Early efficacy of CABG care delivery in a low procedure-volume community hospital: operative and midterm results

BACKGROUND: The Leapfrog Group recommended that coronary artery bypass grafting (CABG) surgery should be done at high volume hospitals (>450 per year) without corresponding surgeon-volume criteria. The latter confounds procedure-volume effects substantially, and it is suggested that high surgeon-volume (>125 per year) rather than hospital-volume may be a more appropriate indicator of CABG quality. METHODS: We assessed 3-year isolated CABG morbidity and mortality outcomes at a low-volume hospital (LVH: 504 cases) and compared them to the corresponding Society of Thoracic Surgeons (STS) national data over the same period (2001–2003). All CABGs were performed by 5 high-volume surgeons (161–285 per year). "Best practice" care at LVH – including effective practice guidelines, protocols, data acquisition capabilities, case review process, dedicated facilities and support personnel – were closely modeled after a high-volume hospital served by the same surgeon-team. RESULTS: Operative mortality was similar for LVH and STS (OM: 2.38% vs. 2.53%), and the corresponding LVH observed-to-expected mortality (O/E = 0.81) indicated good quality relative to the STS risk model (O/E<1). Also, these results were consistent irrespective of risk category: O/E was 0, 0.9 and 1.03 for very-low risk (<1%), low risk (1–3%) and moderate-to-high risk category (>3%), respectively. Postoperative leg wound infections, ventilator hours, renal dysfunction (no dialysis), and atrial fibrillation were higher for LVH, but hospital stay was not. The unadjusted Kaplan-Meier survival for the LVH cohort was 96%, 94%, and 92% at one, two, and three years, respectively. CONCLUSION: Our results demonstrated that high quality CABG care can be achieved at LVH programs if 1) served by high volume surgeons and 2) patient care procedures similar to those of large programs are implemented. This approach may prove a useful paradigm to ensure high quality CABG care and early efficacy at low volume institutions that wish to comply with the Leapfrog standards

Screening chest radiography: results from a Greek cross-sectional survey

BACKGROUND: Public health authorities worldwide discourage the use of chest radiography as a screening modality, as the diagnostic performance of chest radiography does not justify its application for screening and may even be harmful, since people with false positive results may experience anxiety and concern. Despite the accumulated evidence, various reports suggest that primary care physicians throughout the world still prescribe chest radiography for screening. We therefore set out to index the use of chest radiography for screening purposes among the healthy adult population and to analyze its relationship with possible trigger factors. METHODS: The study was designed as a cross-sectional survey. Five thousand four hundred and ninety-nine healthy adults, coming from 26 Greek provinces were surveyed for screening practice habits in the nationwide anticancer study. Data were obtained for the use of screening chest radiography. Impact of age, gender, tobacco exposure, family history positive for malignancies and professional-risk for lung diseases was further analyzed. RESULTS: we found that 20% (n = 1099) of the surveyed individuals underwent chest radiography for screening purposes for at least one time during the previous three years. Among those, 24% do so with a frequency equal or higher than once yearly, and 48% with a frequency equal or higher than every three years. Screening for chest radiography was more commonly adopted among males (OR 1.130, 95% CI 0.988–1.292), pensioners (OR 1.319, CI 1.093–1.593) and individuals with a positive family history for lung cancer (OR 1.251, CI 0.988–1.583). Multivariate analysis confirmed these results. CONCLUSION: Despite formal recommendations, chest radiography for screening purposes was a common practice among the analyzed sample of Greek adults. This practice is of questionable value since the positive predictive value of chest radiography is low. The implementation of even a relatively inexpensive imaging study on a national scale would greatly burden health economics and the workload of radiology departments

Structure-guided evolution of cyan fluorescent proteins towards a quantum yield of 93%

Cyan variants of green fluorescent protein are widely used as donors in Förster resonance energy transfer experiments. The popular, but modestly bright, Enhanced Cyan Fluorescent Protein (ECFP) was sequentially improved into the brighter variants Super Cyan Fluorescent Protein 3A (SCFP3A) and mTurquoise, the latter exhibiting a high-fluorescence quantum yield and a long mono-exponential fluorescence lifetime. Here we combine X-ray crystallography and excited-state calculations to rationalize these stepwise improvements. The enhancement originates from stabilization of the seventh β-strand and the strengthening of the sole chromophore-stabilizing hydrogen bond. The structural analysis highlighted one suboptimal internal residue, which was subjected to saturation mutagenesis combined with fluorescence lifetime-based screening. This resulted in mTurquoise2, a brighter variant with faster maturation, high photostability, longer mono-exponential lifetime and the highest quantum yield measured for a monomeric fluorescent protein. Together, these properties make mTurquoise2 the preferable cyan variant of green fluorescent protein for long-term imaging and as donor for Förster resonance energy transfer to a yellow fluorescent protein

Remote-controlled experiments with cloud chemistry

Developing cleaner chemical processes often involves sophisticated flow-chemistry equipment that is not available in many economically developing countries. For reactions where it is the data that are important rather than the physical product, the networking of chemists across the internet to allow remote experimentation offers a viable solution to this problem

Time-trend of melanoma screening practice by primary care physicians: A meta-regression analysis

Objective. To assess whether the proportion of primary care physicians implementing full body skin examination (FBSE) to screen for melanoma changed over time. Methods. Meta-regression analyses of available data. Data Sources: MEDLINE, ISI, Cochrane Central Register of Controlled Trials. Results. Fifteen studies surveying 10,336 physicians were included in the analyses. Overall, 15%\u201382% of them reported to perform FBSE to screen for melanoma. The proportion of physicians using FBSE screening tended to decrease by 1.72% per year (P =0.086). Corresponding annual changes in European, North American, and Australian settings were 120.68% (P =0.494), 122.02% (P =0.044), and +2.59% (P =0.010), respectively. Changes were not influenced by national guide-lines. Conclusions. Considering the increasing incidence of melanoma and other skin malignancies, as well as their relative potential consequences, the FBSE implementation time-trend we retrieved should be considered a worrisome phenomenon

Leucine-Rich Repeat Kinase 2 Modulates Retinoic Acid-Induced Neuronal Differentiation of Murine Embryonic Stem Cells

Background: Dominant mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most prevalent cause of Parkinson’s disease, however, little is known about the biological function of LRRK2 protein. LRRK2 is expressed in neural precursor cells suggesting a role in neurodevelopment. Methodology/Principal Findings: In the present study, differential gene expression profiling revealed a faster silencing of pluripotency-associated genes, like Nanog, Oct4, and Lin28, during retinoic acid-induced neuronal differentiation of LRRK2deficient mouse embryonic stem cells compared to wildtype cultures. By contrast, expression of neurotransmitter receptors and neurotransmitter release was increased in LRRK2+/2 cultures indicating that LRRK2 promotes neuronal differentiation. Consistently, the number of neural progenitor cells was higher in the hippocampal dentate gyrus of adult LRRK2-deficient mice. Alterations in phosphorylation of the putative LRRK2 substrates, translation initiation factor 4E binding protein 1 and moesin, do not appear to be involved in altered differentiation, rather there is indirect evidence that a regulatory signaling network comprising retinoic acid receptors, let-7 miRNA and downstream target genes/mRNAs may be affected in LRRK2deficient stem cells in culture. Conclusion/Significance: Parkinson’s disease-linked LRRK2 mutations that associated with enhanced kinase activity may affect retinoic acid receptor signaling during neurodevelopment and/or neuronal maintenance as has been shown in othe

Real-time visualization of heterotrimeric G protein Gq activation in living cells

Contains fulltext : 97296.pdf (publisher's version ) (Open Access)BACKGROUND: Gq is a heterotrimeric G protein that plays an important role in numerous physiological processes. To delineate the molecular mechanisms and kinetics of signalling through this protein, its activation should be measurable in single living cells. Recently, fluorescence resonance energy transfer (FRET) sensors have been developed for this purpose. RESULTS: In this paper, we describe the development of an improved FRET-based Gq activity sensor that consists of a yellow fluorescent protein (YFP)-tagged Ggamma2 subunit and a Galphaq subunit with an inserted monomeric Turquoise (mTurquoise), the best cyan fluorescent protein variant currently available. This sensor enabled us to determine, for the first time, the kon (2/s) of Gq activation. In addition, we found that the guanine nucleotide exchange factor p63RhoGEF has a profound effect on the number of Gq proteins that become active upon stimulation of endogenous histamine H1 receptors. The sensor was also used to measure ligand-independent activation of the histamine H1 receptor (H1R) upon addition of a hypotonic stimulus. CONCLUSIONS: Our observations reveal that the application of a truncated mTurquoise as donor and a YFP-tagged Ggamma2 as acceptor in FRET-based Gq activity sensors substantially improves their dynamic range. This optimization enables the real-time single cell quantification of Gq signalling dynamics, the influence of accessory proteins and allows future drug screening applications by virtue of its sensitivity

Current and Future Patterns of Global Marine Mammal Biodiversity

Quantifying the spatial distribution of taxa is an important prerequisite for the preservation of biodiversity, and can provide a baseline against which to measure the impacts of climate change. Here we analyse patterns of marine mammal species richness based on predictions of global distributional ranges for 115 species, including all extant pinnipeds and cetaceans. We used an environmental suitability model specifically designed to address the paucity of distributional data for many marine mammal species. We generated richness patterns by overlaying predicted distributions for all species; these were then validated against sightings data from dedicated long-term surveys in the Eastern Tropical Pacific, the Northeast Atlantic and the Southern Ocean. Model outputs correlated well with empirically observed patterns of biodiversity in all three survey regions. Marine mammal richness was predicted to be highest in temperate waters of both hemispheres with distinct hotspots around New Zealand, Japan, Baja California, the Galapagos Islands, the Southeast Pacific, and the Southern Ocean. We then applied our model to explore potential changes in biodiversity under future perturbations of environmental conditions. Forward projections of biodiversity using an intermediate Intergovernmental Panel for Climate Change (IPCC) temperature scenario predicted that projected ocean warming and changes in sea ice cover until 2050 may have moderate effects on the spatial patterns of marine mammal richness. Increases in cetacean richness were predicted above 40° latitude in both hemispheres, while decreases in both pinniped and cetacean richness were expected at lower latitudes. Our results show how species distribution models can be applied to explore broad patterns of marine biodiversity worldwide for taxa for which limited distributional data are available

Gene expression microarray analysis of early oxygen-induced retinopathy in the rat

Different inbred strains of rat differ in their susceptibility to oxygen-induced retinopathy (OIR), an animal model of human retinopathy of prematurity. We examined gene expression in Sprague–Dawley (susceptible) and Fischer 344 (resistant) neonatal rats after 3 days exposure to cyclic hyperoxia or room air, using Affymetrix rat Genearrays. False discovery rate analysis was used to identify differentially regulated genes. Such genes were then ranked by fold change and submitted to the online database, DAVID. The Sprague–Dawley list returned the term “response to hypoxia,” absent from the Fischer 344 output. Manual analysis indicated that many genes known to be upregulated by hypoxia-inducible factor-1α were downregulated by cyclic hyperoxia. Quantitative real-time RT-PCR analysis of Egln3, Bnip3, Slc16a3, and Hk2 confirmed the microarray results. We conclude that combined methodologies are required for adequate dissection of the pathophysiology of strain susceptibility to OIR in the rat