A serine proteinase PmClipSP2 contributes to prophenoloxidase system and plays a protective role in shrimp defense by scavenging lipopolysaccharide

Serine proteinases (SPs) participate in various biological processes and play vital role in immunity. In this study, we investigated the function of PmClipSP2 from shrimp Penaeus monodon in defense against bacterial infection. PmClipSP2 was identified as a clip-domain SP and its mRNA increased in response to infection with Vibrio harveyi. PmClipSP2-knockdown shrimp displayed a significantly reduced phenoloxidase (PO) activity and increased susceptibility to V. harveyi infection. Injection of LPS and/or β-1,3-glucan induced a dose-dependent mortality and a significant decrease in the number of total hemocytes, with clear morphological changes in the hemocyte surface, of the PmClipSP2-knockdown shrimp. Recombinant PmClipSP2 was shown to bind to LPS and β-1,3-glucan and to activate PO activity. These results reveal that PmClipSP2 acts as a pattern-recognition protein, binding to microbial polysaccharides and likely activating the proPO system, whilst it may play an essential role in the hemocyte homeostasis by scavenging LPS and neutralizing its toxicity.     

Disseminated histoplasmosis in a kidney transplant patient

Patients with impaired cell‐mediated immunity have a higher risk of developing histoplasmosis; however, histoplasmosis after solid organ transplantation is rare. In Thailand, histoplasmosis cases are sporadic, and most cases are associated with human immunodeficiency virus (HIV) infection. Herein, we report a case of disseminated histoplasmosis in a kidney transplant Thai recipient diagnosed by fungal staining of fungal culture from bronchoalveolar lavage and bone marrow biopsy. Liposomal amphotericin B was given followed by oral itraconazole. The patient's clinical condition was improved; however, his graft function was irreversibly declined. The majority of histoplasmosis cases after solid organ transplant presented with disseminated disease with pulmonary involvement. Even in a non‐endemic area of histoplasmosis, suspected cases should be early diagnosed and promptly managed in order to reduce morbidity and mortality, especially in cell‐mediated immunity defect patients like solid organ transplant recipients.     

Anti-Proliferative Effect of Doxorubicin-Loaded AS1411 Aptamer on Colorectal Cancer Cell

Background: Doxorubicin (Dox) inhibits DNA replication and causes DNA damage resulting in cell death. It is a common drug for treatment of many cancers. Treatment efficacy and side effects of Dox are critical issues in using it because the drug lacks of specificity. The objective of this study was to improve the specificity of Dox by the incorporation of this drug with AS1411 aptamer (ASA). Methods: Dox was intercalated into the duplex sites of ASA, a recognition molecule for a number of cancer cells, and formed Dox-loaded ASA. The recognition ability proceeded through specific binding between the aptamer and nucleolin overexpressed in the cancer cells. The tested cells were human colorectal adenocarcinoma cell line (SW480) and human normal colon cell CCD841 CoN (CCD841). Binding of ASA to the cells was tested using flow cytometer and fluorescence microscope. Intercalation of Dox into DNA duplex was confirmed by fluorescence spectrometry. Effect of ASA, Dox, and Dox-loaded ASA on cell viability was examined by cell proliferation assay. Caspase-3 activation was analyzed by western blotting. Results: ASA bound specifically to SW480 cells via interaction between the aptamer and nucleolin because the nucleolin was highly expressed in SW480 cells. ASA decreased the viability of SW480 cells in a dose-dependent manner. Dox was more toxic than ASA. Fluorescence quenching revealed that Dox was able to intercalate in base pairing sites of the aptamer. Dox-loaded ASA inhibited the proliferation of SW480 cells, because the aptamer facilitated the Dox uptake into these cells which caused the cell apoptosis, indicated by the significant decrease in procaspase-3, apoptosis marker protein. Conclusion: This study succeeded to prepare Dox-loaded ASA by intercalation of the drug that inherited the binding function from the aptamer and anti-cancer activity from Dox. Dox-loaded ASA showed promise for effective cancer treatment with lower level of side effects.     

中、低收入国家卫生智囊团的实践经验影响政策改变

近年来,中、低收入国家独立卫生政策研究机构的数量与日俱增,原因在于政府研究能力有限和民主化进程中的压力。本研究的目标是：（1）调查中﹑低收入国家中卫生政策研究机构对卫生政策的议程设置﹑制定﹑执行、监管和评估所作的贡献;（2）评估包括组织形式和结构在内的哪些因素支持中﹑低收入国家的卫生政策研究机构对卫生政策发挥积极作用。本研究在孟加拉﹑加纳﹑印度﹑南非﹑乌干达和越南选取了6家卫生政策研究机构开展案例研究,研究对象包括两个非政府组织、两所大学和两个政府办政策研究机构。案例研究通过文献查阅、财务信息分析、对工作人员和其他利益相关人员进行半结构式访谈,以及对结论草案进行多次反馈等方式开展。其中有些机构对他们各自国家的政策发展作出了巨大贡献。这些机构都积极建言献策,多数从事与政策相关的研究,而开展政治对话﹑系统评价或委托性研究的机构则相对较少。这些机构所开展的工作大多以政府或出资人的需求为导向,多数机构的主要成果一般为研究报告,经常与面向政府官员的口头汇报相结合。在支持对政策的有效参与方面,有几个关键因素,其中包括支持性的政策环境﹑管理和财务的相对独立性,以及与决策者建立可增进信任和影响的密切关系。当研究机构与政府之间的正式关系未处在重要位置时,政府内部单位则面临相当大的困难。     

Randomized study of intradermal compared to intramuscular hepatitis B vaccination in HIV-infected children without severe immunosuppression

HIV infected individuals have poorer response to hepatitis B vaccine (HBV) compared to normal host. Intradermal administration (ID) facilitates the exposure of antigen to antigen-presenting cells compared to intramuscular administration (IM).HIV-infected children aged 1-18 years with CD4% ≥ 15% or 200 cells/mm³ who had negative HBs Ag, antiHBs, and antiHBc were randomized to receive 3-dose of HBV via ID (2 μg/dose) or IM (10 μg/dose) route at months 0, 2, and 6. AntiHBs titers were measured at months 2, 6 and 7 after first HBV. AntiHBs ≥ 10 mIU/mL was considered protective and AntiHBs > 100 mIU/mL was considered good response.Participants included 41 in ID and 39 in IM arms. 64% had completed 3-doses HBV during infancy. The mean (SD) of age, nadir CD4% and current CD4% were 12 (3.3) years, 10.6 (7.9)% and 28 (8.0)% respectively. 91% were on HAART and 84% had undetectable HIV-RNA.Proportion of children with protective antiHBs in ID vs. IM group were 19.5% vs. 25.6% at month 2, 56.1% vs. 76.9% at month 6, and 90.2% vs. 92.3% at month 7 (NS, all). The geometric mean (95% confidence interval) of antiHBs titer in ID vs. IM group were 112.5 (34.4-367.6) vs. 141.2 (49.4-404.1) mIU/mL at month 2 (p = 0.74), 70.4 (39.8-124.4) vs. 132.1 (79.4-219.8) mIU/mL at month 6 (p = 0.10), and 157.0 (103.0-239.3) vs. 458.9 (324.0-647.0) mIU/mL at month 7 (p < 0.001). However, only 56.1% of the ID arm had good response to HBV compared to 82.1% in the IM arm (p = 0.01). The predictors for being a good responder to HBV were IM administration [OR 4.0, 95%CI 1.4-11.8, p = 0.012] and body weight <35 kg at baseline [OR 3.8, 95%CI 1.3-10.8, p = 0.013]. No adverse events grade 3/4 occurred.In conclusion, HIV-infected children without severe immune suppression, both ID and IM routes of HBV resulted in similar rates of protective antibody titers. However, high antibody titers to HBV were more common with IM; therefore, IM administration is preferred.     

Performance of Thailand’s universal health coverage scheme: Evaluating the effectiveness of annual public hearings

BackgroundLegislative provisions in Thailand''s National Health Security Act 2002 mandate annual public hearings for providers, beneficiaries and other stakeholders in order to improve the performance of the Universal Health Coverage Scheme (UCS).ObjectiveThis study aims to explore the annual public hearing process, evaluate its effectiveness and propose recommendations for improvement.MethodIn‐depth interviews were conducted with 29 key informants from various stakeholder groups involved in annual public hearings.ResultsThe evaluation showed that the public hearings fully met the criteria of influence over policy decision and partially met the criteria of appropriate participation approach and social learning. However, there are rooms for improvement on public hearing''s inclusiveness and representativeness of participants, adequacy of information and transparency.ConclusionsThree recommendations were proposed a) informing stakeholders in advance of the agenda and hearing process to enable their active participation; b) identifying experienced facilitators to navigate the discussions across stakeholders with different or conflicting interests, in order to reach consensus and prioritize recommendations; and c) communicating policy and management responses as a result of public hearings to all stakeholders in a timely manner.     

Studies on surface modification of polypropylene composite bipolar plates using an electroless deposition technique

A direct methanol fuel cell (DMFC) is predominantly noticeable because it can convert chemical energy directly into electrical energy with higher energy conversion efficiency (∼65%) compared to the efficiency of traditional combustion engines (40%) and with lower emissions. Henceforth, it is one of the new electrical generators that is becoming an important source of cleaner power in modern life. One of the key obstacles in designing and assembling the DMFC is contact resistance between interfaces of fuel cell components. A major source of the contact resistance in the DMFC arises from the contact between gas diffusion layers (GDLs) and the bipolar plates (BPs). A poor interface contact decreases the actual contact area, leading to an electrical voltage drop across these interfaces. Decreasing surface resistivity of BPs is one of the major approaches to reduce contact resistance in fuel cells. Present-day methods use a polypropylene composite as BPs to replace metallic or graphite BPs to reduce the overall weight of the DMFC stack. Unfortunately, polymeric composites typically provide higher surface resistance than the other BPs do. Coating copper on polypropylene composite plates was strategically manipulated by an electroless deposition (ELD) technique to decrease surface resistance. The coating process consists of pretreatment, adhesion improvement, and electroless deposition. Prior to ELD, the surfaces of the composite plates were treated by plasma treatment and then silanization was conducted using N-3-(trimetylpropylsilyl)diethylenetriamine (TMS) to improve adhesion. Palladium(ii) chloride (PdCl₂) was used as a catalyst for the ELD process. Successful modification of the surfaces was confirmed by morphology investigation via scanning electron microscopy, diagnoses of chemical surface characteristics using ATR-Fourier-transform infrared spectroscopy (ATR-FTIR) and X-ray photoelectron spectroscopy (XPS), physical surface characterizations with a contact angle measurement, electrical conductivity measurements, and surface adhesion test, while also observing corrosion behavior. In order to complete a viability study of using modified copper-coated BP for the DMFC, an in situ cell performance test was conducted. The results of the experiments pave the way for a feasible modification of the BP surfaces to be considered as suitable BPs for usage in fuel cells.

The DMFC is predominantly noticeable because it can convert chemical energy directly into electrical energy with higher energy conversion efficiency (∼65%) compared to the efficiency of traditional combustion engines (40%) and with lower emissions.     

Increased EphB2 expression predicts cholangiocarcinoma metastasis

The activation of Ephrin (Eph) receptors, the largest tyrosine kinase families of cell surface receptor, has recently been addressed in human cholangiocarcinoma (CCA). Therefore, the present study aimed to investigate the role of Eph receptors and its ligands in CCA. Of all 50 cases of human CCA tested, immunohistochemical staining demonstrated that EphB2, EphB4, ephrinB1, and ephrinB2 were 100 % positive in CCA tissues with overexpressions of the above proteins as 56, 56, 70, and 48 % of cases, respectively. High expression of EphB2 was significantly correlated with the metastatic status of patients (P?=?0.027). We also found that the high co-expression level of EphB2/ephrinB1 or EphB2/ephrinB2 were significantly correlated with the metastatic status of the patients (P?=?0.034 and P?=?0.024). Furthermore, we showed that the high co-expression level of EphB4/MVD and ephrinB1/MVD were significantly correlated with the metastasis status of CCA patients (P?=?0.012 and P?=?0.029). We further demonstrated that the EphB2 suppression using siRNA significantly reduced CCA cell migration by decreasing the phosphorylation of focal adhesion kinase (FAK) and paxillin. In conclusion, the upregulation of EphB2 receptors and its specific ligands (ephrinB1 and ephrinB2) leads to CCA metastasis. Suppression of EphB2 expression as well as inhibition of its downstream signaling proteins might serve as possible therapeutic strategies in human CCA.