Usefulness of coronary calcium scoring to myocardial perfusion SPECT in the diagnosis of coronary artery disease in a predominantly high risk population

Coronary calcium scoring (CCS) adds to the diagnostic performance of myocardial perfusion single-photon emission computed tomography (SPECT) to assess the presence of significant coronary artery disease (CAD). Patients with a high pre-test likelihood are expected to have a high CCS which potentially could enhance the diagnostic performance of myocardial perfusion SPECT in this specific patient group. We evaluated the added value of CCS to SPECT in the diagnosis of significant CAD in patients with an intermediate to high pre-test likelihood. In total, 129 patients (mean age 62.7 +/- A 9.7 years, 65 % male) with stable anginal complaints and intermediate to high pre-test likelihood of CAD (median 87 %, range 22-95) were prospectively included in this study. All patients received SPECT and CCS imaging preceding invasive coronary angiography (CA). Fractional flow reserve (FFR) measurements were acquired from patients with angiographically estimated 50-95 % obstructive CAD. For SPECT a SSS > 3 was defined significant CAD. For CCS the optimal cut-off value for significant CAD was determined by ROC curve analysis. The reference standard for significant CAD was a FFR of < 0.80 acquired by CA. Significant CAD was demonstrated in 64 patients (49.6 %). Optimal CCS cut-off value for significant CAD was > 182.5. ROC curve analysis for prediction of the presence of significant CAD for SPECT, CCS and the combination of CCS and SPECT resulted in an area under the curve (AUC) of 0.88 (95 % CI 81-94), 0.75 (95 % CI 66-83 %) and 0.92 (95 % CI 87-97 %) respectively. The difference of the AUC between SPECT and the combination of CCS and SPECT was 0.05 (P = 0.12). The addition of CCS did not significantly improve the diagnostic performance of SPECT in the evaluation of patients with a predominantly high pre-test likelihood of CAD

Phototherapy and exchange transfusion for neonatal hyperbilirubinaemia

The purpose of this document is to address the current lack of consensus  regarding the management of hyperbilirubinaemia in neonates in South Africa. If left untreated, severe neonatal hyperbilirubinaemia may cause kernicterus and ultimately death and the severity of neonatal jaundice is often underestimated clinically. However, if phototherapy is instituted  timeously and at the correct intensity an exchange transfusion can usually be avoided. The literature describing intervention thresholds for  phototherapy and exchange transfusion in both term and preterm infants is therefore reviewed and specific intervention thresholds that can be used throughout South Africa are proposed and presented graphically. A simplified version for use in a primary care setting is also presented. All academic heads of neonatology departments throughout South Africa were consulted in the process of drawing up this document and consensus was achieved

Real-time train driver rescheduling by actor-agent techniques

Passenger railway operations are based on an extensive planning process for generating the timetable, the rolling stock circulation, and the crew duties for train drivers and conductors. In particular, crew scheduling is a complex process. After the planning process has been completed, the plans are carried out in the real-time operations. Preferably, the plans are carried out as scheduled. However, in case of delays of trains or large disruptions of the railway system, the timetable, the rolling stock circulation and the crew duties may not be feasible anymore and must be rescheduled. This paper presents a method based on multi-agent techniques to solve the train driver rescheduling problem in case of a large disruption. It assumes that the timetable and the rolling stock have been rescheduled already based on an incident scenario. In the crew rescheduling model, each train driver is represented by a driver-agent. A driver-agent whose duty has become infeasible by the disruption starts a recursive task exchange process with the other driver-agents in order to solve this infeasibility. The task exchange process is supported by a route-analyzer-agent, which determines whether a proposed task exchange is feasible, conditionally feasible, or not feasible. The task exchange process is guided by several cost parameters, and the aim is to find a feasible set of duties at minimal total cost. The train driver rescheduling method was tested on several realistic disruption instances of Netherlands Railways (NS), the main operator of passenger trains in the Netherlands. In general the rescheduling method finds an appropriate set of rescheduled duties in a short amount of time. This research was carried out in close cooperation by NS and the D-CIS Lab

The developmental effects of media-ideal internalization and self-objectification processes on adolescents’ negative body-feelings, dietary restraint, and binge eating

Despite accumulated experimental evidence of the negative effects of exposure to media-idealized images, the degree to which body image, and eating related disturbances are caused by media portrayals of gendered beauty ideals remains controversial. On the basis of the most up-to-date meta-analysis of experimental studies indicating that media-idealized images have the most harmful and substantial impact on vulnerable individuals regardless of gender (i.e., “internalizers” and “self-objectifiers”), the current longitudinal study examined the direct and mediated links posited in objectification theory among media-ideal internalization, self-objectification, shame and anxiety surrounding the body and appearance, dietary restraint, and binge eating. Data collected from 685 adolescents aged between 14 and 15 at baseline (47 % males), who were interviewed and completed standardized measures annually over a 3-year period, were analyzed using a structural equation modeling approach. Results indicated that media-ideal internalization predicted later thinking and scrutinizing of one’s body from an external observer’s standpoint (or self-objectification), which then predicted later negative emotional experiences related to one’s body and appearance. In turn, these negative emotional experiences predicted subsequent dietary restraint and binge eating, and each of these core features of eating disorders influenced each other. Differences in the strength of these associations across gender were not observed, and all indirect effects were significant. The study provides valuable information about how the cultural values embodied by gendered beauty ideals negatively influence adolescents’ feelings, thoughts and behaviors regarding their own body, and on the complex processes involved in disordered eating. Practical implications are discussed

Intestinal Absorption and First-Pass Metabolism of Polyphenol Compounds in Rat and Their Transport Dynamics in Caco-2 Cells

<div><h3>Background</h3><p>Polyphenols, a group of complex naturally occurring compounds, are widely distributed throughout the plant kingdom and are therefore readily consumed by humans. The relationship between their chemical structure and intestinal absorption, transport, and first-pass metabolism remains unresolved, however.</p> <h3>Methods</h3><p>Here, we investigated the intestinal absorption and first-pass metabolism of four polyphenol compounds, apigenin, resveratrol, emodin and chrysophanol, using the <em>in vitro</em> Caco-2 cell monolayer model system and <em>in situ</em> intestinal perfusion and <em>in vivo</em> pharmacokinetic studies in rats, so as to better understand the relationship between the chemical structure and biological fate of the dietary polyphenols.</p> <h3>Conclusion</h3><p>After oral administration, emodin and chrysophanol exhibited different absorptive and metabolic behaviours compared to apigenin and resveratrol. The differences in their chemical structures presumably resulted in differing affinities for drug-metabolizing enzymes, such as glucuronidase and sulphatase, and transporters, such as MRP2, SGLT1, and P-glycoprotein, which are found in intestinal epithelial cells.</p> </div

MicroRNAs: new players in acute myeloid leukaemia

MicroRNAs (miRNAs) are short non-coding RNAs that have key functions in a wide array of critical cell processes, including haematopoiesis by regulating the expression of multiple genes. Aberrant miRNA expression has been described in acute myeloid leukaemia suggesting a role in leukaemogenesis. In this review we summarise the current knowledge

Distinct regulation of c-myb gene expression by HoxA9, Meis1 and Pbx proteins in normal hematopoietic progenitors and transformed myeloid cells

The proto-oncogenic protein c-Myb is an essential regulator of hematopoiesis and is frequently deregulated in hematological diseases such as lymphoma and leukemia. To gain insight into the mechanisms underlying the aberrant expression of c-Myb in myeloid leukemia, we analyzed and compared c-myb gene transcriptional regulation using two cell lines modeling normal hematopoietic progenitor cells (HPCs) and transformed myelomonocytic blasts. We report that the transcription factors HoxA9, Meis1, Pbx1 and Pbx2 bind in vivo to the c-myb locus and maintain its expression through different mechanisms in HPCs and leukemic cells. Our analysis also points to a critical role for Pbx2 in deregulating c-myb expression in murine myeloid cells cotransformed by the cooperative activity of HoxA9 and Meis1. This effect is associated with an intronic positioning of epigenetic marks and RNA polymerase II binding in the orthologous region of a previously described alternative promoter for c-myb. Taken together, our results could provide a first hint to explain the abnormal expression of c-myb in leukemic cells

β-Adrenoreceptor Stimulation Mediates Reconsolidation of Social Reward-Related Memories

In recent years, the notion that consolidated memories become transiently unstable after retrieval and require reconsolidation to persist for later use has received strong experimental support. To date, the majority of studies on reconsolidation have focused on memories of negative emotions, while the dynamics of positive memories have been less well studied. Social play, the most characteristic social behavior displayed by young mammals, is important for social and cognitive development. It has strong rewarding properties, illustrated by the fact that it can induce conditioned place preference (CPP). In order to understand the dynamics of positive social memories, we evaluated the effect of propranolol, a β-adrenoreceptor antagonist known to influence a variety of memory processes, on acquisition, consolidation, retrieval and reconsolidation of social play-induced CPP in adolescent rats.Systemic treatment with propranolol, immediately before or after a CPP test (i.e. retrieval session), attenuated CPP 24 h later. Following extinction, CPP could be reinstated in saline--but not in propranolol-treated rats, indicating that propranolol treatment had persistently disrupted the CPP memory trace. Propranolol did not affect social play-induced CPP in the absence of memory retrieval or when administered 1 h or 6 h after retrieval. Furthermore, propranolol did not affect acquisition, consolidation or retrieval of social play-induced CPP.We conclude that β-adrenergic neurotransmission selectively mediates the reconsolidation, but not other processes involved in the storage and stability of social reward-related memories in adolescent rats. These data support the notion that consolidation and reconsolidation of social reward-related memories in adolescent rats rely on distinct neural mechanisms