bluuebunny/crossref_metadata_2025 huggingface dataset:
CD4+T Cells Develop Antiretroviral Cytotoxic Activity in the Absence of Regulatory T Cells and CD8+T Cells
Authors: Manzke Nora , Akhmetzyanova Ilseyar , Hasenkrug Kim J. , Trilling Mirko , Zelinskyy Gennadiy , Dittmer Ulf
Published: March 2013

Conventional CD4+T cells play an important role in viral immunity. In most virus infections, they provide essential help for antiviral B and T cell responses. In chronic infections, including HIV infection, an expansion of regulatory T cells (Tregs) has been demonstrated, which can suppress virus-specific CD4+T cell responsesin vitro. However, the suppressive activity of Tregs on effector CD4+T cells in retroviral infection is less well documentedin vivo. We took advantage of a transgenic mouse in which Tregs can be selectively depleted to determine the influence of such cells on retrovirus-specific CD4+T cell responses during an ongoing infection. Mice were infected with Friend retrovirus (FV), and Tregs were depleted during the acute phase of the infection. In nondepleted mice, activated CD4+T cells produced Th1-type cytokines but did not exhibit any antiviral cytotoxicity as determined in a major histocompatibility complex (MHC) class II-restrictedin vivocytotoxic T lymphocyte (CTL) assay. Depletion of Tregs significantly increased the numbers of virus-specific CD4+T cells and improved their cytokine production, whereas it induced only very little CD4+T cell cytotoxicity. However, after dual depletion of Tregs and CD8+T cells, conventional CD4+T cells developed significant cytotoxic activity against FV epitope-labeled target cellsin vivoand contributed to the control of virus replication. Thus, both Tregs and CD8+T cells influence the cytotoxic activity of conventional CD4+T cells during an acute retroviral infection.
Mutational Inactivation of Herpes Simplex Virus 1 MicroRNAs Identifies Viral mRNA Targets and Reveals Phenotypic Effects in Culture
Authors: Flores Omar , Nakayama Sanae , Whisnant Adam W. , Javanbakht Hassan , Cullen Bryan R. , Bloom David C.
Published: March 2013

Herpes simplex virus 1 (HSV-1), a ubiquitous human pathogen, expresses several viral microRNAs (miRNAs). These, along with the latency-associated transcript, represent the only viral RNAs detectable in latently infected neuronal cells. Here, for the first time, we analyze which HSV-1 miRNAs are loaded into the RNA-induced silencing complex (RISC), the key effector of miRNA function. Only 9 of the 17 reported HSV-1 miRNAs, i.e., miR-H1 to miR-H8 plus miR-H11, were found to actually load into the RISC. Surprisingly, this analysis also revealed that HSV-1 miRNAs loaded into the RISC with efficiencies that differed widely; <1% of the miR-H1-3p miRNA detectable in HSV-1-infected cells was loaded into the RISC. Analysis of HSV-1 mutants individually lacking the viral miR-H2, miR-H3, or miR-H4 miRNA revealed that loss of these miRNAs affected the rate of replication of HSV-1 in neuronal cells but not in fibroblasts. Analysis of mRNA and protein expression, as well as assays mapping viral miRNA binding sites in infected cells, showed that endogenous HSV-1 miR-H2 binds to viral ICP0 mRNA and inhibits its expression, while endogenous miR-H4 inhibits the expression of the viral ICP34.5 gene. In contrast, no viral mRNA target for miR-H3 could be detected, even though miR-H3, like miR-H4, is perfectly complementary to ICP34.5 mRNA. Together, these data demonstrate that endogenous HSV-1 miRNA expression can significantly alter viral replication in culture, and they also identify two viral mRNA targets for miR-H2 and miR-H4 that can partially explain this phenotype.
Guanine-Nucleotide Exchange Factor RCC1 Facilitates a Tight Binding between the Encephalomyocarditis Virus Leader and Cellular Ran GTPase
Authors: Petty Ryan V. , Palmenberg Ann C.
Published: March 2013

The leader (L) protein of encephalomyocarditis virus (EMCV) shuts off host cell nucleocytoplasmic trafficking (NCT) by inducing hyperphosphorylation of nuclear pore proteins. This dramatic effect by a nonenzymatic protein of 6 kDa is not well understood but clearly involves L binding to cellular Ran GTPase, a critical factor of active NCT. Exogenous GDP and GTP are inhibitory to L-Ran binding, but the guanine-nucleotide exchange factor RCC1 can relieve this inhibition. In the presence of RCC1, L binds Ran with a

K
D

(equilibrium dissociation constant) of ∼3 nM and reaches saturation within 20 min. The results of fluorescently tagged nucleotide experiments suggest that L-Ran interactions affect the nucleotide-binding pocket of Ran.
A Comparison of Murine Leukemia Viruses That Escape from Human and Rhesus Macaque TRIM5αs
Authors: Ohkura Sadayuki , Stoye Jonathan P.
Published: March 2013

To better understand the binding mechanism of TRIM5α to retrovirus capsid, we had previously selected N-tropic murine leukemia virus (N-MLV) mutants escaping from rhesus macaque TRIM5α (rhTRIM5α) by passaging the virus in rhTRIM5α-expressing cells and selecting for nonrestricted variants. To test the commonality of the findings from the rhTRIM5α study, we have now employed a similar genetic approach using human TRIM5α (huTRIM5α). Consistent with the rhTRIM5α study, the mapped huTRIM5α escape mutations were distributed across the capsid exterior, confirming the extended binding surface between virus and restriction factor. Compared to the results of the previous study, fewer escape mutations were identified, with particular mutants being repeatedly selected. Three out four huTRIM5α escape variants showed resistance to all primate TRIM5αs tested, but two of them sacrificed viral fitness, observations that were not made in the rhTRIM5α study. Moreover, differences in amino acid changes associated with escape from hu- and rhTRIM5αs suggested a charge dependence of the restriction by different TRIM5αs. Taken together, these results suggest that the recognition of the entire capsid surface is a general strategy for TRIM5α to restrict MLV but that significantly different specific interactions are involved in the binding of TRIM5α from different species to the MLV capsid core.
The ULb′ Region of the Human Cytomegalovirus Genome Confers an Increased Requirement for the Viral Protein Kinase UL97
Authors: Wang Depeng , Li Gang , Schauflinger Martin , Nguyen Christopher C. , Hall Ellie D. , Yurochko Andrew D. , von Einem Jens , Kamil Jeremy P.
Published: March 2013

We report a requirement for the viral protein kinase UL97 in human cytomegalovirus (HCMV) replication that maps to the ULb′ region of the viral genome. A UL97-null (Δ97) mutant of strain TB40/E, which encodes a full-length ULb′ region, exhibited replication defects, particularly in production of cell-free virus, that were more severe than those seen with a Δ97 mutant of laboratory strain AD169, which harbors extensive deletions in its ULb′ region. These differences were recapitulated with additional HCMV strains by treatment with a UL97 kinase inhibitor, 1-(β-
l
-ribofuranosyl)-2-isopropylamino-5,6-dichlorobenzimidazole (maribavir). We observed lower levels of viral DNA synthesis and an increased requirement for UL97 in viral late gene expression in strains with full-length ULb′ regions. Analysis of UL97-deficient TB40/E infections by electron microscopy revealed fewer C-capsids in nuclei, unusual viral particles in the cytoplasmic assembly compartment, and defective viral nuclear egress. Partial inhibition of viral DNA synthesis caused defects in production of cell-free virus that were up to ∼100-fold greater than those seen with cell-associated virus in strains TB40/E and TR, suggesting that UL97-dependent defects in cell-free virus production in strains with full-length ULb′ regions were secondary to DNA synthesis defects. Accordingly, a chimeric virus in which the ULb′ region of TB40/E was replaced with that of AD169 showed reduced effects of UL97 inhibition on viral DNA synthesis, late gene expression, and production of cell-free virus compared to parental TB40/E. Together, these results argue that the ULb′ region encodes a factor(s) which invokes an increased requirement for UL97 during viral DNA synthesis.
Sigma-1 Receptor Regulates Early Steps of Viral RNA Replication at the Onset of Hepatitis C Virus Infection
Authors: Friesland Martina , Mingorance Lidia , Chung Josan , Chisari Francis V. , Gastaminza Pablo
Published: March 2013

Hepatitis C virus (HCV) genome replication is thought to occur in a membranous cellular compartment derived from the endoplasmic reticulum (ER). The molecular mechanisms by which these membrane-associated replication complexes are formed during HCV infection are only starting to be unraveled, and both viral and cellular factors contribute to their formation. In this study, we describe the discovery of nonopioid sigma-1 receptor (S1R) as a cellular factor that mediates the early steps of viral RNA replication. S1R is a cholesterol-binding protein that resides in lipid-rich areas of the ER and in mitochondrion-associated ER membranes (MAMs). Several functions have been ascribed to this ER-resident chaperone, many of which are related to Ca
2+
signaling at the MAMs and lipid storage and trafficking. Downregulation of S1R expression by RNA interference (RNAi) in Huh-7 cells leads to a proportional decrease in susceptibility to HCV infection, as shown by reduced HCV RNA accumulation and intra- and extracellular infectivity in single-cycle infection experiments. Similar RNAi studies in persistently infected cells indicate that S1R expression is not rate limiting for persistent HCV RNA replication, as marked reduction in S1R in these cells does not lead to any decrease in HCV RNA or viral protein expression. However, subgenomic replicon transfection experiments indicate that S1R expression is rate limiting for HCV RNA replication without impairing primary translation. Overall, our data indicate that the initial steps of HCV infection are regulated by S1R, a key component of MAMs, suggesting that these structures could serve as platforms for initial RNA replication during HCV infection.
Pandemic influenza in Papua New Guinea: a modelling study comparison with pandemic spread in a developed country
Authors: Milne George J , Baskaran Pravin , Halder Nilimesh , Karl Stephan , Kelso Joel
Published: March 2013

Objectives

The possible occurrence of a highly pathogenic influenza strain is of concern to health authorities worldwide. It is known that during past influenza pandemics developing countries have experienced considerably higher death rates compared with developed countries. Furthermore, many developing countries lack appropriate pandemic preparedness plans. Mathematical modelling studies to guide the development of such plans are largely focused on predicting pandemic influenza spread in developed nations. However, intervention strategies shown by modelling studies to be highly effective for developed countries give limited guidance as to the impact which an influenza pandemic may have on low-income countries given different demographics and resource constraints. To address this, an individual-based model of a Papua New Guinean (PNG) community was created and used to simulate the spread of a novel influenza strain. The results were compared with those obtained from a comparable Australian model.

Design

A modelling study.

Setting

The towns of Madang in PNG (population ∼35 000) and Albany (population ∼30 000) in Australia.

Outcome measures

Daily and cumulative illness attack rates in both models following introduction of a novel influenza strain into a naive population, for an unmitigated scenario and two social distancing intervention scenarios.

Results

The unmitigated scenario indicated an approximately 50% higher attack rate in PNG compared with the Australian model. The two social distancing-based interventions strategies were 60–70% less effective in a PNG setting compared with an Australian setting.

Conclusions

This study provides further evidence that an influenza pandemic occurring in a low-income country such as PNG may have a greater impact than one occurring in a developed country, and that PNG-feasible interventions may be substantially less effective. The larger average household size in PNG, the larger proportion of the population under 18 and greater community-wide contact all contribute to this feature.
Study protocol for a randomised controlled double-blinded trial of the dose-dependent efficacy and safety of primaquine for clearance of gametocytes in children with uncomplicated falciparum malaria in Uganda
Authors: Eziefula Alice Chijioke , Staedke Sarah G , Yeung Shunmay , Webb Emily , Kamya Moses , White Nicholas J , Bousema Teun , Drakeley Chris
Published: March 2013

Objectives

For the purpose of blocking transmission ofPlasmodium falciparummalaria from humans to mosquitoes, a single dose of primaquine is recommended by the WHO as an addition to artemisinin combination therapy. Primaquine clears gametocytes but causes dose-dependent haemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Evidence is needed to inform the optimal dosing of primaquine for malaria elimination programmes and for the purpose of interrupting the spread of artemisinin-resistant malaria. This study investigates the efficacy and safety of reducing doses of primaquine for clearance of gametocytes in participants with normal G6PD status.

Methods and analysis

In this prospective, four-armed randomised placebo-controlled double-blinded trial, children aged 1–10 years, weighing over 10 kg, with haemoglobin ≥8 g/dl and uncomplicatedP falciparummalaria are treated with artemether lumefantrine and randomised to receive a dose of primaquine (0.1, 0.4 or 0.75 mg base/kg) or placebo on the third day of treatment. Participants are followed up for 28 days. Gametocytaemia is measured by quantitative nucleic acid sequence-based analysis on days 0, 2, 3, 7, 10 and 14 with a primary endpoint of the number of days to gametocyte clearance in each treatment arm and secondarily the area under the curve of gametocyte density over time. Analysis is for non-inferiority of efficacy compared to the reference dose, 0.75 mg base/kg. Safety is assessed by pair-wise comparisons of the arithmetic mean (±SD) change in haemoglobin concentration per treatment arm and analysed for superiority to placebo and incidence of adverse events. Ethics and dissemination Approval was obtained from the ethical committees of Makerere University School of Medicine, the Ugandan National Council of Science and Technology and the London School of Hygiene and Tropical Medicine.

Results

These will be disseminated to inform malaria elimination policy, through peer-reviewed publication and academic presentations.
Review of the use of intralesional steroid injections in the management of ileocolonic Crohn's strictures
Authors: Bevan Roisin , Rees Colin J , Rutter Matthew D , Macafee David A L
Published: March 2013

Most patients with Crohn's disease present with either terminal ileal or colonic disease, with 70% requiring surgery by 10 years after diagnosis. Recurrent stricturing at the anastomotic site is common, often symptomatic and can require re-operation with its inherent risks. Balloon dilation has been shown to provide good symptom relief from such strictures. However, repeat dilations may be required, and further surgical intervention to an anastomotic stricture is needed in up to 30% of cases. Injection of corticosteroids has been suggested as an adjunct to dilation in order to improve outcomes. This paper reviews the current literature on the use of intralesional steroid injections following endoscopic balloon dilation of anastomotic and de novo Crohn's strictures. There have been only two randomised placebo controlled trials and five small non-controlled or retrospective studies. Study numbers vary from 10 to 29 patients. The two randomised trials conflict in their conclusions and numbers are small in these studies. Currently therefore, no firm support can be given to the routine use of intralesional steroid injections.
From IEDs to AIDS? Detection of HIV in human corpses by rapid screening tests after suspected intentional transmission in terrorist attacks
Authors: Frickmann Hagen , Wulff B , Loderstædt U , Hagen R M , Sturm D , Polywka S
Published: March 2013

Objectives

We evaluated the feasibility of intentional transmission of HIV by means of suicide bombing and rape as a terrorist tactic in asymmetric conflicts by evaluating the recognised optimum conditions for biological warfare. We also estimated the suitability of a fourth-generation rapid test for HIV detection in the blood of dead terrorists killed in the completion of their mission.

Methods

The feasibility of deliberate transmission of HIV for terroristic ends was evaluated on the basis of published experience from passive biological warfare research. In addition, blood from four recently deceased HIV-positive patients and four HIV-negative control corpses, stored at 4°C in a mortuary, was analysed at 12, 24, 36 and 48 h postmortem by rapid serological testing.

Results

The feasibility of HIV infection for terroristic purposes was established. The fourth-generation HIV rapid test we evaluated identified all HIV-positive samples and was negative for all HIV-negative samples.

Conclusions

Rapid HIV testing from the remains of dead terrorists in the deployed military environment is possible. Samples should be acquired quickly, basic sample preparation is advisable and consequent decisions concerning postexposure prophylaxis should take into account the diagnostic gap in early infections.
Post Cold War transformation of the medical function in support of the deployed soldier
Authors: Vekerdi Zoltan
Published: March 2013

This article summarises the changes that resulted in, and still act towards, final implementation of a separate medical function in operational medical support. This article is not intended to represent an historical account, but to provide concise supplemental material for decision makers to position medical under the commander, which enables medical staff to support and care for the troops and which can be used in the best possible way as an image forming factor for the force. The aim of this article is to clearly articulate the necessity for independence of the medical and logistic functions, while recognising the need for continued close coordination.
A novel protein from Eupolyphaga sinensis inhibits adhesion, migration, and invasion of human lung cancer A549 cells
Authors: Wang Feng-xia , Wu Ning , Wei Jian-teng , Liu Jia , Zhao Jin , Ji Ai-guo , Lin Xiu-kun
Published: March 2013

Eupolyphaga sinensis Walker is an important insect used in Chinese traditional medicine. In this study, we purified a 72-kDa anticancer protein, designated as EPS72, from this species using ammonium sulfate precipitation, ultrafiltration, CM Sepharose Fast Flow cation exchange, Q Sepharose High Performance (HP) anion exchange, Butyl Sepharose HP hydrophobic chromatography, and Superdex 75 gel filtration chromatographic techniques. EPS72 exhibited a potent anticancer activity against the human lung cancer A549 cell line (IC50, 18.76 μg/mL). Further study showed that EPS72 could induce A549 cell detachment and apoptosis, inhibit cell adhesion to fibronectin and collagen IV, and restrain cell migration and invasion. Moreover, EPS72 significantly decreased the expression of β1-integrin. This study suggests that EPS72 could potentially be developed as a novel anticancer therapeutic agent due to its possible antimetastatic activity.
Modulation of arsenic toxicity-induced oxidative damage by coronatine pretreatment in sweet basil (Ocimum basilicum) seedlings
Authors: Zare Dehabadi Saeid , Shoushtari Abdolhamid , Asrar Zahra
Published: March 2013

Coronatine (COR), a functional analogue of jasmonates, affects the accumulation of defense-related metabolites in plants. However, information on how its effects may be mediated by heavy metal stress is scanty. This study was carried out to determine the changes in some physiological parameters in sweet basil (Ocimum basilicum L.) seedlings pretreated with COR under arsenic (As) toxicity. COR was applied to seedlings at the three-leaf stage at 50 and 100 nanomolars (nmol·L−1). Arsenic at 150 and 300 μmol·L−1was imposed after completion of COR treatment. Toxic effects of As were reflected by the reduction in growth parameters and photosynthetic pigments and induction of lipid peroxidation coupled with enhancing hydrogen peroxide and electrolyte leakage in leaves. Under As toxicity, plants treated with COR significantly increased the fresh mass and relative water content in leaves. The increase was accompanied by decreased lipid peroxidation and hydrogen peroxide content and maintenance of chlorophyll pigments. COR supplement also increased the accumulation of phenolic compounds and proline content in the leaf of As-treated seedlings. Pretreatment with COR significantly enhanced activities of catalase (CAT), superoxide dismutase (SOD), and guaiacol peroxidase (POD) in basil leaves under As treatment. The results suggested that COR might alleviate As toxicity in sweet basil by activating antioxidant enzymes and inducing conservative components, thereby preventing membrane peroxidation.
The application of Ussing chambers for determining the impact of microbes and probiotics on intestinal ion transport
Authors: Lomasney Kevin W. , Hyland Niall P.
Published: March 2013

Host–microbe interactions have gained considerable attention in recent years with regards to their role in various organic disorders and diseases. In particular, research efforts have focused on the intestinal microbiota, where the largest and most diverse populations not only co-exist with the host, but also directly influence the state and function of the gastrointestinal (GI) tract. Moreover, both human and animal studies alike are now beginning to show a positive influence of probiotic bacteria on GI disorders associated with diarrhoea or constipation. Diarrheagenic GI diseases, such as those caused by Vibreo cholera or enterpathogenic Eschericia coli, have well-characterised interactions with the host that explain much of the observed symptoms, in particular severe diarrhoea. However, the mechanisms of action of nonpathogenic bacteria or probiotics on host physiology are less clearly understood. In the context of defining the mechanisms of action of probiotics in vitro, the Ussing chamber has proven to be a particularly useful tool. Here, we will present data from several studies that have defined molecular targets for microbes and putative probiotics in the regulation of intestinal secretory and absorptive function, and we will discuss these in the context of their application in pathogen- or inflammation-induced alterations in intestinal ion transport.
HYPERCOMPUTATION: FANTASY OR REALITY? A POSITION PAPER
Authors: SYROPOULOS APOSTOLOS
Published: March 2013

Hypercomputation is about the feasibility of machines and systems that are either more expressive or computationally more powerful than the Turing machine. A number of researchers and thinkers have put forth a number of supposedly knock-out arguments against hypercomputation. Nevertheless, these arguments are not unwavering as they seem to be and here I explain why.
NATURALLY PERTURBED S3 NEUTRINOS
Authors: JORA RENATA , SCHECHTER JOSEPH , NAEEM SHAHID M.
Published: March 2013

We simplify and extend our previous model for the masses and mixing matrix of three Majorana neutrinos based on permutation symmetry S3 and the perturbations which violate this symmetry. The perturbations are arranged such that we get the smaller solar neutrinos mass difference at second-order. We work out the corrections to the tribimaximal mixing matrix with the nonzero value for s13 and the conventional CP-violating phase. It is shown that the results of the model are comparable with the global analysis of neutrino oscillation data.
AUXILIARY ADAPTIVE MECHANISM IN CHAOS SYNCHRONIZATION: ESTIMATORS FOR LIPSCHITZ CONSTANT AND UPPER BOUND OF TIME-DELAY'S CHANGE RATE
Authors: TU JIAN-JUN , HE HAN-LIN , XIONG PING
Published: March 2013

Adaptive robust synchronization method is proposed for chaos synchronization of Lurie systems with time-varying delay. To weaken the restrictions on the change rate of time-varying delay in synchronization problems, adaptive estimations related to the derivative's upper bound of the time-varying delay are designed, so this upper bound can be unknown. The Lipschitz constant of the nonlinear link is also adaptively estimated, rather than being pre-calculated. Whole design is in the framework of robust control, and the synchronization can endure disturbance effectively. In addition, the synchronization of chaotic Lurie system with time-varying delay is realized as an example.
ON FINSLERIZED ABSOLUTE PARALLELISM SPACES
Authors: YOUSSEF NABIL L. , SID-AHMED AMR M. , TAHA EBTSAM H.
Published: March 2013

The aim of this paper is to construct and investigate a Finsler structure within the framework of a Generalized Absolute Parallelism (GAP)-space. The Finsler structure is obtained from the vector fields forming the parallelization of the GAP-space. The resulting space, which we refer to as a Finslerized absolute parallelism (parallelizable) space, combines within its geometric structure the simplicity of GAP-geometry and the richness of Finsler geometry, hence is potentially more suitable for applications and especially for describing physical phenomena. A study of the geometry of the two structures and their interrelation is carried out. Five connections are introduced and their torsion and curvature tensors derived. Some special Finslerized parallelizable spaces are singled out. One of the main reasons to introduce this new space is that both absolute parallelism and Finsler geometries have proved effective in the formulation of physical theories, so it is worthy to try to build a more general geometric structure that would share the benefits of both geometries.
STRESS ANALYSIS OF THICK LAMINATED PLATES USING TRIGONOMETRIC SHEAR DEFORMATION THEORY
Authors: GHUGAL YUWARAJ M. , SAYYAD ATTESHAMUDDIN S.
Published: March 2013

A trigonometric shear deformation theory (TSDT) taking into account transverse shear deformation effect as well as transverse normal strain effect is presented. The inplane displacement field uses sinusoidal function in terms of thickness coordinate to include the shear deformation effect. The cosine function in thickness coordinates is used in transverse displacement to include the effect of transverse normal strain. Governing equations and boundary conditions of the theory are obtained using the principle of virtual work. The results of displacements and stresses for static flexure of simply supported symmetric and anti-symmetric cross-ply laminated square plates subjected to parabolic load and line load are obtained. The results obtained by present theory are compared with those of classical, first-order and higher-order plate theories.
DESIGN AND MECHANICAL PROPERTIES OF LIQUID RUBBER-BASED CONCRETE
Authors: LIU YIPING , TANG LIQUN , AI SHIGANG , LIU ZEJIA , HE TINGHUI , JIANG ZHENYU , FANG DAINING
Published: March 2013

A new type of concrete was developed using liquid rubber (polyurethane) as binder and graded stones as aggregate. The mechanical properties of the prepared liquid rubber-based concrete (LRBC) were systematically investigated through flexural and compressive tests. The dynamic response of LRBC to impact was studied using a spit Hopkinson pressure bar system, which demonstrates a non-monotonic strain rate sensitivity of LRBC. Furthermore, three typical pavement performance tests, i.e., rutting, seepage and sanding tests, were carried out to evaluate the potential of LRBC for the applications in pavement systems. According to the experimental study, the optimum rubber-aggregate ratio was found to be 17% (weight of binder by that of aggregate). The LRBC prepared with this recipe showed the superiority in most pavement performance indicators to other three types of conventional asphalt concrete.
Depression and Cardiovascular Disorders
Authors: Whooley Mary A. , Wong Jonathan M.
Published: March 2013

During the past two decades, research in the field of depression and cardiovascular disorders has exploded. Multiple studies have demonstrated that depression is more prevalent in populations with cardiovascular disease, is a robust risk factor for the development of cardiovascular disease in healthy populations, and is predictive of adverse outcomes (such as myocardial infarction and death) among populations with preexisting cardiovascular disease. Mechanistic studies have shown that poor health behaviors, such as physical inactivity, medication nonadherence, and smoking, strongly contribute to this association. Small randomized trials have found that antidepressant therapies may improve cardiac outcomes. Based on this accumulating evidence, the American Heart Association has recommended routine screening for depression in all patients with coronary heart disease. This review examines the key epidemiological literature on depression and cardiovascular disorders and discusses our current understanding of the mechanisms responsible for this association. We also examine current recommendations for screening, diagnosis, and management of depression. We conclude by highlighting new research areas and discussing therapeutic management of depression in patients with cardiovascular disorders.
Worry and Generalized Anxiety Disorder: A Review and Theoretical Synthesis of Evidence on Nature, Etiology, Mechanisms, and Treatment
Authors: Newman Michelle G. , Llera Sandra J. , Erickson Thane M. , Przeworski Amy , Castonguay Louis G.
Published: March 2013

Generalized anxiety disorder (GAD) is associated with substantial personal and societal cost yet is the least successfully treated of the anxiety disorders. In this review, research on clinical features, boundary issues, and naturalistic course, as well as risk factors and maintaining mechanisms (cognitive, biological, neural, interpersonal, and developmental), are presented. A synthesis of these data points to a central role of emotional hyperreactivity, sensitivity to contrasting emotions, and dysfunctional attempts to cope with strong emotional shifts via worry. Consistent with the Contrast Avoidance model, evidence shows that worry evokes and sustains negative affect, thereby precluding sharp increases in negative emotion. We also review current treatment paradigms and suggest how the Contrast Avoidance model may help to target key fears and avoidance tendencies that serve to maintain pathology in GAD.
Hypertension in mice with transgenic activation of the brain renin-angiotensin system is vasopressin dependent
Authors: Littlejohn Nicole K. , Siel Rick B. , Ketsawatsomkron Pimonrat , Pelham Christopher J. , Pearson Nicole A. , Hilzendeger Aline M. , Buehrer Beth A. , Weidemann Benjamin J. , Li Huiping , Davis Deborah R. , Thompson Anthony P. , Liu Xuebo , Cassell Martin D. , Sigmund Curt D. , Grobe Justin L.
Published: March 2013

An indispensable role for the brain renin-angiotensin system (RAS) has been documented in most experimental animal models of hypertension. To identify the specific efferent pathway activated by the brain RAS that mediates hypertension, we examined the hypothesis that elevated arginine vasopressin (AVP) release is necessary for hypertension in a double-transgenic model of brain-specific RAS hyperactivity (the “sRA” mouse model). sRA mice experience elevated brain RAS activity due to human angiotensinogen expression plus neuron-specific human renin expression. Total daily loss of the 4-kDa AVP prosegment (copeptin) into urine was grossly elevated (≥8-fold). Immunohistochemical staining for AVP was increased in the supraoptic nucleus of sRA mice (∼2-fold), but no quantitative difference in the paraventricular nucleus was observed. Chronic subcutaneous infusion of a nonselective AVP receptor antagonist conivaptan (YM-087, Vaprisol, 22 ng/h) or the V2-selective antagonist tolvaptan (OPC-41061, 22 ng/h) resulted in normalization of the baseline (∼15 mmHg) hypertension in sRA mice. Abdominal aortas and second-order mesenteric arteries displayed AVP-specific desensitization, with minor or no changes in responses to phenylephrine and endothelin-1. Mesenteric arteries exhibited substantial reductions in V1A receptor mRNA, but no significant changes in V2 receptor expression in kidney were observed. Chronic tolvaptan infusion also normalized the (5 mmol/l) hyponatremia of sRA mice. Together, these data support a major role for vasopressin in the hypertension of mice with brain-specific hyperactivity of the RAS and suggest a primary role of V2 receptors.
Exhausting exercise and tissue-specific expression of monocarboxylate transporters in rainbow trout
Authors: Omlin Teye , Weber Jean-Michel
Published: March 2013

Transmembrane lactate movements are mediated by monocarboxylate transporters (MCTs), but these proteins have never been characterized in rainbow trout. Our goals were to clone potential trout MCTs, determine tissue distribution, and quantify the effects of exhausting exercise on MCT expression. Such information could prove important to understand the mechanisms underlying the classic “lactate retention ” seen in trout white muscle after intense exercise. Four isoforms were identified and partially characterized in rainbow trout: MCT1a, MCT1b, MCT2, and MCT4. MCT1b was the most abundant in heart and red muscle but poorly expressed in the gill and brain where MCT1a and MCT2 were prevalent. MCT expression was strongly stimulated by exhausting exercise in brain (MCT2: +260%) and heart (MCT1a: +90% and MCT1b: +50%), possibly to increase capacity for lactate uptake in these highly oxidative tissues. By contrast, the MCTs of gill, liver, and muscle remained unaffected by exercise. This study provides a possible functional explanation for postexercise “lactate retention” in trout white muscle. Rainbow trout may be unable to release large lactate loads rapidly during recovery because: 1) they only poorly express MCT4, the main lactate exporter found in mammalian glycolytic muscles; 2) the combined expression of all trout MCTs is much lower in white muscle than in any other tissue; and 3) exhausting exercise fails to upregulate white muscle MCT expression. In this tissue, carbohydrates act as an “energy spring” that alternates between explosive power release during intense swimming (glycogen to lactate) and recoil during protracted recovery (slow glycogen resynthesis from local lactate).
Transfer of ballistic motor skill between bilateral and unilateral contexts in young and older adults: neural adaptations and behavioral implications
Authors: Hinder Mark R. , Carroll Timothy J. , Summers Jeffery J.
Published: March 2013

Bilateral movement rehabilitation is gaining popularity as an approach to improve the recovery not only of bimanual function but also of unilateral motor tasks. While the neural mechanisms mediating the transfer of bilateral training gains into unimanual contexts are not fully understood, converging evidence from behavioral, neurophysiological, and imaging studies suggests that bimanual movements are not simply the superposition of unimanual tasks undertaken with both (upper) limbs. Here we investigated the neural responses in both hemispheres to bilateral ballistic motor training and the extent to which performance improvements transferred to a unimanual task. Since aging influences interhemispheric interactions during movement production, both young ( n = 9; mean age 19.4 yr; 6 women, 3 men) and older ( n = 9; 66.3 yr; 7 women, 2 men) adults practiced a bilateral motor task requiring simultaneous “fast-as-possible” abductions of their left and right index fingers. Changes in bilateral and unilateral performance, and in corticospinal excitability and intracortical inhibition, were assessed. Strong transfer was observed between bimanual and unimanual contexts for both age groups. However, in contrast to previous reports of substantial bilateral cortical adaptations following unilateral training, increases in corticospinal excitability following bilateral training were not statistically reliable, and a release of intracortical inhibition was only observed for older adults. The results indicate that the neural mechanisms of motor learning for bilateral ballistic tasks differ from those that underlie unimanual ballistic performance improvement but that aging results in a greater overlap of the neural mechanisms mediating bilateral and unilateral ballistic motor performance.
Feasibility of a Microarray-Based Point-of-CareCYP2C19Genotyping Test for Predicting Clopidogrel On-Treatment Platelet Reactivity
Authors: Chae Hyojin , Kim Myungshin , Koh Yoon-Seok , Hwang Byung-Hee , Kang Min-Kyu , Kim Yonggoo , Park Hae-il , Chang Kiyuk
Published: March 2013

Clopidogrel is a prodrug which is converted into active metabolite by cytochrome P450 isoenzyme,CYP2C19. Numerous polymorphisms ofCYP2C19are reported, and a strong link exists between loss-of-function (LOF) or gain-of-function polymorphisms, clopidogrel metabolism, and clinical outcome. Hence, a fully automated point-of-care CYP2C19 genotyping assay is more likely to bring personalized antiplatelet therapy into real practice. We assessed the feasibility of the Verigene 2C19/CBS Nucleic Acid Test, a fully automated microarray-based assay, compared to bidirectional sequencing, and performed VerifyNow P2Y12 assay to evaluate the effect ofCYP2C19polymorphisms on on-treatment platelet reactivity in 57 Korean patients treated with clopidogrel after percutaneous coronary intervention. The Verigene 2C19/CBS assay identified *2, *3, and *17 polymorphisms with 100% concordance to bidirectional sequencing in 180 minutes with little hands-on time. Patients were classified into 4 groups: extensive (*1/*1;n=12, 21.1%), intermediate (*1/*2, *1/*3;n=33, 57.9%), poor (*2/*2, *2/*3, and *3/*3;n=11, 19.3%), and ultrarapid metabolizers (*1/*17;n=1, 1.8%). The prevalence of theCYP2C19  *2, *3, and *17 alleles was 36.0%, 12.3%, and 0.9%. Platelet reactivity showed gene dose response according to the number ofCYP2C19LOF allele. In conclusion, the Verigene 2C19/CBS assay gave accurateCYP2C19genotype results which were in well match with the differing on-treatment platelet reactivity.
Time Synchronization in Wireless Sensor Networks Using Max and Average Consensus Protocol
Authors: Dengchang Zhao , Zhulin An , Yongjun Xu
Published: March 2013

This paper proposes a novel distributed time synchronization scheme for wireless sensor networks, which uses max consensus to compensate for clock drift and average consensus to compensate for clock offset. The main idea is to achieve a global synchronization just using local information. The proposed protocol has the advantage of being totally distributed, asynchronous, and robust to packet drop and sensor node failure. Finally, the protocol has been implemented in MATLAB. Through several simulations, we can see that this protocol can reduce clock error to ±10 ticks, adapt to dynamic topology, and be suitable to large-scale applications.
Viscoelastic-Viscoplastic Modelling of the Scratch Response of PMMA
Authors: Kermouche G. , Aleksy N. , Bergheau J. M.
Published: March 2013

This paper aims at understanding how to model the time-dependent behavior of PMMA during a scratch loading at a constant speed and at middle strain levels. A brief experimental study is first presented, consisting of the analysis of microscratches carried out at various scratching velocities and normal loads. The loading conditions have been chosen in such a way that neither (visco)elasticity nor (visco)plasticity of the PMMA may be neglected a priori. The main analyzed parameter is the tip penetration depth measured during the steady state. Then, a finite element model is used to investigate the potential of classical elastic-viscoplastic constitutive models to reproduce these experimental results. It is mainly shown that these models lead to unsatisfying results. More specifically, it is pointed out here that the time-independent Young modulus used in such models is not suitable. To take into account this feature, a viscoelastic-viscoplastic model based on the connection in series of a viscoelastic part with a viscoplastic part is proposed. It is shown that it leads to more acceptable results, which points out the importance of viscoelasticity in the scratch behavior of solid polymers.
Assessing the Impact of Vaccination on Controlling the Spread of Human Scabies
Authors: Bhunu C. P. , Mushayabasa S. , Monera T. G.
Published: March 2013

Scabies is among the infestations almost forgotten due to its association with poor communities. We formulate a deterministic model to assess the possible impact vaccination will have on scabies control. The Descartes’s rule of signs is used to show the nature of the endemic equilibria. Analysis of the reproduction number and numerical simulations suggest that vaccination in addition to treatment will help greatly in reducing the spread of scabies infestation. This suggests there is a strong need for researchers to come up with a possible vaccine in that order to effectively control scabies especially among the disadvantaged communities.
Headspace Single-Drop Microextraction Gas Chromatography Mass Spectrometry for the Analysis of Volatile Compounds from Herba Asari
Authors: Wang Guan-Jie , Tian Li , Fan Yu-Ming , Qi Mei-Ling
Published: March 2013

A rapid headspace single-drop microextraction gas chromatography mass spectrometry (SDME-GC-MS) for the analysis of the volatile compounds in Herba Asari was developed in this study. The extraction solvent, extraction temperature and time, sample amount, and particle size were optimized. A mixed solvent of n-tridecane and butyl acetate (1 : 1) was finally used for the extraction with sample amount of 0.750 g and 100-mesh particle size at 70°C for 15 min. Under the determined conditions, the pound samples of Herba Asari were directly applied for the analysis. The result showed that SDME-GC–MS method was a simple, effective, and inexpensive way to measure the volatile compounds in Herba Asari and could be used for the analysis of volatile compounds in Chinese medicine.
Acute Transverse Myelitis Associated with Buserelin Use during IVF
Authors: Alleemudder Djavid I. , Sadek Khaled , Fountain Shaun , Davies Sallie
Published: March 2013

A healthy woman undergoing in vitro fertilization (IVF) developed acute transverse myelitis (ATM) following the use of Buserelin. ATM has a multifactorial etiology and may develop as a result of the activation of immune responses. Infectious agents have been postulated as possible triggers of an immune response (Sá, 2009). Gonadotropin-releasing agonists may have a similar role and trigger the acceleration of preexisting disease by the activation of immune responses (Ho et al., 1995, and Umesaki et al., 1999).
Hepatic Encephalopathy after Transjugular Intrahepatic Portosystemic Shunt in Patients with Recurrent Variceal Hemorrhage
Authors: Peter Popovič , Andrej Zore , Katarina Šurlan Popovič , Manca Garbajs , Pavel Skok
Published: March 2013

Purpose. The purpose of this study was to determine the incidence and predictors of hepatic encephalopathy (HE) after transjugular intrahepatic portosystemic shunt (TIPS) and endoscopic therapy (ET) in the elective treatment of recurrent variceal hemorrhage.Methods. Seventy patients were treated with elective TIPS and fifty-six patients with ET. Median observation time was 46.28 months in the TIPS group and 42.31 months in the ET group.Results. 30 patients (42.8%) developed clinically evident portosystemic encephalopathy in TIPS group and 20 patients (35.6%) in ET group. The difference between the groups was not statistically significant (P=0.542;χ2test). The incidence of new or worsening portosystemic encephalopathy was 24.3% in TIPS group and 10.7% in ET group. Multivariate analysis showed that ET treatment (P=0.031), age of>65years (P=0.022), pre-existing HE (P=0.045), and Child's class C (P=0.051) values were independent predictors for the occurrence of HE.Conclusions. Procedure-related HE is a complication in a minority of patients treated with TIPS or ET. Patients with increased age, preexisting HE, and higher Child-Pugh score should be carefully observed after TIPS procedure because the risk of post-TIPS HE in these patients is higher.
Impact of Multiplayer Online Role-Playing Games upon the Psychosocial Well-Being of Adolescents and Young Adults: Reviewing the Evidence
Authors: Scott Jonathan , Porter-Armstrong Alison P.
Published: March 2013

Introduction. For many people, the online environment has become a significant arena for everyday living, and researchers are beginning to explore the multifaceted nature of human interaction with the Internet. The burgeoning global popularity and distinct design features of massively multiplayer online role-playing games (MMORPGs) have received particular attention, and discourses about the phenomenon suggest both positive and negative impact upon gamer health.Aim. The purpose of this paper was to critically appraise the research literature to determine if playing MMORPGs impacts upon the psychosocial well-being of adolescents and young adults.Method. Initial searches were conducted on nine databases spanning the years 2002 to 2012 using key words, such as online gaming, internet gaming, psychosocial, and well-being, which, in addition to hand searching, identified six studies meeting the inclusion and exclusion criteria for this review.Results. All six studies strongly associated MMORPG playing with helpful and harmful impact to the psychosocial well-being of the populations under study; however due to the methodologies employed, only tentative conclusions may be drawn.Conclusion. Since both helpful and harmful effects were reported, further multidisciplinary research is recommended to specifically explore the clinical implications and therapeutic potentialities of this modern, growing phenomenon.
Multilevel Direct Repair Surgery for Three-Level Lumbar Spondylolysis
Authors: Arai Tetsu , Sairyo Koichi , Shibuya Isao , Kato Ko , Dezawa Akira
Published: March 2013

A 45-year-old man presented to our clinic requesting evaluation for surgical treatment of chronic low back pain of more than 20 years duration. He was diagnosed with 3-level lumbar spondylolysis at L3–5. Direct repair using the pedicle screw and hook-rod system was conducted for all three levels. After the surgery, his low back pain completely disappeared. Six months later, he felt discomfort and heard a metallic sound as he twisted his trunk. Computed tomography and radiography indicated that the hook head for L3 and the screw head for L4 were interfering with each other, causing the sound. We confirmed bony union at L3 and removed the L3 system. Surgeons should be aware of such complications if direct repair using a pedicle screw and hook-rod system is conducted for multilevel spondylolysis.