WorldWideScience

Sample records for clearance viral load

  1. Interleukin-28B polymorphisms are associated with hepatitis C virus clearance and viral load in a HIV-1-infected cohort

    DEFF Research Database (Denmark)

    Clausen, L N; Weis, N; Astvad, K;

    2011-01-01

    Summary. Twenty-five per cent of individuals infected with hepatitis C virus (HCV) are able to clear HCV spontaneously. Differences in host genetics are believed to affect the outcome of HCV infection. We analysed an exonic, a promoter and an intronic single nucleotide polymorphism (SNP......) of the interferon-¿3 coding interleukin (IL)-28B gene to study the relationship between IL28B SNPs and outcome of HCV infection. Among 206 HIV-1-infected Europeans with evidence of HCV infection, 47 (23%) individuals had cleared HCV and 159 (77%) had developed chronic infection. The exonic rs8103142 CT......, the promoter rs12979860 CT and the intronic rs11881222 AG genotypes were associated with a decreased HCV clearance rate with adjusted odds ratios (aOR) of 0.3 (95% CI, 0.1-0.7), 0.4 (95% CI, 0.2-0.8) and 0.4 (95% CI, 0.2-0.8), respectively. The haplotype block TCG CTA was associated with a decreased HCV...

  2. Spontaneous viral clearance, viral load, and genotype distribution of hepatitis C virus (HCV) in HIV-infected patients with anti-HCV antibodies in Europe

    DEFF Research Database (Denmark)

    Soriano, Vincent; Mocroft, Amanda; Rockstroh, Juergen;

    2008-01-01

    BACKGROUND: Variables influencing serum hepatitis C virus (HCV) RNA levels and genotype distribution in individuals with human immunodeficiency virus (HIV) infection are not well known, nor are factors determining spontaneous clearance after exposure to HCV in this population. METHODS: All HCV...... antibody (Ab)-positive patients with HIV infection in the EuroSIDA cohort who had stored samples were tested for serum HCV RNA, and HCV genotyping was done for subjects with viremia. Logistic regression was used to identify variables associated with spontaneous HCV clearance and HCV genotype 1. RESULTS......: Of 1940 HCV Ab-positive patients, 1496 (77%) were serum HCV RNA positive. Injection drug users (IDUs) were less likely to have spontaneously cleared HCV than were homosexual men (20% vs. 39%; adjusted odds ratio [aOR], 0.36 [95% confidence interval {CI}, 0.24-0.53]), whereas patients positive...

  3. Analysis of viral clearance unit operations for monoclonal antibodies.

    Science.gov (United States)

    Miesegaes, George; Lute, Scott; Brorson, Kurt

    2010-06-01

    Demonstration of viral clearance is a critical step in assuring the safety of biotechnology products. We generated a viral clearance database that contains product information, unit operation process parameters, and viral clearance data from monoclonal antibody and antibody-related regulatory submissions to FDA. Here we present a broad overview of the database and resulting analyses. We report that the diversity of model viruses tested expands as products transition to late-phase. We also present averages and ranges of viral clearance results by Protein A and ion exchange chromatography steps, low pH chemical inactivation, and virus filtration, focusing on retro- and parvoviruses. For most unit operations, an average log reduction value (LRV, a measure of clearance power) for retrovirus of >4 log(10) were measured. Cases where clearance data fell outside of the anticipated range (i.e., outliers) were rationally explained. Lastly, a historical analysis did not find evidence of any improvement trend in viral clearance over time. The data collectively suggest that many unit operations in general can reliably clear viruses.

  4. Effect of Internal Clearance on Load Distribution and Life of Radially Loaded Ball and Roller Bearings

    Science.gov (United States)

    Oswald, Fred B.; Zaretsky, Erwin V.; Poplawski, Joseph V.

    2012-01-01

    The effect of internal clearance on radially loaded deepgroove ball and cylindrical roller bearing load distribution and fatigue life was determined for four clearance groups defined in the bearing standards. The analysis was extended to negative clearance (interference) conditions to produce a curve of life factor versus internal clearance. Rolling-element loads can be optimized and bearing life maximized for a small negative operating clearance. Life declines gradually with positive clearance and rapidly with increasing negative clearance. Relationships were found between bearing life and internal clearance as a function of ball or roller diameter, adjusted for load. Results are presented as life factors for radially loaded bearings independent of bearing size or applied load. In addition, a modified Stribeck Equation is presented that relates the maximum rolling-element load to internal bearing clearance.

  5. Non-invasive Imaging of Sendai Virus Infection in Pharmacologically Immunocompromised Mice: NK and T Cells, but not Neutrophils, Promote Viral Clearance after Therapy with Cyclophosphamide and Dexamethasone

    Science.gov (United States)

    Mostafa, Heba H.; Vogel, Peter; Srinivasan, Ashok; Russell, Charles J.

    2016-01-01

    In immunocompromised patients, parainfluenza virus (PIV) infections have an increased potential to spread to the lower respiratory tract (LRT), resulting in increased morbidity and mortality. Understanding the immunologic defects that facilitate viral spread to the LRT will help in developing better management protocols. In this study, we immunosuppressed mice with dexamethasone and/or cyclophosphamide then monitored the spread of viral infection into the LRT by using a noninvasive bioluminescence imaging system and a reporter Sendai virus (murine PIV type 1). Our results show that immunosuppression led to delayed viral clearance and increased viral loads in the lungs. After cessation of cyclophosphamide treatment, viral clearance occurred before the generation of Sendai-specific antibody responses and coincided with rebounds in neutrophils, T lymphocytes, and natural killer (NK) cells. Neutrophil suppression using anti-Ly6G antibody had no effect on infection clearance, NK-cell suppression using anti-NK antibody delayed clearance, and T-cell suppression using anti-CD3 antibody resulted in no clearance (chronic infection). Therapeutic use of hematopoietic growth factors G-CSF and GM-CSF had no effect on clearance of infection. In contrast, treatment with Sendai virus—specific polysera or a monoclonal antibody limited viral spread into the lungs and accelerated clearance. Overall, noninvasive bioluminescence was shown to be a useful tool to study respiratory viral progression, revealing roles for NK and T cells, but not neutrophils, in Sendai virus clearance after treatment with dexamethasone and cyclophosphamide. Virus-specific antibodies appear to have therapeutic potential. PMID:27589232

  6. Non-invasive Imaging of Sendai Virus Infection in Pharmacologically Immunocompromised Mice: NK and T Cells, but not Neutrophils, Promote Viral Clearance after Therapy with Cyclophosphamide and Dexamethasone.

    Science.gov (United States)

    Mostafa, Heba H; Vogel, Peter; Srinivasan, Ashok; Russell, Charles J

    2016-09-01

    In immunocompromised patients, parainfluenza virus (PIV) infections have an increased potential to spread to the lower respiratory tract (LRT), resulting in increased morbidity and mortality. Understanding the immunologic defects that facilitate viral spread to the LRT will help in developing better management protocols. In this study, we immunosuppressed mice with dexamethasone and/or cyclophosphamide then monitored the spread of viral infection into the LRT by using a noninvasive bioluminescence imaging system and a reporter Sendai virus (murine PIV type 1). Our results show that immunosuppression led to delayed viral clearance and increased viral loads in the lungs. After cessation of cyclophosphamide treatment, viral clearance occurred before the generation of Sendai-specific antibody responses and coincided with rebounds in neutrophils, T lymphocytes, and natural killer (NK) cells. Neutrophil suppression using anti-Ly6G antibody had no effect on infection clearance, NK-cell suppression using anti-NK antibody delayed clearance, and T-cell suppression using anti-CD3 antibody resulted in no clearance (chronic infection). Therapeutic use of hematopoietic growth factors G-CSF and GM-CSF had no effect on clearance of infection. In contrast, treatment with Sendai virus-specific polysera or a monoclonal antibody limited viral spread into the lungs and accelerated clearance. Overall, noninvasive bioluminescence was shown to be a useful tool to study respiratory viral progression, revealing roles for NK and T cells, but not neutrophils, in Sendai virus clearance after treatment with dexamethasone and cyclophosphamide. Virus-specific antibodies appear to have therapeutic potential. PMID:27589232

  7. Potential Pitfalls in Estimating Viral Load Heritability.

    Science.gov (United States)

    Leventhal, Gabriel E; Bonhoeffer, Sebastian

    2016-09-01

    In HIV patients, the set-point viral load (SPVL) is the most widely used predictor of disease severity. Yet SPVL varies over several orders of magnitude between patients. The heritability of SPVL quantifies how much of the variation in SPVL is due to transmissible viral genetics. There is currently no clear consensus on the value of SPVL heritability, as multiple studies have reported apparently discrepant estimates. Here we illustrate that the discrepancies in estimates are most likely due to differences in the estimation methods, rather than the study populations. Importantly, phylogenetic estimates run the risk of being strongly confounded by unrealistic model assumptions. Care must be taken when interpreting and comparing the different estimates to each other.

  8. Viral clearance by flow-through mode ion exchange columns and membrane adsorbers.

    Science.gov (United States)

    Miesegaes, G R; Lute, S C; Read, E K; Brorson, K A

    2014-01-01

    Anion exchange (AEX) is a common downstream purification operation for biotechnology products manufactured in cell culture such as therapeutic monoclonal antibodies (mAbs) and Fc-fusion proteins. We present a head-to-head comparison of the viral clearance efficiency of AEX adsorbers and column chromatography using the same process fluids and comparable run conditions. We also present overall trends from the CDER viral clearance database. In our comparison of multiple brands of resins and adsorbers, clearance of three model viruses (PPV, X-MuLV, and PR772) was largely comparable, with some exceptions which may reflect run conditions that had not been optimized on a resin/membrane specific basis.

  9. Fecal Viral Load and Norovirus-associated Gastroenteritis

    OpenAIRE

    Martin C W Chan; Sung, Joseph J Y; Lam, Rebecca K. Y.; Chan, Paul K.S.; Nelson L S Lee; Lai, Raymond W.M.; Leung, Wai K

    2006-01-01

    We report the median cDNA viral load of norovirus genogroup II is >100-fold higher than that of genogroup I in the fecal specimens of patients with norovirus-associated gastroenteritis. We speculate that increased cDNA viral load accounts for the higher transmissibility of genogroup II strains through the fecal-oral route.

  10. Viral loads of cerebrospinal fluid in infants with enterovirus meningitis.

    Science.gov (United States)

    Kawashima, Hisashi; Ioi, Hiroaki; Ishii, Chiako; Hasegawa, Yuka; Amaha, Masahiro; Kashiwagi, Yasuyo; Takekuma, Kouji; Hoshika, Akinori; Watanabe, Yasuo

    2008-01-01

    For a better understanding of the role of the viral load, free radicals, and cytokines in viral meningitis, we surveyed cerebrospinal fluid (CSF) obtained from patients below 1 year of age who showed positive for enterovirus. In their first examinations interleukin (IL)-6 and free radicals increased whereas pleocytosis was rarely observed. IL-6 decreased within the short period. Viral loads and free radicals increased simultaneously. IL-6 and free radicals of CSF are helpful for diagnosis and treatment of viral meningitis at an early stage.

  11. Tissue viral load variability in chronic hepatitis C.

    LENUS (Irish Health Repository)

    Fanning, L

    2012-02-03

    OBJECTIVE: Liver biopsy is regarded as the gold standard for assessing disease activity in chronic hepatitis C, but sampling error is a potential limitation. Whether sampling variability applies equally to viral load assessment as it does to histology is uncertain. To examine this, we compared viral load between right- and left-lobe biopsy specimens from patients infected with hepatitis C virus (HCV). METHODS: Bilobe biopsies were taken from 16 patients who were serum positive for HCV RNA by reverse transcription-polymerase chain reaction. Genotype was identified by reverse line probe hybridization. There was an absence of competing risk factors for infectious and other liver diseases in this patient group. Histology and hepatic viral load were assessed blindly. None of the patients had received antiviral therapy at the time of study. RESULTS: Detection of HCV in right and left lobes was concordant with serum positivity in all cases. The viral load between lobes was highly correlated (p = 0.0003, r = 0.79). In contrast, the histological activity indices of inflammation and fibrosis\\/cirrhosis were poorly correlated between lobes (p = 0.038, r = 0.60, and p = 0.098, r = 0.50, respectively). CONCLUSION: Hepatic viral load variability does not suffer from the same degree of heterogeneity of sampling variability as does histology.

  12. Higher Viral Load and Prolonged Viral Shedding Period is Associated with Impaired Th17 Cell Response in Patients with H1N1 Influenza A

    Institute of Scientific and Technical Information of China (English)

    Gui-lin; Yang; Ying-xia; Liu; Mu-tong; Fang; Wei-long; Liu; Xin-chun; Chen; John; Nunnari; Jing-jing; Xie; Ming-feng; Liao; Ming-xia; Zhang; Guo-bao; Li; Pei-ze; Zhang; Yi; Guan; Bo-ping; Zhou

    2012-01-01

    Objective To explore whether age,disease severity,cytokines and lymphocytes in H1N1 influenza A patients correlate with viral load and clearance.Methods Total of 70 mild and 16 severe patients infected with H1N1 influenza A virus were enrolled in this study.Results It was found that the patients under 14 years old and severe patients displayed significantly higher viral loads and prolonged viral shedding periods compared with the patients over 14 years old and mild patients,respectively(P < 0.05).Moreover,the patients under 14 years old and severe patients displayed significantly lower Th17 cell frequency than the patients over 14 years old and mild patients(P < 0.01).The viral shedding period inversely correlated with the frequency of IL-17+IFN-γ-CD4+ T cells.Additionally,the decreased concentration of serum TGF-β correlated with the decreased frequency of IL-17+IFN-γ-CD4+ T cells.Conclusions Both younger and severe patients are associated with higher viral loads and longer viral shedding periods,which may partially be attributed to the impaired Th17 cell response.

  13. Targeting CD45RB alters T cell migration and delays viral clearance.

    Science.gov (United States)

    Lim, Bock; Sutherland, Robyn M; Zhan, Yifan; Deliyannis, Georgia; Brown, Lorena E; Lew, Andrew M

    2006-02-01

    CD45 is a receptor tyrosine phosphatase essential for TCR signaling. One isoform, CD45RB, is down-regulated in memory cells and targeting CD45RB with a specific antibody has been shown to inhibit graft rejection. Its role in immunity to infection, however, has not been tested. Here, we report the effect of anti-CD45RB antibody treatment on the induction of anti-influenza CD8+ T cells and viral clearance. Anti-CD45RB-treated mice had delayed pulmonary viral clearance compared with untreated mice whose infection was completely cleared by day 8 post-infection. In anti-CD45RB-treated mice, the total CD4+ and CD8+ T cell numbers in both the lungs and mediastinal nodes were substantially reduced at days 5 and 8; this effect was less marked for the spleen. CD8+ T cells specific for influenza virus were also reduced compared with the control group in all three organs at day 8. By day 11, when both treated and control groups showed no virus remaining in the lungs, specific CD8+ T cell numbers were at similar low levels. Homing to lymph nodes and lung of dye-labeled T cells was greatly inhibited (by >80%) by anti-CD45RB treatment. This reduced homing corresponded with reduced CD62L and beta1-integrin expression in both uninfected and infected mice. Since CD62L plays a critical role in homing lymphocytes to lymph nodes, and high levels of CD62L and alpha4beta1-integrin are expressed by lymphocytes that home to bronchus-associated lymphoid tissue, we suggest that reduced expression of these molecules is a key explanation for the delay in immune responses. PMID:16361310

  14. Hepatitis C virus genotypes: A plausible association with viral loads

    Directory of Open Access Journals (Sweden)

    Salma Ghulam Nabi

    2013-01-01

    Full Text Available Background and Aim: The basic aim of this study was to find out the association of genotypes with host age, gender and viral load. Material and Methods: The present study was conducted at Social Security Hospital, Pakistan. This study included 320 patients with chronic hepatitis C virus (HCV infection who were referred to the hospital between November 2011 and July 2012. HCV viral detection and genotyping was performed and the association was seen between genotypes and host age, gender and viral load. Results : The analysis revealed the presence of genotypes 1 and 3 with further subtypes 1a, 1b, 3a, 3b and mixed genotypes 1b + 3a, 1b + 3b and 3a + 3b. Viral load quantification was carried out in all 151 HCV ribonucleic acid (RNA positive patients. The genotype 3a was observed in 124 (82.12% patients, 3b was found in 21 (13.91%, 1a was seen in 2 (1.32%, 1b in 1 (0.66%, mixed infection with 1b + 3a in 1 (0.66%, 1b + 3b in 1 (0.66% and 3a + 3b was also found in 1 (0.66% patient. Viral load quantification was carried out in all 151 HCV RNA positive patients and was compared between the various genotypes. The mean viral load in patients infected with genotype 1a was 2.75 × 10 6 , 1b 3.9 × 10 6 , 3a 2.65 × 10 6 , 3b 2.51 × 10 6 , 1b + 3a 3.4 × 106, 1b + 3b 2.7 × 106 and 3a + 3b 3.5 × 10 6 . An association between different types of genotypes and viral load was observed. Conclusion : Further studies should be carried out to determine the association of viral load with different genotypes so that sufficient data is available and can be used to determine the type and duration of therapy needed and predict disease outcome.

  15. Quantitation of viral load using real-time amplification techniques

    NARCIS (Netherlands)

    Niesters, H G

    2001-01-01

    Real-time PCR amplification techniques are currently used to determine the viral load in clinical samples for an increasing number of targets. Real-time PCR reduces the time necessary to generate results after amplification. In-house developed PCR and nucleic acid sequence-based amplification (NASBA

  16. Decreased insulin clearance in individuals with elevated 1-h post-load plasma glucose levels.

    Directory of Open Access Journals (Sweden)

    Maria Adelaide Marini

    Full Text Available Reduced insulin clearance has been shown to predict the development of type 2 diabetes. Recently, it has been suggested that plasma glucose concentrations ≥ 8.6 mmol/l (155 mg/dl at 1 h during an oral glucose tolerance test (OGTT can identify individuals at high risk for type 2 diabetes among those who have normal glucose tolerance (NGT 1 h-high. The aim of this study was to examine whether NGT 1 h-high have a decrease in insulin clearance, as compared with NGT individuals with 1-h post-load glucose <8.6 mmol/l (l (155 mg/dl, NGT 1 h-low. To this end, 438 non-diabetic White individuals were subjected to OGTT and euglycemic-hyperinsulinemic clamp to evaluate insulin clearance and insulin sensitivity. As compared with NGT 1 h-low individuals, NGT 1 h-high had significantly higher 1-h and 2-h post-load plasma glucose and 2-h insulin levels as well as higher fasting glucose and insulin levels. NGT 1 h-high exhibited also a significant decrease in both insulin sensitivity (P<0.0001 and insulin clearance (P = 0.006 after adjusting for age, gender, adiposity measures, and insulin sensitivity. The differences in insulin clearance remained significant after adjustment for fasting glucose (P = 0.02 in addition to gender, age, and BMI. In univariate analyses adjusted for gender and age, insulin clearance was inversely correlated with body weight, body mass index, waist, fat mass, 1-h and 2-h post-load glucose levels, fasting, 1-h and 2-h post-load insulin levels, and insulin-stimulated glucose disposal. In conclusion, our data show that NGT 1 h-high have a reduction in insulin clearance as compared with NGT 1 h-low individuals; this suggests that impaired insulin clearance may contribute to sustained fasting and post-meal hyperinsulinemia.

  17. Measles viral load may reflect SSPE disease progression

    Directory of Open Access Journals (Sweden)

    Jin L

    2006-06-01

    Full Text Available Abstract Subacute sclerosing panencephalitis (SSPE is a rare, slowly progressive neurological disorder caused by the persistent infection with measles virus (MV. Despite much research into SSPE, its pathology remains obscure. We examined autopsy tissues of eight SSPE patients by real time quantitative PCR, immunohistochemistry and immunoblotting to determine viral load. MV N, M and H gene RNA could be detected in the central nervous system (CNS of all patients and in two non-CNS tissues of one patient. The viral burden between patients differed up to four-fold by quantitative PCR and corresponded with detection of MV protein. The level of both viral RNA and antigen in the brain may correlate with disease progression.

  18. Intra-operative colloid administration increases the clearance of a post-operative fluid load

    DEFF Research Database (Denmark)

    Borup, Tine; Hahn, Robert; Holte, K;

    2009-01-01

    BACKGROUND: It is unknown whether an intra-operative colloid infusion alters the dynamics of a crystalloid load administered post-operatively. METHODS: Ten patients received 12.5 ml/kg of Ringer's lactate over 30 min 1-3 days before and 4 h after laparoscopic cholecystectomy, during which 10 ml....../kg of a colloid solution, hydroxyethylstarch (HES 130/0.4), was infused. The total body clearance of the pre- and post-operative test infusions was taken as the ratio between the urinary excretion and the Hb-derived dilution of venous plasma over 150 min. The plasma clearance of the infused fluid was calculated...... using volume kinetics based on the plasma dilution alone. The pre-operative plasma clearance was compared with the post-operative plasma clearance and patients served as their own control. RESULTS: The urinary excretion averaged 350 ml for the pre-operative infusion and 612 ml post-operatively, which...

  19. Psychiatric Distress, Drug Use, and HIV Viral Load Suppression in Russia.

    Science.gov (United States)

    Ustinov, A; Suvorova, A; Belyakov, A; Makhamatova, A; Levina, O; Krupitsky, E; Lioznov, D; Niccolai, L; Heimer, R

    2016-08-01

    To explore the influence of psychiatric distress and substance use on viral load suppression in HIV-infected patients taking ART we analyzed socio-demographic characteristics, CD4+ cells count and viral loads, the Symptom Check List-90 and the Addiction Severity Index of 75 patients who had taken ART for at least 6 month. Using viral load data as the marker of ART success, we divided the sample into two groups. Comparison of the groups showed that education, marriage, and female gender are predictors of optimal viral load suppression. Overall results failed to demonstrate substance use and psychiatric distress as predictors of viral load suppression. PMID:26809193

  20. Impact of Chloroquine on Viral Load in Breast Milk

    Science.gov (United States)

    Semrau, Katherine; Kuhn, Louise; Kasonde, Prisca; Sinkala, Moses; Kankasa, Chipepo; Shutes, Erin; Vwalika, Cheswa; Ghosh, Mrinal; Aldrovandi, Grace; Thea, Donald M.

    2006-01-01

    Summary The anti-malarial agent chloroquine has activity against HIV. We compared the effect of chloroquine (n = 18) to an anti-malarial agent without known anti-HIV-activity, sulfadoxine-pyrimethamine (n = 12), on breast milk HIV RNA levels among HIV-infected breastfeeding women in Zambia. After adjusting for CD4 count and plasma viral load, chloroquine was associated with a trend towards lower levels of HIV RNA in breast milk compared with sulfadoxine-pyrimethamine (P 0.05). Higher breastmilk viral load was also observed among women receiving presumptive treatment = for symptomatic malaria compared with asymptomatic controls and among controls reporting fever in the prior week. Further research is needed to determine the potential role of chloroquine in prevention of HIV transmission through breastfeeding. Impacte de la chloroquine sur la charge virale dans le lait maternelle La chloroquine, agent antimalarique, a une activité contre le VIH. Nous avons comparé l’effet de la chloroquine à celui d’un autre agent antimalarique, la sulfadoxine-pyrimethamine, dont l’activité sur le VIH n’est pas connue, en mesurant les taux d’ARN de VIH dans le lait maternel de femmes allaitantes infectées par le VIH en Zambie. Après ajustement pour les taux de CD4 et la charge virale dans le plasma, la chloroquine comparée à la sulfadoxine pyrimethamine était associée à une tendance vers des teneurs plus bas en ARN de VIH dans le lait maternel (P = 0,05). Des charges virales plus élevées dans le lait maternel étaient aussi observées chez des femmes recevant un traitement présomptif pour des symptômes de malaria par rapport aux contrôles asymptomatiques et par rapport à des contrôles rapportant de la fièvre durant la première semaine. Des études supplémentaires sont nécessaires pour déterminer le rôle potentiel de la chloroquine dans la prévention de la transmission du VIH par l’allaitement maternel. mots clésVIH, malaria, allaitement maternel

  1. Stress analysis method for clearance-fit joints with bearing-bypass loads

    Science.gov (United States)

    Naik, R. A.; Crews, J. H., Jr.

    1989-01-01

    Within a multi-fastener joint, fastener holes may be subjected to the combined effects of bearing loads and loads that bypass the hole to be reacted elsewhere in the joint. The analysis of a joint subjected to search combined bearing and bypass loads is complicated by the usual clearance between the hole and the fastener. A simple analysis method for such clearance-fit joints subjected to bearing-bypass loading has been developed in the present study. It uses an inverse formulation with a linear elastic finite-element analysis. Conditions along the bolt-hole contact arc are specified by displacement constraint equations. The present method is simple to apply and can be implemented with most general purpose finite-element programs since it does not use complicated iterative-incremental procedures. The method was used to study the effects of bearing-bypass loading on bolt-hole contact angles and local stresses. In this study, a rigid, frictionless bolt was used with a plate having the properties of a quasi-isotropic graphite/epoxy laminate. Results showed that the contact angle as well as the peak stresses around the hole and their locations were strongly influenced by the ratio of bearing and bypass loads. For single contact, tension and compression bearing-bypass loading had opposite effects on the contact angle. For some compressive bearing-bypass loads, the hole tended to close on the fastener leading to dual contact. It was shown that dual contact reduces the stress concentration at the fastener and would, therefore, increase joint strength in compression. The results illustrate the general importance of accounting for bolt-hole clearance and contact to accurately compute local bolt-hole stresses for combined bearings and bypass loading.

  2. Diagnosing norovirus-associated infectious intestinal disease using viral load

    Directory of Open Access Journals (Sweden)

    Tam Clarence C

    2009-05-01

    Full Text Available Abstract Background Reverse transcription-polymerase chain reaction (RT-PCR is the main method for laboratory diagnosis of norovirus-associated infectious intestinal disease (IID. However, up to 16% of healthy individuals in the community, with no recent history of IID, may be RT-PCR positive; so it is unclear whether norovirus is actually the cause of illness in an IID case when they are RT-PCR positive. It is important to identify the pathogen causing illness in sporadic IID cases, for clinical management and for community based incidence studies. The aim of this study was to investigate how faecal viral load can be used to determine when norovirus is the most likely cause of illness in an IID case. Methods Real-time RT-PCR was used to determine the viral load in faecal specimens collected from 589 IID cases and 159 healthy controls, who were infected with genogroup II noroviruses. Cycle threshold (Ct values from the real-time RT-PCR were used as a proxy measure of viral load. Receiver-operating characteristic (ROC analysis was used to identify a cut-off in viral load for attributing illness to norovirus in IID cases. Results One hundred and sixty-nine IID cases and 159 controls met the inclusion criteria for the ROC analysis. The optimal Ct value cut-off for attributing IID to norovirus was 31. The same cut-off was selected when using healthy controls, or IID cases who were positive by culture for bacterial pathogens, as the reference negative group. This alternative reference negative group can be identified amongst specimens routinely received in clinical virology laboratories. Conclusion We demonstrated that ROC analysis can be used to select a cut-off for a norovirus real time RT-PCR assay, to aid clinical interpretation and diagnose when norovirus is the cause of IID. Specimens routinely received for diagnosis in clinical virology laboratories can be used to select an appropriate cut-off. Individual laboratories can use this method to

  3. Multilaboratory Comparison of Hepatitis C Virus Viral Load Assays

    OpenAIRE

    Caliendo, A M; Valsamakis, A.; Zhou, Y.; Yen-Lieberman, B; Andersen, J; Young, S.; Ferreira-Gonzalez, A; Tsongalis, G. J.; Pyles, R.; Bremer, J W; Lurain, N. S.

    2006-01-01

    We report a multilaboratory evaluation of hepatitis C virus (HCV) viral load assays to determine their linear range, reproducibility, subtype detection, and agreement. A panel of HCV RNA samples ranging in nominal concentration from 1.0 to 7.0 log10 IU/ml was constructed by diluting a clinical specimen (genotype 1b). Replicates of the panel were tested in multiple laboratories using the Abbott TaqMan analyte-specific reagent (Abbott reverse transcription-PCR [RT-PCR]), Roche TaqMan RUO (Roche...

  4. High heritability is compatible with the broad distribution of set point viral load in HIV carriers.

    Directory of Open Access Journals (Sweden)

    Sebastian Bonhoeffer

    2015-02-01

    Full Text Available Set point viral load in HIV patients ranges over several orders of magnitude and is a key determinant of disease progression in HIV. A number of recent studies have reported high heritability of set point viral load implying that viral genetic factors contribute substantially to the overall variation in viral load. The high heritability is surprising given the diversity of host factors associated with controlling viral infection. Here we develop an analytical model that describes the temporal changes of the distribution of set point viral load as a function of heritability. This model shows that high heritability is the most parsimonious explanation for the observed variance of set point viral load. Our results thus not only reinforce the credibility of previous estimates of heritability but also shed new light onto mechanisms of viral pathogenesis.

  5. In vitro Evaluation of Biofield Treatment on Viral Load Against Human Immunodeficiency-1 and Cytomegalo Viruses

    OpenAIRE

    Trivedi, Mahendra Kumar

    2015-01-01

    Viral load quantification is the amount of particular viral DNA or RNA in a blood samples. It is one of the surrogate biomarker of AIDS. High viral load indicates that the immune system is failed to fight against viruses. The aim of this study was to evaluate the impact of biofield treatment on HIV-1 and HCMV in terms of viral loads as surrogate marker. The viral load assay was performed on stored stock cultures of HIV infected human plasma samples before and after 7 days of biofield treatmen...

  6. Dynamic load sharing behavior of transverse-torsional coupled planetary gear train with multiple clearances

    Institute of Scientific and Technical Information of China (English)

    盛冬平; 朱如鹏; 靳广虎; 陆凤霞; 鲍和云

    2015-01-01

    A new nonlinear transverse-torsional coupled model with backlash and bearing clearance was proposed for planetary gear set. Meanwhile, sun gear and planet’s eccentricity errors, static transmission error, and time-varying meshing stiffness were taken into consideration. The differential governing equations of motion were solved by employing variable step-size Rung-Kutta numerical integration method. The behavior of dynamic load sharing characteristics affected by the system parameters including input rate, sun gear’s supporting stiffness and eccentricity error, planet’s eccentricity error, sun gear’s bearing clearance, backlashes of sun-planet and planet-ring meshes were investigated qualitatively and systematically. Some theoretical results are summarized at last which extend the current understanding of the dynamic load sharing behavior of planet gear train, enrich the related literature and provide references for the design of planetary gear train.

  7. Viral load of human bocavirus-1 in stools from children with viral diarrhoea in Paraguay.

    Science.gov (United States)

    Proenca-Modena, J L; Martinez, M; Amarilla, A A; Espínola, E E; Galeano, M E; Fariña, N; Russomando, G; Aquino, V H; Parra, G I; Arruda, E

    2013-12-01

    Since their discovery, four species of human bocavirus (HBoV) have been described in patients with respiratory and gastrointestinal diseases. However, a clear causal association between HBoV-1 and gastroenteritis has not been demonstrated. In this study, we describe the detection and quantification of HBoV-1 in stools from children with acute non-bacterial gastroenteritis using quantitative polymerase chain reaction. HBoV-1 genome was detected in 10.6% of stools with frequent association with rotavirus and norovirus. The median of HBoV-1 viral load was 1.88 × 104 genome/ml, lower than previously shown in secretions of patients with respiratory infections, without any obvious association between high viral load and presence of HBoV as single agent. Thus, although HBoV-1 was frequently detected in these patients, there is no clear causal association of this agent with diarrhoea. Indeed, HBoV-1 DNA in stools of patients with gastroenteritis without respiratory symptoms may be a remnant of previous infections or associated with prolonged shedding of virus in the respiratory or digestive tracts.

  8. An HIV epidemic model based on viral load dynamics: value in assessing empirical trends in HIV virulence and community viral load.

    Directory of Open Access Journals (Sweden)

    Joshua T Herbeck

    2014-06-01

    Full Text Available Trends in HIV virulence have been monitored since the start of the AIDS pandemic, as studying HIV virulence informs our understanding of HIV epidemiology and pathogenesis. Here, we model changes in HIV virulence as a strictly evolutionary process, using set point viral load (SPVL as a proxy, to make inferences about empirical SPVL trends from longitudinal HIV cohorts. We develop an agent-based epidemic model based on HIV viral load dynamics. The model contains functions for viral load and transmission, SPVL and disease progression, viral load trajectories in multiple stages of infection, and the heritability of SPVL across transmissions. We find that HIV virulence evolves to an intermediate level that balances infectiousness with longer infected lifespans, resulting in an optimal SPVL∼4.75 log10 viral RNA copies/mL. Adaptive viral evolution may explain observed HIV virulence trends: our model produces SPVL trends with magnitudes that are broadly similar to empirical trends. With regard to variation among studies in empirical SPVL trends, results from our model suggest that variation may be explained by the specific epidemic context, e.g. the mean SPVL of the founding lineage or the age of the epidemic; or improvements in HIV screening and diagnosis that results in sampling biases. We also use our model to examine trends in community viral load, a population-level measure of HIV viral load that is thought to reflect a population's overall transmission potential. We find that community viral load evolves in association with SPVL, in the absence of prevention programs such as antiretroviral therapy, and that the mean community viral load is not necessarily a strong predictor of HIV incidence.

  9. Sustainable HIV treatment in Africa through viral-load-informed differentiated care

    DEFF Research Database (Denmark)

    Phillips, Andrew; Shroufi, Amir; Vojnov, Lara;

    2015-01-01

    in returning results to the clinic. We use modelling to synthesize evidence and evaluate the cost-effectiveness of viral-load-informed differentiated care, accounting for limitations of dried blood sample testing. We find that viral-load-informed differentiated care using dried blood sample testing is cost......-effective and is a recommended strategy for patient monitoring, although further empirical evidence as the approach is rolled out would be of value. We also explore the potential benefits of point-of-care viral load tests that may become available in the future.......) provides a direct measure of the current treatment effect. Viral-load-informed differentiated care is a means of tailoring care so that those with suppressed viral load visit the clinic less frequently and attention is focussed on those with unsuppressed viral load to promote adherence and timely switching...

  10. Factors influencing a low rate of hepatitis C viral RNA clearance in heroin users from Southern China

    Institute of Scientific and Technical Information of China (English)

    ShengHan Lai; Jin-Bing Zhang; Wei Liu; Jie Chen; Xiao-Fang Yu

    2008-01-01

    AIM: To study the virological and host factors influencing hepatitis C infection outcomes in heroin users in southern China.METHODS: HCV RNA and associated factors were analyzed among 347 heroin users from Guangxi Zhuang Autonomous Region, southern China who were hepatitis C virus (HCV) EIA positive for two or more consecutive visits.RESULTS: Using the COBAS AMPLICOR HCV TEST, a remarkably low HCV RNA negative rate of 8.6% was detected. After multivariate logistic regression analysis, HCV RNA clearance was significantly associated with the presence of HBsAg (OR = 8.436, P < 0.0001), the lack of HIV-1 infection (OR = 0.256, P = 0.038) and age younger than 25 (OR = 0.400, P = 0.029).CONCLUSION: Our study suggests HCV infection among Chinese heroin users results in high levels of viral persistence even amidst factors previously found to enhance viral clearance. Prospective studies of a possible genetic component within the Chinese population and the pathogenicity of non-genotype 1 HCV infections are needed.

  11. [Viral load survey from geographical areas within Argentina with high hepatitis B virus prevalence].

    Science.gov (United States)

    Amegeiras, Beatriz; González, Jorge Enrique; Jotimliansky, Laura; Zingoni, Carolina; Vulcano, Cristina

    2013-03-01

    Several studies have demonstrated that viral load is a key factor to determine the development of HBV infection and to assess treatment options for the disease. There is a lack of studies analyzing viral load levels in chronic hepatitis B patients in Argentina and the epidemiologic information is limited. The aim of this study was to determine viral load levels and its distribution in patients diagnosed with chronic hepatitis B from geographical areas with high prevalence for HBV in Argentina. Fifty-one per cent of the study population had HBV DNA levels > or = 10(4) copies/ml and a median viral load of 11,910 copies/ml. The viral load was significantly higher in HBeAg seropositive patients compared with those seronegative for HBeAg (P < 0.05). Salta and Entre Ríos provinces showed low viral loads, while Chaco, Misiones and Formosa provinces had a median viral load ranging between 10(4) and 10(5) copies/ ml. This is the first study providing detailed information on viral load in chronic hepatitis B patients from Argentina. Availability of viral load levels in chronic hepatitis B enables evaluation of implementation of actions to analyze follow-up and/or treatment options for preventing disease complications, improving health care and diminishing the potential burden on the health care system. PMID:23650829

  12. Female sex and IL28B, a synergism for spontaneous viral clearance in hepatitis C virus (HCV seroconverters from a community-based cohort.

    Directory of Open Access Journals (Sweden)

    Charlotte H B S van den Berg

    Full Text Available BACKGROUND & AIMS: Since acute hepatitis C virus (HCV infection is often asymptomatic, it is difficult to examine the rate and determinants of spontaneous clearance. Consequently, these studies are subject to bias, which can potentially lead to biased rates of viral clearance and risk estimates. We evaluated determinants of spontaneous HCV clearance among HCV seroconverters identified in a unique community-based cohort. METHODS: Subjects were 106 drug users with documented dates of HCV seroconversion from the Amsterdam Cohort Study. Logistic regression was used to examine sociodemographic, behavioral, clinical, viral and host determinants, measured around acute infection, of HCV clearance. RESULTS: The spontaneous viral clearance rate was 33.0% (95% confidence interval (CI 24.2-42.8. In univariate analyses female sex and fever were significantly associated with spontaneous clearance. The favorable genotypes for rs12979860 (CC and rs8099917 (TT were associated with spontaneous clearance, although borderline significant. In multivariate analysis, females with the favorable genotype for rs12979860 (CC had an increased odds to spontaneously clear HCV infection (adjusted OR 6.62, 95% 2.69-26.13, whereas females with the unfavorable genotype were as likely as men with the favorable and unfavorable genotype to clear HCV. Chronic Hepatitis B infection and absence of HIV coinfection around HCV seroconversion also favor HCV clearance. CONCLUSIONS: This study shows that co-infection with HIV and HBV and genetic variation in the IL28B region play an important role in spontaneous clearance of HCV. Our findings suggest a possible synergistic interaction between female sex and IL28B in spontaneous clearance of HCV.

  13. Soldier-relevant body borne load impacts minimum foot clearance during obstacle negotiation.

    Science.gov (United States)

    Brown, T N; Loverro, K L; Schiffman, J M

    2016-07-01

    Soldiers often trip and fall on duty, resulting in injury. This study examined ten male soldiers' ability to negotiate an obstacle. Participants had lead and trail foot minimum foot clearance (MFC) parameters quantified while crossing a low (305 mm) and high (457 mm) obstacle with (19.4 kg) and without (6 kg) body borne load. To minimize tripping risk, participants increased lead foot MFC (p = 0.028) and reduced lead (p = 0.044) and trail (p = 0.035) foot variability when negotiating an obstacle with body borne load. While obstacle height had no effect on MFC (p = 0.273 and p = 0.126), placing the trail foot closer to the high obstacle when crossing with body borne load, resulted in greater lead (R = 0.640, b = 0.241, p = 0.046) and trail (R = 0.636, b = 0.287, p = 0.048) MFC. Soldiers, when carrying typical military loads, may be able to minimize their risk of tripping over an obstacle by creating a safety margin via greater foot clearance with reduced variability. PMID:26995036

  14. Expression of suppressor of cytokine signaling 1 (SOCS1 impairs viral clearance and exacerbates lung injury during influenza infection.

    Directory of Open Access Journals (Sweden)

    Keer Sun

    2014-12-01

    Full Text Available Suppressor of cytokine signaling (SOCS proteins are inducible feedback inhibitors of cytokine signaling. SOCS1-/- mice die within three weeks postnatally due to IFN-γ-induced hyperinflammation. Since it is well established that IFN-γ is dispensable for protection against influenza infection, we generated SOCS1-/-IFN-γ-/- mice to determine whether SOCS1 regulates antiviral immunity in vivo. Here we show that SOCS1-/-IFN-γ-/- mice exhibited significantly enhanced resistance to influenza infection, as evidenced by improved viral clearance, attenuated acute lung damage, and consequently increased survival rates compared to either IFN-γ-/- or WT animals. Enhanced viral clearance in SOCS1-/-IFN-γ-/- mice coincided with a rapid onset of adaptive immune responses during acute infection, while their reduced lung injury was associated with decreased inflammatory cell infiltration at the resolution phase of infection. We further determined the contribution of SOCS1-deficient T cells to antiviral immunity. Anti-CD4 antibody treatment of SOCS1-/-IFN-γ-/- mice had no significant effect on their enhanced resistance to influenza infection, while CD8+ splenocytes from SOCS1-/-IFN-γ-/- mice were sufficient to rescue RAG1-/- animals from an otherwise lethal infection. Surprisingly, despite their markedly reduced viral burdens, RAG1-/- mice reconstituted with SOCS1-/-IFN-γ-/- adaptive immune cells failed to ameliorate influenza-induced lung injury. In conclusion, in the absence of IFN-γ, the cytoplasmic protein SOCS1 not only inhibits adaptive antiviral immune responses but also exacerbates inflammatory lung damage. Importantly, these detrimental effects of SOCS1 are conveyed through discrete cell populations. Specifically, while SOCS1 expression in adaptive immune cells is sufficient to inhibit antiviral immunity, SOCS1 in innate/stromal cells is responsible for aggravated lung injury.

  15. Evaluation of Biofield Modality on Viral Load of Hepatitis B and C Viruses

    OpenAIRE

    Trivedi, Mahendra Kumar

    2015-01-01

    Study background: Nowadays, hepatitis is a major challenge for clinical research, regulatory bodies, and clinicians who are trying to assess the more effectiveness of antiviral therapy against patients. Viral load count is the amount of particular viral DNA or RNA in a blood samples. It is one of the surrogate biomarker of hepatitis. High viral load indicates that the immune system is failed to fight against viruses. The aim of this study was to evaluate the impact of biofield modality o...

  16. HIV-1 transmitting couples have similar viral load set-points in Rakai, Uganda.

    Directory of Open Access Journals (Sweden)

    T Déirdre Hollingsworth

    2010-05-01

    Full Text Available It has been hypothesized that HIV-1 viral load set-point is a surrogate measure of HIV-1 viral virulence, and that it may be subject to natural selection in the human host population. A key test of this hypothesis is whether viral load set-points are correlated between transmitting individuals and those acquiring infection. We retrospectively identified 112 heterosexual HIV-discordant couples enrolled in a cohort in Rakai, Uganda, in which HIV transmission was suspected and viral load set-point was established. In addition, sequence data was available to establish transmission by genetic linkage for 57 of these couples. Sex, age, viral subtype, index partner, and self-reported genital ulcer disease status (GUD were known. Using ANOVA, we estimated the proportion of variance in viral load set-points which was explained by the similarity within couples (the 'couple effect'. Individuals with suspected intra-couple transmission (97 couples had similar viral load set-points (p = 0.054 single factor model, p = 0.0057 adjusted and the couple effect explained 16% of variance in viral loads (23% adjusted. The analysis was repeated for a subset of 29 couples with strong genetic support for transmission. The couple effect was the major determinant of viral load set-point (p = 0.067 single factor, and p = 0.036 adjusted and the size of the effect was 27% (37% adjusted. Individuals within epidemiologically linked couples with genetic support for transmission had similar viral load set-points. The most parsimonious explanation is that this is due to shared characteristics of the transmitted virus, a finding which sheds light on both the role of viral factors in HIV-1 pathogenesis and on the evolution of the virus.

  17. Combined Effects of Gravity, Bending Moment, Bearing Clearance, and Input Torque on Wind Turbine Planetary Gear Load Sharing: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Y.; Keller, J.; LaCava, W.

    2012-09-01

    This computational work investigates planetary gear load sharing of three-mount suspension wind turbine gearboxes. A three dimensional multibody dynamic model is established, including gravity, bending moments, fluctuating mesh stiffness, nonlinear tooth contact, and bearing clearance. A flexible main shaft, planetary carrier, housing, and gear shafts are modeled using reduced degrees-of-freedom through modal compensation. This drivetrain model is validated against the experimental data of Gearbox Reliability Collaborative for gearbox internal loads. Planet load sharing is a combined effect of gravity, bending moment, bearing clearance, and input torque. Influences of each of these parameters and their combined effects on the resulting planet load sharing are investigated. Bending moments and gravity induce fundamental excitations in the rotating carrier frame, which can increase gearbox internal loads and disturb load sharing. Clearance in carrier bearings reduces the bearing load carrying capacity and thus the bending moment from the rotor can be transmitted into gear meshes. With bearing clearance, the bending moment can cause tooth micropitting and can induce planet bearing fatigue, leading to reduced gearbox life. Planet bearings are susceptible to skidding at low input torque.

  18. Edge loading in metal-on-metal hips: low clearance is a new risk factor

    Science.gov (United States)

    Zografos, Angelos; Sayles, Ritchie S; Hart, Alister; Cann, Philippa

    2012-01-01

    The revision rate of large head metal-on-metal and resurfacing hips are significantly higher than conventional total hip replacements. The revision of these components has been linked to high wear caused by edge loading; which occurs when the head–cup contact patch extends over the cup rim. There are two current explanations for this; first, there is loss of entrainment of synovial fluid resulting in breakdown of the lubricating film and second, edge loading results in a large local increase in contact pressure and consequent film thickness reduction at the cup rim, which causes an increase in wear. This paper develops a method to calculate the distance between the joint reaction force vector and the cup rim – the contact patch centre to rim (CPCR) distance. However, the critical distance for the risk of edge loading is the distance from the contact patch edge to rim (CPER) distance. An analysis of explanted hip components, divided into edge worn and non-edge-worn components showed that there was no statistical difference in CPCR values, but the CPER value was significantly lower for edge worn hips. Low clearance hips, which have a more conformal contact, have a larger diameter contact patch and thus are more at risk of edge loading for similarly positioned hips. PMID:22558836

  19. Remission of bronchial asthma after viral clearance in chronic hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Norihiko Yamamoto; Kazumoto Murata; Takeshi Nakano

    2005-01-01

    A 53-year-old man with a history of blood transfusion at the age of 20 was admitted to our hospital because of liver dysfunction. He had bronchial asthma when he was 18 years old, which naturally resolved within 2 years. However, his bronchial asthma recurred at the age of 45 and was treated with oral theophylline. He was diagnosed as having chronic hepatitis C based on the histological and clinical findings, and then interferon (IFN) therapy was administered. The frequency of bronchial asthma attack was gradually decreasing after IFN therapy with marked improvement of hypereosinophilia. He achieved sustained viral response (SVR) and his bronchial asthma did not worsen even after the cessation of IFN. Hepatitis C virus (HCV) infection and IFN therapy were considered in the remission of asthma in this case. HCV infection could be the cause of bronchial asthma, especially in patients with late appearance of asthma.

  20. Scale-up of HIV Viral Load Monitoring--Seven Sub-Saharan African Countries.

    Science.gov (United States)

    Lecher, Shirley; Ellenberger, Dennis; Kim, Andrea A; Fonjungo, Peter N; Agolory, Simon; Borget, Marie Yolande; Broyles, Laura; Carmona, Sergio; Chipungu, Geoffrey; De Cock, Kevin M; Deyde, Varough; Downer, Marie; Gupta, Sundeep; Kaplan, Jonathan E; Kiyaga, Charles; Knight, Nancy; MacLeod, William; Makumbi, Boniface; Muttai, Hellen; Mwangi, Christina; Mwangi, Jane W; Mwasekaga, Michael; Ng'Ang'A, Lucy W; Pillay, Yogan; Sarr, Abdoulaye; Sawadogo, Souleymane; Singer, Daniel; Stevens, Wendy; Toure, Christiane Adje; Nkengasong, John

    2015-11-27

    To achieve global targets for universal treatment set forth by the Joint United Nations Programme on human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) (UNAIDS), viral load monitoring for HIV-infected persons receiving antiretroviral therapy (ART) must become the standard of care in low- and middle-income countries (LMIC) (1). CDC and other U.S. government agencies, as part of the President's Emergency Plan for AIDS Relief, are supporting multiple countries in sub-Saharan Africa to change from the use of CD4 cell counts for monitoring of clinical response to ART to the use of viral load monitoring, which is the standard of care in developed countries. Viral load monitoring is the preferred method for immunologic monitoring because it enables earlier and more accurate detection of treatment failure before immunologic decline. This report highlights the initial successes and challenges of viral load monitoring in seven countries that have chosen to scale up viral load testing as a national monitoring strategy for patients on ART in response to World Health Organization (WHO) recommendations. Countries initiating viral load scale-up in 2014 observed increases in coverage after scale-up, and countries initiating in 2015 are anticipating similar trends. However, in six of the seven countries, viral load testing coverage in 2015 remained below target levels. Inefficient specimen transport, need for training, delays in procurement and distribution, and limited financial resources to support scale-up hindered progress. Country commitment and effective partnerships are essential to address the financial, operational, technical, and policy challenges of the rising demand for viral load monitoring. PMID:26605986

  1. Decreases in Community Viral Load Are Accompanied by Reductions in New HIV Infections in San Francisco

    OpenAIRE

    Moupali Das; Priscilla Lee Chu; Glenn-Milo Santos; Susan Scheer; Eric Vittinghoff; Willi McFarland; Grant N Colfax

    2010-01-01

    BACKGROUND: At the individual level, higher HIV viral load predicts sexual transmission risk. We evaluated San Francisco's community viral load (CVL) as a population level marker of HIV transmission risk. We hypothesized that the decrease in CVL in San Francisco from 2004-2008, corresponding with increased rates of HIV testing, antiretroviral therapy (ART) coverage and effectiveness, and population-level virologic suppression, would be associated with a reduction in new HIV infections. METHOD...

  2. Sustainable HIV treatment in Africa through viral-load-informed differentiated care.

    Science.gov (United States)

    Phillips, Andrew; Shroufi, Amir; Vojnov, Lara; Cohn, Jennifer; Roberts, Teri; Ellman, Tom; Bonner, Kimberly; Rousseau, Christine; Garnett, Geoff; Cambiano, Valentina; Nakagawa, Fumiyo; Ford, Deborah; Bansi-Matharu, Loveleen; Miners, Alec; Lundgren, Jens D; Eaton, Jeffrey W; Parkes-Ratanshi, Rosalind; Katz, Zachary; Maman, David; Ford, Nathan; Vitoria, Marco; Doherty, Meg; Dowdy, David; Nichols, Brooke; Murtagh, Maurine; Wareham, Meghan; Palamountain, Kara M; Chakanyuka Musanhu, Christine; Stevens, Wendy; Katzenstein, David; Ciaranello, Andrea; Barnabas, Ruanne; Braithwaite, R Scott; Bendavid, Eran; Nathoo, Kusum J; van de Vijver, David; Wilson, David P; Holmes, Charles; Bershteyn, Anna; Walker, Simon; Raizes, Elliot; Jani, Ilesh; Nelson, Lisa J; Peeling, Rosanna; Terris-Prestholt, Fern; Murungu, Joseph; Mutasa-Apollo, Tsitsi; Hallett, Timothy B; Revill, Paul

    2015-12-01

    There are inefficiencies in current approaches to monitoring patients on antiretroviral therapy in sub-Saharan Africa. Patients typically attend clinics every 1 to 3 months for clinical assessment. The clinic costs are comparable with the costs of the drugs themselves and CD4 counts are measured every 6 months, but patients are rarely switched to second-line therapies. To ensure sustainability of treatment programmes, a transition to more cost-effective delivery of antiretroviral therapy is needed. In contrast to the CD4 count, measurement of the level of HIV RNA in plasma (the viral load) provides a direct measure of the current treatment effect. Viral-load-informed differentiated care is a means of tailoring care so that those with suppressed viral load visit the clinic less frequently and attention is focussed on those with unsuppressed viral load to promote adherence and timely switching to a second-line regimen. The most feasible approach to measuring viral load in many countries is to collect dried blood spot samples for testing in regional laboratories; however, there have been concerns over the sensitivity and specificity of this approach to define treatment failure and the delay in returning results to the clinic. We use modelling to synthesize evidence and evaluate the cost-effectiveness of viral-load-informed differentiated care, accounting for limitations of dried blood sample testing. We find that viral-load-informed differentiated care using dried blood sample testing is cost-effective and is a recommended strategy for patient monitoring, although further empirical evidence as the approach is rolled out would be of value. We also explore the potential benefits of point-of-care viral load tests that may become available in the future.

  3. HPV infection, risk factors and viral load among Mexican male college students

    Directory of Open Access Journals (Sweden)

    Carmina Vera-Uehara

    2014-01-01

    Full Text Available Objectives: To determine the prevalence of HPV and the risky sexual behaviors associated to it in a sample of male college students, taking into account genotype and viral load. Methods: From 2002 to 2003, male students from the Autonomous University of Morelos State completed a questionnaire and provided self-collected genital samples to detect and quantify HPV. We performed a bivariate and a multivariate logistic regression analysis to identify correlates associated with the infection and to assess the viral load as a function of the viral infecting type. The fragments of β-globin gene and L1 of HPV, were amplified, purified and cloned, to evaluate viral load. Results: Among 253 subjects, HPV prevalence was 19.4%, and HPV16 was the most common subtype. History of STIs (OR = 4.8; 95% CI 1.2–18.9, contraceptive pill use by female partner (OR = 2.6; 95% CI 1.1–6.3 and exchanging sex for money (OR = 4.9; 95% CI 1.2–20 were associated to the HPV infection. HPV16 viral load was 7.8 copies (HPV/beta-globin compared to 0.9 copies for other HPV types. Discussion: HPV16 displayed the highest viral load, and it was the most prevalent. It was found that using contraceptive pills by female partners was associated with HPV infection.

  4. Antiretroviral treatment, viral load of mothers & perinatal HIV transmission in Mumbai, India

    Directory of Open Access Journals (Sweden)

    Swati P Ahir

    2013-01-01

    Full Text Available Background & objectives: Mother-to-child transmission (MTCT is the most significant route of HIV transmission in children below the age of 15 yr. In India, perinatal HIV transmission, even after treatment, accounts for 5.4 per cent of HIV cases. The present study was conducted to evaluate the efficacy of anti-retro viral therapy (ART or prophylactic treatment (PT to control maternal viral load in HIV positive women, and its effect on vertical HIV transmission to their infants. Methods: A total of 58 HIV positive women were enrolled at the time of delivery and their plasma samples were obtained within 24 h of delivery for estimation of viral load. Viral load analysis was completed in 38 women. Infants received single dose nevirapine within 2 h of birth and zidovudine for 6 wk. At the end of 18 month follow up, HIV positive or negative status was available in 28 infants. Results: Results revealed undetectable levels of viral load in 58.3 per cent of women with ART compared to 30.7 per cent of women with PT. No women on ART had viral load more than 10,000 copies/ml, whereas seven (26.9%, P=0.07 women receiving PT had this viral load. Median CD4 count of women on PT (483 cells/μl was high compared to the women on ART (289 cells/ μl. At the end of 18 months follow up, only two children were HIV positive, whose mothers were on PT. One had in utero transmission; infection detected within 48 h of delivery, while the other child was infected post partum as HIV was detected at six months follow up. Interpretation & conclusions: Women who received a single dose of nevirapine during delivery had higher levels of viral load than women on ART. Combination drug therapy for pregnant women is now a standard of care in most of the western countries; use of nevirapine monotherapy at the time of delivery in our settings is not effective in controlling viral load. This highlights initiation of ART in pregnant women to control their viral load and thus to inhibit

  5. Variables that influence HIV-1 cerebrospinal fluid viral load in cryptococcal meningitis: a linear regression analysis

    Directory of Open Access Journals (Sweden)

    Cecchini Diego M

    2009-11-01

    Full Text Available Abstract Background The central nervous system is considered a sanctuary site for HIV-1 replication. Variables associated with HIV cerebrospinal fluid (CSF viral load in the context of opportunistic CNS infections are poorly understood. Our objective was to evaluate the relation between: (1 CSF HIV-1 viral load and CSF cytological and biochemical characteristics (leukocyte count, protein concentration, cryptococcal antigen titer; (2 CSF HIV-1 viral load and HIV-1 plasma viral load; and (3 CSF leukocyte count and the peripheral blood CD4+ T lymphocyte count. Methods Our approach was to use a prospective collection and analysis of pre-treatment, paired CSF and plasma samples from antiretroviral-naive HIV-positive patients with cryptococcal meningitis and assisted at the Francisco J Muñiz Hospital, Buenos Aires, Argentina (period: 2004 to 2006. We measured HIV CSF and plasma levels by polymerase chain reaction using the Cobas Amplicor HIV-1 Monitor Test version 1.5 (Roche. Data were processed with Statistix 7.0 software (linear regression analysis. Results Samples from 34 patients were analyzed. CSF leukocyte count showed statistically significant correlation with CSF HIV-1 viral load (r = 0.4, 95% CI = 0.13-0.63, p = 0.01. No correlation was found with the plasma viral load, CSF protein concentration and cryptococcal antigen titer. A positive correlation was found between peripheral blood CD4+ T lymphocyte count and the CSF leukocyte count (r = 0.44, 95% CI = 0.125-0.674, p = 0.0123. Conclusion Our study suggests that CSF leukocyte count influences CSF HIV-1 viral load in patients with meningitis caused by Cryptococcus neoformans.

  6. Effects of interferon-α/β on HBV replication determined by viral load.

    Directory of Open Access Journals (Sweden)

    Yongjun Tian

    2011-07-01

    Full Text Available Interferons α and β (IFN-α/β are type I interferons produced by the host to control microbial infections. However, the use of IFN-α to treat hepatitis B virus (HBV patients generated sustained response to only a minority of patients. By using HBV transgenic mice as a model and by using hydrodynamic injection to introduce HBV DNA into the mouse liver, we studied the effect of IFN-α/β on HBV in vivo. Interestingly, our results indicated that IFN-α/β could have opposite effects on HBV: they suppressed HBV replication when viral load was high and enhanced HBV replication when viral load was low. IFN-α/β apparently suppressed HBV replication via transcriptional and post-transcriptional regulations. In contrast, IFN-α/β enhanced viral replication by inducing the transcription factor HNF3γ and activating STAT3, which together stimulated HBV gene expression and replication. Further studies revealed an important role of IFN-α/β in stimulating viral growth and prolonging viremia when viral load is low. This use of an innate immune response to enhance its replication and persistence may represent a novel strategy that HBV uses to enhance its growth and spread in the early stage of viral infection when the viral level is low.

  7. Physical status and viral load in women with positive human papillomavirus (HPV) infection in uterine cervix

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Byoung Gie; Lee, Eui Don; Zin, Yong Jae [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    1998-01-01

    This study was performed to determine the frequency of viral integration and viral load in women with positive HPV type 16 infection, and showing normal findings, CIN, and cervical cancer. Total 75 (normal, 15; CIN I, 20; CIN III, 20; cervical cancer, 20) cervical swab specimens were used. HPV detection, typing, and viral load was determined by PCR method. Seventy of 75 (93.3%) of cervical swab specimens showed same results with hybrid capture assay and PCR method for detecting HPV DNA. HPV type 16 DNA was identified more frequently with progression from normal to cervical cancer (normal, 13 %; CIN I, 15%; CIN III, 40 %; cervical cancer, 55 %). The frequency of HPV type 16 DNA integration also increased with grade of the lesion (normal, 0 %; CIN I, 33 %; CIN III, 87 %; cervical cancer, 91 %) suggesting most of HPV type 16 present as integration forms in the cells. In addition, high-level of HPV 16 viral load also was found more frequently in CIN III and cervical cancer (normal, 0 %; CIN I, 0 %; CIN III, 87 %; cervical cancer, 100 %). These results suggest that viral integration and high-level of viral load may play an important role in cervical carcinogenesis. (author). 13 refs., 5 figs.

  8. Distinct patterns of the lipid alterations between genotype 1 and 2 chronic hepatitis C patients after viral clearance.

    Directory of Open Access Journals (Sweden)

    Ming-Ling Chang

    Full Text Available The hepatitis C virus (HCV genotype-specific impacts on the host metabolic alterations remained inconclusive.A prospective study including 229 (118 genotype 1 (G1 and 111 G2 consecutive chronic HCV patients who had completed a course of anti-HCV treatment and underwent pre- and 24 weeks post-treatment surveys of metabolic profiles was conducted. Patients were stratified according to the therapeutic response, viral genotype and baseline insulin resistance (IR: homeostasis model assessments of IR (HOMA-IR ≥ 2.5. Paired t-tests were used to compare the pre- and post-treatment variables.Significant post-therapeutic increases in cholesterol, triglyceride, HDL, LDL, apolipoprotein A1 and apolipoprotein B were observed in patients with sustained virological response (SVR but not in those without. Among those with SVR, post-therapeutic increases in HDL (p<0.001 and apolipoprotein A1 (p = 0.012 were only found in G2, whereas increased triglyceride/HDL (p = 0.01 ratios were only found in G1 patients. When stratified by baseline IR among those with SVR, a significant increase in post-treatment HDL (p = 0.019 and apolipoprotein A1 (p = 0.012 but a decrease in HOMA-IR (p = 0.04, C-peptide (p = 0.019 and hemoglobin A1c (p = 0.047 were found in patients with baseline IR; a significant increase in HOMA-IR (p = 0.002 was found in patients without baseline IR. The latter change was observed only in G1 (p = 0.01 but not G2 patients. Although the pre-treatment metabolic profiles of G1 and G2 patients were indifferent, G1 had higher post-treatment triglyceride/HDL ratios (p = 0.041 and triglyceride (p = 0.044 levels than G2 patients.G2 benefit more than G1 patients from viral clearance in metabolic alterations, particularly in those without baseline IR.

  9. Correlation analysis of high-risk human papillomavirus viral load and cervical lesions

    Directory of Open Access Journals (Sweden)

    Xiao-xing MA

    2012-05-01

    Full Text Available Objective  To explore the association between high-risk human papillomavirus (HR-HPV viral load and pathological grades of cervical intraepithelial neoplasia (CIN and cervical cancer. Methods  A total of 1248 patients from General Hospital of PLA, who underwent colposcopy and surgery due to cervical lesions between Jan. 2006 and Aug. 2011 were enrolled in this study, and they were divided five groups: cervicitis, CIN Ⅰ, CIN Ⅱ-Ⅲ, stage Ⅰ cervical cancer and stage Ⅱ cervical cancer. HR-HPV viral load (RLU/CO was determined by the Hybrid Capture Ⅱ (HCⅡ system, and they were categorized into five groups: 0-0.99, 1.00-9.99, 10.00-99.99, 100.00-999.99, ≥1000.00. The mean value and standard deviation of different HR-HPV viral load in the patients with cervicitis or with CIN Ⅰ, CINⅡ-Ⅲ, stage Ⅰ cervical cancer or stage Ⅱ cervical cancer were compared, and the correlation of HR-HPV viral load and pathogenesis of cervical lesions was analyzed. Results  HPV viral loads were significantly higher in CINⅠ(842.1±983.9, CINⅡ-Ⅲ (690.1±795.0, stage Ⅰ cervical cancer (893.1±974.2 and stage Ⅱ cervical cancer (699.5±908.3 patients than in cervicitis patients (274.2±613.6, P < 0.05, and the HPV viral loads in CINⅠ(842.1±983.9 and stage Ⅰ cervical cancer patients were higher than those in CINⅡ-Ⅲ patients (P < 0.05. When HR-HPV viral load was ≥100RLU/CO, the risk of CIN and cervical cancer increased with the increase in viral load, but there was no correlation between the viral load and pathological grades of cervical lesions. In the patients with stage ⅠB-Ⅱ cervical squamous cell carcinoma, when the HR-HPV viral load was ≥100RLU/CO, the risk of lymph node metastasis increased (P < 0.05, and the number of patients with maximum diameter of the cervical tumor ≥4cm also increased (P < 0.05. However, the HR-HPV viral load was not correlated with patient age, pathological type of the lesion, depth of cancer

  10. Impact of collection method on assessment of semen HIV RNA viral load.

    Directory of Open Access Journals (Sweden)

    Brendan J W Osborne

    Full Text Available BACKGROUND: The blood HIV RNA viral load is the best-defined predictor of HIV transmission, in part due to ease of measurement and the correlation of blood and genital tract (semen or cervico-vaginal viral load, although recent studies found semen HIV RNA concentration to be a stronger predictor of HIV transmission. There is currently no standardized method for semen collection when measuring HIV RNA concentration. Therefore, we compared two collection techniques in order to study of the impact of antiretroviral therapy on the semen viral load. METHODOLOGY/PRINCIPAL FINDINGS: Semen was collected by masturbation from HIV-infected, therapy-naïve men who have sex with men (MSM either undiluted (Visit 1 or directly into transport medium (Visit 2. Seminal plasma was then isolated, and the HIV RNA concentration obtained with each collection technique was measured and corrected for dilution if necessary. Collection of semen directly into transport medium resulted in a median HIV RNA viral load that was 0.4 log10 higher than undiluted samples. CONCLUSIONS/SIGNIFICANCE: The method of semen collection is an important consideration when quantifying the HIV RNA viral load in this compartment.

  11. Ultrasensitive HCV RNA Quantification in Antiviral Triple Therapy: New Insight on Viral Clearance Dynamics and Treatment Outcome Predictors

    Science.gov (United States)

    Garbuglia, Anna Rosa; Visco-Comandini, Ubaldo; Lionetti, Raffaella; Lapa, Daniele; Castiglione, Filippo; D’Offizi, Gianpiero; Taibi, Chiara; Montalbano, Marzia; Capobianchi, Maria Rosaria; Paci, Paola

    2016-01-01

    Objectives Identifying the predictive factors of Sustained Virological Response (SVR) represents an important challenge in new interferon-based DAA therapies. Here, we analyzed the kinetics of antiviral response associated with a triple drug regimen, and the association between negative residual viral load at different time points during treatment. Methods Twenty-three HCV genotype 1 (GT 1a n = 11; GT1b n = 12) infected patients were included in the study. Linear Discriminant Analysis (LDA) was used to establish possible association between HCV RNA values at days 1 and 4 from start of therapy and SVR. Principal component analysis (PCA) was applied to analyze the correlation between HCV RNA slope and SVR. A ultrasensitive (US) method was established to measure the residual HCV viral load in those samples which resulted “detected <12IU/ml” or undetectable with ABBOTT standard assay, and was retrospectively used on samples collected at different time points to establish its predictive power for SVR. Results According to LDA, there was no association between SVR and viral kinetics neither at time points earlier than 1 week (days 1 and 4) after therapy initiation nor later. The slopes were not relevant for classifying patients as SVR or no-SVR. No significant differences were observed in the median HCV RNA values at T0 among SVR and no-SVR patients. HCV RNA values with US protocol (LOD 1.2 IU/ml) after 1 month of therapy were considered; the area under the ROC curve was 0.70. Overall, PPV and NPV of undetectable HCV RNA with the US method for SVR was 100% and 46.7%, respectively; sensitivity and specificity were 38.4% and 100% respectively. Conclusion HCV RNA “not detected” by the US method after 1 month of treatment is predictive of SVR in first generation Protease inhibitor (PI)-based triple therapy. The US method could have clinical utility for advanced monitoring of virological response in new interferon based DAA combination regimens. PMID:27560794

  12. DNA-guided hepatitis B treatment: Viral load is insufficient with few exceptions

    Institute of Scientific and Technical Information of China (English)

    Pankaj Jain

    2009-01-01

    In DNA-guided hepatitis B treatment, viral load is insufficient, and requires other viral markers for treatment of hepatitis B patients as in patients with acute exacerbation of chronic hepatitis B, end-stage renal disease on dialysis, human immunodeficiency virus co-infected patients. There are exceptions to this rule:a residual level hepatitis B virus (HBV) DNA at 24 wk predicts beneficial outcome and reduced resistance at 1 year. The genotypic viral resistance to antiviral agents and occult HBV infection can be determined by HBV-DNA levels.

  13. Mechanism of antibody-mediated viral clearance in immunotherapy of respiratory syncytial virus infection of cotton rats.

    OpenAIRE

    Prince, G A; Hemming, V G; Horswood, R L; Baron, P A; Murphy, B R; Chanock, R M

    1990-01-01

    Antibody-mediated clearance of respiratory syncytial virus from cotton rat pulmonary tissues occurs in the absence of complement and in the absence of the Fc portion of the immunoglobulin G molecule, suggesting that complement-independent, cell-independent neutralization is the major mechanism of clearance.

  14. Renal clearance of digoxin in man after sodium loading or furosemide treatment.

    Science.gov (United States)

    Naafs, M A; van der Hoek, C; Schopman, W; van Duin, S; Koorevaar, G; Silberbusch, J

    1983-01-01

    To evaluate the influence of different types of natriuresis on the renal clearance of digoxin (Cldig) and the Cldig/Clcr ratio, studies were performed in which sodium-depleted patients were placed on a moderately high sodium diet for 6 days. In another group natriuresis was evoked by furosemide. In the first study, in 10 patients, there was a 10-fold increase in Na excretion and a small rise in diuresis (V) and Clcr, which was accompanied by an increase in Cldig from 57.5 +/- 32, and 60.7 +/- 27.3 (duplicate measurements) to 103.9 +/- 55.4 (p less than 0.01) and 103.8 +/- 46.5 ml min-1 (p less than 0.01). Cldig/Clcr rose from 0.60 +/- 0.24 and 0.61 +/- 0.16 to 0.91 +/- 0.31 and 0.91 +/- 0.21, respectively (both p less than 0.005). Serum digoxin concentration declined from 1.24 +/- 0.35 and 1.19 +/- 0.40 to 1.02 +/- 0.35 and 0.97 +/- 0.32 micrograms/l (both p less than 0.01) during the high sodium diet. In the furosemide-induced natriuresis (6 patients), changes in Na excretion and V were a multiple of those caused by Na loading, but the Cldig/Clcr ratio was not increased. The results are in accordance with the concept of digoxin backdiffusion in the proximal tubules, which is dependent on proximal Na reabsorption. In the more distal segments of the nephron, where the action of furosemide occurs, there does not appear to be any transtubular movement of digoxin. PMID:6628526

  15. Honeybee (Apis mellifera Venom Reinforces Viral Clearance during the Early Stage of Infection with Porcine Reproductive and Respiratory Syndrome Virus through the Up-Regulation of Th1-Specific Immune Responses

    Directory of Open Access Journals (Sweden)

    Jin-A Lee

    2015-05-01

    Full Text Available Porcine reproductive and respiratory syndrome (PRRS is a chronic and immunosuppressive viral disease that is responsible for substantial economic losses for the swine industry. Honeybee venom (HBV is known to possess several beneficial biological properties, particularly, immunomodulatory effects. Therefore, this study aimed at evaluating the effects of HBV on the immune response and viral clearance during the early stage of infection with porcine reproductive and respiratory syndrome virus (PRRSV in pigs. HBV was administered via three routes of nasal, neck, and rectal and then the pigs were inoculated with PRRSV intranasally. The CD4+/CD8+ cell ratio and levels of interferon (IFN-γ and interleukin (IL-12 were significantly increased in the HBV-administered healthy pigs via nasal and rectal administration. In experimentally PRRSV-challenged pigs with virus, the viral genome load in the serum, lung, bronchial lymph nodes and tonsil was significantly decreased, as was the severity of interstitial pneumonia, in the nasal and rectal administration group. Furthermore, the levels of Th1 cytokines (IFN-γ and IL-12 were significantly increased, along with up-regulation of pro-inflammatory cytokines (TNF-α and IL-1β with HBV administration. Thus, HBV administration—especially via the nasal or rectal route—could be a suitable strategy for immune enhancement and prevention of PRRSV infection in pigs.

  16. Quantification of infectious HIV-1 plasma viral load using a boosted in vitro infection protocol.

    Science.gov (United States)

    Rusert, Peter; Fischer, Marek; Joos, Beda; Leemann, Christine; Kuster, Herbert; Flepp, Markus; Bonhoeffer, Sebastian; Günthard, Huldrych F; Trkola, Alexandra

    2004-08-15

    Methods currently used for HIV-1 viral load measurements are very sensitive, but cannot distinguish between infectious and noninfectious particles. Here we describe the development of a novel, sensitive, and highly reproducible method that allows rapid isolation and quantification of infectious particles from patient plasma. By immobilizing HIV-1 particles in human plasma to platelets using polybrene, we observed a 10- to 1000-fold increase in infectivity over infection protocols using free virus particles. Using this method, we evaluated infectivity in plasma from 52 patients at various disease stages. At plasma viral loads of 1000-10000 HIV-1 RNA copies/ml 18%, at 10,000-50,000 copies/ml 73%, at 50,000-100,000 copies/ml 90%, and above 100,000 copies 96% of cultures were positive. We found that infectious titers among patients vary distinctively but are characteristic for a patient over extended time periods. Furthermore, we demonstrate that by evaluating infectious titers in conjunction with total HIV RNA loads, subtle effects of treatment intervention on viremia levels can be detected. The immobilization procedure does not interfere with viral entry and does not restore the infectivity of neutralized virus. Therefore, this assay system can be utilized to investigate the influence of substances that specifically affect virion infectivity such as neutralizing antibodies, soluble CD4, or protease inhibitors. Measuring viral infectivity may thereby function as an additional, useful marker in monitoring disease progression and evaluating efficacy of antivirals in vivo.

  17. DNA-guided hepatitis B treatment, viral load is essential,but not sufficient

    Institute of Scientific and Technical Information of China (English)

    Rafael Bárcena Marugán; Silvia García Garzón

    2009-01-01

    Hepatitis B virus (HBV) infection is a global public health problem that concerns 350 million people worldwide. Individuals with chronic hepatitis B (CHB) are at increased risk of developing liver cirrhosis,hepat i c de- compensation and hepatocellular carcinoma. To maintain undetectable viral load reduces chronic infection complications. There is no treatment that eradicates HBV infection. Current drugs are expensive, are associated with adverse events, and are of limited efficacy. Current guidelines try to standardize the clinical practice. Nevertheless, controversy remains about management of asymptomatic patients with CHB who are hepatitis B e antigen (HBeAg)-positive with normal alanine aminotransferase, and what is the cut-off value of viral load to distinguish HBeAgnegative CHB patients and inactive carriers. We discuss in detail why DNA level alone is not sufficient to begin treatment of CHB.

  18. Development of a modular virus clearance package for anion exchange chromatography operated in weak partitioning mode.

    Science.gov (United States)

    Iskra, Timothy; Sacramo, Ashley; Gallo, Chris; Godavarti, Ranga; Chen, Shuang; Lute, Scott; Brorson, Kurt

    2015-01-01

    Anion exchange chromatography (AEX) operated under weak partitioning mode has been proven to be a powerful polishing step as well as a robust viral clearance step in Pfizer's monoclonal antibody (mAb) platform purification process. A multivariate design of experiment (DoE) study was conducted to understand the impact of operating parameters and feedstream impurity levels on viral clearance by weak partitioning mode AEX. Bacteriophage was used initially as a surrogate for neutral and acidic isoelectric point mammalian viruses (e.g., retrovirus and parvovirus). Five different mAbs were used in the evaluation of process parameters such as load challenge (both product and impurities), load pH, load conductivity, and contact time (bed height and flow-rate). The operating ranges obtained from phage clearance studies and Pfizer's historical data were used to define an appropriate operating range for a subsequent clearance study with model retrovirus and parvovirus. Both phage and virus clearance evaluations included feedstreams containing different levels of impurities such as high molecular mass species (HMMS), host cell proteins (HCPs), and host cell DNA. For all the conditions tested, over 5 log10 of clearance for both retrovirus and parvovirus was achieved. The results demonstrated that weak partitioning mode AEX chromatography is a robust step for viral clearance and has the potential to be included as part of the modular viral clearance approach.

  19. Cerebrospinal fluid human immunodeficiency virus viral load in patients with neurosyphilis

    OpenAIRE

    Almeida, Sergio Monteiro de; Bhatt, Archana; Riggs, Patricia K.; Durelle, Janis; Lazzaretto, Deborah; Marquie-Beck, Jennifer; McCutchan, Allen; Letendre, Scott; Ellis, Ronald

    2010-01-01

    Syphilis is a frequent coinfection with human immunodeficiency virus (HIV). Whereas systemic syphilis infection increases plasma HIV RNA levels (viral load; VL), effects of syphilis on cerebrospinal fluid (CSF) VL are unknown. We hypothesized that intrathecal immune activation in neurosyphilis would selectively increase CSF VL in coinfected patients. In this study, HIV-infected research subjects (N = 225) were categorized into three groups based on serum rapid plasma reagin (RPR), microhemagl...

  20. Effects of medical male circumcision (MC on plasma HIV viral load in HIV+ HAART naive men; Rakai, Uganda.

    Directory of Open Access Journals (Sweden)

    Godfrey Kigozi

    Full Text Available BACKGROUND: Medical male circumcision (MC of HIV-infected men may increase plasma HIV viral load and place female partners at risk of infection. We assessed the effect of MC on plasma HIV viral load in HIV-infected men in Rakai, Uganda. METHODS: 195 consenting HIV-positive, HAART naïve men aged 12 and above provided blood for plasma HIV viral load testing before surgery and weekly for six weeks and at 2 and 3 months post surgery. Data were also collected on baseline social demographic characteristics and CD4 counts. Change in log10 plasma viral load between baseline and follow-up visits was estimated using paired t tests and multivariate generalized estimating equation (GEE. RESULTS: Of the 195 men, 129 had a CD4 count ≧ 350 and 66 had CD4 <350 cells/mm3. Men with CD4 counts <350 had higher baseline mean log10 plasma viral load than those with CD4 counts ≧ 350 cells/mm3 (4.715 vs 4.217 cps/mL, respectively, p = 0.0005. Compared to baseline, there was no statistically significant increase in post-MC HIV plasma viral loads irrespective of CD4. Multivariate analysis showed that higher baseline log10 plasma viral load was significantly associated with reduction in mean log10 plasma viral load following MC (coef.  = -0.134, p<0.001. CONCLUSION: We observed no increase in plasma HIV viral load following MC in HIV-infected, HAART naïve men.

  1. Evaluation of viral load in saliva from patients with chronic hepatitis C infection.

    Science.gov (United States)

    Xavier Santos, Renata L; de Deus, Dayse M V; de Almeida Lopes, Edmundo P; Duarte Coêlho, Maria R C; de Castro, Jurema F L

    2015-01-01

    Hepatitis C virus can be detected in blood and other bodily fluids, such as saliva. The aim of this study was to detect and quantify the HCV-RNA in saliva and plasma from patients with chronic hepatitis C infections, as well as check the level of viral load in sex groups (age, ethnicity and virus subtypes). Whole saliva and blood from 70 patients with chronic hepatitis C infections attended at the department of gastroenterology from University Hospital. The HCV-RNA load was performed by qRT-PCR using Sybr Green I master mix. HCV-RNA was detected in 80% (56/70) of patients in saliva and 92.85% (65/70) in plasma. The median of the viral load in the plasma was of 4.87 log10, and in saliva, it was 3.32log10, (p = 0.0005). Female patients and black patients exhibited a negative correlation between the HCV-RNA load in saliva vs. the HCV-RNA load in plasma (r = -0.3172, CI95% -0.6240 to -0.03736, p = 0.0491) and (r = -0.3141; IC95% -0.6069 to -0.05926; p = 0.0209), respectively. HCV-RNA was detected and quantified in saliva samples, and according to the quantification levels, saliva may be a possible transmission source of HCV, particularly in women and people of black ethnicity who develop chronic HCV infections.

  2. Monitoring HIV viral load in resource limited settings: still a matter of debate?

    Directory of Open Access Journals (Sweden)

    Mireia Arnedo

    Full Text Available INTRODUCTION: Consequences of lack of viral monitoring in predicting the effects of development of HIV drug resistance mutations during HAART in resource-limited settings (RLS is still a matter of debate. DESIGN: To assess, among HIV+ patients receiving their first-line HAART, prevalence of virological failure and genotypic resistance mutations pattern in a Médécins Sans Frontières/Ministry of Health programme in Busia District (Kenya. METHODS: Patients with HAART treatment for ≥12 months were eligible for the study and those with HIV-RNA ≥5000 copies/ml underwent genotypic study. Total HIV-1 RNA from Dried Blood Spots was extracted using Nuclisens method. RESULTS: 926 patients were included. Among 274 (29.6% patients with detectable viral load, 55 (5.9% experienced treatment failure (viral load >5.000 copies/ml; 61.8% were female and 10 (18.2% had clinical failure. Median CD4 cell count was 116 cell/mm3 (IQR: 54-189. Median HIV-RNA was 32,000 copies/ml (IQR: 11000-68000. Eighteen out of 55 (33% samples could be sequenced on PR and RT genes, with resistance associated mutations (RAMs in 15 out of 18 samples (83%. Among patients carrying RAMs, 12/15 (81% harboured RAMs associated to thymidine analogues (TAMs. All of them (100% showed M184V resistance associated mutation to lamivudine as well as NNRTI's RAMS. CONCLUSIONS: Virological failure rate in resource-limited settings are similar to those observed in developed countries. Resistance mutation patterns were concordant with HAART received by failing patients. Long term detectable viral load confers greater probability of developing resistance and as a consequence, making difficult to find out a cost-effective subsequent treatment regimen.

  3. Effect of viral load on T-lymphocyte failure in patients with chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Jing You; Hutcha Sriplung; Alan Geater; Virasakdi Chongsuvivatwong; Lin Zhuang; Hong-Ying Chen; Lan Yu; Bao-Zhang Tang; Jun-Hua Huang

    2008-01-01

    AIM:To investigate peripheral T-lymphocyte subpopulation profile and its correlation with hepatitis B virus (HBV) replication in patients with chronic hepatitis B (CHB).METHODS:Distribution of T-lymphocyte subpopulations in peripheral blood was measured by flow cytometry in 206 CHB patients.HBV markers were detected with ELISA.Serum HBV DNA load was assessed with quantitative real-time polymerase chain reaction (PCR).The relationship between HBV replication and variation in peripheral T-cell subsets was analyzed.RESULTS:CHB patients had significantly decreased CD3,and CD4+ cells and CD4+/CD8+ ratio,and increased CD8+ cells compared with uninfected controls (55.44±12.39 vs 71.07±4.76,30.92±7.48 vs 38.94±3.39,1.01±0.49 vs 1.67±0.33,and 34.39±9.22 vs 24.02±4.35;P<0.001,respectively).Univariate analysis showed a similar pattern of these parameters was significantly associated with high viral load,presence of serum hepatitis B e antigen (HBeAg) expression,liver disease severity,history of maternal HBV infection,and young age at HBV infection,all with P<0.01.There was a significant linear relationship between viral load and these parameters of T-lymphocyte subpopulations (linear trend test P<0.001).There was a negative correlation between the levels of CD3+ and CD4+ cells and CD4+/CD8+ ratio and serum level of viral load in CHB patients (r=-0.68,-0.65 and-0.75,all P<0.0001),and a positive correlation between CD8+ cells and viral load (r=0.70,P<0.0001).There was a significant decreasing trend in CD3+ and CD4+ cells and CD4+/CD8+ratio with increasing severity of hepatocyte damage and decreasing age at HBV infection (linear trend test P<0.01).In multiple regression (after adjustment for age at HBV infection,maternal HBV infection status and hepatocyte damage severity) log copies of HBV DNA maintained a highly significant predictive coefficient on T-lymphocyte subpopulations,and was the strongest predictor of variation in CD3+,CD4+,CD8+ cells and CD4+/CD8

  4. Absence of Siglec-H in MCMV infection elevates interferon alpha production but does not enhance viral clearance.

    Directory of Open Access Journals (Sweden)

    Franz Puttur

    Full Text Available Plasmacytoid dendritic cells (pDCs express the I-type lectin receptor Siglec-H and produce interferon α (IFNα, a critical anti-viral cytokine during the acute phase of murine cytomegalovirus (MCMV infection. The ligands and biological functions of Siglec-H still remain incompletely defined in vivo. Thus, we generated a novel bacterial artificial chromosome (BAC-transgenic "pDCre" mouse which expresses Cre recombinase under the control of the Siglec-H promoter. By crossing these mice with a Rosa26 reporter strain, a representative fraction of Siglec-H⁺ pDCs is terminally labeled with red fluorescent protein (RFP. Interestingly, systemic MCMV infection of these mice causes the downregulation of Siglec-H surface expression. This decline occurs in a TLR9- and MyD88-dependent manner. To elucidate the functional role of Siglec-H during MCMV infection, we utilized a novel Siglec-H deficient mouse strain. In the absence of Siglec-H, the low infection rate of pDCs with MCMV remained unchanged, and pDC activation was still intact. Strikingly, Siglec-H deficiency induced a significant increase in serum IFNα levels following systemic MCMV infection. Although Siglec-H modulates anti-viral IFNα production, the control of viral replication was unchanged in vivo. The novel mouse models will be valuable to shed further light on pDC biology in future studies.

  5. PD-1 blockade in chronically HIV-1-infected humanized mice suppresses viral loads.

    Directory of Open Access Journals (Sweden)

    Edward Seung

    Full Text Available An estimated 34 million people are living with HIV worldwide (UNAIDS, 2012, with the number of infected persons rising every year. Increases in HIV prevalence have resulted not only from new infections, but also from increases in the survival of HIV-infected persons produced by effective anti-retroviral therapies. Augmentation of anti-viral immune responses may be able to further increase the survival of HIV-infected persons. One strategy to augment these responses is to reinvigorate exhausted anti-HIV immune cells present in chronically infected persons. The PD-1-PD-L1 pathway has been implicated in the exhaustion of virus-specific T cells during chronic HIV infection. Inhibition of PD-1 signaling using blocking anti-PD-1 antibodies has been shown to reduce simian immunodeficiency virus (SIV loads in monkeys. We now show that PD-1 blockade can improve control of HIV replication in vivo in an animal model. BLT (Bone marrow-Liver-Thymus humanized mice chronically infected with HIV-1 were treated with an anti-PD-1 antibody over a 10-day period. The PD-1 blockade resulted in a very significant 45-fold reduction in HIV viral loads in humanized mice with high CD8(+ T cell expression of PD-1, compared to controls at 4 weeks post-treatment. The anti-PD-1 antibody treatment also resulted in a significant increase in CD8(+ T cells. PD-1 blockade did not affect T cell expression of other inhibitory receptors co-expressed with PD-1, including CD244, CD160 and LAG-3, and did not appear to affect virus-specific humoral immune responses. These data demonstrate that inhibiting PD-1 signaling can reduce HIV viral loads in vivo in the humanized BLT mouse model, suggesting that blockade of the PD-1-PD-L1 pathway may have therapeutic potential in the treatment of patients already infected with the AIDS virus.

  6. Oral mucosal lesions and HIV viral load in the Women's Interagency HIV Study (WIHS).

    Science.gov (United States)

    Greenspan, D; Komaroff, E; Redford, M; Phelan, J A; Navazesh, M; Alves, M E; Kamrath, H; Mulligan, R; Barr, C E; Greenspan, J S

    2000-09-01

    The prevalence of oral lesions was assessed in a five-center subset of the Women's Interagency HIV Study (WIHS) and correlated with other features of HIV disease. Oral examinations were performed by dental examiners on 729 women (577 HIV-positive and 152 HIV-negative) during baseline examination. Significant differences between the groups were found for the following oral lesions: pseudomembranous candidiasis, 6.1% and 2.0%, respectively; erythematous candidiasis, 6.41% and 0.7%, respectively; all oral candidiasis, pseudomembranous and/or erythematous, 13.7% and 3.3%, respectively. Hairy leukoplakia was observed in 6.1% of HIV-positive women. No significant differences were found for recurrent aphthous ulcers, herpes simplex lesions, or papillomas. Kaposi's sarcoma was seen in 0.5% of HIV-positive and 0% of HIV-negative women. Using multiple logistic regression models controlling for use of antiretrovirals and antifungals, in HIV-positive women the presence of oral candidiasis was associated with a CD4 count <200 cells/microl, cigarette smoking, and heroin/methadone use; the presence of hairy leukoplakia was not related to CD4 count but was associated with high viral load. Oral candidiasis and hairy leukoplakia are confirmed as being common features of HIV infection in women and appear to be associated with HIV viral load, immunosuppression, and various other behaviorally determined variables.

  7. Circulating virus load determines the size of bottlenecks in viral populations progressing within a host.

    Directory of Open Access Journals (Sweden)

    Serafín Gutiérrez

    Full Text Available For any organism, population size, and fluctuations thereof, are of primary importance in determining the forces driving its evolution. This is particularly true for viruses--rapidly evolving entities that form populations with transient and explosive expansions alternating with phases of migration, resulting in strong population bottlenecks and associated founder effects that increase genetic drift. A typical illustration of this pattern is the progression of viral disease within a eukaryotic host, where such demographic fluctuations are a key factor in the emergence of new variants with altered virulence. Viruses initiate replication in one or only a few infection foci, then move through the vasculature to seed secondary infection sites and so invade distant organs and tissues. Founder effects during this within-host colonization might depend on the concentration of infectious units accumulating and circulating in the vasculature, as this represents the infection dose reaching new organs or "territories". Surprisingly, whether or not the easily measurable circulating (plasma virus load directly drives the size of population bottlenecks during host colonization has not been documented in animal viruses, while in plants the virus load within the sap has never been estimated. Here, we address this important question by monitoring both the virus concentration flowing in host plant sap, and the number of viral genomes founding the population in each successive new leaf. Our results clearly indicate that the concentration of circulating viruses directly determines the size of bottlenecks, which hence controls founder effects and effective population size during disease progression within a host.

  8. Persistence of Hepatitis C RNA in Liver Allografts Is Associated with Histologic Progression Independent of Serologic Viral Clearance

    Directory of Open Access Journals (Sweden)

    M. Ghabril

    2009-01-01

    Full Text Available Background. Hepatitis C virus (HCV nondetectability in the liver may predict a sustained viral response (SVR in patients with an end of treatment response. HCV RNA can be detected in liver tissue by in situ hybridization (ISH. Aim. To determine if HCV nondetectability in liver allografts by ISH can predict SVR in patients who cleared virus serologically on treatment. Methods. Twenty five patients with undetectable serum HCV on Interferon/Ribavirin therapy for HCV recurrence post liver transplant (LT were studied. All had biopsies at 4 months post LT (baseline and follow up with HCV ISH analysis performed. Results. 10 were ISH positive (group 1; 15 were ISH negative (group 2. Groups 1 and 2 had similar patient, donor, and viral characteristics at LT, as well as treatment duration at the time of the ISH assayed liver biopsy (13±16 versus 10±4 months P = .24. However, group 1 had longer total treatment duration (24±10 versus 14±5 months, P = .001. Eight (80% group 1 and 9 (60% group 2 patients achieved SVR. Mean grade and stage (modified Ishak score were similar at 4 months, however, group 1 had higher grade (3±1.7 versus 1.6±1.3, P = .039 and stage (1.4±1.4 versus 0.5±0.6, P = .084 on the ISH assayed biopsy, after similar post LT intervals (23±10 versus 24±12 months, P = .91. Conclusion. Allograft HCV ISH nondetectability does not predict SVR in treatment responsive HCV recurrence, but is associated with less severe histologic disease.

  9. CD4 cell count and the risk of AIDS or death in HIV-Infected adults on combination antiretroviral therapy with a suppressed viral load

    DEFF Research Database (Denmark)

    Obel, Niels

    2012-01-01

    Most adults infected with HIV achieve viral suppression within a year of starting combination antiretroviral therapy (cART). It is important to understand the risk of AIDS events or death for patients with a suppressed viral load.......Most adults infected with HIV achieve viral suppression within a year of starting combination antiretroviral therapy (cART). It is important to understand the risk of AIDS events or death for patients with a suppressed viral load....

  10. The semen microbiome and its relationship with local immunology and viral load in HIV infection.

    Directory of Open Access Journals (Sweden)

    Cindy M Liu

    2014-07-01

    Full Text Available Semen is a major vector for HIV transmission, but the semen HIV RNA viral load (VL only correlates moderately with the blood VL. Viral shedding can be enhanced by genital infections and associated inflammation, but it can also occur in the absence of classical pathogens. Thus, we hypothesized that a dysregulated semen microbiome correlates with local HIV shedding. We analyzed semen samples from 49 men who have sex with men (MSM, including 22 HIV-uninfected and 27 HIV-infected men, at baseline and after starting antiretroviral therapy (ART using 16S rRNA gene-based pyrosequencing and quantitative PCR. We studied the relationship of semen bacteria with HIV infection, semen cytokine levels, and semen VL by linear regression, non-metric multidimensional scaling, and goodness-of-fit test. Streptococcus, Corynebacterium, and Staphylococcus were common semen bacteria, irrespective of HIV status. While Ureaplasma was the more abundant Mollicutes in HIV-uninfected men, Mycoplasma dominated after HIV infection. HIV infection was associated with decreased semen microbiome diversity and richness, which were restored after six months of ART. In HIV-infected men, semen bacterial load correlated with seven pro-inflammatory semen cytokines, including IL-6 (p = 0.024, TNF-α (p = 0.009, and IL-1b (p = 0.002. IL-1b in particular was associated with semen VL (r(2  = 0.18, p = 0.02. Semen bacterial load was also directly linked to the semen HIV VL (r(2 = 0.15, p = 0.02. HIV infection reshapes the relationship between semen bacteria and pro-inflammatory cytokines, and both are linked to semen VL, which supports a role of the semen microbiome in HIV sexual transmission.

  11. Proteomics approach to understand reduced clearance of mycobacteria and high viral titers during HIV-mycobacteria co-infection.

    Science.gov (United States)

    Ganji, Rakesh; Dhali, Snigdha; Rizvi, Arshad; Sankati, Swetha; Vemula, Mani Harika; Mahajan, Gaurang; Rapole, Srikanth; Banerjee, Sharmistha

    2016-03-01

    Environmental mycobacteria, highly prevalent in natural and artificial (including chlorinated municipal water) niches, are emerging as new threat to human health, especially to HIV-infected population. These seemingly harmless non-pathogenic mycobacteria, which are otherwise cleared, establish as opportunistic infections adding to HIV-associated complications. Although immune-evading strategies of pathogenic mycobacteria are known, the mechanisms underlying the early events by which opportunistic mycobacteria establish infection in macrophages and influencing HIV infection are unclear. Proteomics of phagosome-enriched fractions from Mycobacterium bovis Bacillus Calmette-Guérin (BCG) mono-infected and HIV-M. bovis BCG co-infected THP-1 cells by LC-MALDI-MS/MS revealed differential distribution of 260 proteins. Validation of the proteomics data showed that HIV co-infection helped the survival of non-pathogenic mycobacteria by obstructing phagosome maturation, promoting lipid biogenesis and increasing intracellular ATP equivalents. In turn, mycobacterial co-infection up-regulated purinergic receptors in macrophages that are known to support HIV entry, explaining increased viral titers during co-infection. The mutualism was reconfirmed using clinically relevant opportunistic mycobacteria, Mycobacterium avium, Mycobacterium kansasii and Mycobacterium phlei that exhibited increased survival during co-infection, together with increase in HIV titers. Additionally, the catalogued proteins in the study provide new leads that will significantly add to the understanding of the biology of opportunistic mycobacteria and HIV coalition. PMID:26332641

  12. Maraviroc and Other HIV-1 Entry Inhibitors Exhibit a Class-Specific Redistribution Effect That Results in Increased Extracellular Viral Load

    OpenAIRE

    Kramer, Victor G; Schader, Susan M.; Oliveira, Maureen; Colby-Germinario, Susan P.; Donahue, Daniel A.; Singhroy, Diane N; Tressler, Randy; Sloan, Richard D.; Mark A Wainberg

    2012-01-01

    HIV entry inhibitors, such as maraviroc (MVC), prevent cell-free viruses from entering the cells. In clinical trials, patients who were treated with MVC often displayed viral loads that were above the limit of conventional viral load detection compared to efavirenz-based regimens. We hypothesize that viruses blocked by entry inhibitors may be redistributed to plasma, where they artificially increase viral load measurements compared to those with the use of antiretroviral drugs (ARVs) that act...

  13. Impact of two different commercial DNA extraction methods on BK virus viral load

    Directory of Open Access Journals (Sweden)

    Massimiliano Bergallo

    2016-03-01

    Full Text Available Background and aim: BK virus, a member of human polyomavirus family, is a worldwide distributed virus characterized by a seroprevalence rate of 70-90% in adult population. Monitoring of viral replication is made by evaluation of BK DNA by quantitative polymerase chain reaction. Many different methods can be applied for extraction of nucleic acid from several specimens. The aim of this study was to assess the impact of two different DNA extraction procedure on BK viral load. Materials and methods: DNA extraction procedure including the Nuclisens easyMAG platform (bioMerieux, Marcy l’Etoile, France and manual QIAGEN extraction (QIAGEN Hilden, Germany. BK DNA quantification was performed by Real Time TaqMan PCR using a commercial kit. Result and discussion: The samples capacity, cost and time spent were compared for both systems. In conclusion our results demonstrate that automated nucleic acid extraction method using Nuclisense easyMAG was superior to manual protocol (QIAGEN Blood Mini kit, for the extraction of BK virus from serum and urine specimens.

  14. Number of Drinks to "Feel a Buzz" by HIV Status and Viral Load in Men.

    Science.gov (United States)

    McGinnis, Kathleen A; Fiellin, David A; Tate, Janet P; Cook, Robert L; Braithwaite, R Scott; Bryant, Kendall J; Edelman, E Jennifer; Gordon, Adam J; Kraemer, Kevin L; Maisto, Stephen A; Justice, Amy C

    2016-03-01

    The impact of HIV and its treatment on the effects of alcohol remain unclear. Blood alcohol concentrations have been noted to be higher in HIV infected individuals prior to antiretroviral initiation. Our goal was to compare number of drinks to "feel a buzz or high" among HIV infected and uninfected men, stratified by viral load (VL) suppression. Data includes 1478 HIV infected and 1170 uninfected men in the veterans aging cohort study who endorsed current drinking. Mean (SD) number of drinks to feel a buzz was 3.1 (1.7) overall. In multivariable analyses, HIV infected men reported a lower mean number of drinks to feel a buzz compared to uninfected men (coef = -14 for VL buzz. Future research on the relationship between alcohol and HIV should consider the role of VL suppression. PMID:26936030

  15. Cell-Mediated Immunity in Elite Controllers Naturally Controlling HIV Viral Load.

    Science.gov (United States)

    Genovese, Luca; Nebuloni, Manuela; Alfano, Massimo

    2013-01-01

    The natural course of human immunodeficiency virus (HIV) infection is characterized by high viral load, depletion of immune cells, and immunodeficiency, ultimately leading to acquired immunodeficiency syndrome phase and the occurrence of opportunistic infections and diseases. Since the discovery of HIV in the early 1980s a naturally selected population of infected individuals has been emerged in the last years, characterized by being infected for many years, with viremia constantly below detectable level and poor depletion of immune cells. These individuals are classified as "elite controllers (EC) or suppressors" and do not develop disease in the absence of anti-retroviral therapy. Unveiling host factors and immune responses responsible for the elite status will likely provide clues for the design of therapeutic vaccines and functional cures. Scope of this review was to examine and discuss differences of the cell-mediated immune responses between HIV+ individuals with disease progression and EC. PMID:23577012

  16. Cell-mediated Immunity in Elite Controllers Naturally Controlling HIV Viral Load

    Directory of Open Access Journals (Sweden)

    Luca eGenovese

    2013-04-01

    Full Text Available The natural course of HIV infection is characterized by high viral load, depletion of immune cells and immunodeficiency, ultimately leading to acquired immunodeficiency syndrome (AIDS phase and the occurrence of opportunistic infections and diseases.Since the discovery of HIV in the early 80’s a naturally selected population of infected individuals has been emerged in the last years, characterized by being infected for many years, with viremia constantly below detectable level and poor depletion of immune cells. These individuals are classified as elite controllers or suppressors and do not develop disease in the absence of anti-retroviral therapy.Unveiling host factors and immune responses responsible for the elite status will likely provide clues for the design of therapeutic vaccines and functional cures. Scope of this review was to examine and discuss differences of the cell-mediated immune responses between HIV+ individuals with disease progression and elite controllers.

  17. Sensitive and specific nested PCR assay for detection of rotavirus A in samples with a low viral load.

    Science.gov (United States)

    Mijatovic-Rustempasic, Slavica; Esona, Mathew D; Williams, Alice L; Bowen, Michael D

    2016-10-01

    Techniques such as the real-time reverse transcription-polymerase chain reaction (qRT-PCR) can detect RNA in samples with a low viral load. However, these amplicons typically are either too short or at insufficient concentrations for use in subsequent sequencing reactions for genotyping and detection confirmation. The assay developed in this study detects rotavirus G genotypes and P genotypes with viral loads as low as 6.2 and 8.2 copies per reaction, respectively. The assay was validated using a panel of 91 stool samples, 32 reference rotavirus strains, and 6 non-target enteric virus samples. PMID:27421626

  18. Clinical value of determination HIV viral load in the cerebrospinal fluid of HIV-infected patients

    Directory of Open Access Journals (Sweden)

    V. B. Musatov

    2015-01-01

    Full Text Available Aim. To analyze the concentration of HIV RNA in the cerebrospinal fluid and to evaluate its significance in the pathology of the central nervous system among HIV infected persons.Materials: We examined 36 patients with HIV infection with signs of pathology of the central nervous system. All patients was done completed a standard investigation of cerebrospinal fluid, cytological examination and detection viral load of HIV in the cerebrospinal fluid and serum.Results. A different of opportunistic and HIV-related disease was diagnosed in 29 patients. The most frequent pathology of the nervous system (12 cases is a diffuse HIV-associated brain damage occurring in 7 patients in the form of aseptic non purulent meningitis and in 5 patients in the form of encephalitis. The average value of the absolute and relative count of CD4-lymphocytes in patients amounted 147,0 cells/μl (40,0; 408,75 and 10.0% (4,00; 18,50. Pathological changes in cellular composition and protein concentration of cerebrospinal fluid detected in 19 cases. Replication of HIV in the cerebrospinal fluid are detected in 31 of 32 patients not receiving antiretroviral therapy, including 17 patients with normal values of cerebrospinal fluid. The average HIV viral load in the cerebrospinal fluid was 15 133,0 copies/ml (2501,0; 30624,0 or 4,18 (3,35; 4,48 lg HIV RNA, average HIV viral load in serum – 62 784,0 copies/ml (6027,5; 173869,0 or 4,80 4,80 (3,7; 5,2 lg HIV RNA. The concentration of HIV in the cerebrospinal fluid was significantly lower than in serum (4,18 and 4,80 lg HIV RNA, p=0.027. 4 patients with severe, multietiology damage of the central nervous system viral, microbial and fungal etiology, there was an inverse relationship between the concentration of HIV in the cerebrospinal fluid and in serum, the concentrations of HIV was higher in the cerebrospinal fluid.Conclusion: Among the majority of HIV-infected patients with signs of the central

  19. TTV viral load as a marker for immune reconstitution after initiation of HAART in HIV-infected patients

    DEFF Research Database (Denmark)

    Madsen, Chris; Eugen-Olsen, Jesper; Kirk, Ole;

    2002-01-01

    PURPOSE: To investigate whether TT virus (TTV) viral load may be used as a surrogate marker for functional immune reconstitution in HIV-infected patients receiving highly active antiretroviral therapy (HAART). METHOD: Fifteen protease inhibitor-naïve HIV-infected patients were included in a longi......PURPOSE: To investigate whether TT virus (TTV) viral load may be used as a surrogate marker for functional immune reconstitution in HIV-infected patients receiving highly active antiretroviral therapy (HAART). METHOD: Fifteen protease inhibitor-naïve HIV-infected patients were included...... in a longitudinal study. From each patient, three serum samples taken before HAART initiation and three samples taken during HAART were analyzed. TTV was detected by polymerase chain reaction (PCR) and was quantitated by competitive PCR. TTV viral heterogeneity was determined by restriction fragment length...

  20. Dual Function of Ccr5 during Langat Virus Encephalitis: Reduction in Neutrophil-Mediated Central Nervous System Inflammation and Increase in T Cell-Mediated Viral Clearance.

    Science.gov (United States)

    Michlmayr, Daniela; Bardina, Susana V; Rodriguez, Carlos A; Pletnev, Alexander G; Lim, Jean K

    2016-06-01

    Tick-borne encephalitis virus (TBEV) is a vector-transmitted flavivirus that causes potentially fatal neurologic infection. There are thousands of cases reported annually, and despite the availability of an effective vaccine, the incidence of TBEV is increasing worldwide. Importantly, up to 30% of affected individuals develop long-term neurologic sequelae. We investigated the role of chemokine receptor Ccr5 in a mouse model of TBEV infection using the naturally attenuated tick-borne flavivirus Langat virus (LGTV). Ccr5-deficient mice presented with an increase in viral replication within the CNS and decreased survival during LGTV encephalitis compared with wild-type controls. This enhanced susceptibility was due to the temporal lag in lymphocyte migration into the CNS. Adoptive transfer of wild-type T cells, but not Ccr5-deficient T cells, significantly improved survival outcome in LGTV-infected Ccr5-deficient mice. Concomitantly, a significant increase in neutrophil migration into the CNS in LGTV-infected Ccr5(-/-) mice was documented at the late stage of infection. Ab-mediated depletion of neutrophils in Ccr5(-/-) mice resulted in a significant improvement in mortality, a decrease in viral load, and a decrease in overall tissue damage in the CNS compared with isotype control-treated mice. Ccr5 is crucial in directing T cells toward the LGTV-infected brain, as well as in suppressing neutrophil-mediated inflammation within the CNS.

  1. Beak and feather disease virus: correlation between viral load and clinical signs in wild Cape parrots (Poicepahlus robustus) in South Africa.

    Science.gov (United States)

    Regnard, Guy L; Boyes, Rutledge S; Martin, Rowan O; Hitzeroth, Inga I; Rybicki, Edward P

    2015-01-01

    Psittacine beak and feather disease (PBFD), the most prevalent viral disease affecting psittacines, is caused by beak and feather disease virus (BFDV). This study assessed viral load using qPCR in a wild Cape parrot population affected by PBFD and compared it to overall physical condition based on clinical signs attributable to PBFD. A significant inverse correlation between viral load and overall physical condition was found, which confirmed that clinical signs may confidently be used to diagnose the relative severity of BFDV infections in wild populations. This is the first assessment of BFDV viral load in a wild psittacine population.

  2. Beak and feather disease virus: correlation between viral load and clinical signs in wild Cape parrots (Poicepahlus robustus) in South Africa.

    Science.gov (United States)

    Regnard, Guy L; Boyes, Rutledge S; Martin, Rowan O; Hitzeroth, Inga I; Rybicki, Edward P

    2015-01-01

    Psittacine beak and feather disease (PBFD), the most prevalent viral disease affecting psittacines, is caused by beak and feather disease virus (BFDV). This study assessed viral load using qPCR in a wild Cape parrot population affected by PBFD and compared it to overall physical condition based on clinical signs attributable to PBFD. A significant inverse correlation between viral load and overall physical condition was found, which confirmed that clinical signs may confidently be used to diagnose the relative severity of BFDV infections in wild populations. This is the first assessment of BFDV viral load in a wild psittacine population. PMID:25193072

  3. Clinical Factors and Viral Load Influencing Severity of Acute Hepatitis A.

    Directory of Open Access Journals (Sweden)

    Hyun Woong Lee

    Full Text Available Clinical manifestations of hepatitis A virus (HAV infection vary from mild to fulminant hepatic failure (FHF in adults. We investigated the relationship between laboratory findings, including viral load, and clinical outcomes in patients with acute hepatitis A (AHA and evaluated predictive factors for severe acute hepatitis (s-AH.We analyzed the clinical manifestations of AHA in 770 patients. Patients with a prothrombin time (PT of less than 40% of normal were classified as s-AH and included 4 patients with FHF, 11 patients with acute renal failure, and 3 patients with prolonged jaundice (n = 128. Other patients were defined as mild acute hepatitis (m-AH (n = 642. Serum samples were obtained from 48 patients with acute hepatitis A. Among them, 20 with s-AH, and 28 with m-AH, were tested for HAV RNA titer.In a multivariate analysis, age (HR = 1.042, P = 0.041, peak creatinine (HR = 4.014, P = 0.001, bilirubin (HR = 1.153, P = 0.003, alanine aminotransferase (ALT (HR = 1.001, P < 0.001, initial lactate dehydrogenase (LDH (HR = 1.000, P = 0.045 and total cholesterol (HR = 0.978, P < 0.001 were independent factors for s-AH. Serum HAV RNA was detected in 20/20 (100% patients with s-AH and 22/28 (78.6% patients with m-AH. In a multivariate analysis of the 48 patients who were tested for HAV RNA, peak ALT (HR = 1.001, P = 0.004 and HAV RNA titer (HR = 2.076, P = 0.012 were independent factors for s-AH.Clinical factors including age, peak creatinine, bilirubin, ALT, initial LDH and total cholesterol were independent factors for s-AH in a multivariate analysis. In particular, HAV load strongly correlated with the severity of hepatitis A.

  4. Using Exclusion-Based Sample Preparation (ESP to Reduce Viral Load Assay Cost.

    Directory of Open Access Journals (Sweden)

    Scott M Berry

    Full Text Available Viral load (VL measurements are critical to the proper management of HIV in developing countries. However, access to VL assays is limited by the high cost and complexity of existing assays. While there is a need for low cost VL assays, performance must not be compromised. Thus, new assays must be validated on metrics of limit of detection (LOD, accuracy, and dynamic range. Patient plasma samples from the Joint Clinical Research Centre in Uganda were de-identified and measured using both an existing VL assay (Abbott RealTime HIV-1 and our assay, which combines low cost reagents with a simplified method of RNA isolation termed Exclusion-Based Sample Preparation (ESP.71 patient samples with VLs ranging from 3,000,000 copies/mL were used to compare the two methods. We demonstrated equivalent LOD (~50 copies/mL and high accuracy (average difference between methods of 0.08 log, R2 = 0.97. Using expenditures from this trial, we estimate that the cost of the reagents and consumables for this assay to be approximately $5 USD. As cost is a significant barrier to implementation of VL testing, we anticipate that our assay will enhance access to this critical monitoring test in developing countries.

  5. Residual viraemia in HIV-1-infected patients with plasma viral load

    DEFF Research Database (Denmark)

    Ostrowski, S.R.; Katzenstein, T.L.; Pedersen, Bente Klarlund;

    2008-01-01

    Despite undetectable viral load in conventional assays, probably all human immunodeficiency virus (HIV)-1 infected patients have residual viraemia (RV) detectable by ultra-sensitive assays. To study this issue, this study investigated virologic and immunologic consequences of RV in highly active...... antiretroviral therapy (HAART)-treated HIV-1-infected patients with plasma HIV-1 RNA or=1 episode with TMA-RV whereas 9 patients had undetectable TMA-RV throughout the study-period. Time-points with TMA-RV and PCR-RV were associated with higher circulating sTNFrII (+0.234 ng/ml, P = 0.030) and beta(2......)-microglobulin (+22 nmol/l, P = 0.016) and time-points with PCR-RV were also associated with higher IgA (+0.82 micromol/l, P = 0.035) and CD8-count (+1.18-fold, P = 0.001). Patients with TMA-RV in the study-period had higher HIV-1 RNA pre-HAART (P = 0.032). RV was not associated with proviral-HIV-1-DNA, CD4...

  6. Dolutegravir treatment response by baseline viral load and NRTI backbone in treatment-naïve HIV-infected individuals

    Directory of Open Access Journals (Sweden)

    C Small

    2012-11-01

    Full Text Available Background: In two 48-week studies in naïve subjects, dolutegravir with NRTI of choice has shown non-inferiority to raltegravir and, with ABC/3TC, superiority to Atripla. Factors that influenced choice of NRTIs included viral load, resistance and safety. Methods: We analysed response rates and time to virologic failure by NRTI backbone and baseline viral load in the pivotal DTG-naïve studies. SPRING-2 randomized participants to DTG 50 mg QD or RAL 400 mg BID, each in combination with investigator-selected NRTIs (TDF/FTC or ABC/3TC. SINGLE randomised participants to DTG 50 mg+ABC/3TC QD or TDF/FTC/EFV (Atripla QD. In SPRING-2, changes in serum creatinine were examined by INI and NRTI backbone. Results: The two studies randomized and treated 1655 subjects, of whom 249 (15% were female, 388 (23% non-white, 495 (30% had HIV-1 RNA >100,000 c/ml, and 224 (14% had CD4+ count <200 cells/mm3. Primary analyses demonstrated non-inferiority of DTG to RAL in SPRING-2 (Δ=2.5%; 95% CI:−2.2% to +7.1%, excluding −10%, and superiority of the DTG regimen in SINGLE (7.4%; +2.5% to +12.3%. In SPRING-2, response rates by NRTI backbone were comparable in each viral load stratum. In SINGLE, a 7% difference in response (favoring DTG+ABC/3TC was observed in each viral load stratum. Exploratory analyses examining time-to-virologic failure showed no difference in response rates between the NRTIs irrespective of baseline viral load or study. Resistance to INIs or NRTIs was not demonstrated in any subject on DTG-based therapy through 48 weeks. Withdrawals due to AEs on DTG-based regimen were few (2% in both studies. In SPRING-2, no significant differences were observed in serum creatinine change from baseline to Week 48 by NRTI backbones. Conclusions: In SPRING-2 and SINGLE, DTG was effective with both ABC/3TC and TDF/FTC, and in subjects with high and low viral load. DTG was well tolerated in both studies. Renal safety also was similar by NRTI backbone. DTG is a once

  7. Prevalence of Oral Manifestations and Their Association with CD4/CD8 Ratio and HIV Viral Load in South India

    Directory of Open Access Journals (Sweden)

    Sharma Gaurav

    2011-01-01

    Full Text Available The objective of the present research was to determine the prevalence of oral manifestations in an HIV infected population from south India and evaluate their association with HIV viral load and CD4/CD8 ratio. Intraoral examination of 103 patients, whose CD4/CD8 ratio was available, were conducted. HIV viral loads were available for thirty patients only. The prevalence of oral manifestations was 80.6% (83/103. The most common oromucosal lesion was erythematous candidiasis (EC (38.8% followed by melanotic hyperpigmentation (35.9%. Patients having any oral manifestation had a mean CD4/CD8 ratio of 0.24. EC had positive predictive value of 85.0% for CD4/CD8 ratio 20,000 copies/mL (20,000 copies/mL.

  8. Dried blood spots for viral load monitoring in Malawi: feasible and effective.

    Directory of Open Access Journals (Sweden)

    Sarah E Rutstein

    Full Text Available To evaluate the feasibility and effectiveness of dried blood spots (DBS use for viral load (VL monitoring, describing patient outcomes and programmatic challenges that are relevant for DBS implementation in sub-Saharan Africa.We recruited adult antiretroviral therapy (ART patients from five district hospitals in Malawi. Eligibility reflected anticipated Ministry of Health VL monitoring criteria. Testing was conducted at a central laboratory. Virological failure was defined as >5000 copies/ml. Primary outcomes were program feasibility (timely result availability and patient receipt and effectiveness (second-line therapy initiation.We enrolled 1,498 participants; 5.9% were failing at baseline. Median time from enrollment to receipt of results was 42 days; 79.6% of participants received results within 3 months. Among participants with confirmed elevated VL, 92.6% initiated second-line therapy; 90.7% were switched within 365 days of VL testing. Nearly one-third (30.8% of participants with elevated baseline VL had suppressed (4 years were more likely to be failing than participants on therapy 1-4 years (RR 1.7, 95% CI 1.0-2.8; older participants were less likely to be failing (RR 0.95, 95% CI 0.92-0.98. There was no difference in likelihood of failure based on clinical symptoms (RR 1.17, 95% CI 0.65-2.11.DBS for VL monitoring is feasible and effective in real-world clinical settings. Centralized DBS testing may increase access to VL monitoring in remote settings. Programmatic outcomes are encouraging, especially proportion of eligible participants switched to second-line therapy.

  9. Ring finger protein 39 genetic variants associate with HIV-1 plasma viral loads and its replication in cell culture

    OpenAIRE

    Lin, Ying-Ju; Chen, Chia-Yen; Jeang, Kuan-Teh; Liu, Xiang; Wang, Jen-Hsien; Hung, Chien-Hui; Tsang, Hsinyi; Lin, Ting-Hsu; Liao, Chiu-Chu; Huang, Shao-Mei; Lin, Cheng-Wen; Ho, Mao-Wang; Chien, Wen-Kuei; Chen, Jin-Hua; Ho, Tsung-Jung

    2014-01-01

    Background The human immunodeficiency virus (HIV-1) exploits host proteins to complete its life cycle. Genome-wide siRNA approaches suggested that host proteins affect HIV-1 replication. However, the results barely overlapped. RING finger protein 39 (RNF39) has been identified from genome-wide association studies. However, its function during HIV-1 replication remains unclear. Methods and results We investigated the relationship between common RNF39 genetic variants and HIV-1 viral loads. The...

  10. Is HCV core antigen a reliable marker of viral load? An evaluation of HCV core antigen automated immunoassay

    OpenAIRE

    Hadziyannis, Emilia; Minopetrou, Martha; Georgiou, Anastasia; Spanou, Fotini; Koskinas, John

    2013-01-01

    Background Hepatitis C viral (HCV) load detection and quantification is routinely accomplished by HCV RNA measurement, an expensive but essential test, both for the diagnosis and treatment of chronic hepatitis C (CHC). HCV core antigen (Ag) testing has been suggested as an attractive alternative to molecular diagnostics. The aim of the study was to evaluate an automated chemiluminescent immunoassay (CLIA) for HCV core Ag measurement in comparison to quantitative HCV RNA determination. Methods...

  11. Impact of Adherence Counseling Dose on Antiretroviral Adherence and HIV Viral Load among HIV-Infected Methadone Maintained Drug Users

    OpenAIRE

    Cooperman, Nina A.; Heo, Moonseong; Berg, Karina M.; Li, Xuan; Litwin, Alain H.; Nahvi, Shadi; Arnsten, Julia H.

    2012-01-01

    Adherence counseling can improve antiretroviral adherence and related health outcomes in HIV-infected individuals. However, little is known about how much counseling is necessary to achieve clinically significant effects. We investigated antiretroviral adherence and HIV viral load relative to the number of hours of adherence counseling received by 60 HIV-infected drug users participating in a trial of directly observed antiretroviral therapy delivered in methadone clinics. Our adherence couns...

  12. Predictors of undetectable plasma viral load in HIV-positive adults receiving antiretroviral therapy in Southern Brazil

    Directory of Open Access Journals (Sweden)

    Marysabel Pinto Telis Silveira

    2002-08-01

    Full Text Available Factors associated with undetectable viral load ( or = 95% of adherence (CI 95% 1,80-13,28; CI 95% 1,73-9,53, compared with less than 60% adherence; it was greater for less than 6 months in treatment (OR = 3.37; CI 95% 1.09-10.46; and smaller for viral load previous to adherence measurement > or = 5.2 log10 (OR = 0.19; CI95% 0.06-0.58, adjusted for these variables and sex, age, clinical status, current immune status, group of drugs and interval between the two measurements of viral load. The crude odds were lower for age 16-24 years and use of Nucleoside Analog Reverse Transcriptase Inhibitors only, but these effects were not significant in the multivariate model. There was no evidence of effect of sex, clinical status, current immune status, and changes in treatment regimen. Treatment adherence gave the largest effect. Motivational interventions directed at adherence may improve treatment effectiveness.

  13. Deformed wing virus: replication and viral load in mites (Varroa destructor).

    Science.gov (United States)

    Gisder, Sebastian; Aumeier, Pia; Genersch, Elke

    2009-02-01

    Deformed wing virus (DWV) normally causes covert infections but can have devastating effects on bees by inducing morphological deformity or even death when transmitted by the ectoparasitic mite Varroa destructor. In order to determine the role of V. destructor in the development of crippled wings, we analysed individual mites for the presence and replication of DWV. The results supported the correlation between viral replication in mites and morphologically deformed bees. Quantification of viral genome equivalents revealed that mites capable of inducing an overt DWV infection contained 10(10)-10(12) genome equivalents per mite. In contrast, mites which could not induce crippled wings contained a maximum of only 10(8) viral genome equivalents per mite. We conclude that the development of crippled wings not only depends on DWV transmission by V. destructor but also on viral replication in V. destructor and on the DWV titre in the parasitizing mites.

  14. Randomized Controlled Trials to Define Viral Load Thresholds for Cytomegalovirus Pre-Emptive Therapy

    Science.gov (United States)

    Griffiths, Paul D.; Rothwell, Emily; Raza, Mohammed; Wilmore, Stephanie; Doyle, Tomas; Harber, Mark; O’Beirne, James; Mackinnon, Stephen; Jones, Gareth; Thorburn, Douglas; Mattes, Frank; Nebbia, Gaia; Atabani, Sowsan; Smith, Colette; Stanton, Anna; Emery, Vincent C.

    2016-01-01

    Background To help decide when to start and when to stop pre-emptive therapy for cytomegalovirus infection, we conducted two open-label randomized controlled trials in renal, liver and bone marrow transplant recipients in a single centre where pre-emptive therapy is indicated if viraemia exceeds 3000 genomes/ml (2520 IU/ml) of whole blood. Methods Patients with two consecutive viraemia episodes each below 3000 genomes/ml were randomized to continue monitoring or to immediate treatment (Part A). A separate group of patients with viral load greater than 3000 genomes/ml was randomized to stop pre-emptive therapy when two consecutive levels less than 200 genomes/ml (168 IU/ml) or less than 3000 genomes/ml were obtained (Part B). For both parts, the primary endpoint was the occurrence of a separate episode of viraemia requiring treatment because it was greater than 3000 genomes/ml. Results In Part A, the primary endpoint was not significantly different between the two arms; 18/32 (56%) in the monitor arm had viraemia greater than 3000 genomes/ml compared to 10/27 (37%) in the immediate treatment arm (p = 0.193). However, the time to developing an episode of viraemia greater than 3000 genomes/ml was significantly delayed among those randomized to immediate treatment (p = 0.022). In Part B, the primary endpoint was not significantly different between the two arms; 19/55 (35%) in the less than 200 genomes/ml arm subsequently had viraemia greater than 3000 genomes/ml compared to 23/51 (45%) among those randomized to stop treatment in the less than 3000 genomes/ml arm (p = 0.322). However, the duration of antiviral treatment was significantly shorter (p = 0.0012) in those randomized to stop treatment when viraemia was less than 3000 genomes/ml. Discussion The results illustrate that patients have continuing risks for CMV infection with limited time available for intervention. We see no need to alter current rules for stopping or starting pre-emptive therapy. PMID:27684379

  15. Liver Fibrosis progression using Fibroscan in HIV/HCV coinfected patients with undetectable HIV viral load

    Directory of Open Access Journals (Sweden)

    Laura Perez-Martinez

    2014-11-01

    Full Text Available Introduction: Several factors such as duration of infection, age, male gender, consumption of alcohol, HIV infection and low CD4 count have been associated with fibrosis progression rate. However, it is relatively scarce, the knowledge about the liver fibrosis progression rate in HIV-infected patients with undetectable HIV viral load (VL. For this reason, we performed the present study. Materials and Methods: Observational and multicenter study (2008–2012 conducted in four hospitals of the northern Spain. HIV/HCV (hepatitis c virus coinfected patients ≥18 years on stable combination antiretroviral therapy (cART (≥6 months and with a HIV VL <50 copies/mL were selected to analyze their liver fibrosis progression. Fibrosis progression was assessed using a Fibroscan® (502 STEP 3 model and measuring a basal test and a second one at least 12 months apart from baseline. This evolution was compared with different variables such as duration of HIV/HCV coinfection, gender, age, previous treatment for HCV, HCV genotype, CD4 lymphocyte counts and the cART employed at the basal test. Results: A total of 608 patients were included (median age 29.4 years, 71.7% men. Of these, 463 patients met the inclusion criteria. In these patients, the liver fibrosis progression was nearly flat and the only variables related to a higher liver fibrosis progression were the increasing age of the patients (p=0.02 and the duration of the coinfection (p=0.001. CD4 lymphocyte counts showed a tendency to improved liver fibrosis (p=0.056. Conclusions: In HIV/HCV coinfected patients on stable cART and HIV undetectable VL, the increase in liver fibrosis rate progression was nearly flat, although it was significantly associated with the duration of the coinfection and the age of the patient. The beneficial effects of the cART were independent of the antiretroviral drug employed. A tendency to a lower fibrosis progression was observed in those patients with a higher CD4 count.

  16. Outcomes from monitoring of patients on antiretroviral therapy in resource-limited settings with viral load, CD4 cell count, or clinical observation alone: a computer simulation model

    DEFF Research Database (Denmark)

    Phillips, Andrew N; Pillay, Deenan; Miners, Alec H;

    2008-01-01

    BACKGROUND: In lower-income countries, WHO recommends a population-based approach to antiretroviral treatment with standardised regimens and clinical decision making based on clinical status and, where available CD4 cell count, rather than viral load. Our aim was to study the potential consequences...... strategies-based on viral load, CD4 cell count, or clinical observation alone-for determining when to switch people starting antiretroviral treatment with the WHO-recommended first-line regimen of stavudine, lamivudine, and nevirapine to second-line antiretroviral treatment. FINDINGS: Over 5 years......, the predicted proportion of potential life-years survived was 83% with viral load monitoring (switch when viral load >500 copies per mL), 82% with CD4 cell count monitoring (switch at 50% drop from peak), and 82% with clinical monitoring (switch when two new WHO stage 3 events or a WHO stage 4 event occur...

  17. Prevalence and Viral Load of Human Parvovirus B19 (B19V) Among Blood Donors in South-East Brazil.

    Science.gov (United States)

    Slavov, Svetoslav Nanev; Otaguiri, Katia Kaori; Covas, Dimas Tadeu; Kashima, Simone

    2016-06-01

    The infection of human parvovirus B19 (B19V) is a common event in the general population, including volunteer blood donors. In some cases it can be asymptomatic and can remain persistent for a long period of time. The objective of this study was to examine the B19V DNA prevalence and viral load in first-time volunteer blood donors. Blood samples were collected from 91 primary blood donors at the Regional Blood Center of Ribeirão Preto, Southeast Brazil. Viral detection and quantitation was performed by an in-house TaqMan(®) real-time PCR with high sensitivity. B19V DNA was detected in one male blood donor (1.0 %) and was characterized by a very low viral load (537.36 copies/mL). Our studies demonstrate that B19V DNA at low titer may be present in apparently healthy individuals. Sensitive molecular diagnostic tools can be applied for the screening of fresh blood derived products in order to prevent transfusion-transmitted B19V infection. PMID:27408426

  18. The effect of antioxidant supplementation on hepatitis C viral load, transaminases and oxidative status: a randomized trial among chronic hepatitis C virus-infected patients

    DEFF Research Database (Denmark)

    Groenbaek, K.; Friis, H.; Hansen, Max;

    2006-01-01

    Objective To assess the effect of antioxidant supplementation on hepatitis C viral load, transaminases and oxidative status. Methods We performed a randomized, placebo-controlled, double-blind trial to assess the effect of antioxidant supplementation on serum alanine aminotransferase, plasma hepa...... and catalase) or plasma levels of oxidative markers (malondialdehyde and 2-amino-adipic semialdehyde) were found. Conclusion Supplementation with vitamin C, E and selenium increased the antioxidant status, but had no effects on alanine aminotransferase, viral load or oxidative markers....

  19. CD4 cell count and viral load-specific rates of AIDS, non-AIDS and deaths according to current antiretroviral use

    DEFF Research Database (Denmark)

    Mocroft, Amanda; Phillips, Andrew N; Gatell, Jose;

    2013-01-01

    CD4 cell count and viral loads are used in clinical trials as surrogate endpoints for assessing efficacy of newly available antiretrovirals. If antiretrovirals act through other pathways or increase the risk of disease this would not be identified prior to licensing. The aim of this study...... was to investigate the CD4 cell count and viral load-specific rates of fatal and nonfatal AIDS and non-AIDS events according to current antiretrovirals....

  20. Fatal and nonfatal AIDS and non-AIDS events in HIV-1-positive individuals with high CD4 cell counts according to viral load strata

    DEFF Research Database (Denmark)

    Reekie, Joanne; Gatell, Jose M; Yust, Israel;

    2011-01-01

    This study compared the incidence of fatal and nonfatal AIDS and non-AIDS events in HIV-positive individuals with a CD4 cell count more than 350¿ cells/µl among viral load strata: low (......This study compared the incidence of fatal and nonfatal AIDS and non-AIDS events in HIV-positive individuals with a CD4 cell count more than 350¿ cells/µl among viral load strata: low (...

  1. Long-term effect of a four-drugs induction regimen for patients with high baseline viral load

    OpenAIRE

    Maggiolo, Franco; Masini,Giulia; Astuti, Noemi; Di Filippo, Elisa; Benatti, Simone; Valenti, Daniela; Callegaro, Anna Paola; Rizzi, Marco

    2014-01-01

    Introduction The long-term effects of an intensified induction regimen are unknown. In this pilot, randomized, prospective study we evaluate the effect of a short-term four-drugs induction regimen in patients with high baseline viral load. Methods Naive patients with HIV-RNA>100.000 copies/ml receiving TDF+FTC+EFV+RAL (group ER) for 4 months and were then simplified to TDF+FTC+EFV. Two randomized control groups treated ab-initio with TDF+FTC+EFV (E) or TDF+FTC+RAL (R) were used. Results 19 pa...

  2. Long-term effect of a four-drugs induction regimen for patients with high baseline viral load

    OpenAIRE

    Franco Maggiolo; Giulia Masini; Noemi Astuti; Elisa Di Filippo; Simone Benatti; Daniela Valenti; Anna Paola Callegaro; Marco Rizzi

    2014-01-01

    Introduction: The long-term effects of an intensified induction regimen are unknown. In this pilot, randomized, prospective study we evaluate the effect of a short-term four-drugs induction regimen in patients with high baseline viral load. Methods: Naive patients with HIV-RNA>100.000 copies/ml receiving TDF+FTC+EFV+RAL (group ER) for 4 months and were then simplified to TDF+FTC+EFV. Two randomized control groups treated ab-initio with TDF+FTC+EFV (E) or TDF+FTC+RAL (R) were used. Results: 19...

  3. Impact of polymorphisms in the HCP5 and HLA-C, and ZNRD1 genes on HIV viral load

    DEFF Research Database (Denmark)

    Thørner, Lise Wegner; Erikstrup, Christian; Harritshøj, Lene Holm;

    2016-01-01

    AIMS: Single nucleotide polymorphisms (SNPs) in the human leucocyte antigen (HLA) complex P5 (HCP5), HLA-C, and near the zinc ribbon domain containing 1 (ZNRD1) have been shown to influence viral load (VL) set point in HIV-infected individuals with a known seroconversion onset. We aimed to determ......AIMS: Single nucleotide polymorphisms (SNPs) in the human leucocyte antigen (HLA) complex P5 (HCP5), HLA-C, and near the zinc ribbon domain containing 1 (ZNRD1) have been shown to influence viral load (VL) set point in HIV-infected individuals with a known seroconversion onset. We aimed...... to determine the influence of HCP5 rs2395029, HLA-C rs9264942, and ZNRD1 rs3869068 on VL in antiretroviral-naïve individuals and on time to the first VLcell recovery after initiation of combination antiretroviral therapy (cART). MATERIAL AND METHODS: We genotyped the rs2395029 (A...... diagnosis and on CD4(+) T-cell recovery during cART. Cox proportional hazard regression analysis assessed the association with time to first VL

  4. Genotypes and viral load of hepatitis C virus among persons attending a voluntary counseling and testing center in Ethiopia.

    Science.gov (United States)

    Abreha, Tesfay; Woldeamanuel, Yimtubezinash; Pietsch, Corinna; Maier, Melanie; Asrat, Daniel; Abebe, Almaz; Hailegiorgis, Bereket; Aseffa, Abraham; Liebert, Uwe Gerd

    2011-05-01

    The prevalence of different genotypes of hepatitis C virus (HCV) in Ethiopia is not known. HCV genotypes influence the response to therapy with alpha-interferon alone or in combination with ribavirin. A cross sectional study was conducted on attendees of voluntary counseling and testing center. Serum samples from 1,954 (734 HIV positive and 1,220 HIV negative) individuals were screened for HCV antibody. Active HCV infection was confirmed by quantitative PCR in 18 of the 71 samples with anti-HCV antibodies. The HCV viral load ranged from 39,650 to 9,878,341 IU/ml (median 1,589,631 IU/ml) with no significant difference [χ(2)(17) = 18.00, P = 0.389] between persons positive or negative for HIV. The viral load of HCV was, however, higher in older study subjects (r = 0.80, P = 0.000). HCV genotypes were determined using the VERSANT HCV Genotype Assay (LiPA) and sequence analysis of the NS5b region of the HCV genome. Diverse HCV genotypes were found including genotypes 1, 2, 4, and 5. There was no difference in the distribution regarding the HIV status. As in other parts of the world, genotyping of HCV must be considered whenever HCV is incriminated as a cause of hepatitis. PMID:21351106

  5. Kinetics of viral load and erythrocytic inclusion body formation in pacific herring artificially infected with erythrocytic necrosis virus

    Science.gov (United States)

    Glenn, Jolene A.; Emmenegger, Eveline J.; Grady, Courtney A.; Roon, Sean R.; Gregg, Jacob L.; Conway, Carla M.; Winton, James R.; Hershberger, Paul K.

    2012-01-01

    Viral erythrocytic necrosis (VEN) is a condition that affects marine and anadromous fish species, including herrings and salmonids, in the Atlantic and Pacific oceans. Infection is frequently associated with severe anemia and causes episodic mortality among wild and hatchery fish when accompanied by additional stressors; VEN can be presumptively diagnosed by (1) light microscopic identification of a single characteristic—a round, magenta-colored, 0.8-μm-diameter inclusion body (IB) within the cytoplasm of erythrocytes and their precursors on Giemsa-stained blood films; or (2) observation (via transmission electron microscopy [TEM]) of the causative iridovirus, erythrocytic necrosis virus (ENV), within erythrocytes or their precursors. To better understand the kinetics of VEN, specific-pathogen-free Pacific herring Clupea pallasii were infected with ENV by intraperitoneal injection. At 1, 4, 7, 10, 14, 21, and 28 d postexposure, samples of blood, spleen, and kidney were collected and assessed (1) via light microscopy for the number of intracytoplasmic IBs in blood smears and (2) via TEM for the number of virions within erythrocytes. The mean prevalence of intracytoplasmic IBs in the blood cells increased from 0% at 0–4 d postexposure to 94% at 28 d postexposure. Viral load within circulating red blood cells peaked at 7 d postexposure, fell slightly, and then reached a plateau. However, blood cells observed within the kidney and spleen tissues demonstrated high levels of ENV between 14 and 28 d postexposure. The results indicate that the viral load within erythrocytes does not correlate well with IB prevalence and that the virus can persist in infected fish for more than 28 d.

  6. Genome-wide association study confirming association of HLA-DP with protection against chronic hepatitis B and viral clearance in Japanese and Korean.

    Directory of Open Access Journals (Sweden)

    Nao Nishida

    Full Text Available Hepatitis B virus (HBV infection can lead to serious liver diseases, including liver cirrhosis (LC and hepatocellular carcinoma (HCC; however, about 85-90% of infected individuals become inactive carriers with sustained biochemical remission and very low risk of LC or HCC. To identify host genetic factors contributing to HBV clearance, we conducted genome-wide association studies (GWAS and replication analysis using samples from HBV carriers and spontaneously HBV-resolved Japanese and Korean individuals. Association analysis in the Japanese and Korean data identified the HLA-DPA1 and HLA-DPB1 genes with P(meta = 1.89×10⁻¹² for rs3077 and P(meta = 9.69×10⁻¹⁰ for rs9277542. We also found that the HLA-DPA1 and HLA-DPB1 genes were significantly associated with protective effects against chronic hepatitis B (CHB in Japanese, Korean and other Asian populations, including Chinese and Thai individuals (P(meta = 4.40×10⁻¹⁹ for rs3077 and P(meta = 1.28×10⁻¹⁵ for rs9277542. These results suggest that the associations between the HLA-DP locus and the protective effects against persistent HBV infection and with clearance of HBV were replicated widely in East Asian populations; however, there are no reports of GWAS in Caucasian or African populations. Based on the GWAS in this study, there were no significant SNPs associated with HCC development. To clarify the pathogenesis of CHB and the mechanisms of HBV clearance, further studies are necessary, including functional analyses of the HLA-DP molecule.

  7. The Breadth of Expandable Memory CD8+ T Cells Inversely Correlates with Residual Viral Loads in HIV Elite Controllers

    Science.gov (United States)

    Ndhlovu, Zaza M.; Stampouloglou, Eleni; Cesa, Kevin; Mavrothalassitis, Orestes; Alvino, Donna Marie; Li, Jonathan Z.; Wilton, Shannon; Karel, Daniel; Piechocka-Trocha, Alicja; Chen, Huabiao; Pereyra, Florencia

    2015-01-01

    ABSTRACT Previous studies have shown that elite controllers with minimal effector T cell responses harbor a low-frequency, readily expandable, highly functional, and broadly directed memory population. Here, we interrogated the in vivo relevance of this cell population by investigating whether the breadth of expandable memory responses is associated with the magnitude of residual viremia in individuals achieving durable suppression of HIV infection. HIV-specific memory CD8+ T cells were expanded by using autologous epitopic and variant peptides. Viral load was measured by an ultrasensitive single-copy PCR assay. Following expansion, controllers showed a greater increase in the overall breadth of Gag responses than did untreated progressors (P = 0.01) as well as treated progressors (P = 0.0003). Nef- and Env-specific memory cells expanded poorly for all groups, and their expanded breadths were indistinguishable among groups (P = 0.9 for Nef as determined by a Kruskal-Wallis test; P = 0.6 for Env as determined by a Kruskal-Wallis test). More importantly, we show that the breadth of expandable, previously undetectable Gag-specific responses was inversely correlated with residual viral load (r = −0.6; P = 0.009). Together, these data reveal a direct link between the abundance of Gag-specific expandable memory responses and prolonged maintenance of low-level viremia. Our studies highlight a CD8+ T cell feature that would be desirable in a vaccine-induced T cell response. IMPORTANCE Many studies have shown that the rare ability of some individuals to control HIV infection in the absence of antiretroviral therapy appears to be heavily dependent upon special HIV-specific killer T lymphocytes that are able to inhibit viral replication. The identification of key features of these immune cells has the potential to inform rational HIV vaccine design. This study shows that a special subset of killer lymphocytes, known as central memory CD8+ T lymphocytes, is at least

  8. Cost-Effectiveness of Testing Hepatitis B–Positive Pregnant Women for Hepatitis B e Antigen or Viral Load

    Science.gov (United States)

    Fan, Lin; Owusu-Edusei, Kwame; Schillie, Sarah F.; Murphy, Trudy V.

    2015-01-01

    OBJECTIVE To estimate the cost-effectiveness of testing pregnant women with hepatitis B (hepatitis B surface antigen [HBsAg]-positive) for hepatitis B e antigen (HBeAg) or hepatitis B virus (HBV) DNA, and administering maternal antiviral prophylaxis if indicated, to decrease breakthrough perinatal HBV transmission from the U.S. health care perspective. METHODS A Markov decision model was constructed for a 2010 birth cohort of 4 million neonates to estimate the cost-effectiveness of two strategies: testing HBsAg-positive pregnant women for 1) HBeAg or 2) HBV load. Maternal antiviral prophylaxis is given from 28 weeks of gestation through 4 weeks postpartum when HBeAg is positive or HBV load is high (108 copies/mL or greater). These strategies were compared with the current recommendation. All neonates born to HBsAg-positive women received recommended active-passive immunoprophylaxis. Effects were measured in quality-adjusted life-years (QALYs) and all costs were in 2010 U.S. dollars. RESULTS The HBeAg testing strategy saved $3.3 million and 3,080 QALYs and prevented 486 chronic HBV infections compared with the current recommendation. The HBV load testing strategy cost $3 million more than current recommendation, saved 2,080 QALYs, and prevented 324 chronic infections with an incremental cost-effectiveness ratio of $1,583 per QALY saved compared with the current recommendations. The results remained robust over a wide range of assumptions. CONCLUSION Testing HBsAg-positive pregnant women for HBeAg or HBV load followed by maternal antiviral prophylaxis if HBeAg-positive or high viral load to reduce perinatal hepatitis B transmission in the United States is cost-effective. PMID:24785842

  9. Effect of Monotherapy with Darunavir/Ritonavir on Viral Load in Seminal Fluid, and Quality Parameters of Semen in HIV-1-Positive Patients

    Science.gov (United States)

    Lopez-Ruz, Miguel A.; Navas, Purificación; López-Zúñiga, Miguel A.; Gonzalvo, María Carmen; Sampedro, Antonio; Pasquau, Juan; Hidalgo-Tenorio, Carmen; Javier, Rosario; Castilla, José A.

    2016-01-01

    Patients with human immunodeficiency virus type 1 (HIV-1) who receive antiretroviral therapy (ART) often achieve increased survival and improved quality of life. In this respect, monotherapy with darunavir/ritonavir (mDRV/r) can be a useful treatment strategy. This prospective study analyses the effect of mDRV/r on sperm quality and viral load in a group of 28 patients who had previously been given conventional ART and who had recorded a viral load 20 copies/ml), and that at V1, after mDRV/r treatment, this figure had fallen to 3%. The quality of seminal fluid was close to normal in 57% of patients at V0 and in 62% at V1. We conclude that, similar to ART, mDRV/r maintains HIV-1 viral load in most patients, and that there is no worsening in seminal fluid quality. PMID:27442068

  10. Synergistic effect of viral load and alcohol consumption on the risk of persistent high-risk human papillomavirus infection.

    Directory of Open Access Journals (Sweden)

    Hea Young Oh

    Full Text Available PURPOSE: This prospective study aimed to examine the combined effect of viral load and alcohol consumption on the risk of persistent high-risk (HR human papillomavirus (HPV infection. METHODS: Among women undergoing health screening between 2002 and 2011 at the National Cancer Center, 284 and 122 women with HR-HPV infection and cytological findings of low-grade squamous intraepithelial or lower-grade lesions were followed up for 1 and 2 years, respectively. Multivariate logistic regression analysis was performed, and the relative excess risk due to interaction (RERI and synergy index (S were calculated. RESULTS: Among drinkers, the risks of 1-year (odds ratio [OR] 4.09, 95% confidence interval [CI] 2.05-8.18 and 2-year persistence (OR 8.08, CI 2.36-27.6 were significantly higher for high HPV loads than for low HPV loads; this association was not seen for non-drinkers. The risks for 1-year (OR 4.14, CI 1.89-9.05 and 2-year persistence (OR 6.61, CI 2.09-20.9 were significantly higher in subjects with a high HPV load who were also drinkers than in those who were non-drinkers. A high HPV load together with a longer drinking duration or higher alcohol consumption was associated with increased risks of 1-year (OR 3.07, CI 1.40-6.75 or OR 2.05, CI 0.87-4.83 and 2-year persistence (OR 6.40, CI 1.72-23.8 or OR 4.14, CI 1.18-14.6. The synergistic effect of alcohol consumption and HR-HPV load was stronger on the risk of 2-year persistence (RERI = 3.26, S = 2.38 than on the risk of 1-year persistence (RERI = 1.21, S = 1.63. CONCLUSIONS: The synergistic effect of HR-HPV load and alcohol consumption was associated with the risk of HR-HPV persistence and was stronger for longer-term HR-HPV infection. Limiting alcohol consumption might be an important measure to prevent the development of cervical cancer in women with a high HR-HPV load.

  11. Melittin-loaded immunoliposomes against viral surface proteins, a new approach to antiviral therapy

    NARCIS (Netherlands)

    Falco Gracia, J.A.; Barrajon-Catalan, E.; Menendez-Gutierrez, M.P.; Coll, J.; Micol, V.; Estepa, A.

    2013-01-01

    In this study, melittin, a well-characterized pore-forming lytic amphiphilic peptide susceptible to be vehiculized in lipid membranes, has been utilized to study their antiviral properties. For this purpose, an assay based on melittin loaded-immunoliposomes previously described by our group was adap

  12. CD4 count and viral load specific rates of AIDS, non-AIDS and deaths according to current antiretroviral use

    Directory of Open Access Journals (Sweden)

    A Mocroft

    2012-11-01

    Full Text Available Background CD4 and viral loads are used in clinical trials as surrogate endpoints for assessing efficacy of newly available antiretrovirals. If antiretrovirals act through other pathways or negatively affect the risk of disease this would not be identified prior to licensing. The aims of this study were to investigate the CD4 and viral load specific rates of fatal and non-fatal AIDS and non-AIDS events according to current antiretrovirals. Methods Poisson regression was used to compare overall events (fatal or non-fatal AIDS, non-AIDS or death, AIDS events (fatal and non-fatal or non-AIDS events (fatal or non-fatal for specific nucleoside pairs and third drugs used with>1000 person-years of follow-up (PYFU after January 1st 2001. Results 9801 patients were included. The median baseline date was January 2004 (interquartile range [IQR] January 2001–February 2007, age was 40.4 (IQR 34.6–47.3 years, and time since starting cART was 3.3 (IQR 0.9–5.1 years. At baseline, the median nadir CD4 was 162 (IQR 71–257/mm3, baseline CD4 was 390 (IQR 249–571/mm3, viral load was 1.9 (IQR 1.7–3.3 log10copies/ml and 2961 (30.2% had a prior AIDS diagnosis and 6.4 years prior to baseline. During 42372.5 PYFU, 1203 (437 AIDS and 766 non-AIDS events occurred. The overall event rate was 2.8 per 100 PYFU (95% confidence interval [CI] 2.7–3.0, of AIDS events was 1.0 (95% CI 0.9–1.1 and of non-AIDS events was 1.8 (95% CI 1.7–1.9. Of the AIDS events, 53 (12.1%were fatal as were 239 (31.2% of the non-AIDS events. After adjustment, there was weak evidence of a difference in the overall events rates between nucleoside pairs (global p-value=0.084, and third drugs (global p-value=0.031. Compared to zidovudine/lamivudine, patients taking abacavir/lamivudine (adjusted incidence rate ratio [aIRR] 1.22; 95% CI 0.99–1.49 and abacavir plus one other nucleoside (aIRR 1.51; 95% CI 1.14–2.02 had an increased incidence of overall events. Comparing the third drugs

  13. High levels of T lymphocyte activation in Leishmania-HIV-1 co-infected individuals despite low HIV viral load

    Directory of Open Access Journals (Sweden)

    Grinsztejn Beatriz

    2010-12-01

    Full Text Available Abstract Background Concomitant infections may influence HIV progression by causing chronic activation leading to decline in T-cell function. In the Americas, visceral (AVL and tegumentary leishmaniasis (ATL have emerged as important opportunistic infections in HIV-AIDS patients and both of those diseases have been implicated as potentially important co-factors in disease progression. We investigated whether leishmaniasis increases lymphocyte activation in HIV-1 co-infected patients. This might contribute to impaired cellular immune function. Methods To address this issue we analyzed CD4+ T absolute counts and the proportion of CD8+ T cells expressing CD38 in Leishmania/HIV co-infected patients that recovered after anti-leishmanial therapy. Results We found that, despite clinical remission of leishmaniasis, AVL co-infected patients presented a more severe immunossupression as suggested by CD4+ T cell counts under 200 cells/mm3, differing from ATL/HIV-AIDS cases that tends to show higher lymphocytes levels (over 350 cells/mm3. Furthermore, five out of nine, AVL/HIV-AIDS presented low CD4+ T cell counts in spite of low or undetectable viral load. Expression of CD38 on CD8+ T lymphocytes was significantly higher in AVL or ATL/HIV-AIDS cases compared to HIV/AIDS patients without leishmaniasis or healthy subjects. Conclusions Leishmania infection can increase the degree of immune system activation in individuals concomitantly infected with HIV. In addition, AVL/HIV-AIDS patients can present low CD4+ T cell counts and higher proportion of activated T lymphocytes even when HIV viral load is suppressed under HAART. This fact can cause a misinterpretation of these laboratorial markers in co-infected patients.

  14. CD4 cell count and viral load-specific rates of AIDS, non-AIDS and deaths according to current antiretroviral use

    NARCIS (Netherlands)

    Mocroft, A.; Phillips, A.N.; Gatell, J.; Horban, A.; Ledergerber, B.; Zilmer, K.; Jevtovic, D.; Maltez, F.; Podlekareva, D.; Lundgren, J.D.; Burger, D.M.

    2013-01-01

    BACKGROUND: CD4 cell count and viral loads are used in clinical trials as surrogate endpoints for assessing efficacy of newly available antiretrovirals. If antiretrovirals act through other pathways or increase the risk of disease this would not be identified prior to licensing. The aim of this stud

  15. Mucosal immunization with recombinant adenoviral vectors expressing murine gammaherpesvirus-68 genes M2 and M3 can reduce latent viral load

    DEFF Research Database (Denmark)

    Hoegh-Petersen, Mette; Thomsen, Allan R; Christensen, Jan P;

    2009-01-01

    of the gammaherpesvirinae speaks against using a similar approach in humans. DNA immunization with plasmids encoding the MHV-68 genes M2 or M3 caused a reduction in either acute or early latent viral load, respectively, but neither immunization had an effect at times later than 14 days post-infection. Adenovirus...

  16. A Prospective Study of Intimate Partner Violence as a Risk Factor for Detectable Plasma Viral Load in HIV-Positive Women Engaged in Transactional Sex in Mombasa, Kenya.

    Science.gov (United States)

    Wilson, Kate S; Wanje, George; Yuhas, Krista; Simoni, Jane M; Masese, Linnet; Vander Stoep, Ann; Jaoko, Walter; Hughes, James P; Richardson, Barbra A; Scott McClelland, R

    2016-09-01

    We conducted a prospective cohort study to evaluate intimate partner violence (IPV) as a risk factor for detectable plasma viral load in HIV-positive female sex workers (FSWs) on antiretroviral therapy (ART) in Kenya. IPV in the past year was defined as ≥1 act of physical, sexual, or emotional violence by the index partner (i.e. boyfriend/husband). The primary outcome was detectable viral load (≥180 copies/ml). In-depth interviews and focus groups were included to contextualize results. Analyses included 195 women (570 visits). Unexpectedly, IPV was associated with significantly lower risk of detectable viral load (adjusted relative risk 0.21, 95 % CI 0.05-0.84, p-value = 0.02). Qualitative findings revealed that women valued emotional and financial support from index partners, despite IPV. IPV was not a major barrier to ART adherence. The observed association between IPV and lower risk of detectable viral load in FSWs may be due to unmeasured personal and relationship factors, warranting further research. PMID:27142058

  17. Factors associated with short-term changes in HIV viral load and CD4+ cell count in antiretroviral-naive individuals

    DEFF Research Database (Denmark)

    Lundgren, Jens

    2014-01-01

    OBJECTIVES: Among antiretroviral therapy (ART)-naive individuals, viral load levels tend to increase and CD4(+) cell counts decline over time. We sought to explore the rate of change and influence of other factors associated with these markers of HIV progression. DESIGN: An observational cohort...

  18. Impact of acute vivax malaria on the immune system and viral load of HIV-positive subjects

    Institute of Scientific and Technical Information of China (English)

    陈小平; 肖斌权; 施文钧; 徐慧芳; 高凯; 饶纪礼; 张周斌

    2003-01-01

    Objective To explore the mechanisms of malariotherapy for human immunodeficiency virus (HIV)-infected patients and to identify which stage(s) of HIV infection is suitable for the treatment of malariotherapy.Methods Therapeutic acute vivax malaria was induced and terminated after 10 fever episodes in 12 HIV-1-infected subjects: Group 1 (G1) had 5 patients with CD4 T-cell counts500/μl at baseline, Group 2 (G2) had 5 patients with CD4 at 499-200/μl and Group 3 had 2 patients with CD4<200/μl (not included in statistical analysis). Enzyme-Linked-Immuno-Sorbent Assay (ELISA) was used to measure plasma levels of cytokines and soluble activation markers. Flow cytometry was used to measure levels of lymphocyte subsets and phenotypes and CD4 cell apoptosis. Bayer bDNA assay was used to test plasma levels of HIV-1 RNA (viral load). Samples were taken and tested twice before malaria (baselines), three times during malaria and seven times after termination of malaria (at day 10 and 1, 3, 6, 12, 18 and 24 months). Results Levels of plasma tumor necrosis factor-α (TNF-α), soluble TNF-α receptor-2 (sTNF-RII), neopterin (NPT) and soluble IL-2 receptor (sIL-2R) significantly increased during malaria and sharply reduced to baselines post malaria in all groups. Stronger responses of the aforementioned factors were seen in G2 than in G1 during malaria (P=0.081, 0.001, 0.013, 0.020). CD4 count and percentage; CD4/CD8 ratio and CD25+ and CD4+CD25+ percentages increased but HLA DR+ percentage decreased either during or post malaria in G2. Most G2 patients experienced sustained increase but most G1 patients underwent natural history decline of CD4 counts and percentages during 2-year follow-up. Percentage of apoptotic CD4 cells decreased post malaria in all groups. G3 patients had weaker immune responses, however, one advanced AIDS patient in this group experienced clinical improvement after malariotherapy. Most of the 12 patients experienced increase of HIV viral load during

  19. Association with Spontaneous Hepatitis C Viral Clearance and Genetic Differentiation of IL28B/IFNL4 Haplotypes in Populations from Mexico

    Science.gov (United States)

    Gonzalez-Aldaco, Karina; Rebello Pinho, João R.; Roman, Sonia; Gleyzer, Ketti; Fierro, Nora A.; Oyakawa, Leticia; Ramos-Lopez, Omar; Ferraz Santana, Rubia A.; Sitnik, Roberta; Panduro, Arturo

    2016-01-01

    Aim To analyze the genetic heterogeneity of the Amerindian and admixed population (Mestizos) based on the IL28B (rs12979860, rs8099917) and IFNL4 (rs368234815) haplotypes, and their association with spontaneous clearance (SC) and liver damage in patients with hepatitis C infection from West Mexico. Methods A total of 711 subjects from West Mexico (181 Amerindians and 530 Mestizos) were studied for the prevalence of IL28B (rs12979860C/T, rs8099917G/T) and IFNL4 (rs368234815∆G/TT) genotypes. A case-control study was performed in 234 treatment-naïve HCV Mestizos (149 chronic hepatitis C and 85 with SC) for the association of haplotypes with SC and liver damage. A real-time PCR assay was used for genotyping, and transitional elastography staged liver damage. Results Significant Fst-values indicated differentiation between the studied populations. The frequencies of the protective C, T, TT alleles were significantly lower in the Amerindians than in Mestizos (p<0.05). The r2 measure of linkage disequilibrium was significant for all variants and the T/G/ΔG risk haplotype predominated in Amerindians and secondly in Mestizos. The protective C/T/TT haplotype was associated with SC (OR = 0.46, 95% IC 0.22–0.95, p = 0.03) and less liver damage (OR = 0.32, 95% IC 0.10–0.97, p = 0.04) in chronic patients. The Structure software analysis demonstrated no significant differences in ancestry among SC and chronic patients. Conclusions West Mexico´s population is genetically heterogeneous at the IL28B/IFNL4 polymorphisms. The T/G/ΔG high-risk haplotype predominated in Amerindians and the beneficial alternative haplotype in Mestizos. The C/T/TT haplotype was associated with SC and less liver damage in chronically infected Mestizo patients. PMID:26741362

  20. Does chronic alcohol use by HIV-infected patients on d4T/3TC/NVP drug regimen effect the HIV viral load and what is the therapeutic window of the drugs, CD4+ count and WBC count in patients with high viral load during the 9 months period of follow up?

    Directory of Open Access Journals (Sweden)

    Godfrey S. Bbosa

    2013-10-01

    Full Text Available The study investigated the effects of chronic alcohol use on HIV viral load in HIV-infected patients on d4T/3TC/NVP drug regimen during 9 months follow up period. It also determined plasma drug concentrations of d4T, 3TC and NVP; CD4+ and WBC counts for patients with high HIV viral load. A case-control study using repeated measures with serial measurements was used. A total of 41 patients (20 alcohol group and 21 control group were screened for alcohol use using WHO AUDIT tool and chronic alcohol use biomarkers. Blood sampling was done at 3 month intervals for a period of 9 months. HIV viral load was determined using Roche Amplicor HIV-1 monitor test, version 1.5 (Amplicor. The d4T, 3TC and NVP concentrations were determined by Shimadzu Class-VPTM HPLC Chromatography data system version 6.1. The CD4+ cell count was determined using FACSCalibur flow cytometer. The WBC was determined using automated hematological Coulter CBC-5 Hematology Analyzer system. Results show that % patients with HIV viral load ≥400 copies/ml in control group was highest (23.8%, n=5 at 3 month while in chronic alcohol use group, it was at 0 month (35%, n=7 for both WHO AUDIT tool and chronic alcohol-use biomarkers groups. Generally patients with high viral load ≥400 copies/ml was observed in chronic alcohol use as compared to control group in both WHO AUDIT tool and biomarkers group despite of patients having high steady state d4T, 3TC and NVP plasma drug concentrations in circulation that is available to suppress HIV virus. The high viral load could be associated with the emergence of resistance of the HIV virus and these patients generally had a low CD4+ cell count. Some of these patients had no detectable d4T plasma drug concentrations in circulation and most of them with high viral load had sub-therapeutic NVP plasma drug concentrations in their blood circulation. Chronic ethanol use by HIV-infected patients on d4T/3TC/NVP drug regimen increased HIV viral load and

  1. Long-term effect of a four-drugs induction regimen for patients with high baseline viral load

    Directory of Open Access Journals (Sweden)

    Franco Maggiolo

    2014-11-01

    Full Text Available Introduction: The long-term effects of an intensified induction regimen are unknown. In this pilot, randomized, prospective study we evaluate the effect of a short-term four-drugs induction regimen in patients with high baseline viral load. Methods: Naive patients with HIV-RNA>100.000 copies/ml receiving TDF+FTC+EFV+RAL (group ER for 4 months and were then simplified to TDF+FTC+EFV. Two randomized control groups treated ab-initio with TDF+FTC+EFV (E or TDF+FTC+RAL (R were used. Results: 19 patients with a mean age of 38 years and mean baseline CD4 count of 334 (SD 216 cells/mcL and HIV-RNA of 5.47 log (SD 0.32 copies/mL were enrolled. No baseline significant difference was observed among groups. Early HIV-RNA reduction was significantly higher in ER compared to the other groups from week 1 to week 4 (P from 0.026 to 0.003 (figure 1, thereafter HIV-RNA values were comparable among the groups. At week 96, all patients had an HIV-RNA < 50 copies/mL, however only patients in the ER group had in all cases an HIV-RNA level < 3 copies/mL with a statistically significant difference compared to E (60%; P=0.038 and R (50%; P=0.020. At 96 weeks, CD4 cell median counts were 765 cells/mcL for ER, 600 cells/mcL for E and 771 for R (P=0.16, however patients in the ER group presented a lower proportion of activated CD4+CD38+HLADR+ cells (1.9% versus 3.9 and 3.8% and CD8+CD38+HLADR+ cells (10.3% versus 16.8 and 16.5% and a significantly better CD4/CD8 ratio (0.98 versus 0.53 and 0.61; P=0.03. Conclusions: A four-drug regimen in naive patients with high pre-therapy viral load improves early virologic response. A quick drop of HIV-RNA seems to correlate with a sustained virologic response. Although limited in time (four months, the four-drug regimens correlates with an improved immunological response as measured by the CD4/CD8 ratio or the percentage of activated CD4+ and CD8+ cells. The reasons why this happens deserve further studies. This study highlights the

  2. Liver stiffness measurement and biochemical markers in Senegalese chronic hepatitis B patients with normal ALT and high viral load.

    Directory of Open Access Journals (Sweden)

    Papa Saliou Mbaye

    Full Text Available BACKGROUND AND AIMS: Despite the high prevalence of chronic hepatitis B (CHB in Africa, few studies have been performed among African patients. We sought to evaluate liver stiffness measurement by FibroScan® (LSM and two biochemical scores (FibroTest®, Fibrometer® to diagnose liver fibrosis in Senegalese CHB patients with HBV plasma DNA load ≥3.2 log(10 IU/mL and normal alanine aminotransferase (ALT values. METHODS: LSM and liver fibrosis biochemical markers were performed on 225 consecutive HBV infected Senegalese patients with high viral load. Patients with an LSM range between 7 and 13 kPa underwent liver biopsy (LB. Two experienced liver pathologists performed histological grading using Metavir and Ishak scoring. RESULTS: 225 patients were evaluated (84% male and LB was performed in 69 patients, showing F2 and F3 fibrosis in 17% and 10% respectively. In these patients with a 7-13 kPa range of LSM, accuracy for diagnosis of significant fibrosis according to LB was unsatisfactory for all non-invasive markers with AUROCs below 0.70. For patients with LSM values below 7 kPa, FibroTest® (FT, and Fibrometer® (FM using the cut-offs recommended by the test promoters suggested a fibrosis in 18% of cases for FT (8% severe fibrosis and 8% for FM. For patients with LSM values greater than 13 kPa, FT, FM suggested a possible fibrosis in 73% and 70%, respectively. CONCLUSION: In highly replicative HBV-infected African patients with normal ALT and LSM value below 13 kPa, FibroScan®, FibroTest® or Fibrometer® were unsuitable to predict the histological liver status of fibrosis.

  3. Systematic review and meta-analysis of hepatitis C virus infection and HIV viral load: new insights into epidemiologic synergy

    Science.gov (United States)

    Petersdorf, Nicholas; Ross, Jennifer M; Weiss, Helen A; Barnabas, Ruanne V; Wasserheit, Judith N

    2016-01-01

    Introduction Hepatitis C virus (HCV) and HIV infection frequently co-occur due to shared transmission routes. Co-infection is associated with higher HCV viral load (VL), but less is known about the effect of HCV infection on HIV VL and risk of onward transmission. Methods We undertook a systematic review comparing 1) HIV VL among ART-naïve, HCV co-infected individuals versus HIV mono-infected individuals and 2) HIV VL among treated versus untreated HCV co-infected individuals. We performed a random-effects meta-analysis and quantified heterogeneity using the I2 statistic. We followed Cochrane Collaboration guidelines in conducting our review and PRISMA guidelines in reporting results. Results and discussion We screened 3925 articles and identified 17 relevant publications. A meta-analysis found no evidence of increased HIV VL associated with HCV co-infection or between HIV VL and HCV treatment with pegylated interferon-alpha-2a/b and ribavirin. Conclusions This finding is in contrast to the substantial increases in HIV VL observed with several other systemic infections. It presents opportunities to elucidate the biological pathways that underpin epidemiological synergy in HIV co-infections and may enable prediction of which co-infections are most important to epidemic control. PMID:27649908

  4. Use of Dried Plasma Spots for HIV-1 Viral Load Determination and Drug Resistance Genotyping in Mexican Patients

    Science.gov (United States)

    Rodriguez-Auad, Juan Pablo; Rojas-Montes, Othon; Maldonado-Rodriguez, Angelica; Alvarez-Muñoz, Ma. Teresa; Muñoz, Onofre; Torres-Ibarra, Rocio; Vazquez-Rosales, Guillermo

    2015-01-01

    Monitoring antiretroviral therapy using measurements of viral load (VL) and the genotyping of resistance mutations is not routinely performed in low- to middle-income countries because of the high costs of the commercial assays that are used. The analysis of dried plasma spot (DPS) samples on filter paper may represent an alternative for resource-limited settings. Therefore, we evaluated the usefulness of analyzing DPS samples to determine VL and identify drug resistance mutations (DRM) in a group of HIV-1 patients. The VL was measured from 22 paired plasma and DPS samples. In these samples, the average VL was 4.7 log10 copies/mL in liquid plasma and 4.1 log10 copies/mL in DPS, with a correlation coefficient of R = 0.83. A 1.1 kb fragment of HIV pol could be amplified in 14/22 (63.6%) of the DPS samples and the same value was amplified in plasma samples. A collection of ten paired DPS and liquid plasma samples was evaluated for the presence of DRM; an excellent correlation was found in the identification of DRM between the paired samples. All HIV-1 pol sequences that were obtained corresponded to HIV subtype B. The analysis of DPS samples offers an attractive alternative for monitoring ARV therapy in resource-limited settings. PMID:26779533

  5. Effect of Hormonal Contraceptive Use Prior to HIV Seroconversion on Viral Load Setpoint among Women in Rakai, Uganda

    Science.gov (United States)

    Polis, Chelsea B.; Gray, Ronald H.; Bwanika, J.B.; Kigozi, Godfrey; Kiwanuka, Noah; Nalugoda, Fred; Kagaayi, Joseph; Lutalo, Tom; Serwadda, David; Wawer, Maria J.

    2010-01-01

    Background High viral load (VL) setpoint is a marker for rapid HIV progression, but few studies have examined whether use of hormonal contraception (HC) prior to HIV seroconversion affects VL setpoint. Methods We determined VL setpoints in 285 HIV seroconverters using blood samples collected six months or more after estimated HIV seroconversion but before disease progression to CD4≤250 or WHO Stage 3 or 4. We used multivariate linear regression to estimate the effect of HC use prior to HIV seroconversion on VL setpoint, and multivariate Cox regression to estimate the hazards ratio of death associated with VL setpoint. Results Of 285 women, 42 (15%) reported using HC prior to HIV seroconversion. Mean VL setpoint was 4.49 (SD 0.79) log10 copies/mL among women who used HC prior to HIV seroconversion and 4.47 (SD 0.86) among non-HC users (p=0.88). In multivariate analysis, HC prior to HIV seroconversion was not associated with VL setpoint (+0.11 log10 copies /mL; p=0.47). Higher socioeconomic status was associated with lower VL setpoint (-0.43 log10 copies/mL; p=0.04). VL setpoints above the median were associated with faster time to death (adjHR: 2.54, 95% CI: 1.30-4.98, p-value <0.01). Conclusions Use of HC prior to HIV seroconversion was not associated with elevated VL setpoint. PMID:21068673

  6. Use of Dried Plasma Spots for HIV-1 Viral Load Determination and Drug Resistance Genotyping in Mexican Patients

    Directory of Open Access Journals (Sweden)

    Juan Pablo Rodriguez-Auad

    2015-01-01

    Full Text Available Monitoring antiretroviral therapy using measurements of viral load (VL and the genotyping of resistance mutations is not routinely performed in low- to middle-income countries because of the high costs of the commercial assays that are used. The analysis of dried plasma spot (DPS samples on filter paper may represent an alternative for resource-limited settings. Therefore, we evaluated the usefulness of analyzing DPS samples to determine VL and identify drug resistance mutations (DRM in a group of HIV-1 patients. The VL was measured from 22 paired plasma and DPS samples. In these samples, the average VL was 4.7 log10 copies/mL in liquid plasma and 4.1 log10 copies/mL in DPS, with a correlation coefficient of R = 0.83. A 1.1 kb fragment of HIV pol could be amplified in 14/22 (63.6% of the DPS samples and the same value was amplified in plasma samples. A collection of ten paired DPS and liquid plasma samples was evaluated for the presence of DRM; an excellent correlation was found in the identification of DRM between the paired samples. All HIV-1 pol sequences that were obtained corresponded to HIV subtype B. The analysis of DPS samples offers an attractive alternative for monitoring ARV therapy in resource-limited settings.

  7. Vaccination with Brucella abortus recombinant in vivo-induced antigens reduces bacterial load and promotes clearance in a mouse model for infection.

    Directory of Open Access Journals (Sweden)

    Jake E Lowry

    Full Text Available Current vaccines used for the prevention of brucellosis are ineffective in inducing protective immunity in animals that are chronically infected with Brucella abortus, such as elk. Using a gene discovery approach, in vivo-induced antigen technology (IVIAT on B. abortus, we previously identified ten loci that encode products up-regulated during infection in elk and consequently may play a role in virulence. In our present study, five of the loci (D15, 0187, VirJ, Mdh, AfuA were selected for further characterization and compared with three additional antigens with virulence potential (Hia, PrpA, MltA. All eight genes were PCR-amplified from B. abortus and cloned into E. coli. The recombinant products were then expressed, purified, adjuvanted, and delivered subcutaneously to BALB/c mice. After primary immunization and two boosts, mice were challenged i.p. with 5 x 10⁴ CFU of B. abortus strain 19. Spleens from challenged animals were harvested and bacterial loads determined by colony count at various time points. While vaccination with four of the eight individual proteins appeared to have some effect on clearance kinetics, mice vaccinated with recombinant Mdh displayed the most significant reduction in bacterial colonization. Furthermore, mice immunized with Mdh maintained higher levels of IFN-γ in spleens compared to other treatment groups. Collectively, our in vivo data gathered from the S19 murine colonization model suggest that vaccination with at least three of the IVIAT antigens conferred an enhanced ability of the host to respond to infection, reinforcing the utility of this methodology for the identification of potential vaccine candidates against brucellosis. Mechanisms for immunity to one protein, Mdh, require further in vitro exploration and evaluation against wild-type B. abortus challenge in mice, as well as other hosts. Additional studies are being undertaken to clarify the role of Mdh and other IVI antigens in B. abortus virulence

  8. Vaccination with Brucella abortus recombinant in vivo-induced antigens reduces bacterial load and promotes clearance in a mouse model for infection.

    Science.gov (United States)

    Lowry, Jake E; Isaak, Dale D; Leonhardt, Jack A; Vernati, Giulia; Pate, Jessie C; Andrews, Gerard P

    2011-01-01

    Current vaccines used for the prevention of brucellosis are ineffective in inducing protective immunity in animals that are chronically infected with Brucella abortus, such as elk. Using a gene discovery approach, in vivo-induced antigen technology (IVIAT) on B. abortus, we previously identified ten loci that encode products up-regulated during infection in elk and consequently may play a role in virulence. In our present study, five of the loci (D15, 0187, VirJ, Mdh, AfuA) were selected for further characterization and compared with three additional antigens with virulence potential (Hia, PrpA, MltA). All eight genes were PCR-amplified from B. abortus and cloned into E. coli. The recombinant products were then expressed, purified, adjuvanted, and delivered subcutaneously to BALB/c mice. After primary immunization and two boosts, mice were challenged i.p. with 5 x 10⁴ CFU of B. abortus strain 19. Spleens from challenged animals were harvested and bacterial loads determined by colony count at various time points. While vaccination with four of the eight individual proteins appeared to have some effect on clearance kinetics, mice vaccinated with recombinant Mdh displayed the most significant reduction in bacterial colonization. Furthermore, mice immunized with Mdh maintained higher levels of IFN-γ in spleens compared to other treatment groups. Collectively, our in vivo data gathered from the S19 murine colonization model suggest that vaccination with at least three of the IVIAT antigens conferred an enhanced ability of the host to respond to infection, reinforcing the utility of this methodology for the identification of potential vaccine candidates against brucellosis. Mechanisms for immunity to one protein, Mdh, require further in vitro exploration and evaluation against wild-type B. abortus challenge in mice, as well as other hosts. Additional studies are being undertaken to clarify the role of Mdh and other IVI antigens in B. abortus virulence and induction of

  9. PLGA-PEG Nanoparticles Coated with Anti-CD45RO and Loaded with HDAC Plus Protease Inhibitors Activate Latent HIV and Inhibit Viral Spread

    Science.gov (United States)

    Tang, Xiaolong; Liang, Yong; Liu, Xinkuang; Zhou, Shuping; Liu, Liang; Zhang, Fujina; Xie, Chunmei; Cai, Shuyu; Wei, Jia; Zhu, Yongqiang; Hou, Wei

    2015-10-01

    Activating HIV-1 proviruses in latent reservoirs combined with inhibiting viral spread might be an effective anti-HIV therapeutic strategy. Active specific delivery of therapeutic drugs into cells harboring latent HIV, without the use of viral vectors, is a critical challenge to this objective. In this study, nanoparticles of poly(lactic-co-glycolic acid)-polyethylene glycol diblock copolymers conjugated with anti-CD45RO antibody and loaded with the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) and/or protease inhibitor nelfinavir (Nel) were tested for activity against latent virus in vitro. Nanoparticles loaded with SAHA, Nel, and SAHA + Nel were characterized in terms of size, surface morphology, zeta potential, entrapment efficiency, drug release, and toxicity to ACH-2 cells. We show that SAHA- and SAHA + Nel-loaded nanoparticles can target latently infected CD4+ T-cells and stimulate virus production. Moreover, nanoparticles loaded with SAHA + NEL were capable of both activating latent virus and inhibiting viral spread. Taken together, these data demonstrate the potential of this novel reagent for targeting and eliminating latent HIV reservoirs.

  10. Some novel insights on HPV16 related cervical cancer pathogenesis based on analyses of LCR methylation, viral load, E7 and E2/E4 expressions.

    Directory of Open Access Journals (Sweden)

    Damayanti Das Ghosh

    Full Text Available This study was undertaken to decipher the interdependent roles of (i methylation within E2 binding site I and II (E2BS-I/II and replication origin (nt 7862 in the long control region (LCR, (ii expression of viral oncogene E7, (iii expression of the transcript (E7-E1/E4 that encodes E2 repressor protein and (iv viral load, in human papillomavirus 16 (HPV16 related cervical cancer (CaCx pathogenesis. The results revealed over-representation (p<0.001 of methylation at nucleotide 58 of E2BS-I among E2-intact CaCx cases compared to E2-disrupted cases. Bisulphite sequencing of LCR revealed overrepresentation of methylation at nucleotide 58 or other CpGs in E2BS-I/II, among E2-intact cases than E2-disrupted cases and lack of methylation at replication origin in case of both. The viral transcript (E7-E1/E4 that produces the repressor E2 was analyzed by APOT (amplification of papillomavirus oncogenic transcript-coupled-quantitative-RT-PCR (of E7 and E4 genes to distinguish episomal (pure or concomitant with integrated from purely integrated viral genomes based on the ratio, E7 C(T/E4 C(T. Relative quantification based on comparative C(T (threshold cycle method revealed 75.087 folds higher E7 mRNA expression in episomal cases over purely integrated cases. Viral load and E2 gene copy numbers were negatively correlated with E7 C(T (p = 0.007 and E2 C(T (p<0.0001, respectively, each normalized with ACTB C(T, among episomal cases only. The k-means clustering analysis considering E7 C(T from APOT-coupled-quantitative-RT-PCR assay, in conjunction with viral load, revealed immense heterogeneity among the HPV16 positive CaCx cases portraying integrated viral genomes. The findings provide novel insights into HPV16 related CaCx pathogenesis and highlight that CaCx cases that harbour episomal HPV16 genomes with intact E2 are likely to be distinct biologically, from the purely integrated viral genomes in terms of host genes and/or pathways involved in cervical

  11. Switching tenofovir/emtricitabine plus lopinavir/r to raltegravir plus Darunavir/r in patients with suppressed viral load did not result in improvement of renal function but could sustain viral suppression: a randomized multicenter trial.

    Directory of Open Access Journals (Sweden)

    Takeshi Nishijima

    Full Text Available BACKGROUND: Whether tenofovir nephrotoxicity is reversible after its withdrawal is unknown. Furthermore, there are no data on the viral efficacy of raltegravir (RAL plus ritonavir-boosted Darunavir (DRV/r in patients with suppressed viral load. METHODS: This multicenter, randomized trial compared renal function and viral efficacy in patients with suppressed viral load treated with RAL+DRV/r and ritonavir-boosted lopinavir (LPV/r plus tenofovir/emtricitabine (TVD, who had been previously on LPV/r+TVD. The primary endpoint was the proportion of patients with >10% improvement in estimated glomerular filtration rate (eGFR at 48 weeks calculated with Cockcroft-Gault equation. RESULTS: 58 randomized and treatment-exposed patients were analyzed (28 on RAL+DRV/r and 30 on LPV/r+TVD. Greater than 10% improvement in eGFR was noted in 6 (25% out of 24 with RAL+DRV/r and 3 (11% of 28 with LPV/r+TVD, and the difference was not statistically significant (p=0.272, 95% CI -0.067 to 0.354. Sensitivity analyses using three other equations for eGFR showed the same results. Urinary β2 microglobulin, a sensitive marker of tenofovir tubulopathy, significantly improved with RAL+DRV/r than with LPV/r+TVD (-271 versus -64 µg/gCr, p=0.026. Per protocol analysis showed that the HIV-RNA was 10% improvement in renal function among those with relatively preserved eGFR. However, the switch improved urinary β2 microglobulin, suggesting that discontinuation of TDF might be beneficial in the long-term. RAL+DRV/r showed favorable viral efficacy in patients with suppressed viral load. TRIAL REGISTRATION: ClinicalTrials.gov NCT01294761 http://clinicaltrials.gov/ct2/show/NCT01294761?term=SPARE&rank=2, Umin Clinical Trials Registry UMIN000005116 http://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000006083&language=J.

  12. Quantitative analysis of viral load per haploid genome revealed the different biological features of Merkel cell polyomavirus infection in skin tumor.

    Directory of Open Access Journals (Sweden)

    Satoshi Ota

    Full Text Available Merkel cell polyomavirus (MCPyV has recently been identified in Merkel cell carcinoma (MCC, an aggressive cancer that occurs in sun-exposed skin. Conventional technologies, such as polymerase chain reaction (PCR and immunohistochemistry, have produced conflicting results for MCPyV infections in non-MCC tumors. Therefore, we performed quantitative analyses of the MCPyV copy number in various skin tumor tissues, including MCC (n = 9 and other sun exposure-related skin tumors (basal cell carcinoma [BCC, n = 45], actinic keratosis [AK, n = 52], Bowen's disease [n = 34], seborrheic keratosis [n = 5], primary cutaneous anaplastic large-cell lymphoma [n = 5], malignant melanoma [n = 5], and melanocytic nevus [n = 6]. In a conventional PCR analysis, MCPyV DNA was detected in MCC (9 cases; 100%, BCC (1 case; 2%, and AK (3 cases; 6%. We then used digital PCR technology to estimate the absolute viral copy number per haploid human genome in these tissues. The viral copy number per haploid genome was estimated to be around 1 in most MCC tissues, and there were marked differences between the MCC (0.119-42.8 and AK (0.02-0.07 groups. PCR-positive BCC tissue showed a similar viral load as MCC tissue (0.662. Immunohistochemistry with a monoclonal antibody against the MCPyV T antigen (CM2B4 demonstrated positive nuclear localization in most of the high-viral-load tumor groups (8 of 9 MCC and 1 BCC, but not in the low-viral-load or PCR-negative tumor groups. These results demonstrated that MCPyV infection is possibly involved in a minority of sun-exposed skin tumors, including BCC and AK, and that these tumors display different modes of infection.

  13. The effect of N-acetylcysteine supplementation upon viral load, CD4, CD8, total lymphocyte count and hematocrit in individuals undergoing antiretroviral treatment.

    Science.gov (United States)

    Spada, Celso; Treitinger, Arício; Reis, Marcellus; Masokawa, Ivete Y; Verdi, Júlio C; Luiz, Magali C; Silveira, Mariete V S; Michelon, Cleonice M; Avila-Junior, Silvio; Gil, lone D O; Ostrowskyl, Stephanie

    2002-05-01

    Individuals infected with the human immunodeficiency virus (HIV-1) present with decreased CD4, a progressive increase in viral load, compromised cell immune defense, and hematologic alterations. The aim of this study was to assess the serum viral load, CD4, CD8, lymphocyte count and hematocrit at the beginning of antiretroviral therapy in individuals who were supplemented with N-acetylcysteine (NAC). Twenty volunteers participated in this double-blind, placebo-controlled 180-day study. Ten participants received 600 mg of NAC per day (NAC group) and the other ten serving as a control group received placebo. The above mentioned parameters were determined before treatment, and after 60, 120 and 180 days. In NAC-treated patients hematocrit remained stable and an increase in CD4 cell count took place earlier than that in the control group.

  14. A cluster randomized trial of routine HIV-1 viral load monitoring in Zambia: study design, implementation, and baseline cohort characteristics.

    Directory of Open Access Journals (Sweden)

    John R Koethe

    Full Text Available BACKGROUND: The benefit of routine HIV-1 viral load (VL monitoring of patients on antiretroviral therapy (ART in resource-constrained settings is uncertain because of the high costs associated with the test and the limited treatment options. We designed a cluster randomized controlled trial to compare the use of routine VL testing at ART-initiation and at 3, 6, 12, and 18 months, versus our local standard of care (which uses immunological and clinical criteria to diagnose treatment failure, with discretionary VL testing when the two do not agree. METHODOLOGY: Dedicated study personnel were integrated into public-sector ART clinics. We collected participant information in a dedicated research database. Twelve ART clinics in Lusaka, Zambia constituted the units of randomization. Study clinics were stratified into pairs according to matching criteria (historical mortality rate, size, and duration of operation to limit the effect of clustering, and independently randomized to the intervention and control arms. The study was powered to detect a 36% reduction in mortality at 18 months. PRINCIPAL FINDINGS: From December 2006 to May 2008, we completed enrollment of 1973 participants. Measured baseline characteristics did not differ significantly between the study arms. Enrollment was staggered by clinic pair and truncated at two matched sites. CONCLUSIONS: A large clinical trial of routing VL monitoring was successfully implemented in a dynamic and rapidly growing national ART program. Close collaboration with local health authorities and adequate reserve staff were critical to success. Randomized controlled trials such as this will likely prove valuable in determining long-term outcomes in resource-constrained settings. TRIAL REGISTRATION: Clinicaltrials.gov NCT00929604.

  15. Valine, a Branched-Chain Amino Acid, Reduced HCV Viral Load and Led to Eradication of HCV by Interferon Therapy in a Decompensated Cirrhotic Patient

    OpenAIRE

    Kawaguchi, Takumi; Torimura, Takuji; Takata, Akio; Satomi, Susumu; Sata, Michio

    2012-01-01

    A decreased serum level of branched-chain amino acid (BCAA) is a distinctive metabolic disorder in patients with liver cirrhosis. Recently, BCAA has been reported to exert various pharmacological activities, and valine, which is a BCAA, has been shown to affect lipid metabolism and the immune system in in vivo experiments. However, the clinical impact of valine supplementation on viral hepatitis C virus (HCV) load has never been reported. Here, we first describe a case of HCV-related advanced...

  16. Association between HSV-2 and HIV-1 viral load in semen, cervico-vaginal secretions and genital ulcers of Thai men and women.

    Science.gov (United States)

    Chu, Kathryn; Jiamton, Sukhum; Pepin, Jacques; Cowan, Frances; Mahakkanukrauh, Bussakorn; Suttent, Ruengpung; Robinson, Noah J; Deslandes, Sylvie; Frost, Eric; Chaisilwattana, Pongsakdi; Suthipinittharm, Puan; Grosskurth, Heiner; Brown, David; Jaffar, Shabbar

    2006-10-01

    We studied the association between herpes simplex virus type-2 (HSV-2) and HIV-1 viralload in plasma, semen, cervico-vaginal secretions and genital ulcers. Forty-seven (68%) men and 57 (80%) women were HSV-2 antibody positive, of whom 12 (26%, 95% confidence interval [CI] 20, 32) and five (8%, 95% CI 4, 12), respectively, had HSV-2 genital shedding detected by polymerase chain reaction. The mean HIV-1 seminal and cervico-vaginal viral loads did not differ significantly according to the presence of HSV-2 shedding. Eleven men and 15 women presented with genital ulcers; all ulcers were due to HSV-2. Ten men and nine women were followed up over six days: the mean (95% CI) HIV-1 log viral load copies/mL in the genital ulcers at baseline and final visits were 2.5 (2.3, 2.7) and 3.1 (2.0, 4.2) for men and 3.0 (2.6, 3.4) and 2.7 (2.3, 3.1) for women. These findings do not support the hypothesis that HSV-2 increases the HIV-1 viral load in genital secretions.

  17. Bio-mathematical models of viral dynamics to tailor antiviral therapy in chronic viral hepatitis

    Institute of Scientific and Technical Information of China (English)

    Maurizia Rossana Brunetto; Piero Colombatto; Ferruccio Bonino

    2009-01-01

    The simulation of the dynamics of viral infections by mathematical equations has been applied successfully to the study of viral infections during antiviral therapy. Standard models applied to viral hepatitis describe the viral load decline in the first 2-4 wk of antiviral therapy, but do not adequately simulate the dynamics of viral infection for the following period. The hypothesis of a constant clearance rate of the infected cells provides an unrealistic estimation of the time necessary to reach the control or the clearance of hepatitis B virus (HBV)/ hepatitis C virus (HCV) infection. To overcome the problem, we have developed a new multiphasic model in which the immune system activity is modulated by a negative feedback caused by the infected cells reduction, and alanine aminotransferase kinetics serve as a surrogate marker of infected-cell clearance. By this approach, we can compute the dynamics of infected cells during the whole treatment course, and find a good correlation between the number of infected cells at the end of therapy and the long-term virological response in patients with chronic hepatitis C. The new model successfully describes the HBV infection dynamics far beyond the third month of antiviral therapy under the assumption that the sum of infected and non-infected cells remains roughly constant during therapy, and both target and infected cells concur in the hepatocyte turnover. In clinical practice, these new models will allow the development of simulators of treatment response that will be used as an "automatic pilot" for tailoring antiviral therapy in chronic hepatitis B as well as chronic hepatitis C patients.

  18. Bio-mathematical models of viral dynamics to tailor antiviral therapy in chronic viral hepatitis

    Science.gov (United States)

    Brunetto, Maurizia Rossana; Colombatto, Piero; Bonino, Ferruccio

    2009-01-01

    The simulation of the dynamics of viral infections by mathematical equations has been applied successfully to the study of viral infections during antiviral therapy. Standard models applied to viral hepatitis describe the viral load decline in the first 2-4 wk of antiviral therapy, but do not adequately simulate the dynamics of viral infection for the following period. The hypothesis of a constant clearance rate of the infected cells provides an unrealistic estimation of the time necessary to reach the control or the clearance of hepatitis B virus (HBV)/hepatitis C virus (HCV) infection. To overcome the problem, we have developed a new multiphasic model in which the immune system activity is modulated by a negative feedback caused by the infected cells reduction, and alanine aminotransferase kinetics serve as a surrogate marker of infected-cell clearance. By this approach, we can compute the dynamics of infected cells during the whole treatment course, and find a good correlation between the number of infected cells at the end of therapy and the long-term virological response in patients with chronic hepatitis C. The new model successfully describes the HBV infection dynamics far beyond the third month of antiviral therapy under the assumption that the sum of infected and non-infected cells remains roughly constant during therapy, and both target and infected cells concur in the hepatocyte turnover. In clinical practice, these new models will allow the development of simulators of treatment response that will be used as an “automatic pilot” for tailoring antiviral therapy in chronic hepatitis B as well as chronic hepatitis C patients. PMID:19195054

  19. Hepatitis C seroprevalence and correlation between viral load and viral genotype among primary care clients in Mexico Seroprevalencia de hepatitis C y correlación entre la carga viral y el genotipo viral en asistentes al nivel primario de atención enMéxico

    Directory of Open Access Journals (Sweden)

    Ana I Burguete-Garcia

    2011-01-01

    Full Text Available OBJECTIVE: To measure hepatitis C virus (HCV sero-prevalence, prevalence, hepatitis risk characteristics frequency, and genotype correlation with viral load among clients attending health care clinics. MATERIAL AND METHODS: Venous blood samples from l12 226 consecutive consenting adults were collected from January 2006 through December 2009. HCV antibodies were detected by immunoassay. HCV RNA was detected by qRT-PCR and viral genotype was performed by PCR and LIPA test. RESULTS: The HCV seroprevalence observed was l.5 % (C.I. 95% l.3-l.7, from seropositive individuals 60.9 % reported previous blood transfusion, 28.3% declared to have relatives with cirrhosis, 25.2% had tattoos or piercings, and 6.9% referred to have used drugs. Male gender and transfusion (pOBJETIVO: Medir la seroprevalencia y prevalencia del virus de hepatitis C (VHC, la frecuencia de caracteristicas de riesgo y la correlacion genotipica con la carga viral en sujetos asistentes a clinicas de medicina familiar. MATERIAL Y METODOS: muestras de sangre venosa se colectaron de l12 226 adultos, previo consentimiento informado, de enero 2006 hasta diciembre 2009, para la deteccion de anticuerpos contra VHC por ELISA. La deteccion de RNA-VHC y el genotipo viral se realizo mediante qRT-PCR. RESULTADOS: La seroprevalencia de VHC fue l.5 % (C.I. 95% l.3-l.7, 60.9% reportaron transfusion sanguinea previa, 28.3% dijo tener familiares cercanos con cirrosis, 25.2% tenian tatuajes o piercing y 6.9% refirio ser usuario de drogas intravenosas. El ser hombre, el antecedente de transfusiones y el uso de drogas (p<0.00l, fueron los factores con mayor frecuencia en el grupo VHC seropositivo. La prevalencia del RNA-VHC en seropositivos fue de 48.3%. El genotipo mas frecuente en todas las areas geograficas de Mexico fue el l (subtipo lA, 33%; subtipo lB, 21.4% seguido por el genotipo 2 (subtipo 2A, 8.50%. Se observó una correlación positiva de 51% con la carga viral más alta y el genotipo viral 1A

  20. Use of maraviroc in patients with undetectable viral load: efficacy, tolerance and predictors of viral response in MARAVIROC-cohort study

    Directory of Open Access Journals (Sweden)

    María Jesús Pérez Elías

    2014-11-01

    Full Text Available Introduction: No controlled clinical trials had studied the role of maraviroc (MRV in fully suppressed patients (1. Materials and Methods: MRV-cohort is an observational, retrospective, multicentric (27 sites large cohort study of patients starting MRV in clinical practice under different circumstances, with at least 48 weeks of follow-up. For the present analysis we selected all those patients starting with an HIV-RNA<50 copies/mL. Demographics, baseline CD4 cell count, past history of antiretroviral treatment (ART, tropism, reasons for MRV use, MRV based therapy and change/end of MRV use were assessed. Paired analysis of lipid, hepatic and kidney profile changes and univariate and multivariate analyses of HIV-RNA<50 copies/mL at 48 weeks were explored. Results: We included 247 out of 667 subjects from the entire cohort. At study entry, their median age was 47 years, 23% were women, 31% MSM, 49% had CDC category C, median CD4+ counts were 468 cells/mm3, 46% were HCV+ and 4.5% AgHBs+. Tropism information was available in 197 (94% R5. Median length of prior ARTV was 10.7 years, with exposure to a median of three drug families. Main reasons for prescribing MRV were: toxicity 38%, inmunodiscordance 23%, simplification 19% and admission in a clinical trial 10.4%. MRV based therapies used were MRV+2NRTIs 9%, MRV+PI 46%, MRV+PI+other 40% and MRV+other 5%. At 48 weeks, 23% of patients had changed or finished MRV therapy due to toxicity 2.4%, virological failure 2%, immunological failure 1.2%, simplification 3,2%, trial requirement 9.7%, medical decision 2.8%, treatment suspension 1.2% and unknown 0.4%. At 48 weeks, no significant changes were observed in lipid, hepatic or kidney profiles, and 85% of patients remained with HIV-RNA<50 copies/mL. Focusing on viral response univariate and multivariate models did not show any significant baseline variable explaining viral failure. Conclusions: In clinical practice MRV was used, mostly in R5 positive

  1. Albuminuria Is Associated with Traditional Cardiovascular Risk Factors and Viral Load in HIV-Infected Patients in Rural South Africa.

    Directory of Open Access Journals (Sweden)

    G Emerens Wensink

    Full Text Available As life expectancy improves among Human Immunodeficiency Virus (HIV patients, renal and cardiovascular diseases are increasingly prevalent in this population. Renal and cardiovascular disease are mutual risk factors and are characterized by albuminuria. Understanding the interactions between HIV, cardiovascular risk factors and renal disease is the first step in tackling this new therapeutic frontier in HIV.In a rural primary health care centre, 903 HIV-infected adult patients were randomly selected and data on HIV-infection and cardiovascular risk factors were collected. Glomerular filtration rate (eGFR was estimated. Albuminuria was defined as an Albumin-Creatinine-Ratio above 30 mg/g. Multivariate logistic regression analysis was used to analyse albuminuria and demographic, clinical and HIV-associated variables.The study population consisted of 903 HIV-infected patients, with a median age of 40 years (Inter-Quartile Range (IQR 34-48 years, and included 625 (69% women. The median duration since HIV diagnosis was 26 months (IQR 12-58 months and 787 (87% received antiretroviral therapy. Thirty-six (4% of the subjects were shown to have diabetes and 205 (23% hypertension. In the cohort, 21% had albuminuria and 2% an eGFR <60 mL/min/1.73m2. Albuminuria was associated with hypertension (adjusted odds ratio (aOR 1.59; 95% confidence interval (CI 1.05-2.41; p<0.05, total cholesterol (aOR 1.31; 95% CI 1.11-1.54; p<0.05, eGFR (aOR 0.98; 95% CI 0.97-0.99; p<0.001 and detectable viral load (aOR 2.74; 95% CI 1.56-4.79; p<0.001. Hypertension was undertreated: 78% were not receiving treatment, while another 11% were inadequately treated. No patients were receiving lipid-lowering medication.Glomerular filtration rate was well conserved, while albuminuria was common amongst HIV-infected patients in rural South Africa. Both cardiovascular and HIV-specific variables were associated with albuminuria. Improved cardiovascular risk prevention as well as adequate

  2. The contribution of Ebola viral load at admission and other patient characteristics to mortality in a Médecins Sans Frontières (MSF) Ebola Case Management Centre (CMC), Kailahun, Sierra Leone, June -October, 2014.

    LENUS (Irish Health Repository)

    Fitzpatrick, Gabriel

    2015-05-22

    This paper describes patient characteristics, including Ebola viral load, associated with mortality in an MSF Ebola case management centre. Out of 780 admissions between June and October 2014, 525 (67%) were positive for Ebola with a known outcome. The crude mortality rate was 51% (270\\/525). Ebola viral load (whole blood sample) data was available on 76% (397\\/525) of patients. Univariate analysis indicated viral load at admission, age, symptom duration prior to admission and distance travelled to the CMC were associated with mortality (p value<0.05). The multivariable model predicted mortality in those with a viral load at admission greater than 10 million copies per millilitre (p value<0.05, Odds Ratio>10), aged 50 years or more (p value=0.08, Odds Ratio=2) and symptom duration prior to admission less than 5 days (p value=0.14). The presence of confusion, diarrhoea and conjunctivitis were significantly higher (p value<0.05) in Ebola patients who died. These findings highlight the importance viral load at admission has on mortality outcomes and could be used to cohort cases with viral loads greater than 10 million copies into dedicated wards with more intensive medical support to further reduce mortality.

  3. Effect of mild-to-moderate smoking on viral load, cytokines, oxidative stress, and cytochrome P450 enzymes in HIV-infected individuals.

    Directory of Open Access Journals (Sweden)

    Anusha Ande

    Full Text Available Mild-to-moderate tobacco smoking is highly prevalent in HIV-infected individuals, and is known to exacerbate HIV pathogenesis. The objective of this study was to determine the specific effects of mild-to-moderate smoking on viral load, cytokine production, and oxidative stress and cytochrome P450 (CYP pathways in HIV-infected individuals who have not yet received antiretroviral therapy (ART. Thirty-two human subjects were recruited and assigned to four different cohorts as follows: a HIV negative non-smokers, b HIV positive non-smokers, c HIV negative mild-to-moderate smokers, and d HIV positive mild-to-moderate smokers. Patients were recruited in Cameroon, Africa using strict selection criteria to exclude patients not yet eligible for ART and not receiving conventional or traditional medications. Those with active tuberculosis, hepatitis B or with a history of substance abuse were also excluded. Our results showed an increase in the viral load in the plasma of HIV positive patients who were mild-to-moderate smokers compared to individuals who did not smoke. Furthermore, although we did not observe significant changes in the levels of most pro-inflammatory cytokines, the cytokine IL-8 and MCP-1 showed a significant decrease in the plasma of HIV-infected patients and smokers compared with HIV negative non-smokers. Importantly, HIV-infected individuals and smokers showed a significant increase in oxidative stress compared with HIV negative non-smoker subjects in both plasma and monocytes. To examine the possible pathways involved in increased oxidative stress and viral load, we determined the mRNA levels of several antioxidant and cytochrome P450 enzymes in monocytes. The results showed that the levels of most antioxidants are unaltered, suggesting their inability to counter oxidative stress. While CYP2A6 was induced in smokers, CYP3A4 was induced in HIV and HIV positive smokers compared with HIV negative non-smokers. Overall, the findings suggest

  4. Longitudinal comparison between plasma and seminal HIV-1 viral loads during antiretroviral treatment Comparação longitudinal entre cargas virais seminais e plasmáticas do HIV-1 durante terapia anti-retroviral

    Directory of Open Access Journals (Sweden)

    Lauro Ferreira da Silva Pinto Neto

    2003-12-01

    Full Text Available This study was designed to investigate the impact of anti-retroviral therapy on both plasma and seminal HIV-1 viral loads and the correlation between viral loads in these compartments after treatment. Viral load, CD4+ and CD8+ T-cell counts were evaluated in paired plasma and semen samples from 36 antiretroviral therapy-naïve patients at baseline and on days 45, 90, and 180 of treatment. Slopes for blood and seminal viral loads in all treated patients were similar (p = 0.21. Median HIV-1 RNA titers in plasma and semen at baseline were 4.95 log10 and 4.48 log10 copies/ml, respectively. After 180 days of therapy, the median viral load declined to 3.15 log10 copies/ml (plasma and 3.2 log10 copies/ml (semen. At this timepoint 22 patients presented HIV-1 viral load below 400 copies/ml in either plasma or semen, but only 9 had viral loads below 400 copies/ml in both compartments.Este estudo foi desenhado para investigar o impacto do tratamento com anti-retrovirais na evolução das cargas virais plasmáticas e seminais do HIV-1. A carga viral do HIV-1 e a contagem de linfócitos T CD4+ e CD8+ foi determinada em amostras pareadas de sangue e sêmen de 36 pacientes virgem de tratamento nos dias 0, 45, 90 e 180 após o início da terapia. As curvas de declínio das cargas virais plasmática e seminal foram semelhantes (p= 0.21. As medianas da carga viral plasmática e seminal no pré-tratamento (dia 0 foram 4.95 e 4.48 log10 cópias/ml, respectivamente. Seis meses após o início da terapia, a mediana da carga viral plasmática era 3.15 log10 cópias/ml e a seminal 3.2 log10 cópias/ml. Neste mesmo periodo, 22 pacientes apresentavam carga viral abaixo de 400 cópias/ml no plasma e/ou sêmen, enquanto apenas 9 pacientes apresentavam carga viral abaixo do limite de detecção nos dois compartimentos.

  5. 前掠对高负荷风扇转子泄漏涡结构的影响%Numerically Investigating Effects of Highly-loaded and Forward-swept Fan Rotor on Tip Clearance Vortex

    Institute of Scientific and Technical Information of China (English)

    王雷; 刘波; 赵鹏程

    2012-01-01

    We numerically calculate the three-dimensional viscous flow field near the blade tip region at the near stall margin of a highly-loaded and forward-swept fan rotor. We compare the effects of the forward-swept fan rotor on the tip clearance vortex structure with those of a conventionally stacked radial rotor that has aerodynamically equal performance. The comparison results show that both the stall margin of the forward-swept fan rotor and the distribu- tion of its aerodynamic tip loading are improved. Our detailed analysis of its flow field reveals that the tip clearance vortex of the forward-swept fan rotor does not break under the near stall condition, thus providing a novel explanation why the tip clearance vortex structure of a forward-swept fan rotor is different from that of a conventional fan rotor.%以高负荷两级风扇第一级前掠转子为研究对象,通过数值模拟手段对近失速点叶尖流场进行了深入分析。为比较前掠对泄漏涡结构的影响,与同等气动性能下的常规转子进行了对比。结果表明前掠转子在近失速工况下泄漏涡涡心并未发生破碎,气动负荷展向分布更加均匀。对前掠转子不同于常规转子的叶尖泄漏涡结构产生机理提出了新的解释。

  6. HPV prophylactic vaccination in males improves the clearance of semen infection.

    Science.gov (United States)

    Foresta, Carlo; Garolla, Andrea; Parisi, Saverio; Ghezzi, Marco; Bertoldo, Alessandro; Di Nisio, Andrea; De Toni, Luca

    2015-10-01

    •We evaluated whether seroconversion in males influences HPV semen infection.•Naturally seroconverted patients showed reduced prevalence of HPV semen infection.•Naturally seroconverted patients also showed virtual absence of HPV multiple infection.•Prophylactic HPV vaccination induced clearance within 12 months from recruitment.•Seroconversion represents a key process involved in the clearance of the HPV.Available prophylactic vaccinations are considered of protective value for genital condyloma and precancerous lesions in female, but cost-effectiveness of the use of HPV vaccine in males is largely underinvestigated. HPV detection in semen is also an emerging problem in couples eligible for assisted reproduction techniques, since persistent infections are not compatible with repeated 6-months counselling-cycles to allow any spontaneous clearance of the virus in older infertile couples.In this study, we provide evidence that the development of seroconversion in human males affected by HPV infection in the genito-urinary tract, detected by HPV-DNA presence in the semen, has beneficial effects on the clearance of a viral load. Moreover, administration of prophylactic vaccination to HPV infected-seronegative patients induced seroconversion within 6 months from the first dosage administration, achieving 10 folds-higher antibody titre compared to natural seroconversion. If vaccine administration ameliorates the clearance of HPV semen infection, this could be a potential benefit to overcome fertility problems related to persistent HPV infections in males, after an obvious cost-effectiveness analysis.

  7. Generation of HIV-1 and Internal Control Transcripts as Standards for an In-House Quantitative Competitive RT-PCR Assay to Determine HIV-1 Viral Load

    Directory of Open Access Journals (Sweden)

    Anny Armas Cayarga

    2011-01-01

    Full Text Available Human immunodeficiency virus type-1 (HIV-1 viral load is useful for monitoring disease progression in HIV-infected individuals. We generated RNA standards of HIV-1 and internal control (IC by in vitro transcription and evaluated its performance in a quantitative reverse transcription polymerase chain reaction (qRT-PCR assay. HIV-1 and IC standards were obtained at high RNA concentrations, without DNA contamination. When these transcripts were included as standards in a qRT-PCR assay, it was obtained a good accuracy (±0.5 log10 unit of the expected results in the quantification of the HIV-1 RNA international standard and controls. The lower limit detection achieved using these standards was 511.0 IU/mL. A high correlation (=0.925 was obtained between the in-house qRT-PCR assay and the NucliSens easyQ HIV-1 test (bioMerieux for HIV-1 RNA quantitation with clinical samples (=14. HIV-1 and IC RNA transcripts, generated in this study, proved to be useful as standards in an in-house qRT-PCR assay for determination of HIV-1 viral load.

  8. PNPLA 3 I148M genetic variant associates with insulin resistance and baseline viral load in HCV genotype 2 but not in genotype 3 infection

    Directory of Open Access Journals (Sweden)

    Rembeck Karolina

    2012-09-01

    Full Text Available Abstract Background Hepatic steatosis in HCV patients has been postulated as a risk factor associated with a higher frequency of fibrosis and cirrhosis. A single genetic variant, PNPLA3 I148M, has been widely associated with increased hepatic steatosis. Previous studies of the PNPLA3 I148M sequence variant in HCV infected individuals have reported an association between this variant and prevalence of steatosis, fibrosis, and cirrhosis. To evaluate the impact of PNPLA3 I148M variant on metabolic traits and treatment response in HCV genotype 2 and 3 infected patients. Methods Three hundred and eighty-two treatment naïve HCV genotype 2 or 3 infected patients were included in a phase III, open label, randomized, multicenter, investigator-initiated trial (the NORDynamIC study, in which pretreatment liver biopsies were mandatory. PNPLA3I148M genotyping was performed in a total of 359 Caucasian patients. Results In HCV genotype 2 infected patients carrying the PNPLA3 148M allele, there was significantly increased insulin resistance (P = 0.023 and lower viral load (P = 0.005 at baseline as well as the first seven days of antiviral treatment. These results were not observed in HCV genotype 3 infected patients. Conclusions Our results suggest a possible association between the PNPLA3 148M allele and insulin resistance as well as baseline viral load in HCV genotype 2, but not in genotype 3.

  9. Protective efficacy of VP1-specific neutralizing antibody associated with a reduction of viral load and pro-inflammatory cytokines in human SCARB2-transgenic mice.

    Directory of Open Access Journals (Sweden)

    Hsuen-Wen Chang

    Full Text Available Hand-foot-mouth diseases (HFMD caused by enterovirus 71 (EV71 and coxsackievirus 16 (CVA16 in children have now become a severe public health issue in the Asian-Pacific region. Recently we have successfully developed transgenic mice expressing human scavenger receptor class B member 2 (hSCARB2, a receptor of EV71 and CVA16 as an animal model for evaluating the pathogenesis of enterovirus infections. In this study, hSCARB2-transgenic mice were used to investigate the efficacy conferred by a previously described EV71 neutralizing antibody, N3. A single injection of N3 effectively inhibited the HFMD-like skin scurfs in mice pre-infected with clinical isolate of EV71 E59 (B4 genotype or prevented severe limb paralysis and death in mice pre-inoculated with 5746 (C2 genotype. This protection was correlated with remarkable reduction of viral loads in the brain, spinal cord and limb muscles. Accumulated viral loads and the associated pro-inflammatory cytokines were all reduced. The protective efficacy of N3 was not observed in animals challenged with CVA16. This could be due to dissimilarity sequences of the neutralizing epitope found in CVA16. These results indicate N3 could be useful in treating severe EV71 infections and the hSCARB2-transgenic mouse could be used to evaluate the protective efficacy of potential anti-enterovirus agent candidates.

  10. The Contribution of Ebola Viral Load at Admission and Other Patient Characteristics to Mortality in a Médecins Sans Frontières Ebola Case Management Centre, Kailahun, Sierra Leone, June-October 2014.

    Science.gov (United States)

    Fitzpatrick, Gabriel; Vogt, Florian; Moi Gbabai, Osman B; Decroo, Tom; Keane, Marian; De Clerck, Hilde; Grolla, Allen; Brechard, Raphael; Stinson, Kathryn; Van Herp, Michel

    2015-12-01

    This paper describes patient characteristics, including Ebola viral load, associated with mortality in a Médecins Sans Frontières Ebola case management centre (CMC).Out of 780 admissions between June and October 2014, 525 (67%) were positive for Ebola with a known outcome. The crude mortality rate was 51% (270/525). Ebola viral load (whole-blood sample) data were available on 76% (397/525) of patients. Univariate analysis indicated viral load at admission, age, symptom duration prior to admission, and distance traveled to the CMC were associated with mortality (P 10), aged ≥ 50 years (P = .08, odds ratio = 2) and symptom duration prior to admission less than 5 days (P = .14). The presence of confusion, diarrhea, and conjunctivitis were significantly higher (P Ebola patients who died.These findings highlight the importance viral load at admission has on mortality outcomes and could be used to cohort cases with viral loads greater than 10 million copies into dedicated wards with more intensive medical support to further reduce mortality.

  11. Immunogenetics: Genome-Wide Association of Non-Progressive HIV and Viral Load Control: HLA Genes and Beyond

    OpenAIRE

    Limou, Sophie; Zagury, Jean-François

    2013-01-01

    Very early after the identification of the human immunodeficiency virus (HIV), host genetics factors were anticipated to play a role in viral control and disease progression. As early as the mid-1990s, candidate gene studies demonstrated a central role for the chemokine co-receptor/ligand (e.g., CCR5) and human leukocyte antigen (HLA) systems. In the last decade, the advent of genome-wide arrays opened a new era for unbiased genetic exploration of the genome and brought big expectations for t...

  12. Messenger RNA-based therapeutics for brain diseases: An animal study for augmenting clearance of beta-amyloid by intracerebral administration of neprilysin mRNA loaded in polyplex nanomicelles.

    Science.gov (United States)

    Lin, Chin-Yu; Perche, Federico; Ikegami, Masaru; Uchida, Satoshi; Kataoka, Kazunori; Itaka, Keiji

    2016-08-10

    Alzheimer's disease (AD) pathogenesis is considered to be the metabolic imbalance between anabolism and clearance of amyloid-beta (Aβ), and the strategy of breaking the equilibrium between soluble and insoluble forms of Aβ is likely to help prevent the progression of AD. Neprilysin (NEP) plays a major role in the clearance of Aβ in the brain, and its supplementation using viral vectors has shown to decrease Aβ deposition and prevent pathogenic changes in the brain. In this study, we developed a new therapeutic strategy by mRNA-based gene introduction. mRNA has the advantages of negligible risk of random integration into genome and not needing to be transcribed precludes the need for nuclear entry. This allows efficient protein expression in slowly-dividing or non-dividing cells, such as neural cells. We constructed mRNA encoding the mouse NEP protein and evaluated its ability degrade Aβ. In vitro transfection of NEP mRNA to primary neurons exhibited Amyloid Precursor Protein (APP) degradation activity superior to that of NEP encoding plasmid DNA. We then evaluated the in vivo activity of NEP mRNA by intracerebroventricular (i.c.v.) infusion using a cationic polymer-based PEGylated nanocarrier to form polyplex nanomicelles, which have been shown to have a high potential to deliver mRNA to various target tissues and organs. Nanomicelles carrying a GFP-NEP fusion mRNA produced efficient protein expression in a diffuse manner surrounding the ventricular space. An ELISA evaluation revealed that the mRNA infusion significantly augmented NEP level and effectively reduced the concentration of Aβ that had been supplemented in the mouse brain. To the best of our knowledge, this is the first study to demonstrate the therapeutic potential of introducing exogenous mRNA for the treatment of brain diseases, opening the new era of mRNA-based therapeutics. PMID:27282413

  13. Association of core promoter mutations of hepatitis B virus and viral load is different in HBeAg(+) and HBeAg(-) patients

    Institute of Scientific and Technical Information of China (English)

    Andi Utama; Benyamin Lukito; Tantoro Harmono; Nasrul Zubir; Julius; Soewignjo Soemohardjo; Laurentius Adrianus Lesmana; Ali Sulaiman; Susan Tai; Marlinang Diarta Siburian; Sigit Purwantomo; Mariana Destila Bayu Intan; Tri Shinta Kurniasih; Rino Alvani Gani; Wenny Astuti Achwan; Arnelis; Syafruddin AR Lelosutan

    2011-01-01

    AIM: To identify the prevalence of hepatitis B e antigen (HBeAg) and to assess the association of hepatitis B virus (HBV) core promoter mutations and viral load in Indonesian patients.METHODS: Sixty-four patients with chronic hepatitis,65 with liver cirrhosis and 50 with hepatocellular carcinoma were included in this study. HBeAg and hepatitis B e antibody (HBeAb) tests were performed using enzyme-linked immunosorbent assay and the mutations were analyzed by sequencing. Viral load was measured by real-time polymerase chain reaction.RESULTS: Of 179 patients, 108 (60.3%) were HBeAg(-) and 86 (79.6%) of these HBeAg(-) patients had been seroconverted. The A1896 mutation was not found in HBeAg(+) patients, however, this mutation was detected in 70.7% of HBeAg(-) patients. This mutation was frequently found when HBeAg was not expressed (87.7%), compared to that found in HBeAg seroconverted patients (65.1%). The A1899 mutation was also more prevalent in HBeAg(-) than in HBeAg(+) patients (P = 0.004). The T1762/A1764 mutation was frequently found in both HBeAg(+) and HBeAg(-) patients, however,the prevalence of this mutation did not significantly differ among the two groups (P = 0.054). In HBeAg(+)patients, the T1762/A1764 mutation was correlated with lower HBV DNA (P < 0.001). The A1899 mutation did not correlate with HBV DNA (P = 0.609). In HBeAg(-)patients, the T1762/A1764 mutation alone was not correlated with HBV DNA (P = 0.095), however, the presence of either the T1762/A1764 or A1896 mutations was associated with increased HBV DNA (P < 0.001).CONCLUSION: The percentage of HBeAg(-) patients is high in Indonesia, and most of the HBeAg(-) patients had been seroconverted. The A1896 mutation was most likely the major cause of HBeAg loss. The T1762/A1764 mutation alone was associated with lower viral loads in HBeAg(+) patients, but not in HBeAg(-) patients.

  14. Characterizing Class-Specific Exposure-Viral Load Suppression Response of HIV Antiretrovirals Using A Model-Based Meta-Analysis.

    Science.gov (United States)

    Xu, Y; Li, Y F; Zhang, D; Dockendorf, M; Tetteh, E; Rizk, M L; Grobler, J A; Lai, M-T; Gobburu, J; Ankrom, W

    2016-08-01

    We applied model-based meta-analysis of viral suppression as a function of drug exposure and in vitro potency for short-term monotherapy in human immunodeficiency virus type 1 (HIV-1)-infected treatment-naïve patients to set pharmacokinetic targets for development of nonnucleoside reverse transcriptase inhibitors (NNRTIs) and integrase strand transfer inhibitors (InSTIs). We developed class-specific models relating viral load kinetics from monotherapy studies to potency normalized steady-state trough plasma concentrations. These models were integrated with a literature assessment of doses which demonstrated to have long-term efficacy in combination therapy, in order to set steady-state trough concentration targets of 6.17- and 2.15-fold above potency for NNRTIs and InSTIs, respectively. Both the models developed and the pharmacokinetic targets derived can be used to guide compound selection during preclinical development and to predict the dose-response of new antiretrovirals to inform early clinical trial design. PMID:27171172

  15. Syphilis and HIV-1 co-infection: influence on CD4 T cell count, HIV-1 viral load and treatment response

    DEFF Research Database (Denmark)

    Kofoed, Kristian; Gerstoft, Jan; Mathiesen, Lars Reinhardt;

    2006-01-01

    OBJECTIVES: To assess the effect of human immunodeficiency virus (HIV)-1 and syphilis coinfection on HIV-ribonucleic acid (RNA) viral load, CD4 cell count, and the response in rapid plasmin reagin (RPR) to treatment of the syphilis infection. STUDY DESIGN: Cases of syphilis diagnosed during 1 year...... (mean 106 cells/mm, P = 0.03). Treatment of syphilis was associated with an increase in the CD4 cell count and a decrease in HIV-RNA in the overall group (mean 66 cells/mm and -0.261 RNA log10 copies/ml, P = 0.02 and 0.04). The serological response rates for 15 patients treated with penicillin and 25...

  16. Targeting of conserved gag-epitopes in early HIV infection is associated with lower plasma viral load and slower CD4+ T cell depletion

    DEFF Research Database (Denmark)

    Perez, Carina L.; Milush, Jeffrey M.; Buggert, Marcus;

    2013-01-01

    a significantly lower median viral load over time compared to patients with responses targeting a variable epitope (0.63 log10 difference). Furthermore, the rate of CD4+ T cell decline was slower for subjects targeting a conserved epitope (0.85% per month) compared to subjects targeting a variable epitope (1......We aimed to investigate whether the character of the immunodominant HIV-Gag peptide (variable or conserved) targeted by CD8+ T cells in early HIV infection would influence the quality and quantity of T cell responses, and whether this would affect the rate of disease progression. Treatment......-naive HIV-infected study subjects within the OPTIONS cohort at the University of California, San Francisco, were monitored from an estimated 44 days postinfection for up to 6 years. CD8+ T cells responses targeting HLA-matched HIV-Gag-epitopes were identified and characterized by multicolor flow cytometry...

  17. Prevalence and risk factors associated to chronic kidney disease in HIV-infected patients on HAART and undetectable viral load in Brazil.

    Directory of Open Access Journals (Sweden)

    Andréia M Menezes

    Full Text Available BACKGROUND: To determine the prevalence and associated factors with chronic kidney disease (CKD in a cohort of HIV-positive individuals with undetectable viral load on HAART. METHODS: From March, 2009 to September 2009, 213 individuals between 18-70 years, period on HAART ≥12 months, viral load < 50 copies/mm(3, and CD4 ≥ 200 cells/mm(3, were consecutively enrolled at the outpatient clinic of Hospital de Clínicas, Porto Alegre, Brazil. Exclusion criteria were obesity, malnourishment, amputee, paraplegic, previous history of renal disease, pregnancy and hepatic insufficiency. Renal function was determined by estimated glomerular filtration rate (eGFR assessed by the modification of diet in renal disease. CKD was defined as an eGFR less or equal than 60 ml/min/1.73 m(2, for a period of at least 3 months. Poisson regression was used to determine factors associated with CKD. RESULTS: CKD was diagnosed in 8.4% of the population, and after adjustment, the risk factors were hypertension (RR = 3.88, 95%CI, 1.84-8.16, time on HAART (RR = 1.15, 95%CI,1.03-1.27 and tenofovir exposure (RR = 2.25, 95%CI, 1.04-4.95. Higher weight (RR = 0.88 95%CI, 0.82-0.96 was associated to normal function. CONCLUSIONS: CKD was a common finding in this cohort of patients and was related to hypertension, time on HAART and tenofovir exposure. We suggest a more frequent monitoring of renal function, especially for those with risk factors to early identify renal impairment.

  18. Twelve-Month Antiretroviral Therapy Suppresses Plasma and Genital Viral Loads but Fails to Alter Genital Levels of Cytokines, in a Cohort of HIV-Infected Rwandan Women.

    Directory of Open Access Journals (Sweden)

    Pascale Ondoa

    Full Text Available Genital viral load (GVL is the main determinant of sexual transmission of human immune-deficiency virus (HIV. The effect of antiretroviral therapy (ART on local cervico-vaginal immunological factors associated with GVL is poorly described. We aimed to identify the risk factors of detectable GVL, and the impact of ART on HIV genital shedding and its correlates in a cohort of HIV-infected women, attending HIV care in Kigali, Rwanda.All participants were evaluated for GVL, plasma viral load (PVL, CD4 count, various sexually-transmitted infections (STIs at baseline and at month 12. Genital concentration of 19 cytokines and mRNA expression of APOBEC3G and BST2, two host HIV restriction factors, were evaluated at baseline in all participants. Cytokine levels were re-assessed at month 12 only in participants eligible for ART at baseline. Risk factors of GVL ≥ 40 copies/mL at baseline and month 12 were assessed using logistic regression. Effect of 12-month ART on various local and systemic immunological parameters was examined using a paired t-test and McNemar as appropriate.96 of the 247 women enrolled in the study were eligible for ART. After 12 months of ART, PVL and GVL decreased to undetectable level in respectively 74 and 88% of treated participants. ART did not affect cytokine levels. HIV genital shedding occurred only when PVL was detectable. At baseline, GVL was independently associated with IL-1β after controlling for PVL, age and N. gonorrhea infection (95% CI 1.32-2.15 and at month 12 with MIP-1β (95% CI 0.96-21.32 after controlling for baseline GVL, PVL and month 12 IL-8.Suppressive ART does not necessarily reduce genital level of immune activation. Minimizing all conditions favoring genital inflammation, including active detection and treatment of STIs, might reduce the risk of HIV transmission as supplement to the provision of potent ART.

  19. Evaluation of Two Techniques for Viral Load Monitoring Using Dried Blood Spot in Routine Practice in Vietnam (French National Agency for AIDS and Hepatitis Research 12338)

    Science.gov (United States)

    Taieb, Fabien; Tram, Tran Hong; Ho, Hien Thi; Pham, Van Anh; Nguyen, Lan; Pham, Ban Hien; Tong, Linh An; Tuaillon, Edouard; Delaporte, Eric; Nguyen, Anh Tuan; Bui, Duc Duong; Do, NhanThi; Madec, Yoann

    2016-01-01

    Background. Although it is the best method to detect early therapeutic failure, viral load (VL) monitoring is still not widely available in many resource-limited settings because of difficulties in specimen transfer, personnel shortage, and insufficient laboratory infrastructures. Dried blood spot (DBS) use, which was introduced in the latest World Health Organization recommendations, can overcome these difficulties. This evaluation aimed at validating VL measurement in DBS, in a laboratory without previous DBS experience and in routine testing conditions. Methods. Human immunodeficiency virus (HIV)-infected adults were observed in a HIV care site in Hanoi, and each patient provided 2 DBS cards with whole blood spots and 2 plasma samples. Viral load was measured in DBS and in plasma using the COBAS Ampliprep/TaqMan and the Abbott RealTime assays. To correctly identify those with VL ≥ 1000 copies/mL, sensitivity and specificity were estimated. Results. A total of 198 patients were enrolled. With the Roche technique, 51 plasma VL were ≥1000 copies/mL; among these, 28 presented a VL in DBS that was also ≥1000 copies/mL (sensitivity, 54.9; 95% confidence interval [CI], 40.3–68.9). On the other hand, all plasma VL CI, 97.5–100). With the Abbott technique, 45 plasma VL were ≥1000 copies/mL; among these, 42 VL in DBS were also ≥1000 copies/mL (sensitivity, 93.3%; 95% CI, 81.7–98.6); specificity was 94.8 (95% CI, 90.0–97.7). Conclusions. The Abbott RealTime polymerase chain reaction assay provided adequate VL results in DBS, thus allowing DBS use for VL monitoring.

  20. Interferon Alpha Induces Sustained Changes in NK Cell Responsiveness to Hepatitis B Viral Load Suppression In Vivo

    Science.gov (United States)

    Gill, Upkar S.; Peppa, Dimitra; Micco, Lorenzo; Singh, Harsimran D.; Carey, Ivana; Foster, Graham R.; Maini, Mala K.; Kennedy, Patrick T. F.

    2016-01-01

    NK cells are important antiviral effectors, highly enriched in the liver, with the potential to regulate immunopathogenesis in persistent viral infections. Here we examined whether changes in the NK pool are induced when patients with eAg-positive CHB are ‘primed’ with PegIFNα and importantly, whether these changes are sustained or further modulated long-term after switching to nucleos(t)ides (sequential NUC therapy), an approach currently tested in the clinic. Longitudinal sampling of a prospectively recruited cohort of patients with eAg+CHB showed that the cumulative expansion of CD56bright NK cells driven by 48-weeks of PegIFNα was maintained at higher than baseline levels throughout the subsequent 9 months of sequential NUCs. Unexpectedly, PegIFNα-expanded NK cells showed further augmentation in their expression of the activating NK cell receptors NKp30 and NKp46 during sequential NUCs. The expansion in proliferating, functional NK cells was more pronounced following sequential NUCs than in comparison cohorts of patients treated with de novo NUCs or PegIFNα only. Reduction in circulating HBsAg concentrations, a key goal in the path towards functional cure of CHB, was only achieved in those patients with enhancement of NK cell IFNγ and cytotoxicity but decrease in their expression of the death ligand TRAIL. In summary, we conclude that PegIFNα priming can expand a population of functional NK cells with an altered responsiveness to subsequent antiviral suppression by NUCs. Patients on sequential NUCs with a distinct NK cell profile show a decline in HBsAg, providing mechanistic insights for the further optimisation of treatment strategies to achieve sustained responses in CHB. PMID:27487232

  1. [Parameters of the CD4-Cell count and viral load in human immunodeficiency virus type 1 (HIV-1) infected patients].

    Science.gov (United States)

    Selimova, L M; Serebrovskaya, L V; Ivanova, L A; Kravchenko, A V; Buravtsova, E V

    2015-01-01

    In this work the specific features of parameters of plasma CD4 T-lymphocytes count and level virus RNA in the HIV-infected patients were studied. 22% correlation between reduction of CD4 cell count and an increase in virus RNA level was observed in persons that did not receive antiretroviral treatment during the third HIV-infection phase. During this phase of infection patients exhibited a growth of the median value of virus load in cases of both rise as decline in CD4 cell count during long observation period. In addition, towards the end of the observation period, the percentage of patients with virus load > 3.3 Ig copies/ml considerably expanded. 43% correlation between CD4 cell count and duration of the HIV-infection was detected during the fourth infection phase in persons that did not receive antiretroviral treatment. Most of the patients in the third and the fourth infection phases had essential CD4 cell count growth during antiretroviral treatment. Best values were observed in patients with the initial value of CD4 > 400 cells/μl belonging to the third HIV-infection phase.

  2. Virological profile of pregnant HIV positive women with high levels of CD4 count in low income settings: Can viral load help as eligibility criteria for maternal triple ARV prophylaxis (WHO 2010 option B?

    Directory of Open Access Journals (Sweden)

    Anne Esther Njom Nlend

    2011-10-01

    Full Text Available INTRODUCTION: The objective of the study was to determine HIV-1 RNA load profile during pregnancy and assess the eligibility for the maternal triple antiretroviral prophylaxis. It was an observational cohort of pregnant HIV positive women ignorant of antiretroviral therapy with CD4 cell count of > 350/mm3. METHODS:Routine CD4 cell count assessment in HIV positive pregnant women completed by non exclusive measurement of the viral load by PCR /ARN in those with CD4 cell count > 350/mm3. Exclusion criteria: highly active antiretroviral therapy prior to pregnancy. RESULTS:Between January and December 2010, CD4 cell count was systematically performed in all pregnant women diagnosed as HIV-infected (n=266 in a referral center of 25 antenatal clinics. 63% (N=170 had CD4 cell count > 350/mm3, median: 528 (IQR: 421-625. 145 underwent measurement of viral load by PCR/RNA at a median gestational of 23 weeks of pregnancy (IQR: 19-28. Median viral load 4.4log10/ml, IQR (3.5-4.9.19/145(13% had an undetectable viral load of=1.8log10/ml. 89/145(61% had a viral load of = 4 log10/ml and were eligible for maternal triple ARV prophylaxis. CONCLUSION: More than 6 in 10 pregnant HIV positive women with CD4 cell count of > 350/mm3 may require triple antiretroviral for prophylaxis of MTCT. Regardless of cost, such results are conclusive and may be considered in HIV high burden countries for universal access to triple antiretroviral prophylaxis in order to move towards virtual elimination of HIV MTCT.

  3. Viral load kinetics of Zika virus in plasma, urine and saliva in a couple returning from Martinique, French West Indies.

    Science.gov (United States)

    Fourcade, Camille; Mansuy, Jean-Michel; Dutertre, Marine; Delpech, Marie; Marchou, Bruno; Delobel, Pierre; Izopet, Jacques; Martin-Blondel, Guillaume

    2016-09-01

    While the rapid spread of Zika virus (ZIKV) in South America has been declared a public health emergency few data are available on the kinetics of the virus load and the specific antibodies in individual patients. This report describes the kinetics of ZIKV decay in the body compartments and the kinetics of anti ZIKV IgG and IgM of two people returning from Martinique, French West Indies. ZIKV remained detectable in the plasma for roughly 2 weeks indicating that mosquito control measures should be prolonged accordingly. Remarkably, their urine samples consistently tested positive for even longer. The antibodies responses were different between the two patients but for both the rapid onset of IgM allowed a diagnosis from the end of the first week. PMID:27389909

  4. Hepatitis C Virus Deletion Mutants Are Found in Individuals Chronically Infected with Genotype 1 Hepatitis C Virus in Association with Age, High Viral Load and Liver Inflammatory Activity.

    Directory of Open Access Journals (Sweden)

    Cristina Cheroni

    Full Text Available Hepatitis C virus (HCV variants characterized by genomic deletions in the structural protein region have been sporadically detected in liver and serum of hepatitis C patients. These defective genomes are capable of autonomous RNA replication and are packaged into infectious viral particles in cells co-infected with the wild-type virus. The prevalence of such forms in the chronically HCV-infected population and the impact on the severity of liver disease or treatment outcome are currently unknown. In order to determine the prevalence of HCV defective variants and to study their association with clinical characteristics, a screening campaign was performed on pre-therapy serum samples from a well-characterized cohort of previously untreated genotype 1 HCV-infected patients who received treatment with PEG-IFNα and RBV. 132 subjects were successfully analyzed for the presence of defective species exploiting a long-distance nested PCR assay. HCV forms with deletions predominantly affecting E1, E2 and p7 proteins were found in a surprising high fraction of the subjects (25/132, 19%. Their presence was associated with patient older age, higher viral load and increased necroinflammatory activity in the liver. While the presence of circulating HCV carrying deletions in the E1-p7 region did not appear to significantly influence sustained virological response rates to PEG-IFNα/RBV, our study indicates that the presence of these subgenomic HCV mutants could be associated with virological relapse in patients who did not have detectable viremia at the end of the treatment.

  5. Hepatitis C Virus Deletion Mutants Are Found in Individuals Chronically Infected with Genotype 1 Hepatitis C Virus in Association with Age, High Viral Load and Liver Inflammatory Activity.

    Science.gov (United States)

    Cheroni, Cristina; Donnici, Lorena; Aghemo, Alessio; Balistreri, Francesca; Bianco, Annalisa; Zanoni, Valeria; Pagani, Massimiliano; Soffredini, Roberta; D'Ambrosio, Roberta; Rumi, Maria Grazia; Colombo, Massimo; Abrignani, Sergio; Neddermann, Petra; De Francesco, Raffaele

    2015-01-01

    Hepatitis C virus (HCV) variants characterized by genomic deletions in the structural protein region have been sporadically detected in liver and serum of hepatitis C patients. These defective genomes are capable of autonomous RNA replication and are packaged into infectious viral particles in cells co-infected with the wild-type virus. The prevalence of such forms in the chronically HCV-infected population and the impact on the severity of liver disease or treatment outcome are currently unknown. In order to determine the prevalence of HCV defective variants and to study their association with clinical characteristics, a screening campaign was performed on pre-therapy serum samples from a well-characterized cohort of previously untreated genotype 1 HCV-infected patients who received treatment with PEG-IFNα and RBV. 132 subjects were successfully analyzed for the presence of defective species exploiting a long-distance nested PCR assay. HCV forms with deletions predominantly affecting E1, E2 and p7 proteins were found in a surprising high fraction of the subjects (25/132, 19%). Their presence was associated with patient older age, higher viral load and increased necroinflammatory activity in the liver. While the presence of circulating HCV carrying deletions in the E1-p7 region did not appear to significantly influence sustained virological response rates to PEG-IFNα/RBV, our study indicates that the presence of these subgenomic HCV mutants could be associated with virological relapse in patients who did not have detectable viremia at the end of the treatment.

  6. Relationships between IL-17(+ subsets, Tregs and pDCs that distinguish among SIV infected elite controllers, low, medium and high viral load rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Ladawan Khowawisetsut

    Full Text Available Comprehensive studies of the frequencies and absolute numbers of the various cell lineages that synthesize IL-17 in the blood and corresponding gastrointestinal (GI tissues, their correlation with CD4(+ Tregs, CD8(+ Tregs, total and IFN-α synthesizing plasmacytoid dendritic cells (pDC relative to plasma viral load in SIV infection has been lacking. The unique availability of SIV infected rhesus macaques (RM classified as Elite Controllers (EC, and those with Low, Intermediate and High Viral Loads (HVL provided a unique opportunity to address this issue. Results of these studies showed that EC demonstrated a remarkable ability to reverse changes that are induced acutely by SIV in the various cell lineages. Highlights of the differences between EC and HVL RM within Gastro-intestinal tissues (GIT was the maintenance and/or increases in the levels of IL-17 synthesizing CD4, CD8, and NK cells and pDCs associated with slight decreases in the levels of CD4(+ Tregs and IFN-α synthesizing pDCs in EC as compared with decreases in the levels of IL-17 synthesizing CD4, CD8 and NK cells associated with increases in pDCs and IFN-α synthesizing pDCs in HVL monkeys. A previously underappreciated role for CD8(+ Tregs was also noted with a moderate increase in ECs but further increases of CD8(+ Tregs with increasing VL in viremic monkeys. Positive correlations between plasma VL and decreases in the levels of Th17, Tc17, NK-17, CD4(+ Tregs and increases in the levels of CD8(+ Tregs, total and IFN-α synthesizing pDCs were also noted. This study also identified 2 additional IL-17(+ subsets in GIT as CD3(-/CD8(+/NKG2a(- and CD3(+/CD8(+/NKG2a(+ subsets. Studies also suggest a limited role for IFN-α synthesizing pDCs in chronic immune activation despite persistent up-regulation of ISGs. Finally, elevated persistent innate immune responses appear associated with poor prognosis. These findings provide an initial foundation for markers important to follow for vaccine

  7. Relationships between IL-17(+) subsets, Tregs and pDCs that distinguish among SIV infected elite controllers, low, medium and high viral load rhesus macaques.

    Science.gov (United States)

    Khowawisetsut, Ladawan; Pattanapanyasat, Kovit; Onlamoon, Nattawat; Mayne, Ann E; Little, Dawn M; Villinger, Francois; Ansari, Aftab A

    2013-01-01

    Comprehensive studies of the frequencies and absolute numbers of the various cell lineages that synthesize IL-17 in the blood and corresponding gastrointestinal (GI) tissues, their correlation with CD4(+) Tregs, CD8(+) Tregs, total and IFN-α synthesizing plasmacytoid dendritic cells (pDC) relative to plasma viral load in SIV infection has been lacking. The unique availability of SIV infected rhesus macaques (RM) classified as Elite Controllers (EC), and those with Low, Intermediate and High Viral Loads (HVL) provided a unique opportunity to address this issue. Results of these studies showed that EC demonstrated a remarkable ability to reverse changes that are induced acutely by SIV in the various cell lineages. Highlights of the differences between EC and HVL RM within Gastro-intestinal tissues (GIT) was the maintenance and/or increases in the levels of IL-17 synthesizing CD4, CD8, and NK cells and pDCs associated with slight decreases in the levels of CD4(+) Tregs and IFN-α synthesizing pDCs in EC as compared with decreases in the levels of IL-17 synthesizing CD4, CD8 and NK cells associated with increases in pDCs and IFN-α synthesizing pDCs in HVL monkeys. A previously underappreciated role for CD8(+) Tregs was also noted with a moderate increase in ECs but further increases of CD8(+) Tregs with increasing VL in viremic monkeys. Positive correlations between plasma VL and decreases in the levels of Th17, Tc17, NK-17, CD4(+) Tregs and increases in the levels of CD8(+) Tregs, total and IFN-α synthesizing pDCs were also noted. This study also identified 2 additional IL-17(+) subsets in GIT as CD3(-/)CD8(+)/NKG2a(-) and CD3(+)/CD8(+)/NKG2a(+) subsets. Studies also suggest a limited role for IFN-α synthesizing pDCs in chronic immune activation despite persistent up-regulation of ISGs. Finally, elevated persistent innate immune responses appear associated with poor prognosis. These findings provide an initial foundation for markers important to follow for vaccine

  8. Relationship of peripheral blood T cell subset levels and PD-1/PD-L1 expression levels with viral load in patients with asymptomatic HIV infection

    Institute of Scientific and Technical Information of China (English)

    Xi-Li Miao; Si-Qing Mei; Gui-Min Gao

    2016-01-01

    Objective:To study the relationship of different T cell subset levels and PD-1/PD-L1 expression levels in peripheral blood with viral load in patients with asymptomatic HIV infection.Methods:Patients with asymptomatic HIV infection treated in our hospital from April 2012 to October 2015 were selected as the HIV group of the study, healthy subjects during the same period were selected as the control group, and peripheral blood was collected to detect CD3+CD4+CD8-, CD3+CD4-CD8+, CD4+CD25+Foxp3+ and CD4+CD25+CD127low/-cell levels as well as PD-1/PD-L1 expression levels.Results:The number and percentage of CD3+CD4+CD8- cells as well as the number of CD4+CD25+Foxp3+ and CD4+CD25+CD127low/-cells in peripheral blood of HIV group were significantly lower than those of control group, the number and percentage of CD3+CD4-CD8+ cells, the percentage of CD4+CD25+Foxp3+and CD4+CD25+CD127low/- cells as well as the expression levels of PD-L1 and PD-1 on CD4+T cell surface were significantly higher than those of control group, and the expression levels of PD-L1 and PD-1 on CD8+T cell surface were not significantly different from those of control group; the greater the viral load in HIV group, the lower the percentage of CD3+CD4+CD8-, and the higher the percentage of CD3+CD4-CD8+, CD4+CD25+Foxp3+ and CD4+CD25+CD127low/-cells as well the PD-1/PD-L1 positive percentage on CD4+T cell surface in peripheral blood. Conclusions:The immune characteristics of patients with asymptomatic HIV infection are the decreased number of CD4+T cells and the increased number of CD8+T cells as well as the decreased absolute content and increased relative content of CD4+CD25+Treg cells, and PD-1/PD-L1 pathway is the molecular mechanism of HIV to act on CD4+T cells.

  9. Switching HIV treatment in adults based on CD4 count versus viral load monitoring: a randomized, non-inferiority trial in Thailand.

    Directory of Open Access Journals (Sweden)

    Gonzague Jourdain

    2013-08-01

    Full Text Available BACKGROUND: Viral load (VL is recommended for monitoring the response to highly active antiretroviral therapy (HAART but is not routinely available in most low- and middle-income countries. The purpose of the study was to determine whether a CD4-based monitoring and switching strategy would provide a similar clinical outcome compared to the standard VL-based strategy in Thailand. METHODS AND FINDINGS: The Programs for HIV Prevention and Treatment (PHPT-3 non-inferiority randomized clinical trial compared a treatment switching strategy based on CD4-only (CD4 monitoring versus viral-load (VL. Consenting participants were antiretroviral-naïve HIV-infected adults (CD4 count 50-250/mm(3 initiating non-nucleotide reverse transcriptase inhibitor (NNRTI-based therapy. Randomization, stratified by site (21 public hospitals, was performed centrally after enrollment. Clinicians were unaware of the VL values of patients randomized to the CD4 arm. Participants switched to second-line combination with confirmed CD4 decline >30% from peak (within 200 cells from baseline in the CD4 arm, or confirmed VL >400 copies/ml in the VL arm. Primary endpoint was clinical failure at 3 years, defined as death, new AIDS-defining event, or CD4 400 copies/ml at switch was 7.2 months (5.8-8.0 in VL versus 15.8 months (8.5-20.4 in CD4 (p=0.002. FDO scores were not significantly different at time of switch. No adverse events related to the monitoring strategy were reported. CONCLUSIONS: The 3-year rates of clinical failure and loss of treatment options did not differ between strategies although the longer-term consequences of CD4 monitoring would need to be investigated. These results provide reassurance to treatment programs currently based on CD4 monitoring as VL measurement becomes more affordable and feasible in resource-limited settings. TRIAL REGISTRATION: ClinicalTrials.govNCT00162682 Please see later in the article for the Editors' Summary.

  10. Security Clearance Tracking System

    Data.gov (United States)

    National Archives and Records Administration — SCTS supports the adjudication process of private background investigations and clearances for potential employees, contractors, interns and student workers.

  11. Complement lysis activity in autologous plasma is associated with lower viral loads during the acute phase of HIV-1 infection.

    Directory of Open Access Journals (Sweden)

    Michael Huber

    2006-11-01

    Full Text Available BACKGROUND: To explore the possibility that antibody-mediated complement lysis contributes to viremia control in HIV-1 infection, we measured the activity of patient plasma in mediating complement lysis of autologous primary virus. METHODS AND FINDINGS: Sera from two groups of patients-25 with acute HIV-1 infection and 31 with chronic infection-were used in this study. We developed a novel real-time PCR-based assay strategy that allows reliable and sensitive quantification of virus lysis by complement. Plasma derived at the time of virus isolation induced complement lysis of the autologous virus isolate in the majority of patients. Overall lysis activity against the autologous virus and the heterologous primary virus strain JR-FL was higher at chronic disease stages than during the acute phase. Most strikingly, we found that plasma virus load levels during the acute but not the chronic infection phase correlated inversely with the autologous complement lysis activity. Antibody reactivity to the envelope (Env proteins gp120 and gp41 were positively correlated with the lysis activity against JR-FL, indicating that anti-Env responses mediated complement lysis. Neutralization and complement lysis activity against autologous viruses were not associated, suggesting that complement lysis is predominantly caused by non-neutralizing antibodies. CONCLUSIONS: Collectively our data provide evidence that antibody-mediated complement virion lysis develops rapidly and is effective early in the course of infection; thus it should be considered a parameter that, in concert with other immune functions, steers viremia control in vivo.

  12. 孔式抽吸对带间隙高负荷压气机性能的影响%Effects of Holes-Type Suction on Performance in a High-Load Compressor with a Clearance

    Institute of Scientific and Technical Information of China (English)

    孙士珺; 陈绍文; 王春雪; 王松涛

    2014-01-01

    实验研究了端壁孔式附面层抽吸对带间隙的高负荷直列叶栅流动特性和气动性能的影响,通过三种附面层抽吸方案与原型方案的对比分析,探讨了附面层抽吸抑制间隙流动、减小损失的机理。对叶片表面和下端壁进行了墨迹流动显示,并利用五孔探针对叶栅出口气动参数进行了测量,对比分析了叶栅流道内的流场特征和损失分布。结果表明,在间隙内布置抽吸孔能有效降低间隙流动动能,削弱间隙流与主流之间的相互掺混作用,减小因间隙流动引起的端壁区域流动分离,从而达到对三维流动分离的抑制,有效降低损失,且最大降幅达16.7%;间隙流动引起的流动分离和损失在流道中占主导地位,尽管在端壁沿周向合理布置抽吸孔能在一定程度上抑制近端壁的附面层或二次流发展,但这种局部效应仍不能显著改善叶栅的整体性能;端壁上不合理的抽吸控制策略反而可能影响主流的正常流动,导致损失增加,其中方案4损失增加了约3%。%The effects of endwall-hole-type boundary layer suction on the airfoil flow characteristic and aerodynamic performance in a highly loaded compressor linear cascade with a clearance was studied experimen-tally. Through a comparative analysis of three different suction schemes and the prototype scheme , the mecha-nism of boundary layer suction inhibiting the clearance flow,reducing the loss was discussed. The ink-trace flow visualization on the airfoil surface and the lower end-wall was carried out and the parameters at outlet were mea-sured by a five-hole probe to comparatively analyze a distribution of the loss and the flow characteristics. The re-sults show that the suction can effectively reduce the kinetic energy of the clearance flow so as to reduce the blending effect between the clearance flow and the main stream and weaken the flow separation induced by clear-ance on

  13. Restoration of Innate and Adaptive Immune Responses by HCV Viral Inhibition with an Induction Approach Using Natural Interferon-Beta in Chronic Hepatitis C

    Directory of Open Access Journals (Sweden)

    Y. Kishida

    2012-01-01

    Full Text Available Chronic hepatitis C (CHC is a serious medical problem necessitating more effective treatment. This study investigated the hypothesis that an induction approach with nIFN-beta for 24 weeks followed by PEG-IFN-alpha+ribavirin (standard of care: SOC for 48 weeks (novel combination treatment: NCT would increase the initial virologic response rate and restore innate and adaptive immune responses in CHC. Seven CHC patients with a high viral load and genotype 1b were treated with NCT. Serum cytokine and chemokine levels were evaluated during NCT. NCT prevented viral escape and breakthrough resulting in persistent viral clearance of HCVRNA. IL-15 was increased at the end of induction therapy in both early virologic responders (EAVRs and late virologic responders (LAVRs; CXCL-8, CXCL-10, and CCL-4 levels were significantly decreased (<0.05 in EAVR but not in LAVR during NCT, and IL-12 increased significantly (<0.05 and CXCL-8 decreased significantly (<0.05 after the end of NCT in EAVR but not in LAVR. NCT prevented viral breakthrough with viral clearance leading to improvement of innate and adaptive immunity resulting in a sustained virologic response (SVR. NCT (=8 achieved a higher SVR rate than SOC (=8 in difficult-to-treat CHC patients with genotype 1 and high viral loads.

  14. Analysis of virological efficacy in trials of antiretroviral regimens: drawbacks of not including viral load measurements after premature discontinuation of therapy

    DEFF Research Database (Denmark)

    Kirk, Ole; Pedersen, Court; Law, Matthew;

    2002-01-01

    OBJECTIVES: To compare two analytic approaches to assess the virological effect of HAART according to the intention-to-treat (ITT) principle. MATERIAL: Data from 2318 patients enrolled in 10 randomised clinical trials (RCTs) and from 3091 patients followed in an observation cohort (EuroSIDA) star......OBJECTIVES: To compare two analytic approaches to assess the virological effect of HAART according to the intention-to-treat (ITT) principle. MATERIAL: Data from 2318 patients enrolled in 10 randomised clinical trials (RCTs) and from 3091 patients followed in an observation cohort (Euro......SIDA) starting their first HAART regimen. METHODS: Two classifications of defining virological response 48 weeks after starting the therapy to be evaluated were compared: 1) only patients remaining on the therapy and having a plasma viral load (pVL) below a given cut-off level at week 48 were classified as...... to ITT/s=f, 22-70% of the patients starting a HAART regimen in a RCT experienced a virological response at week 48. Only two RCTs had complete follow-up data (n=424): between 29 and 62% achieved a virological response at week 48 in the six treatment arms evaluated in the studies according to ITT...

  15. 母乳喂养对婴儿唾液巨细胞病毒载量的影响%Effect of breastfeeding on infant cytomegalovirus viral load

    Institute of Scientific and Technical Information of China (English)

    张琳; 王淮燕; 梅涛; 杨利民; 史烨; 虞斌

    2014-01-01

    目的 对先天性巨细胞病毒(CMV)感染的新生儿进行随访监测,探讨母乳喂养对CMV载量变化的影响.方法 采集2010年11月至2012年2月在常州市妇幼保健院山生的新生儿唾液进行CMV感染筛查,排除早产、严重感染性疾病或畸形等,对阳性感染且.无症状的足月新生儿根据母亲自主选择分成人工喂养组及母乳喂养组,随访至6个月,分别在出生1个月内、3个月、6个月采集唾液及母乳,采取实时荧光定量PCR法检测CMV-DNA的载量变化,同时行体格检查、头颅B超检查、耳声发射听力筛查、肝功能、血常规分析等检查.结果 30例婴儿在随访的6个月中均末发现有CMV感染性疾病的表现.人工喂养组与母乳喂养组婴儿在出生1个月内、3个月、6个月唾液巨细胞DNA载量末见明显变化(t=2.832、3.161、3.475,P均>0.05).母乳喂养组乳汁在山生1个月内、3个月、6个月CMV-DNA载量分别为3.125×103±2.017×102、2.688×103±2.251×102、3.016×103 ±2.613×102,三者比较差异无统计学意义(F=1.725,P=0.667).头颅B超检查、耳声发射听力筛查、肝功能、血常规分析等检查末见明显异常.结论 CMV感染的足月无症状新生儿,即便母乳中CMV 阳性,继续母乳喂养后婴儿体内的病毒载量也不会增加,也末发现继发性的症状感染.%Objective Follow-up monitoring was carried out in infants infected with cytomegalovirus (CMV) so as to find out whether breastfeeding could bring about changes of CMV viral load.Methods Saliva of the neonates born in Changzhou Maternal and Child Health Hospital from Nov.2010 to Feb.2012,was collected for CMV screening.Premature infants,or the infants with seriously infectious diseases and deformities were excluded,such as severe intrauterine infection,congenital immune deficiency disease and so on.The full-term infants with aymptomatic infection were divided into the artificial feeding group and the breastfeeding group

  16. Joint longitudinal hurdle and time-to-event models: an application related to viral load and duration of the first treatment regimen in patients with HIV initiating therapy.

    Science.gov (United States)

    Brilleman, Samuel L; Crowther, Michael J; May, Margaret T; Gompels, Mark; Abrams, Keith R

    2016-09-10

    Shared parameter joint models provide a framework under which a longitudinal response and a time to event can be modelled simultaneously. A common assumption in shared parameter joint models has been to assume that the longitudinal response is normally distributed. In this paper, we instead propose a joint model that incorporates a two-part 'hurdle' model for the longitudinal response, motivated in part by longitudinal response data that is subject to a detection limit. The first part of the hurdle model estimates the probability that the longitudinal response is observed above the detection limit, whilst the second part of the hurdle model estimates the mean of the response conditional on having exceeded the detection limit. The time-to-event outcome is modelled using a parametric proportional hazards model, assuming a Weibull baseline hazard. We propose a novel association structure whereby the current hazard of the event is assumed to be associated with the current combined (expected) outcome from the two parts of the hurdle model. We estimate our joint model under a Bayesian framework and provide code for fitting the model using the Bayesian software Stan. We use our model to estimate the association between HIV RNA viral load, which is subject to a lower detection limit, and the hazard of stopping or modifying treatment in patients with HIV initiating antiretroviral therapy. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27027882

  17. Residual viraemia in HIV-1-infected patients with plasma viral load

    DEFF Research Database (Denmark)

    Ostrowski, S R; Katzenstein, T L; Pedersen, B K;

    2008-01-01

    Despite undetectable viral load in conventional assays, probably all human immunodeficiency virus (HIV)-1 infected patients have residual viraemia (RV) detectable by ultra-sensitive assays. To study this issue, this study investigated virologic and immunologic consequences of RV in highly active...... antiretroviral therapy (HAART)-treated HIV-1-infected patients with plasma HIV-1 RNA or=1 episode with TMA-RV whereas 9 patients had undetectable TMA-RV throughout the study-period. Time-points with TMA-RV and PCR-RV were associated with higher circulating sTNFrII (+0.234 ng/ml, P = 0.030) and beta(2......)-microglobulin (+22 nmol/l, P = 0.016) and time-points with PCR-RV were also associated with higher IgA (+0.82 micromol/l, P = 0.035) and CD8-count (+1.18-fold, P = 0.001). Patients with TMA-RV in the study-period had higher HIV-1 RNA pre-HAART (P = 0.032). RV was not associated with proviral-HIV-1-DNA, CD4...

  18. Joint longitudinal hurdle and time-to-event models: an application related to viral load and duration of the first treatment regimen in patients with HIV initiating therapy.

    Science.gov (United States)

    Brilleman, Samuel L; Crowther, Michael J; May, Margaret T; Gompels, Mark; Abrams, Keith R

    2016-09-10

    Shared parameter joint models provide a framework under which a longitudinal response and a time to event can be modelled simultaneously. A common assumption in shared parameter joint models has been to assume that the longitudinal response is normally distributed. In this paper, we instead propose a joint model that incorporates a two-part 'hurdle' model for the longitudinal response, motivated in part by longitudinal response data that is subject to a detection limit. The first part of the hurdle model estimates the probability that the longitudinal response is observed above the detection limit, whilst the second part of the hurdle model estimates the mean of the response conditional on having exceeded the detection limit. The time-to-event outcome is modelled using a parametric proportional hazards model, assuming a Weibull baseline hazard. We propose a novel association structure whereby the current hazard of the event is assumed to be associated with the current combined (expected) outcome from the two parts of the hurdle model. We estimate our joint model under a Bayesian framework and provide code for fitting the model using the Bayesian software Stan. We use our model to estimate the association between HIV RNA viral load, which is subject to a lower detection limit, and the hazard of stopping or modifying treatment in patients with HIV initiating antiretroviral therapy. Copyright © 2016 John Wiley & Sons, Ltd.

  19. Avaliação de ensaio molecular para determinação de carga viral em indivíduos sorologicamente negativos para o HIV-1 Evaluation of a molecular assay for determining viral load on HIV-1 antibody negative patients

    Directory of Open Access Journals (Sweden)

    José Moreira Pereira

    2002-01-01

    Full Text Available O teste de carga viral foi concebido para acompanhar a evolução e o tratamento do paciente com diagnóstico confirmado de HIV-1. Contudo, sua especificidade diagnóstica não foi ainda avaliada em pessoas que apresentam um teste sorológico negativo. Mesmo assim, ele tem sido erroneamente utilizado para o diagnóstico da infecção primária pelo HIV-1. Este trabalho relata quatro pacientes em que a carga viral plasmática NucliSens (Organon Teknika foi repetidamente positiva na ausência de anticorpos para HIV e chama atenção para o fato de que a carga viral abaixo de 10 mil cópias/ml é de difícil interpretação, como tem sido assinalado em numerosos artigos, em que foram utilizadas outras metodologias.The plasma viral load test for HIV-1,a exquisitely high sensitive assay, were neither developed nor evaluated for the diagnosis of primary HIV infection; therefore, their diagnostic specificity is not well delineated when applied to persons who are negative for HIV antibody. This article reported four cases of false positive results obtained by using NucliSens viral load assay (Organon Teknika and emphasize the importance that low positive plasma viral load (< 10 000 copies/ml may be difficult to interpret how has been assinalated in numerous articles in the medical literature, using other methodologies.

  20. A novel, Q-PCR based approach to measuring endogenous retroviral clearance by capture protein A chromatography.

    Science.gov (United States)

    Zhang, Min; Lute, Scott; Norling, Lenore; Hong, Connie; Safta, Aurelia; O'Connor, Deborah; Bernstein, Lisa J; Wang, Hua; Blank, Greg; Brorson, Kurt; Chen, Qi

    2009-04-01

    Quantification of virus removal by the purification process during production is required for clinical use of biopharmaceuticals. The current validation approach for virus removal by chromatography steps typically involves time-consuming spiking experiments with expensive model viruses at bench scale. Here we propose a novel, alternative approach that can be applied in at least one instance: evaluating retroviral clearance by protein A chromatography. Our strategy uses a quantitative PCR (Q-PCR) assay that quantifies the endogenous type C retrovirus-like particle genomes directly in production Chinese Hamster Ovary (CHO) cell culture harvests and protein A pools. This eliminates the need to perform spiking with model viruses, and measures the real virus from the process. Using this new approach, clearance values were obtained that was comparable to those from the old model-virus spike/removal approach. We tested the concept of design space for CHO retrovirus removal using samples from a protein A characterization study, where a wide range of chromatographic operating conditions were challenged, including load density, flow rate, wash, pooling, temperature, and resin life cycles. Little impact of these variables on CHO retrovirus clearance was found, arguing for implementation of the design space approach for viral clearance to support operational ranges and manufacturing excursions. The viral clearance results from Q-PCR were confirmed by an orthogonal quantitative product-enhanced reverse transcriptase (Q-PERT) assay that quantifies CHO retrovirus by their reverse transcriptase (RT) enzyme activity. Overall, our results demonstrate that protein A chromatography is a robust retrovirus removal step and CHO retrovirus removal can be directly measured at large scale using Q-PCR assays.

  1. 14 CFR 29.411 - Ground clearance: tail rotor guard.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Ground clearance: tail rotor guard. 29.411... System Loads § 29.411 Ground clearance: tail rotor guard. (a) It must be impossible for the tail rotor to contact the landing surface during a normal landing. (b) If a tail rotor guard is required to...

  2. 14 CFR 27.411 - Ground clearance: tail rotor guard.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Ground clearance: tail rotor guard. 27.411... System Loads § 27.411 Ground clearance: tail rotor guard. (a) It must be impossible for the tail rotor to contact the landing surface during a normal landing. (b) If a tail rotor guard is required to...

  3. Viral encephalitis

    Directory of Open Access Journals (Sweden)

    Marcus Tulius T Silva

    2013-09-01

    Full Text Available While systemic viral infections are exceptionally common, symptomatic viral infections of the brain parenchyma itself are very rare, but a serious neurologic condition. It is estimated that viral encephalitis occurs at a rate of 1.4 cases per 100.000 inhabitants. Geography is a major determinant of encephalitis caused by vector-borne pathogens. A diagnosis of viral encephalitis could be a challenge to the clinician, since almost 70% of viral encephalitis cases are left without an etiologic agent identified. In this review, the most common viral encephalitis will be discussed, with focus on ecology, diagnosis, and clinical management.

  4. Clinical Impact of Viral Load on the Development of Hepatocellular Carcinoma and Liver-Related Mortality in Patients with Hepatitis C Virus Infection

    Science.gov (United States)

    Noh, Ran; Lee, Doo Hyuck; Kwon, Byoung Woon; Kim, Yong Hyun

    2016-01-01

    Aim. This study aimed to assess clinical impact of hepatitis C viral load on the development of hepatocellular carcinoma (HCC) and liver-related mortality in HCV-infected patients. Methods. A total of 111 subjects with chronic HCV infection who were available for serum quantitation of HCV RNA were recruited in this retrospective cohort. Cox-proportional hazards models were used to calculate hazard ratio (HR) of developing HCC and liver-related mortality according to serum HCV RNA titers. Results. HCC was developed in 14 patients during follow-up period. The cumulative risk of HCC development was higher in subjects with high HCV RNA titer (log HCV RNA IU/mL > 6) than subjects with low titer (log HCV RNA IU/mL ≦ 6) (HR = 4.63, P = 0.032), giving an incidence rate of 474.1 and 111.5 per 10,000 person-years, respectively. Old age (HR = 9.71, P = 0.014), accompanying cirrhosis (HR = 19.34, P = 0.004), and low platelet count (HR = 13.97, P = 0.009) were other independent risk factors for the development of HCC. Liver-related death occurred in 7 patients. Accompanying cirrhosis (HR = 6.13, P = 0.012) and low albumin level (HR = 9.17, P = 0.002), but not HCV RNA titer, were significant risk factors related to liver-related mortality. Conclusion. Serum HCV RNA titer may be considered an independent risk factor for the development of HCC but not liver-related mortality. PMID:27656205

  5. Positive Predictive Value of the WHO Clinical and Immunologic Criteria to Predict Viral Load Failure among Adults on First, or Second-Line Antiretroviral Therapy in Kenya

    Science.gov (United States)

    Muttai, Hellen; Ng’ang’a, Lucy; Ackers, Marta; Kim, Andrea; Miruka, Fredrick; Erick, Opiyo; Okonji, Julie; Ayuaya, Tolbert; Schwarcz, Sandra

    2016-01-01

    Routine HIV viral load (VL) monitoring is the standard of care for persons receiving antiretroviral therapy (ART) in developed countries. Although the World Health Organization recommends annual VL monitoring of patients on ART, recognizing difficulties in conducting routine VL testing, the WHO continues to recommend targeted VL testing to confirm treatment failure for persons who meet selected immunologic and clinical criteria. Studies have measured positive predictive value (PPV), negative predictive value, sensitivity and specificity of these criteria among patients receiving first-line ART but not specifically among those on second-line or subsequent regimens. Between 2008 and 2011, adult ART patients in Nyanza, Kenya who met national clinical or immunologic criteria for treatment failure received targeted VL testing. We calculated PPV and 95% confidence intervals (CI) of these criteria to detect virologic treatment failure among patients receiving a) first-line ART, b) second/subsequent ART, and c) any regimen. Of 12,134 patient specimens tested, 2,874 (23.7%) were virologically confirmed as treatment failures. The PPV for 2,834 first-line ART patients who met either the clinical or immunologic criteria for treatment failure was 34.4% (95% CI 33.2–35.7), 33.1% (95% CI 24.7–42.3) for the 40 patients on second-line/subsequent regimens, and 33.4% (95% CI 33.1–35.6) for any ART. PPV, regardless of criteria, for first-line ART patients was lowest among patients over 44 years old and highest for patients aged 15 to 34 years. PPV of immunological and clinical criteria for correctly identifying treatment failure was similarly low for adult patients receiving either first-line or second-line/subsequent ART regimens. Our data confirm the inadequacy of clinical and immunologic criteria to correctly identify treatment failure and support the implementation of routine VL testing. PMID:27383834

  6. B cell depletion in HIV-1 subtype A infected Ugandan adults: relationship to CD4 T cell count, viral load and humoral immune responses.

    Directory of Open Access Journals (Sweden)

    Peter Oballah

    Full Text Available To better understand the nature of B cell dysfunctions in subjects infected with HIV-1 subtype A, a rural cohort of 50 treatment-naïve Ugandan patients chronically infected with HIV-1 subtype A was studied, and the relationship between B cell depletion and HIV disease was assessed. B cell absolute counts were found to be significantly lower in HIV-1+ patients, when compared to community matched negative controls (p<0.0001. HIV-1-infected patients displayed variable functional and binding antibody titers that showed no correlation with viral load or CD4+ T cell count. However, B cell absolute counts were found to correlate inversely with neutralizing antibody (NAb titers against subtype A (p = 0.05 and subtype CRF02_AG (p = 0.02 viruses. A positive correlation was observed between subtype A gp120 binding antibody titers and NAb breadth (p = 0.02 and mean titer against the 10 viruses (p = 0.0002. In addition, HIV-1 subtype A sera showed preferential neutralization of the 5 subtype A or CRF02_AG pseudoviruses, as compared with 5 pseudoviruses from subtypes B, C or D (p<0.001. These data demonstrate that in patients with chronic HIV-1 subtype A infection, significant B cell depletion can be observed, the degree of which does not appear to be associated with a decrease in functional antibodies. These findings also highlight the potential importance of subtype in the specificity of cross-clade neutralization in HIV-1 infection.

  7. Cumulative Viral Load and Virologic Decay Patterns after Antiretroviral Therapy in HIV-Infected Subjects Influence CD4 Recovery and AIDS

    Science.gov (United States)

    Marconi, Vincent C.; Grandits, Greg; Okulicz, Jason F.; Wortmann, Glenn; Ganesan, Anuradha; Crum-Cianflone, Nancy; Polis, Michael; Landrum, Michael; Dolan, Matthew J.; Ahuja, Sunil K.; Agan, Brian; Kulkarni, Hemant

    2011-01-01

    Background The impact of viral load (VL) decay and cumulative VL on CD4 recovery and AIDS after highly-active antiretroviral therapy (HAART) is unknown. Methods and Findings Three virologic kinetic parameters (first year and overall exponential VL decay constants, and first year VL slope) and cumulative VL during HAART were estimated for 2,278 patients who initiated HAART in the U.S. Military HIV Natural History Study. CD4 and VL trajectories were computed using linear and nonlinear Generalized Estimating Equations models. Multivariate Poisson and linear regression models were used to determine associations of VL parameters with CD4 recovery, adjusted for factors known to correlate with immune recovery. Cumulative VL higher than the sample median was independently associated with an increased risk of AIDS (relative risk 2.38, 95% confidence interval 1.56–3.62, p<0.001). Among patients with VL suppression, first year VL decay and slope were independent predictors of early CD4 recovery (p = 0.001) and overall gain (p<0.05). Despite VL suppression, those with slow decay during the first year of HAART as well as during the entire therapy period (overall), in general, gained less CD4 cells compared to the other subjects (133 vs. 195.4 cells/µL; p = 0.001) even after adjusting for potential confounders. Conclusions In a cohort with free access to healthcare, independent of established predictors of AIDS and CD4 recovery during HAART, cumulative VL and virologic decay patterns were associated with AIDS and distinct aspects of CD4 reconstitution. PMID:21625477

  8. Cumulative viral load and virologic decay patterns after antiretroviral therapy in HIV-infected subjects influence CD4 recovery and AIDS.

    Directory of Open Access Journals (Sweden)

    Vincent C Marconi

    Full Text Available BACKGROUND: The impact of viral load (VL decay and cumulative VL on CD4 recovery and AIDS after highly-active antiretroviral therapy (HAART is unknown. METHODS AND FINDINGS: Three virologic kinetic parameters (first year and overall exponential VL decay constants, and first year VL slope and cumulative VL during HAART were estimated for 2,278 patients who initiated HAART in the U.S. Military HIV Natural History Study. CD4 and VL trajectories were computed using linear and nonlinear Generalized Estimating Equations models. Multivariate Poisson and linear regression models were used to determine associations of VL parameters with CD4 recovery, adjusted for factors known to correlate with immune recovery. Cumulative VL higher than the sample median was independently associated with an increased risk of AIDS (relative risk 2.38, 95% confidence interval 1.56-3.62, p<0.001. Among patients with VL suppression, first year VL decay and slope were independent predictors of early CD4 recovery (p = 0.001 and overall gain (p<0.05. Despite VL suppression, those with slow decay during the first year of HAART as well as during the entire therapy period (overall, in general, gained less CD4 cells compared to the other subjects (133 vs. 195.4 cells/µL; p = 0.001 even after adjusting for potential confounders. CONCLUSIONS: In a cohort with free access to healthcare, independent of established predictors of AIDS and CD4 recovery during HAART, cumulative VL and virologic decay patterns were associated with AIDS and distinct aspects of CD4 reconstitution.

  9. Apolipoprotein 4 may increase viral load and seizure frequency in mesial temporal lobe epilepsy patients with positive human herpes virus 6B.

    Science.gov (United States)

    Huang, Cheng; Yan, Bo; Lei, Ding; Si, Yang; Li, He; Chen, Ming-Wan; Li, Li; Chen, Fei; Zhou, Qiao; Zhou, Dong; Li, Jin-Mei

    2015-04-23

    This study investigated whether apolipoprotein 4 (ApoE4) was associated with the presence of human herpes virus (HHV)-6B in mesial temporal lobe epilepsy (MTLE). Polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) was used to determine ApoE polymorphism in 46 patients with MTLE and 19 controls. Nested PCR and real-time PCR were applied to determine HHV-6B DNA and immunohistochemistry (IHC) for HHV-6B protein. Viral DNA load was significantly increased in MTLE patients with HHV-6B(+)/ApoE4 compared with those with HHV-6B(+)/non-ApoE4 (p=0.031). Semi-quantitative analysis of IHC showed significantly increased number of positive cells for HHV-6B proteins G116/64/54, P98 and U94 in patients with HHV-6B(+)/ApoE4 than HHV-6B(+)/non-ApoE4 (p=0.009, 0.035 and 0.009, respectively). Patients with HHV-6B(+)/ApoE4 showed higher seizure frequency than those with HHV-6B(+)/non-ApoE4 (p=0.005). There was no significant difference of ApoE alleles between MTLE with and without HHV-6B (p=0.115). ApoE4 was not associated with initial infection of HHV-6B in MTLE. However, ApoE4 may facilitate HHV-6B reactivation, DNA replication, virus protein expression and increase seizure frequency in MTLE. Further investigations are needed to understand the biomolecular mechanism underlying interaction between ApoE and HHV-6B.

  10. Long-term risk of cervical intraepithelial neoplasia grade 3 or worse according to high-risk human papillomavirus genotype and semi-quantitative viral load among 33,288 women with normal cervical cytology

    DEFF Research Database (Denmark)

    Thomsen, Louise T; Frederiksen, Kirsten; Munk, Christian;

    2015-01-01

    2002-2005, residual liquid-based cervical cytology samples were collected from women screened for cervical cancer in Copenhagen, Denmark. Samples were HPV-tested with Hybrid Capture 2 (HC2) and genotyped with INNO-LiPA. Semi-quantitative viral load was measured by HC2 relative light units in women......HPV genotyping during cervical cancer screening may help identify women at highest risk of CIN3+....

  11. Viral marketing

    OpenAIRE

    BLÁHOVÁ, Adéla

    2012-01-01

    The aim of my thesis is to provide a comprehensive overview of the viral marketing and to analyze selected viral campaigns. There is a description of advantages and disadvantages of this marketing tool. In the end I suggest for which companies viral marketing is an appropriate form of the promotion.

  12. The probability for a Pap test to be abnormal is directly proportional to HPV viral load: results from a Swiss study comparing HPV testing and liquid-based cytology to detect cervical cancer precursors in 13,842 women.

    Science.gov (United States)

    Bigras, G; de Marval, F

    2005-09-01

    In a study involving 13,842 women and 113 gynaecologists, liquid-based cytology and HPV testing for detecting cervical cancer were compared. A total of 1334 women were found to be positive for one or both tests and were invited for colposcopy with biopsy. A total of 1031 satisfactory biopsies on 1031 women were thereafter collected using a systematic biopsy protocol, which was random in the colposcopically normal-appearing cervix or directed in the abnormal one. In all, 502 women with negative tests were also biopsied. A total of 82 histologic high-grade squamous intraepithelial lesion (HSIL) were reported in biopsies, all from the group with one or both tests positive. Sensitivity and specificity to detect histologic HSIL were 59 and 97% for cytology, and 97 and 92% for HPV. In total, 14% of reviewed negative cytological preparations associated with histologic HSIL contained no morphologically abnormal cells despite a positive HPV test. This suggested a theoretical limit for cytology sensitivity. HPV viral load analysis of the 1143 HPV-positive samples showed a direct relationship between abnormal Pap test frequency and HPV viral load. Thus, not only does the HPV testing have a greater sensitivity than cytology but the probability of the latter being positive can also be defined as a function of the associated HPV viral load. PMID:16136031

  13. The probability for a Pap test to be abnormal is directly proportional to HPV viral load: results from a Swiss study comparing HPV testing and liquid-based cytology to detect cervical cancer precursors in 13 842 women

    Science.gov (United States)

    Bigras, G; de Marval, F

    2005-01-01

    In a study involving 13 842 women and 113 gynaecologists, liquid-based cytology and HPV testing for detecting cervical cancer were compared. A total of 1334 women were found to be positive for one or both tests and were invited for colposcopy with biopsy. A total of 1031 satisfactory biopsies on 1031 women were thereafter collected using a systematic biopsy protocol, which was random in the colposcopically normal-appearing cervix or directed in the abnormal one. In all, 502 women with negative tests were also biopsied. A total of 82 histologic high-grade squamous intraepithelial lesion (HSIL) were reported in biopsies, all from the group with one or both tests positive. Sensitivity and specificity to detect histologic HSIL were 59 and 97% for cytology, and 97 and 92% for HPV. In total, 14% of reviewed negative cytological preparations associated with histologic HSIL contained no morphologically abnormal cells despite a positive HPV test. This suggested a theoretical limit for cytology sensitivity. HPV viral load analysis of the 1143 HPV-positive samples showed a direct relationship between abnormal Pap test frequency and HPV viral load. Thus, not only does the HPV testing have a greater sensitivity than cytology but the probability of the latter being positive can also be defined as a function of the associated HPV viral load. PMID:16136031

  14. Hepatitis C viral load does not predict disease outcome: going beyond numbers A carga viral do vírus da hepatite C não prediz a evolução: indo além dos números

    Directory of Open Access Journals (Sweden)

    Evaldo Stanislau Affonso de ARAÚJO

    2002-04-01

    Full Text Available The analysis of 58 patients with chronic hepatitis C without cirrhosis and treated with interferon-alpha demonstrated that hepatitis C viral (HCV load does not correlate with the histological evolution of the disease (p = 0.6559 for architectural alterations and p = 0.6271 for the histological activity index. Therefore, the use of viral RNA quantification as an evolutive predictor or determinant of the severity of hepatitis C is incorrect and of relative value. A review of the literature provided fundamental and interdependent HCV (genotype, heterogeneity and mutants, specific proteins, host (sex, age, weight, etc and treatment variables (dosage, time of treatment, type of interferon within the broader context of viral kinetics, interferon-mediated immunological response (in addition to natural immunity against HCV and the role of interferon as a modulator of fibrogenesis. Therefore, viral load implies much more than numbers and the correct interpretation of these data should consider a broader context depending on multiple factors that are more complex than the simple value obtained upon quantification.Através da análise de 58 pacientes tratados com Interferon Alfa em função de hepatite C crônica e sem cirrose, demonstramos que a carga viral do Vírus da Hepatite C (VHC não se correlacionou com a evolução histológica da doença (p = 0,6559 para alterações arquiteturais e p = 0,6271 para o Índice de Atividade Histológica-IAH. Assim a utilização da quantificação do RNA viral como preditor evolutivo ou determinante da gravidade da hepatite C é incorreto e de valor relativo. Revisando o tema encontramos variáveis do VHC (genótipo, heterogeneidade e mutantes, proteínas específicas, do hospedeiro (sexo, idade, peso, etc e dos medicamentos (posologia, tempo de tratamento, tipo de Interferon fundamentais e interdependentes, inseridas no contexto mais amplo da cinética viral, da resposta imunológica mediada pelo Interferon (al

  15. Treatment-associated polymorphisms in protease are significantly associated with higher viral load and lower CD4 count in newly diagnosed drug-naive HIV-1 infected patients

    OpenAIRE

    Theys, Kristof; Deforche, Koen; Vercauteren, Jurgen; Libin, Pieter; van de Vijver, David A M C; Albert, Jan; Åsjø, Birgitta; Balotta, Claudia; Bruckova, Marie; Camacho, Ricardo J; Clotet, Bonaventura; Coughlan, Suzie; Grossman, Zehava; Hamouda, Osamah; Horban, Andrzei

    2012-01-01

    Background: The effect of drug resistance transmission on disease progression in the newly infected patient is not well understood. Major drug resistance mutations severely impair viral fitness in a drug free environment, and therefore are expected to revert quickly. Compensatory mutations, often already polymorphic in wild-type viruses, do not tend to revert after transmission. While compensatory mutations increase fitness during treatment, their presence may also modulate viral fitness and ...

  16. Treatment-associated polymorphisms in protease are significantly associated with higher viral load and lower CD4 count in newly diagnosed drug-naive HIV-1 infected patients.

    OpenAIRE

    Theys, Kristof; Deforche, Koen; Vercauteren, Jurgen; Libin, Pieter; van de Vijver, David Amc; Albert, Jan; Asjo, Birgitta; Balotta, Claudia; Bruckova, Marie; Camacho, Ricardo J; Clotet, Bonaventura; Coughlan, Suzie; Grossman, Zehava; Hamouda, Osamah; Horban, Andrzei

    2012-01-01

    BACKGROUND: The effect of drug resistance transmission on disease progression in the newly infected patient is not well understood. Major drug resistance mutations severely impair viral fitness in a drug free environment, and therefore are expected to revert quickly. Compensatory mutations, often already polymorphic in wild-type viruses, do not tend to revert after transmission. While compensatory mutations increase fitness during treatment, their presence may also modulate viral fitness and ...

  17. Simplified clinical prediction scores to target viral load testing in adults with suspected first line treatment failure in Phnom Penh, Cambodia.

    Directory of Open Access Journals (Sweden)

    Johan van Griensven

    Full Text Available BACKGROUND: For settings with limited laboratory capacity, 2013 World Health Organization (WHO guidelines recommend targeted HIV-1 viral load (VL testing to identify virological failure. We previously developed and validated a clinical prediction score (CPS for targeted VL testing, relying on clinical, adherence and laboratory data. While outperforming the WHO failure criteria, it required substantial calculation and review of all previous laboratory tests. In response, we developed four simplified, less error-prone and broadly applicable CPS versions that can be done 'on the spot'. METHODOLOGY/PRINCIPAL: Findings From May 2010 to June 2011, we validated the original CPS in a non-governmental hospital in Phnom Penh, Cambodia applying the CPS to adults on first-line treatment >1 year. Virological failure was defined as a single VL >1000 copies/ml. The four CPSs included CPS1 with 'current CD4 count' instead of %-decline-from-peak CD4; CPS2 with hemoglobin measurements removed; CPS3 having 'decrease in CD4 count below baseline value' removed; CPS4 was purely clinical. Score development relied on the Spiegelhalter/Knill-Jones method. Variables independently associated with virological failure with a likelihood ratio ≥ 1.5 or ≤ 0.67 were retained. CPS performance was evaluated based on the area-under-the-ROC-curve (AUROC and 95% confidence intervals (CI. The CPSs were validated in an independent dataset. A total of 1490 individuals (56.6% female, median age: 38 years (interquartile range (IQR 33-44; median baseline CD4 count: 94 cells/µL (IQR 28-205, median time on antiretroviral therapy 3.6 years (IQR 2.1-5.1, were included. Forty-five 45 (3.0% individuals had virological failure. CPS1 yielded an AUROC of 0.69 (95% CI: 0.62-0.75 in validation, CPS2 an AUROC of 0.68 (95% CI: 0.62-0.74, and CPS3, an AUROC of 0.67 (95% CI: 0.61-0.73. The purely clinical CPS4 performed poorly (AUROC-0.59; 95% CI: 0.53-0.65. CONCLUSIONS: Simplified CPSs retained

  18. Field evaluation of dried blood spots for routine HIV-1 viral load and drug resistance monitoring in patients receiving antiretroviral therapy in Africa and Asia.

    Science.gov (United States)

    Monleau, Marjorie; Aghokeng, Avelin F; Eymard-Duvernay, Sabrina; Dagnra, Anoumou; Kania, Dramane; Ngo-Giang-Huong, Nicole; Touré-Kane, Coumba; Truong, Lien X T; Chaix, Marie-Laure; Delaporte, Eric; Ayouba, Ahidjo; Peeters, Martine

    2014-02-01

    Dried blood spots (DBS) can be used in developing countries to alleviate the logistic constraints of using blood plasma specimens for viral load (VL) and HIV drug resistance (HIVDR) testing, but they should be assessed under field conditions. Between 2009 and 2011, we collected paired plasma-DBS samples from treatment-experienced HIV-1-infected adults in Burkina Faso, Cameroon, Senegal, Togo, Thailand, and Vietnam. The DBS were stored at an ambient temperature for 2 to 4 weeks and subsequently at -20°C before testing. VL testing was performed on the plasma samples and DBS using locally available methods: the Abbott m2000rt HIV-1 test, generic G2 real-time PCR, or the NucliSENS EasyQ version 1.2 test. In the case of virological failure (VF), i.e., a plasma VL of ≥1,000 copies/ml, HIVDR genotyping was performed on paired plasma-DBS samples. Overall, we compared 382 plasma-DBS sample pairs for DBS VL testing accuracy. The sensitivities of the different assays in different laboratories for detecting VF using DBS varied from 75% to 100% for the m2000rt test in labs B, C, and D, 91% to 93% for generic G2 real-time PCR in labs A and F, and 85% for the NucliSENS test in lab E. The specificities varied from 82% to 97% for the m2000rt and NucliSENS tests and reached only 60% for the generic G2 test. The NucliSENS test showed good agreement between plasma and DBS VL but underestimated the DBS VL. The lowest agreement was observed for the generic G2 test. Genotyping was successful for 96/124 (77%) DBS tested, and 75/96 (78%) plasma-DBS pairs had identical HIVDR mutations. Significant discrepancies in resistance interpretations were observed in 9 cases, 6 of which were from the same laboratory. DBS can be successfully used as an alternative to blood plasma samples for routine VL and HIVDR monitoring in African and Asian settings. However, the selection of an adequate VL measurement method and the definition of the VF threshold should be considered, and laboratory performance

  19. Operationalizing treatment as prevention in Los Angeles County: antiretroviral therapy use and factors associated with unsuppressed viral load in the Ryan White system of care.

    Science.gov (United States)

    Sayles, Jennifer N; Rurangirwa, Jacqueline; Kim, Min; Kinsler, Janni; Oruga, Rangell; Janson, Mike

    2012-08-01

    Despite extensive prevention efforts, an estimated 21% of individuals with HIV/AIDS in the United States are unaware of their status, placing them at greater risk for spreading the virus to others. HIV treatment as prevention (TasP) is rapidly becoming an important public health strategy to reduce HIV transmission at the population level. Data for this study were collected on a sample of 11,397 HIV-positive individuals in the Ryan White system, a publicly funded system of care for HIV-positive individuals in Los Angeles County who are uninsured, in 2009 to examine two components of TasP: baseline rates and factors associated with antiretroviral therapy (ART) use and viral load (VL) suppression in a publicly funded system of care. ART coverage among our sample was 90%. In multivariate analyses, those with a higher odds of having unsuppressed VL included: females compared to males (adjusted odds ratio [AOR]=1.25; 95% confidence interval [CI]=1.06, 1.47); African Americans compared to whites (AOR=1.42; 95% CI=1.24, 1.62); men who have sex with men compared to heterosexuals (AOR=1.15; 95% CI=1.00, 1.32); recent substance abusers compared to nonsubstance abusers (AOR=1.35; 95% CI=1.17, 1.55); those recently incarcerated or ever incarcerated compared to those never incarcerated (AOR=1.37; 95% CI=1.15, 1.63; and AOR=1.28; 95% CI=1.09, 1.50); and those retained in care compared to those not retained in care (AOR=1.98; 95% CI=1.76, 2.22). Understanding the key sociodemographic, geographic and behavioral factors associated with ART use as well as HIV VL suppression will be useful for informing the development and deployment of targeted programming and policies that may further enhance the implementation of the TasP approach in communities across the United States. PMID:22775237

  20. Should viral load thresholds be lowered?: Revisiting the WHO definition for virologic failure in patients on antiretroviral therapy in resource-limited settings.

    Science.gov (United States)

    Labhardt, Niklaus D; Bader, Joëlle; Lejone, Thabo Ishmael; Ringera, Isaac; Hobbins, Michael A; Fritz, Christiane; Ehmer, Jochen; Cerutti, Bernard; Puga, Daniel; Klimkait, Thomas

    2016-07-01

    The World Health Organization (WHO) guidelines on antiretroviral therapy (ART) define treatment failure as 2 consecutive viral loads (VLs) ≥1000 copies/mL. There is, however, little evidence supporting 1000 copies as an optimal threshold to define treatment failure. Objective of this study was to assess the correlation of the WHO definition with the presence of drug-resistance mutations in patients who present with 2 consecutive unsuppressed VL in a resource-limited setting.In 10 nurse-led clinics in rural Lesotho children and adults on first-line ART for ≥6 months received a first routine VL. Those with plasma VL ≥80 copies/mL were enrolled in a prospective study, receiving enhanced adherence counseling (EAC) and a follow-up VL after 3 months. After a second unsuppressed VL genotypic resistance testing was performed. Viruses with major mutations against ≥2 drugs of the current regimen were classified as "resistant".A total of 1563 adults and 191 children received a first routine VL. Of the 138 adults and 53 children with unsuppressed VL (≥80 copies/mL), 165 (116 adults; 49 children) had a follow-up VL after EAC; 108 (74 adults; 34 children) remained unsuppressed and resistance testing was successful. Ninety of them fulfilled the WHO definition of treatment failure (both VL ≥1000 copies/mL); for another 18 both VL were unsuppressed but with definition was 81.1% (73/90) for the presence of resistant virus. Among the 18 with VL levels between 80 and 1000 copies/mL, thereby classified as "non-failures", 17 (94.4%) harbored resistant viruses. Lowering the VL threshold from 1000 copies/mL to 80 copies/mL at both determinations had no negative influence on the PPV (83.3%; 90/108).The current WHO-definition misclassifies patients who harbor resistant virus at VL below 1000 c/mL as "nonfailing." Lowering the threshold to VL ≥80 copies/mL identifies a significantly higher number of patients with treatment-resistant virus and should be

  1. Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load.

    Directory of Open Access Journals (Sweden)

    Art F Y Poon

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 genomes often carry one or more mutations associated with drug resistance upon transmission into a therapy-naïve individual. We assessed the prevalence and clinical significance of transmitted drug resistance (TDR in chronically-infected therapy-naïve patients enrolled in a multi-center cohort in North America. Pre-therapy clinical significance was quantified by plasma viral load (pVL and CD4+ cell count (CD4 at baseline. Naïve bulk sequences of HIV-1 protease and reverse transcriptase (RT were screened for resistance mutations as defined by the World Health Organization surveillance list. The overall prevalence of TDR was 14.2%. We used a Bayesian network to identify co-transmission of TDR mutations in clusters associated with specific drugs or drug classes. Aggregate effects of mutations by drug class were estimated by fitting linear models of pVL and CD4 on weighted sums over TDR mutations according to the Stanford HIV Database algorithm. Transmitted resistance to both classes of reverse transcriptase inhibitors was significantly associated with lower CD4, but had opposing effects on pVL. In contrast, position-specific analyses of TDR mutations revealed substantial effects on CD4 and pVL at several residue positions that were being masked in the aggregate analyses, and significant interaction effects as well. Residue positions in RT with predominant effects on CD4 or pVL (D67 and M184 were re-evaluated in causal models using an inverse probability-weighting scheme to address the problem of confounding by other mutations and demographic or risk factors. We found that causal effect estimates of mutations M184V/I (-1.7 log₁₀pVL and D67N/G (-2.1[³√CD4] and 0.4 log₁₀pVL were compensated by K103N/S and K219Q/E/N/R. As TDR becomes an increasing dilemma in this modern era of highly-active antiretroviral therapy, these results have immediate significance for the clinical management of HIV-1

  2. Generic Clearance Values

    International Nuclear Information System (INIS)

    This paper analyzes the Generic Clearance Values established for natural and artificial radionuclides with the objective of evaluating their degree of conservatism in views of adopting them into the regulatory body. Generic clearance values for natural radionuclides have been chosen by experts judgments as the optimum boundary between, on the one hand, the ubiquitous unmodified soil concentrations and, on the other hand, activity concentrations in ores, mineral sands, industrial residues and wastes. For artificial radionuclides the clearance levels have been derived from the scenarios postulated in the document Safety Reports Series 44 of the IAEA considering quantitative exemption criteria. A set of 8 scenarios were postulated covering external, ingestion and inhalation exposure pathways. For each radionuclide, the generic clearance level was derived as the more restrictive value obtained from the scenarios, that is the lowest ratio between the applicable individual dose and the dose per unit activity concentration (Bq/g). The individual dose was calculated by a formula depending on each scenario and pathway, with different parameters, such as exposure time, dosimetric factors, dilution factor, density of the material, geometric factors, etc. It was concluded that the basis and parameters used for the derivation of the generic clearance levels are quite conservative and therefore its the adoption in Argentina has been recommended. It is expected that their implementation will contribute to optimize the regulatory management system. (authors)

  3. A whole recombinant yeast-based therapeutic vaccine elicits HBV X, S and Core specific T cells in mice and activates human T cells recognizing epitopes linked to viral clearance.

    Directory of Open Access Journals (Sweden)

    Thomas H King

    Full Text Available Chronic hepatitis B infection (CHB is characterized by sub-optimal T cell responses to viral antigens. A therapeutic vaccine capable of restoring these immune responses could potentially improve HBsAg seroconversion rates in the setting of direct acting antiviral therapies. A yeast-based immunotherapy (Tarmogen platform was used to make a vaccine candidate expressing hepatitis B virus (HBV X, surface (S, and Core antigens (X-S-Core. Murine and human immunogenicity models were used to evaluate the type and magnitude of HBV-Ag specific T cell responses elicited by the vaccine. C57BL/6J, BALB/c, and HLA-A*0201 transgenic mice immunized with yeast expressing X-S-Core showed T cell responses to X, S and Core when evaluated by lymphocyte proliferation assay, ELISpot, intracellular cytokine staining (ICS, or tumor challenge assays. Both CD4+ and CD8+ T cell responses were observed. Human T cells transduced with HBc18-27 and HBs183-91 specific T cell receptors (TCRs produced interferon gamma (IFNγ following incubation with X-S-Core-pulsed dendritic cells (DCs. Furthermore, stimulation of peripheral blood mononuclear cells (PBMCs isolated from CHB patients or from HBV vaccine recipients with autologous DCs pulsed with X-S-Core or a related product (S-Core resulted in pronounced expansions of HBV Ag-specific T cells possessing a cytolytic phenotype. These data indicate that X-S-Core-expressing yeast elicit functional adaptive immune responses and supports the ongoing evaluation of this therapeutic vaccine in patients with CHB to enhance the induction of HBV-specific T cell responses.

  4. Correlation between cytokine serum levels, number of CD4+ T cells/mm³ and viral load in HIV-1 infected individuals with or without antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    D. A. Meira

    2004-01-01

    Full Text Available Seventy-nine HIV-1 infected patients were studied in three groups: Group G1 - 11 patients with no antiretroviral therapy; G2 - 40 patients undergoing antiretroviral therapy, 33 with only two nucleoside reverse transcriptase inhibitors (NRTI, and seven with two NRTI and one protease inhibitor (PI, all with viral load (VL equal or higher than 80 copies of plasma RNA/ml; Group G3 - 28 patients, 23 on highly active antiretroviral therapy (HAART, 18 with two NRTI and one PI, and five with two NRTI and one non-nucleoside reverse transcriptase inhibitor (NNRTI, the remaining five with combination of two NRTI. All G3 patients had undetectable viral load for at least the past six months. The control group (Gc included 20 normal blood donors without clinical complaints or signs of disease and negative for anti-HIV-1/2 antibodies. Serum cytokine levels pg/ml (TNF-alpha, INF-gamma, IL-2, IL-4, and IL-10 were determined in all patients including controls. CD4+ T and CD8+ T lymphocyte counts were made in the 79 patients by flow cytometry; VL determination was by NASBA technology. Analysis of results showed that the number of CD4+ T and CD8+ T lymphocytes were higher in G2 than G1, while VL was 0.5 log lower. G3 patients had similar lymphocyte values to G2, however they were chosen for G3 because their VL was undetectable, different by 4.0 log to G2. These results show the effect of antiretroviral treatment in G2 and G3 patients with better performance in the latter. Statistical difference was seen between the three groups and controls for serum cytokine behavior: TNF-alpha [H=48.323; pGc]; INF-gamma[H=28.992; pGc]; IL-4[H=48.323; pGc]; IL-10[H=47.256; pGc. There was no statistical difference in IL-2 values between all groups (H=6.071; p>0.10; G1=G2=G3=Gc. In absolute values however, G3 showed slightly lower TNF-alpha, IL-4, and IL-10, and higher INF-gamma and IL-2, to G1 and G2. This suggests a better performance in G3 patients, especially in IL-2 behavior

  5. CD4 cell count and the risk of AIDS or death in HIV-Infected adults on combination antiretroviral therapy with a suppressed viral load: a longitudinal cohort study from COHERE.

    Directory of Open Access Journals (Sweden)

    Jim Young

    Full Text Available BACKGROUND: Most adults infected with HIV achieve viral suppression within a year of starting combination antiretroviral therapy (cART. It is important to understand the risk of AIDS events or death for patients with a suppressed viral load. METHODS AND FINDINGS: Using data from the Collaboration of Observational HIV Epidemiological Research Europe (2010 merger, we assessed the risk of a new AIDS-defining event or death in successfully treated patients. We accumulated episodes of viral suppression for each patient while on cART, each episode beginning with the second of two consecutive plasma viral load measurements 500 copies/µl, the first of two consecutive measurements between 50-500 copies/µl, cART interruption or administrative censoring. We used stratified multivariate Cox models to estimate the association between time updated CD4 cell count and a new AIDS event or death or death alone. 75,336 patients contributed 104,265 suppression episodes and were suppressed while on cART for a median 2.7 years. The mortality rate was 4.8 per 1,000 years of viral suppression. A higher CD4 cell count was always associated with a reduced risk of a new AIDS event or death; with a hazard ratio per 100 cells/µl (95% CI of: 0.35 (0.30-0.40 for counts <200 cells/µl, 0.81 (0.71-0.92 for counts 200 to <350 cells/µl, 0.74 (0.66-0.83 for counts 350 to <500 cells/µl, and 0.96 (0.92-0.99 for counts ≥500 cells/µl. A higher CD4 cell count became even more beneficial over time for patients with CD4 cell counts <200 cells/µl. CONCLUSIONS: Despite the low mortality rate, the risk of a new AIDS event or death follows a CD4 cell count gradient in patients with viral suppression. A higher CD4 cell count was associated with the greatest benefit for patients with a CD4 cell count <200 cells/µl but still some slight benefit for those with a CD4 cell count ≥500 cells/µl.

  6. [Analysis of the results of the 2010 External Quality Control Program of the Spanish Society of Infectious Diseases and Clinical Microbiology for HIV-1, HCV, and HBV viral loads].

    Science.gov (United States)

    Orta Mira, Nieves; Serrano, María del Remedio Guna; Martínez, José-Carlos Latorre; Ovies, María Rosario; Poveda, Marta; de Gopegui, Enrique Ruiz; Cardona, Concepción Gimeno

    2011-12-01

    Human immunodeficiency virus type 1 (HIV-1) and hepatitis B (HBV) and C virus (HCV) viral load determinations are among the most important markers for the follow-up of patients infected with these viruses. External quality control tools are crucial to ensure the accuracy of the results obtained by microbiology laboratories. This article summarized the results obtained in the 2010 External Quality Control Program of the Spanish Society of Infectious Diseases and Clinical Microbiology for HIV-1, HCV, and HBV viral loads and HCV genotyping. In the HIV-1 program, a total of five standards were sent. One standard consisted of seronegative human plasma, while the remaining four contained plasma from three different viremic patients, in the range of 3-5 log(10) copies/mL; two of these standards were identical, with the aim of determining repeatability. A significant proportion of the laboratories (22.6% on average) obtained values out of the accepted range (mean ± 0.2 log(10)copies/mL), depending on the standard and on the method used for quantification. Repeatability was very good, with up to 95% of laboratories reporting results within the limits (Δ<0.5 log(10)copies/mL). The HBV and HCV program consisted of two standards with different viral load contents. Most of the participants, 86.1% in the case of HCV and 87.1% in HBV, obtained all the results within the accepted range (mean ± 1.96 SD log(10)UI/mL). Post-analytical errors due to mistranscription of the results were detected in these controls. Data from this analysis reinforce the utility of proficiency programs to ensure the quality of the results obtained by a particular laboratory, as well as the importance of the post-analytical phase in overall quality. Due to interlaboratory variability, use of the same method and the same laboratory for patient follow-up is advisable.

  7. Interleukin-27 is differentially associated with HIV viral load and CD4+ T cell counts in therapy-naive HIV-mono-infected and HIV/HCV-co-infected Chinese.

    Directory of Open Access Journals (Sweden)

    Lai He

    Full Text Available Human Immunodeficiency Virus (HIV infection and the resultant Acquired Immunodeficiency Syndrome (AIDS epidemic are major global health challenges; hepatitis C virus (HCV co-infection has made the HIV/AIDS epidemic even worse. Interleukin-27 (IL-27, a cytokine which inhibits HIV and HCV replication in vitro, associates with HIV infection and HIV/HCV co-infection in clinical settings. However, the impact of HIV and HCV viral loads on plasma IL-27 expression levels has not been well characterized. In this study, 155 antiretroviral therapy-naïve Chinese were recruited. Among them 80 were HIV- and HCV-negative healthy controls, 45 were HIV-mono-infected and 30 were HIV/HCV-co-infected. Plasma level HIV, HCV, IL-27 and CD4+ number were counted and their correlation, regression relationships were explored. We show that: plasma IL-27 level was significantly upregulated in HIV-mono-infected and HIV/HCV-co-infected Chinese; HIV viral load was negatively correlated with IL-27 titer in HIV-mono-infected subjects whereas the relationship was opposite in HIV/HCV-co-infected subjects; and the relationships between HIV viral loads, IL-27 titers and CD4+ T cell counts in the HIV mono-infection and HIV/HCV co-infection groups were dramatically different. Overall, our results suggest that IL-27 differs in treatment-naïve groups with HIV mono-infections and HIV/HCV co-infections, thereby providing critical information to be considered when caring and treating those with HIV mono-infection and HIV/HCV co-infection.

  8. Effect of cytokine gene polymorphism on histological activity index, viral load and response to treatment in patients with chronic hepatitis C genotype 3

    Institute of Scientific and Technical Information of China (English)

    Zaigham Abbas; Tariq Moatter; Akber Hussainy; Wasim Jafri

    2005-01-01

    levels were not significantly different among different cytokine polymorphisms. There was a significant correlation of HAI and HCV RNA levels with the duration of disease. TGFβ -10 genotype CC patients had a better end of treatment response than those with other genotypes (P = 0.020). Sustained virological response to the treatment was not influenced by the cytokine polymorphism. No effect of other factors like viral load,degree of fibrosis, gender, steatosis, was observed on sustained virological response in this population infected with genotype 3.CONCLUSION: There is no significant correlation between cytokine polymorphisms and HAI except for the polymorphisms of anti-inflammatory cytokine IL-10,which may influence hepatic inflammatory activity and fibrosis in patients with chronic hepatitis C genotype 3.Sustained virological response in this genotype does not seem to be influenced by cytokine gene polymorphisms.

  9. Effectiveness of first-line antiretroviral therapy based on NNRTIs vs ritonavir-boosted PIs in HIV-1 infected patients with high plasma viral load

    Directory of Open Access Journals (Sweden)

    A Imaz

    2012-11-01

    Full Text Available Purpose of the study: Few clinical trials have compared non-nucleoside reverse transcriptase inhibitors (NNRTI and ritonavir-boosted protease inhibitors (PI/r as initial combined antiretroviral therapy (cART for HIV-1-infected patients with high plasma viral load (pVL, and non-conclusive results have been reported. We compared the effectiveness between NNRTI and PI/r as first-line cART for HIV-1-infected patients with high pVL. Methods: Observational retrospective study of 664 consecutive treatment-naïve HIV-1-infected patients with pVL (HIV-1 RNA >100,000 copies/mL who initiated NNRTI or PI/r-based cART between 2000–2010 in three University hospitals. Only currently preferred or alternative regimens in clinical guidelines were included. Primary endpoint: percentage of therapeutic failures at week 48. Virologic failure was defined as: a lack of virologic response (<1 log RNA HIV-1 decrease in first 3 months; b RNA HIV-1 >50 c/mL at week 48; c confirmed rebound >50 c/ml after a previous value <50 c/mL. Intent-to-treat (ITT noncompleter=failure and on-treatment (OT analyses were performed. Results: 62% of patients initiated NNRTI-regimens (83% efavirenz and 38% PI/r-regimens (62% lopinavir/. Baseline characteristics: male 83%; median age 39 yrs; median CD4 count: 212/µL (NNRTI 232 vs PI/r 177, p=0.028; pVL 5.83 log10 c/mL (NNRTI 5.43 vs PI/r 5.55, p=0.007; AIDS 24% (NNRTI 21% vs PI/r 29%, p=0.015. NRTI backbones were tenofovir plus 3TC or FTC in 72%. The percentage of therapeutic failure was higher in the PI/r group (ITT NC=F 26% vs 18%, p=0.012 with no differences in virologic failures (PI/r 5%, NNRTI 6%, p=0.688. The rate of treatment changes due to toxicity and/or voluntary discontinuations was higher in the PI/r group (15% vs 8%, p=0.008. A multivariate analysis adjusted for age, gender, CD4 count, VL and AIDS showed NNRTI vs PI/r as the only variable associated with treatment response (OR 0.61, 95% CI 0.41–0.88. Median pVL and rate of

  10. 宫颈癌不同治疗方法对HPV病毒载量的影响%Effects of different therapeutic methods of cervical cancer on viral load of HPV

    Institute of Scientific and Technical Information of China (English)

    陈红香; 白生宾; 玛依努尔·尼牙孜; 夏小艳

    2011-01-01

    Objective: To explore the effects of different therapeutic methods of cervical cancer with different clinical stages and grades of differentiation on viral load of human papillomavirus (HPV) . Methods: 227 cases with squamous cell carcinoma of cervix treated in the hospital from January 2007 to January 2010 were selected as study objects, then they were divided into radical surgery group, radical radiotherapy group and radical radiotherapy plus chemotherapy group according to clinical stages; the cervical secretions on admission and after treatment were collected; hybrid capture Ⅱ method was used to detect viral load of HPV. Results: The infection rate of HPV was 99. 11%, after treatment, the infection rate of HPV was 57. 26%; there was significant difference in viral load of HPV among different clinical stages ( P < 0. 05 ), there was no significant difference in viral load of HPV between cervical cancer of high differentiation and cervical cancer of middle differentiation ( P > 0. 05 ), but there was significant difference in viral load of HPV between cervical cancer of middle differentiation and cervical cancer of low differentiation, cervical cancer of high differentiation and cervical cancer of low differentiation (P <0. 05 ); there was significant difference in viral load of HPV among radical surgery group, radical radiotherapy group and radical radiotherapy plus chemotherapy group (P < 0. 05 ) . Conclusion: Cervical cancer with high FIGO stages has low differentiation and high viral load of HPV, radical surgery and radical surgery combined with radiotherapy and chemotherapy may reduce the viral load of HPV significantly, detection of viral load of HPV can be used as a marker of screening of cervical cancer and follow - up and monitoring of the disease.%目的:探讨不同分期及组织分化的宫颈癌患者HPV病毒载量及宫颈癌不同治疗方案对HPV病毒载量的影响.方法:以2007年1月~2010年1月新疆维吾尔自治区人

  11. Treatment-associated polymorphisms in protease are significantly associated with higher viral load and lower CD4 count in newly diagnosed drug-naive HIV-1 infected patients

    NARCIS (Netherlands)

    K. Theys (Kristof); K. Deforche; J. Vercauteren (Jurgen); P. Libin (Pieter); D.A.M.C. van de Vijver (David); J. Albert (Jan); B. Åsjö (Birgitta); M. Bruckova (Marie); R.J. Camacho (Ricardo Jorge); B. Clotet (Bonaventura); Z. Grossman (Zehava); A. Horban (Andrzej); C. Kücherer (Claudia); D. Paraskevis (Dimitrios); E. Puchhammer-Stöckl (Elisabeth); C. Riva (Chiara); L. Ruiz (Lidia); J.-C. Schmit (Jean-Claude); R. Schuurman (Rob); A. Sonnerborg (Anders); D. Stanekova (Danica); D. Struck (Daniel); K. van Laethem (Kristel); A.M.J. Wensing (Annemarie); E. Puchhammer-Stockl E. (E.); M. Sarcletti (M.); B. Schmied (B.); M. Geit (M.); G. Balluch (G.); A.M. Vandamme (Anne Mieke); I. Derdelinck (Inge); A. Sasse (A.); M. Bogaert (M.); H. Ceunen (H.); A. de Roo (Annie); M. De Wit (Meike); F. Echahidi (F.); K. Fransen (K.); J.-C. Goffard (J.); P. Goubau (Patrick); E. Goudeseune (E.); J.-C. Yombi (J.); P. Lacor (Patrick); C. Liesnard (C.); M. Moutschen (M.); L.A. Pierard; R. Rens (R.); J. Schrooten; D. Vaira (D.); A. van den Heuvel (A.); B. van der Gucht (B.); M. van Ranst (Marc); E. van Wijngaerden (Eric); T. Vandercam; M. Vekemans (M.); C. Verhofstede; N. Clumeck (N.); K. van Laethem (K.); L.G. Kostrikis (Leondios); I. Demetriades (I.); I. Kousiappa (Ioanna); V.L. Demetriou (Victoria); J. Hezka (Johana); M. Linka (Marek); L. Machala (L.); L.B. Jrgensen (L.); J. Gerstoft (J.); L. Mathiesen (L.); C. Pedersen (Court); C. Nielsen (Claus); A. Laursen (A.); B. Kvinesdal (B.); K. Liitsola (Kirsi); M. Ristola (M.); J. Suni (J.); J. Sutinen (J.); K. Korn (Klaus); C. K̈ucherer (C.); P. Braun (P.); G. Poggensee (G.); M. Däumer (M.); D. Eberle (David); O. Hamouda (Osamah); H. Heiken (H.); R. Kaiser (R.); H. Knechten (H.); H. M̈uller (H.); S. Neifer (S.); H. Walter (Hauke); B. Gunsenheimer-Bartmeyer (B.); T. Harrer (T.); A. Hatzakis (Angelos); E. Hatzitheodorou (E.); C. Issaris (C.); C. Haida (C.); A. Zavitsanou (A.); G. Magiorkinis (Gkikas); M. Lazanas (M.); L. Chini; N. Magafas (N.); N. Tsogas (N.); V. Paparizos (V.); S. Kourkounti (S.); A. Antoniadou (A.); A. Papadopoulos (A.); P. Panagopoulos (P.); G. Poulakou (G.); V. Sakka (V.); G. Chryssos (G.); S. Drimis (S.); P. Gargalianos (P.); M. Lelekis (M.); G. Xilomenos (G.); M. Psichogiou (M.); G.L. Daikos (G.); G. Panos (G.); G. Haratsis (G.); T. Kordossis (T.); A. Kontos (Angelos); G. Koratzanis (G.); M. Theodoridou (M.); G. Mostrou (G.); V. Spoulou (V.); W. Hall (W.); C. de Gascun (Cillian); C. Byrne (C.); M. Duffy (M.); P. Bergin; D. Reidy (D.); G. Farrell; J. Lambert (Julien); E. O'Connor (E.); A. Rochford (A.); J. Low (J.); P. Coakely (P.); S. Coughlan (Suzie); I. Levi (I.); D. Chemtob (D.); C. Balotta (Claudia); C. Mussini (C.); I. Caramma (I.); A. Capetti (A.); M.C. Colombo (M.); C. Rossi (Cesare); F. Prati (Francesco); F. Tramuto (F.); F. Vitale (F.); M. Ciccozzi (M.); G. Angarano (Guiseppe); G. Rezza (G.); R. Hemmer (R.); V. Arendt (V.); T. Staub (T.); F. Schneider (F.); F. Roman (Francois); C.A.B. Boucher (Charles); P.H.M. van Bentum (P. H M); K. Brinkman; E.L.M. Op de Coul (Eline); M.E. van der Ende (Marchina); I.M. Hoepelman (Ilja Mohandas); M.E.E. van Kasteren (Marjo); J. Juttmann (Job); M. Kuipers (M.); N. Langebeek (Nienke); C. Richter (C.); R.M.W.J. Santegoets (R. M W J); L. Schrijnders-Gudde (L.); R. Schuurman (R.); B.J.M. van de Ven (B. J M); B. Asjö (Birgitta); V. Ormaasen (Vidar); P. Aavitsland (P.); J. Stanczak (J.); G.P. Stanczak (G.); E. Firlag-Burkacka (E.); A. Wiercinska-Drapalo (A.); E. Jablonowska (E.); E. Malolepsza (E.); M. Leszczyszyn-Pynka (M.); W. Szata (W.); A. de Palma (Andre); F. Borges (F.); T. Paix̃ao (T.); V. Duque (V.); F. Aráujo (F.); M. Stanojevic (Maja); D.J. Jevtovic (D.); D. Salemovic (D.); M. Habekova (M.); M. Mokras (M.); P. Truska (P.); M. Poljak (Mario); D. Babic (D.); J. Tomazic (J.); S. Vidmar (Suzanna); P. Karner (P.); C. Gutíerrez (C.); C. deMendoza (C.); I. Erkicia (I.); P. Domingo (P.); X. Camino (X.); M.A. Galindo (Miguel Angel); J.L. Blanco (J.); M. Leal (M.); A. Masabeu (A.); A. Guelar (A.); J.M. Llibre (Josep M.); N. Margall (N.); C. Iribarren (Carlos); S. Gutierrez (S.); J.F. Baldov́i (J.); C.E. Pedreira (Carlos Eduardo); J.M. Gatell (J.); S. Moreno (S.); C. de Mendoza (Carmen); V. Soriano (Virtudes); A. Blaxhult (A.); A. Heidarian (A.); A. Karlsson (A.); K. Aperia-Peipke (K.); I.-M. Bergbrant (I.); M. Gissĺen (M.); M. Svennerholm (M.); P. Bj̈orkman (P.); G. Bratt (G.); M. Carlsson (M.); H. Ekvall (H.); M. Ericsson (M.); M. Ḧofer (M.); B. Johansson (Bert)

    2012-01-01

    textabstractBackground: The effect of drug resistance transmission on disease progression in the newly infected patient is not well understood. Major drug resistance mutations severely impair viral fitness in a drug free environment, and therefore are expected to revert quickly. Compensatory mutatio

  12. Mucociliary clearance in chronic sinusitis

    OpenAIRE

    Birdi, Surinder Mohan; Singh, Sunder; Singh, Ajit

    1998-01-01

    Mucociliary clearance is an important defence mechanism of upper and lower respiratory tracts. Any disturbance in the mechanism leads to stagnation of secretions and secondary infection with prolonged mucociliary clearance time. The present study was undertaken to establish normal mucociliary clearance time in our region and to evaluate its diagnostic and prognostic potential in chronic sinusitis of variable duration with and without obstructive diseases.

  13. VIRAL MARKETING

    OpenAIRE

    OLENTSOVA Y. A

    2016-01-01

    Abstract This project seeks to investigate how the company Gitz can create awareness towards their brand by using viral marketing. To do this we analyze which elements of viral marketing the company can use, to reach their goal. In order to utilize the selected tools of viral marketing best possible, we need to figure out the company’s customer segment and figure out how to reach that segment. This has been done with the use of Henrik Dahl’s Minerva-model that divides the population into f...

  14. Relação entre diagnóstico citopatológico de neoplasia intra-epitelial cervical e índices de células CD4+ e de carga viral em pacientes HIV-soropositivas Association of cervical intraepithelial neoplasia with CD4 T cell counts and viral load in HIV-infected women

    Directory of Open Access Journals (Sweden)

    Raquel Autran Coelho

    2004-03-01

    -RNA viral load in HIV-positive patients. METHODS: one hundred and fifteen HIV patients were evaluated retrospectively in the present study, during the period from January 2002 to April 2003, at a university hospital. Eighty-three patients presented cervical intraepithelial neoplasia (CIN in Pap smear, in comparison with thirty-two with no lesions. Patients were divided into three groups, according to CD4 counts: CD4 more than 500 cells/mm³, between 200 and 500 cells/mm³, and less than 200 cells/mm³, and other three groups, according to HIV viral load: less than 10,000 HIV-RNA copies/mL, between 10,000 and 100,000 HIV-RNA copies/mL, or more than 100,000 HIV-RNA copies/mL. Correlation was investigated by the Fisher test. RESULTS: of the eighty-three patients with CIN, 73% presented CD4 counts less than 500 cells/mm³. In all CD4 groups, more than 50% of the patients presented CIN. According to the viral load, 71.7% of the patients with less than 10,000 HIV-RNA copies/mL presented CIN I, compared with 11.3% that showed CIN III. In the group with higher viral load (>100.000 HIV-RNA copies/mL, 61.5% showed CIN I and 30.8% presented CIN III. CONCLUSION: association between viral load and CIN was established (p=0.013, which was not observed with CD4 cell counts and CIN. Concomitant cervicovaginal infection was considered a potential confounding factor.

  15. Viral pneumonia

    Science.gov (United States)

    More serious infections can result in respiratory failure, liver failure, and heart failure. Sometimes, bacterial infections occur during or just after viral pneumonia, which may lead to more serious forms ...

  16. Viral Hepatitis

    Science.gov (United States)

    ... Hepatitis viruses B and C can cause both acute and chronic infections. Chronic hepatitis B and C are serious health problems. They can lead to: Cirrhosis (suh-ROH-suhs) Liver failure Liver cancer Return to top How is viral ...

  17. Pharyngitis - viral

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/001392.htm Pharyngitis - viral To use the sharing features on this page, please enable JavaScript. Pharyngitis , or sore throat, is swelling, discomfort, pain, or ...

  18. Viral arthritis

    Science.gov (United States)

    Infectious arthritis - viral ... Arthritis may be a symptom of many virus-related illnesses. It usually disappears on its own without ... the rubella vaccine, only a few people develop arthritis. No risk factors are known.

  19. Viral Marketing

    OpenAIRE

    Sorina Raula Gîrboveanu; Silvia Puiu

    2008-01-01

    With consumers showing increasing resistance to traditional forms of advertising such as TV or newspaper ads, marketers have turned to alternate strategies, including viral marketing. Viral marketing exploits existing social networks by encouraging customers to share product information with their friends.In our study we are able to directly observe the effectiveness of person to person word of mouth advertising for hundreds of thousands of products for the first time

  20. Hepatitis C viral load, genotype 3 and interleukin-28B CC genotype predict mortality in HIV and hepatitis C-coinfected individuals

    DEFF Research Database (Denmark)

    Clausen Nygaard, Louise; Astvad, Karen; Ladelund, Steen;

    2012-01-01

    : We hypothesized that hepatitis C virus (HCV) load and genotype may influence all-cause mortality in HIV-HCV-coinfected individuals.......: We hypothesized that hepatitis C virus (HCV) load and genotype may influence all-cause mortality in HIV-HCV-coinfected individuals....

  1. Characterizing clearance of helper adenovirus by a clinical rAAV1 manufacturing process.

    Science.gov (United States)

    Thorne, Barbara A; Quigley, Paulene; Nichols, Gina; Moore, Christine; Pastor, Eric; Price, David; Ament, Jon W; Takeya, Ryan K; Peluso, Richard W

    2008-01-01

    Recombinant adeno-associated viral vectors (rAAV) are being developed as gene therapy delivery vehicles and as genetic vaccines, and some of the most scaleable manufacturing methods for rAAV use live adenovirus to induce production. One aspect of establishing safety of rAAV products is therefore demonstrating adequate and reliable clearance of this helper virus by the vector purification process. The ICH Q5A regulatory guidance on viral safety provides recommendations for process design and characterization of viral clearance for recombinant proteins, and these principles were adapted to a rAAV serotype 1 purification process for clinical vectors. Specific objectives were to achieve overall adenovirus clearance factors significantly greater than input levels by using orthogonal separation and inactivation methods, and to segregate adenovirus from downstream operations by positioning a robust clearance step early in the process. Analytical tools for process development and characterization addressed problematic in-process samples, and a viral clearance validation study was performed using adenovirus and two non-specific model viruses. Overall clearance factors determined were >23 LRV for adenovirus, 11 LRV for BVDV, and >23 LRV for AMuLV.

  2. Viral arthritis.

    Science.gov (United States)

    Marks, Michael; Marks, Jonathan L

    2016-04-01

    Acute-onset arthritis is a common clinical problem facing both the general clinician and the rheumatologist. A viral aetiology is though to be responsible for approximately 1% of all cases of acute arthritis with a wide range of causal agents recognised. The epidemiology of acute viral arthritis continues to evolve, with some aetiologies, such as rubella, becoming less common due to vaccination, while some vector-borne viruses have become more widespread. A travel history therefore forms an important part of the assessment of patients presenting with an acute arthritis. Worldwide, parvovirus B19, hepatitis B and C, HIV and the alphaviruses are among the most important causes of virally mediated arthritis. Targeted serological testing may be of value in establishing a diagnosis, and clinicians must also be aware that low-titre autoantibodies, such as rheumatoid factor and antinuclear antibody, can occur in the context of acute viral arthritis. A careful consideration of epidemiological, clinical and serological features is therefore required to guide clinicians in making diagnostic and treatment decisions. While most virally mediated arthritides are self-limiting some warrant the initiation of specific antiviral therapy. PMID:27037381

  3. Retrospective Evaluation of Low-pH Viral Inactivation and Viral Filtration Data from a Multiple Company Collaboration.

    Science.gov (United States)

    Mattila, John; Clark, Mike; Liu, Shengjiang; Pieracci, John; Gervais, Thomas R; Wilson, Eileen; Galperina, Olga; Li, Xinfang; Roush, David; Zoeller, Konstantin; Brough, Helene; Simpson-Platre, Christelle

    2016-01-01

    Considerable resources are spent within the biopharmaceutical industry to perform viral clearance studies, which are conducted for widely used unit operations that are known to have robust and effective retrovirus clearance capability. The collaborative analysis from the members of the BioPhorum Development Group Viral Clearance Working Team considers two common virus reduction steps in biopharmaceutical processes: low-pH viral inactivation and viral filtration. Analysis included eight parameters for viral inactivation and nine for viral filtration. The extensive data set presented in this paper provides the industry with a reference point for establishing robust processes in addition to other protocols available in the literature (e.g., ASTM Std. E2888-12 for low-pH inactivation). In addition, it identifies points of weakness in the existing data set and instructs the design and interpretation of future studies. Included is an abundance of data that would have been difficult to generate individually but collectively will help support modular viral clearance claims.

  4. Effect of cardiovascular interventional treatment on clearance of biological load on contaminated catheter%心血管介入诊疗中污染导管的生物负载清除效果研究

    Institute of Scientific and Technical Information of China (English)

    张永栋; 柳茵; 刘维军; 李琳

    2012-01-01

    目的 研究通过规范的清洗和灭菌方法对污染的心脏电生理导管微生物负载清除效果.方法 将心脏电生理导管使用HBV血液进行污染,分为5组,每组40根导管,A组采用多酶清洗,B组采用加去污剂清洗,C组采用多酶加去污剂清洗,D组采用去污剂和多酶清洗后环氧乙烷低温灭菌,E组术进行任何处理,作为阳性对照组;再将每段分为各5 mm的两节,其中一节采用PCR检测各组HIV核酸阳性数;另一节与人肝细胞共同培养收集培养上清液检测HBsAg和HBeAg;观察人肝细胞的存活情况.结果 A组检出HBV-DNA阳性39根,阳性率为97.5%,人肝细胞大量死亡;B组检出HBV-DNA阳性37 根,阳性率92.5%,人肝细胞生长状况不良;C组检出HBV-DNA阳性37根,阳性率92.5%,人肝细胞大量死亡;D组未检出 HBV-DNA,入肝细胞生长状况良好;E组检出HBV-DNA阳性40根,阳性率100.0%,人肝细胞大量死亡.结论 清洗(去污剂+酶液)+环氧乙烷低温灭菌法可有效清除心脏电生理导管的HBV污染,从消除导管生物负载的角度为今后探索导管复用、为取得相关政策的支持提供了科学依据.%OBJECTIVE To study the effect of the standardized cleaning and sterilization methods on the clearance of the bacterial load on the contaminated cardiac eiectrophysiology catheter. METHODS The cardiac electrophysiology catheters with HBV blood pollution were divided into five groups with 40 in each, the group A was treated with multiple enzymes, the group B with detergents for cleaning, the group C with detergent plus multi-enzyme, the group D with ethylene oxide for low temperature sterilization after using multiple enzymes and detergent, the group E without any trealmeni as the positive control group; then each section were divided into two 5 mm-segments, one was detected the positive HBV nucleic acid with PCR; the other was measured for the HBsAg and HbeAg with the combined culture with human liver

  5. Site clearance working group

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-03-01

    The Gulf of Mexico and Louisiana continue to be areas with a high level of facility removal, and the pace of removal is projected to increase. Regulations were promulgated for the Gulf of Mexico and Louisiana requiring that abandoned sites be cleared of debris that could interfere with fishing and shrimping activities. The site clearance regulations also required verification that the sites were clear. Additionally, government programs were established to compensate fishermen for losses associated with snagging their equipment on oil and gas related objects that remained on the water bottoms in areas other than active producing sites and sites that had been verified as clear of obstructions and snags. The oil and gas industry funds the compensation programs. This paper reviews the regulations and evolving operating practices in the Gulf of Mexico and Louisiana where site clearance and fisherman`s gear compensation regulations have been in place for a number of years. Although regulations and guidelines may be in place elsewhere in the world, this paper focuses on the Gulf of Mexico and Louisiana. Workshop participants are encouraged to bring up international issues during the course of the workshop. Additionally, this paper raises questions and focuses on issues that are of concern to the various Gulf of Mexico and Louisiana water surface and water bottom stakeholders. This paper does not have answers to the questions or issues. During the workshop participants will debate the questions and issues in an attempt to develop consensus opinions and/or make suggestions that can be provided to the appropriate organizations, both private and government, for possible future research or policy adjustments. Site clearance and facility removal are different activities. Facility removal deals with removal of the structures used to produce oil and gas including platforms, wells, casing, piles, pipelines, well protection structures, etc.

  6. Viral Marketing

    OpenAIRE

    Jelínková, Petra

    2012-01-01

    Diploma thesis is focused on Viral marketing, as a part of internet marketing communication i.e. iPromotion. It’s presented as a „niche” in the way of reaching the target group (audience) that rejects traditional forms of promotion. There’s an explanation of differences between various types of viral marketing as well as proposed possibilities of it’s applying into a practice including the rules of campaign execution. The primary data sources, necessary for the solution of investigated issue...

  7. Veterinary field test as screening tool for mastitis and HIV-1 viral load in breastmilk from HIV-infected Zambian women.

    Science.gov (United States)

    Dorosko, Stephanie M; Thea, Donald M; Saperstein, George; Russell, Robert M; Paape, Max J; Hinckley, Lynn S; Decker, William D; Semrau, Katherine; Sinkala, Moses; Kasonde, Prisca; Kankasa, Chipepo; Aldrovandi, Grace M; Hamer, Davidson H

    2007-09-01

    Clinical and subclinical mastitis increase the risk of mother-to-child transmission (MTCT) of HIV-1 through breastfeeding. We hypothesized that a field test for mastitis used for bovine milk, the California Mastitis Test, would detect high cell counts in milk of HIV-infected women. We also investigated whether total milk cell count would positively correlate with viral HIV-1 RNA in the milk of 128 HIV-positive Zambian women. Mean cell counts in each California Mastitis Test scoring category were significantly different (p tested for HIV-1 RNA, viral RNA levels did not significantly correlate with total cell count (r = 0.166, p = .244). The CMT may serve as a screening tool for mastitis in breastmilk, but total cell count does not correlate with HIV-1 RNA levels. Since both cell-free and cell-associated virus are associated with increased risk of MTCT, investigation of the relationship between total milk cell count and HIV-1 proviral DNA is warranted before a conclusive determination is made regarding use of the CMT as a clinical screening tool to detect cases at high risk for breastmilk transmission. PMID:17903106

  8. Aerosol Delivery of a Candidate Universal Influenza Vaccine Reduces Viral Load in Pigs Challenged with Pandemic H1N1 Virus.

    Science.gov (United States)

    Morgan, Sophie B; Hemmink, Johanneke D; Porter, Emily; Harley, Ross; Shelton, Holly; Aramouni, Mario; Everett, Helen E; Brookes, Sharon M; Bailey, Michael; Townsend, Alain M; Charleston, Bryan; Tchilian, Elma

    2016-06-15

    Influenza A viruses are a major health threat to livestock and humans, causing considerable mortality, morbidity, and economic loss. Current inactivated influenza vaccines are strain specific and new vaccines need to be produced at frequent intervals to combat newly arising influenza virus strains, so that a universal vaccine is highly desirable. We show that pandemic H1N1 influenza virus in which the hemagglutinin signal sequence has been suppressed (S-FLU), when administered to pigs by aerosol can induce CD4 and CD8 T cell immune responses in blood, bronchoalveolar lavage (BAL), and tracheobronchial lymph nodes. Neutralizing Ab was not produced. Detection of a BAL response correlated with a reduction in viral titer in nasal swabs and lungs, following challenge with H1N1 pandemic virus. Intratracheal immunization with a higher dose of a heterologous H5N1 S-FLU vaccine induced weaker BAL and stronger tracheobronchial lymph node responses and a lesser reduction in viral titer. We conclude that local cellular immune responses are important for protection against influenza A virus infection, that these can be most efficiently induced by aerosol immunization targeting the lower respiratory tract, and that S-FLU is a promising universal influenza vaccine candidate. PMID:27183611

  9. VIRAL GASTROENTERITIS

    Science.gov (United States)

    Two virus types have been clearly shown to have epidemiologic importance in viral gastroenteritis, i.e., rotavirus and Norwalk virus. Four other virus types have been associated with gastroenteritis but their epidemiologic importance is not yet known, i.e., enteric adenovirus, ca...

  10. The compliance contact model of cylindrical joints with clearances

    Institute of Scientific and Technical Information of China (English)

    Caishan Liu; Ke Zhang; Lei Yang; Keren Wang

    2005-01-01

    This paper is concerned with the determination of the normal force-displacement (NFD) relation for the contact problem of cylindrical joints with clearance. A simple formulation for this contact problem is developed by modeling the pin as a rigid wedge and the elastic plate as a simple Winkler elastic foundation. The numerical results show that the normal displacement relation based on Hertz theory is only valid for the case of large clearance with a small normal load, and the NFD relation based on Persson theory is only effective in the case of very small clearance. The proposed approximate model in this paper gives better results than Hertz theory and Persson theory in a large range of clearances as seen from the comparison with the results of FEM.

  11. Association between risk factors, basal viral load, virus genotype and the degree of liver fibrosis with the response to the therapy in patients with chronic hepatitis C virus infection

    Directory of Open Access Journals (Sweden)

    Vuković Vuk R.

    2015-01-01

    Full Text Available Background/Aim. Hepatitis C is an important sociomedical problem worldwide due to frequent progression to chronic disease, occurrence of liver cirrhosis and hepatocellular carcinoma. Standard pegylated interferon alfa 2a plus ribavirin therapy results in resolution of infection only in 50% of patients. The aim of this study was to determine the association of various factors with response to the therapy in patients with chronic hepatitis C virus (HCV infection. Age and sex of patients, inoculation risk factors, histopathological changes in the liver, viral load and HCV genotype were analyzed. Methods. The study included a group of 121 patients with chronic HCV infection. The treatment was carried out 24 weeks for virus genotype 2 and 3, and 48 weeks for genotype 1 and 4. The degree of histopathological changes in the liver was determined by hematoxylin and eosin staining, whereas polimerase chain reaction was used for HCV genotyping. Results. In the group of non-responding patients genotype 1 was represented with 100%, while in the other groups, although predominantly present, its percentage was lower. Unresponsiveness to therapy and relapse of disease were associated with higher viral load and advanced fibrosis. Intravenous use of psychoactive substances, as a risk factor, was present in a high percentage in the group of patients with sustained response, while blood transfusion and dialysis were leading risk factors in the group of relapse responders and non-responders. Conclusion. The results of our study showed that the treatment outcome of chronic HCV infection was associated with baseline HCV ribonucleic acid, HCV genotype, route of infection and the degree of histopathological changes in the liver. [Projekat Ministarstva nauke Republike Srbije, br. III41010

  12. Correlation between viral load, plasma levels of CD4 - CD8 T lymphocytes and AIDS-related oral diseases: a multicentre study on 30 HIV+ children in the HAART era.

    Science.gov (United States)

    Nesti, M; Carli, E; Giaquinto, C; Rampon, O; Nastasio, S; Giuca, M R

    2012-01-01

    This experimental retrospective multicenter study carried out on 30 seropositive children treated with Highly Active Antiretroviral Therapy (HAART), between the ages of 18 months and 14 years, in the clinical categories Centers for Disease Control (CDC) classification 1993 A (mildly symptomatic), B (moderately symptomatic) and C (severely symptomatic) aims to: 1) clinically and immunologically demonstrate the therapeutic benefits of HAART; 2) monitor the frequency of AIDS-related oral diseases in seropositive children with HAART therapy; 3) monitor the plasma levels of total CD4, CD4 percent, CD8 percent, CD4-CD8 lymphocytes and viral load from 1997 to 30 April, 2011. The statistic methods used are the analysis of covariance and the Bonferroni Test. More than 100 AIDS-related oral diseases were found in the study samples, the most frequent being: oral candidiasis, oropharyngeal candidiasis, HSV-1 herpetic esophagyitis, herpetic gingivolstomatitis (RHOG), recurrent aphthous stomatitis (RAS), parotid swelling, oral hairy leukoplakia (OHL), Herpes simplex 1 (HSV-1), linear gingival erythema (LGE), necrotizing gingivitis (NUG), facial lipodistrophy, facial-cervical lymphadenopathy (FCL), xerostomia, dysgeusia, hyposmia, oral mucosa hyperpigmentation (OMP). The Bonferroni test showed a significant difference between the mean plasma values (mpVTL) of total CD4, CD4 percentage, CD4-CD8 T lymphocytes and Viral Load (VL) of the various oral diseases found in the study samples. The therapeutic benefits of HAART are: immune reconstitution; reduction of the HIV/AIDS-related stomatology diseases; prevention and cure of the AIDS correlated neoplasias; reduction in maternal-fetal transmission of the HIV virus. The negative effects of HAART in relation to odontostomatolgy are: increase in oral lesions from HPV; xerostomia; dysgeusia/ageusia, hyposmia, perioral paresthesia; hyperpigmentation of oral mucosa; facial lipodystrophy, recurrent aphthous stomatitis (RAS). No case of

  13. Development and optimization of a sensitive TaqMan® real-time PCR with synthetic homologous extrinsic control for quantitation of Human cytomegalovirus viral load.

    Science.gov (United States)

    Slavov, Svetoslav Nanev; Otaguiri, Katia Kaori; de Figueiredo, Glauciane Garcia; Yamamoto, Aparecida Yulie; Mussi-Pinhata, Marisa Marcia; Kashima, Simone; Covas, Dimas Tadeu

    2016-09-01

    Human cytomegalovirus (Human herpesvirus 5, HCMV) causes frequent asymptomatic infections in the general population. However, in immunosuppressed patients or congenitally infected infants, HCMV is related to high morbidity and mortality. In such cases, a rapid viral detection is crucial for monitoring the clinical outcome and the antiviral treatment. In this study, we optimized a sensitive biplex TaqMan® real-time PCR for the simultaneous detection and differentiation of a partial HCMV UL97 sequence and homologous extrinsic control (HEC) in the same tube. HEC was represented by a plasmid containing a modified HCMV sequence retaining the original primer binding sites, while the probe sequence was substituted by a phylogenetically divergent one (chloroplast CF0 subunit plant gene). It was estimated that the optimal HEC concentration, which did not influence the HCMV amplification is 1,000 copies/reaction. The optimized TaqMan® PCR demonstrated high analytical sensitivity (6.97 copies/reaction, CI = 95%) and specificity (100%). Moreover, the reaction showed adequate precision (repeatability, CV = 0.03; reproducibility, CV = 0.0027) and robustness (no carry-over or cross-contamination). The diagnostic sensitivity (100%) and specificity (97.8%) were adequate for the clinical application of the molecular platform. The optimized TaqMan® real-time PCR is suitable for HCMV detection and quantitation in predisposed patients and monitoring of the applied antiviral therapy. J. Med. Virol. 88:1604-1612, 2016. © 2016 Wiley Periodicals, Inc. PMID:26890091

  14. Dynamic changes of dengue viral loads and IgM antibody and their relationships with disease severity%登革病毒载量和IgM抗体水平与疾病严重程度的关系

    Institute of Scientific and Technical Information of China (English)

    赵令斋; 高秀洁; 庾蕾; 洪文昕; 邱爽; 王建; 张复春

    2016-01-01

    Objective To investigate the dynamic changes of dengue viral loads and IgM antibody in patients with dengue fever ( DF) and to analyze their relationships with disease severity. Methods A to-tal of 1 508 serum samples were collected from 1 140 hospitalized patients including 1 050 mild cases and 90 severe cases within 10 days after the onset of DF in Guangzhou in 2014. The viral loads were determined by using fluorescence quantitative RT-PCR. ELISA was performed to measure the dengue virus ( DENV)-spe-cific IgM antibody. Results In general, the DENV viral loads in patients declined gradually from 108 copies/ml on day 1 to 103 copies/ml on day 10 after the onset of DF. The viral loads in severe cases were significantly higher than those in mild cases on days 5 to 7 (P<0. 05). The positive rates of DENV RNA in serum samples also decreased with the disease progression from 100% on day 1 to 40% on day 10. Com-pared with the mild cases, the patients with severe DF showed higher positive rates of DENV RNA on day 6 and day 8 (P<0. 05). The DENV-specific IgM antibody could be detected on day 2 and the secretion of IgM antibody increased gradually with the disease progression. The levels of IgM antibody in mild cases were sig-nificantly higher than those in severe cases (P<0. 001). The positive rates of IgM antibody in patients in-creased form 8% on day 2 to 95% on day 6. Higher positive rates of IgM antibody were detected in mild ca-ses on days 5 and 6 as compared with those in patients with severe DF (P<0. 05). Conclusion High viral load and low level of IgM antibody during the fastigium of DF were closely associated with the disease severity.%目的:探讨登革热( dengue fever ,DF)患者病毒载量和特异性IgM抗体在疾病过程中的动态变化规律及其与疾病严重程度的相关性。方法收集1140例DF患者(其中轻症1050例,重症90例)发病第1~10天的血清1508份,用荧光定量PCR法检测病毒载量,ELISA法检

  15. High Viral Loads of Epstein-Barr Virus DNA in Peripheral Blood of Patients with Chronic Lymphocytic Leukemia Associated with Unfavorable Prognosis.

    Science.gov (United States)

    Grywalska, Ewelina; Roliński, Jacek; Pasiarski, Marcin; Korona-Glowniak, Izabela; Maj, Maciej; Surdacka, Agata; Grafka, Agnieszka; Stelmach-Gołdyś, Agnieszka; Zgurski, Michał; Góźdź, Stanisław; Malm, Anna; Grabarczyk, Piotr; Starosławska, Elżbieta

    2015-01-01

    Epstein-Barr virus (EBV) is a ubiquitous γ-herpesvirus that infects more than 90% of the world population. The potential involvement of EBV in the clinical course of chronic lymphocytic leukemia (CLL) remains unexplained. The aim of this study was to determine whether EBV-DNA load in the peripheral blood mononuclear cells (PBMCs) of CLL patients may influence heterogeneity in the course of the disease. The study included peripheral blood samples from 115 previously untreated patients with CLL (54 women and 61 men) and 40 healthy controls (16 women and 24 men). We analyzed the association between the EBV-DNA load in PBMCs and the stage of the disease, adverse prognostic factors, and clinical outcome. Detectable numbers of EBV-DNA copies in PBMCs were found in 62 out of 115 CLL patients (53.91%). The EBV-DNA copy number/μg DNA was significantly higher in patients who required early implementation of treatment, presented with lymphocyte count doubling time <12 months, displayed CD38-positive or ZAP-70-positive phenotype, and with the del(11q22.3) cytogenetic abnormality. Furthermore, the EBV-DNA copy number/μg DNA showed significant positive correlation with the concentrations of lactate dehydrogenase (LDH) and beta-2-microglobulin. We have shown that in CLL patients, higher EBV-DNA copy number predicted shorter survival and shorter time to disease progression, and it was associated with other established unfavorable prognostic factors. This suggests that EBV may negatively affect the outcome of CLL.

  16. High Viral Loads of Epstein-Barr Virus DNA in Peripheral Blood of Patients with Chronic Lymphocytic Leukemia Associated with Unfavorable Prognosis.

    Directory of Open Access Journals (Sweden)

    Ewelina Grywalska

    Full Text Available Epstein-Barr virus (EBV is a ubiquitous γ-herpesvirus that infects more than 90% of the world population. The potential involvement of EBV in the clinical course of chronic lymphocytic leukemia (CLL remains unexplained. The aim of this study was to determine whether EBV-DNA load in the peripheral blood mononuclear cells (PBMCs of CLL patients may influence heterogeneity in the course of the disease. The study included peripheral blood samples from 115 previously untreated patients with CLL (54 women and 61 men and 40 healthy controls (16 women and 24 men. We analyzed the association between the EBV-DNA load in PBMCs and the stage of the disease, adverse prognostic factors, and clinical outcome. Detectable numbers of EBV-DNA copies in PBMCs were found in 62 out of 115 CLL patients (53.91%. The EBV-DNA copy number/μg DNA was significantly higher in patients who required early implementation of treatment, presented with lymphocyte count doubling time <12 months, displayed CD38-positive or ZAP-70-positive phenotype, and with the del(11q22.3 cytogenetic abnormality. Furthermore, the EBV-DNA copy number/μg DNA showed significant positive correlation with the concentrations of lactate dehydrogenase (LDH and beta-2-microglobulin. We have shown that in CLL patients, higher EBV-DNA copy number predicted shorter survival and shorter time to disease progression, and it was associated with other established unfavorable prognostic factors. This suggests that EBV may negatively affect the outcome of CLL.

  17. 核酸检测中HIV病毒载量对内质控扩增的影响%Effects of HIV viral load on internal control amplification by using NAT technique

    Institute of Scientific and Technical Information of China (English)

    余谨; 毕昊; 陆华新; 王先广; 赵磊; 沈钢

    2012-01-01

    目的 评估酶联免疫法的窗口期HIV血样.方法 将酶联免疫法阴性标本采用六混样用2种试剂进行平行核酸检测,在检测出阳性标本后,亦用2种试剂对其拆分进行单管核酸检测.结果 10个月内共筛查16769例酶联免疫阴性标本中,核酸检测出1例HIV阳性标本,罗氏一代试剂由于该标本病毒载量浓度过高体现出抑制作用,罗氏二代试剂未显示出抑制作用.结论 目前现行开展的检测技术仍有安全隐患,为进一步保证临床用血的安全,开展核酸检测可以提高临床用血质量,为临床安全用血提供强有力的保障.%Objective To determine the prevalence of viral infections (HBV.HCV and HIV) in serological window period in blood donors screened with nucleic acid testing (NAT) . Methods All blood donors were tested with serological tests( Ag-HBVs,Anti-HCV and Anti-HIV)and molecular testing with NAT by PP6 and rPPl for HBV.HCV and HIV. The window period was defined with the positive NAT and negative serological test. Results During ten months, we evaluated 16 769 blood donors. One subject was identified with HIV in serological window period. HIV viral load has the effect on internal control amplification by using NAT technique. Conclusion Unsafe blood in the performance of viral infections due to HIV in serological window period in donors by using NAT technique.

  18. Factors Associated with Spontaneous Clearance of Hepatitis C Virus in Chinese Population

    Directory of Open Access Journals (Sweden)

    Fei Kong

    2014-01-01

    Full Text Available Hepatitis C virus (HCV infections spontaneously clear in approximately 15–45% of infected individuals. Factors which influence spontaneous HCV clearance remain to be identified. The purpose of the present study was to identify variables associated with spontaneous HCV clearance in a referred population of Chinese patients. The prevalence of host, viral, and environmental factors known to influence the outcome of HCV infections was compared in 92 HCV spontaneous clearance subjects and 318 HCV persistent infection subjects. Univariate and multivariate analyses were performed to identify those factors associated with spontaneous HCV clearance. In univariate analysis, female gender, a history of icteric hepatitis, serologic evidence of concurrent HBV infection, and rs12979860 CC genotype were positively associated with spontaneous HCV clearance, while alcohol consumption was negatively associated with clearance. In multivariate analysis, female gender, a history of icteric hepatitis, concurrent HBV infection, and rs12979860 CC genotype remained independent variables associated with spontaneous HCV clearance. Spontaneous HCV clearance is more likely to occur in females, subjects with a history of icteric hepatitis, HBV coinfections, and those with the rs12979860 CC genotype.

  19. Longer duration of homelessness is associated with a lower likelihood of non-detectable plasma HIV-1 RNA viral load among people who use illicit drugs in a Canadian setting.

    Science.gov (United States)

    Loh, Jane; Kennedy, Mary Clare; Wood, Evan; Kerr, Thomas; Marshall, Brandon; Parashar, Surita; Montaner, Julio; Milloy, M-J

    2016-11-01

    Homelessness is common among people who use drugs (PWUD) and, for those living with HIV/AIDS, an important contributor to sub-optimal HIV treatment outcomes. This study aims to investigate the relationship between the duration of homelessness and the likelihood of plasma HIV-1 RNA viral load (VL) non-detectability among a cohort of HIV-positive PWUD. We used data from the ACCESS study, a long-running prospective cohort study of HIV-positive PWUD linked to comprehensive HIV clinical records including systematic plasma HIV-1 RNA VL monitoring. We estimated the longitudinal relationship between the duration of homelessness and the likelihood of exhibiting a non-detectable VL (i.e., homeless in 910 (11%) interviews (median: six months, interquartile range: 6-12 months). A longer duration of homelessness was associated with lower odds of VL non-detectability (adjusted odds ratio = 0.71 per six-month period of homelessness, 95% confidence interval: 0.60-0.83) after adjustment for age, ancestry, drug use patterns, engagement in addiction treatment, and other potential confounders. Longer durations of episodes of homelessness in this cohort of HIV-positive illicit drug users were associated with a lower likelihood of plasma VL non-detectability. Our findings suggest that interventions that seek to promptly house homeless individuals, such as Housing First approaches, might assist in maximizing the clinical and public health benefits of antiretroviral therapy among people living with HIV/AIDS. PMID:27248328

  20. Lithium clearance in chronic nephropathy

    DEFF Research Database (Denmark)

    Kamper, A L; Holstein-Rathlou, N H; Leyssac, P P;

    1989-01-01

    1. Lithium clearance measurements were made in 72 patients with chronic nephropathy of different aetiology and moderate to severely reduced renal function. 2. Lithium clearance was strictly correlated with glomerular filtration rate, and there was no suggestion of distal tubular reabsorption of...... lithium or influence of osmotic diuresis. 3. Fractional reabsorption of lithium was reduced in most patients with glomerular filtration rates below 25 ml/min. 4. Calculated fractional distal reabsorption of sodium was reduced in most patients with glomerular filtration rates below 50 ml/min. 5. Lithium...... lithium clearance may be a measure of the delivery of sodium and water from the renal proximal tubule. With this assumption it was found that adjustment of the sodium excretion in chronic nephropathy initially takes place in the distal parts of the nephron (loop of Henle, distal tubule and collecting duct...

  1. Lactate clearance in cardiorespiratory emergency

    Directory of Open Access Journals (Sweden)

    Serena Greco

    2007-08-01

    Full Text Available Early goal directed therapy has been found to improve prognosis in septic patients, if the therapeutic goal is achieved within the first six hours. The aim of our study is to demonstrate that in patients with acute cardiorespiratory failure, rapid (within 2 hours lactate clearance can help define patients’ prognosis. 67 consecutive patients, admitted to our 16-bed Emergency Medicine ward for acute cardiorespiratory failure (age 75,9 ± 9,8 (APACHE II score 19,0 ± 4,1, were included in the study. Blood lactate concentration was read at admission and after 2, 6 and 24 hours. We evaluated mortality at seven days and the use of orotracheal intubation (patients with negative outcome vs. discharge or transfer to a non-emergency ward with subsequent discharge (patients with negative outcome. Lactate concentration at admission was 4,6 ± 2,5 mmol/l; lactate clearance (% at 2 hours was 40,4 ± 32,1 in patients with a positive outcome and –8,3 ± 5,0 in patients with a negative outcome (p < 0,05. Lactate clearance at 2 hours < 25% is correlated to a negative outcome with an 84,2% sensitivity and a 79,2% specificity. The positive predictive value was 61,5% and the negative predictive value was 92,2%. Systematic lactate clearance monitoring can be used in cases of acute cardiorespiratory insufficiency to identify patients with a high risk of negative outcome. In our study, low clearance at two hours was associated with an increase in mortality and/or the need for orotracheal intubation. Conversely, a clearance at two hours of > 25% in most cases confirms the therapeutic strategy undertaken. Serial evaluation of blood lactate concentration may therefore be useful in guiding treatment strategies.

  2. Numerical analysis of bump foil bearings without nominal radial clearance

    Institute of Scientific and Technical Information of China (English)

    LIU Zhan-sheng; XU Huai-jin; ZHANG Guang-hui

    2008-01-01

    Bump foil bearings without nominal radial clearance were analyzed. An air film thickness model and a bearing theoretical analytical model were developed accounting for air compressibility and foil deformation. To analyze hydrodynamic characteristics of bump foil beatings with different operating eccentricities, the air film thickness equation and Reynolds equation were coupled through pressure and solved by Newton-Raphson Method(NRM) and Finite Difference Method (FDM). The characteristics of an bump foil bearing model were dis-cussed including load carrying capacity, film thickness and pressure distributions. The results of simulation show that bump foil beating without nominal radial clearance can provide better stability and greater load capaci-ty. This numerical analytical method also reveals a good convergence in numerical calculation.

  3. Noninvasive clearance of airway secretions.

    Science.gov (United States)

    Hardy, K A; Anderson, B D

    1996-06-01

    Airway clearance techniques are indicated for specific diseases that have known clearance abnormalities (Table 2). Murray and others have commented that such techniques are required only for patients with a daily sputum production of greater than 30 mL. The authors have observed that patients with diseases known to cause clearance abnormalities can have sputum clearance with some techniques, such as positive expiratory pressure, autogenic drainage, and active cycle of breathing techniques, when PDPV has not been effective. Hasani et al has shown that use of the forced exhalatory technique in patients with nonproductive cough still resulted in movement of secretions proximally from all regions of the lung in patients with airway obstruction. It is therefore reasonable to consider airway clearance techniques for any patient who has a disease known to alter mucous clearance, including CF, dyskinetic cilia syndromes, and bronchiectasis from any cause. Patients with atelectasis from mucous plugs and hypersecretory states, such as asthma and chronic bronchitis, patients with pain secondary to surgical procedures, and patients with neuromuscular disease, weak cough, and abnormal patency of the airway may also benefit from the application of airway clearance techniques. Infants and children up to 3 years of age with airway clearance problems need to be treated with PDPV. Manual percussion with hands alone or a flexible face mask or cup and small mechanical vibrator/percussors, such as the ultrasonic devices, can be used. The intrapulmonary percussive ventilator shows growing promise in this area. The high-frequency oscillator is not supplied with vests of appropriate sizes for tiny babies and has not been studied in this group. Young patients with neuromuscular disease may require assisted ventilation and airway oscillations can be applied. CPAP alone has been shown to improve achievable flow rates that will increase air-liquid interactions for patients with these diseases

  4. Evaluation of the Aptima(®) HIV-1 Quant Dx assay for HIV-1 RNA viral load detection and quantitation in plasma of HIV-1-infected individuals: A comparison with Abbott RealTime HIV-1 assay.

    Science.gov (United States)

    Amendola, Alessandra; Pisciotta, Maria; Aleo, Loredana; Ferraioli, Valeria; Angeletti, Claudio; Capobianchi, Maria Rosaria

    2016-09-01

    The Hologic Aptima(®) HIV-1 Quant Dx assay (Aptima HIV) is a real-time transcription-mediated amplification method CE-approved for use in diagnosis and monitoring of HIV-1 infection. The analytical performance of this new assay was compared to the FDA-approved Abbott RealTime HIV-1 (RealTime). The evaluation was performed using 220 clinical plasma samples, the WHO 3rd HIV-1 International Standard, and the QCMD HIV-1 RNA EQA. Concordance on qualitative results, correlation between quantitative results, accuracy, and reproducibility of viral load data were analyzed. The ability to measure HIV-1 subtypes was assessed on the second WHO International Reference Preparation Panel for HIV-1 Subtypes. With clinical samples, inter-assay agreement for qualitative results was high (91.8%) with Cohen's kappa statistic equal to 0.836. For samples with quantitative results in both assays (n = 93), Lin's concordance correlation coefficient was 0.980 (P R(2)  > 0.970) and showed higher sensitivity compared to RealTime being able to detect HIV-1 RNA in 10 out of 10 replicates containing down to 7 cp/ml (20 IU/ml). Reproducibility was very high, even at low HIV-1 RNA values. The Aptima HIV was able to detect and accurately quantify all the main HIV-1 subtypes in both reference panels and clinical samples. Besides excellent performance, Aptima HIV shows full automation, ease of use, and improved workflow compared to RealTime. J. Med. Virol. 88:1535-1544, 2016. © 2016 Wiley Periodicals, Inc. PMID:26864171

  5. Comparison of HPV detection technologies: Hybrid capture 2, PreTect HPV-Proofer and analysis of HPV DNA viral load in HPV16, HPV18 and HPV33 E6/E7 mRNA positive specimens.

    LENUS (Irish Health Repository)

    Keegan, Helen

    2012-02-01

    Human papillomavirus (HPV) testing using molecular methods in liquid based cytology (LBC) specimens may be useful as an adjunct to cervical screening by cytology. We compared the positivity rate of the commercially available HPV DNA method hybrid capture 2 (hc2) and the commercially available E6\\/E7 mRNA method PreTect HPV-Proofer in cytological specimens (n=299). LBC specimens collected (n=299) represented the following cervical cytological disease categories: Normal (n=60), borderline nuclear abnormalities (BNA) (n=34), CIN1 (n=121), CIN2 (n=60), CIN3 (n=24). Overall, 69% (205\\/299) of the cases were positive by hc2 and 38% (112\\/299) of the cases were positive by PreTect HPV-Proofer. Concordance rates between the two tests were highest in the high-grade cytology cases (CIN2: 67% and CIN3: 83%) and the normal cytology cases (88%) and lowest in the BNA and CIN1 categories (56% and 52%). HPV DNA viral load analyses were carried out on HPV16 (n=55), HPV18 (n=9) and HPV33 (n=13) samples that were positive by PreTect HPV-Proofer. The sensitivity and specificity of PreTect HPV-Proofer and the hc2 DNA test for the detection of high-grade cytology (i.e. CIN2+) were 71.4% and 75.8% vs 100% and 43.7%, respectively. The relatively low detection rate observed by PreTect HPV-Proofer in the whole range of cytological positive cases, combined with a relatively higher specificity and PPV, suggests that PreTect HPV-Proofer may be more useful than hc2 for triage and in predicting high-grade disease.

  6. Inadequate clearance of translocated bacterial products in HIV-infected humanized mice.

    Directory of Open Access Journals (Sweden)

    Ursula Hofer

    2010-04-01

    Full Text Available Bacterial translocation from the gut and subsequent immune activation are hallmarks of HIV infection and are thought to determine disease progression. Intestinal barrier integrity is impaired early in acute retroviral infection, but levels of plasma lipopolysaccharide (LPS, a marker of bacterial translocation, increase only later. We examined humanized mice infected with HIV to determine if disruption of the intestinal barrier alone is responsible for elevated levels of LPS and if bacterial translocation increases immune activation. Treating uninfected mice with dextran sodium sulfate (DSS induced bacterial translocation, but did not result in elevated plasma LPS levels. DSS-induced translocation provoked LPS elevation only when phagocytic cells were depleted with clodronate liposomes (clodrolip. Macrophages of DSS-treated, HIV-negative mice phagocytosed more LPS ex vivo than those of control mice. In HIV-infected mice, however, LPS phagocytosis was insufficient to clear the translocated LPS. These conditions allowed higher levels of plasma LPS and CD8+ cell activation, which were associated with lower CD4+/CD8+ cell ratios and higher viral loads. LPS levels reflect both intestinal barrier and LPS clearance. Macrophages are essential in controlling systemic bacterial translocation, and this function might be hindered in chronic HIV infection.

  7. A randomized, controlled, molecular study of condylomata acuminata clearance during treatment with imiquimod.

    Science.gov (United States)

    Tyring, S K; Arany, I; Stanley, M A; Tomai, M A; Miller, R L; Smith, M H; McDermott, D J; Slade, H B

    1998-08-01

    Imiquimod, an immune response modifier, has been demonstrated to be safe and effective in the treatment of external genital and perianal warts caused by human papillomavirus (HPV). To identify the molecular mechanism(s) by which condylomata acuminata clear during topical treatment with imiquimod, wart skin biopsies were taken from patients before treatment, at treatment week 6, and at the end of treatment. Tissues were analyzed for HPV DNA and for mRNA of several cytokines and HPV gene products. Wart clearance was associated with evidence of tissue production of interferon-alpha, -beta, and -gamma and tumor necrosis factor-alpha. Regression of warts was strongly associated with a decrease in HPV DNA and in mRNA expression for both early and late viral proteins. Thus, topical imiquimod treatment of anogenital warts led to significant increases in local production of multiple interferon mRNAs and a significant reduction in virus load as measured by decreases in HPV DNA and mRNA for early HPV proteins.

  8. HIV-1 and T cell dynamics after interruption of highly active antiretroviral therapy (HAART) in patients with a history of sustained viral suppression

    Science.gov (United States)

    Davey, Richard T.; Bhat, Niranjan; Yoder, Christian; Chun, Tae-Wook; Metcalf, Julia A.; Dewar, Robin; Natarajan, Ven; Lempicki, Richard A.; Adelsberger, Joseph W.; Miller, Kirk D.; Kovacs, Joseph A.; Polis, Michael A.; Walker, Robert E.; Falloon, Judith; Masur, Henry; Gee, Dennis; Baseler, Michael; Dimitrov, Dimiter S.; Fauci, Anthony S.; Lane, H. Clifford

    1999-01-01

    Identifying the immunologic and virologic consequences of discontinuing antiretroviral therapy in HIV-infected patients is of major importance in developing long-term treatment strategies for patients with HIV-1 infection. We designed a trial to characterize these parameters after interruption of highly active antiretroviral therapy (HAART) in patients who had maintained prolonged viral suppression on antiretroviral drugs. Eighteen patients with CD4+ T cell counts ≥ 350 cells/μl and viral load below the limits of detection for ≥1 year while on HAART were enrolled prospectively in a trial in which HAART was discontinued. Twelve of these patients had received prior IL-2 therapy and had low frequencies of resting, latently infected CD4 cells. Viral load relapse to >50 copies/ml occurred in all 18 patients independent of prior IL-2 treatment, beginning most commonly during weeks 2–3 after cessation of HAART. The mean relapse rate constant was 0.45 (0.20 log10 copies) day−1, which was very similar to the mean viral clearance rate constant after drug resumption of 0.35 (0.15 log10 copies) day−1 (P = 0.28). One patient experienced a relapse delay to week 7. All patients except one experienced a relapse burden to >5,000 RNA copies/ml. Ex vivo labeling with BrdUrd showed that CD4 and CD8 cell turnover increased after withdrawal of HAART and correlated with viral load whereas lymphocyte turnover decreased after reinitiation of drug treatment. Virologic relapse occurs rapidly in patients who discontinue suppressive drug therapy, even in patients with a markedly diminished pool of resting, latently infected CD4+ T cells. PMID:10611346

  9. 49 CFR 192.325 - Underground clearance.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Underground clearance. 192.325 Section 192.325... Lines and Mains § 192.325 Underground clearance. (a) Each transmission line must be installed with at least 12 inches (305 millimeters) of clearance from any other underground structure not associated...

  10. 30 CFR 18.24 - Electrical clearances.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Electrical clearances. 18.24 Section 18.24... APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Construction and Design Requirements § 18.24 Electrical clearances. Minimum clearances between uninsulated electrical...

  11. 14 CFR 25.925 - Propeller clearance.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Propeller clearance. 25.925 Section 25.925 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY AIRPLANES Powerplant General § 25.925 Propeller clearance. Unless smaller clearances are substantiated,...

  12. [Viral superantigens].

    Science.gov (United States)

    Us, Dürdal

    2016-07-01

    , expression of endogenous SAgs leads to thymic deletion of responding T cells (bearing Vβ6-9+ TCR) due to self-tolerance induction during the fetal life, and protects the host against future exogenous MMTV infections. The SAg of rabies virus is the N protein found in nucleocapsid structure and stimulates Vβ8+TCR-bearing T cells. The SAg-induced polyclonal activation of T cells leads to turn-off the specific immune response, to enhance the immunopathogenesis and facilitates viral transmission from the initial site of infection (the muscle tissue) to the nerve endings. In case of EBV-associated SAg that activates Vβ13+TCR-bearing T cells, it was detected that the SAg activity was not encoded by EBV itself, but instead was due to the transactivation of HERV-K18 by EBV latent membrane proteins, whose env gene encodes the SAg (Sutkowski, et al. 2001). It has been denoted that EBV-induced SAg expression plays a role in the long-term persistence and latency of virus in memory B cells, in the development of autoimmune diseases and in the oncogenesis mechanisms. The proteins which are identified as SAgs of HIV are Nef and gp120. It is believed that, the massive activation of CD4+ T cells (selectively with Vβ-12+, Vβ-5.3+ and Vβ-18+ TCRs) in early stages of infection and clonal deletion, anergy and apoptosis of bystander T cells in the late stages may be due to SAg property of Nef protein, as well as the other mechanisms. However there are some studies indicating that Nef does not act as a SAg (Lapatschek, et al. 2001). HIV gp120 glycoprotein is a B-cell SAg that binds to VH3-expressing B cell receptors and causes polyclonal B cell activation. In addition, binding of gp120 to IgE on the surface of basophiles and mast cells causes activation of those cells, secretion of high level proinflammatory mediators leading to allergic reactions and tissue damage. In a recent study, the depletion (anergy or deletion) of T cell populations bearing Vβ12+, Vβ13+ and Vβ17+ TCR have been

  13. Analysis of grease contamination influence on the internal radial clearance of ball bearings by thermographic inspection

    OpenAIRE

    Mišković Žarko Z.; Mitrović Radivoje M.; Stamenić Zoran V.

    2016-01-01

    One of the most important factors influencing ball bearings service life is its internal radial clearance. However, this parameter is also very complex because it depends on applied radial load and ball bearings dimensions, surface finish and manufacturing materials. Thermal condition of ball bearings also significantly affects internal radial clearance. Despite many researches performed in order to find out relevant facts about different aspects of ball be...

  14. A novel approach to achieving modular retrovirus clearance for a parvovirus filter.

    Science.gov (United States)

    Stuckey, Juliana; Strauss, Daniel; Venkiteshwaran, Adith; Gao, Jinxin; Luo, Wen; Quertinmont, Michelle; O'Donnell, Sean; Chen, Dayue

    2014-01-01

    Viral filtration is routinely incorporated into the downstream purification processes for the production of biologics produced in mammalian cell cultures (MCC) to remove potential viral contaminants. In recent years, the use of retentive filters designed for retaining parvovirus (~20 nm) has become an industry standard in a conscious effort to further improve product safety. Since retentive filters remove viruses primarily by the size exclusion mechanism, it is expected that filters designed for parvovirus removal can effectively clear larger viruses such as retroviruses (~100 nm). In an attempt to reduce the number of viral clearance studies, we have taken a novel approach to demonstrate the feasibility of claiming modular retrovirus clearance for Asahi Planova 20N filters. Porcine parvovirus (PPV) and xenotropic murine leukemia virus (XMuLV) were co-spiked into six different feedstreams and then subjected to laboratory scale Planova 20N filtration. Our results indicate that Planova 20N filters consistently retain retroviruses and no retrovirus has ever been detected in the filtrates even when significant PPV breakthrough is observed. Based on the data from multiple in-house viral validation studies and the results from the co-spiking experiments, we have successfully claimed a modular retrovirus clearance of greater than 6 log10 reduction factors (LRF) to support clinical trial applications in both USA and Europe.

  15. Principles underlying the epizootiology of viral hemorrhagic septicemia in Pacific herring and other fishes throughout the North Pacific Ocean

    Science.gov (United States)

    Hershberger, Paul K.; Garver, Kyle A.; Winton, James R.

    2016-01-01

    Although viral hemorrhagic septicemia virus (VHSV) typically occurs at low prevalence and intensity in natural populations of Pacific herring (Clupea pallasii) and other marine fishes in the Northeast Pacific Ocean, epizootics of the resulting disease (VHS) periodically occur, often in association with observed fish kills. Here we identify a list of principles, based on a combination of field studies, controlled laboratory experiments, and previously unpublished observations, that govern the epizootiology of VHS in Pacific herring. A thorough understanding of these principles provides the basis for identifying risk factors that predispose certain marine fish populations to VHS epizootics, including the lack of population resistance, presence of chronic viral carriers in a population, copious viral shedding by infected individuals, cool water temperatures, limited water circulation patterns, and gregarious host behavioral patterns. Further, these principles are used to define the epizootiological stages of the disease in Pacific herring, including the susceptible (where susceptible individuals predominate a school or subpopulation), enzootic (where infection prevalence and intensity are often below the limits of reasonable laboratory detection), disease amplification (where infection prevalence and intensity increase rapidly), outbreak (often accompanied by host mortalities with high virus loads and active shedding), recovery (in which the mortality rate and virus load decline owing to an active host immune response), and refractory stages (characterized by little or no susceptibility and where viral clearance occurs in most VHS survivors). In addition to providing a foundation for quantitatively assessing the potential risks of future VHS epizootics in Pacific herring, these principles provide insights into the epizootiology of VHS in other fish communities where susceptible species exist.

  16. Reduced erythrocyte susceptibility and increased host clearance of young parasites slows Plasmodium growth in a murine model of severe malaria

    Science.gov (United States)

    Khoury, David S.; Cromer, Deborah; Best, Shannon E.; James, Kylie R.; Sebina, Ismail; Haque, Ashraful; Davenport, Miles P.

    2015-05-01

    The best correlate of malaria severity in human Plasmodium falciparum (Pf) infection is the total parasite load. Pf-infected humans could control parasite loads by two mechanisms, either decreasing parasite multiplication, or increasing parasite clearance. However, few studies have directly measured these two mechanisms in vivo. Here, we have directly quantified host clearance of parasites during Plasmodium infection in mice. We transferred labelled red blood cells (RBCs) from Plasmodium infected donors into uninfected and infected recipients, and tracked the fate of donor parasites by frequent blood sampling. We then applied age-based mathematical models to characterise parasite clearance in the recipient mice. Our analyses revealed an increased clearance of parasites in infected animals, particularly parasites of a younger developmental stage. However, the major decrease in parasite multiplication in infected mice was not mediated by increased clearance alone, but was accompanied by a significant reduction in the susceptibility of RBCs to parasitisation.

  17. Is There a Need for Viral Load Testing to Assess Treatment Failure in HIV-Infected Patients Who Are about to Change to Tenofovir-Based First-Line Antiretroviral Therapy? Programmatic Findings from Myanmar

    Science.gov (United States)

    Thiha, Nay; Chinnakali, Palanivel; Harries, Anthony D.; Shwe, Myint; Balathandan, Thanumalaya Perumal; Thein Than Tun, Sai; Das, Mrinalini; Tin, Htay Htay; Yi, Yi; Babin, François Xavier; Lwin, Thi Thi; Clevenbergh, Philippe Albert

    2016-01-01

    Background WHO recommends that stavudine is phased out of antiretroviral therapy (ART) programmes and replaced with tenofovir (TDF) for first-line treatment. In this context, the Integrated HIV Care Program, Myanmar, evaluated patients for ART failure using HIV RNA viral load (VL) before making the change. We aimed to determine prevalence and determinants of ART failure in those on first-line treatment. Methods Patients retained on stavudine-based or zidovudine-based ART for >12 months with no clinical/immunological evidence of failure were offered VL testing from August 2012. Plasma samples were tested using real time PCR. Those with detectable VL>250 copies/ml on the first test were provided with adherence counseling and three months later a second test was performed with >1000 copies/ml indicating ART failure. We calculated the prevalence of ART failure and adjusted relative risks (aRR) to identify associated factors using log binomial regression. Results Of 4934 patients tested, 4324 (87%) had an undetectable VL at the first test while 610 patients had a VL>250 copies/ml. Of these, 502 had a second VL test, of whom 321 had undetectable VL and 181 had >1000 copies/ml signifying ART failure. There were 108 who failed to have the second test. Altogether, there were 94% with an undetectable VL, 4% with ART failure and 2% who did not follow the VL testing algorithm. Risk factors for ART failure were age 15–24 years (aRR 2.4, 95% CI: 1.5–3.8) compared to 25–44 years and previous ART in the private sector (aRR 1.6, 95% CI: 1.2–2.2) compared to the public sector. Conclusions This strategy of evaluating patients on first-line ART before changing to TDF was feasible and identified a small proportion with ART failure, and could be considered by HIV/AIDS programs in Myanmar and other countries. PMID:27505228

  18. Sensitive detection of viral transcripts in human tumor transcriptomes.

    Directory of Open Access Journals (Sweden)

    Sven-Eric Schelhorn

    Full Text Available In excess of 12% of human cancer incidents have a viral cofactor. Epidemiological studies of idiopathic human cancers indicate that additional tumor viruses remain to be discovered. Recent advances in sequencing technology have enabled systematic screenings of human tumor transcriptomes for viral transcripts. However, technical problems such as low abundances of viral transcripts in large volumes of sequencing data, viral sequence divergence, and homology between viral and human factors significantly confound identification of tumor viruses. We have developed a novel computational approach for detecting viral transcripts in human cancers that takes the aforementioned confounding factors into account and is applicable to a wide variety of viruses and tumors. We apply the approach to conducting the first systematic search for viruses in neuroblastoma, the most common cancer in infancy. The diverse clinical progression of this disease as well as related epidemiological and virological findings are highly suggestive of a pathogenic cofactor. However, a viral etiology of neuroblastoma is currently contested. We mapped 14 transcriptomes of neuroblastoma as well as positive and negative controls to the human and all known viral genomes in order to detect both known and unknown viruses. Analysis of controls, comparisons with related methods, and statistical estimates demonstrate the high sensitivity of our approach. Detailed investigation of putative viral transcripts within neuroblastoma samples did not provide evidence for the existence of any known human viruses. Likewise, de-novo assembly and analysis of chimeric transcripts did not result in expression signatures associated with novel human pathogens. While confounding factors such as sample dilution or viral clearance in progressed tumors may mask viral cofactors in the data, in principle, this is rendered less likely by the high sensitivity of our approach and the number of biological replicates

  19. Experimental Investigation of Factors Influencing Operating Rotor Tip Clearance in Multistage Compressors

    Directory of Open Access Journals (Sweden)

    Reid A. Berdanier

    2015-01-01

    Full Text Available An analysis of compressor rotor tip clearance measurements using capacitance probe instrumentation is discussed for a three-stage axial compressor. Thermal variations and centrifugal effects related to rotational speed changes affect clearance heights relative to the assembled configuration. These two primary contributions to measured changes are discussed both independently and in combination. Emphasis is given to tip clearance changes due to changing loading condition and at several compressor operating speeds. Measurements show a tip clearance change approaching 0.1 mm (0.2% rotor span when comparing a near-choke operating condition to a near-stall operating condition for the third stage. Additional consideration is given to environmental contributions such as ambient temperature, for which changes in tip clearance height on the order of 0.05 mm (0.1% rotor span were noted for temperature variations of 15°C. Experimental compressor operating clearances are presented for several temperatures, operating speeds, and loading conditions, and comparisons are drawn between these measured variations and predicted changes under the same conditions.

  20. Effect of clearance on cartilage tribology in hip hemi-arthroplasty.

    Science.gov (United States)

    Lizhang, Jia; Taylor, Simon D; Jin, Zhongmin; Fisher, John; Williams, Sophie

    2013-12-01

    Hemi-arthroplasty of the hip (an artificial femoral head articulating against the natural acetabulum) is used to treat fractured necks of femur; however, there is evidence that articulation causes erosion of the cartilage, resulting in pain for the patient. Parameters that may influence this cartilage erosion include head material and roughness, clearance between the head and acetabulum and activity levels of the patient. This study has assessed the effect of clearance of hemi-arthroplasty articulations on the contact stress, friction and cartilage deformation in an in vitro tribological simulation of the hemi-arthroplasty joint that applied dynamic loads and motion. It has been demonstrated that peak contact stress increased from 5.6 to 10.6 MPa as radial clearance increased from small (1.8 mm). In all samples, friction factor increased with time and was significantly less with extra-large clearances compared to small (<0.6 mm), medium (0.6-1.2 mm) and large (1.2-1.8 mm) clearances. The cartilage deformation observed was significantly greater in acetabulum samples paired to give small or extra-large clearances compared to those with medium or large clearances.

  1. TNFα Impairs Rhabdoviral Clearance by Inhibiting the Host Autophagic Antiviral Response

    Science.gov (United States)

    Roca, Francisco J.; López-Muñoz, Azucena; Tyrkalska, Sylwia D.; Candel, Sergio; García-Moreno, Diana; Falco, Alberto; Meseguer, José

    2016-01-01

    TNFα is a pleiotropic pro-inflammatory cytokine with a key role in the activation of the immune system to fight viral infections. Despite its antiviral role, a few viruses might utilize the host produced TNFα to their benefit. Some recent reports have shown that anti-TNFα therapies could be utilized to treat certain viral infections. However, the underlying mechanisms by which TNFα can favor virus replication have not been identified. Here, a rhabdoviral infection model in zebrafish allowed us to identify the mechanism of action by which Tnfa has a deleterious role for the host to combat certain viral infections. Our results demonstrate that Tnfa signals through its receptor Tnfr2 to enhance viral replication. Mechanistically, Tnfa does not affect viral adhesion and delivery from endosomes to the cytosol. In addition, the host interferon response was also unaffected by Tnfa levels. However, Tnfa blocks the host autophagic response, which is required for viral clearance. This mechanism of action provides new therapeutic targets for the treatment of SVCV-infected fish, and advances our understanding of the previously enigmatic deleterious role of TNFα in certain viral infections. PMID:27351838

  2. How Can Viral Dynamics Models Inform Endpoint Measures in Clinical Trials of Therapies for Acute Viral Infections?

    Directory of Open Access Journals (Sweden)

    Carolin Vegvari

    Full Text Available Acute viral infections pose many practical challenges for the accurate assessment of the impact of novel therapies on viral growth and decay. Using the example of influenza A, we illustrate how the measurement of infection-related quantities that determine the dynamics of viral load within the human host, can inform investigators on the course and severity of infection and the efficacy of a novel treatment. We estimated the values of key infection-related quantities that determine the course of natural infection from viral load data, using Markov Chain Monte Carlo methods. The data were placebo group viral load measurements collected during volunteer challenge studies, conducted by Roche, as part of the oseltamivir trials. We calculated the values of the quantities for each patient and the correlations between the quantities, symptom severity and body temperature. The greatest variation among individuals occurred in the viral load peak and area under the viral load curve. Total symptom severity correlated positively with the basic reproductive number. The most sensitive endpoint for therapeutic trials with the goal to cure patients is the duration of infection. We suggest laboratory experiments to obtain more precise estimates of virological quantities that can supplement clinical endpoint measurements.

  3. 19 CFR 122.77 - Clearance certificate.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Clearance certificate. 122.77 Section 122.77 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY AIR COMMERCE REGULATIONS Documents Required for Clearance and Permission To Depart;...

  4. 14 CFR 23.925 - Propeller clearance.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Propeller clearance. 23.925 Section 23.925 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT AIRWORTHINESS STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY AIRPLANES Powerplant General § 23.925 Propeller clearance. Unless...

  5. Effect of Guide Vane Clearance Gap on Francis Turbine Performance

    Directory of Open Access Journals (Sweden)

    Ravi Koirala

    2016-04-01

    Full Text Available Francis turbine guide vanes have pivoted support with external control mechanism, for conversion of pressure to kinetic energy and to direct them to runner vanes. This movement along the support is dependent on variation of load and flow (operating conditions. Small clearance gaps between facing plates and the upper and lower guide vane tips are available to aid this movement, through which leakage flow occurs. This secondary flow disturbs the main flow stream, resulting performance loss. Additionally, these increased horseshoe vortex, in presence of sand, when crosses through the gaps, both the surfaces are eroded. This causes further serious effect on performance and structural property by increasing gaps. This paper discusses the observation of the severity in hydropower plants and effect of clearance gaps on general performance of the Francis turbine through computational methods. It also relates the primary result with the empirical relation for leakage flow prediction. Additionally, a possible method to computationally estimate thickness depletion has also been presented. With increasing clearance gap, leakage increases, which lowers energy conversion and turbine efficiency along with larger secondary vortex.

  6. 北京地区男男性接触人类免疫缺陷病毒感染者人类白细胞抗原-Ⅰ类分子多态性对病毒载量的影响%The influence of human leucocyte antigen-Ⅰ polymorphisms on plasma viral load in human immunodeficiency virus infected male homosexual population in Beijing

    Institute of Scientific and Technical Information of China (English)

    张欣; 王熠; 王爽; 李伟华; 胡文静; 赵丹彤; 闫惠平

    2013-01-01

    目的 分析北京地区男男性接触人群HIV感染者人类白细胞抗原(HLA)-Ⅰ的多态性及其对病毒载量的影响.方法 用序列特异性引物-聚合酶链反应(SSP-PCR)对157例慢性HIV感染者的HLA-A、HLA-B、HLA-C等位基因分型,同时检测HIV载量.正态分布的计量资料采用单因素或多因素方差分析,非正态分布的计量资料用Mann-Whitney U检验.结果 157例HIV感染者中,HLA-B携带Bw4表位簇个数与低病毒载量有关(F=3.01,P=0.045),HLA-B携带Bw4/4纯合子的感染者HIV载量为(4.19±0.76) lg IU/mL,Bw6/6纯合子的感染者为(4.63±0.74) lg IU/mL(t=2.27,P=0.010).HLA-A、HLA-B同时携带3个Bw4的感染者HIV载量为(3.92±0.97)lg IU/mL,显著低于携带1个Bw4的感染者HIV载量(4.54±0.88) lg IU/mL和不携带Bw4者HIV载量(4.60±0.72) lg IU/mL(t=2.11,P=0.039;t=2.53,P=0.015).HLA-Ⅰ类分子(HLA-A、HLA-B、HLA-C)均携带杂合子的感染者,其病毒载量与任一座位携带纯合子的感染者病毒载量比较,差异无统计学意义.HLA-Ⅰ类分子均携带杂合子且HLA-B携带Bw4/4纯合子的感染者其HIV载量中位数为4.09 lg IU/mL,低于HLA-B携带Bw6/6纯合子感染者的4.55 lg IU/mL(U=210.50,P=0.041).携带A30/B13/C06单体型或A33/B58/C03单体型的感染者其HIV载量与不携带A30/B13/C06单体型或A33/B58/C03单体型感染者比较,差异无统计学意义(t=0.40,P=0.69;t=0.68,P=0.49).结论 HIV感染者HLA-B携带Bw4/4纯合子与低病毒载量有关,且HLA Ⅰ类分子携带杂合子的个体可受HLA-B携带Bw4/4纯合子影响,这些HIV感染者病毒载量更低.%Objective To analyze the influence of the polymorphisms of human leucocyte antigen (HLA)-Ⅰ molecule and the effects on plasma viral load of human immunodeficiency virus (HIV) infected male homosexual population in Beijing.Methods The HLA-A,HLA-B,HLA-C allele were typed by sequence specific primer-polymerase chain reaction (SSP-PCR),and viral load was detected in 157 chronic HIV infected

  7. Viral Haemorrhagic Septicaemia Virus

    DEFF Research Database (Denmark)

    Olesen, Niels Jørgen; Skall, Helle Frank

    2013-01-01

    This chapter covers the genetics (genotypes and serotypes), clinical signs, host species, transmission, prevalence, diagnosis, control and prevention of viral haemorrhagic septicaemia virus.......This chapter covers the genetics (genotypes and serotypes), clinical signs, host species, transmission, prevalence, diagnosis, control and prevention of viral haemorrhagic septicaemia virus....

  8. [Emergent viral infections

    NARCIS (Netherlands)

    Galama, J.M.D.

    2001-01-01

    The emergence and re-emergence of viral infections is an ongoing process. Large-scale vaccination programmes led to the eradication or control of some viral infections in the last century, but new viruses are always emerging. Increased travel is leading to a rise in the importation of exotic infecti

  9. Viral-templated Palladium Nanocatalysts

    Science.gov (United States)

    Yang, Cuixian

    Despite recent progress on nanocatalysis, there exist several critical challenges in simple and readily controllable nanocatalyst synthesis including the unpredictable particle growth, deactivation of catalytic activity, cumbersome catalyst recovery and lack of in-situ reaction monitoring. In this dissertation, two novel approaches are presented for the fabrication of viral-templated palladium (Pd) nanocatalysts, and their catalytic activities for dichromate reduction reaction and Suzuki Coupling reaction were thoroughly studied. In the first approach, viral template based bottom-up assembly is employed for the Pd nanocatalyst synthesis in a chip-based format. Specifically, genetically displayed cysteine residues on each coat protein of Tobacco Mosaic Virus (TMV) templates provide precisely spaced thiol functionalities for readily controllable surface assembly and enhanced formation of catalytically active Pd nanoparticles. Catalysts with the chip-based format allow for simple separation and in-situ monitoring of the reaction extent. Thorough examination of synthesis-structure-activity relationship of Pd nanoparticles formed on surface-assembled viral templates shows that Pd nanoparticle size, catalyst loading density and catalytic activity of viral-templated Pd nanocatalysts can be readily controlled simply by tuning the synthesis conditions. The viral-templated Pd nanocatalysts with optimized synthesis conditions are shown to have higher catalytic activity per unit Pd mass than the commercial Pd/C catalysts. Furthermore, tunable and selective surface assembly of TMV biotemplates is exploited to control the loading density and location of Pd nanocatalysts on solid substrates via preferential electroless deposition. In addition, the catalytic activities of surface-assembled TMV-templated Pd nanocatalysts were also investigated for the ligand-free Suzuki Coupling reaction under mild reaction conditions. The chip-based format enables simple catalyst separation and

  10. Effects of sustained exercise on pulmonary clearance of aerosolized 99mTc-DTPA

    International Nuclear Information System (INIS)

    The effects of intensive prolonged exercise on the pulmonary clearance rate of aerosolized 99mTc-labeled diethylenetriaminepentaacetate (99mTc-DTPA) and pulmonary mechanics were studied in seven healthy nonsmoking volunteers. 99mTc-DTPA clearance and pulmonary mechanics (lung volumes and compliance) were assessed before and after 75 min of constant-load exercise performed on a treadmill, corresponding to 75% of maximal O2 uptake. Because both clearance measurements were made in similar conditions of pulmonary blood flow, respiratory rate, and tidal volume, changes in clearance rate can be assumed to represent changes of alveolar epithelial permeability. After exercise, total, apical, and basal clearance were significantly increased (P less than 0.01, 0.05, and 0.05, respectively) and the increases in total clearance and tidal volume observed during exercise were significantly correlated (P less than 0.05). In contrast, no significant change was found in pulmonary mechanics. These results show that prolonged intensive exercise induces an increase in epithelial permeability, which appears to be related to the mechanical effects of sustained increased ventilation. Because no change was evidenced in pulmonary volumes or in lung elasticity, our results suggest that this increase may result from alteration of the intercellular tight junctions rather than from a surfactant deficiency

  11. SKIN KINETICS AND DERMAL CLEARANCE

    Directory of Open Access Journals (Sweden)

    Prakash Shashi

    2012-08-01

    Full Text Available Availability of several therapeutic and cosmetic formulations for topical application has made the research on skin kinetics as a topic of current interest. Topical formulations are typically meant for local effect although there is always a chance that the low molecular weight chemicals are easily transported across the skin layer and make it available in the systemic circulation. Thus there is a major concern about the transport of chemical moieties following the topical application of cosmetics and therapeutic formulations and the real time measurement of the molecules in the skin layer has become obligatory. It is well known that the properties of both drug and the excipients have identical role in determining the skin permeability of chemical moieties. In the last decade several investigations have been carried out in this filed using several in vitro and in vivo models. This review provides a brief account on the basics of skin kinetics, parameters assessed, various techniques and methods adapted in skin kinetic studies. Moreover, we have also discussed about the micro-environment inside the skin layer and the possible mechanism of drug depot formation, skin metabolism and clearance of molecules from the skin layers.

  12. Nucleotide-mediated airway clearance.

    Science.gov (United States)

    Schmid, Andreas; Clunes, Lucy A; Salathe, Mathias; Verdugo, Pedro; Dietl, Paul; Davis, C William; Tarran, Robert

    2011-01-01

    A thin layer of airway surface liquid (ASL) lines the entire surface of the lung and is the first point of contact between the lung and the environment. Surfactants contained within this layer are secreted in the alveolar region and are required to maintain a low surface tension and to prevent alveolar collapse. Mucins are secreted into the ASL throughout the respiratory tract and serve to intercept inhaled pathogens, allergens and toxins. Their removal by mucociliary clearance (MCC) is facilitated by cilia beating and hydration of the ASL by active ion transport. Throughout the lung, secretion, ion transport and cilia beating are under purinergic control. Pulmonary epithelia release ATP into the ASL which acts in an autocrine fashion on P2Y(2) (ATP) receptors. The enzymatic network describes in Chap. 2 then mounts a secondary wave of signaling by surface conversion of ATP into adenosine (ADO), which induces A(2B) (ADO) receptor-mediated responses. This chapter offers a comprehensive description of MCC and the extensive ramifications of the purinergic signaling network on pulmonary surfaces. PMID:21560046

  13. Viral marketing on the Internet

    OpenAIRE

    ŠTVERÁK, Martin

    2008-01-01

    Thesis provides an overview of viral marketing. It describes the process by which you can be inspired to implement viral campaign. The thesis includes analysis of specific viral Web project. The aim of this thesis is to create a breakdown of the various components of viral marketing, to establish conditions that should be satisfied for the viral marketing to success, suggesting how to use viral marketing on social network Facebook and evaluate the various components of this service for the pr...

  14. Deposition of aerosols and bronchial clearance measurements

    International Nuclear Information System (INIS)

    A special inhalative device is described for reproducible deposition patterns of radioactive aerosols to measure mucociliary and tussive clearance and to evaluate the effect of drugs on the bronchial tree is described. Additive actions on mucus transport exist between β2-agonists and theophylline, but not incombination with inhalative quarternary ammonium compounds (ipatropium and oxitropium bromide). Mucolytics are generally less effective on mucociliary clearance than β2-agonists and theophylline, positive, negative and nonresponders are ofter seen due to the different viscoelastic properties of the mucus. Mucus transport is more than mucociliary clearance. Two-phase gas/liquid movement and coughing are also important transport mechanisms for bronchial mucus. Therefore, bronchodilators enhance mucus transport by increasing airway patency, which increases total and regional air flow and improves cough clearance. (orig.)

  15. Plasma Creatinine Clearance in the Dog

    Science.gov (United States)

    Frazier, Loy W.

    1977-01-01

    Lists materials and methods for an experiment that demonstrates the concept of glomerular filtration rate (GFR) using anesthesized dogs. In the dog, GFR is equivalent to the renal plasma clearance of exogenous creatinine. (CS)

  16. To Go Viral

    CERN Document Server

    Cintron-Arias, Ariel

    2014-01-01

    Mathematical models are validated against empirical data, while examining potential indicators for an online video that went viral. We revisit some concepts of infectious disease modeling (e.g. reproductive number) and we comment on the role of model parameters that interplay in the spread of innovations. The dataset employed here provides strong evidence that the number of online views is governed by exponential growth patterns, explaining a common feature of viral videos.

  17. Human viral gastroenteritis.

    OpenAIRE

    Christensen, M.L.

    1989-01-01

    During the last 15 years, several different groups of fastidious viruses that are responsible for a large proportion of acute viral gastroenteritis cases have been discovered by the electron microscopic examination of stool specimens. This disease is one of the most prevalent and serious clinical syndromes seen around the world, especially in children. Rotaviruses, in the family Reoviridae, and fastidious fecal adenoviruses account for much of the viral gastroenteritis in infants and young ch...

  18. Immigration and viral hepatitis.

    Science.gov (United States)

    Sharma, Suraj; Carballo, Manuel; Feld, Jordan J; Janssen, Harry L A

    2015-08-01

    WHO estimates reveal that the global prevalence of viral hepatitis may be as high as 500 million, with an annual mortality rate of up to 1.3 million individuals. The majority of this global burden of disease is borne by nations of the developing world with high rates of vertical and iatrogenic transmission of HBV and HCV, as well as poor access to healthcare. In 2013, 3.2% of the global population (231 million individuals) migrated into a new host nation. Migrants predominantly originate from the developing countries of the south, into the developed economies of North America and Western Europe. This mass migration of individuals from areas of high-prevalence of viral hepatitis poses a unique challenge to the healthcare systems of the host nations. Due to a lack of universal standards for screening, vaccination and treatment of viral hepatitis, the burden of chronic liver disease and hepatocellular carcinoma continues to increase among migrant populations globally. Efforts to increase case identification and treatment among migrants have largely been limited to small outreach programs in urban centers, such that the majority of migrants with viral hepatitis continue to remain unaware of their infection. This review summarizes the data on prevalence of viral hepatitis and burden of chronic liver disease among migrants, current standards for screening and treatment of immigrants and refugees, and efforts to improve the identification and treatment of viral hepatitis among migrants. PMID:25962882

  19. 48 CFR 801.602-76 - Business clearance review.

    Science.gov (United States)

    2010-10-01

    ... obtain a business clearance review prior to award of any contract, task or delivery order, or blanket... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Business clearance review... Authority, and Responsibilities 801.602-76 Business clearance review. (a) A business clearance review is...

  20. Lower metabolic clearance of tizanidine in Japanese subjects.

    Science.gov (United States)

    Momo, Kenji; Homma, Masato; Kohda, Yukinao

    2013-12-01

    Our aim was to determine whether metabolic clearance, renal clearance, or both elimination pathways contribute to ethnic differences in tizanidine clearance, which is ~ 2-fold higher in Caucasians than in Asians. The pharmacokinetic parameters of tizanidine in 9 healthy male Japanese subjects were compared with those of Caucasians in previous studies. Metabolic clearance of tizanidine was lower in Japanese than in Caucasian subjects (5.9 vs. 8.1 - 10.9 l/h/kg), although renal clearances were similar (0.040 vs. 0.047 - 0.055 l/h/kg). The results suggest that ethnic differences in tizanidine clearance are due to differences in metabolic clearance.

  1. Bile acids for viral hepatitis

    DEFF Research Database (Denmark)

    Chen, Weikeng; Liu, J; Gluud, C

    2003-01-01

    The viral hepatitides are common causes of liver diseases globally. Trials have assessed bile acids for patients with viral hepatitis, but no consensus was reached regarding their usefulness.......The viral hepatitides are common causes of liver diseases globally. Trials have assessed bile acids for patients with viral hepatitis, but no consensus was reached regarding their usefulness....

  2. Effect of blade tip configuration on tip clearance loss of a centrifugal impeller

    Science.gov (United States)

    Ishida, Masahiro; Ueki, Hironobu; Senoo, Yasutoshi

    1989-06-01

    The effect of blade tip configuration on the tip clearance loss was examined experimentally using an unshrouded centrifugal impeller with backward-leaning blades. Tips with rounded edges, sharp square edges, and edges with end plates were tested. The observed tip clearance effects could be theoretically predicted by assuming reasonable values of the contraction coefficent alpha = 0.91 for the round edge, 0.73 for the sharp square edge, and 0.53 for the end-plate edge. The impeller efficiency was improved by about 1.5 point by reducing the contraction coefficient from 0.91 to 0.53. The effect of contraction coefficient on impeller efficiency depends on the ratio of leakage loss to the tip clearance loss. Improved efficiency for impellers with highly loaded blades is expected from reducing the contraction coefficient.

  3. 人类博卡病毒载量与儿童呼吸道感染临床特征的相关性%The correlation study of viral load of human bocavirus and clinical features of children with acute respiratory tract infection

    Institute of Scientific and Technical Information of China (English)

    尹芳; 周卫芳; 王美娟; 严永东; 季伟

    2014-01-01

    导致患儿细胞免疫功能紊乱,且HBoV载量愈高,愈能引起婴幼儿发生喘息.对于HBoV低病毒载量的患儿,要考虑存在其他病原体混合感染可能.%Objective To investigate the detection of human bocavirus (HBoV) in children with acute respiratory infection and to explore the relationship between viral load and clinical characteristics of acute respiratory infection in children.Methods A total of 4 501 nasopharyngeal secretion samples were collected from hospitalized children with acute respiratory infection from January 2013 to June 2013.HBoV-positive children were divided into simple infection group and mixed infection group.Children with HBoV DNA≥1 × 104 copy/mL were categorized into high viral load group,while those with HBoV DNA <1 × 104 copy/mL were categorized into low viral load group.HBoV was determined by fluorescence quantitative polymerase chain reaction (PCR).Respiratory syncytial virus (RSV),influenza virus (Inf)-A,Inf-B,parainfluenza virus (Pinf)-Ⅰ 、Pinf-Ⅱ 、Pinf-Ⅲ and adeno virus antigen were detected by direct antigen-specific immunofluorescence assays.Mycoplasm Pnuemonia was detected by real-time fluorescence quantitative PCR.Serum mycoplasma antibodies were detected by enzyme-linked immunosorbent assay (ELISA).Bacteria was detected by sputum culture.Over the same period,23 children undergoing elective inguinal hernia operation with no respiratory infection or fever were considered as control group.The percentage of peripheral blood T lymphocyte subsets were tested by flow cytometry.Inter-group differences were compared using Chi-square test or Fisher exact test.Viral loads were compared using Mann-Whitney test.Results Two hundred and twenty-two HBoV-positive cases were detected with a positive rate of 5.41% (222/4 105),33.33% (74/222) of which were with high viral load and 66.67% (148/222) were with low viral load.There was a high incidence in the age group of 1-2 years.The simple HBoV infection

  4. Multiplex RT Q-PCR assay for simultaneous quantification of three viruses used for validation of virus clearance by biopharmaceutical production.

    Science.gov (United States)

    Lute, Scott; Wang, Hua; Sanchez, Davonie; Barletta, Janet; Chen, Qi; Brorson, Kurt

    2009-10-01

    Virus removal studies are used to insure the safety of biopharmaceutical products by quantitatively estimating the viral clearance capacity by the manufacturing process. Virus quantification assays are used to measure the log(10) clearance factor of individual purification unit operations in spike recovery studies. We have developed a multiplex RT Q-PCR assay that detects and quantifies three commonly used model viruses X-MuLV, SV40, and MMV simultaneously. This RT Q-PCR multiplex assay has a 6log(10) dynamic range with a limit of detection (LOD) of approximately 1 genome copy/microL. Amplification profiles are similar to existing singleplex assays. Overall, this RT Q-PCR multiplex assay is highly quantitative, accurately identifies multiple viruses simultaneously, and may prove useful to validate viral clearance of biological products in small scale studies.

  5. Nosocomial viral respiratory infections.

    Science.gov (United States)

    Graman, P S; Hall, C B

    1989-12-01

    Nosocomial infections with respiratory tract viruses, particularly influenza and respiratory syncytial viruses, account for the majority of serious nosocomial viral disease. Chronically ill, immunocompromised, elderly, and very young hosts are especially vulnerable to potentially life-threatening involvement of the lower respiratory tract. Effective preventive strategies are based upon early accurate viral diagnosis and an appreciation of the epidemiology and mechanisms of transmission for each viral agent. Influenza viruses spread via airborne dispersion of small particle aerosols, resulting in explosive outbreaks; control measures emphasize immunization and chemoprophylaxis of susceptible patients and personnel, and isolation of those already infected. Transmission of respiratory syncytial virus, in contrast, seems to require closer contact, with virus passed on hands, fomites, or in large droplets inoculated into the eyes and nose at close range. Strategies for control of nosocomial respiratory syncytial virus are designed to interrupt hand carriage and inoculation of virus onto mucous membranes.

  6. [Viral hepatitis in travellers].

    Science.gov (United States)

    Abreu, Cândida

    2007-01-01

    Considering the geographical asymmetric distribution of viral hepatitis A, B and E, having a much higher prevalence in the less developed world, travellers from developed countries are exposed to a considerable and often underestimated risk of hepatitis infection. In fact a significant percentage of viral hepatitis occurring in developed countries is travel related. This results from globalization and increased mobility from tourism, international work, humanitarian and religious missions or other travel related activities. Several studies published in Europe and North America shown that more than 50% of reported cases of hepatitis A are travel related. On the other hand frequent outbreaks of hepatitis A and E in specific geographic areas raise the risk of infection in these restricted zones and that should be clearly identified. Selected aspects related with the distribution of hepatitis A, B and E are reviewed, particularly the situation in Portugal according to the published studies, as well as relevant clinical manifestations and differential diagnosis of viral hepatitis. Basic prevention rules considering enteric transmitted hepatitis (hepatitis A and hepatitis E) and parenteral transmitted (hepatitis B) are reviewed as well as hepatitis A and B immunoprophylaxis. Common clinical situations and daily practice "pre travel" advice issues are discussed according to WHO/CDC recommendations and the Portuguese National Vaccination Program. Implications from near future availability of a hepatitis E vaccine, a currently in phase 2 trial, are highlighted. Potential indications for travellers to endemic countries like India, Nepal and some regions of China, where up to 30% of sporadic cases of acute viral hepatitis are caused by hepatitis E virus, are considered. Continued epidemiological surveillance for viral hepatitis is essential to recognize and control possible outbreaks, but also to identify new viral hepatitis agents that may emerge as important global health

  7. Viral meningitis and encephalitis.

    Science.gov (United States)

    Tuppeny, Misti

    2013-09-01

    Meningitis is an inflammation of the meninges, whereas encephalitis is inflammation of the parenchymal brain tissue. The single distinguishing element between the 2 diagnoses is the altered state of consciousness, focal deficits, and seizures found in encephalitis. Consequently meningoencephalitis is a term used when both findings are present in the patient. Viral meningitis is not necessarily reported as it is often underdiagnosed, whereas encephalitis cases are on the increase in various areas of North America. Improved imaging and viral diagnostics, as well as enhanced neurocritical care management, have improved patient outcomes to date.

  8. Viral infections in pigeons.

    Science.gov (United States)

    Marlier, D; Vindevogel, H

    2006-07-01

    This review provides a current update on the major viral diseases of the domestic pigeon (Columba livia domestica), based on scientific reports and clinical experience. Paramyxovirus 1, adenovirus, rotavirus, herpesvirus 1, poxvirus and circovirus infections are described according to common clinical signs and target tissues. Since pigeons are sometimes treated as if they were poultry, the review also summarises the common viral infections of poultry for which pigeons are considered resistant. It is hoped that the review will provide a useful reference for veterinarians and others and offer advice on the diagnosis, treatment and prevention of the major infectious diseases of pigeons.

  9. Pharmacologic agents for mucus clearance in bronchiectasis.

    Science.gov (United States)

    Nair, Girish B; Ilowite, Jonathan S

    2012-06-01

    There are no approved pharmacologic agents to enhance mucus clearance in non-cystic fibrosis (CF) bronchiectasis. Evidence supports the use of hyperosmolar agents in CF, and studies with inhaled mannitol and hypertonic saline are ongoing in bronchiectasis. N-acetylcysteine may act more as an antioxidant than a mucolytic in other lung diseases. Dornase α is beneficial to patients with CF, but is not useful in patients with non-CF bronchiectasis. Mucokinetic agents such as β-agonists have the potential to improve mucociliary clearance in normals and many disease states, but have not been adequately studied in patients with bronchiectasis.

  10. Pharmacologic agents for mucus clearance in bronchiectasis.

    Science.gov (United States)

    Nair, Girish B; Ilowite, Jonathan S

    2012-06-01

    There are no approved pharmacologic agents to enhance mucus clearance in non-cystic fibrosis (CF) bronchiectasis. Evidence supports the use of hyperosmolar agents in CF, and studies with inhaled mannitol and hypertonic saline are ongoing in bronchiectasis. N-acetylcysteine may act more as an antioxidant than a mucolytic in other lung diseases. Dornase α is beneficial to patients with CF, but is not useful in patients with non-CF bronchiectasis. Mucokinetic agents such as β-agonists have the potential to improve mucociliary clearance in normals and many disease states, but have not been adequately studied in patients with bronchiectasis. PMID:22640851

  11. Clinical evaluation of amylase-creatinine clearance ratio and amylase isoenzyme clearance in chronic renal failure.

    Science.gov (United States)

    Maeda, M; Otsuki, M; Okano, K; Yamasaki, T; Baba, S

    1981-01-01

    Amylase-creatinine clearance ratio (ACCR) and amylase isoenzyme clearance were determined simultaneously in patients with chronic renal failure. ACCR in patients with compensated renal failure (3.5 +/- 0.4%) was not significantly different from normals (2.6 +/- 0.2%), while that in patients with non-compensated renal failure (6.7 +/- 0.4%) was significantly higher than that in normals. Clearance ratio of pancreatic isoamylase (Amylase-1) relative to creatinine clearance (CAmy . 1/Ccr) in patients with both compensated (5.9 +/- 1.0%) and non-compensated (6.8 +/- 0.4%) renal failure was as high as that in patients with acute pancreatitis (6.6 +/- 0.5%). On the other hand, clearance ratio of salivary isoamylase (Amylase-3) relative to creatinine clearance (CAmy . 3/CCr) in patients with compensated renal failure (1.5 +/- 0.3%) was almost the same as that in normals (2.1 +/- 0.1%), while that in patients with non-compensated renal failure was 5.9 +/- 0.7%, which was significantly higher than that in normals. The present study revealed that elevated ACCR in patients with severely impaired renal function was due to the increase of the clearance ratio for both pancreatic and salivary amylase. These facts suggested that glomerular permeability and tubular reabsorption for pancreatic and salivary amylase might play an important role on ACCR in patients with severely impaired renal function.

  12. Clinical evaluation of amylase-creatinine clearance ratio and amylase isoenzyme clearance in chronic renal failure.

    Science.gov (United States)

    Maeda, M; Otsuki, M; Okano, K; Yamasaki, T; Baba, S

    1981-01-01

    Amylase-creatinine clearance ratio (ACCR) and amylase isoenzyme clearance were determined simultaneously in patients with chronic renal failure. ACCR in patients with compensated renal failure (3.5 +/- 0.4%) was not significantly different from normals (2.6 +/- 0.2%), while that in patients with non-compensated renal failure (6.7 +/- 0.4%) was significantly higher than that in normals. Clearance ratio of pancreatic isoamylase (Amylase-1) relative to creatinine clearance (CAmy . 1/Ccr) in patients with both compensated (5.9 +/- 1.0%) and non-compensated (6.8 +/- 0.4%) renal failure was as high as that in patients with acute pancreatitis (6.6 +/- 0.5%). On the other hand, clearance ratio of salivary isoamylase (Amylase-3) relative to creatinine clearance (CAmy . 3/CCr) in patients with compensated renal failure (1.5 +/- 0.3%) was almost the same as that in normals (2.1 +/- 0.1%), while that in patients with non-compensated renal failure was 5.9 +/- 0.7%, which was significantly higher than that in normals. The present study revealed that elevated ACCR in patients with severely impaired renal function was due to the increase of the clearance ratio for both pancreatic and salivary amylase. These facts suggested that glomerular permeability and tubular reabsorption for pancreatic and salivary amylase might play an important role on ACCR in patients with severely impaired renal function. PMID:6167484

  13. Container scanning to reduce time of customs clearance process

    Directory of Open Access Journals (Sweden)

    Yuri da Cunha Ferreira,

    2015-12-01

    Full Text Available One way to increase customs clearance efficiency and to assure supply chain security is the use of non-intrusive inspection equipment, such as scanners. In Brazil, scanners are new, but their use at port terminals is growing rapidly. Considering the possibility of Brazilian Customs requesting 100% scanning of loads, this study aims to assess the operational impacts of this possible request at a specific port terminal. This is the originality of this research. To do so, this study uses applied simulation methods in a case study. Results show that for the current scenario, scanners do not appear to be an operational bottleneck at this port, but the scanning capacity will be exceeded with the planned port expansion. Hence, scheduling rules for single machines were applied to optimize scanning performance. These heuristics provided good performance, suggesting that scanners can provide benefits to priority cargo handling, and could eventually increase the performance of port terminals throughout the country.

  14. Viral diseases of the rabbit.

    Science.gov (United States)

    Krogstad, Aric P; Simpson, Janet E; Korte, Scott W

    2005-01-01

    Viral disease in the rabbit is encountered infrequently by the clinical practitioner; however, several viral diseases were reported to occur in this species. Viral diseases that are described in the rabbit primarily may affect the integument, gastrointestinal tract or, central nervous system or maybe multi-systemic in nature. Rabbit viral diseases range from oral papillomatosis, with benign clinical signs, to rabbit hemorrhagic disease and myxomatosis, which may result in significant clinical disease and mortality. The wild rabbit may serve as a reservoir for disease transmission for many of these viral agents. In general, treatment of viral disease in the rabbit is supportive in nature. PMID:15585192

  15. Clearance of a Mucus Plug

    Science.gov (United States)

    Bian, Shiyao; Zheng, Ying; Grotberg, James B.

    2008-11-01

    Mucus plugging may occur in pulmonary airways in asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis. How to clear the mucus plug is essential and of fundamental importance. Mucus is known to have a yield stress and a mucus plug behaves like a solid plug when the applied stresses are below its yield stress τy. When the local stresses reaches τy, the plug starts to move and can be cleared out of the lung. It is then of great importance to examine how the mucus plug deforms and what is the minimum pressure required to initiate its movement. The present study used the finite element method (FEM) to study the stress distribution and deformation of a solid mucus plug under different pressure loads using ANSYS software. The maximum shear stress is found to occur near the rear transition region of the plug, which can lead to local yielding and flow. The critical pressure increases linearly with the plug length and asymptotes when the plug length is larger than the half channel width. Experimentally a mucus simulant is used to study the process of plug deformation and critical pressure difference required for the plug to propagate. Consistently, the fracture is observed to start at the rear transition region where the plug core connects the films. However, the critical pressure is observed to be dependent on not only the plug length but also the interfacial shape.

  16. Viral Haemorrhagic Septicaemia

    OpenAIRE

    Institute, Marine

    2011-01-01

    This leaflet gives information on viral haemorrhagic septicaemia (VHS). VHS is caused by a single stranded RNA virus of the family Rhabdoviridae, genus Novirhabdoviridae. VHS is listed as a non-exotic disease under EU Directive 2006/88/EC, and is notifiable in Ireland, according to S.I. No. 261 of 2008.

  17. BOVINE VIRAL DIARRHEA VIRUSES

    Science.gov (United States)

    Bovine viral diarrhea virus (BVDV) is an umbrella term for two species of viruses, BVDV1 and BVDV2, within the Pestivirus genus of the Flavivirus family. BVDV viruses are further subclassified as cytopathic and noncytopathic based on their activity in cultured epithelial cells. Noncytopathic BVDV p...

  18. BIOMARKERS OF VIRAL EXPOSURE

    Science.gov (United States)

    Viral and protozoan pathogens associated with raw sludge can cause encephalitis, gastroenteritis, hepatitis, myocarditis, and a number of other diseases. Raw sludge that has been treated to reduce these pathogens can be used for land application according to the regulations spec...

  19. WATERBORNE VIRAL GASTROENTERITIS

    Science.gov (United States)

    In the study of human gastroenteritis, the use of electron microscopy and related techniques has led to the identification of new viral agents which had previously escaped detection by routine cell-culture procedures. Efforts to characterize and further study these agents are cur...

  20. Uptake and clearance of uranium by misgurnus

    International Nuclear Information System (INIS)

    The author studied the bioconcentration and clearance of uranium in misgurnus and determined bioconcentration factors (BCF) as well as uptake and depuration rate constants. The test was performed under semi-static conditions. The depuration of uranium was best described by a two-compartment first order kinetic model

  1. 32 CFR 154.16 - Security clearance.

    Science.gov (United States)

    2010-07-01

    ... requirements for clearance—(1) Top Secret. (i) Final Clearance: (A) BI. (B) Established billet per § 154.13(e... initiated (D) Favorable review of local personnel, base/military police, medical, and other security records...) Provisions of paragraph § 154.14(e) (1) and (2) have been met regarding civilian personnel. (2) Secret....

  2. Bile acids for viral hepatitis

    DEFF Research Database (Denmark)

    Chen, Weikeng; Liu, J; Gluud, C

    2007-01-01

    Trials have assessed bile acids for patients with viral hepatitis, but no consensus has been reached regarding their usefulness.......Trials have assessed bile acids for patients with viral hepatitis, but no consensus has been reached regarding their usefulness....

  3. Viral Marketing and Academic Institution

    OpenAIRE

    Koktová, Silvie

    2010-01-01

    This bachelor thesis examines modern and constantly developing kind of internet marketing -- the so called viral marketing. It deals with its origin, principle, process, advantages and disadvantages, types of viral marketing and presumptions of creating successful viral campaign. The aim of the theoretical part is especially the understanding of viral marketing as one of the effective instruments of contemporary marketing. In this theoretical part the thesis also elaborates a marketing school...

  4. The DNA load of six high-risk human papillomavirus types and its association with cervical lesions

    OpenAIRE

    Río Ospina, Luisa del; Soto de León, Sara; Camargo, Milena; Moreno Pérez, Darwin Andrés; Sánchez, Ricardo; Pérez Prados, Antonio; Patarroyo, Manuel Elkin; Patarroyo, Manuel Alfonso

    2015-01-01

    Background: Analysing human papillomavirus (HPV) viral load is important in determining the risk of developing cervical cancer (CC); most knowledge to date regarding HPV viral load and cervical lesions has been related to HPV-16. This study evaluated the association between the viral load of the six most prevalent high-risk viral types in Colombia and cervical intraepithelial neoplasia (CIN) frequency. Methods: 114 women without CIN and 59 women having CIN confirmed by colposcopy, all of them...

  5. Dynamics modeling and simulation of mechanism with joint clearance

    Institute of Scientific and Technical Information of China (English)

    BAI Zheng-feng; TIAN Hao; ZHAO Yang

    2010-01-01

    The existence of clearance in the joints of mechanisms system is inevitable.The movements of the real mechanism are deftection from the ideal mechanism due to the clearances and the motion accuracv is decreased.The effects of the hinge clearance on the crank and rocker mechanism system are studied.The svstem dynamics equation with clearance is presented.The contact dynamics model is established using the nonlinear equivalent spring-damp model and the friction effect is considered by using Coulomb friction model.Then the models are incorporated into ADAMS,and based on the model,large numbers numeric simulations are made.The regularity of contact forces in clearance are studied in detail.And the effects of clearance size.clearance friction on the mechanism dynamics characteristic are analyzed.The simulation resuhs Can predict the effects of clearance on the mechanism dynamics characteristic preferably.

  6. 19 CFR 122.26 - Entry and clearance.

    Science.gov (United States)

    2010-04-01

    ... AIR COMMERCE REGULATIONS Private Aircraft § 122.26 Entry and clearance. Private aircraft, as defined... information as set forth in § 122.22(c), and grants electronic clearance via electronic mail or telephone....

  7. Modelling Virus and Antibody Dynamics during Dengue Virus Infection Suggests a Role for Antibody in Virus Clearance.

    Directory of Open Access Journals (Sweden)

    Hannah E Clapham

    2016-05-01

    Full Text Available Dengue is an infection of increasing global importance, yet uncertainty remains regarding critical aspects of its virology, immunology and epidemiology. One unanswered question is how infection is controlled and cleared during a dengue infection. Antibody is thought to play a role, but little past work has examined the kinetics of both virus and antibody during natural infections. We present data on multiple virus and antibody titres measurements recorded sequentially during infection from 53 Vietnamese dengue patients. We fit mechanistic mathematical models of the dynamics of viral replication and the host immune response to these data. These models fit the data well. The model with antibody removing virus fits the data best, but with a role suggested for ADCC or other infected cell clearance mechanisms. Our analysis therefore shows that the observed viral and antibody kinetics are consistent with antibody playing a key role in controlling viral replication. This work gives quantitative insight into the relationship between antibody levels and the efficiency of viral clearance. It will inform the future development of mechanistic models of how vaccines and antivirals might modify the course of natural dengue infection.

  8. Diminished creatinine clearance in anorexia nervosa: reversal with weight gain.

    OpenAIRE

    Boag, F.; Weerakoon, J; Ginsburg, J; Havard, C W; Dandona, P

    1985-01-01

    To assess whether patients with anorexia nervosa have abnormalities in creatinine clearance, we measured plasma creatinine concentration, urinary creatinine excretion, and creatinine clearance in 10 patients with anorexia nervosa before and during treatment. Urinary creatinine excretion and creatinine clearance were diminished in all patients. Nine patients had significant decreases in their plasma creatinine and creatinine clearance was increased even when corrected for body weight and body ...

  9. Dengue viral infections

    OpenAIRE

    Malavige, G; Fernando, S; Fernando, D; Seneviratne, S.

    2004-01-01

    Dengue viral infections are one of the most important mosquito borne diseases in the world. They may be asymptomatic or may give rise to undifferentiated fever, dengue fever, dengue haemorrhagic fever (DHF), or dengue shock syndrome. Annually, 100 million cases of dengue fever and half a million cases of DHF occur worldwide. Ninety percent of DHF subjects are children less than 15 years of age. At present, dengue is endemic in 112 countries in the world. No vaccine is available for preventing...

  10. Engineering influenza viral vectors

    OpenAIRE

    Li, Junwei; Arévalo, Maria T; Zeng, Mingtao

    2013-01-01

    The influenza virus is a respiratory pathogen with a negative-sense, segmented RNA genome. Construction of recombinant influenza viruses in the laboratory was reported starting in the 1980s. Within a short period of time, pioneer researchers had devised methods that made it possible to construct influenza viral vectors from cDNA plasmid systems. Herein, we discuss the evolution of influenza virus reverse genetics, from helper virus-dependent systems, to helper virus-independent 17-plasmid sys...

  11. Relevance research of viral load and peripheral T lymphocyte subset in patients with HIV and HBV coinfection%HIV、HBV共感染患者病毒载量和外周T淋巴细胞亚群的相关性研究

    Institute of Scientific and Technical Information of China (English)

    郑立娜; 金明珠

    2015-01-01

    Objective To investigate the correlation between viral load and peripheral T lymphocyte subset in patients with HIV and HBV coinfection. Methods From January 2011 to January 2014 in Yueqing Blood Supply Center of Out-patient and Inpatient Department, 1230 cases of untreated HIV infected patients with highly active antiretroviral thera-py were selected as simple infection group, 148 patients with HIV and HBV coinfection were selected as coinfection group. RT-PCR, fluorescent quantitative PCR and flow cytometry were adopted to detect the HIV and HBC viral load and T lymphocyte subsets count. Fully automatic biochemical analyzer was adopted to detect related biochemical index. The detection results between two groups were compared. The correlations between viral load and T lymphocyte subsets count in HIV and HBV coinfection patients were analyzed. Results ALT, AST, TP, ALB, TBIL level and HIV RNA load between two groups was compared respectively, there were significantly statistical differences (P< 0.01). CD4+, CD8+, CD3+T lymphocyte subsets count and CD4+/CD8+was compared respectively, there were significantly statistical differences (P<0.01).There was a positive correlation of HIV RNA load and HBV DNA load in coinfection patients (r=0.471). CD4+/CD8+was negatively correlate with HBV DNA load (r=-0.412). CD4+, CD4+/CD8+were negatively corre-late with HIV RNA load (r =-0.841,-0.583). Conclusion HBV may has promoting HIV RNA replication effect which makes a worse liver damage and immune system damage in coinfection patients than HIV infection along patients, should pay attention to in clinic.%目的:研究HIV、HBV共感染患者病毒载量与外周T淋巴细胞亚群的相关性。方法选取2011年1月~2014年1月就诊于乐清市血站门诊和住院部未经高效抗逆转录病毒治疗的HIV感染患者1230例为单纯感染组和HIV、HBV共感染患者148例为共感染组。采用RT-PCR、荧光定量PCR和流式细胞仪进行HIV、HBV病毒载量和T

  12. Wear analysis of revolute joints with clearance in multibody systems

    Science.gov (United States)

    Bai, ZhengFeng; Zhao, Yang; Wang, XingGui

    2013-08-01

    In this work, the prediction of wear for revolute joint with clearance in multibody systems is investigated using a computational methodology. The contact model in clearance joint is established using a new hybrid nonlinear contact force model and the friction effect is considered by using a modified Coulomb friction model. The dynamics model of multibody system with clearance is established using dynamic segmentation modeling method and the computational process for wear analysis of clearance joint in multibody systems is presented. The main computational process for wear analysis of clearance joint includes two steps, which are dynamics analysis and wear analysis. The dynamics simulation of multibody system with revolute clearance joint is carried out and the contact forces are drawn and used to calculate the wear amount of revolute clearance joint based on the Archard's wear model. Finally, a four-bar multibody mechanical system with revolute clearance joint is used as numerical example application to perform the simulation and show the dynamics responses and wear characteristics of multibody systems with revolute clearance joint. The main results of this work indicate that the contact between the joint elements is wider and more frequent in some specific regions and the wear phenomenon is not regular around the joint surface, which causes the clearance size increase non-regularly after clearance joint wear. This work presents an effective method to predict wear of revolute joint with clearance in multibody systems.

  13. 10 CFR 706.31 - Clearance of conciliators and arbitrators.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Clearance of conciliators and arbitrators. 706.31 Section... RELATIONS Contract Negotiation and Administration § 706.31 Clearance of conciliators and arbitrators. Conciliators and arbitrators who are regularly assigned to DOE cases may be processed for “Q” clearance at...

  14. Guangzhou Customs Guide to Clearance of Import/Export Goods

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    @@ Management of the Enterprises Granted for Convenient and Quick Customs Clearance 1.What is the enterprise granted for convenient and quick customs clearance? Customs General Administration and the Ministry of Foreign Trade and Economic Cooperation jointly issued policy measures to facilitate customs clearance in 2001 to further support the development of hightech industries.The enterprise .

  15. 14 CFR 1260.63 - Customs clearance and visas.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Customs clearance and visas. 1260.63 Section 1260.63 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION GRANTS AND COOPERATIVE AGREEMENTS General Special Conditions § 1260.63 Customs clearance and visas. Customs Clearance and Visas...

  16. 14 CFR 27.661 - Rotor blade clearance.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Rotor blade clearance. 27.661 Section 27... AIRWORTHINESS STANDARDS: NORMAL CATEGORY ROTORCRAFT Design and Construction Rotors § 27.661 Rotor blade clearance. There must be enough clearance between the rotor blades and other parts of the structure...

  17. 14 CFR 29.661 - Rotor blade clearance.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Rotor blade clearance. 29.661 Section 29... AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Design and Construction Rotors § 29.661 Rotor blade clearance. There must be enough clearance between the rotor blades and other parts of the structure...

  18. 32 CFR 644.517 - Clearance of Army lands.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Clearance of Army lands. 644.517 Section 644.517 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) REAL PROPERTY REAL... and Improvements § 644.517 Clearance of Army lands. The responsibility for performing clearance...

  19. Viral membrane fusion

    Energy Technology Data Exchange (ETDEWEB)

    Harrison, Stephen C., E-mail: harrison@crystal.harvard.edu

    2015-05-15

    Membrane fusion is an essential step when enveloped viruses enter cells. Lipid bilayer fusion requires catalysis to overcome a high kinetic barrier; viral fusion proteins are the agents that fulfill this catalytic function. Despite a variety of molecular architectures, these proteins facilitate fusion by essentially the same generic mechanism. Stimulated by a signal associated with arrival at the cell to be infected (e.g., receptor or co-receptor binding, proton binding in an endosome), they undergo a series of conformational changes. A hydrophobic segment (a “fusion loop” or “fusion peptide”) engages the target-cell membrane and collapse of the bridging intermediate thus formed draws the two membranes (virus and cell) together. We know of three structural classes for viral fusion proteins. Structures for both pre- and postfusion conformations of illustrate the beginning and end points of a process that can be probed by single-virion measurements of fusion kinetics. - Highlights: • Viral fusion proteins overcome the high energy barrier to lipid bilayer merger. • Different molecular structures but the same catalytic mechanism. • Review describes properties of three known fusion-protein structural classes. • Single-virion fusion experiments elucidate mechanism.

  20. Viral membrane fusion

    International Nuclear Information System (INIS)

    Membrane fusion is an essential step when enveloped viruses enter cells. Lipid bilayer fusion requires catalysis to overcome a high kinetic barrier; viral fusion proteins are the agents that fulfill this catalytic function. Despite a variety of molecular architectures, these proteins facilitate fusion by essentially the same generic mechanism. Stimulated by a signal associated with arrival at the cell to be infected (e.g., receptor or co-receptor binding, proton binding in an endosome), they undergo a series of conformational changes. A hydrophobic segment (a “fusion loop” or “fusion peptide”) engages the target-cell membrane and collapse of the bridging intermediate thus formed draws the two membranes (virus and cell) together. We know of three structural classes for viral fusion proteins. Structures for both pre- and postfusion conformations of illustrate the beginning and end points of a process that can be probed by single-virion measurements of fusion kinetics. - Highlights: • Viral fusion proteins overcome the high energy barrier to lipid bilayer merger. • Different molecular structures but the same catalytic mechanism. • Review describes properties of three known fusion-protein structural classes. • Single-virion fusion experiments elucidate mechanism

  1. Sequential bottlenecks drive viral evolution in early acute hepatitis C virus infection.

    Directory of Open Access Journals (Sweden)

    Rowena A Bull

    2011-09-01

    Full Text Available Hepatitis C is a pandemic human RNA virus, which commonly causes chronic infection and liver disease. The characterization of viral populations that successfully initiate infection, and also those that drive progression to chronicity is instrumental for understanding pathogenesis and vaccine design. A comprehensive and longitudinal analysis of the viral population was conducted in four subjects followed from very early acute infection to resolution of disease outcome. By means of next generation sequencing (NGS and standard cloning/Sanger sequencing, genetic diversity and viral variants were quantified over the course of the infection at frequencies as low as 0.1%. Phylogenetic analysis of reassembled viral variants revealed acute infection was dominated by two sequential bottleneck events, irrespective of subsequent chronicity or clearance. The first bottleneck was associated with transmission, with one to two viral variants successfully establishing infection. The second occurred approximately 100 days post-infection, and was characterized by a decline in viral diversity. In the two subjects who developed chronic infection, this second bottleneck was followed by the emergence of a new viral population, which evolved from the founder variants via a selective sweep with fixation in a small number of mutated sites. The diversity at sites with non-synonymous mutation was higher in predicted cytotoxic T cell epitopes, suggesting immune-driven evolution. These results provide the first detailed analysis of early within-host evolution of HCV, indicating strong selective forces limit viral evolution in the acute phase of infection.

  2. Early changes in hepatitis C viral quasispecies during interferon therapy predict the therapeutic outcome

    Science.gov (United States)

    Farci, Patrizia; Strazzera, Rita; Alter, Harvey J.; Farci, Stefania; Degioannis, Daniela; Coiana, Alessandra; Peddis, Giovanna; Usai, Francesco; Serra, Giancarlo; Chessa, Luchino; Diaz, Giacomo; Balestrieri, Angelo; Purcell, Robert H.

    2002-01-01

    Despite recent treatment advances, the majority of patients with chronic hepatitis C fail to respond to antiviral therapy. Although the genetic basis for this resistance is unknown, accumulated evidence suggests that changes in the heterogeneous viral population (quasispecies) may be an important determinant of viral persistence and response to therapy. Sequences within hepatitis C virus (HCV) envelope 1 and envelope 2 genes, inclusive of the hypervariable region 1, were analyzed in parallel with the level of viral replication in serial serum samples obtained from 23 patients who exhibited different patterns of response to therapy and from untreated controls. Our study provides evidence that although the viral diversity before treatment does not predict the response to treatment, the early emergence and dominance of a single viral variant distinguishes patients who will have a sustained therapeutic response from those who subsequently will experience a breakthrough or relapse. A dramatic reduction in genetic diversity leading to an increasingly homogeneous viral population was a consistent feature associated with viral clearance in sustained responders and was independent of HCV genotype. The persistence of variants present before treatment in patients who fail to respond or who experience a breakthrough during therapy strongly suggests the preexistence of viral strains with inherent resistance to IFN. Thus, the study of the evolution of the HCV quasispecies provides prognostic information as early as the first 2 weeks after starting therapy and opens perspectives for elucidating the mechanisms of treatment failure in chronic hepatitis C. PMID:11880647

  3. Optimizing Viral Discovery in Bats.

    Science.gov (United States)

    Young, Cristin C W; Olival, Kevin J

    2016-01-01

    Viral discovery studies in bats have increased dramatically over the past decade, yet a rigorous synthesis of the published data is lacking. We extract and analyze data from 93 studies published between 2007-2013 to examine factors that increase success of viral discovery in bats, and specific trends and patterns of infection across host taxa and viral families. Over the study period, 248 novel viruses from 24 viral families have been described. Using generalized linear models, at a study level we show the number of host species and viral families tested best explained number of viruses detected. We demonstrate that prevalence varies significantly across viral family, specimen type, and host taxonomy, and calculate mean PCR prevalence by viral family and specimen type across all studies. Using a logistic model, we additionally identify factors most likely to increase viral detection at an individual level for the entire dataset and by viral families with sufficient sample sizes. Our analysis highlights major taxonomic gaps in recent bat viral discovery efforts and identifies ways to improve future viral pathogen detection through the design of more efficient and targeted sample collection and screening approaches. PMID:26867024

  4. Non-cytolytic antigen clearance in DNA-vaccinated mice with electropotation

    Institute of Scientific and Technical Information of China (English)

    Jin-liang PENG; Yong-gang ZHAO; Jun-hua MAI; Wen-ka PANG; Wei GUO; Guang-ming CHEN; Guo-yu MO; Gui-rong RAO; Yu-hong XU

    2007-01-01

    Aim: To explore the potential of electroporation (EP)-mediated hepatitis B virus (HBV) DNA vaccination for the treatment of chronic HBV infection. Methods: BALB/c mice were vaccinated with HBV DNA vaccine encoding for the HBV preS2-S antigen, combined with or without EP. HBV surface antigen expression plasmid was administered into mice liver via a hydrodynamic injection to mimic HBV infection. The clearance of antigen in the serum and liver was detected by ELISA assay and immunohistochemical staining. The histopathology of the liver tissues was examined by HE staining and serum alanine aminotransferase assay.Results: The immunogenicity ofHBV DNA vaccine encoding for the HBV preS2-S antigen can be improved by EP-mediated vaccine delivery. The elicited immune responses can indeed reduce the expression of HBV surface antigen (HBsAg) in hepatocytes of the mouse model that was transfected to express HBsAg using the hydrodynamic injection method. The antigen clearance process did not cause significant toxicity to liver tissue, suggesting a non-cytolytic mechanism. Conclusion: The EP-aided DNA vaccination may have potential in mediating viral clearance in chronic hepatitis B patients.

  5. COMPARISON OF TWO METHODS TO INCREASE TIP CLEARANCE AND ITS EFFECT ON PERFORMANCE OF TURBOCHARGER CENTRIFUGAL COMPRESSOR STAGE

    Institute of Scientific and Technical Information of China (English)

    SYED Noman Danish; MA Chaochen; YANG Ce; L(U) Wei

    2007-01-01

    Tip clearance between the blade tip and casing of a centrifugal compressor can be varied through two methods: by changing the blade height (M1) or by changing the casing diameter (M2). Numerical simulations are carried out to compare these two methods and their effect on the stage and impeller performance. The impeller and diffuser are connected through rotor Stator boundary using frozen rotor approach. Overall stage performance and the flow configuration have been investigated for nine tip clearance levels from no gap to 1 mm. Impeller and diffuser performances are also presented separately. It has been found that the overall and impeller performance are comparatively better for Ml below tip clearance of 0.5 mm whereas M2 is found advantageous above 0.5 mm of tip clearance. Both M1 and M2 show performance degradation with the increase in tip clearance. Two models have been proposed for the stage total pressure ratio and efficiency, which are found to be in agreement with experimental results. The impeller efficiency and the pressure ratio are found to be maximum at tip clearance of 0.1 mm for both the cases however minimum diffuser effectiveness is also observed at the same clearance level. Diffuser effectiveness is found to be maximum at zero gap for both cases. As it is practically impossible to have zero gap for unshrouded impellers so it is concluded that the Optimum thickness is 0.5 mm onwards for Ml and 0.5 mm for M2 in terms of diffuser effectiveness. Mass averaged flow parameters, entropy, blade loading diagram and relative pressure fields are presented, showing the loss production within the impeller passage with tip clearance.

  6. Glial K(+) Clearance and Cell Swelling

    DEFF Research Database (Denmark)

    Macaulay, Nanna; Zeuthen, Thomas

    2012-01-01

    An important feature of neuronal signalling is the increased concentration of K(+) in the extracellular space. The K(+) concentration is restored to its original basal level primarily by uptake into nearby glial cells. The molecular mechanisms by which K(+) is transferred from the extracellular...... space into the glial cell are debated. Although spatial buffer currents may occur, their quantitative contribution to K(+) clearance is uncertain. The concept of spatial buffering of K(+) precludes intracellular K(+) accumulation and is therefore (i) difficult to reconcile with the K(+) accumulation...... repeatedly observed in glial cells during K(+) clearance and (ii) incompatible with K(+)-dependent glial cell swelling. K(+) uptake into non-voltage clamped cultured glial cells is carried out by the Na(+)/K(+)-ATPase and the Na(+)/K(+)/Cl(-) cotransporter in combination. In brain slices and intact optic...

  7. HIV–1 Dynamics: A Reappraisal of Host and Viral Factors, as well as Methodological Issues

    Directory of Open Access Journals (Sweden)

    Jianming Tang

    2012-10-01

    Full Text Available The dynamics of HIV–1 viremia is a complex and evolving landscape with clinical and epidemiological (public health implications. Most studies have relied on the use of set–point viral load (VL as a readily available proxy of viral dynamics to assess host and viral correlates. This review highlights recent findings from population–based studies of set–point VL, focusing primarily on robust data related to host genetics. A comprehensive understanding of viral dynamics will clearly need to consider both host and viral characteristics, with close attention to (i the timing of VL measurements, (ii the biology of viral evolution, (iii compartments of active viral replication, (iv the transmission source partner as the immediate past microenvironment, and (v proper application of statistical models.

  8. ADSORBENTS USED IN THE CLEARANCE OF ENDOTOXIN

    Institute of Scientific and Technical Information of China (English)

    YU Mei; LIU Tao; Hou Guanghui; YUAN Zhi

    2003-01-01

    A series of modified poly (methyl methacrylate, PMMA) resins were prepared and compared their adsorption abilities to endotoxin. The results showed that adsorbents, which were grafted with tertiary amine and long spacing arms, had the best adsorption capacities and good blood compatibility, It is hopeful to be used as adsorbent in hemoperfusion for clinical clearance of endotoxin. The influence of original concentration of endotoxin on adsorption and the adsorption mechanism were also investigated.

  9. Analysis of grease contamination influence on the internal radial clearance of ball bearings by thermographic inspection

    Directory of Open Access Journals (Sweden)

    Mišković Žarko Z.

    2016-01-01

    Full Text Available One of the most important factors influencing ball bearings service life is its internal radial clearance. However, this parameter is also very complex because it depends on applied radial load and ball bearings dimensions, surface finish and manufacturing materials. Thermal condition of ball bearings also significantly affects internal radial clearance. Despite many researches performed in order to find out relevant facts about different aspects of ball bearings thermal behaviour, only few of them are dealing with the real working conditions, where high concentration of solid contaminant particles is present. That’s why the main goal of research presented in this paper was to establish statistically significant correlation between ball bearings temperatures, their working time and concentration of contaminant particles in their grease. Because of especially difficult working conditions, the typical conveyor idlers bearings were selected as representative test samples and appropriate solid particles from open pit coal mines were used as artificial contaminants. Applied experimental methodology included thermographic inspection, as well as usage of custom designed test rig for ball bearings service life testing. Finally, by obtained experimental data processing in advanced software, statistically significant mathematical correlation between mentioned bearings characteristics was determined and applied in commonly used internal radial clearance equation. That is the most important contribution of performed research - the new equation and methodology for ball bearings internal clearance determination which could be used for eventual improvement of existing bearings service life equations. [Projekat Ministarstva nauke Republike Srbije, br. TR35029 i br. TR14033

  10. Loss of CARD9-mediated innate activation attenuates severe influenza pneumonia without compromising host viral immunity.

    Science.gov (United States)

    Uematsu, Takayuki; Iizasa, Ei'ichi; Kobayashi, Noritada; Yoshida, Hiroki; Hara, Hiromitsu

    2015-01-01

    Influenza virus (IFV) infection is a common cause of severe viral pneumonia associated with acute respiratory distress syndrome (ARDS), which is difficult to control with general immunosuppressive therapy including corticosteroids due to the unfavorable effect on viral replication. Studies have suggested that the excessive activation of the innate immunity by IFV is responsible for severe pathologies. In this study, we focused on CARD9, a signaling adaptor known to regulate innate immune activation through multiple innate sensor proteins, and investigated its role in anti-IFV defense and lung pathogenesis in a mouse model recapitulating severe influenza pneumonia with ARDS. We found that influenza pneumonia was dramatically attenuated in Card9-deficient mice, which showed improved mortality with reduced inflammatory cytokines and chemokines in the infected lungs. However, viral clearance, type-I interferon production, and the development of anti-viral B and T cell immunity were not compromised by CARD9 deficiency. Syk or CARD9-deficient DCs but not macrophages showed impaired cytokine but not type-I interferon production in response to IFV in vitro, indicating a possible role for the Syk-CARD9 pathway in DCs in excessive inflammation of IFV-infected lungs. Therefore, inhibition of this pathway is an ideal therapeutic target for severe influenza pneumonia without affecting viral clearance. PMID:26627732

  11. Airway Clearance Devices for Cystic Fibrosis

    Science.gov (United States)

    2009-01-01

    Executive Summary Objective The purpose of this evidence-based analysis is to examine the safety and efficacy of airway clearance devices (ACDs) for cystic fibrosis and attempt to differentiate between devices, where possible, on grounds of clinical efficacy, quality of life, safety and/or patient preference. Background Cystic fibrosis (CF) is a common, inherited, life-limiting disease that affects multiple systems of the human body. Respiratory dysfunction is the primary complication and leading cause of death due to CF. CF causes abnormal mucus secretion in the airways, leading to airway obstruction and mucus plugging, which in turn can lead to bacterial infection and further mucous production. Over time, this almost cyclical process contributes to severe airway damage and loss of respiratory function. Removal of airway secretions, termed airway clearance, is thus an integral component of the management of CF. A variety of methods are available for airway clearance, some requiring mechanical devices, others physical manipulation of the body (e.g. physiotherapy). Conventional chest physiotherapy (CCPT), through the assistance of a caregiver, is the current standard of care for achieving airway clearance, particularly in young patients up to the ages of six or seven. CF patients are, however, living much longer now than in decades past. The median age of survival in Canada has risen to 37.0 years for the period of 1998-2002 (5-year window), up from 22.8 years for the 5-year window ending in 1977. The prevalence has also risen accordingly, last recorded as 3,453 in Canada in 2002, up from 1,630 in 1977. With individuals living longer, there is a greater need for independent methods of airway clearance. Airway Clearance Devices There are at least three classes of airway clearance devices: positive expiratory pressure devices (PEP), airway oscillating devices (AOD; either handheld or stationary) and high frequency chest compression (HFCC)/mechanical percussion (MP

  12. Viral infections of rabbits.

    Science.gov (United States)

    Kerr, Peter J; Donnelly, Thomas M

    2013-05-01

    Viral diseases of rabbits have been used historically to study oncogenesis (e.g. rabbit fibroma virus, cottontail rabbit papillomavirus) and biologically to control feral rabbit populations (e.g. myxoma virus). However, clinicians seeing pet rabbits in North America infrequently encounter viral diseases although myxomatosis may be seen occasionally. The situation is different in Europe and Australia, where myxomatosis and rabbit hemorrhagic disease are endemic. Advances in epidemiology and virology have led to detection of other lapine viruses that are now recognized as agents of emerging infectious diseases. Rabbit caliciviruses, related to rabbit hemorrhagic disease, are generally avirulent, but lethal variants are being identified in Europe and North America. Enteric viruses including lapine rotavirus, rabbit enteric coronavirus and rabbit astrovirus are being acknowledged as contributors to the multifactorial enteritis complex of juvenile rabbits. Three avirulent leporid herpesviruses are found in domestic rabbits. A fourth highly pathogenic virus designated leporid herpesvirus 4 has been described in Canada and Alaska. This review considers viruses affecting rabbits by their clinical significance. Viruses of major and minor clinical significance are described, and viruses of laboratory significance are mentioned. PMID:23642871

  13. Viral marketing as epidemiological model

    OpenAIRE

    Rodrigues, Helena Sofia; Fonseca, Manuel José

    2015-01-01

    In epidemiology, an epidemic is defined as the spread of an infectious disease to a large number of people in a given population within a short period of time. In the marketing context, a message is viral when it is broadly sent and received by the target market through person-to-person transmission. This specific marketing communication strategy is commonly referred as viral marketing. Due to this similarity between an epidemic and the viral marketing process and because the understanding of...

  14. Viral Load and Infection Status of HPV Type 58 in Cervical Cancer in Eastern of Guangdong Province%HPV58型在粤东地区宫颈癌中的病毒含量和感染状态研究

    Institute of Scientific and Technical Information of China (English)

    周莉; 魏晓龙; 黄萍; 关明飞

    2013-01-01

    [Purpose]To establish a sensitive and stable method for measuring human papilloma virus (HPV) type 58 infection status of cervical cancer patients in eastern region of Guangdong province.[Methods] HPV58E2/E6 genes were amplified,PCR products were purified and linked to T vector,and constructed the standard plasmid. HPV5S viral load and infection status of 30 cervical cancer patients and 40 controls were detected. [ Results ] The standard plasmid of realtime fluorescence quantitative PCR for detecting HPV5& E2/E6 fragments was stable and sensitive. HPV58 infection rate and viral load in cervical carcinoma were higher than those of controls. Further, HPV58 infection status were integrated (66.67%) and mixed status (33.33%) in cervical cancer,which were different from controls. [Conclusion] The standard plasmid of fluorescence quantitative PCR is a high sensitivity and stability method to detect HPV58 virus load and infection status,and integration status is the main infection status of HPV58 in the cervical cancer patients in eastern region of Guangdong province.%[目的]建立灵敏而稳定的人乳头状瘤病毒(human papillomavirus,HPV) 58型病毒含量与整合状态检测方法,并探讨HPV58型在我国粤东地区妇女宫颈癌中的感染特征.[方法] PCR扩增HPV58E2和E6基因,PCR产物纯化,连接入T载体,构建标准品;检测30例宫颈癌和40例对照组织样本中HPV58的病毒含量和整合状态.[结果]成功构建含有HPV58 E2或E6片段的T载体质粒作为检测HPV58型的病毒含量和判断感染状态标准品.HPV58型在宫颈癌中的感染率和病毒含量较正常宫颈组织均高,并且HPV58在粤东地区宫颈癌中的感染状态以整合型(66.67%)和混合型(33.33%)为主,和正常宫颈组织中感染状态分布有显著差异.[结论]采用荧光定量PCR法所建立的HPV58型病毒含量和整合状态的检测方法具有灵敏性和稳定性,HPV58型在粤东地区宫颈癌中的感染以整合状态为主.

  15. [Ratio of amylase clearance and creatinine clearance in the diagnosis of acute pancreatitis].

    Science.gov (United States)

    Haffter, D; Reichlin, B; Gyr, K

    1981-05-30

    In 21 healthy volunteers the ratio of amylase clearance and creatinine clearance (Cam/Ccr) was determined in urine collected at admission, after a 1-hour collection period and after a 2-hour collection period. The normal values were 1.8 +/- 1.6%, 1.9 +/- 2% and 2.0 +/- 1.7% respectively. They were comparable with those published by others. The reproducibility of the method was acceptable (r = 0.62). When compared with serum amylase determinations, Cam/Ccr showed neither better sensitivity in 19 patients suffering an acute episode of proven pancreatitis, nor better specificity in 19 patients with acute abdomen but no evidence of pancreatitis.

  16. Clearance of extractables and leachables from single-use technologies via ultrafiltration/diafiltration operations.

    Science.gov (United States)

    Magarian, Nicholas; Lee, Kate; Nagpal, Kunal; Skidmore, Ken; Mahajan, Ekta

    2016-05-01

    Quantifying the clearance of extractables and leachables (E/L) throughout ultrafiltration/diafiltration (UFDF) operations allows for greater flexibility in the implementation of single-use technologies in steps upstream of the UFDF process. A proof-of-concept study was completed in which the clearance of 7 E/L from single-use technologies (trimethylsilanol, hexanoic acid, butyrolactone, t-butyl alcohol, caprolactam, acetonitrile, and benzyl alcohol) in four representative proteins were measured and monitored during the UFDF process using quantitative NMR. This study demonstrated that the defined E/L spiked into a variety of protein solutions can be cleared to 1 ppm, which is explained in detail. The overall clearance trend observed for both buffer control and protein-containing solutions resembled the ideal clearance trend where no apparent interactions were observed between E/L with the protein, UFDF system, or with other defined E/L which may be present in the system. Additionally, the UFDF system is capable of clearing these potential E/L from single-use technologies below 1 ppm irrespective of initial concentrations in the load (1,000 or 100 ppm), independently from the type of protein. In general, mass recoveries were within ±15% of each spiked compound in protein solutions and their respective buffer controls, suggesting spiked E/L do not interact strongly with protein. By demonstrating the product independent clearance trends of the spiked E/L across UFDF, these results will contribute to the simplification of the E/L toxicology assessment and allow modular manufacturing approach for single-use technologies in biopharmaceutical manufacturing. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:718-724, 2016. PMID:27071939

  17. Oral immune regulation: a novel method for modulation of anti-viral immunity.

    Science.gov (United States)

    Margalit, Maya; Ilan, Yaron

    2004-12-01

    Chronic viral infections, including hepatitis B and C and human immunodeficiency virus (HIV) infections, afflict a significant part of the world's population. In many of these diseases, chronicity has been linked to defective anti-viral immunity that damages host tissues without producing viral clearance. Currently available therapeutic measures for chronic viral infections are limited. Oral immune regulation, the manipulation of immune responses towards antigens by their oral administration, is a relatively simple and antigen-specific immune-modulatory tool. Recent evidence suggests that induction of oral immune-regulation towards viral antigens may entail a complex immune effect, characterized by simultaneous enhancement and suppression of different elements of the immune response in a manner that benefits the host. Such manipulation of the immune response towards viruses may achieve a combination of upregulated specific anti-viral immunity and inhibition of immune-mediated damage. Oral immune regulation may prove to be an important addition to the available therapeutic arsenal for chronic viral infections. PMID:15567096

  18. Influenza infection suppresses NADPH oxidase-dependent phagocytic bacterial clearance and enhances susceptibility to secondary MRSA infection

    Science.gov (United States)

    Sun, Keer; Metzger, Dennis W.

    2014-01-01

    Methicillin-resistant S. aureus (MRSA) has emerged as a leading contributor to mortality during recent influenza pandemics. The mechanism for this influenza-induced susceptibility to secondary S. aureus infection is poorly understood. Here we show that innate antibacterial immunity was significantly suppressed during the recovery stage of influenza infection, despite the fact that MRSA super-infection had no significant effect on viral burdens. Compared to mice infected with bacteria alone, post-influenza MRSA infected mice exhibited impaired bacterial clearance, which was not due to defective phagocyte recruitment, but rather coincided with reduced intracellular reactive oxygen species (ROS) levels in alveolar macrophages and neutrophils. NADPH oxidase is responsible for ROS production during phagocytic bacterial killing, a process also known as oxidative burst. We found that gp91phox-containing NADPH oxidase activity in macrophages and neutrophils was essential for optimal bacterial clearance during respiratory MRSA infections. In contrast to WT animals, gp91phox−/− mice exhibited similar defects in MRSA clearance before and after influenza infection. Using gp91phox+/− mosaic mice, we further demonstrate that influenza infection inhibits a cell-intrinsic contribution of NADPH oxidase to phagocyte bactericidal activity. Together, our results establish that influenza infection suppresses NADPH oxidase-dependent bacterial clearance and leads to susceptibility to secondary MRSA infection. PMID:24563256

  19. Stormwater runoff drives viral community composition changes in inland freshwaters

    Directory of Open Access Journals (Sweden)

    Kurt E. Williamson

    2014-03-01

    Full Text Available Storm events impact freshwater microbial communities by transporting terrestrial viruses and other microbes to freshwater systems, and by potentially resuspending microbes from bottom sediments. The magnitude of these impacts on freshwater ecosystems is unknown and largely unexplored. Field studies carried out at two discrete sites in coastal Virginia (USA were used to characterize the viral load carried by runoff and to test the hypothesis that terrestrial viruses introduced through stormwater runoff change the composition of freshwater microbial communities. Field data gathered from an agricultural watershed indicated that primary runoff can contain viral densities approximating those of receiving waters. Furthermore, viruses attached to suspended colloids made up a large fraction of the total load, particularly in early stages of the storm. At a second field site (stormwater retention pond, RAPD-PCR profiling showed that the viral community of the pond changed dramatically over the course of two intense storms while relatively little change was observed over similar time scales in the absence of disturbance. Comparisons of planktonic and particle-associated viral communities revealed two completely distinct communities, suggesting that particle-associated viruses represent a potentially large and overlooked portion of aquatic viral abundance and diversity. Our findings show that stormwater runoff can quickly change the composition of freshwater microbial communities. Based on these findings, increased storms in the coastal mid-Atlantic region predicted by most climate change models will likely have important impacts on the structure and function of local freshwater microbial communities.

  20. Dynamics of viral replication in blood and lymphoid tissues during SIVmac251 infection of macaques

    Directory of Open Access Journals (Sweden)

    Mannioui Abdelkrim

    2009-01-01

    Full Text Available Abstract Background Extensive studies of primary infection are crucial to our understanding of the course of HIV disease. In SIV-infected macaques, a model closely mimicking HIV pathogenesis, we used a combination of three markers -- viral RNA, 2LTR circles and viral DNA -- to evaluate viral replication and dissemination simultaneously in blood, secondary lymphoid tissues, and the gut during primary and chronic infections. Subsequent viral compartmentalization in the main target cells of the virus in peripheral blood during the chronic phase of infection was evaluated by cell sorting and viral quantification with the three markers studied. Results The evolutions of viral RNA, 2LTR circles and DNA levels were correlated in a given tissue during primary and early chronic infection. The decrease in plasma viral load principally reflects a large decrease in viral replication in gut-associated lymphoid tissue (GALT, with viral RNA and DNA levels remaining stable in the spleen and peripheral lymph nodes. Later, during chronic infection, a progressive depletion of central memory CD4+ T cells from the peripheral blood was observed, accompanied by high levels of viral replication in the cells of this subtype. The virus was also found to replicate at this point in the infection in naive CD4+ T cells. Viral RNA was frequently detected in monocytes, but no SIV replication appeared to occur in these cells, as no viral DNA or 2LTR circles were detected. Conclusion We demonstrated the persistence of viral replication and dissemination, mostly in secondary lymphoid tissues, during primary and early chronic infection. During chronic infection, the central memory CD4+ T cells were the major site of viral replication in peripheral blood, but viral replication also occurred in naive CD4+ T cells. The role of monocytes seemed to be limited to carrying the virus as a cargo because there was an observed lack of replication in these cells. These data may have important

  1. Clearance and release from control - An international perspective

    International Nuclear Information System (INIS)

    This paper tries to give an overview of the clearance, or release from regulatory control, on an international scale, including some of those countries where clearance has become or is about to become vital for D and D. The emphasis lies on the impact of clearance, and in particular of differences between clearance levels of various countries, on D and D. Relevance of clearance for D and D of nuclear installations Clearance is an essential part of waste management (or more general, material management) in nuclear installations, and in particular during the decommissioning phase where waste streams continues to arise. Of course, the relevance of clearance in a particular country depends on a number of factors, like: availability of a final repository and its price; prevailing decommissioning strategy; number of nuclear installations reaching decommissioning phase. This small selection of reasons why clearance may be of varying importance for different countries may already suffice to illustrate why up to now clearance has been developed and implemented in quite different ways. If one thinks of additional reasons that may influence clearance, like politics, the public opinion, availability of funds etc., the situation becomes even more complex. It is, however safe to draw the conclusion that countries with a certain number of nuclear installations which have been or will soon be shut down or which are already in the decommissioning phase will need to implement provisions for clearance. This has indeed been the case with countries like the UK, Germany, the USA, Sweden, and a number of others. It is not essential for clearance levels to be exactly equal between various countries. They may differ as long as the difference is not too large, e.g. the values fall into the same order of magnitude. This is the reason why for example Germany has no problems with clearance levels which differ from the EU recommendation RP 122 partially adopted in a number of EU countries

  2. Amylase creatinine clearance ratio after biliary surgery.

    Science.gov (United States)

    Donaldson, L A; McIntosh, W; Joffe, S N

    1977-01-01

    The amylase creatinine clearance ratio (ACCR) is considered to be a more sensitive index of acute pancreatitis than the serum amylase level. Serial ACCR estimations were undertaken in 25 patients undergoing an elective cholecystectomy. Using accepted criteria, 28% of these patients developed, in the postoperative period, biochemical evidence of pancreatic gland damage, although the serum amylase level remained normal. This raised ACCR was particularly noted in patients who had undergone an exploration of the common bile duct. The ACCR would appear to be a more sensitive index of pancreatic gland disruption secondary to biliary surgery than the serum amylase level.

  3. Amylase creatinine clearance ratio after biliary surgery.

    Science.gov (United States)

    Donaldson, L A; McIntosh, W; Joffe, S N

    1977-01-01

    The amylase creatinine clearance ratio (ACCR) is considered to be a more sensitive index of acute pancreatitis than the serum amylase level. Serial ACCR estimations were undertaken in 25 patients undergoing an elective cholecystectomy. Using accepted criteria, 28% of these patients developed, in the postoperative period, biochemical evidence of pancreatic gland damage, although the serum amylase level remained normal. This raised ACCR was particularly noted in patients who had undergone an exploration of the common bile duct. The ACCR would appear to be a more sensitive index of pancreatic gland disruption secondary to biliary surgery than the serum amylase level. PMID:402305

  4. Load Measurements

    DEFF Research Database (Denmark)

    Kock, Carsten Weber; Vesth, Allan

    The report describes Load measurements carried out on a given wind turbine. The aim of the measurement program regarding the loads on the turbine is to verify the basic characteristics of the wind turbine and loads on the blades, the rotor and the tower, using [Ref 1], [Ref2] and [Ref 3]. Regarding...... the fatigue loads, the rotor, blades and tower moments are presented. The fatigue loads are evaluated using rainflow counting described in detail in Ref. [1]. The 1Hz equivalent load ranges are calculated at different wind speeds. All information regarding the instrumentation is collected in [ref 4] and [ref...

  5. Study of blade clearance effects on centrifugal pumps

    Science.gov (United States)

    Hoshide, R. K.; Nielson, C. E.

    1972-01-01

    A program of analysis, design, fabrication, and testing has been conducted to develop and experimentally verify analytical models to predict the effects of impeller blade clearance on centrifugal pumps. The effect of tip clearance on pump efficiency, and the relationship between the head coefficient and torque loss with tip clearance was established. Analysis were performed to determine the cost variation in design, manufacture, and test that would occur between unshrouded and shrouded impellers. An impeller, representative of typical rocket engine impellers, was modified by removing its front shroud to permit variation of its blade clearances. It was tested in water with special instrumentation to provide measurements of blade surface pressures during operation. Pump performance data were obtained from tests at various impeller tip clearances. Blade pressure data were obtained at the nominal tip clearance. Comparisons of predicted and measured data are given.

  6. A unified framework of immunological and epidemiological dynamics for the spread of viral infections in a simple network-based population

    Directory of Open Access Journals (Sweden)

    Vickers David M

    2007-12-01

    Full Text Available Abstract Background The desire to better understand the immuno-biology of infectious diseases as a broader ecological system has motivated the explicit representation of epidemiological processes as a function of immune system dynamics. While several recent and innovative contributions have explored unified models across cellular and organismal domains, and appear well-suited to describing particular aspects of intracellular pathogen infections, these existing immuno-epidemiological models lack representation of certain cellular components and immunological processes needed to adequately characterize the dynamics of some important epidemiological contexts. Here, we complement existing models by presenting an alternate framework of anti-viral immune responses within individual hosts and infection spread across a simple network-based population. Results Our compartmental formulation parsimoniously demonstrates a correlation between immune responsiveness, network connectivity, and the natural history of infection in a population. It suggests that an increased disparity between people's ability to respond to an infection, while maintaining an average immune responsiveness rate, may worsen the overall impact of an outbreak within a population. Additionally, varying an individual's network connectivity affects the rate with which the population-wide viral load accumulates, but has little impact on the asymptotic limit in which it approaches. Whilst the clearance of a pathogen in a population will lower viral loads in the short-term, the longer the time until re-infection, the more severe an outbreak is likely to be. Given the eventual likelihood of reinfection, the resulting long-run viral burden after elimination of an infection is negligible compared to the situation in which infection is persistent. Conclusion Future infectious disease research would benefit by striving to not only continue to understand the properties of an invading microbe, or

  7. Multiple Inhibitory Pathways Contribute to Lung CD8+ T Cell Impairment and Protect against Immunopathology during Acute Viral Respiratory Infection.

    Science.gov (United States)

    Erickson, John J; Rogers, Meredith C; Tollefson, Sharon J; Boyd, Kelli L; Williams, John V

    2016-07-01

    Viruses are frequent causes of lower respiratory infection (LRI). Programmed cell death-1 (PD-1) signaling contributes to pulmonary CD8(+) T cell (TCD8) functional impairment during acute viral LRI, but the role of TCD8 impairment in viral clearance and immunopathology is unclear. We now find that human metapneumovirus infection induces virus-specific lung TCD8 that fail to produce effector cytokines or degranulate late postinfection, with minimally increased function even in the absence of PD-1 signaling. Impaired lung TCD8 upregulated multiple inhibitory receptors, including PD-1, lymphocyte activation gene 3 (LAG-3), T cell Ig mucin 3, and 2B4. Moreover, coexpression of these receptors continued to increase even after viral clearance, with most virus-specific lung TCD8 expressing three or more inhibitory receptors on day 14 postinfection. Viral infection also increased expression of inhibitory ligands by both airway epithelial cells and APCs, further establishing an inhibitory environment. In vitro Ab blockade revealed that multiple inhibitory receptors contribute to TCD8 impairment induced by either human metapneumovirus or influenza virus infection. In vivo blockade of T cell Ig mucin 3 signaling failed to enhance TCD8 function or reduce viral titers. However, blockade of LAG-3 in PD-1-deficient mice restored TCD8 effector functions but increased lung pathology, indicating that LAG-3 mediates lung TCD8 impairment in vivo and contributes to protection from immunopathology during viral clearance. These results demonstrate that an orchestrated network of pathways modifies lung TCD8 functionality during viral LRI, with PD-1 and LAG-3 serving prominent roles. Lung TCD8 impairment may prevent immunopathology but also contributes to recurrent lung infections. PMID:27259857

  8. Load Measurements

    DEFF Research Database (Denmark)

    Vesth, Allan; Kock, Carsten Weber

    The report describes Load measurements carried out on a given wind turbine. The aim of the measurement program regarding the loads on the turbine is to verify the basic characteristics of the wind turbine and loads on the blades, the rotor and the tower, using [Ref 1], [Ref2] and [Ref 3]. Regardi...

  9. Load Measurements

    DEFF Research Database (Denmark)

    Kock, Carsten Weber; Vesth, Allan

    The report describes Load measurements carried out on a given wind turbine. The aim of the measurement program regarding the loads on the turbine is to verify the basic characteristics of the wind turbine and loads on the blades, the rotor and the tower, using [Ref 1], [Ref2] and [Ref 3]. Regarding...

  10. 干扰素α-1b联合恩替卡韦治疗高病毒载量慢性乙型肝炎疗效评价%Efficacy of interferon alfa-1b combined with entecavir in treatment of patients with chronic hepatitis B and high serum viral load

    Institute of Scientific and Technical Information of China (English)

    占国清; 李芳; 李儒贵; 刘翔; 谭华炳

    2016-01-01

    目的:探讨干扰素α-1b联合恩替卡韦(ETV)治疗高病毒载量慢性乙型肝炎(CHB)患者的临床疗效。方法92例高病毒载量(血清HBV DNA≥1×107 IU/ml)CHB患者被分为观察组48例和对照组44例。对照组采用干扰素α-1b治疗,观察组采用干扰素α-1b联合ETV治疗,疗程48 w。比较两组治疗后第12、24、48 w血清丙氨酸氨基转移酶(ALT)复常率、HBV DNA不可检出率、HBeAg阴转率和HBeAg转换率。采用ELISA法检测血清乙型肝炎病毒标记物;使用自动生化分析仪检测肝功能指标;采用荧光定量PCR法检测HBV DNA。结果在治疗第24 w和48 w时,观察组血清ALT复常率分别为68.8%和91.7%,显著高于对照组的34.1%和63.6%(P<0.01);在治疗第12 w、24 w和48 w时,观察组血清HBV DNA不可检测率分别为45.8%、72.9%和87.5%,显著高于对照组的11.4%、31.8%和47.7%(P<0.01);在治疗第48 w时,观察组HBeAg阴转率和HBeAg转换率分别为67.6%和62.2%,显著高于对照组的42.9%和37.1%(P<0.05)。结论干扰素α-1b联合ETV治疗血清高病毒载量的CHB患者疗效优于单用干扰素α-1b。%Objective To investigate the clinical efficacy of interferon alfa-1b combined with entecavir (ETV)in treatment of patients with chronic hepatitis B (CHB) and high serum viral loads. Methods 92 patients with CHB and high serum viral load (HBV DNA≥1×107 IU/ml) were divided into observation group (n=48) and control group (n=44). Patients in the control group were treated with interferon alfa-1b,and patients in the observation group were treated with interferon alfa-1b combined with ETV. The treatment course in two groups lasted for 48 weeks. The recovery rates of serum alanine aminotransferase (ALT),rates of serum HBV DNA loss, negative rates of HBeAg and the conversion rates of HBeAg to anti-HBe were compared at 12,24 and 48 weeks. Serum HBV markers and HBV DNA levels were routinely detected. Results The

  11. Analysis of the Viral Load and Clinical Features of Children With Hand,Foot and Mouth Disease by Different Enteroviruses%不同肠道病毒感染手足口病患儿病毒载量及临床特征对比分析

    Institute of Scientific and Technical Information of China (English)

    陈苏; 杜潘艳; 郑红; 王宝林; 高翠红; 张双

    2016-01-01

    Objective To analyze the viral load and clinical features of children with hand,foot and mouth disease (HFMD)by EV71 and CoxA16. Methods A total of 430 children who were definitely diagnosed with HFMD in the Department of Pediatrics in Tangshan Women and Children Health - care Hospital from May to September in 2015 were enrolled. According to clinical symptoms,physical signs and species of virus,the children were divided into EV71 mild group(162 cases),EV71 severe group(87 cases),CoxA16 mild group(158 cases)and CoxA16 severe group(23 cases). Throat swabs of the children were collected and the RNA of EV71 and CoxA16 was detected by real - time fluorescent quantitative RT-qPCR method,and viral load was calculated. Length of disease,temperature,length of fever,dental ulcer,salivation,cough,hand rash,foot rash, somnolence,convulsion,vomit,change of consciousness,limb jitter,and myospasm of the children were recorded. Results Cycle threshold(Ct value)shown by standard curve had highly negative correlation with the viral load( r = - 1. 000,P 0. 05). EV71 severe group and CoxA16 severe group had longer length of disease than EV71 mild group and CoxA16 mild group(P 0. 05). EV71 severe group and CoxA16 severe group had higher incidence rate of the length of fever ≥3 d than EV71 mild group and CoxA16 mild group(P 0.05)。EV71重度组、CoxA16重度组 HFMD 患儿病程较 EV71轻度组、CoxA16轻度组延长(P 0.05)。EV71重度组、CoxA16重度组 HFMD 患儿热程≥3 d 发生率较 EV71轻度组、CoxA16轻度组升高(P <0.007);EV71重度组、CoxA16重度组 HFMD 患儿体温≥38.5℃+热程≥3 d 发生率较 EV71轻度组、CoxA16轻度组升高,EV71轻度组 HFMD 患儿体温≥38.5℃+热程≥3 d发生率较 CoxA16轻度组升高,EV71重度组 HFMD 患儿体温≥38.5℃+热程≥3 d 发生率较 CoxA16重度组升高(P <0.007);CoxA16轻度组、CoxA16重度组 HFMD 患儿咳嗽、手部出疹数≥15个(

  12. Insulated Foamy Viral Vectors.

    Science.gov (United States)

    Browning, Diana L; Collins, Casey P; Hocum, Jonah D; Leap, David J; Rae, Dustin T; Trobridge, Grant D

    2016-03-01

    Retroviral vector-mediated gene therapy is promising, but genotoxicity has limited its use in the clinic. Genotoxicity is highly dependent on the retroviral vector used, and foamy viral (FV) vectors appear relatively safe. However, internal promoters may still potentially activate nearby genes. We developed insulated FV vectors, using four previously described insulators: a version of the well-studied chicken hypersensitivity site 4 insulator (650cHS4), two synthetic CCCTC-binding factor (CTCF)-based insulators, and an insulator based on the CCAAT box-binding transcription factor/nuclear factor I (7xCTF/NF1). We directly compared these insulators for enhancer-blocking activity, effect on FV vector titer, and fidelity of transfer to both proviral long terminal repeats. The synthetic CTCF-based insulators had the strongest insulating activity, but reduced titers significantly. The 7xCTF/NF1 insulator did not reduce titers but had weak insulating activity. The 650cHS4-insulated FV vector was identified as the overall most promising vector. Uninsulated and 650cHS4-insulated FV vectors were both significantly less genotoxic than gammaretroviral vectors. Integration sites were evaluated in cord blood CD34(+) cells and the 650cHS4-insulated FV vector had fewer hotspots compared with an uninsulated FV vector. These data suggest that insulated FV vectors are promising for hematopoietic stem cell gene therapy. PMID:26715244

  13. Dengue viral infections

    Directory of Open Access Journals (Sweden)

    Gurugama Padmalal

    2010-01-01

    Full Text Available Dengue viral infections are one of the most important mosquito-borne diseases in the world. Presently dengue is endemic in 112 countries in the world. It has been estimated that almost 100 million cases of dengue fever and half a million cases of dengue hemorrhagic fever (DHF occur worldwide. An increasing proportion of DHF is in children less than 15 years of age, especially in South East and South Asia. The unique structure of the dengue virus and the pathophysiologic responses of the host, different serotypes, and favorable conditions for vector breeding have led to the virulence and spread of the infections. The manifestations of dengue infections are protean from being asymptomatic to undifferentiated fever, severe dengue infections, and unusual complications. Early recognition and prompt initiation of appropriate supportive treatment are often delayed resulting in unnecessarily high morbidity and mortality. Attempts are underway for the development of a vaccine for preventing the burden of this neglected disease. This review outlines the epidemiology, clinical features, pathophysiologic mechanisms, management, and control of dengue infections.

  14. Comparative analysis of measures of viral reservoirs in HIV-1 eradication studies.

    Directory of Open Access Journals (Sweden)

    Susanne Eriksson

    2013-02-01

    Full Text Available HIV-1 reservoirs preclude virus eradication in patients receiving highly active antiretroviral therapy (HAART. The best characterized reservoir is a small, difficult-to-quantify pool of resting memory CD4(+ T cells carrying latent but replication-competent viral genomes. Because strategies targeting this latent reservoir are now being tested in clinical trials, well-validated high-throughput assays that quantify this reservoir are urgently needed. Here we compare eleven different approaches for quantitating persistent HIV-1 in 30 patients on HAART, using the original viral outgrowth assay for resting CD4(+ T cells carrying inducible, replication-competent viral genomes as a standard for comparison. PCR-based assays for cells containing HIV-1 DNA gave infected cell frequencies at least 2 logs higher than the viral outgrowth assay, even in subjects who started HAART during acute/early infection. This difference may reflect defective viral genomes. The ratio of infected cell frequencies determined by viral outgrowth and PCR-based assays varied dramatically between patients. Although strong correlations with the viral outgrowth assay could not be formally excluded for most assays, correlations achieved statistical significance only for integrated HIV-1 DNA in peripheral blood mononuclear cells and HIV-1 RNA/DNA ratio in rectal CD4(+ T cells. Residual viremia was below the limit of detection in many subjects and did not correlate with the viral outgrowth assays. The dramatic differences in infected cell frequencies and the lack of a precise correlation between culture and PCR-based assays raise the possibility that the successful clearance of latently infected cells may be masked by a larger and variable pool of cells with defective proviruses. These defective proviruses are detected by PCR but may not be affected by reactivation strategies and may not require eradication to accomplish an effective cure. A molecular understanding of the discrepancy

  15. Allometric scaling for predicting human clearance of bisphenol A

    Energy Technology Data Exchange (ETDEWEB)

    Collet, Séverine H., E-mail: s.collet@envt.fr; Picard-Hagen, Nicole, E-mail: n.hagen-picard@envt.fr; Lacroix, Marlène Z., E-mail: m.lacroix@envt.fr; Puel, Sylvie, E-mail: s.puel@envt.fr; Viguié, Catherine, E-mail: c.viguie@envt.fr; Bousquet-Melou, Alain, E-mail: a.bousquet-Melou@envt.fr; Toutain, Pierre-Louis, E-mail: pltoutain@wanadoo.fr; Gayrard, Véronique, E-mail: v.gayrard@envt.fr

    2015-05-01

    The investigation of interspecies differences in bisphenol A (BPA) pharmacokinetics (PK) may be useful for translating findings from animal studies to humans, identifying major processes involved in BPA clearance mechanisms, and predicting BPA PK parameters in man. For the first time, a large range of species in terms of body weight, from 0.02 kg (mice) to 495 kg (horses) was used to predict BPA clearance in man by an allometric approach. BPA PK was evaluated after intravenous administration of BPA in horses, sheep, pigs, dogs, rats and mice. A non-compartmental analysis was used to estimate plasma clearance and steady state volume of distribution and predict BPA PK parameters in humans from allometric scaling. In all the species investigated, BPA plasma clearance was high and of the same order of magnitude as their respective hepatic blood flow. By an allometric scaling, the human clearance was estimated to be 1.79 L/min (equivalent to 25.6 mL/kg.min) with a 95% prediction interval of 0.36 to 8.83 L/min. Our results support the hypothesis that there are highly efficient and hepatic mechanisms of BPA clearance in man. - Highlights: • Allometric scaling was used to predict BPA pharmacokinetic parameters in humans. • In all species, BPA plasma clearance approached hepatic blood flow. • Human BPA clearance was estimated to be 1.79 L/min.

  16. Clearance systems in the brain-implications for Alzheimer disease.

    Science.gov (United States)

    Tarasoff-Conway, Jenna M; Carare, Roxana O; Osorio, Ricardo S; Glodzik, Lidia; Butler, Tracy; Fieremans, Els; Axel, Leon; Rusinek, Henry; Nicholson, Charles; Zlokovic, Berislav V; Frangione, Blas; Blennow, Kaj; Ménard, Joël; Zetterberg, Henrik; Wisniewski, Thomas; de Leon, Mony J

    2015-08-01

    Accumulation of toxic protein aggregates-amyloid-β (Aβ) plaques and hyperphosphorylated tau tangles-is the pathological hallmark of Alzheimer disease (AD). Aβ accumulation has been hypothesized to result from an imbalance between Aβ production and clearance; indeed, Aβ clearance seems to be impaired in both early and late forms of AD. To develop efficient strategies to slow down or halt AD, it is critical to understand how Aβ is cleared from the brain. Extracellular Aβ deposits can be removed from the brain by various clearance systems, most importantly, transport across the blood-brain barrier. Findings from the past few years suggest that astroglial-mediated interstitial fluid (ISF) bulk flow, known as the glymphatic system, might contribute to a larger portion of extracellular Aβ (eAβ) clearance than previously thought. The meningeal lymphatic vessels, discovered in 2015, might provide another clearance route. Because these clearance systems act together to drive eAβ from the brain, any alteration to their function could contribute to AD. An understanding of Aβ clearance might provide strategies to reduce excess Aβ deposits and delay, or even prevent, disease onset. In this Review, we describe the clearance systems of the brain as they relate to proteins implicated in AD pathology, with the main focus on Aβ. PMID:26195256

  17. Do dialysate conductivity measurements provide conductivity clearance or ionic dialysance?

    Science.gov (United States)

    Petitclerc, T

    2006-11-01

    Dialysate conductivity measurements allow on-line estimation of urea clearance during hemodialysis session. Conductivity measurements provide a value of 'conductivity clearance' for some authors, but a value of 'ionic dialysance' for others. This paper aims at explaining which term should be the more appropriate. Clearance is a parameter defined for measuring the power of a mechanism, which aims at 'clearing' a solution by depurating some solutes. In hemodialysis, clearance measures the efficacy of patient's depuration. In contrast, dialysance measures the capability of transferring solutes between blood and dialysate. The conventional definition of dialysance, requiring the absence of convective transfer, should be generalized to the case of the usual presence of ultrafiltration during the hemodialysis session. For a solute (as urea) absent from the dialysate delivered to the dialyzer inlet, the clearance is equal to its dialysance. In order to avoid a dramatic fall in ionic concentrations during hemodialysis treatment, the clearance of ions is reduced by adding these ions in the dialysate and becomes lower than their dialysance. Conductivity measurements provide a value of electrolytes dialysance. Thus the term of 'ionic dialysance' is more appropriate than the term of 'conductivity clearance'. Nevertheless ionic dialysance represents a good estimation of urea clearance.

  18. Radioaerosol delivery and clearance in patients with respiratory failure

    International Nuclear Information System (INIS)

    A technique for radioaerosol delivery to patients requiring mechanical ventilation is described. Ventilation images and pulmonary radioaerosol clearance rates were successfully obtained in 35 patients regardless of ventilator type or level of positive end-expiratory pressure (PEEP). Those patients with noncardiogenic pulmonary edema (NPE) had significantly increased clearance rates relative to those patients in whom NPE was not present

  19. 48 CFR 32.502-2 - Contract finance office clearance.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Contract finance office clearance. 32.502-2 Section 32.502-2 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION... finance office clearance. The contracting officer shall obtain the approval of the contract finance...

  20. 48 CFR 1432.502-2 - Contract finance office clearance.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Contract finance office clearance. 1432.502-2 Section 1432.502-2 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR... finance office clearance. The CO shall obtain approval of the bureau finance office prior to...

  1. 48 CFR 832.502-2 - Contract finance office clearance.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Contract finance office clearance. 832.502-2 Section 832.502-2 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS... finance office clearance. Contracting officers must obtain approval from the DSPE before taking...

  2. 32 CFR 644.522 - Clearance of military scrap.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Clearance of military scrap. 644.522 Section 644... Excess Land and Improvements § 644.522 Clearance of military scrap. Military scrap can contain or be... determining whether scrap metal will be removed should be the safety of persons coming on the land in...

  3. Benefits of Improved HP Turbine Active Clearance Control

    Science.gov (United States)

    Ruiz, Rafael; Albers, Bob; Sak, Wojciech; Seitzer, Ken; Steinetz, Bruce M.

    2007-01-01

    As part of the NASA Propulsion 21 program, GE Aircraft Engines was contracted to develop an improved high pressure turbine(HPT) active clearance control (ACC) system. The system is envisioned to minimize blade tip clearances to improve HPT efficiency throughout the engine operation range simultaneously reducing fuel consumption and emissions.

  4. Allometric scaling for predicting human clearance of bisphenol A

    International Nuclear Information System (INIS)

    The investigation of interspecies differences in bisphenol A (BPA) pharmacokinetics (PK) may be useful for translating findings from animal studies to humans, identifying major processes involved in BPA clearance mechanisms, and predicting BPA PK parameters in man. For the first time, a large range of species in terms of body weight, from 0.02 kg (mice) to 495 kg (horses) was used to predict BPA clearance in man by an allometric approach. BPA PK was evaluated after intravenous administration of BPA in horses, sheep, pigs, dogs, rats and mice. A non-compartmental analysis was used to estimate plasma clearance and steady state volume of distribution and predict BPA PK parameters in humans from allometric scaling. In all the species investigated, BPA plasma clearance was high and of the same order of magnitude as their respective hepatic blood flow. By an allometric scaling, the human clearance was estimated to be 1.79 L/min (equivalent to 25.6 mL/kg.min) with a 95% prediction interval of 0.36 to 8.83 L/min. Our results support the hypothesis that there are highly efficient and hepatic mechanisms of BPA clearance in man. - Highlights: • Allometric scaling was used to predict BPA pharmacokinetic parameters in humans. • In all species, BPA plasma clearance approached hepatic blood flow. • Human BPA clearance was estimated to be 1.79 L/min

  5. Study of global operational needs for mine clearance equipment

    Science.gov (United States)

    Blagden, Paddy M.

    2003-09-01

    The Geneva International Centre for Humanitarian Demining studied the needs of landmine clearance groups for equipment to carry out specific functions of mine clearance. This was done on a global level, and useful results were obtained, which will provide the basis for further analysis.

  6. Nonlinear Dynamics Behaviors of a Rotor Roller Bearing System with Radial Clearances and Waviness Considered

    Institute of Scientific and Technical Information of China (English)

    Wang Liqin; Cui Li; Zheng Dezhi; Gu Le

    2008-01-01

    A rotor system supported by roller bearings displays very complicated nonlinear behaviors due to nonlinear Hertzian contact forces, radial clearances and bearing waviness. This paper presents nonlinear bearing forces of a roller bearing under four-dimensional loads and establishes 4-DOF dynamics equations of a rotor roller bearing system. The methods of Newmark-β and of Newton-Laphson are used to solve the nonlinear equations. The dynamics behaviors of a rigid rotor system are studied through the bifurcation, the Poincar bility caused by the quasi-periodic bifurcation, the periodic-doubling bifurcation and chaos routes as the rotational speed increases.Clearances, outer race waviness, inner race waviness, roller waviness, damping, radial forces and unbalanced forces-all these bring a significant influence to bear on the system stability. As the clearance increases, the dynamics behaviors become complicated with the number and the scale of instable regions becoming larger. The vibration frequencies induced by the roller bearing waviness and the orders of the waviness might cause severe vibrations. The system is able to eliminate non-periodic vibration by reasonable choice and optimization of the parameters.

  7. A stochastic model of latently infected cell reactivation and viral blip generation in treated HIV patients.

    Directory of Open Access Journals (Sweden)

    Jessica M Conway

    2011-04-01

    Full Text Available Motivated by viral persistence in HIV+ patients on long-term anti-retroviral treatment (ART, we present a stochastic model of HIV viral dynamics in the blood stream. We consider the hypothesis that the residual viremia in patients on ART can be explained principally by the activation of cells latently infected by HIV before the initiation of ART and that viral blips (clinically-observed short periods of detectable viral load represent large deviations from the mean. We model the system as a continuous-time, multi-type branching process. Deriving equations for the probability generating function we use a novel numerical approach to extract the probability distributions for latent reservoir sizes and viral loads. We find that latent reservoir extinction-time distributions underscore the importance of considering reservoir dynamics beyond simply the half-life. We calculate blip amplitudes and frequencies by computing complete viral load probability distributions, and study the duration of viral blips via direct numerical simulation. We find that our model qualitatively reproduces short small-amplitude blips detected in clinical studies of treated HIV infection. Stochastic models of this type provide insight into treatment-outcome variability that cannot be found from deterministic models.

  8. Neuroanatomy goes viral!

    Directory of Open Access Journals (Sweden)

    Jonathan eNassi

    2015-07-01

    Full Text Available The nervous system is complex not simply because of the enormous number of neurons it contains but by virtue of the specificity with which they are connected. Unraveling this specificity is the task of neuroanatomy. In this endeavor, neuroanatomists have traditionally exploited an impressive array of tools ranging from the Golgi method to electron microscopy. An ideal method for studying anatomy would label neurons that are interconnected, and, in addition, allow expression of foreign genes in these neurons. Fortuitously, nature has already partially developed such a method in the form of neurotropic viruses, which have evolved to deliver their genetic material between synaptically connected neurons while largely eluding glia and the immune system. While these characteristics make some of these viruses a threat to human health, simple modifications allow them to be used in controlled experimental settings, thus enabling neuroanatomists to trace multi-synaptic connections within and across brain regions. Wild-type neurotropic viruses, such as rabies and alpha-herpes virus, have already contributed greatly to our understanding of brain connectivity, and modern molecular techniques have enabled the construction of recombinant forms of these and other viruses. These newly engineered reagents are particularly useful, as they can target genetically defined populations of neurons, spread only one synapse to either inputs or outputs, and carry instructions by which the targeted neurons can be made to express exogenous proteins, such as calcium sensors or light-sensitive ion channels, that can be used to study neuronal function. In this review, we address these uniquely powerful features of the viruses already in the neuroanatomist's toolbox, as well as the aspects of their biology that currently limit their utility. Based on the latter, we consider strategies for improving viral tracing methods by reducing toxicity, improving control of transsynaptic

  9. Neuroanatomy goes viral!

    Science.gov (United States)

    Nassi, Jonathan J; Cepko, Constance L; Born, Richard T; Beier, Kevin T

    2015-01-01

    The nervous system is complex not simply because of the enormous number of neurons it contains but by virtue of the specificity with which they are connected. Unraveling this specificity is the task of neuroanatomy. In this endeavor, neuroanatomists have traditionally exploited an impressive array of tools ranging from the Golgi method to electron microscopy. An ideal method for studying anatomy would label neurons that are interconnected, and, in addition, allow expression of foreign genes in these neurons. Fortuitously, nature has already partially developed such a method in the form of neurotropic viruses, which have evolved to deliver their genetic material between synaptically connected neurons while largely eluding glia and the immune system. While these characteristics make some of these viruses a threat to human health, simple modifications allow them to be used in controlled experimental settings, thus enabling neuroanatomists to trace multi-synaptic connections within and across brain regions. Wild-type neurotropic viruses, such as rabies and alpha-herpes virus, have already contributed greatly to our understanding of brain connectivity, and modern molecular techniques have enabled the construction of recombinant forms of these and other viruses. These newly engineered reagents are particularly useful, as they can target genetically defined populations of neurons, spread only one synapse to either inputs or outputs, and carry instructions by which the targeted neurons can be made to express exogenous proteins, such as calcium sensors or light-sensitive ion channels, that can be used to study neuronal function. In this review, we address these uniquely powerful features of the viruses already in the neuroanatomist's toolbox, as well as the aspects of their biology that currently limit their utility. Based on the latter, we consider strategies for improving viral tracing methods by reducing toxicity, improving control of transsynaptic spread, and extending

  10. Predicting clearance in humans from in vitro data.

    Science.gov (United States)

    Obach, R Scott

    2011-01-01

    The use of in vitro metabolism in scaling to predict human clearance of new chemical entities has become a commonplace activity in the research and development of new drugs. The measurement of in vitro lability in human liver microsomes, a rich source of drug metabolizing cytochrome P450 enzymes, has become a high throughput screen in many research organizations which is a testament to its usefulness in drug design. In this chapter, the methods used to scale in vitro clearance data to predict in vivo clearance are described. Importantly, the numerous assumptions that are required in order to use in vitro data in this manner are laid out. These include assumptions regarding the scaling process as well as technical aspects of the generation of the in vitro data. Finally, some other drug clearance processes that have been emerging as important are described with regard to ongoing research efforts to develop clearance prediction methods.

  11. FastStats: Viral Hepatitis

    Science.gov (United States)

    ... Submit What's this? Submit Button NCHS Home Viral Hepatitis Recommend on Facebook Tweet Share Compartir Data are for the U.S. Morbidity Number of new hepatitis A cases: 1,781 (2013) Number of new ...

  12. Aseptic meningitis and viral myelitis.

    Science.gov (United States)

    Irani, David N

    2008-08-01

    Meningitis and myelitis represent common and very infrequent viral infections of the central nervous system, respectively. The number of cases of viral meningitis that occurs annually exceeds the total number of meningitis cases caused by all other etiologies combined. Focal central nervous system infections, such as occur in the spinal cord with viral myelitis, are much less common and may be confused with noninfectious disorders that cause acute flaccid paralysis. This article reviews some of the important clinical features, epidemiology, diagnostic approaches, and management strategies for patients with aseptic meningitis and viral myelitis. Particular focus is placed on the diseases caused by enteroviruses, which as a group account for most aseptic meningitis cases and many focal infections of the spinal cord.

  13. Viral marketing as epidemiological model

    CERN Document Server

    Rodrigues, Helena Sofia

    2015-01-01

    In epidemiology, an epidemic is defined as the spread of an infectious disease to a large number of people in a given population within a short period of time. In the marketing context, a message is viral when it is broadly sent and received by the target market through person-to-person transmission. This specific marketing communication strategy is commonly referred as viral marketing. Due to this similarity between an epidemic and the viral marketing process and because the understanding of the critical factors to this communications strategy effectiveness remain largely unknown, the mathematical models in epidemiology are presented in this marketing specific field. In this paper, an epidemiological model SIR (Susceptible- Infected-Recovered) to study the effects of a viral marketing strategy is presented. It is made a comparison between the disease parameters and the marketing application, and simulations using the Matlab software are performed. Finally, some conclusions are given and their marketing impli...

  14. Analysis of conservativity analysis for clearance levels. Final report

    International Nuclear Information System (INIS)

    When deriving clearance levels for material from nuclear installations it is necessary to proceed with a certain degree of conservativity. This can, however, differ between various sets of clearance levels leading to inconsistencies between clearance pathways. The aim of the work therefore is to compare levels of conservativity for the following two sets of clearance levels: clearance levels for disposal as conventional waste and for metallic materials for recycling/reuse. A method was developed to quantify the degree of conservativity and make it comparable. The actual and future situation for disposal of (conventional) wastes in Germany was analysed. In addition, the masses, nuclide vectors, geographical distribution etc. for slightly radioactive material being cleared for conventional disposal was analysed and modelled and the resulting dose distributions were calculated. The values for the clearance levels were taken from the 1995 recommendation by the German Commission on Radiation Protection (SSK). By using realistic scenarios, the exposure was calculated for the personnel on the landfills and for persons of the general public being exposed via groundwater pathways. It could be shown that the trivial dose range will not be exceeded even if the masses of cleared material per landfill site exceed 100 Mg/a. Because of the types and distribution of nuclear installations in Germany and because of the nuclide vectors it is therefore not necessary to limit the masses per landfill sites. Clearance levels that are determined by the exposure pathways external exposure to and the inhalation of dust by the landfill personnel show a similar level of conservativity as those for metal scrap. This means that the clearance levels for gamma emitting nuclides are not overly restrictive. Although radiologically justified, raising the clearance levels would not lead to an increase of the material quantities because other nuclides of the respective nuclide vectors are limiting. In

  15. Viral infection, inflammation and schizophrenia

    OpenAIRE

    Kneeland, Rachel E.; Fatemi, S. Hossein

    2012-01-01

    Schizophrenia is a severe neurodevelopmental disorder with genetic and environmental etiologies. Prenatal viral/bacterial infections and inflammation play major roles in the genesis of schizophrenia. In this review, we describe a viral model of schizophrenia tested in mice whereby the offspring of mice prenatally infected with influenza at E7, E9, E16, and E18 show significant gene, protein, and brain structural abnormalities postnatally. Similarly, we describe data on rodents exposed to bact...

  16. Viral diseases of northern ungulates

    OpenAIRE

    Frölich, K.

    2000-01-01

    This paper describes viral diseases reported in northern ungulates and those that are a potential threat to these species. The following diseases are discussed: bovine viral diarrhoea/mucosal disease (BVD/MD), alphaherpesvirus infections, malignant catarrhal fever (MCF), poxvirus infections, parainfluenza type 3 virus infection, Alvsborg disease, foot-and-mouth disease, epizootic haemorrhage disease of deer and bluetongue disease, rabies, respiratory syncytial virus infection, adenovirus infe...

  17. Viral RNAs are unusually compact.

    Directory of Open Access Journals (Sweden)

    Ajaykumar Gopal

    Full Text Available A majority of viruses are composed of long single-stranded genomic RNA molecules encapsulated by protein shells with diameters of just a few tens of nanometers. We examine the extent to which these viral RNAs have evolved to be physically compact molecules to facilitate encapsulation. Measurements of equal-length viral, non-viral, coding and non-coding RNAs show viral RNAs to have among the smallest sizes in solution, i.e., the highest gel-electrophoretic mobilities and the smallest hydrodynamic radii. Using graph-theoretical analyses we demonstrate that their sizes correlate with the compactness of branching patterns in predicted secondary structure ensembles. The density of branching is determined by the number and relative positions of 3-helix junctions, and is highly sensitive to the presence of rare higher-order junctions with 4 or more helices. Compact branching arises from a preponderance of base pairing between nucleotides close to each other in the primary sequence. The density of branching represents a degree of freedom optimized by viral RNA genomes in response to the evolutionary pressure to be packaged reliably. Several families of viruses are analyzed to delineate the effects of capsid geometry, size and charge stabilization on the selective pressure for RNA compactness. Compact branching has important implications for RNA folding and viral assembly.

  18. Nuclear regulation. NRC's security clearance program can be strengthened

    International Nuclear Information System (INIS)

    Because of the national security implications of its programs, the Nuclear Regulatory Commission (NRC) investigates the background of its employees and consultants as well as others to ensure that they are reliable and trustworthy. If the investigation indicates that an employee will not endanger national security, NRC grants a security clearance that allows access to classified information, material, and facilities. NRC also requires periodic checks for some clearance holders to ensure their continued clearance eligibility. The Chairman, Subcommittee on Environment, Energy, and Natural Resources, House Committee on Government Operations, asked GAO to review NRC's personnel security clearance program and assess the procedures that NRC uses to ensure that those who operate nuclear power plants do not pose a threat to the public. The Atomic Energy Act of 1954 requires NRC to conduct background investigations of its employees and consultants as well as others who have access to classified information, material, or facilities. To do this, NRC established a personnel security clearance program. Under NRC policies, a security clearance is granted after the Office of Personnel Management (OPM) or the Federal Bureau of Investigation checks the background of those applying for an NRC clearance. NRC also periodically reassesses the integrity of those holding the highest level clearance. NRC employees, consultants, contractors, and licensees as well as other federal employees hold approximately 10,600 NRC clearances. NRC does not grant clearances to commercial nuclear utility employees unless they require access to classified information or special nuclear material. However, the utilities have voluntarily established screening programs to ensure that their employees do not pose a threat to nuclear plants. NRC faces a dilemma when it hires new employees. Although its policy calls for new hires to be cleared before they start work, the security clearance process takes so long

  19. Plasma HIV Viral Rebound following Protocol-Indicated Cessation of ART Commenced in Primary and Chronic HIV Infection

    DEFF Research Database (Denmark)

    Hamlyn, Elizabeth; Ewings, Fiona M; Porter, Kholoud;

    2012-01-01

    OBJECTIVES: The magnitude of HIV viral rebound following ART cessation has consequences for clinical outcome and onward transmission. We compared plasma viral load (pVL) rebound after stopping ART initiated in primary (PHI) and chronic HIV infection (CHI). DESIGN: Two populations with protocol-in...

  20. [Neuropsychiatric sequelae of viral meningitis in adults].

    Science.gov (United States)

    Damsgaard, Jesper; Hjerrild, Simon; Renvillard, Signe Groth; Leutscher, Peter Derek Christian

    2011-10-10

    Viral meningitis is considered to be a benign illness with only mild symptoms. In contrast to viral encephalitis and bacterial meningitis, the prognosis is usually good. However, retrospective studies have demonstrated that patients suffering from viral meningitis may experience cognitive impairment following the acute course of infection. Larger controlled studies are needed to elucidate the potential neuropsychiatric adverse outcome of viral meningitis.

  1. Effects of drugs on mucus clearance.

    Science.gov (United States)

    Houtmeyers, E; Gosselink, R; Gayan-Ramirez, G; Decramer, M

    1999-08-01

    Mucociliary clearance (MCC), the process in which airway mucus together with substances trapped within are moved out of the lungs, is an important defence mechanism of the human body. Drugs may alter this process, such that it is necessary to know the effect of the drugs on MCC. Indeed, agents stimulating MCC may be used therapeutically in respiratory medicine, especially in patients suspected of having an impairment of their mucociliary transport system. In contrast, caution should be taken with drugs depressing MCC as an undesired side-effect, independently of their therapeutic indication. Since cough clearance (CC) serves as a back-up system when MCC fails, the influence of drugs must be examined not only on MCC but also on CC. Ultimately, the clinical repercussions of alterations in mucus transport induced by drug administration must be studied. Tertiary ammonium compounds (anticholinergics), aspirin, anaesthetic agents and benzodiazepines have been shown to be capable of depressing the mucociliary transport system. Cholinergics, methylxanthines, sodium cromoglycate, hypertonic saline, saline as well as water aerosol have been shown to increase MCC. Adrenergic antagonists, guaifenesin, S-carboxymethylcysteine, sodium 2-mercapto-ethane sulphonate and frusemide have been reported not to alter the mucociliary transport significantly. Amiloride, uridine 5'-triphosphate (UTP), quaternary ammonium compounds (anticholinergics), adrenergic agonists, corticosteroids, recombinant human deoxyribonuclease (rhDNase), N-acetylcysteine, bromhexine and ambroxol have been reported either not to change or to augment MCC. Indirect data suggest that surfactant as well as antibiotics may improve the mucociliary transport system. As for the influence of drugs on CC, amiloride and rhDNase have been demonstrated to increase the effectiveness of cough. A trend towards an improved CC was noted after treatment with adrenergic agonists. The anticholinergic agent ipratropium bromide, which

  2. DNA-AuNP networks on cell membranes as a protective barrier to inhibit viral attachment, entry and budding.

    Science.gov (United States)

    Li, Chun Mei; Zheng, Lin Ling; Yang, Xiao Xi; Wan, Xiao Yan; Wu, Wen Bi; Zhen, Shu Jun; Li, Yuan Fang; Luo, Ling Fei; Huang, Cheng Zhi

    2016-01-01

    Viral infections have caused numerous diseases and deaths worldwide. Due to the emergence of new viruses and frequent virus variation, conventional antiviral strategies that directly target viral or cellular proteins are limited because of the specificity, drug resistance and rapid clearance from the human body. Therefore, developing safe and potent antiviral agents with activity against viral infection at multiple points in the viral life cycle remains a major challenge. In this report, we propose a new modality to inhibit viral infection by fabricating DNA conjugated gold nanoparticle (DNA-AuNP) networks on cell membranes as a protective barrier. The DNA-AuNPs networks were found, via a plaque formation assay and viral titers, to have potent antiviral ability and protect host cells from human respiratory syncytial virus (RSV). Confocal immunofluorescence image analysis showed 80 ± 3.8% of viral attachment, 91.1 ± 0.9% of viral entry and 87.9 ± 2.8% of viral budding were inhibited by the DNA-AuNP networks, which were further confirmed by real-time fluorescence imaging of the RSV infection process. The antiviral activity of the networks may be attributed to steric effects, the disruption of membrane glycoproteins and limited fusion of cell membrane bilayers, all of which play important roles in viral infection. Therefore, our results suggest that the DNA-AuNP networks have not only prophylactic effects to inhibit virus attachment and entry, but also therapeutic effects to inhibit viral budding and cell-to-cell spread. More importantly, this proof-of-principle study provides a pathway for the development of a universal, broad-spectrum antiviral therapy.

  3. Integrated Turbine Tip Clearance and Gas Turbine Engine Simulation

    Science.gov (United States)

    Chapman, Jeffryes W.; Kratz, Jonathan; Guo, Ten-Huei; Litt, Jonathan

    2016-01-01

    Gas turbine compressor and turbine blade tip clearance (i.e., the radial distance between the blade tip of an axial compressor or turbine and the containment structure) is a major contributing factor to gas path sealing, and can significantly affect engine efficiency and operational temperature. This paper details the creation of a generic but realistic high pressure turbine tip clearance model that may be used to facilitate active tip clearance control system research. This model uses a first principles approach to approximate thermal and mechanical deformations of the turbine system, taking into account the rotor, shroud, and blade tip components. Validation of the tip clearance model shows that the results are realistic and reflect values found in literature. In addition, this model has been integrated with a gas turbine engine simulation, creating a platform to explore engine performance as tip clearance is adjusted. Results from the integrated model explore the effects of tip clearance on engine operation and highlight advantages of tip clearance management.

  4. A comparative review of HLA associations with hepatitis B and C viral infections across global populations

    Institute of Scientific and Technical Information of China (English)

    Rashmi Singh; Rashmi Kaul; Anil Kaul; Khalid Khan

    2007-01-01

    Hepatitis B (HBV) and hepatitis C (HCV) viral infection or co-infection leads to risk of development of chronic infection, cirrhosis and hepatocellular carcinoma (HCC). Immigration and globalization have added to the challenges of public health concerns regarding chronic HBV and HCV infections worldwide. The aim of this study is to review existing global literature across ethnic populations on HBV and HCV related human leukocyte antigen (HLA) associations in relation to susceptibility, viral persistence and treatment. Extensive literature search was conducted to explore the HLA associations in HBV and HCV infections reported across global populations over the past decade to understand the knowledge status, weaknesses and strengths of this information in different ethnic populations. HLA DR13 is consistently associated with HBV clearance globally. HLADRB1*11/*12 alleles and DQB1*0301 are associated with HBV persistence but with HCV clearance worldwide. Consistent association of DRB1*03 and *07 is observed with HCV susceptibility and non-responsiveness to HBV vaccination across the population. HLA DR13 is protective for vertical HBV and HCV transmission in Chinese and Italian neonates, but different alleles are associated with their susceptibility in these populations. HLA class I molecule interactions with Killer cell immunoglobulin like receptors (KIR) of natural killer (NK) cells modulate HCV infection outcome via regulating immune regulatory cells and molecules. HLA associations with HBV vaccination, interferon therapy in HBV and HCV, and with extra hepatic manifestations of viral hepatitis are also discussed. Systematic studies in compliance with global regulatory standards are required to identify the HLA specific viral epitope, stage specific T cell populations interacting with different HLA alleles during disease progression and viral clearance ofchronic HBV or HCV infections among different ethnic populations. These studies would facilitate stage specific

  5. [Pathology and viral metagenomics, a recent history].

    Science.gov (United States)

    Bernardo, Pauline; Albina, Emmanuel; Eloit, Marc; Roumagnac, Philippe

    2013-05-01

    Human, animal and plant viral diseases have greatly benefited from recent metagenomics developments. Viral metagenomics is a culture-independent approach used to investigate the complete viral genetic populations of a sample. During the last decade, metagenomics concepts and techniques that were first used by ecologists progressively spread into the scientific field of viral pathology. The sample, which was first for ecologists a fraction of ecosystem, became for pathologists an organism that hosts millions of microbes and viruses. This new approach, providing without a priori high resolution qualitative and quantitative data on the viral diversity, is now revolutionizing the way pathologists decipher viral diseases. This review describes the very last improvements of the high throughput next generation sequencing methods and discusses the applications of viral metagenomics in viral pathology, including discovery of novel viruses, viral surveillance and diagnostic, large-scale molecular epidemiology, and viral evolution.

  6. A mouse model for studying the clearance of hepatitis B virus in vivo using a luciferase reporter.

    Directory of Open Access Journals (Sweden)

    Sheng-qiang Liang

    Full Text Available Hepatitis B virus(HBV infection remains a global problem, despite the effectiveness of the Hepatitis B vaccine in preventing infection. The resolution of Hepatitis B virus infection has been believed to be attributable to virus-specific immunity. In vivo direct evaluation of anti-HBV immunity in the liver is currently not possible. We have developed a new assay system that detects HBV clearance in the liver after the hydrodynamic transfer of a reporter gene and over-length, linear HBV DNA into hepatocytes, followed by bioluminescence imaging of the reporter gene (Fluc. We employed bioluminescence detection of luciferase expression in HBV-infected hepatocytes to measure the Hepatitis B core antigen (HBcAg-specific immune responses directed against these infected hepatocytes. Only HBcAg-immunized, but not mock-treated, animals decreased the amounts of luciferase expression, HBsAg and viral DNA from the liver at day 28 after hydrodynamic infection with over-length HBV DNA, indicating that control of luciferase expression correlates with viral clearance from infected hepatocytes.

  7. Modeling latently infected cell activation: viral and latent reservoir persistence, and viral blips in HIV-infected patients on potent therapy.

    Directory of Open Access Journals (Sweden)

    Libin Rong

    2009-10-01

    Full Text Available Although potent combination therapy is usually able to suppress plasma viral loads in HIV-1 patients to below the detection limit of conventional clinical assays, a low level of viremia frequently can be detected in plasma by more sensitive assays. Additionally, many patients experience transient episodes of viremia above the detection limit, termed viral blips, even after being on highly suppressive therapy for many years. An obstacle to viral eradication is the persistence of a latent reservoir for HIV-1 in resting memory CD4(+ T cells. The mechanisms underlying low viral load persistence, slow decay of the latent reservoir, and intermittent viral blips are not fully characterized. The quantitative contributions of residual viral replication to viral and the latent reservoir persistence remain unclear. In this paper, we probe these issues by developing a mathematical model that considers latently infected cell activation in response to stochastic antigenic stimulation. We demonstrate that programmed expansion and contraction of latently infected cells upon immune activation can generate both low-level persistent viremia and intermittent viral blips. Also, a small fraction of activated T cells revert to latency, providing a potential to replenish the latent reservoir. By this means, occasional activation of latently infected cells can explain the variable decay characteristics of the latent reservoir observed in different clinical studies. Finally, we propose a phenomenological model that includes a logistic term representing homeostatic proliferation of latently infected cells. The model is simple but can robustly generate the multiphasic viral decline seen after initiation of therapy, as well as low-level persistent viremia and intermittent HIV-1 blips. Using these models, we provide a quantitative and integrated prospective into the long-term dynamics of HIV-1 and the latent reservoir in the setting of potent antiretroviral therapy.

  8. NUMERICAL SIMULATION OF TIP-CLEARANCE FLOW IN CASCADE

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    The tip-clearance flow in a cascade was numerically simulated by solving the RANS equations of incompressible fluids. The computational model was based upon the artificial compressibility formulation proposed by Chorin. The Baldwin-Lomax turbulence model was used to make the governing equations closed. For the specific structure of tip-clearance flow, a multi-block grid structure was adopted to facilitate numerical computations. The comparison of numerical results with experimental data indicates that the present method is capable of simulating tip-clearance flows with satisfactory accuracy.

  9. Clearance from the anterior chamber of RBCs from human diabetics

    International Nuclear Information System (INIS)

    Erythrocytes from diabetic patients manifest decreased deformability and increased adherence. These abnormal membrane properties may diminish the ability of erythrocytes (RBCs) from diabetics to undergo deformation in passage through the trabecular meshwork. Using sodium chromate Cr 51-labeled RBCs from type I diabetic patients with proliferative retinopathy and normal control subjects, we studied RBC clearance from the rabbit anterior chamber. The mean time for 50% clearance (T50) of RBCs from diabetics (76 hours) was significantly longer than that for RBCs from normal subjects (19.5 hours). In this model, RBCs from diabetics have a slower clearance from the anterior chamber than do RBCs from normal subjects

  10. Viral metagenomics and blood safety.

    Science.gov (United States)

    Sauvage, V; Eloit, M

    2016-02-01

    The characterization of the human blood-associated viral community (also called blood virome) is essential for epidemiological surveillance and to anticipate new potential threats for blood transfusion safety. Currently, the risk of blood-borne agent transmission of well-known viruses (HBV, HCV, HIV and HTLV) can be considered as under control in high-resource countries. However, other viruses unknown or unsuspected may be transmitted to recipients by blood-derived products. This is particularly relevant considering that a significant proportion of transfused patients are immunocompromised and more frequently subjected to fatal outcomes. Several measures to prevent transfusion transmission of unknown viruses have been implemented including the exclusion of at-risk donors, leukocyte reduction of donor blood, and physicochemical treatment of the different blood components. However, up to now there is no universal method for pathogen inactivation, which would be applicable for all types of blood components and, equally effective for all viral families. In addition, among available inactivation procedures of viral genomes, some of them are recognized to be less effective on non-enveloped viruses, and inadequate to inactivate higher viral titers in plasma pools or derivatives. Given this, there is the need to implement new methodologies for the discovery of unknown viruses that may affect blood transfusion. Viral metagenomics combined with High Throughput Sequencing appears as a promising approach for the identification and global surveillance of new and/or unexpected viruses that could impair blood transfusion safety. PMID:26778104

  11. Longitudinal serum HIV RNA quantification: correlation to viral phenotype at seroconversion and clinical outcome

    DEFF Research Database (Denmark)

    Katzenstein, T L; Pedersen, C; Nielsen, C;

    1996-01-01

    . Harbouring syncytium-inducing (SI) virus at seroconversion was associated with faster progression to AIDS than non-SI (NSI; P < 0.005). The increased in vitro replication rate of SI over NSI was not translated into significantly higher serum HIV RNA. CONCLUSION: Serum HIV RNA is high around the time of......OBJECTIVE: To investigate the longitudinal changes in serum HIV RNA, and to clarify whether the viral load early in infection has a predictive value for the clinical outcome; also, to correlate viral phenotype at seroconversion and changes in CD4 cell counts with viral burden. DESIGN: Twenty...... seroconverters with HIV isolates available at seroconversion had HIV RNA quantified by polymerase chain reaction (PCR) at seroconversion and thereafter every 6 months. Mean follow-up time was 65 months. Patients were classified according to viral phenotype at seroconversion, time to AIDS progression, serum viral...

  12. Impact of Load Behavior on Transient Stability and Power Transfer Limitations

    OpenAIRE

    Gordon, Mark

    2009-01-01

    This paper presents utility based load modeling practices and explores the interaction between loads and the power system and the effect of the interaction on transient stability and power transfer limitations. The effect of load composition is investigated at major load centers together with the impact on rotor angle excursions of large scale generators during the transient and post-transient period. Responses of multi-induction motor stalling are also considered for different fault clearanc...

  13. Comparative genotypic study of viral RNA and proviral DNA in HIV-1 patients

    OpenAIRE

    Chan, Wing-tsin, Alison; 陳穎芊

    2015-01-01

    Highly Active Antiretroviral Therapy (HAART) has been used for HIV-1 treatment for more than a decade. Prior identification of drug resistance associated mutations and viral tropism provides valuable information for physicians in optimizing the best HAART regimens for each patient. Plasma RNA has long been used as the major laboratory marker as it reflects the status of circulating virus. However, it might not be as informative in patients with low viral loads. Proviral DNA was therefore sugg...

  14. Enterovirus 71-induced autophagy increases viral replication and pathogenesis in a suckling mouse model

    OpenAIRE

    Lee, Ying-Ray; Wang, Po-Shun; Wang, Jen-Ren; Liu, Hsiao-Sheng

    2014-01-01

    Background We previously reported that Enterovirus 71 (EV71) infection activates autophagy, which promotes viral replication both in vitro and in vivo. In the present study we further investigated whether EV71 infection of neuronal SK-N-SH cells induces an autophagic flux. Furthermore, the effects of autophagy on EV71-related pathogenesis and viral load were evaluated after intracranial inoculation of mouse-adapted EV71 (MP4 strain) into 6-day-old ICR suckling mice. Results We demonstrated th...

  15. Direct association between pharyngeal viral secretion and host cytokine response in severe pandemic influenza

    Directory of Open Access Journals (Sweden)

    Castro Carmen

    2011-08-01

    Full Text Available Abstract Background Severe disease caused by 2009 pandemic influenza A/H1N1virus is characterized by the presence of hypercytokinemia. The origin of the exacerbated cytokine response is unclear. As observed previously, uncontrolled influenza virus replication could strongly influence cytokine production. The objective of the present study was to evaluate the relationship between host cytokine responses and viral levels in pandemic influenza critically ill patients. Methods Twenty three patients admitted to the ICU with primary viral pneumonia were included in this study. A quantitative PCR based method targeting the M1 influenza gene was developed to quantify pharyngeal viral load. In addition, by using a multiplex based assay, we systematically evaluated host cytokine responses to the viral infection at admission to the ICU. Correlation studies between cytokine levels and viral load were done by calculating the Spearman correlation coefficient. Results Fifteen patients needed of intubation and ventilation, while eight did not need of mechanical ventilation during ICU hospitalization. Viral load in pharyngeal swabs was 300 fold higher in the group of patients with the worst respiratory condition at admission to the ICU. Pharyngeal viral load directly correlated with plasma levels of the pro-inflammatory cytokines IL-6, IL-12p70, IFN-γ, the chemotactic factors MIP-1β, GM-CSF, the angiogenic mediator VEGF and also of the immuno-modulatory cytokine IL-1ra (p Conclusions Severe respiratory disease caused by the 2009 pandemic influenza virus is characterized by the existence of a direct association between viral replication and host cytokine response, revealing a potential pathogenic link with the severe disease caused by other influenza subtypes such as H5N1.

  16. Discussing viral load levels after HIV/AIDS merges HBV/HCV infection and its relationship with T lymphocytes%HIV/AIDS合并HBV/HCV感染病毒载量水平及与T淋巴细胞相关性的探讨

    Institute of Scientific and Technical Information of China (English)

    张茹薏; 游晶; 杨微波; 饶少锋

    2016-01-01

    目的:探讨人类免疫缺陷病毒(HIV)/艾滋病(AIDS)合并乙型肝炎病毒(HBV)/丙型肝炎病毒(HCV)感染后病毒载量水平变化及对机体T淋巴细胞免疫机制的影响。方法分别测定 HIV/AIDS单纯感染组,HIV/HBV合并感染组,HIV/HCV合并感染组3组的 HIV RNA、HBV DNA、HCV RNA、CD4+ T淋巴细胞频数、CD8+ T淋巴细胞频数、CD4/CD8比值,并分析各组T淋巴细胞与HIV RNA的关系,HBV DNA/HCV RNA与HIV RNA、CD4+ T淋巴细胞、CD8+ T淋巴细胞、CD4/CD8比值的相关性。结果 HIV/AIDS单纯感染组、HIV/HBV合并感染组及 HIV/HCV合并感染组的CD4+ T 淋巴细胞与各自组的HIV RNA呈负相关,差异有统计学意义(P<0.05);HIV/AIDS单纯感染组、HIV/HBV合并感染组的CD8+ T淋巴细胞与各自组的HIV RNA呈负相关,差异有统计学意义(P<0.05);HIV/AIDS单纯感染组、HIV/HBV合并感染组及 HIV/HCV合并感染组的CD4/CD8与各自组的HIV RNA呈负相关,差异有统计学意义(P<0.05)。结论合并感染 HBV后,HIV/AIDS患者T细胞的数量下降更明显,致HIV RNA、HBV DNA高载量,加速了 HIV病情进展;感染 HBV后CD4+ T细胞的数量下降比感染HCV更明显。%Objective To explore the viral load levels after HIV/AIDS merges HBV/HCV infection and its relationship with T lymphocytes .Methods HIV RNA ,HBV DNA ,HCV RNA ,CD4+ T lymphocyte frequency ,CD8+ T lymphocyte frequency ,CD4/CD8 measured in HIV/AIDS simple infection group ,mixed HIV/HBV infection group and mixed HIV/HCV infection group .Ana‐lyze relationship of T lymphocyte and HIV RNA ,the correlation of HBV DNA/HCV RNA ,HIV RNA ,CD4+ T lymphocyte fre‐quency ,CD8+ T lymphocyte frequency ,CD4/CD8 .Results CD4+ T lymphocyte frequency of HIV/AIDS simple infection group , mixed HIV/HBV infection group and mixed HIV/HCV infection group showed negative correlated with their respective

  17. System-Level Design of a Shape Memory Alloy Actuator for Active Clearance Control in the High-Pressure Turbine

    Science.gov (United States)

    DeCastro, Jonathan A.; Melcher, Kevin J.; Noebe, Ronald D.

    2005-01-01

    This paper describes results of a numerical analysis evaluating the feasibility of high-temperature shape memory alloys (HTSMA) for active clearance control actuation in the high-pressure turbine section of a modern turbofan engine. The prototype actuator concept considered here consists of parallel HTSMA wires attached to the shroud that is located on the exterior of the turbine case. A transient model of an HTSMA actuator was used to evaluate active clearance control at various operating points in a test bed aircraft engine simulation. For the engine under consideration, each actuator must be designed to counteract loads from 380 to 2000 lbf and displace at least 0.033 inches. Design results show that an actuator comprised of 10 wires 2 inches in length is adequate for control at critical engine operating points and still exhibits acceptable failsafe operability and cycle life. A proportional-integral-derivative (PID) controller with integrator windup protection was implemented to control clearance amidst engine transients during a normal mission. Simulation results show that the control system exhibits minimal variability in clearance control performance across the operating envelope. The final actuator design is sufficiently small to fit within the limited space outside the high-pressure turbine case and is shown to consume only small amounts of bleed air to adequately regulate temperature.

  18. 低水平病毒载量长期不进展人类免疫缺陷病毒-1感染者的人类免疫缺陷病毒-1的遗传分析%Genetic analysis of human immunodeficieney virus-1 in long-term non-progress human immunodeficiency virus-1 infected individuals with low viral load

    Institute of Scientific and Technical Information of China (English)

    陈伟烈; 唐小平; 唐漾波; 魏绍静

    2009-01-01

    目的 分析低水平病毒载量长期不进展(LTNP)HIV-1感染者HIV-1的遗传特征.方法 采用有限稀释套式PCR、终点PCR和序列确证分析等技术对5例低病毒载量LTNP HIV-1感染者不同随访时间点HIV-1前病毒enw基因c2-v3-c3区域和gag基因p17区域进行扩增和序列分析.分别计算不同时间点内以及不同时间点与用于分析的最早时间点之间上述两个基因区域的基因多样性和基因离散率,依据基因离散率计算基因的进化率,统计学分析用GraphPad Prism 5软件.结果 5例患者在21个随访时间点共获得115条c2-v3-c3序列和173条p17序列.进化树分析表明,不同患者的序列分开,同一患者的序列特异地聚集,序列质量可靠.5例患者env基因c2-v3-c3区域不同时间点基因多样性为0~6.38%,平均为2.1%,病例1、3和5基因多样性随感染时间的增加逐渐升高(r=0.7257、0.4954、0.3288),病例2和4基因多样性随感染时间的增加逐渐下降(r=-0.3759、-0.5028);基因离散率为0.1%~6.5%,平均为2.9%,除病例1外,基因离散率均随感染时间间隔的增加逐渐升高,进化率分别为每年每位点-0.13%、0.81%、0.09%、0.14%和0.16%,平均为0.21%.gag基因p17区域基因多样性为0~2.5%,平均为1.2%,基因离散率为0.2%~2.7%,平均为1.4%,除病例3基因多样性和基因离散率随感染时间或时间间隔的增加下降外,其余病例均随感染时间或时间间隔的增加而逐渐升高,进化率分别为每年每位点0.087%、0.064%、-0.014%、0.081%和0.087%,平均为0.061%.结论 低水平病毒载量LTNP HIV-1感染者HIV-1有复制能力,病毒基因维持较低水平的进化;HIV-1 env基因变化的程度大于gag基因.%Objective To analyze the genetic characteristics of human immunodeficiency virus (HIV)-1 in long-term non-progress (LTNP) HIV-1 infected individuals with low viral load. Methods Limiting dilution nested polymerase chain reaction (PCR) and end-point PCR were used to

  19. Integrin Activation and Viral Infection

    Institute of Scientific and Technical Information of China (English)

    Shan-dian GAO; Jun-zheng DU; Jian-hua ZHOU; Hui-yun CHANG; Qing-ge XIE

    2008-01-01

    Integrins are members of a ubiquitous membrane receptor family which includes 18 different α subunits and 8 β subunits forming more than 20 α/β heterodimers. Integrins play key functions in vascular endothelial cell and tumour cell adhesion, lymphocyte trafficking, tumor growth and viral infection. Current understanding of the molecular basis of integrins as viral receptors has been achieved through many decades of study into the biology of transmembrane glycoproteins and their interactions with several viruses. This review provides a summary of the current knowledge on the molecular bases of interactions between viruses and integrins, which are of potential practical significance. Inhibition of virus-integrin interactions at the points of virus attachment or entry will provide a novel approach for the therapeutic treatment of viral diseases.

  20. T Cell Memory in the Context of Persistent Herpes Viral Infections

    Directory of Open Access Journals (Sweden)

    Nicole Torti

    2012-07-01

    Full Text Available The generation of a functional memory T cell pool upon primary encounter with an infectious pathogen is, in combination with humoral immunity, an essential process to confer protective immunity against reencounters with the same pathogen. A prerequisite for the generation and maintenance of long-lived memory T cells is the clearance of antigen after infection, which is fulfilled upon resolution of acute viral infections. Memory T cells play also a fundamental role during persistent viral infections by contributing to relative control and immuosurveillance of active replication or viral reactivation, respectively. However, the dynamics, the phenotype, the mechanisms of maintenance and the functionality of memory T cells which develop upon acute/resolved infection as opposed to chronic/latent infection differ substantially. In this review we summarize current knowledge about memory CD8 T cell responses elicited during α-, β-, and γ-herpes viral infections with major emphasis on the induction, maintenance and function of virus-specific memory CD8 T cells during viral latency and we discuss how the peculiar features of these memory CD8 T cell responses are related to the biology of these persistently infecting viruses.

  1. TDP-43 regulates endogenous retrovirus-K viral protein accumulation.

    Science.gov (United States)

    Manghera, Mamneet; Ferguson-Parry, Jennifer; Douville, Renée N

    2016-10-01

    The concomitant expression of neuronal TAR DNA binding protein 43 (TDP-43) and human endogenous retrovirus-K (ERVK) is a hallmark of ALS. Since the involvement of TDP-43 in retrovirus replication remains controversial, we sought to evaluate whether TDP-43 exerts an effect on ERVK expression. In this study, TDP-43 bound the ERVK promoter in the context of inflammation or proteasome inhibition, with no effect on ERVK transcription. However, over-expression of ALS-associated aggregating forms of TDP-43, but not wild-type TDP-43, significantly enhanced ERVK viral protein accumulation. Human astrocytes and neurons further demonstrated cell-type specific differences in their ability to express and clear ERVK proteins during inflammation and proteasome inhibition. Astrocytes, but not neurons, were able to clear excess ERVK proteins through stress granule formation and autophagy. In vitro findings were validated in autopsy motor cortex tissue from patients with ALS and neuro-normal controls. We further confirmed marked enhancement of ERVK in cortical neurons of patients with ALS. Despite evidence of enhanced stress granule and autophagic response in ALS cortical neurons, these cells failed to clear excess ERVK protein accumulation. This highlights how multiple cellular pathways, in conjunction with disease-associated mutations, can converge to modulate the expression and clearance of viral gene products from genomic elements such as ERVK. In ALS, ERVK protein aggregation is a novel aspect of TDP-43 misregulation contributing towards the pathology of this neurodegenerative disease. PMID:27370226

  2. Overview of hepatitis B viral replication and genetic variability.

    Science.gov (United States)

    Tong, Shuping; Revill, Peter

    2016-04-01

    Chronic infection with hepatitis B virus (HBV) greatly increases the risk for liver cirrhosis and hepatocellular carcinoma (HCC). HBV isolates worldwide can be divided into ten genotypes. Moreover, the immune clearance phase selects for mutations in different parts of the viral genome. The outcome of HBV infection is shaped by the complex interplay of the mode of transmission, host genetic factors, viral genotype and adaptive mutations, as well as environmental factors. Core promoter mutations and mutations abolishing hepatitis B e antigen (HBeAg) expression have been implicated in acute liver failure, while genotypes B, C, subgenotype A1, core promoter mutations, preS deletions, C-terminal truncation of envelope proteins, and spliced pregenomic RNA are associated with HCC development. Our efforts to treat and prevent HBV infection are hampered by the emergence of drug resistant mutants and vaccine escape mutants. This paper provides an overview of the HBV life cycle, followed by review of HBV genotypes and mutants in terms of their biological properties and clinical significance. PMID:27084035

  3. 99mTc-HEPIDA hepatic clearance as a diagnostic tool: usefulness of plasma and hepatic clearance for assessment of hepatic parenchyma performance.

    Science.gov (United States)

    Frieske, Izabela; Surma, Marian J; Bieńkiewicz, Małgorzata; Białkowska-Warzecha, Jolanta; Liniecki, Julian; Kuydowicz, Jan; Kuśmierek, Jacek

    2003-01-01

    Plasma clearance of (99m)Tc-HEPIDA (Cl(Pl)) has been used for two decades for assessment of liver function in patients with diseases of this organ. A specific determination of (99m)Tc-HEPIDA liver clearance (Cl(Hp)) has been developed that provides more direct possibility to evaluate performance of liver parenchyma. Both tests have been studied in healthy volunteers of varying age (48 individuals) and in 83 patients with varying degree of liver damage. The liver damage has been evaluated on the basis of 5 biochemical tests (AspAT, ALAT, GGTP, bilirubine serum concentration, proteinogram) and a score system used for total impairment, which was calculated for each patient. Normal range of Cl(Pl) and Cl(Hp) was determined from a study on healthy individuals (volunteers). The results seem independent of age, but show sex differences. The following values (mean +/- SD) of Cl(Hp) were found in males and females of: (181 +/- 31) ml//min/1.73 m(2) and (158 +/- 22) ml/min/1.73m(2), and of Cl(Pl) were (224 +/- 33) ml/min/1.73 m(2) and (202 +/- 25) ml/min/1.73 m(2) respectively. Accepted lower boundaries of both quantities (mean -2SD) are 115 ml/min/1.73 m(2) and 150 ml/min/1.73 m(2) correspondingly. Negative correlation of individual values of both clearances in all patients with individual score of liver damage were highly significant and correlation coefficients obtained were higher for Cl(Hp) (r = -0.63) than those for Cl(Pl) (r= -0.56). Factorial analysis was performed with the intention of seeing which of the studied factors had the highest factor loading for parenchyma performance that was assumed as the common factor responsible for correlations. The highest value was obtained for hepatic clearance (Cl(Hp)) of (99m)Tc-HEPIDA. In conclusion this quantity seems highly promising as a clinically useful test for assessment of liver performance, both in screening for liver damage and for monitoring of organ conditions during therapy and follow-up of patients.

  4. Design Optimization of Ground Clearance of Domestic Cars

    Directory of Open Access Journals (Sweden)

    Debojyoti Mitra

    2010-07-01

    Full Text Available Drag and lift forces plays a vital role in the performance and stability of vehicles. Less drag means less fuel consumption and hence less vehicular pollution. Also, lower lift force means higher chance of adhesion of the car body with the ground causing less overturning of the vehicle, which improves the vehicle performance. Both drag and lift forces can be manipulated by varying the ground clearance of the cars. The present study concentrates on studying the effect of ground clearance on these aerodynamic forces experimentally. Wind tunnel studies with a notch-back car model revealed increase in drag and decrease in lift with increase in ground clearance. Therefore, optimization is required for designing the best ground clearance and a preferable value of the same is thus obtained.

  5. 49 CFR 229.71 - Clearance above top of rail.

    Science.gov (United States)

    2010-10-01

    ..., DEPARTMENT OF TRANSPORTATION RAILROAD LOCOMOTIVE SAFETY STANDARDS Safety Requirements Suspension System § 229.71 Clearance above top of rail. No part or appliance of a locomotive except the wheels,...

  6. Enhancement of the amylase-creatinine clearance ratio in pregnancy.

    Science.gov (United States)

    Naeije, R; Neuray, F; Van Melsen, A; Delcourt, A

    1979-01-01

    The renal clearance of amylase, expressed as a proportion of simultaneous creatinine clearance (Cam/-Ccr), was determined in 131 women in various stages of pregnancy. No abnormal serum levels of amylase were found. A moderate but significant increase in Cam/Ccr occurred during the last 15 weeks of pregnancy. Possible causes for this change were investigated in smaller groups of subjects. No increase in rapidly cleared isoamylase could be detected. No modification in renal tubular handling of protein could be evidenced, as assessed by measurements of the renal clearance of beta 2 microglobulin, expressed as a proportion of simultaneous creatinine clearance. An incrased glomerular permeability to amylase probably accounts for elevated Cam/Ccr in pregnancy.

  7. IFNL4 affects clearance of hepatitis C virus

    Science.gov (United States)

    Scientists have discovered a new human interferon gene, Interferon Lambda 4 (IFNL4), that affects clearance of the hepatitis C virus. They also identified an inherited genetic variant within IFNL4 that predicts how people respond to treatment for hepatit

  8. 吲哚胺2,3双加氧酶与乙肝病毒不同感染状态T淋巴细胞亚群及病毒载量的相关性研究%Investigation of the correlation between indoleamine 2,3-dioxygenase and T cell subsets,viral load in different hepatitis B virus infection status

    Institute of Scientific and Technical Information of China (English)

    曾道炳; 卢实春; 李军峰; 胡冬; 周育森

    2012-01-01

    目的 探讨乙肝病毒(HBV)不同感染状态下,吲哚胺2,3双加氧酶(indoleamine 2,3-dioxygenase,IDO)表达水平及其与T淋巴细胞亚群及病毒载量的相关性.方法 检测受检者外周静脉血IDO mRNA、IDO蛋白、IDO活性,T淋巴细胞亚群及病毒载量(对照组除外);进行各组间均数比较及相关性分析.结果 IDO mRNA、IDO蛋白及IDO活性从高到低依次为急性乙型肝炎组(acute hepatitis B,AHB)、肝硬化组(HBV-related liver cirrhosis,LC)、慢性乙型肝炎组(chronic hepatitis B,CHB)、肝癌组(HBV-related hepatocellular carcinoma,HCC)、对照组.HCC组及对照组均明显低于其他3组(P<0.01),其余各组间两两比较,差异有统计学意义(P<0.05).CD3+、CD4+T淋巴细胞在AHB组最高,对照组次之,LC组最低;AHB组、对照组及CHB组均明显高于LC组(P< 0.05);AHB组、对照组明显高于HCC组(P<0.05).CD8+T淋巴细胞在对照组最高,AHB组次之,LC组最低;但仅AHB组、对照组明显高于LC组(P<0.05).AHB组CD4+/CD8+明显高于其他组(P<0.01).CHB及LC组病毒载量最高,均明显高于HCC及AHB组(P<0.05).CD3+、CD4+、CD8+T淋巴细胞与病毒载量、IDO蛋白及IDO活性均呈负相关,CD8+T淋巴细胞与IDO mRNA呈负相关(r=-0.287,P=0.039);CD4+/CD8+与IDO蛋白及IDO活性均呈正相关(r=0.470,P=0.000;r=0.285,P=0.040),病毒载量与IDO mRNA、IDO蛋白及IDO活性均呈正相关(r=0.530,P=0.001;r=0.416,P=0.002;r=0.649,P=0.000).结论 HBV感染者IDO表达明显增强,与病毒载量呈正相关,与T淋巴细胞呈负相关,其早期升高有利于病毒清除,但持续升高会导致HBV特异性T淋巴细胞功能抑制,使HBV慢性化.%Objective To investigate the expression levels of indoleamine 2,3-dioxygenase(IDO) and the correlation between IDO level, T cell subsets and viral load in hepatitis B related liver disease subjects. Methods Peripheral blood samples were collected, and the the expression level of IDO Mrna and IDO protein in PBMC

  9. 病毒载量和细胞因子在发热伴血小板减少综合征致病机制中的作用%Viral load and cytokines in the pathogenesis of severe fever with thrombocytopenia syndrome

    Institute of Scientific and Technical Information of China (English)

    韩亚萍; 李军; 董莉; 孔练花; 章莉莉; 刘宁; 陈念; 金柯; 王茜; 黄祖瑚

    2014-01-01

    -0.608,均 P <0.01),与病毒载量(r 值分别为0.560和0.758)、ALT(r 值分别为0.412和0.390)、AST(r 值分别为0.686和0.764)、LDH(r 值分别为0.633和0.677)、CK(r 值分别为0.527和0.636)等酶学指标呈正相关(均 P <0.01)。结论SFTS 患者血清病毒载量、IL-6、IL-10以及血清酶学水平与疾病严重程度密切相关,新型布尼亚病毒感染后血清中炎性因子和抑炎因子风暴,可能参与了SFTS 患者的免疫病理损伤。%Objective To observe the relationship of viral load,serum cytokines and tissue damage after severe fever with thrombocytopenia syndrome virus (SFTSV)infection,and to explore the impact of SFTSV levels on tissue injury and prognosis.Methods Twenty-four ambulatory and hospitalized patients who were infected with SFTSV were enrolled between May 2011 and July 2012 at Department of Infectious Disease, First Affiliated Hospital with Nanjiang Medical University. According to their prognosis,they were divided into cure and death group,while 32 healthy blood donators were also enrolled from center blood station in Nanjing as control.The serum SFTSV load was detected using fluorescence quantitative polymerase chain reaction (PCR).The serum T helper (Th)1/Th2/Th17 cytokines in patients with severe fever with thrombocytopenia syndrome (SFTS)were determined dynamically and quantitatively by flow cytometry.The relationships between viral load,cytokines and serum enzymes, white blood cell (WBC),platelet (PLT)counts were analyzed.Comparisons among groups were achieved by rank sum test and correlation analysis among serum cytokines,blood cell counts and tissue damage was done by Spearman correlation test.Results All of the 24 patients showed a positive reaction to SFTSV RNA.The SFTSV loads of 21 cured cases,those of 2 were > 7.0 lg copy/mL,and those of 3 death patients were 6.7 lg copy/mL,8.8 lg copy/mL and 9.8 lg copy/mL,respectively.Serum level of

  10. Iron load

    Directory of Open Access Journals (Sweden)

    Filippo Cassarà

    2013-03-01

    Full Text Available Recent research addressed the main role of hepcidin in the regulation of iron metabolism. However, while this mechanism could be relevant in causing iron load in Thalassemia Intermedia and Sickle-Cell Anemia, its role in Thalassemia Major (TM is marginal. This is mainly due to the high impact of transfusional requirement into the severe increase of body iron. Moreover, the damage of iron load may be worsened by infections, as HCV hepatitis, or liver and endocrinological damage. One of the most relevant associations was found between splenectomy and increase of risk for mortality due,probably, to more severe iron load. These issues suggest as morbidity and mortality of this group of patients they do not depend only by our ability in controlling heart damage but even in preventing or treating particular infections and complications. This finding is supported by the impairment of survival curves in patients with complications different from heart damage. However, because, during recent years different direct and indirect methods to detect iron overload in patients affected by secondary hemochromatosis have been implemented, our ability to maintain under control iron load is significantly improved. Anyway, the future in iron load management remains to be able to have an iron load map of our body for targeting chelation and other medical treatment according to the single organ damage.

  11. The optimal clearance design of micro-punching die

    Directory of Open Access Journals (Sweden)

    K.S. Lee

    2008-07-01

    Full Text Available Purpose: The purpose of this research paper is focused on the optimal clearance design of micro-punching die by abductive network and SA method.Design/methodology/approach: The punching data (input and wear size (output were collected for a training database. In order to select proper clearance to evaluate the wear of die, the abductive network was used to establish an efficient relationship between input parameters and output result. This can help to predict wear size under any degree of clearance and hence to replace worn punches and dies at the right time. A simulated annealing (SA optimization algorithm with a performance index is then applied to the neural network for searching the optimal clearance parameters, and obtains rather satisfactory result as compared with the corresponding experiment verification.Findings: This study aims to identify the relationship between clearance and service life of micro punches using the Neural Network, and to find relational data involving the service life of punches and punching parameters in non-metal blanking processes. The result can be used to estimate optimal clearance between punch and die for industrial applications.Research limitations/implications: In this study, the practical punching processes with different punching conditions were carried out for a set of training data. A trained model exhibited a relationship between service life and clearance of micro punch and die through an abductive network system. The predicted value of wear by abductive network is very close to the actual experimental value, with an error of less than 8%. This result satisfies the required standard for IC factory production.Originality/value: A good clearance design not only increases the quality of product manufactured, but also reduces product’s burr. As a result, the wear of punches and dies can be greatly reduced and the life expectancy of punching dies increased.

  12. Fluid damping clearance in a control valve of injector

    Institute of Scientific and Technical Information of China (English)

    ZHANG Jianming; ZHANG Weigang; YANG Bing; WANG Yawei

    2007-01-01

    A force model of a control valve of injector is set up, and the changes of the fluid damping clearance are investigated on the basis of the results of the computational fluid dynamics (CFD) and the experiments of control valve of injector. Results indicate that a damping clearance of 0.02-0.03 mm between the poppet and the valve guide is the most sufficient to dampen any excessive control valve poppet bouncing.

  13. Evaluation of circulating levels and renal clearance of natural amino acids in patients with Cushing's disease.

    Science.gov (United States)

    Faggiano, A; Pivonello, R; Melis, D; Alfieri, R; Filippella, M; Spagnuolo, G; Salvatore, F; Lombardi, G; Colao, A

    2002-02-01

    Although the hypercortisolism-induced impairment of protein homeostasis is object of several studies, a detailed evaluation of the complete amino acid profile of patients with Cushing's syndrome (CS) has never been performed. The aim of the current open transversal controlled study was to evaluate serum and urinary concentrations as well as renal clearance of the complete series of natural amino acids and their relationship with glucose tolerance in patients with Cushing's disease (CD). Twenty patients with CD (10 active and 10 cured) and 20 sex- and age-matched healthy controls entered the study. Measurement of serum and urinary levels of the complete series of natural amino acids was performed in all patients analyzed by cationic exchange high performance liquid cromatography (HPLC) after 2 weeks of a standardized protein intake regimen. The renal clearance (renal excretion rate) of each amino acid was calculated on the basis of the serum and urinary concentrations of creatinine and the specific amino acid. Fasting glucose and insulin levels, glucose and insulin response to standard glucose load, insulinogenic and homeostasis model insulin resistance (Homa-R) indexes were also evaluated and correlated to the circulating levels and renal clearances of each amino acid. Significantly higher serum (p<0.01) and urinary (p<0.05) levels of alanine and cystine, lower serum and higher urinary levels of leucine, isoleucine and valine (p<0.05) and higher renal excretion rates of leucine, isoleucine and valine (p<0.01) were found in patients with active CD than in patients cured from the disease and in controls. No difference was found between cured patients and controls. Creatinine clearance was similar in active and cured patients and in controls. In patients with active CD, urinary cortisol levels were significantly correlated to urinary cystine levels (r=0.85; p<0.01) and renal excretion rate of leucine (r=-0.76; p<0.05), isoleucine (r=-0.76; p<0.05) and valine (r=-0

  14. Experimental study on fluid flow in arciform clearance

    Institute of Scientific and Technical Information of China (English)

    邵俊鹏; 汤卉; 贾慧娟

    2002-01-01

    The system damping and dynamic characteristics can be further improved by properly increasing thedamping coefficient ξh. For a special hydraulic damping structure, an arciform damping clearance often used inFCS, a mathematical model has been established for fluid flow using the theory of laminar flow in the clearanceof parallel plates. Analytical calculations are made for fluid flow in the arciform clearance and relational expres-sion is deduced for flow rate along the arciform cleaance height, pressure difference, maximum arciform clear-ance height, the flow rate for the fluid flow in arciform clearance as well, and its simplified formula is obtainedby using the theory of hydrodynamics and the curve - fitting method. This paper consists of two sections: the firstsection focuses on the theoretical analysis by using the simplified mathematical model and the second sectionmainly describes experimental analysis. The simplified formula is corrected with experimental results by consid-erig various boundary conditions of the damping clearance. Experimental results show that this study of arciformdamping clearance is reliable and practical.

  15. Model of mucociliary clearance in cystic fibrosis lungs.

    Science.gov (United States)

    Kurbatova, P; Bessonov, N; Volpert, V; Tiddens, H A W M; Cornu, C; Nony, P; Caudri, D

    2015-05-01

    Mucus clearance is a primary innate defense mechanism in the human airways. Cystic fibrosis (CF) is a genetic disease caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein. CF is characterized by dehydration of airway surface liquid and impaired mucociliary clearance. As a result, microorganisms are not efficiently removed from the airways, and patients experience chronic pulmonary infections and inflammation. We propose a new physiologically based mathematical model of muco-ciliary transport consisting of the two major components of the mucociliary clearance system: (i) periciliary liquid layer (PCL) and (ii) mucus layer. We study mucus clearance under normal conditions and in CF patients. Restoring impaired clearance of airway secretions in one of the major goals of therapy in patients with CF. We consider the action of the aerosolized and inhaled medication dornase alfa, which reduces the viscosity of cystic fibrosis mucus, by selectively cleaving the long DNA strands it contains. The results of the model simulations stress the potential relevance of the location of the drug deposition in the central or peripheral airways. Mucus clearance was increased in case the drug was primarily deposited peripherally, i.e. in the small airways. PMID:25746843

  16. A highly intensified ART regimen induces long-term viral suppression and restriction of the viral reservoir in a simian AIDS model.

    Directory of Open Access Journals (Sweden)

    Iart Luca Shytaj

    Full Text Available Stably suppressed viremia during ART is essential for establishing reliable simian models for HIV/AIDS. We tested the efficacy of a multidrug ART (highly intensified ART in a wide range of viremic conditions (10³-10⁷ viral RNA copies/mL in SIVmac251-infected rhesus macaques, and its impact on the viral reservoir. Eleven macaques in the pre-AIDS stage of the disease were treated with a multidrug combination (highly intensified ART consisting of two nucleosidic/nucleotidic reverse transcriptase inhibitors (emtricitabine and tenofovir, an integrase inhibitor (raltegravir, a protease inhibitor (ritonavir-boosted darunavir and the CCR5 blocker maraviroc. All animals stably displayed viral loads below the limit of detection of the assay (i.e. <40 RNA copies/mL after starting highly intensified ART. By increasing the sensitivity of the assay to 3 RNA copies/mL, viral load was still below the limit of detection in all subjects tested. Importantly, viral DNA resulted below the assay detection limit (<2 copies of DNA/5*10⁵ cells in PBMCs and rectal biopsies of all animals at the end of the follow-up, and in lymph node biopsies from the majority of the study subjects. Moreover, highly intensified ART decreased central/transitional memory, effector memory and activated (HLA-DR⁺ effector memory CD4⁺ T-cells in vivo, in line with the role of these subsets as the main cell subpopulations harbouring the virus. Finally, treatment with highly intensified ART at viral load rebound following suspension of a previous anti-reservoir therapy eventually improved the spontaneous containment of viral load following suspension of the second therapeutic cycle, thus leading to a persistent suppression of viremia in the absence of ART. In conclusion, we show, for the first time, complete suppression of viral load by highly intensified ART and a likely associated restriction of the viral reservoir in the macaque AIDS model, making it a useful platform for testing

  17. Host - hepatitis C viral interactions: The role of genetics.

    Science.gov (United States)

    Heim, Markus H; Bochud, Pierre-Yves; George, Jacob

    2016-10-01

    Hepatitis C virus (HCV) is a major cause of chronic viral hepatitis that can lead to cirrhosis and hepatocellular carcinoma. Only a minority of patients can clear the virus spontaneously. Elimination of HCV during acute infection correlates with a rapid induction of innate, especially interferon (IFN)-induced genes, and a delayed induction of adaptive immune responses. There is a strong association between genetic variants in the IFNλ (IL28B) locus with the rate of spontaneous clearance. Individuals with the ancestral IFNλ4 allele capable of producing a fully active IFNλ4 are paradoxically not able to clear HCV in the acute phase and develop chronic hepatitis C (CHC) with more than 90% probability. In the chronic phase of HCV infection, the wild-type IFNλ4 genotype is strongly associated with an induction of hundreds of classical type I/type III IFN stimulated genes in hepatocytes. However, the activation of the endogenous IFN system in the liver is ineffective in clearing HCV, and is even associated with impaired therapeutic responses to pegylated (Peg)IFNα containing treatments. While the role of genetic variation in the IFNλ locus to the outcome of CHC treatment has declined, it is clear that variation not only at this locus, but also at other loci, modulate clinically important liver phenotypes, including inflammation, fibrosis progression and the development of hepatocellular cancer. In this review, we summarize current knowledge about the role of genetics in the host response to viral hepatitis and the potential future evolution of knowledge in understanding host-viral interactions. PMID:27641986

  18. Evidence for hydrogen-deuterium exchange in viral particles

    Institute of Scientific and Technical Information of China (English)

    MAO Jiangsen; LIU Ziyang; TANG Caihua; HE Yihui; ZHU Jiahong; WANG Chengyu; CHAI Shaoai; CHEN Yueqing; QIAN Wen

    2004-01-01

    Heavy water (D2O) could enhance thermostability of some viruses. However, the underlying mechanism is not clear. Here we report the development of a matrix-aided gas-isotope-ratio mass spectrometry method that allows direct determination of deuterium/hydrogen (D/H) ratio in D2O-treated Japanese encephalitis virus (JEV), hepatitis A virus (HAV) and RNA from D2O-treated HAV. The D/H ratio was expressed as δDSMOW. Our experiments showed that δDSMOW values increased significantly in D2O-treated viral samples compared to normal controls, and increment in δDSMOW of D2O, treated viral samples was in a fine linear relationship with increment in amount of samples loaded in BSA matrix. Our experiments also indicated that increased δDSMOW of D2O-treated virus correlated well with its enhanced thermostability. The results suggested that hydrogen-deuterium exchange occurred in viral particles and its RNA structure as a result of D2O-treatment. Furthermore, such exchange could cause changes in viral phenotype, such as enhanced thermostability.

  19. Information Overload and Viral Marketing: Countermeasures and Strategies

    Science.gov (United States)

    Cheng, Jiesi; Sun, Aaron; Zeng, Daniel

    Studying information diffusion through social networks has become an active research topic with important implications in viral marketing applications. One of the fundamental algorithmic problems related to viral marketing is the Influence Maximization (IM) problem: given an social network, which set of nodes should be considered by the viral marketer as the initial targets, in order to maximize the influence of the advertising message. In this work, we study the IM problem in an information-overloaded online social network. Information overload occurs when individuals receive more information than they can process, which can cause negative impacts on the overall marketing effectiveness. Many practical countermeasures have been proposed for alleviating the load of information on recipients. However, how these approaches can benefit viral marketers is not well understood. In our work, we have adapted the classic Information Cascade Model to incorporate information overload and study its countermeasures. Our results suggest that effective control of information overload has the potential to improve marketing effectiveness, but the targeting strategy should be re-designed in response to these countermeasures.

  20. Autistic disorder and viral infections.

    Science.gov (United States)

    Libbey, Jane E; Sweeten, Thayne L; McMahon, William M; Fujinami, Robert S

    2005-02-01

    Autistic disorder (autism) is a behaviorally defined developmental disorder with a wide range of behaviors. Although the etiology of autism is unknown, data suggest that autism results from multiple etiologies with both genetic and environmental contributions, which may explain the spectrum of behaviors seen in this disorder. One proposed etiology for autism is viral infection very early in development. The mechanism, by which viral infection may lead to autism, be it through direct infection of the central nervous system (CNS), through infection elsewhere in the body acting as a trigger for disease in the CNS, through alteration of the immune response of the mother or offspring, or through a combination of these, is not yet known. Animal models in which early viral infection results in behavioral changes later in life include the influenza virus model in pregnant mice and the Borna disease virus model in newborn Lewis rats. Many studies over the years have presented evidence both for and against the association of autism with various viral infections. The best association to date has been made between congenital rubella and autism; however, members of the herpes virus family may also have a role in autism. Recently, controversy has arisen as to the involvement of measles virus and/or the measles, mumps, rubella (MMR) vaccine in the development of autism. Biological assays lend support to the association between measles virus or MMR and autism whereas epidemiologic studies show no association between MMR and autism. Further research is needed to clarify both the mechanisms whereby viral infection early in development may lead to autism and the possible involvement of the MMR vaccine in the development of autism.

  1. Mast cells in viral infections

    Directory of Open Access Journals (Sweden)

    Piotr Witczak

    2012-04-01

    Full Text Available  There are some premises suggesting that mast cells are involved in the mechanisms of anti-virus defense and in viral disease pathomechanisms. Mast cells are particularly numerous at the portals of infections and thus may have immediate and easy contact with the external environment and invading pathogens. These cells express receptors responsible for recognition of virus-derived PAMP molecules, mainly Toll-like receptors (TLR3, TLR7/8 and TLR9, but also RIG-I-like and NOD-like molecules. Furthermore, mast cells generate various mediators, cytokines and chemokines which modulate the intensity of inflammation and regulate the course of innate and adaptive anti-viral immunity. Indirect evidence for the role of mast cells in viral infections is also provided by clinical observations and results of animal studies. Currently, more and more data indicate that mast cells can be infected by some viruses (dengue virus, adenoviruses, hantaviruses, cytomegaloviruses, reoviruses, HIV-1 virus. It is also demonstrated that mast cells can release pre formed mediators as well as synthesize de novo eicosanoids in response to stimulation by viruses. Several data indicate that virus-stimulated mast cells secrete cytokines and chemokines, including interferons as well as chemokines with a key role in NK and Tc lymphocyte influx. Moreover, some information indicates that mast cell stimulation via TLR3, TLR7/8 and TLR9 can affect their adhesion to extracellular matrix proteins and chemotaxis, and influence expression of some membrane molecules. Critical analysis of current data leads to the conclusion that it is not yet possible to make definitive statements about the role of mast cells in innate and acquired defense mechanisms developing in the course of viral infection and/or pathomechanisms of viral diseases.

  2. Cross-reactive anti-viral T cells increase prior to an episode of viral reactivation post human lung transplantation.

    Directory of Open Access Journals (Sweden)

    Thi H O Nguyen

    Full Text Available Human Cytomegalovirus (CMV reactivation continues to influence lung transplant outcomes. Cross-reactivity of anti-viral memory T cells against donor human leukocyte antigens (HLA may be a contributing factor. We identified cross-reactive HLA-A*02:01-restricted CMV-specific cytotoxic T lymphocytes (CTL co-recognizing the NLVPMVATV (NLV epitope and HLA-B27. NLV-specific CD8+ T cells were expanded for 13 days from 14 HLA-A*02:01/CMV seropositive healthy donors and 11 lung transplant recipients (LTR then assessed for the production of IFN-γ and CD107a expression in response to 19 cell lines expressing either single HLA-A or -B class I molecules. In one healthy individual, we observed functional and proliferative cross-reactivity in response to B*27:05 alloantigen, representing approximately 5% of the NLV-specific CTL population. Similar patterns were also observed in one LTR receiving a B27 allograft, revealing that the cross-reactive NLV-specific CTL gradually increased (days 13-193 post-transplant before a CMV reactivation event (day 270 and reduced to basal levels following viral clearance (day 909. Lung function remained stable with no acute rejection episodes being reported up to 3 years post-transplant. Individualized immunological monitoring of cross-reactive anti-viral T cells will provide further insights into their effects on the allograft and an opportunity to predict sub-clinical CMV reactivation events and immunopathological complications.

  3. Effect of delivery modes on blocking mother-to-child transmission of HBV in HBV-infected mothers with high viral load%分娩方式对高病毒载量的HBV感染母亲母婴阻断的影响

    Institute of Scientific and Technical Information of China (English)

    周明芳; 刘敏; 易为; 蔡晧东

    2016-01-01

    目的 探讨HBV高病毒载量孕妇的分娩方式对母婴阻断结果的影响.方法 选择2012年1月1日—2014年12月31日在我院分娩且HBV DNA≥1×106 copies/ml的孕妇570例,分析其分娩方式,检测所生婴儿出生时和完成全程乙型肝炎疫苗免疫后(7~12月龄)的HBV血清学标志物.结果 570例中,289例(50.7%)剖宫产分娩292例活婴(双胎3例),其中新生儿免疫成功270例(92.5%),免疫无应答3例(1.0%),HBV感染19例(6.5%);281例(49.3%)阴道分娩281例活婴,其中新生儿免疫成功252例(89.7%),免疫无应答4例(1.4%),HBV感染25例(8.9%).阴道分娩组所生婴儿母婴阻断失败率稍高于剖宫产组,但差异无统计学意义(8.9%vs 6.5%,χ2=1.153,P=0.283).结论 分娩方式对HBV从母亲血液渗透到婴儿体内无明显影响,对HBV母婴阻断效果无明显影响.%Objective To investigate the effect of delivery modes on blocking mother-to-child transmission of HBV in HBV-infected mothers with high viral load.Methods A total of 570 pregnant women with HBV DNA levels≥1×106 copies/ml, who delivered their babies at our hospital from January 1, 2012 to December 31, 2014, were selected. Their delivery modes were analyzed, and HBV serological markers at neonatal birth and after the whole hepatitis B vaccination (7-12 months old) were detected.Results Totally 292 infants (3 pairs of twins) were born to 289 mothers (50.7%) by caesarean section delivery, of whom 270 newborn infants (92.5%) had immune response to hepatitis B vaccine, 3 (1.0%) didn't have immune response, and 19 (6.5%) were infected with HBV. Totally 281 infants were born to 281 mothers (49.3%) by vaginal delivery, of whom 252 newborn infants (89.7%) had immune response to hepatitis B vaccine, 4 (1.4%) didn't have immune response, and 25 (8.9%) were infected with HBV. The failure rate in blocking mother-to-child transmission in the group of vaginal delivery was higher than that in the group of cesarean section delivery, but the

  4. Beam loading

    CERN Document Server

    Gamp, Alexander

    2013-01-01

    We begin by giving a description of the radio-frequency generator-cavity-beam coupled system in terms of basic quantities. Taking beam loading and cavity detuning into account, expressions for the cavity impedance as seen by the generator and as seen by the beam are derived. Subsequently methods of beam-loading compensation by cavity detuning, radio-frequency feedback and feedforward are described. Examples of digital radio-frequency phase and amplitude control for the special case of superconducting cavities are also given. Finally, a dedicated phase loop for damping synchrotron oscillations is discussed.

  5. Exploring the viral world through metagenomics.

    Science.gov (United States)

    Rosario, Karyna; Breitbart, Mya

    2011-10-01

    Viral metagenomics, or shotgun sequencing of purified viral particles, has revolutionized the field of environmental virology by allowing the exploration of viral communities in a variety of sample types throughout the biosphere. The introduction of viral metagenomics has demonstrated that dominant viruses in environmental communities are not well-represented by the cultured viruses in existing sequence databases. Viral metagenomic studies have provided insights into viral ecology by elucidating the genetic potential, community structure, and biogeography of environmental viruses. In addition, viral metagenomics has expanded current knowledge of virus-host interactions by uncovering genes that may allow viruses to manipulate their hosts in unexpected ways. The intrinsic potential for virus discovery through viral metagenomics can help advance a wide array of disciplines including evolutionary biology, pathogen surveillance, and biotechnology.

  6. Faktor Risiko Non Viral Pada Karsinoma Nasofaring

    Directory of Open Access Journals (Sweden)

    Sukri Rahman

    2015-09-01

    Full Text Available Abstrak           Latar belakang: Karsinoma nasofaring adalah tumor ganas epitel nasofaring yang sampai saat ini penyebabnya belum diketahui, infeksi virus Epstein Barr dilaporkan sebagai faktor dominan terjadinya karsinoma nasofaring tetapi faktor non viral juga berperan untuk timbulnya keganasan nasofaring. Tujuan: Untuk mengetahui faktor non viral  yang dapat meningkatkan kejadian karsinoma nasofaring sehingga dapat mencegah dan menghindari faktor-faktor non viral tersebut. Tinjauan Pustaka: Karsinoma nasofaring merupakan tumor ganas epitel nasofaring yang penyebabnya berhubungan dengan faktor viral dan non viral diantaranya asap rokok, ikan asin, formaldehid, genetik, asap kayu bakar , debu kayu, infeksi kronik telinga hidung tenggorok, alkohol dan obat tradisional. Kesimpulan: Pembuktian secara klinis dan ilmiah terhadap faktor non viral sebagai penyebab timbulnya karsinoma nasofaring masih belum dapat dijelaskan secara pasti. Faktor non viral merupakan salah satu faktor risiko yang dapat meningkatkan angka kejadian timbulnya keganasan nasofaring Kata kunci: karsinoma nasofaring, faktor risiko, non viral AbstractBackground: Nasopharyngeal carcinoma is a malignant epithelial nasopharyngeal tumor that until now the cause still unknown, Epstein barr virus infection had reported as predominant occurance of nasopharyngeal carcinoma but non viral factors may also contribute to the onset of the incidence of nasopharyngeal malignancy. Purpose: To find non viral factors that may increase the incidence of nasopharyngel carcinoma in order to prevent and avoid non-viral factors Literature: Nasopharyngeal carcinoma is a malignant tumor that causes nasopharyngeal epithelium associated with viral and non-viral factors such as cigarette smoke, salt fish, formaldehyde, genetic, wood smoke ,wood dust, ear nose throat chronic infections, alcohol, and traditional medicine. Conclusion: Clinically and scientifically proving the non-viral factors as

  7. Brain-resident memory T cells represent an autonomous cytotoxic barrier to viral infection.

    Science.gov (United States)

    Steinbach, Karin; Vincenti, Ilena; Kreutzfeldt, Mario; Page, Nicolas; Muschaweckh, Andreas; Wagner, Ingrid; Drexler, Ingo; Pinschewer, Daniel; Korn, Thomas; Merkler, Doron

    2016-07-25

    Tissue-resident memory T cells (TRM) persist at sites of prior infection and have been shown to enhance pathogen clearance by recruiting circulating immune cells and providing bystander activation. Here, we characterize the functioning of brain-resident memory T cells (bTRM) in an animal model of viral infection. bTRM were subject to spontaneous homeostatic proliferation and were largely refractory to systemic immune cell depletion. After viral reinfection in mice, bTRM rapidly acquired cytotoxic effector function and prevented fatal brain infection, even in the absence of circulating CD8(+) memory T cells. Presentation of cognate antigen on MHC-I was essential for bTRM-mediated protective immunity, which involved perforin- and IFN-γ-dependent effector mechanisms. These findings identify bTRM as an organ-autonomous defense system serving as a paradigm for TRM functioning as a self-sufficient first line of adaptive immunity. PMID:27377586

  8. [Nebulized hypertonic saline and acute viral bronchiolitis in infants: current aspects].

    Science.gov (United States)

    Sauvaget, E; David, M; Bresson, V; Retornaz, K; Bosdure, E; Dubus, J-C

    2012-06-01

    Acute viral bronchiolitis affects infants, is frequent, and can be severe. Its treatment is only based on symptoms. Hypertonic saline (HS) may act favorably in this situation by fighting virus-induced dehydration of the airway liquid surface. Because of an osmotic action, HS attracts the water from the epithelial cells and improves mucociliary clearance. Five double-blind placebo-controlled studies concerning hospitalized infants with acute viral bronchiolitis showed that repeated nebulizations of 3% HS induce a 20% improvement in the clinical severity score and reduced the hospital length of stay by 24h. Tolerance is excellent. On the other hand, a few questions remain unresolved: what is the optimal salt concentration? What is the recommended nebulizer? What is the best frequency for nebulizer use? Can nebulized HS be used at home? What are the results with systematic physiotherapy when HS is used?

  9. Respiratory dysfunction and proinflammatory chemokines in the pneumonia virus of mice (PVM) model of viral bronchiolitis.

    Science.gov (United States)

    Bonville, Cynthia A; Bennett, Nicholas J; Koehnlein, Melissa; Haines, Deborah M; Ellis, John A; DelVecchio, Alfred M; Rosenberg, Helene F; Domachowske, Joseph B

    2006-05-25

    We explore relationships linking clinical symptoms, respiratory dysfunction, and local production of proinflammatory chemokines in the pneumonia virus of mice (PVM) model of viral bronchiolitis. With a reduced inoculum of this natural rodent pathogen, we observe virus clearance by day 9, while clinical symptoms and respiratory dysfunction persist through days 14 and 17 postinoculation, respectively. Via microarray and ELISA, we identify expression profiles of proinflammatory mediators MIP-1alpha, MCP-1, and MIP-2 that correlate with persistent respiratory dysfunction. MIP-1alpha is localized in bronchial epithelium, which is also the major site of PVM replication. Interferon-gamma was detected in lung tissue, but at levels that do not correlate with respiratory dysfunction. Taken together, we present a modification of our pneumovirus infection model that results in improved survival and data that stand in support of a connection between local production of specific mediators and persistent respiratory dysfunction in the setting of acute viral bronchiolitis.

  10. Viral O-GalNAc peptide epitopes

    DEFF Research Database (Denmark)

    Olofsson, Sigvard; Blixt, Klas Ola; Bergström, Tomas;

    2016-01-01

    Viral envelope glycoproteins are major targets for antibodies that bind to and inactivate viral particles. The capacity of a viral vaccine to induce virus-neutralizing antibodies is often used as a marker for vaccine efficacy. Yet the number of known neutralization target epitopes is restricted o...

  11. Viral commercials: the consumer as marketeer

    NARCIS (Netherlands)

    Ketelaar, P.E.; Lucassen, P.; Kregting, G.H.J.

    2010-01-01

    Research into the reasons why consumers pass along viral commercials: their motives, the content characteristics of viral commercials and the medium context in which viral commercials appear. Based on the uses and gratifications perspective this study has determined which motives of consumers, conte

  12. Virale commercials: De consument als marketeer

    NARCIS (Netherlands)

    Ketelaar, P.E.; Lucassen, P.; Kregting, G.H.J.

    2010-01-01

    Research into the reasons why consumers pass along viral commercials: their motives, the content characteristics of viral commercials and the medium context in which viral commercials appear. Based on the uses and gratifications perspective this study has determined which motives of consumers, conte

  13. Load sensor

    NARCIS (Netherlands)

    Van den Ende, D.; Almeida, P.M.R.; Dingemans, T.J.; Van der Zwaag, S.

    2007-01-01

    The invention relates to a load sensor comprising a polymer matrix and a piezo-ceramic material such as PZT, em not bedded in the polymer matrix, which together form a compos not ite, wherein the polymer matrix is a liquid crystalline resin, and wherein the piezo-ceramic material is a PZT powder for

  14. Carbohydrate Loading.

    Science.gov (United States)

    Csernus, Marilyn

    Carbohydrate loading is a frequently used technique to improve performance by altering an athlete's diet. The objective is to increase glycogen stored in muscles for use in prolonged strenuous exercise. For two to three days, the athlete consumes a diet that is low in carbohydrates and high in fat and protein while continuing to exercise and…

  15. Metamaterial Loading

    Directory of Open Access Journals (Sweden)

    F. Paredes

    2012-01-01

    Full Text Available It is shown that printed antennas loaded with metamaterial resonators can be designed to exhibit multiband functionality. Two different antenna types and metamaterial loading are considered: (i printed dipoles or monopoles loaded with open complementary split ring resonators (OCSRRs and (ii meander line or folded dipole antennas loaded with split ring resonators (SRRs or spiral resonators (SRs. In the first case, multiband operation is achieved by series connecting one or more OCSRRs within the dipole/monopole. Such resonators force opens at their positions, and by locating them at a quarter wavelength (at the required operating frequencies from the feeding point, it is possible to achieve multiple radiation bands. In the second case, dual-band functionality is achieved through the perturbation of the antenna characteristics caused by the presence of the metamaterial resonators. This latter strategy is specially suited to achieve conjugate matching between the antenna and the chip in radiofrequency identification (RFID tags at two of the regulated UHF-RFID bands.

  16. [Amniocentesis and viral risk (hepatitis B, C virus and HIV)].

    Science.gov (United States)

    Ducarme, G; Ceccaldi, P-F; Bernuau, J; Luton, D

    2009-10-01

    Very few studies have properly addressed to the risk of fetal hepatitis B (HBV), hepatitis C (HCV) or human immunodeficiency virus (HIV) infection through amniocentesis. For HBV, this risk is low. However, knowledge of the maternal hepatitis B e antigen status is valuable in the counselling of risks associated with amniocentesis. For HCV, the risk is not well known but cannot be excluded. For HIV, it seems rational to propose a viral test before amniocentesis for patients with contamination's risk and to postpone the sampling in cases with positive results in order to obtain an undetectable HIV-1 RNA viral load. For these reasons, it can be useful to analyse for each virus the benefit of amniocentesis and the risk of mother-to-infant transmission, and to inform the patient. PMID:19679409

  17. Questing for an optimal, universal viral agent for oncolytic virotherapy

    CERN Document Server

    Paiva, L R; Ferreira, S C

    2011-01-01

    One of the most promising strategies to treat cancer is attacking it with viruses designed to exploit specific altered pathways. Here, the effects of oncolytic virotherapy on tumors having compact, papillary and disconnected morphologies are investigated through computer simulations of a multiscale model coupling macroscopic reaction diffusion equations for the nutrients with microscopic stochastic rules for the actions of individual cells and viruses. The interaction among viruses and tumor cells involves cell infection, intracellular virus replication and release of new viruses in the tissue after cell lysis. The evolution in time of both viral load and cancer cell population, as well as the probabilities for tumor eradication were evaluated for a range of multiplicities of infection, viral entries and burst sizes. It was found that in immunosuppressed hosts, the antitumor efficacy of a virus is primarily determined by its entry efficiency, its replicative capacity within the tumor, and its ability to sprea...

  18. Radioactive Aerosols in the Clinical Study of Pulmonary Clearance

    International Nuclear Information System (INIS)

    The study of pulmonary clearance mechanisms has acquired particular importance owing to the growing pollution of the environment and to the increasing incidence and seriousness of cases of pneumoconiosis. Such research is particularly important in radiopathology because of the frequent occurrence of respiratory radioactive contamination. The authors' aim is to tackle this problem and in particular to study long-term clearance mechanisms. Before starting this work, however, they propose to determine the contamination parameters as accurately as possible. For this purpose they plan to study respiratory function in normal subjects by administering labelled aerosols with well-defined physico-chemical characteristics; the first stage of the investigation is then to observe the kinetics of fixation and clearance in the short term. They describe the installations used for this voluntary contamination which must provide a means of producing the aerosols and administering them in controlled amounts and must also ensure efficient protection of the operators against irradiation arid contamination. The choice of the aerosols is also discussed: this is governed mainly by the nature of the vectors, the particle size and the physical characteristics of the tracers. Finally, the authors outline the detection and measuring techniques which they are using to study contamination kinetics, evaluate contamination burdens and follow the short-term clearance. These data constitute a preliminary basis for the study of long-term clearance. (author)

  19. Viral diseases and human evolution

    Directory of Open Access Journals (Sweden)

    Élcio de Souza Leal

    2000-01-01

    Full Text Available The interaction of man with viral agents was possibly a key factor shaping human evolution, culture and civilization from its outset. Evidence of the effect of disease, since the early stages of human speciation, through pre-historical times to the present suggest that the types of viruses associated with man changed in time. As human populations progressed technologically, they grew in numbers and density. As a consequence different viruses found suitable conditions to thrive and establish long-lasting associations with man. Although not all viral agents cause disease and some may in fact be considered beneficial, the present situation of overpopulation, poverty and ecological inbalance may have devastating effets on human progress. Recently emerged diseases causing massive pandemics (eg., HIV-1 and HCV, dengue, etc. are becoming formidable challenges, which may have a direct impact on the fate of our species.

  20. STUDY OF PERSISTENT VIRAL INFECTION IN AN ANIMAL MODEL OF VIRAL MYOCARDITIS BY PCR

    Institute of Scientific and Technical Information of China (English)

    马睿; 陈曙霞; 刘晶星

    2000-01-01

    ffeStnn6 Objectif Etudier ie r6le de l'infection virale persistante dans ie pethog4de de la myOCardite virale.ANt~ L' ARN viral dens ie my~rde et ie mug et l' alteration potholedque du m~rde ent ate ewilnd per la techniquede PCR adns un mangle de myrmrdite virale chez ies ~ris. Rhaltats L 'ARN viral a ate detects an 3'jour dens ie mug etie myrmrde. An 8'jour, I 'ARN viral an niveau du mug a ate pertiellement dewnu then f lorsque l' alteration pethologiquedu myocarde a atteint un maximum. he 12'jour, L' ARN ...

  1. Treatment of acute viral bronchiolitis.

    Science.gov (United States)

    Eber, Ernst

    2011-01-01

    Acute viral bronchiolitis represents the most common lower respiratory tract infection in infants and young children and is associated with substantial morbidity and mortality. Respiratory syncytial virus is the most frequently identified virus, but many other viruses may also cause acute bronchiolitis. There is no common definition of acute viral bronchiolitis used internationally, and this may explain part of the confusion in the literature. Most children with bronchiolitis have a self limiting mild disease and can be safely managed at home with careful attention to feeding and respiratory status. Criteria for referral and admission vary between hospitals as do clinical practice in the management of acute viral bronchiolitis, and there is confusion and lack of evidence over the best treatment for this condition. Supportive care, including administration of oxygen and fluids, is the cornerstone of current treatment. The majority of infants and children with bronchiolitis do not require specific measures. Bronchodilators should not be routinely used in the management of acute viral bronchiolitis, but may be effective in some patients. Most of the commonly used management modalities have not been shown to have a clear beneficial effect on the course of the disease. For example, inhaled and systemic corticosteroids, leukotriene receptor antagonists, immunoglobulins and monoclonal antibodies, antibiotics, antiviral therapy, and chest physiotherapy should not be used routinely in the management of bronchiolitis. The potential effect of hypertonic saline on the course of the acute disease is promising, but further studies are required. In critically ill children with bronchiolitis, today there is little justification for the use of surfactant and heliox. Nasal continuous positive airway pressure may be beneficial in children with severe bronchiolitis but a large trial is needed to determine its value. Finally, very little is known on the effect of the various

  2. Viral diseases and human evolution

    OpenAIRE

    Leal Élcio de Souza; Zanotto Paolo Marinho de Andrade

    2000-01-01

    The interaction of man with viral agents was possibly a key factor shaping human evolution, culture and civilization from its outset. Evidence of the effect of disease, since the early stages of human speciation, through pre-historical times to the present suggest that the types of viruses associated with man changed in time. As human populations progressed technologically, they grew in numbers and density. As a consequence different viruses found suitable conditions to thrive and establish l...

  3. Recycling Endosomes and Viral Infection

    Directory of Open Access Journals (Sweden)

    Sílvia Vale-Costa

    2016-03-01

    Full Text Available Many viruses exploit specific arms of the endomembrane system. The unique composition of each arm prompts the development of remarkably specific interactions between viruses and sub-organelles. This review focuses on the viral–host interactions occurring on the endocytic recycling compartment (ERC, and mediated by its regulatory Ras-related in brain (Rab GTPase Rab11. This protein regulates trafficking from the ERC and the trans-Golgi network to the plasma membrane. Such transport comprises intricate networks of proteins/lipids operating sequentially from the membrane of origin up to the cell surface. Rab11 is also emerging as a critical factor in an increasing number of infections by major animal viruses, including pathogens that provoke human disease. Understanding the interplay between the ERC and viruses is a milestone in human health. Rab11 has been associated with several steps of the viral lifecycles by unclear processes that use sophisticated diversified host machinery. For this reason, we first explore the state-of-the-art on processes regulating membrane composition and trafficking. Subsequently, this review outlines viral interactions with the ERC, highlighting current knowledge on viral-host binding partners. Finally, using examples from the few mechanistic studies available we emphasize how ERC functions are adjusted during infection to remodel cytoskeleton dynamics, innate immunity and membrane composition.

  4. Problems in diagnosing viral hepatitis.

    Science.gov (United States)

    Bonino, F; Colloredo Mels, G; Bellati, G; Ideo, G; Oliveri, F; Colombatto, P; Brunetto, M R

    1993-01-01

    The most reliable method of making a specific aetiological diagnosis of chronic viral hepatitis would be to identify virus specific cytotoxic T lymphocytes responsible for the killing of virus infected hepatocytes in each patient's liver. Unfortunately, this can not be proposed for routine diagnosis and surrogate tests are required. The detection of virus markers, and even of the virus itself, does not imply that liver damage is caused by virus infection. Indirect markers of the host's antiviral immunoresponse have to be used to confirm more specifically the diagnosis of viral hepatitis. IgM antibodies against viral antigens implicated in the elimination of the virus seem to be suitable alternative candidates. Significant changes in the serum values of viraemia and aminotransferases occur within a few days, while a significant variation in liver histology takes much longer. Only the kinetics of the highly variable parameters can be used for an appropriate study of the relationship between viraemia, antiviral immunoresponse, and liver cell necrosis. Quantitative and dynamic analyses of hepatitis virus markers seem the most suitable and reliable methods of monitoring the patients eligible for antiviral treatment and identifying the most appropriate time to start this. PMID:8314490

  5. 人类免疫缺陷病毒,艾滋病病毒1型艾滋病患者CD4+T淋巴细胞水平与机会感染及病毒载量的相关性分析%Correlation of CD4+T lymphocyte level with opportunistic infections and viral load in AIDS patients infected with HIV-1

    Institute of Scientific and Technical Information of China (English)

    李铃; 古雪; 敬雨佳; 李芸; 梅小平

    2016-01-01

    目的:分析人类免疫缺陷病毒,艾滋病病毒-1(HIV-1)型艾滋病(AIDS)患者体内CD4+T淋巴细胞水平与艾滋病病毒载量及机会性感染的相关性。方法通过Real- time PCR OBASAmpliPrep/COBAS Taq-Man全自动病毒载量仪(Roche公司)和流式细胞仪(FACSCOUNT)绝对计数法对95例HIV-1型AIDS患者定量检测血浆中HIV-1 RNA和CD4+T淋巴细胞数。结果低文化程度的35~50岁已婚男性农民是HIV-1型AIDS患者的多见人群,主要通过性传播途径感染;机会感染最常见部位是呼吸系统感染90例次(51.5%);机会感染发病率最多的是细菌性肺炎48例次(27.4%);根据CD4+T淋巴细胞计数分层水平分为5组,细菌性肺炎、卡氏肺孢子虫肺炎、肺结核、口腔念珠菌感染、隐球菌脑膜炎、感染性腹泻及单纯疱疹各自在5组间比较差异有统计学意义(0.05);CD4+T细胞计数低于200个/μl时,机会感染发生例次率为97.7%;病毒量<103拷贝/ml的AIDS中,以CD4+T细胞数在200~399个/μl的个体较多(75%),病毒量≥105拷贝/ml的AIDS中,CD4+T细胞数在<200个/μl的个体45例(73.8%);CD4+T淋巴细胞值与病毒载量对数值呈负相关(=-0.34,<0.01)。结论 AIDS患者机会性感染的发生率高,随病毒载量上升CD4+T淋巴细胞数呈现不同程度的下降趋势,CD4+T细胞计数是AIDS患者发生机会性感染的独立危险因素,加强对患者CD4+T细胞计数观察是预测机会性感染的重要手段。%Objective To analyze the correlation of CD4+T cell level with HIV load and opportunistic infections in AIDS patients with type 1 human immunodeficiency virus (HIV-1). Methods The plasma load of HIV-1 RNA was detected using real-time PCR OBASAmpliPrep/COBAS TaqMan automatic viral load meter (Roche), and CD4+ T lymphocytes were counted by flow cytometry (FACSCOUNT) absolute counting method for 95 patients with AIDS of HIV-1 infection. Results

  6. Viral Hepatitis: Information for Gay and Bisexual Men

    Science.gov (United States)

    VIRAL HEPATITIS Information for Gay and Bisexual Men What is viral hepatitis? Viral hepatitis is an infection of the liver caused by ... United States, the most common types of viral hepatitis are Hepatitis A, Hepatitis B, and Hepatitis C. ...

  7. Progress with volunteer studies of nasal deposition and clearance

    International Nuclear Information System (INIS)

    Inhalation is the main route of intake of radioactive material for workers, and can be an important pathway for members of the public following accidental releases of radioactivity to the environment. Much of the inhaled radioactivity initially deposits in the nose, typically over 40% for particles of aerodynamic diameter (dae) greater than 2 μm. However, there is remarkably little information on the clearance from the human nose of particles deposited during inhalation and, until now, none on the clearance of the significant fraction of material that remains in the nasal passage for more than 12 hours. NRPB is conducting a volunteer study to determine the effects of particle size and breathing pattern on particle deposition in, and clearance from, the human nasal passage. This article summarises results obtained to date. (author)

  8. Improving mucociliary clearance in chronic obstructive pulmonary disease.

    Science.gov (United States)

    Bhowmik, Angshu; Chahal, Kamaljeet; Austin, Gillian; Chakravorty, Indranil

    2009-04-01

    Patients with COPD usually experience mucus hypersecretion as a result of airway inflammation and response to noxious stimuli. These in turn lead to worsening airway resistance, impaired airflow, increased work of breathing, dyspnoea and exercise intolerance. Mucus hypersecretion may also lead to increased exacerbations and poor health related quality of life (HRQL). Institution based pulmonary rehabilitation programs incorporating airway clearance techniques have been shown to improve HRQL, reduce dyspnoea and improve exercise tolerance but are often difficult to provide due to restricted accessibility and resource implications. This review examines the current evidence base and best clinical practice in the area of airway clearance. Mechanical devices such as the flutter valves, positive end expiratory pressure and high frequency chest wall oscillation (HFCWO) may be able to provide the benefits of improved airway clearance in the patient's home potentially with reduced demands on healthcare resources.

  9. Pharmacometabonomic Prediction of Busulfan Clearance in Hematopoetic Cell Transplant Recipients.

    Science.gov (United States)

    Navarro, Sandi L; Randolph, Timothy W; Shireman, Laura M; Raftery, Daniel; McCune, Jeannine S

    2016-08-01

    Intravenous (IV) busulfan doses are often personalized to a concentration at steady state (Css) using the patient's clearance, which is estimated with therapeutic drug monitoring. We sought to identify biomarkers of IV busulfan clearance using a targeted pharmacometabonomics approach. A total of 200 metabolites were quantitated in 106 plasma samples, each obtained before IV busulfan administration in hematopoietic cell transplant (HCT) recipients. Both univariate linear regression with false discovery rate (FDR) and pathway enrichment analyses using the Global test were performed. In the univariate analysis, glycine, N-acetylglycine, 2-hydroxyisovaleric acid, creatine, serine, and tyrosine were statistically significantly associated with IV busulfan clearance at P 0.1. Glycine is a component of glutathione, which is conjugated with busulfan via glutathione transferase enzymes. These results demonstrate the potential utility of pharmacometabonomics to inform IV busulfan dosing. Future studies are required to validate these findings. PMID:27350098

  10. Bromosulphophthalein clearance rates in sheep with pyrrolizidine liver damage.

    Science.gov (United States)

    Lanigan, G W; Peterson, J E

    1979-05-01

    Sheep fed a ration containing 50% of dried Heliotropium europaeum showed a marked decline in bromosulphophthalein (BSP) fractional clearance rate during the first 3 months feeding. Thereafter, the response of individual animals varied widely on a time basis, although 3 groups could be identified. In the terminal stages, mean clearance rates were below 20% of initial values, with some sheep showing a decline in excess of 90%. Loss of liver functional capacity was generally much greater than indicated by the degree of damage revealed by histopathology. Thus, a suitably modified test could have considerable prognostic value in the field. In this investigation, all sheep with clearance rates below 0.15 died when exposed to a further period of H. europaeum feeding. PMID:475677

  11. Periodic response of multi-disk rotors with bearing clearances

    Science.gov (United States)

    Kim, Y. B.; Noah, S. T.; Choi, Y. S.

    1991-02-01

    The forced steady state response of a multi-disk rotor system involving a clearance at one of the bearings is determined by using a harmonic balance approach. The impedance method is applied to each of the harmonic steady state components in order to reduce the system to its displacement at the non-linear bearing support. The results reveal the interrelated roles of the bearing clearance, mass eccentricity and side force in producing dangerous subharmonics. The significant effects of the strong non-linearity of a bearing clearance are studied as related to the various system parameters. The results show that the approach developed in this study is computationally superior to numerical integration methods in analyzing multi-disk rotor systems with strong non-linearity.

  12. APPLICATION OF DSM IN OBSTACLE CLEARANCE SURVEYING OF AERODROME

    Directory of Open Access Journals (Sweden)

    X. Qiao

    2016-06-01

    Full Text Available Compared to the wide use of digital elevation model (DEM, digital surface model (DSM receives less attention because that it is composed by not only terrain surface, but also vegetations and man-made objects which are usually regarded as useless information. Nevertheless, these objects are useful for the identification of obstacles around an aerodrome. The primary objective of the study was to determine the applicability of DSM in obstacle clearance surveying of aerodrome. According to the requirements of obstacle clearance surveying at QT airport, aerial and satellite imagery were used to generate DSM, by means of photogrammetry, which was spatially analyzed with the hypothetical 3D obstacle limitation surfaces (OLS to identify the potential obstacles. Field surveying was then carried out to retrieve the accurate horizontal position and height of the obstacles. The results proved that the application of DSM could make considerable improvement in the efficiency of obstacle clearance surveying of aerodrome.

  13. Mucociliary clearance, airway inflammation and nasal symptoms in urban motorcyclists

    Directory of Open Access Journals (Sweden)

    Tereza C.S. Brant

    2014-01-01

    Full Text Available OBJECTIVES: There is evidence that outdoor workers exposed to high levels of air pollution exhibit airway inflammation and increased airway symptoms. We hypothesized that these workers would experience increased airway symptoms and decreased nasal mucociliary clearance associated with their exposure to air pollution. METHODS: In total, 25 non-smoking commercial motorcyclists, aged 18-44 years, were included in this study. These drivers work 8-12 hours per day, 5 days per week, driving on urban streets. Nasal mucociliary clearance was measured by the saccharine transit test; airway acidification was measured by assessing the pH of exhaled breath condensate; and airway symptoms were measured by the Sino-nasal Outcome Test-20 questionnaire. To assess personal air pollution exposure, the subjects used a passive-diffusion nitrogen dioxide (NO2 concentration-monitoring system during the 14 days before each assessment. The associations between NO2 and the airway outcomes were analyzed using the Mann-Whitney test and the Chi-Square test. Clinicaltrials.gov: NCT01976039. RESULTS: Compared with clearance in healthy adult males, mucociliary clearance was decreased in 32% of the motorcyclists. Additionally, 64% of the motorcyclists had airway acidification and 92% experienced airway symptoms. The median personal NO2 exposure level was 75 mg/m3 for these subjects and a significant association was observed between NO2 and impaired mucociliary clearance (p = 0.036. CONCLUSION: Non-smoking commercial motorcyclists exhibit increased airway symptoms and airway acidification as well as decreased nasal mucociliary clearance, all of which are significantly associated with the amount of exposure to air pollution.

  14. Load sensor

    OpenAIRE

    van den Ende, D.; Almeida, P.M.R.; Dingemans, T.J.; Van der Zwaag, S.

    2007-01-01

    The invention relates to a load sensor comprising a polymer matrix and a piezo-ceramic material such as PZT, em not bedded in the polymer matrix, which together form a compos not ite, wherein the polymer matrix is a liquid crystalline resin, and wherein the piezo-ceramic material is a PZT powder forming 30-60% by volume of the composite, and wherein the PZT powder forms 40-50% by volume of the composite.

  15. Extracting viral RNAs from plant protoplasts.

    Science.gov (United States)

    Fabian, Marc R; Andrew White, K

    2007-08-01

    The analysis of viral RNA is a fundamental aspect of plant RNA virus research. Studies that focus on viral RNAs often involve virus infections of plant protoplasts (see UNITS 16D.1-16D.4). Protoplast offer the advantage of simultaneous initiation of infections, which allows for superior temporal and quantitative analyses of viral RNAs. The efficient isolation of intact viral RNA is key to any such investigations. This unit describes two basic protocols for extracting viral RNAs from plant protoplasts. An approach for preparing double-stranded viral RNA from total RNA pools is also provided. The viral RNA prepared by using these techniques can be used for further analyses such as primer extension, reverse transcription-PCR, and northern blotting.

  16. Host and viral factors contributing to CD8+ T cell failure in hepatitis C virus infection

    Institute of Scientific and Technical Information of China (English)

    Christoph Neumann-Haefelin; Hans Christian Spangenberg; Hubert E Blum; Robert Thimme

    2007-01-01

    Virus-specific CD8+ T cells are thought to be the major anti-viral effector cells in hepatitis C virus (HCV)infection. Indeed, viral clearance is associated with vigorous CD8+ T cell responses targeting multiple epitopes. In the chronic phase of infection, HCV-specific CD8+ T cell responses are usually weak, narrowly focused and display often functional defects regarding cytotoxicity, cytokine production, and proliferative capacity. In the last few years, different mechanisms which might contribute to the failure of HCV-specific CD8+ T cells in chronic infection have been identified,including insufficient CD4+ help, deficient CD8+ T cell differentiation, viral escape mutations, suppression by viral factors, inhibitory cytokines, inhibitory ligands, and regulatory T cells. In addition, host genetic factors such as the host's human leukocyte antigen (HLA) background may play an important role in the efficiency of the HCVspecific CD8+ T cell response and thus outcome of infection. The growing understanding of the mechanisms contributing to T cell failure and persistence of HCV infection will contribute to the development of successful immunotherapeutical and -prophylactical strategies.

  17. Effect of oral N-acetylcysteine on mucus clearance.

    Science.gov (United States)

    Millar, A B; Pavia, D; Agnew, J E; Lopez-Vidriero, M T; Lauque, D; Clarke, S W

    1985-07-01

    Oral N-acetylcysteine has been advocated as a mucolytic agent for use in chronic bronchitis. We have investigated the effects of regular use of this drug at a dose of 200 mg thrice daily for 4 weeks in nine patients with chronic bronchitis on lung function, lung mucociliary clearance and sputum viscosity in a controlled, double-blind, crossover study. No significant differences were found in lung function, mucociliary clearance curves or sputum viscosity following treatment with N-acetylcysteine compared to control or placebo measurements.

  18. The influence of body posture on lithium clearance

    DEFF Research Database (Denmark)

    Kamper, A L; Strandgaard, S; Holstein-Rathlou, N H;

    1988-01-01

    fall in the sitting position, and fell significantly to 26 +/- 5 ml/min (p less than 0.025) in walking subjects. Absolute proximal tubular reabsorption rate of fluid correspondingly rose from 83 +/- 16 to 92 +/- 15 ml/min (p less than 0.005) and sodium clearance fell from 1.52 +/- 0.81 to 1.00 +/- 0...... during moderate physical activity. Hence, when renal tubular function is studied with the lithium clearance method, standardization of posture and physical activity is important. In such studies physical activity such as walking should particularly be avoided....

  19. Derivation methods for clearance levels applied to reactors

    Energy Technology Data Exchange (ETDEWEB)

    Okoshi, Minoru; Seki, Takeo [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    2001-12-01

    In order to support the discussion by the Nuclear Safety Commission, JAERI derived the unconditional clearance levels for concrete and metal arising from the operation and dismantling of nuclear reactors. The clearance levels of 20 radionuclides were derived from 10 {mu}Sv/y of individual doses by deterministic approach. In this approach, calculation models were established to assess individual doses resulting from 73 exposure pathways related to disposal and recycle/reuse, and realistic parameter values were selected considering Japanese natural and social conditions. The appropriateness of selected parameter values was confirmed by stochastic analyses. (author)

  20. The microbiota mediates pathogen clearance from the gut lumen after non-typhoidal Salmonella diarrhea.

    Directory of Open Access Journals (Sweden)

    Kathrin Endt

    Full Text Available Many enteropathogenic bacteria target the mammalian gut. The mechanisms protecting the host from infection are poorly understood. We have studied the protective functions of secretory antibodies (sIgA and the microbiota, using a mouse model for S. typhimurium diarrhea. This pathogen is a common cause of diarrhea in humans world-wide. S. typhimurium (S. tm(att, sseD causes a self-limiting gut infection in streptomycin-treated mice. After 40 days, all animals had overcome the disease, developed a sIgA response, and most had cleared the pathogen from the gut lumen. sIgA limited pathogen access to the mucosal surface and protected from gut inflammation in challenge infections. This protection was O-antigen specific, as demonstrated with pathogens lacking the S. typhimurium O-antigen (wbaP, S. enteritidis and sIgA-deficient mice (TCRβ(-/-δ(-/-, J(H (-/-, IgA(-/-, pIgR(-/-. Surprisingly, sIgA-deficiency did not affect the kinetics of pathogen clearance from the gut lumen. Instead, this was mediated by the microbiota. This was confirmed using 'L-mice' which harbor a low complexity gut flora, lack colonization resistance and develop a normal sIgA response, but fail to clear S. tm(att from the gut lumen. In these mice, pathogen clearance was achieved by transferring a normal complex microbiota. Thus, besides colonization resistance ( = pathogen blockage by an intact microbiota, the microbiota mediates a second, novel protective function, i.e. pathogen clearance. Here, the normal microbiota re-grows from a state of depletion and disturbed composition and gradually clears even very high pathogen loads from the gut lumen, a site inaccessible to most "classical" immune effector mechanisms. In conclusion, sIgA and microbiota serve complementary protective functions. The microbiota confers colonization resistance and mediates pathogen clearance in primary infections, while sIgA protects from disease if the host re-encounters the same pathogen. This has

  1. Dynamics of nasopharyngeal pneumococcal carriage during the course of viral bronchiolitis.

    Science.gov (United States)

    Faber, Tina E; Schuurs, Theo A; Veeger, Nic J G M; Hennus, Marije P; Bont, Louis J

    2016-08-01

    The effect of viral infection on nasopharyngeal carriage of Streptococcus pneumoniae during childhood is not well known. We studied dynamics of pneumococcal colonization by quantitative PCR during the natural course of viral bronchiolitis. At time of admission, 47 (47%) of 100 patients with bronchiolitis carried pneumococci. In patients with viral bronchiolitis who did not receive antibiotics, pneumococcal load decreased from time of admission to discharge (n = 35, cycle threshold 23 vs. 25, P = 0.0017) and from discharge to follow-up (n = 22, cycle threshold 25 vs. 40, P = 0.003). We conclude that viral respiratory infection is negatively associated with pneumococcal colonization of the upper airways. Pediatr Pulmonol. 2016;51:863-867. © 2016 Wiley Periodicals, Inc. PMID:26859410

  2. Dynamics of nasopharyngeal pneumococcal carriage during the course of viral bronchiolitis.

    Science.gov (United States)

    Faber, Tina E; Schuurs, Theo A; Veeger, Nic J G M; Hennus, Marije P; Bont, Louis J

    2016-08-01

    The effect of viral infection on nasopharyngeal carriage of Streptococcus pneumoniae during childhood is not well known. We studied dynamics of pneumococcal colonization by quantitative PCR during the natural course of viral bronchiolitis. At time of admission, 47 (47%) of 100 patients with bronchiolitis carried pneumococci. In patients with viral bronchiolitis who did not receive antibiotics, pneumococcal load decreased from time of admission to discharge (n = 35, cycle threshold 23 vs. 25, P = 0.0017) and from discharge to follow-up (n = 22, cycle threshold 25 vs. 40, P = 0.003). We conclude that viral respiratory infection is negatively associated with pneumococcal colonization of the upper airways. Pediatr Pulmonol. 2016;51:863-867. © 2016 Wiley Periodicals, Inc.

  3. 人类免疫缺陷病毒,艾滋病病毒1型艾滋病患者CD4+T淋巴细胞水平与机会感染及病毒载量的相关性分析%Correlation of CD4+T lymphocyte level with opportunistic infections and viral load in AIDS patients infected with HIV-1

    Institute of Scientific and Technical Information of China (English)

    李铃; 古雪; 敬雨佳; 李芸; 梅小平

    2016-01-01

    Objective To analyze the correlation of CD4+T cell level with HIV load and opportunistic infections in AIDS patients with type 1 human immunodeficiency virus (HIV-1). Methods The plasma load of HIV-1 RNA was detected using real-time PCR OBASAmpliPrep/COBAS TaqMan automatic viral load meter (Roche), and CD4+ T lymphocytes were counted by flow cytometry (FACSCOUNT) absolute counting method for 95 patients with AIDS of HIV-1 infection. Results The majority of the patients with HIV-1 type AIDS were mainly married male farmers with low education level at the age of 35-50 years. They got the infection mainly through sexual transmission. Opportunis-tic infections most commonly occurred in the respiratory system (90 times, 51.5%) and bacterial pneumonia account-ed for the highest incidence (48 times, 27.4%). Based on CD4+T lymphocyte count level the opportunistic infections were divided into 5 groups. Bacterial pneumonia, Pneumoaystis carrii pneumonia, pulmonary tuberculosis, oral Candi-da infection, cryptococcal meningitis, infectious diarrhea and herpes simplex were significantly different among the 5 groups ( 0.05);CD4+T细胞计数低于200个/μl时,机会感染发生例次率为97.7%;病毒量<103拷贝/ml的AIDS中,以CD4+T细胞数在200~399个/μl的个体较多(75%),病毒量≥105拷贝/ml的AIDS中,CD4+T细胞数在<200个/μl的个体45例(73.8%);CD4+T淋巴细胞值与病毒载量对数值呈负相关(=-0.34,<0.01)。结论 AIDS患者机会性感染的发生率高,随病毒载量上升CD4+T淋巴细胞数呈现不同程度的下降趋势,CD4+T细胞计数是AIDS患者发生机会性感染的独立危险因素,加强对患者CD4+T细胞计数观察是预测机会性感染的重要手段。

  4. 轴承游隙计算分析%Analysis and calculation of bearing clearance

    Institute of Scientific and Technical Information of China (English)

    郭玉朋

    2014-01-01

    This paper analyzes the original common bearing clearance, installation clearance,clearance work,what used to solve bearing in C0,C3 clearance clearance work group size,select the project for future reference bearing clearance.%本文通过分析常用轴承的原始游隙,安装游隙,工作游隙,来求解一下常用轴承在C0,C3游隙组中的工作游隙的大小,作为以后项目选取轴承游隙的参考。

  5. 干扰素α-2b与聚乙二醇干扰素α-2a治疗低病毒载量慢性丙型肝炎快速及早期病毒学应答临床观察%Interferonα-2b and pegylated interferonα-2a in therapy of chronic hepatitis C patients with low viral load:Clinical observation on the rapid and early virological

    Institute of Scientific and Technical Information of China (English)

    徐菁; 欧亚非

    2014-01-01

    目的:研究干扰素类型在低病毒载量慢性丙型肝炎抗病毒治疗应答的影响。方法选择120例慢性丙型肝炎患者为研究对象,将120例患者分为聚乙二醇干扰素α-2a(派罗欣,Peg-IFN)组58例和普通干扰素α2b(凯因益生)组62例。所有患者用干扰素联合利巴韦林抗病毒治疗。Peg-IFN组选用180μg每周注射1次,普通干扰素组为600 MU隔日注射1次。利巴韦林使用剂量900~1200mg/d。疗程:达RVR之后再应用24周;达EVR之后再应用36周;对于12周未达EVR者再应用48周。对抗病毒治疗的应答情况与干扰素类型及丙肝病毒载量的关系进行回顾性分析。结果两组中,普通干扰素组RVR获得率为79%,EVR获得率为85.4%,派罗欣组的RVR获得率为81%,EVR获得率为89.6%。对于RVR的获得,χ2=0.009,P>0.05,对于EVR的获得,χ2=0.036,P>0.05,对于SVR的获得,χ2=0.010,P>0.05,组间比较差异无统计学意义。结论在病毒载量较低的情况下,聚乙二醇干扰素α-2a与普通干扰素α-2b抗病毒治疗的RVR、EVR、SVR获得率差异无统计学意义。%Objective To observe the response of chronic hepatitis C patients with low viral load to anti⁃viral treatment by different interferon(IFN) modality. Methods 120 patients with chronic hepatitis C were as⁃signed to Peg-IFN group(n=58, treated with Peginterferon alfa-2a injection in dose of 180μg once a week) and recombinant human interferon α-2b injection group(n=62, administered in dose of 600 MU once every other day), and the two groups were given additional dosage of ribavirin by 900~1200 mg/d. The treatment course was as follows:24 weeks were extended after rapid virological response(RVR), and 36 weeks after early virological response(EVR). For patients failed to meet EVR by the 12th week, 48 weeks were extended. The data were retrospectively analyzed on response to antiviral treatment, interferon modality and

  6. Airway epithelial NF-κB activation promotes Mycoplasma pneumoniae clearance in mice.

    Directory of Open Access Journals (Sweden)

    Di Jiang

    Full Text Available Respiratory infections including atypical bacteria Mycoplasma pneumoniae (Mp contribute to the pathobiology of asthma and chronic obstructive pulmonary disease (COPD. Mp infection mainly targets airway epithelium and activates various signaling pathways such as nuclear factor κB (NF-κB. We have shown that short palate, lung, and nasal epithelium clone 1 (SPLUNC1 serves as a novel host defense protein and is up-regulated upon Mp infection through NF-κB activation in cultured human and mouse primary airway epithelial cells. However, the in vivo role of airway epithelial NF-κB activation in host defense against Mp infection has not been investigated. In the current study, we investigated the effects of in vivo airway epithelial NF-κB activation on lung Mp clearance and its association with airway epithelial SPLUNC1 expression.Non-antimicrobial tetracycline analog 9-t-butyl doxycycline (9-TB was initially optimized in mouse primary tracheal epithelial cell culture, and then utilized to induce in vivo airway epithelial specific NF-κB activation in conditional NF-κB transgenic mice (CC10-(CAIKKβ with or without Mp infection. Lung Mp load and inflammation were evaluated, and airway epithelial SPLUNC1 protein was examined by immunohistochemistry. We found that 9-TB treatment in NF-κB transgene positive (Tg+, but not transgene negative (Tg- mice significantly reduced lung Mp load. Moreover, 9-TB increased airway epithelial SPLUNC1 protein expression in NF-κB Tg+ mice.By using the non-antimicrobial 9-TB, our study demonstrates that in vivo airway epithelial NF-κB activation promotes lung bacterial clearance, which is accompanied by increased epithelial SPLUNC1 expression.

  7. Influences of Taper Geometry Modified Oil-Grooves on Load Carrying Capacity of Crosshead Bearings

    Science.gov (United States)

    Kitahara, Tatsumi; Otsubo, Masaru; Nakahara, Daisuke

    The crosshead bearing in large two-stroke diesel engines operates under severe lubrication conditions, because the bearing oscillates within a small angle at a low speed and is always subject to a high downward load. The recent trend towards more compact engines with increased output raises the bearing specific load, thereby causing the lubrication severity to increase significantly. Thus it is very important to improve the load carrying capacity of the crosshead bearing. In the present study, experiments using a dynamically loaded bearing seizure test apparatus were carried out to clarify the influences of the clearance ratio and the oil-groove geometry on the load carrying capacity. The electrical resistance of the oil film was also measured to evaluate the extent of the oil film formation. The major results are: (1) A decrease in the clearance ratio is effective in enhancing squeeze action on the entirety of the bearing pads, thereby improving the load carrying capacity. When the clearance ratio becomes too low, however, the ability to form an adequate wedge film is degraded, causing the load carrying capacity to decrease; (2) A significant improvement in the load carrying capacity can be expected, because incorporating the taper geometry on both sides of the oil-groove promotes a thicker oil film; and (3) A taper geometry with a subtended length of 5 degrees and a taper angle of 0.1 degree produces the maximum load carrying capacity.

  8. Identification and characterization of HIV-1 latent viral reservoirs in peripheral blood.

    Science.gov (United States)

    Chargin, Amanda; Yin, Fangfang; Song, Min; Subramaniam, Srividyabhuvaneswari; Knutson, Grace; Patterson, Bruce K

    2015-01-01

    Plasma viral load and CD4 counts are effective for clinical monitoring, but they do not give a full representation of HIV-1 quasispecies in cellular reservoirs, the major repository of replication-competent HIV-1 in infected individuals. We sought to develop a diagnostic system that might stimulate the replication-competent HIV-1 reservoirs for enhanced clinical monitoring, including selection of antiretroviral regimens. Whole-blood samples from 45 HIV-infected individuals were collected into 1 ViraStim HIV-1 activation tube and 1 EDTA tube. Samples were tested for viral load and cell type-specific HIV-1 replication. Further, 7 matched activated/nonactivated samples were sequenced using the Trugene HIV-1 genotyping kit. The percentage of patients with replication-competent virus in peripheral blood mononuclear cells (PBMCs) varied, depending on the baseline plasma viral load in the EDTA tubes. Six out of 24 patients with a starting plasma viral load of 20 and 1,000 all showed increases in viral replication of >5-fold. These increases came from cellular reservoirs in blood as determined by simultaneous ultrasensitive subpopulation staining/hybridization in situ (SUSHI). When resistance genotypes in plasma from activation tubes were compared to those from EDTA tubes for 7 patients, all patients showed additional mutations in the activation tube, while 3 patients demonstrated additional genotypic resistance determinants. We show that HIV-1 viral replication can be stimulated directly from infected whole blood. The sequencing results showed that 3 of 7 cases demonstrated additional drug resistance following stimulation. PMID:25339403

  9. Platelets prevent IFN-alpha/beta-induced lethal hemorrhage promoting CTL-dependent clearance of lymphocytic choriomeningitis virus.

    Science.gov (United States)

    Iannacone, Matteo; Sitia, Giovanni; Isogawa, Masanori; Whitmire, Jason K; Marchese, Patrizia; Chisari, Francis V; Ruggeri, Zaverio M; Guidotti, Luca G

    2008-01-15

    We found that mice infected with different isolates of lymphocytic choriomeningitis virus (LCMV) develop a mild hemorrhagic anemia, which becomes severe and eventually lethal in animals depleted of platelets or lacking integrin beta3. Lethal hemorrhagic anemia is mediated by virus-induced IFN-alpha/beta that causes platelet dysfunction, mucocutaneous blood loss and suppression of erythropoiesis. In addition to the life-threatening hemorrhagic anemia, platelet-depleted mice fail to mount an efficient cytotoxic T lymphocyte (CTL) response and cannot clear LCMV. Transfusion of functional platelets into these animals reduces hemorrhage, prevents death and restores CTL-induced viral clearance in a manner partially dependent on CD40 ligand (CD40L). These results indicate that, upon activation, platelets expressing integrin beta3 and CD40L are required for protecting the host against the induction of an IFN-alpha/beta-dependent lethal hemorrhagic diathesis and for clearing LCMV infection through CTLs.

  10. Loads and loads and loads: the influence of prospective load, retrospective load, and ongoing task load in prospective memory

    OpenAIRE

    Beat eMeier; Zimmermann, Thomas D.

    2015-01-01

    In prospective memory tasks different kinds of load can occur. Adding a prospective memory task can impose a load on ongoing task performance. Adding ongoing task load can affect prospective memory performance. The existence of multiple target events increases prospective load and adding complexity to the to-be-remembered action increases retrospective load. In two experiments, we systematically examined the effects of these different types of load on prospective memory performance. Results s...

  11. Evaluation of Viral Meningoencephalitis Cases

    Directory of Open Access Journals (Sweden)

    Handan Ilhan

    2012-08-01

    Full Text Available AIM: To evaluate retrospectively adult cases of viral encephalitis. METHOD: Fifteen patients described viral encephalitis hospitalized between the years 2006-2011 follow-up and treatment at the infectious diseases clinic were analyzed retrospectively. RESULTS: Most of the patients (%60 had applied in the spring. Fever (87%, confusion (73%, neck stiffness (73%, headache (73%, nausea-vomiting (33%, loss of consciousness (33%, amnesia (33%, agitation (20%, convulsion (%20, focal neurological signs (13%, Brudzinski-sign (13% were most frequently encountered findings. Electroencephalography test was applied to 13 of 14 patients, and pathological findings compatible with encephalitis have been found. Radiological imaging methods such as CT and MRI were performed in 9 of the 14 patients, and findings consistent with encephalitis were reported. All of initial cerebrospinal fluid (CSF samples were abnormal. The domination of the first examples was lymphocytes in 14 patients; only one patient had an increase in neutrophilic cells have been found. CSF protein level was high in nine patients, and low glucose level was detected in two patients. Herpes simplex virus polymerized chain reaction (PCR analyze was performed to fourteen patients CSF. Only two of them (14% were found positive. One of the patients sample selectively examined was found to be Parvovirus B19 (+, the other patient urine sample Jacobs-creutzfeld virus PCR was found to be positively. Empiric acyclovir therapy was given to all patients. Neuropsychiatric squeal developed at the one patient. CONCLUSION: The cases in the forefront of change in mental status viral meningoencephalitis should be considered and empirical treatment with acyclovir should be started. [TAF Prev Med Bull 2012; 11(4.000: 447-452

  12. Encefalitis virales en la infancia

    Directory of Open Access Journals (Sweden)

    Monserrat Téllez de Meneses

    2013-09-01

    Full Text Available La encefalitis viral es una enfermedad grave que implica el compromiso inflamatorio del parénquima cerebral. Las infecciones virales del SNC ocurren con frecuencia como complicación de infecciones virales sistémicas. Más de 100 virus están implicados como agentes causales, entre los cuales el virus Herpes simplex tipo I, es el agente causal más frecuente de encefalitis no epidémica en todos los grupos poblacionales del mundo; es el responsable de los casos más graves en todas las edades. Muchos de los virus para los cuales existe vacunas también pueden causar encefalitis como: sarampión, paperas, polio, rabia, rubéola, varicela. El virus produce una inflamación del tejido cerebral, la cual puede evolucionar a una destrucción de neuronas, provocar hemorragia y daño cerebral, dando lugar a encefalitis graves, como la encefalitis necrotizante o hemorrágica, con mucho peor pronóstico, produciendo secuelas graves, incluso la muerte. El cuadro clínico, incluye la presencia de cefalea, fiebre y alteración de la conciencia, de rápida progresión. El pronóstico de las encefalitis víricas es variable, algunos casos son leves, con recuperación completa, sin embargo existen casos graves que pueden ocasionar secuelas importantes a nivel cerebral. Es fundamental realizar un diagnóstico lo antes posible, a través de pruebas de laboratorio (bioquímica, PCR, cultivos y de neuroimagen (TAC, RM y ante todo, la instauración de un tratamiento precoz para evitar la evolución del proceso y sus posibles complicaciones. El pronóstico empeora si se retrasa la instauración del tratamiento.

  13. [Microbiological diagnosis of viral hepatitis].

    Science.gov (United States)

    Alonso, Roberto; Aguilera, Antonio; Córdoba, Juan; Fuertes, Antonio

    2015-11-01

    Liver inflammation or hepatitis has many different causes, both infectious and non-infectious. Among the former, viral infection is responsible for at least half of all hepatitis worldwide. Different viruses have been described with primary tropism for liver tissue. These microorganisms have been successively named with letters of the alphabet: A, B, C, D, E and G. The aim of this paper is to review this heterogeneous group of viruses in its most basic aspects, including clinical implications, treatment, main control, and prophylactic measures and, of special interest, diagnostic approaches, both serological and molecular, which are used for their detection, quantification and characterization. PMID:25742731

  14. Virally encoded 7TM receptors

    DEFF Research Database (Denmark)

    Rosenkilde, M M; Waldhoer, M; Lüttichau, H R;

    2001-01-01

    A number of herpes- and poxviruses encode 7TM G-protein coupled receptors most of which clearly are derived from their host chemokine system as well as induce high expression of certain 7TM receptors in the infected cells. The receptors appear to be exploited by the virus for either immune evasion...... expression of this single gene in certain lymphocyte cell lineages leads to the development of lesions which are remarkably similar to Kaposi's sarcoma, a human herpesvirus 8 associated disease. Thus, this and other virally encoded 7TM receptors appear to be attractive future drug targets....

  15. Mucociliary and cough clearance as a biomarker for therapeutic development

    DEFF Research Database (Denmark)

    Bennett, William D; Daviskas, Evangelia; Hasani, Amir;

    2010-01-01

    A workshop/symposium on “Mucociliary and Cough Clearance (MCC/CC) as a Biomarker for Therapeutic Development” was held on October 21–22, 2008, in Research Triangle Park, NC, to discuss the methods for measurement of MCC/CC and how they may be optimized for assessing new therapies designed...

  16. Highly fluorescent resorcinarene cavitand nanocapsules with efficient renal clearance

    Science.gov (United States)

    Mahadevan, Kalpana; Patthipati, Venkata Suresh; Han, Sangbum; Swanson, R. James; Whelan, Eoin C.; Osgood, Christopher; Balasubramanian, Ramjee

    2016-08-01

    Nanomaterial based imaging approaches hold substantial promise in addressing current diagnostic and therapeutic challenges. One of the key requirements for the successful clinical translation of nanomaterials is their complete clearance from the body within a reasonable time period preferably via the renal filtration route. This article describes the synthesis of highly fluorescent, water soluble, resorcinarene cavitand nanocapsules and demonstrates their effective renal clearance in mice. The synthesis and functionalization of nanocapsules was accomplished in a one-pot operation via thiol-ene reactions without involving self-assembly, sacrificial templates or emulsions. Water soluble resorcinarene cavitand nanocapsules obtained by this approach were covalently functionalized with Alexa Fluor 750. Highly fluorescent nanocapsules with hydrodynamic diameters of 122 nm and 68 nm and extinction coefficients of 1.3 × 109 M-1 cm-1 and 1.5 × 108 M-1 cm-1 respectively were prepared by varying the reaction conditions. The in vivo biodistribution and clearance of these nanocapsules in mice followed by whole-body fluorescence imaging showed that they were both cleared renally within a few hours. Given the inherent encapsulation capabilities of nanocapsules, the renal clearance demonstrated in this work opens up new opportunities for their theranostic applications especially for targeting and treating the urinary tract.

  17. Decreased renal clearance of digoxin in chronic congestive heart failure.

    Science.gov (United States)

    Naafs, M A; van der Hoek, C; van Duin, S; Koorevaar, G; Schopman, W; Silberbusch, J

    1985-01-01

    Renal digoxin clearance was compared in patients suffering from atrial fibrillation with well preserved cardiac function (n = 9; salt intake +/- 170 mmol daily) and patients with chronic congestive heart failure (n = 10; salt intake 50 mmol daily and maintenance treatment with diuretics). There was no difference between the groups concerning digoxin dosage, creatinine clearance, diuresis or sodium excretion in the urine. Digoxin clearance in chronic heart failure proved to be significantly lower than in atrial fibrillation (48 +/- 21 vs 71 +/- 36 ml X min-1, p less than 0.05), and Cdig/Ccreat was similarly reduced at 0.73 +/- 0.15 compared to 1.09 +/- 0.27 (p less than 0.005). Steady state serum digoxin concentration was significantly higher in patients with congestive heart failure (1.44 +/- 0.47 vs 0.87 +/- 0.33 micrograms X 1(-1), p less than 0.01). Chronic congestive heart failure is a state with reduced digoxin clearance by the kidney, which could lead to digoxin intoxication not explicable by overdose, reduced renal function or the effect of interacting drugs. PMID:4007028

  18. In Vivo Renal Clearance, Biodistribution, Toxicity of Gold nanoclusters

    CERN Document Server

    Zhang, Xiao-Dong; Shen, Xiu; Liu, Pei-Xun; Fan, Fei-Yue; Fan, Sai-Jun; 10.1016/j.biomaterials.2012.03.020

    2012-01-01

    Gold nanoparticles have shown great prospective in cancer diagnosis and therapy, but they can not be metabolized and prefer to accumulate in liver and spleen due to their large size. The gold nanoclusters with small size can penetrate kidney tissue and have promise to decrease in vivo toxicity by renal clearance. In this work, we explore the in vivo renal clearance, biodistribution, and toxicity responses of the BSA- and GSH-protected gold nanoclusters for 24 hours and 28 days. The BSA-protected gold nanoclusters have low-efficient renal clearance and only 1% of gold can be cleared, but the GSH-protected gold nanoclusters have high-efficient renal clearance and 36 % of gold can be cleared after 24 hours. The biodistribution further reveals that 94% of gold can be metabolized for the GSH-protected nanoclusters, but only less than 5% of gold can be metabolized for the BSA-protected nanoclusters after 28 days. Both of the GSH- and BSA-protected gold nanoclusters cause acute infection, inflammation, and kidney fu...

  19. Early clearance of Mycobacterium tuberculosis: a new frontier in prevention

    NARCIS (Netherlands)

    Verrall, A.J.; Netea, M.G.; Alisjahbana, B.; Hill, P.C.; Crevel, R. van

    2014-01-01

    Early clearance (EC) is the successful eradication of inhaled Mycobacterium tuberculosis before an adaptive immune response develops. Evidence for EC comes from case contact studies that consistently show that a proportion of heavily exposed individuals do not develop M. tuberculosis infection. Furt

  20. 46 CFR 61.20-23 - Tailshaft clearance; bearing weardown.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Tailshaft clearance; bearing weardown. 61.20-23 Section...; bearing weardown. (a) Water lubricated bearings, other than rubber, must be rebushed as follows: (1) Where the propelling machinery is located amidship, the after stern tube bearing must be rebushed when it...

  1. Spontaneous Clearance of Hepatitis C after Liver and Renal Transplantation

    Directory of Open Access Journals (Sweden)

    CH Dale

    2009-01-01

    Full Text Available Spontaneous clearance of hepatitis C virus (HCV is rare in immunocompromised patients, such as those who have undergone organ transplantation. It has been recognized that patients receiving liver transplantation for HCV-related disease have decreased graft and patient survival compared with those transplanted for other etiologies. There is a growing trend toward treating HCV recurrence aggressively after liver transplantation. For other organ transplant recipients with concurrent HCV, treatment is not often an option, given the high rates of graft rejection and loss secondary to interferon and its immunomodulatory effects. Although spontaneous clearance of HCV has been reported in recipients of solitary liver and renal transplants, a common factor arising in these cases has been previous exposure to interferon. To date, no reports of spontaneous clearance of HCV RNA have been reported in a multiorgan transplant recipient. A case of spontaneous clearance of HCV RNA in an immunocompromised patient, within five months of simultaneous liver and kidney retransplantation is described. Importantly, this patient had no previous exposure to interferon.

  2. Mucociliary clearance, airway inflammation and nasal symptoms in urban motorcyclists

    OpenAIRE

    Brant, Tereza C S; Yoshida, Carolina T; Tomas de S. Carvalho; Nicola, Marina L; Jocimar. A. Martins; Lays M. Braga; Regiani C. de Oliveira; Vilma Leyton; Carmen S. de André; Saldiva, Paulo H. N.; Rubin, Bruce K.; Naomi K. Nakagawa

    2014-01-01

    OBJECTIVES: There is evidence that outdoor workers exposed to high levels of air pollution exhibit airway inflammation and increased airway symptoms. We hypothesized that these workers would experience increased airway symptoms and decreased nasal mucociliary clearance associated with their exposure to air pollution. METHODS:...

  3. Influence of clearance model on numerical simulation of centrifugal pump

    Science.gov (United States)

    Wang, Z.; Gao, B.; Yang, L.; Du, W. Q.

    2016-05-01

    Computing models are always simplified to save the computing resources and time. Particularly, the clearance that between impeller and pump casing is always ignored. But the completer model is, the more precise result of numerical simulation is in theory. This paper study the influence of clearance model on numerical simulation of centrifugal pump. We present such influence via comparing performance, flow characteristic and pressure pulsation of two cases that the one of two cases is the model pump with clearance and the other is not. And the results show that the head decreases and power increases so that efficiency decreases after computing with front and back cavities. Then no-leakage model would improve absolute velocity magnitude in order to reach the rated flow rate. Finally, more disturbance induced by front cavity flow and wear-ring flow would change the pressure pulsation of impeller and volute. The performance of clearance flow is important for the whole pump in performance, flow characteristic, pressure pulsation and other respects.

  4. 19 CFR 4.61 - Requirements for clearance.

    Science.gov (United States)

    2010-04-01

    ... either on the Customs Form 1300 or by approved electronic means. Customs port directors may permit the.... Customs may take local resources into consideration in allowing clearance to be transacted on board... thereto by any means of communication that is satisfactory to the local Customs port director, and...

  5. Modifications of lung clearance mechanisms by acute influenza A infection

    International Nuclear Information System (INIS)

    Four volunteers with naturally acquired, culture-proved influenza A infection inhaled a radiolabeled aerosol to permit investigation of lung mucociliary clearance mechanisms during and after symptomatic illness. Mucus transport in the trachea was undetectable when monitored with an external multidetector probe within 48 hours of the onset of the illness, but was found at a normal velocity by 1 week in three of the four subjects. In two volunteers who coughed 23 to 48 times during the 4.5-hour observation period, whole lung clearance was as fast within the first 48 hours of illness as during health 3 months later in spite of the absence of measurable tracheal mucus transport. Conversely, in spite of the return 1 week later of mucus transport at velocities expected in the trachea, whole lung clearance for the 4.5-hour period was slowed in two volunteers who coughed less than once an hour. The data offer evidence that cough is important in maintaining lung clearance for at least several days after symptomatic influenza A infection when other mechanisms that depend on ciliary function are severely deficient

  6. Effect of lindane on the clearance rate of Daphnia magna

    NARCIS (Netherlands)

    Hartgers, E.M.; Heugens, E.W.; Deneer, J.W.

    1999-01-01

    The impact of the insecticide lindane (%-hexachlorocyclohexane) on the clearance rate (CR) of Daphnia magna was investigated using artificial beads. CR (24-h EC50: 65 7g Lm1) was found to be a more sensitive endpoint than acute lethality for D. magna (48-h LC50: 516 7g Lm1). The onset of the effect

  7. 75 FR 52798 - State-07, Cryptographic Clearance Records

    Science.gov (United States)

    2010-08-27

    ...: Unclassified. SYSTEM LOCATION: Department of State, 301 4th St., SW., Room 750 Washington, DC 20547. CATEGORIES... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF STATE State-07, Cryptographic Clearance Records Summary: Notice is hereby given that the Department of State proposes to...

  8. CLEARANCE OF INDOMETHACIN OCCURS PREDOMINANTLY BY RENAL GLUCURONIDATION

    NARCIS (Netherlands)

    MOOLENAAR, F; CRANCRINUS, S; VISSER, J; DEZEEUW, D; MEIJER, DKF

    1992-01-01

    In this report we describe the conditions of collection, storage and handling of urine samples, collected after oral dosing with indometacin in man, in order to maintain the integrity of the labile glucuronide formed. We found that the body clearance occurs predominantly by renal metabolism, due to

  9. Low Molecular Weight pDMAEMA-block-pHEMA Block-Copolymers Synthesized via RAFT-Polymerization: Potential Non-Viral Gene Delivery Agents?

    OpenAIRE

    Thomas Kissel; Christian Pfeiffer; Olga Samsonova; Markus Hellmund; Merkel, Olivia M.

    2011-01-01

    The aim of this study was to investigate non-viral pDNA carriers based on diblock-copolymers consisting of poly(2-(dimethyl amino)ethyl methacrylate) (pDMAEMA) and poly(2-hydroxyethyl methacrylate) (pHEMA). Specifically the block-lengths and molecular weights were varied to determine the minimal requirements for transfection. Such vectors should allow better transfection at acceptable toxicity levels and the entire diblock-copolymer should be suitable for renal clearance. For this purpose, a ...

  10. Metabolism of nanomaterials in vivo: blood circulation and organ clearance.

    Science.gov (United States)

    Wang, Bing; He, Xiao; Zhang, Zhiyong; Zhao, Yuliang; Feng, Weiyue

    2013-03-19

    Before researchers apply nanomaterials (NMs) in biomedicine, they need to understand the blood circulation and clearance profile of these materials in vivo. These qualities determine the balance between nanomaterial-induced activity and unwanted toxicity. NMs have heterogeneous characteristics: they combine the bulk properties of solids with the mobility of molecules, and their highly active contact interfaces exhibit diverse functionalities. Any new and unexpected circulation features and clearance patterns are of great concern in toxicological studies and pharmaceutical screens. A number of studies have reported that NMs can enter the bloodstream directly during their application or indirectly via inhalation, ingestion, and dermal exposure. Due to the small size of NMs, the blood can then transport them throughout the circulation and to many organs where they can be stored. In this Account, we discuss the blood circulation and organ clearance patterns of NMs in the lung, liver, and kidney. The circulation of NMs in bloodstream is critical for delivery of inhalable NMs to extrapulmonary organs, the delivery of injectable NMs, the dynamics of tissue redistribution, and the overall targeting of drug carriers to specific cells and organs. The lung, liver, and kidney are the major distribution sites and target organs for NMs exposure, and the clearance patterns of NMs in these organs are critical for understanding the in vivo fate of NMs. Current studies suggest that multiple factors control the circulation and organ clearance of NMs. The size, shape, surface charge, surface functional groups, and aspect ratio of NMs as well as tissue microstructures strongly influence the circulation of NMs in bloodstream, their site-specific extravasation, and their clearance profiles within organs. Therefore structure design and surface modification can improve biocompatibility, regulate the in vivo metabolism, and reduce the toxicity of NMs. The biophysicochemical interactions

  11. Type I IFN Signaling Is Dispensable during Secondary Viral Infection.

    Science.gov (United States)

    Hosking, Martin P; Flynn, Claudia T; Whitton, J Lindsay

    2016-08-01

    Innate immune responses in general, and type I interferons (T1IFNs) in particular, play an important and often essential role during primary viral infections, by directly combatting the virus and by maximizing the primary adaptive immune response. Several studies have suggested that T1IFNs also contribute very substantially to the secondary (recall) response; they are thought (i) to be required to drive the early attrition of memory T cells, (ii) to support the subsequent expansion of surviving virus-specific memory cells, and (iii) to assist in the suppression and clearance of the infectious agent. However, many of these observations were predicated upon models in which T1IFN signaling was interrupted prior to a primary immune response, raising the possibility that the resulting memory cells might be intrinsically abnormal. We have directly addressed this by using an inducible-Cre model system in which the host remains genetically-intact during the primary response to infection, and in which T1IFN signaling can be effectively ablated prior to secondary viral challenge. We report that, in stark contrast to primary infection, T1IFN signaling is not required during the recall response. IFNαβR-deficient memory CD8+ and CD4+ memory T cells undergo attrition and expansion with kinetics that are indistinguishable from those of receptor-sufficient cells. Moreover, even in the absence of functional T1IFN signaling, the host's immune capacity to rapidly suppress, and then to eradicate, a secondary infection remains intact. Thus, this study shows that T1IFN signaling is dispensable during the recall response to a virus infection. Moreover, two broader implications may be drawn. First, a T cell's requirement for a cytokine is highly dependent on the cell's maturation / differentiation status. Consequently, second, these data underscore the importance of evaluating a gene's impact by modulating its expression or function in a temporally-controllable manner. PMID:27580079

  12. Viral Infection in Renal Transplant Recipients

    Directory of Open Access Journals (Sweden)

    Jovana Cukuranovic

    2012-01-01

    Full Text Available Viruses are among the most common causes of opportunistic infection after transplantation. The risk for viral infection is a function of the specific virus encountered, the intensity of immune suppression used to prevent graft rejection, and other host factors governing susceptibility. Although cytomegalovirus is the most common opportunistic pathogen seen in transplant recipients, numerous other viruses have also affected outcomes. In some cases, preventive measures such as pretransplant screening, prophylactic antiviral therapy, or posttransplant viral monitoring may limit the impact of these infections. Recent advances in laboratory monitoring and antiviral therapy have improved outcomes. Studies of viral latency, reactivation, and the cellular effects of viral infection will provide clues for future strategies in prevention and treatment of viral infections. This paper will summarize the major viral infections seen following transplant and discuss strategies for prevention and management of these potential pathogens.

  13. Total HIV-1 DNA, a Marker of Viral Reservoir Dynamics with Clinical Implications.

    Science.gov (United States)

    Avettand-Fènoël, Véronique; Hocqueloux, Laurent; Ghosn, Jade; Cheret, Antoine; Frange, Pierre; Melard, Adeline; Viard, Jean-Paul; Rouzioux, Christine

    2016-10-01

    HIV-1 DNA persists in infected cells despite combined antiretroviral therapy (cART), forming viral reservoirs. Recent trials of strategies targeting latent HIV reservoirs have rekindled hopes of curing HIV infection, and reliable markers are thus needed to evaluate viral reservoirs. Total HIV DNA quantification is simple, standardized, sensitive, and reproducible. Total HIV DNA load influences the course of the infection and is therefore clinically relevant. In particular, it is predictive of progression to AIDS and death, independently of HIV RNA load and the CD4 cell count. Baseline total HIV DNA load is predictive of the response to cART. It declines during cART but remains quantifiable, at a level that reflects both the history of infection (HIV RNA zenith, CD4 cell count nadir) and treatment efficacy (residual viremia, cumulative viremia, immune restoration, immune cell activation). Total HIV DNA load in blood is also predictive of the presence and severity of some HIV-1-associated end-organ disorders. It can be useful to guide individual treatment, notably, therapeutic de-escalation. Although it does not distinguish between replication-competent and -defective latent viruses, the total HIV DNA load in blood, tissues, and cells provides insights into HIV pathogenesis, probably because all viral forms participate in host cell activation and HIV pathogenesis. Total HIV DNA is thus a biomarker of HIV reservoirs, which can be defined as all infected cells and tissues containing all forms of HIV persistence that participate in pathogenesis. This participation may occur through the production of new virions, creating new cycles of infection and disseminating infected cells; maintenance or amplification of reservoirs by homeostatic cell proliferation; and viral transcription and synthesis of viral proteins without new virion production. These proteins can induce immune activation, thus participating in the vicious circle of HIV pathogenesis. PMID:27559075

  14. Sequencing Needs for Viral Diagnostics

    Energy Technology Data Exchange (ETDEWEB)

    Gardner, S N; Lam, M; Mulakken, N J; Torres, C L; Smith, J R; Slezak, T

    2004-01-26

    We built a system to guide decisions regarding the amount of genomic sequencing required to develop diagnostic DNA signatures, which are short sequences that are sufficient to uniquely identify a viral species. We used our existing DNA diagnostic signature prediction pipeline, which selects regions of a target species genome that are conserved among strains of the target (for reliability, to prevent false negatives) and unique relative to other species (for specificity, to avoid false positives). We performed simulations, based on existing sequence data, to assess the number of genome sequences of a target species and of close phylogenetic relatives (''near neighbors'') that are required to predict diagnostic signature regions that are conserved among strains of the target species and unique relative to other bacterial and viral species. For DNA viruses such as variola (smallpox), three target genomes provide sufficient guidance for selecting species-wide signatures. Three near neighbor genomes are critical for species specificity. In contrast, most RNA viruses require four target genomes and no near neighbor genomes, since lack of conservation among strains is more limiting than uniqueness. SARS and Ebola Zaire are exceptional, as additional target genomes currently do not improve predictions, but near neighbor sequences are urgently needed. Our results also indicate that double stranded DNA viruses are more conserved among strains than are RNA viruses, since in most cases there was at least one conserved signature candidate for the DNA viruses and zero conserved signature candidates for the RNA viruses.

  15. Commercialization of veterinary viral vaccines.

    Science.gov (United States)

    Flore, P H

    2004-12-01

    If vaccines are to reliably prevent disease, they must be developed, produced and quality-controlled according to very strict regulations and procedures. Veterinary viral vaccine registrations are governed by different rules in different countries, but these rules all emphasize that the quality of the raw materials--the cells, eggs, animals or plants that are used in production--need to be carefully controlled. The veterinary vaccine business is also very cost-conscious. Emphasis over the last 5-10 years has therefore been to develop culture systems that minimize labor and sterility problems and thus provide for reliable and cost-effective production. Implementing these often more complex systems in a production environment takes considerable effort, first in scale-up trials and further down the line in convincing production personnel to change their familiar system for something new and possibly untried. To complete scale-up trials successfully, it is absolutely necessary to understand the biochemistry of the cells and the influence of the virus on the cells under scale-up and later production conditions. Once a viral product can be produced on a large scale, it is imperative that the quality of the end-product is controlled in an intelligent way. One needs to know whether the end-product performs in the animal as was intended during its conception in the research and development department. The development of the appropriate tests to demonstrate this plays an important role in the successful development of a vaccine.

  16. Population Dynamics of Viral Inactivation

    Science.gov (United States)

    Freeman, Krista; Li, Dong; Behrens, Manja; Streletzky, Kiril; Olsson, Ulf; Evilevitch, Alex

    We have investigated the population dynamics of viral inactivation in vitrousing time-resolved cryo electron microscopy combined with light and X-ray scattering techniques. Using bacteriophage λ as a model system for pressurized double-stranded DNA viruses, we found that virions incubated with their cell receptor eject their genome in a stochastic triggering process. The triggering of DNA ejection occurs in a non synchronized manner after the receptor addition, resulting in an exponential decay of the number of genome-filled viruses with time. We have explored the characteristic time constant of this triggering process at different temperatures, salt conditions, and packaged genome lengths. Furthermore, using the temperature dependence we determined an activation energy for DNA ejections. The dependences of the time constant and activation energy on internal DNA pressure, affected by salt conditions and encapsidated genome length, suggest that the triggering process is directly dependent on the conformational state of the encapsidated DNA. The results of this work provide insight into how the in vivo kinetics of the spread of viral infection are influenced by intra- and extra cellular environmental conditions. This material is based upon work supported by the National Science Foundation Graduate Research Fellowship under Grant No. DGE-1252522.

  17. Biologically-directed modeling reflects cytolytic clearance of SIV-infected cells in vivo in macaques.

    Directory of Open Access Journals (Sweden)

    W David Wick

    Full Text Available The disappointing outcomes of cellular immune-based vaccines against HIV-1 despite strong evidence for the protective role of CD8⁺ T lymphocytes (CTLs has prompted revisiting the mechanisms of cellular immunity. Prior data from experiments examining the kinetics of Simian Immunodeficiency Virus (SIV clearance in infected macaques with or without in vivo CD8 depletion were interpreted as refuting the concept that CTLs suppress SIV/HIV by direct killing of infected cells. Here we briefly review the biological evidence for CTL cytolytic activity in viral infections, and utilize biologically-directed modeling to assess the possibility of a killing mechanism for the antiviral effect of CTLs, taking into account the generation, proliferation, and survival of activated CD4⁺ and CD8⁺ T lymphocytes, as well as the life cycle of the virus. Our analyses of the published macaque data using these models support a killing mechanism, when one considers T lymphocyte and HIV-1 lifecycles, and factors such as the eclipse period before release of virions by infected cells, an exponential pattern of virion production by infected cells, and a variable lifespan for acutely infected cells. We conclude that for SIV/HIV pathogenesis, CTLs deserve their reputation as being cytolytic.

  18. 77 FR 19673 - Proposed Collection; Comment Request; Generic Clearance To Conduct Voluntary Customer/Partner...

    Science.gov (United States)

    2012-04-02

    ... HUMAN SERVICES National Institutes of Health Proposed Collection; Comment Request; Generic Clearance To... and Budget (OMB) for review and approval. Proposed Collection: Title: Generic Clearance to Conduct... strategy in ] accomplishing reinvention goals is the ability to periodically receive input and...

  19. A comparison of analytic procedures for measurement of fractional dextran clearances

    NARCIS (Netherlands)

    Hemmelder, MH; de Jong, PE; de Zeeuw, D

    1998-01-01

    Fractional dextran clearances have been extensively used to study glomerular size selectivity. We report on an analysis of different laboratory procedures involved in measuring fractional dextran clearances. The deproteinization of plasma samples by 20% trichloroacetic acid (TCA) revealed a protein

  20. 19 CFR 122.66 - Clearance or permission to depart denied.

    Science.gov (United States)

    2010-04-01

    ...; DEPARTMENT OF THE TREASURY AIR COMMERCE REGULATIONS Clearance of Aircraft and Permission To Depart § 122.66 Clearance or permission to depart denied. If advance electronic air cargo information is not received...