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

Probing the short range spin dependent interactions by polarized 3^{3} 3 He atom beams

Experiments using polarized 3He atom beams to search for short range spin dependent forces are proposed. High intensity, high polarization, small beam size 3He atom beams have been successfully produced and used in surface science researches. By incorporating background reduction designs as combination shielding by µ-metal and superconductor and double beam paths, the precision of spin rotation angle per unit length could be improved by a factor of ~104. By this precision, in combination with a high density and low magnetic susceptibility sample source mass, and reversing one beam path if necessary, sensitivities on three different types of spin dependent interactions could be improved by as much as ~102 to ~108 over the current experiments at the millimeter range

Effects of regular salt marsh haying on marsh plants, algae, invertebrates and birds at Plum Island Sound, Massachusetts

Author Posting. © The Author(s), 2009. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Wetlands Ecology and Management 17 (2009): 469-487, doi: 10.1007/s11273-008-9125-3.The haying of salt marshes, a traditional activity since colonial times in New England, still occurs in about 400 ha of marsh in the Plum Island Sound estuary in northeastern Massachusetts. We took advantage of this haying activity to investigate how the periodic large-scale removal of aboveground biomass affects a number of marsh processes. Hayed marshes were no different from adjacent reference marshes in plant species density (species per area) and end-of-year aboveground biomass, but did differ in vegetation composition. Spartina patens was more abundant in hayed marshes than S. alterniflora, and the reverse was true in reference marshes. The differences in relative covers of these plant species were not associated with any differences between hayed and reference marshes in the elevations of the marsh platform. Instead it suggested that S. patens was more tolerant of haying than S. alterniflora. S. patens had higher stem densities in hayed marshes than it did in reference marshes, suggesting that periodic cutting stimulated tillering of this species. Although we predicted that haying would stimulate benthic chlorophyll production by opening up the canopy, we found differences to be inconsistent, possibly due to the relatively rapid regrowth of S. patens and to grazing by invertebrates on the algae. The pulmonate snail, Melampus bidendatus was depleted in its δ13C content in the hayed marsh compared to the reference, suggesting a diet shift to benthic algae in hayed marshes. The stable isotope ratios of a number of other consumer species were not affected by haying activity. Migratory shorebirds cue in to recently hayed marshes and may contribute to short term declines in some invertebrate species, however the number of taxa per unit area of marsh surface invertebrates and their overall abundances were unaffected by haying over the long term. Haying had no impact on nutrient concentrations in creeks just downstream from hayed plots, but the sediments of hayed marshes were lower in total N and P compared to references. In sum, haying appeared to affect plant species composition but had only short-term affects on consumer organisms. This contrasts with many grassland ecosystems, where an intermediate level of disturbance, such as by grazing, increases species diversity and may stimulate productivity. From a management perspective, periodic mowing could be a way to maintain S. patens habitats and the suite of species with which they are associated.This research was supported by the Plum Island Ecosystem Long Term Ecological Research program (OCE-972692 and OCE 0423565) of the National Science Foundation (NSF). J. Horowitz and J. Ludlam were supported by NSF Research Experience for Undergraduate (REU) grants when they were students at Hampshire College and Gordon College respectively

Reactive Oxygen Species Suppress Cardiac NaV1.5 Expression through Foxo1

NaV1.5 is a cardiac voltage-gated Na+ channel αsubunit and is encoded by the SCN5a gene. The activity of this channel determines cardiac depolarization and electrical conduction. Channel defects, including mutations and decrease of channel protein levels, have been linked to the development of cardiac arrhythmias. The molecular mechanisms underlying the regulation of NaV1.5 expression are largely unknown. Forkhead box O (Foxo) proteins are transcriptional factors that bind the consensus DNA sequences in their target gene promoters and regulate the expression of these genes. Comparative analysis revealed conserved DNA sequences, 5′-CAAAACA-3′ (insulin responsive element, IRE), in rat, mouse and human SCN5a promoters with the latter two containing two overlapping Foxo protein binding IREs, 5′-CAAAACAAAACA-3′. This finding led us to hypothesize that Foxo1 regulates NaV1.5 expression by directly binding the SCN5a promoter and affecting its transcriptional activity. In the present study, we determined whether Foxo1 regulates NaV1.5 expression at the transcriptional level and also defined the role of Foxo1 in hydrogen peroxide (H2O2)-mediated NaV1.5 suppression in HL-1 cardiomyocytes using chromatin immunoprecipitation (ChIP), constitutively nuclear Foxo1 expression, and RNAi Foxo1 knockdown as well as whole cell voltage-clamp recordings. ChIP with anti-Foxo1 antibody and follow-up semi-quantitative PCR with primers flanking Foxo1 binding sites in the proximal SCN5a promoter region clearly demonstrated enrichment of DNA, confirming Foxo1 recruitment to this consensus sequence. Foxo1 mutant (T24A/S319A-GFP, Foxo1-AA-GFP) was retained in nuclei, leading to a decrease of NaV1.5 expression and Na+ current, while silencing of Foxo1 expression by RNAi resulted in the augmentation of NaV1.5 expression. H2O2 significantly reduced NaV1.5 expression by promoting Foxo1 nuclear localization and this reduction was prevented by RNAi silencing Foxo1 expression. These studies indicate that Foxo1 negatively regulates NaV1.5 expression in cardiomyocytes and reactive oxygen species suppress NaV1.5 expression through Foxo1

Protective Effector Memory CD4 T Cells Depend on ICOS for Survival

Memory CD4 T cells play a vital role in protection against re-infection by pathogens as diverse as helminthes or influenza viruses. Inducible costimulator (ICOS) is highly expressed on memory CD4 T cells and has been shown to augment proliferation and survival of activated CD4 T cells. However, the role of ICOS costimulation on the development and maintenance of memory CD4 T cells remains controversial. Herein, we describe a significant defect in the number of effector memory (EM) phenotype cells in ICOS−/− and ICOSL−/− mice that becomes progressively more dramatic as the mice age. This decrease was not due to a defect in the homeostatic proliferation of EM phenotype CD4 T cells in ICOS−/− or ICOSL−/− mice. To determine whether ICOS regulated the development or survival of EM CD4 T cells, we utilized an adoptive transfer model. We found no defect in development of EM CD4 T cells, but long-term survival of ICOS−/− EM CD4 T cells was significantly compromised compared to wild-type cells. The defect in survival was specific to EM cells as the central memory (CM) ICOS−/− CD4 T cells persisted as well as wild type cells. To determine the physiological consequences of a specific defect in EM CD4 T cells, wild-type and ICOS−/− mice were infected with influenza virus. ICOS−/− mice developed significantly fewer influenza-specific EM CD4 T cells and were more susceptible to re-infection than wild-type mice. Collectively, our findings demonstrate a role for ICOS costimulation in the maintenance of EM but not CM CD4 T cells

Genome-Scale Modeling of Light-Driven Reductant Partitioning and Carbon Fluxes in Diazotrophic Unicellular Cyanobacterium Cyanothece sp. ATCC 51142

Genome-scale metabolic models have proven useful for answering fundamental questions about metabolic capabilities of a variety of microorganisms, as well as informing their metabolic engineering. However, only a few models are available for oxygenic photosynthetic microorganisms, particularly in cyanobacteria in which photosynthetic and respiratory electron transport chains (ETC) share components. We addressed the complexity of cyanobacterial ETC by developing a genome-scale model for the diazotrophic cyanobacterium, Cyanothece sp. ATCC 51142. The resulting metabolic reconstruction, iCce806, consists of 806 genes associated with 667 metabolic reactions and includes a detailed representation of the ETC and a biomass equation based on experimental measurements. Both computational and experimental approaches were used to investigate light-driven metabolism in Cyanothece sp. ATCC 51142, with a particular focus on reductant production and partitioning within the ETC. The simulation results suggest that growth and metabolic flux distributions are substantially impacted by the relative amounts of light going into the individual photosystems. When growth is limited by the flux through photosystem I, terminal respiratory oxidases are predicted to be an important mechanism for removing excess reductant. Similarly, under photosystem II flux limitation, excess electron carriers must be removed via cyclic electron transport. Furthermore, in silico calculations were in good quantitative agreement with the measured growth rates whereas predictions of reaction usage were qualitatively consistent with protein and mRNA expression data, which we used to further improve the resolution of intracellular flux values

Maturation-Dependent Licensing of Naive T Cells for Rapid TNF Production

The peripheral naïve T cell pool is comprised of a heterogeneous population of cells at various stages of development, which is a process that begins in the thymus and is completed after a post-thymic maturation phase in the periphery. One hallmark of naïve T cells in secondary lymphoid organs is their unique ability to produce TNF rapidly after activation and prior to acquiring other effector functions. To determine how maturation influences the licensing of naïve T cells to produce TNF, we compared cytokine profiles of CD4+ and CD8+ single positive (SP) thymocytes, recent thymic emigrants (RTEs) and mature-naïve (MN) T cells during TCR activation. SP thymocytes exhibited a poor ability to produce TNF when compared to splenic T cells despite expressing similar TCR levels and possessing comparable activation kinetics (upregulation of CD25 and CD69). Provision of optimal antigen presenting cells from the spleen did not fully enable SP thymocytes to produce TNF, suggesting an intrinsic defect in their ability to produce TNF efficiently. Using a thymocyte adoptive transfer model, we demonstrate that the ability of T cells to produce TNF increases progressively with time in the periphery as a function of their maturation state. RTEs that were identified in NG-BAC transgenic mice by the expression of GFP showed a significantly enhanced ability to express TNF relative to SP thymocytes but not to the extent of fully MN T cells. Together, these findings suggest that TNF expression by naïve T cells is regulated via a gradual licensing process that requires functional maturation in peripheral lymphoid organs