An optically stimulated superconducting-like phase in K3C60 far above equilibrium Tc

The control of non-equilibrium phenomena in complex solids is an important research frontier, encompassing new effects like light induced superconductivity. Here, we show that coherent optical excitation of molecular vibrations in the organic conductor K3C60 can induce a non-equilibrium state with the optical properties of a superconductor. A transient gap in the real part of the optical conductivity and a low-frequency divergence of the imaginary part are measured for base temperatures far above equilibrium Tc=20 K. These findings underscore the role of coherent light fields in inducing emergent order.Comment: 40 pages, 23 figure

Ucma/GRP inhibits phosphate-induced vascular smooth muscle cell calcification via SMAD-dependent BMP signalling

Vascular calcification (VC) is the process of deposition of calcium phosphate crystals in the blood vessel wall, with a central role for vascular smooth muscle cells (VSMCs). VC is highly prevalent in chronic kidney disease (CKD) patients and thought, in part, to be induced by phosphate imbalance. The molecular mechanisms that regulate VC are not fully known. Here we propose a novel role for the mineralisation regulator Ucma/GRP (Upper zone of growth plate and Cartilage Matrix Associated protein/Gla Rich Protein) in phosphate-induced VSMC calcification. We show that Ucma/GRP is present in calcified atherosclerotic plaques and highly expressed in calcifying VSMCs in vitro. VSMCs from Ucma/GRP(-/-) mice showed increased mineralisation and expression of osteo/chondrogenic markers (BMP-2, Runx2, beta-catenin, p-SMAD1/5/8, ALP, OCN), and decreased expression of mineralisation inhibitor MGP, suggesting that Ucma/GRP is an inhibitor of mineralisation. Using BMP signalling inhibitor noggin and SMAD1/5/8 signalling inhibitor dorsomorphin we showed that Ucma/GRP is involved in inhibiting the BMP-2-SMAD1/5/8 osteo/chondrogenic signalling pathway in VSMCs treated with elevated phosphate concentrations. Additionally, we showed for the first time evidence of a direct interaction between Ucma/GRP and BMP-2. These results demonstrate an important role of Ucma/GRP in regulating osteo/chondrogenic differentiation and phosphate-induced mineralisation of VSMCs.NWO ZonMw [MKMD 40-42600-98-13007]; FCT [SFRH/BPD/70277/2010]info:eu-repo/semantics/publishedVersio

Potential health impacts of heavy metals on HIV-infected population in USA.

Noninfectious comorbidities such as cardiovascular diseases have become increasingly prevalent and occur earlier in life in persons with HIV infection. Despite the emerging body of literature linking environmental exposures to chronic disease outcomes in the general population, the impacts of environmental exposures have received little attention in HIV-infected population. The aim of this study is to investigate whether individuals living with HIV have elevated prevalence of heavy metals compared to non-HIV infected individuals in United States. We used the National Health and Nutrition Examination Survey (NHANES) 2003-2010 to compare exposures to heavy metals including cadmium, lead, and total mercury in HIV infected and non-HIV infected subjects. In this cross-sectional study, we found that HIV-infected individuals had higher concentrations of all heavy metals than the non-HIV infected group. In a multivariate linear regression model, HIV status was significantly associated with increased blood cadmium (p=0.03) after adjusting for age, sex, race, education, poverty income ratio, and smoking. However, HIV status was not statistically associated with lead or mercury levels after adjusting for the same covariates. Our findings suggest that HIV-infected patients might be significantly more exposed to cadmium compared to non-HIV infected individuals which could contribute to higher prevalence of chronic diseases among HIV-infected subjects. Further research is warranted to identify sources of exposure and to understand more about specific health outcomes

Galanin Transgenic Mice with Elevated Circulating Galanin Levels Alleviate Demyelination in a Cuprizone-Induced MS Mouse Model

Multiple Sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system (CNS) with a presumed autoimmune etiology. Approved treatments for MS are immunoregulatory and are able to reduce the inflammatory components of the disease. However, these treatments do not suppress progressive clinical disability. Approaches that directly protect myelin-producing oligodendrocytes and enhance remyelination are likely to improve long-term outcomes and reduce the rate of axonal damage. Galanin (GAL) is a bioactive neuropeptide that is widely distributed throughout the nervous system and has diverse neuromodulatory effects. In this study, using the cuprizone (CPZ) demyelination model of MS, we demonstrate that GAL has pronounced neuroprotective effects with respect to demyelination and remyelination. Using our GAL transgenic mouse (GAL-Tg), we identified a novel attenuation of OLs against CPZ induced demyelination, which was exerted independently of progenitor cells. Alleviation of myelin breakdown in the GAL-Tg mice was observed to be significant. Furthermore, we observed changes in the expression of the GAL receptor GalR1 during the demyelination and remyelination processes. Our data strongly indicate that GAL has the capacity to influence the outcome of primary insults that directly target OLs, as opposed to cases where immune activation is the primary pathogenic event. Taken together, these results suggest that GAL is a promising next-generation target for the treatment of MS

Development of a heart failure filter for Medline: an objective approach using evidence-based clinical practice guidelines as an alternative to hand searching

<p>Abstract</p> <p>Background</p> <p>Heart failure is a highly debilitating syndrome with a poor prognosis primarily affecting the elderly. Clinicians wanting timely access to heart failure evidence to provide optimal patient care can face many challenges in locating this evidence.</p> <p>This study developed and validated a search filter of high clinical utility for the retrieval of heart failure articles in OvidSP Medline.</p> <p>Methods</p> <p>A Clinical Advisory Group was established to advise study investigators. The study set of 876 relevant articles from four heart failure clinical practice guidelines was divided into three datasets: a Term Identification Set, a Filter Development Set, and a Filter Validation Set. A further validation set (the Cochrane Validation Set) was formed using studies included in Cochrane heart failure systematic reviews. Candidate search terms were identified via word frequency analysis. The filter was developed by creating combinations of terms and recording their performance in retrieving items from the Filter Development Set. The filter's recall was then validated in both the Filter Validation Set and the Cochrane Validation Set. A precision estimate was obtained post-hoc by running the filter in Medline and screening the first 200 retrievals for relevance to heart failure.</p> <p>Results</p> <p>The four-term filter achieved a recall of 96.9% in the Filter Development Set; 98.2% in the Filter Validation Set; and 97.8% in the Cochrane Validation Set. Of the first 200 references retrieved by the filter when run in Medline, 150 were deemed relevant and 50 irrelevant. The post-hoc precision estimate was therefore 75%.</p> <p>Conclusions</p> <p>This study describes an objective method for developing a validated heart failure filter of high recall performance and then testing its precision post-hoc. Clinical practice guidelines were found to be a feasible alternative to hand searching in creating a gold standard for filter development. Guidelines may be especially appropriate given their clinical utility. A validated heart failure filter is now available to support health professionals seeking reliable and efficient access to the heart failure literature.</p

Emergence of 3D Printed Dosage Forms: Opportunities and Challenges

The recent introduction of the first FDA approved 3D-printed drug has fuelled interest in 3D printing technology, which is set to revolutionize healthcare. Since its initial use, this rapid prototyping (RP) technology has evolved to such as extent that it is currently being used in a wide range of applications including in tissue engineering, dentistry, construction, automotive and aerospace. However, in the pharmaceutical industry this technology is still in its infancy and its potential yet to be fully explored. This paper presents various 3D printing technologies such as stereolithographic, powder based, selective laser sintering, fused deposition modelling and semi-solid extrusion 3D printing. It also provides a comprehensive review of previous attempts at using 3D printing technologies on the manufacturing dosage forms with a particular focus on oral tablets. Their advantages particularly with adaptability in the pharmaceutical field have been highlighted, including design flexibility and control and manufacture which enables the preparation of dosage forms with complex designs and geometries, multiple actives and tailored release profiles. An insight into the technical challenges facing the different 3D printing technologies such as the formulation and processing parameters is provided. Light is also shed on the different regulatory challenges that need to be overcome for 3D printing to fulfil its real potential in the pharmaceutical industry

To what extent do nurses use research in clinical practice? A systematic review

Background : In the past forty years, many gains have been made in our understanding of the concept of research utilization. While numerous studies exist on professional nurses\u27 use of research in practice, no attempt has been made to systematically evaluate and synthesize this body of literature with respect to the extent to which nurses use research in their clinical practice. The objective of this study was to systematically identify and analyze the available evidence related to the extent to which nurses use research findings in practice. Methods : This study was a systematic review of published and grey literature. The search strategy included 13 online bibliographic databases: Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, MEDLINE, CINAHL, EMBASE, HAPI, Web of Science, SCOPUS, OCLC Papers First, OCLC WorldCat, ABI Inform, Sociological Abstracts, and Dissertation Abstracts. The inclusion criteria consisted of primary research reports that assess professional nurses\u27 use of research in practice, written in the English or Scandinavian languages. Extent of research use was determined by assigning research use scores reported in each article to one of four quartiles: low, moderate-low, moderate-high, or high. Results : Following removal of duplicate citations, a total of 12,418 titles were identified through database searches, of which 133 articles were retrieved. Of the articles retrieved, 55 satisfied the inclusion criteria. The 55 final reports included cross-sectional/survey (n = 51) and quasi-experimental (n = 4) designs. A sensitivity analysis, comparing findings from all reports with those rated moderate (moderate-weak and moderate-strong) and strong quality, did not show significant differences. In a majority of the articles identified (n = 38, 69%), nurses reported moderate-high research use. Conclusions : According to this review, nurses\u27 reported use of research is moderate-high and has remained relatively consistent over time until the early 2000\u27s. This finding, however, may paint an overly optimistic picture of the extent to which nurses use research in their practice given the methodological problems inherent in the majority of studies. There is a clear need for the development of standard measures of research use and robust well-designed studies examining nurses\u27 use of research and its impact on patient outcomes. The relatively unchanged self-reports of moderate-high research use by nurses is troubling given that over 40 years have elapsed since the first studies in this review were conducted and the increasing emphasis in the past 15 years on evidence-based practice. More troubling is the absence of studies in which attempts are made to assess the effects of varying levels of research use on patient outcomes.<br /

The ELBA Force Field for Coarse-Grain Modeling of Lipid Membranes

A new coarse-grain model for molecular dynamics simulation of lipid membranes is presented. Following a simple and conventional approach, lipid molecules are modeled by spherical sites, each representing a group of several atoms. In contrast to common coarse-grain methods, two original (interdependent) features are here adopted. First, the main electrostatics are modeled explicitly by charges and dipoles, which interact realistically through a relative dielectric constant of unity (). Second, water molecules are represented individually through a new parametrization of the simple Stockmayer potential for polar fluids; each water molecule is therefore described by a single spherical site embedded with a point dipole. The force field is shown to accurately reproduce the main physical properties of single-species phospholipid bilayers comprising dioleoylphosphatidylcholine (DOPC) and dioleoylphosphatidylethanolamine (DOPE) in the liquid crystal phase, as well as distearoylphosphatidylcholine (DSPC) in the liquid crystal and gel phases. Insights are presented into fundamental properties and phenomena that can be difficult or impossible to study with alternative computational or experimental methods. For example, we investigate the internal pressure distribution, dipole potential, lipid diffusion, and spontaneous self-assembly. Simulations lasting up to 1.5 microseconds were conducted for systems of different sizes (128, 512 and 1058 lipids); this also allowed us to identify size-dependent artifacts that are expected to affect membrane simulations in general. Future extensions and applications are discussed, particularly in relation to the methodology's inherent multiscale capabilities