bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid Induction of Multiple Resistance Mechanisms in Aspergillus fumigatus during Azole Therapy: a Case Study and Review of the Literature
Authors: Camps Simone M. T. , van der Linden Jan W. M. , Li Yi , Kuijper Ed J. , van Dissel Jaap T. , Verweij Paul E. , Melchers Willem J. G. 
Published: October 2011

ABSTRACT

Nine consecutive isogenic
Aspergillus fumigatus
isolates cultured from a patient with aspergilloma were investigated for azole resistance. The first cultured isolate showed a wild-type phenotype, but four azole-resistant phenotypes were observed in the subsequent eight isolates. Four mutations were found in the
cyp51A
gene of these isolates, leading to the substitutions A9T, G54E, P216L, and F219I. Only G54 substitutions were previously proved to be associated with azole resistance. Using a Cyp51A homology model and recombination experiments in which the mutations were introduced into a susceptible isolate, we show that the substitutions at codons P216 and F219 were both associated with resistance to itraconazole and posaconazole. A9T was also present in the wild-type isolate and thus considered a Cyp51A polymorphism. Isolates harboring F219I evolved further into a pan-azole-resistant phenotype, indicating an additional acquisition of a non-Cyp51A-mediated resistance mechanism. Review of the literature showed that in patients who develop azole resistance during therapy, multiple resistance mechanisms commonly emerge. Furthermore, the median time between the last cultured wild-type isolate and the first azole-resistant isolate was 4 months (range, 3 weeks to 23 months), indicating a rapid induction of resistance.
Effect of Usnic Acid on Candida orthopsilosis and C. parapsilosis
Authors: Pires Regina Helena , Lucarini Rodrigo , Mendes-Giannini Maria Jose Soares 
Published: October 2011

ABSTRACT

The activity of usnic acid against
Candida orthopsilosis
and
Candida parapsilosis
on planktonic and biofilm conditions was investigated by using a broth microdilution and microplate methods. Potent
in vitro
activities against different
Candida
species were obtained. The metabolic activity of sessile cells of
C. parapsilosis
complex was reduced by 80% at four times the 80% inhibitory concentration. The
in vitro
studies support further efforts to determine whether usnic acid can be used clinically to cure patients with
Candida
infections.
Profound Alterations of Intestinal Microbiota following a Single Dose of Clindamycin Results in Sustained Susceptibility to Clostridium difficile-Induced Colitis
Authors: Buffie Charlie G. , Jarchum Irene , Equinda Michele , Lipuma Lauren , Gobourne Asia , Viale Agnes , Ubeda Carles , Xavier Joao , Pamer Eric G. 
Published: October 2011

ABSTRACT

Antibiotic-induced changes in the intestinal microbiota predispose mammalian hosts to infection with antibiotic-resistant pathogens.
Clostridium difficile
is a Gram-positive intestinal pathogen that causes colitis and diarrhea in patients following antibiotic treatment. Clindamycin predisposes patients to
C. difficile
colitis. Here, we have used Roche-454 16S rRNA gene pyrosequencing to longitudinally characterize the intestinal microbiota of mice following clindamycin treatment in the presence or absence of
C. difficile
infection. We show that a single dose of clindamycin markedly reduces the diversity of the intestinal microbiota for at least 28 days, with an enduring loss of ca. 90% of normal microbial taxa from the cecum. Loss of microbial complexity results in dramatic sequential expansion and contraction of a subset of bacterial taxa that are minor contributors to the microbial consortium prior to antibiotic treatment. Inoculation of clindamycin-treated mice with
C. difficile
(VPI 10463) spores results in rapid development of diarrhea and colitis, with a 4- to 5-day period of profound weight loss and an associated 40 to 50% mortality rate. Recovering mice resolve diarrhea and regain weight but remain highly infected with toxin-producing vegetative
C. difficile
bacteria and, in comparison to the acute stage of infection, have persistent, albeit ameliorated cecal and colonic inflammation. The microbiota of “recovered” mice remains highly restricted, and mice remain susceptible to
C. difficile
infection at least 10 days following clindamycin, suggesting that resolution of diarrhea and weight gain may result from the activation of mucosal immune defenses.
Factor XI-Deficient Mice Display Reduced Inflammation, Coagulopathy, and Bacterial Growth during Listeriosis
Authors: Luo Deyan , Szaba Frank M. , Kummer Lawrence W. , Johnson Lawrence L. , Tucker Erik I. , Gruber Andras , Gailani David , Smiley Stephen T. 
Published: October 2011

ABSTRACTIn mice infected sublethally withListeria monocytogenes, fibrin is deposited at low levels within hepatic tissue, where it functions protectively by limiting bacterial growth and suppressing hemorrhagic pathology. Here we demonstrate that mice infected with lethal doses ofL. monocytogenesproduce higher levels of fibrin and display evidence of systemic coagulopathy (i.e., thrombocytopenia, fibrinogen depletion, and elevated levels of thrombin-antithrombin complexes). When the hepatic bacterial burden exceeds 1 × 106CFU, levels of hepatic fibrin correlate with the bacterial burden, which also correlates with levels of hepatic mRNA encoding the hemostatic enzyme factor XI (FXI). Gene-targeted FXI-deficient mice show significantly improved survival upon challenge with high doses ofL. monocytogenesand also display reduced levels of hepatic fibrin, decreased evidence of coagulopathy, and diminished cytokine production (interleukin-6 [IL-6] and IL-10). While fibrin limits the bacterial burden during sublethal listeriosis in wild-type mice, FXI-deficient mice display a significantly improved capacity to restrain the bacterial burden during lethal listeriosis despite their reduced fibrin levels. They also show less evidence of hepatic necrosis. In conjunction with suboptimal antibiotic therapy, FXI-specific monoclonal antibody 14E11 improves survival when administered therapeutically to wild-type mice challenged with high doses ofL. monocytogenes.Together, these findings demonstrate the utility of murine listeriosis as a model for dissecting qualitative differences between protective and pathological host responses and reveal novel roles for FXI in exacerbating inflammation and pathogen burden during a lethal bacterial infection.
Eph-B2/Ephrin-B2 Interaction Plays a Major Role in the Adhesion and Proliferation of Waldenstrom's Macroglobulinemia
Authors: Azab Feda , Azab Abdel Kareem , Maiso Patricia , Calimeri Teresa , Flores Ludmila , Liu Yang , Quang Phong , Roccaro Aldo M. , Sacco Antonio , Ngo Hai T. , Zhang Yong , Morgan Brittany L. , Carrasco Ruben D. , Ghobrial Irene M. 
Published: October 2011

Abstract
Purpose: The ephrin receptors (Eph) are found in a wide range of cancers and correlate with metastasis. In this study, we characterized the role of Eph-B2 receptor in the interaction of Waldenstrom's macroglobulinemia (WM) cells with the bone marrow microenvironment.
Experimental Design: We screened the activity of different receptor tyrosine kinases in WM patients and found that Eph-B2 was overexpressed compared with control. Also, we tested the expression of ephrin-B2 ligand on endothelial cells and bone marrow stromal cells (BMSC) isolated from WM patients. We then tested the role of Eph-B2/Ephrin-B2 interaction in the adhesion of WM cells to endothelial cells and BMSCs; the cell signaling induced by the coculture in both the WM cells and the endothelial cells; WM cell proliferation, apoptosis, and cell cycle in vitro and tumor progression in vivo; and in angiogenesis.
Results: Eph-B2 receptor was found to be activated in WM patients compared with control, with a 5-fold increase in CD19+ WM cells, and activated cell adhesion signaling, including focal adhesion kinase, Src, P130, paxillin, and cofilin, but decreased WM cell chemotaxis. Ephrin-B2 ligand was highly expressed on endothelial cells and BMSCs isolated from WM patients and on human umbilical vein endothelial cells and induced signaling in the endothelial cells promoting adhesion and angiogenesis. Blocking of ephrin-B2 or Eph-B2 inhibited adhesion, cytoskeletal signaling, proliferation, and cell cycle in WM cells, which was induced by coculture with endothelial cells and decreased WM tumor progression in vivo.
Conclusion: Ephrin-B2/Eph-B2 axis regulates adhesion, proliferation, cell cycle, and tumor progression in vivo through the interaction of WM with the cells in the bone marrow microenvironment. Clin Cancer Res; 18(1); 91–104. ©2011 AACR.
Unusual Complications of Percutaneous Epicardial Access and Epicardial Mapping and Ablation of Cardiac Arrhythmias
Authors: Koruth Jacob S. , Aryana Arash , Dukkipati Srinivas R. , Pak Hui-Nam , Kim Young-Hoon , Sosa Eduardo A. , Scanavacca Mauricio , Mahapatra Srijoy , Ailawadi Gorav , Reddy Vivek Y. , d'Avila Andre 
Published: October 2011

Background—
Percutaneous epicardial access and mapping/ablation of cardiac arrhythmias are being increasingly performed. Although complications such as pericardial effusion are relatively common, other unusual complications may occur due to the complex anatomic architecture of the heart and surrounding tissues. In this report, we report a series of rare and unusual complications related to percutaneous epicardial procedures.

Methods and Results—
Between 2006 and 2011, 334 patients underwent attempts at percutaneous, subxiphoid access for epicardial mapping/ablation at 5 experienced centers. Seven selected complications are highlighted in this case series. Patient 1 had a 1-cm right ventricular pseudoaneurysm after several unsuccessful attempts at epicardial access. This was successfully managed conservatively. Patient 2 had intra-abdominal bleeding related to puncture of the left lobe of the liver during access that required surgical repair. Patient 3 had a subcapsular hepatic hematoma that was probably related to percutaneous access and was successfully managed conservatively. Patient 4 had severe pericardial bleeding followed by ventricular fibrillation, immediately after obtaining percutaneous epicardial access. A lacerated middle cardiac vein was repaired surgically. However, the patient ultimately died of complications. Patient 5 had a history of cardiothoracic surgery and developed a right ventricle-abdominal fistula after multiple attempts at percutaneous access. This was surgically repaired without major sequelae. Patient 6 had cardiac tamponade caused by a lacerated coronary sinus branch during epicardial catheter ablation and required surgical repair. Patient 7 had severe left coronary vasospasm and ventricular fibrillation during catheter manipulation in the pericardium. This complication was successfully managed with intracoronary nitrates.

Conclusions—
Though generally safe, percutaneous epicardial access and mapping/ablation can result in uncommon complications. Awareness of these rare complications may facilitate early detection and successful management.
Abnormal Response of Superior Sinoatrial Node to Sympathetic Stimulation Is a Characteristic Finding in Patients With Atrial Fibrillation and Symptomatic Bradycardia
Authors: Joung Boyoung , Hwang Hye Jin , Pak Hui-Nam , Lee Moon-Hyoung , Shen Changyu , Lin Shien-Fong , Chen Peng-Sheng 
Published: October 2011

Background—
We hypothesized that unresponsiveness of superior sinoatrial node (SAN) to sympathetic stimulation is strongly associated with the development of symptomatic bradycardia in patients with atrial fibrillation (AF).

Methods and Results—

We performed 3D endocardial mapping in healthy controls (group 1, n=10) and patients with AF without (group 2, n=57) or with (group 3, n=15) symptomatic bradycardia at baseline and during isoproterenol infusion. Corrected SAN recovery time was abnormal in 0%, 11%, and 36% of groups 1, 2, and 3, respectively (
P
=0.02). At baseline, 90%, 26%, and 7% (
P
<0.001) of the patients had multicentric SAN activation patterns. For groups 1, 2, and 3, the median distance from the superior vena cava-right atrial junction to the most cranial earliest activation site (EAS) was 5.0 (25–75 percentile range, 3.5–21.3), 10.0 (4–20), and 17.5 (12–34) mm at baseline (
P
=0.01), respectively, and 4.0 (0–5), 5.0 (1–10), and 15.0 (5.4–33.3) mm, respectively, during isoproterenol infusion (
P
=0.01), suggesting an upward shift of EAS during isoproterenol infusion. However, although the EAS during isoproterenol infusion was at the upper one third of the crista terminalis in 100% of group 1 and 78% of group 2 patients, only 20% of group 3 patients showed a move of the EAS to that region (
P
<0.001).

Conclusions—
Superior SAN serves as the EAS during sympathetic stimulation in patients without AF and in most patients with AF without symptomatic bradycardia. In contrast, unresponsiveness of superior SAN to sympathetic stimulation is a characteristic finding in patients with AF and symptomatic bradycardia.
Single dose myocardial protection technique utilizing del Nido cardioplegia solution during congenital heart surgery procedures
Authors: Charette K , Gerrah R , Quaegebeur J , Chen J , Riley D , Mongero L , Corda R , Bacha E 
Published: October 2011

Background: The single dose cardioplegia technique for myocardial protection during congenital heart surgery is a viable alternative to multidose protocols. Methods: Thirty-four pediatric patients with aortic cross clamp times greater than 90 minutes were grouped by modified adult (MA) multidose solution or del Nido (dN) single dose solution. Also, data from eight patients where the cross clamp times were greater than two hours on one dose of dN solution were included. Results: In the 90-minute plus arm of the study, there were no significant differences between the groups when comparing the risk adjustment for congenital heart surgery (RACHS) (p=0.6), cardiopulmonary bypass times (CPB) (p=0.5), aortic cross camp times (p=0.5), weights (p=0.7) and number of intraoperative exogenous blood units (p=0.5). There were significant differences between the groups (p<0.05) in the number of cardioplegia doses and with perioperative glucose levels. In the greater than two hours group, the incidence of complete heart block (CHB) was 0.125% and there were no deaths or mechanical circulatory support (MCS) devices used. Conclusion: del Nido cardioplegia solution is a reasonable tool for myocardial protection during congenital heart surgery that significantly decreased the number of cardioplegic interventions and perioperative glucose values in our study groups.
Genetic Enhancement Technologies and the New Society
Authors: Smith George P. 
Published: October 2011

So long as procreation continues to remain a central driving force in a marital relationship, and the family the very core of progressive society, efforts will be undertaken to expand the period of fecundity and combat infertility. Genetic planning and eugenic programming are more rational and humane alternatives to population regulation than death by famine and war. Genetic enhancement technologies and the scientific research undertaken to advance them should be viewed as not only aiding (or, sometimes resolving) the tragedy of infertility in family planning, but as a tool for enhancing the health of a Nation's citizens by engineering man's genetic weaknesses out of the line of inheritance. Put simply, healthier and genetically sound individuals have a much better opportunity for pursuing and achieving the “good life” and making a significant contribution to society's greater well being.
Giving the Reasonable Patient a Voice: Information Disclosure and the Relevance of Empirical Evidence
Authors: MaClean Alasdair 
Published: October 2011

In England the standard of risk disclosure required of doctors to avoid liability in negligence is governed by the Bolam test. The test is determined by what would be accepted as reasonable by the responsible doctor. Although able to lay down an independent standard, the courts have usually been guided by the medical expert's evidence. The judge's duty to scrutinise expert evidence was reaffirmed by the recent House of Lords ruling in Bolitho v City and Hackney HA. 1 In Pearce v United Bristol Healthcare NHS Trust, 2 Lord Woolf MR confirmed that this also applied to risk disclosure. Brazier & Miola argue that Pearce effectively introduces the prudent patient standard into English law. 3 This paper examines that claim and considers whether it is justified by the Pearce judgment. The implications of Pearce are explored and, given the appeal to the concept of a material risk, I discuss the relevance of empirical research to determining the standard of disclosure. Finally, a small piece of empirical work is presented as an illustration of the pros and cons of such an approach and as a possible springboard for future research.
Patents, Morality and DNA: Should there be Intellectual Property Protection of the Human Genome Project?
Authors: Gannon Philippa , Guthrie Tom , Laurie Graeme 
Published: October 2011

This article examines the appropriateness of using existing patent laws in various jurisdictions in an effort to secure protection of the work currently being carried out on the Human Genome Project. Certain ethical and practical problems which arise from current practices in Europe, USA and Japan are explored. It is submitted that the nature of the problems are such that it might be appropriate to consider alternative means of rewarding those involved in unravelling human DNA. An attempt is made to outline some appropriate matters to consider in developing such an alternative.
Assessing Damages for the Costs of Care
Authors: Lewis Richard 
Published: October 2011

This article examines the compensating benefits which may be taken into account to reduce the amount which a plaintiff may claim for the costs of care in English law. The concern is not with payments of money to the plaintiff, but with savings resulting either from the plaintiff receiving care free of charge, or from paying for a comprehensive care package which saves on the living expenses which the plaintiff would otherwise have had to meet. These compensating benefits therefore include the gratuitous care and nursing provided by family and friends at home; and the care provided in a hospital, nursing home or other institution, when board and lodging is then also supplied. Similar policy issues arise no matter whether the plaintiff is provided with money to purchase care (eg an attendance allowance) or is provided with that care directly and free of charge. There is no necessary distinction between, on the one hand, the provision of free medical and hospital treatment and, on the other, the reimbursement of medical expenses through the mechanism of insurance.1 Although in its present review of damages the Law Commission treat gratuitous nursing services as distinct from “collateral benefits,” it accepts that if the plaintiff is seen as incurring a need for services and this constitutes an initial pecuniary loss, the question of whether to deduct the value of the services as a collateral benefit does then arise.2 This article examines the basic rules relevant to such deduction, but it begins by considering the effect upon damages of the existence of free health care under the NHS.
Reform of United Kingdom Discrimination Law: Philosophy, Principle or Pragmatism?
Authors: Townshend-Smith Richard 
Published: October 2011

United Kingdom sex and race discrimination legislation has been in place for 25 years. There is general agreement both that the legislation has had some degree of beneficial impact but that change is long overdue. There is a need to take greater and more sophisticated account of the limits of law as a medium for the promotion of social change. At the same time, international and other developments continue to press for the extension of legislation to different grounds of discrimination. The University of Cambridge Centre for Public Law and the Judge Institute of Management Studies recently published a report entitled ‘Equality: a New Framework.’ At approximately the same time the Runnymede Trust (which is concerned solely with racial justice) published a report entitled ‘The Future of Multi-Ethnic Britain.’ This review article examines both reports, concentrating on the issues relevant to the legal control of employment discrimination. It congratulates the authors of both reports for their detailed and sophisticated understanding of the issues, and their proposals for law reform, but remains somewhat sceptical of the capacity of even a reformed law to transform the behaviour and attitude of employers, especially small and medium-sized employers.
Age Discrimination: Equal Treatment with Exceptions
Authors: Sargeant Malcolm 
Published: October 2011

The likelihood of age discrimination in relation to employment increases the older a person becomes. The concern is that, partly as a result of this discrimination, large numbers of older workers leave the workforce and become economically inactive. This in turn brings increased pressures on the remaining members of the workforce and increased pressures on public finances in relation to pensions and healthcare. The Equal Treatment in Employment and Occupation Directive (2000/78/EC) approaches this problem by introducing the principle of equal treatment in a number of areas related to employment, including age. The reasons for action on age discrimination rests upon two potentially conflicting justifications. The first is a human rights one based upon the right of all persons to equality before the law and the second is one concerned with implementing EC Employment Guidelines on integrating disadvantaged groups into the workforce. This second justification is likely to lead to a much more pragmatic approach which in turn may compromise the principle of equality of treatment. This article, uses survey material, to argue that the potential conflict between an equal treatment approach and the functional, more pragmatic, approach may lead to a lessening of the effectiveness of measures prohibiting age discrimination.
Withholding Party Funding from a ‘Discriminating’ Political Party
Authors: Busstra Marjolein , Vrielink Jogchum 
Published: October 2011

On 7 September 2005 the District Court in The Hague judged that it was unlawful for the Dutch State to continue providing party funding to the ‘Staatkundig Gereformeerde Partij’. On the basis of religious considerations, this Calvinist political party excluded women from full membership and denied women the possibility of taking up political and administrative mandates on behalf of the party. This amounted to discrimination of women with regard to their right to political participation, according to the court. Public funding of the SGP was thus contrary to the obligations contained in the Convention on the Elimination of All Forms of Discrimination against Women (CEDAW). This contribution analyses the court's decision and reasoning to conclude that it is premised on a number of untenable assumptions, regarding the nature and requirements of the principle of nondiscrimination — contained in CEDAW — vis-à-vis other rights and liberties.