Italian intersociety consensus statement on antithrombotic prophylaxis in hip and knee replacement and in femoral neck fracture surgery

Anticoagulant prophylaxis for preventing venous thromboembolism (VTE) is a worldwide established procedure in hip and knee replacement surgery, as well as in the treatment of femoral neck fractures (FNF). Different guidelines are available in the literature, with quite different recommendations. None of them is a multidisciplinary effort as the one presented. The Italian Society for Studies on Haemostasis and Thrombosis (SISET), the Italian Society of Orthopaedics and Traumatology (SIOT), the association of Orthopaedists and Traumatologists of Italian Hospitals (OTODI), together with the Italian Society of Anesthesia, Analgesia, Resuscitation, and Intensive Care (SIAARTI) have set down easy and quick suggestions for VTE prophylaxis in hip and knee surgery as well as in FNF treatment. This inter-society consensus statement aims at simplifying the grading system reported in the literature, and its goal is to benefit its clinical application. Special focus is given to fragile patients, those with high bleeding risk, and those receiving chronic antiplatelet (APT) and vitamin K antagonists treatment. A special chapter is dedicated to regional anaesthesia and VTE prophylaxis

Dynamics of carbon pools in post-agrogenic sandy soils of southern taiga of Russia

<p>Abstract</p> <p>Background</p> <p>Until recently, a lot of arable lands were abandoned in many countries of the world and, especially, in Russia, where about half a million square kilometers of arable lands were abandoned in 1961-2007. The soils at these fallows undergo a process of natural restoration (or self-restoration) that changes the balance of soil organic matter (SOM) supply and mineralization.</p> <p>Results</p> <p>A soil chronosequence study, covering the ecosystems of 3, 20, 55, 100, and 170 years of self-restoration in southern taiga zone, shows that soil organic content of mineral horizons remains relatively stable during the self-restoration. This does not imply, however, that SOM pools remain steady. The C/N ratio of active SOM reached steady state after 55 years, and increased doubly (from 12.5 - 15.6 to 32.2-33.8). As to the C/N ratio of passive SOM, it has been continuously increasing (from 11.8-12.7 to 19.0-22.8) over the 170 years, and did not reach a steady condition.</p> <p>Conclusion</p> <p>The results of the study imply that soil recovery at the abandoned arable sandy lands of taiga is incredibly slow process. Not only soil morphological features of a former ploughing remained detectable but also the balance of soil organic matter input and mineralization remained unsteady after 170 years of self-restoration.</p

Barley <i>SIX-ROWED SPIKE3</i> encodes a putative Jumonji C-type H3K9me2/me3 demethylase that represses lateral spikelet fertility

The VRS genes of barley control the fertility of the lateral spikelets on the barley inflorescence. Here, Bull et al. show that VRS3 encodes a putative Jumonji C-type histone demethylase that regulates expression of other VRS genes, and genes involved in stress, hormone and sugar metabolism

Global Regulation of Nucleotide Biosynthetic Genes by c-Myc

The c-Myc transcription factor is a master regulator and integrates cell proliferation, cell growth and metabolism through activating thousands of target genes. Our identification of direct c-Myc target genes by chromatin immunoprecipitation (ChIP) coupled with pair-end ditag sequencing analysis (ChIP-PET) revealed that nucleotide metabolic genes are enriched among c-Myc targets, but the role of Myc in regulating nucleotide metabolic genes has not been comprehensively delineated.Here, we report that the majority of genes in human purine and pyrimidine biosynthesis pathway were induced and directly bound by c-Myc in the P493-6 human Burkitt's lymphoma model cell line. The majority of these genes were also responsive to the ligand-activated Myc-estrogen receptor fusion protein, Myc-ER, in a Myc null rat fibroblast cell line, HO.15 MYC-ER. Furthermore, these targets are also responsive to Myc activation in transgenic mouse livers in vivo. To determine the functional significance of c-Myc regulation of nucleotide metabolism, we sought to determine the effect of loss of function of direct Myc targets inosine monophosphate dehydrogenases (IMPDH1 and IMPDH2) on c-Myc-induced cell growth and proliferation. In this regard, we used a specific IMPDH inhibitor mycophenolic acid (MPA) and found that MPA dramatically inhibits c-Myc-induced P493-6 cell proliferation through S-phase arrest and apoptosis.Taken together, these results demonstrate the direct induction of nucleotide metabolic genes by c-Myc in multiple systems. Our finding of an S-phase arrest in cells with diminished IMPDH activity suggests that nucleotide pool balance is essential for c-Myc's orchestration of DNA replication, such that uncoupling of these two processes create DNA replication stress and apoptosis

Monitoring Winter and Summer Abundance of Cetaceans in the Pelagos Sanctuary (Northwestern Mediterranean Sea) Through Aerial Surveys

Systematic long-term monitoring of abundance is essential to inform conservation measures and evaluate their effectiveness. To instigate such work in the Pelagos Sanctuary in the Mediterranean, two aerial surveys were conducted in winter and summer 2009. A total of 467 (131 in winter, 336 in summer) sightings of 7 species was made. Sample sizes were sufficient to estimate abundance of fin whales in summer (148; 95% CI = 87–254) and striped dolphins in winter (19,462; 95% CI = 12 939–29 273) and in summer (38 488; 95% CI = 27 447–53 968). Numbers of animals within the Sanctuary are significantly higher in summer, when human activities and thus potential population level impacts are highest. Comparisons with data from past shipboard surveys suggest an appreciable decrease in fin whales within the Sanctuary area and an appreciable increase in striped dolphins. Aerial surveys proved to be more efficient than ship surveys, allowing more robust estimates, with smaller CIs and CVs. These results provide essential baseline data for this marine protected area and continued regular surveys will allow the effectiveness of the MPA in terms of cetacean conservation to be evaluated and inform future management measures. The collected data may also be crucial in assessing whether ship strikes, one of the main causes of death for fin whales in the Mediterranean, are affecting the Mediterranean population

Gene Regulation and Epigenetic Remodeling in Murine Embryonic Stem Cells by c-Myc

BACKGROUND:The Myc oncoprotein, a transcriptional regulator involved in the etiology of many different tumor types, has been demonstrated to play an important role in the functions of embryonic stem (ES) cells. Nonetheless, it is still unclear as to whether Myc has unique target and functions in ES cells. METHODOLOGY/PRINCIPAL FINDINGS:To elucidate the role of c-Myc in murine ES cells, we mapped its genomic binding sites by chromatin-immunoprecipitation combined with DNA microarrays (ChIP-chip). In addition to previously identified targets we identified genes involved in pluripotency, early development, and chromatin modification/structure that are bound and regulated by c-Myc in murine ES cells. Myc also binds and regulates loci previously identified as Polycomb (PcG) targets, including genes that contain bivalent chromatin domains. To determine whether c-Myc influences the epigenetic state of Myc-bound genes, we assessed the patterns of trimethylation of histone H3-K4 and H3-K27 in mES cells containing normal, increased, and reduced levels of c-Myc. Our analysis reveals widespread and surprisingly diverse changes in repressive and activating histone methylation marks both proximal and distal to Myc binding sites. Furthermore, analysis of bulk chromatin from phenotypically normal c-myc null E7 embryos demonstrates a 70-80% decrease in H3-K4me3, with little change in H3-K27me3, compared to wild-type embryos indicating that Myc is required to maintain normal levels of histone methylation. CONCLUSIONS/SIGNIFICANCE:We show that Myc induces widespread and diverse changes in histone methylation in ES cells. We postulate that these changes are indirect effects of Myc mediated by its regulation of target genes involved in chromatin remodeling. We further show that a subset of PcG-bound genes with bivalent histone methylation patterns are bound and regulated in response to altered c-Myc levels. Our data indicate that in mES cells c-Myc binds, regulates, and influences the histone modification patterns of genes involved in chromatin remodeling, pluripotency, and differentiation

Rational drug repurposing using sscMap analysis in a HOX-TALE model of leukemia

Drug discovery and development are often hampered by lack of target identification and clinical tractability. Repurposing of approved drugs to life-threatening diseases such as leukemia is emerging as a promising alternative approach. Connectivity mapping systems link approved drugs with disease-related gene signatures. Relevant preclinical models provide essential tools for system validation and proof-of-concept studies. Herein we describe procedures aimed at generating disease-based gene signatures and applying them to established cross-referencing databases of potential candidate drugs. As a proof of principle, we present the identification of Entinostat as a candidate drug for the treatment of HOX TALE-related leukemia

From staff-mix to skill-mix and beyond: towards a systemic approach to health workforce management

Throughout the world, countries are experiencing shortages of health care workers. Policy-makers and system managers have developed a range of methods and initiatives to optimise the available workforce and achieve the right number and mix of personnel needed to provide high-quality care. Our literature review found that such initiatives often focus more on staff types than on staff members' skills and the effective use of those skills. Our review describes evidence about the benefits and pitfalls of current approaches to human resources optimisation in health care. We conclude that in order to use human resources most effectively, health care organisations must consider a more systemic approach - one that accounts for factors beyond narrowly defined human resources management practices and includes organisational and institutional conditions