Policy and Institutional Support for CA Development (Examples from Europe, Africa, Asia)

Policy and Institutional Support for CA Development (Examples from Europe, Africa, Asia

Valproic acid influences the expression of genes implicated with hyperglycaemia-induced complement and coagulation pathways

Because the liver plays a major role in metabolic homeostasis and secretion of clotting factors and inflammatory innate immune proteins, there is interest in understanding the mechanisms of hepatic cell activation under hyperglycaemia and whether this can be attenuated pharmacologically. We have previously shown that hyperglycaemia stimulates major changes in chromatin organization and metabolism in hepatocytes, and that the histone deacetylase inhibitor valproic acid (VPA) is able to reverse some of these metabolic changes. In this study, we have used RNA-sequencing (RNA-seq) to investigate how VPA influences gene expression in hepatocytes. Interesting, we observed that VPA attenuates hyperglycaemia-induced activation of complement and coagulation cascade genes. We also observe that many of the gene activation events coincide with changes to histone acetylation at the promoter of these genes indicating that epigenetic regulation is involved in VPA action11CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP304668/2014-12010/50015-6; 2012/03238-5; 2014/10198-5; 2015/10356-2NHMRC; International Joint Program. Professor Sam El-Osta is a National Health and Medical Research Council; Senior Research Fello

The Effect of Financial Incentives on Patient Decisions to Undergo Low‐value Head Computed Tomography Scans

BackgroundExcessive diagnostic testing and defensive medicine contribute to billions of dollars in avoidable costs in the United States annually. Our objective was to determine the influence of financial incentives, accompanied with information regarding test risk and benefit, on patient preference for diagnostic testing.MethodsWe conducted a cross‐sectional survey of patients at the University of Michigan emergency department (ED). Each participant was presented with a hypothetical scenario involving an ED visit following minor traumatic brain injury. Participants were given information regarding potential benefit (detecting brain hemorrhage) and risk (developing cancer) of head computed tomography scan, as well as an incentive of $0 or$100 to forego testing. We used 0.1 and 1% for test benefit and risk, and values for risk, benefit, and financial incentive varied across participants. Our primary outcome was patient preference to undergo testing. We also collected demographic and numeracy information. We then used logistic regression to estimate odds ratios (ORs), which were adjusted for multiple potential confounders. Our sample size was designed to find at least 300 events (preference for testing) to allow for inclusion of up to 30 covariates in fully adjusted models. We had 85% to 90% power to detect a 10% absolute difference in testing rate across groups, assuming a 95% significance level.ResultsWe surveyed 913 patients. Increasing test benefit from 0.1% to 1% significantly increased test acceptance (adjusted OR [AOR] = 1.6, 95% confidence interval [CI] = 1.2 to 2.1) and increasing test risk from 0.1% to 1% significantly decreased test acceptance (AOR = 0.70, 95% CI = 0.52 to 0.93). Finally, a $100 incentive to forego low‐value testing significantly reduced test acceptance (AOR = 0.6; 95% CI = 0.4 to 0.8).ConclusionsProviding financial incentives to forego testing significantly decreased patient preference for testing, even when accounting for test benefit and risk. This work is preliminary and hypothetical and requires confirmation in larger patient cohorts facing these actual decisions.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151851/1/acem13823_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151851/2/acem13823-sup-0001-DataSupplementS1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151851/3/acem13823.pd

On Aharonov-Casher bound states

In this work bound states for the Aharonov-Casher problem are considered. According to Hagen's work on the exact equivalence between spin-1/2 Aharonov-Bohm and Aharonov-Casher effects, is known that the $\boldsymbol{\nabla}\cdot\mathbf{E}$ term cannot be neglected in the Hamiltonian if the spin of particle is considered. This term leads to the existence of a singular potential at the origin. By modeling the problem by boundary conditions at the origin which arises by the self-adjoint extension of the Hamiltonian, we derive for the first time an expression for the bound state energy of the Aharonov-Casher problem. As an application, we consider the Aharonov-Casher plus a two-dimensional harmonic oscillator. We derive the expression for the harmonic oscillator energies and compare it with the expression obtained in the case without singularity. At the end, an approach for determination of the self-adjoint extension parameter is given. In our approach, the parameter is obtained essentially in terms of physics of the problem.Comment: 11 pages, matches published versio

The transcriptional response of Caenorhabditis elegans to ivermectin exposure identifies novel genes involved in the response to reduced food intake

We have examined the transcriptional response of Caenorhabditis elegans following exposure to the anthelmintic drug ivermectin (IVM) using whole genome microarrays and real-time QPCR. Our original aim was to identify candidate molecules involved in IVM metabolism and/or excretion. For this reason the IVM tolerant strain, DA1316, was used to minimise transcriptomic changes related to the phenotype of drug exposure. However, unlike equivalent work with benzimidazole drugs, very few of the induced genes were members of xenobiotic metabolising enzyme families. Instead, the transcriptional response was dominated by genes associated with fat mobilization and fatty acid metabolism including catalase, esterase, and fatty acid CoA synthetase genes. This is consistent with the reduction in pharyngeal pumping, and consequential reduction in food intake, upon exposure of DA1316 worms to IVM. Genes with the highest fold change in response to IVM exposure, cyp-37B1, mtl-1 and scl-2, were comparably up-regulated in response to short–term food withdrawal (4 hr) independent of IVM exposure, and GFP reporter constructs confirm their expression in tissues associated with fat storage (intestine and hypodermis). These experiments have serendipitously identified novel genes involved in an early response of C. elegans to reduced food intake and may provide insight into similar processes in higher organisms

Assessment of pain during rest and during activities in the postoperative period of cardiac surgery

OBJECTIVE: to assess the intensity and site of pain after Cardiac Surgery through sternotomy during rest and while performing five activities. METHOD: descriptive study with a prospective cohort design. A total of 48 individuals participated in the study. A Multidimensional Scale for Pain Assessment was used. RESULTS: postoperative pain from cardiac surgery was moderate during rest and decreased over time. Pain was also moderate during activities performed on the 1st and 2nd postoperative days and decreased from the 3rd postoperative day, with the exception of coughing, which diminished only on the 6th postoperative day. Coughing, turning over, deep breathing and rest are presented in decreased order of intensity. The region of the sternum was the most frequently reported site of pain. CONCLUSION: the assessment of pain in the individuals who underwent cardiac surgery during rest and during activities is extremely important to adapt management and avoid postoperative complications and delayed surgical recovery

Review NMR studies of RNA dynamics and structural plasticity using NMR residual dipolar couplings

An increasing number of RNAs are being discovered that perform their functions by undergoing large changes in conformation in response to a variety of cellular signals, including recognition of proteins and small molecular targets, changes in temperature, and RNA synthesis itself. The measurement of NMR residual dipolar couplings (RDCs) in partially aligned systems is providing new insights into the structural plasticity of RNA through combined characterization of large-amplitude collective helix motions and local flexibility in noncanonical regions over a wide window of biologically relevant timescales (<milliseconds). Here, we review RDC methodology for studying RNA structural dynamics and survey what has been learnt thus far from application of these methods. Future methodological challenges are also identified. © 2007 Wiley Periodicals, Inc. Biopolymers 86: 384–402, 2007. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at [email protected] Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56044/1/20765_ftp.pd