alteration. Oxidative stress and lipid peroxidation induced by PAHs may partly explain the alteration in immunological parameters.
DNA Repair Protein Biomarkers Associated with Time to Recurrence in Triple-Negative Breast Cancer
Authors: Alexander Brian M. , Sprott Kam , Farrow D. Allan , Wang XiaoZhe , D'Andrea Alan D. , Schnitt Stuart J. , Collins Laura C. , Weaver David T. , Garber Judy E.
Published: December 2010

Purpose: To evaluate the prognostic utility of immunohistochemical assessment of key proteins in multiple DNA repair pathways in triple-negative breast cancer (TNBC; estrogen receptor negative, progesterone receptor negative, and HER2/neu negative by immunohistochemistry).

Experimental Design: Archived clinically annotated tumor specimens from 112 women with TNBC were immunostained with antibodies against DNA repair proteins and scored using digital image analysis. The cohort was divided into training and test sets for development of a multiantibody model. Scores were combined with clinical data to assess association with outcome.

Results: Low XPF (P = 0.005), pMK2 (P = 0.01), MLH; P = 0.002), and FANCD2 (P = 0.001) were each associated with shorter time to recurrence (TTR) in univariate analysis. A 4-antibody model could segregate high-risk and low-risk groups on the basis of TTR in both the training (relative risk [RR] = 3.52; P = 9.05E-07) and test (RR 2.67; P = 0.019) cohorts.

Conclusions: DNA repair proteins may be useful as prognostic markers in TNBC. Further study in larger, uniformly treated cohorts with additional clinical parameters is warranted. Clin Cancer Res; 16(23); 5796–804. ©2010 AACR.
Seamless Phase I-II Trial Design for Assessing Toxicity and Efficacy for Targeted Agents
Authors: Hoering Antje , LeBlanc Mike , Crowley John
Published: December 2010

Purpose: The premise for phase I trials for cytostatic agents is different from that of cytotoxic agents. For cytostatic agents, toxicity and efficacy do not necessarily increase monotonically with increasing dose levels, but likely plateau after they reach maximal toxicity or efficacy. Here, we propose a phase I-II trial design to assess both toxicity and efficacy to find the best dose as well as a good dose.

Experimental Design: We propose a 2-step dose-finding trial for assessing both toxicity and efficacy for a targeted agent. The 1st step uses a traditional phase I trial design. This step only assesses toxicity and finds the maximal tolerated dose (MTD). For the 2nd step, we propose a modified phase II selection design for 2 or 3 dose levels at and below the MTD to determine efficacy and evaluate each dose level by both efficacy and toxicity.

Results and Conclusion: Simulation studies are done on several combinations of toxicity and efficacy scenarios to assess the operating statistics of our proposed trial design. We then compare our results with a traditional phase I trial followed by a single-arm phase II trial using the same total sample size. The proposed design does better in most cases than a traditional design using the same overall sample size. This design allows assessing a few dose levels more closely for both efficacy and toxicity and provides greater certainty of having correctly determined the best dose level before launching into a large efficacy trial. Clin Cancer Res; 17(4); 1–7. ©2010 AACR.
Quercetin Induces Tumor-Selective Apoptosis through Downregulation of Mcl-1 and Activation of Bax
Authors: Cheng Senping , Gao Ning , Zhang Zhuo , Chen Gang , Budhraja Amit , Ke Zunji , Son Young-ok , Wang Xin , Luo Jia , Shi Xianglin
Published: December 2010

Purpose: To investigate the in vivo antitumor efficacy of quercetin in U937 xenografts and the functional roles of Mcl-1 and Bax in quercetin-induced apoptosis in human leukemia.

Experimental Design: Leukemia cells were treated with quercetin, after which apoptosis, Mcl-1 expression, and Bax activation and translocation were evaluated. The efficacy of quercetin as well as Mcl-1 expression and Bax activation were investigated in xenografts of U937 cells.

Results: Administration of quercetin caused pronounced apoptosis in both transformed and primary leukemia cells but not in normal blood peripheral mononuclear cells. Quercetin-induced apoptosis was accompanied by Mcl-1 downregulation and Bax conformational change and mitochondrial translocation that triggered cytochrome c release. Knockdown of Bax by siRNA reversed quercetin-induced apoptosis and abrogated the activation of caspase and apoptosis. Ectopic expression of Mcl-1 attenuated quercetin-mediated Bax activation, translocation, and cell death. Conversely, interruption of Mcl-1 by siRNA enhanced Bax activation and translocation, as well as lethality induced by quercetin. However, the absence of Bax had no effect on quercetin-mediated Mcl-1 downregulation. Furthermore, in vivo administration of quercetin attenuated tumor growth in U937 xenografts. The TUNEL-positive apoptotic cells in tumor sections increased in quercetin-treated mice as compared with controls. Mcl-1 downregulation and Bax activation were also observed in xenografts.

Conclusions: These data suggest that quercetin may be useful for the treatment of leukemia by preferentially inducing apoptosis in leukemia versus normal hematopoietic cells through a process involving Mcl-1 downregulation, which, in turn, potentiates Bax activation and mitochondrial translocation, culminating in apoptosis. Clin Cancer Res; 16(23); 5679–91. ©2010 AACR.
Practical Utility of On-Line Clearance and Blood Temperature Monitors as Noninvasive Techniques to Measure Hemodialysis Blood Access Flow
Authors: Fontseré Néstor , Blasco Miquel , Maduell Francisco , Vera Manel , Arias-Guillen Marta , Herranz Sandra , Blanco Teresa , Barrufet Marta , Burrel Marta , Montaña Javier , Real Maria Isabel , Mestres Gaspar , Riambau Vicenç , Campistol Josep M.
Published: December 2010

Background/Aims: Access blood flow (Qa) measurements are recommended by the current guidelines as one of the most important components in vascular access maintenance programs. This study evaluates the efficiency of Qa measurement with on-line conductivity (OLC-Qa) and blood temperature monitoring (BTM-Qa) in comparison with the gold standard saline dilution method (SDM-Qa). Subjects and Methods: 50 long-term hemodialysis patients (42 arteriovenous fistulas/8 arteriovenous grafts) were studied. Bland-Altman and Lin’s coefficient (ρc) were used to study accuracy and precision. Results: Mean values were 1,021.7 ± 502.4 ml/min SDM-Qa, 832.8 ± 574.3 ml/min OLC-Qa (p = 0.007) and 1,094.9 ± 491.9 ml/min with BTM-Qa (p = NS). Biases and ρc obtained were –188.8 ml/min (ρc 0.58) OLC-Qa and 73.2 ml/min (ρc 0.89) BTM-Qa. The limits of agreement (bias ± 1.96 SD) obtained were from –1,119 to 741.3 ml/min (OLC-Qa) and –350.6 to 497.2 ml/min (BTM-Qa). Conclusions: BTM-Qa and OLC-Qa are valid noninvasive and practical methods to estimate Qa, although BTM-Qa was more accurate and had better concordance than OLC-Qa compared with SDM-Qa.
Effect of Diclofenac on Cyclooxygenase-2 Levels and Early Breaking Strength of Experimental Colonic Anastomoses and Skin Incisions
Authors: Klein M. , Krarup P.-M. , Burcharth J. , Ågren M.S. , Gögenur I. , Jorgensen L.N. , Rosenberg J.
Published: December 2010

Background: Recently, there has been a focus on the effect of the nonsteroidal anti-inflammatory drugs on the anastomotic leakage rate after colorectal surgery. Methods: An experimental, randomized, placebo-controlled prospective study on 32 male Wistar rats was carried out. We examined the effect of diclofenac 4 mg/kg/day on the cyclooxygenase-2 (COX-2) enzyme in the anastomotic tissue and on the breaking strength of anastomotic and incisional wounds. The operation was performed with colonic resection and hand-sewn anastomosis. After 3 days, the rats were sacrificed and the breaking strength and the COX-2 content of the anastomosis were measured. Results: There was a significantly reduced level of COX-2 in the rats treated with diclofenac (p = 0.001); no significant differences in any of the breaking strength measurements and no significant correlation between COX-2 levels and breaking strength of the anastomotic or incisional wounds could be found (p = 0.073 and p = 0.727). Conclusion: This study for the first time showed that a diclofenac dose of 4 mg/kg/24 h was sufficient to reduce the level of COX-2 enzymes in the anastomotic tissue in rats. This inhibition of the inflammatory response did not lead to reduced breaking strength of either anastomotic or incisional wounds. Whether there is a detrimental effect of COX inhibition on colorectal anastomoses in the clinical setting remains controversial.
Serum Brain-Derived Neurotrophic Factor Levels Are Specifically Associated with Memory Performance among Alzheimer’s Disease Cases
Authors: O’Bryant Sid E. , Hobson Valerie L. , Hall James R. , Barber Robert C. , Zhang Song , Johnson Leigh , Diaz-Arrastia Ramon
Published: December 2010

Aims: Our purpose was to study the link between serum brain-derived neurotrophic factor (BDNF) levels and neuropsychological functioning through the Texas Alzheimer’s Research Consortium cohort. Methods: A total of 399 participants [probable Alzheimer’s disease (AD) n = 198, controls n = 201] were available for analysis. The BDNF levels were assayed via multiplex immunoassay. Regression analyses were utilized to examine the relation between BDNF levels and neuropsychological functioning. Results: There were no significant mean differences in BDNF levels between cases and controls. In the AD group, the BDNF levels were significantly negatively associated with the scores on immediate [B = –0.07 (0.02), t = –3.55, p = 0.001] and delayed [B = –0.05 (0.02), t = –2.79, p = 0.01] verbal memory and immediate [B = –0.12 (0.05), t = –2.70, p = 0.01] visual memory. No other neuropsychological variables were significantly related to the BDNF levels. The BDNF levels were not significantly related to the neuropsychological test scores in the control group. Conclusions: Increased serum BDNF levels were associated with poorer visual and verbal memory, but only among AD cases. The current findings point toward an upregulation of serum BDNF as one possible mechanism linked to memory disturbances in AD though it does not appear to be linked to disease severity.
Cerebrospinal Fluid Tau, p-Tau 181 and Amyloid-β38/40/42 in Frontotemporal Dementias and Primary Progressive Aphasias
Authors: Bibl Mirko , Mollenhauer Brit , Lewczuk Piotr , Esselmann Hermann , Wolf Stefanie , Otto Markus , Kornhuber Johannes , Rüther Eckart , Wiltfang Jens
Published: December 2010

Background/Aims: We determined cerebrospinal fluid (CSF) concentrations of amyloid-β (Aβ)1–38, Aβ1–40, Aβ1–42, total tau and phospho-tau (p-tau) in order to study their differential expression in frontotemporal dementia (FTD, n = 25) and primary progressive aphasia (PPA, n = 12) as compared to Alzheimer’s dementia (AD, n = 25) and nondemented controls (n = 20). Methods: Commercially available ELISA and electrochemiluminescence methods were applied. Results: High CSF p-tau and low ratios of Aβ1–42/Aβ1–40 and Aβ1–42/Aβ1–38, respectively, were specific for AD. CSF Aβ1–38 was reduced in FTD as compared to each of the other diagnostic groups, including PPA. CSF tau and p-tau levels were elevated in PPA as compared to FTD. Conclusion: This is the first detailed report on biomarker patterns in PPA, indicating distinct CSF biomarker patterns in FTD and PPA as major subgroups of frontotemporal lobar degeneration. The diagnostic and pathophysiological implications of our results warrant further studies on larger and neuropathologically diagnosed patient populations.
Differential cytotoxic actions of Shiga toxin 1 and Shiga toxin 2 on microvascular and macrovascular endothelial cells
Authors: Bauwens Andreas , Bielaszewska Martina , Kemper Björn , Langehanenberg Patrik , Bally Gert von , Reichelt Rudolf , Mulac Dennis , Humpf Hans-Ulrich , Friedrich Alexander , Kim Kwang , Karch Helge , Müthing Johannes
Published: December 2010

Shiga toxin (Stx)-mediated injury to vascular endothelial cells in the kidneys, brain and other organs underlies the pathogenesis of haemolytic uraemic syndrome (HUS) caused by enterohaemorrhagic Escherichia coli (EHEC). We present a direct and comprehensive comparison of cellular injury induced by the two major Stx types, Stx1 and Stx2, in human brain microvascular endothelial cells (HBMECs) and EA.hy 926 macro-vascular endothelial cells. Scanning electron microscopy of microcarrier-based cell cultures, digital holographic microscopy of living single cells, and quantitative apoptosis/necrosis assays demonstrate that Stx1 causes both necrosis and apoptosis, whereas Stx2 induces almost exclusively apoptosis in both cell lines. Moreover, microvascular and macrovascular endothelial cells have different susceptibilities to the toxins: EA.hy 926 cells are slightly, but significantly (~ 10 times) more susceptible to Stx1, whereas HBMECs are strikingly (≥ 1,000 times) more susceptible to Stx2. These findings have implications in the pathogenesis of HUS, and suggest the existence of yet to be delineated Stx type-specific mechanisms of endothelial cell injury beyond inhibition of protein bio-synthesis.
β3Adrenergic Stimulation of the Cardiac Na+-K+Pump by Reversal of an Inhibitory Oxidative Modification
Authors: Bundgaard Henning , Liu Chia-Chi , Garcia Alvaro , Hamilton Elisha J. , Huang Yifei , Chia Karin K.M. , Hunyor Stephen N. , Figtree Gemma A. , Rasmussen Helge H.
Published: December 2010

Background—

Inhibition of L-type Ca2+current contributes to negative inotropy of β3adrenergic receptor (β3AR) activation, but effects on other determinants of excitation-contraction coupling are not known. Of these, the Na+-K+pump is of particular interest because of adverse effects attributed to high cardiac myocyte Na+levels and upregulation of the β3AR in heart failure.

Methods and Results—

We voltage clamped rabbit ventricular myocytes and identified electrogenic Na+-K+pump current (Ip) as the shift in holding current induced by ouabain. The synthetic β3AR agonists BRL37344 and CL316,243 and the natural agonist norepinephrine increasedIp. Pump stimulation was insensitive to the β1/β2AR antagonist nadolol and the protein kinase A inhibitor H-89 but sensitive to the β3AR antagonist L-748,337. Blockade of nitric oxide synthase abolished pump stimulation and an increase in fluorescence of myocytes loaded with a nitric oxide–sensitive dye. Exposure of myocytes to β3AR agonists decreased β1Na+-K+pump subunit glutathionylation, an oxidative modification that causes pump inhibition. The in vivo relevance of this was indicated by an increase in myocardial β1pump subunit glutathionylation with elimination of β3AR–mediated signaling in β3AR−/−mice. The in vivo effect of BRL37344 on contractility of the nonfailing and failing heart in sheep was consistent with a beneficial effect of Na+-K+pump stimulation in heart failure.

Conclusions—

The β3AR mediates decreased β1subunit glutathionylation and Na+-K+pump stimulation in the heart. Upregulation of the receptor in heart failure may be a beneficial mechanism that facilitates the export of excess Na+.