Surgical outcomes of patients with neuroblastoma in a tertiary centre in Hong Kong: A 12-year experience

Introduction: Neuroblastoma has a heterogeneous clinical course. The prognosis varies widely depending on the age of diagnosis, extent of disease and tumour biology. However, the specific clinical outcome of this disease in Hong Kong has not been well characterised thus far. Complete tumour excision has been demonstrated to confer survival benefit on patients with advanced disease even if there is metastasis. Since year 2004, we have adopted a revised, more aggressive surgical approach in managing these patients. Here, we aim to review our experience in the management of this disease. Methods: A retrospective review was performed for the past 12 years to include all patients who presented with neuroblastoma in our institution. Data such as the survival, age at diagnosis, MYCN amplification status, the extent of tumour excision, and stage of the disease were recorded and analysed. Results: 37 patients were included in this study. Overall survival of our patients was 67.6%. Patients with Stage 1, 2 and 4S have 100% survival whereas stage 4 patients only have 41.4% survival. Since our revised surgical approach in 2004, patients who had been operated had a better survival. Survival of stage 4 patients with operation after 2004 was 57.1% whereas the survival of patients at the same stage before 2004 was only 30%. Age at diagnosis, completeness of tumour excision and stage of disease are also correlated with overall prognosis. Further, patients with the presence of MYCN gene amplification have apparently poorer survival but it is not statistically significant due to the small sample size. Conclusion: The management of patients with neuroblastoma remains a challenge. Advanced stage of disease, incomplete tumour excision and increased age at diagnosis were all associated with poor survival. We demonstrated a better survival for those who underwent a more aggressive surgical approach, though this is a technically demanding and time consuming procedure. Thus, the management of advanced neuroblastoma should be centralised in a centre with combined surgical, oncological and paediatric intensive care expertise.published_or_final_versio

Soy Isoflavones Genistein and Daidzein Exert Anti-Apoptotic Actions via a Selective ER-mediated Mechanism in Neurons following HIV-1 Tat1–86 Exposure

HIV-1 viral protein Tat partially mediates the neural dysfunction and neuronal cell death associated with HIV-1 induced neurodegeneration and neurocognitive disorders. Soy isoflavones provide protection against various neurotoxic insults to maintain neuronal function and thus help preserve neurocognitive capacity.We demonstrate in primary cortical cell cultures that 17β-estradiol or isoflavones (genistein or daidzein) attenuate Tat(1-86)-induced expression of apoptotic proteins and subsequent cell death. Exposure of cultured neurons to the estrogen receptor antagonist ICI 182,780 abolished the anti-apoptotic actions of isoflavones. Use of ERα or ERβ specific antagonists determined the involvement of both ER isoforms in genistein and daidzein inhibition of caspase activity; ERβ selectively mediated downregulation of mitochondrial pro-apoptotic protein Bax. The findings suggest soy isoflavones effectively diminished HIV-1 Tat-induced apoptotic signaling.Collectively, our results suggest that soy isoflavones represent an adjunctive therapeutic option with combination anti-retroviral therapy (cART) to preserve neuronal functioning and sustain neurocognitive abilities of HIV-1 infected persons

Viral epidemics in a cell culture: novel high resolution data and their interpretation by a percolation theory based model

Because of its relevance to everyday life, the spreading of viral infections has been of central interest in a variety of scientific communities involved in fighting, preventing and theoretically interpreting epidemic processes. Recent large scale observations have resulted in major discoveries concerning the overall features of the spreading process in systems with highly mobile susceptible units, but virtually no data are available about observations of infection spreading for a very large number of immobile units. Here we present the first detailed quantitative documentation of percolation-type viral epidemics in a highly reproducible in vitro system consisting of tens of thousands of virtually motionless cells. We use a confluent astroglial monolayer in a Petri dish and induce productive infection in a limited number of cells with a genetically modified herpesvirus strain. This approach allows extreme high resolution tracking of the spatio-temporal development of the epidemic. We show that a simple model is capable of reproducing the basic features of our observations, i.e., the observed behaviour is likely to be applicable to many different kinds of systems. Statistical physics inspired approaches to our data, such as fractal dimension of the infected clusters as well as their size distribution, seem to fit into a percolation theory based interpretation. We suggest that our observations may be used to model epidemics in more complex systems, which are difficult to study in isolation.Comment: To appear in PLoS ONE. Supporting material can be downloaded from http://amur.elte.hu/BDGVirus

Agent-Based Modeling of Endotoxin-Induced Acute Inflammatory Response in Human Blood Leukocytes

Inflammation is a highly complex biological response evoked by many stimuli. A persistent challenge in modeling this dynamic process has been the (nonlinear) nature of the response that precludes the single-variable assumption. Systems-based approaches offer a promising possibility for understanding inflammation in its homeostatic context. In order to study the underlying complexity of the acute inflammatory response, an agent-based framework is developed that models the emerging host response as the outcome of orchestrated interactions associated with intricate signaling cascades and intercellular immune system interactions.An agent-based modeling (ABM) framework is proposed to study the nonlinear dynamics of acute human inflammation. The model is implemented using NetLogo software. Interacting agents involve either inflammation-specific molecules or cells essential for the propagation of the inflammatory reaction across the system. Spatial orientation of molecule interactions involved in signaling cascades coupled with the cellular heterogeneity are further taken into account. The proposed in silico model is evaluated through its ability to successfully reproduce a self-limited inflammatory response as well as a series of scenarios indicative of the nonlinear dynamics of the response. Such scenarios involve either a persistent (non)infectious response or innate immune tolerance and potentiation effects followed by perturbations in intracellular signaling molecules and cascades.The ABM framework developed in this study provides insight on the stochastic interactions of the mediators involved in the propagation of endotoxin signaling at the cellular response level. The simulation results are in accordance with our prior research effort associated with the development of deterministic human inflammation models that include transcriptional dynamics, signaling, and physiological components. The hypothetical scenarios explored in this study would potentially improve our understanding of how manipulating the behavior of the molecular species could manifest into emergent behavior of the overall system

Heparan sulfates upregulate regeneration of transected sciatic nerves of adult guinea pigs

An acoustic microscope has been proven to be a very effective tool for visualization and characterization of small internal defects in solids[l]. The distinction of internal defects such as cracks and voids from solid inclusions is sometimes necessary for material evaluation. For example in case of light metal casting alloys ultrasonic scattered echo from pores and heavy metal inclusions used for strengthening purposes can give the ultrasonic signal of the same order of magnitude [2]. In this paper it is shown how the phase information of the reflected echo can be used to distinguish void signals from solid inclusion signals. Conventional acoustic imaging techniques that use only amplitude information and ignores the phase information can not distinguish between voids and inclusions