Displaced distal forearm fractures in children with an indication for reduction under general anesthesia should be percutaneously fixated

Surger

Methylation-associated down-regulation of RASSF1A and up-regulation of RASSF1C in pancreatic endocrine tumors

<p>Abstract</p> <p>Background</p> <p><it>RASSF1A </it>gene silencing by DNA methylation has been suggested as a major event in pancreatic endocrine tumor (PET) but <it>RASSF1A </it>expression has never been studied. The <it>RASSF1 </it>locus contains two CpG islands (<it>A </it>and <it>C</it>) and generates seven transcripts (<it>RASSF1A</it>-<it>RASSF1G</it>) by differential promoter usage and alternative splicing.</p> <p>Methods</p> <p>We studied 20 primary PETs, their matched normal pancreas and three PET cell lines for the (i) methylation status of the <it>RASSF1 </it>CpG islands using methylation-specific PCR and pyrosequencing and (ii) expression of <it>RASSF1 </it>isoforms by quantitative RT-PCR in 13 cases. CpG island A methylation was evaluated by methylation-specific PCR (MSP) and by quantitative methylation-specific PCR (qMSP); pyrosequencing was applied to quantify the methylation of 51 CpGs also encompassing those explored by MSP and qMSP approaches.</p> <p>Results</p> <p>MSP detected methylation in 16/20 (80%) PETs and 13/20 (65%) normal pancreas. At qMSP, 11/20 PETs (55%) and 9/20 (45%) normals were methylated in at least 20% of <it>RASSF1A </it>alleles.</p> <p>Pyrosequencing showed variable distribution and levels of methylation within and among samples, with PETs having average methylation higher than normals in 15/20 (75%) cases (<it>P </it>= 0.01). The evaluation of mRNA expression of <it>RASSF1 </it>variants showed that: i) <it>RASSF1A </it>was always expressed in PET and normal tissues, but it was, on average, expressed 6.8 times less in PET (<it>P </it>= 0.003); ii) <it>RASSF1A </it>methylation inversely correlated with its expression; iii) <it>RASSF1 </it>isoforms were rarely found, except for <it>RASSF1B </it>that was always expressed and <it>RASSF1C </it>whose expression was 11.4 times higher in PET than in normal tissue (<it>P </it>= 0.001). A correlation between <it>RASSF1A </it>expression and gene methylation was found in two of the three PET cell lines, which also showed a significant increase in <it>RASSF1A </it>expression upon demethylating treatment.</p> <p>Conclusions</p> <p><it>RASSF1A </it>gene methylation in PET is higher than normal pancreas in no more than 75% of cases and as such it cannot be considered a marker for this neoplasm. <it>RASSF1A </it>is always expressed in PET and normal pancreas and its levels are inversely correlated with gene methylation. Isoform <it>RASSF1C </it>is overexpressed in PET and the recent demonstration of its involvement in the regulation of the Wnt pathway points to a potential pathogenetic role in tumor development.</p

How does it really feel to act together? : Shared emotions and the phenomenology of we-agency

Research on the phenomenology of agency for joint action has so far focused on the sense of agency and control in joint action, leaving aside questions on how it feels to act together. This paper tries to fill this gap in a way consistent with the existing theories of joint action and shared emotion. We first reconstruct Pacherie’s (Phenomenology and the Cognitive Sciences, 13, 25–46, 2014) account on the phenomenology of agency for joint action, pointing out its two problems, namely (1) the necessary trade-off between the sense of self- and we-agency; and (2) the lack of affective phenomenology of joint action in general. After elaborating on these criticisms based on our theory of shared emotion, we substantiate the second criticism by discussing different mechanisms of shared affect—feelings and emotions—that are present in typical joint actions. We show that our account improves on Pacherie’s, first by introducing our agentive model of we-agency to overcome her unnecessary dichotomy between a sense of self- and we-agency, and then by suggesting that the mechanisms of shared affect enhance not only the predictability of other agents’ actions as Pacherie highlights, but also an agentive sense of we-agency that emerges from shared emotions experienced in the course and consequence of joint action.Peer reviewe

Mating alters gene expression patterns in Drosophila melanogaster male heads

<p>Abstract</p> <p>Background</p> <p>Behavior is a complex process resulting from the integration of genetic and environmental information. <it>Drosophila melanogaster </it>rely on multiple sensory modalities for reproductive success, and mating causes physiological changes in both sexes that affect reproductive output or behavior. Some of these effects are likely mediated by changes in gene expression. Courtship and mating alter female transcript profiles, but it is not known how mating affects male gene expression.</p> <p>Results</p> <p>We used <it>Drosophila </it>genome arrays to identify changes in gene expression profiles that occur in mated male heads. Forty-seven genes differed between mated and control heads 2 hrs post mating. Many mating-responsive genes are highly expressed in non-neural head tissues, including an adipose tissue called the fat body. One fat body-enriched gene, <it>female-specific independent of transformer </it>(<it>fit</it>), is a downstream target of the somatic sex-determination hierarchy, a genetic pathway that regulates <it>Drosophila</it> reproductive behaviors as well as expression of some fat-expressed genes; three other mating-responsive loci are also downstream components of this pathway. Another mating-responsive gene expressed in fat, <it>Juvenile hormone esterase </it>(<it>Jhe</it>), is necessary for robust male courtship behavior and mating success.</p> <p>Conclusions</p> <p>Our study demonstrates that mating causes changes in male head gene expression profiles and supports an increasing body of work implicating adipose signaling in behavior modulation. Since several mating-induced genes are sex-determination hierarchy target genes, additional mating-responsive loci may be downstream components of this pathway as well.</p

Emotional Engineers: Toward Morally Responsible Design

Engineers are normally seen as the archetype of people who make decisions in a rational and quantitative way. However, technological design is not value neutral. The way a technology is designed determines its possibilities, which can, for better or for worse, have consequences for human wellbeing. This leads various scholars to the claim that engineers should explicitly take into account ethical considerations. They are at the cradle of new technological developments and can thereby influence the possible risks and benefits more directly than anybody else. I have argued elsewhere that emotions are an indispensable source of ethical insight into ethical aspects of risk. In this paper I will argue that this means that engineers should also include emotional reflection into their work. This requires a new understanding of the competencies of engineers: they should not be unemotional calculators; quite the opposite, they should work to cultivate their moral emotions and sensitivity, in order to be engaged in morally responsible engineering

Order in Spontaneous Behavior

Brains are usually described as input/output systems: they transform sensory input into motor output. However, the motor output of brains (behavior) is notoriously variable, even under identical sensory conditions. The question of whether this behavioral variability merely reflects residual deviations due to extrinsic random noise in such otherwise deterministic systems or an intrinsic, adaptive indeterminacy trait is central for the basic understanding of brain function. Instead of random noise, we find a fractal order (resembling Lévy flights) in the temporal structure of spontaneous flight maneuvers in tethered Drosophila fruit flies. Lévy-like probabilistic behavior patterns are evolutionarily conserved, suggesting a general neural mechanism underlying spontaneous behavior. Drosophila can produce these patterns endogenously, without any external cues. The fly's behavior is controlled by brain circuits which operate as a nonlinear system with unstable dynamics far from equilibrium. These findings suggest that both general models of brain function and autonomous agents ought to include biologically relevant nonlinear, endogenous behavior-initiating mechanisms if they strive to realistically simulate biological brains or out-compete other agents

Effectiveness of preoperative beta-blockade on intra-operative heart rate in vascular surgery cases conducted under regional or local anesthesia

BACKGROUND: Preoperative β-blockade has been posited to result in better outcomes for vascular surgery patients by attenuating acute hemodynamic changes associated with stress. However, the incremental effectiveness, if any, of β-blocker usage in blunting heart rate responsiveness for vascular surgery patients who avoid general anesthesia remains unknown. METHODS: We reviewed an existing database and identified 213 consecutive vascular surgery cases from 2005–2011 conducted without general anesthesia (i.e., under monitored anesthesia care or regional anesthesia) at a tertiary care Veterans Administration medical center and categorized patients based on presence or absence of preoperative β-blocker prescription. For this series of patients, with the primary outcome of maximum heart rate during the interval between operating room entry to surgical incision, we examined the association of maximal heart rate and preoperative β-blocker usage by performing crude and multivariate linear regression, adjusting for relevant patient factors. RESULTS: Of 213 eligible cases, 137 were prescribed preoperative β-blockers, and 76 were not. The two groups were comparable across baseline patient factors and intraoperative medication doses. The β-blocker group experienced lower maximal heart rates during the period of evaluation compared to the non-β-blocker group (85 ± 22 bpm vs. 98 ± 36 bpm, respectively; p = 0.002). Adjusted linear regression confirmed a statistically-significant association between lower maximal heart rate and the use of β-blockers (Beta = -11.5; 95% CI [-3.7, -19.3] p = 0.004). CONCLUSIONS: The addition of preoperative β-blockers, even when general anesthesia is avoided, may be beneficial in further attenuating stress-induced hemodynamic changes for vascular surgery patients