bluuebunny/crossref_metadata_2025 huggingface dataset:
The activity of adenosine deaminase and oxidative stress biomarkers in scraping samples of acne lesions
Authors: Perihan Ozturk , Ergul Kurutas B , Neslihan Dokur , Filiz Atalay
Published: November 2012

Background

Acne vulgaris is one of the most common dermatological diseases, and its pathogenesis is multifactorial. Although there are some reports about role of oxidative stress biomarkers in blood, serum, plasma in the pathogenesis of acne, there has been no report about oxidative stress biomarkers in scraping samples. For this reason, the aim of our study is to determine the role of oxidative stress biomarkers and adenosine deaminase (ADA) in scraping samples of acne lesion and to determine a possible link with the clinical severity. Fifty patients with different severity of acne vulgaris and forty healthy controls were enrolled. In both groups, ADA and oxidative stress biomarkers such as the levels of malondialdehyde (MDA), and reduced glutathione (GSH), the activities of superoxide dismutase (SOD) and catalase (CAT) in scraping samples were measured spectrophotometrically. The levels of SOD, CAT, GSH, MDA, and ADA of patients with acne were higher than the control patients (P < 0.05). ADA and MDA levels in patients with severe acne were significantly higher about two‐ to four‐fold compared with other acne groups (P < 0.05). However, CAT, SOD, and GSH levels were lower in patients with severe acne vulgaris than the others (P < 0.05). Increased antioxidant enzyme levels of scraping samples in patients might be a local response of the organism to increased oxidative stress. Also, we believe that oxidative stress increases in parallel with the disease severity, hence antioxidant therapy may be beneficial if given in addition to the routine treatment of severe acne.
The Mutation of Professionalism as a Contested Diffusion Process: Clinical Guidelines as Carriers of Institutional Change in Medicine
Authors: Adler Paul S. , Kwon Seok‐Woo
Published: November 2012

The Anglo‐American institution of the profession is mutating: we propose to analyse this mutation as a contested diffusion process that spreads new organizing practices among professionals. We offer an integrated account of the roles played in this diffusion/mutation process by facilitating and impeding factors at three levels: individual professionals (their autonomy, expertise, values, identities, and ties), professional organizations (their strategies, structures, cultures, skills, and systems), and the broader institutional field (professional associations, accountability demands, and competition). At the occupational and organizational level, we show how the distinctive and evolving features of professionalism moderate the mechanisms found in prior research on diffusion in other, non‐professional settings; and at the field level, we show how field‐level forces moderate the impact of professionalism on these diffusion dynamics. Changes at each of these levels interact with changes at the others, with influences flowing both downward and upward. We ground and illustrate this theoretical synthesis with evidence from the case of clinical guidelines as carriers of institutional change in the medical profession.
Alternative Pathways of Change in Professional Services Firms: The Case of Management Consulting
Authors: Kipping Matthias , Kirkpatrick Ian
Published: November 2012

This paper contributes to the debate about new organizational forms in professional service firms (PSFs) by suggesting an alternative to extant accounts of how change takes place. To explain the displacement of community forms of organizing by more corporate forms, much of the literature has so far focused on intra‐archetype adaptation and evolutionary processes, looking mainly at establishedPSFsin law and accounting. Drawing on ideas from the sociology of professions and institutional theory, we suggest that, in more weakly regulated and open professional fields, change might also come from firms entering from the margins or the outside and bringing with them different models of organizing. We explore this possibility through a historical case study of the management consulting field in theUKover a 50 year period, based on a wide range of data sources. Our study shows that despite good intentions at the outset the main professional association was unable and – increasingly – unwilling to restrict entry. This resulted in growing fragmentation of the field through new entrants and, consequently, in greater diversity of organizational forms. Such findings draw attention not only to alternative pathways of change inPSFs, but also to the importance of distinguishing between professional organizational fields more generally.
Strategy, Discourse and Practice: The Intensification of Power
Authors: Hardy Cynthia , Thomas Robyn
Published: November 2012

We adopt a Foucauldian approach to discourse to show how power relations shape the constitution of strategy. By exploring two particular discourses associated with the strategy of a global telecommunications company, our study shows how the power effects of discourses are intensified through particular discursive and material practices, leading to the production of objects and subjects that are clearly aligned with the strategy. In this way, our study contributes to understanding: the mechanisms whereby discourse bears down on strategy through intensification practices; different forms of resistance; and the way in which strategy objects and subjects reproduce (or undermine) discourse.
Cigarette smoke condensate promotes pro‐tumourigenic stromal–epithelial interactions by suppressing miR‐145
Authors: Pal A. , Melling G. , Hinsley E. E. , Kabir T. D. , Colley H. E. , Murdoch C. , Lambert D. W.
Published: November 2012

Background

Exposure to factors released from tobacco during chewing or smoking is recognized as a major risk factor for oral carcinogenesis and influences the phenotype of oral epithelial cells and fibroblasts within the underlying stroma. Micro(mi)RNA can regulate the expression of genes within cells, and previous studies show that tobacco products can alter the miRNA profiles in lung epithelial cells. However, the molecular alterations occurring in oral fibroblasts exposed to tobacco constituents remain to be elucidated.

Methods

Oral fibroblasts were exposed to cigarette smoke condensate (CSC) and miRNA expression compared to untreated controls using tiling low‐density arrays (TLDA). Expression of miRNA‐145 was confirmed by quantitative (q)RT‐PCR. The effect of CSC on fibroblast cell viability, motility and matrix metalloproteinase (MMP)‐2 expression was measured using MTS, a wound scratch assay and qRT‐PCR, respectively. Oral cancer cell migration in response to culture supernatants from mock, control or pre‐miR‐145‐transfected CSC‐treated fibroblasts was analysed by chemotaxis assay.

Results

TLDA analysis identified widespread changes in the miRNA expression profile of fibroblasts exposed to CSC. Pri‐, pre‐ and mature miRNA‐145 were significantly down‐regulated in response to CSC, and this was accompanied by up‐regulated expression of MMP‐2 and increased migration of fibroblasts compared to untreated controls. Re‐expression of miR‐145 abrogated the ability of fibroblasts to promote oral cancer cell chemotaxis in response to CSC.

Conclusion

These findings suggest that tobacco constituents influence the expression of miRNA within oral fibroblasts promoting a phenotype that increases oral cancer migration and sheds new light on the mechanisms underlying oral cancer pathogenesis.
Rumen‐protected methionine supplementation and fibre production in alpacas (Vicugna pacos)
Authors: Moore K. E. , Maloney S. K. , Vaughan J. L. , Milton J. T. B. , Blache D.
Published: November 2012

Sulphur‐containing amino acids are a crucial requirement for fibre production and may be supplemented in the diet of fibre‐producing animals to stimulate fibre growth. The alpaca fibre industry is a developing industry in Australia with high variability in fibre production. To date, there is no evidence whether supplementing the diet of alpacas with sulphur amino acids improves fibre production. We hypothesised that supplementation with the rumen‐protected sulphur amino acid, methionine would increase fibre growth in alpacas. Three groups of eight huacaya alpaca wethers were fed daily a maintenance diet supplemented with 0, 2 or 4 g of rumen‐protected methionine for 7 weeks. Fibre samples were taken at the beginning and end of the study with a blood sample taken by jugular venipuncture prior to feeding on the first day of each week. Methionine supplementation had no effect on fibre diameter (p = 0.92), fibre length (p = 0.91) or fibre yield (p = 0.33). The change of season over the study affected plasma glucose (p < 0.001), plasma urea nitrogen (p < 0.001) and fibre diameter (p < 0.001). The indifference between groups may be due to the maintenance diet supplying sufficient levels of methionine, the lack of genetic potential of the experimental animals to respond to additional methionine or that the supplemental methionine was not protected in alpacas and deaminated for glucose production.
Korean red ginseng extract prevents APAP‐induced hepatotoxicity through metabolic enzyme regulation: The role of ginsenoside Rg3, a protopanaxadiol
Authors: Gum Sang Il , Cho Min Kyung
Published: November 2012

Background

Inappropriate use of acetaminophen (APAP) can lead to morbidity and mortality secondary to hepatic necrosis.

Aims

We evaluated the beneficial effect and molecular mechanism of Korean red ginseng (KRG) on the APAP‐mediated hepatotoxicity and identified a major component of KRG for hepatoprotection.

Methods

Survival test, liver function test, histopathological study, APAP‐metabolic profiling and gene expression were examined in mice. We determined the enzyme expression and upstream signalling in H4IIE cells analysed by RT‐PCR, immunoblotting, siRNA gene knockdown and promoter‐luciferase assay.

Results

High doses of KRG reduced mortality at the LD50 of APAP. APAP increased AST and ALT activities, which were abrogated by low doses of KRG. These protective effects were consistent with the results from histopathological examinations. KRG altered APAP metabolic profiles through inhibition of cytochrome P450 2E1 and induction of glutathione S‐transferase A2 (GSTA2). Knockdown of GSTA2 catalyses the conjugation of glutathione reversed KRG‐mediated protection against N‐acetyl‐p‐benzoquinone imine in H4IIE cells. The nuclear Nrf2 and C/EBPβ, which are essential transcriptional factors for GSTA2 were increased by KRG. These effects were downstream of multiple signalling, including PI3K, JNK or PKA. Ginsenoside Rg3 but not Rb1, Rc and Rg1 significantly increased GSTA2 protein expression. Rg3 resulted in the transcriptional activation of GSTA2 downstream of the multiple cellular signalling.

Conclusions

These results demonstrate that KRG is efficacious in protection against APAP‐induced hepatotoxicity and mortality through metabolic regulation and that Rg3 is a major component of KRG for the GST induction, implying that Rg3 should be considered to be a potential hepatoprotective agent.
Population genomics based on low coverage sequencing: how low should we go?
Authors: Alex Buerkle C. , Gompert Zachariah
Published: November 2012

Research in molecular ecology is now often based on large numbers of DNA sequence reads. Given a time and financial budget for DNA sequencing, the question arises as to how to allocate the finite number of sequence reads among three dimensions: (i) sequencing individual nucleotide positions repeatedly and achieving high confidence in the true genotype of individuals, (ii) sampling larger numbers of individuals from a population, and (iii) sampling a larger fraction of the genome. Leaving aside the question of what fraction of the genome to sample, we analyze the trade‐off between repeatedly sequencing the same nucleotide position (coverage depth) and the number of individuals in the sample. We review simple Bayesian models for allele frequencies and utilize these in the analysis of how to obtain maximal information about population genetic parameters. The models indicate that sampling larger numbers of individuals, at the expense of coverage depth per nucleotide position, provides more information about population parameters. Dividing the sequencing effort maximally among individuals and obtaining approximately one read per locus and individual (1 × coverage) yields the most information about a population. Some analyses require genetic parameters for individuals, in which case Bayesian population models also support inference from lower coverage sequence data than are required for simple likelihood models. Low coverage sequencing is not only sufficient to support inference, but it is optimal to design studies to utilize low coverage because they will yield highly accurate and precise parameter estimates based on more individuals or sites in the genome.
The role of selection in driving landscape genomic structure of the waterflea Daphnia magna
Authors: Orsini Luisa , Mergeay Joachim , Vanoverbeke Joost , De Meester Luc
Published: November 2012

The combined analysis of neutral and adaptive genetic variation is crucial to reconstruct the processes driving population genetic structure in the wild. However, such combined analysis is challenging because of the complex interaction among neutral and selective processes in the landscape. Overcoming this level of complexity requires an unbiased search for the evidence of selection in the genomes of populations sampled from their natural habitats and the identification of demographic processes that lead to present‐day populations' genetic structure. Ecological model species with a suite of genomic tools and well‐understood ecologies are best suited to resolve this complexity and elucidate the role of selective and demographic processes in the landscape genomic structure of natural populations. Here we investigate the water flea Daphnia magna, an emerging model system in genomics and a renowned ecological model system. We infer past and recent demographic processes by contrasting patterns of local and regional neutral genetic diversity at markers with different mutation rates. We assess the role of the environment in driving genetic variation in our study system by identifying correlates between biotic and abiotic variables naturally occurring in the landscape and patterns of neutral and adaptive genetic variation. Our results indicate that selection plays a major role in determining the population genomic structure of D. magna. First, environmental selection directly impacts genetic variation at loci hitchhiking with genes under selection. Second, priority effects enhanced by local genetic adaptation (cf. monopolization) affect neutral genetic variation by reducing gene flow among populations and genetic diversity within populations.
Genetic basis of male colour dimorphism in a Lake Tanganyika cichlid fish
Authors: Takahashi T. , Sota T. , Hori M.
Published: November 2012

Phenotypic polymorphisms can be applied to study the micro‐evolutionary forces that maintain genetic variation and can mediate speciation, but it can be difficult to determine the genetic basis of polymorphisms. Recently, restriction‐site‐associated DNA (RAD) sequencing has become popular, which can easily produce multiple single nucleotide polymorphisms from whole genomes. Here, we combined RAD sequencing, allele‐specific PCR and Sanger sequencing to determine the genetic basis underlying male colour dimorphism of a Lake Tanganyika cichlid fish, Cyprichromis leptosoma. Our analyses using both a cross‐family (two parents and 12 F2 males) and 64 wild individuals do not contradict a hypothesis that two alleles of one‐locus control male colour dimorphism. Also, the locus may be located on a genome region that experiences reduced levels of recombination. Although more analyses will be needed to conclude these findings, this study is the first to suggest the genetic basis of a colour polymorphism using RAD sequencing.
Senescence, ageing and death of the whole plant
Authors: Thomas Howard
Published: November 2012

This review considers the relationship between the lifespan of an individual plant and the longevity of its component cells, tissues and organs. It begins by defining the terms senescence, growth, development, turnover, ageing, death and program. Genetic and epigenetic mechanisms regulating phase change from juvenility to maturity influence directly the capacity for responding to senescence signals and factors determining reproduction‐related patterns of deteriorative ageing and death. Senescence is responsive to communication between sources and sinks in which sugar signalling and hormonal regulation play central roles. Monocarpy and polycarpy represent contrasting outcomes of the balance between the determinacy of apical meristems and source–sink cross‐talk. Even extremely long‐lived perennials sustain a high degree of meristem integrity. Factors associated with deteriorative ageing in animals, such as somatic mutation, telomere attrition and the costs of repair and maintenance, do not seem to be particularly significant for plant lifespan, but autophagy‐related regulatory networks integrated with nutrient signalling may have a part to play. Size is an important influence on physiological function and fitness of old trees. Self‐control of modular structure allows trees to sustain viability over prolonged lifespans. Different turnover patterns of structural modules can account for the range of plant life histories and longevities.

Contents

Summary
696

I.
Endgame theory
697

II.
Terms and conditions
697

III.
Juvenility and maturity
699

IV.
Sources and sinks
700

V.
Monocarpy and polycarpy
703

VI.
Longevity and ageing
704

VII.
Last words
707

Acknowledgements
708

References
708
Assessing the potential effectiveness of food and beverage taxes and subsidies for improving public health: a systematic review of prices, demand and body weight outcomes
Authors: Powell L. M. , Chriqui J. F. , Khan T. , Wada R. , Chaloupka F. J.
Published: November 2012

Taxes and subsidies are increasingly being considered as potential policy instruments to incentivize consumers to improve their food and beverage consumption patterns and related health outcomes. This study provided a systematic review of recent U.S. studies on the price elasticity of demand for sugar‐sweetened beverages (SSBs), fast food, and fruits and vegetables, as well as the direct associations of prices/taxes with body weight outcomes. Based on the recent literature, the price elasticity of demand for SSBs, fast food, fruits and vegetables was estimated to be −1.21, −0.52, −0.49 and −0.48, respectively. The studies that linked soda taxes to weight outcomes showed minimal impacts on weight; however, they were based on existing state‐level sales taxes that were relatively low. Higher fast‐food prices were associated with lower weight outcomes particularly among adolescents, suggesting that raising prices would potentially impact weight outcomes. Lower fruit and vegetable prices were generally found to be associated with lower body weight outcomes among both low‐income children and adults, suggesting that subsidies that would reduce the cost of fruits and vegetables for lower‐socioeconomic populations may be effective in reducing obesity. Pricing instruments should continue to be considered and evaluated as potential policy instruments to address public health risks.
Why do few food‐allergic adolescents treat anaphylaxis with adrenaline? – reviewing a pressing issue
Authors: Marrs Tom , Lack Gideon
Published: November 2012

Food allergic adolescents are at higher risk of fatal anaphylaxis than other children. Both allergen avoidance and maintaining access to adrenaline auto‐injectors (AAI) are key goals in effective food allergy management, for which written guidance is often supplied. However, adolescents are rarely sufficiently prepared to use adrenaline during anaphylaxis. It is likely that further didactic education would bring limited improvement in management in this population. Focused discussion of each adolescent's perspectives and current management practice may allow more effective behavioural strategies to be adopted. Key areas for appraisal include subjects' experiences after previous allergen exposure with reference to worst response, recognising specific symptoms requiring AAI administration, and appropriate priority being given to timeliness of administering adrenaline. Behavioural strategies should be discussed to increase AAI accessibility. Rigor of allergen avoidance should not be compromised by false reassurance of proximity to emergency medication or medical services. Food allergic adolescents are motivated by the psychological impact of their condition, which often makes them feel different to their peers and may result in bullying. Methods of appropriately empowering adolescents may be considered, such as involvement of close friends and lay organisations to support appropriate management. Open discussion is crucial in engaging with adolescents' reasoning for adopting their chosen management strategies. Further research is warranted to identify cognitive patterns associated with high‐risk behaviour, and to design appropriate interventions for the augmentation of adolescent self‐management skills.
Plasma‐mediated immune suppression: a neonatal perspective
Authors: Belderbos Mirjam E. , Levy Ofer , Meyaard Linde , Bont Louis
Published: November 2012

Plasma is a rich mixture of immune regulatory factors that shape immune cell function. This immunomodulatory role of plasma is especially important in neonates. To maintain in utero feto‐maternal tolerance and to allow for microbial colonization after birth, the neonatal immune system is biased against pro‐inflammatory responses while favoring immune suppression. Therefore, the neonatal period provides a unique opportunity to study the physiologic mechanisms regulating the immune system. Several recent studies in neonates have identified plasma factors that play a key role in immune regulation. Insight into immune regulation by neonatal and adult plasma may have clinical implications, because plasma is easily accessible, affordable, and widely available. Herein, we review plasma‐mediated immune regulation, with specific focus on neonatal plasma. We discuss how immune suppression is a key function of plasma and provide a systematic overview of the published literature regarding plasma‐derived immune suppressive proteins, lipids, purines, and sugars. Finally, we outline how immune regulation by these factors, which are particularly abundant in neonatal plasma, may eventually be used to treat immune‐mediated diseases, such as autoimmune, allergic, and inflammatory diseases.
Factors Influencing Stillbirth in Bangladesh: A Case–Control Study
Authors: Nahar Shamsun , Rahman Atiya , Nasreen Hashima E.
Published: November 2012

Background

Studies on a limited scale in urban settings of Bangladesh report stillbirth rates that do not specifically provide information on the situation of underprivileged slum populations. This study aims to estimate the prevalence of, and risk factors associated with, stillbirth in a developing population.

Methods

A case–control study was conducted on women having a singleton birth between November 2008 and April 2009 in 34 slum areas in Dhaka. Data were collected on 231 women with stillbirth (cases) and 464 women having livebirth (controls). This study utilised the records of the Manoshi programme and supplemented it with data obtained through interview of the women.

Results

The stillbirth rate was 26 per 1000 total births, of which 62% occurred during the intrapartum period. Obstetrical complications contributed to 61.4% of stillbirths. Illiterate women [odds ratio (OR) 1.6 [95% confidence interval (CI) 1.1, 2.2]], women aged ≥35 years (OR 2.9 [95% CI 1.5, 25.5]), preterm delivery (OR 5.2 [95% CI, 3.2, 8.5]), prolonged labour (OR 2.8 [95% CI 1.6, 4.6]) and failure of labour progress (OR 2.4 [95% CI 1.1, 5.5]) were significant maternal risk factors, while decreased fetal movement, fetal malpresentation and fetal distress were the fetal risk factors associated with stillbirth.

Conclusions

Risk factors associated with stillbirths are amenable to intervention. There is an urgent need to educate pregnant women about risk factors for stillbirths during antenatal visits. Encouraging women to deliver at health facilities and better management of obstetrical complications may help reduce the burden of stillbirths in Bangladesh.
Precautionary Saving, Financial Risk, and Portfolio Choice
Authors: Deidda Manuela
Published: November 2012

Relying on a direct question about the desired amount of precautionary wealth from the 2002 wave of the Italian “Survey of Household Income and Wealth,” I assess the main determinants of the precautionary motive for saving, focusing on the role played by financial risk on households' saving decisions. Households that invest mainly in safe assets do not need to protect themselves against future and unexpected financial losses. Consequently, once we control for households' sources of risk beside financial ones, the amount of precautionary savings of a household investing exclusively in safe assets should be lower compared to households who detain a non‐negligible share of risky assets in their portfolio. Results show that, as expected, a strong and negative correlation exists between the desired amount of precautionary wealth and the ownership of a portfolio made exclusively of safe assets.
Dentin decalcification during lithium treatment: case report
Authors: Eduardo Carlos de P. , Simões Alyne , de Freitas Patricia M. , Arana‐Chavez Victor E. , Nicolau José , Gentil Valentim
Published: November 2012

Severe dental decay and changes in tooth structure have been reported in association with the use of lithium in Psychiatry, but lithium effects on tooth inorganic composition remain unknown. A 30‐year‐old woman with bipolar disorder, treated with lithium carbonate presented severe dental decay. Dentin samples from lithium and healthy volunteers were collected and submitted to ionic and ultrastructural analysis. Samples from the lithium patient exhibited irregular peritubular walls and the mineral crystals were irregularly arranged in the intertubular dentin. In addition, a decrease in Mg/P/Ca and an increase of Zn concentrations were detected. These data suggest that the severe dental decay and changes in the tooth structure observed for the lithium‐treated patient are related to dentin mineral loss and that this pathological condition is different from caries lesions.
Age Should Be Considered in the Allocation of Deceased Donor Kidneys
Authors: Shapiro Michael E.
Published: November 2012

Organ allocation is a specific example of the allocation of scarce resources in a pluralistic society. As such, it is subject to both governmental and public scrutiny. It must follow the requirements of the federal legislation and regulations regarding “equitable allocation of organs.” An ideal allocation system should balance the ethical concepts of equity, or fairness, and utility, or usefulness. The current kidney allocation system has been in place, with some modifications over time, since the mid‐1980s. It suffers from the changing demographics in ESRD, notably the aging of these groups, and in the growing length of the kidney waiting list. The current algorithm is thus imbalanced and requires reexamination. In particular, the system fails to match kidneys with long‐projected function to recipients with long‐projected lifespans, and vice versa. To improve the utility of kidney transplantation and lengthen the useful lifespan of these organs, a system that better matches kidneys and recipients is necessary, and this will require the use of recipient age in those calculations. The ethical questions and justification of such a system are presented.
Optimal Hemodialysis Vascular Access in the Elderly Patient
Authors: Moist Louise M. , Lok Charmaine E. , Vachharajani Tushar J. , Xi Wang , AlJaishi Ahmed , Polkinghorne Kevan R. , Vazquez Miguel , Lee Timmy C.
Published: November 2012

The optimal vascular access for elderly patients remains a challenge due to the difficulty balancing the benefits and risks in a population with increased comorbidity and decreased survival. Age is commonly associated with failure to mature in fistula and decreased rates of primary and secondary patency in both fistula and grafts. In the elderly, at 1 and 2 years, primary patency rates range from 43% to 74% and from 29% to 67%, respectively. Secondary patency rates at 1 and 2 years range from 56% to 82% and 44% to 67%, respectively. Cumulative fistula survival is no better than grafts survival when primary failures are included. Several observational studies consistently demonstrate a lower adjusted mortality among those using a fistula compared with a catheter; however, catheter use in the elderly is increasing in most countries with the exception of Japan. Both guidelines and quality initiatives do not acknowledge the trade‐offs involved in managing the elderly patients with multiple chronic conditions and limited life expectancy or the value that patients place on achieving these outcomes. The framework for choice of vascular access presented in this article considers: (1) likelihood of disease progression before death, (2) patient life expectancy, (3) risks and benefits by vascular access type, and (4) patient preference. Future studies evaluating the timing and type of vascular access with careful assessments of complications, functionality, cost benefit, and patients’ preference will provide relevant information to individualize and optimize care to improve morbidity, mortality, and quality of life in the elderly patient.
Advance Care Planning in Patients With Chronic Kidney Disease
Authors: Davison Sara N.
Published: November 2012

Poor communication and failure to establish goals of care result in unnecessary admissions to hospital, invasive procedures, suffering, and prolongation of the dying process for many CKD patients. Comprehensive CKD care requires systematic integration of advance care planning (ACP). This report describes an approach to ACP for patients with CKD, discusses essential aspects of how to facilitate these conversations, and briefly reviews the empirical evidence supporting the value of ACP.
When Should a Patient Receive an Arteriovenous Graft Rather Than a Fistula?
Authors: Lee Ho‐Won , Allon Michael
Published: November 2012

There has been a dramatic increase in the placement and use of arteriovenous fistulas (AVF) in US patients with chronic kidney disease over the past few years, in accordance with strong recommendations by Fistula First Initiative and KDOQI guidelines. However, AVF nonmaturation remains a substantial obstacle to achieving functional AVFs in a subset of patients, despite the widespread use of preoperative vascular mapping to assist surgeons in planning access surgery, and the growing use of interventions to salvage nonmaturing AVFs. In the right patient, aggressive efforts result in a functioning AVF, which provides adequate dialysis with relatively few interventions required to maintain its long‐term patency for dialysis. In the wrong patient, aggressive efforts to achieve a mature AVF may result in numerous failed surgical and percutaneous procedures and prolonged catheter dependence, with all its associated complications. Thus, strict recommendations to place an AVF in all dialysis patients might not benefit every patient, and may actually harm some patients. There are no randomized clinical trials to address which patients are more suitable for placement of an arteriovenous graft (AVG), rather than an AVF. However, there is a wealth of observational studies, which taken cumulatively, may assist clinicians in identifying those patients who should receive an AVG. In this article, we review the relevant published literature regarding this topic and provide suggestions for stratifying patients who should receive each type of vascular access.
Transradial Approach for Cardiovascular Interventions and Its Implications for Hemodialysis Vascular Access
Authors: Wang Shouwen , Asif Arif
Published: November 2012

Because of its advantages, the transradial approach for cardiovascular interventions has gained significant popularity. However, this approach can be associated with radial artery thrombosis and occlusion. The complication generates a major concern for its potential impact on the future creation of an arteriovenous hemodialysis access. The issue gains more importance as a significant number of patients with cardiovascular disease suffer from underlying chronic kidney disease (CKD) and might need an arteriovenous access for hemodialysis therapy. In this context, the preservation of the arterial system is of equal importance to the frequently highlighted venous conservation for the successful creation of an arteriovenous access. It is for this reason that the Fistula First Breakthrough Initiative recommends avoiding the use of the radial artery for performing percutaneous interventions in patients with advanced CKD. Furthermore, there is scarce clinical data and publication regarding the impact of transradial approach on hemodialysis access. Is it possible to utilize the potential benefits and minimize the potential risks of transradial approach in chronic kidney disease patients? On the basis of current knowledge, this review discusses related issues of transradial approach to raise awareness and understanding, which are essential to proper caring of CKD patients undergoing cardiovascular interventions.
Cost analysis in favor of a combined approach for cytomegalovirus after kidney transplantation: a single‐center experience
Authors: Hellemans R. , Beutels P. , Ieven M. , Verpooten G.A. , Bosmans J.L.
Published: November 2012

Background

In kidney transplant recipients, cytomegalovirus (CMV) can cause significant morbidity, mortality, and costs, which can be prevented by universal antiviral prophylaxis or preemptive therapy.

Methods

With the aim to improve our understanding of the advantages and disadvantages of these interventions, we documented resource use for 101 consecutive kidney transplant recipients in our center receiving preemptive therapy and estimated resource use for 2 alternative scenarios.

Results

At 100 days after transplantation, the mean total costs of our preemptive strategy including monitoring and treatment with intravenous ganciclovir was €2545 per patient. At €4853 per patient, these costs were highest for the CMV‐positive donor/CMV‐negative recipient (D+/R−) patient subgroup (n = 28), who frequently require recurrent treatment. A treatment scenario with valganciclovir prophylaxis for D+/R− and R+ patients, in which we ignored late‐onset disease after discontinuation of prophylaxis, resulted in an estimated cost of €1892 per patient. A combined approach using valganciclovir prophylaxis in the D+/R− group and a preemptive strategy in the R+ groups would result in the lowest mean and median costs per patient (€1701).

Conclusion

Our study suggests that a combined approach, using valganciclovir prophylaxis in D+/R− patients and preemptive treatment in R+ patients, may result in the lowest cost. This approach seems reasonable as it restricts expensive prophylactic drug therapy to those who would benefit the most, whereas it limits the risk for drug toxicity and late‐onset disease in those at lower risk for CMV.
Vancomycin‐resistant enterococcal meningitis in an autologous stem cell transplant recipient cured with linezolid
Authors: Frasca K.L. , Schuster M.G.
Published: November 2012

Enterococci are an unusual cause of meningitis, with most cases reported in the literature preceded by neurosurgical procedures. Spread to the meninges from an enterococcal bloodstream infection is even more rare, with few cases reported in the literature. We report the first documented case, to our knowledge, of successful treatment of vancomycin‐resistant enterococcal (VRE) meningitis with linezolid therapy in an immunosuppressed hematopoietic stem cell transplant recipient. Our case highlights the success of monotherapy with linezolid for VRE meningitis. A literature review is provided, which reveals that there is little evidenced‐based data on the optimal therapy for VRE meningitis.
C2‐mediated decrease in DNA methylation, accumulation of siRNAs, and increase in expression for genes involved in defense pathways in plants infected with beet severe curly top virus
Authors: Yang Li‐Ping , Fang Yuan‐Yuan , An Chun‐Peng , Dong Li , Zhang Zhong‐Hui , Chen Hao , Xie Qi , Guo Hui‐Shan
Published: November 2012

Cytosine methylation is one of epigenetic information marked on the DNA sequence. In plants, small interfering RNAs (siRNAs) target homologous genomic DNA sequences for cytosine methylation. This process, known as RNA‐directed DNA methylation (RdDM), plays an important role in transposon control, regulation of gene expression and virus resistance. In this paper, we demonstrate that the C2 protein encoded by a geminivirus (beet severe curly top virus, BSCTV) mediated a decrease in DNA methylation of repeat regions in the promoters of ACD6, an upstream regulator of the salicylic acid defense pathway, and GSTF14, an endogenous gene of the glutathione S‐transferase superfamily that is implicated in numerous stress responses. C2‐mediated decreases in DNA methylation reduced accumulation of the siRNAs derived from the promoter repeats and enhanced the steady‐state expression of both ACD6 and GSTF14 transcripts. Reduced accumulation of BSCTV‐derived siRNAs was detected in BSCTV‐infected plants, but not in plants infected with C2‐deficient BSCTV (c2− BSCTV). C2 protein exhibited no siRNA‐binding activity. Instead, our results revealed that C2 protein‐mediated decreases in DNA methylation appeared to affect the production of siRNAs that are required for targeting and reinforcing RdDM, a process that activated expression of defense‐related genes that are normally dampened by these siRNAs in the host plants. However, C2‐dependent reduction in virus‐derived siRNAs also benefits the viruses by disrupting the feedback loop reinforcing DNA methylation‐mediated antiviral silencing.
On the Efficacy and Safety of Vaccination with Live Tachyzoites of Neospora caninum for Prevention of Neospora-Associated Fetal Loss in Cattle
Authors: Weber Fred H. , Jackson James A. , Sobecki Brian , Choromanski Les , Olsen Mary , Meinert Todd , Frank Rodney , Reichel Michael P. , Ellis John T.
Published: November 2012

Infection of cattle withNeospora caninummay result in abortion or the birth of a congenitally infected calf. Vaccination with liveN. caninumprotects against experimental infection of cattle and mice, and the naturally attenuated Nc-Nowra strain ofN. caninumis of particular interest as a potential vaccine candidate. Vaccination of heifers prior to breeding with live Nc-Nowra tachyzoites by either the subcutaneous or the intravenous route reduced the rate of abortion and the presence of the parasite in calves as determined by PCR and serology after infection of cows with a virulent isolate. Protected fractions were 55.6% to 85.2% depending on the route of vaccination and growth conditions of the vaccine strain, with cryopreserved Nc-Nowra tachyzoites being less effective, with a 25.9% protected fraction. Vaccination appeared to reduce the rate of pregnancy after artificial insemination in some groups compared to nonvaccinated, nonchallenged controls. One animal that was vaccinated but not challenged experienced an abortion, but Nc-Nowra could not be detected in any of the cows in this group or their progeny. This study confirms that live vaccination can be an effective method of preventing neosporosis in cattle and yet highlights the technical hurdle of preservation of live parasites that must be overcome for a vaccine to be commercially successful.
Incidence Rates of Clinical Mastitis among Canadian Holsteins Classified as High, Average, or Low Immune Responders
Authors: Thompson-Crispi Kathleen A. , Miglior Filippo , Mallard Bonnie A.
Published: November 2012

The objective of this study was to compare the incidence rate of clinical mastitis (IRCM) between cows classified as high, average, or low for antibody-mediated immune responses (AMIR) and cell-mediated immune responses (CMIR). In collaboration with the Canadian Bovine Mastitis Research Network, 458 lactating Holsteins from 41 herds were immunized with a type 1 and a type 2 test antigen to stimulate adaptive immune responses. A delayed-type hypersensitivity test to the type 1 test antigen was used as an indicator of CMIR, and serum antibody of the IgG1 isotype to the type 2 test antigen was used for AMIR determination. By using estimated breeding values for these traits, cows were classified as high, average, or low responders. The IRCM was calculated as the number of cases of mastitis experienced over the total time at risk throughout the 2-year study period. High-AMIR cows had an IRCM of 17.1 cases per 100 cow-years, which was significantly lower than average and low responders, with 27.9 and 30.7 cases per 100 cow-years, respectively. Low-AMIR cows tended to have the most severe mastitis. No differences in the IRCM were noted when cows were classified based on CMIR, likely due to the extracellular nature of mastitis-causing pathogens. The results of this study demonstrate the desirability of breeding dairy cattle for enhanced immune responses to decrease the incidence and severity of mastitis in the Canadian dairy industry.
Factors Influencing the Sensitivity and Specificity of Conventional Sequencing in Human Immunodeficiency Virus Type 1 Tropism Testing
Authors: Knapp David J. H. F. , McGovern Rachel A. , Dong Winnie , Poon Art F. Y. , Swenson Luke C. , Zhong Xiaoyin , Woods Conan K. , Harrigan P. Richard
Published: November 2012

Human immunodeficiency virus type 1 (HIV-1) V3 loop sequence can be used to infer viral coreceptor use. The effect of input copy number on population-based sequencing of the V3 loop of HIV-1 was examined through replicate deep and population-based sequencing of samples with known tropism, a heterogeneous clinical sample (624 population-based sequences and 47 deep-sequencing replicates), and a large cohort of clinical samples from phase III clinical trials of maraviroc including the MOTIVATE/A4001029 studies (n= 1,521). Proviral DNA from two independent samples from each of 101 patients from the MOTIVATE/A4001029 studies was also analyzed. Cumulative technical error occurred at a rate of 3 × 10−4mismatches/bp, without observed effect on inferred tropism. Increasing PCR replication increased minority species detection with an ∼10% minority population detected in 18% of cases using a single replicate at a viral load of 1,072 copies/ml and in 44% of cases using three replicates. The nucleotide prevalence detected by population-based and deep sequencing were highly correlated (Spearman's ρ, 0.73), and the accuracy increased with increasing input copy number (P< 0.001). Triplicate sequencing was able to predict tropism changes in the MOTIVATE/A4001029 studies for both low (P= 0.05) and high (P= 0.02) viral loads. Sequences derived from independently extracted and processed samples of proviral DNA for the same patient were equivalent to replicates from the same extraction (P= 0.45) and had correlated position-specific scoring matrix scores (Spearman's ρ, 0.75;P≪ 0.001); however, concordance in tropism inference was only 83%. Input copy number and PCR replication are important factors in minority species detection in samples with significant heterogeneity.
Optimization of a Combined Human Parechovirus-Enterovirus Real-Time Reverse Transcription-PCR Assay and Evaluation of a New Parechovirus 3-Specific Assay for Cerebrospinal Fluid Specimen Testing
Authors: Selvaraju Suresh B. , Nix W. Allan , Oberste M. Steven , Selvarangan Rangaraj
Published: November 2012

Human parechoviruses (HPeVs), particularly type 3 (HPeV3), are known central nervous system (CNS) pathogens, causing serious infections in infants similar to those caused by enteroviruses (EVs). The primary aim of this study was to combine and validate HPeV and EV real-time reverse transcription-PCR (RT-PCR) detection assays with the best available RT-PCR reagents and conditions for parallel detection of HPeV and EV on a single platform. The secondary aim was to develop and validate a newly developed HPeV3-specific real-time RT-PCR assay. Five commercially available RT-PCR kits were evaluated with the pan-HPeV and EV assays in one-step and two-step RT-PCRs. Two-step RT-PCR with the AgPath ID RT-PCR (AGP) kit performed best for both pan-HPeV and EV assays. The pan-HPeV-specific assay performed best with the AGP kit in a one-step RT-PCR. Frozen aliquots of 145 (for HPeV,
n
= 70; for EV,
n
= 75) previously characterized cerebrospinal fluid (CSF) specimens were tested by EV-, pan-HPeV-, and HPeV3-specific (HPeV specimens only) assays. The pan-HPeV and EV assays demonstrated 100% analytical sensitivity and specificity compared to historic results, while the HPeV3-specific assay demonstrated 97% sensitivity and 100% specificity. We propose a real-time pan-HPeV, EV two-step RT-PCR algorithm for simultaneous detection of HPeV and EV from CSF specimens on a single platform. The HPeV3-specific one-step RT-PCR assay can be used as a rapid and cost-effective assay to detect and identify HPeV3 in pan-HPeV RT-PCR assay-positive CSF specimens.
Simultaneous Detection, Genotyping, and Quantification of Human Papillomaviruses by Multicolor Real-Time PCR and Melting Curve Analysis
Authors: Liao Yiqun , Zhou Yulin , Guo Qiwei , Xie Xiaoting , Luo Ena , Li Jian , Li Qingge
Published: November 2012

Long-term infection with high-risk human papillomavirus (HPV) is the leading cause of cervical cancer, while infection with low-risk HPV is the major reason for condylomata acuminata. An accurate, rapid, and convenient assay that is able to simultaneously detect, genotype, and quantify HPV would be of great clinical value yet remains to be achieved. We developed a three-color real-time PCR assay that is able to analyze 30 predominant HPV types in three reactions. The amplification curves indicated the presence of HPV, melting curve analysis identified the HPV genotype, and the quantification cycle value determined the quantity. We applied this assay to 647 cervical swab samples, and the results were compared with those obtained with a commercial genotyping system. The proposed assay had a limit of detection of 5 to 50 copies per reaction and a dynamic range of 5 × 10
1
to 5 × 10
6
copies per reaction. A comparison study showed that the overall sample concordance with the comparison method was 91.6% and the type agreement was greater than 98.7%. The quantification study demonstrated that the loads of HPV type 16 in 30 samples with cervical intraepithelial neoplasia grade III (CIN III) lesions were significantly higher than those in samples with CIN I lesions or CIN II lesions, and the results were concordant with those of the comparison method. The increased information content, high throughput, and low cost would facilitate the use of this real-time PCR-based assay in a variety of clinical settings.