bluuebunny/crossref_metadata_2025 huggingface dataset:
Reprint: Six-Month Continuous Intraputamenal Infusion Toxicity Study of Recombinant Methionyl Human Glial Cell Line-Derived Neurotrophic Factor (r-metHuGDNF) in Rhesus Monkeys
Authors: Hovland David N. , Boyd Robert B. , Butt Mark T. , Engelhardt Jeffery A. , Moxness Michael S. , Ma Mark H. , Emery Maurice G. , Ernst Nadia B. , Reed Randall P. , Zeller Jillynne R. , Gash Don M. , Masterman Donna M. , Potter Beth M. , Cosenza Mary E. , Lightfoot Ruth M.
Published: April 2008

Recombinant human glial cell line-derived neurotrophic factor (r-metHuGDNF) is a potent neuronal growth and survival factor that has been considered for clinical use in the treatment of Parkinson’s disease (PD). Here we present results of a 6-month toxicology study in rhesus monkeys conducted to support clinical evaluation of chronic intraputamenal infusion of r-metHuGDNF for PD. Monkeys (6–9/sex/group) were treated with 0 (vehicle), 15, 30, or 100 μg/day r-metHuGDNF by continuous unilateral intraputamenal infusion (150 μl/day flow rate) for 6 months; a subset of animals (2–3/sex/group) underwent a subsequent 3-month treatment-free recovery period. Notable observations included reduced food consumption and body weight at 100 μg/day and meningeal thickening underlying the medulla oblongata and/or overlying various spinal cord segments at 30 and 100 μg/day. In addition, multifocal cerebellar Purkinje cell loss (with associated atrophy of the molecular layer and, in some cases, granule cell loss) was observed in 4 monkeys in the 100-μg/day group. This cerebellar finding has not been observed in previous nonclinical studies evaluating r-metHuGDNF. The small number of affected animals precludes definitive conclusions regarding the pathogenesis of the cerebellar lesion, but the data support an association with r-metHuGDNF treatment.
Oral Cyclophosphamide for Active Scleroderma Lung Disease: A Decision Analysis
Authors: Khanna Dinesh , Furst Daniel E. , Clements Philip J. , Tashkin Donald P. , Eckman Mark H.
Published: April 2008

Background. Results from the recent Scleroderma Lung Study (SLS) show that oral cyclophosphamide (CYC) is better than placebo in preventing the progression of scleroderma-related interstitial lung disease (SSc-ILD) at 12 mo but is associated with adverse events. Also, the long-term balance of risk and benefit remains unclear. Methods. The authors evaluate the risk-benefit tradeoffs using a Markov decision analytic model to project the quality-adjusted life years (QALYs) for strategies of CYC versus no CYC in SSc-ILD. The base case examined a 50-y-old woman with SSc of 1.5 y, SSc-ILD with moderate ventilatory restriction. The authors analyze the decision to treat with 1 y of daily CYC versus no SSc-ILD— specific therapy. Based on 2-y data from the SLS, the authors assume CYC resulted in no survival benefit and only a transient beneficial impact on pulmonary function. They explore the impact of changes in model parameters through sensitivity analyses, including the efficacy of CYC in preventing progression of lung disease and SSc-ILD— related death. Results. In the base-case analysis, CYC-treated patients fared worse, with a small loss of 0.21 QALYs (16.84 v. 17.15). CYC remained inferior across sensitivity analyses for most variables. In analyses assuming a survival benefit with CYC, CYC resulted in a clinically significant gain (18.17 v. 17.15 QALYs). Conclusions. CYC therapy for 1 y results in a small loss in QALYs compared with no CYC for SSc-ILD. The lack of a beneficial impact on survival and the transience of CYC's impact on decline in pulmonary function drive this conclusion.
The Association of a Varus Hindfoot and Fracture of the Fifth Metatarsal Metaphyseal-Diaphyseal Junction
Authors: Raikin Steven M. , Slenker Nicholas , Ratigan Brian
Published: April 2008

Background

Fractures to the fifth metatarsal metaphyseal-diaphyseal junction (Jones fracture) have high nonunion rates. Surgical intramedullary screw fixations have excellent results but a high refracture rate. This has been associated with inadequate screw size and too early return to activity.

Hypothesis

Varus hindfoot alignment overloads the lateral column of the foot and acts as a predisposing factor to the development of and failure of treatment of Jones fractures.

Study Design

Case series; Level of evidence, 4.

Methods

Twenty-one primary Jones fractures (20 patients) treated surgically with a 4.5-mm cannulated screw were retrospectively reviewed. Detailed clinical and radiographic data and outcomes were recorded, including measurements of hindfoot alignment.

Results

A 100% union rate with return to prior activity level and no refractures were found at a mean follow-up of 49 months. Clinical varus was present in 16 feet, whereas radiographic measurements revealed 18 of 21 hindfeet to be in varus. The mean calcaneal pitch angle was 28.5°, and the mean Meary angle was 13° convex upward. Patients with varus alignment were fitted postoperatively with lateral hindfoot and forefoot posted orthotic inserts to correct alignment.

Conclusion

The majority of patients sustaining Jones fractures have evidence of varus hindfoot alignment. This may be a predisposing factor to developing the fracture or refracture after fixation. Postoperative varus unloading (lateral hindfoot and forefoot posting) orthotic insert appears to be helpful in preventing reinjury or refracture of Jones fractures.
Intensive Care Management of the Patient With Cystic Fibrosis
Authors: Kremer Ted M. , Zwerdling Robert G. , Michelson Peter H. , O'Sullivan Brian P.
Published: April 2008

Cystic fibrosis was previously thought to be a disease of childhood. With a better understanding of this condition along with improvements in therapy, patients with cystic fibrosis are now living well into adulthood. The aim of this article is to familiarize the intensive care unit physician with cystic fibrosis care, to discuss complications associated with cystic fibrosis specifically related to the intensive care unit, and to detail the current recommendations for the clinical management of the patient with cystic fibrosis. With advancing disease, the most severely affected organs are the lungs. Obstruction, infection, and inflammation contribute to the decline of pulmonary function, ultimately leading to death. Some patients may be eligible for lung transplantation, but choosing wisely will affect posttransplant survival. Because other organs are affected by the genetic defect and associated treatments, serious complications related to the liver, pancreas, intestines, and kidneys must be considered by the intensivist faced with a patient with cystic fibrosis. As practitioners, the fact that not all patients will survive and help our patients and families gracefully through the end-of-life process should be accepted.
Religion, Risk, and Medical Decision Making at the End of Life
Authors: Van Ness Peter H. , Towle Virginia R. , O'Leary John R. , Fried Terri R.
Published: April 2008

Objectives: The purpose of this study is to present empirical evidence about whether religious patients are more or less willing to undergo the risks associated with potentially life-sustaining treatment. Methods: At least every 4 months 226 older community-dwelling persons with advanced cancer, congestive heart failure, or chronic obstructive pulmonary disease were asked questions about several dimensions of religiousness and about their willingness to accept potentially life-sustaining treatment. Results: Results were mixed but persons who said that during their illness they grew closer to God (odds ratio [OR] = 1.79; 95% confidence intervals [CI] = 1.15, 2.78) or those grew spiritually (OR = 1.61; 95% CI = 1.03, 2.52) were more willing to accept risk associated with potentially life-sustaining treatment than were persons who did not report such growth. Discussion: Not all dimensions of religiousness have the same association with willingness to undergo potentially life-sustaining treatment. Seriously ill older, religious patients are not especially predisposed to avoid risk and resist treatment.
Pacioli and humanism: pitching the text in Summa Arithmetica
Authors: McCarthy Patricia , Sangster Alan , Stoner Greg
Published: April 2008

Despite the wide cross-disciplinary influence of Fra' Luca Pacioli's Summa de Arithmetica, Geometria, Proportioni et Proportionalita (Summa), it has been criticized as being both difficult to read and written in a mixture of bad Italian and bad Latin; but, paradoxically, intellectuals of Pacioli's day praised the style of writing in Summa. Can both viewpoints be correct? The answer to this question is sought by identifying what may have inspired Pacioli to write Summa in the manner he did. In doing so, the article considers the times in which he lived and, in particular, the impact that Renaissance Humanism and Humanist Education may have had upon his writing style. The article finds both views were correct in their own timeframes and contexts and that Pacioli's writing style was both an appropriate one with which to address a contemporary merchant society and one which would impress and gain the approval of his fellow humanist educators and patrons.
The biblical jubilee: old wineskin for a new wine?
Authors: Moerman Lee
Published: April 2008

In the Biblical Old Testament a religious framework, Jubilee Law, provides a mandated procedure for dealing with the indebted Hebrew and his property. 1 Emerging from Mosaic Law, this framework is based on alternative perspectives of stewardship and societal economic relationships to the current domination of neo-liberalism in supranational organizations, in particular the international financial institutions. Themes and concepts emerging from Jubilee Law can offer the critical accounting literature a theological lens to critique accounting in the current global arena, especially the debt crisis of poor countries. A theological perspective, grounded in laws that protect the economically vulnerable, provides an alternative emancipatory discourse which has resonated with activist groups and others, and which challenges and critiques contemporary economic practices and offers an ethical framework for mandating social justice.
Some Common Problems Faced by Hospice Palliative Care Volunteers
Authors: Claxton-Oldfield Stephen , Claxton-Oldfield Jane
Published: April 2008

This paper examines 4 common problems that many hospice palliative care volunteers in Canada (and the United States) encounter, namely, being underutilized, being placed with a patient too late in the patient's illness, feeling undervalued by some members of the medical staff, and not being able to do more to help patients and their families. The implications of each of these problems are discussed along with suggestions for overcoming them. Finally, some ideas for future research are proposed.
Methadone
Authors: Chhabra Shalini , Bull Janet
Published: April 2008

Methadone hydrochloride is an old drug that has been in vogue off and on. It has complex pharmacodynamics and can be potentially fatal in inexperienced settings. Drug switching from an opioid to methadone or vice versa requires knowledge of equianalgesic dosing. It is critical when using the drug to monitor for signs and symptoms of toxicity so that overdosing or toxicity can be identified in a timely manner. This review discusses these important topics so that methadone can be used safely and effectively.
Parents' perceptions of communication with professionals during the diagnosis of autism
Authors: Osborne Lisa A. , Reed Phil
Published: April 2008

In order to obtain the views of parents concerning their perceptions of the process of getting a diagnosis of an autistic spectrum disorder (ASD) for their child, 15 focus groups were conducted across a range of locations in England. These groups were split into parents of preschool-, primary- and secondary-aged children who had recently received an ASD diagnosis. At the time of diagnosis, most of the parents wished for a quicker and easier process. In particular, they would prefer the procedure to have a more coherent structure and content. They also requested greater professional training about ASD, in particular, regarding the information that professionals possess, and the interpersonal skills of some professionals. The idea of broad information sheets to be provided to parents at the time of diagnosis would be of value, especially to combat negative information provided from other sources.
Acetaminophen (paracetamol) use, measles-mumps-rubella vaccination, and autistic disorder
Authors: Schultz Stephen T. , Klonoff-Cohen Hillary S. , Wingard Deborah L. , Akshoomoff Natacha A. , Macera Caroline A. , Ming Ji
Published: April 2008

The present study was performed to determine whether acetaminophen (paracetamol) use after the measles-mumps-rubella vaccination could be associated with autistic disorder. This case-control study used the results of an online parental survey conducted from 16 July 2005 to 30 January 2006, consisting of 83 children with autistic disorder and 80 control children. Acetaminophen use after measles-mumps-rubella vaccination was significantly associated with autistic disorder when considering children 5 years of age or less (OR 6.11, 95% CI 1.42—26.3), after limiting cases to children with regression in development (OR 3.97, 95% CI 1.11—14.3), and when considering only children who had post-vaccination sequelae (OR 8.23, 95% CI 1.56—43.3), adjusting for age, gender, mother's ethnicity, and the presence of illness concurrent with measles-mumps-rubella vaccination. Ibuprofen use after measles-mumps-rubella vaccination was not associated with autistic disorder. This preliminary study found that acetaminophen use after measles-mumps-rubella vaccination was associated with autistic disorder.
A comparison of contexts for assessing joint attention in toddlers on the autism spectrum
Authors: Roos Elizabeth M. , McDuffie Andrea S. , Weismer Susan Ellis , Gernsbacher Morton Ann
Published: April 2008

Children on the autism spectrum often demonstrate atypical joint attention, leading some researchers to consider joint attention defecits a core feature of the autism spectrum. Structured measures, such as the Early Social Communication Scales (ESCS), are commonly used to provide a metric of joint attention. To explore the assessment of joint attention in multiple contexts, we implemented an alternative system for coding joint attention behaviors. We compared initiation of joint attention (IJA) and response to joint attention (RJA) behaviors coded from naturalistic examiner—child play samples with similar IJA and RJA behaviors elicited within the structured ESCS protocol. Participants were 20 toddlers on the autism spectrum. Levels of IJA and RJA within the two assessment contexts were significantly and positively correlated, providing support for the use of naturalistic sampling of joint attention skills as a viable alternative, or supplement, to structured measures.
Affirmative action, meritocracy, and efficiency
Authors: Durlauf Steven N.
Published: April 2008

This article provides a framework for comparing meritocratic and affirmative action admissions policies. The context of the analysis is admissions to public universities; admission rules are evaluated as part of the public investment problem faced by a state government. Meritocratic and affirmative admissions policies are compared in terms of their effects on the level and distribution of human capital. I argue that (a) meritocratic admissions are not necessarily efficient and (b) affirmative action policies may be efficiency enhancing relative to meritocratic ones. Both these claims, as well as their negations, depend on features of individual behavior for which there is little empirical evidence. The implications of this absence of evidence are then explored, with a focus on policy evaluation when equality and efficiency are both desiderata. I argue that standard statistical decision theoretic approaches do not apply to the affirmative action case, even if equality and efficiency are rendered commensurable based on a scalar payoff function. In this context, I suggest that a presumption for equality-enhancing policies leads to support for affirmative action, but I emphasize the contingent nature of this conclusion.
Discrimination and the aim of proportional representation
Authors: Lippert-Rasmussen Kasper
Published: April 2008

Many organizations, companies, and so on are committed to certain representational aims as regards the composition of their workforce. One motivation for such aims is the assumption that numerical underrepresentation of groups manifests discrimination against them. In this article, I articulate representational aims in a way that best captures this rationale. My main claim is that the achievement of such representational aims is reducible to the elimination of the effects of wrongful discrimination on individuals and that this very important concern is, in principle, compatible with the representation of various groups diverging widely from their share of the overall population. The discussion also shows that we should ensure that a preoccupation with groups' numbers in relation to the population as a whole does not lead us away from our real aim, for example because we are blinded to the effects of discrimination against numerically overrepresented groups, or overlook the innocently different ambitions of some numerically underrepresented groups. In relation to the latter point, I appeal to the fact that many luck egalitarians think justice should be ambition sensitive (but endowment insensitive). Also, the time-relative account of representational aims expounded shows that, and how, representational aims should accommodate the changing composition of populations over time.
The difference principle and time
Authors: Attas Daniel
Published: April 2008

Rawls's difference principle contains a certain normative ambiguity, so that opposing views, including strong inegalitarian ones, might find a home under it. The element that introduces this indeterminacy is the absence of an explicit reference to time. Thus, a society that agrees on the difference principle as the proper justification of basic political-economic institutions, might nevertheless disagree on whether their specific institutions are justified by that principle. Such disagreement would most often centre on issues of fact: will a more egalitarian policy in fact prioritize the least well off or will a more libertarian policy do so? But facts are not the only possible points of contention. According to the fundamental indeterminacy, considering merely the sum of advantages to the least well off, the difference principle is indifferent among different flows of equal income over time. It cannot adjudicate among more or less unequal distributions across social groups when the sum income of the least advantaged group is constant. The fundamental indeterminacy lies at the bottom of three derivative indeterminacies: an adequate future discount rate, an acceptable absolute minimum, and a reasonable time interval. These might form the basis of political disagreement among self-proclaimed endorsers of the difference principle of left and right over the way the principal social-economic institutions ought to be structured and the distributions that ensue.
A Dialogue-Building Pilot Intervention Involving Traditional and Biomedical Health Providers Focusing on STIs and HIV/AIDS Care in Zambia
Authors: Kaboru Berthollet Bwira , Ndubani Phillimon , Falkenberg Torkel , Pharris Anastasia , Muchimba Maureen , Solo Kashita , Höjer Bengt , Faxelid Elisabeth
Published: April 2008

Collaboration between traditional and biomedically trained health workers is regarded as key in HIV/AIDS control. However, few studies have focused on exploring ways of enhancing this collaboration. Using a pre- and postintervention questionnaire, the authors assessed changes in attitudes to and practices of collaboration among 19 biomedical and 28 traditional health care providers following a 12-month dialogue-building intervention in Ndola, Zambia. The intervention consisted of peer group discussions, interactive group discussions, training sessions, and peer-influenced networking. The results show that although both groups of providers had fairly positive attitudes toward each other before the intervention, further improvements in attitudes were observed after the intervention. Referrals between the two sectors and cross visits increased. However, some attitudes to collaboration became more negative and cautious after the intervention. Dialogue-building interventions involving traditional and biomedical providers are not only feasible but also complex. Intersectoral collaboration needs time and coordination between all relevant actors in the community.
Safe Effective Nondrug Treatment of Chronic Depression: A Review of Research on Low-Voltage Cranial Electrical Stimulation and Other Adjunctive Therapies
Authors: Shealy C. Norman , Thomlinson Paul
Published: April 2008

Although clinical practice guidelines tend to emphasize pharmacological treatments for chronic depression, safe and effective nondrug treatments are available. This article reviews three decades of research at the Shealy Institute on nonpharmacological treatments for chronic depression in chronic pain patients via low-voltage electrical stimulation and other adjunctive therapies. More than 30,000 chronically depressed patients have been treated with cranial electrical stimulation at 1 to 2 mA at 15,000 Hz, modulated at 500 and 15 Hz. Approximately half of patients treated with this approach experienced marked clinical improvement. When combined with photostimulation at 1 to 7 Hz, 85% of patients improved adequately without use of antidepressant drugs and without complications. Magnesium replacement and nutrition education are useful adjuncts. This program is cost effective and can be carried out by a nurse practitioner and an assistant. Further controlled clinical research and research on mechanisms of action would strengthen the validity of these findings and increase the application of these therapeutic approaches.
Video Games and Embodiment
Authors: Gee James Paul
Published: April 2008

In this article, the author discusses one way in which modern video games can illuminate the nature of human thinking and problem solving as situated and embodied. The author first discusses why, over the last several years, many people have become interested in video games as a site to study human thinking, problem solving, and learning. The author then discusses what he call the “projective stance,” a type of embodied thinking characteristic of many (but not all) video games, as well as a form of thinking that is also, but more subtly, pervasive in everyday life and social interaction as well.
Decreases in a Slot Machine's Coefficient of Variation Lead to Increases in Customer Play Time
Authors: Lucas Anthony F. , Singh A.K.
Published: April 2008

Profits generated from slot operations are critical to the success of all casinos, yet little research has addressed the nature of the customer experience regarding game interaction. The relationship between a reel slot player's time on device and the pay table's coefficient of variation (CV) is examined via computer simulation. The pay table CV is found to be inversely related to the player's expected time on device, as measured by pulls per losing player (PPLP). Findings confound the popular notion that par alone (i.e., house advantage) serves as a legitimate proxy for play time and bolster the research suggesting that standard deviation is the dominant force behind time on device, at the single-trip grain.
Fear and Managing in Las Vegas
Authors: Eisendrath David , Bernhard BO J. , Lucas Anthony F. , Murphy Dennis J.
Published: April 2008

This article provides an analysis of the impacts of the events of September 11, 2001, on certain gaming business volume on the Las Vegas Strip. Almost immediately after these events, management teams commenced with layoffs and project postponements, in anticipation of a long and painful recovery period. The authors' intervention analysis, however, reveals an abrupt decline lasting five months, indicating a relatively rapid recovery. Interestingly, this type of recovery appears to be similar to that which has been observed in other literature examining previous terrorist attacks. In the concluding discussion, the authors highlight the lessons of both history and empirical inquiry in hopes of helping managers understand the dynamics of terrorism impacts on the hospitality industry in general and on the gaming industry in particular.
A Qualitative Analysis of Slot Clubs as Drivers of Casino Loyalty
Authors: Hendler Flavia , Latour Kathryn A.
Published: April 2008

The slot club is a very common type of loyalty program in the casino industry. In this research, the authors look at the deep meanings and emotions of a slot club for tourists and frequent local customers at a Las Vegas mega casino resort using an in-depth interview technique, the Zaltman Metaphor Elicitation Technique (ZMET). Results indicate that the opportunities for casino loyalty programs to establish emotional bonds with the customer lie in the capacity of reflecting human qualities in the slot club service delivery process, such as memory, creativity, and flexibility. The results also indicate that the slot club brings different meanings to different customer groups and that these emotional connections (or lack thereof) are best elucidated via this qualitative research technique that uses images, rather than words, to guide the in-depth interview. The authors discuss the implications of the results for loyalty programs as well as how this research technique might be used in other sectors of the hospitality industry.
Radio Frequency Identification
Authors: Wyld David C.
Published: April 2008

Radio frequency identification (RFID) allows for objects to be identified electronically through the use of radio waves. RFID can be applied to table games in casinos by allowing gaming operators to gain the same levels of customer and game-play data in table game operations as they presently have in the slot area. Using chips imprinted with RFID, gaming companies can monitor game play, prevent instances of chip counterfeiting and theft, and (by identifying addicted gamblers) promote responsible gaming. Beyond casino chips, casinos will eventually be able to install RFID on playing cards, again to give casinos a better picture of their customers, but also to reduce opportunities for cheating.
Hamilton, New Zealand
Authors: Mohsin Asad , Lockyer Tim
Published: April 2008

The introduction of a casino into a community, as evidenced from a large number of studies undertaken over the years in different parts of the globe, suggests that casino business affects the community's social and economic structure. This research considers the case of the introduction of a casino into Hamilton, a city in New Zealand with a population of approximately 129,000. Based on 945 responses, it is of particular note that differences in views regarding the casino were evident between the two genders and between those who had patronized the casino and those who had not visited. The results indicate that women and nonvisitors were consistently more negative about the casino's effects on the community than were men and those who patronized the casino.
PKF Industry Analysis
Authors: Mandelbaum Robert , Lerner Gabrielle
Published: April 2008

It is commonly understood that spas were once an afterthought for operators of hotels and resorts. Yet, as living a healthy and better lifestyle has become one of the population's top priorities, spas have grown in popularity and are viewed as essential elements to a hotel or resort's success rather than being just a luxury. To aid hotel owners and operators during the spa investment decision process, as well as assist spa department managers benchmark their operations, PKF Hospitality Research (PKF-HR) has analyzed the 2006 financial performance of hotel spa departments. The sample was divided into two categories: resorts and urban hotels. The data come from PKF-HR's Trends in the Hotel Industry database.
Commentary on “Driving Demand for the Quarterdeck”
Authors: Kelly Bill
Published: April 2008

The Quarterdeck Beachside Villas are certainly not unique in facing the challenges of seasonality in beachside resorts. Can Doug justify financially keeping the Quarterdeck open from November to March with an average occupancy of 16 percent or 1.9 rooms per day? His number one focus should be investment. If Doug wants to make the Quarterdeck a year-round destination, he needs to invest and give the customers a year-round product—weatherproof the building, open the restaurant and bar area, maybe build a small spa facility. Selling “experience” and integrated product bundles rather than discounts will improve the ARR and also the customer experience. The viability of these options may be dependent on increasing the existing villa stock.
Mapping proteins to disease terminologies: from UniProt to MeSH
Authors: Mottaz Anaïs , Yip Yum L , Ruch Patrick , Veuthey Anne-Lise
Published: April 2008

Background

Although the UniProt KnowledgeBase is not a medical-oriented database, it contains information on more than 2,000 human proteins involved in pathologies. However, these annotations are not standardized, which impairs the interoperability between biological and clinical resources. In order to make these data easily accessible to clinical researchers, we have developed a procedure to link diseases described in the UniProtKB/Swiss-Prot entries to the MeSH disease terminology.

Results

We mapped disease names extracted either from the UniProtKB/Swiss-Prot entry comment lines or from the corresponding OMIM entry to the MeSH. Different methods were assessed on a benchmark set of 200 disease names manually mapped to MeSH terms. The performance of the retained procedure in term of precision and recall was 86% and 64% respectively. Using the same procedure, more than 3,000 disease names in Swiss-Prot were mapped to MeSH with comparable efficiency.

Conclusions

This study is a first attempt to link proteins in UniProtKB to the medical resources. The indexing we provided will help clinicians and researchers navigate from diseases to genes and from genes to diseases in an efficient way. The mapping is available at: http://research.isb-sib.ch/unimed.
Phylogenetic and comparative gene expression analysis of barley (Hordeum vulgare) WRKY transcription factor family reveals putatively retained functions between monocots and dicots
Authors: Mangelsen Elke , Kilian Joachim , Berendzen Kenneth W , Kolukisaoglu Üner H , Harter Klaus , Jansson Christer , Wanke Dierk
Published: April 2008

Background

WRKY proteins belong to the WRKY-GCM1 superfamily of zinc finger transcription factors that have been subject to a large plant-specific diversification. For the cereal crop barley (Hordeum vulgare), three different WRKY proteins have been characterized so far as regulators in sucrose signaling, pathogen defense, and in response to cold and drought. However, their phylogenetic relationship remained unresolved.

Results

In this study, we used available sequence information to identify a minimum number of 45 barley WRKY transcription factor (HvWRKY) genes. According to their structural features, the HvWRKY factors were classified into the previously defined polyphyletic WRKY subgroups 1 to 3. Furthermore, we could assign putative orthologs of the HvWRKY proteins in Arabidopsis and rice. While in most cases clades of orthologous proteins were formed within each group or subgroup, other clades were composed of paralogous proteins for the grasses and Arabidopsis only, which is indicative of specific gene radiation events. To gain insight into their putative functions, we examined expression profiles of WRKY genes from publicly available microarray data resources and found group specific expression patterns. While putative orthologs of the HvWRKY transcription factors have been inferred from phylogenetic sequence analysis, we performed a comparative expression analysis of WRKY genes in Arabidopsis and barley. Indeed, highly correlative expression profiles were found between some of the putative orthologs.

Conclusion

HvWRKY genes have not only undergone radiation in monocot or dicot species, but exhibit evolutionary traits specific to grasses. HvWRKY proteins exhibited not only sequence similarities between orthologs with Arabidopsis, but also relatedness in their expression patterns. This correlative expression is indicative for a putative conserved function of related WRKY proteins in monocot and dicot species.
Array-CGH in patients with Kabuki-like phenotype: Identification of two patients with complex rearrangements including 2q37 deletions and no other recurrent aberration
Authors: Cuscó Ivon , del Campo Miguel , Vilardell Mireia , González Eva , Gener Blanca , Galán Enrique , Toledo Laura , Pérez-Jurado Luis A
Published: April 2008

Background

Kabuki syndrome (KS) is a multiple congenital anomaly syndrome characterized by specific facial features, mild to moderate mental retardation, postnatal growth delay, skeletal abnormalities, and unusual dermatoglyphic patterns with prominent fingertip pads. A 3.5 Mb duplication at 8p23.1-p22 was once reported as a specific alteration in KS but has not been confirmed in other patients. The molecular basis of KS remains unknown.

Methods

We have studied 16 Spanish patients with a clinical diagnosis of KS or KS-like to search for genomic imbalances using genome-wide array technologies. All putative rearrangements were confirmed by FISH, microsatellite markers and/or MLPA assays, which also determined whether the imbalance was de novo or inherited.

Results

No duplication at 8p23.1-p22 was observed in our patients. We detected complex rearrangements involving 2q in two patients with Kabuki-like features: 1) a de novo inverted duplication of 11 Mb with a 4.5 Mb terminal deletion, and 2) a de novo 7.2 Mb-terminal deletion in a patient with an additional de novo 0.5 Mb interstitial deletion in 16p. Additional copy number variations (CNV), either inherited or reported in normal controls, were identified and interpreted as polymorphic variants. No specific CNV was significantly increased in the KS group.

Conclusion

Our results further confirmed that genomic duplications of 8p23 region are not a common cause of KS and failed to detect other recurrent rearrangement causing this disorder. The detection of two patients with 2q37 deletions suggests that there is a phenotypic overlap between the two conditions, and screening this region in the Kabuki-like patients should be considered.
Association between promoter -1607 polymorphism of MMP1 and Lumbar Disc Disease in Southern Chinese
Authors: Song You-Qiang , Ho Daniel WH , Karppinen Jaro , Kao Patrick YP , Fan Bao-Jian , Luk Keith DK , Yip Shea-Ping , Leong John CY , Cheah Kathryn SE , Sham Pak , Chan Danny , Cheung Kenneth MC
Published: April 2008

Background

Matrix metalloproteinases (MMPs) are involved in the degradation of the extracellular matrix of the intervertebral disc. A SNP for guanine insertion/deletion (G/D), the -1607 promoter polymorphism, of the MMP1 gene was found significantly affecting promoter activity and corresponding transcription level. Hence it is a good candidate for genetic studies in DDD.

Methods

Southern Chinese volunteers between 18 and 55 years were recruited from the population. DDD in the lumbar spine was defined by MRI using Schneiderman's classification. Genomic DNA was isolated from the leukocytes and genotyping was performed using the Sequenom® platform. Association and Hardy-Weinberg equilibrium checking were assessed by Chi-square test and Mann-Whitney U test.

Results

Our results showed substantial evidence of association between -1607 promoter polymorphism of MMP1 and DDD in the Southern Chinese subjects. D allelic was significantly associated with DDD (p value = 0.027, odds ratio = 1.41 with 95% CI = 1.04–1.90) while Genotypic association on the presence of D allele was also significantly associated with DDD (p value = 0.046, odds ratio = 1.50 with 95% CI = 1.01–2.24). Further age stratification showed significant genotypic as well as allelic association in the group of over 40 years (genotypic: p value = 0.035, odds ratio = 1.617 with 95% CI = 1.033–2.529; allelic: p value = 0.033, odds ratio = 1.445 with 95% CI = 1.029–2.029). Disc bulge, annular tears and the Schmorl's nodes were not associated with the D allele.

Conclusion

We demonstrated that individuals with the presence of D allele for the -1607 promoter polymorphism of MMP1 are about 1.5 times more susceptible to develop DDD when compared with those having G allele only. Further association was identified in individuals over 40 years of age. Disc bulge, annular tear as well as Schmorl's nodes were not associated with this polymorphism.
Evaluation of patients on sertindole treatment after failure of other antipsychotics: A retrospective analysis
Authors: Azorin Jean-Michel , Murteira Susana , Hansen Karina , Toumi Mondher
Published: April 2008

Background

Use of the atypical antipsychotic sertindole was suspended for four years due to safety concerns. During the suspension, the regulatory authorities required further studies, including this one, to be conducted. The purpose of this study was to determine if a subset of patients with psychotic illness exists which particularly benefits from sertindole treatment after failure of other antipsychotic drugs, including atypical antipsychotics.

Methods

This was a retrospective single-arm observational crossover study of 344 patients, who served as their own controls. Patients mainly from the Sertindole Safety Study who had shown good response to sertindole, and who had followed up to four alternating six month periods of treatment with sertindole and other antipsychotics, were included. (In Period 1 patients took non-sertindole treatment, in Period 2, sertindole was taken, in Period 3, patients reverted to non-sertindole treatment, and in Period 4, sertindole was taken again.) Patient records for each period of treatment were assessed for objective data: number and duration of hospitalizations due to worsening of psychotic symptoms; the amount of self-harming behaviour; indicators of social status. Retrospective evaluation of changes in clinical symptoms from the patients' records was also conducted. Dates and reasons for stopping and/or switching medication were also recorded.

Results

There was improvement in all objective measured parameters during the periods of sertindole treatment. In particular, the average number of hospitalizations per year due to worsening of psychotic symptoms was reduced in the following way in the group studied over four treatment periods: Period 1 (non-sertindole treatment) 3.4; Period 2 (sertindole treatment) 1.0; Period 3 (non-sertindole treatment) 2.0; Period 4 (sertindole treatment) 1.8. The duration of hospitalizations also decreased significantly during the periods of sertindole treatment. Results showed that patients improved in objective social parameters when switched to sertindole treatment; assessment of the patients' affective lives showed a significant increase in the number of patients having a stable relationship during sertindole treatment; and assessment of the number of patients employed showed an increase after the first and second switch to sertindole treatment (from Period 1 to Period 2 and from Period 3 to Period 4, respectively).

Adverse events and lack of efficacy were the main reasons for switching to sertindole.

Conclusion

A group of patients benefited from sertindole after other antipsychotic treatments, including that with atypical antipsychotics, had failed. Further studies are needed to investigate if there is a specific patient profile that corresponds to these responders.
Multiple origins of resistance-conferring mutations in Plasmodium vivax dihydrofolate reductase
Authors: Hawkins Vivian N , Auliff Alyson , Prajapati Surendra Kumar , Rungsihirunrat Kanchana , Hapuarachchi Hapuarachchige C , Maestre Amanda , O'Neil Michael T , Cheng Qin , Joshi Hema , Na-Bangchang Kesara , Sibley Carol Hopkins
Published: April 2008

Background

In order to maximize the useful therapeutic life of antimalarial drugs, it is crucial to understand the mechanisms by which parasites resistant to antimalarial drugs are selected and spread in natural populations. Recent work has demonstrated that pyrimethamine-resistance conferring mutations in Plasmodium falciparum dihydrofolate reductase (dhfr) have arisen rarely de novo, but spread widely in Asia and Africa. The origin and spread of mutations in Plasmodium vivax dhfr were assessed by constructing haplotypes based on sequencing dhfr and its flanking regions.

Methods

The P. vivax dhfr coding region, 792 bp upstream and 683 bp downstream were amplified and sequenced from 137 contemporary patient isolates from Colombia, India, Indonesia, Papua New Guinea, Sri Lanka, Thailand, and Vanuatu. A repeat motif located 2.6 kb upstream of dhfr was also sequenced from 75 of 137 patient isolates, and mutational relationships among the haplotypes were visualized using the programme Network.

Results

Synonymous and non-synonymous single nucleotide polymorphisms (SNPs) within the dhfr coding region were identified, as was the well-documented in-frame insertion/deletion (indel). SNPs were also identified upstream and downstream of dhfr, with an indel and a highly polymorphic repeat region identified upstream of dhfr. The regions flanking dhfr were highly variable. The double mutant (58R/117N) dhfr allele has evolved from several origins, because the 58R is encoded by at least 3 different codons. The triple (58R/61M/117T) and quadruple (57L/61M/117T/173F, 57I/58R/61M/117T and 57L/58R/61M/117T) mutant alleles had at least three independent origins in Thailand, Indonesia, and Papua New Guinea/Vanuatu.

Conclusion

It was found that the P. vivax dhfr coding region and its flanking intergenic regions are highly polymorphic and that mutations in P. vivax dhfr that confer antifolate resistance have arisen several times in the Asian region. This contrasts sharply with the selective sweep of rare antifolate resistant alleles observed in the P. falciparum populations in Asia and Africa. The finding of multiple origins of resistance-conferring mutations has important implications for drug policy.
The botanical integrity of wheat products influences the gastric distention and satiety in healthy subjects
Authors: Hlebowicz Joanna , Lindstedt Sandra , Björgell Ola , Höglund Peter , Almér Lars-Olof , Darwiche Gassan
Published: April 2008

Background

Maintenance of the botanical integrity of cereal kernels and the addition of acetic acid (as vinegar) in the product or meal has been shown to lower the postprandial blood glucose and insulin response and to increase satiety. However, the mechanism behind the benefits of acetic acid on blood glucose and satiety is not clear. We hypothesized that the gastric emptying rate could be involved. Thus, the aim of this study was to evaluate the possible influence of maintained botanical integrity of cereals and the presence of acetic acid (vinegar) on gastric emptying rate (GER), postprandial blood glucose and satiety.

Methods

Fifteen healthy subjects were included in a blinded crossover trial, and thirteen of the subjects completed the study. Equicarbohydrate amounts of the following wheat-based meals were studied: white wheat bread, whole-kernel wheat bread or wholemeal wheat bread served with white wine vinegar. The results were compared with a reference meal consisting of white wheat bread without vinegar. The GER was measured with standardized real-time ultrasonography using normal fasting blood glucose <6.1 mmol/l or plasma glucose <7.0 mmol/l as an inclusion criterion. The GER was calculated as the percentage change in the antral cross-sectional area 15 and 90 minutes after ingestion of the various meals. Satiety scores were estimated and blood glucose was measured before and 15, 30, 45, 60, 90 and 120 min after the start of the meal.

Results

The whole-kernel wheat bread with vinegar resulted in significantly higher (<0.05) satiety than the wholemeal wheat bread and white wheat bread with vinegar and the reference bread. Wheat fiber present in the wholemeal wheat bread, or the presence of wheat kernels per se, did not affect the postprandial blood glucose or GER significantly compared with white wheat bread, neither did the addition of vinegar to white bread affect these variables. There was no correlation found between the satiety with antral areas or GER

Conclusion

The present study shows higher satiety after a whole-kernel wheat bread meal with vinegar. This may be explained by increased antral distension after ingestion of intact cereal kernels but, in this study, not by a lower gastric emptying rate or higher postprandial blood glucose response.

Trial registration

NTR1116
Whole tumor antigen vaccination using dendritic cells: Comparison of RNA electroporation and pulsing with UV-irradiated tumor cells
Authors: Benencia Fabian , Courrèges Maria C , Coukos George
Published: April 2008

Because of the lack of full characterization of tumor associated antigens for solid tumors, whole antigen use is a convenient approach to tumor vaccination. Tumor RNA and apoptotic tumor cells have been used as a source of whole tumor antigen to prepare dendritic cell (DC) based tumor vaccines, but their efficacy has not been directly compared. Here we compare directly RNA electroporation and pulsing of DCs with whole tumor cells killed by ultraviolet (UV) B radiation using a convenient tumor model expressing human papilloma virus (HPV) E6 and E7 oncogenes. Although both approaches led to DCs presenting tumor antigen, electroporation with tumor cell total RNA induced a significantly higher frequency of tumor-reactive IFN-gamma secreting T cells, and E7-specific CD8+ lymphocytes compared to pulsing with UV-irradiated tumor cells. DCs electroporated with tumor cell RNA induced a larger tumor infiltration by T cells and produced a significantly stronger delay in tumor growth compared to DCs pulsed with UV-irradiated tumor cells. We conclude that electroporation with whole tumor cell RNA and pulsing with UV-irradiated tumor cells are both effective in eliciting antitumor immune response, but RNA electroporation results in more potent tumor vaccination under the examined experimental conditions.
Imbalanced effector and regulatory cytokine responses may underlie mycobacterial immune restoration disease
Authors: Lim Andrew , D'Orsogna Lloyd , Price Patricia , French Martyn A
Published: April 2008

Background

Immune restoration disease (IRD) is an adverse consequence of antiretroviral therapy, where the restored pathogen-specific response causes immunopathology. Mycobacteria are the pathogens that most frequently provoke IRD and mycobacterial IRD is a common cause of morbidity in HIV-infected patients co-infected with mycobacteria. We hypothesised that the excessive effector immune response in mycobacterial IRD reflects impaired regulation by IL-10.

Results

We studied two patients who experienced mycobacterial IRD during ART. One patient developed a second episode of IRD with distinct clinical characteristics. Findings were compared with patients 'at risk' of developing IRD who had uneventful immune recovery. Peripheral blood mononuclear cells (PBMC) from all subjects were stimulated with mycobacterial antigens in the form of purified protein derivative (PPD). Supernatants were assayed for IFNγ and IL-10. In response to PPD, PBMC from IRD patients generated IFNγ during the first IRD episode, whilst cells from non-IRD controls produced more IL-10.

Conclusion

We present preliminary data from two HIV-infected patients showing an imbalance between IFNγ and IL-10 responses to mycobacterial antigens during mycobacterial IRD. Our findings suggest that imbalanced effector and regulatory cytokine responses should be investigated as a cause of IRD.