Label-free imaging of zebrafish larvae in vivo by photoacoustic microscopy

Zebrafish play an important role in biological and biomedical research. Traditional in vivo imaging methods for studying zebrafish larvae primarily require fluorescence labeling. In this work, relying on tissue intrinsic optical absorption contrast, we acquired high resolution label-free 3D images of zebrafish larvae by using photoacoustic microscopy (PAM) in vivo. The spatial resolution reaches several microns, allowing the study of microstructures in various living organs. We demonstrated that our method has the potential to be a powerful non-invasive imaging method for studying various small animal models, including zebrafish larvae, Caenorhabditis elegans, frogs and drosophila larvae

East Asian Welfare States in Transition

Summaries After the spectacular economic crisis of late 1997, there has been a call for social welfare reform as well as economic restructuring in East Asia. Covering Japan, South Korea and Taiwan, this article first seeks to identify the strengths and weaknesses of the East Asian welfare states. Second, it examines the pressures for reform of the welfare systems. Finally, it addresses the question of whether the low spending East Asian welfare regimes will be maintained in the future. The strength.of the East Asian welfare states mainly lies in their promotion of an ideology of developmentalism and their relatively low cost; while their weakness is that they tend to reinforce socio?economic inequalities. Economic recession and socio?economic pressures as well as inefficiencies within the welfare states create pressure for change. The governments in Japan, South Korea and Taiwan have responded with reform measures appropriate to these nations' social and political context. Despite different policy responses, the welfare states in these countries will become more expensive, although they will remain low spenders among the developed nations

The price of tumor control: an analysis of rare side effects of anti-CTLA-4 therapy in metastatic melanoma from the ipilimumab network

Background: Ipilimumab, a cytotoxic T-lymphocyte antigen-4 (CTLA-4) blocking antibody, has been approved for the treatment of metastatic melanoma and induces adverse events (AE) in up to 64% of patients. Treatment algorithms for the management of common ipilimumab-induced AEs have lead to a reduction of morbidity, e.g. due to bowel perforations. However, the spectrum of less common AEs is expanding as ipilimumab is increasingly applied. Stringent recognition and management of AEs will reduce drug-induced morbidity and costs, and thus, positively impact the cost-benefit ratio of the drug. To facilitate timely identification and adequate management data on rare AEs were analyzed at 19 skin cancer centers. Methods and Findings: Patient files (n = 752) were screened for rare ipilimumab-associated AEs. A total of 120 AEs, some of which were life-threatening or even fatal, were reported and summarized by organ system describing the most instructive cases in detail. Previously unreported AEs like drug rash with eosinophilia and systemic symptoms (DRESS), granulomatous inflammation of the central nervous system, and aseptic meningitis, were documented. Obstacles included patientś delay in reporting symptoms and the differentiation of steroid-induced from ipilimumab-induced AEs under steroid treatment. Importantly, response rate was high in this patient population with tumor regression in 30.9% and a tumor control rate of 61.8% in stage IV melanoma patients despite the fact that some patients received only two of four recommended ipilimumab infusions. This suggests that ipilimumab-induced antitumor responses can have an early onset and that severe autoimmune reactions may reflect overtreatment. Conclusion: The wide spectrum of ipilimumab-induced AEs demands doctor and patient awareness to reduce morbidity and treatment costs and true ipilimumab success is dictated by both objective tumor responses and controlling severe side effects

A translational approach to studying preterm labour

Preterm labour continues to be a major contributor to neonatal and infant morbidity. Recent data from the USA indicate that the number of preterm deliveries (including those associated with preterm labour) has risen in the last 20 years by 30%. This increase is despite considerable efforts to introduce new therapies for the prevention and treatment of preterm labour and highlights the need to assess research in this area from a fresh perspective. In this paper we discuss i) the limitations of our knowledge concerning prediction, prevention and treatment of preterm labour and ii) future multidisciplinary strategies for improving our approach

Paleopolyploidy in the Brassicales: Analyses of the Cleome Transcriptome Elucidate the History of Genome Duplications in Arabidopsis and Other Brassicales

The analysis of the Arabidopsis genome revealed evidence of three ancient polyploidy events in the evolution of the Brassicaceae, but the exact phylogenetic placement of these events is still not resolved. The most recent event is called the At-α (alpha) or 3R, the intermediate event is referred to as the At-β (beta) or 2R, and the oldest is the At-γ (gamma) or 1R. It has recently been established that At-γ is shared with other Rosids, including papaya (Carica), poplar (Populus), and grape (Vitis), whereas data to date suggest that At-α is Brassicaceae specific. To address more precisely when the At-α and At-β events occurred and which plant lineages share these paleopolyploidizations, we sequenced and analyzed over 4,700 normalized expressed sequence tag sequences from the Cleomaceae, the sister family to the Brassicaceae. Analysis of these Cleome data with homologous sequences from other Rosid genomes (Arabidopsis, Carica, Gossypium, Populus, and Vitis) yielded three major findings: 1) confirmation of a Cleome-specific paleopolyploidization (Cs-α) that is independent of the Brassicaceae At-α paleopolyploidization; 2) Cleome and Arabidopsis share the At-β duplication, which is lacking from papaya within the Brassicales; and 3) rates of molecular evolution are faster for the herbaceous annual taxa Arabidopsis and Cleome than the other predominantly woody perennial Rosid lineages. These findings contribute to our understanding of the dynamics of genome duplication and evolution within one of the most comprehensively surveyed clades of plants, the Rosids, and clarify the complex history of the At-α, At-β, and At-γ duplications of Arabidopsis

Comparison of (semi-)automatic and manually adjusted measurements of left ventricular function in dual source computed tomography using three different software tools

To assess the accuracy of (semi-)automatic measurements of left ventricular (LV) functional parameters in cardiac dual-source computed tomography (DSCT) compared to manually adjusted measurements in three different workstations. Forty patients, who underwent cardiac DSCT, were included (31 men, mean age 58 ± 14 years). Multiphase reconstructions were made with ten series at every 10% of the RR-interval. LV function analysis was performed on three different, commercially available workstations. On all three workstations, end-systolic volume (ESV), end-diastolic volume (EDV), LV ejection fraction (LVEF) and myocardial mass (MM) were calculated as automatically as possible. With the same DSCT datasets, LV functional parameters were also calculated with as many manual adjustments as needed for accurate assessment for all three software tools. For both semi-automatic as well as manual methods, time needed for evaluation was recorded. Paired t-tests were employed to calculate differences in LV functional parameters. Repeated measurements were performed to determine intra-observer and inter-observer variability. (Semi-)automatic measurements revealed a good correlation with manually adjusted measurements for Vitrea (LVEF r = 0.93, EDV r = 0.94, ESV r = 0.98 and MM r = 0.94) and Aquarius (LVEF r = 0.96, EDV r = 0.94, ESV r = 0.98 and MM r = 0.96). Also, good correlation was obtained for Circulation, except for LVEF (LVEF r = 0.45, EDV r = 0.93, ESV r = 0.92 and MM r = 0.86). However, statistically significant differences were found between (semi-)automatically and manually adjusted measurements for LVEF (P < 0.05) and ESV (P < 0.001) in Vitrea, all LV functional parameters in Circulation (P < 0.001) and EDV, ESV and MM (<0.001) in Aquarius Workstation. (Semi-)automatic measurement of LV functional parameters is feasible, but significant differences were found for at least two different functional parameters in all three workstations. Therefore, expert manual correction is recommended at all times

Contrast-enhancement cardiac magnetic resonance imaging beyond the scope of viability

The clinical applications of cardiovascular magnetic resonance imaging with contrast enhancement are expanding. Besides the direct visualisation of viable and non-viable myocardium, this technique is increasingly used in a variety of cardiac disorders to determine the exact aetiology, guide proper treatment, and predict outcome and prognosis. In this review, we discuss the value of cardiovascular magnetic resonance imaging with contrast enhancement in a range of cardiac disorders, in which this technique may provide insights beyond the scope of myocardial viability

Transient integral boundary layer method to calculate the translesional pressure drop and the fractional flow reserve in myocardial bridges

BACKGROUND: The pressure drop – flow relations in myocardial bridges and the assessment of vascular heart disease via fractional flow reserve (FFR) have motivated many researchers the last decades. The aim of this study is to simulate several clinical conditions present in myocardial bridges to determine the flow reserve and consequently the clinical relevance of the disease. From a fluid mechanical point of view the pathophysiological situation in myocardial bridges involves fluid flow in a time dependent flow geometry, caused by contracting cardiac muscles overlying an intramural segment of the coronary artery. These flows mostly involve flow separation and secondary motions, which are difficult to calculate and analyse. METHODS: Because a three dimensional simulation of the haemodynamic conditions in myocardial bridges in a network of coronary arteries is time-consuming, we present a boundary layer model for the calculation of the pressure drop and flow separation. The approach is based on the assumption that the flow can be sufficiently well described by the interaction of an inviscid core and a viscous boundary layer. Under the assumption that the idealised flow through a constriction is given by near-equilibrium velocity profiles of the Falkner-Skan-Cooke (FSC) family, the evolution of the boundary layer is obtained by the simultaneous solution of the Falkner-Skan equation and the transient von-Kármán integral momentum equation. RESULTS: The model was used to investigate the relative importance of several physical parameters present in myocardial bridges. Results have been obtained for steady and unsteady flow through vessels with 0 – 85% diameter stenosis. We compare two clinical relevant cases of a myocardial bridge in the middle segment of the left anterior descending coronary artery (LAD). The pressure derived FFR of fixed and dynamic lesions has shown that the flow is less affected in the dynamic case, because the distal pressure partially recovers during re-opening of the vessel in diastole. We have further calculated the wall shear stress (WSS) distributions in addition to the location and length of the flow reversal zones in dependence on the severity of the disease. CONCLUSION: The described boundary layer method can be used to simulate frictional forces and wall shear stresses in the entrance region of vessels. Earlier models are supplemented by the viscous effects in a quasi three-dimensional vessel geometry with a prescribed wall motion. The results indicate that the translesional pressure drop and the mean FFR compares favourably to clinical findings in the literature. We have further shown that the mean FFR under the assumption of Hagen-Poiseuille flow is overestimated in developing flow conditions

Varicella zoster virus glycoprotein C increases chemokine-mediated leukocyte migration

Varicella zoster virus (VZV) is a highly prevalent human pathogen that establishes latency in neurons of the peripheral nervous system. Primary infection causes varicella whereas reactivation results in zoster, which is often followed by chronic pain in adults. Following infection of epithelial cells in the respiratory tract, VZV spreads within the host by hijacking leukocytes, including T cells, in the tonsils and other regional lymph nodes, and modifying their activity. In spite of its importance in pathogenesis, the mechanism of dissemination remains poorly understood. Here we addressed the influence of VZV on leukocyte migration and found that the purified recombinant soluble ectodomain of VZV glycoprotein C (rSgC) binds chemokines with high affinity. Functional experiments show that VZV rSgC potentiates chemokine activity, enhancing the migration of monocyte and T cell lines and, most importantly, human tonsillar leukocytes at low chemokine concentrations. Binding and potentiation of chemokine activity occurs through the C-terminal part of gC ectodomain, containing predicted immunoglobulin-like domains. The mechanism of action of VZV rSgC requires interaction with the chemokine and signalling through the chemokine receptor. Finally, we show that VZV viral particles enhance chemokine-dependent T cell migration and that gC is partially required for this activity. We propose that VZV gC activity facilitates the recruitment and subsequent infection of leukocytes and thereby enhances VZV systemic dissemination in humans