Caregivers' experiences and coping strategies relating to patient's subjective treatment-related cognitive impairment following Haematopoietic Stem Cell Transplant (HSCT)

The treatments involved in cancers of the blood and bone marrow can be physically and psychologically challenging and be associated with adverse secondary effects, including cognitive impairment. The incidence and severity of treatment-related cognitive impairment varies widely, however it can significantly impact quality of life by interfering with patients’ activities of daily living, relationships and future plans. It can also pose challenges for the patients’ caregivers, an area which has received comparatively less research attention. The aim of this study was to investigate caregivers’ experiences of treatment-related cognitive impairment in patients who have undergone Haematopoietic Stem Cell Transplant (HSCT); how they coped, both practically and emotionally, and what supports they believe could help them. Participants were caregivers to individuals who had undergone HSCT within the past 20 years and who had reported cognitive changes at the HSCT Late Effects Clinic, Beatson West of Scotland Cancer Centre. Five participants completed a single semi-structured interview. The data was then analysed using Interpretative Phenomenological Analysis (IPA). Results of this analysis illustrated four super-ordinate themes: noticing change; managing expectations, managing personal feelings and commitment. Findings from the current study highlighted the importance of caregiver education regarding post HSCT cognitive and behavioural changes and providing caregiver emotional support. Future research should explore the mutual needs of both care recipient and caregiver.

Firepolished glass microtools for human embryonic stem cell (HESC) cultivation

Abstract not available

Graft versus host disease in oncology nursing practice

INTRODUCTION: Gastrointestinal graft-versus-host disease (GI-GvHD) is extremely debilitating and is multifactorial in its causative factors, management and treatment. It is an exaggeration of normal physiological mechanisms wherein the donor immune system attempts to rid itself of the host. The inflammatory process that follows has the benefit of providing an anti-tumour effect for many diseases, but unfortunately in patients undergoing human stem-cell transplantation, the nature of the inflammation can result in disability, wasting and death. AIM: The aim of this article is to discuss the pathophysiology of this often misunderstood or misdiagnosed condition, as well as its signs and symptoms, management and considerations for nursing care. Considerations for nursing practice: While the medical management is aimed at minimising GvHD through the reduction of T-cell production and proliferation and gastrointestinal decolonisation, the nursing care is often focused on the signs and symptoms that can have the most prominent impact on patients. CONCLUSION: GI-GvHD has serious life-threatening complications, namely wasting syndrome, diarrhoea and dehydration. The basis of signs and symptomology is easily recognisable owing to the stages of progression through the human stem-cell transplantation process. Oncology nurses are in a prime position to identify these serious risks, initiate treatment immediately and collaborate effectively within the multidisciplinary team to minimise GvHD onset and provide expert support to patients, family and caregivers.

Mesenchymal stromal cells transiently alter the inflammatory milieu post-transplant to delay graft-versus-host disease

Background: Multipotent mesenchymal stromal cells suppress T-cell function in vitro, a property that has underpinned their use in treating clinical steroid-refractory graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. However the potential of mesenchymal stromal cells to resolve graft-versus-host disease is confounded by a paucity of pre-clinical data delineating their immunomodulatory effects in vivo. Design and Methods: We examined the influence of timing and dose of donor-derived mesenchymal stromal cells on the kinetics of graft-versus-host disease in two murine models of graft-versus-host disease (major histocompatibility complex-mismatched: UBI-GFP/BL6 [H-2b]→BALB/c [H-2d] and the sibling transplant mimic, UBI-GFP/BL6 [H-2b]→BALB.B [H-2b]) using clinically relevant conditioning regimens. We also examined the effect of mesenchymal stromal cell infusion on bone marrow and spleen cellular composition and cytokine secretion in transplant recipients. Results: Despite T-cell suppression in vitro, mesenchymal stromal cells delayed but did not prevent graft-versus-host disease in the major histocompatibility complex-mismatched model. In the sibling transplant model, however, 30% of mesenchymal stromal cell-treated mice did not develop graft-versus-host disease. The timing of administration and dose of the mesenchymal stromal cells influenced their effectiveness in attenuating graft-versus-host disease, such that a low dose of mesenchymal stromal cells administered early was more effective than a high dose of mesenchymal stromal cells given late. Compared to control-treated mice, mesenchymal stromal cell-treated mice had significant reductions in serum and splenic interferon-γ, an important mediator of graft-versus-host disease. Conclusions: Mesenchymal stromal cells appear to delay death from graft-versus-host disease by transiently altering the inflammatory milieu and reducing levels of interferon-γ. Our data suggest that both the timing of infusion and the dose of mesenchymal stromal cells likely influence these cells’ effectiveness in attenuating graft-versus-host disease.

Survivorship care provision for patients with hematologic malignancies: The quest for quality evidence

This is an editorial that depicts the importance for developing more quality evidence to guide the survivorship care provision for patients with hematologic malignancies. Treatments for hematologic malignancies are often complex and debilitating, with increased risk of immune suppression and infections1. Some patients receive allogeneic stem cell transplantation that often requires in-patient stay of several weeks and life-long medical follow up. In recent years, advances in treatment regimens, and an aging population saw an increasing number of patients living with a hematologic malignancies or surviving curative therapy.2 The increased use of targeted therapies in hematologic malignancies (e.g. rituximab for non-Hodgkin lymphoma, bortezomib in multiple myeloma and imatinib in Chronic Myelogenous Leukemia has also resulted in improved overall survival...

Modern diagnosis of Epstein-Barr virus infections and post-transplant lymphoproliferative disease

Infection by Epstein-Barr virus (EBV) occurs in approximately 95% of the world s population. EBV was the first human virus implicated in oncogenesis. Characteristic for EBV primary infection are detectable IgM and IgG antibodies against viral capsid antigen (VCA). During convalescence the VCA IgM disappears while the VCA IgG persists for life. Reactivations of EBV occur both among immunocompromised and immunocompetent individuals. In serological diagnosis, measurement of avidity of VCA IgG separates primary from secondary infections. However, in serodiagnosis of mononucleosis it is quite common to encounter, paradoxically, VCA IgM together with high-avidity VCA IgG, indicating past immunity. We determined the etiology of this phenomenon and found that, among patients with cytomegalovirus (CMV) primary infection a large proportion (23%) showed antibody profiles of EBV reactivation. In contrast, EBV primary infection did not appear to induce immunoreactivation of CMV. EBV-associated post-transplant lymphoproliferative disease (PTLD) is a life threatening complication of allogeneic stem cell or solid organ transplantation. PTLD may present with a diverse spectrum of clinical symptoms and signs. Due to rapidity of PTLD progression especially after stem cell transplantation, the diagnosis must be obtained quickly. Pending timely detection, the evolution of the fatal disease may be halted by reduction of immunosuppression. A promising new PTLD treatment (also in Finland) is based on anti-CD-20 monoclonal antibodies. Diagnosis of PTLD has been demanding because of immunosuppression, blood transfusions and the latent nature of the virus. We set up in 1999 to our knowledge first in Finland for any microbial pathogen a real-time quantitative PCR (qPCR) for detection of EBV DNA in blood serum/plasma. In addition, we set up an in situ hybridisation assay for EBV RNA in tissue sections. In collaboration with a group of haematologists at Helsinki University Central Hospital we retrospectively determined the incidence of PTLD among 257 allogenic stem cell transplantations (SCT) performed during 1994-1999. Post-mortem analysis revealed 18 cases of PTLD. From a subset of PTLD cases (12/18) and a series of corresponding controls (36), consecutive samples of serum were studied by the new EBV-qPCR. All the PTLD patients were positive for EBV-DNA with progressively rising copy numbers. In most PTLD patients EBV DNA became detectable within 70 days of SCT. Of note, the appearance of EBV DNA preceded the PTLD symptoms (fever, lymphadenopathy, atypical lymphocytes). Among the SCT controls, EBV DNA occurred only sporadically, and the EBV-DNA levels remained relatively low. We concluded that EBV qPCR is a highly sensitive (100%) and specific (96%) new diagnostic approach. We also looked for and found risk factors for the development of PTLD. Together with a liver transplantation group at the Transplantation and Liver Surgery Clinic we wanted to clarify how often and how severely do EBV infections occur after liver transplantation. We studied by the EBV qPCR 1284 plasma samples obtained from 105 adult liver transplant recipients. EBV DNA was detected in 14 patients (13%) during the first 12 months. The peak viral loads of 13 asymptomatic patients were relatively low (<6600/ml), and EBV DNA subsided quickly from circulation. Fatal PTLD was diagnosed in one patient. Finally, we wanted to determine the number and clinical significance of EBV infections of various types occurring among a large, retrospective, nonselected cohort of allogenic SCT recipients. We analysed by EBV qPCR 5479 serum samples of 406 SCT recipients obtained during 1988-1999. EBV DNA was seen in 57 (14%) patients, of whom 22 (5%) showed progressively rising and ultimately high levels of EBV DNA (median 54 million /ml). Among the SCT survivors, EBV DNA was transiently detectable in 19 (5%) asymptomatic patients. Thereby, low-level EBV-DNA positivity in serum occurs relatively often after SCT and may subside without specific treatment. However, high molecular copy numbers (>50 000) are diagnostic for life-threatening EBV infection. We furthermore developed a mathematical algorithm for the prediction of development of life-threatening EBV infection.

Novel prognostic factors in chronic myeloid leukemia

Chronic myeloid leukemia (CML) is a malignant clonal blood disease that originates from a pluripotent hematopoietic stem cell. The cytogenetic hallmark of CML, the Philadelphia chromosome (Ph), is formed as a result of reciprocal translocation between chromosomes 9 and 22, which leads to a formation of a chimeric BCR-ABL fusion gene. The BCR-ABL protein is a constitutively active tyrosine kinase that changes the adhesion properties of cells, constitutively activates mitogenic signaling, enhances cell proliferation and reduces apoptosis. This results in leukemic growth and the clinical disease, CML. With the advent of targeted therapies against the BCR-ABL fusion protein, the treatment of CML has changed considerably during the recent decade. In this thesis, the clinical significance of different diagnostic methods and new prognostic factors in CML have been assessed. First, the association between two different methods for measuring CML disease burden (the RQ-PCR and the high mitotic index metaphase FISH) was assessed in bone marrow and peripheral blood samples. The correlation between positive RQ-PCR and metaphase FISH samples was high. However, RQ-PCR was more sensitive and yielded measurable transcripts in 40% of the samples that were negative by metaphase FISH. The study established a laboratory-specific conversion factor for setting up the International Scale when standardizing RQ-PCR measurements. Secondly, the amount of minimal residual disease (MRD) after allogeneic hematopoietic stem cell transplantation (alloHSCT) was determined. For this, metaphase FISH was done for the bone marrow samples of 102 CML patients. Most (68%), had no residual cells during the entire follow-up time. Some (12 %) patients had minor (<1%) MRD which decreased even further with time, whereas 19% had a progressive rise in MRD that exceeded 1% or had more than 1% residual cells when first detected. Residual cells did not become eradicated spontaneously if the frequency of Ph+ cells exceeded 1% during follow-up. Next, the impact of deletions in the derivative chromosome 9, was examined. Deletions were observed in 15% of the CML patients who later received alloHSCT. After alloHSCT, there was no difference in the total relapse rate in patients with or without deletions. Nor did the estimates of overall survival, transplant-related mortality, leukemia-free survival and relapse-free time show any difference between these groups. When conventional treatment regimens are used, the der(9) status could be an important criterion, in conjunction with other prognostic factors, when allogeneic transplantation is considered. The significance of der(9) deletions for patients treated with tyrosine kinase inhibitors is not clear and requires further investigation. In addition to the der(9) status of the patient, the significance of bone marrow lymphocytosis as a prognostic factor in CML was assessed. Bone marrow lymphocytosis during imatinib therapy was a positive predictive factor and heralded optimal response. When combined with major cytogenetic response at three months of treatment, bone marrow lymphocytosis predicted a prognostically important major molecular response at 18 months of imatinib treatment. Although the validation of these findings is warranted, the determination of the bone marrow lymphocyte count could be included in the evaluation of early response to imatinib treatment already now. Finally, BCR-ABL kinase domain mutations were studied in CML patients resistant against imatinib treatment. Point mutations detected in the kinase domain were the same as previously reported, but other sequence variants, e.g. deletions or exon splicing, were also found. The clinical significance of the other variations remains to be determined.

Dasatinib, nilotinib and standard-dose imatinib for the first line treatment of chronic myeloid leukaemia: Systematic reviews and economic analyses

- Background Nilotinib and dasatinib are now being considered as alternative treatments to imatinib as a first-line treatment of chronic myeloid leukaemia (CML). - Objective This technology assessment reviews the available evidence for the clinical effectiveness and cost-effectiveness of dasatinib, nilotinib and standard-dose imatinib for the first-line treatment of Philadelphia chromosome-positive CML. - Data sources Databases [including MEDLINE (Ovid), EMBASE, Current Controlled Trials, ClinicalTrials.gov, the US Food and Drug Administration website and the European Medicines Agency website] were searched from search end date of the last technology appraisal report on this topic in October 2002 to September 2011. - Review methods A systematic review of clinical effectiveness and cost-effectiveness studies; a review of surrogate relationships with survival; a review and critique of manufacturer submissions; and a model-based economic analysis. - Results Two clinical trials (dasatinib vs imatinib and nilotinib vs imatinib) were included in the effectiveness review. Survival was not significantly different for dasatinib or nilotinib compared with imatinib with the 24-month follow-up data available. The rates of complete cytogenetic response (CCyR) and major molecular response (MMR) were higher for patients receiving dasatinib than for those with imatinib for 12 months' follow-up (CCyR 83% vs 72%, p < 0.001; MMR 46% vs 28%, p < 0.0001). The rates of CCyR and MMR were higher for patients receiving nilotinib than for those receiving imatinib for 12 months' follow-up (CCyR 80% vs 65%, p < 0.001; MMR 44% vs 22%, p < 0.0001). An indirect comparison analysis showed no difference between dasatinib and nilotinib for CCyR or MMR rates for 12 months' follow-up (CCyR, odds ratio 1.09, 95% CI 0.61 to 1.92; MMR, odds ratio 1.28, 95% CI 0.77 to 2.16). There is observational association evidence from imatinib studies supporting the use of CCyR and MMR at 12 months as surrogates for overall all-cause survival and progression-free survival in patients with CML in chronic phase. In the cost-effectiveness modelling scenario, analyses were provided to reflect the extensive structural uncertainty and different approaches to estimating OS. First-line dasatinib is predicted to provide very poor value for money compared with first-line imatinib, with deterministic incremental cost-effectiveness ratios (ICERs) of between £256,000 and £450,000 per quality-adjusted life-year (QALY). Conversely, first-line nilotinib provided favourable ICERs at the willingness-to-pay threshold of £20,000-30,000 per QALY. - Limitations Immaturity of empirical trial data relative to life expectancy, forcing either reliance on surrogate relationships or cumulative survival/treatment duration assumptions. - Conclusions From the two trials available, dasatinib and nilotinib have a statistically significant advantage compared with imatinib as measured by MMR or CCyR. Taking into account the treatment pathways for patients with CML, i.e. assuming the use of second-line nilotinib, first-line nilotinib appears to be more cost-effective than first-line imatinib. Dasatinib was not cost-effective if decision thresholds of £20,000 per QALY or £30,000 per QALY were used, compared with imatinib and nilotinib. Uncertainty in the cost-effectiveness analysis would be substantially reduced with better and more UK-specific data on the incidence and cost of stem cell transplantation in patients with chronic CML. - Funding The Health Technology Assessment Programme of the National Institute for Health Research.

Concise review: Humanized models of tumor immunology in the 21st century: Convergence of cancer research and tissue engineering

Despite positive testing in animal studies, more than 80% of novel drug candidates fail to proof their efficacy when tested in humans. This is primarily due to the use of preclinical models that are not able to recapitulate the physiological or pathological processes in humans. Hence, one of the key challenges in the field of translational medicine is to “make the model organism mouse more human.” To get answers to questions that would be prognostic of outcomes in human medicine, the mouse's genome can be altered in order to create a more permissive host that allows the engraftment of human cell systems. It has been shown in the past that these strategies can improve our understanding of tumor immunology. However, the translational benefits of these platforms have still to be proven. In the 21st century, several research groups and consortia around the world take up the challenge to improve our understanding of how to humanize the animal's genetic code, its cells and, based on tissue engineering principles, its extracellular microenvironment, its tissues, or entire organs with the ultimate goal to foster the translation of new therapeutic strategies from bench to bedside. This article provides an overview of the state of the art of humanized models of tumor immunology and highlights future developments in the field such as the application of tissue engineering and regenerative medicine strategies to further enhance humanized murine model systems.

Lapsuusiän kantasolusiirrot HUS:ssa vuosina 1993-2006

Tutkielma kuvaa lapsuusiän kantasolusiirtojen merkittävimmät tulokset ja komplikaatiot keskeisissä tautiryhmissä modernin hoidon aikakaudella HUS:ssä. Aineistona on HUS:n Lasten ja nuorten sairaalan veri- ja syöpätautien sekä kantasolusiirtoyksikön potilaista kerätty, vuonna 1993 perustetun ProLapsi-rekisterin sisältämä kliininen kantasolusiirtoaineisto vuosilta 1993-2006. Aineisto sisältää runsaat 90% Suomessa tehdyistä lasten allogeenisista kantasolusiirroista (n=233) sekä kaikki HUS:in autologiset siirrot (n=117) ko. aikajaksolla. Tutkielma on toteutettu kvantitatiivisia tutkimusmenetelmiä käyttäen. Suurin allogeenisen kantasolusiirron saaneiden potilaiden diagnoosiryhmä oli akuutti lymfoblastileukemia, ja suurin autologisen kantasolusiirron saaneiden ryhmä neuroblastoomapotilaat. Allogeenisista kantasolusiirroista 38% tehtiin HLA-identtiseltä sukulaisluovuttajalta ja 53% rekisteriluovuttajan soluilla. Kumulatiivinen kokonaisselviytyminen oli merkitsevästi parempaa sukulaisluovuttajan soluilla tehdyissä siirroissa kuin rekisteriluovuttajan (p=0,003). Allogeenisen kantasolusiirron saaneista potilaista 71% sai jonkin asteisen akuutin ja 42% kroonisen käänteishyljinnän (GVHD). Sekä akuutin että kroonisen GVHD:n vaikeus puolestaan korreloi kuolleisuuteen. Allogeenisen kantasolusiirron pitkäaikaisvaikutusta arvioitiin seurantatietojen perusteella. 58%:lla elämänlaatu arvioitiin normaaliksi, 35%:lla hieman rajoittuneeksi ja 7%:lla heikoksi.

O adolescente frente ao transplante de células tronco-hematopoiéticas: contribuições para as ações do Enfermeiro na equipe multiprofissional

O câncer constitui um problema de saúde pública para o mundo desenvolvido e também para nações em desenvolvimento. Segundo a estimativa realizada pelo Inca para o ano de 2012, a partir dos dados dos Registros de Câncer de Base Populacional (RCBP), o percentual mediano dos tumores pediátricos encontrava-se próximo de 3%. Para o ano de 2012, com exceção dos tumores da pele não melanoma, estavam previstos 384.340 casos novos de câncer. Destes, ocorrerão cerca de 11.530 casos novos de câncer em crianças e adolescentes até os 19 anos. Este estudo teve por objeto as expectativas de vida do adolescente frente ao transplante de células tronco hematopoiéticas (TCTH) e como objetivos: descrever as expectativas dos adolescentes que se submeteram ao TCTH e analisar compreensivamente as expectativas de vida destes jovens que se submeteram ao TCTH. Trata-se de estudo de natureza qualitativa, pautado no referencial teórico-metodológico da fenomenologia sociológica de Alfred Schutz. O cenário para sua realização foi uma unidade de Transplante de Medula Óssea, localizada em um hospital federal de referência nacional, localizado na cidade do Rio de Janeiro. Os participantes do estudo foram oito adolescentes, na faixa etária entre 12 e 18 anos de idade, que se encontravam em fase pós-TCTH, em acompanhamento no hospital diariamente ou já de alta hospitalar da unidade. Para a realização do trabalho de campo, foi utilizada a entrevista fenomenológica como instrumento de captação das falas, as quais foram guiadas pelas seguintes questões orientadoras: fale para mim como foi esse período de adoecimento para você. Quais as suas expectativas em relação ao transplante de células tronco hematopoiéticas? O que você espera da sua vida diária/cotidiana agora após a realização do transplante de células tronco hematopoiéticas? As falas foram transcritas, analisadas para então serem categorizadas. A partir da análise compreensiva, emergiram quatro categorias: Ser curado; Ter uma vida normal; Ter uma profissão; Constituir família; e Apresentando o motivo porque. O estudo possibilitou através dos relatos dos adolescentes mergulhar e adentrar no seu universo de significados sobre o que eles esperam do TCTH para a apreensão do que pensam sobre a sua inserção no mundo da vida após a sua realização, como também remeteu para a ação profissional que vislumbra a atuação multidisciplinar na perspectiva do nós, na qual o adolescente, sua família e a equipe sejam parte integrantes desse processo.

Screening of genes related to ovary development in Chinese shrimp Fenneropenaeus chinensis by suppression subtractive hybridization

The ovary of triploid shrimp Fenneropenaeus chinensis was apparently impaired compared to that of the diploid shrimp at the same age. Therefore triploid shrimp ovary is possible to be taken as a model to understand the mechanism of ovary development of shrimp compared to that of the ovary of diploid shrimp at the same age. In the present study, a suppression subtractive hybridization (SSH) technique was applied to identify differentially expressed genes in the ovary between diploid and triploid shrimp. For the forward library (RNA from the ovary of triploid shrimp as the tester), 54 genes were identified. For the reverse library (RNA from the ovary of diploid shrimp as the tester), 16 genes were identified. The identified genes encoded proteins with multiple functions, including extracellular matrix components, cytoskeleton, cell growth and death, metabolism, genetic information processing, signal transduction/transport or immunity related proteins. Eleven differentially expressed genes were selected to be confirmed in the ovaries of triploid and diploid shrimp by semi-quantitative RT-PCR. Genes encoding spermatogonial stem-cell renewal factor, cytochrome c oxidase subunits I and II, clottable protein, antimicrobial peptide and transposase showed up-regulated expressions in the ovary of triploid shrimp. Genes encoding tubulin, cellular apoptosis susceptibility protein, farnesoic acid O-methyltransferase, thrombospondin and heat shock protein 90 genes showed higher expressions in the ovary of diploid shrimp. The differential expressions of the above genes are suggested to be related to the ovary development of shrimp. It will provide a new clue to uncover the molecular mechanisms underlying the ovarian development in penaeid shrimp. (C) 2010 Elsevier Inc. All rights reserved.

中国明对虾三倍体性腺发育机理的初步研究

三倍体培育是水产动物遗传改良的重要途径之一，它在提高养殖产量、改良品质方面发挥着重要作用。对虾三倍体在性腺发育和性别比率方面与二倍体之间存在明显差异。本论文对三倍体性腺发育的分子机理进行了初步探讨，为阐明甲壳动物的性腺发育和性别控制机理提供重要依据。本论文取得的主要进展如下： 利用联会复合体的分析技术，比较分析了雄性二倍体和三倍体中精母细胞的减数分裂行为。二倍体对虾具有典型的真核生物联会复合体的形态，联会复合体在二价体联会处沿同源染色体长轴分布；未见明显的异型性别染色体；三倍体对虾精母细胞的联会行为复杂，可见二价体、单价体、非同源联会的三价体、同源转换和同源区完全配对的双联会复合体等不同形态；三倍体对虾在晚粗线期普遍表现为三价体同源区完全配对的双联会复合体形态，这种联会行为可能是导致其产生 3n 倍性精子的关键原因。 利用抑制性消减杂交技术，建立了对虾二倍体和三倍体卵巢间的2个消减文库；在正向消减文库（以三倍体卵巢作为实验组，二倍体卵巢作为驱动组）中，鉴定到54个基因；在反向消减文库（以二倍体卵巢为实验组，三倍体卵巢为驱动组）中，鉴定到16个基因；选取11个差异表达的基因，利用半定量RT-PCR的方法对其在二倍体和三倍体卵巢间的表达进行了检测，均能很好地与消减结果相吻合；这些差异基因编码多种功能的蛋白，分析表明染色体的三倍化使三倍体卵巢中的基因调控网络受到了影响；为深入揭示维持卵巢正常发育的关键分子调控事件奠定了基础。 为进一步分析特定基因对对虾性腺发育的调控机制，选取了在对虾三倍体和二倍体卵巢中差异表达显著的 3 个不同基因，PCNA （proliferating cell nuclear antigen）、CAS/CSE1 （cellular apoptosis susceptibility protein/chromosome segregation 1）和 SSRF （spermatogonial stem-cell renewal factor），进行了相关研究分析，为深入探讨特定基因对对虾性腺发育的调控机制以及三倍体中的基因表达调控机制奠定了基础； 中国明对虾PCNA基因在增殖旺盛的性腺组织及造血组织中表达量最高；在二倍体卵巢中的表达水平显著高于三倍体卵巢；在不同病原刺激下的造血组织中的表达模式不同，与对虾对抗不同病原刺激的免疫反应相关；PCNA在序列上的高度保守性，提示了其功能的保守性；利用PCNA基因可以指示细胞的增殖活性的特点，将辅助我们在对虾发育生物学和二倍体、三倍体对虾比较发育生物学的研究； 中国明对虾CAS/CSE1基因在二倍体卵巢中高表达；在卵母细胞中，其mRNA大量分布于细胞质及细胞核周围；是早期胚胎发育的母源性因子；在其氨基酸序列的N端具有importin-β 家族蛋白的保守结构，提示其可能通过参与核质运输在发育过程中发挥重要作用；利用原核表达系统成功地对其进行了体外重组表达，为进一步在蛋白水平上的功能研究提供了条件； 中国明对虾SSRF（暂时命名）基因在三倍体卵巢中高表达；在正常二倍体对虾的神经组织中表达量最高，提示该基因在神经发育中可能发挥重要作用；在氨基酸序列上与胸苷磷酸化酶（TP）具有最高的相似性；利用原核表达系统成功地对其进行了体外重组表达，为进一步在蛋白水平上的功能研究奠定了基础；对对虾SSRF活性蛋白的酶活及功能验证亟待进行。

Exercise training can induce cardiac autophagy at end-stage chronic conditions: Insights from a graft-versus-host-disease mouse model

Chronic graft-versus-host disease (cGVHD) is a frequent cause of morbimortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and severely compromises patients' physical capacity. Despite the aggressive nature of the disease, aerobic exercise training can positively impact survival as well as clinical and functional parameters. We analyzed potential mechanisms underlying the recently reported cardiac function improvement in an exercise-trained cGVHD murine model receiving lethal total body irradiation and immunosuppressant treatment (Fiuza-Luces et al., 2013. Med Sci Sports Exerc 45, 1703-1711). We hypothesized that a cellular quality-control mechanism that is receiving growing attention in biomedicine, autophagy, was involved in such improvement. Our results suggest that exercise training elicits a positive autophagic adaptation in the myocardium that may help preserve cardiac function even at the end-stage of a devastating disease like cGVHD. These preliminary findings might provide new insights into the cardiac exercise benefits in chronic/debilitating conditions.

Factors associated with mortality in transplant patients with invasive aspergillosis.

BACKGROUND: Invasive aspergillosis (IA) is an important cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients. The purpose of this study was to evaluate factors associated with mortality in transplant patients with IA. METHODS: Transplant patients from 23 US centers were enrolled from March 2001 to October 2005 as part of the Transplant Associated Infection Surveillance Network. IA cases were identified prospectively in this cohort through March 2006, and data were collected. Factors associated with 12-week all-cause mortality were determined by logistic regression analysis and Cox proportional hazards regression. RESULTS: Six-hundred forty-two cases of proven or probable IA were evaluated, of which 317 (49.4%) died by the study endpoint. All-cause mortality was greater in HSCT patients (239 [57.5%] of 415) than in SOT patients (78 [34.4%] of 227; P<.001). Independent poor prognostic factors in HSCT patients were neutropenia, renal insufficiency, hepatic insufficiency, early-onset IA, proven IA, and methylprednisolone use. In contrast, white race was associated with decreased risk of death. Among SOT patients, hepatic insufficiency, malnutrition, and central nervous system disease were poor prognostic indicators, whereas prednisone use was associated with decreased risk of death. Among HSCT or SOT patients who received antifungal therapy, use of an amphotericin B preparation as part of initial therapy was associated with increased risk of death. CONCLUSIONS: There are multiple variables associated with survival in transplant patients with IA. Understanding these prognostic factors may assist in the development of treatment algorithms and clinical trials.