bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE IMPORTANCE OF RENIN‐ANGIOTENSIN BLOCKADE IN PATIENTS WITH CARDIO‐RENAL DISEASE
Authors: Benavente David , Chue Colin D. , Ferro Charles J. 
Published: May 2010

SUMMARYThe existence of the renin–angiotensin–aldosterone system was first postulated over 100 years ago. Following the identification of all the major components, came the discovery of their potential pathogenicity in cardiovascular and renal disease. The introduction of drugs that inhibit the synthesis or actions of this system has prompted a number of trials that have largely shaped how cardiovascular and renal disease is managed today. The continued discovery of yet more components of this system promises to further our understanding of its influence on disease processes and herald the development of more highly selective drugs, ensuring that the renin–angiotensin–aldosterone system will continue to be a key area of interest for many years to come.
SCREENING FOR CARDIOVASCULAR DISEASE IN PATIENTS WITH ADVANCED CHRONIC KIDNEY DISEASE
Authors: Sharma Rajan 
Published: May 2010

SUMMARYCardiovascular disease remains the major cause of mortality and morbidity in patients with advanced chronic kidney disease (CKD) and after renal transplantation. The mechanisms for cardiotoxicity are multiple. Identifying high‐risk patients remains a challenge. Given, the poor long‐term outcome of dialysis patients who do not receive renal transplantation and the lower supply of donor kidneys relative to demand, optimal selection of renal transplantation candidates is crucial. This requires a clear understanding of the validity of cardiac tests in this patient group. This paper explores the strengths and weaknesses of currently available diagnostic tools in patients with advanced CKD. Echocardiography is very useful for the detection of cardiomyopathy and prognosis. Stress echocardiography, myocardial perfusion imaging and coronary angiography are the best tools for the assessment of coronary artery disease. All predict outcome. No single gold standard investigation exists. At present, there is not an optimal technique for predicting sudden cardiac death in this patient group. Ultimately, the choice of cardiac test will always be determined by patient preference, local expertise and availability.
THE ASSOCIATION OF CHRONIC KIDNEY DISEASE‐MINERAL BONE DISORDER AND CARDIOVASCULAR RISK
Authors: Eddington Helen , Kalra Philip A. 
Published: May 2010

SUMMARYChronic kidney disease‐mineral bone disorder (CKD‐MBD) is a multifaceted definition used to help describe the systemic derangement of mineral bone metabolism in renal disease. This was previously referred to, rather simplistically, as ‘renal osteodystrophy’ or ‘renal bone disease’. In this review, we will try to show the evidence relating these factors to cardiovascular morbidity and mortality and give some evidence as to the mechanisms for this. The treatments used for this condition are also integral to the increased cardiovascular mortality seen in renal patients and a summary of these effects will also be covered.
LIPIDS IN CHRONIC KIDNEY DISEASE
Authors: Lewis David , Haynes Richard , Landray Martin J. 
Published: May 2010

SUMMARYPatients with chronic kidney disease (CKD) develop premature cardiovascular disease. In the general population (without CKD), there are strong associations between cholesterol fractions and the risk of coronary disease and weaker associations with stroke. Randomised trials in the general population demonstrate that lowering blood cholesterol (chiefly with a statin) reduces the risk of vascular events. Patients with CKD differ significantly from the general population. They have markedly disturbed lipid metabolism manifesting as elevated triglyceride concentrations, reduced HDL cholesterol concentrations and a preponderance of small, dense LDL particles that are potentially more atherogenic; the observed association between lipids and vascular disease is bizarre, and is confounded by co‐morbidity; the nature of the vascular disease appears less strongly associated with classical atherosclerosis. Randomised trials are required to determine the relevance of blood lipids to the development of vascular disease in CKD patients, but the results of such studies have been inconclusive to date. CKD patients are at risk of end‐stage renal disease. Lipids may be involved in the progression of renal disease. Modifying them may delay the progression of CKD. The current data are based on effects on markers of progression (e.g. proteinuria). The ongoing SHARP (Study of Heart and Renal Protection) trial should provide reliable information about the effects of statins on both vascular and renal risk.
CARDIO‐RENAL SYNDROMES
Authors: Goh Ching Yan , Ronco Claudio 
Published: May 2010

SUMMARY ‘Cardio‐Renal syndromes’ (CRS) are disorders of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other. The current definition has been expanded into five subtypes whose etymology reflects the primary and secondary pathology, the time‐frame and simultaneous cardiac and renal co‐dysfunction secondary to systemic disease: CRS type I: acute worsening of heart function (AHF‐ACS) leading to kidney injury and/or dysfunction. CRS type II: chronic abnormalities in heart function (CHF‐CHD) leading to kidney injury or dysfunction. CRS type III: acute worsening of kidney function (AKI) leading to heart injury and/or dysfunction. CRS type IV: chronic kidney disease leading to heart injury, disease and/or dysfunction. CRS type V: systemic conditions leading to simultaneous injury and/or dysfunction of heart and kidney. These different subtypes may have a different pathophysiological mechanism and they may represent separate entities in terms of prevention and therapy.
PRACTICAL MANAGEMENT OF DIET AND LIFESTYLE INTERVENTIONS FOR PEOPLE WITH DIABETES OR CARDIOVASCULAR DISEASE
Authors: Symes Fiona , Sutton Debbie 
Published: May 2010

SUMMARYIncreased collaboration between the vascular specialities is clearly leading to increased understanding of the interrelationships between the different disease states and how each impacts and influences the other. This advantage will be reflected in improved patient care if the practical outputs of this growing knowledge are carefully implemented at service level. This article outlines how the aspects of diet and lifestyle associated with vascular‐related disease complement, contrast and in some cases contradict each other. It gives information and guidelines as to how the expertise of dietitians working in the different specialist areas might usefully be shared to be of maximum advantage to all patients.
Tyrosine phosphatase TpbA of Pseudomonas aeruginosa controls extracellular DNA via cyclic diguanylic acid concentrations
Authors: Ueda Akihiro , Wood Thomas K. 
Published: May 2010

SummaryInactivating the tyrosine phosphatase TpbA of Pseudomonas aeruginosa PA14 induces biofilm formation by 150‐fold via increased production of the second messenger cyclic diguanylic acid (c‐di‐GMP). Here, we show the tpbA mutation reduces extracellular DNA (eDNA) and that increased expression of tpbA increases eDNA; hence, eDNA is inversely proportional to c‐di‐GMP concentrations. Mutations in diguanylate cyclases PA0169, PA4959 and PA5487 and phosphodiesterase PA4781 corroborate this trend. The tpbA mutation also decreases cell lysis while overexpression of tpbA increases cell lysis. To further link c‐di‐GMP concentrations and eDNA, the gene encoding phosphodiesterase PA2133 was overexpressed which increased eDNA and decreased biofilm formation by decreasing c‐di‐GMP. Furthermore, the effect of the tpbB mutation along with the tpbA mutation was examined because loss of TpbB restored the phenotypes controlled by enhanced c‐di‐GMP in the tpbA mutant. The tpbA tpbB double mutations restored eDNA to that of the PA14 wild‐type level. These findings suggest that c‐di‐GMP, rather than TpbA, controls eDNA. Hence, TpbA acts as a positive regulator of eDNA and cell lysis by reducing c‐di‐GMP concentrations.
Antibiotic selection leads to inadvertent selection of nfxC‐type phenotypic mutants in Pseudomonas aeruginosa
Authors: Mooij Marlies J. , O'Connor Hazel F. , Tian Zhe‐Xian , Wang Yi‐Ping , Adams Claire , Morrissey John P. , O'Gara Fergal 
Published: May 2010

SummarySpontaneous nfxC‐type phenotypic mutants of Pseudomonas aeruginosa are characterized by chloramphenicol resistance and increased expression of the multidrug efflux pump, MexEF‐OprN. These mutants frequently arise during the propagation of bacteria in laboratory conditions. This study shows that some of the discrepancies in transcriptomic/phenotypic profiles of two rsmA mutants, PAZH13 (rsmA mutant in strain PAO1) and PAKΔrsmA, are due to the nfxC‐type nature of PAZH13. This indicates that awareness of the possible occurrence of these spontaneous nfxC‐type phenotypes is necessary. Screening of mexE levels could provide clarity when an nfxC‐type phenotype is suspected.
THE NECESSITY OF TOMORROW'S SEA BATTLE
Authors: Byrd Jeremy 
Published: May 2010

abstractIn chapter 9 of De Interpretatione, Aristotle offers a defense of free will against the threat of fatalism. According to the traditional interpretation, Aristotle concedes the validity of the fatalist's arguments and then proceeds to reject the Principle of Bivalence in order to avoid the fatalist's conclusion. Assuming that the traditional interpretation is right on this point, it remains to be seen why Aristotle felt compelled to reject such an intuitive semantic principle rather than challenge the fatalist's inference from truth to necessity. The answer, I contend, lies in Aristotle's theory of truth and truthmakers.
“STANDING APART IN THE SHELTER OF THE CITY WALL”: THE CONTEMPLATIVE IDEAL VS. THE POLITICALLY ENGAGED PHILOSOPHER IN PLATO'S POLITICAL THEORY
Authors: McKeen Catherine 
Published: May 2010

abstractNatural philosophers seem to have good reasons to prefer that the kallipolis, the maximally just community of the Republic, is never realized. If such a community is realized, philosophers are under the obligation of a just demand that they govern. However, a life that contains governance as a significant part is not the happiest life a philosopher can live. The happiest life for a philosopher is one consisting entirely or largely in philosophical contemplation. I confront this puzzle by arguing that natural philosophers gain benefits in the kallipolis that are not available to them in other communities, primarily opportunities for correction and punishment. While other communities may offer philosophers more opportunities for philosophical contemplation, these communities do not provide a reliable mechanism for counteracting potentially dangerous moral blindness. In contrast to other communities, the kallipolis institutionalizes and reliably replicates the structures necessary for counteracting moral blindness.
A
Histoplasma capsulatum
-Specific IgG1 Isotype Monoclonal Antibody, H1C, to a 70-Kilodalton Cell Surface Protein Is Not Protective in Murine Histoplasmosis
Authors: Lopes Livia Cristina Liporagi , Guimarães Allan J. , de Cerqueira Mariana Duarte , Gómez Beatriz L. , Nosanchuk Joshua D. 
Published: May 2010

ABSTRACT

Monoclonal antibodies to
Histoplasma capsulatum
can modify pathogenesis. We now show that monoclonal antibody H1C to a 70-kDa antigen increases intracellular fungal growth and reduces macrophage nitric oxide release but has no effect on fungal burden or survival in murine infection. This further demonstrates the complexities of host-pathogen interactions.
Evaluation of Effect of Specimen-Handling Parameters for Plasma Preparation Tubes on Viral Load Measurements Obtained by Using the Abbott RealTi
me
HIV-1 Load Assay
Authors: Fernandes Helen , Morosyuk Svetlana , Abravaya Klara , Ramanathan Madhuri , Rainen Lynne 
Published: May 2010

ABSTRACT

HIV-1 viral load testing is essential to the management of HIV-1-infected patients, and proper specimen handling ensures accurate viral load (VL) results. This study was performed to (i) evaluate the effect of freezing plasma
in situ
in BD Vacutainer plasma preparation tubes (PPT) on the accuracy of HIV-1 viral load results using the Abbott RealTi
me
HIV-1 assay and (ii) evaluate the effect of whole-blood storage in the PPT for 6 h at room temperature prior to centrifugation (PPT6H) rather than 2 h as specified in the PPT product insert. Of the 64 HIV-positive subjects evaluated, 29 had average viral load counts of >40 copies/ml in at least one of the tubes tested and 35 subjects had a result of either “undetected target” or “below the limit of quantification” (LOQ) for all or some of the tubes regardless of handling condition. For the 29 subjects with VLs that were >LOQ, the mean biases between plasma from Vacutainer K
2
EDTA tubes and plasma frozen
in situ
in PPT and between K
2
EDTA tube plasma and plasma from PPT6H (log
10
copies/ml) were 0.005 and −0.001, respectively, and
r
2
was >0.92 for all correlations. We conclude that VLs determined from plasma frozen
in situ
in PPT are equivalent to VLs in K
2
EDTA tube plasma and can be used for accurate quantification of HIV-1 RNA in the Abbott RealTi
m
e HIV-1 assay. Furthermore specimens collected in PPT can be stored for 6 h at room temperature with no effect on viral load results as measured by the Abbott RealTi
m
e HIV-1 assay.
Mycobacterium haemophilum
as a Novel Etiology of Cervical Lymphadenitis in an Otherwise Healthy Adult Patient
Authors: Minani Theobald J. C. , Saubolle Michael A. , Yu Edwin , Sussland Zdenek 
Published: May 2010

ABSTRACT

We describe a case and summarize six additional cases of cervical lymphadenitis in otherwise healthy adults caused by
Mycobacterium haemophilum
. The organism causes cervicofacial lymphadenitis in healthy children and severe disease in immunocompromised patients but has not been previously reported to cause cervical lymphadenitis in nonimmunocompromised, healthy adults.
Prevalence of
Salmonella enterica
in Poultry and Eggs in Uruguay during an Epidemic Due to
Salmonella enterica
Serovar Enteritidis
Authors: Betancor L. , Pereira M. , Martinez A. , Giossa G. , Fookes M. , Flores K. , Barrios P. , Repiso V. , Vignoli R. , Cordeiro N. , Algorta G. , Thomson N. , Maskell D. , Schelotto F. , Chabalgoity J. A. 
Published: May 2010

ABSTRACT

Salmonella enterica
serovar Enteritidis (
S
. Enteritidis) is frequently associated with food-borne disease worldwide. Poultry-derived products are a major source. An epidemic of human infection with
S
. Enteritidis occurred in Uruguay, and to evaluate the extent of poultry contamination, we conducted a nationwide survey over 2 years that included the analysis of sera from 5,751 birds and 12,400 eggs. Serological evidence of infection with
Salmonella
group O:9 was found in 24.4% of the birds. All positive sera were retested with a gm flagellum-based enzyme-linked immunosorbent assay, and based on these results, the national prevalence of
S
. Enteritidis infection was estimated to be 6.3%. Salmonellae were recovered from 58 of 620 pools made up of 20 eggs each, demonstrating a prevalence of at least 1 in every 214 eggs. Surprisingly, the majority of the isolates were not
S
. Enteritidis. Thirty-nine isolates were typed as
S
. Derby, 9 as
S
. Gallinarum, 8 as
S
. Enteritidis, and 2 as
S
. Panama. Despite the highest prevalence in eggs,
S
. Derby was not isolated from humans in the period of analysis, suggesting a low capacity to infect humans. Microarray-based comparative genomic hybridization analysis of
S
. Derby and
S
. Enteritidis revealed more than 350 genetic differences.
S
. Derby lacked pathogenicity islands 13 and 14, the fimbrial
lpf
operon, and other regions encoding metabolic functions. Several of these regions are present not only in serovar Enteritidis but also in all sequenced strains of
S
. Typhimurium, suggesting that these regions might be related to the capacity of
Salmonella
to cause food-borne disease.
Enhancement of Autophagy during Lytic Replication by the Kaposi's Sarcoma-Associated Herpesvirus Replication and Transcription Activator
Authors: Wen Hui-Ju , Yang Zhilong , Zhou You , Wood Charles 
Published: May 2010

ABSTRACT
Autophagy is one of two major degradation systems in eukaryotic cells. The degradation mechanism of autophagy is required to maintain the balance between the biosynthetic and catabolic processes and also contributes to defense against invading pathogens. Recent studies suggest that a number of viruses can evade or subvert the host cell autophagic pathway to enhance their own replication. Here, we investigated the effect of autophagy on the KSHV (Kaposi's sarcoma-associated herpesvirus) life cycle. We found that the inhibition of autophagy reduces KSHV lytic reactivation from latency, and an enhancement of autophagy can be detected during KSHV lytic replication. In addition, RTA (replication and transcription activator), an essential viral protein for KSHV lytic reactivation, is able to enhance the autophagic process, leading to an increase in the number of autophagic vacuoles, an increase in the level of the lipidated LC3 protein, and the formation of autolysosomes. Moreover, the inhibition of autophagy affects RTA-mediated lytic gene expression and viral DNA replication. These results suggest that RTA increases autophagy activation to facilitate KSHV lytic replication. This is the first report demonstrating that autophagy is involved in the lytic reactivation of KSHV.
Cellular Transcription Factor ZASC1 Regulates Murine Leukemia Virus Transcription
Authors: Bruce James W. , Hierl Michael , Young John A. T. , Ahlquist Paul 
Published: May 2010

ABSTRACT
To identify cellular processes involved in retroviral infection, we employed a high-volume forward genetic screen of insertionally mutagenized somatic cells using a murine leukemia virus (MLV) vector. This approach identified a clonal cell line that exhibited approximately 10-fold reduced gene expression from MLV vectors following infection despite supporting normal levels of MLV reverse transcription and integration. The defect in this cell line was specific for the MLV long terminal repeat (LTR) promoter, as normal levels of reporter gene expression were obtained from both an internal cytomegalovirus (CMV) promoter contained within an LTR-defective MLV vector and LTR expression from an avian sarcoma and leukosis virus (ASLV) vector. Complementation and shRNA knockdown experiments demonstrated that the defective gene in these cells is ZASC1 (ZNF639), a transcription factor with strong links to cancer and inherited ataxias. We demonstrated that ZASC1 is a sequence-specific DNA binding protein with three closely related binding sites located within the MLV LTR promoter, but it does not bind to the ASLV promoter. Mutating these putative ZASC1 binding sites significantly reduced levels of MLV gene expression. While wild-type ZASC1 activated expression from the MLV promoter, a green fluorescent protein-ZASC1 fusion protein showed dominant-negative inhibition of MLV gene expression. These studies identify the cellular transcription factor ZASC1 as an activator of MLV gene expression and provide tools that should be useful in studying the links between ZASC1 and human diseases.
Structural Basis for the Inhibition of RNase H Activity of HIV-1 Reverse Transcriptase by RNase H Active Site-Directed Inhibitors
Authors: Su Hua-Poo , Yan Youwei , Prasad G. Sridhar , Smith Robert F. , Daniels Christopher L. , Abeywickrema Pravien D. , Reid John C. , Loughran H. Marie , Kornienko Maria , Sharma Sujata , Grobler Jay A. , Xu Bei , Sardana Vinod , Allison Timothy J. , Williams Peter D. , Darke Paul L. , Hazuda Daria J. , Munshi Sanjeev 
Published: May 2010

ABSTRACT
HIV/AIDS continues to be a menace to public health. Several drugs currently on the market have successfully improved the ability to manage the viral burden in infected patients. However, new drugs are needed to combat the rapid emergence of mutated forms of the virus that are resistant to existing therapies. Currently, approved drugs target three of the four major enzyme activities encoded by the virus that are critical to the HIV life cycle. Although a number of inhibitors of HIV RNase H activity have been reported, few inhibit by directly engaging the RNase H active site. Here, we describe structures of naphthyridinone-containing inhibitors bound to the RNase H active site. This class of compounds binds to the active site via two metal ions that are coordinated by catalytic site residues, D443, E478, D498, and D549. The directionality of the naphthyridinone pharmacophore is restricted by the ordering of D549 and H539 in the RNase H domain. In addition, one of the naphthyridinone-based compounds was found to bind at a second site close to the polymerase active site and non-nucleoside/nucleotide inhibitor sites in a metal-independent manner. Further characterization, using fluorescence-based thermal denaturation and a crystal structure of the isolated RNase H domain reveals that this compound can also bind the RNase H site and retains the metal-dependent binding mode of this class of molecules. These structures provide a means for structurally guided design of novel RNase H inhibitors.
The Proteasome Inhibitor Velcade Enhances rather than Reduces Disease in Mouse Hepatitis Coronavirus-Infected Mice
Authors: Raaben Matthijs , Grinwis Guy C. M. , Rottier Peter J. M. , de Haan Cornelis A. M. 
Published: May 2010

ABSTRACTMany viruses, including coronaviruses (CoVs), depend on a functional cellular proteasome for efficient infectionin vitro. Hence, the proteasome inhibitor Velcade (bortezomib), a clinically approved anticancer drug, shown in an accompanying study (M. Raaben et al., J. Virol. 84:7869-7879, 2010) to strongly inhibit mouse hepatitis CoV (MHV) infection in cultured cells, seemed an attractive candidate for testing its antiviral propertiesin vivo. Surprisingly, however, the drug did not reduce replication of the virus in mice. Rather, inhibition of the proteasome caused enhanced infection with lethal outcome, calling for caution when using this type of drug during infection.
Potential for the
Anopheles gambiae
Densonucleosis Virus To Act as an “Evolution-Proof” Biopesticide
Authors: Ren Xiaoxia , Rasgon Jason L. 
Published: May 2010

ABSTRACT

“Evolution-proof” or “late-life-acting” insecticides (LLAIs) preferentially kill older adult mosquitoes and are of extreme interest to control vector-borne diseases such as malaria. We used quantitative PCR to assess whether the
Anopheles gambiae
densonucleosis virus (AgDNV) had potential as an LLAI. After infection, AgDNV titers increased modestly during larval development but replicated slower than the host cells, resulting in a significant decrease in the normalized virus titer during larval and pupal development. Normalized virus titers dramatically increased after adult emergence, peaking in 7- to 10-day-old adults. Unlike other DNVs, AgDNV does not significantly replicate in preadult mosquitoes but rather preferentially replicates in older adults. The natural dynamics of AgDNV make it ideal for expression of insect-specific toxin genes as a biological LLAI.