bluuebunny/crossref_metadata_2025_split huggingface dataset:
Towards the use of non‐psychoactive cannabinoids for prostate cancer
Authors: Pacher Pál 
Published: July 2012

The palliative effects of Cannabis sativa (marijuana), and its putative main active ingredient, Δ9‐tetrahydrocannabinol (THC), which include appetite stimulation, attenuation of nausea and emesis associated with chemo‐ or radiotherapy, pain relief, mood elevation, and relief from insomnia in cancer patients, are well‐known. Because of the adverse psychoactive effects of THC, numerous recent preclinical studies have been focused on investigating other non‐psychoactive constituents of C. sativa, such as cannabidiol, for potential therapeutic use. In this issue of the British Journal of Pharmacology, De Petrocellis and colleagues present comprehensive evidence that plant‐derived cannabinoids, especially cannabidiol, are potent inhibitors of prostate carcinoma viability in vitro. They also showed that the extract was active in vivo, either alone or when administered with drugs commonly used to treat prostate cancer (the anti‐mitotic chemotherapeutic drug docetaxel (Taxotere) or the anti‐androgen bicalutamide (Casodex)) and explored the potential mechanisms behind these antineoplastic effects.Linked ArticleThis article is a commentary on De Petrocellis et al., pp. 79–102 of this issue. To view this paper visit http://dx.doi.org/10.1111/j.1476‐5381.2012.02027.x
Coagulation profile of liquid‐state plasma
Authors: Gosselin Robert C. , Marshall Carol , Dwyre Denis M. , Gresens Chris , Davis Diana , Scherer Lynette , Taylor Douglas 
Published: July 2012

BACKGROUND: Use of liquid plasma (LP) has been reported as early as the mid 1930s. Unlike fresh‐frozen plasma (FFP), LP is maintained at 1 to 6°C for up to 40 days after collection and processing. Despite its approved use by the US Food and Drug Administration, the coagulation profile of LP is incompletely described. In this study we evaluate the coagulation profile of LP stored up to 30 days.STUDY DESIGN AND METHODS: LP was prepared by removing plasma from nonleukoreduced whole blood within 24 hours of collection. Three LP units from each ABO group were collected and stored at 1 to 6°C. Plasma aliquots were obtained at Postcollection Days 1 to 5, 10, 15, 20, 25, and 30 and then stored at −70°C. Each aliquot was tested for prothrombin time, activated partial thromboplastin time, and other coagulation and fibrinolytic factors.RESULTS: There was a significant decrease in Factor (F)V, FVII, FVIII, von Willebrand factor (VWF), protein S (PS) activity, and endogenous thrombin potential on Day 15 compared with Day 1. No significant difference was observed for PS antigen, D‐dimer, or thrombin‐antithrombin complex. At least 50% activity of all measured factors was noted on Day 15, compared to Day 1. Considerable heterogeneity was observed between the different blood groups for FVII, FVIII, and VWF.CONCLUSION: These data demonstrate that LP maintains at least 50% of factor activity and thrombin‐generating capacity up to 15 days of refrigerated storage. It may be more appropriate to limit LP storage and supplement with FFP when used for management of massively bleeding patients.
Red blood cell alloimmunization in transfused patients with myelodysplastic syndrome or chronic myelomonocytic leukemia
Authors: Sanz Cristina , Nomdedeu Meritxell , Belkaid Mohamad , Martinez Irene , Nomdedeu Benet , Pereira Arturo 
Published: July 2012

BACKGROUND: Red blood cell (RBC) alloimmunization is a major problem in chronically transfused patients because of the risk of hemolytic reactions and limited availability of compatible blood. This study was aimed at determining the characteristics of RBC alloimmunization in transfusion‐dependent patients with myelodysplastic syndrome or chronic myelomonocytic leukemia (MDS/CMML).STUDY DESIGN AND METHODS: The transfusion and clinical records of all patients with MDS/CMML seen at our hospital from 1990 to 2009 were reviewed. The cumulative incidence of RBC alloimmunization was calculated by taking death as a competing risk. Incidence rates were compared by Poisson multivariate regression.RESULTS: A total of 272 patients were included. Median age was 74 years; 55% were men and had received a median of 33 (range, 4‐421) RBC units. Forty‐two (15%) patients formed 81 alloantibodies and seven autoantibodies. Three additional patients developed autoantibodies without alloantibodies. The incidence rate of RBC alloimmunization was 1 per 10.5 person‐years and was independent of sex, age, and MDS diagnostic category. The cumulative incidence of alloimmunization increased with the number of RBC transfusions, reaching a plateau at 19.5% after 130 RBC units. The most common antibody specificities were Kell (26 cases), E (19), c (5), and Jka (5). In 26 (62%) of the 42 alloimmunized patients, only the Rh system and Kell were involved.CONCLUSION: RBC alloimmunization occurs in 15% of MDS/CMML patients on chronic transfusion support and mostly involves the Rh system and Kell. Transfusing these patients with extended antigen‐matched blood, including Kell and CcEe antigens, would presumably reduce the RBC immunization rate.
A Cost‐effectiveness Analysis of Dexamethasone Versus Prednisone in Pediatric Acute Asthma Exacerbations
Authors: Andrews Annie Lintzenich , Wong Kelli A. , Heine Daniel , Scott Russell W. 
Published: July 2012

ACADEMIC EMERGENCY MEDICINE 2012; 19:943–948 © 2012 by the Society for Academic Emergency MedicineAbstractObjectives:  The objective was to evaluate the cost‐effectiveness of dexamethasone versus prednisone for the treatment of pediatric asthma exacerbations in the emergency department (ED).Methods:  This was a cost‐effectiveness analysis using a decision analysis model to compare two oral steroid options for pediatric asthma patients: 5 days of oral prednisone and 2 days of oral dexamethasone (with two dispensing possibilities: either a prescription for the second dose or the second dose dispensed at the time of ED discharge). Using estimates from published studies for rates of prescription filling, compliance, and steroid efficacy, the projected rates of ED relapse visits, hospitalizations within 7 to 10 days of the sentinel ED visit, direct costs, and indirect costs between the two arms were compared.Results:  The rate of return to the ED per 100 patients within 7 to 10 days of the sentinel ED visit for the prednisone arm was 12, for the dexamethasone/prescription arm was 10, and for the dexamethasone/dispense arm was 8. Rates of hospitalization per 100 patients were 2.8, 2.4, and 1.9, respectively. Direct costs per 100 patients for each arm were $20,500, $17,200, and $13,900, respectively. Including indirect costs related to missed parental work, total costs per 100 patients were $22,000, $18,500, and $15,000, respectively. Total cost savings per 100 patients for the dexamethasone/prescription arm compared to the prednisone arm was $3,500 and for the dexamethasone/dispense arm compared to the prednisone arm was $7,000.Conclusions:  This decision analysis model illustrates that use of 2 days of dexamethasone instead of 5 days of prednisone at the time of ED visit for asthma leads to a decreased number of ED visits and hospital admissions within 7 to 10 days of the sentinel ED visit and provides cost savings.
A Creative Approach to the Development of an Agenda for Knowledge Utilization: Outputs from the 11th International Knowledge Utilization Colloquium (KU 11)
Authors: Wilkinson Joyce E. , Rycroft‐Malone Jo , Davies Huw T.O. , McCormack Brendan 
Published: July 2012

ABSTRACTA group of researchers and practitioners interested in advancing knowledge utilization met as a colloquium in Belfast (KU 11) and used a “world café” approach to exploit the social capital and shared understanding built up over previous events to consider the research and practice agenda. We considered three key areas of relevance to knowledge use: (1) understanding the nature of research use, influence and impact; (2) blended and collaborative approaches to knowledge production and use; and (3) supporting sustainability and spread of evidence‐informed innovations.The approach enabled the development of artifacts that reflected the three areas and these were analyzed using a creative hermeneutic approach.The themes that emerged and which are outlined in this commentary are not mutually exclusive. There was much overlap in the discussions and therefore of the themes, reflecting the complex nature of knowledge translation work. The agenda that has emerged from KU 11 also reflects the participatory and creative approach in which the meeting was structured and focused, and therefore emphasizes the processual, relational and contingent nature of some of the challenges we face.The past 20 years has seen an explosion in activity around understanding KU, and we have learned much about the difficulties. Whilst the agenda for the next decade may be becoming clearer, colloquia such as KU 11, using creative and engaging approaches, have a key role to play in dissecting, articulating and sharing that agenda. In this way, we also build an ever‐expanding international community that is dedicated to working towards increasing the chances of success for better patient care.
Host‐specific morphologies but no host races in the commensal bivalveNeaeromya rugifera
Authors: Li Jingchun , Ó Foighil Diarmaid 
Published: July 2012

AbstractSpeciation by host shift is one of the explicit models of ecological speciation. A prerequisite of this model is the formation of host races (sympatric populations that show host‐specific genetic structuring and phenotypes). Many members of the diverse marine bivalve superfamilyGaleommatoidea have obligate commensal relationships with invertebrate hosts. Some species have the ability to occupy multiple host species, thereby providing potential opportunities to test for the formation of host races. TheNortheastPacific galeommatoideanNeaeromya rugiferaattaches to two strikingly different hosts: the blue mud shrimpUpogebia pugettensisand the polychaete sea mouseAphroditaspp. We tested if this host difference has resulted in the formation of host races using shell morphologies and genetic markers. We found that populations from different hosts differ significantly in shell morphology. However, based on mitochondrial makers,N. rugiferashowed no distinct host‐specific genetic structuring, indicating the existence of a panmictic population. We conclude that the host‐specific morphologies these clams exhibit may reflect ecophenotypic plasticity rather than the existence of host races, but this needs to be corroborated with additional genetic data and larger sample sizes. The pronounced conchological variation withinN. rugiferacalls for further investigation of its taxonomic relationship with its poorly studied, but morphologically similar, sympatric congenerNeaeromya compressa.
Linear and Nonlinear Rheology of Mixed Polysaccharide Gels. Pt.I. Young's Modulus, Ring Extension and Uniaxial Compression Tests
Authors: Brenner Tom , Achayuthakan Piyada , Nishinari Katsuyoshi 
Published: July 2012

AbstractSmall and large deformation tests were performed on polysaccharide‐based gels containing konjac glucomannan, locust bean gum andκ‐carrageenan. LowpHdegradation ofκ‐carrageenan during heating led to lower gel strength. Whenκ‐carrageenan degradation was avoided, the linear‐regime rheology was dominated by theκ‐carrageenan content, and the storageYoung's modulus (E′) was found to decrease with decreasingκ‐carrageenan concentration. The large deformation behavior, however, was dominated by the konjac glucomannan concentration, and the rupture strain increased strongly with increasing konjac concentration. These two opposing trends led to a maximum in rupture stress in extension tests. No rupture was observed in compression of the gels at the polysaccharide concentrations tested. The compression force of konjac‐rich gels was lower than that observed for gels without konjac at low‐compression degrees, but it was similar to or higher at high‐compression degrees, above 60–80%, indicating the higher degree of strain hardening of konjac‐rich gels.Practical ApplicationsMixing of different polysaccharides has been used for widening the texture range, and it was shown in this report that the mixture of konjac glucomannan, locust bean gum andκ‐carrageenan in the presence of sucrose and acid can produce jellies with various textures.
Suboptimal performance of simple noninvasive tests for advanced fibrosis in Chinese patients with nonalcoholic fatty liver disease
Authors: Xun Yun Hao , Fan Jian Gao , Zang Guo Qing , Liu Hong , Jiang Yan Ming , Xiang Jing , Huang Qian , Shi Jun Ping 
Published: July 2012

ObjectiveTo evaluate the diagnostic accuracy of some noninvasive fibrosis models in Chinese patients with nonalcoholic fatty liver disease (NAFLD).MethodsConsecutive biopsy‐proven NAFLD patients were recruited from a single center from January 2005 to December 2010. Advanced fibrosis (stage 3 and 4) was defined using Kleiner criteria. The area under the receiver operating characteristic curve (AUROC) was used to compare the diagnostic accuracy of the NAFLD fibrosis score (NFS), FIB‐4 index, aspartate transaminase (AST)/platelet ratio index (APRI), AST/alanine transaminase (ALT) ratio (AAR) and body mass index (BMI)‐AAR‐Diabetes (BARD) score.ResultsOf the patients with NAFLD, 79.6% were males with a mean age of 37.1 years, mean BMI of 26.1 kg/m2 and 41.4% of them had nonalcoholic steatohepatitis, and 24 (15.8%) had advanced fibrosis. The AUROC of the FIB‐4 index, APRI, AAR, NFS and BARD score for advanced fibrosis were 0.756, 0.742, 0.670, 0.653 and 0.642 (P < 0.05 for all), respectively. A concordant negative predictive value of approximately 90% was indicated whereas the positive predictive values were modest for all tests, and only the FIB‐4 index yielded a higher positive likelihood ratio of 7.65. Using these cut‐off values of tests for excluding advanced fibrosis could reduce the use of liver biopsy in 56.6–74.3% of the patients, with a minor false negative rate of 5.3–9.9%.ConclusionsAlthough slightly less accurate than liver biopsy, simple noninvasive tests can reliably exclude advanced fibrosis in Chinese NAFLD patients in our center. FIB‐4 index performs better than the other tests under examination.
Coronary artery anomalies in adults: Imaging at dual source CT coronary angiography
Authors: Laspas Fotios , Roussakis Arkadios , Mourmouris Christos , Kritikos Nikolaos , Efthimiadou Roxani , Andreou John 
Published: July 2012

SummaryCongenital abnormalities of the coronary arteries have an incidence of 1%, and most of these are benign. However, a small number are associated with myocardial ischaemia and sudden death. Various imaging modalities are available for coronary artery assessment. Recently, multi‐detector CT has emerged as an accurate diagnostic tool for defining coronary artery anomalies. The purpose of this pictorial essay is to review the dual source CT appearance of congenital anomalies of the coronary arteries in adults.
Photodynamic therapy: a review and its prospective role in the management of oral potentially malignant disorders
Authors: Saini R , Poh CF 
Published: July 2012

AbstractWith the unreliability of epithelial dysplasia as a predictor to determine the risk of future malignant development, subjectivity associated in evaluating dysplasia by pathologists and paucity of biomarkers that could accurately predict the progression risks in oral potentially malignant disorders (PMDs), eradication of the lesions appears to be the most desirable approach to minimize the risk of invasive cancer formation. Interventions, such as surgery and chemoprevention, have not shown promising long‐term results in the treatment of these lesions, and lack of guidelines and general consensus on their management has incited much anxiety and doubts in both patients and community clinicians. Topical photodynamic therapy (PDT) is a minimally invasive and minimally toxic technique that in recent years has shown great promise in the management of PMDs. In this review, we describe the historical developments in the field of PDT, its basic mechanisms, as well as related clinical studies, and its challenges in the management of oral PMDs. Based on its high efficacy and low side effects, its high patient acceptance/compliance, the simplicity of the procedure and its minimal pretreatment preparation, topical PDT is believed to have potential to play an important role in the management of PMDs, especially of the low‐grade dysplasia.
The wonders of the Wanderer
Authors: Clancy Jennifer A. , Deuchars Susan A. , Deuchars Jim 
Published: July 2012

New findings
What is the topic for this review?Vagus nerve stimulation is now used as a treatment for refractory epilepsy and depression, despite an incomplete understanding of the mechanisms involved.
What advances does it highlight?We review current and potential therapeutic applications of vagus nerve stimulation and some potential mechanisms by which these effects could be mediated.
Vagus is Latin for wandering, and the vagus nerve fully deserves this name due to its extensive distribution through the body. Indeed, one of the lines of the song that accompanied the 2012 G. L. Brown Prize Lecture exaggerates this diversity, ‘My function's almost anythin’, and vagus is my name’. Alteration of vagal activity was first investigated in the 1880s as a treatment for epilepsy, and vagus nerve stimulation is now an approved treatment for refractory epilepsy and depression in the USA, despite an incomplete understanding of the mechanisms involved. Vagus nerve stimulation could be beneficial in many other conditions, including heart failure, tinnitus, chronic hiccups, Alzheimer's disease and inflammatory diseases. Inhibition of vagal activity could also be beneficial in some conditions, e.g. reducing activation of vagal respiratory afferents to treat chronic cough. This review discusses evidence underlying some current and potential therapeutic applications of vagal modulation, illustrating the wonders of the Wanderer.
The Nlrp3 inflammasome promotes myocardial dysfunction in structural cardiomyopathy through interleukin‐1β
Authors: Bracey Nathan A. , Beck Paul L. , Muruve Daniel A. , Hirota Simon A. , Guo Jiqing , Jabagi Habib , Wright Jr James R. , MacDonald Justin A. , Lees‐Miller James P. , Roach Daniel , Semeniuk Lisa M. , Duff Henry J. 
Published: July 2012

New findings
What is the central question of this study?Heart failure is associated with persistent sterile inflammation that worsens disease severity; however, the molecular mechanisms behind cytokine recruitment and their relevance in the diseased myocardium remain unknown.
What is the main finding and its importance?We show that interleukin‐1β is activated downstream of the Nlrp3 inflammasome in calcineurin‐transgene‐induced structural heart disease. Genetic deletion of Nlrp3 abrogated inflammasome signalling and interleukin‐1β release, improving function. The role of Nlrp3 in non‐ischaemic cardiomyopathy and the utility of inflammasome antagonism have not yet been explored, revealing potential for translational application.
Heart failure is associated with a low‐grade and chronic cardiac inflammation that impairs function; however, the mechanisms by which this sterile inflammation occurs in structural heart disease remain poorly defined. Cardiac‐specific heterozygous overexpression of the calcineurin transgene (CNTg) in mice results in cardiac hypertrophy, inflammation, apoptosis and ventricular dilatation. We hypothesized that activation of the Nlrp3 inflammasome, an intracellular danger‐sensing pathway required for processing the pro‐inflammatory cytokine interleukin‐1β (IL‐1β), may contribute to myocardial dysfunction and disease progression. Here we report that Nlrp3 mRNA was increased in CNTg mice compared with wild‐type. Consistent with inflammasome activation, CNTg animals had increased conversion of pro‐caspase‐1 to cleaved and activated forms, as well as markedly increased serum IL‐1β. Blockade of IL‐1β signalling via chronic IL‐1 receptor antagonist therapy reduced cardiac inflammation and myocyte pathology in CNTg mice, resulting in improved systolic performance. Furthermore, genetic ablation of Nlrp3 in CNTg mice reduced pro‐inflammatory cytokine maturation and cardiac inflammation, as well as improving systolic performance. These findings indicate that activation of the Nlrp3 inflammasome in CNTg mice promotes myocardial inflammation and systolic dysfunction through the production of pro‐inflammatory IL‐1β. Blockade of IL‐1β signalling with the IL‐1 receptor antagonist reverses these phenotypes and offers a possible therapeutic approach in the management of heart failure.
The time course of the adaptations of human muscle proteome to bed rest and the underlying mechanisms
Authors: Brocca Lorenza , Cannavino Jessica , Coletto Luisa , Biolo Gianni , Sandri Marco , Bottinelli Roberto , Pellegrino Maria Antonietta 
Published: July 2012

Key points
It is still debated whether an imbalance between production and removal of reactive oxygen species is a major trigger of disuse skeletal muscle atrophy in human limb muscles and what the underlying mechanisms are.
In the bed rest model of human disuse, redox imbalance, impairment of antioxidant defence systems and metabolic derangement occurred early, before vastus lateralis muscle atrophy developed, and persisted through 35 days of bed rest.
Down‐regulation of PGC‐1α, a master controller of muscle metabolism, and up‐regulation of SREBP‐1, a master controller of lipid synthesis, are likely to have triggered disuse adaptations through mitochondrial dysfunction, whereas AMP kinase, an energy sensor pathway, was unaltered.
The present and previous results on the same subjects suggest a causal link between muscle atrophy, impaired skeletal muscle metabolism, impaired whole body oxidative metabolism, and insulin sensitivity and moderate inflammation, which are major risk factors of physical inactivity related diseases.
Abstract  In order to get a comprehensive picture of the complex adaptations of human skeletal muscle to disuse and further the understanding of the underlying mechanisms, we participated in two bed rest campaigns, one lasting 35 days and one 24 days. In the first bed rest (BR) campaign, myofibrillar proteins, metabolic enzymes and antioxidant defence systems were found to be down‐regulated both post‐8 days and post‐35 days BR by proteomic analysis of vastus lateralis muscle samples from nine subjects. Such profound alterations occurred early (post‐8 days BR), before disuse atrophy developed, and persisted through BR (post‐35 days BR). To understand the mechanisms underlying the protein adaptations observed, muscle biopsies from the second bed rest campaign (nine subjects) were used to evaluate the adaptations of master controllers of the balance between muscle protein breakdown and muscle protein synthesis (MuRF‐1 and atrogin‐1; Akt and p70S6K), of autophagy (Beclin‐1, p62, LC3, bnip3, cathepsin‐L), of expression of antioxidant defence systems (NRF2) and of energy metabolism (PGC‐1α, SREBP‐1, AMPK). The results indicate that: (i) redox imbalance and remodelling of muscle proteome occur early and persist through BR; (ii) impaired energy metabolism is an early and persistent phenomenon comprising both the oxidative and glycolytic one; (iii) although both major catabolic systems, ubiquitin proteasome and autophagy, could contribute to the progression of atrophy late into BR, a decreased protein synthesis cannot be ruled out; (iv) a decreased PGC‐1α, with the concurrence of SREBP‐1 up‐regulation, is a likely trigger of metabolic impairment, whereas the AMPK pathway is unaltered.