bluuebunny/crossref_metadata_2025 huggingface dataset:
Coordinated Punishment and the Evolution of Cooperation
Authors: OLCINA GONZALO , CALABUIG VICENTE
Published: October 2013

In this paper, we analyze a team trust game with coordinated punishment of the allocator by investors and where there is also a final stage of peer punishment. We study the effect of punishment on the reward and the investment decisions, when the effectiveness and cost of coordinated punishment depend on the number of investors adhering to this activity. The interaction takes place in an overlapping‐generations model with heterogeneous preferences and incomplete information. The only long‐run outcomes of the dynamics are either a fully cooperative culture (FCC) with high levels of trust and cooperation and fair returns or a non‐cooperative culture with no cooperation at all. The basin of attraction of the FCC is larger; the higher the institutional capacity of coordinated punishment, the higher the level of peer pressure and the smaller the individual cost of coordinated punishment.
Assessment of parental oral health knowledge and behaviors among American Indians of a Northern Plains tribe
Authors: Wilson Anne , Brega Angela G. , Batliner Terrence S. , Henderson William , Campagna Elizabeth J. , Fehringer Karen , Gallegos Joaquin , Daniels Dallas , Albino Judith
Published: October 2013

Objectives

Investigate the relationship between sociodemographic variables and oral health knowledge and behaviors of American Indian (AI) parents as the initial step in a program aimed at reducing caries experience among AI children.

Methods

Survey data were collected from a sample of 147 AI parents of children ages 0‐7 years who are residents of a Northern Plains reservation. Questions addressed sociodemographic variables for parents/their children and parent oral health knowledge and behavior. Overall knowledge was measured as percentage of items answered correctly. Overall behavior was measured as percentage of items reflecting behavior consistent with accepted oral health recommendations. Oral health knowledge and behaviors, and the relationship between them, were evaluated across groups defined by quartiles.

Results

Parent sociodemographic variables were not significantly associated with behavior scores. Female gender, higher level of education, and higher income were significantly and positively associated with mean knowledge scores. Behavior and knowledge scores were significantly correlated. On average, survey participants identified the best answer for 75 percent of knowledge items and engaged in 58 percent of optimal oral health behaviors. Participants in higher oral health knowledge quartiles had greater adherence with recommended oral health behaviors than those in lower quartiles.

Conclusions

Surveyed AI parents had reasonably high levels of knowledge about oral health and caries prevention for their children but engaged at relatively lower levels in parental behaviors necessary to promote oral health. Strategies focused on behavior change, rather than knowledge alone, may be most likely to affect oral health outcomes for AI children.
Implication of novel bis-imidazopyridines for management of Alzheimer's disease and establishment of its role on protein phosphatase 2A activity in brain
Authors: Parekh Kauntay D , Dash Ranjeet Prasad , Pandya Amit N , Vasu Kamala K , Nivsarkar Manish
Published: October 2013

Objectives

The objective of this study was to synthesize and identify potential leads for the management of Alzheimer's disease (AD).

Methods

A series of bis-imidazopyridines were synthesized and assessed preclinically for anti-inflammatory and antioxidant activity in aluminium chloride-induced rat model for AD. The two targets, anti-inflammatory and antioxidant, hold a significant relevance in AD. The compounds were also screened for their role of protein phosphatase 2A (PP2A) activity in brain which is responsible for tau dephosphorylation and alleviation of AD.

Key findings

The results of our study identified NIPERAMCD-KTB7 (dose: 50 mg/kg bodyweight, orally), as a potential molecule with good inhibitory activity in acute (67% oedema protection) as well as chronic (61% oedema protection) model of inflammation. This compound also showed good antioxidant activity as inferred from the inhibition of lipid peroxidation and superoxide dismutase activity in rats at the dose mentioned above. More significantly, PP2A activity was found to be increased in the brains of the animals treated with NIPERAMCD-KTB7 suggesting its potential role in management of AD.

Conclusions

These preliminary findings indicate that NIPERAMCD-KTB7 holds potential to serve as a basic lead for further structural modification and development of other new chemical entities for combating AD.
The Role of Public and Private Protection in Disruptive Innovation: The Automotive Industry and the Emergence of Low‐Emission Vehicles
Authors: Pinkse Jonatan , Bohnsack René , Kolk Ans
Published: October 2013

In the automotive industry, the need to move toward more sustainable trajectories of innovation has received much attention. Car manufacturers have started to develop lower emission alternatives for the internal combustion engine, particularly electric, hybrid, and fuel‐cell vehicles. They face the challenge, however, of how to make a potentially disruptive, systemic, and societally embedded technology such as a low‐emission vehicle attractive to mainstream customers. While literature has suggested that companies can empower the initial stages of disruptive innovation by creating protected spaces themselves and/or by taking advantage of such spaces created by public actors, the specific role of these different types of protection levers—private and/or public—has remained unclear. This article therefore investigates to what extent and how private and public protection levers affect firm‐level strategies to increase the attractiveness of disruptive and systemic innovations to mainstream customers. This is explored empirically through a multiple case study of the emergence of low‐emission vehicles within three car manufacturers—Daimler, General Motors, and Toyota—in the context of European, Japanese, and U.S. policies. The empirical analysis is conducted on a data set consisting of more than 9000 articles from two trade magazines, a car magazine and a financial newspaper for the period of 1997–2010. As main findings, the article identifies regulation, tax incentives, and public–private partnerships as the public protection levers that impose or stimulate “new” performance metrics such as fuel economy and vehicle emissions. It also finds that resource allocation, niche occupation, and collaboration‐integration act as the main private protection levers. In addition, two protection levers emerge from the data that are rather prominent in this context: the use of regulation imposing large‐scale commercialization of low‐emission vehicles and dumping of products in the market below cost price. The article concludes with two different protection trajectories—a public protection trajectory and a private protection trajectory—which explain how car manufacturers leverage the various protection levers to deal with disruptive technology. The main implication of the two trajectories is that while the public protection trajectory stalled due to the systemic, socially embedded technological impediments of electric vehicles and fuel‐cell vehicles, the private protection trajectory picked up the remains of the public protection trajectory and has gained momentum, continuing until today.
The Effects of Supplier Involvement and Knowledge Protection on Product Innovation in Customer–Supplier Relationships: A Study of Global Automotive Suppliers in China
Authors: Jean Ruey‐Jer “Bryan” , Sinkovics Rudolf R. , Hiebaum Thomas P.
Published: October 2013

Globalization drives firms to develop product innovation through their global supply chains. While innovations generated by supply channel members, as opposed to individual partners, are playing an increasingly important role in the success of all supply chain partners, there has been limited research on how supply chain relationships cultivate the process of such innovation generation, particularly in emerging markets. Correspondingly, this study explores how multinational suppliers can develop adaptive product innovation to create competitive advantage in emerging markets. Drawing on the knowledge‐based view and transaction cost economics, this study investigates the influence of supplier involvement and other factors on supplier innovation and performance. The results of a survey of 170 multinational automobile suppliers in China provide support for most of the hypotheses. Specifically, supplier involvement in codesign has an inverted U‐shaped relationship with product innovation. Furthermore, knowledge protection, trust, and technological uncertainty are all found to drive greater product innovation. In addition, the institutional environment moderates the effect of product innovation on performance. Overall, this study enhances our understanding of how MNEs can acquire local knowledge and develop adaptive products in emerging markets.
Featuring Capability: How Carmakers Organize to Deploy Innovative Features across Products
Authors: Maniak Rémi , Midler Christophe , Beaume Romain , von Pechmann Felix
Published: October 2013

Innovative features such as hands‐free car entry and ignition systems, stop‐start devices, telematics systems, and panoramic windshields are increasingly important to carmakers' innovation strategies. However, while product‐centric innovation has been extensively studied, there is less insight into the way companies implement their feature‐innovation strategies. The capability to explore, integrate, and deploy such attractive features is a critical dynamic capability; it allows carmakers to refresh their products, develop their competences, and maintain the efficiency of their traditional new product development. This research investigates the structures and processes of feature innovation in the automotive industry. It is based on a global investigation encompassing 9 generalist carmakers and 26 cases of feature innovation. The results show a clear trend, over the past decade, toward a structure of autonomous “advanced engineering” units and processes that are responsible for exploring innovative features and transferring them to multiple products. This paper details the key attributes of these units, and the role they play along the multiproduct learning cycle. Supplementing this structural analysis, the paper also identifies the coordination patterns between exploration and new product development activities. These results provide industry‐level insights into the way firms organize their feature‐innovation capability, and bring empirical elements to the ambidexterity literature.
Do External Knowledge Sourcing Modes Matter for Service Innovation? Empirical Evidence from South Korean Service Firms
Authors: Kang Ki H. , Kang Jina
Published: October 2013

To source external knowledge, firms in the service area use various sourcing modes simultaneously suitable for their internal needs or external environments. Each external knowledge sourcing mode has distinctive characteristics, and as such, they can offer different advantages and/or disadvantages to the firms. Thus, the effects of external knowledge sourcing on service innovation may vary depending on the sourcing modes. The current study aims to empirically examine the different effects of various external knowledge sourcing modes on service innovation. The study identifies three external knowledge sourcing modes: joint development, technology purchasing, and external information acquisition. Three hypotheses are established to examine the relationships between the extent of utilizing each mode and service innovation performance in terms of new service introduction. The data for analysis are selected from the “Korean Innovation Survey 2006: Service Sector” (KIS 2006). It is regarded as South Korea's version of the Community Innovation Survey (CIS). The KIS 2006 data set covers joint development, technology purchasing, and external information acquisition activities of corporations in the service sector in South Korea. The study empirically analyzes the data set using a negative binomial regression model. The results first demonstrate that the extent of the joint development has an inverted U‐shaped relationship with the service innovation performance. Second, the results indicate that, on the other hand, service innovation performance decreases with the increase to the extent of the technology purchasing when the extent is below the threshold. On the other hand, it increases with the increase to the extent of the technology purchasing; this occurs when the extent exceeds the threshold. Third, the results show that external information acquisition has a positive effect on service innovation performance. These findings support that the extent of utilizing each mode has different relationships with service innovation performance. The findings suggest that service firms need to utilize joint development at a moderate level, active technology purchasing, and as much external information acquisition as possible to maximize service innovation performance. In practice, this finding can help managers of service firms select appropriate external knowledge sourcing modes and determine the optimum level of use for each mode. This study also can help firms build up strategies for external knowledge sourcing.
Constraints of Internally and Externally Derived Knowledge and the Innovativeness of Technological Output: The Case of the United States
Authors: Rosenzweig Stav , Mazursky David
Published: October 2013

A major resource of technological innovativeness is knowledge, which can be either internally or externally derived, and constrained or abundant. We employ a longitudinal case study of U.S. industries to assess whether knowledge sources—internal or external to a country's domestic technology—affect an industry's technological innovativeness, and whether knowledge constraints affect technological innovativeness. We use more than 175,000 U.S. patents over 16 years. In contrast to the prevalent thinking that resource constraints inhibit innovation, we find trade‐related knowledge constraints are largely positively associated with the innovativeness of technological output. Moreover, although one may expect a negative relationship between internally derived knowledge based on prior technology and technological innovativeness, we find this relationship is curvilinear.
Troubling ‘lived experience’: a post‐structural critique of mental health nursing qualitative research assumptions
Authors: Grant A.
Published: October 2013

Accessible summary

This paper critiques conventional qualitative assumptions around ‘lived experience’ from a post‐structural qualitative inquiry perspective.

On the basis of this critique, it describes and discusses some broad emerging implications for qualitative inquiry in mental health nursing, identifying published work which illustrates these implications.

The paper ends with an outline of the arguable benefits of, and some challenges for, qualitative research in mental health nursing embracing post‐structural sensibilities.

Qualitative studies in mental health nursing research deploying the ‘lived experience’ construct are often written on the basis of conventional qualitative inquiry assumptions. These include the presentation of the ‘authentic voice’ of research participants, related to their ‘lived experience’ and underpinned by a meta‐assumption of the ‘metaphysics of presence’. This set of assumptions is critiqued on the basis of contemporary post‐structural qualitative scholarship. Implications for mental health nursing qualitative research emerging from this critique are described in relation to illustrative published work, and some benefits and challenges for researchers embracing post‐structural sensibilities are outlined.
Effect of physical effectiveness on digestibility of ration for cows in early lactation
Authors: Stojanovic B. , Grubic G. , Djordjevic N. , Bozickovic A. , Ivetic A. , Davidovic V.
Published: October 2013

A study was conducted to investigate the effects of a diet particle size on nutrient digestibility in cows in early lactation. Treatments were diets with forage to concentrate ratio 43:57% in diet dry matter, with four different physically effective fibres (peNDF) content based on different cut length of corn silage and alfalfa haylage. The physical effectiveness factors (pef) and peNDF content of TMRs (total mixed ration) were determined using Penn State Particle Separator (PSPS) with two (pef8.0, peNDF8.0) or three (pef1.18, peNDF1.18) sieves. The reducing of cut length of forages and particle size of diets did not affect on dry matter intake, while decreased peNDF intake by 16.34 and 8.83%, for peNDF8.0 and peNDF1.18 respectively. Apparent total tract digestibility of the nutrients was measured using two indicators: acid insoluble ash (AIA) and acid detergent insoluble lignin (ADL). Decreasing of forages cut length significantly increased apparent total tract digestibility of neutral detergent fibre (NDF) from 48.39% to 53.84% and from 53.9% to 58.66%, of crude protein from 73.96% to 79.24% and from 71.56% to 77.90%, with contemporary decreasing of non‐fibre carbohydrate from 90.89% to 84.81% and from 91.99% to 86.80%, with AIA or ADL as indicator respectively. Dietary value of net energy for lactation (NEL) and energy intake was not affected by the peNDF content of the diet.
Continuous hydrogen peroxide production by organic buffers in phytoplankton culture media
Authors: Jeffrey Morris J. , Zinser Erik R.
Published: October 2013

We investigated the production of hydrogen peroxide (HOOH) in illuminated seawater media containing a variety of zwitterionic buffers. Production rates varied extensively among buffers, with 4‐(2‐hydroxyethyl)1‐piperazineethanesulfonic acid (HEPES) highest and N‐Tris(hydroxymethyl)methyl‐3‐aminopropanesulfonic acid (TAPS) among the lowest. The rate of HOOH accumulation was remarkably consistent over many days, and increased linearly with buffer concentration, natural seawater concentration, and light level. Concentrations of HEPES commonly used in culture media (1–10 mM) generated enough HOOH to kill the axenic Prochlorococcus strain VOL1 during growth in enriched seawater media at lower, environmentally realistic cell concentrations and/or under high light exposure. We also demonstrated that HEPES can be used experimentally to study the biological effects of chronic exposure to sublethal levels of HOOH such as may be experienced by light‐exposed microorganisms.
Reactive oxygen species and theAntarctic macroalgal wound response
Authors: McDowell Ruth E. , Amsler Charles D. , Dickinson Dale A. , McClintock James B. , Baker Bill J.
Published: October 2013

Reactive oxygen species (ROS) are commonly produced by algal, vascular plant, and animal cells involved in the innate immune response as cellular signals promoting defense and healing and/or as a direct defense against invading pathogens. The production of reactive species in macroalgae upon injury, however, is largely uncharacterized. In this study, we surveyed 13 species of macroalgae from theWesternAntarcticPeninsula and show that the release of strong oxidants is common after macroalgal wounding. Most species released strong oxidants within 1 min of wounding and/or showed cellular accumulation of strong oxidants over an hour post‐wounding. Exogenous catalase was used to show that hydrogen peroxide was a component of immediate oxidant release in one of five species, but was not responsible for the entire oxidative wound response as is common in vascular plants. The other component(s) of the oxidant cocktail released upon wounding are unknown. We were unable to detect protein nitration in extracts of four oxidant‐producing species flash frozen 30 s after wounding, but a role for reactive nitrogen species such as peroxynitrite cannot be completely ruled out. Two species showed evidence for the production of a catalase‐activated oxidant, a mechanism previously known only from the laboratory and from the synthetic drug isoniazid used to kill the human pathogenMycobacterium tuberculosis. The rhodophytePalmaria decipiens, which released strong oxidants after wounding, also produced strong oxidants upon grazing by a sympatric amphipod, suggesting that oxidants are involved in the response to grazing.
Phylogenetic relationships, morphological variation, and toxin patterns in theAlexandrium ostenfeldii(Dinophyceae) complex: implications for species boundaries and identities
Authors: Kremp Anke , Tahvanainen Pia , Litaker Wayne , Krock Bernd , Suikkanen Sanna , Leaw Chui Pin , Tomas Carmelo
Published: October 2013

Alexandrium ostenfeldii(Paulsen) Balech and Tangen andA. peruvianum(Balech and B.R. Mendiola) Balech and Tangen are morphologically closely related dinoflagellates known to produce potent neurotoxins. Together withGonyaulax dimorphaBiecheler, they constitute theA. ostenfeldiispecies complex. Due to the subtle differences in the morphological characters used to differentiate these species, unambiguous species identification has proven problematic. To better understand the species boundaries within theA. ostenfeldiicomplex we compared rDNAdata, morphometric characters and toxin profiles of multiple cultured isolates from different geographic regions. Phylogenetic analysis of rDNAsequences from cultures characterized asA. ostenfeldiiorA. peruvianumformed a monophyletic clade consisting of six distinct groups. Each group examined contained strains morphologically identified as eitherA. ostenfeldiiorA. peruvianum. Though key morphological characters were generally found to be highly variable and not consistently distributed, selected plate features and toxin profiles differed significantly among phylogenetic clusters. Additional sequence analyses revealed a lack of compensatory base changes inITS2 rRNAstructure, low to intermediateITS/5.8S uncorrected genetic distances, and evidence of reticulation. Together these data (criteria currently used for species delineation in dinoflagellates) imply that theA. ostenfeldiicomplex should be regarded a single genetically structured species until more material and alternative criteria for species delimitation are available. Consequently, we propose thatA. peruvianumis a heterotypic synonym ofA. ostenfeldiiand this taxon name should be discontinued.
Simvastatin inhibits lipopolysaccharide‐induced osteoclastogenesis and reduces alveolar bone loss in experimental periodontal disease
Authors: Jin J. , Zhang X. , Lu Z. , Li Y. , Lopes‐Virella M. F. , Yu H. , Haycraft C. J. , Li Q. , Kirkwood K.L. , Huang Y.
Published: October 2013

Background and Objective

Statins are inhibitors of 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase and have anti‐inflammatory effects independent of cholesterol lowering. Recent clinical studies have indicated that statin intake has a beneficial effect on periodontal disease. However, the underlying mechanisms have not been well understood. In the current study, we employed a rat model with lipopolysaccharide (LPS)‐induced periodontal disease and determined the effect of simvastatin, a commonly prescribed statin, on osteoclastogenesis, gingival inflammation and alveolar bone loss.

Material and Methods

Sprague–Dawley rats were injected with Aggregatibacter actinomycetemcomitans LPS in periodontal tissue three times per week for 8 wk and part of the rats with LPS injection were also given simvastatin via gavage. After the treatments, the rat maxillae were scanned by microcomputed tomography and the images were analyzed to determine alveolar bone loss. To explore the underlying mechanisms, the effect of simvastatin on osteoclastogenesis and gingival expression of proinflammatory cytokines were also determined by tartrate‐resistant acid phosphatase staining and real‐time polymerase chain reaction assays, respectively.

Results

Results showed that LPS treatment markedly increased bone loss, but administration of simvastatin significantly alleviated the bone loss. Results also showed that LPS treatment stimulated osteoclastogenesis and the expression of inflammatory cytokines, but simvastatin significantly modulates the stimulatory effect of LPS on osteoclastogenesis and cytokine expression.

Conclusion

This study demonstrated that simvastatin treatment inhibits LPS‐induced osteoclastogenesis and gingival inflammation and reduces alveolar bone loss, indicating that the intake of simvastatin may hinder the progression of periodontal disease.
Unexpected resilience to experimental gingivitis of subepithelial connective tissue grafts in gingival recession defects: a clinical–molecular evaluation
Authors: Graziano A. , Cirillo N. , Pallotti S. , Cricenti L. , Romano F. , Aimetti M.
Published: October 2013

Background and objective

The subepithelial connective tissue graft (SCTG) is the most widely used procedure for the treatment of gingival recession defects. Little is known, however, as to whether the apposed gingival flaps are more predisposed to develop plaque‐related inflammation compared to healthy sites. This has salient clinical implications, as the long‐term results of root coverage will depend largely on the level of inflammation of the grafted tissue.

Methods

In the present split‐mouth case–control study, clinical and biomolecular parameters were used to assess the level of inflammation of periodontal sites 12 mo after treatment with SCTG (test) and healthy non‐treated gingivae (control) following the induction of plaque‐related gingivitis in 19 patients.

Results

The data showed that test sites had a significantly (P < 0.05) lower gingival index and angulated bleeding score compared to control sites (gingival index = 1.05 ± 0.23 vs. 1.34 ± 0.47; angulated bleeding score = 0.34 ± 0.37 vs. 0.61 ± 0.39) after induction of experimental gingivitis, whereas the plaque index did not differ in the two groups (P > 0.05). With regard to the biomolecular parameters, baseline levels of the proinflammatory cytokine interleukin‐1β were higher in the gingival crevicular fluid of test sites. However, control sites exhibited more pronounced increase in the levels of interleukin‐1β compared to test sites, upon plaque accumulation, so that the final concentration was similar in both groups. No changes were recorded in the gingival crevicular fluid volume.

Conclusion

Analysis of the data demonstrates that the sites of gingival recession treated with SCTG develop a lower degree of plaque‐induced inflammation compared to healthy gingivae. This strongly suggests that SCTG does not predispose to inflammation and to further gingival recession and makes it a safe technique in the treatment of gingival defects.
Inflammatory myofibroblastic tumour in the nasal cavity of a dog
Authors: Swinbourne F. , Kulendra E. , Smith K. , Leo C. , Ter Haar G.
Published: October 2013

A 4·5‐year‐old, female neutered Leonberger was presented with a 2‐month history of sneezing, nasal discharge and epistaxis. A presumptive diagnosis of nasal aspergillosis was made based on a suspected (fungal) granuloma on rhinoscopic examination and fungal hyphae on cytological examination. A poor response to targeted therapy was observed and computed tomography 16 months after initial presentation revealed a progressive, locally invasive mass lesion. Histopathological and immunohistochemical analysis of deep surgical biopsies revealed a spindle cell population and a plasma cell rich inflammatory infiltrate, with diffuse expression of vimentin, supporting a diagnosis of inflammatory myofibroblastic tumour. Complete resolution of the nasal discharge and reduced sneezing frequency was reported 9 months post‐surgical debridement via rhinotomy. To the authors’ knowledge, this is the first report of IMT in the nasal cavity of a dog. IMT should be considered when presented with a nasal mass lesion, particularly if histopathological features and clinical course are inconsistent.
Molecular phylogeography and conservation genetics of Sladenia celastrifolia inferred from chloroplast DNA sequence variation
Authors: LU Xi , CHEN Li , CHEN Ya‐Ping , PENG Hua
Published: October 2013

The genetic variation and structure of Sladenia celastrifolia Kurz, a species of conservation concern, were investigated. Analyses of two chloroplast DNA loci (trnS‐trnG and atpB‐rbcL intergenic regions) were carried out for 24 populations of S. celastrifolia and five haplotypes were identified. High levels of genetic differentiation (GST = 1, FST = 1) were detected, which may be a result of limited gene flow caused by geographic isolation. Analysis of molecular variance suggests that the existence of marked phylogeographical structure within the haplotype distribution is probably due to geographic barriers among populations. The haplotype network and mismatch distribution analyses did not detect any signals for recent population expansions in S. celastrifolia. Thus, it can be inferred that the species likely persisted in situ during climatic oscillations. Considering its genetic diversity and uniqueness, conservation strategies are further discussed for this species.
Vardenafil Improves Penile Erection in Type 2 Diabetes Mellitus Patients with Erectile Dysfunction: Role of Tropomyosin
Authors: Zamorano-León Jose J. , Olivier Carlos , de las Heras Natalia , Mateos-Cáceres Petra J. , Brime Menéndez Ricardo , Rodríguez-Sierra Pablo , Martín Palacios Naihara , Manso Luis San José , Modrego Javier , Segura Antonio , Macaya Carlos , López-Farré Antonio J.
Published: October 2013

Introduction

Evidences have been suggested that phosphodiesterase type 5 (PDE5) inhibition promotes vasculoprotective benefits in patients with cardiovascular diseases.

Aim

The aim of this study is to analyze the systemic effect of PDE5 inhibition in type 2 diabetes mellitus patients with erectile dysfunction (ED) determining changes in the expression levels of plasma proteins.

Methods

Seventeen patients with controlled type 2 diabetes mellitus and ED were included in the study. Patients received vardenafil hydrochloride 20mg on demand during 12weeks. At the beginning and 12weeks after vardenafil administration, plasma samples were collected and analyzed using proteomics.

Main Outcome Measures

International Index of Erectile Function-Erectile Function Domain (IIEF-EFD) and plasma protein expression before and after vardenafil administration. Nitrate/nitrite release, PDE5, and soluble guanylate cyclase (sGC) expression and cyclic guanosine monophosphate (cGMP) content in cultured bovine aortic endothelial cells (BAECs).

Results

The IIEF-EFD score was markedly improved after 12weeks of vardenafil administration. Plasma levels of alpha 1-antitrypsin isotypes 4 and 6 and β-tropomyosin were decreased, whereas apolipoprotein AI isoype 5 was increased 12weeks after vardenafil administration. Only β-tropomyosin plasma levels were inversely correlated with IIEF-EFD score. Tropomyosin has been added to cultured BAECs and after 24hours reduced the protein expression level of sGC-β1 subunit and decreased the cGMP content. Tropomyosin did not modify PDE5 expression and nitric oxide release in BAECs as compared with control BAECs. Vardenafil (10μg/mL) did not modify sGC-β1 subunit expression in tropomyosin+vardenafil-incubated BAECs; however, vardenafil significantly reversed the reduction of cGMP content induced by tropomyosin.

Conclusion

Vardenafil administration improved erectile functionality in controlled type 2 diabetes mellitus patients with ED, which was associated with reduction of circulating plasma β-tropomyosin levels. Tropomyosin affected by itself the cGMP generating system suggesting a possible new mechanism involved in ED. Vardenafil reversed the reduction effect of cGMP content elicited by tropomyosin in BAECs.
Uric Acid Level and Erectile Dysfunction in Patients with Coronary Artery Disease
Authors: Solak Yalcin , Akilli Hakan , Kayrak Mehmet , Aribas Alpay , Gaipov Abduzhappar , Turk Suleyman , Perez-Pozo Santos E. , Covic Adrian , McFann Kim , Johnson Richard J. , Kanbay Mehmet
Published: October 2013

Introduction

Erectile dysfunction (ED) is a frequent complaint of elderly subjects and is closely associated with endothelial dysfunction and cardiovascular disease (CVD). Uric acid is also associated with endothelial dysfunction, oxidative stress, and CVD, raising the hypothesis that an increased serum uric acid might predict ED in patients who are at risk for coronary artery disease (CAD).

Aim

This study aims to evaluate the association of serum uric acid levels with presence and severity of ED in patients presenting with chest pain of presumed cardiac origin.

Methods

This is a cross-sectional study of 312 adult male patients with suspected CAD who underwent exercise stress test (EST) for workup of chest pain and completed a sexual health inventory for men survey form to determine the presence and severity of ED. Routine serum biochemistry (and uric acid levels) were measured. Logistic regression analysis was used to assess risk factors for ED.

Main Outcome Measures

The short version of the International Index of Erectile Function questionnaire diagnosed ED (cutoff score ≤ 21). Serum uric acid levels were determined. Patients with chest pain of suspected cardiac origin underwent an EST.

Results

One hundred forty-nine of 312 (47.7%) male subjects had ED by survey criteria. Patients with ED were older and had more frequent CAD, hypertension, diabetes and impaired renal function, and also had significantly higher levels of uric acid, fibrinogen, glucose, C-reactive protein, triglycerides compared with patients without ED. Uric acid levels were associated with ED by univariate analysis (odds ratio = 1.36, P = 0.002); however, this association was not observed in multivariate analysis adjusted for estimated glomerular filtration rate.

Conclusion

Subjects presenting with chest pain of presumed cardiac origin are more likely to have ED if they have elevated uric acid levels.
Catalogue of knowledge and skills for sleep medicine
Authors: Penzel Thomas , Pevernagie Dirk , Dogas Zoran , Grote Ludger , de Lacy Simone , Rodenbeck Andrea , Bassetti Claudio , Berg Søren , Cirignotta Fabio , d'Ortho Marie‐Pia , Garcia‐Borreguero Diego , Levy Patrick , Nobili Lino , Paiva Teresa , Peigneux Philippe , Pollmächer Thomas , Riemann Dieter , Skene Debra J. , Zucconi Marco , Espie Colin ,   The Sleep Medicine Committee and The European Sleep Research Society
Published: October 2013

Summmary

Sleep medicine is evolving globally into a medical subspeciality in its own right, and in parallel, behavioural sleep medicine and sleep technology are expanding rapidly. Educational programmes are being implemented at different levels in many European countries. However, these programmes would benefit from a common, interdisciplinary curriculum. This ‘catalogue of knowledge and skills’ for sleep medicine is proposed, therefore, as a template for developing more standardized curricula across Europe. The Board and The Sleep Medicine Committee of the European Sleep Research Society (ESRS) have compiled the catalogue based on textbooks, standard of practice publications, systematic reviews and professional experience, validated subsequently by an online survey completed by 110 delegates specialized in sleep medicine from different European countries. The catalogue comprises 10 chapters covering physiology, pathology, diagnostic and treatment procedures to societal and organizational aspects of sleep medicine. Required levels of knowledge and skills are defined, as is a proposed workload of 60 points according to the European Credit Transfer System (ECTS). The catalogue is intended to be a basis for sleep medicine education, for sleep medicine courses and for sleep medicine examinations, serving not only physicians with a medical speciality degree, but also PhD and MSc health professionals such as clinical psychologists and scientists, technologists and nurses, all of whom may be involved professionally in sleep medicine. In the future, the catalogue will be revised in accordance with advances in the field of sleep medicine.
Are we missing a simple treatment for most adult sleep apnea patients? The avoidance of the supine sleep position
Authors: Oksenberg Arie , Gadoth Natan
Published: October 2013

Obstructive sleep apnea (OSA) is a sleep disorder which has been gradually accepted as an important cause of increased morbidity and mortality. The treatment of moderate–severe OSA has improved dramatically since the introduction of continuous positive airway pressure (CPAP) devices; however, the adherence of patients to CPAP treatment is relatively low. Adherence appears to be even worse in patients with mild or asymptomatic OSA. The failure to identify and treat mildly symptomatic or asymptomatic OSA patients may be costly, as such patients comprise about 20% of the general adult population. OSA patients could be divided into positional and non‐positional patients. Positional patients show most of their breathing abnormalities while sleeping in the supine position. Simply, by sleeping in the lateral postures, they eliminate or reduce significantly the number of apneas and hypopneas. On the contrary, non‐positional patients suffer from breathing abnormalities in the supine and lateral postures, and as a consequence those are the most severe OSA patients for whom CPAP is the treatment of choice. In this paper we intend to argue that positional therapy, i.e. avoidance of the supine posture during sleep, could represent a valuable therapy mainly for mild–moderate OSA. Considering the fact that the vast majority of mild–moderate OSA patients are positional patients (between 65 and 87%), positional therapy may be a simple, cheap and effective solution for them. High‐quality research regarding this issue is needed to evaluate the real effectiveness of this mode of therapy.
Viral determinants predicting hepatitis B surface antigen (HBsAg) seroclearance in HIV‐/HBV‐coinfected patients
Authors: Strassl R. , Reiberger T. , Honsig C. , Payer B. A. , Mandorfer M. , Grabmeier‐Pfistershammer K. , Rieger A. , Kundi M. , Grundtner P. , Peck‐Radosavljevic M. , Popow‐Kraupp T.
Published: October 2013

The aim of this retrospective study was the identification of clinically useful viral determinants for the prediction of hepatitis B surface antigen (HBsAg) seroclearance and sustained virological response in hepatitis B virus/human immunodeficiency virus (HBV‐/HIV)‐coinfected patients receiving HBV‐active combined antiretroviral therapy (cART). Quantification of HBsAg, HBeAg and HBV DNA before and after initiation of HBV‐active cART in a cohort of 59 HIV‐/HBV‐coinfected patients was performed. Calculations of receiver operating characteristics (ROC) and Kaplan–Meier analysis were used for the identification of predictors of HBsAg seroclearance for HBeAg‐positive [HBeAg(+); n = 36] and HBeAg‐negative [HBeAg(−);n = 23] patients. HBeAg(+) patients with an HBsAg on‐treatment decline ≥1 log IU/mL per year achieved higher HBsAg loss rates (P = 0.0294), whereas the quantification of HBeAg had no predictive value for HBsAg seroclearance. Among HBeAg(−) patients, a pretreatment baseline cut‐off level of HBsAg ≤100 IU/mL was highly predictive for HBsAg seroclearance. No significant influence of the HBV genotype on HBsAg seroclearance was observed among the entire cohort. Quantitative determination of HBsAg provides a clinically useful viral parameter for the prediction of HBsAg seroclearance both in HBeAg(+) and HBeAg(−) HIV‐/HBV‐coinfected patients receiving HBV‐active cART.
IFNL3 (IL28B) polymorphism does not predict long‐term response to interferon therapy in HBeAg‐positive chronic hepatitis B patients
Authors: Zhang Q. , Lapalus M. , Asselah T. , Laouénan C. , Moucari R. , Martinot‐Peignoux M. , Bieche I. , Estrabaud E. , De Muynck S. , Boyer N. , Bedossa P. , Vidaud M. , Marcellin P. , Lada O.
Published: October 2013

The impact of IFNL3 (IL28B) polymorphism on response to interferon (IFN) treatment in patients infected with hepatitis B virus (HBV) is controversial. We aimed to investigate whether IFNL3 polymorphism (rs12979860) influences the long‐term response of chronic hepatitis B (CHB) treatment to conventional IFN. Design: Ninety‐seven HBeAg‐positive patients treated with IFN were evaluated in this study. Associations were investigated between IFNL3 genotypes and (i) HBeAg seroconversion at the end of treatment (EOT), (ii) sustained virological response (SVR) and (iii) HBsAg seroconversion through long‐term follow‐up (LTFU). Patients were followed for a median of 14 years. The majority of patients were infected with HBV genotype A (69.6%) and were Caucasian (77.9%). Ninety‐five patients were genotyped at rs12979860. Similar IFNL3 distribution was observed among the different ethnicities (P = 0.62) or across HBV genotypes A through G (P = 0.70). Thirty‐six patients experienced HBeAg seroconversion at EOT; HBeAg seroconversion rates were 37.0 and 35.5% in patients with CC and CT/TT genotypes, respectively (P = 0.82). Among the 44 patients (45%) who achieved a SVR, SVR rates were 48.9 and 39.6% in patients with CC and CT/TT IL28B genotypes, respectively (P = 0.80). HBsAg seroconversion occurred through LTFU in 28 patients. HBsAg seroconversion rates were 25.5 and 31.2% in patients with CC and CT/TT genotypes, respectively (P = 0.51). No significant relationship between IFNL3 rs12979860 and fibrosis stage was observed (P = 0.85). IFNL3 genotype was neither associated with SVR, nor with HBeAg seroconversion and long‐term HBsAg seroconversion in HBeAg‐positive CHB patients responding to IFN therapy.
A Pilot Phase II Study of the Efficacy and Biosafety of Doxorubicin Chemotherapy in Tumor‐Bearing Equidae
Authors: Théon A.P. , Pusterla N. , Magdesian K.G. , Wittenburg L. , Marmulak T. , Wilson W.D.
Published: October 2013

Background

The efficacy and biosafety of a previously established tolerable dosage of doxorubicin have not been established in horses.

Objectives

To provide preliminary evidence of the efficacy of doxorubicin in tumor‐bearing horses, explore drug pharmacokinetics profile, and estimate period of risk of exposure to drug residues.

Animals

Twelve horses with 37 tumors.

Procedures

Treatment protocol included 6 treatments at 3‐week intervals. Eight horses were uniformly treated at a dosage of 70 mg/m2 and 4 horses received 4 of 6 treatment cycles at 70 mg/m2. Clinical signs, tumor responses, and toxicoses were evaluated. Drug residue concentrations were quantitated in 3 horses receiving of 65, 70, and 75 mg/m2 by high‐performance liquid chromatography with ultraviolet detection (plasma, feces) and liquid chromatography and tandem mass spectrometry (urine).

Results

Thirty tumors, including lymphomas, carcinomas, sarcoids, and melanoma, were evaluated for efficacy. The overall response rate was 47% (95% CI, 28–65%). Doxorubicin was not found to be effective against melanomas. Lymphomas and carcinomas were most responsive. Pooled serum Cmax and half‐life of doxorubicin were 121.3 ng/mL and 12.9 hours, respectively. There were no detectable residues in fecal samples up to 3 weeks after treatment and in plasma and urine after 2 and 3 days, respectively.

Conclusion and Clinical Relevance

This study provides preliminary evidence that single‐agent doxorubicin at a dosage of 70 mg/m2 has a broad spectrum of activity. The risk of exposure to drug residues in plasma and feces was low. Direct contact with urine‐contaminated wastes should be avoided for 2 days after treatment.
Transesophageal Echocardiography Guided Patent Ductus Arteriosus Occlusion with a Duct Occluder
Authors: Silva J. , Domenech O. , Mavropoulou A. , Oliveira P. , Locatelli C. , Bussadori C.
Published: October 2013

Background

Angiography and fluoroscopy are the standard methods to guide transcatheter occlusion of patent ductus arteriosus (PDA). The use of iodinated contrast agents and radiation exposure pose risks of animals and staff.

Objectives

To assess feasibility of transesophageal echocardiography (TEE) for device size selection and procedure monitoring for PDA occlusion with a duct occluder (DO) without the use of angiography.

Animals

Eighty client‐owned dogs with left‐to‐right PDA.

Methods

Prospective study. Dogs with left‐to‐right PDA undergoing transcatheter occlusion were included. Procedures were performed without angiography and device size selection was based on TEE measurements. Procedures were monitored with simultaneous TEE and fluoroscopy and both methods were compared. Visualization of the ductus and dimensions obtained by TEE and transthoracic echocardiography (TTE) were compared.

Results

Complete PDA occlusion was achieved in 79/80 cases. TEE was consistently superior to TTE for PDA visualization and the latter showed higher values for ductal dimensions when compared to the former. TEE provided adequate procedure monitoring in 73 cases (91%). Fluoroscopy exposure time (2.77 ± 1.2 minutes (mean, SD)) was lower than previously reported for the same procedure.

Conclusions and Clinical Importance

TEE is a useful and efficient tool for device size selection and can be used for procedure monitoring in most cases. Fluoroscopy exposure time can be reduced and the use of contrast agents can be avoided. However, fluoroscopy is required in a minority of cases when TEE monitoring is not feasible or incomplete and should be available for this procedure.
Understanding the pharmacokinetics of tulathromycin: a pulmonary perspective
Authors: Villarino N. , Brown S. A. , Martín‐Jiménez T.
Published: October 2013

Tulathromycin is approved in theUnitedStates for the treatment of respiratory disease in bovine and swine, infectious bovine keratoconjunctivitis associated withMoraxella bovis,and interdigital necrobacillosis in bovine. This macrolide highly concentrates in lung tissue and persists in the intra‐airway compartment for a long time after a single administration. It also accumulates in inflammatory cells, including neutrophils and macrophages. This article reviews pharmacokinetic information about tulathromycin in different veterinary species with particular emphasis on the respiratory system.
Enticing Business to Create a HealthierAmerican Diet: Performance‐Based Regulation of Food and Beverage Retailers
Authors: Sugarman Stephen D.
Published: October 2013

TheAmerican public could enjoy a much healthier diet if we enticed food and beverage retailers (stores and restaurants) to substantially reduce the calories, added sugar, sodium, and saturated fat that pass through their cash registers—say, a 25 percent reduction in sugar, salt, and fat and a 10 percent reduction in calories. Rather than ordering firms to make specific changes in what they sell, this strategy—called performance‐based regulation—leaves industry to figure out what is the best way to transform theAmerican diet in a positive way. Because it calls for real changes in outcomes, this regulatory strategy could be far more effective than information disclosure policies that rely on consumer choices, and because it does not require adding extra cost to the price of food and beverages, it could be politically far more attractive than taxing unhealthy foods. Appealing to both conservative and liberal values, instead of relying on the professional expertise of public health regulators, performance‐based regulation enlists America's large food retailers to serve the public good—or suffer substantial financial penalties for failing to do so.