Factors associated with the overall survival of elderly patients with hepatocellular carcinoma

AIM:To identify the factors associated with overall survival of elderly patients with hepatocellular carcinoma(HCC).METHODS:A total of 286 patients with HCC(male/female:178/108,age:46-100 years),who were diagnosed and treated by appropriate therapeutic procedures between January 2000 and December 2010,were enrolled in this study.Patients were stratified into two groups on the basis of age:Elderly(≥ 75 years old) and non-elderly(< 75 years old).Baseline clinical characteristics as well as cumulative survival rates were then compared between the two groups.Univariate and multivariate analyses were used to identify the factors associated with prolonged overall survival of patients in each group.Cumulative survival rates in the two groups were calculated separately for each modified Japan Integrated Stage score(mJIS score) category by the Kaplan-Meier method.In addition,we compared the cumulative survival rates of elderly and non-elderly patients with good hepatic reserve capacity(≤ 2 points as per mJIS).RESULTS:In the elderly group,the proportion of female patients,patients with absence of hepatitis B or hepatitis C viral infection,and patients with coexisting extrahepatic comorbid illness was higher(56.8% vs 31.1%,P < 0.001;27.0% vs 16.0%,P = 0.038;33.8% vs 22.2%,P = 0.047;respectively) than that in the nonelderly group.In the non-elderly group,the proportion of hepatitis B virus(HBV)-infected patients was higher than that in the elderly group(9.4% vs 0%,P = 0.006).The cumulative survival rates in the elderly group were 53.7% at 3 years and 32.9% at 5 years,which were equivalent to those in the non-elderly group(55.9% and 39.4%,respectively),as shown by a log-rank test(P = 0.601).In multivariate analysis,prolonged survival was significantly associated with the extent of liver damage and stage(P < 0.001 and P < 0.001,respectively),but was not associated with patient age.However,on individual evaluation of factors in both groups,stage was significantly(P < 0.001) associated with prolonged survival.Regarding mJIS scores of ≤ 2,the rate of female patients with this score was higher in the elderly group when compared to that in the non-elderly group(P = 0.012) and patients ≥ 80 years of age tended to demonstrate shortened survival.CONCLUSION:Survival of elderly HCC patients was associated with liver damage and stage,but not age,except for patients ≥ 80 years with mJIS score ≤ 2.

Could quantitative liver function tests gain wide acceptance among hepatologists?

It has been emphasized that the assessment of residual liver function is of paramount importance to determine the following： severity of acute or chronic liver diseases independent of etiology; long-term prognosis; step-bystep disease progression; surgical risk; and efficacy of antiviral treatment. The most frequently used tools are the galactose elimination capacity to asses hepatocyte cytosol activity, plasma clearance of indocyanine green to assess excretory function, and antipyrine clearance to estimate microsomal activity. However, a widely accepted liver test （not necessarily a laboratory one） to assess quantitative functional hepatic reserve still needs to be established, although there have been various proposals. Furthermore, who are the operators that should order these tests？ Advances in analytic methods are expected to allow quantitative liver function tests to be used in clinical practice.

PRODUCTION IN PICHIAPASTORISAND CHARACTERIZATION OF GENETIC ENGINEERED CHIMERIC HBV/HEV VIRUS-LIKE PARTICLES

Objective To investigate the presentation of a neutralization epitope-containing peptide antigen of hepatitis E virus (HEV) on chimeric virus-like particles (VLPs) of hepatitis B surface antigen (HBsAg). MethodsThe gene fragment corresponding to amino acids (aa) 551-607 (HEnAg) of HEV capsid protein, which contains the only neutralization epitope identified to date, was fused via a synthetic glycine linker in frame with the gene of HBsAg. The resulted fusion gene was then integrated through transformation into the genome of Pichiapastorisunder the control of a methanol-induced alcohol oxidase 1 (AOX1) promoter and expressed intracellularly. The expression products in the soluble cell extracts were characterized by Western blot, ELISA, CsCl density gradient analysis, and electron microscopic visualiza-tion. Results The novel fusion protein incorporating HBsAg and the neutralization epitope-containing HEnAg was expressed successfully in Pichiapastoriswith an expected molecular weight of approximately 32 kD. It was found to possess the ability to assemble into chimeric HBV/HEV VLPs with immunological, physical and morphological characteristics akin to HBsAg particles. Not only did the chimeric VLPs show high activity levels in a HBsAg particle-specific ELISA but they were also strongly immunoreactive with hepatitis E (HE) positive human serum in a HEV specific ELISA, indicating that HEnAg peptide fragments were exposed on VLP surfaces and would be expected to be readily accessible by cells and molecules of the immune system. Similarity between chimeric VLPs to highly immunogenic HBsAg particles may confer good immuno-genicity on surface-displayed HEnAg. Conclusion The chimeric HBV/HEV VLPs produced in this study may have potential to be a recombinant HBV/HEV bivalent vaccine candidate.

Blood micronutrient, oxidative stress, and viral load in patients with chronic hepatitis C

AIM: To assess the extent of micronutrient and oxidative stress in blood and to examine their linkages with viral loads in chronic hepatitis C patients.METHODS: Hepatitis C virus (HCV)-RNA levels were quantified in the serum from 37 previously untreated patients with chronic hepatitis C. The plasma and erythrocyte micronutrients (zinc, selenium, copper, and iron) were estimated, and malondialdehyde (MDA)contents were determined as a marker to detect oxidative stress. Antioxidant enzymes, superoxide dismutase (SOD),glutathione peroxidase (GPX) and glutathione reductase (GR) activities in blood were also measured. The control group contained 31 healthy volunteers.RESULTS: The contents of zinc (Zn), and selenium (Se)in plasma and erythrocytes were significantly lower in hepatitis C patients than in the controls. On the contrary,copper (Cu) levels were significantly higher. Furthermore,plasma and erythrocyte MDA levels, and the SOD and GR activities in erythrocytes significantly increased in hepatitis C patients compared to the controls. However, the plasma GPX activity in patients was markedly lower. Plasma Se (r= -0.730, P<0.05), Cu (r = 0.635), and GPX (r = -0.675)demonstrated correlations with HCV-RNA loads. Significant correlation coefficients were also observed between HCV-RNA levels and erythrocyte Zn (r = -0.403), Se (r = -0.544), Cu (r = 0.701) and MDA (r = 0.629) and GR (r = 0.441).CONCLUSION: The levels of Zn, Se, Cu, and oxidative stress (MDA), as well as related anti-oxidative enzymes (GR and GPX) in blood have important impact on the viral factors in chronic hepatitis C. The distribution of these parameters might be significant biomarkers for HCV.

Impact of Hepatits B Vaccination as an Important Indicator for Immunization Program in Albania

Albania has been a country with a high prevalence of hepatitis B virus. Hepatitis B vaccine has been introduced nationwide in Albanian Immunization Program in 1994. Hepatitis B is given at birth, as a separate antigen, followed by three doses at 2, 4 and 6 months, where Hepatitis B, starting from 2009, is part of pentavalent vaccine of DTP-HepB-Hib. The aim of this study was to evaluate Immunization Program with Hepatitis B vaccination in order to prove program efficacy, increase public confidence in immunizations and advocate for sustainable immunization programs. Methodology was based on three components such as Immunization coverage surveys, serologic surveys and surveillance for acute cases of Hepatitis B. Results of this study showed that vaccination coverage is really high, more than 95% all over the country and with drop-out rates less than 10%. Anti-HBs levels in immunized children were very high in comparison with unimmunized ones. Incidence of HBV in children 0-14 years old is almost zero. Such results tell us that Hepatitis B vaccination is one of the most fruitful strategies for long term control of Hepatitis B disease.

Optimization of Sonication Process for High Newcastle Disease Virus （NDV） Titer

Cell disruption focuses on obtaining a desired bioproduct within a cell, and it is the cell wall that must be disrupted to allow access to the contents of the cell. In animal cells, the plasma membrane is the only barrier separating cell contents from the environment. Sound waves from sonication, a mechanical technique for cell disintegration, have been used to disrupt as well as to aggregate cells as a step towards purification of a desired bioproduct. In the present study, an improved sonication process for the high yield of Newcastle disease virus （NDV） propagated in tissue culture was described. DF-I cell was cultured in 25cm^2 T flask. When cells were about 80% confluent, a lentogenic strain of NDV （F strain） was used to infect the cell monolayer. With evident cytopathic effect, cells were subjected to cycles of freeze-thaw before sonicating with varying combinations of amplitude, temperature and time. Cells were sonicated using a water bath Sonicator, Jac Ultrasonic 1505 JEIO TECH 4 KHz. From ANOVA analysis, a significant interaction between sonication time and amplitude was observed. This also corresponds to the highest F value observed.

The Fallacy of Participation in Behaviour Change Programming： The Case of Gweru Women AIDS Prevention Association （GWAPA）, Zimbabwe

Gweru Women AIDS Prevention Association （GWAPA） is an organization that works with commercial sex-workers in the Midlands Province to try and stymie the tide of HIV/AIDS. The organization premises its activities upon the belief that sex workers are forced into prostitution by poverty and thus offers them alternative livelihood strategies such as piggery projects, chicken rearing, and vegetable vending projects as well as seed money with which to start flea market projects. The organization also runs a condom promotion project, a legal literacy project, and an advocacy project, all in a bid to empower the sex workers cognitively. The study was carried out between April and October 2008, using bar-based observations, interviews, focus group discussions, and documentary evidence. The study found participation to have been more of a fallacy in as far as programming depended more on the whims of donor funders than the actual needs of programme beneficiaries. In the top-down manner that is typical of development communication, the organization would engage donors and secure funding for certain projects which they would then try to convince the sex workers to take up, with mixed results. The research also found limited evidence of real empowerment of beneficiaries in the long run, with the sex workers themselves insisting that the ＂piece-meal＂ efforts of the organization were not sustainable enough to induce them to abandon sex work altogether. The study did, however, find that the organization and its programming had actually managed to score notable success in promoting safer sex within the context of prostitution, albeit without eradicating sex work altogether.

The Process of Policy Implementation： The Policy of HIV/AIDS Prevention in Youth Groups in Thailand

Thailand was implementing the policy of HIV/A1DS prevention in risky group, The youth is one of groups with sexual risk behaviors to HIV/AIDS. This research aims to elucidate the process of policy implementation at the national and regional levels, and to explain the obstacles of policy implementation. The method was qualitative study. The stakeholders were 88 people. The data were collected by in-depth interview and coded by a computer program. The policy was transferred from the national AIDS committee to the Department of Disease Control （DDC） and provincial level. This process was lacking budget support. The provincial AIDS committee was monitored by the provincial health office, cooperating with the central level. The major role was to transfer the policy to the school, Local Administration Organization （LAO） and associated organization. The activity was funded by provincial, global funds, and outside sources. In the community, the core activities were AIDS knowledge, establishing core youth groups, and building the network of AIDS. The obstacle at the national level was changing the policy process from one with a budget to one without budget. In the area of practice, the AIDS problem and the effects of the risk behavior in youth groups were slightly concerned.

Peritrophin-like protein from Litopenaeus vannamei (LvPT) involved in white spot syndrome virus (WSSV) infection in digestive tract challenged with reverse gavage

The peritrophic membrane plays an important role in the defense system of the arthropod gut. The digestive tract is considered one of the major tissues targeted by white spot syndrome virus （WSSV） in shrimp. In this study, the nucleotide sequence encoding peritrophin-like protein of Litopenaeus vannamei （LvPT） was amplified from a yeast two-hybrid library of L. vannamei. The epitope peptide of LvPT was predicted with the GenScript OptimumAntigenTM design tool. An anti-LvPT polyclonal antibody was produced and shown to specifically bind a band at -27 kDa, identified as LvPT. The LvPT protein was expressed and its concentration determined. LvPT dsRNA （4 pg per shrimp） was used to inhibit LvPT expression in shrimp, and a WSSV challenge experiment was then performed with reverse gavage. The pleopods, stomachs, and guts were collected from the shrimp at 0, 24, 48, and 72 h post-infection （hpi）. Viral load quantification showed that the levels of WSSV were significantly lower in the pleopods, stomachs, and guts of shrimp after LvPT dsRNA interference than in those of the controls at 48 and 72 hpi. Our results imply that LvPT plays an important role during WSSV infection of the digestive tract.

Photochemical Degradation of the Ciprofloxacin Antibiotic and Its Microbiological Validation

In this research, it used advanced oxidation processes for the recovery, detoxification and mineralization of wastewater mainly contaminated by antibiotics （ciprofloxacin）. These processes can be used alone or in combination with each other or by complementing traditional methods, even allowing the disinfection of bacterial and viral inactivation. With the use of experimental systems UV/H202/O3, UV/H202, it can achieve total mineralization of the compound. Ciprofloxacin solutions used at 50, 100, 200, 300, 400 and 500 ppm, degraded to 100% of antibiotics and by a microbiological method show that the loss of biological activity is inversely proportional to the time of irradiation.

菜鸟数据恢复速成法

随着电脑应用的普及,生活中有越来越多的人在用电脑,但由于对数据安全知识的缺乏,同时又由于对数据安全的认识程度不够,经常会产生各种各样的数据安全问题,比如存储设备的损坏(磁盘、光盘、电子盘等)。

A comparative study of the characteristics of two Coxsackie A virus type 16 strains (genotype B)

Coxsackie A virus is one of the major pathogens associated with hand, foot and mouth disease (HFMD). The etiological characteristics of Coxsackie A virus type 16 (CA16) are thought to correlate with the pathological process of its infection. Two CA16 strains that were isolated from a severe HFMD patient presented with different plaque forms. This observation, along with biological analysis, indicated that the differences in the strains' biological characteristics, such as proliferation kinetics and immunogenicity, correlate with differences in their pathogenicity toward neonatal mice. Furthermore, these differences are thought to be associated with the sequence of the 5′ non-coding region of the viral genome and the VP1 structural region sequence. The results suggest that the biological and genetic characteristics of the CA16 viral strains are relevant to their pathogenicity.

Stress Granule Formation is One of the Early Antiviral Mechanisms for Host Cells Against Coxsackievirus B Infection

Stress granules(SGs) are intracellular granules formed when cellular translation is blocked and have been reported to be involved in a variety of viral infections. Our previous studies revealed that SGs are involved in the coxsackievirus B(CVB)infection process, but the role of SGs in CVB infection has not been fully explored. In this study, we found that CVB type 3(CVB3) could induce SG formation in the early phase of infection. Results showed that levels of CVB3 RNA and protein were significantly inhibited during the early stage of CVB3 infection by the elevated formation of SGs, while viral RNA and protein synthesis were significantly promoted when SG formation was blocked. Our findings suggest that SG formation is one of the early antiviral mechanisms for host cells against CVB infection.

Immunosenescence and age-related viral diseases

Immunosenescence is described as a decline in the normal functioning of the immune system associated with physiologic ageing.Immunosenescence contributes to reduced efficacy to vaccination and increased susceptibility to infectious diseases in the elderly.Extensive studies of laboratory animal models of ageing or donor lymphocyte analysis have identified changes in immunity caused by the ageing process.Most of these studies have identified phenotypic and functional changes in innate and adaptive immunity.However,it is unclear which of these defects are critical for impaired immune defense against infection.This review describes the changes that occur in innate and adaptive immunity with ageing and some age-related viral diseases where defects in a key component of immunity contribute to the high mortality rate in mouse models of ageing.

Stability of a CD4^＋ T cell viral infection model with diffusion

This paper is devoted to the study of the stability of a CD4^＋ T cell viral infection model with diffusion. First, we discuss the well-posedness of the model and the existence of endemic equilibrium. Second, by analyzing the roots of the characteristic equation, we establish the local stability of the virus-free equilibrium. Furthermore, by constructing suitable Lyapunov functions, we show that the virus-free equilibrium is globally asymptotically stable if the threshold value R0 ≤1; the endemic equilibrium is globally asymptotically stable if R0 〉 1 and du^＊ - δw^＊ ≥0. Finally, we give an application and numerical simulations to illustrate the main results.

Comparison of particle swarm and bacterial foraging optimization algorithms for therapy planning in HIV/AIDS patients

In HIV/AIDS patients, antiretroviral therapy （ART） is used for reducing the viral load and helps in increasing the life span of the individual. However, severe side effects are associated with the use of antiretroviral drugs. Hence, a treatment schedule, using minimal amount of drugs, is required for maintaining a low viral load and a healthy immune system. The objective of this work is to compute the optimal dosage of antiretroviral drugs for therapy planning in HIV/AIDS patients, using intelligent optimization techniques. In this work, two computational swarm intelligence techniques known as the particle swarm optimization （PSO） and bacterial foraging optimization （BFO） in conjunction with the three-dimensional mathematical model of HIV/AIDS have been used for estimating the optimal drug dosage for administering therapy by minimization of viral load as well as the total drug concentration. Results demonstrate that, using the proposed method, it is possible to achieve minimal viral load and an improved immune system, with the estimated drug dosage. Further, it was observed that the efficiency of BFO （CD4 cells = 757 cells/mm^3 at seventh year of infection） for estimation of optimal drug dosage is higher than the PSO method （CD4 cells = 817 cells/mm^3 at seventh year of infection）. This work seems to be of high clini- cal relevance since, at present, ART is the widely used procedure for treatment of HIV infected patients.

The effect of vaccination to dendritic cell and immune cell interaction in HIV disease progression

In this research paper, our main objective is to find out the meticulous role of activated dendritic cells （DCs） during the human immunodeficiency virus （HIV） infection process. DCs play a dual role by enhancing both HIV infection progression, as well as antiviral immune response. To explore the implications of these dual roles, we have formulated our mathematical model and analyzed the model by both analytical and numerical approaches. By using an impulsive differential equation, we have studied the effect of DC-based vaccination. Analytically we have determined the threshold value of drug dosage and dosing interval for optimum levels of injection. We have also investigated the effect of perfect adherence of drug dose on the immune cell count in extreme cases and observed that, systematic drug dose of the immune cells leads to its maximum level.

Statistical Diagnosis for HIV Dynamics Based on Mean Shift Outlier Model

Ordinary differential equation(ODE) are widely used for quantifying HIV viral dynamics.It is interesting but challenging to estimate ODE parameters from noisy data, especially when the data have some outliers. In this study, the authors use the Mean Shift Outlier Model(MSOM) to detect outliers in HIV model based on the two-step estimation of ODE. Approximate formula for shift parameter is derived. Furthermore, a score test statistic is constructed and its approximating distribution is established. The simulation results show that: 1) The boundary points have more impact on the parameter estimation relative to interior points. 2) The proposed procedure can detect the outliers effectively. The authors illustrate the proposed approach using an application example from an HIV clinical trial and find similar pattern to the simulation studies.

The V1 region of gp120 is preferentially selected during SIV/HIV transmission and is indispensable for envelope function and virus infection

A transmission bottleneck occurs during each human immunodeficiency virus(HIV) transmission event, which allows only a few viruses to establish new infection. However, the genetic characteristics of the transmitted viruses that are preferentially selected have not been fully elucidated. Here, we analyzed amino acids changes in the envelope protein during simian immunodeficiency virus(SIV)/HIV deep transmission history and current HIV evolution within the last 15–20 years. Our results confirmed that the V1V2 region of gp120 protein, particularly V1, was preferentially selected. A shorter V1 region was preferred during transmission history, while during epidemic, HIV may evolve to an expanded V1 region gradually and thus escape immune recognition. We then constructed different HIV-1 V1 mutants using different HIV-1 subtypes to elucidate the role of the V1 region in envelope function. We found that the V1 region, although highly variable, was indispensable for virus entry and infection, probably because V1 deletion mutants exhibited impaired processing of gp160 into mature gp120 and gp41. Additionally, the V1 region affected Env incorporation. These results indicated that the V1 region played a critical role in HIV transmission and infection.

Stability and multi-parametric Hopf bifurcation analyses of viral infection model with time delay

Ever since HIV was first diagnosed in human, a great number of scientific works have been undertaken to explore the biological mechanisms involved in the infection and progression of the disease. This paper deals with stability and bifurcation analyses of mathematical model that represents the dynamics of HIV infection of thymus. The existence and stability of the equilibria are investigated. The model is described by a system of delay differential equations with logistic growth term, cure rate and discrete type of time delay. Choosing the time delay as a bifurcation parameter, the analysis is mainly focused on the Hopf bifurcation problem to predict the existence of a limit cycle bifurcating from the infected steady state.Further, using center manifold theory and normal form method we derive explicit formulae to determine the stability and direction of the limit cycles. Moreover the mitosis rate r also plays a vital role in the model, so we fix it as second bifurcation parameter in the incidence of viral infection. Our analysis shows that, while both the bifurcation parameters can destabilize the equilibrium E＊ and cause limit cycles. Numerical simulations are performed to investigate the qualitative behaviors of the inherent model.