The Journal of Visualized Experiments (JoVE) is a peer reviewed, PubMed-indexed video journal. Our mission is to increase the productivity of scientific research.

Recommend to Librarian

In JoVE (1)

Other Publications (200)

Articles by Lina M. Carrillo in JoVE

 JoVE Immunology and Infection

Cutaneous Leishmaniasis in the Dorsal Skin of Hamsters: a Useful Model for the Screening of Antileishmanial Drugs


JoVE 3533 4/21/2012

1Program for the Study and Control of Tropical Diseases -PECET-School of Medicine, University of Antioquia, 2School of Agrarian Sciences, University of Antioquia

Optimization of the experimental hamster model for cutaneous leishmaniasis by intradermal injection of Leishmania promastigotes at the dorsal skin. This approach is useful during inoculation, follow-up, characterization of lesions, application of treatments and obtaining of clinical samples. Locomotion, search for food and water, play and social activities are preserved.

Other articles by Lina M. Carrillo on PubMed

The Diagnosis of Dementia Due to Alzheimer's Disease: Recommendations from the National Institute on Aging-Alzheimer's Association Workgroups on Diagnostic Guidelines for Alzheimer's Disease

The National Institute on Aging and the Alzheimer's Association charged a workgroup with the task of revising the 1984 criteria for Alzheimer's disease (AD) dementia. The workgroup sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers without access to neuropsychological testing, advanced imaging, and cerebrospinal fluid measures, and specialized investigators involved in research or in clinical trial studies who would have these tools available. We present criteria for all-cause dementia and for AD dementia. We retained the general framework of probable AD dementia from the 1984 criteria. On the basis of the past 27 years of experience, we made several changes in the clinical criteria for the diagnosis. We also retained the term possible AD dementia, but redefined it in a manner more focused than before. Biomarker evidence was also integrated into the diagnostic formulations for probable and possible AD dementia for use in research settings. The core clinical criteria for AD dementia will continue to be the cornerstone of the diagnosis in clinical practice, but biomarker evidence is expected to enhance the pathophysiological specificity of the diagnosis of AD dementia. Much work lies ahead for validating the biomarker diagnosis of AD dementia.

Search for High Mass Resonances Decaying to Muon Pairs in ˆs=1.96 TeV Pp Collisions

We present a search for a new narrow, spin-1, high mass resonance decaying to μ(+)μ⁻+X, using a matrix-element-based likelihood and a simultaneous measurement of the resonance mass and production rate. In data with 4.6 fb⁻¹ of integrated luminosity collected by the CDF detector in pp collisions at √s=1960 GeV, the most likely signal cross section is consistent with zero at 16% confidence level. We therefore do not observe evidence for a high mass resonance and place limits on models predicting spin-1 resonances, including M>1071 GeV/c² at 95% confidence level for a Z' boson with the same couplings to fermions as the Z boson.

Measurement of B Hadron Lifetimes in Exclusive Decays Containing a J/ψ in Pp Collisions at ˆs=1.96 TeV

We report on a measurement of b-hadron lifetimes in the fully reconstructed decay modes B(+)→J/ψK(+), B⁰→J/ψK*(892)⁰, B⁰→J/ψK(s)⁰, and Λ(b)⁰→J/ψΛ⁰ using data corresponding to an integrated luminosity of 4.3 fb⁻¹, collected by the CDF II detector at the Fermilab Tevatron. The measured lifetimes are τ(B(+))=[1.639±0.009(stat)±0.009(syst)] ps, τ(B⁰)=[1.507±0.010(stat)±0.008(syst)] ps, and τ(Λ(b)⁰)=[1.537±0.045(stat)±0.014(syst)] ps. The lifetime ratios are τ(B(+))/τ(B⁰)=[1.088±0.009(stat)±0.004(syst)] and τ(Λ(b)⁰)/τ(B⁰)=[1.020±0.030(stat)±0.008(syst)]. These are the most precise determinations of these quantities from a single experiment.

Organocatalytic Enantioselective Formal Conjugate Addition of a Hydroxymoyl Anion to α,β-unsaturated Aldehydes

Development of Naturally Selected and Molecularly Engineered Intrachain and Competitive FRET-aptamers and Aptamer Beacons

Several different approaches have been taken to development of homogeneous fluorescent aptamer assays including end-labeled beacons and signaling aptamers which are intrinsically quenched by nucleotides. Two new strategies dubbed "intrachain" and "competitive" FRET-aptamer assays are summarized in this review. Intrachain and competitive FRET-aptamers can be engineered on the molecular level through a series exploratory experiments involving prior knowledge of aptamer secondary or tertiary structures and hypotheses about aptamer conformational changes. However, there is an intrinsic risk of altering aptamer affinity or specificity associated with chemical modifications of an aptamer. Natural selection methods for FRET-aptamers have also been devised to potentially obviate the chemical modification problem. The naturally selected aptamers are subjected to fluorophore (F)- and or quencher (Q)-conjugated nucleotide triphosphate (NTP) incorporation by polymerase chain reaction (PCR) with permissive polymerases such as Deep Vent exo-, but still demonstrate sensitive and specific assay performance despite modified bases, because they are ultimately selected after decoration with F and Q. This paper summarizes work in this area and presents some new examples of the engineered and naturally selected FRET-aptamers for detection of vitamin D.

Cerebellarlike Corrective Model Inference Engine for Manipulation Tasks

This paper presents how a simple cerebellumlike architecture can infer corrective models in the framework of a control task when manipulating objects that significantly affect the dynamics model of the system. The main motivation of this paper is to evaluate a simplified bio-mimetic approach in the framework of a manipulation task. More concretely, the paper focuses on how the model inference process takes place within a feedforward control loop based on the cerebellar structure and on how these internal models are built up by means of biologically plausible synaptic adaptation mechanisms. This kind of investigation may provide clues on how biology achieves accurate control of non-stiff-joint robot with low-power actuators which involve controlling systems with high inertial components. This paper studies how a basic temporal-correlation kernel including long-term depression (LTD) and a constant long-term potentiation (LTP) at parallel fiber-Purkinje cell synapses can effectively infer corrective models. We evaluate how this spike-timing-dependent plasticity correlates sensorimotor activity arriving through the parallel fibers with teaching signals (dependent on error estimates) arriving through the climbing fibers from the inferior olive. This paper addresses the study of how these LTD and LTP components need to be well balanced with each other to achieve accurate learning. This is of interest to evaluate the relevant role of homeostatic mechanisms in biological systems where adaptation occurs in a distributed manner. Furthermore, we illustrate how the temporal-correlation kernel can also work in the presence of transmission delays in sensorimotor pathways. We use a cerebellumlike spiking neural network which stores the corrective models as well-structured weight patterns distributed among the parallel fibers to Purkinje cell connections.

Clinical Validation of the EORTC QLQ-OG25 Questionnaire for the Evaluation of Health-related Quality of Life in Mexican Patients with Esophagogastric Cancers

Background: Quality of life questionnaires (QLQ) QLQ-STO22 and QLQ-OES18 are currently available to measure Health-related quality of life (HRQL) in patients with Esophageal (EC) or Gastric cancer (GC). The QLQ-OG25 integrates questions from both questionnaires to be useful for EC, Esophagogastric junction carcinoma (EGJC), and GC. Our aim was to validate the Mexican-Spanish version. Patients and Methods: The translation procedure followed European Organization for Research and Treatment of Cancer (EORTC) guidelines. QLQ-C30 and QLQ-OG25 instruments were completed by patients with EC, EGJC, and GC. Patients were divided into three groups: (1) palliative treatment; (2) treatment with curative intent, and (3) survivors. Reliability and validity tests were performed. Results: One-hundred sixty-three patients were included: 62 women and 101 men (mean age, 54.9 years; range, 22-82 years). Sixty-nine, seventy-three, and twenty-one patients were allocated into groups 1, 2, and 3, respectively. Questionnaire compliance rates were high and were well accepted. Group 3 patients reported better functional HRQL scores and lower symptom scores than patients in groups 2 and 1. Scales in the QLQ-C30 and QLQ-OG25 distinguished among other clinically distinct groups of patients. Cronbach's α coefficients of all multi-item scales of the QLQ-OG25 instrument were >0.7 (range, 0.7-0.83). Multitrait scaling analysis demonstrated good convergent and discriminant validity, even adjusting by location. Test-retest scores were consistent. Conclusion: The Mexican-Spanish version of the EORTC QLQ-OG25 questionnaire is reliable and valid for HRQL measurement in patients with esophagogastric cancer and can be used in clinical trials in the Mexican community. Copyright © 2011 John Wiley & Sons, Ltd.

Influence of Early Life Factors on Elite Performance

Autonomic Nervous System Modulation During an Archery Competition in Novice and Experienced Adolescent Archers

We assessed autonomic nervous system modulation through changes in heart rate variability during an archery competition as well as archery performance by comparing novice and experienced adolescent archers. Seven novice (age 14.0 ± 8.5 years, body mass index 22.9 ± 4.3 kg · m(-2), training experience 0.4 ± 0.3 years) and ten experienced archers (age 16.5 ± 10.3 years, body mass index 22.4 ± 3.1 kg · m(-2), training experience 4.1 ± 0.9 years) volunteered. Using beat-by-beat heart rate monitoring, heart rate variability was measured for 20 s before each arrow shot during two rounds of competition. We found that, compared with novices, experienced adolescent archers: (i) take more time per shot; (ii) have a higher low frequency band, square root of the mean of squared differences between successive R-R intervals (i.e. the time elapsing between two consecutive R waves in the electrocardiogram), and percentage of successive normal-to-normal intervals greater than 50 ms; and (iii) demonstrate an increase in parasympathetic nervous system activity compared with pre-competition values. We propose that these characteristics of experienced archers are appropriate for optimal performance during competition.

Laser-induced Thrombosis in Zebrafish

In the event of injury to the vasculature in vertebrate organisms bleeding is stopped by a defense mechanism called hemostasis. Even though biochemical studies characterized a number of factors, classical genetic methods have not been applied to study hemostasis. We introduced zebrafish as an animal model to study genetics of hemostasis. To conduct genetic studies of hemostasis, we required a global screening method to address all the factors of hemostasis such as those present in plasma, in platelets or those present in the endothelium. Therefore, we developed a global laser induced thrombosis method which can assay all these components. In this paper, we describe the principle of this method as well as provide the detailed protocol so this could be used as a screening tool to measure hemostasis in any laboratory.

Defining and Targeting Health Care Access Barriers

The impact of social and economic determinants of health status and the existence of racial and ethnic health care access disparities have been well-documented. This paper describes a model, the Health Care Access Barriers Model (HCAB), which provides a taxonomy and practical framework for the classification, analysis and reporting of those modifiable health care access barriers that are associated with health care disparities. The model describes three categories of modifiable health care access barriers: financial, structural, and cognitive. The three types of barriers are reciprocally reinforcing and affect health care access individually or in concert. These barriers are associated with screening, late presentation to care, and lack of treatment, which in turn result in poor health outcomes and health disparities. By targeting those barriers that are measurable and modifiable the model facilitates root-cause analysis and intervention design.

Search for Heavy Bottomlike Quarks Decaying to an Electron or Muon and Jets in Pp Collisions at ˆs = 1.96  TeV

We report the most sensitive direct search for pair production of fourth-generation bottomlike chiral quarks (b') each decaying promptly to tW. We search for an excess of events with an electron or muon, at least five jets (one identified as due to a b or c quark), and an imbalance of transverse momentum by using data from pp collisions collected by the CDF II detector at Fermilab with an integrated luminosity of 4.8  fb(-1). We observe events consistent with background expectation, calculate upper limits on the b' pair-production cross section (σ(bb')) ≲30  fb for m(b') > 375  GeV/c2), and exclude m(b') < 372  GeV/c2 at 95% confidence level assuming a 100% branching ratio of b' to tW.

A Novel Retrograde Laser Extraction Technique Using a Transatrial Approach: an Alternative for Complex Lead Extractions

The use of percutaneous lead extraction techniques in a patient with extracardiac or protruding atrial leads could have disastrous consequences. Traditionally, the management of these patients has included a median sternotomy. We describe a minimally invasive technique that involves a transatrial, retrograde laser lead extraction using a video-assisted thoracoscopic approach.

Measurement of the Mass Difference Between T and T Quarks

We present a direct measurement of the mass difference between t and t quarks using tt candidate events in the lepton+jets channel, collected with the CDF II detector at Fermilab's 1.96 TeV Tevatron pp Collider. We make an event by event estimate of the mass difference to construct templates for top quark pair signal events and background events. The resulting mass difference distribution of data is compared to templates of signals and background using a maximum likelihood fit. From a sample corresponding to an integrated luminosity of 5.6  fb(-1), we measure a mass difference, ΔM(top) = M(t) - M(t) = -3.3 ± 1.4(stat) ± 1.0(syst)  GeV/c2, approximately 2 standard deviations away from the CPT hypothesis of zero mass difference.

[Analysis of Reperfusion Delay in Patients with Acute Myocardial Infarction Treated with Primary Angioplasty Based on First Medical Contact and Time of Presentation]

In primary angioplasty, the interval between first medical contact (FMC) and reperfusion should be less than 120 minutes. The time to reperfusion varies depending on where FMC is established. Recent studies suggest longer times in patients presenting in off-hours. The objective is to evaluate the time intervals between the onset of symptoms and reperfusion according to where the FMC occurs and time of day of patient presentation.

Assessment of Multichannel Lung Sounds Parameterization for Two-class Classification in Interstitial Lung Disease Patients

This work deals with the assessment of different parameterization techniques for lung sounds (LS) acquired on the whole posterior thoracic surface for normal versus abnormal LS classification. Besides the conventional technique of power spectral density (PSD), the eigenvalues of the covariance matrix and both the univariate autoregressive (UAR) and the multivariate autoregressive models (MAR) were applied for constructing feature vectors as input to a supervised neural network (SNN). The results showed the effectiveness of the UAR modeling for multichannel LS parameterization, using new data, with classification accuracy of 75% and 93% for healthy subjects and patients, respectively.

A Straightforward Synthesis of 2-aminobenzothiazoles from Herz Compounds

2-Aminobenzothiazoles are readily synthesised from anilines, sulfur monochloride and isocyanides. The key step consists of an iodine-catalysed insertion of isocyanides into the S-S bond of hydrolysed Herz salts, with concomitant extrusion of sulfur monoxide.

Stress Response of Transgenic Tobacco Plants Expressing a Cyanobacterial Ferredoxin in Chloroplasts

Expression of the chloroplast electron shuttle ferredoxin is induced by light through mechanisms that partially depend on sequences lying in the coding region of the gene, complicating its manipulation by promoter engineering. Ferredoxin expression is also down-regulated under virtually all stress situations, and it is unclear if light-dependent induction and stress-dependent repression proceed through the same or similar mechanisms. Previous reports have shown that expression of a cyanobacterial flavodoxin in tobacco plastids results in plants with enhanced tolerance to adverse environmental conditions such as drought, chilling and xenobiotics (Tognetti et al. in Plant Cell 18:2035-2050, 2006). The protective effect of flavodoxin was linked to functional replacement of ferredoxin, suggesting the possibility that tolerant phenotypes might be obtained by simply increasing ferredoxin contents. To bypass endogenous regulatory constraints, we transformed tobacco plants with a ferredoxin gene from Anabaena sp. PCC7120, which has only 53% identity with plant orthologs. The cyanobacterial protein was able to interact in vitro with ferredoxin-dependent plant enzymes and to mediate NADP(+) photoreduction by tobacco thylakoids. Expression of Anabaena ferredoxin was constitutive and light-independent. However, homozygous lines accumulating threefold higher ferredoxin levels than the wild-type failed to show enhanced tolerance to oxidative stress and chilling temperatures. Under these adverse conditions, Anabaena ferredoxin was down-regulated even faster than the endogenous counterparts. The results indicate that: (1) light- and stress-dependent regulations of ferredoxin expression proceed through different pathways, and (2) overexpression of ferredoxin is not an alternative to flavodoxin expression for the development of increased stress tolerance in plants.

Measurement of the Forward-backward Asymmetry in the B→K*μ(+)μ(-) Decay and First Observation of the B(s)0→ϕμ(+)μ(-) Decay

We reconstruct the rare decays B(+)→K(+)μ(+0μ(-0, B90)→K*(892)(0)μ(+)μ(-), and B(s)(0)→ϕ(1020)μ(+)μ(-) in a data sample corresponding to 4.4  fb(-1) collected in pp collisions at √[s]=1.96  TeV by the CDF II detector at the Tevatron Collider. Using 121±16 B(+)→K(+)μ(+)μ(-) and 101±12 B(0)→K(*0)μ(+)μ(-) decays we report the branching ratios. In addition, we report the differential branching ratio and the muon forward-backward asymmetry in the B(+) and B(0) decay modes, and the K(*0) longitudinal polarization fraction in the B(0) decay mode with respect to the squared dimuon mass. These are consistent with the predictions, and most recent determinations from other experiments and of comparable accuracy. We also report the first observation of the B(s)(0)→ϕμ(+)μ(-) decay and measure its branching ratio BR(B(s)(0)→ϕμ(+)μ(-))=[1.44±0.33±0.46]×10(-6) using 27±6 signal events. This is currently the most rare B(s)(0) decay observed.

A Cell-to-cell HIV Transfer Assay Identifies Humoral Responses with Broad Neutralization Activity

Cell-to-cell HIV spread through virological synapses proceeds in two steps, first HIV particles are rapidly transferred to target cells in a CD4-dependent manner and then coreceptor-dependent events allow for infection or death of single target cells and cell-to-cell fusion.

Genistein Selectively Inhibits Estrogen-induced Cell Proliferation and Other Responses to Hormone Stimulation in the Prepubertal Rat Uterus

Sex hormone replacement therapy helps improve quality of life in climacteric women. However, estrogen-induced cell proliferation in the uterus and mammary gland increases the risk for cancer in these organs. The lower incidence of mammary cancer in Asian women than in western women has been attributed to high intake of soy isoflavones, including genistein. Our previous work in the prepubertal rat uterus model showed that genistein (0.5 mg/kg body weight subcutaneously) caused an estradiol-like hypertrophy in myometrial and uterine luminal epithelial cells and an increase in RNA content in luminal epithelium; however, it did not induce cell proliferation, uterine eosinophilia, or endometrial edema. The present study investigated, in the same animal model, the effect of genistein administration (0.5 mg/kg body weight subcutaneously) before treatment with estradiol-17β (0.33 mg/kg body weight subcutaneously) on uterine responses that were not induced by genistein. Pretreatment with this phytoestrogen completely inhibited estradiol-induced mitoses in uterine luminal epithelium, endometrial stroma, and myometrium and partially inhibited estradiol-induced uterine eosinophilia and endometrial edema. These findings indicate that genistein protects against estrogen-induced cell proliferation in the uterus and suggest that future studies should investigate the possibility of using this agent to decrease the risk for uterine cancer after hormone replacement therapy in climacteric women.

Arginine Kinase in Phytomonas, a Trypanosomatid Parasite of Plants

Phytomonas are trypanosomatid plant parasites closely related to parasites that cause several human diseases. Little is known about the biology of these organisms including aspects of their metabolism. Arginine kinase (E.C. 2.7.3.3) is a phosphotransferase which catalyzes the interconversion between the phosphagen phosphoarginine and ATP. This enzyme is present in some invertebrates and is a homolog of another widely distributed phosphosphagen kinase, creatine kinase. In this work, a single canonical arginine kinase isoform was detected in Phytomonas Jma by enzymatic activity assays, PCR, and Western Blot. This arginine kinase is very similar to the canonical isoforms found in T. cruzi and T. brucei, presenting about 70% of amino acid sequence identity and a very similar molecular weight (40kDa). The Phytomonas phosphagen system seems to be very similar to T. cruzi, which has only one isoform, or T. brucei (three isoforms); establishing a difference with other trypanosomatids, such as Leishmania, which completely lacks phosphagen kinases, probably by the presence of the arginine-consuming enzyme, arginase. Finally, phylogenetic analysis suggests that Kinetoplastids' arginine kinase was acquired, during evolution, from the arthropod vectors by horizontal gene transfer.

The Dilemma of Transvenous Cardiac Rhythm Devices in Hemodialysis Patients: Time to Consider the Epicardial Approach?

Variants and Haplotypes in Angiotensinogen Gene Are Associated with Plasmatic Angiotensinogen Level in Mexican Population

The plasmatic angiotensinogen (AGT) level has been associated with essential hypertension. Linkage analysis has found a relationship between the AGT gene locus and hypertension in the Mexican-American population, but studies have failed to identify genetic variants associated with hypertension or plasma AGT levels. This study analyzes the relationship between polymorphisms in the AGT gene and plasmatic AGT levels in Mexican population.

Invariant Mass Distribution of Jet Pairs Produced in Association with a W Boson in Pp Collisions at Sqrt[s]=1.96  TeV

We report a study of the invariant mass distribution of jet pairs produced in association with a W boson using data collected with the CDF detector which correspond to an integrated luminosity of 4.3  fb(-1). The observed distribution has an excess in the 120-160  GeV/c(2) mass range which is not described by current theoretical predictions within the statistical and systematic uncertainties. In this Letter, we report studies of the properties of this excess.

Measurements of Direct CP Violating Asymmetries in Charmless Decays of Strange Bottom Mesons and Bottom Baryons

We report measurements of direct CP-violating asymmetries in charmless decays of neutral bottom hadrons to pairs of charged hadrons with the upgraded Collider Detector at the Fermilab Tevatron. Using a data sample corresponding to 1 fb(-1) of integrated luminosity, we obtain the first measurements of direct CP violation in bottom strange mesons, A(CP)(B(s)(0)→K(-)π(+))=+0.39±0.15(stat)±0.08(syst), and bottom baryons, A(CP)(Λ(b)(0)→pπ(-))=+0.03±0.17(stat)±0.05(syst) and A(CP)(Λ(b)(0)→pK(-))=+0.37±0.17(stat)±0.03(syst). In addition, we measure CP violation in B(0)→K(+)π(-) decays with 3.5σ significance, A(CP)(B(0)→K(+)π(-))=-0.086±0.023(stat)±0.009(syst), in agreement with the current world average. Measurements of branching fractions of B(s)(0)→K(+)K(-) and B(0)→π(+)π(-) decays are also updated.

Sensory Perception Changes Induced by Transcranial Magnetic Stimulation over the Primary Somatosensory Cortex in Parkinson's Disease

Sensory symptoms are common nonmotor manifestations of Parkinson's disease. It has been hypothesized that abnormal central processing of sensory signals occurs in Parkinson's disease and is related to dopaminergic treatment. The objective of this study was to investigate the alterations in sensory perception induced by transcranial magnetic stimulation of the primary somatosensory cortex in patients with Parkinson's disease and the modulatory effects of dopaminergic treatment. Fourteen patients with Parkinson's disease with and without dopaminergic treatment and 13 control subjects were included. Twenty milliseconds after peripheral electrical tactile stimuli in the contralateral thumb, paired-pulse transcranial magnetic stimulation over the right primary somatosensory cortex was delivered. We evaluated the perception of peripheral electrical tactile stimuli at 2 conditioning stimulus intensities, set at 70% and 90% of the right resting motor threshold, using different interstimulus intervals. At 70% of the resting motor threshold, paired-pulse transcranial magnetic stimulation over the right primary somatosensory cortex induced an increase in positive responses at short interstimulus intervals (1-7 ms) in controls but not in patients with dopaminergic treatment. At 90% of the resting motor threshold, controls and patients showed similar transcranial magnetic stimulation effects. Changes in peripheral electrical tactile stimuli perception after paired-pulse transcranial magnetic stimulation over the primary somatosensory cortex are altered in patients with Parkinson's disease with dopaminergic treatment compared with controls. These findings suggest that primary somatosensory cortex excitability could be involved in changes in somatosensory integration in Parkinson's disease with dopaminergic treatment.

Lower Resistance and Higher Tolerance of Invasive Host Plants: Biocontrol Agents Reach High Densities but Exert Weak Control

Invasive plants often have novel biotic interactions in their introduced ranges. Their defense to herbivory may differ from their native counterparts, potentially influencing the effectiveness of biological control. If invasive plants have decreased resistance but increased tolerance to enemies, insect herbivores may rapidly build up their populations but exert weak control. Moreover, resource availability to plants may affect the efficacy of biological control agents. We tested these predictions using Chinese tallow tree (Triadica sebifera) and two specialist herbivores (Heterapoderopsis bicallosicollis and Gadirtha inexacta) that are candidates for biological control. We performed a pair of field common garden experiments in China in which Triadica seedlings from the native or introduced range were grown in low or high light conditions and subjected to different levels of herbivory by each herbivore in a factorial design. We found that Heterapoderopsis achieved greater densities on tallow trees from the introduced range or when trees were grown in high light conditions. When Gadirtha was raised in the lab on tallow tree foliage we found that it performed better (larger pupal size) when fed foliage from introduced populations. However, introduced populations generally had greater herbivore tolerance such that the impact of each agent on plant performance was lower than on native populations despite higher herbivore loads. Tallow trees grew more slowly and achieved smaller sizes in lower light levels, but the impact of biological control agents was comparable to that found for higher light levels. Plants from introduced populations grew larger than those from native populations in all conditions. Our results suggest that reduced resistance and increased tolerance to herbivory in introduced populations may impede success of biological control programs. Biological control practitioners should include plants from the introduced range in the prerelease evaluation, which will help predict insect impact on target weeds.

DNA Aptamer Beacon Assay for C-telopeptide and Handheld Fluorometer to Monitor Bone Resorption

A novel DNA aptamer beacon is described for quantification of a 26-amino acid C-telopeptide (CTx) of human type I bone collagen. One aptamer sequence and its reverse complement dominated the aptamer pool (31.6% of sequenced clones). Secondary structures of these aptamers were examined for potential binding pockets. Three-dimensional computer models which analyzed docking topologies and binding energies were in agreement with empirical fluorescence experiments used to select one candidate loop for beacon assay development. All loop structures from the aptamer finalists were end-labeled with TYE 665 and Iowa Black quencher for comparison of beacon fluorescence levels as a function of CTx concentration. The optimal beacon, designated CTx 2R-2h yielded a low ng/ml limit of detection using a commercially available handheld fluorometer. The CTx aptamer beacon bound full-length 26-amino acid CTx peptide, but not a shorter 8-amino acid segment of CTx peptide which is a common target for commercial CTx ELISA kits. The prototype assay was shown to detect CTx peptide from human urine after creatinine and urea were removed by size-exclusion chromatography to prevent nonspecific denaturing of the aptamer beacon. This work demonstrates the potential of aptamer beacons to be utilized for rapid and sensitive bone health monitoring in a handheld or point-of-care format.

Evaluating the Sensitization Potential of Surfactants: Integrating Data from the Local Lymph Node Assay, Guinea Pig Maximization Test, and in Vitro Methods in a Weight-of-evidence Approach

An integral part of hazard and safety assessments is the estimation of a chemical's potential to cause skin sensitization. Currently, only animal tests (OECD 406 and 429) are accepted in a regulatory context. Nonanimal test methods are being developed and formally validated. In order to gain more insight into the responses induced by eight exemplary surfactants, a battery of in vivo and in vitro tests were conducted using the same batch of chemicals. In general, the surfactants were negative in the GPMT, KeratinoSens and hCLAT assays and none formed covalent adducts with test peptides. In contrast, all but one was positive in the LLNA. Most were rated as being irritants by the EpiSkin assay with the additional endpoint, IL1-alpha. The weight of evidence based on this comprehensive testing indicates that, with one exception, they are non-sensitizing skin irritants, confirming that the LLNA tends to overestimate the sensitization potential of surfactants. As results obtained from LLNAs are considered as the gold standard for the development of new nonanimal alternative test methods, results such as these highlight the necessity to carefully evaluate the applicability domains of test methods in order to develop reliable nonanimal alternative testing strategies for sensitization testing.

Simultaneous Two-vessel Very Late Stent Thrombosis and Coronary Aneurysm Formation After Sirolimus-eluting Stent Implantation: an Intravascular Ultrasound Evaluation

Very late stent thrombosis is a rare but devastating complication. Several factors are known to contribute to its occurrence, and are related to the patient, procedure, lesion and premature discontinuation of antiplatelet therapy. This report describes the case of a 49-year-old patient with simultaneous two-vessel stent thrombosis (left anterior descending and circumflex arteries) 24 months after sirolimus-eluting stent implantation. The importance of intravascular ultrasound is enhanced. The potential contributing factors to the stent thrombosis are analyzed.

Potential Use of a Serpin from Arabidopsis for Pest Control

Although genetically modified (GM) plants expressing toxins from Bacillus thuringiensis (Bt) protect agricultural crops against lepidopteran and coleopteran pests, field-evolved resistance to Bt toxins has been reported for populations of several lepidopteran species. Moreover, some important agricultural pests, like phloem-feeding insects, are not susceptible to Bt crops. Complementary pest control strategies are therefore necessary to assure that the benefits provided by those insect-resistant transgenic plants are not compromised and to target those pests that are not susceptible. Experimental GM plants producing plant protease inhibitors have been shown to confer resistance against a wide range of agricultural pests. In this study we assessed the potential of AtSerpin1, a serpin from Arabidopsis thaliana (L). Heynh., for pest control. In vitro assays were conducted with a wide range of pests that rely mainly on either serine or cysteine proteases for digestion and also with three non-target organisms occurring in agricultural crops. AtSerpin1 inhibited proteases from all pest and non-target species assayed. Subsequently, the cotton leafworm Spodoptera littoralis Boisduval and the pea aphid Acyrthosiphon pisum (Harris) were fed on artificial diets containing AtSerpin1, and S. littoralis was also fed on transgenic Arabidopsis plants overproducing AtSerpin1. AtSerpin1 supplied in the artificial diet or by transgenic plants reduced the growth of S. littoralis larvae by 65% and 38%, respectively, relative to controls. Nymphs of A. pisum exposed to diets containing AtSerpin1 suffered high mortality levels (LC(50) = 637 µg ml(-1)). The results indicate that AtSerpin1 is a good candidate for exploitation in pest control.

Oral Administration of an Enzymatic Protein Hydrolysate from the Green Microalga Chlorella Vulgaris Enhances the Nutritional Recovery of Malnourished Mice

This study examined the effects of oral administration of an enzymatic protein hydrolysate from green microalga Chlorella vulgaris (Cv-PH) on the nutritional recovery of malnourished Balb/c mice after a 3-day fasting period. Mice were refed with commercial diet supplemented or not supplemented with Cv-PH (500 mg/kg) for 8 days. Regardless of the diet used during refeeding, animal body weights and serum protein concentrations did not differ between groups. Mice given Cv-PH had a significant increase in hemoglobin concentrations. Most serum amino acid levels were similar in the control and Cv-PH animals. Starved mice refed with Cv-PH showed normal liver functions, as judged by liver weight, protein concentration, and the enzymatic activities of cholinesterase and arginase. Cv-PH increased DNA, protein content, and gut-mucosal weight. In addition, brush-border oligosaccharidase activities were also higher in the Cv-PH group. These findings suggest that Chlorella protein hydrolysate can be used to develop specific formulations suitable for pharmacologic nutrition.

[One-step Nucleic Acid Amplification (OSNA) Assay for Sentinel Lymph Node Metastases As an Alternative to Conventional Postoperative Histology in Breast Cancer: A Cost-benefit Analysis]

Intraoperative molecular analysis for sentinel lymph node (SLN) metastases using the OSNA (one-step nucleic acid amplification) method has been already validated in breast cancer. The authors compared the cost of OSNA versus the conventional postoperative histopathologic evaluation in patients with breast cancer.

Search for Production of Heavy Particles Decaying to Top Quarks and Invisible Particles in Pp Collisions at ˆs = 1.96  TeV

We present a search for a new particle T' decaying to top quark via T' → t + X, where X is an invisible particle. In a data sample with 4.8  fb(-1) of integrated luminosity collected by the CDF II detector at Fermilab in pp collisions with √s = 1.96  TeV, we search for pair production of T' in the lepton + jets channel, pp → tt + X + X → ℓνbqq'b + X + X. We interpret our results primarily in terms of a model where T' are exotic fourth generation quarks and X are dark matter particles. Current direct and indirect bounds on such exotic quarks restrict their masses to be between 300 and 600  GeV/c2, the dark matter particle mass being anywhere below m(T'). The data are consistent with standard model expectations, and we set 95% confidence level limits on the generic production of T'T' → tt + X + X. For the dark matter model we exclude T' at 95% confidence level up to m(T') = 360  GeV/c2 for m(X) ≤ 100  GeV/c2.

Infestation by Triatomine Bugs in Indigenous Communities of Valledupar, Colombia

To calculate triatomine infestation indices in indigenous communities in Colombia.

Management of Symptomatic Inadvertently Placed Endocardial Leads in the Left Ventricle

There are limited data regarding the clinical care of inadvertently placed endocardial leads in the left ventricle (LV). We clarified the appropriate management within the context of our experience and published literature.

Safety and Efficacy of High-intensity Focused Ultrasound Atop Coronary Arteries During Epicardial Catheter Ablation

Coronary arterial injury continues to be a limitation of epicardial catheter ablation using currently available energy sources. Application of high intensity focused ultrasound (HIFU) energy may avoid such injury due to its theoretical ability to focus energy beyond the ablation element and create lesions at depth.

Trypanosoma Cruzi Coexpressing Ornithine Decarboxylase and Green Fluorescence Proteins As a Tool to Study the Role of Polyamines in Chagas Disease Pathology

Polyamines are essential for Trypanosoma cruzi, the causative agent of Chagas disease. As T. cruzi behaves as a natural auxotrophic organism, it relies on host polyamines biosynthesis. In this paper we obtained a double-transfected T. cruzi parasite that expresses the green fluorescent protein (GFP) and a heterologous ornithine decarboxylase (ODC), used itself as a novel selectable marker. These autotrophic and fluorescent parasites were characterized; the ODC presented an apparent Km for ornithine of 0.51 ± 0.16 mM and an estimated V(max) value of 476.2 nmoles/h/mg of protein. These expressing ODC parasites showed higher metacyclogenesis capacity than the auxotrophic counterpart, supporting the idea that polyamines are engaged in this process. This double-transfected T. cruzi parasite results in a powerful tool-easy to follow by its fluorescence-to study the role of polyamines in Chagas disease pathology and in related processes such as parasite survival, invasion, proliferation, metacyclogenesis, and tissue spreading.

Demodicosis Successfully Treated with Repeated Doses of Oral Ivermectin and Permethrin Cream

Cerebellar Input Configuration Toward Object Model Abstraction in Manipulation Tasks

It is widely assumed that the cerebellum is one of the main nervous centers involved in correcting and refining planned movement and accounting for disturbances occurring during movement, for instance, due to the manipulation of objects which affect the kinematics and dynamics of the robot-arm plant model. In this brief, we evaluate a way in which a cerebellar-like structure can store a model in the granular and molecular layers. Furthermore, we study how its microstructure and input representations (context labels and sensorimotor signals) can efficiently support model abstraction toward delivering accurate corrective torque values for increasing precision during different-object manipulation. We also describe how the explicit (object-related input labels) and implicit state input representations (sensorimotor signals) complement each other to better handle different models and allow interpolation between two already stored models. This facilitates accurate corrections during manipulations of new objects taking advantage of already stored models.

Determination of Fsh Quantity and Bioactivity During Sex Differentiation and Oogenesis in European Sea Bass

Follicle-stimulating hormone (FSH) is a glycoprotein hormone that plays a key role in the regulation of gonadal functions in vertebrates. The present study reports the monitoring of pituitary and plasma Fsh levels during sex differentiation and oogenesis in European sea bass (Dicentrarchus labrax) using a homologous immunoassay and an in vitro bioassay. Both assays were used complementarily for the first time in a fish species. High levels of Fsh bioactivity in plasma were found during the initial phases of sexual differentiation. Plasma and pituitary Fsh (quantity and bioactivity) levels and biological to immunological (B:I) ratios were higher in females than in males, suggesting sexual dimorphism in the synthesis and potency of Fsh. In females, the B:I ratios in adult were lower than during sex differentiation indicating that Fsh would be less biopotent in the adult stage. Plasma Fsh bioactivity levels increased during vitellogenesis, suggesting that Fsh would be involved in the regulation of the midphases of oogenesis, whereas luteinizing hormone would be responsible for the final events.

Mutational Analysis of the LDL Receptor and APOB Genes in Mexican Individuals with Autosomal Dominant Hypercholesterolemia

The goal of this project was to identify families with autosomal dominant hypercholesterolemia (ADH) to facilitate early detection and treatment and to provide genetic counselling as well as to approximate the mutational diversity of ADH in Mexico. Mutational analysis of the LDLR and APOB genes in 62 index cases with a clinical and/or biochemical diagnosis of ADH was performed. Twenty-five mutations (24 LDLR, 1 APOB) were identified in 38 index cases. A total of 162 individuals with ADH were identified using familial segregation analysis performed in 269 relatives of the index cases. In addition, a novel PCSK9 mutation, c.1850 C>A (p.Ala617Asp), was detected. The LDLR mutations showed the following characteristics: (1) four mutations are novel: c.695 -1G>T, c.1034_1035insA, c.1586 G>A, c.2264_2273del; (2) the most common mutations were c.682 G>A (FH-Mexico), c.1055 G>A (FH-Mexico 2), and c.1090 T>C (FH-Mexico 3); (3) five mutations were identified in 3 or more apparently unrelated probands; (4) three mutations were observed in a true homozygous state; and (5) four index cases were compound heterozygous, and one was a carrier of two mutations in the same allele. These results suggest that, in Mexico, ADH exhibits allelic heterogeneity with 5 relatively common LDLR mutations and that mutations in the APOB gene are not a common cause of ADH. This knowledge is important for the genotype-phenotype correlation and for optimising both cholesterol lowering therapies and mutational analysis protocols. In addition, these data contribute to the understanding of the molecular basis of ADH in Mexico.

[Solution to Case 35. Multiple Gastrointestinal Stromal Tumors of the Small Bowel in Association with Neurofibromatosis Type 1]

Role of Reactive Oxygen Species in the Early Stages of Liver Regeneration in Streptozotocin-induced Diabetic Rats

Diabetes mellitus is a risk factor for prognosis after liver resection. In previous work, we found a pro-apoptotic state in the diabetic rat liver. In this work, this was also observed 1 hour post-partial hepatectomy (PH) and resulted in a deficient regenerative response 24 hours post-PH. Treatment with insulin and/or Desferoxamine (DES) (iron chelator) or Tempol (TEM) (free radicals scavenger) was effective in preventing the liver reactive oxygen species (ROS) production induced by diabetic state. High levels of ROS play a role in hepatic lipid peroxidation in diabetes before and after PH, and lead to increased pro-apoptotic events, which contribute to a reduced regenerative response. This becomes of relevance for the potential use of antioxidants/free radical scavengers plus insulin for improvement of post-surgical recovery of diabetic patients subjected to a PH.

Drug-eluting Stents for Off-label Indications in Real Clinical World: Evidence Based or 'intuition' Based Clinical Practice?

BACKGROUND: The use of drug-eluting stents (DES) is an example of the disparity between recommendations given by regulatory agencies and the real clinical world. Such disparity might lead cardiologists to adopt different routines in the use of DES. We aimed to assess variability of off-label DES use between hospitals and to what extent it can be explained by differences in patient or hospital characteristics. METHODS: Characteristics of consecutive patients receiving DES in 29 hospitals were recorded. Individual and hospital determinants of receiving DES for off-label indications were assessed by multilevel logistic regression. RESULTS: 1903 patients were recruited and 1188 (62.4%) received DES for off-label indications. Individual variables associated with off-label use were age (OR 1.01 (1-1.02)), previous percutaneous (OR 2.24 (1.68-2.97)) or surgical (2.41 (1.52-3.84)) revascularization, repeated procedure at the same admission (OR 4.66 (2.7-8.05)), receiving two (OR 4.17 (3.24-5.37)) or three or more DES (OR 14.12 (9.08-21.96)) vs one. Adjusting for individual variables, the Odds of receiving DES for off-label indication was higher in public funding hospitals with surgery availability vs private hospitals: 1.49 (0.86-2.6), and in public hospitals without surgery vs public with surgery availability: OR 1.76 (1.02-3.03). Interhospital variability reminded significant after adjustment for individual and contextual variables. CONCLUSION: Off-label DES use is highly variable between centers. Although this variability is partially determined by hospital type of funding and cardiac surgery availability, the substantial interhospital variability after multilevel adjustment suggests heterogeneity in the process of care.

Optimizing Electrocardiographic Interpretation in Acute ST-elevation Myocardial Infarction May Be Very Beneficial

Posttranscriptional Regulation of the β2-subunit of Cardiac L-type Ca2+ Channels by MicroRNAs During Long-term Exposure to Isoproterenol in Rats

The effects of long-term β-adrenergic administration on the expression levels of the cardiac L-type Ca channel β2 subunit, which regulates channel trafficking and function, were characterized in adult rats.

Prospective Application of Pre-defined Intravascular Ultrasound Criteria for Assessment of Intermediate Left Main Coronary Artery Lesions Results from the Multicenter LITRO Study

This study is a prospective validation of 6 mm(2) as a minimum lumen area (MLA) cutoff value for revascularization of left main coronary artery (LMCA) lesions.

Post Traumatic Splenic Function Depending on Severity of Injury and Management

Because splenectomy has been linked to overwhelming infection years ago, management of splenic traumatisms has become progressively conservative. To assess the immunological function of the spleen in patients with splenic traumatism of different intensity, 43 patients with splenic injury (grades I through V) undergoing either nonoperative management, splenectomy, splenectomy with autotransplantation, or splenic embolization were analyzed for lymphocyte subpopulations and antibody responses to Streptococcus pneumoniae and Haemophilus influenzae vaccinations. Patients treated with splenectomy exhibited a significant decrease in CD4+ T lymphocytes and in Immunoglobulin (Ig) M(high)IgD(low) B cells (related to T-cell independent responses). Median fluorescence intensity of CD54+ in B cells also was reduced. The percent of IgM(high)IgD(low) B cells-a marker of marginal zone function-was inversely correlated with the number of pitted-red blood cells-a marker of red pulp function loss. IgM anti-S pneumoniae identified those patients with a defective rapid response to polysaccharide antigens. These results reinforce the importance of conservative options in the treatment of splenic traumatism for even a severely damaged organ. Despite the significant differences among the groups reported, it remains difficult to predict the IgM response to S pneumoniae vaccine of the individual patients. Better markers to assess splenic function and vaccination response after severe splenic traumatism-even in patients with nonoperative management-might improve risk assessment for overwhelming postsplenectomy infection.

First Measurement of the Angular Coefficients of Drell-Yan E(+)e(-) Pairs in the Z Mass Region from Pp¯ Collisions at ˆs=1.96 TeV

We report on the first measurement of the angular distributions of final state electrons in pp¯ → γ*/Z → e(+)e(-) + X events produced in the Z boson mass region at √s1.96 TeV. The data sample collected by the CDF II detector for this result corresponds to 2.1  fb(-1) of integrated luminosity. The angular distributions are studied as a function of the transverse momentum of the electron-positron pair and show good agreement with the Lam-Tung relation, consistent with a spin-1 description of the gluon, and demonstrate that, at high values of the transverse momentum, Z bosons are produced via quark-antiquark annihilation and quark-gluon Compton processes.

Left and Right Ventricular Power: Outputs Are the Strongest Hemodynamic Correlates to Allow Identification of Acute Responders to Vasodilator Treatment in Idiopathic Pulmonary Arterial Hypertension

Introduction: Despite the prognostic importance of traditionally derived measurements, the significance of right heart catheterization (RHC) remains controversial. Thus, a continued search for hemodynamic markers that define better responsive patients is required. Since, right ventricular failure is the most fatal pathway, right (RVPO) and left (LVPO) ventricular power output are parameters that could provide input for a better understanding of the hemodynamics involved in idiopathic pulmonary artery hypertension (IPAH). Method: We retrospectively analyzed how demographics and outcome correlate with hemodynamics to identify responders among IPAH patients. Results: Ninety patients fulfilled the following criteria for inclusion in this study: (1) complete RHC at baseline; (2) an acute evaluation for vasodilators (AEFV, including a positive response, that is, an increase in CO, a decrease in both mPAP and pulmonary vascular resistance (≥ 20% from baseline, respectively); and (3) a long-term follow-up under accepted IPAH treatments. If RVPO decreased (p < 0.001) and LVPO increased (p < 0.012) during AEFV, it is considered that these findings reinforce our ability to identify responders; that is, patients that remained as responders after 6.4 ± 3 years under nifedipine treatment (37.7% of the studied IPAH population). After multivariate analysis, age, RVPO, and LVPO remained as independent variables (OR = 0.927, 95%CI: 0.87-0.98, p = 0.01; OR = 0.114, 95%CI: 0.00-0.91, p = 0.045; and OR = 171.5, 95% CI: 5.3-549, p = 0.004, respectively) when estimating the probability of being a responder. On this basis, an equation was derived to identify responders among IPAH patients, where the probability of being a responder = 1.0196-0.0631 (age) - 4.7693 (RVPO) + 3.8152 (LVPO), ROC: 0.76, 95% CI: 0.63-0.89; p = 0.001. Conclusion: based on the proposed equation, LVPO and RVPO could be used for the identification of responders among IPAH patients.

Lead Sorption-desorption from Organic Residues

Sorption and desorption are mechanisms involved in the reduction of metal mobility and bioavailability in organic materials. Metal release from substrates is controlled by desorption. The capacity of coffee husk and pulp residues, vermicompost and cow manure to adsorb Pb2+ was evaluated. The mechanisms involved in the sorption process were also studied. Organic materials retained high concentrations of lead (up to 36,000 mg L(-1)); however, the mechanisms of sorption varied according to the characteristics of each material: degree of decomposition, pH, cation exchange capacity and percentage of organic matter. Vermicompost and manure removed 98% of the Pb from solution. Lead precipitated in manure and vermicompost, forming lead oxide (PbO) and lead ferrite (PbFe4O7). Adsorption isotherms did not fit to the typical Freundlich and Langmuir equations. Not only specific and non-specific adsorption was observed, but also precipitation and coprecipitation. Lead desorption from vermicompost and cow manure was less than 2%. For remediation of Pb-polluted sites, the application of vermicompost and manure is recommended in places with alkaline soils because Pb precipitation can be induced, whereas coffee pulp residue is recommended for acidic soils where Pb is adsorbed.

Output of the Working Group on Magnetic Resonance Imaging Abnormalities and Treatment with Amyloid-modifying Agents

Amyloid-related Imaging Abnormalities in Amyloid-modifying Therapeutic Trials: Recommendations from the Alzheimer's Association Research Roundtable Workgroup

Amyloid imaging related abnormalities (ARIA) have now been reported in clinical trials with multiple therapeutic avenues to lower amyloid-β burden in Alzheimer's disease (AD). In response to concerns raised by the Food and Drug Administration, the Alzheimer's Association Research Roundtable convened a working group to review the publicly available trial data, attempts at developing animal models, and the literature on the natural history and pathology of related conditions. The spectrum of ARIA includes signal hyperintensities on fluid attenuation inversion recoverysequences thought to represent "vasogenic edema" and/or sulcal effusion (ARIA-E), as well as signal hypointensities on GRE/T2* thought to represent hemosiderin deposits (ARIA-H), including microhemorrhage and superficial siderosis. The etiology of ARIA remains unclear but the prevailing data support vascular amyloid as a common pathophysiological mechanism leading to increased vascular permeability. The workgroup proposes recommendations for the detection and monitoring of ARIA in ongoing AD clinical trials, as well as directions for future research.

The Alzheimer's Association External Quality Control Program for Cerebrospinal Fluid Biomarkers

The cerebrospinal fluid (CSF) biomarkers amyloid β (Aβ)-42, total-tau (T-tau), and phosphorylated-tau (P-tau) demonstrate good diagnostic accuracy for Alzheimer's disease (AD). However, there are large variations in biomarker measurements between studies, and between and within laboratories. The Alzheimer's Association has initiated a global quality control program to estimate and monitor variability of measurements, quantify batch-to-batch assay variations, and identify sources of variability. In this article, we present the results from the first two rounds of the program.

Early Life Mammalian Biology and Later Life Physical Performance: Maximising Physiological Adaptation

The malleability of mammalian biology during early life, which carries considerable weight throughout the course of the lifespan, may contribute to the creation of a human phenotype ideal for prime physical performance. In this article, the authors consider the East African cohort of exceptional athletes that dominate marathon performance. Since entering international marathon competition in 1960, East Africans have competed at the front of the pack and now hold the top 10 men's marathon times. The authors present lines of evidence supporting that exposure to factors such as altitude and early metabolic adjustments that are inherent in East African early life exert a strong influence in later life physical performance and may collide with a genetic advantage to induce biological changes that allow for a more robust biological response to training in later life.

Interaction Between Brush Layers of Bottle-brush Polyelectrolytes: Molecular Dynamics Simulations

Interactions between tethered layers composed of aggrecan (charged bottle-brush) macromolecules are responsible for the molecular origin of cartilage biomechanical behavior. To elucidate the role of the electrostatic forces in interaction between bottle-brush layers, we have performed molecular dynamics simulations of charged and neutral bottle-brush macromolecules tethered to substrates. In the case of charged bottle-brush layers, the disjoining pressure P between two brush layers in salt-free solutions increases with decreasing distance D between substrates as P ∝ D(-1.8). A stronger dependence of the disjoining pressure P on the surface separation D was observed for neutral bottle-brushes, P ∝ D(-4.6), in the same interval of disjoining pressures. These scaling laws for dependence of disjoining pressure P on distance D are due to bending energy of the bottle-brush macromolecules within compressed brush layers. The weaker distance dependence observed in polyelectrolyte bottle-brushes is due to interaction between counterion clouds surrounding the bottle-brush macromolecules preventing strong brush overlap.

C4 Grasses Prosper As Carbon Dioxide Eliminates Desiccation in Warmed Semi-arid Grassland

Global warming is predicted to induce desiccation in many world regions through increases in evaporative demand. Rising CO(2) may counter that trend by improving plant water-use efficiency. However, it is not clear how important this CO(2)-enhanced water use efficiency might be in offsetting warming-induced desiccation because higher CO(2) also leads to higher plant biomass, and therefore greater transpirational surface. Furthermore, although warming is predicted to favour warm-season, C(4) grasses, rising CO(2) should favour C(3), or cool-season plants. Here we show in a semi-arid grassland that elevated CO(2) can completely reverse the desiccating effects of moderate warming. Although enrichment of air to 600 p.p.m.v. CO(2) increased soil water content (SWC), 1.5/3.0 °C day/night warming resulted in desiccation, such that combined CO(2) enrichment and warming had no effect on SWC relative to control plots. As predicted, elevated CO(2) favoured C(3) grasses and enhanced stand productivity, whereas warming favoured C(4) grasses. Combined warming and CO(2) enrichment stimulated above-ground growth of C(4) grasses in 2 of 3 years when soil moisture most limited plant productivity. The results indicate that in a warmer, CO(2)-enriched world, both SWC and productivity in semi-arid grasslands may be higher than previously expected.

Immune Correlates of HIV Control

The development of an effective HIV vaccine is still hampered by the lack of clearly defined immune correlates of HIV control. Although a number of immune markers have been associated over last years with relative viral control and slower HIV disease progression, these associations are oftentimes complicated by the causality dilemma that does not allow to directly assign cause or effect to the identified parameters. In addition, many of these immune markers may act in concert or represent surrogate makers for otherwise controlled HIV infection. This review will revisit the current knowledge of host genetic and immune markers and their associations with HIV control, particularly examining the roles of virus-specific T cells and humoral immune responses and testing their role as direct correlates of control.

EBM in Primary Care: a Qualitative Multicenter Study in Spain

Evidence based medicine (EBM) has made a substantial impact on primary care in Spain over the last few years. However, little research has been done into family physicians (FPs)' attitudes related to EBM. The present study investigates FPs' perceptions of EBM in the primary care context.

A Single Exposure to Voluntary Ethanol Self-administration Produces Adaptations in Ethanol Consumption and Accumbal Dopamine Signaling

In well-trained animals, accumbal dopamine release is stimulated during operant ethanol self-administration, but the time course of development of this dopaminergic response, particularly during the acquisition of ethanol drinking behavior, remains unknown. To examine this, we trained male Long-Evans rats to self-administer 10% ethanol plus 10% sucrose, using a protocol in which the concentration of ethanol was kept constant throughout the study. The animals were required to press the lever four times to gain continuous access to the drinking solution for 20 minutes, and microdialysis was performed on either the first or second day of 10% ethanol plus 10% sucrose self-administration or 10% sucrose as controls. Ethanol and dopamine were both analyzed in the dialysates. All groups (day 1 and 2 ethanol and their corresponding sucrose controls) showed an increase in accumbal dopamine during the transfer from the home cage into the operant chamber. Our main finding was an increase in dopamine in the nucleus accumbens core-shell border during the first 5 minutes of consumption on the second day but not on the first day of ethanol self-administration. Our results suggest that a single exposure to a 10% ethanol plus 10% sucrose drinking solution may be sufficient to learn the association between ethanol cues and its reinforcing properties. Furthermore, we speculate that the dopamine response during ethanol consumption likely reflects the reward-prediction role of the mesolimbic dopamine system.

Search for a Very Light CP-odd Higgs Boson in Top Quark Decays from Pp Collisions at Sqrt(s)]=1.96  TeV

We present the results of a search for a very light CP-odd Higgs boson a(1)(0) originating from top quark decays t → H(±)b → W(±(*)) a(1)(0)b, and subsequently decaying into τ+ τ-. Using a data sample corresponding to an integrated luminosity of 2.7  fb(-1) collected by the CDF II detector in pp collisions at 1.96 TeV, we perform a search for events containing a lepton, three or more jets, and an additional isolated track with transverse momentum in the range 3 to 20  GeV/c. Observed events are consistent with background sources, and 95% C.L. limits are set on the branching ratio of t → H(±)b for various masses of H(±) and a(1)(0).

Interferon-α2b and Transforming Growth Factor-β1 Treatments on HCC Cell Lines: Are Wnt/β-catenin Pathway and Smads Signaling Connected in Hepatocellular Carcinoma?

Wnt/β-catenin pathway is often dysregulated in hepatocellular carcinoma (HCC). Activated β-catenin accumulates in the cytosol and nucleus and forms a nuclear complex with TCF/LEF factors like TCF4. Interferon-α (IFN-α) has recently been recognized to harbor therapeutic potential in prevention and treatment of HCC. Transforming Growth Factor-β1 (TGF-β1) is a mediator of apoptosis, exerting its effects via Smads proteins. One mode of interaction between Wnt/β-catenin and TGF-β1/Smads pathways is the association of Smads with β-catenin/TCF4. In this study we analyzed the effects of IFN-α2b and TGF-β1 treatments on Wnt/β-catenin pathway, Smads proteins levels, β-catenin/TCF4/Smads interaction and proliferation and apoptotic death in HepG2/C3A and Huh7 cell lines. IFN-α2b and TGF-β1 attenuated Wnt/β-catenin signal by decreasing β-catenin and Frizzled7 receptor proteins contents and the interaction of β-catenin with TCF4. Truncated β-catenin form present in C3A cell line also diminished after treatments. Both cytokines declined Smads proteins and their interaction with TCF4. The overall cellular response to cytokines was the decrease in proliferation and increase in apoptotic death. Treatment with Wnt3a, which elevates β-catenin protein levels, also generated the increment of Smads proteins contents when comparing with untreated cells. In conclusion, IFN-α2b and TGF-β1 proved to be effective as modulators of Wnt/β-catenin pathway in HCC cell lines holding both wild-type and truncated β-catenin. Since the inhibition of β-catenin/TCF4/Smads complexes formation may have a critical role in slowing down oncogenesis, IFN-α2b and TGF-β1 could be useful as potential treatments in patients with HCC.

Anidulafungin in Treatment of Experimental Invasive Infection by Candida Parapsilosis: in Vitro Activity, (1-->3)-beta-D-glucan and Mannan Serum Levels, Histopathological Findings, and in Vivo Efficacy

We have evaluated the in vitro activity of anidulafungin (AFG) against 31 strains of Candida parapsilosis sensu stricto by using broth microdilution, disk diffusion, and minimal fungicidal concentration (MFC) determination procedures. The two first methods showed a high level of activity of the drug, while MFCs were 1 to 5 dilutions higher than their corresponding MICs. To assess if MICs were predictive of in vivo outcomes, six strains representing different AFG MICs (0.12 to 2 μg/ml) were tested in a murine model of disseminated infection treated with different doses of the drug (1, 5, or 10 mg/kg of body weight). AFG was able to prolong the survival of mice infected with all the strains tested but was able to reduce the tissue burden of those mice infected only with the strains that showed the lowest MIC (0.12 μg/ml).

Chest Compressions Versus Ventilation Plus Chest Compressions: a Randomized Trial in a Pediatric Asphyxial Cardiac Arrest Animal Model

To compare survival, oxygenation, ventilation, and hemodynamic variables achieved with chest compressions or ventilation plus chest compressions.

The Meyerhoff Way: How the Meyerhoff Scholarship Program Helps Black Students Succeed in the Sciences

The Meyerhoff Scholarship Program (MSP) is widely recognized for its comprehensive approach of integrating students into the science community. The supports provided by the program aim to develop students, primarily Blacks, into scientists by offering them academic, social, and professional opportunities to achieve their academic and career goals. The current study allowed for a rich understanding of the perceptions of current Meyerhoff students and Meyerhoff alumni about how the program works. Three groups of MSP students were included in the study: 1) new Meyerhoff students participating in Summer Bridge (n=45), 2) currently enrolled Meyerhoff students (n=92), and 3) graduates of the MSP who were currently enrolled in STEM graduate studies or had completed an advanced STEM degree (n=19). Students described the importance of several key aspects of the Meyerhoff Scholars Program: financial support, the Summer Bridge Program, formation of Meyerhoff identity, belonging to the Meyerhoff family, and developing networks - all of which serve to integrate students both academically and socially.

Glutamate and the Aggression Neural Circuit in Adolescent Anabolic Steroid-treated Syrian Hamsters (Mesocricetus Auratus)

Adolescent exposure to anabolic androgenic steroids (AAS) alters the development and activity of the glutamate neural system in the latero-anterior hypothalamus (LAH) in hamsters (Mesocricetus auratus); that is, an important neural component of the adolescent AAS-induced aggressive response. In this article, we used retrograde tracing to investigate glutamate-specific alterations in the connections between the LAH and several other nuclei implicated in adolescent AAS-induced aggression. Briefly, hamsters were treated with AAS or sesame-oil control during adolescence and then microinjected with retrograde tracer into the medial amygdala (MeA), lateral septum (LS), or bed nucleus of the stria terminalis (BNST). Brains were then processed for vesicular glutamate transporter 2 (VGLUT2) and examined for AAS-induced changes in the number VGLUT2 cells containing retrograde tracer (VGLUT2/tracer) within the LAH. It is interesting to note that while aggressive AAS-treated hamsters injected retrograde tracer into the MeA showed a significant reduction in the number of VGLUT2/tracer cells in the LAH, aggressive AAS-treated hamsters injected tracer into the BNST showed a significant increase in the number of VGLUT2/tracer cells in the LAH when compared with controls. Last, AAS hamsters injected with tracer into the LS had a comparable number of LAH-VGLUT2/tracer cells to controls. The current results indicate that glutamate likely functions as the major aggression output system from the LAH and that adolescent AAS treatment significantly alters the neural circuitry modulating aggression. Moreover, increases in the number of glutamate projections from the LAH to the BNST in AAS hamsters identify the BNST as an area particularly important for the regulation of AAS-induced aggression.

Activation of Human Neutrophils by Oleic Acid Involves the Production of Reactive Oxygen Species and a Rise in Cytosolic Calcium Concentration: a Comparison with N-6 Polyunsaturated Fatty Acids

There is a growing body of evidence showing that dietary constituents and lipids in particular, influence the function of the human immune system. However, although the beneficial effects of oleic acid (OA) are clear, its mechanism of action at the molecular level is poorly understood.

First Search for Multijet Resonances in Sqrt(s) = 1.96  TeV Pp Collisions

We present the first model independent search for three-jet hadronic resonances within multijet events in sqrt(s) = 1.96  TeV pp collisions at the Fermilab Tevatron using the CDF II detector. Pair production of supersymmetric gluinos and squarks with hadronic R-parity violating decays is employed as an example of a new physics benchmark for this signature. Selection criteria based on the kinematic properties of an ensemble of jet combinations within each event help to extract signal from copious QCD background. No significant excess outside the top quark mass window is observed in data with an integrated luminosity of 3.2  fb(-1). We place 95% confidence level limits on the production cross section σ(pp → XX')×BR(gg → 3  jet + 3  jet) where X, X' = g, q, or q, with q, q → g + jet, as a function of gluino mass, in the range of 77  GeV/c2 to 240  GeV/c2.

Search for New Dielectron Resonances and Randall-Sundrum Gravitons at the Collider Detector at Fermilab

A search for new dielectron-mass resonances using data recorded by the CDF II detector and corresponding to an integrated luminosity of 5.7  fb(-1) is presented. No significant excess over the expected standard model prediction is observed. In this data set, an event with the highest dielectron mass ever observed (960  GeV/c(2)) was recorded. The results are interpreted in the Randall-Sundrum (RS) model. Combined with the 5.4  fb(-1) diphoton analysis, the RS-graviton lower-mass limit for the coupling k/M¯(Pl)=0.1 is 1058  GeV/c(2), making it the strongest limit to date.

Limits on Anomalous Trilinear Gauge Couplings in Zγ Events from Pp¯ Collisions at ˆs=1.96  TeV

Using Zγ candidate events collected by the CDF detector at the Tevatron Collider, we search for potential anomalous (non-standard-model) couplings between the Z boson and the photon. Zγ couplings vanish at tree level and are heavily suppressed at higher orders; hence any evidence of couplings indicates new physics. Measurements are performed using data corresponding to an integrated luminosity of 4.9  fb(-1) in the Z→νν¯ decay channel and 5.1  fb(-1) in the Z→l(+)l(-) (l=μ, e) decay channels. The combination of these measurements provides the most stringent limits to date on Zγ trilinear gauge couplings. Using an energy scale of Λ=1.5  TeV to allow for a direct comparison with previous measurements, we find limits on the CP-conserving parameters that describe Zγ couplings to be |h(3)(γ,Z)|<0.022 and |h(4)(γ,Z)|<0.0009. These results are consistent with standard model predictions.

Neuropsychiatric Symptoms in Alzheimer's Disease

Neuropsychiatric symptoms (NPS) are core features of Alzheimer's disease and related dementias. Once thought to emerge primarily in people with late-stage disease, these symptoms are currently known to manifest commonly in very early disease and in prodromal phases, such as mild cognitive impairment. Despite decades of research, reliable treatments for dementia-associated NPS have not been found, and those that are in widespread use present notable risks for people using these medications. An Alzheimer's Association Research Roundtable was convened in the spring of 2010 to review what is known about NPS in Alzheimer's disease, to discuss classification and underlying neuropathogenesis and vulnerabilities, and to formulate recommendations for new approaches to tailored therapeutics.

Cranial Trepanation in Sinuhe the Egyptian

INTRODUCTION: Medicine and literature have been linked from ancient times; proof of this shown by the many doctors who have been dedicated to Literature and many writers have described medical activities and illnesses in their works. An example is Sinuhe, the Egyptian from the work of Mika Waltari that masterly narrates the medical activity of the protagonist and describes the trepanation technique. DEVELOPMENT: The present work begins with the analysis of trepanations since Prehistory and illustrates the practice of the trepanation in Sinuhe, the Egyptian. Trepanation is mentioned often in this work and it is illustrated how to practice it and which instruments are required to perform it. Trepanation is one of the oldest surgical interventions carried out with a therapeutic purpose in cranial traumatism and in neurological diseases, but also with a magic-religious purpose in order to expel the evil spirits which caused the mental illness or the epilepsy and migraine symptoms. CONCLUSIONS: Trepanation is a surgical practice carried out since Prehistory in cranial traumatisms epilepsy, migraines and psychiatric illness. In the book Sinuhe the Egyptian it illustrates the trepan, the trepanation technique and the required set of instruments in full detail.

A Randomized, Double-blind, Pilot Study of Rifaximin 550 Mg Versus Placebo in the Prevention of Travelers' Diarrhea in Mexico During the Dry Season

Rifaximin has been shown to be effective in treating and preventing travelers' diarrhea (TD) during the summer season.

Expression of a Secreted Version of the Hemagglutinin-neuraminidase Glycoprotein of Newcastle Disease Virus: Its Evaluation As a Diagnostic Reagent

The hemagglutinin-neuraminidase (HN) glycoprotein of Newcastle disease virus (NDV) constitutes, together with the fusion glycoprotein, the main surface antigen of this avian pathogen, which causes a highly contagious disease, relevant economically worldwide. The purpose of this work was to obtain the HN glycoprotein as a soluble antigen in culture supernatants of recombinant baculovirus-infected Spodoptera frugiperda (Sf9) cells and to evaluate its application to the development of a recombinant enzyme-linked immunosorbent assay (rELISA) for the analysis of chicken sera. A transfer vector for baculovirus containing the sequence of a melittin signal peptide was constructed and the sequence coding for HN protein without its own signal peptide was cloned. The recombinant protein was secreted and recovered easily from the culture medium of Sf9-infected cells. The recombinant protein was evaluated as antigen for ELISA coating the plates with the recovered HN using 79 positive and 142 negative samples. The Cohen kappa value resulted 0.91, indicating excellent agreement between the rELISA and the hemagglutinin inhibition tests. The rELISA was also compared with a commercial ELISA, finding high levels of agreement between both assays. The present results show that the cloning strategy developed yielded the HN protein free in the cell culture supernatant and that the recombinant protein retained its reactivity with anti-NDV HN antibodies in chicken sera.

Prey-stage Preferences and Functional and Numerical Responses of Amblyseius Largoensis (Acari: Phytoseiidae) to Raoiella Indica (Acari: Tenuipalpidae)

Raoiella indica Hirst (Acari: Tenuipalpidae) is a phytophagous mite that recently invaded the Western Hemisphere. This mite is a multivoltine and gregarious species that can reach very high population densities and cause significant damage to various palm species (Arecaceae). The predatory mite Amblyseius largoensis (Muma) (Acari: Phytoseiidae) has been found associated with R. indica in Florida. This study evaluated A. largoensis for potential to control R. indica by (1) determining predator preferences among developmental stages of R. indica, and (2) estimating predator functional and numerical responses to varying densities of its most preferred prey-stage. Under no-choice conditions A. largoensis consumed significantly more eggs than other stages of R. indica. In choice tests A. largoensis showed a significant preference for R. indica eggs over all other prey stages. Amblyseius largoensis displayed a type II functional response showing an increase in number of prey killed with an increase in prey population density. Consumption of prey stabilized at approximately 45 eggs/day, the level at which oviposition by the predator was maximized (2.36 ± 0.11 eggs/day; mean ± SEM). Results of this study suggest that A. largoensis can play a role in controlling R. indica populations, particularly when prey densities are low.

Host Plant Range of Raoiella Indica (Acari: Tenuipalpidae) in Areas of Invasion of the New World

Raoiella indica has spread rapidly through the Neotropical region where the mite damages economically and ecologically important plants. Three studies were conducted to determine the host plant range of R. indica, using the presence of colonies containing all life stages as an indicator of reproductive suitability. Periodic surveys at the Fairchild Tropical Botanic Garden (Miami Dade County, FL, USA) and the Royal Botanical Gardens (Port of Spain, Trinidad and Tobago) identified 27 new reproductive host plants. The reproductive suitability of two dicotyledonous species and three native Florida palm species was examined. An updated list of reproductive host plants of R. indica is presented. All reported reproductive hosts (91 plant species) of R. indica are monocots from the orders Arecales (Arecaceae), Zingiberales (Heliconiaceae, Musaceae, Strelitziaceae, Zingiberaceae) and Pandanales (Pandanaceae). Most are palms of the family Arecaceae that originated in areas of the Eastern Hemisphere; about one fourth of the reported hosts are native to the New World and could be considered new host associations of R. indica. Six years after the initial detection in the Caribbean, R. indica has expanded its host plant range. Here we report 27 new reproductive host of R. indica that represent 30% of increase on previous host plant records. As this mite continues spreading in the Neotropical region a great diversity of plants is potentially affected.

Coarse-grained Representation of Protein Flexibility. Foundations, Successes, and Shortcomings

Flexibility is the key magnitude to understand the variety of functions of proteins. Unfortunately, its experimental study is quite difficult, and in fact, most experimental procedures are designed to reduce flexibility and allow a better definition of the structure. Theoretical approaches have become then the alternative but face serious timescale problems, since many biologically relevant deformation movements happen in a timescale that is far beyond the possibility of current atomistic models. In this complex scenario, coarse-grained simulation methods have emerged as a powerful and inexpensive alternative. Along this chapter, we will review these coarse-grained methods, and explain their physical foundations and their range of applicability.

Prevention Trials in Alzheimer's Disease: an EU-US Task Force Report

Despite enormous financial and scientific efforts, still no approved disease-modifying therapies exist for Alzheimer's disease (AD). During the last decade all Phase III clinical trials on disease modifiers in AD have failed. The dementia stage of AD being probably too late in order to allow for successful disease modification has been identified as a possible culprit that could explain the failure of so many clinical trials. In parallel, a major development in the diagnostic research field of AD was achieved by the recent proposal of new diagnostic criteria for AD, which also specifically incorporate the use of biomarkers as defining criteria for preclinical stages of AD, thus extending the traditional definition of disease to very early stages that may be a more feasible target for various disease modifying therapeutic interventions. This ongoing paradigm shift in AD definition and diagnosis represents a fundamental basis for redefinition of interventional trials in AD, allowing to specifically focus on preventative measures during very early pathophysiologically confirmed stages of disease. This consensus paper reflects the outcome from a European Union and North American Task Force meeting comprised of experts from academia, industry, private foundations, and regulatory agencies that was convened in Toulouse, France on November 5, 2010 and that focused on prevention trials in AD. This position paper thoroughly analyzes prerequisites for successful preventative trials in AD and concludes with concrete recommendations on biomarkers, statistical tools and other variables important for improved study designs suitable for preventative as well as for early therapeutic interventional trials in AD.

Prognostic Factors in Patients with Minor Salivary Gland Carcinoma of the Oral Cavity and Oropharynx

This study was performed to define prognostic factors and management of minor salivary gland carcinoma of the oral cavity and oropharynx .

Enantioselective Cooperativity Between Intra-receptor Interactions and Guest Binding: Quantification of Reinforced Chiral Recognition

Yard Flooding by Irrigation Canals Increased the Risk of West Nile Disease in El Paso, Texas

To investigate the effects of use of water from irrigation canals to flood residential yards on the risk of West Nile disease in El Paso, Texas.

A Novel Model to Predict Cutaneous Finger Blood Flow Via Finger and Rectal Temperatures

To generate a model that predicts fingertip blood flow (BF(f) ) and to cross-validate it in another group of subjects.

Endotracheal Tube Size Does Not Affect Time to Extubation in Adult Cardiac Surgery

Managed care over the last 20 years has brought considerable attention to the impact of clinical variables on time to extubation in adult cardiac surgery. One variable that has not yet been analyzed is the endotracheal tube (ETT) size. Our retrospective electronic database review was performed on adult subjects that had a primary, non-emergent cardiac surgery in the last four years. The records of 936 patients were analyzed to find 193 patients meeting inclusion criteria. Due to the low number of 7.0 ETTs used in the study, this group was eliminated from analysis. The means for times to extubation for the two remaining groups were 7:45 standard deviation (SD) 4:27 (hrs:min) and 7:30 SD 4:48 (hrs:min) for patients managed with 8.0 and 9.0 ETTs respectively, with no statistically significant differences between the tube sizes p=0.2389. Analysis of variance did not demonstrate a statistically significant impact with age (p=0.3199), gender (p=0.5394), body mass index (BMI) (p=0.4060), nor intravenous (IV) anesthetic adjuvants midazolam (p= 0.4815) or opiates (p=0.3617) used in the operating room (OR), but length of time on cardiopulmonary bypass did play a role (p=0.0274). These data suggest that the size of the ETT utilized during cardiovascular surgery in adult patients does not play a role in the length of time of postoperative ventilation.

Oleic Acid Inhibits Store-operated Calcium Entry in Human Colorectal Adenocarcinoma Cells

AIMS: Much evidence indicates the association between dietary fat and colorectal cancer risk. However, most of the studies focus on polyunsaturated fatty acids, and little is known about the role of monounsaturated ones and their precise mechanism of action. Being store-operated Ca(2+) entry (SOCE) a Ca(2+) influx pathway involved in the control of multiple cellular and physiological processes including cell proliferation, we studied the effect of oleic acid in Ca(2+) signals of colorectal cancer cells, paying particular attention to SOCE. METHODS: Carbachol was used to induce SOCE in Fura 2-loaded HT29 cells. We tested a saturated fatty acid to compare the physiological relevance of our results. RESULTS: We show that oleic acid is a potent inhibitor of SOCE. By contrast, stearic acid failed to have a SOCE-inhibitory effect. The SOCE-inhibition induced by oleic acid was protein kinase C-independent and restored by albumin. We also demonstrated that oleic acid induced increases in [Ca(2+)](i). The novelty of our report is that little variability in the concentration could end in a large different physiological effect. CONCLUSIONS: In conclusion, we suggest a physiological pathway for the beneficial effect of oleic acid in colon carcinoma cells.

Adaptive Cerebellar Spiking Model Embedded in the Control Loop: Context Switching and Robustness Against Noise

This work evaluates the capability of a spiking cerebellar model embedded in different loop architectures (recurrent, forward, and forward&recurrent) to control a robotic arm (three degrees of freedom) using a biologically-inspired approach. The implemented spiking network relies on synaptic plasticity (long-term potentiation and long-term depression) to adapt and cope with perturbations in the manipulation scenario: changes in dynamics and kinematics of the simulated robot. Furthermore, the effect of several degrees of noise in the cerebellar input pathway (mossy fibers) was assessed depending on the employed control architecture. The implemented cerebellar model managed to adapt in the three control architectures to different dynamics and kinematics providing corrective actions for more accurate movements. According to the obtained results, coupling both control architectures (forward&recurrent) provides benefits of the two of them and leads to a higher robustness against noise.

[Coronary Disease Extension Determines Mobilization of Endothelial Progenitor Cells and Cytokines After a First Myocardial Infarction with ST Elevation]

Multivessel coronary disease is still a postinfarction prognostic marker despite new forms of reperfusion, such as primary angioplasty. The aim of this study was to determine the time sequence of various sets of endothelial progenitor cells and angiogenic cytokines (vascular endothelial growth factor, hepatocyte growth factor) according to the degree of extension of the postinfarction coronary disease.

A Review of the Natural Enemies of the Red Palm Mite, Raoiella Indica (Acari: Tenuipalpidae)

A review of all the available information about the natural enemies reported in association with the red palm mite, Raoiella indica is presented. Twenty-eight species of predatory arthropods, including mites and insects, have been reported in association with R. indica in Asia, Africa and the Neotropics. In addition, pathogenic fungi associated with R. indica in the Caribbean have been reported. The available literature indicates that each site has a different natural enemy complex with only one predator species, Amblyseius largoensis (Acari: Phytoseiidae), present in all the geographical areas. The phytoseiids, Amblyseius caudatus Berlese, Amblyseius channabasavanni Gupta and A. largoensis, were regarded as important natural enemies of R. indica, and their predatory efficiency was studied in some detail. Among the predatory insects the coccinellids Stethorus keralicus Kapur and Telsimia ephippiger Chapin were reported as major predators of R. indica. The known distribution, abundance and relative importance of each species reported in association with R. indica are discussed.

Changes in Radial Artery Volume Assessed Using Intravascular Ultrasound: a Comparison of Two Vasodilator Regimens in Transradial Coronary Interventions

This study used intravascular ultrasound (IVUS) to evaluate radial artery volume changes after intraarterial administration of nitroglycerin and/or verapamil.

A Regional Health Collaborative Formed By NewYork-Presbyterian Aims to Improve the Health of a Largely Hispanic Community

Communities of poor, low-income immigrants with limited English proficiency and disproportionate health burdens pose unique challenges to health providers and policy makers. NewYork-Presbyterian Hospital developed the Regional Health Collaborative, a population-based health care model to improve the health of the residents of Washington Heights-Inwood. This area is a predominantly Hispanic community in New York City with high rates of asthma, diabetes, heart disease, and depression. NewYork-Presbyterian created an integrated network of patient-centered medical homes to form a "medical village" linked to other providers and community-based resources. The initiative set out to document the priority health needs of the community, target high-prevalence conditions, improve cultural competence among providers, and introduce integrated information systems across care sites. The first six months of the program demonstrated a significant 9.2 percent decline in emergency department visits for ambulatory care-sensitive conditions and a 5.8 percent decrease in hospitalizations that was not statistically significant. This initiative offers a model for other urban academic medical centers to better serve populations facing social and cultural barriers to care.

Effectiveness of Pulse Oximetry Versus Fetal Electrocardiography for the Intrapartum Evaluation of Nonreassuring Fetal Heart Rate

To compare the effectiveness of pulse oximetry and fetal electrocardiography in the management of labor with nonreassuring fetal heart rate (NRFHR).

Observation of the Ξ(b)(0) Baryon

The observation of the bottom, strange baryon Ξ(b)(0) through the decay chain Ξ(b)(0)→Ξ(c)(+)π-, where ΞΞ(c)(+)→Ξ- π+ π+, Ξ-→Λπ-, and Λ→pπ-, is reported by using data corresponding to an integrated luminosity of 4.2  fb(-1) from pp collisions at square root(s)=1.96  TeV recorded with the Collider Detector at Fermilab. A signal of 25.3(-5.4)(+5.6) candidates is observed whose probability of arising from a background fluctuation is 3.6×10(-12), corresponding to 6.8 gaussian standard deviations. The Ξ(b)(0) mass is measured to be 5787.8±5.0(stat)±1.3(syst)  MeV/c2. In addition, the Ξ(b)- baryon is observed through the process Ξ(b)-→Ξ(c)(0)π-, where Ξ(c)(0)→Ξ- π+, Ξ-→Λπ-, and Λ→pπ-.

Measurement of the Cross Section for Prompt Isolated Diphoton Production in Pp Collisions at Square Root(s) = 1.96  TeV

This Letter reports a measurement of the cross section of prompt isolated photon pair production in pp collisions at a total energy square root(s)=1.96  TeV using data of 5.36  fb(-1) integrated luminosity collected with the CDF II detector at the Fermilab Tevatron. The measured cross section, differential in basic kinematic variables, is compared with three perturbative QCD predictions, a leading order parton shower calculation and two next-to-leading order calculations. The next-to-leading order calculations reproduce most aspects of the data. By including photon radiation from quarks before and after hard scattering, the parton shower prediction becomes competitive with the next-to-leading order predictions.

Metformin Reduces Risk of Ovarian Hyperstimulation Syndrome in Patients with Polycystic Ovary Syndrome During Gonadotropin-stimulated In Vitro Fertilization Cycles: a Randomized, Controlled Trial

To test whether metformin administration reduces the incidence of ovarian hyperstimulation syndrome (OHSS) in infertile high-risk patients with polycystic ovary syndrome (PCOS) who have been treated with gonadotropins for IVF.

PH-Driven Dynamic Stereoinduction: Epimerization Upon Dimerization in Rhenium(I) Complexes

Stereochemistry at the metal centre in a Re(I) complex can be modified by manipulating the pH: while acidic conditions favour a monomeric system, basic conditions induce a dimerization which concomitantly epimerizes the metal centre.

A Holistic Approach for the Detection of Media-adventitia Border in IVUS

In this paper we present a methodology for the automatic detection of media-adventitia border (MAb) in Intravascular Ultrasound. A robust computation of the MAb is achieved through a holistic approach where the position of the MAb with respect to other tissues of the vessel is used. A learned quality measure assures that the resulting MAb is optimal with respect to all other tissues. The mean distance error computed through a set of 140 images is 0.2164 (+/- 0.1326) mm.

Maternal Hemoglobin Concentration and Adverse Pregnancy Outcomes at Low and Moderate Altitudes in Peru

Objective: To identify associations of maternal hemoglobin (Hb) with perinatal outcomes at low and moderate altitudes in Peru. Methods: Study of records with sequential information using perinatal database system. The study included 295 651 pregnant women with their products. Using multiple logistic regression analysis, we estimated the probability of stillbirths, preterm and small for gestational age (SGA) births associated with maternal Hb levels at low (0-1999 m) and moderate altitudes (2000-2999 m). Results: Maternal Hb decreased as pregnancy progressed from first to third trimester at both altitudes. Hb was higher at moderate than at low altitude (p < 0.001). Risks for stillbirths increased with low maternal Hb (odds ratio [OR]: 1.39 for Hb 9-9.9; OR: 1.84 for Hb 8-8.9; OR: 3.25 for Hb 7-7.9; and OR: 7.8 for Hb <7 g/dl); with Hb higher than 14.5 g/dl (OR: 1.31) and with altitudes ≥2000 m (OR: 1.2). High preterm rates were also observed with low Hbs (OR: 1.16 for Hb 9-9.9; OR: 1.64 for Hb 8-8.9; OR: 2.25 for Hb 7-7.9; and OR:2.87 for Hb<7 g/dl) and with Hb higher than 14.5 g/dl (OR: 1.14). High SGA rates were observed in neonates with maternal Hb of 7-7.9 (OR: 1.35) and <7 g/dl (OR:1.57), and higher than 14.5 g/dl (OR: 1.33), and with moderate altitudes (OR: 1.12). The cut-off points for lower risks of stillbirth and preterm births was 10 g/dl, and for SGA 9 g/dl of hemoglobin. Conclusion: Low and high maternal Hb levels and moderate altitude were independent risk factors for adverse perinatal outcomes.

Laser Lead Extraction in the Octogenarian Patient

In the United States, patients aged >75 years are the most rapidly growing segment in the population, with an expected increase of 126% by 2050. These patients account for >70% of the pacemakers and up to two thirds of the implantable cardioverter-defibrillators implanted annually. Our aim was to explore the clinical outcomes of device complications in the octogenarian population.

Organocatalytic Enantioselective (3+2) Cycloaddition Using Stable Azomethine Ylides

We have developed a highly efficient procedure for carrying out the catalytic enantioselective (3+2) cycloaddition between enals and stable azomethine ylides such as isoquinolinium and phthalizinium methylides. Under the optimized reaction conditions highly substituted chiral pyrroloisoquinolines and pyrrolophthalazines have been obtained in high yields and excellent diastereo- and enantioselectivities.

Complexity and Safety

Evidence for Sequenced Molecular Evolution of IDH1 Mutant Glioblastoma from a Distinct Cell of Origin

Mutation in isocitrate dehydrogenase 1 (IDH1) at R132 (IDH1(R132MUT)) is frequent in low-grade diffuse gliomas and, within glioblastoma (GBM), has been proposed as a marker for GBMs that arise by transformation from lower-grade gliomas, regardless of clinical history. To determine how GBMs arising with IDH1(R132MUT) differ from other GBMs, we undertook a comprehensive comparison of patients presenting clinically with primary GBM as a function of IDH1(R132) mutation status.

Safety and Feasibility of Percutaneous Retrograde Coronary Sinus Delivery of Autologous Bone Marrow Mononuclear Cell Transplantation in Patients with Chronic Refractory Angina

Chronic refractory angina is a challenging clinical problem with limited treatment options. The results of early cardiovascular stem cell trials using ABMMC have been promising but have utilized intracoronary or intramyocardial delivery. The goal of the study was to evaluate the safety and early efficacy of autologous bone marrow derived mononuclear cells (ABMMC) delivered via percutaneous retrograde coronary sinus perfusion (PRCSP) to treat chronic refractory angina (CRA).

Management of Cardiac Device-related Infections: A Review of Protocol-driven Care

BACKGROUND: The prevalence of cardiac device-related infections (CDIs) has mirrored the unprecedented increase in device usage. CDIs are currently one of the leading indications for extraction. Despite this, there is limited data regarding the clinical trends, management and outcomes associated with this complication. METHODS: A review of a prospective registry of all patients undergoing device extraction between January 1, 2004, and June 15, 2009, at a single high-volume tertiary referral center was performed. RESULTS: A total of 506 consecutive patients were identified. From these, 350 patients were identified as having a CDI (205 ICD, 145 PPM). The mean age was 69.9±13.7. Although most patients presented clinically with signs of a pocket infection (PI) (42%), the most common final diagnosis was cardiac device infective endocarditis (CDIE) (57%). The two most common pathogens were methicillin-resistant Staphylococcus aureus (27%) and methicillin-resistant Staphylococcus epidermidis (23%); they accounted for 69% of all deaths. Cultures taken from pocket tissue as opposed to exudates displayed higher concordance with lead-tip cultures (56% and 31% respectively). The mean time from explantation to device reimplantation for PIs, bacteremia and CDIE was 6.7±4.7, 10.25±4.7 and 11.39±16.6days respectively. CONCLUSION: CDIs are a serious complication associated with device usage. Diagnosis and management protocols for CDIs should feature transesophageal echocardiography; complete hardware extraction; broad-spectrum antibiotics that cover methicillin-resistant Staphylococci and cultures derived from lead-tips and preferably pocket tissue. Immediate device reimplantation is possible in noninfectious cases; several factors should be considered regarding reimplantation in cases involving CDIs.

Delivered Oxygen Fraction During Simulated Cardiopulmonary Resuscitation Depending on the Kind of Resuscitation Bag and Oxygen Flow

Emergency cases for resuscitation include built-in oxygen cylinders with limited oxygen supply. The use of a bag-valve mask device (BVMD) with a reservoir requires a high constant flow of oxygen to maintain a high concentration of delivered oxygen. The goal of the study was to analyze what fraction of inspired oxygen (FiO2) can be reached and how long it takes using different BVMD with their reservoir device and different oxygen flows in order to allow a reduction in oxygen requirements during simulated cardiopulmonary resuscitation (CPR). Experimental analysis was carried out during simulated CPR on the effect in the final FiO2 and the time required to reach it using two different models of BVMD with their reservoir device: Mark IV and Revivator-Plus and four different oxygen flows 5, 10, 15, and 10 l/min during 1 min, followed by 5 l/min (10-5). With both the BVMDs studied, the FiO2 values reached at 10, 15, and 10-5 l/min were higher than 0.85 [Mark IV=0.87 (0.01); Revivator=0.93 (0.03)] in 60 s. At 5 l/min FiO2 were lower in 60 s (P<0.001) and were higher than 0.85 [Mark IV=0.90 (0.005); Revivator=0.90 (0.005)] in 80 s. The mean FiO2 was lower with the Mark IV (P<0.05) (Table 1). To allow a substantial reduction in oxygen requirements, a 10 l/min for 1 min, followed by 5 l/min of oxygen flow can be used during CPR with both BVMDs studied. Increasing supplemental oxygen flow did not appreciably increase the FiO2.

Friction Between Brush Layers of Charged and Neutral Bottle-brush Macromolecules. Molecular Dynamics Simulations

Using molecular dynamics simulations, we study the lubricating properties of neutral and charged bottle-brush coatings as a function of the compression and shear stresses and brush grafting density. Our simulations have shown that in charged bottle-brush systems under shear there is a layer with excess counterions located in the middle between brush-bearing surfaces. The main deformation mode of the charged bottle-brush layers is associated with the backbone deformation, resulting in the backbone deformation ratio, α, and shear viscosity, η, being universal functions of the Weissenberg number. In the case of neutral bottle-brush systems, in addition to the backbone deformation there is also side chain deformation. The coupling between backbone and side chain deformation violates universality in the deformation ratio, α, dependence on the Weissenberg number and results in scaling exponents varying with the compression stress and brush grafting density. The existence of different length scales controlling deformation of neutral bottle brushes manifests itself in the shear viscosity, η, dependence on the shear rate, ̇γ. Shear viscosity, η, as a function of the shear rate, ̇γ, has two plateaus and two shear thinning regimes. The low shear rate plateau and shear thinning regime correspond to the backbone deformation, while the second plateau and shear thinning regime at moderate shear rates are due to side chain deformation. For both systems the value of the friction coefficient increases with increasing shear rate. The values of the friction coefficient for charged bottle-brush systems are about ten times smaller than corresponding values for neutral systems at the same shear rate.

Partnering with REACH to Create a "diabetes-friendly" Restaurant: a Restaurant Owner's Experience

We describe a Latino restaurateur's perspectives and partnership with Seattle-King County REACH to improve the healthfulness of his restaurant as a step toward tackling diabetes in his community. We interviewed the owner and reviewed other documentation to capture his perspectives and identify key elements in this restaurant intervention. The impact of diabetes in the owner's family and Latino community motivated him to make changes at his restaurant. If changes were successful, he hoped this would motivate other Latino restaurateurs to make similar changes. At his request, REACH gathered consumer feedback, provided diabetes education and nutritional guidance, and worked with him to develop simple, economically feasible, healthier items. Positive consumer response and media coverage motivated the owner to explore additional changes at his restaurant and encourage other restaurateurs to make healthful changes. This intervention illustrates the potential for local businesses to collaborate with community partners, like REACH, to promote healthy food environments.

[Maternal Hemoglobin in Peru: Regional Differences and Its Association with Adverse Perinatal Outcomes]

To evaluate hemoglobin (Hb) levels in pregnant women from different geographical regions from Peru; to establish anemia and erythrocytocis rates and to establish the role of Hb on adverse perinatal outcomes using the Perinatal Information System (PIS) database of Peruvian Ministry of Health.

Matrix Completion Based ECG Compression

An innovative electrocardiogram compression algorithm is presented in this paper. The proposed method is based on matrix completion, a new paradigm in signal processing that seeks to recover a low-rank matrix based on a small number of observations. The low-rank matrix is obtained via normalization of electrocardiogram records. Using matrix completion, the ECG data matrix is recovered from a few number of entries, thereby yielding high compression ratios comparable to those obtained by existing compression techniques. The proposed scheme offers a low-complexity encoder, good tolerance to quantization noise, and good quality reconstruction.

Colour and Pulsed Doppler Ultrasonographic Study of the Canine Testis

This study was performed to characterize the normal blood flow of the canine testis and to measure the peak systolic velocity (PSV), end-diastolic velocity (EDV), resistive index (RI) and pulsatility index (PI) of testicular arteries weekly during a period of 6 months in five healthy Beagle dogs and to evaluate whether there were any change along this time. The ultrasonographic exams were made with an 11 MHz linear transducer. The vessels of the testes were subdivided into three categories: supratesticular arteries, marginal artery and intratesticular vessels. At the supratesticular arteries, two measurements were recorded at the cranial and the looping parts. No significant differences in any of the parameters studied were observed for the 6 months that the study was performed. The cranial part of the supratesticular artery showed a flow pattern of high-resistive vessel, whereas in the looping part of the supratesticular artery, marginal and intratesticular arteries, the flow showed a low-resistance pattern. PSV, RI and PI values were higher at the cranial part of the supratesticular artery, followed by the looping part of the supratesticular artery, marginal and intratesticular vessels. EDV measurements were higher in the looping part of the supratesticular artery.

Emerging Trends in Estimating Energy Expenditure

High-Flow Oxygen Therapy: Pressure Analysis in a Pediatric Airway Model

BACKGROUND: The mechanism of high-flow oxygen therapy and the pressures reached in the airway have not been defined. We hypothesize that flow would generate continuous positive pressure is low, and that elevated flow rates in this model could produce moderate pressures. The objective of this study is to analyze the pressure generated by a high-flow oxygen therapy system in an experimental model of the pediatric airway. METHODS: An experimental in vitro study was performed. A high-flow oxygen therapy system was connected to three types of interface (nasal cannulae, nasal mask, and face mask) and applied to two types of pediatric manikin (infant and neonatal). The pressures generated in the circuit, in the airway, and in the pharynx were measured at different flow rates (5, 10, 15, and 20 L/min). The experiment was conducted with and without a leak (mouth sealed and unsealed). Linear regression analyses were performed for each set of measurements. RESULTS: The pressures generated with the different interfaces were very similar. The maximum pressure recorded was 4 cmH₂O with a flow of 20 L/min via nasal cannulae and the nasal mask. When the mouth of the manikins was held open, the pressures reached in the airway and pharynx were undetectable. Linear regression analyses showed similar linear relationship between flow and pressures measured in the pharynx (Pressure = -0,375 + 0,138 * Flow) and in the airway (Pressure = -0,375 + 0,158* Flow) with closed mouth condition. CONCLUSIONS: According to our hypothesis high-flow oxygen therapy systems produce a low-level CPAP in an experimental pediatric model, even with the use of very high flow rates. Linear regression analyses showed similar linear relationship between flow and pressures measured in the pharynx and in the airway. This finding suggests that, at least in part, the effects may be due to other mechanisms.

Gef Gene Expression in MCF-7 Breast Cancer Cells is Associated with a Better Prognosis and Induction of Apoptosis by P53-Mediated Signaling Pathway

Breast cancer research has developed rapidly in the past few decades, leading to longer survival times for patients and opening up the possibility of developing curative treatments for advanced breast cancer. Our increasing knowledge of the biological pathways associated with the progression and development of breast cancer, alongside the failure of conventional treatments, has prompted us to explore gene therapy as an alternative therapeutic strategy. We previously reported that gef gene from E. coli has shown considerable cytotoxic effects in breast cancer cells. However, its action mechanism has not been elucidated. Indirect immunofluorescence technique using flow cytometry and immunocytochemical analysis were used to detect breast cancer markers: estrogen (ER) and progesterone (PR) hormonal receptors, human epidermal growth factor receptor-2 proto-oncogene (c-erbB-2), ki-67 antigen and p53 protein. gef gene induces an increase in ER and PR expressions and a decrease in ki-67 and c-erbB-2 gene expressions, indicating a better prognosis and response to treatment and a longer disease-free interval and survival. It also increased p53 expression, suggesting that gef-induced apoptosis is regulated by a p53-mediated signaling pathway. These findings support the hypothesis that the gef gene offers a new approach to gene therapy in breast cancer.

Search for B(s)(0) † μ+ μ- and B(0) † μ+ μ- Decays with CDF II

A search has been performed for B(s)(0) → μ+ μ- and B(0) → μ+ μ- decays using 7 fb(-1) of integrated luminosity collected by the CDF II detector at the Fermilab Tevatron collider. The observed number of B(0) candidates is consistent with background-only expectations and yields an upper limit on the branching fraction of B(B(0) → μ+ μ-) < 6.0 × 10(-9) at 95% confidence level. We observe an excess of B(s)(0) candidates. The probability that the background processes alone could produce such an excess or larger is 0.27%. The probability that the combination of background and the expected standard model rate of B(s)(0) → μ+ μ- could produce such an excess or larger is 1.9%. These data are used to determine B(B(s)(0)→ μ+ μ-) = (1.8(-0.9) (+1.1)) × 10(-8) and provide an upper limit of B(B(s)(0) → μ+ μ-) < 4.0 × 10(-8) at 95% confidence level.

Search for New T' Particles in Final States with Large Jet Multiplicities and Missing Transverse Energy in P P Collisions at Sqrt[s] = 1.96 TeV

We present a search for a new particle T' decaying to a top quark via T' → t + X, where X goes undetected. We use a data sample corresponding to 5.7 fb(-1) of integrated luminosity of p p collisions with sqrt[s] = 1.96 TeV, collected at Fermilab Tevatron by the CDF II detector. Our search for pair production of T' is focused on the hadronic decay channel, pp → T'T' → tt + XX → bqq b qq + XX. We interpret our results in terms of a model where T' is an exotic fourth generation quark and X is a dark matter particle. The data are consistent with standard model expectations. We set a limit on the generic production of T'T' → tt + XX, excluding the fourth generation exotic quarks T' at 95% confidence level up to m(T') = 400 GeV/c(2) for m(X) ≤ 70 GeV/c(2).

Observation of the Baryonic Flavor-Changing Neutral Current Decay Λ_{b}^{0}→Λμ^{+}μ^{-}

We report the first observation of the baryonic flavor-changing neutral current decay Λ_{b}^{0}→Λμ^{+}μ^{-} with 24 signal events and a statistical significance of 5.8 Gaussian standard deviations. This measurement uses a pp[over ¯] collisions data sample corresponding to 6.8  fb^{-1} at sqrt[s]=1.96  TeV collected by the CDF II detector at the Tevatron collider. The total and differential branching ratios for Λ_{b}^{0}→Λμ^{+}μ^{-} are measured. We find B(Λ_{b}^{0}→Λμ^{+}μ^{-})=[1.73±0.42(stat)±(syst)]×10^{-6}. We also report the first measurement of the differential branching ratio of B_{s}^{0}→ϕμ^{+}μ^{-}, using 49 signal events. In addition, we report branching ratios for B^{+}→K^{+}μ^{+}μ^{-}, B^{0}→K^{0}μ^{+}μ^{-}, and B→K^{*}(892)μ^{+}μ^{-} decays.

Top-quark Mass Measurement Using Events with Missing Transverse Energy and Jets at CDF

We present a measurement of the top-quark mass using a sample of t ̄t events in 5.7 fb(-1) of integrated luminosity from p ̄p collisions at the Fermilab Tevatron with √s=1.96 TeV and collected by the CDF II Detector. We select events having large missing transverse energy, and four, five, or six jets with at least one jet tagged as coming from a b quark, and reject events with identified charged leptons. This analysis considers events from the semileptonic t ̄t decay channel, including events that contain tau leptons. The measurement is based on a multidimensional template method. We fit the data to signal templates of varying top-quark masses and background templates, and measure a top-quark mass of M(top)=172.32±2.4(stat)±1.0(syst)  GeV/c(2).

Vitamin D Supplementation During Exercise Training Does Not Alter Inflammatory Biomarkers in Overweight and Obese Subjects

The purpose of this study was to examine the effects of vitamin D supplementation on inflammatory biomarkers in overweight and obese adults participating in a progressive resistance exercise training program. Twenty-three (26.1 ± 4.7 years) overweight and obese (BMI 31.3 ± 3.2 kg/m(2)) adults were randomized into a double-blind vitamin D supplementation (Vit D 4,000 IU/day; female 5, male 5) or placebo (PL, female 7; male 6) intervention trial. Both groups performed 12 weeks (3 days/week) of progressive resistance exercise training (three sets of eight exercises) at 70-80% of one repetition maximum. Whole-blood lipopolysaccharide (LPS)-stimulated tumor necrosis factor (TNF) α production as well as circulating C-reactive protein (CRP), TNFα, interleukin 6 (IL-6), and alanine aminotransferase (ALT) were assessed at baseline and after the 12-week intervention. No main effects of group or time were detected for circulating CRP, TNFα, IL-6, and ALT. As expected, when PL and Vit D groups were combined, there was a significant correlation between percent body fat and CRP at baseline (r = 0.45, P = 0.04), and between serum 25OHD and CRP at 12 weeks (r = 0.49, P = 0.03). The PL group had a significant increase in 25 μg/ml LPS + polymixin B-stimulated TNFα production (P = 0.04), and both groups had a significant reduction in unstimulated TNFα production (P < 0.05) after the 12-week intervention. Vitamin D supplementation in healthy, overweight, and obese adults participating in a resistance training intervention did not augment exercise-induced changes in inflammatory biomarkers.

"Antelope": a Hybrid-logic Model Checker for Branching-time Boolean GRN Analysis

ABSTRACT:

Comments on Point: Counterpoint: High Altitude Is/is Not for the Birds!

Comparison of N-Acetyltransferase-2 Enzyme Genotype-Phenotype and Xanthine Oxidase Enzyme Activity Between Swedes and Koreans

The aim of this study was to compare xanthine oxidase (XO) and N-acetyltransferase-2 (NAT2) genotype and phenotype between Swedes (n = 113) and Koreans (n = 150), as well as to investigate the effect of sex, smoking, age, and oral contraceptive (OC) use on enzyme activities, using caffeine as a probe. XO and NAT2 activities were estimated by 1U/(1U+1X) and AFMU/(AFMU+1X+1U) urinary ratios, respectively. Participants were genotyped for 191G>A, 341T>C, 590G>A, and 857G>A NAT2 polymorphisms. There was no significant difference in XO activity between Swedes and Koreans. In Swedes, higher XO activity was observed in women (P < .003). There were significant differences in NAT2 genotype and phenotype between Swedes and Koreans. Koreans display significantly higher frequency of NAT2 fast acetylator genotype (89%), whereas the slow acetylator genotype is predominant (62%) in Swedes (P < .0001). Significantly higher NAT2 activity was observed in Koreans compared to Swedes (P < .0001). Having the same NAT2 fast acetylator genotype, Koreans display higher enzyme activity than Swedes (P < .004). OC use significantly increased NAT2 activity in Swedish women. In conclusion, Koreans display higher NAT2 activity than Swedes regardless of NAT2 genotype. Ethnicity, OC use, and genotype determine NAT2 activity, whereas sex is the only determinant of XO activity.

Search for New Physics in High P_{T} Like-Sign Dilepton Events at CDF II

We present a search for new physics in events with two high p_{T} leptons of the same electric charge, using data with an integrated luminosity of 6.1  fb^{-1}. The observed data are consistent with standard model predictions. We set 95% C.L. lower limits on the mass of doubly charged scalars decaying to like-sign dileptons, m_{H^{±±}}>190-245  GeV/c^{2}, assuming 100% BR to ee, μμ or eμ.

Immunolocalization of Endocan During the Endothelial-mesenchymal Transition Process

Endocan is a dermatan sulfate proteoglycan (DSPG) that has been observed in the cytoplasm of endothelial cells of small and large vessels in lung, kidney, liver, colon, ovary and brain tumors. This DSPG has been implicated in the regulation of cellular activities such as adhesion, migration, and proliferation. Given the important roles played by endocan in such processes, we sought to determine whether this DSPG is present in the chicken embryo aortic wall in embryonic days 12 and 14, when intimal thickening and endothelial transformation are notorious. Immunolabeling of serial paraffin cross-sections revealed endocan immunoreactivity at the endothelium and some mesenchymal cells constituting the intimal thickening but not in the cells arranged in lamellar layers. We also investigated whether endocan was present in monolayers of primary embryonic aortic endothelial cells attached to fibronectin when they were deprived of serum and stimulated with epidermal growth factor. Immunofluorescence determined that in the epidermal growth factor (EGF) condition where separating, detaching, and migrating cells were observed, endocan appeared organized in arrays typical of focal complexes in the leading edge of these cells. In serum-free medium condition in which the endothelial cells displayed a cobblestone appearance, endocan appeared mainly delineating the margin of many cells. This study demonstrates for the first time the presence of endocan during the aortic wall remodeling, and provides evidence that suggests a possible contribution of this DSPG in the endothelial-mesenchymal transition (EndoMT) process.

Chest Neoplasms with Infectious Etiologies

A wide spectrum of thoracic tumors have known or suspected viral etiologies. Oncogenic viruses can be classified by the type of genomic material they contain. Neoplastic conditions found to have viral etiologies include post-transplant lymphoproliferative disease, lymphoid granulomatosis, Kaposi's sarcoma, Castleman's disease, recurrent respiratory papillomatosis, lung cancer, malignant mesothelioma, leukemia and lymphomas. Viruses involved in these conditions include Epstein-Barr virus, human herpes virus 8, human papillomavirus, Simian virus 40, human immunodeficiency virus, and Human T-lymphotropic virus. Imaging findings, epidemiology and mechanism of transmission for these diseases are reviewed in detail to gain a more thorough appreciation of disease pathophysiology for the chest radiologist.

Search for a Heavy Toplike Quark in Pp Collisions at ˆs=1.96 TeV

We present the results of a search for pair production of a heavy toplike (t') quark decaying to Wq final states using data corresponding to an integrated luminosity of 5.6 fb(-1) collected by the CDF II detector in pp collisions at √s=1.96 TeV. We perform parallel searches for t'→Wb and t'→Wq (where q is a generic down-type quark) in events containing a lepton and four or more jets. By performing a fit to the two-dimensional distribution of total transverse energy versus reconstructed t' quark mass, we set upper limits on the t't' production cross section and exclude a standard model fourth-generation t' quark decaying to Wb (Wq) with mass below 358 (340) GeV/c(2) at 95% C.L.

Measurement of Polarization and Search for CP Violation in B(s)0→φφ Decays

We present the first measurement of polarization and CP-violating asymmetries in a B(s)(0) decay into two light vector mesons, B(s)(0)→φφ, and an improved determination of its branching ratio using 295 decays reconstructed in a data sample corresponding to 2.9 fb(-1) of integrated luminosity collected by the CDF experiment at the Fermilab Tevatron collider. The fraction of longitudinal polarization is determined to be f(L)=0.348±0.041(stat)±0.021(syst), and the branching ratio B(B(s)(0)→φφ)=[2.32±0.18(stat)±0.82(syst)]×10(-5). Asymmetries of decay angle distributions sensitive to CP violation are measured to be A(u)=-0.007±0.064(stat)±0.018(syst) and A(v)=-0.120±0.064(stat)±0.016(syst).

Measurement of the B(s)0 Lifetime in Fully and Partially Reconstructed B(s)0→D(s)(-)(ϕπ(-))X Decays in P¯p Collisions at ˆs=1.96 TeV

We present a measurement of the B(s)(0) lifetime in fully and partially reconstructed B(s)(0)→D(s)(-)(ϕπ(-))X decays in 1.3  fb(-1) collected in pp ¯ collisions at √s=1.96 TeV by the CDF II detector at the Fermilab Tevatron. We measure τ(B(s)(0))=1.518±0.041(stat)±0.027(syst)  ps. The ratio of this result and the world average B(0) lifetime yields τ(B(s)(0))/τ(B(0))=0.99±0.03, which is in agreement with recent theoretical predictions.

Organocatalytic Enantioselective Synthesis of 2,3-dihydropyridazines

We have developed an efficient procedure for the easy and straightforward preparation of functionalized dihydropyridazines as highly enantiopure materials by reaction of pyruvaldehyde 2-tosyl hydrazone with a variety of α,β-unsaturated aldehydes using a chiral secondary amine as catalyst. The overall process consists of a cascade reaction involving an initial aza-Michael reaction, in which the stereocentre is installed, followed by an intramolecular aldol reaction/dehydration step.

Development of a Homologous Enzyme-linked Immunosorbent Assay for European Sea Bass FSH. Reproductive Cycle Plasma Levels in Both Sexes and in Yearling Precocious and Non-precocious Males

Since the late 1980s, gonadotropins have been isolated and characterized in several fish species, but specific immunoassays for the follicle-stimulating hormone (FSH) have only been developed for a few. The present study reports the development and use of a specific and homologous competitive ELISA for measuring FSH in European sea bass (Dicentrarchus labrax) using a recombinant FSH and its specific antiserum. Recombinant European sea bass FSHβ and FSH heterodimer were produced in the methylotrophic yeast Pichia pastoris and a baculovirus expression system, respectively. Specific polyclonal antibodies, generated by rabbit immunization against recombinant FSHβ, were used at a final dilution of 1:8000. Recombinant FSH heterodimer was used to generate a standard curve and for coating of microplates (166 μg/ml). The sensitivity of the assay was 0.5 ng/ml [B(0)-2SD], and the intra- and inter-assay coefficients of variation were 2.12% (n=10) and 5.44% (n=16) (B(i)/B(0) ∼45%), respectively. A high degree of parallelism was observed between the standard curve and serially diluted plasma and pituitary samples of European sea bass. The ELISA developed was used to study the plasma FSH profiles of mature males and females during the reproductive cycle, and those of immature juvenile males under different light regimes. The analysis showed that FSH increased significantly during the intermediate stages of spermatogenesis and during vitellogenesis. Analyses in immature juvenile males showed that the continuous light photoperiod significantly reduced plasma FSH levels, and consequently, testicular growth and precocious puberty. In conclusion, the immunoassay developed has proven to be sensitive, specific and accurate for measuring European sea bass FSH, and it represents a valuable tool for future studies on the reproductive endocrinology of this species.

Automatic Bifurcation Detection in Coronary IVUS Sequences

In this paper, we present a fully automatic method which identifies every bifurcation in an intravascular ultrasound (IVUS) sequence, the corresponding frames, the angular orientation with respect to the IVUS acquisition, and the extension. This goal is reached using a two-level classification scheme: first, a classifier is applied to a set of textural features extracted from each image of a sequence. A comparison among three state-of-the-art discriminative classifiers (AdaBoost, random forest, and support vector machine) is performed to identify the most suitable method for the branching detection task. Second, the results are improved by exploiting contextual information using a multiscale stacked sequential learning scheme. The results are then successively refined using a-priori information about branching dimensions and geometry. The proposed approach provides a robust tool for the quick review of pullback sequences, facilitating the evaluation of the lesion at bifurcation sites. The proposed method reaches an F-Measure score of 86.35%, while the F-Measure scores for inter- and intraobserver variability are 71.63% and 76.18%, respectively. The obtained results are positive. Especially, considering the branching detection task is very challenging, due to high variability in bifurcation dimensions and appearance.

Enzymatically Synthesized Polyaniline Film Deposition Studied by Simultaneous Open Circuit Potential and Electrochemical Quartz Crystal Microbalance Measurements

The chemical and enzymatic deposition of polyaniline (PANI) films by in situ polymerization was studied and the resulting films were characterized. The film formation and polymerization processes were simultaneously monitored by the evolution of the open circuit potential and quartz-crystal microbalance measurements. Different substrates, such as Indium-Tin oxide electrodes and gold-coated quartz-crystal electrodes were used as substrates for PANI deposition. Electroactive PANI films were successfully deposited by in situ enzymatic polymerization at low oxidation potential. The electrogravimetric response of the enzymatically deposited PANI film was studied by cyclic voltammetry in monomer-free acidic medium. The morphology of the films was observed by scanning electron microscopy, revealing a granular structure in enzymatically deposited PANI. The PANI films were also characterized by thermogravimetric analysis, electrochemical impedance spectroscopy, and X-ray photoelectron and Fourier-transformed infrared spectroscopy. The simultaneous use of quartz crystal microbalance and open circuit potential is presented as a very useful technique to monitor enzymatic reactions involving oxidoreductases.

Development of Aptamer Beacons for Rapid Presumptive Detection of Bacillus Spores

A library of 92 DNA aptamer sequences was developed against Bacillus anthracis (nonpathogenic Sterne strain) spores and anthrose sugar immobilized on magnetic beads. The selected DNA sequences were studied for similarities and potential binding pockets between the B. anthracis spore and anthrose aptamers. Several recurring loop structures were identified and tested for their potential to act as aptamer beacons when labeled with TYE 665 dye on their 5' ends and Iowa Black quencher on their 3' ends. Of these candidate sequences, two beacons designated BAS-6F and BAS-6R emerged which gave strong fluorescence responses at high spore concentrations (greater than 30,000 spores/ml). These aptamer beacons also detect B. cereus and B. thuringiensis spores with greater fluorescence intensity, but do not strongly detect vegetative cells from an array of other bacterial species. BAS-6F and 6R are also not capable of detecting pure anthrose, thereby probably ruling that epitope out as a spore surface target for these particular beacons. While not extremely sensitive, the BAS-6F and 6R aptamer beacons are potentially valuable for rapid presumptive detection of anthrax or Bacillus spores in suspect powders or bioterrorist activity where spore concentrations are anticipated to be high. The sequence similarities of these beacons to other published Bacillus spore aptamers are also discussed.

Clinical Validation of the European Panel on the Appropriateness of Gastrointestinal Endoscopy (EPAGE) II Criteria in an Open-access Unit: a Prospective Study

The European Panel on the Appropriateness of Gastrointestinal Endoscopy (EPAGE I) criteria were recently updated (EPAGE II), but no prospective studies have used these criteria in clinical practice. The aim of the current study was to validate the EPAGE II criteria in an open-access endoscopy unit.

Results of Fractional Flow Reserve Measurement to Evaluate Nonculprit Coronary Artery Stenoses in Patients with Acute Coronary Syndrome

Multivessel disease is usually present in almost half of patients with acute coronary syndromes. Angiography is insufficiently accurate to decide on coronary revascularization in moderate nonculprit lesions. There is some debate about the usefulness of fractional flow reserve assessed by intracoronary pressure wire in acute coronary syndromes. We studied the results of using fractional flow reserve values to decide whether to perform coronary revascularization of nonculprit angiographically moderate lesions in patients with acute coronary syndrome and multivessel disease.

[Factors Influencing Mobilisation of Endothelial Progenitor Cells and Angiogenic Cytokines After an Extensive Acute Myocardial Infarction]

Following an acute myocardial infarction (AMI), bone-marrow derived endothelial progenitor cells (EPC) are mobilised into the peripheral blood. Our aim was to examine the factors influencing this spontaneous cell mobilisation.

Positive Traits Linked to Less Pain Through Lower Pain Catastrophizing

The present study examined the association between positive traits, pain catastrophizing, and pain perceptions. We hypothesized that pain catastrophizing would mediate the relationship between positive traits and pain. First, participants (n = 114) completed the Trait Hope Scale, the Life Orientation Test- Revised, and the Pain Catastrophizing Scale. Participants then completed the experimental pain stimulus, a cold pressor task, by submerging their hand in a circulating water bath (0º Celsius) for as long as tolerable. Immediately following the task, participants completed the Short-Form McGill Pain Questionnaire (MPQ-SF). Pearson correlation found associations between hope and pain catastrophizing (r = -.41, p < .01) and MPQ-SF scores (r = -.20, p < .05). Optimism was significantly associated with pain catastrophizing (r = -.44, p < .01) and MPQ-SF scores (r = -.19, p < .05). Bootstrapping, a non-parametric resampling procedure, tested for mediation and supported our hypothesis that pain catastrophizing mediated the relationship between positive traits and MPQ-SF pain report. To our knowledge, this investigation is the first to establish that the protective link between positive traits and experimental pain operates through lower pain catastrophizing.

Influence of Nutritional Knowledge on the Use and Interpretation of Spanish Nutritional Food Labels

The present study analyzed the nutritional knowledge of Spanish consumers and its relationship with the correct use of food labels. Consumers were asked about their nutritional knowledge and some functional foods and about their understanding of food labeling and their use of it to select healthy food. A 2-part questionnaire was employed. The 1st part concerned their knowledge of nutritional facts, including their knowledge about macronutrients and perception of certain functional foods, while the 2nd part addressed some questions regarding food labels. The results revealed no statistically significant differences in nutritional knowledge by either age or gender, but a direct relationship with educational level. The association between nutritional knowledge and the perception and understanding of food labeling showed that the nutritional label rarely influenced the food purchases of the group with low nutritional knowledge, who considered that this information was too technical. More than half of the consumers did not consider the calorie or sugar content important for selecting food. In addition, the group with low nutritional knowledge stated that they never or rarely looked at the food labels to check whether it was low-fat food that they were buying. PRACTICAL APPLICATION: Knowing the status of the consumer's nutritional knowledge allows health campaigns to be designed; considering the influence of cultural factors and the perception of food labeling is very useful for promoting better nutritional information.

Complete Regression of an Atypical Fibroxanthoma

Comparative Insights of the Kisspeptin/kisspeptin Receptor System: Lessons from Non-mammalian Vertebrates

Kisspeptins, the peptide products of the Kiss1 gene, were initially identified in mammals as ligands of the G protein-coupled receptor 54 (GPR54; also termed Kiss1R) with ability to suppress tumor metastasis. In late 2003, the indispensable role of kisspeptins in the control of reproductive function was disclosed by the seminal observations that humans and mice carrying inactivating mutations of GPR54 displayed hypogonadotropic hypogonadism. Since then, numerous experimental studies, conducted initially in several mammalian species, have substantiated the roles of kisspeptins as essential players in the physiologic regulation of key aspects of reproductive maturation and function, including the timing of puberty onset, the dynamic control of gonadotropin secretion via stimulation of GnRH neurons, the transmission of the negative and positive feedback effects of sex steroids, the metabolic regulation of fertility and the control of reproductive function by environmental (photoperiodic) cues. Notably, while studies about kisspeptins in non-mammals appeared initially to lag behind, significant efforts have been devoted recently to define the genomic organization and functional characteristics of kiss/kisspeptins and gpr54 in different non-mammalian species, including fish, reptiles and amphibians. These analyses, which will be comprehensively revised herein, have not only substantiated the conserved, essential roles of kisspeptins in the control of reproduction, but have also disclosed intriguing evolutionary aspects of kisspeptins and their receptors. Such comparative approaches will be instrumental to fuel further studies on the molecular regulation and physiological roles of kisspeptins, thus helping to unveil the complex biology of this system as indispensable regulator of the reproductive axis in a wide diversity of animal species.

Modulation of Innate Immunity in Chickens Induced by in Vivo Administration of Baculovirus

Baculoviruses stimulate cytokine production in mammalian cells. They induce a strong innate immune response in animals and have adjuvant properties. The purpose of this work was to study the in vivo effect of baculovirus on chicken innate immune response. SPF chickens were inoculated intravenously with Autographa californica nuclear polyhedrosis virus (BV). Three hours later, chickens were bled, euthanized and their spleen, duodenum and cecal tonsils were excised in order to take samples for RNA extraction and real time PCR, and to isolate lymphocytes, which were stained and analyzed by flow cytometry. The results obtained showed that baculovirus inoculation up-regulates the expression of IFN-γ, IL-6 and LITAF in spleen cells. This result (IFN-γ) correlated with that obtained by ELISA which showed a very strong increase of IFN-γ in chicken plasma. Flow cytometry analysis revealed that BV inoculation induced in spleen an increase in the percentage of monocyte/macrophage population together with an increase in CD3(+)CD4(+) T lymphocytes. On the other hand, BV inoculation decreased the percentage of CD3(+)CD4(+) T lymphocytes and increased the percentage of NK cells in cecal tonsils. However, intraepithelial lymphocytes of the gut did not show differences between BV and control treated animals. Even though further studies in order to understand the mechanisms by which BVs affect the avian immune response are needed, results obtained in the present work demonstrate the ability of BVs to stimulate the innate immunity in chickens, modifying the expression pattern of related genes and the profile of the immune cells involved.

Layer-by-layer Assembly of Polyelectrolyte Chains and Nanoparticles on Nanoporous Substrates: Molecular Dynamics Simulations

We performed molecular dynamics simulations of a multilayered assembly of oppositely charged polyelectrolyte chains and nanoparticles on porous substrates with cylindrical pores. The film was constructed by the sequential adsorption of oppositely charged species in a layer-by-layer fashion from dilute solutions. The multilayer assembly proceeds through surface overcharging after the completion of each deposition step. The substrate overcharging fraction fluctuates around 0.5 for nanoparticle-polyelectrolyte systems and around 0.4 for polyelectrolyte-polyelectrolyte systems. The surface coverage increases linearly with the number of deposition steps. The rate of surface coverage increases as a function of the number of deposition step changes when the pore is blocked. The closing of the pore occurs from the pore entrance for nanoparticle-polyelectrolyte systems. In the case of polyelectrolyte-polyelectrolyte systems, the pore plug is formed inside the pore and then spreads toward the pore ends.

Cardiac Device-related Endocarditis Complicated by Spinal Abscess

Infective endocarditis is the most serious manifestation of cardiac device infection and metastatic seeding of distant sites has been reported. However, the association between device-related endocarditis and spinal abscess has not been fully described.

Effects of Androgenization on the White Matter Microstructure of Female-to-male Transsexuals. A Diffusion Tensor Imaging Study

Diffusion tensor imaging (DTI) can sensitively detect white matter sex differences and the effects of pharmacological treatments. Before cross-sex hormone treatment, the white matter microstructure of several brain bundles in female-to-male transsexuals (FtMs) differs from those in females but not from that in males. The purpose of this study was to investigate whether cross-sex hormone treatment (androgenization) affects the brain white matter microstructure. Using a Siemens 3 T Trio Tim Magneton, DTI was performed twice, before and during cross-sex hormonal treatment with testosterone in 15 FtMs scanned. Fractional anisotropy (FA) was analyzed on white matter of the whole brain, and the latter was spatially analyzed using Tract-Based Spatial Statistics. Before each scan the subjects were assessed for serum testosterone, sex hormone binding globulin level (SHBG), and their free testosterone index. After at least seven months of cross-gender hormonal treatment, FA values increased in the right superior longitudinal fasciculus (SLF) and the right corticospinal tract (CST) in FtMs compared to their pre-treatment values. Hierarchical regression analyses showed that the increments in the FA values in the SLF and CST are predicted by the free testosterone index before hormonal treatment. All these observations suggest that testosterone treatment changes white matter microstructure in FtMs.

National Institute on Aging-Alzheimer's Association Guidelines for the Neuropathologic Assessment of Alzheimer's Disease

A consensus panel from the United States and Europe was convened recently to update and revise the 1997 consensus guidelines for the neuropathologic evaluation of Alzheimer's disease (AD) and other diseases of brain that are common in the elderly. The new guidelines recognize the pre-clinical stage of AD, enhance the assessment of AD to include amyloid accumulation as well as neurofibrillary change and neuritic plaques, establish protocols for the neuropathologic assessment of Lewy body disease, vascular brain injury, hippocampal sclerosis, and TDP-43 inclusions, and recommend standard approaches for the workup of cases and their clinico-pathologic correlation.

Polyneuropathy While on Duodenal Levodopa Infusion in Parkinson's Disease Patients: We Must Be Alert

Some reports have emerged describing the occurrence of Guillain-Barré syndrome and polyneuropathy related to vitamin B(12) deficiency in some patients with Parkinson's disease (PD) treated with continuous duodenal levodopa infusion. We describe five PD patients who developed axonal polyneuropathy and vitamin B(12) deficiency while on treatment with duodenal levodopa infusion, review other cases reported in the literature, discuss potential etiologic factors, and suggest a possible algorithm for the management and prevention of this complication. One case of Guillain-Barré syndrome and at least 12 cases of polyneuropathy related to vitamin B(12) deficiency have been reported in PD patients treated with duodenal levodopa infusion. Levodopa gel infusion may induce a decrease in vitamin B(12) levels, leading to peripheral neuropathy. Additional pathogenetic mechanisms include alterations related to the metabolism of L: -dopa, abnormal L: -dopa absorption, and direct neurotoxicity of L: -dopa at high doses. Vitamin B(12) supplementation may need to be considered in PD patients on duodenal levodopa infusion therapy. Vitamin B(12) deficiency in patients on duodenal levodopa infusion therapy may be more frequent than the published data suggest. We must be alert.

Functional Diffusion Maps (fDMs) Evaluated Before and After Radiochemotherapy Predict Progression-free and Overall Survival in Newly Diagnosed Glioblastoma

Functional diffusion mapping (fDM) has shown promise as a sensitive imaging biomarker for predicting survival in initial studies consisting of a small number of patients, mixed tumor grades, and before routine use of anti-angiogenic therapy. The current study tested whether fDM performed before and after radiochemotherapy could predict progression-free and overall survival in 143 patients with newly diagnosed glioblastoma from 2007 through 2010, many treated with anti-angiogenic therapy after recurrence. Diffusion and conventional MRI scans were obtained before and 4 weeks after completion of radiotherapy and concurrent temozolomide treatment. FDM was created by coregistering pre- and posttreatment apparent diffusion coefficient (ADC) maps and then performing voxel-wise subtraction. FDMs were categorized according to the degree of change in ADC in pre- and posttreatment fluid-attenuated inversion recovery (FLAIR) and contrast-enhancing regions. The volume fraction of fDM-classified increasing ADC(+), decreasing ADC(-), and change in ADC(+/-) were tested to determine whether they were predictive of survival. Both Bonferroni-corrected univariate log-rank analysis and Cox proportional hazards modeling demonstrated that patients with decreasing ADC in a large volume fraction of pretreatment FLAIR or contrast-enhancing regions were statistically more likely to progress earlier and expire sooner than in patients with a lower volume fraction. The current study supports the hypothesis that fDM is a sensitive imaging biomarker for predicting survival in glioblastoma.

Decarbonylative Approach to the Synthesis of Enamides from Amino Acids: Stereoselective Synthesis of the (Z)-aminovinyl-D-cysteine Unit of Mersacidin

The Pd- and Ni-promoted decarbonylation of amino acid thioesters proceeds smoothly to yield enamides. The synthesis of the (S)-(Z)-AviMeCys subunit of mersacidin, an MRSA-active lantibiotic, via this approach, is described.

Synthesis of the AviMeCys-containing D-ring of Mersacidin

A chemical synthesis of the D-ring of mersacidin is reported. The synthetic route relied upon development of a method for late-stage introduction of an unusual S-[(Z)-2-aminovinyl]-(3S)-3-methyl-D-cysteine (AviMeCys) functional group via an oxidative decarbonylation/decarboxylation reaction.

Search for a Higgs Boson in the Diphoton Final State in Pp Collisions at Sqrt[s]=1.96  TeV

A search for a narrow Higgs boson resonance in the diphoton mass spectrum is presented based on data corresponding to 7.0  fb{-1} of integrated luminosity from pp collisions at sqrt[s]=1.96  TeV collected by the CDF experiment. No evidence of such a resonance is observed, and upper limits are set on the cross section times branching ratio of the resonant state as a function of Higgs boson mass. The limits are interpreted in the context of the standard model and one fermiophobic benchmark model where the data exclude fermiophobic Higgs bosons with masses below 114  GeV/c{2} at a 95% Bayesian credibility level.

Role of Zebrafish Thrombocyte and Non-thrombocyte Microparticles in Hemostasis

Hemostasis is a defense mechanism that protects an organism from bleeding in the event of injury. We have previously demonstrated the utility of the zebrafish as a model to study human hemostasis. However, there are no studies on the role of microparticles in hemostasis in early vertebrates. Studying microparticles in zebrafish may provide insight into the evolution of microparticle function in hemostasis and may lead to direct observation of these microparticles in zebrafish larvae due to transparency of the vessels. In this investigation we demonstrate the presence of cellular microparticles in fish blood by both immunostaining as well as by using zebrafish whose thrombocytes are labeled with green fluorescent protein. Further investigation showed that microparticles were also labeled by fluorescein isothiocyanate annexin V, suggesting that these particles are derived via apoptosis. A portion of the fluorescein isothiocyanate annexin V labeled microparticles was also labeled by DiI-C18. Labeling by DiI-C18 suggests that some microparticles are derived from young thrombocytes. Additionally, GpIIb antibody labels almost all thrombocyte-derived microparticles and a greater percentage of microparticles are labeled by GpIIb antibody than by DiI-C18. This suggests that thrombocyte microparticles are derived from both young and mature thrombocytes. Furthermore, the increase of microparticles by adding excessive microparticles into blood in vitro and through intravenous injections led to an increased hemostatic response. In addition, treatment with tumor necrosis factor alpha resulted in an increased number of thrombocyte microparticles and enhanced hemostasis; in contrast, treatment with zVAD-FMK, a caspase inhibitor, resulted in a decrease in thrombocyte microparticles and decreased hemostasis. We also found that thrombocyte microparticles agglutinate, along with other cells and cellular microparticles, in the presence of an excess of either ristocetin or ultra-large von Willebrand factor. Also, stimulation of von Willebrand factor release in vivo resulted in clusters of thrombocyte microparticles in the veins. Moreover, thrombocyte microparticles were the first to appear at the site of arterial injury. We found that thrombocyte microparticles are functionally equivalent to platelet microparticles. The microparticles initiate arterial thrombus formation in a von Willebrand factor-dependent manner and further enhance thrombus formation by forming clusters of microparticles in venous thrombosis. This finding may have applications for understanding the role of platelet microparticles in humans and may have diagnostic applications.

Diacylglycerol-containing Oleic Acid Induces Increases in [Ca(2+)](i) Via TRPC3/6 Channels in Human T-cells

Though most of the studies have focused on the effects of free fatty acids on T-cell activation, fatty acids incorporated into plasma membrane phospholipids may also affect cell signaling via diacylglycerol (DAG), generally produced by phospholipid hydrolysis. In the present study, we have synthesized a DAG-containing oleic acid and studied its implication in the modulation of calcium signaling in human Jurkat T-cells. 1-palmitoyl-2-oleoyl-sn-glycerol (POG) induced a dose-dependent increase in [Ca(2+)](i). This effect was due to the presence of oleic acid at the sn-2 position as no differences were observed between POG and 1-stearoly-2-oleoyl-sn-glycerol (SOG). However, the substitution of oleic acid with arachidonic acid at the sn-2 position of the DAG moiety exerted a different response on the increases in [Ca(2+)](i) in these cells. POG-evoked increases in [Ca(2+)](i) were not due to its metabolites. Furthermore, POG-induced increases in [Ca(2+)](i) were due to the opening of TRPC3/TRPC6 channels as silencing of TRPC3 and TRPC6 genes by shRNA abolished calcium entry. Moreover, disruption of lipid rafts with methyl-β-cyclodextrin completely abolished POG-evoked increases in [Ca(2+)](i). In conclusion, our results demonstrate that oleic acid can influence T-lymphocyte functions, in the conjugated form of DAG, via opening TRPC3/6 channels.

What is Your Diagnosis? Splenic Myelolipoma

Viremic HIV Infected Individuals with High CD4 T Cells and Functional Envelope Proteins Show Anti-gp41 Antibodies with Unique Specificity and Function

CD4 T-cell decay is variable among HIV-infected individuals. In exceptional cases, CD4 T-cell counts remain stable despite high plasma viremia. HIV envelope glycoprotein (Env) properties, namely tropism, fusion or the ability to induce the NK ligand NKp44L, or host factors that modulate Env cytopathic mechanisms may be modified in such situation.

Cardiac Implantable Electronic Devices in End-stage Renal Disease Patients: Preservation of Central Venous Circulation

Non-invasive Ventilation in Community-acquired Pneumonia and Severe Acute Respiratory Failure

The use of non-invasive ventilation (NIV) in severe acute respiratory failure (ARF) due to community-acquired pneumonia (CAP) is controversial, and the risk factors for NIV failure in these patients are not well known. We assessed the characteristics and predictors of outcome of patients with CAP and severe ARF treated with NIV.

Timing of the Most Recent Device Procedure Influences the Clinical Outcome of Lead-associated Endocarditis Results of the MEDIC (Multicenter Electrophysiologic Device Infection Cohort)

The purpose of this study was to determine whether the timing of the most recent cardiac implantable electronic device (CIED) procedure, either a permanent pacemaker or implantable cardioverter-defibrillator, influences the clinical presentation and outcome of lead-associated endocarditis (LAE).

Relationship Between Tumor Enhancement, Edema, IDH1 Mutational Status, MGMT Promoter Methylation, and Survival in Glioblastoma

BACKGROUND AND PURPOSE:Both IDH1 mutation and MGMT promoter methylation are associated with longer survival. We investigated the ability of imaging correlates to serve as noninvasive biomarkers for these molecularly defined GBM subtypes.MATERIALS AND METHODS:MR imaging from 202 patients with GBM was retrospectively assessed for nonenhancing tumor and edema among other imaging features. IDH1 mutational and MGMT promoter methylation status were determined by DNA sequencing and methylation-specific PCR, respectively. Overall survival was determined by using a multivariate Cox model and the Kaplan-Meier method with a log rank test. A logistic regression model followed by ROC analysis was used to classify the IDH1 mutation and methylation status by using imaging features.RESULTS:MGMT promoter methylation and IDH1 mutation were associated with longer median survival. Edema levels stratified survival for methylated but not unmethylated tumors. Median survival for methylated tumors with little/no edema was 2476 days (95% CI, 795), compared with 586 days (95% CI, 507-654) for unmethylated tumors or tumors with edema. All IDH1 mutant tumors were nCET positive, and most (11/14, 79%) were located in the frontal lobe. Imaging features including larger tumor size and nCET could be used to determine IDH1 mutational status with 97.5% accuracy, but poorly predicted MGMT promoter methylation.CONCLUSIONS:Imaging features are potentially predictive of IDH1 mutational status but were poorly correlated with MGMT promoter methylation. Edema stratifies survival in MGMT promoter methylated but not in unmethylated tumors; patients with methylated tumors with little or no edema have particularly long survival.

Dietary Protein Quality Differentially Regulates Trypsin Enzymes at the Secretion and Transcription Level in Panulirus Argus by Distinct Signaling Pathways

The effects of pelleted diets with different protein composition (fish, squid or soybean meals as main protein sources) on trypsin secretion and expression were studied in the lobster Panulirus argus. Trypsin secretion was shown to be maximal 4 h after ingestion. At this time, fish- and squid-based diets induced trypsin secretion, as well as up-regulation of the major trypsin isoform at the transcription level. While fish- and squid-based diets elicited a prandial response, soybean-based diet failed to stimulate the digestive gland to secrete trypsin into the gastric fluid or induce trypsin expression above the levels observed in fasting lobsters. In vitro assays showed that intact proteins rather than protein hydrolysates stimulate trypsin secretion in the lobster. However, the signal for trypsin transcription appears to be different to that for secretion and is probably mediated by the appearance of free amino acids in the digestive gland, suggesting a stepwise regulation of trypsin enzymes during digestion. We conclude that trypsin enzymes in P. argus are regulated at the transcription and secretion level by the quality of dietary proteins through two distinct signaling pathways. Our results indicate that protein digestion efficiency in spiny lobsters can be improved by selecting appropriated protein sources. However, other factors like the poor solubility of dietary proteins in dry diets could hamper further enhancement of digestion efficiency.

5-Fluorouracil Derivatives: a Patent Review

INTRODUCTION: The fluorinated analog of uracil 5-FU is an antimetabolite, active against a wide range of solid tumors. The main mechanism of action consists in interfering with DNA synthesis and mRNA translation. However, patients treated with 5-FU display several side effects, a result of its nonspecific cytotoxicity for tumor cells. Numerous modifications of the 5-FU structure have been performed in order to overcome these disadvantages. AREAS COVERED: In this review, the metabolic pathways, pharmacokinetics and clinical pharmacology of 5-FU are briefly introduced. Moreover, several derivatives developed and patented, including oral 5-FU prodrugs and combinations with other active compounds, are presented. Finally, new innovative methods for administration and vehiculization of 5-FU and its derivatives are described. EXPERT OPINION: The search for less toxic 5-FU derivatives, which diminish or circumvent some of its disadvantages, has allowed the development of selective antitumor prodrugs and novel methods for tissue-specific drug delivery. Although some of these oral prodrugs are being used clinically, either alone or in combination therapy with other anticancer agents, it seems that the potential of personalized medicine, including pharmacogenomics and targeted therapy with novel 5-FU derivatives, will improve the management and clinical responses of patients treated with 5-FU-based therapy.

Interstitial Lung Disease Related to Rheumatoid Arthritis: Evolution After Treatment

To describe the evolution of lung function in a cohort of rheumatoid arthritis (RA) patients with interstitial lung disease (ILD) treated according to the medical judgment of attending physicians.

Transvenous Cardiac Implantable Electronic Devices and Hemodialysis Catheters: Recommendations to Curtail a Potentially Lethal Combination

Abnormal renal function is an independent risk factor for cardiac implantable electronic device (CIED) infection. The risk of CIED infection increases as the degree of renal dysfunction worsens with the highest risk observed in patients with stage V chronic kidney disease. A significant portion of these patients use a tunneled hemodialysis catheter (TDC) for dialysis therapy. These devices are associated with very high rates of catheter-related bacteremia (1.6-5.5 episodes of bacteremia per 1000 catheter days), and have been known to cause infection of CIED indwelling in the bloodstream. In this context, the cardiac device is exposed to the risk of infection due to the presence of renal failure and episodes of bacteremia related to TDCs. Both increase the risk of CIED infection. Once infected, a cardiac rhythm device carries a marked increase in morbidity and mortality. In this context, the combination of a TDC and a CIED indwelling in the bloodstream becomes a potentially deadly combination. Recent data have emphasized that epicardial CIED implantation reduces cardiac device infection in TDC patients. This report highlights the risk of CIED infection in renal patients, presents TDC's contribution to the cardiac device infection, and suggests recommendations to minimize the risk of CIED infection in chronic hemodialysis patients dialyzing with a TDC.

Association of Hemoglobin Values at Booking with Adverse Maternal Outcomes Among Peruvian Populations Living at Different Altitudes

To determine hemoglobin values associated with adverse maternal outcomes among Peruvian populations at different altitudes.

Hypercontrols in Genotype-phenotype Analysis Reveal Ancestral Haplotypes Associated with Essential Hypertension

The angiotensinogen gene locus has been associated with essential hypertension in most populations analyzed to date. Increased plasma angiotensinogen levels have been proposed as an underlying cause of essential hypertension in whites; however, differences in the genetic regulation of plasma angiotensinogen levels have also been reported for other populations. The aim of this study was to analyze the relationship between angiotensinogen gene polymorphisms and haplotypes with plasma angiotensinogen levels and the risk of essential hypertension in the Mexican population. We genotyped 9 angiotensinogen gene polymorphisms in 706 individuals. Four polymorphisms, A-6, C4072, C6309, and G12775, were associated with increased risk, and the strongest association was found for the C6309 allele (χ(2)=23.9; P=0.0000009), which resulted in an odds ratio of 3.0 (95% CI: 1.8-4.9; P=0.000006) in the recessive model. Two polymorphisms, A-20C (P=0.003) and C3389T (P=0.0001), were associated with increased plasma angiotensinogen levels but did not show association with essential hypertension. The haplotypes H1 (χ(2)=8.1; P=0.004) and H5 (χ(2)=5.1; P=0.02) were associated with essential hypertension. Using phylogenetic analysis, we found that haplotypes 1 and 5 are the human ancestral haplotypes. Our results suggest that the positive association between angiotensinogen gene polymorphisms and haplotypes with essential hypertension is not simply explained by an increase in plasma angiotensinogen concentration. Complex interactions between risk alleles suggest that these haplotypes act as "superalleles."

Targeting Werner Syndrome Protein Sensitizes U-2 OS Osteosarcoma Cells to Selenium-induced DNA Damage Response and Necrotic Death

Mutations in the Werner syndrome protein (WRN), a caretaker of the genome, result in Werner syndrome, which is characterized by premature aging phenotypes and cancer predisposition. Methylseleninic acid (MSeA) can activate DNA damage responses and is a superior compound to suppress tumorigenesis in mouse models of cancer. To test the hypothesis that targeting WRN can potentiate selenium toxicity in cancer cells, isogenic WRN small hairpin RNA (shRNA) and control shRNA U-2 OS osteosarcoma cells were treated with MSeA for 2d, followed by recovery for up to 7d. WRN deficiency sensitized U-2 OS cells to MSeA-induced necrotic death. Co-treatment with the ataxia-telangiectasia mutated (ATM) kinase inhibitor KU55933 desensitized the control shRNA cells, but not WRN shRNA cells, to MSeA treatment. WRN did not affect MSeA-induced ATM phosphorylation on Ser-1981 or H2A.X phosphorylation on Ser-139, but promoted recovery from the MSeA-induced DNA damage. Taken together, WRN protects U-2 OS osteosarcoma cells against MSeA-induced cytotoxicity, suggesting that oxidative DNA repair pathway is a promising target for improving the efficacy of selenium on tumor suppression.

Stabilization of Graphene Sheets by a Structured Benzene/hexafluorobenzene Mixed Solvent

Applications requiring pristine graphene derived from graphite demand a solution stabilization method that utilizes an easily removable media. Using a combination of molecular dynamics simulations and experimental techniques, we investigate the solublization/suspension of pristine graphene sheets by an equimolar mixture of benzene and hexafluorobenzene (C(6)H(6)/C(6)F(6)) that is known to form an ordered structure solidifying at 23.7 °C. Our simulations show that the graphene surface templates the self-assembly of the mixture into periodic layers extending up to 30 Å from both sides of the graphene sheet. The solvent structuring is driven by quadrupolar interactions and consists of stacks of alternating C(6)H(6)/C(6)F(6) molecules rising from the surface of the graphene. These stacks result in density oscillations with a period of about 3.4 Å. The high affinity of the 1:1 C(6)H(6)/C(6)F(6) mixture with graphene is consistent with observed hysteresis in Wilhelmy plate measurements using highly ordered pyrolytic graphite (HOPG). AFM, SEM, and TEM techniques verify the state of the suspended material after sonication. As an example of the utility of this mixture, graphene suspensions are freeze-dried at room temperature to produce a sponge-like morphology that reflects the structure of the graphene sheets in solution.

How is Gene Transfection Able to Improve Current Chemotherapy? The Role of Combined Therapy in Cancer Treatment

Despite advances in cancer treatment, a large number of patients eventually develop metastatic disease that is generally incurable. Systemic chemotherapy remains the standard treatment for these patients. Several chemotherapeutic combinations have proven effective in the management of cancer. Paradoxically, although the purpose of polychemotherapy is to improve the prognosis and prolong the survival of patients, it often carries considerable toxicity that causes substantial adverse symptoms. For this reason, a major goal of cancer research is to improve the effectiveness of these cytotoxic agents and reduce their adverse effects. Gene transfer has been proposed as a new strategy to enhance the efficacy of anti-tumor drugs in the treatment of intractable or metastatic cancers. In fact, the association of gene therapy and drugs (combined therapy) has been reported to increase the anti-proliferative effect of classical treatments in lung, bladder, pancreatic, colorectal and breast cancers, among others. Various especially promising therapies have been proposed in this context, including the use of suicide genes, antisense oligonucleotides, ribozymes and RNA interference. In this chapter, we review recent progress in the development of novel anti-cancer strategies that associate cytotoxic agents with gene transfer to enhance their antitumor effect.

Very Late Thrombosis in a Bifurcation

Fusion Positron Emission/Computed Tomography Underestimates the Presence of Hilar Nodal Metastases in Patients With Resected Non-Small Cell Lung Cancer

BACKGROUND: The 5-year survival for patients with resected stage II (N1) non-small cell lung cancer ranges from 40% to 55%. No data exist addressing the benefit of neoadjuvant therapy for patients with stage II disease. This is largely in part due to the lack of a reliable, minimally invasive method to assess hilar nodes. This study is aimed at determining the ability of fusion positron emission/computed tomography (PET/CT) to identify hilar metastases in patients with resected non-small cell lung cancer. METHODS: A retrospective review of surgically resected patients with fusion PET/CT within 30 days of resection was performed. The sensitivity, specificity, positive predictive value, and negative predictive value for PET/CT in detecting hilar nodal metastases was calculated for a range of maximum standardized uptake values (SUVmax). Hilar nodes from patients with falsely positive PET/CT scans were analyzed for the presence of histoplasmosis. Additionally, the impact of hilar node size greater than 1 centimeter on the calculated values was assessed. RESULTS: There were 119 patients evaluated. The number of lymph nodes resected ranged from 1 to 12 (X = 2.98). There was decreased sensitivity and increased specificity with higher SUVmax cutoff values. At the standard SUVmax value of 2.5, the sensitivity and specificity were only 48.5% and 80.2%. The addition of size of hilar node by CT led to a modest improvement in sensitivity at all SUVmax cutoff values. CONCLUSIONS: Fusion PET/CT lacks sensitivity and specificity in identifying hilar nodal metastasis in patients with resected non-small cell lung cancer. Further prospective studies assessing the utility of PET/CT versus alternative sampling techniques are warranted.

Cooperative Dienamine/hydrogen-bonding Catalysis: Enantioselective Formal [2+2] Cycloaddition of Enals with Nitroalkenes

Two can play this game: The title reaction is catalyzed by a chiral secondary amine in the presence of an achiral thiourea for the enantio- and diastereoselective synthesis of highly functionalized cyclobutanes (see scheme; TMS=trimethylsilyl). Mechanistically, two consecutive Michael reactions proceed through an unprecedented combination of an dienamine/iminium activation mode.

Multicenter Experience with Transvenous Lead Extraction of Active Fixation Coronary Sinus Leads

Background/Objective: Active fixation coronary sinus (CS) leads limit dislodgement and represent an attractive option to the implanter. Although extraction of passive fixation CS leads is a common and frequently uncomplicated procedure, data regarding extraction of chronically implanted active fixation CS leads are limited. Methods: We performed a retrospective cohort study of patients undergoing active fixation CS lead extraction at six centers. Patient and procedural characteristics, indications for extraction, use of extraction sheath (ES) assistance, and outcomes are reported. Results: Between January 2009 and February 2011, 12 patients underwent transvenous lead extraction (TLE) of Medtronic StarFix® lead (Medtronic Inc., Minneapolis, MN, USA). The cohort was 83% male with mean age 71 ± 14 years. Average implant duration was 14.2 ± 5.7 months (2.3-23.6). All leads but one were removed for infectious indications (67% systemic infection). At the time of explant, the fixation lobes were completely retracted in only one of the 12 cases and ES assistance was required for lead removal in all cases (58% laser, 25% cutting, 25% mechanical, and 25% femoral). The majority of cases required advancement of the sheath into the CS (75.0%) and often into a branch vessel (41.7%). One lead could not be removed transvenously and required surgical lead extraction. There were no major complications. Examination of the leads after extraction frequently revealed significant tissue growth into the fixation lobes. Conclusions: Although TLE of active fixation CS leads can be a safe procedure in select patients and experienced hands, powered sheaths and aggressive techniques are frequently required for successful removal despite relatively short implant durations. This raises significant concern regarding future TLE of active fixation CS leads with longer implant durations. (PACE 2012;1-7).

Characterizing Roles of Met31 and Met32 in Coordinating Met4-activated Transcription in the Absence of Met30

Yeast sulfur metabolism is transcriptionally regulated by the activator Met4. Met4 lacks DNA-binding ability and relies on interactions with Met31 and Met32, paralogous proteins that bind the same cis-regulatory element, to activate its targets. While Met31 and Met32 are redundant for growth in the absence of methionine, studies indicate that Met32 has a prominent role over Met31 when Met30, a negative regulator of Met4 and Met32, is inactive. To characterize different roles of Met31 and Met32 in coordinating Met4-activated transcription, we examined transcription in strains lacking either Met31 or Met32 upon Met4 induction in the absence of Met30. Microarray analysis revealed transcripts involved in sulfate assimilation and sulfonate metabolism were dramatically decreased in met32Δ cells compared to its wild-type and met31Δ counterparts. Despite this difference, both met31Δ and met32Δ cells utilized inorganic sulfur compounds and sulfonates as sole sulfur sources in minimal media when Met30 was present. This discrepancy may be explained by differential binding of Met31 to Cbf1-dependent promoters between these two conditions. In the absence of Met30, ChIP-chip analyses found Met32 bound all Met4-bound targets, supporting Met32 as the main platform for Met4 recruitment. Finally, Met31 and Met32 levels were differentially regulated, with Met32 levels mimicking the profile for active Met4. These different properties of Met32 likely contribute to its prominent role in Met4-activated transcription when Met30 is absent.

Alternative Chemotherapeutic Agents: Nitrosoureas, Cisplatin, Irinotecan

Irinotecan, cisplatin, and nitrosoureas have a long history of use in brain tumors, with demonstrated efficacy in the adjuvant treatment of malignant gliomas. In the era of temozolomide with concurrent radiotherapy given as the standard of care, their use has shifted to treatment at progression or recurrence. Now with the widespread use of bevacizumab in the recurrent setting, irinotecan and other chemotherapies are seeing increased use in combination with bevacizumab and alone in the recurrent setting. The activity of these chemotherapeutic agents in brain tumors will likely ensure a place in the armamentarium of neuro-oncologists for many years.

A Retrospective Comparison of 1,022 Implants: Immediate Versus Nonimmediate

Purpose: The aim of this study was to compare the survival of implants placed in mature bone with the survival of implants placed in fresh extraction sockets in the same patients. Materials and Methods: A retrospective study of patients treated simultaneously with at least one immediate and one nonimmediate implant was carried out for the period 2005 to 2008. Data were recorded for patient age and sex; implant length, diameter, and position; and, for postextraction implants, distance between the implant and the alveolar bone. Results: One thousand twenty-two implants were placed in 150 patients; 480 were placed immediately and 542 were placed in mature bone. The mean implant survival rate was 93.4%; survival rates were 93.8% for immediate implants and 93.2% for nonimmediate implants. The failure rate in the maxilla was 5.2% and in the mandible it was 2.8%. The failure rate for immediate implants in the posterior maxilla was 8.5%, which was statistically significantly higher than for implants placed elsewhere. Of the failed implants, 72% were early failures. Conclusions: The survival rate of implants placed in fresh extraction sockets was similar to that of implants placed in mature bone. A statistically significantly higher failure rate was seen with immediate implants placed in the posterior maxilla.

Measurement of ZZ Production in Leptonic Final States at Sqrt[s] of 1.96 TeV at CDF

In this Letter, we present a precise measurement of the total ZZ production cross section in pp[over ¯] collisions at sqrt[s]=1.96  TeV, using data collected with the CDF II detector corresponding to an integrated luminosity of approximately 6  fb^{-1}. The result is obtained by combining separate measurements in the four-charged (ℓℓℓ^{'}ℓ^{'}) and two-charged-lepton and two-neutral-lepton (ℓℓνν) decay modes of the Z boson pair. The combined measured cross section for pp[over ¯]→ZZ is 1.64_{-0.38}^{+0.44}  pb. This is the most precise measurement of the ZZ production cross section in 1.96 TeV pp[over ¯] collisions to date.

Observation of Exclusive γγ Production in Pp[over ¯] Collisions at Sqrt[s]=1.96  TeV

We have observed exclusive γγ production in proton-antiproton collisions at sqrt[s]=1.96  TeV, using data from 1.11±0.07  fb^{-1} integrated luminosity taken by the Run II Collider Detector at Fermilab. We selected events with two electromagnetic showers, each with transverse energy E_{T}>2.5  GeV and pseudorapidity |η|<1.0, with no other particles detected in -7.4<η<+7.4. The two showers have similar E_{T} and azimuthal angle separation Δϕ∼π; 34 events have two charged particle tracks, consistent with the QED process pp[over ¯]→p+e^{+}e^{-}+p[over ¯] by two-photon exchange, while 43 events have no charged tracks. The number of these events that are exclusive π^{0}π^{0} is consistent with zero and is <15 at 95% C.L. The cross section for pp[over ¯]→p+γγ+p[over ¯] with |η(γ)|<1.0 and E_{T}(γ)>2.5  GeV is 2.48_{-0.35}^{+0.40}(stat)_{-0.51}^{+0.40}(syst)  pb.

Measurements of the Angular Distributions in the Decays B→K^{(*)}μ^{+}μ^{-} at CDF

We report an indirect search for nonstandard model physics using the flavor-changing neutral current decays B→K^{(*)}μ^{+}μ^{-}. We reconstruct the decays and measure their angular distributions, as a function of q^{2}=M_{μμ}^{2}c^{2}, where M_{μμ} is the dimuon mass, in pp[over ¯] collisions at sqrt[s]=1.96  TeV using a data sample corresponding to an integrated luminosity of 6.8  fb^{-1}. The transverse polarization asymmetry A_{T}^{(2)} and the time-reversal-odd charge-and-parity asymmetry A_{im} are measured for the first time, together with the K^{*} longitudinal polarization fraction F_{L} and the muon forward-backward asymmetry A_{FB} for the decays B^{0}→K^{*0}μ^{+}μ^{-} and B^{+}→K^{*+}μ^{+}μ^{-}. The B→K^{*}μ^{+}μ^{-} forward-backward asymmetry in the most sensitive kinematic regime, 1≤q^{2}<6  GeV^{2}/c^{2}, is measured to be A_{FB}=0.29_{-0.23}^{+0.20}(stat)±0.07(syst), the most precise result to date. No deviations from the standard model predictions are observed.

Sleep Loss Exacerbates Fatigue, Depression, and Pain in Rheumatoid Arthritis

Disturbances of sleep are hypothesized to contribute to pain. However, experimental data are limited to healthy pain-free individuals. This study evaluated the effect of sleep loss during part of the night on daytime mood symptoms and pain perceptions in patients with rheumatoid arthritis in comparison with control subjects.

Evaluation of Contractility and Postloading in the Intensive Care Unit

Cardiovascular failure is a common disorder in critical care medicine. When admitted to the ICU, patients with hemodynamic deterioration should be examined rapidly to correctly assess the main determinants of cardiovascular function (preload, afterload and contractility). This review examines the assessment of contractility and afterload involving the combined use of several hemodynamic monitors, which allows different approaches to the same problem, with a view to improving the efficiency of management and treatment in critically ill patients.

Skip the Alignment: Degenerate, Multiplex Primer and Probe Design Using K-mer Matching Instead of Alignments

PriMux is a new software package for selecting multiplex compatible, degenerate primers and probes to detect diverse targets such as viruses. It requires no multiple sequence alignment, instead applying k-mer algorithms, hence it scales well for large target sets and saves user effort from curating sequences into alignable groups. PriMux has the capability to predict degenerate primers as well as probes suitable for TaqMan or other primer/probe triplet assay formats, or simply probes for microarray or other single-oligo assay formats. PriMux employs suffix array methods for efficient calculations on oligos 10-∼100 nt in length. TaqMan® primers and probes for each segment of Rift Valley fever virus were designed using PriMux, and lab testing comparing signatures designed using PriMux versus those designed using traditional methods demonstrated equivalent or better sensitivity for the PriMux-designed signatures compared to traditional signatures. In addition, we used PriMux to design TaqMan® primers and probes for unalignable or poorly alignable groups of targets: that is, all segments of Rift Valley fever virus analyzed as a single target set of 198 sequences, or all 2863 Dengue virus genomes for all four serotypes available at the time of our analysis. The PriMux software is available as open source from http://sourceforge.net/projects/PriMux.

Does Phylogeny Matter? Assessing the Impact of Phylogenetic Information in Ecological Meta-analysis

Meta-analysis is increasingly used in ecology and evolutionary biology. Yet, in these fields this technique has an important limitation: phylogenetic non-independence exists among taxa, violating the statistical assumptions underlying traditional meta-analytic models. Recently, meta-analytical techniques incorporating phylogenetic information have been developed to address this issue. However, no syntheses have evaluated how often including phylogenetic information changes meta-analytic results. To address this gap, we built phylogenies for and re-analysed 30 published meta-analyses, comparing results for traditional vs. phylogenetic approaches and assessing which characteristics of phylogenies best explained changes in meta-analytic results and relative model fit. Accounting for phylogeny significantly changed estimates of the overall pooled effect size in 47% of datasets for fixed-effects analyses and 7% of datasets for random-effects analyses. Accounting for phylogeny also changed whether those effect sizes were significantly different from zero in 23 and 40% of our datasets (for fixed- and random-effects models, respectively). Across datasets, decreases in pooled effect size magnitudes after incorporating phylogenetic information were associated with larger phylogenies and those with stronger phylogenetic signal. We conclude that incorporating phylogenetic information in ecological meta-analyses is important, and we provide practical recommendations for doing so.

Alligator Wrestling: The Ultimate Wrestling Match

Interactive Effects of Herbivory and Competition Intensity Determine Invasive Plant Performance

Herbivory can reduce plant fitness, and its effects can be increased by competition. Though numerous studies have examined the joint effects of herbivores and competitors on plant performance, these interactive effects are seldom considered in the context of plant invasions. Here, we examined variation in plant performance within a competitive environment in response to both specialist and generalist herbivores using Chinese tallow as a model species. We combined tallow plants from native and invasive populations to form all possible pairwise combinations, and designated invasive populations as stronger neighbours and native populations as weaker neighbours. We found that when no herbivory was imposed, invasive populations always had higher total biomass than natives, regardless of their neighbours, which is consistent with our assumption of increased competitive ability. Defoliation by either generalist or specialist herbivores suppressed plant growth but the effects of specialists were generally stronger for invasive populations. Invasive populations had their lowest biomass when fed upon by specialists while simultaneously competing with stronger neighbours. The root/shoot ratios of invasive populations were lower than those of native populations under almost all conditions, and invasive plants were taller than native plants overall, especially when herbivores were present, suggesting that invasive populations may adopt an "aboveground first" strategy to cope with herbivory and competition. These results suggest that release from herbivores, especially specialists, improves an invader's performance and helps to increase its competitive ability. Therefore, increasing interspecific competition intensity by planting a stronger neighbour while simultaneously releasing a specialist herbivore may be an especially effective method of managing invasive plants.

Classical Swine Fever Virus P7 Protein is a Viroporin Involved in Virulence in Swine

The non-structural protein p7 of Classical Swine Fever Virus (CSFV) is a small hydrophobic polypeptide with an apparent molecular mass of 6 to 7 kDa. The protein contains two hydrophobic stretches of amino acids interrupted by a short charged segment that are predicted to form transmembrane helices and a cytosolic loop respectively. Using reverse genetics, partial in-frame deletions of p7 were deleterious for virus growth, demonstrating that CSFV p7 function is critical for virus production in cell cultures. A panel of CSFV recombinant mutant viruses was created using alanine scanning mutagenesis of the p7 gene harboring sequential three to six amino acid residues long substitutions spanning the entire protein. These recombinant viruses allowed the identification of the regions within p7 that are critical for virus production in vitro. In vivo, some of these viruses were partially or completely attenuated in swine relative to the highly virulent parental CSFV Brescia strain indicating a significant role of p7 in CSFV virulence. Structure-function analyses in model membranes emulating the ER lipid composition confirmed that CSFV p7 is a pore forming protein, and that pore-forming activity resides in the C-terminal transmembrane helix. Therefore, p7 is a viroporin which is clearly involved in the process of CSFV virulence in swine.

Alzheimer's Disease Therapeutic Trials: EU/US Task Force Report on Recruitment, Retention, and Methodology

While we may not be able to find a cure for Alzheimer's disease (AD) in the near future, several drugs presently in trials have shown promise as possible modifiers of disease progression. However, we may not be able to demonstrate efficacy due to issues of recruitment, retention, site-to-site variability, and other methodological issues. It is thus incumbent on the scientific community to find solutions to these problems, particularly as the field moves toward preventing illness or treating the disease in its prodromal stages, where these methodological issues will become even more critical. We need to better understand why participants agree or refuse to enter drug trials, and why both primary care physicians and Alzheimer's specialists agree or refuse to involve their patients. We also need to quantify the impact of requiring imaging studies, extensive questionnaires, cognitive testing, and lumbar punctures on recruitment and retention. With these concerns in mind, an international task force meeting of experts from academia and industry in the United States, European Union, and Japan in San Diego, California on November 2, 2011 to focus on recruitment, retention and other methodological issues related to clinical trials for AD. Based on the recommendations of this Task force meeting, this Perspectives article critically reflects on the most critical and timely methodological issues related to recruitment and retention in prevention and therapeutic trials in AD, which are paralleled by a paradigm shift in the diagnostic conceptualization of this disease, as reflected by recently new proposed diagnostic criteria involving preclinical stages of the disease.

Fetal Sex and Perinatal Outcomes

Abstract Objective: To evaluate the relationship of fetal sex with obstetric risk factors and perinatal outcomes. Material and methods: Retrospective study of deliveries during 2003-2009 at a tertiary hospital based on the analysis of obstetric and neonatal risk variables according to neonatal sex. Results: Of the 29,530 deliveries studied, the neonate was a boy in 15,038 (50.92%) and a girl in 14,492 (49.08%). The rates of gestational diabetes, prematurity, true umbilical cord knot and nuchal cord were higher for male newborns, whereas the rate of echographic diagnosis of intrauterine fetal growth retardation was higher for female newborns. Mothers of male fetuses had higher rates of cesarean delivery and instrumental vaginal delivery. The indication for ending labor due to the non-reassuring fetal heart rate was also more frequent among male newborns. This group had higher rates of acidemia, although there were no significant differences between sexes in other short-term neonatal outcomes. In all subgroups analyzed here, fetal weight was higher in male newborns. Conclusions: Male sex is an independent risk factor for unfavorable outcomes of pregnancy and delivery.

Lack of Sequence Variations in THAP1 Gene and THAP1-binding Sites in TOR1A Promoter of DYT1 Patients

How Can We Improve the Results of Cardiopulmonary Resuscitation in Out-of-hospital Cardiac Arrest in Children? Dispatcher-assisted Cardiopulmonary Resuscitation is a Link in the Chain of Survival*

An Amine-Catalyzed Enantioselective [3+2] Cycloaddition of Azomethine Ylides and α,β-Unsaturated Aldehydes: Applications and Mechanistic Implications

The catalytic enantioselective [3+2] cycloaddition between azomethine ylides and α,β-unsaturated aldehydes catalyzed by α,α-diphenylprolinol has been studied in detail. In particular, the reaction has been extended to the use of 2-alkenylidene aminomalonates generated in situ as azomethine ylide precursors. These reactions lead to the formation of pyrrolidines containing a 5-alkenyl side chain with potential for chemical manipulation. Moreover, a detailed and concise computational study has been carried out to understand the exact nature of the mechanism of this reaction and especially the consequences derived from the incorporation of the chiral secondary amine catalyst on the reaction pathway.

Effect of Lesion Length on Functional Significance of Intermediate Long Coronary Lesions

OBJECTIVE: to assess the relationship between lesion length and other angiographic parameters on the functional significance of long coronary lesions with moderate stenosis. BACKGROUND-: Coronary revascularization is usually based on angiographic percent stenosis. Coronary stenosis length is not usually considered in daily clinical practice for revascularization decision making. The relevance of lesion length might be greater in longer lesions with intermediate stenosis. METHODS.: All coronary lesions >20 mm and of 40-70% percent stenosis assessed by intracoronary pressure wire between 2007 and 2009 were included. Interventionists performing digital quantification of lesion stenosis were blinded to the result of fractional flow reserve (FFR). Correlations between angiographic data and FFR were analyzed. RESULTS.: One hundred and six lesions from 103 patients were included. Reference diameter: 2.9±0.56 mm; maximal stenosis: 49.0±8.7%; minimal luminal diameter (MinimalLD): 1.48±0.4 mm; mean luminal diameter (MeanLD): 2.3±0.5 mm; mean lesion length: 28.7±10.6 mm. Lesions with FFR <0.75 accounted for 33% (n=35). Weak correlations were obtained between FFR and MinimalLD(r=0.36;p<0,0005), MeanLD(r=0.24;p=0,014), maximal(r=0,31;p=0,001) and mean stenosis(r=0,018;p=0,85); strong correlations were observed between FFR and lesion length(r=0,63;p<0,0005), lesion length/MinimalLD(r=0,67;p<0,0005) and lesion length/MeanLD(0,72;p<0,0005). The predictive values of lesion length, lesion length/MinimalLD and lesion length/MeanLD for FFR <0.75 were 0.86, 0.91 and 0.92, respectively. CONCLUSIONS-: In long lesions (>20 mm) with moderate angiographic stenosis, lesion length might be the strongest determinant of functional repercussion. Lesion length should be considered when judging the benefit of revascularization and when seeking functional measures that overcome the limitations of simple stenosis quantification. © 2012 Wiley Periodicals, Inc.

Nurse Staffing and Deficiencies in the Largest For-profit Nursing Home Chains and Chains Owned by Private Equity Companies

To compare staffing levels and deficiencies of the 10 largest U.S. for-profit nursing home chains with five other ownership groups and chain staffing and deficiencies before and after purchase by four private equity (PE) companies.

[Abortive or Minimal-growth Hemangiomas. A Review of 14 Cases]

An Aptamer Beacon Responsive to Botulinum Toxins

Sixty candidate DNA aptamers were developed against botulinum neurotoxin (BoNT) type A light chain (LC) from ten rounds of selection, resulting in several identical sequences. Secondary structures of the identical aptamers were compared to structures of previously reported BoNT A DNA aptamers. A series of ten candidate loop structures were selected from this comparison as potential binding pockets and aptamer beacons. These candidate beacons were synthesized with 5'-TYE 665 and 3'-Iowa Black quencher labels for comparison of fluorescence levels as a function of BoNT A LC concentration. Only three of the ten candidates exhibited any fluorescence response to increasing levels of BoNT A LC. However, of the two most responsive candidates, one represented a subset loop of the larger more intensely fluorescent double-looped structure, designated Beacon 10. This beacon yielded a lower limit of detection of 1 ng/mL in buffer using a spectrofluorometer and a portable handheld fluorometer, but also responded substantially to BoNT A, B, E holotoxins and heavy or light chain components even in a dilute soil suspension, but not in 50% human serum. Beacon 10 did not respond strongly to a variety of other divergent peptides, suggesting that it is relatively specific to the level of botulinum toxins and is only useful for environmental testing. Beacon 10 also shared short sequence segments with other published BoNT aptamer DNA sequences, suggesting that these may be points of physical contact between the aptamers and BoNTs.

IL-1 Receptor-associated Kinase 3 Gene (IRAK3) Variants Associate with Asthma in a Replication Study in the Spanish Population

Role of Arginine-56 Within the Structural Protein VP3 of Foot-and-mouth Disease Virus (FMDV) O1 Campos in Virus Virulence

FMDV O1 subtype undergoes antigenic variation under diverse growth conditions. Of particular interest is the amino acid variation observed at position 56 within the structural protein VP3. Selective pressures influence whether histidine (H) or arginine (R) is present at this position, ultimately influencing in vitro plaque morphology and in vivo pathogenesis in cattle. Using reverse genetics techniques, we have constructed FMDV type O1 Campos variants differing only at VP3 position 56, possessing either an H or R (O1Ca-VP3-56H and O1Ca-VP3-56R, respectively), and characterized their in vitro phenotype and virulence in the natural host. Both viruses showed similar growth kinetics in vitro. Conversely, they had distinct temperature-sensitivity (ts) and displayed significantly different pathogenic profiles in cattle and swine. O1Ca-VP3-56H was thermo stable and induced typical clinical signs of FMD, whereas O1Ca-VP3-56R presented a ts phenotype and was nonpathogenic unless VP3 position 56 reverted in vivo to either H or cysteine (C).

Comparison of Continuous PH-meter and Intermittent PH Paper Monitoring of Gastric PH in Critically Ill Children

A gastric pH below 4 increases the risk of gastrointestinal hemorrhage in critically ill patients. The pH can be monitored intermittently by testing the gastric aspirate using pH paper or continuously using a pH-meter (often in combination with multichannel intraluminal impedance). The objective of this study was to compare these two methods of pH measurement.

[Thrombolytic Therapy Using a Low Dose of Tissue Plasminogen Activator in Children]

To analyse the efficacy and side effects of low doses of tissue plasminogen activator for the treatment of acute arterial and/or venous thrombosis in children.

[Relationship Between PAO2/FIO2 and SATO2/FIO2 with Mortality and Duration of Admission in Critically Ill Children]

The aim of this study is to analyse the relationships and the association between PaO(2)/FiO(2) and SatO(2)/FiO(2with) the duration of admission in Paediatric Intensive Care Units (PICU) and mortality, and to study the relationships between both ratios.

Serum Inverts and Improves the Fluorescence Response of an Aptamer Beacon to Various Vitamin D Analytes

A dominant aptamer loop structure from a library of nearly 100 candidate aptamer sequences developed against immobilized 25-hydroxyvitamin D(3) (calcidiol) was converted into a 5'-TYE 665 and 3'-Iowa black-labelled aptamer beacon. The aptamer beacon exhibited a mild 'lights on' reaction in buffer as a function of increasing concentrations of several vitamin D analogues and metabolites, with a limit of detection of approximately 200 ng/mL, and was not specific for any particular congener. In 10% or 50% human serum, the same aptamer beacon inverted its fluorescence behaviour to become a more intense 'lights off' reaction with an improved limit of detection in the range 4-16 ng/mL. We hypothesized that this drastic change in fluorescence behaviour was due to the presence of creatinine and urea in serum, which might destabilize the quenched beacon, causing an increase in fluorescence followed by decreasing fluorescence as a function of vitamin D concentrations that may bind and quench increasingly greater fractions of the denatured beacons. However, the results of several control experiments in the presence of physiological or greater concentrations of creatinine and urea, alone or combined in buffer, failed to produce the beacon fluorescence inversion. Other possible mechanistic hypotheses are also discussed.

Surface Display of AcMNPV Occlusion-derived P74 Does Not Enhance Oral Infectivity of Budded Viruses

Baculovirus occlusion-derived viruses (ODVs) and budded viruses (BVs) are morphologically and functionally distinct. ODVs are responsible for primary infection in insect hosts because of their high per os infectivity. On the contrary, BVs poorly infect endothelial gut cells, but propagate the infection in the tissues of insects with a high efficiency. P74 is one of the most important proteins from ODVs, and it participates in the attachment of this viral phenotype to endothelial cells in the midgut. We evaluated the possibility of pseudotyping BVs of Autographa californica multiple nucleopolyhedrovirus with two versions of P74 and its effect on their oral infectivity. Both recombinant BVs contained P74 and replicated similarly to wild-type viruses. Nevertheless, the presence of P74 on the BV's surface does not enhance the oral infectivity of this phenotype, suggesting that the presence of P74 in the membrane of budded virions interferes with their mechanism of infecting midgut cells.

Purification and Long-term Expansion of Multipotent Endothelial-like Cells with Potential Cardiovascular Regeneration

Endothelial progenitor cells (EPC) represent a relatively rare cell population, and expansion of sufficient cell numbers remains a challenge. Nevertheless, human adipose-derived stem cells (hASC) can be easily isolated and possess the ability to differentiate into endothelial cells. Here, we propose the isolation and characterization of multipotent endothelial-like cells (ME-LC) with the capacity to maintain their vascular progenitor properties for long periods. hASC were isolated from lipoaspirates and cultured through distinct consecutive culture stages for 2 months to enrich ME-LC: first in Dulbecco's modified Eagle's medium-fetal bovine serum (stage I), followed by a stage of culture in absent of fetal bovine serum (stage II), a culture in SFO3 medium (stage III), and, finally, the culture of ME-LC into collagen IV-coated flasks in endothelial growth medium (EGM-2) (stage IV). ME-LC display increased expression levels of endothelial and hematopoietic lineage markers (CD45, KDR, and CXCR4) and EPC markers (CD34 and CD133), whereas the expression of CD31 was barely detectable. Reverse transcription (RT)-polymerase chain reaction assays showed expression of genes involved in early stages of EPC differentiation and decreased expression of genes associated to differentiated EPC (TIE-2, DLL4, and FLT-1). ME-LC formed capillary-like structures when grown on Matrigel, secreted increased levels of stromal cell-derived factor-1 (SDF-1), and showed the ability to migrate attracted by SDF-1, vascular endothelial growth factor, and hematopoietic growth factor cytokines. Importantly, ME-LC retained the capacity to differentiate into cardiomyocyte-like cells. We present a simplified and efficient method to generate large numbers of autologous ME-LC from lipoaspirates-derived hASC, opening up potential cell-based therapies for cardiovascular regenerative medicine.

Waiting
simple hit counter