bluuebunny/crossref_metadata_2025 huggingface dataset:
Assertiveness process of Iranian nurse leaders: A grounded theory study
Authors: Mahmoudirad Gholamhossein , Ahmadi Fazlollah , Vanaki Zohreh , Hajizadeh Ebrahim
Published: April 2009

The purpose of this study was to explore the assertiveness process in Iranian nursing leaders. A qualitative design based on the grounded theory approach was used to collect and analyze the assertiveness experiences of 12 nurse managers working in four hospitals in Iran. Purposeful and theoretical sampling methods were employed for the data collection and selection of the participants, and semistructured interviews were held. During the data analysis, 17 categories emerged and these were categorized into three themes: “task generation”, “assertiveness behavior”, and “executive agents”. From the participants' experiences, assertiveness theory emerged as being fundamental to the development of a schematic model describing nursing leadership behaviors. From another aspect, religious beliefs also played a fundamental role in Iranian nursing leadership assertiveness. It was concluded that bringing a change in the current support from top managers and improving self‐learning are required in order to enhance the assertiveness of the nursing leaders in Iran.
Effect of long‐term, community‐based daily exercise on the ability to control the dynamic standing balance of Japanese elderly persons in relation to falls
Authors: Maejima Hiroshi , Sunahori Hitoshi , Otani Takuya , Sakamoto Nozomi , Yoshimura Osamu , Tobimatsu Yoshiko
Published: April 2009

It is widely accepted that daily exercise improves the dynamic standing balance of elderly persons. In the current study, 77 community‐dwelling Japanese elderly persons (aged 71.1 ± 0.5 years) participated in a daily exercise program to assess its effect on their dynamic standing balance. The daily exercise consisted of walking, stretching, muscle strengthening, and balance exercises. The program ran for 31 months and the dynamic standing balance was assessed at the start of the program and again at 3, 7, 12, 19, 24, and 31 months. In most of the tests of dynamic standing balance, the measured values improved drastically in the first 7 months; thereafter, they either reached a plateau or continued to improve more slowly. These findings can contribute to the future planning of community‐based exercise programs; in particular, the length of the program and the timing of changes to the exercise load.
Norwegian and Swedish preceptors' views of their role before and after taking part in a group supervision program
Authors: Danielsson Agneta , Sundin‐Andersson Christina , Hov Reidun , Athlin Elsy
Published: April 2009

The research literature has shown the expectations towards preceptors and their need of support in their role. Group supervision has been used for many years to promote nurses in their professional role, but no study has been found on how group supervision can support them as preceptors. This study aimed to explore how group supervision could influence the preceptors' views of their role and how they valued this participation. Forty‐eight preceptors, who took part in a 1 year group supervision program conducted by nurse lecturers, filled in open‐ended questionnaires before the first and after the last session. The data were analyzed by means of qualitative content analysis. The findings showed changes in the participants' views of the preceptor role, indicating that this group supervision model had a positive influence on the preceptors' pedagogical and professional thinking and supported their attainment of good preceptorship. Further research is needed in using group supervision as a tool to support preceptors.
Long‐term visual and microperimetry outcomes following autologous retinal pigment epithelium choroid graft for neovascular age‐related macular degeneration
Authors: Chen Fred K , Uppal Gurmit S , MacLaren Robert E , Coffey Peter J , Rubin Gary S , Tufail Adnan , Aylward G William , Da Cruz Lyndon
Published: April 2009

Abstract

Background:  To describe the 2‐ to 4‐year visual and microperimetry outcomes of autologous retinal pigment epithelium (RPE)‐choroid graft in patients with neovascular age‐related macular degeneration (AMD).

Methods:  In this retrospective cohort study, 12 patients with subfoveal neovascular AMD who had undergone autologous RPE‐choroid graft between August 2004 and June 2005 were reviewed. Change in visual acuity (VA), contrast sensitivity (CS), fixation stability and retinal sensitivity on microperimetry after 2–3 years and the rates of late postoperative complications were examined.

Results:  Patients were followed for 26–48 months (mean, 39). Median preoperative VA (logMAR) was 0.87 but declined to 1.43 (1 year), 1.46 (2 years) and 1.38 (3 years), P = 0.001. Median CS (logCS) was 0.75 preoperatively but declined to 0.45 at 2 years. Six patients had serial microperimetry. Fixation stability declined in 1 but improved in 2 patients. All 6 had decline in retinal sensitivity over the graft during follow up. Retinal detachment did not occur after 12 months but 8 developed epiretinal membrane, 12 had cystic retinal change over the graft and 4 developed recurrent choroidal neovascularization. However, 10 grafts retained autofluorescence signal at 18–48 months of follow up.

Conclusions:  Autologous RPE‐choroid graft can maintain VA, stable fixation and retinal sensitivity in some patients for over 3 years. The spatial correlation between graft autofluorescence, outer retinal structures on optical coherence tomography and retinal sensitivity are consistent with photoreceptor cell rescue. However, we caution the use of this technique as there is high complication rate and delayed loss of retinal function.
The efficacy of anal fistula plug in fistula‐in‐ano: a systematic review
Authors: Garg P. , Song J. , Bhatia A. , Kalia H. , Menon G. R.
Published: April 2009

Aims  To assess the efficacy of anal fistula plug (AFP) procedure for the treatment of fistula‐in‐ano especially the complex fistulas.

Method  The database of PUBMED, MEDLINE, SCOPUS, EMBASE and COCHRANE LIBRARY for the period 1995–2009 was searched. A systematic analysis was carried to evaluate the success rate of AFP procedure in fistula‐in‐ano.

Results  A total of 25 studies were extracted and 12 (n = 317) were finally included in the systematic review. The follow‐up period ranged from 3.5 to 12 months. The AFP procedure had a success rate (patient cure rate) ranging from 24% to 92%. In complex fistula‐in‐ano in prospective studies (8/12 studies), the success rate was 35–87%. The success rate in patients with Crohn’s disease was 29–86%. The success rate in the patients with single tracts was 44–93% and in patients with multiple tracts, success ranged from 20% to 71%. The abscess formation/sepsis rate was 4–29% (11/108) and the plug extrusion rate was 4–41% (42/232–19%).

Conclusion  Anal fistula plug procedure has a success rate ranging from 24% to 92% in different studies. In prospective studies of complex fistula‐in‐ano, there was a moderate success rate of 35–87%. As AFP is associated with low morbidity and sepsis, it appears to be a safe procedure. Further randomized controlled trials studying objective parameters of fistula healing are needed to substantiate these findings.
Assessment of posterior compartment prolapse: a comparison of evacuation proctography and 3D transperineal ultrasound
Authors: Steensma A. B. , Oom D. M. J. , Burger C. W. , Schouten W. R.
Published: April 2009

Introduction  Evacuation proctography (EP) is considered to be the gold standard investigation for the diagnosis of posterior compartment prolapse. 3D transperineal ultrasound (3DTPUS) imaging of the pelvic floor is a noninvasive investigation for detection of pelvic floor abnormalities. This study compared EP with 3DTPUS in diagnosing posterior compartment prolapse.

Method  In a prospective observational study, patients with symptoms related to posterior compartment prolapse participated in a standardized interview, clinical examination, 3DTPUS and EP. Both examinations were analysed separately by two experienced investigators, blinded against the clinical data and against the results of the other imaging technique. After the examinations, all patients were asked to fill out a standardized questionnaire concerning their subjective experience.

Results  Between 2005 and 2007, 75 patients were included with a median age of 59 years (range 22–83). The Cohen’s Kappa Index for enterocole was 0.65 (good) and for rectocele it was 0.55 (moderate). The level of correlation for intussusception was fair (κ = 0.21).

Conclusion  This study showed moderate to good agreement between 3DTPUS and EP for detecting enterocele and rectocele.
From Agreement to Application: An Analysis of Determinations under the WTO Antidumping Agreement
Authors: Reynolds Kara M.
Published: April 2009

Although the World Trade Organization's (WTO) Antidumping Agreement includes rules that govern the application of antidumping duties, countries still have a great deal of latitude in how they decide whether to impose this form of protection. This research is one of the first papers to explore country‐specific differences in the determinants of antidumping injury decisions. Using a series of probit regressions, I compare the leading determinants of injury determinations in nine of the largest users of antidumping protection at the WTO. The results prove that investigating authorities in one country may be swayed by a very different set of economic and political factors than their counterparts in other countries.
TRANSITIONING OUT OF POVERTY
Authors: Brasington David , Kato Mika , Semmler Willi
Published: April 2009

We analyze the role of social environment and human capital formation in persistence of poverty and inequality. We present a Romer type variety model where the presence of economies of agglomeration in social environment may cause two basins of attraction; whereby we may interpret the lower basin as a poverty trap and the upper basin as a take‐off region. We then consider the size of income transfer to regions and its effect on inequality and welfare. We provide supporting evidence of existing inequality and poverty trap using educational attainment data for the USA.
From welfare state to welfare society: toward a viable system of welfare in Japan and England
Authors: Laratta Rosario
Published: April 2009

Laratta R. From welfare state to welfare society: toward a viable system of welfare in Japan and England Int J Soc Welfare 2010: 19: 131–141 © 2009 The Author(s), Journal compilation © 2009 Blackwell Publishing Ltd and the International Journal of Social Welfare.

This article compares the impact that public welfare reforms during the 1980s and 1990s had, and are still having, on the relationship between statutory organisations and the non‐profit sector in two developed countries, England and Japan. The author argues that the failure of these reforms clearly shows that, although non‐profit organisations may not be able to effectively replace the state in the provision of welfare services, they can contribute, working closely with the statutory organisations, to the shaping, financing and delivery of public services in a variety of ways. It is also interesting to note that, while the public welfare reforms of the late 1990s in England produced a shift away from a culture based on privatisation and contracting‐out toward a partnership culture of collaboration between state and non‐profit entities, similar reforms in Japan have resulted instead in an uncertain area of deregulation and privatisation.
Social security for China's rural aged: a proposal based on a universal non‐contributory pension
Authors: Yang Yinan , Williamson John B. , Shen Ce
Published: April 2009

Yang Y, Williamson JB, Shen C. Social security for China's rural aged: a proposal based on a universal non‐contributory pension

Int J Soc Welfare 2010: 19: 236–245 © 2009 The Author(s), Journal compilation © 2009 Blackwell Publishing Ltd and the International Journal of Social Welfare.

China's relative lack of social security coverage for rural elders exacerbates the already severe rural–urban economic disparity, slows the rate of rural poverty reduction, and raises social justice concerns. Our analysis draws on evidence from a number of sources including interviews with experts on China, Chinese government documents, Chinese newspaper accounts, and other sources from other countries. Based on our analysis of what has been tried in other countries and the current situation in rural China, we offer some suggestions for Chinese policy makers. We suggest that, for rural China, a universal non‐contributory old‐age pension deserves serious consideration, and refer to our proposed model as a Rural Old‐Age Social Pension. It will reduce the level of poverty in rural areas and the degree of income inequality between rural and urban areas while simultaneously promoting social and political stability.
Bacterial pathogens in wild birds: a review of the frequency and effects of infection
Authors: Benskin Clare McW. H. , Wilson Kenneth , Jones Keith , Hartley Ian R.
Published: April 2009

The importance of wild birds as potential vectors of disease has received recent renewed empirical interest, especially regarding human health. Understanding the spread of bacterial pathogens in wild birds may serve as a useful model for examining the spread of other disease organisms, both amongst birds, and from birds to other taxa. Information regarding the normal gastrointestinal bacterial flora is limited for the majority of wild bird species, with the few well‐studied examples concentrating on bacteria that are zoonotic and/or relate to avian species of commercial interest. However, most studies are limited by small sample sizes, the frequent absence of longitudinal data, and the constraints of using selective techniques to isolate specific pathogens. The pathogenic genera found in the gut are often those suspected to exist in the birds’ habitat, and although correlations are made between bacterial pathogens in the avian gut and those found in their foraging grounds, little is known about the effect of the pathogen on the host, unless the causative organism is lethal. In this review, we provide an overview of the main bacterial pathogens isolated from birds (with particular emphasis on enteropathogenic bacteria) which have the potential to cause disease in both birds and humans, whilst drawing attention to the limitations of traditional detection methods and possible study biases. We consider factors likely to affect the susceptibility of birds to bacterial pathogens, including environmental exposure and heterogeneities within the host population, and present probable avenues of disease transmission amongst birds and from birds to other animal taxa. Our primary aim is to identify gaps in current knowledge and to propose areas for future study.
The quality of preterm infants’ spontaneous movements: an early indicator of intelligence and behaviour at school age
Authors: Butcher Phillipa R. , Van Braeckel Koen , Bouma Anke , Einspieler Christa , Stremmelaar Elisabeth F. , Bos Arend F.
Published: April 2009

Background:  The quality of very preterm infants’ spontaneous movements at 11 to 16 weeks post‐term age is a powerful predictor of their later neurological status. This study investigated whether early spontaneous movements also have predictive value for the intellectual and behavioural problems that children born very preterm often experience.

Methods:  Spontaneous movement quality was assessed, using Prechtl’s method, at 11 to 16 weeks post‐term in 65 infants born at ≤ 33 weeks of gestation in a single centre. Intelligence and behaviour were assessed with standardised tests at 7 to 11 years of age. Neurological status was assessed with Touwen’s test. Multiple regression was used to determine the predictive value of movement quality for intelligence and behavioural problems. The Sobel test was used to determine if neurological status mediated associations found between early movement quality and outcome.

Results:  Spontaneous movement quality at 11 to 16 weeks post‐term was significantly, positively associated with later intelligence. The number of normal postural patterns displayed contributed most strongly to the association, which was not mediated by neurological status. Fidgety movements, strong predictors of later neurological dysfunction, were not associated with intelligence. Spontaneous movement quality was not associated with internalising or externalising problems but showed a trend to an association with attention problems.

Conclusion:  These findings suggest that, in children born preterm, early spontaneous movement quality has clear prognostic value for neurological and intellectual outcome, and to a lesser extent, for attentional outcome. However, cognitive outcome was associated with the presence of specific, age‐appropriate postural patterns, while neurological outcome has been associated with the presence of global movement abnormalities. The presence of specific, age‐appropriate postural patterns may reflect the integrity of areas of the brain involved in cognitive processing and the regulation of attention later in childhood. Alternately, it may facilitate cognitive and attentional development.
Cyclic AMP‐dependent activation of rhodopsin gene transcription in cultured retinal precursor cells of chicken embryo
Authors: Voisin Pierre , Bernard Marianne
Published: April 2009

The present study describes a robust 50‐fold increase in rhodopsin gene transcription by cAMP in cultured retinal precursor cells of chicken embryo. Retinal cells isolated at embryonic day 8 (E8) and cultured for 3 days in serum‐supplemented medium differentiated mostly into red‐sensitive cones and to a lesser degree into green‐sensitive cones, as indicated by real‐time RT‐PCR quantification of each specific opsin mRNA. In contrast, both rhodopsin mRNA concentration and rhodopsin gene promoter activity required the presence of cAMP‐increasing agents [forskolin and 3‐isobutyl‐1‐methylxanthine (IBMX)] to reach significant levels. This response was rod‐specific and was sufficient to activate rhodopsin gene transcription in serum‐free medium. The increase in rhodopsin mRNA levels evoked by a series of cAMP analogs suggested the response was mediated by protein kinase A, not by EPAC. Membrane depolarization by high KCl concentration also increased rhodopsin mRNA levels and this response was strongly potentiated by IBMX. The rhodopsin gene response to cAMP‐increasing agents was developmentally gated between E6 and E7. Rod‐specific transducin α subunit mRNA levels also increased up to 50‐fold in response to forskolin and IBMX, while rod‐specific phosphodiesterase‐VI and rod arrestin transcripts increased 3‐ to 10‐fold. These results suggest a cAMP‐mediated signaling pathway may play a role in rod differentiation.
STAKEHOLDER PERSPECTIVES ON ETHICAL CHALLENGES IN HIV VACCINE TRIALS IN SOUTH AFRICA
Authors: ESSACK ZAYNAB , KOEN JENNIFER , BARSDORF NICOLA , SLACK CATHERINE , QUAYLE MICHAEL , MILFORD CECILIA , LINDEGGER GRAHAM , RANCHOD CHITRA , MUKUKA RICHARD
Published: April 2009

There is little published literature on the ethical concerns of stakeholders in HIV vaccine trials. This study explored the ethical challenges identified by various stakeholders, through an open‐ended, in‐depth approach. While the few previous studies have been largely quantitative, respondents in this study had the opportunity to spontaneously identify the issues that they perceived to be of priority concern in the South African context. Stakeholders spontaneously identified the following as ethical priorities: informed consent, social harms, collaborative relationships between research stakeholders, the participation of children and adolescents, access to treatment for participants who become infected with HIV, physical harms, fair participant and community selection, confidentiality, benefits, and payment.

While there is some speculation that research in developing countries poses special ethical challenges, overall no issues were identified that have not been anticipated in international guidance, literature and popular frameworks. However, the South African context affords a distinctive gloss to these expected issues; for example, respondents were concerned that the predominant selection of black participants may perpetuate racist practices of apartheid. Stakeholders should be aware of contextual factors impacting on the implementation of ethical principles. We make a series of recommendations for South African trials, including amendments to the ethical‐legal framework and research policies, and, for further research.
STUDY OF ROMAN ANCHOR FROM THE DEAD SEA SHORE*
Authors: HADAS G. , SEGAL I. , YOFFE O. , STEIN M.
Published: April 2009

A wooden Roman anchor was discovered at the retreating shore of the Dead Sea, north of Ein Gedi. The anchor's wood material was coated by a thick veneer of aragonite and gypsum crusts. The wood was dated by radiocarbon to the early Roman time in the Levant. Lead isotope analyses carried out on the Pb–Fe–Cu anchor material (remains of the anchor's metal parts) yielded ratios that indicate origin of the metal in Italian ores (maybe Tuscan). For the wooden part of the anchor a local tree was used.
The hepoxilins and some analogues: a review of their biology
Authors: Pace‐Asciak Cecil R
Published: April 2009

The hepoxilin pathway was discovered over two decades ago. Products in this pathway are derived through the 12S‐lipoxygenase/hepoxilin synthase enzyme system and contain intrinsic biological activity. This activity relates to the reorganization of calcium and potassium ions within the cell, and in inflammation and insulin secretion. Although the natural hepoxilins are chemically unstable, chemical analogues (PBTs) have been synthesized with chemical and biological stability. The PBTs antagonize the natural hepoxilins. The PBTs showed bioavailability, excellent tolerance and stability in vivo. In proof of principle studies in vivo in animal models, the PBTs have shown actions as anti‐inflammatory agents, anti‐thrombotic agents, anti‐cancer agents and anti‐diabetic agents. These studies demonstrate the effectiveness of the base structure of the hepoxilin (and PBT) molecule and serve as an excellent framework for the design and preparation of second‐generation compounds with improved pharmaceutical properties as therapeutics for the above‐mentioned diseases.

This article is part of a themed issue on Mediators and Receptors in the Resolution of Inflammation. To view this issue visit http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009
Intrathecal injection of the neurosteroid, DHEAS, produces mechanical allodynia in mice: involvement of spinal sigma‐1 and GABAAreceptors
Authors: Yoon Seo‐Yeon , Roh Dae‐Hyun , Seo Hyoung‐Sig , Kang Suk‐Yun , Han Ho‐Jae , Beitz Alvin J , Lee Jang‐Hern
Published: April 2009

Background and purpose: The neurosteroid, dehydroepiandrosterone sulphate (DHEAS) and its non‐sulphated form, DHEA, are considered as crucial endogenous modulators of a number of important physiological events. Evidence suggests that DHEAS and DHEA modulate central nervous system‐related functions by activating sigma‐1 receptors and/or allosterically inhibiting γ‐aminobutyric acic receptor type A (GABAA) receptors. As both the sigma‐1 receptor and the GABAAreceptor play important roles in spinal pain transmission, the present study was designed to examine whether intrathecally injected DHEAS or DHEA affect nociceptive signalling at the spinal cord level.

Experimental approach: We first determined whether intrathecal (i.t.) DHEA or DHEAS injection was able to affect nociceptive thresholds to peripheral mechanical stimulation and subsequently examined whether this effect was mediated by sigma‐1 or the GABAAreceptors.

Key results: The i.t. DHEAS injection dose‐dependently decreased the nociceptive threshold to mechanical stimulation, thus producing mechanical allodynia. Moreover, this DHEAS‐induced mechanical allodynia was significantly reduced by administration of the sigma‐1 receptor antagonist, BD‐1047 or the GABAAreceptor agonist, muscimol. Conversely, i.t. DHEA had no effect on mechanical sensitivity. However, when i.t. DHEA was combined with the GABAAreceptor antagonist bicuculline, DHEA dose‐dependently produced mechanical allodynia similar to that of DHEAS. This effect was blocked by BD‐1047 and by muscimol.

Conclusions and implications: These findings indicate that i.t. injection of DHEAS produces mechanical allodynia and that the development of this mechanical allodynia is mediated by sigma‐1 and GABAAreceptors. The findings of this study raise several interesting questions for further investigations into the mechanisms underlying neurosteroid modulation of spinal pain transmission.

British Journal of Pharmacology(2009)157,666–673; doi:10.1111/j.1476‐5381.2009.00197.x; published online 30 April 2009
The plasma–occupancy relationship of the novel GABAAreceptor benzodiazepine site ligand, α5IA, is similar in rats and primates
Authors: Atack John R , Eng Wai‐si , Gibson Ray E , Ryan Christine , Francis Barbara , Sohal Bindi , Dawson Gerard R , Hargreaves Richard J , Burns H Donald
Published: April 2009

Background and purpose: α5IA (3‐(5‐methylisoxazol‐3‐yl)‐6‐[(1‐methyl‐1,2,3‐triazol‐4‐yl)methyloxy]‐1,2,4‐triazolo[3,4‐a]phthalazine) is a triazolophthalazine with subnanomolar affinity for α1‐, α2‐, α3‐ and α5‐containing GABAAreceptors. Here we have evaluated the relationship between plasma α5IA concentrations and benzodiazepine binding site occupancy in rodents and primates (rhesus monkey).

Experimental approach: In awake rats, occupancy was measured at various times after oral dosing with α5IA (0.03–30 mg·kg−1) using anin vivo{[3H]flumazenil (8‐fluoro 5,6‐dihydro‐5‐methyl‐6‐oxo‐4H‐imidazo[1,5‐a][1,4]benzodiazepine‐3‐carboxylic acid ethyl ester)} binding assay. In anaesthetized rhesus monkeys, occupancy was measured using {[123I]iomazenil (ethyl 5,6‐dihydro‐7‐iodo‐5‐methyl‐6‐oxo‐4H‐imidazo[1,5‐a][1,4]benzodiazepine‐3‐carboxylic acid ethyl ester)} γ‐scintigraphy and a bolus/infusion paradigm. In both rat and rhesus monkey, the plasma drug concentration corresponding to 50% occupancy (EC50) was calculated.

Key results: In rats, α5IA occupancy was dose‐ and time‐dependent with maximum occupancy occurring within the first 2 h. However, rat plasma EC50was time‐independent, ranging from 42 to 67 ng·mL−1over a 24 h time course with the average being 52 ng·mL−1(i.e. occupancy decreased as plasma drug concentrations fell). In rhesus monkeys, the EC50for α5IA displacing steady‐state [123I]iomazenil binding was 57 ng·mL−1.

Conclusions and implications: Rat plasma EC50values did not vary as a function of time indicating that α5IA dissociates readily for the GABAAreceptorin vivo. These data also suggest that despite the different assays used (terminal assays of [3H]flumazenilin vivobinding in rats and [123I]iomazenil γ‐scintigraphy in anaesthetized rhesus monkeys), these techniques produced similar plasma α5IA EC50values (52 and 57 ng·mL−1respectively) and that the plasma–occupancy relationship for α5IA translates across these two species.
Comprehensive evaluation of a novel nuclear factor‐κB inhibitor, quinoclamine, by transcriptomic analysis
Authors: Cheng W‐Y , Lien J‐C , Hsiang C‐Y , Wu S‐L , Li C‐C , Lo H‐Y , Chen J‐C , Chiang S‐Y , Liang J‐A , Ho T‐Y
Published: April 2009

Background and purpose:  The transcription factor nuclear factor‐κB (NF‐κB) has been linked to the cell growth, apoptosis and cell cycle progression. NF‐κB blockade induces apoptosis of cancer cells. Therefore, NF‐κB is suggested as a potential therapeutic target for cancer. Here, we have evaluated the anti‐cancer potential of a novel NF‐κB inhibitor, quinoclamine (2‐amino‐3‐chloro‐1,4‐naphthoquinone).

Experimental approach:  In a large‐scale screening test, we found that quinoclamine was a novel NF‐κB inhibitor. The global transcriptional profiling of quinoclamine in HepG2 cells was therefore analysed by transcriptomic tools in this study.

Key results:  Quinoclamine suppressed endogenous NF‐κB activity in HepG2 cells through the inhibition of IκB‐α phosphorylation and p65 translocation. Quinoclamine also inhibited induced NF‐κB activities in lung and breast cancer cell lines. Quinoclamine‐regulated genes interacted with NF‐κB or its downstream genes by network analysis. Quinoclamine affected the expression levels of genes involved in cell cycle or apoptosis, suggesting that quinoclamine exhibited anti‐cancer potential. Furthermore, quinoclamine down‐regulated the expressions of UDP glucuronosyltransferase genes involved in phase II drug metabolism, suggesting that quinoclamine might interfere with drug metabolism by slowing down the excretion of drugs.

Conclusion and implications:  This study provides a comprehensive evaluation of quinoclamine by transcriptomic analysis. Our findings suggest that quinoclamine is a novel NF‐κB inhibitor with anti‐cancer potential.
Characterizing and Reaching High‐Risk Drinkers Using Audience Segmentation
Authors: Moss Howard B. , Kirby Susan D. , Donodeo Fred
Published: April 2009

Background:  Market or audience segmentation is widely used in social marketing efforts to help planners identify segments of a population to target for tailored program interventions. Market‐based segments are typically defined by behaviors, attitudes, knowledge, opinions, or lifestyles. They are more helpful to health communication and marketing planning than epidemiologically defined groups because market‐based segments are similar in respect to how they behave or might react to marketing and communication efforts. However, market segmentation has rarely been used in alcohol research. As an illustration of its utility, we employed commercial data that describes the sociodemographic characteristics of high‐risk drinkers as an audience segment, including where they tend to live, lifestyles, interests, consumer behaviors, alcohol consumption behaviors, other health‐related behaviors, and cultural values. Such information can be extremely valuable in targeting and planning public health campaigns, targeted mailings, prevention interventions, and research efforts.

Methods:  We described the results of a segmentation analysis of those individuals who self‐reported to consume 5 or more drinks per drinking episode at least twice in the last 30 days. The study used the proprietary PRIZM™ (Claritas, Inc., San Diego, CA) audience segmentation database merged with the Center for Disease Control and Prevention’s (CDC) Behavioral Risk Factor Surveillance System (BRFSS) database. The top 10 of the 66 PRIZM™ audience segments for this risky drinking pattern are described. For five of these segments we provided additional in‐depth details about consumer behavior and the estimates of the market areas where these risky drinkers resided.

Results:  The top 10 audience segments (PRIZM clusters) most likely to engage in high‐risk drinking are described. The cluster with the highest concentration of binge‐drinking behavior is referred to as the “Cyber Millenials.” This cluster is characterized as “the nation’s tech‐savvy singles and couples living in fashionable neighborhoods on the urban fringe.” Almost 65% of Cyber Millenials households are found in the Pacific and Middle Atlantic regions of the United States. Additional consumer behaviors of the Cyber Millenials and other segments are also described.

Conclusions:  Audience segmentation can assist in identifying and describing target audience segments, as well as identifying places where segments congregate on‐ or offline. This information can be helpful for recruiting subjects for alcohol prevention research as well as planning health promotion campaigns. Through commercial data about high‐risk drinkers as “consumers,” planners can develop interventions that have heightened salience in terms of opportunities, perceptions, and motivations, and have better media channel identification.
The Dopamine Response in the Nucleus Accumbens Core–Shell Border Differs From That in the Core and Shell During Operant Ethanol Self‐Administration
Authors: Howard Elaina C. , Schier Christina J. , Wetzel Jeremy S. , Gonzales Rueben A.
Published: April 2009

Background: Ethanol self‐administration has been shown to increase dopamine in the nucleus accumbens; however, dopamine levels in the accumbal subregions (core, shell, and core–shell border) have not yet been measured separately in this paradigm. This study was designed to determine if dopamine responses during operant ethanol self‐administration are similar in the core, core–shell border, and shell, particularly during transfer from the home cage to the operant chamber and during consumption of the drinking solution.

Methods: Six groups of male Long–Evans rats were trained to lever‐press for either 10% sucrose (10S) or 10% sucrose + 10% ethanol (10S10E) (with a guide cannula above the core, core–shell border, or shell of the accumbens). On experiment day, 5‐minute microdialysis samples were collected from the core, core–shell border, or shell before, during, and after drinking. Dopamine and ethanol concentrations were analyzed in these samples.

Results: A significant increase in dopamine occurred during transfer of the rats from the home cage into the operant chamber in all 6 groups, with those trained to drink 10S10E exhibiting a significantly higher increase than those trained to drink 10S in the core and shell. No significant increases were observed during drinking of either solution in the core or shell. A significant increase in dopamine was observed during consumption of ethanol in the core–shell border.

Conclusions: We conclude that dopamine responses to operant ethanol self‐administration are subregion specific. After operant training, accumbal dopamine responses in the core and shell occur when cues that predict ethanol availability are presented and not when the reinforcer is consumed. However, core–shell border dopamine responses occur at the time of the cue and consumption of the reinforcer.
Carisbamate, a Novel Antiepileptic Candidate Compound, Attenuates Alcohol Intake in Alcohol‐Preferring Rats
Authors: Rezvani Amir H. , Overstreet David H. , Vaidya Anil H. , Zhao Boyu , Levin Edward D.
Published: April 2009

Background:  Since 1994, when naltrexone (Revia®) was approved by the FDA for the treatment of alcoholism, only 2 other drugs (Campral® and Topamax®) have been approved for alcoholism treatment. However, various experimental drugs, including antiepileptic medications, have been tested in both animal models and in humans with some promising results. The purpose of this project was to study the effect of the novel neuromodulator carisbamate, which is in development for epilepsy treatment, on alcohol intake in selectively bred alcohol‐preferring rats.

Methods:  Male alcohol‐preferring inbred P rats were allowed to freely drink water or alcohol (10%, v/v) using a 2‐bottle choice procedure. After stable baselines for alcohol and water intakes were established, the acute effects of oral carisbamate (0, 10, 30, 45, 60, and 90 mg/kg) were assessed. Then, the chronic effect of the compound (60 mg/kg/day for 14 consecutive days) on alcohol intake was assessed in a separate group of male P rats. In another set of experiments, the effects of carisbamate and naltrexone on alcohol withdrawal‐induced elevated drinking of alcohol, an index of craving, were compared. Rats were withdrawn from alcohol for 24 hours and were given vehicle, 20 mg/kg naltrexone or 60 mg/kg carisbamate 30 minutes before re‐exposure to alcohol. Alcohol and water intake was measured 6 hours after alcohol re‐exposure. To determine the effects of carisbamate on saccharin preference, rats were put on a 2‐bottle choice of water versus a solution of 2% saccharin. Then, the effect of the highest dose of carisbamate (90 mg/kg) and naltrexone (20 mg/kg) and the vehicle on saccharin preference was determined.

Results:  Our results showed that there was a selective dose‐dependent reduction in alcohol intake and preference in the alcohol‐preferring P rat after an acute oral administration of carisbamate. There were no significant effects on food or water intake. Chronic administration of carisbamate significantly reduced alcohol intake and preference initially, but partial tolerance developed after the 10th treatment. The degree of tolerance development was less than that observed for naltrexone. Acute administration of carisbamate was more effective than naltrexone in reducing enhanced alcohol intake after a period of alcohol deprivation. Compared with control vehicle neither carisbamate nor naltrexone had a significant effect on saccharin intake and preference.

Conclusion:  The novel neuromodulator compound carisbamate has a favorable profile of effects on alcohol intake and related measures and should be considered for testing on human alcoholics.
Translating Effective Web‐Based Self‐Help for Problem Drinking Into the Real World
Authors: Riper Heleen , Kramer Jeannet , Conijn Barbara , Smit Filip , Schippers Gerard , Cuijpers Pim
Published: April 2009

Background:  Drinking Less (DL) is a 24/7 free‐access anonymous interactive web‐based self‐help intervention without therapeutic guidance for adult problem drinkers in the community. In a randomized controlled trial (referred to here as DL‐RCT), DL has been shown effective in reducing risky alcohol consumption.

Objective:  To assess whether the findings of DL‐RCT are generalizable to a naturalistic setting (DL‐RW) in terms of ability to reach the target group and alcohol treatment response.

Methods:  Pretest–posttest study with 6‐month follow‐up. An online survey was conducted of 378 of the 1,625 people who used DL‐RW from May to November 2007. Primary outcome measures were (1) problem drinking, defined as alcohol consumption in the previous 4 weeks averaging >21 or >14 standard units (male/female) per week or ≥6 or ≥4 units (m/f) on 1 or more days per week; and (2) mean weekly alcohol consumption. DL‐RW and DL‐RCT data were compared and pooled. Intention‐to‐treat (ITT) analysis was performed to analyze and compare changes in drinking from baseline to follow‐up.

Results:  In the DL‐RW group, 18.8% (n = 71) were drinking successfully within the limits of the Dutch guideline for low‐risk drinking (p < 0.001) 6 months after baseline (ITT). The DL‐RW group also decreased its mean weekly alcohol intake by 7.4 units, t(377) = 6.67, p < 0.001, d = 0.29. Drinking reduction in DL‐RW was of a similar magnitude to that in the DL‐RCT condition in terms of drinking within the guideline [χ2(1) = 1.83, CI: 0.82–3.00, p = 0.18, RD = 0.05, OR = 1.55] and mean weekly consumption (a negligible difference of d = 0.03 in favor of DL‐RW group).

Conclusion:  The results from DL‐RCT and DL‐RW were similar, and they demonstrate that web‐based self‐help without therapeutic guidance is feasible, well accepted, and effective for curbing adult problem drinking in the community.
Provider Competition in a Dynamic Setting
Authors: Allard Marie , Thomas Léger Pierre , Rochaix Lise
Published: April 2009

We examine provider and patient behavior in a dynamic model where effort is noncontractible, competition between providers is modeled in an explicit way and where patients' outside options are solved for in equilibrium. Physicians are characterized by an individual‐specific ethical constraint which allows for unobserved heterogeneity. This introduces uncertainty in the patient's expected treatment if he were to leave his current physician to seek care elsewhere. We also introduce switching costs and uncertainty in the treatment–outcome relationship. Our model generates equilibria with treatment heterogeneity, unstable physician–patient relationships, and overtreatment (a form of defensive medicine).
Increasing Dietary Protein Requirements in Elderly People for Optimal Muscle and Bone Health
Authors: Gaffney‐Stomberg Erin , Insogna Karl L. , Rodriguez Nancy R. , Kerstetter Jane E.
Published: April 2009

Osteoporosis and sarcopenia are degenerative diseases frequently associated with aging. The loss of bone and muscle results in significant morbidity, so preventing or attenuating osteoporosis and sarcopenia is an important public health goal. Dietary protein is crucial for development of bone and muscle, and recent evidence suggests that increasing dietary protein above the current Recommended Dietary Allowance (RDA) may help maintain bone and muscle mass in older individuals. Several epidemiological and clinical studies point to a salutary effect of protein intakes above the current RDA (0.8 g/kg per day) for adults aged 19 and older. There is evidence that the anabolic response of muscle to dietary protein is attenuated in elderly people, and as a result, the amount of protein needed to achieve anabolism is greater. Dietary protein also increases circulating insulin‐like growth factor, which has anabolic effects on muscle and bone. Furthermore, increasing dietary protein increases calcium absorption, which could be anabolic for bone. Available evidence supports a beneficial effect of short‐term protein intakes up to 1.6 to 1.8 g/kg per day, although long‐term studies are needed to show safety and efficacy. Future studies should employ functional measures indicative of protein adequacy, as well as measures of muscle protein synthesis and maintenance of muscle and bone tissue, to determine the optimal level of dietary protein. Given the available data, increasing the RDA for older individuals to 1.0 to 1.2 g/kg per day would maintain normal calcium metabolism and nitrogen balance without affecting renal function and may represent a compromise while longer‐term protein supplement trials are pending. J Am Geriatr Soc 57:1073–1079, 2009.
Low‐oxygen and high‐carbon‐dioxide atmosphere improves the conservation of hematopoietic progenitors in hypothermia
Authors: Jeanne Michel , Kovacevic‐Filipovic Milica , Szyporta Milène , Vlaski Marija , Hermitte Francis , Lafarge Xavier , Duchez Pascale , Boiron Jean‐Michel , Praloran Vincent , Ivanovic Zoran
Published: April 2009

BACKGROUND: During short‐term storage of hematopoietic cells (HCs) at 4°C a substantial decline in number and in functional capacity of progenitors occurs after 3 days. We hypothesized that physiologic O2 and CO2 concentrations of hematopoietic tissue microenvironment (approx. 3% O2 and approx. 6% CO2) could improve cell viability and functionality during storage at 4°C.

STUDY DESIGN AND METHODS: Mobilized peripheral blood (PB) CD34+ cells from multiple myeloma or non‐Hodgkin's lymphoma patients were stored in flasks containing air (approx. 20% O2 and approx. 0.05% CO2) or 3% O2/6% CO2 atmosphere, for 3, 5, and 7 days at 4°C. The total number of cells, the number of cells in G0 or G1 phase of cell cycle, and the apoptosis rate were determined. The functional capacity of stored cells was assessed by the capacity of progenitors to form colonies in methylcellulose (colony‐forming cells [CFCs]) and of stem cells to repopulate the bone marrow (BM) of immunodeficient mice (SCID‐repopulating cell [SRC] assay).

RESULTS: The total number of viable cells and cells in G1 phase as well as the number of total CFCs were significantly higher at 3% O2/6% CO2 than in air at all time points. Cells in G0 phase and SRC were equally preserved in both conditions.

CONCLUSION: Atmosphere with low O2 and high CO2 concentration (3% O2/6% CO2) in hypothermia (+4°C) during 7 days of storage prevents cell damage and preserves a high number of functional HSCs and progenitors mobilized in PB by granulocyte–colony‐stimulating factor.
Synergistic Effects of Inward Rectifier (IK1) and Pacemaker (If) Currents on the Induction of Bioengineered Cardiac Automaticity
Authors: CHAN YAU‐CHI , SIU CHUNG‐WAH , LAU YEE‐MAN , LAU CHU‐PAK , LI RONALD A. , TSE HUNG‐FAT
Published: April 2009

Introduction: Normal heart rhythms originate in the sinoatrial node. HCN‐encoded funny current (If) and the Kir2‐encoded inward rectifier (IK1) counteract each other by respectively oscillating and stabilizing the negative resting membrane potential, and controlling action potential firing. Therefore, IK1 suppression and If overexpression have been independently exploited to convert cardiomyocytes (CMs) into AP‐firing bioartificial pacemakers. Although the 2 strategies have been largely assumed synergistic, their complementarity has not been investigated.

Methods and Results: We explored the interrelationships of automaticity, If and IK1 by transducing single left ventricular (LV) CMs isolated from guinea pig hearts with the recombinant adenoviruses Ad‐CMV‐GFP‐IRES‐HCN1‐ÄÄÄ and/or Ad‐CGI‐Kir2.1 to mediate their current densities via a whole‐cell patch clamp technique at 37°C. Results showed that Ad‐CGI‐HCN1‐ÄÄÄ but not Ad‐CGI‐Kir2.1 transduction induced automaticity (181.1 ± 13.1 bpm). Interestingly, Ad‐CGI‐HCN1‐ÄÄÄ/Ad‐CGI‐Kir2.1 cotransduction significantly promoted the induced firing frequency (320.0 ± 15.8 bpm; P < 0.05). Correlation analysis revealed that the firing frequency, phase‐4 slope and APD90 of AP‐firing LV CMs were correlated with If (R2 > 0.7) only when −2 >IK1 >−4 pA/pF but not with IK1 over the entire If ranges examined (0.02 < R2 < 0.4). Unlike If, IK1 displayed correlation with neither the phase‐4 slope (R2= 0.02) nor phase‐4 length (R2= 0.04) when −2 > If > −4 pA/pF. As anticipated, however, APD90 was correlated with IK1 (R2= 0.4).

Conclusion: We conclude that an optimal level of IK1 maintains a voltage range for If to operate most effectively during a dynamic cardiac cycle.
Ibutilide‐Induced Changes in the Temporal Lability of Ventricular Repolarization in Patients with and without Structural Heart Disease
Authors: CHENG ALAN , DALAL DARSHAN , FETICS BARRY J. , ANGKEOW PIAMSOOK , SPRAGG DAVID D. , CALKINS HUGH , TOMASELLI GORDON F. , BERGER RONALD D.
Published: April 2009

Introduction: Ibutilide has been shown to prolong repolarization times and increase the risk of ventricular tachyarrhythmias particularly in patients with structural heart disease. The mechanisms underlying its proarrhythmic effects remain incompletely understood. We sought to define the effects of ibutilide on the temporal lability of ventricular repolarization in patients with and without structural heart disease.

Methods: Twenty‐four patients referred for electrophysiology study underwent monophasic action potential (MAP) recordings in the right ventricle during sinus rhythm and random interval right atrial pacing (RIAP). Ibutilide was subsequently administered and the recordings repeated both in sinus rhythm and with RIAP. Digitized recordings were analyzed offline for calculation of the QT variability index (QTVI) based on surface ECG, and the MAP duration variability index (MAPDVI) based on the intracardiac MAP signal.

Results: Of 24 patients enrolled, analyses were performed in 21 patients (mean age 59 ± 15 years, 38% women). In three patients, the data were not analyzed due to frequent premature ventricular complexes. Ibutilide resulted in significant changes in heart rate (mean difference: −7.4 ± 0.91 bpm, P < 0.0001) and the surface QT interval (mean difference: 59.6 ± 12.2 ms, P = 0.0001) during sinus rhythm. After ibutilide, QTVI remained unchanged from baseline during sinus rhythm but was significantly different in the setting of RIAP (mean difference: 0.345 ± 0.098, P = 0.0022). With subgroup analyses, these differences remained significant regardless of the presence or absence of heart disease.

Conclusion: Ibutilide results in overall prolongation of ventricular repolarization and reductions in baseline sinus rates. Ibutilide increases temporal lability of repolarization only with enriched fluctuations in heart rate.
A Museum Exhibit Honoring Factory Workers
Authors: Dauria Susan R.
Published: April 2009

This photographic essay describes an innovative museum exhibit at the Walter Elwood Museum in Amsterdam, New York. The process of constructing and presenting a community's collective industrial history for the museum was multidimensional, using many different approaches to represent the industrial history of the town. New representation strategies, such as object theater, were utilized to re‐create space so that visitors can experience a discussion‐simulation of depicted settings through lighting and audio.