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Sample records for therapy controls viral

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

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    Paul D Griffiths

    Full Text Available 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.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.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.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.

  2. Molecular imaging of oncolytic viral therapy

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    Dana Haddad

    2014-01-01

    Full Text Available Oncolytic viruses have made their mark on the cancer world as a potential therapeutic option, with the possible advantages of reduced side effects and strengthened treatment efficacy due to higher tumor selectivity. Results have been so promising, that oncolytic viral treatments have now been approved for clinical trials in several countries. However, clinical studies may benefit from the ability to noninvasively and serially identify sites of viral targeting via molecular imaging in order to provide safety, efficacy, and toxicity information. Furthermore, molecular imaging of oncolytic viral therapy may provide a more sensitive and specific diagnostic technique to detect tumor origin and, more importantly, presence of metastases. Several strategies have been investigated for molecular imaging of viral replication broadly categorized into optical and deep tissue imaging, utilizing several reporter genes encoding for fluorescence proteins, conditional enzymes, and membrane protein and transporters. Various imaging methods facilitate molecular imaging, including computer tomography, magnetic resonance imaging, positron emission tomography, single photon emission CT, gamma-scintigraphy, and photoacoustic imaging. In addition, several molecular probes are used for medical imaging, which act as targeting moieties or signaling agents. This review will explore the preclinical and clinical use of in vivo molecular imaging of replication-competent oncolytic viral therapy.

  3. Predicting Early Viral Control under Direct-Acting Antiviral Therapy for Chronic Hepatitis C Virus Using Pretreatment Immunological Markers

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    James A. Hutchinson

    2018-02-01

    Full Text Available Recent introduction of all-oral direct-acting antiviral (DAA treatment has revolutionized care of patients with chronic hepatitis C virus (HCV infection. Regrettably, the high cost of DAA treatment is burdensome for healthcare systems and may be prohibitive for some patients who would otherwise benefit. Understanding how patient-related factors influence individual responses to DAA treatment may lead to more efficient prescribing. In this observational study, patients with chronic HCV infection were comprehensively monitored by flow cytometry to identify pretreatment immunological variables that predicted HCV RNA negativity within 4 weeks of commencing DAA treatment. Twenty-three patients [genotype 1a (n = 10, 1b (n = 9, and 3 (n = 4] were treated with daclatasvir plus sofosbuvir (SOF (n = 15, ledipasvir plus SOF (n = 4, or ritonavir-boosted paritaprevir, ombitasvir, and dasabuvir (n = 4. DAA treatment most prominently altered the distribution of CD8+ memory T cell subsets. Knowing only pretreatment frequencies of CD3+ and naive CD8+ T cells allowed correct classification of 83% of patients as “fast” (HCV RNA-negative by 4 weeks or “slow” responders. In a prospective cohort, these parameters correctly classified 90% of patients. Slow responders exhibited higher frequencies of CD3+ T cells, CD8+ TEM cells, and CD5high CD27− CD57+ CD8+ chronically activated T cells, which is attributed to bystander hyperactivation of virus-non-specific CD8+ T cells. Taken together, non-specific, systemic CD8+ T cell activation predicted a longer time to viral clearance. This discovery allows pretreatment identification of individuals who may not require a full 12-week course of DAA therapy; in turn, this could lead to individualized prescribing and more efficient resource allocation.

  4. Interferon therapy of acute respiratory viral infections in children

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    A.E. Abaturov

    2017-04-01

    within the age limit and corresponded to the temperature response. Analyzing the dynamics of clinical symptoms of acute respiratory viral infection in both groups, it should be noted that there was a persistent tendency to lower body temperature in patients, both in the main and control groups. However, in the group of patients receiving Laferobionum®, the decrease in the temperature curve occurred faster, its normalization was noted already on the 4th day of therapy in 100 % of patients, whereas in the control group on the 4th day of the disease the body temperature remained subfebrile in 12 (28.6 %, on the 5th day — in 2 (4.8 % children. Complete blood count in children of the main and control groups at the beginning of the disease showed leukopenia of varying severity, relative lymphocytosis, and accelerated erythrocyte sedimentation rate (ESR. On the 5th day of therapy in patients of the main group, the number of leukocytes was normalized, the relative lymphocytosis persisted against the background of a decrease in ESR. While in the control group, the number of leukocytes in peripheral blood remained lower with an elevated level of ESR. During the whole period of observation, the presence and nature of possible complications of acute respiratory viral infection was assessed. The total duration of the observation period was 14 days. During the observation period, no complications were detected in any of the patients in the main or control groups. During the time of the clinical trial, no adverse reactions were recorded that could be associated with the administration of Laferobionum®. There were no cases of exacerbation of existing chronic diseases in the children of the main group, while 1 (2.4 % person from the control group had exacerbation of chronic tonsillitis. Evaluation of the effectiveness of therapy with the drug was carried out on the 5th day of treatment. Since one of the effectiveness criteria was the absence of clinical signs of the disease at the

  5. Repeated nebulisation of non-viral CFTR gene therapy in patients with cystic fibrosis: a randomised, double-blind, placebo-controlled, phase 2b trial.

    Science.gov (United States)

    Alton, Eric W F W; Armstrong, David K; Ashby, Deborah; Bayfield, Katie J; Bilton, Diana; Bloomfield, Emily V; Boyd, A Christopher; Brand, June; Buchan, Ruaridh; Calcedo, Roberto; Carvelli, Paula; Chan, Mario; Cheng, Seng H; Collie, D David S; Cunningham, Steve; Davidson, Heather E; Davies, Gwyneth; Davies, Jane C; Davies, Lee A; Dewar, Maria H; Doherty, Ann; Donovan, Jackie; Dwyer, Natalie S; Elgmati, Hala I; Featherstone, Rosanna F; Gavino, Jemyr; Gea-Sorli, Sabrina; Geddes, Duncan M; Gibson, James S R; Gill, Deborah R; Greening, Andrew P; Griesenbach, Uta; Hansell, David M; Harman, Katharine; Higgins, Tracy E; Hodges, Samantha L; Hyde, Stephen C; Hyndman, Laura; Innes, J Alastair; Jacob, Joseph; Jones, Nancy; Keogh, Brian F; Limberis, Maria P; Lloyd-Evans, Paul; Maclean, Alan W; Manvell, Michelle C; McCormick, Dominique; McGovern, Michael; McLachlan, Gerry; Meng, Cuixiang; Montero, M Angeles; Milligan, Hazel; Moyce, Laura J; Murray, Gordon D; Nicholson, Andrew G; Osadolor, Tina; Parra-Leiton, Javier; Porteous, David J; Pringle, Ian A; Punch, Emma K; Pytel, Kamila M; Quittner, Alexandra L; Rivellini, Gina; Saunders, Clare J; Scheule, Ronald K; Sheard, Sarah; Simmonds, Nicholas J; Smith, Keith; Smith, Stephen N; Soussi, Najwa; Soussi, Samia; Spearing, Emma J; Stevenson, Barbara J; Sumner-Jones, Stephanie G; Turkkila, Minna; Ureta, Rosa P; Waller, Michael D; Wasowicz, Marguerite Y; Wilson, James M; Wolstenholme-Hogg, Paul

    2015-09-01

    Lung delivery of plasmid DNA encoding the CFTR gene complexed with a cationic liposome is a potential treatment option for patients with cystic fibrosis. We aimed to assess the efficacy of non-viral CFTR gene therapy in patients with cystic fibrosis. We did this randomised, double-blind, placebo-controlled, phase 2b trial in two cystic fibrosis centres with patients recruited from 18 sites in the UK. Patients (aged ≥12 years) with a forced expiratory volume in 1 s (FEV1) of 50-90% predicted and any combination of CFTR mutations, were randomly assigned, via a computer-based randomisation system, to receive 5 mL of either nebulised pGM169/GL67A gene-liposome complex or 0.9% saline (placebo) every 28 days (plus or minus 5 days) for 1 year. Randomisation was stratified by % predicted FEV1 (<70 vs ≥70%), age (<18 vs ≥18 years), inclusion in the mechanistic substudy, and dosing site (London or Edinburgh). Participants and investigators were masked to treatment allocation. The primary endpoint was the relative change in % predicted FEV1. The primary analysis was per protocol. This trial is registered with ClinicalTrials.gov, number NCT01621867. Between June 12, 2012, and June 24, 2013, we randomly assigned 140 patients to receive placebo (n=62) or pGM169/GL67A (n=78), of whom 116 (83%) patients comprised the per-protocol population. We noted a significant, albeit modest, treatment effect in the pGM169/GL67A group versus placebo at 12 months' follow-up (3.7%, 95% CI 0.1-7.3; p=0.046). This outcome was associated with a stabilisation of lung function in the pGM169/GL67A group compared with a decline in the placebo group. We recorded no significant difference in treatment-attributable adverse events between groups. Monthly application of the pGM169/GL67A gene therapy formulation was associated with a significant, albeit modest, benefit in FEV1 compared with placebo at 1 year, indicating a stabilisation of lung function in the treatment group. Further improvements in

  6. Differences in serum IgA responses to HIV-1 gp41 in elite controllers compared to viral suppressors on highly active antiretroviral therapy.

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    Rafiq Nabi

    Full Text Available Mechanisms responsible for natural control of human immunodeficiency type 1 (HIV replication in elite controllers (EC remain incompletely defined. To determine if EC generate high quality HIV-specific IgA responses, we used Western blotting to compare the specificities and frequencies of IgA to HIV antigens in serum of gender-, age- and race-matched EC and aviremic controllers (HC and viremic noncontrollers (HN on highly active antiretroviral therapy (HAART. Concentrations and avidity of IgA to HIV antigens were measured using ELISA or multiplex assays. Measurements for IgG were performed in parallel. EC were found to have stronger p24- and V1V2-specific IgG responses than HN, but there were no IgG differences for EC and HC. In contrast, IgA in EC serum bound more frequently to gp160 and gag proteins than IgA in HC or HN. The avidity of anti-gp41 IgA was also greater in EC, and these subjects had stronger IgA responses to the gp41 heptad repeat region 1 (HR1, a reported target of anti-bacterial RNA polymerase antibodies that cross react with gp41. However, EC did not demonstrate greater IgA responses to E. coli RNA polymerase or to peptides containing the shared LRAI sequence, suggesting that most of their HR1-specific IgA antibodies were not induced by intestinal microbiota. In both EC and HAART recipients, the concentrations of HIV-specific IgG were greater than HIV-specific IgA, but their avidities were comparable, implying that they could compete for antigen. Exceptions were C1 peptides and V1V2 loops. IgG and IgA responses to these antigens were discordant, with IgG reacting to V1V2, and IgA reacting to C1, especially in EC. Interestingly, EC with IgG hypergammaglobulinemia had greater HIV-specific IgA and IgG responses than EC with normal total IgG levels. Heterogeneity in EC antibody responses may therefore be due to a more focused HIV-specific B cell response in some of these individuals. Overall, these data suggest that development of

  7. DNA/MVA Vaccination of HIV-1 Infected Participants with Viral Suppression on Antiretroviral Therapy, followed by Treatment Interruption: Elicitation of Immune Responses without Control of Re-Emergent Virus.

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    Thompson, Melanie; Heath, Sonya L; Sweeton, Bentley; Williams, Kathy; Cunningham, Pamela; Keele, Brandon F; Sen, Sharon; Palmer, Brent E; Chomont, Nicolas; Xu, Yongxian; Basu, Rahul; Hellerstein, Michael S; Kwa, Suefen; Robinson, Harriet L

    2016-01-01

    GV-TH-01, a Phase 1 open-label trial of a DNA prime—Modified Vaccinia Ankara (MVA) boost vaccine (GOVX-B11), was undertaken in HIV infected participants on antiretroviral treatment (ART) to evaluate safety and vaccine-elicited T cell responses, and explore the ability of elicited CD8+ T cells to control viral rebound during analytical treatment interruption (TI). Nine men who began antiretroviral therapy (ART) within 18 months of seroconversion and had sustained plasma HIV-1 RNA HIV-1 RNA was 140,000 copies/ml and mean baseline CD4 count was 755/μl. Two DNA, followed by 2 MVA, inoculations were given 8 weeks apart. Eight subjects completed all vaccinations and TI. Clinical and laboratory adverse events were generally mild, with no serious or grade 4 events. Only reactogenicity events were considered related to study drug. No treatment emergent viral resistance was seen. The vaccinations did not reduce viral reservoirs and virus re-emerged in all participants during TI, with a median time to re-emergence of 4 weeks. Eight of 9 participants had CD8+ T cells that could be stimulated by vaccine-matched Gag peptides prior to vaccination. Vaccinations boosted these responses as well as eliciting previously undetected CD8+ responses. Elicited T cells did not display signs of exhaustion. During TI, temporal patterns of viral re-emergence and Gag-specific CD8+ T cell expansion suggested that vaccine-specific CD8+ T cells had been stimulated by re-emergent virus in only 2 of 8 participants. In these 2, transient decreases in viremia were associated with Gag selection in known CD8+ T cell epitopes. We hypothesize that escape mutations, already archived in the viral reservoir, plus a poor ability of CD8+ T cells to traffic to and control virus at sites of re-emergence, limited the therapeutic efficacy of the DNA/MVA vaccine. clinicaltrials.gov NCT01378156.

  8. Oncolytic viral therapy: targeting cancer stem cells

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    Smith TT

    2014-02-01

    Full Text Available Tyrel T Smith,1 Justin C Roth,1 Gregory K Friedman,1 G Yancey Gillespie2 1Department of Pediatrics, The University of Alabama at Birmingham, Birmingham, AL, USA; 2Department of Neurosurgery, The University of Alabama at Birmingham, Birmingham, AL, USA Abstract: Cancer stem cells (CSCs are defined as rare populations of tumor-initiating cancer cells that are capable of both self-renewal and differentiation. Extensive research is currently underway to develop therapeutics that target CSCs for cancer therapy, due to their critical role in tumorigenesis, as well as their resistance to chemotherapy and radiotherapy. To this end, oncolytic viruses targeting unique CSC markers, signaling pathways, or the pro-tumor CSC niche offer promising potential as CSCs-destroying agents/therapeutics. We provide a summary of existing knowledge on the biology of CSCs, including their markers and their niche thought to comprise the tumor microenvironment, and then we provide a critical analysis of the potential for targeting CSCs with oncolytic viruses, including herpes simplex virus-1, adenovirus, measles virus, reovirus, and vaccinia virus. Specifically, we review current literature regarding first-generation oncolytic viruses with their innate ability to replicate in CSCs, as well as second-generation viruses engineered to enhance the oncolytic effect and CSC-targeting through transgene expression. Keywords: oncolytic virotherapy, cancer stem cell niche

  9. DNA/MVA Vaccination of HIV-1 Infected Participants with Viral Suppression on Antiretroviral Therapy, followed by Treatment Interruption: Elicitation of Immune Responses without Control of Re-Emergent Virus.

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    Melanie Thompson

    Full Text Available GV-TH-01, a Phase 1 open-label trial of a DNA prime—Modified Vaccinia Ankara (MVA boost vaccine (GOVX-B11, was undertaken in HIV infected participants on antiretroviral treatment (ART to evaluate safety and vaccine-elicited T cell responses, and explore the ability of elicited CD8+ T cells to control viral rebound during analytical treatment interruption (TI. Nine men who began antiretroviral therapy (ART within 18 months of seroconversion and had sustained plasma HIV-1 RNA <50 copies/mL for at least 6 months were enrolled. Median age was 38 years, median pre-ART HIV-1 RNA was 140,000 copies/ml and mean baseline CD4 count was 755/μl. Two DNA, followed by 2 MVA, inoculations were given 8 weeks apart. Eight subjects completed all vaccinations and TI. Clinical and laboratory adverse events were generally mild, with no serious or grade 4 events. Only reactogenicity events were considered related to study drug. No treatment emergent viral resistance was seen. The vaccinations did not reduce viral reservoirs and virus re-emerged in all participants during TI, with a median time to re-emergence of 4 weeks. Eight of 9 participants had CD8+ T cells that could be stimulated by vaccine-matched Gag peptides prior to vaccination. Vaccinations boosted these responses as well as eliciting previously undetected CD8+ responses. Elicited T cells did not display signs of exhaustion. During TI, temporal patterns of viral re-emergence and Gag-specific CD8+ T cell expansion suggested that vaccine-specific CD8+ T cells had been stimulated by re-emergent virus in only 2 of 8 participants. In these 2, transient decreases in viremia were associated with Gag selection in known CD8+ T cell epitopes. We hypothesize that escape mutations, already archived in the viral reservoir, plus a poor ability of CD8+ T cells to traffic to and control virus at sites of re-emergence, limited the therapeutic efficacy of the DNA/MVA vaccine.clinicaltrials.gov NCT01378156.

  10. Development of Viral Vectors for Gene Therapy for Chronic Pain

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    Yu Huang

    2011-01-01

    Full Text Available Chronic pain is a major health concern that affects millions of people. There are no adequate long-term therapies for chronic pain sufferers, leading to significant cost for both society and the individual. The most commonly used therapy for chronic pain is the application of opioid analgesics and nonsteroidal anti-inflammatory drugs, but these drugs can lead to addiction and may cause side effects. Further studies of the mechanisms of chronic pain have opened the way for development of new treatment strategies, one of which is gene therapy. The key to gene therapy is selecting safe and highly efficient gene delivery systems that can deliver therapeutic genes to overexpress or suppress relevant targets in specific cell types. Here we review several promising viral vectors that could be applied in gene transfer for the treatment of chronic pain and further discuss the possible mechanisms of genes of interest that could be delivered with viral vectors for the treatment of chronic pain.

  11. siRNA as an alternative therapy against viral infections

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    Hana A. Pawestri

    2012-07-01

    Full Text Available siRNA (small interfering ribonucleic acid adalah sebuah metode yang dapat digunakan untuk mengatasi infeksi virus yang prinsip kerjanya berdasarkan metode komplementer dsRNA (double stranded RNA pada RNA virus sehingga menyebabkan kegagalan proses transkripsi (silencing.  Untuk lebih memahami bagaimana proses kerja dan ulasan penelitian siRNA yang terkini, di dalam tulisan ini ditinjau siRNA sebagai metoda yang dikembangkan untuk mengatasi infeksi dan meneliti efeknya pada replikasi beberapa virus seperti Hepatitis C, Influenza, Polio, dan HIV. Kami menemukan bahwa urutan basa nukleotida dari target siRNA sangat penting. Hal tersebut harus homolog dengan target RNA virus dan tidak menganggu RNA sel inang. Untuk mengurangi kegagalan terapi siRNA oleh adanya mutasi, digunakan beberapa siRNA yang sekaligus menjadi target RNA virus yang berbeda. Namun demikian, terapi siRNA masih menghadapi beberapa kesulitan seperti pengiriman (transfer khusus ke jaringan yang terinfeksi dan perlindungan siRNA dari perusakan oleh nuklease. Berdasarkan beberapa penelitian yang telah dilakukan, siRNA dapat digunakan sebagai alternatif untuk mengobati infeksi yang disebabkan oleh virus. Terapi tersebut direkomendasikan untuk dilakukan uji klinis dengan memperhatikan beberapa aspek seperti desain siRNA dan mekanisme transfer. (Health Science Indones 2010; 1: 58 - 65 Kata kunci: siRNA, infeksi virus, target virus, alternatif terapi Abstract SiRNA is a promising method to deal with viral infections. The principle of siRNA is based on the complementarily of (synthetic dsRNA to an RNA virus which, in consequence, will be silenced. Many studies are currently examining the effects of siRNA on replication of diverse virus types like Hepatitis C, polio and HIV. The choice of the siRNA target sequence is crucial. It has to be very homologous to the target RNA, but it cannot target RNA of the host cell. To reduce the possibility for the virus to escape from the siRNA therapy by

  12. Impact of CD4 and CD8 dynamics and viral rebounds on loss of virological control in HIV controllers

    DEFF Research Database (Denmark)

    Chereau, Fanny; Madec, Yoann; Sabin, Caroline

    2017-01-01

    OBJECTIVE: HIV controllers (HICs) spontaneously maintain HIV viral replication at low level without antiretroviral therapy (ART), a small number of whom will eventually lose this ability to control HIV viremia. The objective was to identify factors associated with loss of virological control. MET...

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

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    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.

  14. HIV infection and treatment: beyond viral control

    NARCIS (Netherlands)

    Sprenger, Herman

    2017-01-01

    Since 1996, Infection caused by the human immunodeficiency virus(HIV) can be successfully treated with a combination therapy of 3 antiviral drugs from 2 different classes. Life expectancy has increased dramatically by this treatment. Especially in the early years these combination therapies had many

  15. The F4/AS01B HIV-1 Vaccine Candidate Is Safe and Immunogenic, But Does Not Show Viral Efficacy in Antiretroviral Therapy-Naive, HIV-1-Infected Adults: A Randomized Controlled Trial.

    Science.gov (United States)

    Dinges, Warren; Girard, Pierre-Marie; Podzamczer, Daniel; Brockmeyer, Norbert H; García, Felipe; Harrer, Thomas; Lelievre, Jean-Daniel; Frank, Ian; Colin De Verdière, Nathalie; Yeni, Guy-Patrick; Ortega Gonzalez, Enrique; Rubio, Rafael; Clotet Sala, Bonaventura; DeJesus, Edwin; Pérez-Elias, Maria Jesus; Launay, Odile; Pialoux, Gilles; Slim, Jihad; Weiss, Laurence; Bouchaud, Olivier; Felizarta, Franco; Meurer, Anja; Raffi, François; Esser, Stefan; Katlama, Christine; Koletar, Susan L; Mounzer, Karam; Swindells, Susan; Baxter, John D; Schneider, Stefan; Chas, Julie; Molina, Jean-Michel; Koutsoukos, Marguerite; Collard, Alix; Bourguignon, Patricia; Roman, François

    2016-02-01

    The impact of the investigational human immunodeficiency virus type 1 (HIV-1) F4/AS01B vaccine on HIV-1 viral load (VL) was evaluated in antiretroviral therapy (ART)-naive HIV-1 infected adults.This phase IIb, observer-blind study (NCT01218113), included ART-naive HIV-1 infected adults aged 18 to 55 years. Participants were randomized to receive 2 (F4/AS01B_2 group, N = 64) or 3 (F4/AS01B_3 group, N = 62) doses of F4/AS01B or placebo (control group, N = 64) at weeks 0, 4, and 28. Efficacy (HIV-1 VL, CD4 T-cell count, ART initiation, and HIV-related clinical events), safety, and immunogenicity (antibody and T-cell responses) were evaluated during 48 weeks.At week 48, based on a mixed model, no statistically significant difference in HIV-1 VL change from baseline was demonstrated between F4/AS01B_2 and control group (0.073 log10 copies/mL [97.5% confidence interval (CI): -0.088; 0.235]), or F4/AS01B_3 and control group (-0.096 log10 copies/mL [97.5% CI: -0.257; 0.065]). No differences between groups were observed in HIV-1 VL change, CD4 T-cell count, ART initiation, or HIV-related clinical events at intermediate timepoints. Among F4/AS01B recipients, the most frequent solicited symptoms were pain at injection site (252/300 doses), fatigue (137/300 doses), myalgia (105/300 doses), and headache (90/300 doses). Twelve serious adverse events were reported in 6 participants; 1 was considered vaccine-related (F4/AS01B_2 group: angioedema). F4/AS01B induced polyfunctional F4-specific CD4 T-cells, but had no significant impact on F4-specific CD8 T-cell and anti-F4 antibody levels.F4/AS01B had a clinically acceptable safety profile, induced F4-specific CD4 T-cell responses, but did not reduce HIV-1 VL, impact CD4 T-cells count, delay ART initiation, or prevent HIV-1 related clinical events.

  16. Viral infections as controlling factors for the deep biosphere? (Invited)

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    Engelen, B.; Engelhardt, T.; Sahlberg, M.; Cypionka, H.

    2009-12-01

    The marine deep biosphere represents the largest biotope on Earth. Throughout the last years, we have obtained interesting insights into its microbial community composition. However, one component that was completely overlooked so far is the viral inventory of deep-subsurface sediments. While viral infections were identified to have a major impact on the benthic microflora of deep-sea surface sediments (Danavaro et al. 2008), no studies were performed on deep-biosphere samples, so far. As grazers probably play only a minor role in anoxic and highly compressed deep sediments, viruses might be the main “predators” for indigenous microorganisms. Furthermore, the release of cell components, called “the viral shunt”, could have a major impact on the deep biosphere in providing labile organic compounds to non-infected microorganisms in these generally nutrient depleted sediments. However, direct counting of viruses in sediments is highly challenging due to the small size of viruses and the high background of small particles. Even molecular surveys using “universal” PCR primers that target phage-specific genes fail due to the vast phage diversity. One solution for this problem is the lysogenic viral life cycle as many bacteriophages integrate their DNA into the host genome. It is estimated that up to 70% of cultivated bacteria contain prophages within their genome. Therefore, culture collections (Batzke et al. 2007) represent an archive of the viral composition within the respective habitat. These prophages can be induced to become free phage particles in stimulation experiments in which the host cells are set under certain stress situations such as a treatment with UV exposure or DNA-damaging antibiotics. The study of the viral component within the deep biosphere offers to answer the following questions: To which extent are deep-biosphere populations controlled by viral infections? What is the inter- and intra-specific diversity and the host-specific viral

  17. Use of medicinal plants as the additional therapy of viral hepatitis

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    I.B. Ershova

    2017-04-01

    Full Text Available Dear colleagues, continuing the rubric of the journal about the treatment of infectious diseases by medicinal plants, we want to present the methods of using medicinal plants as an additional therapy for treatment of viral hepatitis in addition to the main treatment according to the generally clinical standards of antiviral therapy. Viral hepatitis compiles a large group of human infectious diseases characterized by a predominant liver damage. “Currently, viral hepatitis is recognized as a major public health problem requiring urgent action”, said Dr Margaret Chan, WHO Director-General (WHO Global hepatitis report, 2017. Treatment of viral hepatitis is a complex task and involves the use of generally clinical recommendations or standards. There are criteria for determining the need for pharmacotherapy and the most rational scheme for antiviral treatment in every case of viral hepatitis. The purpose of antiviral therapy is to achieve a stable virologic response, to prevent the progression of the disease, the development of cirrhosis and hepatocellular carcinoma. However, at the present stage a stable virologic response in the general population of patients can be achieved in approximately 60 % of cases. In addition, standard antiviral drugs have side effects, are of high cost and are contraindicated in a number of clinical situations, for example, with a decrease in the number of blood elements (thrombocytopenia, leukopenia, anemia, at the stage of decompensated liver cirrhosis. Probably, all this induces to use alternative methods of therapy, which remain popular both among general practitioners and patients with this infection. The question of the treatment of viral hepatitis with medicinal herbs has been studied for a long time. According to some authors, there is no scientific evidence that hepatitis C can be cured by herbs. The only scientifically proven method of fighting the virus is antiviral therapy. However, there are other points

  18. CCR5 Targeted Cell Therapy for HIV and Prevention of Viral Escape

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    Gero Hütter

    2015-07-01

    Full Text Available Allogeneic transplantation with CCR5-delta 32 (CCR5-d32 homozygous stem cells in an HIV infected individual in 2008, led to a sustained virus control and probably eradication of HIV. Since then there has been a high degree of interest to translate this approach to a wider population. There are two cellular ways to do this. The first one is to use a CCR5 negative cell source e.g., hematopoietic stem cells (HSC to copy the initial finding. However, a recent case of a second allogeneic transplantation with CCR5-d32 homozygous stem cells suffered from viral escape of CXCR4 quasi-species. The second way is to knock down CCR5 expression by gene therapy. Currently, there are five promising techniques, three of which are presently being tested clinically. These techniques include zinc finger nucleases (ZFN, clustered regularly interspaced palindromic repeats/CRISPR-associated protein 9 nuclease (CRISPR/Cas9, transcription activator-like effectors nuclease (TALEN, short hairpin RNA (shRNA, and a ribozyme. While there are multiple gene therapy strategies being tested, in this review we reflect on our current knowledge of inhibition of CCR5 specifically and whether this approach allows for consequent viral escape.

  19. Principles of etiopathogenetic therapy for acute respiratory viral infections in frequently ill children

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    L. A. Kharitonova

    2015-01-01

    Full Text Available Objective: to investigate the impact of incorporation of cycloferon into a therapy regimen on the efficiency of treatment for acute respiratory viral infections (ARVI in frequently ill children. Subjects and methods. The results of treatment were analyzed in 117 children divided into three groups according to the therapy regimen. Thus, symptomatic and local antiviral therapies (interferon nasal ointment and viferon suppositories were prescribed to all the children; furthermore, Group 1 (control used antibiotic therapy; Group 2 (Comparison Group 1 took antibiotics and cycloferon (tablets, and Group 3 (Comparison Group 2 had Cycloferon. Results: At the beginning of treatment, there was a reduction in interferon-a and interferon-y values with preserved serum interferon levels, suggesting the diminished compensatory responses ensuring antiviral protection. Analysis of the immune status revealed that virtually half of the children exhibited activation of compensatory mechanisms (stimulation of CD4+ and CD8+ production and an increase in NST test activity, one third displayed a disturbance (decreases in CD4+, CDlfrf, IgA, and NST test activity. After treatment, interferonogenesis was recovered in the majority (86,7% of the patients taking Cycloferon, in 74,1% of those who had a treatment regimen containing cycloferon and antibiotics, and only in 47,1 % of those who received antibiotics. Comparison of the immunological indicators during therapy with antibiotics alone or in combination with cycloferon demonstrated a more noticeable and balanced response to the latter: the normalized CD4+ and CD8+ values in the patients on antibiotic therapy was 8,9 and 5,8%, respectively, and 11,1 % in those who received antibiotics and cycloferon. Conclusion. Incorporation of cycloferon into ARVI treatment regimens for frequently ill patients has the positive effect on immunological indicators, which shows itself as recovery of initially diminished interferonogenesis

  20. Progress in developing cationic vectors for non-viral systemic gene therapy against cancer.

    Science.gov (United States)

    Morille, Marie; Passirani, Catherine; Vonarbourg, Arnaud; Clavreul, Anne; Benoit, Jean-Pierre

    2008-01-01

    Initially, gene therapy was viewed as an approach for treating hereditary diseases, but its potential role in the treatment of acquired diseases such as cancer is now widely recognized. The understanding of the molecular mechanisms involved in cancer and the development of nucleic acid delivery systems are two concepts that have led to this development. Systemic gene delivery systems are needed for therapeutic application to cells inaccessible by percutaneous injection and for multi-located tumor sites, i.e. metastases. Non-viral vectors based on the use of cationic lipids or polymers appear to have promising potential, given the problems of safety encountered with viral vectors. Using these non-viral vectors, the current challenge is to obtain a similarly effective transfection to viral ones. Based on the advantages and disadvantages of existing vectors and on the hurdles encountered with these carriers, the aim of this review is to describe the "perfect vector" for systemic gene therapy against cancer.

  1. Improved osteogenic vector for non-viral gene therapy

    Directory of Open Access Journals (Sweden)

    ARA Hacobian

    2016-03-01

    Full Text Available Therapeutic compensation of deficient bone regeneration is a challenging task and a topic of on-going search for novel treatment strategies. One promising approach for improvement involves non-viral gene delivery using the bone morphogenetic protein-2 (BMP-2 gene to provide transient, local and sustained expression of the growth factor. However, since efficiency of non-viral gene delivery is low, this study focused on the improvement of a BMP-2 gene expression system, aiming for compensation of poor transfection efficiency. First, the native BMP-2 gene sequence was modified by codon optimisation and altered by inserting a highly truncated artificial intron (96 bp. Transfection of multiple cell lines and rat adipose-derived mesenchymal stem cells with plasmids harbouring the improved BMP-2 sequence led to a several fold increased expression rate and subsequent osteogenic differentiation. Additionally, comparing expression kinetics of elongation factor 1 alpha (EF1α promoter with a state of the art CMV promoter revealed significantly higher BMP-2 expression when under the influence of the EF1α promoter. Results obtained by quantification of bone markers as well as osteogenic assays showed reduced sensitivity to promoter silencing effects of the EF1α promoter in rat adipose-derived mesenchymal stem cells. Finally, screening of several protein secretion signals using either luciferase or BMP-2 as reporter protein revealed no superior candidates for potential replacement of the native BMP-2 secretion signal. Taken together, by enhancing the exogenous BMP-2 expression system, low transfection efficiencies in therapeutic applications can be compensated, making safe non-viral systems even more suitable for tissue regeneration approaches.

  2. Dynamics of HPV viral loads reflect the treatment effect of photodynamic therapy in genital warts.

    Science.gov (United States)

    Hu, Zhili; Liu, Lishi; Zhang, Wenjing; Liu, Hui; Li, Junpeng; Jiang, Lifen; Zeng, Kang

    2018-03-01

    Photodynamic therapy (PDT) has demonstrated good clinical cure rates and low recurrence rates in the treatment of genital warts. Human papillomavirus (HPV) genotypes and viral load assays can reflect the status of persistent or latent infection and serve as a predictor of infection clearance. Specimens from 41 patients with HPV infection were obtained, and the HPV genotypes and viral load were analyzed using real-time polymerase chain reaction (PCR) assays. Traditional treatment, such as radiofrequency, microwave, or surgical therapy, was used to remove the visible lesions, and then PDT treatment was performed every week. HPV DNA testing was performed at every patient visit and the frequency of PDT treatment was determined by changes in HPV viral loads. HPV viral loads decreased significantly after PDT treatment. There were significant differences in HPV viral loads between pretherapy and three or six rounds of PDT treatment. Significant differences were also observed between single and multiple type HPV infection after six rounds of PDT treatment. Patients with single type HPV infection had significantly higher rates of negative HPV DNA test results, as compared with patients with multiple infections after six rounds of PDT treatment; however, there was no difference in recurrence rates between the two groups. Dynamic monitoring of HPV genotypes and viral loads can be used to guide PDT treatment and indicate PDT treatment efficacy in eliminating HPV. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Non-viral gene therapy for bone tissue engineering.

    Science.gov (United States)

    Wegman, Fiona; Oner, F Cumhur; Dhert, Wouter J A; Alblas, Jacqueline

    2013-01-01

    The possibilities of using gene therapy for bone regeneration have been extensively investigated. Improvements in the design of new transfection agents, combining vectors and delivery/release systems to diminish cytotoxicity and increase transfection efficiencies have led to several successful in vitro, ex vivo and in vivo strategies. These include growth factor or short interfering ribonucleic acid (siRNA) delivery, or even enzyme replacement therapies, and have led to increased osteogenic differentiation and bone formation in vivo. These results provide optimism to consider use in humans with some of these gene-delivery strategies in the near future.

  4. Prospects for Foamy Viral Vector Anti-HIV Gene Therapy

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    Arun K. Nalla

    2016-03-01

    Full Text Available Stem cell gene therapy approaches for Human Immunodeficiency Virus (HIV infection have been explored in clinical trials and several anti-HIV genes delivered by retroviral vectors were shown to block HIV replication. However, gammaretroviral and lentiviral based retroviral vectors have limitations for delivery of anti-HIV genes into hematopoietic stem cells (HSC. Foamy virus vectors have several advantages including efficient delivery of transgenes into HSC in large animal models, and a potentially safer integration profile. This review focuses on novel anti-HIV transgenes and the potential of foamy virus vectors for HSC gene therapy of HIV.

  5. Oncolytic Herpes Simplex Viral Therapy: A Stride toward Selective Targeting of Cancer Cells.

    Science.gov (United States)

    Sanchala, Dhaval S; Bhatt, Lokesh K; Prabhavalkar, Kedar S

    2017-01-01

    Oncolytic viral therapy, which makes use of replication-competent lytic viruses, has emerged as a promising modality to treat malignancies. It has shown meaningful outcomes in both solid tumor and hematologic malignancies. Advancements during the last decade, mainly genetic engineering of oncolytic viruses have resulted in improved specificity and efficacy of oncolytic viruses in cancer therapeutics. Oncolytic viral therapy for treating cancer with herpes simplex virus-1 has been of particular interest owing to its range of benefits like: (a) large genome and power to infiltrate in the tumor, (b) easy access to manipulation with the flexibility to insert multiple transgenes, (c) infecting majority of the malignant cell types with quick replication in the infected cells and (d) as Anti-HSV agent to terminate HSV replication. This review provides an exhaustive list of oncolytic herpes simplex virus-1 along with their genetic alterations. It also encompasses the major developments in oncolytic herpes simplex-1 viral therapy and outlines the limitations and drawbacks of oncolytic herpes simplex viral therapy.

  6. 77 FR 22333 - Prospective Grant of Exclusive License: Development of Oncolytic Viral Cancer Therapies

    Science.gov (United States)

    2012-04-13

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Prospective Grant of Exclusive License: Development of Oncolytic Viral Cancer Therapies AGENCY: National Institutes of Health... administration of the recombinant virus to a human or animal subject, the foreign gene is expressed in vivo to...

  7. MODERN APPROACHES TO THE THERAPY OF VIRAL PAPILLOMA SKIN INFECTION IN INFANCY

    Directory of Open Access Journals (Sweden)

    L.K. Aslamazian

    2006-01-01

    Full Text Available To improve the methods of prevention and treatment of viral papilloma infection, the researchers examined 80 children, suffering from skin forms of a disease. They examined peculiarities of a disease and interferon status of all the children. The data of clinic and laboratory research allowed them to assume that viral papilloma infection grows along with the reduction of immune mechanisms and it grows among the children, suffering from the genetic burden to viral diseases. All the patients, suffering from the disorder of interferon status, have undergone the complex therapy, which included medications of recombinant interferon (Viferon in suppositories and extrinsic. For the first time, the researchers removed the skin papillomas by a combination method: cryofreezing and photovaporization. The analysis of treatment and observation within a year and a half showed that in a group of children, who received a combination treatment, including Viferon therapy and removal of verrucas by 2 surgical methods. No backset of a disease detected. In general, the findings of the research pointed out the high efficiency of topical and systemic Viferon medications, as well as combination method of verruca removal in complex treatment of viral papilloma skin infection among the children.Key words: interferon status of children, interferon al'fa 2b, verrucas, viral papilloma infection.

  8. Efficacy and safety on tenofovire therapy in patients with hepatitis B viral infections resistent to lamivudin

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    Katanić N.

    2015-01-01

    Full Text Available Chronic viral hepatitis B (CHB still represents a significant world health problem despite obligatory and worldwide immunization against infections of viral hepatitis B. In some patients with chronic viral hepatitis B infections, in the natural course of the disease, progression towards cirhossis and hepatocellular carcinoma is primarily targeted by antiviral CHB therapy stopping further progression of the disease. Today on the market there exist two classes of pharmnaceutical drugs for treatment of CHB: a immunomodulatory therapy with conventional interferon alpha (INF and PEGylated interferon alpha-2a, b and oral antiviral therapy with nucleos( tide analogues. Lamivudine was for quite a period the only medicament available on our market for the treatment of HVB and in most of our patients led to the development of resistance. As of two years ago, a new oral analogue from the group of nucleotides is being registered in Serbia for market use: tenofovir disoproxil (TDF. In our work we have analysed 69 patients with chronic viral hepatitis B treated in the Clinic for Infectious and Tropical Diseases KCS Belgrade in the period between years 2012 and 2014. All patients involved in this reasearch were previously treated with LAM, and on subsequent development of resistance to LAM, TDF was used. TDF showed an excellent efficacy, a high resistance barrier and very few unwanted side effects over several years of treatment. Our experience with the use of this drug does not pertain to and acount for its long term use, in view of its brief availability on our market.

  9. Efficacy of VIFERON® in the combination therapy of viral encephalitis in infants

    Directory of Open Access Journals (Sweden)

    N. V. Skripchenko

    2015-01-01

    Full Text Available The paper provides the clinical and ettological characteristics of viral encephalitis in 103 children aged 1 month to 3 years and the results of a comparative study of the efficiency of recombinant interferon-a 2b (VIFERON® as rectal suppositories incorporated into the combination therapy of the disease. The VIFERON® regimen and duration in the study were determined by the pattern of encephalitis. In the acute course of the latter, VIFERON® was given twice daily for 14 days; in its protracted or chronical course, the drug was used twice daily for 14 days, then thrice daily for 1 and 3 months, respectively. The administration of VIFERON® in viral encephalitis was established to accelerate sanogenetic processes and to reduce the time of progression and preservation of major extracerebral and cerebral symptoms and the length of sanitization of cerebrospinal fluid (CSF and viremia. The use of VIFERON® resulted in better disease outcomes, prevented deaths, decreased the rate of an autonomic state from 8 to 1,8%, increased recovery rates without defects from 22 to 51%, and reduced the rate of cystic and gliotic changes in the brain by 2,1 times. Slower CSF sanitization and longer viremia were ascertained in children with chronic and protracted viral encephalitis, which necessitated the longer administration of VIFERON®. Incorporation of recombinant interferon-a 2b into the therapy of viral encephalitis in infants ensures higher serum concentrations of interferon-a and helps keep compensatory capacities for its production, leading to the promptest recovery. The findings suggest that the incorporation of VIFERON® as rectal suppositories into the therapy of viral encephalitis is effective and safe in infants.

  10. Viral vectors for cystic fibrosis gene therapy: What does the future hold?

    Directory of Open Access Journals (Sweden)

    Uta Griesenbach

    2010-12-01

    Full Text Available Uta Griesenbach1, Makoto Inoue2, Mamoru Hasegawa2, Eric WFW Alton11Department of Gene Therapy, Imperial College London, UK; The UK Cystic Fibrosis Gene Therapy Consortium; 2DNAVEC Corporation, Tsukuba, JapanAbstract: Gene transfer to the airway epithelium has been more difficult than originally anticipated, largely because of significant extra- and intracellular barriers in the lung. In general, viral vectors are more adapted to overcoming these barriers than nonviral gene transfer agents and are, therefore, more efficient in transferring genes into recipient cells. Viral vectors derived from adenovirus, adeno-associated virus, and Sendai virus, which all have a natural tropism for the airway epithelium, have been evaluated for cystic fibrosis (CF gene therapy. Although these vectors transduce airway epithelial cells efficiently, gene expression is transient and repeated administration is inefficient. They are, therefore, unlikely to be suitable for CF gene therapy. More recently, lentiviruses (LV have been assessed for lung gene transfer. In contrast to retroviruses, they transduce nondividing cells and randomly integrate into the genome. However, LVs do not have a natural tropism for the lung, and a significant amount of effort has been put into pseudotyping these vectors with proteins suitable for airway gene transfer. Several studies have shown that LV-mediated transduction leads to persistent gene expression (for the lifetime of the animal in the airways and, importantly, repeated administration is feasible. Thus, appropriately pseudotyped LV vectors are promising candidates for CF gene therapy. Here, we will review preclinical and clinical research related to viral CF gene therapy.Keywords: cystic fibrosis, gene therapy, adenovirus, AAV, lentivirus, Sendai virus

  11. Differential impact of transplantation on peripheral and tissue-associated viral reservoirs: Implications for HIV gene therapy.

    Science.gov (United States)

    Peterson, Christopher W; Wang, Jianbin; Deleage, Claire; Reddy, Sowmya; Kaur, Jasbir; Polacino, Patricia; Reik, Andreas; Huang, Meei-Li; Jerome, Keith R; Hu, Shiu-Lok; Holmes, Michael C; Estes, Jacob D; Kiem, Hans-Peter

    2018-04-01

    Autologous transplantation and engraftment of HIV-resistant cells in sufficient numbers should recapitulate the functional cure of the Berlin Patient, with applicability to a greater number of infected individuals and with a superior safety profile. A robust preclinical model of suppressed HIV infection is critical in order to test such gene therapy-based cure strategies, both alone and in combination with other cure strategies. Here, we present a nonhuman primate (NHP) model of latent infection using simian/human immunodeficiency virus (SHIV) and combination antiretroviral therapy (cART) in pigtail macaques. We demonstrate that transplantation of CCR5 gene-edited hematopoietic stem/progenitor cells (HSPCs) persist in infected and suppressed animals, and that protected cells expand through virus-dependent positive selection. CCR5 gene-edited cells are readily detectable in tissues, namely those closely associated with viral reservoirs such as lymph nodes and gastrointestinal tract. Following autologous transplantation, tissue-associated SHIV DNA and RNA levels in suppressed animals are significantly reduced (p ≤ 0.05), relative to suppressed, untransplanted control animals. In contrast, the size of the peripheral reservoir, measured by QVOA, is variably impacted by transplantation. Our studies demonstrate that CCR5 gene editing is equally feasible in infected and uninfected animals, that edited cells persist, traffic to, and engraft in tissue reservoirs, and that this approach significantly reduces secondary lymphoid tissue viral reservoir size. Our robust NHP model of HIV gene therapy and viral persistence can be immediately applied to the investigation of combinatorial approaches that incorporate anti-HIV gene therapy, immune modulators, therapeutic vaccination, and latency reversing agents.

  12. Differential impact of transplantation on peripheral and tissue-associated viral reservoirs: Implications for HIV gene therapy.

    Directory of Open Access Journals (Sweden)

    Christopher W Peterson

    2018-04-01

    Full Text Available Autologous transplantation and engraftment of HIV-resistant cells in sufficient numbers should recapitulate the functional cure of the Berlin Patient, with applicability to a greater number of infected individuals and with a superior safety profile. A robust preclinical model of suppressed HIV infection is critical in order to test such gene therapy-based cure strategies, both alone and in combination with other cure strategies. Here, we present a nonhuman primate (NHP model of latent infection using simian/human immunodeficiency virus (SHIV and combination antiretroviral therapy (cART in pigtail macaques. We demonstrate that transplantation of CCR5 gene-edited hematopoietic stem/progenitor cells (HSPCs persist in infected and suppressed animals, and that protected cells expand through virus-dependent positive selection. CCR5 gene-edited cells are readily detectable in tissues, namely those closely associated with viral reservoirs such as lymph nodes and gastrointestinal tract. Following autologous transplantation, tissue-associated SHIV DNA and RNA levels in suppressed animals are significantly reduced (p ≤ 0.05, relative to suppressed, untransplanted control animals. In contrast, the size of the peripheral reservoir, measured by QVOA, is variably impacted by transplantation. Our studies demonstrate that CCR5 gene editing is equally feasible in infected and uninfected animals, that edited cells persist, traffic to, and engraft in tissue reservoirs, and that this approach significantly reduces secondary lymphoid tissue viral reservoir size. Our robust NHP model of HIV gene therapy and viral persistence can be immediately applied to the investigation of combinatorial approaches that incorporate anti-HIV gene therapy, immune modulators, therapeutic vaccination, and latency reversing agents.

  13. Scientific rationale for antiretroviral therapy in 2005: viral reservoirs and resistance evolution.

    Science.gov (United States)

    Siliciano, Robert F

    2005-01-01

    Hope for a cure for HIV-1 infection was dampened by the discovery of a latent form of the virus that persists in resting CD4+ cells. This reservoir of latently HIV-infected resting memory T cells represents an archive of viral genotypes produced in an individual from the onset of infection. Entry into the reservoir is stopped with suppressive antiretroviral therapy, but the archived viruses are capable of re-initiating active infections, are released continuously from this reservoir, and can cause viral rebound if antiretroviral therapy is stopped. Studies of residual low-level viremia (Robert F. Siliciano, MD, PhD, at the International AIDS Society-USA course in New York in March 2005.

  14. Viral Response to Specifically Targeted Antiviral Therapy for Hepatitis C and the Implications for Treatment Success

    Directory of Open Access Journals (Sweden)

    Curtis L Cooper

    2010-01-01

    Full Text Available Currently, hepatitis C virus (HCV antiviral therapy is characterized by long duration, a multitude of side effects, difficult administration and suboptimal success; clearly, alternatives are needed. Collectively, specifically targeted antiviral therapy for HCV (STAT-C molecules achieve rapid viral suppression and very high rapid virological response rates, and improve sustained virological response rates. The attrition rate of agents within this class has been high due to various toxicities. Regardless, several STAT-C molecules are poised to become the standard of care for HCV treatment in the foreseeable future. Optimism must be tempered with concerns related to the rapid development of drug resistance with resulting HCV rebound. Strategies including induction dosing with interferon and ribavirin, use of combination high-potency STAT-C molecules and an intensive emphasis on adherence to HCV antiviral therapy will be critical to the success of this promising advance in HCV therapy.

  15. History of viral suppression on combination antiretroviral therapy as a predictor of virological failure after a treatment change

    DEFF Research Database (Denmark)

    Reekie, J; Mocroft, A; Ledergerber, B

    2010-01-01

    OBJECTIVES: HIV-infected persons experience different patterns of viral suppression after initiating combination antiretroviral therapy (cART). The relationship between such differences and risk of virological failure after starting a new antiretroviral could help with patient monitoring strategi...

  16. Viral hepatitis screening in transgender patients undergoing gender identity hormonal therapy.

    Science.gov (United States)

    Mangla, Neeraj; Mamun, Rifat; Weisberg, Ilan S

    2017-11-01

    Viral hepatitis is a global health issue and can lead to cirrhosis, liver failure, and hepatocellular carcinoma. Guidelines for viral hepatitis screening in the transgender population do not exist. Transgender patients may be at higher risk for contracting viral hepatitis due to socioeconomic and behavioral factors. The aim of this study was to measure the quality of screening, prevalence, and susceptibility of viral hepatitis, and to identify barriers to screening in transgender patients undergoing gender identity hormonal therapy. LGBTQ-friendly clinic visits from transgender patients older than 18 years in New York City from 2012 to 2015 were reviewed. Approximately 13% of patients were screened for any viral hepatitis on initial consultation. Screening rates for hepatitis C virus (HCV), hepatitis B virus (HBV), and hepatitis A virus (HAV) at any point were 27, 22, and 20%. HAV screening was performed in 28% of the female to male (FtM) patients and 16% of male to female (MtF) (P0.05). Prevalence of HCV, HBV, and HIV in FtM was 0, 0, and 0.44% and that in MtF was 1.78, 0.89, and 1.78%, respectively. Percentage of patients immune to hepatitis A in FtM and MtF subgroups were 55 and 47% (P>0.05). Percentage of patients immune to HBV in FtM and MtF subgroups were 54 and 48% (P>0.05). This study indicates a significant lack of hepatitis screening in the transgender population and a concerning proportion of patients susceptible to disease.

  17. Clinical experience with ursodeoxycholic acid (Urdoxa in complex therapy of chronic viral hepatitis

    Directory of Open Access Journals (Sweden)

    E. V. Esaulenko

    2011-01-01

    Full Text Available Patients with chronic virus hepatitis (32 patients, 13 with chronic hepatitis B and 19 with chronic hepatitis C ages from 20 to 72 with elevated levels of bilirubin and active alanine aminotransferase, aspartate aminotransferase, gamma- glutamyl transpeptidase, received ursodeoxycholic acid (Urdoxa over the course of 12 weeks. During therapy alanine aminotransferase, aspartate aminotransferase, bilirubin and gamma-glutamyl transpeptidase levels decreased. Urdoxa demonstrated good tolerance, efficacy and no visible side effects. Thus, Urdoxa could be used in treatment of chronic viral hepatitis with cytolytic and cholestatic syndromes.

  18. Oncolytic Viral Therapy and the Immune System: A Double-Edged Sword Against Cancer.

    Science.gov (United States)

    Marelli, Giulia; Howells, Anwen; Lemoine, Nicholas R; Wang, Yaohe

    2018-01-01

    Oncolytic viral therapy is a new promising strategy against cancer. Oncolytic viruses (OVs) can replicate in cancer cells but not in normal cells, leading to lysis of the tumor mass. Beside this primary effect, OVs can also stimulate the immune system. Tumors are an immuno-suppressive environment in which the immune system is silenced in order to avoid the immune response against cancer cells. The delivery of OVs into the tumor wakes up the immune system so that it can facilitate a strong and durable response against the tumor itself. Both innate and adaptive immune responses contribute to this process, producing an immune response against tumor antigens and facilitating immunological memory. However, viruses are recognized by the immune system as pathogens and the consequent anti-viral response could represent a big hurdle for OVs. Finding a balance between anti-tumor and anti-viral immunity is, under this new light, a priority for researchers. In this review, we provide an overview of the various ways in which different components of the immune system can be allied with OVs. We have analyzed the different immune responses in order to highlight the new and promising perspectives leading to increased anti-tumor response and decreased immune reaction to the OVs.

  19. Stem cell gene therapy for HIV: strategies to inhibit viral entry and replication.

    Science.gov (United States)

    DiGiusto, David L

    2015-03-01

    Since the demonstration of a cure of an HIV+ patient with an allogeneic stem cell transplant using naturally HIV-resistant cells, significant interest in creating similar autologous products has fueled the development of a variety of "cell engineering" approaches to stem cell therapy for HIV. Among the more well-studied strategies is the inhibition of viral entry through disruption of expression of viral co-receptors or through competitive inhibitors of viral fusion with the cell membrane. Preclinical evaluation of these approaches often starts in vitro but ultimately is tested in animal models prior to clinical implementation. In this review, we trace the development of several key approaches (meganucleases, short hairpin RNA (shRNA), and fusion inhibitors) to modification of hematopoietic stem cells designed to impart resistance to HIV to their T-cell and monocytic progeny. The basic evolution of technologies through in vitro and in vivo testing is discussed as well as the pros and cons of each approach and how the addition of postentry inhibitors may enhance the overall antiviral efficacy of these approaches.

  20. Influenza A Virus-Host Protein Interactions Control Viral Pathogenesis.

    Science.gov (United States)

    Zhao, Mengmeng; Wang, Lingyan; Li, Shitao

    2017-08-01

    The influenza A virus (IAV), a member of the Orthomyxoviridae family, is a highly transmissible respiratory pathogen and represents a continued threat to global health with considerable economic and social impact. IAV is a zoonotic virus that comprises a plethora of strains with different pathogenic profiles. The different outcomes of viral pathogenesis are dependent on the engagement between the virus and the host cellular protein interaction network. The interactions may facilitate virus hijacking of host molecular machinery to fulfill the viral life cycle or trigger host immune defense to eliminate the virus. In recent years, much effort has been made to discover the virus-host protein interactions and understand the underlying mechanisms. In this paper, we review the recent advances in our understanding of IAV-host interactions and how these interactions contribute to host defense and viral pathogenesis.

  1. Pest control through viral disease: mathematical modeling and analysis.

    Science.gov (United States)

    Bhattacharyya, S; Bhattacharya, D K

    2006-01-07

    This paper deals with the mathematical modeling of pest management under viral infection (i.e. using viral pesticide) and analysis of its essential mathematical features. As the viral infection induces host lysis which releases more virus into the environment, on the average 'kappa' viruses per host, kappain(1,infinity), the 'virus replication parameter' is chosen as the main parameter on which the dynamics of the infection depends. We prove that there exists a threshold value kappa(0) beyond which the endemic equilibrium bifurcates from the free disease one. Still for increasing kappa values, the endemic equilibrium bifurcates towards a periodic solution. We further analyse the orbital stability of the periodic orbits arising from bifurcation by applying Poor's condition. A concluding discussion with numerical simulation of the model is then presented.

  2. Maintenance of T1 response as induced during PEG-IFNalpha plus ribavirin therapy controls viral replication in genotype-1 patients with chronic hepatitis C La respuesta inmune T1 inducida durante el tratamiento con PEG-IFNα mαs ribavirina controla la replicaciσn viral en pacientes con hepatitis crónica C

    Directory of Open Access Journals (Sweden)

    M. Trapero

    2005-07-01

    (1-1,2 g/día durante 48 semanas. Los 28 pacientes (edad media 45 ± 8 años finalizaron el tratamiento y seguimiento: 12 (43% presentaron respuesta viral sostenida (RVS, 13 recidivaron (47% y sólo 3 fueron no respondedores (10%. Se estudiaron 16 controles sanos (edad media de 39 ± 17 años. Se analizó mediante citometría de flujo la producción intracitoplásmica de IL-4, IFNγ y TNFα por los linfocitos T CD8+ en reposo y tras ser estimulados con un ιster de forbol. Anαlisis estadístico: t de Student, test de χ² y ANOVA; se agrupan los pacientes recidivantes y no respondedores para obtener mayor potencia estadística. Resultados: no se encontraron diferencias significativas entre los niveles de citocinas de controles sanos y pacientes con HCC. Al tercer mes de tratamiento, los niveles de IL-4 inducidos tendían a ser menores en los pacientes que obtuvieron una RVS que en el resto de pacientes (0,97 vs. 2,58; p = 0,1; tampoco se encontró significación estadística en relación a los niveles de IIFNγ y de TTNFα. Al final del tratamiento, la producciσn de IIFNγ estimulado fue significativamente mayor en los pacientes que obtuvieron una RVS (20 vs. 8; p < 0,05. Por el contrario, la producción de IL-4 fue mayor en los pacientes no respondedores, aunque estos datos no alcanzaron significación estadística (p < 0,1. No se encontraron diferencias en relación con los niveles de TTNFα (14 vs. 7; p < 0,2. Conclusiones: el mantenimiento de la respuesta inmune tipo T1 durante el tratamiento combinado, medida en función de la síntesis de IIFNγ por los linfocitos T CD8, se asocia con RVS y sugiere el control de la replicaciσn y el aclaramiento posterior de los pacientes infectados con el genotipo 1 del VHC.

  3. Succesful therapy of viral leukemia by transplantation of histocompatibly unmatched marrow

    International Nuclear Information System (INIS)

    Meredith, R.F.; OKunewick, J.P.; Kuhnert, P.M.; Brozovich, B.J.; Weaver, E.V.

    1978-01-01

    The therapeutic effectiveness on murine viral-leukemia of allogeneic or hybrid hematopoietic cells transplanted from leukemia-virus resistant donors was evaluated and compared with that of syngeneic cells. Transplantation of syngeneic cells gave no protection to the viral-leukemic mice. Transplantation of spleen cells from allogeneic donors resulted in early deaths of both leukemic and non-leukemic recipients. Transplantation of hybrid spleen cells resulted in no long-term survival of the leukemic mice. However, there were a number of long-term survivors among the leukemic recipients of allogeneic or hybrid marrow cells. Engraftment of allogeneic marrow resulted in a large number of survivors. Hybrid marrow recipients showed an even better survival, but some leukemia relapses. Tests of the longterm survivors revealed that even though they gave no evidence of leukemia they still harbored the active virus. This suggests that the mechanism of protection may be related to some inherent characteristic of the donor cells rendering them refractory to viral transformation. A difference in graft-versus-host (GvH) response between the leukemic and control mice was also found after transplantation of allogeneic cells. While all of the controls died of GvH reaction, none of the leukemic recipients showed severe GvH response, suggesting a possible effect of the leukemia on histocompatibility. No GvH reaction was found with hybrid marrow engraftment, although some of the leukemic recipients reconstituted with F 1 cells did die of leukemic relapse. (author)

  4. Viral control of bacterial biodiversity - Evidence from a nutrient enriched mesocosm experiment

    DEFF Research Database (Denmark)

    Sandaa, R.-A.; Gómez-Consarnau, L.; Pinhassi, J.

    2009-01-01

    . As predicted, the total number of viral populations was the same in all treatments, while the composition of the viral community varied. Our results support the theoretical prediction that there is one control mechanism for the number of niches for coexisting virus-host pairs (top-down control), and another......We demonstrate here results showing that bottom-up and top-down control mechanisms can operate simultaneously and in concert in marine microbial food webs, controlling prokaryote diversity by a combination of viral lysis and substrate limitation. Models in microbial ecology predict that a shift...... in the type of bacterial growth rate limitation is expected to have a major effect on species composition within the community of bacterial hosts, with a subsequent shift in the composition of the viral community. Only moderate effects would, however, be expected in the absolute number of coexisting virus...

  5. Non-viral gene delivery strategies for cancer therapy, tissue engineering and regenerative medicine

    Science.gov (United States)

    Bhise, Nupura S.

    Gene therapy involves the delivery of deoxyribonucleic acid (DNA) into cells to override or replace a malfunctioning gene for treating debilitating genetic diseases, including cancer and neurodegenerative diseases. In addition to its use as a therapeutic, it can also serve as a technology to enable regenerative medicine strategies. The central challenge of the gene therapy research arena is developing a safe and effective delivery agent. Since viral vectors have critical immunogenic and tumorogenic safety issues that limit their clinical use, recent efforts have focused on developing non-viral biomaterial based delivery vectors. Cationic polymers are an attractive class of gene delivery vectors due to their structural versatility, ease of synthesis, biodegradability, ability to self-complex into nanoparticles with negatively charged DNA, capacity to carry large cargo, cellular uptake and endosomal escape capacity. In this thesis, we hypothesized that developing a biomaterial library of poly(betaamino esters) (PBAE), a newer class of cationic polymers consisting of biodegradable ester groups, would allow investigating vector design parameters and formulating effective non-viral gene delivery strategies for cancer drug delivery, tissue engineering and stem cell engineering. Consequently, a high-throughput transfection assay was developed to screen the PBAE-based nanoparticles in hard to transfect fibroblast cell lines. To gain mechanistic insights into the nanoparticle formulation process, biophysical properties of the vectors were characterized in terms of molecular weight (MW), nanoparticle size, zeta potential and plasmid per particle count. We report a novel assay developed for quantifying the plasmid per nanoparticle count and studying its implications for co-delivery of multiple genes. The MW of the polymers ranged from 10 kDa to 100 kDa, nanoparticle size was about 150 run, zeta potential was about 30 mV in sodium acetate buffer (25 mM, pH 5) and 30 to 100

  6. Advances in Viral Vector-Based TRAIL Gene Therapy for Cancer

    International Nuclear Information System (INIS)

    Norian, Lyse A.; James, Britnie R.; Griffith, Thomas S.

    2011-01-01

    Numerous biologic approaches are being investigated as anti-cancer therapies in an attempt to induce tumor regression while circumventing the toxic side effects associated with standard chemo- or radiotherapies. Among these, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has shown particular promise in pre-clinical and early clinical trials, due to its preferential ability to induce apoptotic cell death in cancer cells and its minimal toxicity. One limitation of TRAIL use is the fact that many tumor types display an inherent resistance to TRAIL-induced apoptosis. To circumvent this problem, researchers have explored a number of strategies to optimize TRAIL delivery and to improve its efficacy via co-administration with other anti-cancer agents. In this review, we will focus on TRAIL-based gene therapy approaches for the treatment of malignancies. We will discuss the main viral vectors that are being used for TRAIL gene therapy and the strategies that are currently being attempted to improve the efficacy of TRAIL as an anti-cancer therapeutic

  7. Baicalin benefits the anti-HBV therapy via inhibiting HBV viral RNAs

    International Nuclear Information System (INIS)

    Huang, Hai; Zhou, Wei; Zhu, Haiyan; Zhou, Pei; Shi, Xunlong

    2017-01-01

    Background: Although current antiviral treatments (nucleoside analogs, NAs) for chronic hepatitis B virus (HBV) infection are effective in suppressing HBV-DNA replication, their clinical outcomes can be compromised by the increasing drug resistance and the inefficiency in promoting HBsAg/HBeAg seroconversion. Objectives: In this study, we will explore possible effects and mechanism of a natural product baicalin (BA) with the anti-HBV efficacy of entecavir (ETV), a first-line anti-HBV drug, in HBV-DNA, HBsAg/HBeAg seroconversion and drug-resistance. Methods: The co-effects of BA and ETV were conducted in wild-type/NA-resistance mutant HBV cell lines and DHBV-infected duckling models. HBV-DNA/RNAs, HBsAg/HBeAg, host factors (hepatocyte nuclear factors) were explored for possible anti-HBV mechanism. Results and discussion: BA could significantly enhance and reduced HBsAg and HBeAg in hepG2.2.15, a wild-type HBV cell line. Co-treatment of BA and ETV had a more dramatic effect in NA-resistant HBV rtM204V/rtLl80M transfected hepG2 cells. Our study further revealed that BA mainly inhibited the production of HBV RNAs (3.5, 2.4, 2.1 kb), the templates for viral proteins and HBV-DNA synthesis. BA blocked HBV RNAs transcription possibly by down-regulating transcription and expression of HBV replication dependent hepatocyte nuclear factors (HNF1α and HNF4α). Thus, BA may benefit the anti-HBV therapy via inhibiting HBV viral RNAs. - Highlights: • Baicalin benefits the anti-HBV therapy. • Baicalin enhances ETV antiviral efficacy and overcomes NA-resistant HBV mutation. • The anti-HBV effect of baicalin is achieved by inhibiting HBV RNAs. • Baicalin down-regulates HBV replication-dependent host factors HNF 1α and HNF 4α.

  8. E1B-attenuated onco lytic adenovirus enhances antitumor effect of radionuclide therapy by P53-independent way: cellular basic for radionuclide-viral therapy

    Energy Technology Data Exchange (ETDEWEB)

    Zhenwei, Zhang [Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai (China); Hua, Wu; Xuemei, Zhang [Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan (China); Xinyuan, Liu [Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai (China)

    2004-07-01

    Purpose: Chemotherapy or external radiation therapy can potentiate the therapeutic effect of E1 B-attenuated oncolytic adenovirus. In this study, the antitumor efficacy of oncolytic adenovirus combined with internal radionuclide therapy was evaluated. Methods: Firstly, viral replication was examined by plaque assay and Southern blotting, after oncolytic adenovirus, ZD55, was exposed to iodine-131. Cell viability was evaluated qualitatively by crystal violet staining and quantitatively by MTT assay. FACS analysis was performed to determine the synergic proapoptotic effect of iodine-131 combined with ZD55. Results: Irradiation of iodine-131 does not influence ZD55 viral DNA replication. In combination with ZD55, iodine-131 can efficiently kill tumor cells in a p53-independent model. ZD55 augments the proapoptotic effect of iodine-131. Conclusion: Radionuclide-viral therapy might be a novel tool for treatment of hepatocarcinoma. (authors)

  9. Interferon Lambda Genetics and Biology in Regulation of Viral Control

    Directory of Open Access Journals (Sweden)

    Emily A. Hemann

    2017-12-01

    Full Text Available Type III interferons, also known as interferon lambdas (IFNλs, are the most recent addition to the IFN family following their discovery in 2003. Initially, IFNλ was demonstrated to induce expression of interferon-stimulated genes and exert antiviral properties in a similar manner to type I IFNs. However, while IFNλ has been described to have largely overlapping expression and function with type I IFNs, it has become increasingly clear that type III IFNs also have distinct functions from type I IFNs. In contrast to type I IFNs, whose receptor is ubiquitously expressed, type III IFNs signal and function largely at barrier epithelial surfaces, such as the respiratory and gastrointestinal tracts, as well as the blood–brain barrier. In further support of unique functions for type III IFNs, single nucleotide polymorphisms in IFNL genes in humans are strongly associated with outcomes to viral infection. These biological linkages have also been more directly supported by studies in mice highlighting roles of IFNλ in promoting antiviral immune responses. In this review, we discuss the current understanding of type III IFNs, and how their functions are similar to, and different from, type I IFN in various immune cell subtypes and viral infections.

  10. Viral infection and antiviral therapy in the neonatal intensive care unit.

    Science.gov (United States)

    Barford, Galina; Rentz, Alison C; Faix, Roger G

    2004-01-01

    Viral diseases are leading causes of mortality and morbidity among infants requiring care in the neonatal intensive care unit (NICU), with ongoing discoveries of new viral pathology likely to add to the burdens posed. Many viral diseases in NICU infants are undiagnosed or appreciated only late in the course because of subtle or asymptomatic presentation, confusion with bacterial disease, and failure to consider viral disease. We present an overview of viral disease in NICU infants, with emphasis on pharmacologic agents currently employed for prophylaxis and treatment of such diseases. Advances in molecular biology and popular demand to develop antiviral agents for viral diseases (eg, human immunodeficiency virus) offer great promise for the future.

  11. Computerized counseling reduces HIV-1 viral load and sexual transmission risk: findings from a randomized controlled trial.

    Science.gov (United States)

    Kurth, Ann E; Spielberg, Freya; Cleland, Charles M; Lambdin, Barrot; Bangsberg, David R; Frick, Pamela A; Severynen, Anneleen O; Clausen, Marc; Norman, Robert G; Lockhart, David; Simoni, Jane M; Holmes, King K

    2014-04-15

    Evaluate a computerized intervention supporting antiretroviral therapy (ART) adherence and HIV transmission prevention. Longitudinal randomized controlled trial. An academic HIV clinic and a community-based organization in Seattle. In a total of 240 HIV-positive adults on ART, 209 completed 9-month follow-up (87% retention). Randomization to computerized counseling or assessment only, 4 sessions over 9 months. HIV-1 viral suppression, and self-reported ART adherence and transmission risks, compared using generalized estimating equations. Overall, intervention participants had reduced viral load: mean 0.17 log10 decline, versus 0.13 increase in controls, P = 0.053, and significant difference in ART adherence baseline to 9 months (P = 0.046). Their sexual transmission risk behaviors decreased (odds ratio = 0.55, P = 0.020), a reduction not seen among controls (odds ratio = 1.1, P = 0.664), and a significant difference in change (P = 0.040). Intervention effect was driven by those most in need; among those with detectable virus at baseline (>30 copies/mL, n = 89), intervention effect was mean 0.60 log10 viral load decline versus 0.15 increase in controls, P = 0.034. ART adherence at the final follow-up was 13 points higher among intervention participants versus controls, P = 0.038. Computerized counseling is promising for integrated ART adherence and safer sex, especially for individuals with problems in these areas. This is the first intervention to report improved ART adherence, viral suppression, and reduced secondary sexual transmission risk behavior.

  12. Optimal Control of Drug Therapy in a Hepatitis B Model

    Directory of Open Access Journals (Sweden)

    Jonathan E. Forde

    2016-08-01

    Full Text Available Combination antiviral drug therapy improves the survival rates of patients chronically infected with hepatitis B virus by controlling viral replication and enhancing immune responses. Some of these drugs have side effects that make them unsuitable for long-term administration. To address the trade-off between the positive and negative effects of the combination therapy, we investigated an optimal control problem for a delay differential equation model of immune responses to hepatitis virus B infection. Our optimal control problem investigates the interplay between virological and immunomodulatory effects of therapy, the control of viremia and the administration of the minimal dosage over a short period of time. Our numerical results show that the high drug levels that induce immune modulation rather than suppression of virological factors are essential for the clearance of hepatitis B virus.

  13. Perinatal HIV-infection in Sankt Petersburg and Modern Therapy Concomitant Viral Infections

    Directory of Open Access Journals (Sweden)

    V. N. Timchenko

    2016-01-01

    Full Text Available The study included 338 HIV-infected children (B-23 and 350 children with perinatal contact HIV infection (R-75, consisting on the dispensary in the department of maternal and child the St. Petersburg City AIDS Center. In 32 persons (9.5% diagnosed with secondary infections. In the structure of viral opportunistic infections (herpesvirus, SARS amounted to 39.8%, bacterial (bronchitis, tonsillitis, pyoderma, tuberculosis — 34.8%, fungal and parasitic (candidiasis of the oral mucosa, PCP — 25.4 %. Combined therapy (causal, pathogenetic, symptomatic SARS in children with B-23 and R-75, allows you to get in early (6th d. Treatment regress the main symptoms of acute respiratory diseases. Modern therapy of congenital cytomegalovirus infection (VTSMI in children with B-23 and R-75 of the first year of life with antitsitomegalovirusnogo immunoglobulin and preparation of human recombinant interferon alfa-2b in the form of rectal suppositories — VIFERON, causes persistent normalization of clinical and laboratory parameters.

  14. Knowledge Gaps Impacting the Development of Bovine Viral Diarrhea Virus Control Programs in the United States

    Science.gov (United States)

    This paper identifies knowledge gaps that impact on the design of programs to control and or eradicate bovine viral diarrhea viruses (BVDV) in the United States. Currently there are several voluntary regional BVDV control programs in place. These control programs are aimed at the removal of animals ...

  15. Baicalin benefits the anti-HBV therapy via inhibiting HBV viral RNAs.

    Science.gov (United States)

    Huang, Hai; Zhou, Wei; Zhu, Haiyan; Zhou, Pei; Shi, Xunlong

    2017-05-15

    Although current antiviral treatments (nucleoside analogs, NAs) for chronic hepatitis B virus (HBV) infection are effective in suppressing HBV-DNA replication, their clinical outcomes can be compromised by the increasing drug resistance and the inefficiency in promoting HBsAg/HBeAg seroconversion. In this study, we will explore possible effects and mechanism of a natural product baicalin (BA) with the anti-HBV efficacy of entecavir (ETV), a first-line anti-HBV drug, in HBV-DNA, HBsAg/HBeAg seroconversion and drug-resistance. The co-effects of BA and ETV were conducted in wild-type/NA-resistance mutant HBV cell lines and DHBV-infected duckling models. HBV-DNA/RNAs, HBsAg/HBeAg, host factors (hepatocyte nuclear factors) were explored for possible anti-HBV mechanism. BA could significantly enhance and reduced HBsAg and HBeAg in hepG2.2.15, a wild-type HBV cell line. Co-treatment of BA and ETV had a more dramatic effect in NA-resistant HBV rtM204V/rtLl80M transfected hepG2 cells. Our study further revealed that BA mainly inhibited the production of HBV RNAs (3.5, 2.4, 2.1kb), the templates for viral proteins and HBV-DNA synthesis. BA blocked HBV RNAs transcription possibly by down-regulating transcription and expression of HBV replication dependent hepatocyte nuclear factors (HNF1α and HNF4α). Thus, BA may benefit the anti-HBV therapy via inhibiting HBV viral RNAs. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Non-viral gene therapy that targets motor neurons in vivo

    Directory of Open Access Journals (Sweden)

    Mary-Louise eRogers

    2014-10-01

    Full Text Available A major challenge in neurological gene therapy is safe delivery of transgenes to sufficient cell numbers from the circulation or periphery. This is particularly difficult for diseases involving spinal cord motor neurons such as amyotrophic lateral sclerosis (ALS. We have examined the feasibility of non-viral gene delivery to spinal motor neurons from intraperitoneal injections of plasmids carried by ‘immunogene’ nanoparticles targeted for axonal retrograde transport using antibodies. PEGylated polyethylenimine (PEI-PEG12 as DNA carrier was conjugated to an antibody (MLR2 to the neurotrophin receptor p75 (p75NTR. We used a plasmid (pVIVO2 designed for in vivo gene delivery that produces minimal immune responses, has improved nuclear entry into post mitotic cells and also expresses green fluorescent protein (GFP. MLR2-PEI-PEG12 carried pVIVO2 and was specific for mouse motor neurons in mixed cultures containing astrocytes. While only 8% of motor neurons expressed GFP 72 h post transfection in vitro, when the immunogene was given intraperitonealy to neonatal C57BL/6J mice GFP specific motor neuron expression was observed in 25.4% of lumbar, 18.3% of thoracic and 17.0 % of cervical motor neurons, 72 h post transfection. PEI-PEG12 carrying pVIVO2 by itself did not transfect motor neurons in vivo, demonstrating the need for specificity via the p75NTR antibody MLR2. This is the first time that specific transfection of spinal motor neurons has been achieved from peripheral delivery of plasmid DNA as part of a non-viral gene delivery agent. These results stress the specificity and feasibility of immunogene delivery targeted for p75NTR expressing motor neurons, but suggests that further improvements are required to increase the transfection efficiency of motor neurons in vivo.

  17. Glycolytic control of vacuolar-type ATPase activity: A mechanism to regulate influenza viral infection

    Energy Technology Data Exchange (ETDEWEB)

    Kohio, Hinissan P.; Adamson, Amy L., E-mail: aladamso@uncg.edu

    2013-09-15

    As new influenza virus strains emerge, finding new mechanisms to control infection is imperative. In this study, we found that we could control influenza infection of mammalian cells by altering the level of glucose given to cells. Higher glucose concentrations induced a dose-specific increase in influenza infection. Linking influenza virus infection with glycolysis, we found that viral replication was significantly reduced after cells were treated with glycolytic inhibitors. Addition of extracellular ATP after glycolytic inhibition restored influenza infection. We also determined that higher levels of glucose promoted the assembly of the vacuolar-type ATPase within cells, and increased vacuolar-type ATPase proton-transport activity. The increase of viral infection via high glucose levels could be reversed by inhibition of the proton pump, linking glucose metabolism, vacuolar-type ATPase activity, and influenza viral infection. Taken together, we propose that altering glucose metabolism may be a potential new approach to inhibit influenza viral infection. - Highlights: • Increased glucose levels increase Influenza A viral infection of MDCK cells. • Inhibition of the glycolytic enzyme hexokinase inhibited Influenza A viral infection. • Inhibition of hexokinase induced disassembly the V-ATPase. • Disassembly of the V-ATPase and Influenza A infection was bypassed with ATP. • The state of V-ATPase assembly correlated with Influenza A infection of cells.

  18. Glycolytic control of vacuolar-type ATPase activity: A mechanism to regulate influenza viral infection

    International Nuclear Information System (INIS)

    Kohio, Hinissan P.; Adamson, Amy L.

    2013-01-01

    As new influenza virus strains emerge, finding new mechanisms to control infection is imperative. In this study, we found that we could control influenza infection of mammalian cells by altering the level of glucose given to cells. Higher glucose concentrations induced a dose-specific increase in influenza infection. Linking influenza virus infection with glycolysis, we found that viral replication was significantly reduced after cells were treated with glycolytic inhibitors. Addition of extracellular ATP after glycolytic inhibition restored influenza infection. We also determined that higher levels of glucose promoted the assembly of the vacuolar-type ATPase within cells, and increased vacuolar-type ATPase proton-transport activity. The increase of viral infection via high glucose levels could be reversed by inhibition of the proton pump, linking glucose metabolism, vacuolar-type ATPase activity, and influenza viral infection. Taken together, we propose that altering glucose metabolism may be a potential new approach to inhibit influenza viral infection. - Highlights: • Increased glucose levels increase Influenza A viral infection of MDCK cells. • Inhibition of the glycolytic enzyme hexokinase inhibited Influenza A viral infection. • Inhibition of hexokinase induced disassembly the V-ATPase. • Disassembly of the V-ATPase and Influenza A infection was bypassed with ATP. • The state of V-ATPase assembly correlated with Influenza A infection of cells

  19. Virological Blips and Predictors of Post Treatment Viral Control After Stopping ART Started in Primary HIV Infection.

    Science.gov (United States)

    Fidler, Sarah; Olson, Ashley D; Bucher, Heiner C; Fox, Julie; Thornhill, John; Morrison, Charles; Muga, Roberto; Phillips, Andrew; Frater, John; Porter, Kholoud

    2017-02-01

    Few individuals commencing antiretroviral therapy (ART) in primary HIV infection (PHI) maintain undetectable viremia after treatment cessation. Associated factors remain unclear given the importance of the phenomenon to cure research. Using CASCADE data of seroconverters starting ART in PHI (≤6 months from seroconversion), we estimated proportions experiencing viral blips (>400 copies followed by HIV-RNA/mL without alteration of regimen) while on ART. We used Cox models to examine the association between time from ART stop to loss of control (2 consecutive measurements >1000 copies per milliliter) and magnitude and frequency of blips while on ART, time from seroconversion to ART, time on ART, adjusting for mean number of HIV-RNA measurements/year while on ART, and other confounders. Seven hundred seventy-eight seroconverters started ART in PHI with ≥3 HIV-RNA measurements. Median interquartile range (IQR) ART duration was 16.2 (8.0-35.9) months, within which we observed 13% with ≥1 blip. Of 228 who stopped ART, 119 rebounded; time to loss of control was associated with longer interval between seroconversion and ART initiation [hazard ratio (HR) = 1.16 per month; 1.04, 1.28], and blips while on ART (HR = 1.71 per blip; 95% confidence interval = 0.94 to 3.10). Longer time on ART (HR = 0.84 per additional month; 0.76, 0.92) was associated with lower risk of losing control. Of 228 stopping ART, 22 (10%) maintained post treatment control (PTC), ie, HIV-RNA HIV viral blips on therapy are associated with subsequent viral rebound on stopping ART among individuals treated in PHI. Longer duration on ART is associated with a greater chance of PTC.

  20. Baicalin benefits the anti-HBV therapy via inhibiting HBV viral RNAs

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Hai, E-mail: HHai3552@sina.cn [Department of Microbiology and Biopharmacy, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203 (China); Zhou, Wei, E-mail: zhouw@fudan.edu.cn [Department of Chemistry, Fudan University, 220 Han Dan Road, Shanghai 200433 (China); Zhu, Haiyan, E-mail: haiyanzhu@fudan.edu.cn [Department of Microbiology and Biopharmacy, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203 (China); Zhou, Pei, E-mail: pzhou@shmu.edu.cn [Department of Microbiology and Biopharmacy, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203 (China); Shi, Xunlong, E-mail: xunlongshi@fudan.edu.cn [Department of Microbiology and Biopharmacy, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203 (China)

    2017-05-15

    Background: Although current antiviral treatments (nucleoside analogs, NAs) for chronic hepatitis B virus (HBV) infection are effective in suppressing HBV-DNA replication, their clinical outcomes can be compromised by the increasing drug resistance and the inefficiency in promoting HBsAg/HBeAg seroconversion. Objectives: In this study, we will explore possible effects and mechanism of a natural product baicalin (BA) with the anti-HBV efficacy of entecavir (ETV), a first-line anti-HBV drug, in HBV-DNA, HBsAg/HBeAg seroconversion and drug-resistance. Methods: The co-effects of BA and ETV were conducted in wild-type/NA-resistance mutant HBV cell lines and DHBV-infected duckling models. HBV-DNA/RNAs, HBsAg/HBeAg, host factors (hepatocyte nuclear factors) were explored for possible anti-HBV mechanism. Results and discussion: BA could significantly enhance and reduced HBsAg and HBeAg in hepG2.2.15, a wild-type HBV cell line. Co-treatment of BA and ETV had a more dramatic effect in NA-resistant HBV{sup rtM204V/rtLl80M} transfected hepG2 cells. Our study further revealed that BA mainly inhibited the production of HBV RNAs (3.5, 2.4, 2.1 kb), the templates for viral proteins and HBV-DNA synthesis. BA blocked HBV RNAs transcription possibly by down-regulating transcription and expression of HBV replication dependent hepatocyte nuclear factors (HNF1α and HNF4α). Thus, BA may benefit the anti-HBV therapy via inhibiting HBV viral RNAs. - Highlights: • Baicalin benefits the anti-HBV therapy. • Baicalin enhances ETV antiviral efficacy and overcomes NA-resistant HBV mutation. • The anti-HBV effect of baicalin is achieved by inhibiting HBV RNAs. • Baicalin down-regulates HBV replication-dependent host factors HNF 1α and HNF 4α.

  1. Structural equation modelling of viral tropism reveals its impact on achieving viral suppression within 6 months in treatment-naive HIV-1-infected patients after combination antiretroviral therapy.

    Science.gov (United States)

    Mengoli, Carlo; Andreis, Samantha; Scaggiante, Renzo; Cruciani, Mario; Bosco, Oliviero; Ferretto, Roberto; Leoni, Davide; Maffongelli, Gaetano; Basso, Monica; Torti, Carlo; Sarmati, Loredana; Andreoni, Massimo; Palù, Giorgio; Parisi, Saverio Giuseppe

    2017-01-01

    To evaluate the role of pre-treatment co-receptor tropism of plasma HIV on the achievement of viral suppression (plasma HIV RNA 1.69 log 10 copies/mL) at the sixth month of combination antiretroviral therapy (cART) in a cohort of naive patients using, for the first time in this context, a path analysis (PA) approach. Adult patients with chronic infection by subtype B HIV-1 were consecutively enrolled from the start of first-line cART (T0). Genotypic analysis of viral tropism was performed on plasma and interpreted using the bioinformatic tool Geno2pheno, with a false positive rate of 10%. A Bayesian network starting from the viro-immunological data at T0 and at the sixth month of treatment (T1) was set up and this model was evaluated using a PA approach. A total of 262 patients (22.1% bearing an X4 virus) were included; 178 subjects (67.9%) achieved viral suppression. A significant positive indirect effect of bearing X4 virus in plasma at T0 on log 10 HIV RNA at T1 was detected (P = 0.009), the magnitude of this effect was, however, over 10-fold lower than the direct effect of log 10 HIV RNA at T0 on log 10 HIV RNA at T1 (P = 0.000). Moreover, a significant positive indirect effect of bearing an X4 virus on log 10 HIV RNA at T0 (P = 0.003) was apparent. PA overcame the limitations implicit in common multiple regression analysis and showed the possible role of pre-treatment viral tropism at the recommended threshold on the outcome of plasma viraemia in naive patients after 6 months of therapy. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. Modeling Viral Infectious Diseases and Development of Antiviral Therapies Using Human Induced Pluripotent Stem Cell-Derived Systems.

    Science.gov (United States)

    Trevisan, Marta; Sinigaglia, Alessandro; Desole, Giovanna; Berto, Alessandro; Pacenti, Monia; Palù, Giorgio; Barzon, Luisa

    2015-07-13

    The recent biotechnology breakthrough of cell reprogramming and generation of induced pluripotent stem cells (iPSCs), which has revolutionized the approaches to study the mechanisms of human diseases and to test new drugs, can be exploited to generate patient-specific models for the investigation of host-pathogen interactions and to develop new antimicrobial and antiviral therapies. Applications of iPSC technology to the study of viral infections in humans have included in vitro modeling of viral infections of neural, liver, and cardiac cells; modeling of human genetic susceptibility to severe viral infectious diseases, such as encephalitis and severe influenza; genetic engineering and genome editing of patient-specific iPSC-derived cells to confer antiviral resistance.

  3. Modeling Viral Infectious Diseases and Development of Antiviral Therapies Using Human Induced Pluripotent Stem Cell-Derived Systems

    Directory of Open Access Journals (Sweden)

    Marta Trevisan

    2015-07-01

    Full Text Available The recent biotechnology breakthrough of cell reprogramming and generation of induced pluripotent stem cells (iPSCs, which has revolutionized the approaches to study the mechanisms of human diseases and to test new drugs, can be exploited to generate patient-specific models for the investigation of host–pathogen interactions and to develop new antimicrobial and antiviral therapies. Applications of iPSC technology to the study of viral infections in humans have included in vitro modeling of viral infections of neural, liver, and cardiac cells; modeling of human genetic susceptibility to severe viral infectious diseases, such as encephalitis and severe influenza; genetic engineering and genome editing of patient-specific iPSC-derived cells to confer antiviral resistance.

  4. Buccal viral DNA as a trigger for brincidofovir therapy in the mousepox model of smallpox.

    Science.gov (United States)

    Crump, Ryan; Korom, Maria; Buller, R Mark; Parker, Scott

    2017-03-01

    Orthopoxviruses continue to pose a significant threat to the population as potential agents of bioterrorism. An intentional release of natural or engineered variola virus (VARV) or monkeypox viruses would cause mortality and morbidity in the target population. To address this, antivirals have been developed and evaluated in animal models of smallpox and monkeypox. One such antiviral, brincidofovir (BCV, previously CMX001), has demonstrated high levels of efficacy against orthopoxviruses in animal models and is currently under clinical evaluation for prevention and treatment of diseases caused by cytomegaloviruses and adenoviruses. In this study we use the mousepox model of smallpox to evaluate the relationship between the magnitude of the infectious virus dose and an efficacious BCV therapy outcome when treatment is initiated concomitant with detection of ectromelia virus viral DNA (vDNA) in mouse buccal swabs. We found that vDNA could be detected in buccal swabs of some, but not all infected mice over a range of challenge doses by day 3 or 4 postexposure, when initiation of BCV treatment was efficacious, suggesting that detection of vDNA in buccal swabs could be used as a trigger to initiate BCV treatment of an entire potentially exposed population. However, buccal swabs of some mice did not become positive until 5 days postexposure, when initiation of BCV therapy failed to protect mice that received high doses of virus. And finally, the data suggest that the therapeutic window for efficacious BCV treatment decreases as the virus infectious dose increases. Extrapolating these findings to VARV, the data suggest that treatment should be initiated as soon as possible after exposure and not rely on a diagnostic tool such as the measurement of vDNA in buccal cavity swabs; however, consideration should be given to the fact that the behavior/disease-course of VARV in humans is different from that of ectromelia virus in the mouse. Copyright © 2016 Elsevier B.V. All

  5. The current status of oncolytic viral therapy for head and neck cancer

    Directory of Open Access Journals (Sweden)

    Matthew O. Old

    2016-06-01

    Full Text Available Objective: Cancer affects the head and neck region frequently and leads to significant morbidity and mortality. Oncolytic viral therapy has the potential to make a big impact in cancers that affect the head and neck. We intend to review the current state of oncolytic viruses in the treatment of cancers that affect the head and neck region. Method: Data sources are from National clinical trials database, literature, and current research. Results: There are many past and active trials for oncolytic viruses that show promise for treating cancers of the head and neck. The first oncolytic virus was approved by the FDA October 2015 (T-VEC, Amgen for the treatment of melanoma. Active translational research continues for this and many other oncolytic viruses. Conclusion: The evolving field of oncolytic viruses is impacting the treatment of head and neck cancer and further trials and agents are moving forward in the coming years. Keywords: Head and neck squamous cell carcinoma, Oncolytic viruses, Clinical trials, Novel therapeutics

  6. Pillbox organizers are associated with improved adherence to HIV antiretroviral therapy and viral suppression: a marginal structural model analysis.

    Science.gov (United States)

    Petersen, Maya L; Wang, Yue; van der Laan, Mark J; Guzman, David; Riley, Elise; Bangsberg, David R

    2007-10-01

    Pillbox organizers are inexpensive and easily used; however, their effect on adherence to antiretroviral medications is unknown. Data were obtained from an observational cohort of 245 human immunodeficiency virus (HIV)-infected subjects who were observed from 1996 through 2000 in San Francisco, California. Adherence was the primary outcome and was measured using unannounced monthly pill counts. Plasma HIV RNA level was considered as a secondary outcome. Marginal structural models were used to estimate the effect of pillbox organizer use on adherence and viral suppression, adjusting for confounding by CD4+ T cell count, viral load, prior adherence, recreational drug use, demographic characteristics, and current and past treatment. Pillbox organizer use was estimated to improve adherence by 4.1%-4.5% and was associated with a decrease in viral load of 0.34-0.37 log10 copies/mL and a 14.2%-15.7% higher probability of achieving a viral load organizers appear to significantly improve adherence to antiretroviral therapy and to improve virologic suppression. We estimate that pillbox organizers may be associated with a cost of approximately $19,000 per quality-adjusted life-year. Pillbox organizers should be a standard intervention to improve adherence to antiretroviral therapy.

  7. Restored Circulating Invariant NKT Cells Are Associated with Viral Control in Patients with Chronic Hepatitis B

    Science.gov (United States)

    Jiang, Xiaotao; Zhang, Mingxia; Lai, Qintao; Huang, Xuan; Li, Yongyin; Sun, Jian; Abbott, William G.H.; Ma, Shiwu; Hou, Jinlin

    2011-01-01

    Invariant NKT (iNKT) cells are involved in the pathogenesis of various infectious diseases. However, their role in hepatitis B virus (HBV) infection is not fully understood, especially in human species. In this study, 35 chronic hepatitis B (CHB) patients, 25 inactive carriers (IC) and 36 healthy controls (HC) were enrolled and the proportions of circulating iNKT cells in fresh isolated peripheral blood mononuclear cells (PBMC) were detected by flow cytometry. A longitudinal analysis was also conducted in 19 CHB patients who received antiviral therapy with telbivudine. Thereafter, the immune functions of iNKT cells were evaluated by cytokine secretion and a two-chamber technique. The median frequency of circulating iNKT cells in CHB patients (0.13%) was lower than that in HC (0.24%, P = 0.01) and IC (0.19%, P = 0.02), and increased significantly during antiviral therapy with telbivudine (P = 0.0176). The expressions of CC chemokine receptor 5 (CCR5) and CCR6 were dramatically higher on iNKT cells (82.83%±9.87%, 67.67%±16.83% respectively) than on conventional T cells (30.5%±5.65%, 14.02%±5.92%, both P<0.001) in CHB patients. Furthermore, iNKT cells could migrate toward the CC chemokine ligand 5. Patients with a high ratio (≥1.0) of CD4−/CD4+ iNKT cells at baseline had a higher rate (58.33%) of HBeAg seroconversion than those with a low ratio (<1.0, 0%, P = 0.0174). In conclusion, there is a low frequency of peripheral iNKT cells in CHB patients, which increases to normal levels with viral control. The ratio of CD4−/CD4+ iNKT cells at baseline may be a useful predictor for HBeAg seroconversion in CHB patients on telbivudine therapy. PMID:22194934

  8. CLINICAL EFFICACY OF IBUPROFEN IN THERAPY FOR VIRAL UPPER RESPIRATORY TRACT INFECTIONS IN INFANTS

    Directory of Open Access Journals (Sweden)

    I.O. Skugarevskaya

    2006-01-01

    Full Text Available A study of use of ibuprofen in cases of viral upper respiratory tract infections (Vuri in children of early childhood has proved its' safety and efficacy. This medical agent has not only terminate fever but also diminished some other symptoms of Vuri.Key words: ibuprofen, viral upper respiratory tract infections, children.

  9. Impact of Active Drug Use on Antiretroviral Therapy Adherence and Viral Suppression in HIV-infected Drug Users

    OpenAIRE

    Arnsten, Julia H; Demas, Penelope A; Grant, Richard W; Gourevitch, Marc N; Farzadegan, Homayoon; Howard, Andrea A; Schoenbaum, Ellie E

    2002-01-01

    Despite a burgeoning literature on adherence to HIV therapies, few studies have examined the impact of ongoing drug use on adherence and viral suppression, and none of these have utilized electronic monitors to quantify adherence among drug users. We used 262 electronic monitors to measure adherence with all antiretrovirals in 85 HIV-infected current and former drug users, and found that active cocaine use, female gender, not receiving Social Security benefits, not being married, screening po...

  10. Proton beam therapy control system

    Science.gov (United States)

    Baumann, Michael A [Riverside, CA; Beloussov, Alexandre V [Bernardino, CA; Bakir, Julide [Alta Loma, CA; Armon, Deganit [Redlands, CA; Olsen, Howard B [Colton, CA; Salem, Dana [Riverside, CA

    2008-07-08

    A tiered communications architecture for managing network traffic in a distributed system. Communication between client or control computers and a plurality of hardware devices is administered by agent and monitor devices whose activities are coordinated to reduce the number of open channels or sockets. The communications architecture also improves the transparency and scalability of the distributed system by reducing network mapping dependence. The architecture is desirably implemented in a proton beam therapy system to provide flexible security policies which improve patent safety and facilitate system maintenance and development.

  11. CRISPR/Cas9-Mediated Knockin Application in Cell Therapy: A Non-viral Procedure for Bystander Treatment of Glioma in Mice

    Directory of Open Access Journals (Sweden)

    Oscar Meca-Cortés

    2017-09-01

    Full Text Available The use of non-viral procedures, together with CRISPR/Cas9 genome-editing technology, allows the insertion of single-copy therapeutic genes at pre-determined genomic sites, overcoming safety limitations resulting from random gene insertions of viral vectors with potential for genome damage. In this study, we demonstrate that combination of non-viral gene delivery and CRISPR/Cas9-mediated knockin via homology-directed repair can replace the use of viral vectors for the generation of genetically modified therapeutic cells. We custom-modified human adipose mesenchymal stem cells (hAMSCs, using electroporation as a transfection method and CRISPR/Cas9-mediated knockin for the introduction and stable expression of a 3 kb DNA fragment including the eGFP (selectable marker and a variant of the herpes simplex virus 1 thymidine kinase genes (therapeutic gene, under the control of the human elongation factor 1 alpha promoter in exon 5 of the endogenous thymidine kinase 2 gene. Using a U87 glioma model in SCID mice, we show that the therapeutic capacity of the new CRISPR/Cas9-engineered hAMSCs is equivalent to that of therapeutic hAMSCs generated by introduction of the same therapeutic gene by transduction with a lentiviral vector previously published by our group. This strategy should be of general use to other applications requiring genetic modification of therapeutic cells. Keywords: CRISPR/Cas9, cell therapy, mesenchymal stem cells, bystander suicide therapy, glioblastoma, non-invasive bioluminescence imaging, CRISPR/Cas9, CRISPR/Cas9 knockin

  12. “Computerized Counseling Reduces HIV-1 Viral Load and Sexual Transmission Risk: Findings from a Randomized Controlled Trial”

    Science.gov (United States)

    KURTH, Ann E.; SPIELBERG, Freya; CLELAND, Charles M.; LAMBDIN, Barrot; BANGSBERG, David R.; FRICK, Pamela A.; SEVERYNEN, Anneleen O.; CLAUSEN, Marc; NORMAN, Robert G.; LOCKHART, David; SIMONI, Jane M.; HOLMES, King K.

    2014-01-01

    Objective Evaluate a computerized intervention supporting antiretroviral therapy (ART) adherence and HIV transmission prevention. Design Longitudinal RCT. Settings An academic HIV clinic and a community-based organization in Seattle. Subjects 240 HIV-positive adults on ART; 209 completed nine-month follow-up (87% retention). Intervention Randomization to computerized counseling or assessment-only, 4 sessions over 9 months. Main Outcome Measures HIV-1 viral suppression, and self-reported ART adherence, and transmission risks, compared using generalized estimating equations. Results Overall, intervention participants had reduced viral load (VL): mean 0.17 log10 decline, versus 0.13 increase in controls, p = 0.053, and significant difference in ART adherence baseline to 9 months (p = 0.046). Their sexual transmission risk behaviors decreased (OR = 0.55, p = 0.020), a reduction not seen among controls (OR = 1.1, p = 0.664), and a significant difference in change (p = 0.040). Intervention effect was driven by those most in need: among those with detectable virus at baseline (>30 copies/milliliter, n=89), intervention effect was mean 0.60 log10 VL decline versus 0.15 increase in controls, p=0.034. ART adherence at the final follow-up was 13 points higher among intervention participants versus controls, p = 0.038. Conclusions Computerized counseling is promising for integrated ART adherence and safer sex, especially for individuals with problems in these areas. This is the first intervention to report improved ART adherence, viral suppression, and reduced secondary sexual transmission risk behavior. PMID:24384803

  13. Portal control of viral prohead expansion and DNA packaging

    International Nuclear Information System (INIS)

    Ray, Krishanu; Oram, Mark; Ma, Jinxia; Black, Lindsay W.

    2009-01-01

    Bacteriophage T4 terminase packages DNA in vitro into empty small or large proheads (esps or elps). In vivo maturation of esps yields the more stable and voluminous elps required to contain the 170 kb T4 genome. Functional proheads can be assembled containing portal-GFP fusion proteins. In the absence of terminase activity these accumulated in esps in vivo, whereas wild-type portals were found in elps. By nuclease protection assay dsDNAs of lengths 0.1, 0.2, 0.5, 5, 11, 20, 40 or 170 kb were efficiently packaged into wild-type elps in vitro, but less so into esps and gp20-GFP elps; particularly with DNAs shorter than 11 kb. However, 0.1 kb substrates were equally efficiently packaged into all types of proheads as judged by fluorescence correlation spectroscopy. These data suggest the portal controls the expansion of the major capsid protein lattice during prohead maturation, and that this expansion is necessary for DNA protection but not for packaging.

  14. Development of Non-Viral, Trophoblast-Specific Gene Delivery for Placental Therapy.

    Directory of Open Access Journals (Sweden)

    Noura Abd Ellah

    Full Text Available Low birth weight is associated with both short term problems and the fetal programming of adult onset diseases, including an increased risk of obesity, diabetes and cardiovascular disease. Placental insufficiency leading to intrauterine growth restriction (IUGR contributes to the prevalence of diseases with developmental origins. Currently there are no therapies for IUGR or placental insufficiency. To address this and move towards development of an in utero therapy, we employ a nanostructure delivery system complexed with the IGF-1 gene to treat the placenta. IGF-1 is a growth factor critical to achieving appropriate placental and fetal growth. Delivery of genes to a model of human trophoblast and mouse placenta was achieved using a diblock copolymer (pHPMA-b-pDMAEMA complexed to hIGF-1 plasmid DNA under the control of trophoblast-specific promoters (Cyp19a or PLAC1. Transfection efficiency of pEGFP-C1-containing nanocarriers in BeWo cells and non-trophoblast cells was visually assessed via fluorescence microscopy. In vivo transfection and functionality was assessed by direct placental-injection into a mouse model of IUGR. Complexes formed using pHPMA-b-pDMAEMA and CYP19a-923 or PLAC1-modified plasmids induce trophoblast-selective transgene expression in vitro, and placental injection of PLAC1-hIGF-1 produces measurable RNA expression and alleviates IUGR in our mouse model, consequently representing innovative building blocks towards human placental gene therapies.

  15. Current status and strategies for the control of viral hepatitis A in Korea.

    Science.gov (United States)

    Yoon, Eileen L; Sinn, Dong Hyun; Lee, Hyun Woong; Kim, Ji Hoon

    2017-09-01

    Hepatitis A virus is one of the most frequent causes of foodborne infection, which is closely associated with sanitary conditions and hygienic practices. The clinical spectrum of acute hepatitis A is wide, ranging from mild case without any noticeable symptoms to severe case with acute liver failure leading to mortality. The severity and outcome are highly correlated with age at infection. In developing countries, most people are infected in early childhood without significant symptom. Ironically, in area where sanitary condition has improved rapidly, adults who do not have immunity for viral hepatitis A (VH-A) in early childhood is accumulating. Adults without immunity are exposed to risks of symptomatic disease and large outbreaks in society. In Korea, where hygiene has improved rapidly, acute hepatitis A is a significant health burden that needs to be managed with nationwide health policy. The incidence of symptomatic VH-A has increased since 2000 and peaked in 2009. Korea has designated hepatitis A as a group 1 nationally notifiable infectious disease in 2001. Since 2001, mandatory surveillance system has been established to detect every single case of acute hepatitis A. Universal, nationwide vaccination program for newborns was introduced in 2015. In this review, we will present the current epidemiologic status of viral hepatitis A, and evaluate the effectiveness of the current nationwide strategies for the control of viral hepatitis A in Korea. Furthermore, we presented some action proposals that can help eliminate viral hepatitis A, which is a significant health burden in Korea.

  16. Definitive Management of Oligometastatic Melanoma in a Murine Model Using Combined Ablative Radiation Therapy and Viral Immunotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Blanchard, Miran [Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota (United States); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Shim, Kevin G. [Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota (United States); Department of Immunology, Mayo Clinic, Rochester, Minnesota (United States); Grams, Michael P. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Rajani, Karishma; Diaz, Rosa M. [Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota (United States); Furutani, Keith M. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Thompson, Jill [Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota (United States); Olivier, Kenneth R.; Park, Sean S. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Markovic, Svetomir N. [Department of Immunology, Mayo Clinic, Rochester, Minnesota (United States); Department of Medical Oncology, Mayo Clinic, Rochester, Minnesota (United States); Pandha, Hardev [The Postgraduate Medical School, University of Surrey, Guildford (United Kingdom); Melcher, Alan [Leeds Institute of Cancer Studies and Pathology, University of Leeds, Leeds (United Kingdom); Harrington, Kevin [Targeted Therapy Laboratory, The Institute of Cancer Research, London (United Kingdom); Zaidi, Shane [Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota (United States); Targeted Therapy Laboratory, The Institute of Cancer Research, London (United Kingdom); Vile, Richard, E-mail: vile.richard@mayo.edu [Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota (United States); Department of Immunology, Mayo Clinic, Rochester, Minnesota (United States); Leeds Institute of Cancer Studies and Pathology, University of Leeds, Leeds (United Kingdom)

    2015-11-01

    Purpose: The oligometastatic state is an intermediate state between a malignancy that can be completely eradicated with conventional modalities and one in which a palliative approach is undertaken. Clinically, high rates of local tumor control are possible with stereotactic ablative radiation therapy (SABR), using precisely targeted, high-dose, low-fraction radiation therapy. However, in oligometastatic melanoma, virtually all patients develop progression systemically at sites not initially treated with ablative radiation therapy that cannot be managed with conventional chemotherapy and immunotherapy. We have demonstrated in mice that intravenous administration of vesicular stomatitis virus (VSV) expressing defined tumor-associated antigens (TAAs) generates systemic immune responses capable of clearing established tumors. Therefore, in the present preclinical study, we tested whether the combination of systemic VSV-mediated antigen delivery and SABR would be effective against oligometastatic disease. Methods and Materials: We generated a model of oligometastatic melanoma in C57BL/6 immunocompetent mice and then used a combination of SABR and systemically administered VSV-TAA viral immunotherapy to treat both local and systemic disease. Results: Our data showed that SABR generates excellent control or cure of local, clinically detectable, and accessible tumor through direct cell ablation. Also, the immunotherapeutic activity of systemically administered VSV-TAA generated T-cell responses that cleared subclinical metastatic tumors. We also showed that SABR induced weak T-cell-mediated tumor responses, which, particularly if boosted by VSV-TAA, might contribute to control of local and systemic disease. In addition, VSV-TAA therapy alone had significant effects on control of both local and metastatic tumors. Conclusions: We have shown in the present preliminary murine study using a single tumor model that this approach represents an effective, complementary

  17. Definitive Management of Oligometastatic Melanoma in a Murine Model Using Combined Ablative Radiation Therapy and Viral Immunotherapy

    International Nuclear Information System (INIS)

    Blanchard, Miran; Shim, Kevin G.; Grams, Michael P.; Rajani, Karishma; Diaz, Rosa M.; Furutani, Keith M.; Thompson, Jill; Olivier, Kenneth R.; Park, Sean S.; Markovic, Svetomir N.; Pandha, Hardev; Melcher, Alan; Harrington, Kevin; Zaidi, Shane; Vile, Richard

    2015-01-01

    Purpose: The oligometastatic state is an intermediate state between a malignancy that can be completely eradicated with conventional modalities and one in which a palliative approach is undertaken. Clinically, high rates of local tumor control are possible with stereotactic ablative radiation therapy (SABR), using precisely targeted, high-dose, low-fraction radiation therapy. However, in oligometastatic melanoma, virtually all patients develop progression systemically at sites not initially treated with ablative radiation therapy that cannot be managed with conventional chemotherapy and immunotherapy. We have demonstrated in mice that intravenous administration of vesicular stomatitis virus (VSV) expressing defined tumor-associated antigens (TAAs) generates systemic immune responses capable of clearing established tumors. Therefore, in the present preclinical study, we tested whether the combination of systemic VSV-mediated antigen delivery and SABR would be effective against oligometastatic disease. Methods and Materials: We generated a model of oligometastatic melanoma in C57BL/6 immunocompetent mice and then used a combination of SABR and systemically administered VSV-TAA viral immunotherapy to treat both local and systemic disease. Results: Our data showed that SABR generates excellent control or cure of local, clinically detectable, and accessible tumor through direct cell ablation. Also, the immunotherapeutic activity of systemically administered VSV-TAA generated T-cell responses that cleared subclinical metastatic tumors. We also showed that SABR induced weak T-cell-mediated tumor responses, which, particularly if boosted by VSV-TAA, might contribute to control of local and systemic disease. In addition, VSV-TAA therapy alone had significant effects on control of both local and metastatic tumors. Conclusions: We have shown in the present preliminary murine study using a single tumor model that this approach represents an effective, complementary

  18. Environmental viral contamination in a pediatric hospital outpatient waiting area: implications for infection control.

    Science.gov (United States)

    D'Arcy, Nikki; Cloutman-Green, Elaine; Klein, Nigel; Spratt, David A

    2014-08-01

    Nosocomial outbreaks of viral etiology are costly and can have a major impact on patient care. Many viruses are known to persist in the inanimate environment and may pose a risk to patients and health care workers. We investigate the frequency of environmental contamination with common health care-associated viruses and explore the use of torque-teno virus as a marker of environmental contamination. Environmental screening for a variety of clinically relevant viruses was carried out over 3 months in a UK pediatric hospital using air sampling and surface swabbing. Swabs were tested for the presence of virus nucleic acid by quantitative polymerase chain reactions. Viral nucleic acid was found on surfaces and in the air throughout the screening period, with adenovirus DNA being the most frequent. Door handles were frequently contaminated. Torque-teno virus was also found at numerous sites. Evidence of environmental contamination with viral pathogens is present in health care environments and may be indicative of an infectious virus being present. Screening for viruses should be included in infection control strategies. Torque-teno virus may provide a better marker of contamination and reduce time and cost of screening for individual viruses. Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

  19. Genetic associations with viral respiratory illnesses and asthma control in children

    DEFF Research Database (Denmark)

    Loisel, D A; Du, G; Ahluwalia, T S

    2016-01-01

    of asthma control phenotypes was performed in 2128 children in the Copenhagen Prospective Study on Asthma in Childhood (COPSAC). Significant associations in RhinoGen were further validated using virus-induced wheezing illness and asthma phenotypes in an independent sample of 122 children enrolled...... in the Childhood Origins of Asthma (COAST) birth cohort study. RESULTS: A significant excess of P values smaller than 0.05 was observed in the analysis of the 10 RhinoGen phenotypes. Polymorphisms in 12 genes were significantly associated with variation in the four phenotypes showing a significant enrichment...... differences in childhood viral respiratory illnesses and virus-induced exacerbations of asthma. Defining mechanisms of these associations may provide insight into the pathogenesis of viral respiratory infections and virus-induced exacerbations of asthma....

  20. Alcohol use and depression: link with adherence and viral suppression in adult patients on antiretroviral therapy in rural Lesotho, Southern Africa: a cross-sectional study

    OpenAIRE

    Cerutti, Bernard; Broers, Barbara; Masetsibi, Motlomelo; Faturiyele, Olatunbosun; Toti-Mokoteli, Likabelo; Motlatsi, Mokete; Bader, Joelle; Klimkait, Thomas; Labhardt, Niklaus D

    2016-01-01

    Abstract Background Depression and alcohol use disorder have been shown to be associated with poor adherence to antiretroviral therapy (ART). Studies examining their association with viral suppression in rural Africa are, however, scarce. Methods This study reports prevalence of depressive symptoms and alcohol use disorder, and their potential association with adherence and viral suppression in adult patients on ART in ten clinics in rural Lesotho, Southern Africa. Results Among 1,388 adult p...

  1. RUNX2 Mediates Plasmacytoid Dendritic Cell Egress from the Bone Marrow and Controls Viral Immunity

    Directory of Open Access Journals (Sweden)

    Michaël Chopin

    2016-04-01

    Full Text Available Plasmacytoid dendritic cells (pDCs represent a unique immune cell type that responds to viral nucleic acids through the rapid production of type I interferons. Within the hematopoietic system, the transcription factor RUNX2 is exclusively expressed in pDCs and is required for their peripheral homeostasis. Here, we show that RUNX2 plays an essential role in promoting pDC localization and function. RUNX2 is required for the appropriate expression of the integrin-mediated adhesion machinery, as well as for the down-modulation of the chemokine receptor CXCR4, which allows pDC egress into the circulation. RUNX2 also facilitates the robust response to viral infection through the control of IRF7, the major regulator of type I interferon production. Mice lacking one copy of Runx2 have reduced numbers of peripheral pDCs and IFN-α expression, which might contribute to the reported difficulties of individuals with cleidocranial dysplasia, who are haploinsufficient for RUNX2, to clear viral infections.

  2. Viral infections in transplant recipients.

    Science.gov (United States)

    Razonable, R R; Eid, A J

    2009-12-01

    Solid organ and hematopoietic stem cell transplant recipients are uniquely predisposed to develop clinical illness, often with increased severity, due to a variety of common and opportunistic viruses. Patients may acquire viral infections from the donor (donor-derived infections), from reactivation of endogenous latent virus, or from the community. Herpes viruses, most notably cytomegalovirus and Epstein Barr virus, are the most common among opportunistic viral pathogens that cause infection after solid organ and hematopoietic stem cell transplantation. The polyoma BK virus causes opportunistic clinical syndromes predominantly in kidney and allogeneic hematopoietic stem cell transplant recipients. The agents of viral hepatitis B and C present unique challenges particularly among liver transplant recipients. Respiratory viral illnesses due to influenza, respiratory syncytial virus, and parainfluenza virus may affect all types of transplant recipients, although severe clinical disease is observed more commonly among lung and allogeneic hematopoietic stem cell transplant recipients. Less common viral infections affecting transplant recipients include those caused by adenoviruses, parvovirus B19, and West Nile virus. Treatment for viruses with proven effective antiviral drug therapies should be complemented by reduction in the degree of immunosuppression. For others with no proven antiviral drugs for therapy, reduction in the degree of immunosuppression remains as the sole effective strategy for management. Prevention of viral infections is therefore of utmost importance, and this may be accomplished through vaccination, antiviral strategies, and aggressive infection control measures.

  3. Prediction of therapy response to interferon-alpha in chronic viral hepatitis-B by liver and hepatobiliary scintigraphy

    International Nuclear Information System (INIS)

    Caglar, M.; Sari, O.; Akcan, Y.

    2002-01-01

    Interferon (IFN) provides effective treatment in some patients with chronic hepatitis. The clarification of factors predictive of therapy response would be helpful in identifying patients who would benefit from treatment. In this study, we evaluated the potential utility of Tc-99m sulfur colloid liver/spleen and Tc-99m-disofenin hepatobiliary scintigraphy to predict therapy response to IFN in patients with chronic active hepatitis. The study group consisted of ten patients with chronic viral hepatitis B who were treated with 4.5 units of interferon alpha for 12 months. Prior to the start of the therapy, sulfur colloid scintigraphy was obtained by which the liver/spleen ratios were derived. Hepatobiliary scintigraphy was performed on a separate day and time-activity curves were generated from regions of interest drawn over the liver, heart and gall-bladder. The index of blood and liver clearance time was calculated. Histological grading and laboratory values were obtained for clinical correlation. Responders (n=6) to IFN were defined as those who improved clinically with normalized transaminase levels and had hepatitis B envelope antigen (HBeAg) seroconversion. On sulfur colloid (SC) scintigraphy, the liver/spleen ratio of non-responders was significantly lower than responders (median values: 0.69 vs. 1.16, p=0.01) but on hepatobiliary scintigraphy no statistically significant parameters were found to predict response to interferon therapy. (author)

  4. Using viral e-mails to distribute tobacco control advertisements: an experimental investigation.

    Science.gov (United States)

    Carter, Owen B J; Donovan, Robert; Jalleh, Geoffrey

    2011-08-01

    The authors' objective was to conduct a trial of viral e-mail marketing as a distribution method for tobacco control advertisements. University students (n = 200) in the state of Western Australia were randomly allocated to receive 1 of 2 e-mails with hyperlinks to tobacco control advertisements ("Toilet" and "Rubbish") emphasizing the disgusting nature of smoking. Recipients followed a hyperlink to a Web page playing Toilet or Rubbish on endless loop. Viewers were encouraged to forward the e-mail to their friends and invited to complete an online survey about the advertisement. Unique downloads for each advertisement were identified by internet provider (IP) location and tallied by date and geographical location to assess subsequent dissemination beyond the initial 200 students. There were 826 unique viewings of the advertisements averaging 26.9 viewings per day for the first fortnight, followed by a lower average of 4.1 hits per day for the next 3.5 months. IP addresses identified hits from 3 other Australian states and 7 other countries. Online surveys were completed by 103 respondents (12.5% of total hits) but included few smokers (n = 9). Significantly more respondents rated Toilet as "funny" compared with Rubbish (40% vs. 11%; p e-mail sent but daily hits rapidly deteriorated over time. Entertainment appears to facilitate viral e-mails being forwarded onwards but only exceptionally compelling tobacco control materials are ever likely to become self-perpetuating.

  5. Dietary Selenium in Adjuvant Therapy of Viral and Bacterial Infections12

    Science.gov (United States)

    Steinbrenner, Holger; Al-Quraishy, Saleh; Dkhil, Mohamed A; Wunderlich, Frank; Sies, Helmut

    2015-01-01

    Viral and bacterial infections are often associated with deficiencies in macronutrients and micronutrients, including the essential trace element selenium. In selenium deficiency, benign strains of Coxsackie and influenza viruses can mutate to highly pathogenic strains. Dietary supplementation to provide adequate or supranutritional selenium supply has been proposed to confer health benefits for patients suffering from some viral diseases, most notably with respect to HIV and influenza A virus (IAV) infections. In addition, selenium-containing multimicronutrient supplements improved several clinical and lifestyle variables in patients coinfected with HIV and Mycobacterium tuberculosis. Selenium status may affect the function of cells of both adaptive and innate immunity. Supranutritional selenium promotes proliferation and favors differentiation of naive CD4-positive T lymphocytes toward T helper 1 cells, thus supporting the acute cellular immune response, whereas excessive activation of the immune system and ensuing host tissue damage are counteracted through directing macrophages toward the M2 phenotype. This review provides an up-to-date overview on selenium in infectious diseases caused by viruses (e.g., HIV, IAV, hepatitis C virus, poliovirus, West Nile virus) and bacteria (e.g., M. tuberculosis, Helicobacter pylori). Data from epidemiologic studies and intervention trials, with selenium alone or in combination with other micronutrients, and animal experiments are discussed against the background of dietary selenium requirements to alter immune functions. PMID:25593145

  6. Viral control in chronic HIV-1 subtype C infection is associated with enrichment of p24 IgG1 with Fc effector activity.

    Science.gov (United States)

    Chung, Amy; Makuba, Jenniffer M; Ndlovu, Bongiwe; Licht, Anna; Robinson, Hannah; Ramlakhan, Yathisha; Ghebremichael, Musie; Reddy, Tarylee; Goulder, Philip; Walker, Bruce; Ndung'u, Thumbi; Alter, Galit

    2018-04-03

    Postinfection HIV viral control and immune correlates analysis of the RV144 vaccine trial indicate a potentially critical role for Fc receptor-mediated antibody functions. However, the influence of functional antibodies in clade C infection is largely unknown. Plasma samples from 361 chronic subtype C-infected, antiretroviral therapy-naïve participants were tested for their HIV-specific isotype and subclass distributions, along with their Fc receptor-mediated functional potential. Total IgG, IgG subclasses and IgA binding to p24 clade B/C and gp120 consensus C proteins were assayed by multiplex. Antibody-dependent uptake of antigen-coated beads and Fc receptor-mediated natural killer cell degranulation were evaluated as surrogates for antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cellular cytotoxicity (ADCC), respectively. p24 IgG1 was the only subclass associated with viral control (P = 0.01), with higher p24-specific ADCP and ADCC responses detected in individuals with high p24 IgG1. Although p24 IgG1 levels were enriched in patients with elevated Gag-specific T-cell responses, these levels remained an independent predictor of low-viral loads (P = 0.04) and high CD4 counts (P = 0.004) after adjusting for Gag-specific T-cell responses and for protective HLA class I alleles. p24 IgG1 levels independently predict viral control in HIV-1 clade C infection. Whether these responses contribute to direct antiviral control via the recruited killing of infected cells via the innate immune system or simply mark a qualitatively superior immune response to HIV, is uncertain, but highlights the role of p24-specific antibodies in control of clade C HIV-1 infection.

  7. Correlates of HIV-1 viral suppression in a cohort of HIV-positive drug users receiving antiretroviral therapy in Hanoi, Vietnam

    Science.gov (United States)

    Jordan, Michael R; La, Hanh; Nguyen, Hien Duc; Sheehan, Heidi; Lien, Trinh Thi Minh; Van Dang, Duong; Hellinger, James; Wanke, Christine; Tang, Alice M

    2009-01-01

    Summary Injection drug users bear the burden of HIV in Vietnam and are a focus of national treatment programs. To date, determinants of successful therapy in this population are unknown. Substance use and clinical correlates of viral suppression were studied in 100 HIV-1 infected drug users receiving antiretroviral therapy (ART) for at least 6 months in Hanoi, Vietnam. Mean age of the cohort was 29.9 + 4.9 years; all were men. A majority of patients (73%) achieved viral suppression (HIV-RNA 95% adherence (p<0.01) and current use of trimethoprim/sulfamethoxazole (p<0.01); current or ever diagnosed with tuberculosis was associated with viral non-suppression (p=0.006). Tobacco use was prevalent (84%), and surprisingly 48% of patients reported active drug use; neither was associated with viral non-suppression. This is the first study to document successful ART treatment in a population of Vietnamese drug users; rates of viral suppression are comparable to other international populations. The 28% of patients without HIV-1 suppression highlights the need for adherence promotion, risk reduction programs, and population based surveillance strategies for assessing the emergence of HIV drug resistance in settings where access to viral load and drug resistance testing is limited. PMID:19451329

  8. Long-term control of recurrent or refractory viral infections after allogeneic HSCT with third-party virus-specific T cells.

    Science.gov (United States)

    Withers, Barbara; Blyth, Emily; Clancy, Leighton E; Yong, Agnes; Fraser, Chris; Burgess, Jane; Simms, Renee; Brown, Rebecca; Kliman, David; Dubosq, Ming-Celine; Bishop, David; Sutrave, Gaurav; Ma, Chun Kei Kris; Shaw, Peter J; Micklethwaite, Kenneth P; Gottlieb, David J

    2017-11-14

    Donor-derived adoptive T-cell therapy is a safe and effective treatment of viral infection posttransplant, but it is limited by donor serostatus and availability and by its personalized nature. Off-the-shelf, third-party virus-specific T cells (VSTs) appear promising, but the long-term safety and durability of responses have yet to be established. We conducted a prospective study of 30 allogeneic hemopoietic stem cell transplant (HSCT) patients with persistent or recurrent cytomegalovirus (CMV) (n = 28), Epstein-Barr virus (n = 1), or adenovirus (n = 1) after standard therapy. Patients were treated with infusions of partially HLA-matched, third-party, ex vivo-expanded VSTs (total = 50 infusions) at a median of 75 days post-HSCT (range, 37 to 349 days). Safety, viral dynamics, and immune recovery were monitored for 12 months. Infusions were safe and well tolerated. Acute graft versus host disease occurred in 2 patients, despite a median HLA match between VSTs and the recipient of 2 of 6 antigens. At 12 months, the cumulative incidence of overall response was 93%. Virological control was durable in the majority of patients; the reintroduction of antiviral therapy after the final infusion occurred in 5 patients. CMV-specific T-cell immunity rose significantly and coincided with a rise in CD8 + terminal effector cells. PD-1 expression was elevated on CD8 + lymphocytes before the administration of third-party T cells and remained elevated at the time of viral control. Third-party VSTs show prolonged benefit, with virological control achieved in association with the recovery of CD8 + effector T cells possibly facilitated by VST infusion. This trial was registered at www.clinicaltrials.gov as #NCT02779439 and www.anzctr.org.au as #ACTRN12613000603718.

  9. Effective photodynamic therapy in drug-resistant prostate cancer cells utilizing a non-viral antitumor vector (a secondary publication).

    Science.gov (United States)

    Yamauchi, Masaya; Honda, Norihiro; Hazama, Hisanao; Tachikawa, Shoji; Nakamura, Hiroyuki; Kaneda, Yasufumi; Awazu, Kunio

    2016-03-31

    There is an urgent need to develop an efficient strategy for the treatment of drug-resistant prostate cancer. Photodynamic therapy (PDT), in which low incident levels of laser energy are used to activate a photosensitizer taken up by tumor cells, is expected as a novel therapy for the treatment of prostate cancer because of the minimal invasive nature of PDT. The present study was designed to assess the efficacy of a novel vector approach combined with a conventional porphyrin-based photosensitizer. Our group focused on a non-viral vector (hemagglutinating virus of Japan envelope; HVJ-E) combined with protoporphyrin IX (PpIX) lipid, termed the porphyrus envelope (PE). It has been previously confirmed that HVJ-E has drug-delivering properties and can induce cancer-specific cell death. The PE (HVJ-E contained in PpIX lipid) was developed as a novel photosensitizer. In this study, the antitumor and PDT efficacy of the PE against hormone-antagonistic human prostate cancer cells (PC-3) were evaluated. Our results demonstrated that, under specific circumstances, PDT using the PE was very effective against PC-3 cells. A novel therapy for drug-resistant prostate cancer based on this vector approach is eagerly anticipated.

  10. Control strategy for viral diseases of salmonid fish, flounders and shrimp at hatchery and seed production facility in Japan

    OpenAIRE

    Yoshimizu, Mamoru

    2009-01-01

    Salmonid fish are important species for hatchery reared and released fish. Flounders and shrimp are also important species for seed production and sea-farming in Japan. Viral disease is one of the limitations of successful propagation of these species. Methods currently used to control viral diseases are 1) hygiene and sanitation in facilities, 2) disinfection of rearing and waste water using U. V. irradiation, ozonization and electrolyzation, 3) selection of pathogen-free brood stock by cell...

  11. Chitosan in Non-Viral Gene Delivery: Role of Structure, Characterization Methods, and Insights in Cancer and Rare Diseases Therapies

    Directory of Open Access Journals (Sweden)

    Beatriz Santos-Carballal

    2018-04-01

    Full Text Available Non-viral gene delivery vectors have lagged far behind viral ones in the current pipeline of clinical trials of gene therapy nanomedicines. Even when non-viral nanovectors pose less safety risks than do viruses, their efficacy is much lower. Since the early studies to deliver pDNA, chitosan has been regarded as a highly attractive biopolymer to deliver nucleic acids intracellularly and induce a transgenic response resulting in either upregulation of protein expression (for pDNA, mRNA or its downregulation (for siRNA or microRNA. This is explained as the consequence of a multi-step process involving condensation of nucleic acids, protection against degradation, stabilization in physiological conditions, cellular internalization, release from the endolysosome (“proton sponge” effect, unpacking and enabling the trafficking of pDNA to the nucleus or the siRNA to the RNA interference silencing complex (RISC. Given the multiple steps and complexity involved in the gene transfection process, there is a dearth of understanding of the role of chitosan’s structural features (Mw and degree of acetylation, DA% on each step that dictates the net transfection efficiency and its kinetics. The use of fully characterized chitosan samples along with the utilization of complementary biophysical and biological techniques is key to bridging this gap of knowledge and identifying the optimal chitosans for delivering a specific gene. Other aspects such as cell type and administration route are also at play. At the same time, the role of chitosan structural features on the morphology, size and surface composition of synthetic virus-like particles has barely been addressed. The ongoing revolution brought about by the recent discovery of CRISPR-Cas9 technology will undoubtedly be a game changer in this field in the short term. In the field of rare diseases, gene therapy is perhaps where the greatest potential lies and we anticipate that chitosans will be key players

  12. Structural Determinants of Antiretroviral Therapy Use, HIV Care Attendance, and Viral Suppression among Adolescents and Young Adults Living with HIV.

    Directory of Open Access Journals (Sweden)

    Shoshana Y Kahana

    Full Text Available The authors examined associations between structural characteristics and HIV disease management among a geographically diverse sample of behaviorally and perinatally HIV-infected adolescents and young adults in the United States.The sample included 1891 adolescents and young adults living with HIV (27.8% perinatally infected; 72.2% behaviorally infected who were linked to care through 20 Adolescent Medicine Trials Network for HIV/AIDS Interventions Units. All completed audio computer-assisted self-interview surveys. Chart abstraction or blood draw provided viral load data. Geographic-level variables were extracted from the United States Census Bureau (e.g., socioeconomic disadvantage, percent of Black and Latino households, percent rural and Esri Crime (e.g., global crime index databases as Zip Code Tabulation Areas. AIDSVu data (e.g., prevalence of HIV among youth were extracted at the county-level. Using HLM v.7, the authors conducted means-as-outcomes random effects multi-level models to examine the association between structural-level and individual-level factors and (1 being on antiretroviral therapy (ART currently; (2 being on ART for at least 6 months; (3 missed HIV care appointments (not having missed any vs. having missed one or more appointments over the past 12 months; and (4 viral suppression (defined by the corresponding assay cutoff for the lower limit of viral load at each participating site which denoted nondetectability vs. detectability.Frequencies for the 4 primary outcomes were as follows: current ART use (n = 1120, 59.23%; ART use for ≥6 months (n = 861, 45.53%; at least one missed HIV care appointment (n = 936, 49.50; and viral suppression (n = 577, 30.51%. After adjusting for individual-level factors, youth living in more disadvantaged areas (defined by a composite score derived from 2010 Census indicators including percent poverty, percent receiving public assistance, percent of female, single-headed households, percent

  13. PECULIARITIES OF CLINICAL TREATMENT, DIAGNOSTICS AND APPROACHES TO PAPILLOMA VIRAL THERAPY IN CHILDHOOD

    Directory of Open Access Journals (Sweden)

    L.P. Mazitova

    2006-01-01

    Full Text Available In recent years, human papillomavirus infection in childhood is an urgent problem in the practice of doctors of various specialties. The urgency of the problem is due to the widespread presence of the nosology, the difficulties of the therapy, the frequent recurrence of the disease. In addition, the pathogenesis of this disease in children is poorly understood, the optimal algorithm of examination of this group of patients is not defined which makes the therapy irrational and provides the lack of primary and secondary prevention methods.Keywords: papillomavirus, diagnosis, treatment, children.

  14. Analysis of Pan-European attitudes to the eradication and control of bovine viral diarrhoea.

    Science.gov (United States)

    Heffernan, C; Misturelli, F; Nielsen, L; Gunn, G J; Yu, J

    2009-02-07

    At present, national-level policies concerning the eradication and control of bovine viral diarrhoea (BVD) differ widely across Europe. Some Scandinavian countries have enacted strong regulatory frameworks to eradicate the disease, whereas other countries have few formal policies. To examine these differences, the attitudes of stakeholders and policy makers in 17 European countries were investigated. A web-based questionnaire was sent to policy makers, government and private sector veterinarians, and representatives of farmers' organisations. In total, 131 individuals responded to the questionnaire and their responses were analysed by applying a method used in sociolinguistics: frame analysis. The results showed that the different attitudes of countries that applied compulsory or voluntary frameworks were associated with different views about the attribution or blame for BVD and the roles ascribed to farmers and other stakeholders in its eradication and control.

  15. Relationship between viral load and behavioral measures of adherence to antiretroviral therapy in children living with human immunodeficiency virus in Latin America

    Directory of Open Access Journals (Sweden)

    Horacio A. Duarte

    2015-05-01

    Full Text Available Few studies have examined antiretroviral therapy adherence in Latin American children. Standardized behavioral measures were applied to a large cohort of human immunodeficiency virus-infected children in Brazil, Mexico, and Peru to assess adherence to prescribed antiretroviral therapy doses during the three days prior to study visits, assess timing of last missed dose, and evaluate the ability of the adherence measures to predict viral suppression. Time trends in adherence were modeled using a generalized estimating equations approach to account for possible correlations in outcomes measured repeatedly in the same participants. Associations of adherence with human immunodeficiency virus viral load were examined using linear regression. Mean enrollment age of the 380 participants was 5 years; 57.6% had undetectable’ viral load ( 0.3. Last time missed any antiretroviral therapy dose was reported as “never” for 52.0% at enrollment, increasing to 60.7% and 65.9% at the 6- and 12-month visits, respectively (p < 0.001 for test of trend. The proportion with undetectable viral load was higher among those who never missed a dose at enrollment and the 12-month visit (p ≤ 0.005, but not at the 6-month visit (p = 0.2. While antiretroviral therapy adherence measures utilized in this study showed some association with viral load for these Latin American children, they may not be adequate for reliably identifying non-adherence and consequently children at risk for viral resistance. Other strategies are needed to improve the evaluation of adherence in this population.

  16. Impact of viral hepatitis co-infection on response to antiretroviral therapy and HIV disease progression in the HIV-NAT cohort

    NARCIS (Netherlands)

    Law, W. Phillip; Duncombe, Chris J.; Mahanontharit, Apicha; Boyd, Mark A.; Ruxrungtham, Kiat; Lange, Joep M. A.; Phanuphak, Praphan; Cooper, David A.; Dore, Gregory J.

    2004-01-01

    OBJECTIVE: To examine the impact of viral hepatitis co-infection on HIV disease outcomes following commencement of combination antiretroviral therapy in a developing country setting. METHODS: HIV RNA suppression, CD4 cell count recovery, and HIV disease progression were examined within a cohort of

  17. Progress in developing cationic vectors for non-viral systemic gene therapy against cancer.

    OpenAIRE

    Morille , Marie; Passirani , Catherine; Vonarbourg , Arnaud; Clavreul , Anne; Benoit , Jean-Pierre

    2008-01-01

    International audience; Initially, gene therapy was viewed as an approach for treating hereditary diseases, but its potential role in the treatment of acquired diseases such as cancer is now widely recognized. The understanding of the molecular mechanisms involved in cancer and the development of nucleic acid delivery systems are two concepts that have led to this development. Systemic gene delivery systems are needed for therapeutic application to cells inaccessible by percutaneous injection...

  18. Therapy for influenza and acute respiratory viral infection in young and middle-aged schoolchildren: Effect of Ingavirin® on intoxication, fever, and catarrhal syndromes

    Directory of Open Access Journals (Sweden)

    I. M. Farber

    2016-01-01

    Full Text Available The paper presents the clinical results of a double-blind, randomized, placebo-controlled multicenter phase III study evaluating the clinical efficacy and safety of Ingavirin® capsules 30 mg at a daily dose of 60 mg for the treatment of influenza and other acute respiratory viral infections (ARVI in 7–12-year-old children.The study included 310 children of both sexes. The study participants took Ingavirin® 60 mg/day or placebo for 5 days. The drug was shown to be effective in normalizing temperature and alleviating intoxication and catarrhal syndromes just at day 3 of therapy. Ingavirin® was demonstrated to considerably reduce the risk of bacterial complications of ARVI/influenza, which require antibiotic therapy, which is important for clinical use in children. This clinical trial has shown the high safety and tolerance of the drug. Ingavirin® contributes to accelerated virus elimination, shorter disease duration, and lower risk of complications.

  19. A Different Perspective for Management of Diabetes Mellitus: Controlling Viral Liver Diseases.

    Science.gov (United States)

    Zhao, Yingying; Xing, Huichun

    2017-01-01

    Knowing how to prevent and treat diabetes mellitus (DM) earlier is essential to improving outcomes. Through participating in synthesis and catabolism of glycogen, the liver helps to regulate glucose homeostasis. Viral related liver diseases are associated with glycometabolism disorders, which means effective management of viral liver diseases may be a therapeutic strategy for DM. The present article reviews the correlation between DM and liver diseases to give an update of the management of DM rooted by viral liver diseases.

  20. Multiple parasitic and viral infections in a patient living with HIV/AIDS on antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    K Deepika

    2017-01-01

    Full Text Available Patients with human immunodeficiency virus (HIV infection are more prone for gastrointestinal infections causing diarrhoea, particularly with parasites. Parasitic infections have been regularly reported in such patients. A female patient confirmed positive for HIV 1 on antiretroviral therapy came with complaints of chronic diarrhoea for the past 7 months. Her initial CD4 count was 89 cells/μl of blood, and antibodies to cytomegalovirus and herpes simplex virus 1 and 2 virus were found to be positive in the patient's serum, but there was no HIV-associated retinopathy. Her stool examination showed decorticated fertilised eggs of Ascaris lumbricoides, cysts of Blastocystis sp. and Entamoeba species in the unconcentrated sample and oocysts of Cystoisospora species, egg of Schistosoma haematobium and eggs of Trichuris trichiura in the concentrated. The patient responded well to cotrimoxazole and albendazole, and repeat samples were negative for all these parasites.

  1. Intensive Insulin Therapy: Tight Blood Sugar Control

    Science.gov (United States)

    ... specific situation. McCulloch DK. General principles of insulin therapy in diabetes mellitus. http://www.uptodate.com/home. Accessed Dec. ... Diabetes Association. http://www.diabetes.org/living-with-diabetes/treatment-and-care/blood-glucose-control/checking-your-blood- ...

  2. Viral Hepatitis

    Science.gov (United States)

    ... Home A-Z Health Topics Viral hepatitis Viral hepatitis > A-Z Health Topics Viral hepatitis (PDF, 90 ... liver. Source: National Cancer Institute Learn more about hepatitis Watch a video. Learn who is at risk ...

  3. Alcohol use and depression: link with adherence and viral suppression in adult patients on antiretroviral therapy in rural Lesotho, Southern Africa: a cross-sectional study.

    Science.gov (United States)

    Cerutti, Bernard; Broers, Barbara; Masetsibi, Motlomelo; Faturiyele, Olatunbosun; Toti-Mokoteli, Likabelo; Motlatsi, Mokete; Bader, Joelle; Klimkait, Thomas; Labhardt, Niklaus D

    2016-09-08

    Depression and alcohol use disorder have been shown to be associated with poor adherence to antiretroviral therapy (ART). Studies examining their association with viral suppression in rural Africa are, however, scarce. This study reports prevalence of depressive symptoms and alcohol use disorder, and their potential association with adherence and viral suppression in adult patients on ART in ten clinics in rural Lesotho, Southern Africa. Among 1,388 adult patients (69 % women), 80.7 % were alcohol abstinent, 6.3 % were hazardous drinkers (men: 10.7 %, women: 4.4 %, p women 32.7 %, p suppression. Whereas the results of this study confirm previously reported association of alcohol use disorder with adherence to ART, there was no association with viral suppression. April 28th 2014; NCT02126696 .

  4. Anti-viral therapy is associated with improved survival but is underutilised in patients with hepatitis B virus-related hepatocellular carcinoma: real-world east and west experience.

    Science.gov (United States)

    Chen, V L; Yeh, M-L; Le, A K; Jun, M; Saeed, W K; Yang, J D; Huang, C-F; Lee, H Y; Tsai, P-C; Lee, M-H; Giama, N; Kim, N G; Nguyen, P P; Dang, H; Ali, H A; Zhang, N; Huang, J-F; Dai, C-Y; Chuang, W-L; Roberts, L R; Jun, D W; Lim, Y-S; Yu, M-L; Nguyen, M H

    2018-07-01

    Hepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma (HCC) worldwide. It remains incompletely understood in the real world how anti-viral therapy affects survival after HCC diagnosis. This was an international multicentre cohort study of 2518 HBV-related HCC cases diagnosed between 2000 and 2015. Cox proportional hazards models were utilised to estimate hazard ratios (HR) with 95% (CI) for anti-viral therapy and cirrhosis on patients' risk of death. Approximately, 48% of patients received anti-viral therapy at any time, but only 17% were on therapy at HCC diagnosis (38% at US centres, 11% at Asian centres). Anti-viral therapy would have been indicated for >60% of the patients not on anti-viral therapy based on American criteria. Patients with cirrhosis had lower 5-year survival (34% vs 46%; P < 0.001) while patients receiving anti-viral therapy had increased 5-year survival compared to untreated patients (42% vs 25% with cirrhosis and 58% vs 36% without cirrhosis; P < 0.001 for both). Similar findings were seen for other patient subgroups by cancer stages and cancer treatment types. Anti-viral therapy was associated with a decrease in risk of death, whether started before or after HCC diagnosis (adjusted HR 0.62 and 0.79, respectively; P < 0.001). Anti-viral therapy improved overall survival in patients with HBV-related HCC across cancer stages and treatment types but was underutilised at both US and Asia centres. Expanded use of anti-viral therapy in HBV-related HCC and better linkage-to-care for HBV patients are needed. © 2018 John Wiley & Sons Ltd.

  5. Hepatocellular Carcinoma after Sustained Viral Response to Interferon and Ribavirin Therapy in Cirrhosis Secondary to Chronic Hepatitis C

    International Nuclear Information System (INIS)

    Khokhar, N.; Qureshi, M.U.; Niazi, T.K.

    2013-01-01

    Objective: To determine the frequency of development of hepatocellular carcinoma in patients with chronic liver disease secondary to hepatitis C who had achieved sustained virological response with Interferon and Ribavirin therapy. Study Design: Retrospective descriptive study. Place and Duration of Study: Shifa International Hospital, Islamabad, Pakistan, from January 2007 to January 2012. Methodology: Hepatitis C related chronic liver disease patients who were treated with interferon and ribavirin, after they achieved sustained virological response, they were followed for a mean of 42 A+- 17 months. During this time, development of hepatocellular carcinoma was ascertained. All underwent surveillance with alpha-feto-protein and ultrasonography every 6 months. Results: Out of the 58 patients who had achieved sustained virological response, 3 developed hepatocellular carcinoma after a mean follow-up of 38 A+- 14 months. It was multifocal in 2 cases and was single lesion in the 3rd. Two patients ultimately died, one with upper GI bleeding and the other with hepatic encephalopathy, while 3rd patient with single lesion is still surviving. Conclusion: Three out of 58 patients of hepatitis C related chronic liver disease developed hepatocellular carcinoma during follow-up in patients who had achieved sustained virological response. These patients need closer follow-up, for development of complications, even if they have achieved sustained viral response. (author)

  6. Simultaneous splenectomy during liver transplantation augments anti-viral therapy in patients infected with hepatitis C virus.

    Science.gov (United States)

    Chu, Heng-Cheng; Hsieh, Chung-Bao; Hsu, Kuo-Feng; Fan, Hsiu-Lung; Hsieh, Tsai-Yuan; Chen, Teng-Wei

    2015-01-01

    Simultaneous splenectomy in liver transplantation (LT) is selectively indicated because of splenoportal venous thromboses and increased sepsis. Therefore, its impact should be further investigated. Of the 160 liver transplant patients, only 40 underwent simultaneous splenectomy. Clinicopathologic characteristics and outcomes were compared between the splenectomy and non-splenectomy group using retrospective analysis. Although the groups were similar and had no significant difference in the intra- and postoperative data, non-splenectomy group had more male patients. However, splenectomy group showed significantly higher platelet and leukocyte counts at 1 month and 6 months after the transplantation and higher hepatitis C virus anti-viral therapy completion. Furthermore, 3 patients developed portal or splenic vein thrombosis during the postoperative follow-up, but the overall survival rate did not significantly differ between these groups. Simultaneous splenectomy in LT can be safely performed, particularly in patients with hepatitis C virus cirrhosis, small-for-size grafts, hypersplenism, and ABO blood group incompatible (ABO - incompatible) LT. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. It takes a combination of biosecurity, testing, and vaccination to keep bovine viral diarrhea (BVD) under control

    Science.gov (United States)

    This is the third installment of a 3 part series on bovine viral diarrhea (BVD), written for a lay publication whose core audience in dairy producers. Control of BVD in any dairy operation must rely on the implementation of an organized strategy combining biosecurity, surveillance and increased herd...

  8. Antibody-independent control of gamma-herpesvirus latency via B cell induction of anti-viral T cell responses.

    Directory of Open Access Journals (Sweden)

    Kelly B McClellan

    2006-06-01

    Full Text Available B cells can use antibody-dependent mechanisms to control latent viral infections. It is unknown whether this represents the sole function of B cells during chronic viral infection. We report here that hen egg lysozyme (HEL-specific B cells can contribute to the control of murine gamma-herpesvirus 68 (gammaHV68 latency without producing anti-viral antibody. HEL-specific B cells normalized defects in T cell numbers and proliferation observed in B cell-/- mice during the early phase of gammaHV68 latency. HEL-specific B cells also reversed defects in CD8 and CD4 T cell cytokine production observed in B cell-/- mice, generating CD8 and CD4 T cells necessary for control of latency. Furthermore, HEL-specific B cells were able to present virally encoded antigen to CD8 T cells. Therefore, B cells have antibody independent functions, including antigen presentation, that are important for control of gamma-herpesvirus latency. Exploitation of this property of B cells may allow enhanced vaccine responses to chronic virus infection.

  9. Socioeconomic factors explain suboptimal adherence to antiretroviral therapy among HIV-infected Australian adults with viral suppression.

    Directory of Open Access Journals (Sweden)

    Krista J Siefried

    Full Text Available Missing more than one tablet of contemporary antiretroviral therapy (ART per month increases the risk of virological failure. Recent studies evaluating a comprehensive range of potential risk factors for suboptimal adherence are not available for high-income settings.Adults on ART with undetectable viral load (UDVL were recruited into a national, multi-centre cohort, completing a comprehensive survey assessing demographics, socio-economic indicators, physical health, well-being, life stressors, social supports, HIV disclosure, HIV-related stigma and discrimination, healthcare access, ART regimen, adherence, side effects, costs and treatment beliefs. Baseline data were assessed, and suboptimal adherence was defined as self-reported missing ≥1 ART dose/month over the previous 3-months; associated factors were identified using bivariate and multivariate binary logistic regression.We assessed 522 participants (494 [94.5%] men, mean age = 50.8 years, median duration UDVL = 3.3 years [IQR = 1.2-6.8] at 17 sexual health, hospital, and general practice clinics across Australia. Seventy-eight participants (14.9% reported missing ≥1 dose/month over the previous three months, which was independently associated with: being Australian-born (AOR [adjusted odds ratio] = 2.4 [95%CI = 1.2-4.9], p = 0.014, not being in a relationship (AOR = 3.3 [95%CI = 1.5-7.3], p = 0.004, reaching the "Medicare safety net" (capping annual medical/pharmaceutical costs (AOR = 2.2 [95%CI = 1.1-4.5], p = 0.024, living in subsidised housing (AOR = 2.5 [95%CI = 1.0-6.2], p = 0.045, receiving home-care services (AOR = 4.4 [95%CI = 1.0-18.8], p = 0.046, HIV community/outreach services linkage (AOR = 2.4 [95%CI = 1.1-5.4], p = 0.033, and starting ART following self-request (AOR = 3.0 [95%CI = 1.3-7.0], p = 0.012.In this population, 15% reported recent suboptimal ART adherence at levels associated in prospective studies with subsequent virological failure, despite all having an

  10. Time to viral load suppression in antiretroviral-naive and -experienced HIV-infected pregnant women on highly active antiretroviral therapy: implications for pregnant women presenting late in gestation.

    Science.gov (United States)

    Aziz, N; Sokoloff, A; Kornak, J; Leva, N V; Mendiola, M L; Levison, J; Feakins, C; Shannon, M; Cohan, D

    2013-11-01

    To compare time to achieve viral load HIV-infected antiretroviral (ARV) -naive versus ARV-experienced pregnant women on highly active antiretroviral therapy (HAART). Retrospective cohort study. Three university medical centers, USA. HIV-infected pregnant women initiated or restarted on HAART during pregnancy. We calculated time to viral load HIV-infected pregnant women on HAART who reported at least 50% adherence, stratifying based on previous ARV exposure history. Time to HIV viral load HIV-infected pregnant women, comprising 76 ARV-naive and 62 ARV-experienced. Ninety-three percent of ARV-naive women achieved a viral load HIV log10 viral load was associated with a later time of achieving viral load HIV log10 viral load was associated with a longer time of achieving viral load Pregnant women with ≥50% adherence, whether ARV-naive or ARV-experienced, on average achieve a viral load HIV log10 viral load were all statistically significant predictors of earlier time to achieve viral load <400 copies/ml and <1000 copies/ml. Increased CD4 count was statistically significant as a predictor of earlier time to achieve viral load <1000 copies/ml. © 2013 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2013 RCOG.

  11. Follicular bronchiolitis in an HIV-infected individual on combination antiretroviral therapy with low CD4+ cell count but sustained viral suppression

    DEFF Research Database (Denmark)

    Rasmussen, Line D; Pedersen, Court; Madsen, Helle D

    2017-01-01

    A 36-year-old Danish man, living in Asia, was diagnosed with Pneumocystis pneumonia (PCP) and HIV in 2013 (CD4+ count: 6 cells/µL; viral load: 518 000 copies/mL). He initiated combination antiretroviral therapy. Later that year, he was also diagnosed with granulomatosis with polyangiitis and was ......A 36-year-old Danish man, living in Asia, was diagnosed with Pneumocystis pneumonia (PCP) and HIV in 2013 (CD4+ count: 6 cells/µL; viral load: 518 000 copies/mL). He initiated combination antiretroviral therapy. Later that year, he was also diagnosed with granulomatosis with polyangiitis...... tests demonstrated severely reduced lung capacity with an obstructive pattern and a moderately reduced diffusion capacity. High resolution computer tomography revealed minor areas with tree-in-bud pattern and no signs of air trapping on expiratory views. Lung biopsy showed lymphocytic infiltration...

  12. Halting angiogenesis by non-viral somatic gene therapy alleviates psoriasis and murine psoriasiform skin lesions

    DEFF Research Database (Denmark)

    Zibert, John Robert; Wallbrecht, Katrin; Schön, Margarete

    2011-01-01

    Dysregulated angiogenesis is a hallmark of chronic inflammatory diseases, including psoriasis, a common skin disorder that affects approximately 2% of the population. Studying both human psoriasis in 2 complementary xenotransplantation models and psoriasis-like skin lesions in transgenic mice......-15) by in vivo electroporation reduced cutaneous angiogenesis and vascularization in all 3 models. As demonstrated using red fluorescent protein-coupled RDD, the treatment resulted in muscular expression of the gene product and its deposition within the cutaneous hyperangiogenic connective tissue....... High-resolution ultrasound revealed reduced cutaneous blood flow in vivo after electroporation with RDD but not with control plasmids. In addition, angiogenesis- and inflammation-related molecular markers, keratinocyte proliferation, epidermal thickness, and clinical disease scores were downregulated...

  13. How viral capsids adapt to mismatched cargoes—identifying mechanisms of morphology control with simulations

    Science.gov (United States)

    Elrad, Oren

    2009-03-01

    During the replication of many viruses, hundreds to thousands of protein subunits assemble around the viral nucleic acid to form a protein shell called a capsid. Most viruses form one particular structure with astonishing fidelity; yet, recent experiments demonstrate that capsids can assemble with different sizes and morphologies to accommodate nucleic acids or other cargoes such as functionalized nanoparticles. In this talk, we will explore the mechanisms of simultaneous assembly and cargo encapsidation with a computational model that describes the assembly of icosahedral capsids around functionalized nanoparticles. With this model, we find parameter values for which subunits faithfully form empty capsids with a single morphology, but adaptively assemble into different icosahedral morphologies around nanoparticles with different diameters. Analyzing trajectories in which adaptation is or is not successful sheds light on the mechanisms by which capsid morphology may be controlled in vitro and in vivo, and suggests experiments to test these mechanisms. We compare the simulation results to recent experiments in which Brome Mosaic Virus capsid proteins assemble around functionalized nanoparticles, and describe how future experiments can test the model predictions.

  14. Co-financing for viral load monitoring during the course of antiretroviral therapy among patients with HIV/AIDS in Vietnam: A contingent valuation survey.

    Science.gov (United States)

    Nguyen, Quyen Le Thi; Nguyen, Long Hoang; Tran, Bach Xuan; Phan, Huong Thi Thu; Le, Huong Thi; Nguyen, Hinh Duc; Tran, Tho Dinh; Do, Cuong Duy; Nguyen, Cuong Manh; Thuc, Vu Thi Minh; Latkin, Carl; Zhang, Melvyn W B; Ho, Roger C M

    2017-01-01

    Viral load testing is considered the gold standard for monitoring HIV treatment; however, given its high cost, some patients cannot afford viral load testing if this testing is not subsidized. Since foreign aid for HIV/AIDS in Vietnam is rapidly decreasing, we sought to assess willingness to pay (WTP) for viral load and CD4 cell count tests among HIV-positive patients, and identified factors that might inform future co-payment schemes. A multi-site cross-sectional survey was conducted with 1133 HIV-positive patients on antiretroviral therapy (ART) in Hanoi and Nam Dinh. Patients' health insurance coverage, quality of life, and history of illicit drug use were assessed. A contingent valuation approach was employed to measure patients' WTP for CD4 cell count and viral load testing. HIV-positive patients receiving ART at provincial sites reported more difficulty obtaining health insurance (HI) and had the overall the poorest quality of life. Most patients (90.9%) were willing to pay for CD4 cell count testing; here, the mean WTP was valued at US$8.2 (95%CI = 7.6-8.8 US$) per test. Most patients (87.3%) were also willing to pay for viral load testing; here, mean WTP was valued at US$18.6 (95%CI = 16.3-20.9 US$) per test. High income, high education level, and hospitalization were positively associated with WTP, while co-morbidity with psychiatric symptoms and trouble paying for health insurance were both negatively related to WTP. These findings raise concerns that HIV-positive patients in Vietnam might have low WTP for CD4 cell count and viral load testing. This means that without foreign financial subsidies, many of these patients would likely go without these important tests. Treating psychiatric co-morbidities, promoting healthcare services utilization, and removing barriers to accessing health insurance may increase WTP for monitoring of HIV/AIDS treatment among HIV+-positive Vietnamese patients.

  15. Plasma HIV-1 RNA viral load rebound among people who inject drugs receiving antiretroviral therapy (ART) in a Canadian setting: an ethno-epidemiological study.

    Science.gov (United States)

    Small, Will; Milloy, M J; McNeil, Ryan; Maher, Lisa; Kerr, Thomas

    2016-01-01

    People who inject drugs (PWID) living with HIV often experience sub-optimal antiretroviral therapy (ART) treatment outcomes, including HIV plasma viral load (PVL) rebound. While previous studies have identified risk factors for PVL rebound among PWID, no study has examined the perspectives of PWID who have experienced PVL rebound episodes. We conducted an ethno-epidemiological study to investigate the circumstances surrounding the emergence of rebound episodes among PWID in Vancouver, BC, Canada. Comprehensive clinical records linked to a community-based prospective observational cohort of HIV-positive drug users were used to identify PWID who had recently experienced viral rebound. In-depth qualitative interviews with 16 male and 11 female participants explored participant perspectives regarding the emergence of viral rebound. A timeline depicting each participant's HIV viral load and adherence to ART was used to elicit discussion of circumstances surrounding viral rebound. Viral rebound episodes were shaped by interplay between various individual, social, and environmental factors that disrupted routines facilitating adherence. Structural-environmental influences resulting in non-adherence included housing transitions, changes in drug use patterns and intense drug scene involvement, and inadequate care for co-morbid health conditions. Social-environmental influences on ART adherence included poor interactions between care providers and patients producing non-adherence, and understandings of HIV treatment that fostered intentional treatment discontinuation. This study describes key pathways which led to rebound episodes among PWID receiving ART and illustrates how environmental forces may increase vulnerability for non-adherence leading to treatment failure. Our findings have potential to help inform interventions and supports that address social-structural forces that foster non-adherence among PWID.

  16. The Patient-Related Burden of Pegylated-Interferon-α Therapy and Adverse Events among Patients with Viral Hepatitis C in Japan.

    Science.gov (United States)

    Kumada, Hiromitsu; daCosta DiBonaventura, Marco; Yuan, Yong; Kalsekar, Anupama; Kopenhafer, Lewis; Tang, Ann; Victor, Timothy W; L'Italien, Gilbert; Chayama, Kazuaki; Toyota, Joji

    2014-05-01

    Pegylated-interferon-α (IFN-α)-based therapies for viral hepatitis C (HCV) are effective, but they are associated with several adverse events (AEs). The primary objectives of this study were to quantify the burden of IFN-α-based treatment and to measure the prevalence and burden of IFN-α-related AEs in Japan. A cross-sectional survey was administered online to patients with HCV in 2013. Patients who were currently taking IFN-α-based therapy (n = 188) were compared with patients who were taking a liver protectant but not IFN-α-based therapy (n = 180) and with patients who were untreated (n = 365) on measures of health-related quality of life (using the Hepatitis Quality of Life Questionnaire, version 2), work productivity, and health care resource use, controlling for sociodemographic characteristics and health history. Among patients taking IFN-α-based therapy, the prevalence and burden of AEs was examined on the same set of health outcomes as noted above along with treatment satisfaction and adherence. Compared with untreated patients, patients using IFN-α reported poorer health-related quality of life (physical component summary score, 50.13 vs. 52.04; mental component summary score, 44.12 vs. 47.97), more overall work impairment (32.73 vs. 25.64), more physician visits in the past 6 months (14.51 vs. 8.36), and an increased likelihood of an emergency room visit (odds ratio = 7.25) and hospitalization (odds ratio = 4.05) (all P < 0.05). The mean number of AEs was 6.05 for patients using IFN-α. All AEs were associated with poorer health outcomes (particularly the mental component summary score), and most were also associated with lower treatment satisfaction and medication adherence. A significant patient burden for IFN-α treatment itself and various AEs was observed. The results suggest that effective, non-IFN-α-based treatments may reduce the societal burden. Copyright © 2014 International Society for Pharmacoeconomics and Outcomes Research (ISPOR

  17. A Multicenter, Prospective, Randomized Controlled Trial to Evaluate the Additional Benefit of a Multistrain Synbiotic (Prodefen® in the Clinical Management of Acute Viral Diarrhea in Children

    Directory of Open Access Journals (Sweden)

    Emilia García-Menor MD

    2016-11-01

    Full Text Available This randomized, open-label study evaluated the additional benefits of the synbiotic Prodefen® in the clinical management of acute diarrhea of suspected viral origin in children between 6 months and 12 years of age. Study outcomes included the duration of diarrhea, the recovery from diarrhea, and the tolerability and acceptance of the treatment. The proportion of patients without diarrhea over the study period was greater in the synbiotic group than in the control group at all study time points, showing a statistically significant difference on the fifth day (95% vs 79%, p < 0.001. The duration of diarrhea (median and interquartile range was reduced by 1 day in the synbiotic-treated patients (3 [2-5] vs 4 [3-5], p = 0.377. The tolerability of the treatment regimen, as evaluated by the parents, was significantly better in those receiving the synbiotic than in the control group. Overall, 96% of the parents of children receiving the synbiotic reported being satisfied to very satisfied with the treatment regimen. The results of this study indicate that the addition of the synbiotic Prodefen® is a well-tolerated and well-accepted approach that provides an additional benefit to the standard supportive therapy in the management of acute viral diarrhea in children.

  18. 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....

  19. Alcohol use and depression: link with adherence and viral suppression in adult patients on antiretroviral therapy in rural Lesotho, Southern Africa: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Bernard Cerutti

    2016-09-01

    Full Text Available Abstract Background Depression and alcohol use disorder have been shown to be associated with poor adherence to antiretroviral therapy (ART. Studies examining their association with viral suppression in rural Africa are, however, scarce. Methods This study reports prevalence of depressive symptoms and alcohol use disorder, and their potential association with adherence and viral suppression in adult patients on ART in ten clinics in rural Lesotho, Southern Africa. Results Among 1,388 adult patients (69 % women, 80.7 % were alcohol abstinent, 6.3 % were hazardous drinkers (men: 10.7 %, women: 4.4 %, p < 0.001. The prevalence of depressive symptoms was 28.8 % (men 20.2 %, women 32.7 %, p < 0.001. Both alcohol consumption (adjusted odds-ratio: 2.09, 95 % CI: 1.58-2.77 and alcohol use disorder (2.73, 95 % CI: 1.68-4.42 were significantly associated with poor adherence. There was, however, no significant association with viral suppression. Conclusions Whereas the results of this study confirm previously reported association of alcohol use disorder with adherence to ART, there was no association with viral suppression. Trial registration April 28th 2014; NCT02126696 .

  20. Viral Meningitis

    Science.gov (United States)

    ... better from treatment such as an antiviral medicine. Antibiotics do not help viral infections, so they are not useful in the treatment of viral meningitis. However, antibiotics do fight bacteria, so they are very important ...

  1. Pharyngitis - viral

    Science.gov (United States)

    ... throat is due to a viral infection. The antibiotics will not help. Using them to treat viral infections helps bacteria become resistant to antibiotics. With some sore throats (such as those caused ...

  2. Superior virologic and treatment outcomes when viral load is measured at 3 months compared to 6 months on antiretroviral therapy.

    Science.gov (United States)

    Kerschberger, Bernhard; Boulle, Andrew M; Kranzer, Katharina; Hilderbrand, Katherine; Schomaker, Michael; Coetzee, David; Goemaere, Eric; Van Cutsem, Gilles

    2015-01-01

    Routine viral load (VL) monitoring is utilized to assess antiretroviral therapy (ART) adherence and virologic failure, and it is currently scaled-up in many resource-constrained settings. The first routine VL is recommended as late as six months after ART initiation for early detection of sub-optimal adherence. We aimed to assess the optimal timing of first VL measurement after initiation of ART. This was a retrospective, cohort analysis of routine monitoring data of adults enrolled at three primary care clinics in Khayelitsha, Cape Town, between January 2002 and March 2009. Primary outcomes were virologic failure and switch to second-line ART comparing patients in whom first VL done was at three months (VL3M) and six months (VL6M) after ART initiation. Adjusted hazard ratios (aHR) were estimated using Cox proportional hazard models. In total, 6264 patients were included for the time to virologic failure and 6269 for the time to switch to second-line ART analysis. Patients in the VL3M group had a 22% risk reduction of virologic failure (aHR 0.78, 95% CI 0.64-0.95; p=0.016) and a 27% risk reduction of switch to second-line ART (aHR 0.73, 95% CI 0.58-0.92; p=0.008) when compared to patients in the VL6M group. For each additional month of delay of the first VL measurement (up to nine months), the risk of virologic failure increased by 9% (aHR 1.09, 95% CI 1.02-1.15; p=0.008) and switch to second-line ART by 13% (aHR 1.13, 95% CI 1.05-1.21; p<0.001). A first VL at three months rather than six months with targeted adherence interventions for patients with high VL may improve long-term virologic suppression and reduce switches to costly second-line ART. ART programmes should consider the first VL measurement at three months after ART initiation.

  3. Immune control of HIV-1 infection after therapy interruption: immediate versus deferred antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Bernaschi Massimo

    2009-10-01

    Full Text Available Abstract Background The optimal stage for initiating antiretroviral therapies in HIV-1 bearing patients is still a matter of debate. Methods We present computer simulations of HIV-1 infection aimed at identifying the pro et contra of immediate as compared to deferred Highly Active Antiretroviral Therapy (HAART. Results Our simulations highlight that a prompt specific CD8+ cytotoxic T lymphocytes response is detected when therapy is delayed. Compared to very early initiation of HAART, in deferred treated patients CD8+ T cells manage to mediate the decline of viremia in a shorter time and, at interruption of therapy, the virus experiences a stronger immune pressure. We also observe, however, that the immunological effects of the therapy fade with time in both therapeutic regimens. Thus, within one year from discontinuation, viral burden recovers to the value at which it would level off in the absence of therapy. In summary, simulations show that immediate therapy does not prolong the disease-free period and does not confer a survival benefit when compared to treatment started during the chronic infection phase. Conclusion Our conclusion is that, since there is no therapy to date that guarantees life-long protection, deferral of therapy should be preferred in order to minimize the risk of adverse effects, the occurrence of drug resistances and the costs of treatment.

  4. A novel homologous model for gene therapy of dwarfism by non-viral transfer of the mouse growth hormone gene into immunocompetent dwarf mice.

    Science.gov (United States)

    Cecchi, Claudia R; Higuti, Eliza; Oliveira, Nelio A J; Lima, Eliana R; Jakobsen, Maria; Dagnaes-Hansen, Frederick; Gissel, Hanne; Aagaard, Lars; Jensen, Thomas G; Jorge, Alexander A L; Bartolini, Paolo; Peroni, Cibele N

    2014-02-01

    The possibilities for non-viral GH gene therapy are studied in immunocompetent dwarf mice (lit/lit). As expression vector we used a plasmid previously employed in immunodeficient dwarf mice (pUBI-hGH-gDNA) by replacing the human GH gene with the genomic sequence of mouse-GH DNA (pUBI-mGH-gDNA). HEK-293 human cells transfected with pUBI-mGH-gDNA produced 3.0 µg mGH/10(6) cells/day compared to 3.7 µg hGH/10(6) cells/day for pUBIhGH- gDNA transfected cells. The weight of lit/lit mice treated with the same two plasmids (50 µg DNA/mouse) by electrotransfer into the quadriceps muscle was followed for 3 months. The weight increase up to 15 days for mGH, hGH and saline treated mice were 0.130, 0.112 and 0.027 g/mouse/day. Most sera from hGH-treated mice contained anti-hGH antibodies already on day 15, with the highest titers on day 45, while no significant anti-mGH antibodies were observed in mGH-treated mice. At the end of 3 months, the weight increase for mGH-treated mice was 34.3%, while the nose-to-tail and femur lengths increased 9.5% and 24.3%. Mouse-GH and hGH circulating levels were 4-5 ng/mL 15 days after treatment, versus control levels of ~0.7 ng GH/mL (Pdeficiency.

  5. [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

  6. Association of Implementation of a Universal Testing and Treatment Intervention With HIV Diagnosis, Receipt of Antiretroviral Therapy, and Viral Suppression in East Africa.

    Science.gov (United States)

    Petersen, Maya; Balzer, Laura; Kwarsiima, Dalsone; Sang, Norton; Chamie, Gabriel; Ayieko, James; Kabami, Jane; Owaraganise, Asiphas; Liegler, Teri; Mwangwa, Florence; Kadede, Kevin; Jain, Vivek; Plenty, Albert; Brown, Lillian; Lavoy, Geoff; Schwab, Joshua; Black, Douglas; van der Laan, Mark; Bukusi, Elizabeth A; Cohen, Craig R; Clark, Tamara D; Charlebois, Edwin; Kamya, Moses; Havlir, Diane

    2017-06-06

    increase of 35.5 percentage points (95% CI, 34.4-36.6). After 2 years, 95.9% of HIV-positive individuals had been previously diagnosed (95% CI, 95.3%-96.5%; 6780 of 7068 residents); 93.4% of those previously diagnosed had received ART (95% CI, 92.8%-94.0%; 6334 of 6780 residents); and 89.5% of those treated had achieved HIV viral suppression (95% CI, 88.6%-90.3%; 5666 of 6334 residents). Among individuals with HIV in rural Kenya and Uganda, implementation of community-based testing and treatment was associated with an increased proportion of HIV-positive adults who achieved viral suppression, along with increased HIV diagnosis and initiation of antiretroviral therapy. In these communities, the UNAIDS population-level viral suppression target was exceeded within 2 years after program implementation. clinicaltrials.gov Identifier: NCT01864683.

  7. Chronic viral hepatitis: policy, regulation, and strategies for its control and elimination in Ethiopia

    Directory of Open Access Journals (Sweden)

    Fassil Shiferaw

    2016-08-01

    Full Text Available Abstract Background Hepatitis B and C are silent killers not yet recognized as major public health challenges in many developing countries with huge disease burden. In Ethiopia, Hepatitis B is endemic with an average prevalence of 10.8 %, and the prevalence of Hepatitis C is 2 %. The prevalence of both infections, however, is likely to be underreported due to the lack of diagnostic facilities and appropriate surveillance systems. Ethiopia is also among the many Sub-Sahara African countries lacking a coordinated and systematic national response to chronic viral hepatitis. The objective of this study is to examine the current level of response to viral Hepatitis B & C in Ethiopia with the aim to bring identified gaps to the attention of relevant stakeholders and policy makers. Methods This cross-sectional qualitative study was based on semi-structured in-depth interviews with 21 key informants from health facilities, health offices, pharmaceutical companies, regulatory bodies, professional association and blood bank units. Participants were selected purposively based on their role in the national hepatitis response. The investigators also reviewed available policy and strategy documents, standards of practice and surveys, and paid visits to pharmaceutical premises to check the availability of antiviral drugs. Thematic analysis was employed to make sense of the data. During the data analysis process, all the authors critically read the materials, and data was triangulated by source, interpreter view and thematic perspective to ensure accurate representation and comprehensiveness, and validation of the interviewees’ responses. Once each investigator reviewed the data independently, the team reached a common understanding of the scope and contexts of the information attained. Data were subsequently reduced to key concepts, and case stories were taken with successive revisions. The key concepts were later coded into most basic meaningful

  8. Chronic viral hepatitis: policy, regulation, and strategies for its control and elimination in Ethiopia.

    Science.gov (United States)

    Shiferaw, Fassil; Letebo, Mekitew; Bane, Abate

    2016-08-11

    Hepatitis B and C are silent killers not yet recognized as major public health challenges in many developing countries with huge disease burden. In Ethiopia, Hepatitis B is endemic with an average prevalence of 10.8 %, and the prevalence of Hepatitis C is 2 %. The prevalence of both infections, however, is likely to be underreported due to the lack of diagnostic facilities and appropriate surveillance systems. Ethiopia is also among the many Sub-Sahara African countries lacking a coordinated and systematic national response to chronic viral hepatitis. The objective of this study is to examine the current level of response to viral Hepatitis B & C in Ethiopia with the aim to bring identified gaps to the attention of relevant stakeholders and policy makers. This cross-sectional qualitative study was based on semi-structured in-depth interviews with 21 key informants from health facilities, health offices, pharmaceutical companies, regulatory bodies, professional association and blood bank units. Participants were selected purposively based on their role in the national hepatitis response. The investigators also reviewed available policy and strategy documents, standards of practice and surveys, and paid visits to pharmaceutical premises to check the availability of antiviral drugs. Thematic analysis was employed to make sense of the data. During the data analysis process, all the authors critically read the materials, and data was triangulated by source, interpreter view and thematic perspective to ensure accurate representation and comprehensiveness, and validation of the interviewees' responses. Once each investigator reviewed the data independently, the team reached a common understanding of the scope and contexts of the information attained. Data were subsequently reduced to key concepts, and case stories were taken with successive revisions. The key concepts were later coded into most basic meaningful categories. The World Health Organization (WHO) global

  9. A Critical Role of IL-21-Induced BATF in Sustaining CD8-T-Cell-Mediated Chronic Viral Control

    Directory of Open Access Journals (Sweden)

    Gang Xin

    2015-11-01

    Full Text Available Control of chronic viral infections by CD8 T cells is critically dependent on CD4 help. In particular, helper-derived IL-21 plays a key role in sustaining the CD8 T cell response; however, the molecular pathways by which IL-21 sustains CD8 T cell immunity remain unclear. We demonstrate that IL-21 causes a phenotypic switch of transcription factor expression in CD8 T cells during chronic viral infection characterized by sustained BATF expression. Importantly, BATF expression during chronic infection is both required for optimal CD8 T cell persistence and anti-viral effector function and sufficient to rescue “unhelped” CD8 T cells. Mechanistically, BATF sustains the response by cooperating with IRF4, an antigen-induced transcription factor that is also critically required for CD8 T cell maintenance, to preserve Blimp-1 expression and thereby sustain CD8 T cell effector function. Collectively, these data suggest that CD4 T cells “help” the CD8 response during chronic infection via IL-21-induced BATF expression.

  10. Inhibition of post-transcriptional RNA processing by CDK inhibitors and its implication in anti-viral therapy.

    Directory of Open Access Journals (Sweden)

    Jitka Holcakova

    Full Text Available Cyclin-dependent kinases (CDKs are key regulators of the cell cycle and RNA polymerase II mediated transcription. Several pharmacological CDK inhibitors are currently in clinical trials as potential cancer therapeutics and some of them also exhibit antiviral effects. Olomoucine II and roscovitine, purine-based inhibitors of CDKs, were described as effective antiviral agents that inhibit replication of a broad range of wild type human viruses. Olomoucine II and roscovitine show high selectivity for CDK7 and CDK9, with important functions in the regulation of RNA polymerase II transcription. RNA polymerase II is necessary for viral transcription and following replication in cells. We analyzed the effect of inhibition of CDKs by olomoucine II on gene expression from viral promoters and compared its effect to widely-used roscovitine. We found that both roscovitine and olomoucine II blocked the phosphorylation of RNA polymerase II C-terminal domain. However the repression of genes regulated by viral promoters was strongly dependent on gene localization. Both roscovitine and olomoucine II inhibited expression only when the viral promoter was not integrated into chromosomal DNA. In contrast, treatment of cells with genome-integrated viral promoters increased their expression even though there was decreased phosphorylation of the C-terminal domain of RNA polymerase II. To define the mechanism responsible for decreased gene expression after pharmacological CDK inhibitor treatment, the level of mRNA transcription from extrachromosomal DNA was determined. Interestingly, our results showed that inhibition of RNA polymerase II C-terminal domain phosphorylation increased the number of transcribed mRNAs. However, some of these mRNAs were truncated and lacked polyadenylation, which resulted in decreased translation. These results suggest that phosphorylation of RNA polymerase II C-terminal domain is critical for linking transcription and posttrancriptional

  11. Utilisation of hepatocellular carcinoma screening in Australians at risk of hepatitis B virus-related carcinoma and prescribed anti-viral therapy.

    Science.gov (United States)

    Sheppard-Law, Suzanne; Zablotska-Manos, Iryna; Kermeen, Melissa; Holdaway, Susan; Lee, Alice; George, Jacob; Zekry, Amany; Maher, Lisa

    2018-07-01

    To investigate hepatocellular carcinoma screening utilisation and factors associated with utilisation among patients prescribed hepatitis B virus anti-viral therapy and at risk of hepatocellular carcinoma. The incidence of hepatocellular carcinoma has increased in Australia over the past three decades with chronic hepatitis B virus infection a major contributor. hepatocellular carcinoma surveillance programs aim to detect cancers early enabling curative treatment options, longer survival and longer times to recurrence. Multi-site cross-sectional survey. An online study questionnaire was administered to eligible participants attending three Sydney tertiary hospitals. Data were grouped into six mutually exclusive hepatocellular carcinoma risk factor categories as per American Association for the Study of Liver Diseases guidelines. All analyses were undertaken in STATA. Logistic regression was used to assess the associations between covariates and screening utilisation. Multivariate models described were assessed using the Hosmer-Lemeshow goodness of fit. Of the 177 participants, 137 (77.4%) self-reported that US had been performed in the last six months. Awareness that screening should be performed and knowing the correct frequency of US screening were independently associated with screening utilisation. Participants who knew that screening should be undertaken were three times more likely to have had pretreatment education or were prescribed hepatitis B virus anti-viral treatment for >4 years. Participants reporting a family history of hepatocellular carcinoma were less likely to know that screening should be undertaken every 6 months. While utilisation of hepatocellular carcinoma surveillance programs was higher in this study than in previous reports, strategies to further improve surveillance remain necessary. Findings from this research form the basis for proposing strategies to improve utilisation of hepatocellular carcinoma screening, inform hepatitis B virus

  12. Epigenetic control of viral life-cycle by a DNA-methylation dependent transcription factor.

    Directory of Open Access Journals (Sweden)

    Kirsty Flower

    Full Text Available Epstein-Barr virus (EBV encoded transcription factor Zta (BZLF1, ZEBRA, EB1 is the prototype of a class of transcription factor (including C/EBPalpha that interact with CpG-containing DNA response elements in a methylation-dependent manner. The EBV genome undergoes a biphasic methylation cycle; it is extensively methylated during viral latency but is reset to an unmethylated state following viral lytic replication. Zta is expressed transiently following infection and again during the switch between latency and lytic replication. The requirement for CpG-methylation at critical Zta response elements (ZREs has been proposed to regulate EBV replication, specifically it could aid the activation of viral lytic gene expression from silenced promoters on the methylated genome during latency in addition to preventing full lytic reactivation from the non-methylated EBV genome immediately following infection. We developed a computational approach to predict the location of ZREs which we experimentally assessed using in vitro and in vivo DNA association assays. A remarkably different binding motif is apparent for the CpG and non-CpG ZREs. Computational prediction of the location of these binding motifs in EBV revealed that the majority of lytic cycle genes have at least one and many have multiple copies of methylation-dependent CpG ZREs within their promoters. This suggests that the abundance of Zta protein coupled with the methylation status of the EBV genome act together to co-ordinate the expression of lytic cycle genes at the majority of EBV promoters.

  13. 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

    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.

  14. [Control, elimination and eradication of viral immuno preventable diseases in Venezuela].

    Science.gov (United States)

    Valero, Nereida; Maldonado, Mery

    2005-09-01

    Vaccination has demonstrated the capacity for the drastic decrease of the prevalence and incidence of several diseases of viral etiology and it has allowed their eradication. Among these human immuno preventable diseases are included poliomyelitis, measles, mumps, chicken pox, rubella, hepatitis A and B, influenza A and yellow fever. In residents, travelers to endemic areas and personal at risk, the vaccines to Japanese and equine encephalitis, rabies and adenovirus can be applied. Venezuela has not escaped from the positive impact in the epidemiology of these illnesses as a consequence of the organization and implementation of big national vaccination campaigns; however, and in spite of these efforts, important outbreaks of measles, yellow fever, chicken pox and hepatitis have occurred in the last few years. The tools to eliminate the majority of these viral diseases exist in Venezuela as well as in other countries, and are readily available, effective and relatively not expensive, but require on the whole of an effort of authorities and communities. The implementation of these strategies should have the support of the World Health Organization and the Panamerican Health Organization. This is a priority for the next few years if our aim is the eradication of these illnesses from Venezuela, the continent and the world.

  15. Foxp3+ regulatory T cells control persistence of viral CNS infection.

    Directory of Open Access Journals (Sweden)

    Dajana Reuter

    Full Text Available We earlier established a model of a persistent viral CNS infection using two week old immunologically normal (genetically unmodified mice and recombinant measles virus (MV. Using this model infection we investigated the role of regulatory T cells (Tregs as regulators of the immune response in the brain, and assessed whether the persistent CNS infection can be modulated by manipulation of Tregs in the periphery. CD4(+ CD25(+ Foxp3(+ Tregs were expanded or depleted during the persistent phase of the CNS infection, and the consequences for the virus-specific immune response and the extent of persistent infection were analyzed. Virus-specific CD8(+ T cells predominantly recognising the H-2D(b-presented viral hemagglutinin epitope MV-H(22-30 (RIVINREHL were quantified in the brain by pentamer staining. Expansion of Tregs after intraperitoneal (i.p. application of the superagonistic anti-CD28 antibody D665 inducing transient immunosuppression caused increased virus replication and spread in the CNS. In contrast, depletion of Tregs using diphtheria toxin (DT in DEREG (depletion of regulatory T cells-mice induced an increase of virus-specific CD8(+ effector T cells in the brain and caused a reduction of the persistent infection. These data indicate that manipulation of Tregs in the periphery can be utilized to regulate virus persistence in the CNS.

  16. [Therapy control of specific hymenoptera venom allergy].

    Science.gov (United States)

    Aust, W; Wichmann, G; Dietz, A

    2010-12-01

    In Germany anaphylactic reactions after insect stings are mostly caused by honey bee (Apis mellifera) and wasp (Vespula vulgaris, Vespula germanica). In the majority of cases venom immunotherapy is a successful therapy and protects patients from recurrent systemic anaphylactic reaction. In some patients persistent severe reactions after insect sting can even occur in spite of venom therapy, as a sign of therapy failure. It is important to identify these patients, who do not benefit from venom immunotherapy, in an early stage of therapy. In this case dose rate of venom immunotherapy must be adjusted for a successful therapy outcome. Up to now skin prick tests, specific IgE-antibodies and in vitro diagnostics are not suitable for detecting therapy failure. Patients with treatment failure can be diagnosed by insect sting test and almost all of them will become fully protected by increasing the maintenance dose. © Georg Thieme Verlag KG Stuttgart · New York.

  17. On the temperature control in self-controlling hyperthermia therapy

    Energy Technology Data Exchange (ETDEWEB)

    Ebrahimi, Mahyar, E-mail: ebrahimi_m@mehr.sharif.ir

    2016-10-15

    In self-controlling hyperthermia therapy, once the desired temperature is reached, the heat generation ceases and overheating is prevented. In order to design a system that generates sufficient heat without thermal ablation of surrounding healthy tissue, a good understanding of temperature distribution and its change with time is imperative. This study is conducted to extend our understanding about the heat generation and transfer, temperature distribution and temperature rise pattern in the tumor and surrounding tissue during self-controlling magnetic hyperthermia. A model consisting of two concentric spheres that represents the tumor and its surrounding tissue is considered and temperature change pattern and temperature distribution in tumor and surrounding tissue are studied. After describing the model and its governing equations and constants precisely, a typical numerical solution of the model is presented. Then it is showed that how different parameters like Curie temperature of nanoparticles, magnetic field amplitude and nanoparticles concentration can affect the temperature change pattern during self-controlling magnetic hyperthermia. The model system herein discussed can be useful to gain insight on the self-controlling magnetic hyperthermia while applied to cancer treatment in real scenario and can be useful for treatment strategy determination. - Highlights: • Temperature change pattern in tumor and surrounding tissue are studied. • The model system herein can be useful for treatment strategy determination. • In the work described herein, emphasis is on the effect of low Curie temperature. • If the equilibrium temperature can be tuned appropriately, the stay time will be infinite.

  18. On the temperature control in self-controlling hyperthermia therapy

    International Nuclear Information System (INIS)

    Ebrahimi, Mahyar

    2016-01-01

    In self-controlling hyperthermia therapy, once the desired temperature is reached, the heat generation ceases and overheating is prevented. In order to design a system that generates sufficient heat without thermal ablation of surrounding healthy tissue, a good understanding of temperature distribution and its change with time is imperative. This study is conducted to extend our understanding about the heat generation and transfer, temperature distribution and temperature rise pattern in the tumor and surrounding tissue during self-controlling magnetic hyperthermia. A model consisting of two concentric spheres that represents the tumor and its surrounding tissue is considered and temperature change pattern and temperature distribution in tumor and surrounding tissue are studied. After describing the model and its governing equations and constants precisely, a typical numerical solution of the model is presented. Then it is showed that how different parameters like Curie temperature of nanoparticles, magnetic field amplitude and nanoparticles concentration can affect the temperature change pattern during self-controlling magnetic hyperthermia. The model system herein discussed can be useful to gain insight on the self-controlling magnetic hyperthermia while applied to cancer treatment in real scenario and can be useful for treatment strategy determination. - Highlights: • Temperature change pattern in tumor and surrounding tissue are studied. • The model system herein can be useful for treatment strategy determination. • In the work described herein, emphasis is on the effect of low Curie temperature. • If the equilibrium temperature can be tuned appropriately, the stay time will be infinite.

  19. 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.

  20. Massage therapy and exercise therapy in patients with multiple sclerosis: a randomized controlled pilot study.

    Science.gov (United States)

    Negahban, Hossein; Rezaie, Solmaz; Goharpey, Shahin

    2013-12-01

    The primary aim was to investigate the comparative effects of massage therapy and exercise therapy on patients with multiple sclerosis. The secondary aim was to investigate whether combination of both massage and exercise has an additive effect. Randomized controlled pilot trial with repeated measurements and blinded assessments. Local Multiple Sclerosis Society. A total of 48 patients with multiple sclerosis were randomly assigned to four equal subgroups labelled as massage therapy, exercise therapy, combined massage-exercise therapy and control group. The treatment group received 15 sessions of supervised intervention for five weeks. The massage therapy group received a standard Swedish massage. The exercise therapy group was given a combined set of strength, stretch, endurance and balance exercises. Patients in the massage-exercise therapy received a combined set of massage and exercise treatments. Patients in the control group were asked to continue their standard medical care. Pain, fatigue, spasticity, balance, gait and quality of life were assessed before and after intervention. Massage therapy resulted in significantly larger improvement in pain reduction (mean change 2.75 points, P = 0.001), dynamic balance (mean change, 3.69 seconds, P = 0.009) and walking speed (mean change, 7.84 seconds, P = 0.007) than exercise therapy. Patients involved in the combined massage-exercise therapy showed significantly larger improvement in pain reduction than those in the exercise therapy (mean change, 1.67 points, P = 0.001). Massage therapy could be more effective than exercise therapy. Moreover, the combination of massage and exercise therapy may be a little more effective than exercise therapy alone.

  1. Higher baseline viral diversity correlates with lower HBsAg decline following PEGylated interferon-alpha therapy in patients with HBeAg-positive chronic hepatitis B.

    Science.gov (United States)

    Li, Hu; Zhang, Li; Ren, Hong; Hu, Peng

    2018-01-01

    Viral diversity seems to predict treatment outcomes in certain viral infections. The aim of this study was to evaluate the association between baseline intra-patient viral diversity and hepatitis B surface antigen (HBsAg) decline following PEGylated interferon-alpha (Peg-IFN-α) therapy. Twenty-six HBeAg-positive patients who were treated with Peg-IFN-α were enrolled. Nested polymerase chain reaction (PCR), cloning, and sequencing of the hepatitis B virus S gene were performed on baseline samples, and normalized Shannon entropy (Sn) was calculated as a measure of small hepatitis B surface protein (SHBs) diversity. Multiple regression analysis was used to estimate the association between baseline Sn and HBsAg decline. Of the 26 patients enrolled in the study, 65.4% were male and 61.5% were infected with hepatitis B virus genotype B. The median HBsAg level at baseline was 4.5 log 10 IU/mL (interquartile range: 4.1-4.9) and declined to 3.0 log 10 IU/mL (interquartile range: 1.7-3.9) after 48 weeks of Peg-IFN-α treatment. In models adjusted for baseline alanine aminotransferase (ALT) and HBsAg, the adjusted coefficients (95% CI) for ΔHBsAg and relative percentage HBsAg decrease were -1.3 (-2.5, -0.2) log 10 IU/mL for higher SHBs diversity (Sn≥0.58) patients and -26.4% (-50.2%, -2.5%) for lower diversity (Sndiversity. Baseline intra-patient SHBs diversity was inverse to HBsAg decline in HBeAg-positive chronic hepatitis B (CHB) patients receiving Peg-IFN-α monotherapy. Also, more sequence variations within the "a" determinant upstream flanking region and the first loop of the "a" determinant were the main sources of the higher SHBs diversity.

  2. Asthma Severity in patients initiating controller monotherapy versus combination therapy.

    Science.gov (United States)

    Diette, Gregory B; Fuhlbrigge, Anne L; Allen-Ramey, Felicia; Hopper, April; Sajjan, Shiva G; Markson, Leona E

    2011-04-01

    Asthma treatment guidelines recommend medications based on the level of asthma control. To evaluate differences in asthma control between patients who initiated asthma controller monotherapy versus combination therapy. Children (5-16 years; n = 488) and adults (17-80 years; n = 530) with asthma and no controller therapy in the prior 6 months were included. Telephone surveys were conducted within 5 days of filling a new asthma controller prescription with either the caregiver of children or the adult patient. Demographics, asthma control before therapy, and asthma-related resource use were assessed for patients initiating monotherapy (filling one asthma controller prescription) and combination therapy (filling more than one controller medication or a fixed-dose combination). Mean pediatric age was 10 years; 53% were male. Mean adult age was 47 years; 25% were male. There were no significant differences in asthma control score between patients receiving monotherapy and combination therapy. Children on combination therapy did not have more nighttime awakening or short-acting β-agonist use but were more likely to have been hospitalized due to asthma attack (p = .05) and have more unscheduled (p = .0374) and scheduled (p = .009) physician visits. Adults on combination therapy were more likely to have been hospitalized due to asthma attack (p asthma (p asthma control scores in the 4 weeks before index medication suggests that asthma severity during a treatment-free period did not differ significantly for patients initiating controller monotherapy versus combination therapy. From these findings, it appears that although physicians may not focus on asthma control when choosing the intensity of initial controller therapy, the intensity of health-care encounters may be an influence.

  3. The clinical benefits of antiretroviral therapy in severely immunocompromised HIV-1-infected patients with and without complete viral suppression

    DEFF Research Database (Denmark)

    Mocroft, Amanda; Bannister, Wendy P; Kirk, Ole

    2012-01-01

    The aim of this study was to determine whether there is a protective effect of combination antiretroviral therapy (cART) on the development of clinical events in patients with ongoing severe immunosuppression.......The aim of this study was to determine whether there is a protective effect of combination antiretroviral therapy (cART) on the development of clinical events in patients with ongoing severe immunosuppression....

  4. 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

  5. Acupuncture therapy for fever induced by viral upper respiratory tract infection (URTI) in military medical service: a case series.

    Science.gov (United States)

    Kwon, SeungWon; Shin, KyoungHo; Jung, WooSang; Moon, SangKwan; Cho, KiHo

    2014-12-01

    We report the cases of eight military patients with fever (≥38°C) induced by viral upper respiratory tract infection (URTI) who requested treatment with acupuncture in the military medical service room. All patients were treated immediately after diagnosis with classical acupuncture (GV14, GB20, TE8 points) and a new type of acupuncture, equilibrium acupuncture (Feibing and Ganmao points). After one treatment session (20 min), reduction of body temperature was confirmed in all patients. Accompanying symptoms such as headache, myalgia and nasal obstruction also showed a tendency to decrease. Within 3 days of treatment, six of the eight patients had recovered from the URTI. No adverse effects of acupuncture treatment were reported. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  6. Curcumin suppression of cytokine release and cytokine storm. A potential therapy for patients with Ebola and other severe viral infections.

    Science.gov (United States)

    Sordillo, Peter P; Helson, Lawrence

    2015-01-01

    The terminal stage of Ebola and other viral diseases is often the onset of a cytokine storm, the massive overproduction of cytokines by the body's immune system. The actions of curcumin in suppressing cytokine release and cytokine storm are discussed. Curcumin blocks cytokine release, most importantly the key pro-inflammatory cytokines, interleukin-1, interleukin-6 and tumor necrosis factor-α. The suppression of cytokine release by curcumin correlates with clinical improvement in experimental models of disease conditions where a cytokine storm plays a significant role in mortality. The use of curcumin should be investigated in patients with Ebola and cytokine storm. Intravenous formulations may allow achievement of therapeutic blood levels of curcumin. Copyright © 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  7. Nonsteroidal Anti-Inflammatory Drug without Antibiotics for Acute Viral Infection Increases the Empyema Risk in Children: A Matched Case-Control Study.

    Science.gov (United States)

    Le Bourgeois, Muriel; Ferroni, Agnès; Leruez-Ville, Marianne; Varon, Emmanuelle; Thumerelle, Caroline; Brémont, François; Fayon, Michael J; Delacourt, Christophe; Ligier, Caroline; Watier, Laurence; Guillemot, Didier

    2016-08-01

    To investigate the risk factors of empyema after acute viral infection and to clarify the hypothesized association(s) between empyema and some viruses and/or the use of nonsteroidal anti-inflammatory drugs (NSAIDs). A case-control study was conducted in 15 centers. Cases and controls were enrolled for a source population of children 3-15 years of age with acute viral infections between 2006 and 2009. Among 215 empyemas, 83 cases (children with empyema and acute viral infection within the 15 preceding days) were included, and 83 controls (children with acute viral infection) were matched to cases. Considering the intake of any drug within 72 hours after acute viral infection onset and at least 6 consecutive days of antibiotic use and at least 1 day of NSAIDs exposure, the multivariable analysis retained an increased risk of empyema associated with NSAIDs exposure (aOR 2.79, 95% CI 1.4-5.58, P = .004), and a decreased risk associated with antibiotic use (aOR 0.32, 95% CI 0.11-0.97, P = .04). The risk of empyema associated with NSAIDs exposure was greater for children not prescribed an antibiotic and antibiotic intake diminished that risk for children given NSAIDs. NSAIDs use during acute viral infection is associated with an increased risk of empyema in children, and antibiotics are associated with a decreased risk. The presence of antibiotic-NSAIDs interaction with this risk is suggested. These findings suggest that NSAIDs should not be recommended as a first-line antipyretic treatment during acute viral infections in children. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Emerging zoonotic viral diseases.

    Science.gov (United States)

    Wang, L-F; Crameri, G

    2014-08-01

    Zoonotic diseases are infectious diseases that are naturally transmitted from vertebrate animals to humans and vice versa. They are caused by all types of pathogenic agents, including bacteria, parasites, fungi, viruses and prions. Although they have been recognised for many centuries, their impact on public health has increased in the last few decades due to a combination of the success in reducing the spread of human infectious diseases through vaccination and effective therapies and the emergence of novel zoonotic diseases. It is being increasingly recognised that a One Health approach at the human-animal-ecosystem interface is needed for effective investigation, prevention and control of any emerging zoonotic disease. Here, the authors will review the drivers for emergence, highlight some of the high-impact emerging zoonotic diseases of the last two decades and provide examples of novel One Health approaches for disease investigation, prevention and control. Although this review focuses on emerging zoonotic viral diseases, the authors consider that the discussions presented in this paper will be equally applicable to emerging zoonotic diseases of other pathogen types.

  9. Protocol for a randomised controlled implementation trial of point-of-care viral load testing and task shifting: the Simplifying HIV TREAtment and Monitoring (STREAM) study

    OpenAIRE

    Dorward, Jienchi; Garrett, Nigel; Quame-Amaglo, Justice; Samsunder, Natasha; Ngobese, Hope; Ngomane, Noluthando; Moodley, Pravikrishnen; Mlisana, Koleka; Schaafsma, Torin; Donnell, Deborah; Barnabas, Ruanne; Naidoo, Kogieleum; Abdool Karim, Salim; Celum, Connie; Drain, Paul K

    2017-01-01

    Introduction Achieving the Joint United Nations Programme on HIV and AIDS 90-90-90 targets requires models of HIV care that expand antiretroviral therapy (ART) coverage without overburdening health systems. Point-of-care (POC) viral load (VL) testing has the potential to efficiently monitor ART treatment, while enrolled nurses may be able to provide safe and cost-effective chronic care for stable patients with HIV. This study aims to demonstrate whether POC VL testing combined with task shift...

  10. ENGENHARIA DE SEGURANÇA E MEDIDAS DE CONTROLE DE UM LABORATÓRIO DE VACINA VIRAL VETERINÁRIA - ESTUDO DE CASO / ENGINEERING AND SAFETY ACTIONS OF A VETERINARY VIRAL VACCINE LABORATORY - A CASE STUDY

    OpenAIRE

    Glaucia Aparecida PRATES; Maria Cristina Pacheco do NASCIMENTO; Danielle GOVEIA; Cristiane Inácio de CAMPOS; Maristela GAVA

    2013-01-01

    O presente trabalho tem como objetivos avaliar as medidas de controle em um laboratório de vacina viral veterinária de Curitiba através de análise documental. Avaliar o uso de equipamentos de proteção individual (EPIs) e (EPCs) através de análise do Programa de Prevenção de Riscos Ambientais - PPRA e identificar a conformidade dos riscos biológico, químico e físico de acordo com as Normas Regulamentadoras 6 (NR 6) e 9 (NR 9) . O objeto de estudo foi o laboratório de vacina viral de uma instit...

  11. Efficiency of Photodynamic Therapy in the Treatment of Diffuse Facial Viral Warts in an Immunosuppressed Patient: Towards a Gold Standard

    Directory of Open Access Journals (Sweden)

    M. Caucanas

    2010-12-01

    Full Text Available A 64-year-old man with a pulmonary transplant developed diffuse verrucae vulgares of the neck. After the failure of multiple cryotherapy treatments, 3 sessions of photodynamic therapy resulted in rapid therapeutic clinical success. This moderately painful and well-tolerated treatment is reproducible and can be very useful in treating papillomavirus infections in the immunosuppressed patient.

  12. Socioeconomic factors explain suboptimal adherence to antiretroviral therapy among HIV-infected Australian adults with viral suppression

    NARCIS (Netherlands)

    Siefried, Krista J; Mao, Limin; Kerr, Stephen; Cysique, Lucette A; Gates, Thomas M; McAllister, John; Maynard, Anthony; de Wit, John; Carr, Andrew

    2017-01-01

    BACKGROUND: Missing more than one tablet of contemporary antiretroviral therapy (ART) per month increases the risk of virological failure. Recent studies evaluating a comprehensive range of potential risk factors for suboptimal adherence are not available for high-income settings. METHODS: Adults on

  13. Antiretroviral therapy programme on control of HIV transmission in ...

    African Journals Online (AJOL)

    Antiretroviral therapy programme on control of HIV transmission in Morogoro municipality, Tanzania: A challenge for development. ... The government and partners should improve access to ART services to enable many PLHIV to access the services. Key words: Antiretroviral Therapy, Highly Active Antiretroviral Treatment, ...

  14. Art Therapy and Cognitive Processing Therapy for Combat-Related PTSD: A Randomized Controlled Trial

    Science.gov (United States)

    Campbell, Melissa; Decker, Kathleen P.; Kruk, Kerry; Deaver, Sarah P.

    2016-01-01

    This randomized controlled trial was designed to determine if art therapy in conjunction with Cognitive Processing Therapy (CPT) was more effective for reducing symptoms of combat posttraumatic stress disorder (PTSD) than CPT alone. Veterans (N = 11) were randomized to receive either individual CPT, or individual CPT in conjunction with individual…

  15. Manual therapy, physical therapy, or continued care by a general practitioner for patients with neck pain: a randomized, controlled trial.

    NARCIS (Netherlands)

    Hoving, J.L.; Koes, B.W.; Vet, H.C.W. de; Windt, D.A.W.M. van der; Assendelft, W.J.J.; Mameren, H. van; Devillé, W.L.J.M.; Pool, J.J.M.; Scholten, R.J.P.M.; Bouter, L.M.

    2002-01-01

    BACKGROUND: Neck pain is a common problem, but the effectiveness of frequently applied conservative therapies has never been directly compared. OBJECTIVE: To determine the effectiveness of manual therapy, physical therapy, and continued care by a general practitioner. DESIGN: Randomized, controlled

  16. Manual therapy, physical therapy, or continued care by a general practitioner for patients with neck pain. A randomized, controlled trial

    NARCIS (Netherlands)

    Hoving, Jan Lucas; Koes, Bart W.; de Vet, Henrica C. W.; van der Windt, Danielle A. W. M.; Assendelft, Willem J. J.; van Mameren, Henk; Devillé, Walter L. J. M.; Pool, Jan J. M.; Scholten, Rob J. P. M.; Bouter, Lex M.

    2002-01-01

    BACKGROUND: Neck pain is a common problem, but the effectiveness of frequently applied conservative therapies has never been directly compared. OBJECTIVE: To determine the effectiveness of manual therapy, physical therapy, and continued care by a general practitioner. DESIGN: Randomized, controlled

  17. Virally mediated Kcnq1 gene replacement therapy in the immature scala media restores hearing in a mouse model of human Jervell and Lange-Nielsen deafness syndrome.

    Science.gov (United States)

    Chang, Qing; Wang, Jianjun; Li, Qi; Kim, Yeunjung; Zhou, Binfei; Wang, Yunfeng; Li, Huawei; Lin, Xi

    2015-08-01

    Mutations in the potassium channel subunit KCNQ1 cause the human severe congenital deafness Jervell and Lange-Nielsen (JLN) syndrome. We applied a gene therapy approach in a mouse model of JLN syndrome (Kcnq1(-/-) mice) to prevent the development of deafness in the adult stage. A modified adeno-associated virus construct carrying a Kcnq1 expression cassette was injected postnatally (P0-P2) into the endolymph, which resulted in Kcnq1 expression in most cochlear marginal cells where native Kcnq1 is exclusively expressed. We also found that extensive ectopic virally mediated Kcnq1 transgene expression did not affect normal cochlear functions. Examination of cochlear morphology showed that the collapse of the Reissner's membrane and degeneration of hair cells (HCs) and cells in the spiral ganglia were corrected in Kcnq1(-/-) mice. Electrophysiological tests showed normal endocochlear potential in treated ears. In addition, auditory brainstem responses showed significant hearing preservation in the injected ears, ranging from 20 dB improvement to complete correction of the deafness phenotype. Our results demonstrate the first successful gene therapy treatment for gene defects specifically affecting the function of the stria vascularis, which is a major site affected by genetic mutations in inherited hearing loss. © 2015 The Authors. Published under the terms of the CC BY 4.0 license.

  18. Randomized Trial Evaluating the Impact of Ribavirin Mono-Therapy and Double Dosing on Viral Kinetics, Ribavirin Pharmacokinetics and Anemia in Hepatitis C Virus Genotype 1 Infection

    DEFF Research Database (Denmark)

    Waldenström, Jesper; Westin, Johan; Nyström, Kristina

    2016-01-01

    In this pilot study (RibaC), 58 hepatitis C virus (HCV) genotype 1 infected treatment-naïve patients were randomized to (i) 2 weeks ribavirin double dosing concomitant with pegylated interferon-α (pegIFN-α), (ii) 4 weeks ribavirin mono-therapy prior to adding pegIFN-α, or (iii) standard-of-care (......In this pilot study (RibaC), 58 hepatitis C virus (HCV) genotype 1 infected treatment-naïve patients were randomized to (i) 2 weeks ribavirin double dosing concomitant with pegylated interferon-α (pegIFN-α), (ii) 4 weeks ribavirin mono-therapy prior to adding pegIFN-α, or (iii) standard......, by day 14, double dosing entailed a greater hemoglobin decline as compared to SOC (2.2 vs. 1.4 g/dL; P = 0.03). Conclusion: Ribavirin down-regulates IP-10, and may have an anti-viral effect differently regulated across IL28B genotypes....

  19. A single CD4 test with 250 cells/mm3 threshold predicts viral suppression in HIV-infected adults failing first-line therapy by clinical criteria.

    Science.gov (United States)

    Gilks, Charles F; Walker, A Sarah; Munderi, Paula; Kityo, Cissy; Reid, Andrew; Katabira, Elly; Goodall, Ruth L; Grosskurth, Heiner; Mugyenyi, Peter; Hakim, James; Gibb, Diana M

    2013-01-01

    In low-income countries, viral load (VL) monitoring of antiretroviral therapy (ART) is rarely available in the public sector for HIV-infected adults or children. Using clinical failure alone to identify first-line ART failure and trigger regimen switch may result in unnecessary use of costly second-line therapy. Our objective was to identify CD4 threshold values to confirm clinically-determined ART failure when VL is unavailable. 3316 HIV-infected Ugandan/Zimbabwean adults were randomised to first-line ART with Clinically-Driven (CDM, CD4s measured but blinded) or routine Laboratory and Clinical Monitoring (LCM, 12-weekly CD4s) in the DART trial. CD4 at switch and ART failure criteria (new/recurrent WHO 4, single/multiple WHO 3 event; LCM: CD4tiebreaker' of ≥250 cells/mm(3) for clinically-monitored patients failing first-line could identify ∼80% with VL<400 copies/ml, who are unlikely to benefit from second-line. Targeting CD4s to single WHO stage 3 'clinical failures' would particularly avoid premature, costly switch to second-line ART.

  20. Neonatal Gene Therapy for Hemophilia B by a Novel Adenovirus Vector Showing Reduced Leaky Expression of Viral Genes.

    Science.gov (United States)

    Iizuka, Shunsuke; Sakurai, Fuminori; Tachibana, Masashi; Ohashi, Kazuo; Mizuguchi, Hiroyuki

    2017-09-15

    Gene therapy during neonatal and infant stages is a promising approach for hemophilia B, a congenital disorder caused by deficiency of blood coagulation factor IX (FIX). An adenovirus (Ad) vector has high potential for use in neonatal or infant gene therapy for hemophilia B due to its superior transduction properties; however, leaky expression of Ad genes often reduces the transduction efficiencies by Ad protein-mediated tissue damage. Here, we used a novel Ad vector, Ad-E4-122aT, which exhibits a reduction in the leaky expression of Ad genes in liver, in gene therapy studies for neonatal hemophilia B mice. Ad-E4-122aT exhibited significantly higher transduction efficiencies than a conventional Ad vector in neonatal mice. In neonatal hemophilia B mice, a single neonatal injection of Ad-E4-122aT expressing human FIX (hFIX) (Ad-E4-122aT-AHAFIX) maintained more than 6% of the normal plasma hFIX activity levels for approximately 100 days. Sequential administration of Ad-E4-122aT-AHAFIX resulted in more than 100% of the plasma hFIX activity levels for more than 100 days and rescued the bleeding phenotypes of hemophilia B mice. In addition, immunotolerance to hFIX was induced by Ad-E4-122aT-AHAFIX administration in neonatal hemophilia B mice. These results indicated that Ad-E4-122aT is a promising gene delivery vector for neonatal or infant gene therapy for hemophilia B.

  1. Evaluation of bovine viral diarrhoea virus control strategies in dairy herds in Hokkaido, Japan, using stochastic modelling.

    Science.gov (United States)

    Sekiguchi, S; Presi, P; Omori, R; Staerk, K; Schuppers, M; Isoda, N; Yoshikawa, Y; Umemura, T; Nakayama, H; Fujii, Y; Sakoda, Y

    2018-02-01

    Bovine viral diarrhoea virus (BVDV) infection in cattle can result in growth retardation, reduced milk production, reproductive disorders and death. Persistently infected animals are the primary source of infection. In Hokkaido, Japan, all cattle entering shared pastures in summer are vaccinated before movement for disease control. Additionally, these cattle may be tested for BVDV and culled if positive. However, the effectiveness of this control strategy aiming to reduce the number of BVDV-infected animals has not been assessed. The aim of this study was to evaluate the effectiveness of various test-and-cull and/or vaccination strategies on BVDV control in dairy farms in two districts of Hokkaido, Nemuro and Hiyama. A stochastic model was developed to compare the different control strategies over a 10-year period. The model was individual-based and simulated disease dynamics both within and between herds. Parameters included in the model were obtained from the literature, the Hokkaido government and the Japanese Ministry of Agriculture, Forestry and Fisheries. Nine different scenarios were compared as follows: no control, test-and-cull strategies based on antigen testing of either calves or only cattle entering common pastures, vaccination of all adult cattle or only cattle entering shared pastures and combinations thereof. The results indicate that current strategies for BVDV control in Hokkaido slightly reduced the number of BVDV-infected animals; however, alternative strategies such as testing all calves and culling any positives or vaccinating all susceptible adult animals dramatically reduced those. To our knowledge, this is the first report regarding the comparison of the effectiveness between the current strategies in Hokkaido and the alternative strategies for BVDV control measures. © 2017 Blackwell Verlag GmbH.

  2. Radiation therapy quality control in MRCCC radiotherapy units

    International Nuclear Information System (INIS)

    Fielda Djuita; Rina Taurisia; Andreas Nainggolan

    2011-01-01

    Increasing cancer patients in Indonesia is not supported with the number of equipment that is able to treat cancer patients, especially in the radiation therapy field. Therefore, several private hospitals have joined to provide radiation therapy services and one of them is MRCCC. As a new hospital providing services in radiotherapy field, the writer tries to present our quality control program that we have done in our hospital. Purpose: As quality control to radiation therapy clinical practice. Methods: Descriptive essay of what we do in our institution. Conclusion: Average output photon and electron lower more than tolerance dose. (author)

  3. High levels of adherence and viral suppression in a nationally representative sample of HIV-infected adults on antiretroviral therapy for 6, 12 and 18 months in Rwanda.

    Directory of Open Access Journals (Sweden)

    Batya Elul

    Full Text Available BACKGROUND: Generalizable data are needed on the magnitude and determinants of adherence and virological suppression among patients on antiretroviral therapy (ART in Africa. METHODS: We conducted a cross-sectional survey with chart abstraction, patient interviews and site assessments in a nationally representative sample of adults on ART for 6, 12 and 18 months at 20 sites in Rwanda. Adherence was assessed using 3- and 30-day patient recall. A systematically selected sub-sample had viral load (VL measurements. Multivariable logistic regression examined predictors of non-perfect (40 copies/ml. RESULTS: Overall, 1,417 adults were interviewed and 837 had VL measures. Ninety-four percent and 78% reported perfect adherence for the last 3 and 30 days, respectively. Eighty-three percent had undetectable VL. In adjusted models, characteristics independently associated with higher odds of non-perfect 30-day adherence were: being on ART for 18 months (vs. 6 months; younger age; reporting severe (vs. no or few side effects in the prior 30 days; having no documentation of CD4 cell count at ART initiation (vs. having a CD4 cell count of <200 cells/µL; alcohol use; and attending sites which initiated ART services in 2003-2004 and 2005 (vs. 2006-2007; sites with ≥600 (vs. <600 patients on ART; or sites with peer educators. Participation in an association for people living with HIV/AIDS; and receiving care at sites which regularly conduct home-visits were independently associated with lower odds of non-adherence. Higher odds of having a detectable VL were observed among patients at sites with peer educators. Being female; participating in an association for PLWHA; and using a reminder tool were independently associated with lower odds of having detectable VL. CONCLUSIONS: High levels of adherence and viral suppression were observed in the Rwandan national ART program, and associated with potentially modifiable factors.

  4. Prolonged control of replication-competent dual- tropic human immunodeficiency virus-1 following cessation of highly active antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Salgado Maria

    2011-12-01

    Full Text Available Abstract Background While initiation of highly active antiretroviral therapy (HAART during primary HIV-1 infection occasionally results in transient control of viral replication after treatment interruption, the vast majority of patients eventually experience a rebound in plasma viremia. Results Here we report a case of a patient who was started on HAART during symptomatic primary infection and who has subsequently maintained viral loads of + T cells. In addition, he does not have any known protective HLA alleles. Thus it is unlikely that he was destined to become a natural elite controller or suppressor. The mechanism of control of viral replication is unclear; he is infected with a CCR5/CXCR4 dual-tropic virus that is fully replication-competent in vitro. In addition, his spouse, who transmitted the virus to him, developed AIDS. The patient's CD4+ T cells are fully susceptible to HIV-1 infection, and he has low titers of neutralizing antibodies to heterologous and autologous HIV-1 isolates. Furthermore, his CD8+ T cells do not have potent HIV suppressive activity. Conclusion This report suggests that some patients may be capable of controlling pathogenic HIV-1 isolates for extended periods of time after the cessation of HAART through a mechanism that is distinct from the potent cytotoxic T lymphocyte (CTL mediated suppression that has been reported in many elite suppressors.

  5. Factors associated with recent unsuppressed viral load in HIV-1-infected patients in care on first-line antiretroviral therapy in South Africa.

    Science.gov (United States)

    Joseph Davey, D; Abrahams, Z; Feinberg, M; Prins, M; Serrao, C; Medeossi, B; Darkoh, E

    2018-05-01

    Unsuppressed viral load (VL) in patients on antiretroviral therapy (ART) occurs when treatment fails to suppress a person's VL and is associated with decreased survival and increased HIV transmission. The objective of this study was to evaluate factors associated with unsuppressed VL (VL > 400 copies/ml) in patients currently in care on first-line ART for ≥ 6 months attending South African public healthcare facilities. We analysed electronic medical records of ART patients with a VL result on record who started ART between January 2004 and April 2016 from 271 public health facilities. We present descriptive and multivariable logistic regression for unsuppressed VL at last visit using a priori variables. We included 244,370 patients (69% female) on first-line ART in April 2016 for ≥ 6 months. Median age at ART start was 33 years (7% were < 15 years old). Median duration on ART was 3.7 years. Adjusting for other variables, factors associated with having an unsuppressed VL at the most recent visit among patients in care included: (1) < 15 years old at ART start (adjusted odds ratio [aOR]=2.58; 95% CI = 2.37, 2.81) versus 15-49 years at ART start, (2) male gender (aOR = 1.29; 95% CI = 1.25, 1.35), (3) 6-12 months on ART versus longer (aOR = 1.34; 95% CI = 1.29, 1.40), (4) on tuberculosis (TB) treatment (aOR = 1.78; 95% CI = 1.48, 2.13), and (5) prior ART exposure versus none (aOR = 1.20; 95% CI = 1.08, 1.32). Approximately 85% of the ART cohort who were in care had achieved viral suppression, though men, youth/adolescents, patients with prior ART exposure, those with short duration of ART, and patients on TB treatment had increased odds of not achieving viral suppression. There is a need to develop and evaluate targeted interventions for ART patients in care who are at high risk of unsuppressed VL.

  6. Sub-optimal CD4 reconstitution despite viral suppression in an urban cohort on antiretroviral therapy (ART) in sub-Saharan Africa: frequency and clinical significance.

    Science.gov (United States)

    Nakanjako, Damalie; Kiragga, Agnes; Ibrahim, Fowzia; Castelnuovo, Barbara; Kamya, Moses R; Easterbrook, Philippa J

    2008-10-28

    A proportion of individuals who start antiretroviral therapy (ART) fail to achieve adequate CD4 cell reconstitution despite sustained viral suppression. We determined the frequency and clinical significance of suboptimal CD4 reconstitution despite viral suppression (SO-CD4) in an urban HIV research cohort in Kampala, Uganda. We analyzed data from a prospective research cohort of 559 patients initiating ART between 04/04-04/05. We described the patterns of SO-CD4 both in terms of:- I) magnitude of CD4 cell increase (a CD4 count increase ART) and II) failure to achieve a CD4 cell count above 200 cells/microl at 6,12 and 24 months of ART. Using criteria I) we used logistic regression to determine the predictors of SO-CD4. We compared the cumulative risk of clinical events (death and/or recurrent or new AIDS-defining illnesses) among patients with and without SO-CD4. Of 559 patients initiating ART, 386 (69%) were female. Median (IQR) age and baseline CD4 counts were 38 yrs (33-44) and 98 cells/microl (21-163) respectively; 414 (74%) started a d4T-based regimen (D4T+3TC+NVP) and 145 (26%) a ZDV-based regimen (ZDV+3TC+EFV). After 6, 12 and 24 months of ART, 380 (68%), 339 (61%) and 309 (55%) had attained and sustained HIV-RNA viral suppression. Of these, 78 (21%), 151 (45%) and 166 (54%) respectively had SO-CD4 based on criteria I), and 165(43%), 143(42%) and 58(19%) respectively based on criteria II). With both criteria combined, 56 (15%) and 129 (38%) had SO-CD4 at 6 and 12 months respectively. A high proportion (82% and 58%) of those that had SO-CD4 at 6 months (using criteria I) maintained SO-CD4 at 12 and 24 months respectively. There were no statistically significant differences in the incidence of clinical events among patients with [19/100PYO (12-29)] and without SO-CD4 [23/100PYO (19-28)]. Using criteria I), the frequency of SO-CD4 was 21% at 6 months. Majority of patients with SO-CD4 at 6 months maintained SO-CD4 up to 2 years. We recommend studies of CD4 T

  7. Valuable Virality

    NARCIS (Netherlands)

    Akpinar, E.; Berger, Jonah

    2017-01-01

    Given recent interest in social media, many brands now create content that they hope consumers will view and share with peers. While some campaigns indeed go “viral,” their value to the brand is limited if they do not boost brand evaluation or increase purchase. Consequently, a key question is how

  8. Effects of Music Therapy on Drug Therapy of Adult Psychiatric Outpatients: A Pilot Randomized Controlled Study

    Science.gov (United States)

    Degli Stefani, Mario; Biasutti, Michele

    2016-01-01

    Objective: Framed in the patients’ engagement perspective, the current study aims to determine the effects of group music therapy in addition to drug care in comparison with drug care in addition to other non-expressive group activities in the treatment of psychiatric outpatients. Method: Participants (n = 27) with ICD-10 diagnoses of F20 (schizophrenia), F25 (schizoaffective disorders), F31 (bipolar affective disorder), F32 (depressive episode), and F60 (specific personality disorders) were randomized to receive group music therapy plus standard care (48 weekly sessions of 2 h) or standard care only. The clinical measures included dosages of neuroleptics, benzodiazepines, mood stabilizers, and antidepressants. Results: The participants who received group music therapy demonstrated greater improvement in drug dosage with respect to neuroleptics than those who did not receive group music therapy. Antidepressants had an increment for both groups that was significant only for the control group. Benzodiazepines and mood stabilizers did not show any significant change in either group. Conclusion: Group music therapy combined with standard drug care was effective for controlling neuroleptic drug dosages in adult psychiatric outpatients who received group music therapy. We discussed the likely applications of group music therapy in psychiatry and the possible contribution of music therapy in improving the psychopathological condition of adult outpatients. In addition, the implications for the patient-centered perspective were also discussed. PMID:27774073

  9. Effects of music therapy on drug therapy of adult psychiatric outpatients: A pilot randomised controlled study

    Directory of Open Access Journals (Sweden)

    Mario Degli Stefani

    2016-10-01

    Full Text Available Objective: Framed in the patients’ engagement perspective, the current study aims to determine the effects of group music therapy in addition to drug care in comparison with drug care in the treatment of psychiatric outpatients. Method: Participants (n = 27 with ICD-10 diagnoses of F20 (schizophrenia, F25 (schizoaffective disorders, F31 (bipolar affective disorder, F32 (depressive episode and F60 (specific personality disorders were randomised to receive group music therapy plus standard care (48 weekly sessions of two hours or standard care only. The clinical measures included dosages of neuroleptics, benzodiazepines, mood stabilisers and antidepressants. Results: The participants who received group music therapy demonstrated greater improvement in drug dosage relative to neuroleptics than those who did not receive group music therapy. Antidepressants had an increment for both groups that was significant only for the control group. Benzodiazepines and mood stabilisers did not show any significant change in either group. Conclusions: Group music therapy combined with standard drug care is effective for controlling neuroleptic drug dosages in adult psychiatric outpatients who received group music therapy. We discuss the likely applications of group music therapy in psychiatry and the possible contribution of music therapy in improving the psychopathological condition of adult outpatients. In addition, the implications for the patient-centred perspective were also discussed.

  10. Baseline prediction of combination therapy outcome in hepatitis C virus 1b infected patients by discriminant analysis using viral and host factors.

    Science.gov (United States)

    Saludes, Verónica; Bracho, Maria Alma; Valero, Oliver; Ardèvol, Mercè; Planas, Ramón; González-Candelas, Fernando; Ausina, Vicente; Martró, Elisa

    2010-11-30

    Current treatment of chronic hepatitis C virus (HCV) infection has limited efficacy -especially among genotype 1 infected patients-, is costly, and involves severe side effects. Thus, predicting non-response is of major interest for both patient wellbeing and health care expense. At present, treatment cannot be individualized on the basis of any baseline predictor of response. We aimed to identify pre-treatment clinical and virological parameters associated with treatment failure, as well as to assess whether therapy outcome could be predicted at baseline. Forty-three HCV subtype 1b (HCV-1b) chronically infected patients treated with pegylated-interferon alpha plus ribavirin were retrospectively studied (21 responders and 22 non-responders). Host (gender, age, weight, transaminase levels, fibrosis stage, and source of infection) and viral-related factors (viral load, and genetic variability in the E1-E2 and Core regions) were assessed. Logistic regression and discriminant analyses were used to develop predictive models. A "leave-one-out" cross-validation method was used to assess the reliability of the discriminant models. Lower alanine transaminase levels (ALT, p=0.009), a higher number of quasispecies variants in the E1-E2 region (number of haplotypes, nHap_E1-E2) (p=0.003), and the absence of both amino acid arginine at position 70 and leucine at position 91 in the Core region (p=0.039) were significantly associated with treatment failure. Therapy outcome was most accurately predicted by discriminant analysis (90.5% sensitivity and 95.5% specificity, 85.7% sensitivity and 81.8% specificity after cross-validation); the most significant variables included in the predictive model were the Core amino acid pattern, the nHap_E1-E2, and gamma-glutamyl transferase and ALT levels. Discriminant analysis has been shown as a useful tool to predict treatment outcome using baseline HCV genetic variability and host characteristics. The discriminant models obtained in this

  11. A single CD4 test with 250 cells/mm3 threshold predicts viral suppression in HIV-infected adults failing first-line therapy by clinical criteria.

    Directory of Open Access Journals (Sweden)

    Charles F Gilks

    Full Text Available In low-income countries, viral load (VL monitoring of antiretroviral therapy (ART is rarely available in the public sector for HIV-infected adults or children. Using clinical failure alone to identify first-line ART failure and trigger regimen switch may result in unnecessary use of costly second-line therapy. Our objective was to identify CD4 threshold values to confirm clinically-determined ART failure when VL is unavailable.3316 HIV-infected Ugandan/Zimbabwean adults were randomised to first-line ART with Clinically-Driven (CDM, CD4s measured but blinded or routine Laboratory and Clinical Monitoring (LCM, 12-weekly CD4s in the DART trial. CD4 at switch and ART failure criteria (new/recurrent WHO 4, single/multiple WHO 3 event; LCM: CD4<100 cells/mm(3 were reviewed in 361 LCM, 314 CDM participants who switched over median 5 years follow-up. Retrospective VLs were available in 368 (55% participants.Overall, 265/361 (73% LCM participants failed with CD4<100 cells/mm(3; only 7 (2% switched with CD4≥250 cells/mm(3, four switches triggered by WHO events. Without CD4 monitoring, 207/314 (66% CDM participants failed with WHO 4 events, and 77(25%/30(10% with single/multiple WHO 3 events. Failure/switching with single WHO 3 events was more likely with CD4≥250 cells/mm(3 (28/77; 36% (p = 0.0002. CD4 monitoring reduced switching with viral suppression: 23/187 (12% LCM versus 49/181 (27% CDM had VL<400 copies/ml at failure/switch (p<0.0001. Amongst CDM participants with CD4<250 cells/mm(3 only 11/133 (8% had VL<400 copies/ml, compared with 38/48 (79% with CD4≥250 cells/mm(3 (p<0.0001.Multiple, but not single, WHO 3 events predicted first-line ART failure. A CD4 threshold 'tiebreaker' of ≥250 cells/mm(3 for clinically-monitored patients failing first-line could identify ∼80% with VL<400 copies/ml, who are unlikely to benefit from second-line. Targeting CD4s to single WHO stage 3 'clinical failures' would particularly avoid premature, costly

  12. Chapter 10: Glucose control: insulin therapy*

    African Journals Online (AJOL)

    Insulin and its analogues lower blood glucose by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulin inhibits ... control on 2 or 3 oral glucose lowering drugs.

  13. Delivering precision antimicrobial therapy through closed-loop control systems

    Science.gov (United States)

    Rawson, T M; O’Hare, D; Herrero, P; Sharma, S; Moore, L S P; de Barra, E; Roberts, J A; Gordon, A C; Hope, W; Georgiou, P; Cass, A E G; Holmes, A H

    2018-01-01

    Abstract Sub-optimal exposure to antimicrobial therapy is associated with poor patient outcomes and the development of antimicrobial resistance. Mechanisms for optimizing the concentration of a drug within the individual patient are under development. However, several barriers remain in realizing true individualization of therapy. These include problems with plasma drug sampling, availability of appropriate assays, and current mechanisms for dose adjustment. Biosensor technology offers a means of providing real-time monitoring of antimicrobials in a minimally invasive fashion. We report the potential for using microneedle biosensor technology as part of closed-loop control systems for the optimization of antimicrobial therapy in individual patients. PMID:29211877

  14. 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

  15. Art Therapy and Cognitive Processing Therapy for Combat-Related PTSD: A Randomized Controlled Trial

    Science.gov (United States)

    Campbell, Melissa; Decker, Kathleen P.; Kruk, Kerry; Deaver, Sarah P.

    2018-01-01

    This randomized controlled trial was designed to determine if art therapy in conjunction with Cognitive Processing Therapy (CPT) was more effective for reducing symptoms of combat posttraumatic stress disorder (PTSD) than CPT alone. Veterans (N = 11) were randomized to receive either individual CPT, or individual CPT in conjunction with individual art therapy. PTSD Checklist–Military Version and Beck Depression Inventory–II scores improved with treatment in both groups with no significant difference in improvement between the experimental and control groups. Art therapy in conjunction with CPT was found to improve trauma processing and veterans considered it to be an important part of their treatment as it provided healthy distancing, enhanced trauma recall, and increased access to emotions. PMID:29332989

  16. Immunological Control of Viral Infections in Bats and the Emergence of Viruses Highly Pathogenic to Humans

    Directory of Open Access Journals (Sweden)

    Tony Schountz

    2017-09-01

    Full Text Available Bats are reservoir hosts of many important viruses that cause substantial disease in humans, including coronaviruses, filoviruses, lyssaviruses, and henipaviruses. Other than the lyssaviruses, they do not appear to cause disease in the reservoir bats, thus an explanation for the dichotomous outcomes of infections of humans and bat reservoirs remains to be determined. Bats appear to have a few unusual features that may account for these differences, including evidence of constitutive interferon (IFN activation and greater combinatorial diversity in immunoglobulin genes that do not undergo substantial affinity maturation. We propose these features may, in part, account for why bats can host these viruses without disease and how they may contribute to the highly pathogenic nature of bat-borne viruses after spillover into humans. Because of the constitutive IFN activity, bat-borne viruses may be shed at low levels from bat cells. With large naive antibody repertoires, bats may control the limited virus replication without the need for rapid affinity maturation, and this may explain why bats typically have low antibody titers to viruses. However, because bat viruses have evolved in high IFN environments, they have enhanced countermeasures against the IFN response. Thus, upon infection of human cells, where the IFN response is not constitutive, the viruses overwhelm the IFN response, leading to abundant virus replication and pathology.

  17. Physical non-viral gene delivery methods for tissue engineering

    Science.gov (United States)

    Mellott, Adam J.; Forrest, M. Laird; Detamore, Michael S.

    2016-01-01

    The integration of gene therapy into tissue engineering to control differentiation and direct tissue formation is not a new concept; however, successful delivery of nucleic acids into primary cells, progenitor cells, and stem cells has proven exceptionally challenging. Viral vectors are generally highly effective at delivering nucleic acids to a variety of cell populations, both dividing and non-dividing, yet these viral vectors are marred by significant safety concerns. Non-viral vectors are preferred for gene therapy, despite lower transfection efficiencies, and possess many customizable attributes that are desirable for tissue engineering applications. However, there is no single non-viral gene delivery strategy that “fits-all” cell types and tissues. Thus, there is a compelling opportunity to examine different non-viral vectors, especially physical vectors, and compare their relative degrees of success. This review examines the advantages and disadvantages of physical non-viral methods (i.e., microinjection, ballistic gene delivery, electroporation, sonoporation, laser irradiation, magnetofection, and electric field-induced molecular vibration), with particular attention given to electroporation because of its versatility, with further special emphasis on Nucleofection™. In addition, attributes of cellular character that can be used to improve differentiation strategies are examined for tissue engineering applications. Ultimately, electroporation exhibits a high transfection efficiency in many cell types, which is highly desirable for tissue engineering applications, but electroporation and other physical non-viral gene delivery methods are still limited by poor cell viability. Overcoming the challenge of poor cell viability in highly efficient physical non-viral techniques is the key to using gene delivery to enhance tissue engineering applications. PMID:23099792

  18. Physical non-viral gene delivery methods for tissue engineering.

    Science.gov (United States)

    Mellott, Adam J; Forrest, M Laird; Detamore, Michael S

    2013-03-01

    The integration of gene therapy into tissue engineering to control differentiation and direct tissue formation is not a new concept; however, successful delivery of nucleic acids into primary cells, progenitor cells, and stem cells has proven exceptionally challenging. Viral vectors are generally highly effective at delivering nucleic acids to a variety of cell populations, both dividing and non-dividing, yet these viral vectors are marred by significant safety concerns. Non-viral vectors are preferred for gene therapy, despite lower transfection efficiencies, and possess many customizable attributes that are desirable for tissue engineering applications. However, there is no single non-viral gene delivery strategy that "fits-all" cell types and tissues. Thus, there is a compelling opportunity to examine different non-viral vectors, especially physical vectors, and compare their relative degrees of success. This review examines the advantages and disadvantages of physical non-viral methods (i.e., microinjection, ballistic gene delivery, electroporation, sonoporation, laser irradiation, magnetofection, and electric field-induced molecular vibration), with particular attention given to electroporation because of its versatility, with further special emphasis on Nucleofection™. In addition, attributes of cellular character that can be used to improve differentiation strategies are examined for tissue engineering applications. Ultimately, electroporation exhibits a high transfection efficiency in many cell types, which is highly desirable for tissue engineering applications, but electroporation and other physical non-viral gene delivery methods are still limited by poor cell viability. Overcoming the challenge of poor cell viability in highly efficient physical non-viral techniques is the key to using gene delivery to enhance tissue engineering applications.

  19. Transgenic Clustered Regularly Interspaced Short Palindromic Repeat/Cas9-Mediated Viral Gene Targeting for Antiviral Therapy of Bombyx mori Nucleopolyhedrovirus.

    Science.gov (United States)

    Chen, Shuqing; Hou, Chengxiang; Bi, Honglun; Wang, Yueqiang; Xu, Jun; Li, Muwang; James, Anthony A; Huang, Yongping; Tan, Anjiang

    2017-04-15

    We developed a novel antiviral strategy by combining transposon-based transgenesis and the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system for the direct cleavage of Bombyx mori nucleopolyhedrovirus (BmNPV) genome DNA to promote virus clearance in silkworms. We demonstrate that transgenic silkworms constitutively expressing Cas9 and guide RNAs targeting the BmNPV immediate early-1 ( ie-1 ) and me53 genes effectively induce target-specific cleavage and subsequent mutagenesis, especially large (∼7-kbp) segment deletions in BmNPV genomes, and thus exhibit robust suppression of BmNPV proliferation. Transgenic animals exhibited higher and inheritable resistance to BmNPV infection than wild-type animals. Our approach will not only contribute to modern sericulture but also shed light on future antiviral therapy. IMPORTANCE Pathogen genome targeting has shown its potential in antiviral research. However, transgenic CRISPR/Cas9 system-mediated viral genome targeting has not been reported as an antiviral strategy in a natural animal host of a virus. Our data provide an effective approach against BmNPV infection in a real-world biological system and demonstrate the potential of transgenic CRISPR/Cas9 systems in antiviral research in other species. Copyright © 2017 Chen et al.

  20. Association of Adolescent- and Caregiver-Reported Antiretroviral Therapy Adherence with HIV Viral Load Among Perinatally-infected South African Adolescents.

    Science.gov (United States)

    Brittain, Kirsty; Asafu-Agyei, Nana Akua; Hoare, Jacqueline; Bekker, Linda-Gail; Rabie, Helena; Nuttall, James; Roux, Paul; Stein, Dan J; Zar, Heather J; Myer, Landon

    2018-03-01

    Accurate measurement of antiretroviral therapy (ART) adherence remains challenging and there are few data assessing the validity of self-reported adherence among perinatally HIV-infected adolescents. We examined adolescent and caregiver reports of adolescent adherence among perinatally-infected adolescents aged 9-14 years in Cape Town, South Africa, and explored factors that may modify associations between reported adherence and elevated viral load (VL). Among 474 adolescents (median age 12.0 years; median duration of ART use 7.5 years), elevated VL and caregiver- and adolescent-report of missed ART doses were common. Elevated VL was particularly prevalent among older, male adolescents. Low-moderate concordance was observed between caregiver and adolescent report. Among adolescents aged ≥ 12 years, caregiver- and adolescent-reported adherence was associated with elevated VL across most items assessed, but few significant associations were observed among adolescents adolescents who require adherence interventions are needed in this context.

  1. Viral Delivery of dsRNA for Control of Insect Agricultural Pests and Vectors of Human Disease: Prospects and Challenges

    Directory of Open Access Journals (Sweden)

    Anna Kolliopoulou

    2017-06-01

    Full Text Available RNAi is applied as a new and safe method for pest control in agriculture but efficiency and specificity of delivery of dsRNA trigger remains a critical issue. Various agents have been proposed to augment dsRNA delivery, such as engineered micro-organisms and synthetic nanoparticles, but the use of viruses has received relatively little attention. Here we present a critical view of the potential of the use of recombinant viruses for efficient and specific delivery of dsRNA. First of all, it requires the availability of plasmid-based reverse genetics systems for virus production, of which an overview is presented. For RNA viruses, their application seems to be straightforward since dsRNA is produced as an intermediate molecule during viral replication, but DNA viruses also have potential through the production of RNA hairpins after transcription. However, application of recombinant virus for dsRNA delivery may not be straightforward in many cases, since viruses can encode RNAi suppressors, and virus-induced silencing effects can be determined by the properties of the encoded RNAi suppressor. An alternative is virus-like particles that retain the efficiency and specificity determinants of natural virions but have encapsidated non-replicating RNA. Finally, the use of viruses raises important safety issues which need to be addressed before application can proceed.

  2. Viral infection and oral habits as risk factors for oral squamous cell carcinoma in Yemen: a case-control study.

    Science.gov (United States)

    Nasher, Akram T; Al-Hebshi, Nezar N; Al-Moayad, Ebtisam E; Suleiman, Ahmed M

    2014-11-01

    The role of qat chewing, tobacco (shammah) dipping, smoking, alcohol drinking, and oral viral infection as risk factors for oral squamous cell carcinoma (OSCC) in Yemen was assessed. A total of 60 cases of OSCC and 120 age- and gender-matched controls were analyzed with respect to demographic data, history of oral habits, and the presence of human papillomavirus (HPV)-16, HPV-18, or Epstein-Barr virus (EBV) as determined by Taqman quantitative polymerase chain reaction. Logistic regression analysis was used to identify independent predictors of the disease. Shammah use was the only risk factor for OSCC, with an odds ratio of 12.6 (CI, 3.3-48.2) and 39 (CI, 14-105) for the ex-users and current users, respectively. The association of shammah use alone with OSCC exceeded that of shammah use in combination with qat chewing, smoking, or both. EBV infection, smoking, and qat chewing showed no association with OSCC, while neither HPV-16 nor HPV-18 were detected in any sample. Shammah use is a major risk factor for oral cancer in Yemen. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Viral hijacking of a replicative helicase loader and its implications for helicase loading control and phage replication

    Energy Technology Data Exchange (ETDEWEB)

    Hood, Iris V.; Berger, James M.

    2016-05-31

    Replisome assembly requires the loading of replicative hexameric helicases onto origins by AAA+ ATPases. How loader activity is appropriately controlled remains unclear. Here, we use structural and biochemical analyses to establish how an antimicrobial phage protein interferes with the function of theStaphylococcus aureusreplicative helicase loader, DnaI. The viral protein binds to the loader’s AAA+ ATPase domain, allowing binding of the host replicative helicase but impeding loader self-assembly and ATPase activity. Close inspection of the complex highlights an unexpected locus for the binding of an interdomain linker element in DnaI/DnaC-family proteins. We find that the inhibitor protein is genetically coupled to a phage-encoded homolog of the bacterial helicase loader, which we show binds to the host helicase but not to the inhibitor itself. These findings establish a new approach by which viruses can hijack host replication processes and explain how loader activity is internally regulated to prevent aberrant auto-association.

  4. Growth, immune and viral responses in HIV infected African children receiving highly active antiretroviral therapy: a prospective cohort study

    Directory of Open Access Journals (Sweden)

    Bagenda Danstan

    2010-08-01

    Full Text Available Abstract Background Scale up of paediatric antiretroviral therapy in resource limited settings continues despite limited access to routine laboratory monitoring. We documented the weight and height responses in HIV infected Ugandan children on highly active antiretroviral therapy and determined clinical factors associated with successful treatment outcomes. Methods A prospective cohort of HIV infected children were initiated on HAART and followed for 48 weeks. Body mass index for age z scores(BAZ, weight and height-for-age z scores (WAZ & HAZ were calculated: CD4 cell % and HIV-1 RNA were measured at baseline and every 12 weeks. Treatment outcomes were classified according to; both virological and immunological success (VS/IS, virological failure and immunological success (VF/IS. virological success and immunological failure (VS/IF and both virological and immunological failure (VF/IF. Results From March 2004 until May 2006, 124 HIV infected children were initiated on HAART. The median age (IQR was 5.0 years (2.1 - 7.0 and 49% (61/124 were female. The median [95% confidence interval (CI] BAZ, WAZ and HAZ at baseline were 0.29 (-2.9, -1.2, -1.2 (-2.1, -0.5 and -2.06 (-2.9, -1.2 respectively. Baseline median CD4 cell % and log10 HIV-1 RNA were; 11.8% (7.5-18.0 and 5.6 (5.2-5.8 copies/ml. By 48 weeks, mean WAZ and HAZ in the VF/IS group, which was younger, increased from - 0.98 (SD 1.7 to + 1.22 (SD 1.2 and from -1.99 (1.7 to + 0.76 (2.4 respectively. Mean increase in WAZ and HAZ in the VS/IF group, an older group was modest, from -1.84 (1.3 to - 0.41 (1.2 and -2.25 (1.2 to -1.16 (1.3 respectively. Baseline CD4 cell % [OR 6.97 95% CI (2.6 -18.6], age [OR 4.6 95% CI (1.14 -19.1] and WHO clinical stage [OR 3.5 95%CI (1.05 -12.7] were associated with successful treatment outcome. Conclusions HIV infected Ugandan children demonstrated a robust increase in height and weight z scores during the first 48 weeks of HAART, including those who failed to

  5. Peg-interferon plus nucleotide analogue treatment versus no treatment in patients with chronic hepatitis B with a low viral load: a randomised controlled, open-label trial.

    Science.gov (United States)

    de Niet, Annikki; Jansen, Louis; Stelma, Femke; Willemse, Sophie B; Kuiken, Sjoerd D; Weijer, Sebastiaan; van Nieuwkerk, Carin M J; Zaaijer, Hans L; Molenkamp, Richard; Takkenberg, R Bart; Koot, Maarten; Verheij, Joanne; Beuers, Ulrich; Reesink, Hendrik W

    2017-08-01

    Antiviral treatment is currently not recommended for patients with chronic hepatitis B with a low viral load. However, they might benefit from acquiring a functional cure (hepatitis B surface antigen [HBsAg] loss with or without formation of antibodies against hepatitis B surface antigen [anti-HBs]). We assessed HBsAg loss during peg-interferon-alfa-2a (peg-IFN) and nucleotide analogue combination therapy in patients with chronic hepatitis B with a low viral load. In this randomised controlled, open-label trial, patients were enrolled from the Academic Medical Center (AMC), Amsterdam, Netherlands. Eligible patients were HBsAg positive and hepatitis B e antigen (HBeAg) negative for more than 6 months, could be treatment naive or treatment experienced, and had alanine aminotransferase (ALT) concentrations less than 5 × upper limit of normal (ULN). Participants were randomly assigned (1:1:1) by a computerised randomisation programme (ALEA Randomisation Service) to receive peg-IFN 180 μg/week plus adefovir 10 mg/day, peg-IFN 180 μg/week plus tenofovir disoproxil fumarate 245 mg/day, or no treatment for 48 weeks. The primary endpoint was the proportion of patients with serum HBsAg loss among those who received at least one dose of study drug or had at least one study visit (modified intention-to-treat population [mITT]). All patients have finished the initial study of 72 weeks and will be observed for up to 5 years of follow-up. This study is registered with ClinicalTrials.gov, number NCT00973219. Between Aug 4, 2009, and Oct 17, 2013, 167 patients were screened for enrolment, of whom 151 were randomly assigned (52 to peg-IFN plus adefovir, 51 to peg-IFN plus tenofovir, and 48 to no treatment). 46 participants in the peg-IFN plus adefovir group, 45 in the peg-IFN plus tenofovir group, and 43 in the no treatment group began treatment or observation and were included in the mITT population. At week 72, two (4%) patients in the peg-IFN plus adefovir group and two (4

  6. Specific micro RNA-regulated TetR-KRAB transcriptional control of transgene expression in viral vector-transduced cells.

    Directory of Open Access Journals (Sweden)

    Virginie Pichard

    Full Text Available Precise control of transgene expression in a tissue-specific and temporally regulated manner is desirable for many basic and applied investigations gene therapy applications. This is important to regulate dose of transgene products and minimize unwanted effects. Previously described methods have employed tissue specific promoters, miRNA-based transgene silencing or tetR-KRAB-mediated suppression of transgene promoters. To improve on versatility of transgene expression control, we have developed expression systems that use combinations of a tetR-KRAB artificial transgene-repressor, endogenous miRNA silencing machinery and tissue specific promoters. Precise control of transgene expression was demonstrated in liver-, macrophage- and muscle-derived cells. Efficiency was also demonstrated in vivo in murine muscle. This multicomponent and modular regulatory system provides a robust and easily adaptable method for achieving regulated transgene expression in different tissue types. The improved precision of regulation will be useful for many gene therapy applications requiring specific spatiotemporal transgene regulation.

  7. THERAPY: A RANDOMIZED CONTROLLED PILOT STUDY

    Directory of Open Access Journals (Sweden)

    SOFIA VON HUMBOLDT

    2013-01-01

    Full Text Available El objetivo del estudio que se informa fue ex- plorar si una intervención individual de terapia centrada en la persona (TCP en personas adul- tas mayores puede promover su sentido de cohe- rencia, en comparación con un grupo control (lista de espera. Se plantea que los participantes asignados al azar a TCP informarían mejoras en SDC de pre y post-intervención en comparación con el grupo control. Un grupo de 87 participantes de 65 a 86 años (M = 72.4; DE = 5.15 fue evaluado con la Escala de Sentido de Coherencia (ESDC y el cuestio- nario sociodemográfico en tres momentos dife- rentes: al inicio del estudio (t1, post-tratamiento (t2 y a los 12 meses de seguimiento (t3. Los resultados indicaron que los participan- tes en TCP evidenciaron un aumento significa- tivo en cuanto a su SDC (16.7%, mientras que en el grupo control se encontró una disminu- ción significativa (-2.7%, entre el inicio del es- tudio y el momento de seguimiento. El tamaño del efecto en el grupo TCP fue alto (η2p = .776. En concreto, tanto en la post-intervención como en el momento del seguimiento, los participan- tes que se sometieron a TCP tenían un SDC sig- nificativamente mayor (M = 3.84, DE = .219 Se encontraron diferencias significativas entre el grupo de intervención y el grupo control en la post-intervención y en el seguimiento. Se concluye que los cambios en SDC fueron positivos y mantenidos, por lo tanto, los resul- tados sugieren que la TCP es favorable a la me- jora de SDC. Por otra parte, ya que la SDC se asocia con el bienestar relacionado con la salud de las poblaciones de mayor edad, hay que en- fatizar el desarrollo de SDC en la vejez.

  8. Anti-viral drug treatment along with immune activator IL-2: a control-based mathematical approach for HIV infection

    Science.gov (United States)

    Nath Chatterjee, Amar; Roy, Priti Kumar

    2012-02-01

    Recent development in antiretroviral treatment against HIV can help AIDS patients to fight against HIV. But the question that whether the disease is to be partially or totally eradicated from HIV infected individuals still remains unsolved. Usually, the most effective treatment for the disease is HAART which can only control the disease progression. But as the immune system becomes weak, the patients can not fight against other diseases. Immune cells are activated and proliferated by IL-2 after the identification of antigen. IL-2 production is impaired in HIV positive patients and intermitted administration of immune activator IL-2 together with HAART which is a more effective treatment to fight against the disease. Thus, its expediency is essential and is yet to be explored. In this article we anticipated a mathematical model of the effect of IL-2 together with RTIs therapy in HIV positive patients. Our analytical as well as numerical study shows that the optimal schedule of treatment for best result is to be obtained by systematic drug therapy. But at the last stage of treatment, the infection level raises again due to minimisation of drug dosage. Thus we study the perfect adherence of the drugs and found out if RTIs are taken with sufficient interval then for fixed interval of IL-2 therapy, certain amount of drug dosages may be able to sustain the immune system at pre-infection stage and the infected CD4+T cells are going towards extinction.

  9. High level of viral suppression and low switch rate to second-line antiretroviral therapy among HIV-infected adult patients followed over five years: retrospective analysis of the DART trial.

    Directory of Open Access Journals (Sweden)

    Cissy Kityo

    Full Text Available In contrast to resource-rich countries, most HIV-infected patients in resource-limited countries receive treatment without virological monitoring. There are few long-term data, in this setting, on rates of viral suppression or switch to second-line antiretroviral therapy. The DART trial compared clinically driven monitoring (CDM versus routine laboratory (CD4/haematology/biochemistry and clinical monitoring (LCM in HIV-infected adults initiating therapy. There was no virological monitoring in either study group during follow-up, but viral load was measured in Ugandan participants at trial closure. Two thousand three hundred and seventeen (2317 participants from this country initiated antiretroviral therapy with zidovudine/lamivudine plus tenofovir (n = 1717, abacavir (n = 300, or nevirapine (n = 300. Of 1896 (81.8% participants who were alive and in follow-up at trial closure (median 5.1 years after therapy initiation, 1507 (79.5% were on first-line and 389 (20.5% on second-line antiretroviral therapy. The overall switch rate after the first year was 5.6 per 100 person-years; the rate was substantially higher in participants with low baseline CD4 counts (<50 cells/mm3. Among 1207 (80.1% first-line participants with viral load measured, HIV RNA was <400 copies/ml in 963 (79.8%, 400-999 copies/ml in 37 (3.1%, 1,000-9,999 copies/ml in 110 (9.1%, and ≥10,000 copies/ml in 97 (8.0%. The proportion with HIV RNA <400 copies/ml was slightly lower (difference 7.1%, 95% CI 2.5 to 11.5% in CDM (76.3% than in LCM (83.4%. Among 252 (64.8% second-line participants with viral load measured (median 2.3 years after switch, HIV RNA was <400 copies/ml in 226 (89.7%, with no difference between monitoring strategies. Low switch rates and high, sustained levels of viral suppression are achievable without viral load or CD4 count monitoring in the context of high-quality clinical care.ISRCTN13968779.

  10. HCV Specific IL-21 Producing T Cells but Not IL-17A Producing T Cells Are Associated with HCV Viral Control in HIV/HCV Coinfection.

    Directory of Open Access Journals (Sweden)

    Sonya A MacParland

    Full Text Available Decreased hepatitis C virus (HCV clearance, faster cirrhosis progression and higher HCV RNA levels are associated with Human Immunodeficiency virus (HIV coinfection. The CD4+ T helper cytokines interleukin (IL-21 and IL-17A are associated with virus control and inflammation, respectively, both important in HCV and HIV disease progression. Here, we examined how antigen-specific production of these cytokines during HCV mono and HIV/HCV coinfection was associated with HCV virus control.We measured HCV-specific IL-21 and IL-17A production by transwell cytokine secretion assay in PBMCs from monoinfected and coinfected individuals. Viral control was determined by plasma HCV RNA levels.In acutely infected individuals, those able to establish transient/complete HCV viral control tended to have stronger HCV-specific IL-21-production than non-controllers. HCV-specific IL-21 production also correlated with HCV viral decline in acute infection. Significantly stronger HCV-specific IL-21 production was detected in HAART-treated coinfected individuals. HCV-specific IL-17A production was not associated with lower plasma HCV RNA levels in acute or chronic HCV infection and responses were stronger in HIV coinfection. HCV-specific IL-21/ IL-17A responses did not correlate with microbial translocation or fibrosis. Exogenous IL-21 treatment of HCV-specific CD8+ T cells from monoinfected individuals enhanced their function although CD8+ T cells from coinfected individuals were somewhat refractory to the effects of IL-21.These data show that HCV-specific IL-21 and IL-17A-producing T cells are induced in HIV/HCV coinfection. In early HIV/HCV coinfection, IL-21 may contribute to viral control, and may represent a novel tool to enhance acute HCV clearance in HIV/HCV coinfected individuals.

  11. Impact of long-term viral suppression in CD4+ recovery of HIV-children on Highly Active Antiretroviral Therapy

    Directory of Open Access Journals (Sweden)

    Gurbindo-Gutierrez Dolores

    2006-01-01

    Full Text Available Abstract Background The effects of HAART may differ between children and adults because children have a developing immune system, and the long-term immunological outcome in HIV-infected children on HAART is not well-known. A major aim of our study was to determine CD4+ evolution associated with long-term VL control during 4 years of observation on HAART. Methods We carried out a retrospective study on a cohort of 160 vertically HIV-infected children. It was carried out from 1996 to 2004 in six large Spanish pediatric referral hospitals. We compared 33 children who had long-term VL suppression (VL ≤400 copies/ml in the first 12 months of follow-up and maintained that level throughout follow-up (Responders-group, and 127 children with persistently detectable VL in spite of ART switches (Non-Responders-group. Results We observed a quick initial and significant increase in CD4+ counts from the baseline to 12 months on HAART in both groups (p Non-Responders group sustained CD4+ increases and most of these children maintained high CD4+ level counts (≥25%. The Non-Responders group reached a plateau between 26% and 27% CD4+ at the first 12 months of follow-up that remained stable during the following 3 years. However, the Responders group reached a plateau between 30% and 32% CD4+ at 24, 36 and 48 months of follow-up. We found that the Responders group had higher CD4+ count values and higher percentages of children with CD4+ ≥25% than the Non-Responders group (p Conclusion Long-term VL suppression in turn induces large beneficial effects in immunological responses. However, it is not indispensable to recover CD4+ levels.

  12. [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

  13. Standardisation of the Laboratory Control of Anticoagulant Therapy

    African Journals Online (AJOL)

    1974-09-11

    Sep 11, 1974 ... Anticoagulant therapy with the coumarin group of drugs has been used in clinical practice for more than a quarter of a century. The most widely used form of laboratory control of the treatment is the Quick one-stage prothrom·- bin time. I. This simple test proved to be satisfactory in most cases, but discrepant ...

  14. 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.

  15. Alternative and Complementary Therapies for Hepatitis C

    Science.gov (United States)

    ... and Complementary Therapies Viral Hepatitis Menu Menu Viral Hepatitis Viral Hepatitis Home For Veterans and the Public Veterans ... treatments which have been proven to reduce the hepatitis C viral load. Just because something is "natural" (an herb, ...

  16. HIV DNA Is Frequently Present within Pathologic Tissues Evaluated at Autopsy from Combined Antiretroviral Therapy-Treated Patients with Undetectable Viral Loads.

    Science.gov (United States)

    Lamers, Susanna L; Rose, Rebecca; Maidji, Ekaterina; Agsalda-Garcia, Melissa; Nolan, David J; Fogel, Gary B; Salemi, Marco; Garcia, Debra L; Bracci, Paige; Yong, William; Commins, Deborah; Said, Jonathan; Khanlou, Negar; Hinkin, Charles H; Sueiras, Miguel Valdes; Mathisen, Glenn; Donovan, Suzanne; Shiramizu, Bruce; Stoddart, Cheryl A; McGrath, Michael S; Singer, Elyse J

    2016-10-15

    HIV infection treatment strategies have historically defined effectiveness through measuring patient plasma HIV RNA. While combined antiretroviral therapy (cART) can reduce plasma viral load (pVL) to undetectable levels, the degree that HIV is eliminated from other anatomical sites remains unclear. We investigated the HIV DNA levels in 229 varied autopsy tissues from 20 HIV-positive (HIV(+)) cART-treated study participants with low or undetectable plasma VL and cerebrospinal fluid (CSF) VL prior to death who were enrolled in the National Neurological AIDS Bank (NNAB) longitudinal study and autopsy cohort. Extensive medical histories were obtained for each participant. Autopsy specimens, including at least six brain and nonbrain tissues per participant, were reviewed by study pathologists. HIV DNA, measured in tissues by quantitative and droplet digital PCR, was identified in 48/87 brain tissues and 82/142 nonbrain tissues at levels >200 HIV copies/million cell equivalents. No participant was found to be completely free of tissue HIV. Parallel sequencing studies from some tissues recovered intact HIV DNA and RNA. Abnormal histological findings were identified in all participants, especially in brain, spleen, lung, lymph node, liver, aorta, and kidney. All brain tissues demonstrated some degree of pathology. Ninety-five percent of participants had some degree of atherosclerosis, and 75% of participants died with cancer. This study assists in characterizing the anatomical locations of HIV, in particular, macrophage-rich tissues, such as the central nervous system (CNS) and testis. Additional studies are needed to determine if the HIV recovered from tissues promotes the pathogenesis of inflammatory diseases, such as HIV-associated neurocognitive disorders, cancer, and atherosclerosis. It is well-known that combined antiretroviral therapy (cART) can reduce plasma HIV to undetectable levels; however, cART cannot completely clear HIV infection. An ongoing question is

  17. Viral-specific T-cell transfer from HSCT donor for the treatment of viral infections or diseases after HSCT.

    Science.gov (United States)

    Qian, C; Wang, Y; Reppel, L; D'aveni, M; Campidelli, A; Decot, V; Bensoussan, D

    2018-02-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative option for treatment of some malignant and non-malignant hematological diseases. However, post-HSCT patients are severely immunocompromised and susceptible to viral infections, which are a major cause of morbidity and mortality. Although antiviral agents are now available for most types of viral infections, they are not devoid of side effects and their efficacy is limited when there is no concomitant antiviral immune reconstitution. In recent decades, adoptive transfer of viral-specific T cells (VSTs) became an alternative treatment for viral infection after HSCT. However, two major issues are concerned in VST transfer: the risk of GVHD and antiviral efficacy. We report an exhaustive review of the published studies that focus on prophylactic and/or curative therapy by donor VST transfer for post-HSCT common viral infections. A low incidence of GVHD and a good antiviral efficacy was observed after adoptive transfer of VSTs from HSCT donor. Viral-specific T-cell transfer is a promising approach for a broad clinical application. Nevertheless, a randomized controlled study in a large cohort of patients comparing antiviral treatment alone to antiviral treatment combined with VSTs is still needed to demonstrate efficacy and safety.

  18. IP-10 predicts the first phase decline of HCV RNA and overall viral response to therapy in patients co-infected with chronic hepatitis C virus infection and HIV

    DEFF Research Database (Denmark)

    Falconer, Karolin; Askarieh, Galia; Weis, Nina Margrethe

    2010-01-01

    The aim of this study was to investigate the utility of baseline plasma interferon-gamma inducible protein-10 (IP-10) levels in human immunodeficiency virus (HIV)-hepatitis C virus (HCV) co-infected patients. Baseline IP-10 was monitored during HCV combination therapy in 21 HIV-HCV co-infected pa......The aim of this study was to investigate the utility of baseline plasma interferon-gamma inducible protein-10 (IP-10) levels in human immunodeficiency virus (HIV)-hepatitis C virus (HCV) co-infected patients. Baseline IP-10 was monitored during HCV combination therapy in 21 HIV-HCV co......-10 viral response to HCV therapy in HIV-HCV co-infected patients, and may thus be useful in encouraging such difficult-to-treat patients to initiate therapy....

  19. Tumor Restrictive Suicide Gene Therapy for Glioma Controlled by the FOS Promoter.

    Directory of Open Access Journals (Sweden)

    Jianqing Pan

    Full Text Available Effective suicide gene delivery and expression are crucial to achieving successful effects in gene therapy. An ideal tumor-specific promoter expresses therapeutic genes in tumor cells with minimal normal tissue expression. We compared the activity of the FOS (FBJ murine osteosarcoma viral oncogene homolog promoter with five alternative tumor-specific promoters in glioma cells and non-malignant astrocytes. The FOS promoter caused significantly higher transcriptional activity in glioma cell lines than all alternative promoters with the exception of CMV. The FOS promoter showed 13.9%, 32.4%, and 70.8% of the transcriptional activity of CMV in three glioma cell lines (U87, U251, and U373. Importantly, however, the FOS promoter showed only 1.6% of the transcriptional activity of CMV in normal astrocytes. We also tested the biologic activity of recombinant adenovirus containing the suicide gene herpes simplex virus thymidine kinase (HSV-tk driven by the FOS promoter, including selective killing efficacy in vitro and tumor inhibition rate in vivo. Adenoviral-mediated delivery of the HSV-tk gene controlled by the FOS promoter conferred a cytotoxic effect on human glioma cells in vitro and in vivo. This study suggests that use of the FOS-tk adenovirus system is a promising strategy for glioma-specific gene therapy but still much left for improvement.

  20. An Intrinsically Disordered Peptide from Ebola Virus VP35 Controls Viral RNA Synthesis by Modulating Nucleoprotein-RNA Interactions

    Directory of Open Access Journals (Sweden)

    Daisy W. Leung

    2015-04-01

    Full Text Available During viral RNA synthesis, Ebola virus (EBOV nucleoprotein (NP alternates between an RNA-template-bound form and a template-free form to provide the viral polymerase access to the RNA template. In addition, newly synthesized NP must be prevented from indiscriminately binding to noncognate RNAs. Here, we investigate the molecular bases for these critical processes. We identify an intrinsically disordered peptide derived from EBOV VP35 (NPBP, residues 20–48 that binds NP with high affinity and specificity, inhibits NP oligomerization, and releases RNA from NP-RNA complexes in vitro. The structure of the NPBP/ΔNPNTD complex, solved to 3.7 Å resolution, reveals how NPBP peptide occludes a large surface area that is important for NP-NP and NP-RNA interactions and for viral RNA synthesis. Together, our results identify a highly conserved viral interface that is important for EBOV replication and can be targeted for therapeutic development.

  1. An Intrinsically Disordered Peptide from Ebola Virus VP35 Controls Viral RNA Synthesis by Modulating Nucleoprotein-RNA Interactions.

    Science.gov (United States)

    Leung, Daisy W; Borek, Dominika; Luthra, Priya; Binning, Jennifer M; Anantpadma, Manu; Liu, Gai; Harvey, Ian B; Su, Zhaoming; Endlich-Frazier, Ariel; Pan, Juanli; Shabman, Reed S; Chiu, Wah; Davey, Robert A; Otwinowski, Zbyszek; Basler, Christopher F; Amarasinghe, Gaya K

    2015-04-21

    During viral RNA synthesis, Ebola virus (EBOV) nucleoprotein (NP) alternates between an RNA-template-bound form and a template-free form to provide the viral polymerase access to the RNA template. In addition, newly synthesized NP must be prevented from indiscriminately binding to noncognate RNAs. Here, we investigate the molecular bases for these critical processes. We identify an intrinsically disordered peptide derived from EBOV VP35 (NPBP, residues 20-48) that binds NP with high affinity and specificity, inhibits NP oligomerization, and releases RNA from NP-RNA complexes in vitro. The structure of the NPBP/ΔNPNTD complex, solved to 3.7 Å resolution, reveals how NPBP peptide occludes a large surface area that is important for NP-NP and NP-RNA interactions and for viral RNA synthesis. Together, our results identify a highly conserved viral interface that is important for EBOV replication and can be targeted for therapeutic development. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Meta-analysis of two randomized controlled trials comparing combined zidovudine and didanosine therapy with combined zidovudine, didanosine, and nevirapine therapy in patients with HIV. INCAS study team.

    Science.gov (United States)

    Raboud, J M; Rae, S; Vella, S; Harrigan, P R; Bucciardini, R; Fragola, V; Ricciardulli, D; Montaner, J S

    1999-11-01

    To extend the range of CD4 counts in which a plasma viral load nadir (pVL) 100,000 copies/ml. Among triple therapy patients, the relative risk of virologic failure was higher for patients with higher baseline pVL (rate ratio [RR] = 2.51/log10 copies/ ml; p = .01), after controlling for compliance and pVL nadir. The relative risks of virologic failure associated with pVL nadir 400 copies/ml. We have extended our earlier results that achieving a pVL nadir <20 copies/ml is important for maintaining virologic suppression. In particular, we have demonstrated that a pVL nadir <20 copies/ml is at least fivefold more protective against virologic failure than achieving a pVL nadir between 20 and 400 copies/ml. Baseline pVL is significantly associated with the probability of achieving and sustaining virologic suppression.

  3. The Response of Heterotrophic Prokaryote and Viral Communities to Labile Organic Carbon Inputs Is Controlled by the Predator Food Chain Structure.

    Science.gov (United States)

    Sandaa, Ruth-Anne; Pree, Bernadette; Larsen, Aud; Våge, Selina; Töpper, Birte; Töpper, Joachim P; Thyrhaug, Runar; Thingstad, Tron Frede

    2017-08-23

    Factors controlling the community composition of marine heterotrophic prokaryotes include organic-C, mineral nutrients, predation, and viral lysis. Two mesocosm experiments, performed at an Arctic location and bottom-up manipulated with organic-C, had very different results in community composition for both prokaryotes and viruses. Previously, we showed how a simple mathematical model could reproduce food web level dynamics observed in these mesocosms, demonstrating strong top-down control through the predator chain from copepods via ciliates and heterotrophic nanoflagellates. Here, we use a steady-state analysis to connect ciliate biomass to bacterial carbon demand. This gives a coupling of top-down and bottom-up factors whereby low initial densities of ciliates are associated with mineral nutrient-limited heterotrophic prokaryotes that do not respond to external supply of labile organic-C. In contrast, high initial densities of ciliates give carbon-limited growth and high responsiveness to organic-C. The differences observed in ciliate abundance, and in prokaryote abundance and community composition in the two experiments were in accordance with these predictions. Responsiveness in the viral community followed a pattern similar to that of prokaryotes. Our study provides a unique link between the structure of the predator chain in the microbial food web and viral abundance and diversity.

  4. Multi-layered control of Galectin-8 mediated autophagy during adenovirus cell entry through a conserved PPxY motif in the viral capsid.

    Directory of Open Access Journals (Sweden)

    Charlotte Montespan

    2017-02-01

    Full Text Available Cells employ active measures to restrict infection by pathogens, even prior to responses from the innate and humoral immune defenses. In this context selective autophagy is activated upon pathogen induced membrane rupture to sequester and deliver membrane fragments and their pathogen contents for lysosomal degradation. Adenoviruses, which breach the endosome upon entry, escape this fate by penetrating into the cytosol prior to autophagosome sequestration of the ruptured endosome. We show that virus induced membrane damage is recognized through Galectin-8 and sequesters the autophagy receptors NDP52 and p62. We further show that a conserved PPxY motif in the viral membrane lytic protein VI is critical for efficient viral evasion of autophagic sequestration after endosomal lysis. Comparing the wildtype with a PPxY-mutant virus we show that depletion of Galectin-8 or suppression of autophagy in ATG5-/- MEFs rescues infectivity of the PPxY-mutant virus while depletion of the autophagy receptors NDP52, p62 has only minor effects. Furthermore we show that wildtype viruses exploit the autophagic machinery for efficient nuclear genome delivery and control autophagosome formation via the cellular ubiquitin ligase Nedd4.2 resulting in reduced antigenic presentation. Our data thus demonstrate that a short PPxY-peptide motif in the adenoviral capsid permits multi-layered viral control of autophagic processes during entry.

  5. Protocol for a randomised controlled implementation trial of point-of-care viral load testing and task shifting: the Simplifying HIV TREAtment and Monitoring (STREAM) study.

    Science.gov (United States)

    Dorward, Jienchi; Garrett, Nigel; Quame-Amaglo, Justice; Samsunder, Natasha; Ngobese, Hope; Ngomane, Noluthando; Moodley, Pravikrishnen; Mlisana, Koleka; Schaafsma, Torin; Donnell, Deborah; Barnabas, Ruanne; Naidoo, Kogieleum; Abdool Karim, Salim; Celum, Connie; Drain, Paul K

    2017-09-27

    Achieving the Joint United Nations Programme on HIV and AIDS 90-90-90 targets requires models of HIV care that expand antiretroviral therapy (ART) coverage without overburdening health systems. Point-of-care (POC) viral load (VL) testing has the potential to efficiently monitor ART treatment, while enrolled nurses may be able to provide safe and cost-effective chronic care for stable patients with HIV. This study aims to demonstrate whether POC VL testing combined with task shifting to enrolled nurses is non-inferior and cost-effective compared with laboratory-based VL monitoring and standard HIV care. The STREAM (Simplifying HIV TREAtment and Monitoring) study is an open-label, non-inferiority, randomised controlled implementation trial. HIV-positive adults, clinically stable at 6 months after ART initiation, will be recruited in a large urban clinic in South Africa. Approximately 396 participants will be randomised 1:1 to receive POC HIV VL monitoring and potential task shifting to enrolled nurses, versus laboratory VL monitoring and standard South African HIV care. Initial clinic follow-up will be 2-monthly in both arms, with VL testing at enrolment, 6 months and 12 months. At 6 months (1 year after ART initiation), stable participants in both arms will qualify for a differentiated care model involving decentralised ART pickup at community-based pharmacies. The primary outcome is retention in care and virological suppression at 12 months from enrolment. Secondary outcomes include time to appropriate entry into the decentralised ART delivery programme, costs per virologically suppressed patient and cost-effectiveness of the intervention compared with standard care. Findings will inform the scale up of VL testing and differentiated care in HIV-endemic resource-limited settings. Ethical approval has been granted by the University of KwaZulu-Natal Biomedical Research Ethics Committee (BFC296/16) and University of Washington Institutional Review Board (STUDY

  6. Selective therapy in equine parasite control--application and limitations.

    Science.gov (United States)

    Nielsen, M K; Pfister, K; von Samson-Himmelstjerna, G

    2014-05-28

    Since the 1960s equine parasite control has relied heavily on frequent anthelmintic treatments often applied with frequent intervals year-round. However, increasing levels of anthelmintic resistance in cyathostomins and Parascaris equorum are now forcing the equine industry to change to a more surveillance-based treatment approach to facilitate a reduction in treatment intensity. The principle of selective therapy has been implemented with success in small ruminant parasite control, and has also found use in horse populations. Typically, egg counts are performed from all individuals in the population, and those exceeding a predetermined cutoff threshold are treated. Several studies document the applicability of this method in populations of adult horses, where the overall cyathostomin egg shedding can be controlled by only treating about half the horses. However, selective therapy has not been evaluated in foals and young horses, and it remains unknown whether the principle is adequate to also provide control over other important parasites such as tapeworms, ascarids, and large strongyles. One recent study associated selective therapy with increased occurrence of Strongylus vulgaris. Studies are needed to evaluate potential health risks associated with selective therapy, and to assess to which extent development of anthelmintic resistance can be delayed with this approach. The choice of strongyle egg count cutoff value for anthelmintic treatment is currently based more on tradition than science, and a recent publication illustrated that apparently healthy horses with egg counts below 100 eggs per gram (EPG) can harbor cyathostomin burdens in the range of 100,000 luminal worms. It remains unknown whether leaving such horses untreated constitutes a potential threat to equine health. The concept of selective therapy has merit for equine strongyle control, but several questions remain as it has not been fully scientifically evaluated. There is a great need for new and

  7. Quality control of radiation therapy in clinical trials

    International Nuclear Information System (INIS)

    Kramer, S.; Lustig, R.; Grundy, G.

    1983-01-01

    The RTOG is a group of participating institutions which has a major interest in furthering clinical radiation oncology. They have formulated protocols for clinical investigation in which radiation therapy is the major modality of treatment. In addition, other modalities, such as chemotherapy, radiation sensitizers, and hyperthermia, are used in combined approach to cancer. Quality control in all aspects of patient management is necessary to insure quality data. These areas include evaluation of pathology, physics, and dosimetry, and clinical patient data. Quality control is both time consuming and expensive. However, by dividing these tasks into various levels and time frames, by using computerized data-control mechanisms, and by employing appropriate levels of ancillary personnel expertise, quality control can improve compliance and decrease the cost of investigational trials

  8. International network for capacity building for the control of emerging viral vector-borne zoonotic diseases: ARBO-ZOONET.

    Science.gov (United States)

    Ahmed, J; Bouloy, M; Ergonul, O; Fooks, Ar; Paweska, J; Chevalier, V; Drosten, C; Moormann, R; Tordo, N; Vatansever, Z; Calistri, P; Estrada-Pena, A; Mirazimi, A; Unger, H; Yin, H; Seitzer, U

    2009-03-26

    Arboviruses are arthropod-borne viruses, which include West Nile fever virus (WNFV), a mosquito-borne virus, Rift Valley fever virus (RVFV), a mosquito-borne virus, and Crimean-Congo haemorrhagic fever virus (CCHFV), a tick-borne virus. These arthropod-borne viruses can cause disease in different domestic and wild animals and in humans, posing a threat to public health because of their epidemic and zoonotic potential. In recent decades, the geographical distribution of these diseases has expanded. Outbreaks of WNF have already occurred in Europe, especially in the Mediterranean basin. Moreover, CCHF is endemic in many European countries and serious outbreaks have occurred, particularly in the Balkans, Turkey and Southern Federal Districts of Russia. In 2000, RVF was reported for the first time outside the African continent, with cases being confirmed in Saudi Arabia and Yemen. This spread was probably caused by ruminant trade and highlights that there is a threat of expansion of the virus into other parts of Asia and Europe. In the light of global warming and globalisation of trade and travel, public interest in emerging zoonotic diseases has increased. This is especially evident regarding the geographical spread of vector-borne diseases. A multi-disciplinary approach is now imperative, and groups need to collaborate in an integrated manner that includes vector control, vaccination programmes, improved therapy strategies, diagnostic tools and surveillance, public awareness, capacity building and improvement of infrastructure in endemic regions.

  9. Latency of Epstein-Barr virus is stabilized by antisense-mediated control of the viral immediate-early gene BZLF-1.

    Science.gov (United States)

    Prang, N; Wolf, H; Schwarzmann, F

    1999-12-01

    The ability of the Epstein-Barr virus (EBV) to avoid lytic replication and to establish a latent infection in B-lymphocytes is fundamental for its lifelong persistence and the pathogenesis of various EBV-associated diseases. The viral immediate-early gene BZLF-1 plays a key role for the induction of lytic replication and its activity is strictly regulated on different levels of gene expression. Recently, it was demonstrated that BZLF-1 is also controlled by a posttranscriptional mechanism. Transient synthesis of a mutated competitor RNA saturated this mechanism and caused both expression of the BZLF-1 protein and the induction of lytic viral replication. Using short overlapping fragments of the competitor, it is shown that this control acts on the unspliced primary transcript. RT-PCR demonstrated unspliced BZLF-1 RNA in latently infected B-lymphocytes in the absence of BZLF-1 protein. Due to the complementarity of the gene BZLF-1 and the latency-associated gene EBNA-1 on the opposite strand of the genome, we propose an antisense-mediated mechanism. RNase protection assays demonstrated transcripts in antisense orientation to the BZLF-1 transcript during latency, which comprise a comparable constellation to other herpesviruses. A combined RNAse protection/RT-PCR assay detected the double-stranded hybrid RNA, consisting of the unspliced BZLF-1 transcript and a noncoding intron of the EBNA-1 gene. Binding of BZLF-1 transcripts is suggested to be an important backup control mechanism in addition to transcriptional regulation, stabilizing latency and preventing inappropriate lytic viral replication in vivo. Copyright 1999 Wiley-Liss, Inc.

  10. Interference with the Autophagic Process as a Viral Strategy to Escape from the Immune Control: Lesson from Gamma Herpesviruses

    Directory of Open Access Journals (Sweden)

    Roberta Santarelli

    2015-01-01

    Full Text Available We summarized the most recent findings on the role of autophagy in antiviral immune response. We described how viruses have developed strategies to subvert the autophagic process. A particular attention has been given to Epstein-Barr and Kaposi’s sarcoma associated Herpesvirus, viruses studied for many years in our laboratory. These two viruses belong to γ-Herpesvirus subfamily and are associated with several human cancers. Besides the effects on the immune response, we have described how autophagy subversion by viruses may also concur to the enhancement of their replication and to viral tumorigenesis.

  11. 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 consequenc...... laboratory monitoring-is currently the highest priority....

  12. Non-viral gene delivery strategies for gene therapy: a “ménage à trois” among nucleic acids, materials, and the biological environment

    International Nuclear Information System (INIS)

    Pezzoli, Daniele; Candiani, Gabriele

    2013-01-01

    Gene delivery is the science of transferring genetic material into cells by means of a vector to alter cellular function or structure at a molecular level. In this context, a number of nucleic acid-based drugs have been proposed and experimented so far and, as they act on distinct steps along the gene transcription–translation pathway, specific delivery strategies are required to elicit the desired outcome. Cationic lipids and polymers, collectively known as non-viral delivery systems, have thus made their breakthrough in basic and medical research. Albeit they are promising alternatives to viral vectors, their therapeutic application is still rather limited as high transfection efficiencies are normally associated to adverse cytotoxic side effects. In this scenario, drawing inspiration from processes naturally occurring in vivo, major strides forward have been made in the development of more effective materials for gene delivery applications. Specifically, smart vectors sensitive to a variety of physiological stimuli such as cell enzymes, redox status, and pH are substantially changing the landscape of gene delivery by helping to overcome some of the systemic and intracellular barriers that viral vectors naturally evade. Herein, after summarizing the state-of-the-art information regarding the use of nucleic acids as drugs, we review the main bottlenecks still limiting the overall effectiveness of non-viral gene delivery systems. Finally, we provide a critical outline of emerging stimuli-responsive strategies and discuss challenges still existing on the road toward conceiving more efficient and safer multifunctional vectors.

  13. ENGENHARIA DE SEGURANÇA E MEDIDAS DE CONTROLE DE UM LABORATÓRIO DE VACINA VIRAL VETERINÁRIA - ESTUDO DE CASO / ENGINEERING AND SAFETY ACTIONS OF A VETERINARY VIRAL VACCINE LABORATORY - A CASE STUDY

    Directory of Open Access Journals (Sweden)

    Glaucia Aparecida PRATES

    2013-12-01

    Full Text Available O presente trabalho tem como objetivos avaliar as medidas de controle em um laboratório de vacina viral veterinária de Curitiba através de análise documental. Avaliar o uso de equipamentos de proteção individual (EPIs e (EPCs através de análise do Programa de Prevenção de Riscos Ambientais - PPRA e identificar a conformidade dos riscos biológico, químico e físico de acordo com as Normas Regulamentadoras 6 (NR 6 e 9 (NR 9 . O objeto de estudo foi o laboratório de vacina viral de uma instituição pública de Curitiba-PR. Tendo como metodologia a pesquisa documental e bibliográfica e a avaliação das condições de segurança de um laboratório com base no documento PPRA. Comparando com a Ficha de Informação de Segurança de Produto Químico - FISPQ, observou-se que nos setores avaliados houve lacunas com relação ao EPI protetor respiratório em 9%. Comparando o PPRA com a FISPQ constatou-se que 183 EPIs foram registrados,  faltando a inclusão de 16  EPIs em produtos químicos diversos. Sendo esta ausência de 9% . Detectou-se detalhadamente a não inclusão de EPIs na porcentagem de 7%, 10%, 12%, 6%, 17%, 2%, 27% e 8% respectivamente do setor 1  ao setor 8. Considerando os resultados e análise, pôde-se concluir que os objetivos supracitados analisados foram alcançados apesar das limitações de obtenção dos dados devido a correta restrição de entrada nas dependências pelas normas de biossegurança. 

  14. Locoregional control and survival after breast conserving therapy

    International Nuclear Information System (INIS)

    Rajer, M.; Majdic, E.

    2006-01-01

    Background. The purpose of our study was to present a 5-year survival and locoregional control rates in breast cancer patients and to establish eventual impact of the treatment and patient characteristics on locoregional control and survival. Methods. From January 1998 to December 1999 564 stage 1 and 2 breast cancer patients were treated with breast conserving therapy. We evaluated the following characteristics: age, histological diagnosis, grade, size, number of metastatic lymph nodes, hormonal receptor status, extensive intraductal component (EIDC), vascular invasion, pathologic tumour margins, type of surgery and use of adjuvant therapy. Results. The mean age of our patients was 54.2 years. Invasive ductal carcinoma was the most common diagnosis (82.4%), followed by invasive lobular carcinoma (10.6%). Most of the tumours were grade 2. Seventy-two % of patients had T1 tumours, 24% T2 and 3% T is tumours. Metastatic lymph nodes were present in 44% of patients. All patients were treated with breast conserving surgery followed by radiotherapy (RT). Fifty % of patients received adjuvant chemotherapy and/ or hormonal therapy. The 5-year survival rate was 88.5%. Tumour size, number of metastatic lymph nodes, grade, hormonal receptors and vascular invasion proved to be statistically significant prognostic factors for the survival, while age and histological diagnosis were not. Local recurrence developed in 4.3% of our patients, while in 3.4% regional recurrence developed. Conclusions. Breast conserving surgery followed by RT was associated with good rates of locoregional control and survival, comparable to those reported in the literature. (author)

  15. High levels of viral suppression among East African HIV-infected women and men in serodiscordant partnerships initiating antiretroviral therapy with high CD4 counts and during pregnancy.

    Science.gov (United States)

    Mujugira, Andrew; Baeten, Jared; Kidoguchi, Lara; Haberer, Jessica; Celum, Connie; Donnell, Deborah; Ngure, Kenneth; Bukusi, Elizabeth; Mugo, Nelly; Asiimwe, Stephen; Odoyo, Josephine; Tindimwebwa, Edna; Bulya, Nulu; Katabira, Elly; Heffron, Renee

    2017-09-13

    People who are asymptomatic and feel healthy, including pregnant women, may be less motivated to initiate ART or achieve high adherence. We assessed whether ART initiation, and viral suppression 6, 12 and 24-months after ART initiation, were lower in HIV-infected members of serodiscordant couples who initiated during pregnancy or with higher CD4 counts. We used data from the Partners Demonstration Project, an open-label study of the delivery of integrated PrEP and ART (at any CD4 count) for HIV prevention among high-risk HIV serodiscordant couples in Kenya and Uganda. Differences in viral suppression (HIV RNA 500 cells/mm3) and during pregnancy were estimated using Poisson regression. Of 865 HIV-infected participants retained after becoming eligible for ART during study follow-up, 95% initiated ART. Viral suppression 24-months after ART initiation was high overall (97%), and comparable among those initiating ART at CD4 counts >500, 351-500 and ≤350 cells/mm3 (96% vs 97% vs 97%; relative risk [RR] 0.98; 95% CI: 0.93-1.03 for CD4 >500 vs <350 and RR 0.99; 95% CI: (0.93-1.06) for CD4 351-500 vs ≤350). Viral suppression was as likely among women initiating ART primarily to prevent perinatal transmission as ART initiation for other reasons (p=0.9 at 6 months and p=0.5 at 12 months). Nearly all HIV-infected partners initiating ART were virally suppressed by 24 months, irrespective of CD4 count or pregnancy status. These findings suggest that people initiating ART at high CD4 counts or due to pregnancy can adhere to ART as well as those starting treatment with symptomatic HIV disease or low CD4 counts.

  16. The value of point-of-care CD4+ and laboratory viral load in tailoring antiretroviral therapy monitoring strategies to resource limitations.

    Science.gov (United States)

    Hyle, Emily P; Jani, Ilesh V; Rosettie, Katherine L; Wood, Robin; Osher, Benjamin; Resch, Stephen; Pei, Pamela P; Maggiore, Paolo; Freedberg, Kenneth A; Peter, Trevor; Parker, Robert A; Walensky, Rochelle P

    2017-09-24

    To examine the clinical and economic value of point-of-care CD4 (POC-CD4) or viral load monitoring compared with current practices in Mozambique, a country representative of the diverse resource limitations encountered by HIV treatment programs in sub-Saharan Africa. We use the Cost-Effectiveness of Preventing AIDS Complications-International model to examine the clinical impact, cost (2014 US$), and incremental cost-effectiveness ratio [$/year of life saved (YLS)] of ART monitoring strategies in Mozambique. We compare: monitoring for clinical disease progression [clinical ART monitoring strategy (CLIN)] vs. annual POC-CD4 in rural settings without laboratory services and biannual laboratory CD4 (LAB-CD4), biannual POC-CD4, and annual viral load in urban settings with laboratory services. We examine the impact of a range of values in sensitivity analyses, using Mozambique's 2014 per capita gross domestic product ($620) as a benchmark cost-effectiveness threshold. In rural settings, annual POC-CD4 compared to CLIN improves life expectancy by 2.8 years, reduces time on failed ART by 0.6 years, and yields an incremental cost-effectiveness ratio of $480/YLS. In urban settings, biannual POC-CD4 is more expensive and less effective than viral load. Compared to biannual LAB-CD4, viral load improves life expectancy by 0.6 years, reduces time on failed ART by 1.0 year, and is cost-effective ($440/YLS). In rural settings, annual POC-CD4 improves clinical outcomes and is cost-effective compared to CLIN. In urban settings, viral load has the greatest clinical benefit and is cost-effective compared to biannual POC-CD4 or LAB-CD4. Tailoring ART monitoring strategies to specific settings with different available resources can improve clinical outcomes while remaining economically efficient.

  17. [Immunotherapy for refractory viral infections].

    Science.gov (United States)

    Morio, Tomohiro; Fujita, Yuriko; Takahashi, Satoshi

    Various antiviral agents have been developed, which are sometimes associated with toxicity, development of virus-resistant strain, and high cost. Virus-specific T-cell (VST) therapy provides an alternative curative therapy that can be effective for a prolonged time without eliciting drug resistance. VSTs can be directly separated using several types of capture devices and can be obtained by stimulating peripheral blood mononuclear cells with viral antigens (virus, protein, or peptide) loaded on antigen-presenting cells (APC). APC can be transduced with virus-antigen coding plasmid or pulsed with overlapping peptides. VST therapy has been studied in drug non-responsive viral infections after hematopoietic cell transplantation (HCT). Several previous studies have demonstrated the efficacy of VST therapy without significant severe GVHD. In addition, VSTs from a third-party donor have been prepared and administered for post-HCT viral infection. Although target viruses of VSTs include herpes virus species and polyomavirus species, a wide variety of pathogens, such as papillomavirus, intracellular bacteria, and fungi, can be treated by pathogen-specific T-cells. Perhaps, these specific T-cells could be used for opportunistic infections in other immunocompromised hosts in the near future.

  18. Comparison of prevalence, viral load, physical status and expression of human papillomavirus-16, -18 and -58 in esophageal and cervical cancer: a case-control study

    International Nuclear Information System (INIS)

    Zhang, Donghong; Zhang, Qingying; Zhou, Li; Huo, Leijun; Zhang, Yi; Shen, Zhongying; Zhu, Yi

    2010-01-01

    Human papillomavirus (HPV) infection is a major risk factor for the development of nearly all cases of cervical cancer worldwide. The presence of HPV DNA in cases of esophageal squamous-cell carcinoma (ESCC) has been reported repeatedly from Shantou, China, and other regions with a high incidence of esophageal carcinoma (EC). However, unlike in cervical squamous-cell carcinoma (CSCC), in ESCC, the characteristics of HPV are unclear. Thus, the role of high-risk HPV types in the carcinogenesis of ESCC remains uncertain. Seventy cases of ESCC with 60 controls and 39 cases of CSCC with 54 controls collected from patients in Shantou region in China were compared for the distributions of HPV-16, -18 and -58; viral load; and viral integration using real-time PCR assay and HPV-16 expression using immunostaining. The detection rates and viral loads of HR-HPV infection were significantly lower in ESCC than in CSCC (50.0% vs. 79.48%, P = 0.005; 2.55 ± 3.19 vs. 361.29 ± 441.75, P = 0.002, respectively). The combined integration level of HPV-16, -18 and -58 was slightly lower in ESCC than in CSCC (P = 0.022). HPV-16 expression was detected in 59.26% of ESCC tissue and significantly associated with tumour grade (P = 0.027). High levels of HR-HPV expression and integration may be an indicator of the risk of ESCC, at least for patients in the Shantou region of China. However, a relatively low HPV copy number and infection rate in ESCC is unlikely to play an essential a role in the carcinogenesis of ESCC as in cervical cancer. Factors other than HR-HPV infection may contribute to the carcinogenesis of ESCC

  19. 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 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.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.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.

  20. The F4/AS01B HIV-1 Vaccine Candidate Is Safe and Immunogenic, But Does Not Show Viral Efficacy in Antiretroviral Therapy-Naive, HIV-1-Infected Adults

    Science.gov (United States)

    Dinges, Warren; Girard, Pierre-Marie; Podzamczer, Daniel; Brockmeyer, Norbert H.; García, Felipe.; Harrer, Thomas; Lelievre, Jean-Daniel; Frank, Ian; Colin De Verdière, Nathalie; Yeni, Guy-Patrick; Ortega Gonzalez, Enrique; Rubio, Rafael; Clotet Sala, Bonaventura; DeJesus, Edwin; Pérez-Elias, Maria Jesus; Launay, Odile; Pialoux, Gilles; Slim, Jihad; Weiss, Laurence; Bouchaud, Olivier; Felizarta, Franco; Meurer, Anja; Raffi, François; Esser, Stefan; Katlama, Christine; Koletar, Susan L.; Mounzer, Karam; Swindells, Susan; Baxter, John D.; Schneider, Stefan; Chas, Julie; Molina, Jean-Michel; Koutsoukos, Marguerite; Collard, Alix; Bourguignon, Patricia; Roman, François

    2016-01-01

    Abstract The impact of the investigational human immunodeficiency virus type 1 (HIV-1) F4/AS01B vaccine on HIV-1 viral load (VL) was evaluated in antiretroviral therapy (ART)-naive HIV-1 infected adults. This phase IIb, observer-blind study (NCT01218113), included ART-naive HIV-1 infected adults aged 18 to 55 years. Participants were randomized to receive 2 (F4/AS01B_2 group, N = 64) or 3 (F4/AS01B_3 group, N = 62) doses of F4/AS01B or placebo (control group, N = 64) at weeks 0, 4, and 28. Efficacy (HIV-1 VL, CD4+ T-cell count, ART initiation, and HIV-related clinical events), safety, and immunogenicity (antibody and T-cell responses) were evaluated during 48 weeks. At week 48, based on a mixed model, no statistically significant difference in HIV-1 VL change from baseline was demonstrated between F4/AS01B_2 and control group (0.073 log10 copies/mL [97.5% confidence interval (CI): −0.088; 0.235]), or F4/AS01B_3 and control group (−0.096 log10 copies/mL [97.5% CI: −0.257; 0.065]). No differences between groups were observed in HIV-1 VL change, CD4+ T-cell count, ART initiation, or HIV-related clinical events at intermediate timepoints. Among F4/AS01B recipients, the most frequent solicited symptoms were pain at injection site (252/300 doses), fatigue (137/300 doses), myalgia (105/300 doses), and headache (90/300 doses). Twelve serious adverse events were reported in 6 participants; 1 was considered vaccine-related (F4/AS01B_2 group: angioedema). F4/AS01B induced polyfunctional F4-specific CD4+ T-cells, but had no significant impact on F4-specific CD8+ T-cell and anti-F4 antibody levels. F4/AS01B had a clinically acceptable safety profile, induced F4-specific CD4+ T-cell responses, but did not reduce HIV-1 VL, impact CD4+ T-cells count, delay ART initiation, or prevent HIV-1 related clinical events. PMID:26871794

  1. [Analysis of the results of the HIV-1, HCV and HBV viral load of SEIMC External Quality Control Program. Year 2014].

    Science.gov (United States)

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

    2016-07-01

    Human immunodeficiency virus type 1 (HIV-1), hepatitis B virus (HBV) and hepatitis C virus (HCV) viral load determinations are among the most relevant markers for the follow up of patients infected with these viruses. External quality control tools are crucial to ensure the accuracy of results obtained by microbiology laboratories. This article summarizes the results obtained from the 2014 SEIMC (Spanish Society of Infectious Diseases and Clinical Microbiology) External Quality Control Programme for HIV-1, HCV, and HBV viral loads. In the HIV-1 program, a total of 5 standards were sent. One standard consisted in seronegative human plasma, while the remaining 4 contained plasma from 3 different viremic patients, in the range of 2-5 log10 copies/mL; 2 of these standards were identical aiming to determine repeatability. A significant proportion of the laboratories (30.8% on average) obtained values out of the accepted range (mean ± 0.25 log10 copies/mL), depending on the standard and on the method used for quantification. Repeatability was excellent, with up to 95.8% of laboratories reporting results within the limits (Δ quality of the results obtained by a particular laboratory, as well as the importance of the post-analytical phase on the overall quality. Due to the remarkable interlaboratory variability, it is advisable to use the same method and the same laboratory for patient follow up. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  2. Control of thermal therapies with moving power deposition field

    International Nuclear Information System (INIS)

    Arora, Dhiraj; Minor, Mark A; Skliar, Mikhail; Roemer, Robert B

    2006-01-01

    A thermal therapy feedback control approach to control thermal dose using a moving power deposition field is developed and evaluated using simulations. A normal tissue safety objective is incorporated in the controller design by imposing constraints on temperature elevations at selected normal tissue locations. The proposed control technique consists of two stages. The first stage uses a model-based sliding mode controller that dynamically generates an 'ideal' power deposition profile which is generally unrealizable with available heating modalities. Subsequently, in order to approximately realize this spatially distributed idealized power deposition, a constrained quadratic optimizer is implemented to compute intensities and dwell times for a set of pre-selected power deposition fields created by a scanned focused transducer. The dwell times for various power deposition profiles are dynamically generated online as opposed to the commonly employed a priori-decided heating strategies. Dynamic intensity and trajectory generation safeguards the treatment outcome against modelling uncertainties and unknown disturbances. The controller is designed to enforce simultaneous activation of multiple normal tissue temperature constraints by rapidly switching between various power deposition profiles. The hypothesis behind the controller design is that the simultaneous activation of multiple constraints substantially reduces treatment time without compromising normal tissue safety. The controller performance and robustness with respect to parameter uncertainties is evaluated using simulations. The results demonstrate that the proposed controller can successfully deliver the desired thermal dose to the target while maintaining the temperatures at the user-specified normal tissue locations at or below the maximum allowable values. Although demonstrated for the case of a scanned focused ultrasound transducer, the developed approach can be extended to other heating modalities with

  3. Virtual reality therapy versus cognitive behavior therapy for social phobia: a preliminary controlled study.

    Science.gov (United States)

    Klinger, E; Bouchard, S; Légeron, P; Roy, S; Lauer, F; Chemin, I; Nugues, P

    2005-02-01

    Social phobia is one of the most frequent mental disorders and is accessible to two forms of scientifically validated treatments: anti-depressant drugs and cognitive behavior therapies (CBT). In this last case, graded exposure to feared social situations is one of the fundamental therapeutic ingredients. Virtual reality technologies are an interesting alternative to the standard exposure in social phobia, especially since studies have shown its usefulness for the fear of public speaking. This paper reports a preliminary study in which a virtual reality therapy (VRT), based on exposure to virtual environments, was used to treat social phobia. The sample consisted of 36 participants diagnosed with social phobia assigned to either VRT or a group-CBT (control condition). The virtual environments used in the treatment recreate four situations dealing with social anxiety: performance, intimacy, scrutiny, and assertiveness. With the help of the therapist, the patient learns adapted cognitions and behaviors in order to reduce anxiety in the corresponding real situations. Both treatments lasted 12 weeks, and sessions were delivered according to a treatment manual. Results showed statistically and clinically significant improvement in both conditions. The effect-sizes comparing the efficacy of VRT to the control traditional group-CBT revealed that the differences between the two treatments are trivial.

  4. Emerging Viral Diseases of Tomato Crops

    NARCIS (Netherlands)

    Hanssen, I.M.; Lapidot, M.; Thomma, B.P.H.J.

    2010-01-01

    Viral diseases are an important limiting factor in many crop production systems. Because antiviral products are not available, control strategies rely on genetic resistance or hygienic measures to prevent viral diseases, or on eradication of diseased crops to control such diseases. Increasing

  5. Determinants of virological failure among patients on highly active antiretroviral therapy in University of Gondar Referral Hospital, Northwest Ethiopia: a case-control study.

    Science.gov (United States)

    Bayu, Belete; Tariku, Amare; Bulti, Abera Balcha; Habitu, Yohannes Ayanaw; Derso, Terefe; Teshome, Destaw Fetene

    2017-01-01

    Viral load monitoring is used as an important biomarker for diagnosing treatment failure in patients with HIV infection/AIDS. Ethiopia has started targeted viral load monitoring. However, factors leading to virological failure are not well understood and studied. Thus, the aim of this study was to identify the determinants of virological failure among HIV-infected patients on highly active antiretroviral therapy at the University of Gondar Referral Hospital, Northwest Ethiopia. A case-control study was conducted from May to June 2015. Cases were subjects who had already experienced virological failure; controls were those without virological failure. Data were extracted from 153 cases and 153 controls through chart review. A multivariate logistic regression analysis was carried out to identify factors associated with virological failure, and variables with a p -value failure was observed among patients aged failure. Therefore, evidence-based intervention should be implemented to improve adherence to ART, which in turn helps to boost immunity (CD4) and suppresses viral replication and load. Moreover, attention should be given to younger patients who have had ART for longer periods.

  6. Acceptance and Commitment Therapy and Cognitive-Behavioral Therapy as Treatments for Academic Procrastination: A Randomized Controlled Group Session

    Science.gov (United States)

    Wang, Shuo; Zhou, Ya; Yu, Shi; Ran, Li-Wen; Liu, Xiang-Ping; Chen, Yu-Fei

    2017-01-01

    Objective: This study tested the efficacy of Acceptance and Commitment Therapy (ACT), compared with Cognitive-Behavioral Therapy (CBT), in alleviating academic procrastination. Method: A total of 60 (53.3% male) undergraduates suffering from academic procrastination were randomly assigned to two treatment groups (ACT and CBT) and a control group.…

  7. Melodic intonation therapy in chronic aphasia: Evidence from a pilot randomized controlled trial

    NARCIS (Netherlands)

    I. van der Meulen (Ineke); W.M.E. van de Sandt-Koenderman (Mieke); Heijenbrok, M.H. (Majanka H.); E.G. Visch-Brink (Evy); Ribber, G.M. (Gerard M.)

    2016-01-01

    textabstractMelodic Intonation Therapy (MIT) is a language production therapy for severely nonfluent aphasic patients using melodic intoning and rhythm to restore language. Although many studies have reported its beneficial effects on language production, randomized controlled trials (RCT) examining

  8. SHAPE analysis of the FIV Leader RNA reveals a structural switch potentially controlling viral packaging and genome dimerization.

    Science.gov (United States)

    Kenyon, Julia C; Tanner, Sian J; Legiewicz, Michal; Phillip, Pretty S; Rizvi, Tahir A; Le Grice, Stuart F J; Lever, Andrew M L

    2011-08-01

    Feline immunodeficiency virus (FIV) infects many species of cat, and is related to HIV, causing a similar pathology. High-throughput selective 2' hydroxyl acylation analysed by primer extension (SHAPE), a technique that allows structural interrogation at each nucleotide, was used to map the secondary structure of the FIV packaging signal RNA. Previous studies of this RNA showed four conserved stem-loops, extensive long-range interactions (LRIs) and a small, palindromic stem-loop (SL5) within the gag open reading frame (ORF) that may act as a dimerization initiation site (DIS), enabling the virus to package two copies of its genome. Our analyses of wild-type (wt) and mutant RNAs suggest that although the four conserved stem-loops are static structures, the 5' and 3' regions previously shown to form LRI also adopt an alternative, yet similarly conserved conformation, in which the putative DIS is occluded, and which may thus favour translational and splicing functions over encapsidation. SHAPE and in vitro dimerization assays were used to examine SL5 mutants. Dimerization contacts appear to be made between palindromic loop sequences in SL5. As this stem-loop is located within the gag ORF, recognition of a dimeric RNA provides a possible mechanism for the specific packaging of genomic over spliced viral RNAs.

  9. Persistent humoral immune defect in highly active antiretroviral therapy-treated children with HIV-1 infection: loss of specific antibodies against attenuated vaccine strains and natural viral infection

    NARCIS (Netherlands)

    Bekker, Vincent; Scherpbier, Henriëtte; Pajkrt, Dasja; Jurriaans, Suzanne; Zaaijer, Hans; Kuijpers, Taco W.

    2006-01-01

    OBJECTIVE: In the pre-highly active antiretroviral therapy era, a loss of specific antibodies was seen. Our objective with this study was to describe the loss of specific antibodies during treatment with highly active antiretroviral therapy. METHODS: In a prospective, single-center, cohort study of

  10. Expression and characterization of antimicrobial peptides Retrocyclin-101 and Protegrin-1 in chloroplasts to control viral and bacterial infections.

    Science.gov (United States)

    Lee, Seung-Bum; Li, Baichuan; Jin, Shuangxia; Daniell, Henry

    2011-01-01

    Retrocyclin-101 (RC101) and Protegrin-1 (PG1) are two important antimicrobial peptides that can be used as therapeutic agents against bacterial and/or viral infections, especially those caused by the HIV-1 or sexually transmitted bacteria. Because of their antimicrobial activity and complex secondary structures, they have not yet been produced in microbial systems and their chemical synthesis is prohibitively expensive. Therefore, we created chloroplast transformation vectors with the RC101 or PG1 coding sequence, fused with GFP to confer stability, furin or Factor Xa cleavage site to liberate the mature peptide from their fusion proteins and a His-tag to aid in their purification. Stable integration of RC101 into the tobacco chloroplast genome and homoplasmy were confirmed by Southern blots. RC101 and PG1 accumulated up to 32%-38% and 17%∼26% of the total soluble protein. Both RC101 and PG1 were cleaved from GFP by corresponding proteases in vitro, and Factor Xa-like protease activity was observed within chloroplasts. Confocal microscopy studies showed location of GFP fluorescence within chloroplasts. Organic extraction resulted in 10.6-fold higher yield of RC101 than purification by affinity chromatography using His-tag. In planta bioassays with Erwinia carotovora confirmed the antibacterial activity of RC101 and PG1 expressed in chloroplasts. RC101 transplastomic plants were resistant to tobacco mosaic virus infections, confirming antiviral activity. Because RC101 and PG1 have not yet been produced in other cell culture or microbial systems, chloroplasts can be used as bioreactors for producing these proteins. Adequate yield of purified antimicrobial peptides from transplastomic plants should facilitate further preclinical studies. © 2010 The Authors. Plant Biotechnology Journal © 2010 Society for Experimental Biology and Blackwell Publishing Ltd.

  11. Whole-body protein turnover and energy expenditure in post-viral hepatocirrhotic patients. A study using multiple stable isotope tracers to estimate protein and energy requirements and the efficacy of a new diet therapy based on Chinese food

    International Nuclear Information System (INIS)

    Xia, Z.Q.; Dai, T.C.; Luo, W.

    1993-01-01

    L-[1- 13 C]-leucine and 15 N-glycine doubly-labelled tracer experiments revealed accelerated kinetics of leucine, glycine and whole-body protein in post-viral hepatocirrhotic patients. Together with the results of nitrogen balance measurement, the daily protein requirement of these patients was estimated to be higher than 1.2 g/kg/d. Doubly labelled water experiments and NaH 13 CO 3 experiments revealed that the freely living and basal energy expenditure of post-viral hepatocirrhotic patients was not different from that in normal subjects with comparable physical and mental activities. For those freely living in hospital, the energy requirements is estimated to be 150-160 kJ/kg/d. According to the above results, a therapeutic diet formulation based on Chinese food was designed for the patients which contained 1.5 g/kg/d of protein and 150-160 kJ/kg/d. 60-70% of the dietary protein was of vegetable origin, with a branched chain amino acid/aromatic amino acid ratio slightly but significantly higher than the common hospital diet. Patients with compensated post-viral hepatocirrhosis adapted to the diet rapidly. After two months' therapy, the negative nitrogen balance turned positive along with an increase of body weight and urinary creatinine, indicating and improvement of general nutritional status, probably with accumulation of muscle protein. The diet is relatively cheap, can be easily handled by the patients themselves, and hence is also applicable to outpatients. 54 refs, 8 tabs

  12. Association between tinnitus retraining therapy and a tinnitus control instrument.

    Science.gov (United States)

    Ito, Mari; Soma, Keiko; Ando, Reiko

    2009-10-01

    Tinnitus retraining therapy (TRT), which is an adaptation therapy for tinnitus based on the neurophysiological model proposed by Jastreboff in 1990,consists of directive counseling and acoustic therapy with a tinnitus control instrument (TCI) or other devices. For the past 5 years, our hospital has administered TRT characterized by the use of a TCI. In this study, we reviewed the clinical course of patients with tinnitus who presented to our outpatient clinic for tinnitus and hearing loss during the 3-year period from April 2004 to March 2007 and underwent TRT with a TCI. Among 188 patients with tinnitus (105 males and 83 females), 88 patients (51 males and 37 females, excluding dropouts) who purchased a TCI and continued therapy were included in the study. Significant improvement in Tinnitus Handicap Inventory (THI) and Visual Analogue Scale (VAS) scores was found as early as 1 month of treatment and later compared with those on initial examination, suggesting that TRT with a TCI may be an effective treatment for tinnitus. Among the noises generated by the TCI, the sound pressure output from the TCI was set at just below tinnitus loudness level both of the first adjustment and the second adjustment. Speech noise and white noise were frequently selected, whereas high-frequency noise and pink noise were infrequently selected. Speech noise was most frequently selected at the first adjustment, and the number of patients selecting white noise increased at the second adjustment. The results that we compared the two also revealed that the mean hearing level and tinnitus loudness levels were higher in the white noise group than in the speech noise group, which suggested that the inner ear disorder was more harder in the white noise group. Both the THI score and VAS grade improved after 1 month of treatment in the speech noise group, whereas improvement in these parameters was observed in the white noise group after 6 months of treatment. These results suggest that it took

  13. Post-treatment HIV-1 controllers with a long-term virological remission after the interruption of early initiated antiretroviral therapy ANRS VISCONTI Study.

    Directory of Open Access Journals (Sweden)

    Asier Sáez-Cirión

    2013-03-01

    Full Text Available Combination antiretroviral therapy (cART reduces HIV-associated morbidities and mortalities but cannot cure the infection. Given the difficulty of eradicating HIV-1, a functional cure for HIV-infected patients appears to be a more reachable short-term goal. We identified 14 HIV patients (post-treatment controllers [PTCs] whose viremia remained controlled for several years after the interruption of prolonged cART initiated during the primary infection. Most PTCs lacked the protective HLA B alleles that are overrepresented in spontaneous HIV controllers (HICs; instead, they carried risk-associated HLA alleles that were largely absent among the HICs. Accordingly, the PTCs had poorer CD8+ T cell responses and more severe primary infections than the HICs did. Moreover, the incidence of viral control after the interruption of early antiretroviral therapy was higher among the PTCs than has been reported for spontaneous control. Off therapy, the PTCs were able to maintain and, in some cases, further reduce an extremely low viral reservoir. We found that long-lived HIV-infected CD4+ T cells contributed poorly to the total resting HIV reservoir in the PTCs because of a low rate of infection of naïve T cells and a skewed distribution of resting memory CD4+ T cell subsets. Our results show that early and prolonged cART may allow some individuals with a rather unfavorable background to achieve long-term infection control and may have important implications in the search for a functional HIV cure.

  14. Waiting-List Controlled Trial of Cognitive Marital Therapy in Severe Marital Discord.

    Science.gov (United States)

    Waring, Edward M.; And Others

    1991-01-01

    Evaluated effectiveness of marital therapy designed to enhance intimacy through self-disclosure of personal constructs. Couples in therapy (n=22) and controls (n=19) showed significant reduction in symptoms of nonpsychotic emotional illness. Couples in therapy subjectively reported improvement. Found significant pattern of improvement for wives in…

  15. The impact of albendazole treatment on the incidence of viral- and bacterial-induced diarrhea in school children in southern Vietnam: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Leung, Jacqueline M; Hong, Chau Tran Thi; Trung, Nghia Ho Dang; Thi, Hoa Nhu; Minh, Chau Nguyen Ngoc; Thi, Thuy Vu; Hong, Dinh Thanh; Man, Dinh Nguyen Huy; Knowles, Sarah C L; Wolbers, Marcel; Hoang, Nhat Le Thanh; Thwaites, Guy; Graham, Andrea L; Baker, Stephen

    2016-06-06

    Anthelmintics are one of the more commonly available classes of drugs to treat infections by parasitic helminths (especially nematodes) in the human intestinal tract. As a result of their cost-effectiveness, mass school-based deworming programs are becoming routine practice in developing countries. However, experimental and clinical evidence suggests that anthelmintic treatments may increase susceptibility to other gastrointestinal infections caused by bacteria, viruses, or protozoa. Hypothesizing that anthelmintics may increase diarrheal infections in treated children, we aim to evaluate the impact of anthelmintics on the incidence of diarrheal disease caused by viral and bacterial pathogens in school children in southern Vietnam. This is a randomized, double-blinded, placebo-controlled trial to investigate the effects of albendazole treatment versus placebo on the incidence of viral- and bacterial-induced diarrhea in 350 helminth-infected and 350 helminth-uninfected Vietnamese school children aged 6-15 years. Four hundred milligrams of albendazole, or placebo treatment will be administered once every 3 months for 12 months. At the end of 12 months, all participants will receive albendazole treatment. The primary endpoint of this study is the incidence of diarrheal disease assessed by 12 months of weekly active and passive case surveillance. Secondary endpoints include the prevalence and intensities of helminth, viral, and bacterial infections, alterations in host immunity and the gut microbiota with helminth and pathogen clearance, changes in mean z scores of body weight indices over time, and the number and severity of adverse events. In order to reduce helminth burdens, anthelmintics are being routinely administered to children in developing countries. However, the effects of anthelmintic treatment on susceptibility to other diseases, including diarrheal pathogens, remain unknown. It is important to monitor for unintended consequences of drug treatments in

  16. Sign and Symptom and Ability to Control Violent Behaviour with Music Therapy and Rational Emotive Cognitive Behaviour Therapy

    Directory of Open Access Journals (Sweden)

    Heri Setiawan

    2015-10-01

    Full Text Available Introduction: Prevalence of violence is highly occur in mental disorders clients at psychiatric hospitals. The impact is injure to others. This research aims to examine the effectiveness of music therapy and RECBT to sign and symptom and ability to control violent behaviour. Methods: Quasi-experimental research design with a sample of 64 respondents. Result: The study found a decrease symptoms of violent behaviour, ability to control violent behavior include relaxation, change negative thingking, irational belief, and negative behavior have increased significantly than the clients that did not receiving therapy. Discussion: Music therapy and RECBT is recommended as a therapeutic nursing at the client’s violent behaviour. Key Word: violent, sign and simptom, ability, music therapy, RECBT

  17. A combinational CRISPR/Cas9 gene-editing approach can halt HIV replication and prevent viral escape

    NARCIS (Netherlands)

    Lebbink, Robert Jan; de Jong, Dorien C M; Wolters, Femke; Kruse, Elisabeth M; van Ham, Petra M; Wiertz, Emmanuel J H J; Nijhuis, Monique

    2017-01-01

    HIV presents one of the highest evolutionary rates ever detected and combination antiretroviral therapy is needed to overcome the plasticity of the virus population and control viral replication. Conventional treatments lack the ability to clear the latent reservoir, which remains the major obstacle

  18. Resource-oriented music therapy for psychiatric patients with low therapy motivation: Protocol for a randomised controlled trial [NCT00137189

    Directory of Open Access Journals (Sweden)

    Aarre Trond

    2005-10-01

    Full Text Available Abstract Background Previous research has shown positive effects of music therapy for people with schizophrenia and other mental disorders. In clinical practice, music therapy is often offered to psychiatric patients with low therapy motivation, but little research exists about this population. The aim of this study is to examine whether resource-oriented music therapy helps psychiatric patients with low therapy motivation to improve negative symptoms and other health-related outcomes. An additional aim of the study is to examine the mechanisms of change through music therapy. Methods 144 adults with a non-organic mental disorder (ICD-10: F1 to F6 who have low therapy motivation and a willingness to work with music will be randomly assigned to an experimental or a control condition. All participants will receive standard care, and the experimental group will in addition be offered biweekly sessions of music therapy over a period of three months. Outcomes will be measured by a blind assessor before and 1, 3, and 9 months after randomisation. Discussion The findings to be expected from this study will fill an important gap in the knowledge of treatment effects for a patient group that does not easily benefit from treatment. The study's close link to clinical practice, as well as its size and comprehensiveness, will make its results well generalisable to clinical practice.

  19. Volumetric modulated arc therapy for lung stereotactic radiation therapy can achieve high local control rates.

    Science.gov (United States)

    Yamashita, Hideomi; Haga, Akihiro; Takahashi, Wataru; Takenaka, Ryousuke; Imae, Toshikazu; Takenaka, Shigeharu; Nakagawa, Keiichi

    2014-11-11

    The aim of this study was to report the outcome of primary or metastatic lung cancer patients undergoing volumetric modulated arc therapy for stereotactic body radiation therapy (VMAT-SBRT). From October 2010 to December 2013, consecutive 67 lung cancer patients received single-arc VMAT-SBRT using an Elekta-synergy system. All patients were treated with an abdominal compressor. The gross tumor volumes were contoured on 10 respiratory phases computed tomography (CT) datasets from 4-dimensional (4D) CT and merged into internal target volumes (ITVs). The planning target volume (PTV) margin was isotropically taken as 5 mm. Treatment was performed with a D95 prescription of 50 Gy (43 cases) or 55 Gy (12 cases) in 4 fractions for peripheral tumor or 56 Gy in 7 fractions (12 cases) for central tumor. Among the 67 patients, the median age was 73 years (range, 59-95 years). Of the patients, male was 72% and female 28%. The median Karnofsky performance status was 90-100% in 39 cases (58%) and 80-90% in 20 cases (30%). The median follow-up was 267 days (range, 40-1162 days). Tissue diagnosis was performed in 41 patients (61%). There were T1 primary lung tumor in 42 patients (T1a in 28 patients, T1b in 14 patients), T2 in 6 patients, three T3 in 3 patients, and metastatic lung tumor in 16 patients. The median mean lung dose was 6.87 Gy (range, 2.5-15 Gy). Six patients (9%) developed radiation pneumonitis required by steroid administration. Actuarial local control rate were 100% and 100% at 1 year, 92% and 75% at 2 years, and 92% and 75% at 3 years in primary and metastatic lung cancer, respectively (p =0.59). Overall survival rate was 83% and 84% at 1 year, 76% and 53% at 2 years, and 46% and 20% at 3 years in primary and metastatic lung cancer, respectively (p =0.12). Use of VMAT-based delivery of SBRT in primary in metastatic lung tumors demonstrates high local control rates and low risk of normal tissue complications.

  20. Volumetric modulated arc therapy for lung stereotactic radiation therapy can achieve high local control rates

    International Nuclear Information System (INIS)

    Yamashita, Hideomi; Haga, Akihiro; Takahashi, Wataru; Takenaka, Ryousuke; Imae, Toshikazu; Takenaka, Shigeharu; Nakagawa, Keiichi

    2014-01-01

    The aim of this study was to report the outcome of primary or metastatic lung cancer patients undergoing volumetric modulated arc therapy for stereotactic body radiation therapy (VMAT-SBRT). From October 2010 to December 2013, consecutive 67 lung cancer patients received single-arc VMAT-SBRT using an Elekta-synergy system. All patients were treated with an abdominal compressor. The gross tumor volumes were contoured on 10 respiratory phases computed tomography (CT) datasets from 4-dimensional (4D) CT and merged into internal target volumes (ITVs). The planning target volume (PTV) margin was isotropically taken as 5 mm. Treatment was performed with a D95 prescription of 50 Gy (43 cases) or 55 Gy (12 cases) in 4 fractions for peripheral tumor or 56 Gy in 7 fractions (12 cases) for central tumor. Among the 67 patients, the median age was 73 years (range, 59–95 years). Of the patients, male was 72% and female 28%. The median Karnofsky performance status was 90-100% in 39 cases (58%) and 80-90% in 20 cases (30%). The median follow-up was 267 days (range, 40–1162 days). Tissue diagnosis was performed in 41 patients (61%). There were T1 primary lung tumor in 42 patients (T1a in 28 patients, T1b in 14 patients), T2 in 6 patients, three T3 in 3 patients, and metastatic lung tumor in 16 patients. The median mean lung dose was 6.87 Gy (range, 2.5-15 Gy). Six patients (9%) developed radiation pneumonitis required by steroid administration. Actuarial local control rate were 100% and 100% at 1 year, 92% and 75% at 2 years, and 92% and 75% at 3 years in primary and metastatic lung cancer, respectively (p = 0.59). Overall survival rate was 83% and 84% at 1 year, 76% and 53% at 2 years, and 46% and 20% at 3 years in primary and metastatic lung cancer, respectively (p = 0.12). Use of VMAT-based delivery of SBRT in primary in metastatic lung tumors demonstrates high local control rates and low risk of normal tissue complications

  1. P2X7-Regulated Protection from Exacerbations and Loss of Control Is Independent of Asthma Maintenance Therapy

    Science.gov (United States)

    Manthei, David M.; Seibold, Max A.; Ahn, Kwangmi; Bleecker, Eugene; Boushey, Homer A.; Calhoun, William J.; Castro, Mario; Chinchili, Vernon M.; Fahy, John V.; Hawkins, Greg A.; Icitovic, Nicolina; Israel, Elliot; Jarjour, Nizar N.; King, Tonya; Kraft, Monica; Lazarus, Stephen C.; Lehman, Erik; Martin, Richard J.; Meyers, Deborah A.; Peters, Stephen P.; Sheerar, Dagna; Shi, Lei; Sutherland, E. Rand; Szefler, Stanley J.; Wechsler, Michael E.; Sorkness, Christine A.; Lemanske, Robert F.

    2013-01-01

    Rationale: The function of the P2X7 nucleotide receptor protects against exacerbation in people with mild-intermittent asthma during viral illnesses, but the impact of disease severity and maintenance therapy has not been studied. Objectives: To evaluate the association between P2X7, asthma exacerbations, and incomplete symptom control in a more diverse population. Methods: A matched P2RX7 genetic case-control was performed with samples from Asthma Clinical Research Network trial participants enrolled before July 2006, and P2X7 pore activity was determined in whole blood samples as an ancillary study to two trials completed subsequently. Measurements and Main Results: A total of 187 exacerbations were studied in 742 subjects, and the change in asthma symptom burden was studied in an additional 110 subjects during a trial of inhaled corticosteroids (ICS) dose optimization. African American carriers of the minor G allele of the rs2230911 loss-of-function single nucleotide polymorphism were more likely to have a history of prednisone use in the previous 12 months, with adjustment for ICS and long-acting β2-agonists use (odds ratio, 2.7; 95% confidence interval, 1.2–6.2; P = 0.018). Despite medium-dose ICS, attenuated pore function predicted earlier exacerbations in incompletely controlled patients with moderate asthma (hazard ratio, 3.2; confidence interval, 1.1–9.3; P = 0.033). After establishing control with low-dose ICS in patients with mild asthma, those with attenuated pore function had more asthma symptoms, rescue albuterol use, and FEV1 reversal (P < 0.001, 0.03, and 0.03, respectively) during the ICS adjustment phase. Conclusions: P2X7 pore function protects against exacerbations of asthma and loss of control, independent of baseline severity and the maintenance therapy. PMID:23144325

  2. 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

  3. Antigenic differences between bovine viral diarrhea viruses and HoBi virus: Possible impacts on diagnosis and control

    Science.gov (United States)

    Compare antigenic differences between HoBi virus and BVDV strains that might impact on diagnostics and control. Eighteen non-cytopathic isolates of pestiviruses including the 5 genotypic groups (BVDV1a-c, BVDV2, BDV) and HoBi virus, were tested using antigen capture enzyme-linked immunosorbent assay...

  4. Virologic response to tipranavir-ritonavir or darunavir-ritonavir based regimens in antiretroviral therapy experienced HIV-1 patients: a meta-analysis and meta-regression of randomized controlled clinical trials.

    Directory of Open Access Journals (Sweden)

    Asres Berhan

    Full Text Available The development of tipranavir and darunavir, second generation non-peptidic HIV protease inhibitors, with marked improved resistance profiles, has opened a new perspective on the treatment of antiretroviral therapy (ART experienced HIV patients with poor viral load control. The aim of this study was to determine the virologic response in ART experienced patients to tipranavir-ritonavir and darunavir-ritonavir based regimens.A computer based literature search was conducted in the databases of HINARI (Health InterNetwork Access to Research Initiative, Medline and Cochrane library. Meta-analysis was performed by including randomized controlled studies that were conducted in ART experienced patients with plasma viral load above 1,000 copies HIV RNA/ml. The odds ratios and 95% confidence intervals (CI for viral loads of <50 copies and <400 copies HIV RNA/ml at the end of the intervention were determined by the random effects model. Meta-regression, sensitivity analysis and funnel plots were done. The number of HIV-1 patients who were on either a tipranavir-ritonavir or darunavir-ritonavir based regimen and achieved viral load less than 50 copies HIV RNA/ml was significantly higher (overall OR = 3.4; 95% CI, 2.61-4.52 than the number of HIV-1 patients who were on investigator selected boosted comparator HIV-1 protease inhibitors (CPIs-ritonavir. Similarly, the number of patients with viral load less than 400 copies HIV RNA/ml was significantly higher in either the tipranavir-ritonavir or darunavir-ritonavir based regimen treated group (overall OR = 3.0; 95% CI, 2.15-4.11. Meta-regression showed that the viral load reduction was independent of baseline viral load, baseline CD4 count and duration of tipranavir-ritonavir or darunavir-ritonavir based regimen.Tipranavir and darunavir based regimens were more effective in patients who were ART experienced and had poor viral load control. Further studies are required to determine their consistent

  5. Mobil Viral Pazarlama

    OpenAIRE

    Barutçu, Süleyman

    2011-01-01

    OBJECTIVE: Mobile Viral Marketing, with using mobile phones, is one of the most importantinnovations after Word of Mouth Marketing performed by face to face amongpeople and Viral Marketing performed in the İnternet. The main objective of thisstudy is to call marketing communicators’ and academicians’ attentions whowant to increase the recognition of companies’ products, services and brands tobecome a current issue in the marketplace using Mobile Viral Marketingapplications by reason of techno...

  6. Paraconsistents artificial neural networks applied to the study of mutational patterns of the F subtype of the viral strains of HIV-1 to antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    PAULO C.C. DOS SANTOS

    2016-03-01

    Full Text Available ABSTRACT The high variability of HIV-1 as well as the lack of efficient repair mechanisms during the stages of viral replication, contribute to the rapid emergence of HIV-1 strains resistant to antiretroviral drugs. The selective pressure exerted by the drug leads to fixation of mutations capable of imparting varying degrees of resistance. The presence of these mutations is one of the most important factors in the failure of therapeutic response to medications. Thus, it is of critical to understand the resistance patterns and mechanisms associated with them, allowing the choice of an appropriate therapeutic scheme, which considers the frequency, and other characteristics of mutations. Utilizing Paraconsistents Artificial Neural Networks, seated in Paraconsistent Annotated Logic Et which has the capability of measuring uncertainties and inconsistencies, we have achieved levels of agreement above 90% when compared to the methodology proposed with the current methodology used to classify HIV-1 subtypes. The results demonstrate that Paraconsistents Artificial Neural Networks can serve as a promising tool of analysis.

  7. TCRγδ+CD4−CD8− T Cells Suppress the CD8+ T-Cell Response to Hepatitis B Virus Peptides, and Are Associated with Viral Control in Chronic Hepatitis B

    Science.gov (United States)

    Lai, Qintao; Ma, Shiwu; Ge, Jun; Huang, Zuxiong; Huang, Xuan; Jiang, Xiaotao; Li, Yongyin; Zhang, Mingxia; Zhang, Xiaoyong; Sun, Jian; Abbott, William G. H.; Hou, Jinlin

    2014-01-01

    The immune mechanisms underlying failure to achieve hepatitis B e antigen (HBeAg) seroconversion associated with viral control in chronic hepatitis B (CHB) remain unclear. Here we investigated the role of CD4−CD8− T (double-negative T; DNT) cells including TCRαβ+ DNT (αβ DNT) and TCRγδ+ DNT (γδ DNT) cells. Frequencies of circulating DNT cell subsets were measured by flow cytometry in a retrospective cohort of 51 telbivudine-treated HBeAg-positive CHB patients, 25 immune tolerant carriers (IT), 33 inactive carriers (IC), and 37 healthy controls (HC). We found that γδ DNT cell frequencies did not significantly change during treatment, being lower at baseline (P = 0.019) in patients with HBeAg seroconversion after 52 weeks of antiviral therapy (n = 20) than in those without (n = 31), and higher in the total CHB and IT than IC and HC groups (P<0.001). αβ DNT cell frequencies were similar for all groups. In vitro, γδ DNT cells suppressed HBV core peptide-stimulated interferon-γ and tumor necrosis factor-α production in TCRαβ+CD8+ T cells, which may require cell–cell contact, and could be partially reversed by anti-NKG2A. These findings suggest that γδ DNT cells limit CD8+ T cell response to HBV, and may impede HBeAg seroconversion in CHB. PMID:24551107

  8. Pediatric selective mutism therapy: a randomized controlled trial.

    Science.gov (United States)

    Esposito, Maria; Gimigliano, Francesca; Barillari, Maria R; Precenzano, Francesco; Ruberto, Maria; Sepe, Joseph; Barillari, Umberto; Gimigliano, Raffaele; Militerni, Roberto; Messina, Giovanni; Carotenuto, Marco

    2017-10-01

    Selective mutism (SM) is a rare disease in children coded by DSM-5 as an anxiety disorder. Despite the disabling nature of the disease, there is still no specific treatment. The aims of this study were to verify the efficacy of six-month standard psychomotor treatment and the positive changes in lifestyle, in a population of children affected by SM. Randomized controlled trial registered in the European Clinical Trials Registry (EuDract 2015-001161-36). University third level Centre (Child and Adolescent Neuropsychiatry Clinic). Study population was composed by 67 children in group A (psychomotricity treatment) (35 M, mean age 7.84±1.15) and 71 children in group B (behavioral and educational counseling) (37 M, mean age 7.75±1.36). Psychomotor treatment was administered by trained child therapists in residential settings three times per week. Each child was treated for the whole period by the same therapist and all the therapists shared the same protocol. The standard psychomotor session length is of 45 minutes. At T0 and after 6 months (T1) of treatments, patients underwent a behavioral and SM severity assessment. To verify the effects of the psychomotor management, the Child Behavior Checklist questionnaire (CBCL) and Selective Mutism Questionnaire (SMQ) were administered to the parents. After 6 months of psychomotor treatment SM children showed a significant reduction among CBCL scores such as in social relations, anxious/depressed, social problems and total problems (Pselective mutism, even if further studies are needed. The present study identifies in psychomotricity a safe and efficacy therapy for pediatric selective mutism.

  9. Viral-Associated GN: Hepatitis C and HIV.

    Science.gov (United States)

    Kupin, Warren L

    2017-08-07

    Viruses are capable of inducing a wide spectrum of glomerular disorders that can be categorized on the basis of the duration of active viremia: acute, subacute, or chronic. The variable responses of the adaptive immune system to each time period of viral infection results mechanistically in different histologic forms of glomerular injury. The unique presence of a chronic viremic carrier state with either hepatitis C (HCV) or HIV has led to the opportunity to study in detail various pathogenic mechanisms of viral-induced glomerular injury, including direct viral infection of renal tissue and the development of circulating immune complexes composed of viral antigens that deposit along the glomerular basement membrane. Epidemiologic data show that approximately 25%-30% of all HIV patients are coinfected with HCV and 5%-10% of all HCV patients are coinfected with HIV. This situation can often lead to a challenging differential diagnosis when glomerular disease occurs in this dual-infected population and requires the clinician to be familiar with the clinical presentation, laboratory workup, and pathophysiology behind the development of renal disease for both HCV and HIV. Both of these viruses can be categorized under the new classification of infection-associated GN as opposed to being listed as causes of postinfectious GN as has previously been applied to them. Neither of these viruses lead to renal injury after a latent period of controlled and inactive viremia. The geneses of HCV- and HIV-associated glomerular diseases share a total dependence on the presence of active viral replication to sustain renal injury so the renal disease cannot be listed under "postinfectious" GN. With the new availability of direct-acting antivirals for HCV and more effective combined antiretroviral therapy for HIV, successful remission and even regression of glomerular lesions can be achieved if initiated at an early stage. Copyright © 2017 by the American Society of Nephrology.

  10. Ultrasound therapy applicators for controlled thermal modification of tissue

    Science.gov (United States)

    Burdette, E. Clif; Lichtenstiger, Carol; Rund, Laurie; Keralapura, Mallika; Gossett, Chad; Stahlhut, Randy; Neubauer, Paul; Komadina, Bruce; Williams, Emery; Alix, Chris; Jensen, Tor; Schook, Lawrence; Diederich, Chris J.

    2011-03-01

    Heat therapy has long been used for treatments in dermatology and sports medicine. The use of laser, RF, microwave, and more recently, ultrasound treatment, for psoriasis, collagen reformation, and skin tightening has gained considerable interest over the past several years. Numerous studies and commercial devices have demonstrated the efficacy of these methods for treatment of skin disorders. Despite these promising results, current systems remain highly dependent on operator skill, and cannot effectively treat effectively because there is little or no control of the size, shape, and depth of the target zone. These limitations make it extremely difficult to obtain consistent treatment results. The purpose of this study was to determine the feasibility for using acoustic energy for controlled dose delivery sufficient to produce collagen modification for the treatment of skin tissue in the dermal and sub-dermal layers. We designed and evaluated a curvilinear focused ultrasound device for treating skin disorders such as psoriasis, stimulation of wound healing, tightening of skin through shrinkage of existing collagen and stimulation of new collagen formation, and skin cancer. Design parameters were examined using acoustic pattern simulations and thermal modeling. Acute studies were performed in 201 freshly-excised samples of young porcine underbelly skin tissue and 56 in-vivo treatment areas in 60- 80 kg pigs. These were treated with ultrasound (9-11MHz) focused in the deep dermis. Dose distribution was analyzed and gross pathology assessed. Tissue shrinkage was measured based on fiducial markers and video image registration and analyzed using NIH Image-J software. Comparisons were made between RF and focused ultrasound for five energy ranges. In each experimental series, therapeutic dose levels (60degC) were attained at 2-5mm depth. Localized collagen changes ranged from 1-3% for RF versus 8-15% for focused ultrasound. Therapeutic ultrasound applied at high

  11. Prolonged Expression of Secreted Enzymes in Dogs After Liver-Directed Delivery of Sleeping Beauty Transposons: Implications for Non-Viral Gene Therapy of Systemic Disease.

    Science.gov (United States)

    Aronovich, Elena L; Hyland, Kendra A; Hall, Bryan C; Bell, Jason B; Olson, Erik R; Rusten, Myra Urness; Hunter, David W; Ellinwood, N Matthew; McIvor, R Scott; Hackett, Perry B

    2017-07-01

    The non-viral, integrating Sleeping Beauty (SB) transposon system is efficient in treating systemic monogenic disease in mice, including hemophilia A and B caused by deficiency of blood clotting factors and mucopolysaccharidosis types I and VII caused by α-L-iduronidase (IDUA) and β-glucuronidase (GUSB) deficiency, respectively. Modified approaches of the hydrodynamics-based procedure to deliver transposons to the liver in dogs were recently reported. Using the transgenic canine reporter secreted alkaline phosphatase (cSEAP), transgenic protein in the plasma was demonstrated for up to 6 weeks post infusion. This study reports that immunosuppression of dogs with gadolinium chloride (GdCl 3 ) prolonged the presence of cSEAP in the circulation up to 5.5 months after a single vector infusion. Transgene expression declined gradually but appeared to stabilize after about 2 months at approximately fourfold baseline level. Durability of transgenic protein expression in the plasma was inversely associated with transient increase of liver enzymes alanine transaminase and aspartate transaminase in response to the plasmid delivery procedure, which suggests a deleterious effect of hepatocellular toxicity on transgene expression. GdCl 3 treatment was ineffective for repeat vector infusions. In parallel studies, dogs were infused with potentially therapeutic transposons. Activities of transgenic IDUA and GUSB in plasma peaked at 50-350% of wildtype, but in the absence of immunosuppression lasted only a few days. Transposition was detectable by excision assay only when the most efficient transposase, SB100X, was used. Dogs infused with transposons encoding canine clotting factor IX (cFIX) were treated with GdCl 3 and showed expression profiles similar to those in cSEAP-infused dogs, with expression peaking at 40% wt (2 μg/mL). It is concluded that GdCl 3 can support extended transgene expression after hydrodynamic introduction of SB transposons in dogs, but that alternative

  12. Spa therapy adjunct to pharmacotherapy is beneficial in rheumatoid arthritis: a crossover randomized controlled trial

    Science.gov (United States)

    Karagülle, Mine; Kardeş, Sinan; Dişçi, Rian; Karagülle, Müfit Zeki

    2018-02-01

    This study aims to investigate whether 2-week spa therapy, as an adjunct to usual pharmacological therapy, has any beneficial effect in patients with rheumatoid arthritis (RA). In this single-blind crossover study, 50 patients were randomly assigned in a 1:1 manner to receive usual pharmacological therapy plus 2-week spa therapy or usual pharmacological therapy alone (period 1.6 months); after a 9-month washout, patients were crossed over to the opposite assignment (period 2.6 months). Spa therapy program included a daily saline balneotherapy session at 36-37 °C for 20 min except Sundays. The clinical outcomes were evaluated at baseline, after spa therapy (2 weeks) and 3 and 6 months after the spa therapy in both period and were pain (Visual Analogue Scale (VAS)), patient and physician global assessments (VAS), Health Assessment Questionnaire (HAQ), and Disease Activity Score (DAS28). Spa therapy was superior to control therapy in improving all the assessed clinical outcomes at the end of the spa therapy. This superiority persisted significantly in physician global assessment ( p = 0.010) and with a trend in favor of spa group in patient global assessment ( p = 0.058), function ( p = 0.092), and disease activity ( p = 0.098) at 3 months. Statistically significant improvements were found in spa therapy compared to control in disease activity ( p = 0.006) and patient ( p = 0.020) and physician global ( p = 0.011) assessments, and a trend toward improvements in pain ( p = 0.069) and swollen joints ( p = 0.070) at 6 months. A 2-week spa therapy adjunct to usual pharmacological therapy provided beneficial clinical effects compared to usual pharmacological therapy alone, in RA patients treated with traditional disease-modifying antirheumatic drugs. These beneficial effects may last for 6 months.

  13. Vaccination with Gag, Vif, and Nef gene fragments affords partial control of viral replication after mucosal challenge with SIVmac239.

    Science.gov (United States)

    Martins, Mauricio A; Wilson, Nancy A; Piaskowski, Shari M; Weisgrau, Kim L; Furlott, Jessica R; Bonaldo, Myrna C; Veloso de Santana, Marlon G; Rudersdorf, Richard A; Rakasz, Eva G; Keating, Karen D; Chiuchiolo, Maria J; Piatak, Michael; Allison, David B; Parks, Christopher L; Galler, Ricardo; Lifson, Jeffrey D; Watkins, David I

    2014-07-01

    Broadly targeted cellular immune responses are thought to be important for controlling replication of human and simian immunodeficiency viruses (HIV and SIV). However, eliciting such responses by vaccination is complicated by immunodominance, the preferential targeting of only a few of the many possible epitopes of a given antigen. This phenomenon may be due to the coexpression of dominant and subdominant epitopes by the same antigen-presenting cell and may be overcome by distributing these sequences among several different vaccine constructs. Accordingly, we tested whether vaccinating rhesus macaques with "minigenes" encoding fragments of Gag, Vif, and Nef resulted in broadened cellular responses capable of controlling SIV replication. We delivered these minigenes through combinations of recombinant Mycobacterium bovis BCG (rBCG), electroporated recombinant DNA (rDNA) along with an interleukin-12 (IL-12)-expressing plasmid (EP rDNA plus pIL-12), yellow fever vaccine virus 17D (rYF17D), and recombinant adenovirus serotype 5 (rAd5). Although priming with EP rDNA plus pIL-12 increased the breadth of vaccine-induced T-cell responses, this effect was likely due to the improved antigen delivery afforded by electroporation rather than modulation of immunodominance. Indeed, Mamu-A*01(+) vaccinees mounted CD8(+) T cells directed against only one subdominant epitope, regardless of the vaccination regimen. After challenge with SIVmac239, vaccine efficacy was limited to a modest reduction in set point in some of the groups and did not correlate with standard T-cell measurements. These findings suggest that broad T-cell responses elicited by conventional vectors may not be sufficient to substantially contain AIDS virus replication. Immunodominance poses a major obstacle to the generation of broadly targeted, HIV-specific cellular responses by vaccination. Here we attempted to circumvent this phenomenon and thereby broaden the repertoire of SIV-specific cellular responses by

  14. Did medieval trade activity and a viral etiology control the spatial extent and seasonal distribution of Black Death mortality?

    Science.gov (United States)

    Bossak, Brian H; Welford, Mark R

    2009-06-01

    Recent research into the world's greatest recorded epidemic, the Medieval Black Death (MBD), has cast doubt on Bubonic Plague as the etiologic agent. Prior research has recently culminated in outstanding advances in our understanding of the spatio-temporal pattern of MBD mortality, and a characterization of the incubation, latent, infectious, and symptomatic periods of the MBD. However, until now, several mysteries remained unexplained, including perhaps the biggest quandary of all: why did the MBD exhibit inverse seasonal peaks in mortality from diseases recorded in modern times, such as seasonal Influenza or the Indian Plague Epidemics of the early 1900 s? Although some have argued that climate changes likely explain the observed differences between modern clinical Bubonic Plague seasonality and MBD mortality accounts, we believe that another factor explains these dissimilarities. Here, we provide a synthetic hypothesis which builds upon previous theories developed in the last ten years or so. Our all-encompassing theory explains the causation, dissemination, and lethality of the MBD. We theorize that the MBD was a human-to-human transmitted virus, originating in East-Central Asia and not Africa (as some recent work has proposed), and that its areal extent during the first great epidemic wave of 1347-1350 was controlled hierarchically by proximity to trade routes. We also propose that the seasonality of medieval trade controlled the warm-weather mortality peaks witnessed during 1347-1350; during the time of greatest market activity, traders, fairgoers, and religious pilgrims served as unintentional vectors of a lethal virus with an incubation period of approximately 32 days, including a largely asymptomatic yet infectious period of roughly three weeks. We include a description of the rigorous research agenda that we have proposed in order to subject our theory to scientific scrutiny and a description of our plans to generate the first publicly available

  15. The Elav-like protein HuR exerts translational control of viral internal ribosome entry sites

    International Nuclear Information System (INIS)

    Rivas-Aravena, Andrea; Ramdohr, Pablo; Vallejos, Maricarmen; Valiente-Echeverria, Fernando; Dormoy-Raclet, Virginie; Rodriguez, Felipe; Pino, Karla; Holzmann, Cristian; Huidobro-Toro, J. Pablo; Gallouzi, Imed-Eddine; Lopez-Lastra, Marcelo

    2009-01-01

    The human embryonic-lethal abnormal vision (ELAV)-like protein, HuR, has been recently found to be involved in the regulation of protein synthesis. In this study we show that HuR participates in the translational control of the HIV-1 and HCV IRES elements. HuR functions as a repressor of HIV-1 IRES activity and acts as an activator of the HCV IRES. The effect of HuR was evaluated in three independent experimental systems, rabbit reticulocyte lysate, HeLa cells, and Xenopus laevis oocytes, using both overexpression and knockdown approaches. Furthermore, results suggest that HuR mediated regulation of HIV-1 and HCV IRESes does not require direct binding of the protein to the RNA nor does it need the nuclear translocation of the IRES-containing RNAs. Finally, we show that HuR has a negative impact on post-integration steps of the HIV-1 replication cycle. Thus, our observations yield novel insights into the role of HuR in the post-transcriptional regulation of HCV and HIV-1 gene expression.

  16. The effects of mirror therapy on the gait of subacute stroke patients: a randomized controlled trial.

    Science.gov (United States)

    Ji, Sang Gu; Kim, Myoung Kwon

    2015-04-01

    To investigate the effect of mirror therapy on the gait of patients with subacute stroke. Randomized controlled experimental study. Outpatient rehabilitation hospital. Thirty-four patients with stroke were randomly assigned to two groups: a mirror therapy group (experimental) and a control group. The stroke patients in the experimental group underwent comprehensive rehabilitation therapy and mirror therapy for the lower limbs. The stroke patients in the control group underwent sham therapy and comprehensive rehabilitation therapy. Participants in both groups received therapy five days per week for four weeks. Temporospatial gait characteristics, such as single stance, stance phase, step length, stride, swing phase, velocity, and cadence, were assessed before and after the four weeks therapy period. A significant difference was observed in post-training gains for the single stance (10.32 SD 4.14 vs. 6.54 SD 3.23), step length (8.47 SD 4.12 vs. 4.83 SD 2.14), and stride length (17.03 SD 6.57 vs 10.54 SD 4.34) between the experimental group and the control group (p two groups on stance phase, swing phase, velocity, cadence, and step width (P > 0.05). We conclude that mirror therapy may be beneficial in improving the effects of stroke on gait ability. © The Author(s) 2014.

  17. Anti-viral effect of herbal medicine Korean traditional Cynanchum ...

    African Journals Online (AJOL)

    Background: Pestiviruses in general, and Bovine Viral Diarrhea (BVD) in particular, present several potential targets for directed antiviral therapy. Material and Methods: The antiviral effect of Cynanchum paniculatum (Bge.) Kitag (Dog strangling vine: DS) extract on the bovine viral diarrhea (BVD) virus was tested. First ...

  18. Viral Disease Networks?

    Science.gov (United States)

    Gulbahce, Natali; Yan, Han; Vidal, Marc; Barabasi, Albert-Laszlo

    2010-03-01

    Viral infections induce multiple perturbations that spread along the links of the biological networks of the host cells. Understanding the impact of these cascading perturbations requires an exhaustive knowledge of the cellular machinery as well as a systems biology approach that reveals how individual components of the cellular system function together. Here we describe an integrative method that provides a new approach to studying virus-human interactions and its correlations with diseases. Our method involves the combined utilization of protein - protein interactions, protein -- DNA interactions, metabolomics and gene - disease associations to build a ``viraldiseasome''. By solely using high-throughput data, we map well-known viral associated diseases and predict new candidate viral diseases. We use microarray data of virus-infected tissues and patient medical history data to further test the implications of the viral diseasome. We apply this method to Epstein-Barr virus and Human Papillomavirus and shed light into molecular development of viral diseases and disease pathways.

  19. Epitope specificity is critical for high and moderate avidity cytotoxic T lymphocytes associated with control of viral load and clinical disease in horses with equine infectious anemia virus

    International Nuclear Information System (INIS)

    Mealey, Robert H.; Zhang Baoshan; Leib, Steven R.; Littke, Matt H.; McGuire, Travis C.

    2003-01-01

    Equine infectious anemia virus (EIAV) is a lentivirus that causes persistent infections in horses. We hypothesized that high-avidity CTL specific for nonvariable epitopes might be associated with low viral load and minimal disease in EIAV-infected horses. To test this hypothesis, memory CTL (CTLm) responses were analyzed in two infected horses with high plasma viral loads and recurrent disease (progressors), and in two infected horses with low-to-undetectable viral loads and mild disease (nonprogressors). High-avidity CTLm in one progressor recognized an envelope gp90 epitope, and the data documented for the first time in EIAV that viral variation led to CTL escape. Each of the nonprogressors had high-to-moderate avidity CTLm directed against epitopes within Rev, including the nuclear export and nuclear localization domains. These results suggested that the epitope specificity of high- and moderate-avidity CTLm was an important determinant for disease outcome in the EIAV-infected horses examined

  20. A novel duplex real-time reverse transcriptase-polymerase chain reaction assay for the detection of hepatitis C viral RNA with armored RNA as internal control

    Directory of Open Access Journals (Sweden)

    Meng Shuang

    2010-06-01

    Full Text Available Abstract Background The hepatitis C virus (HCV genome is extremely heterogeneous. Several HCV infections can not be detected using currently available commercial assays, probably because of mismatches between the template and primers/probes. By aligning the HCV sequences, we developed a duplex real-time reverse transcriptase-polymerase chain reaction (RT-PCR assay using 2 sets of primers/probes and a specific armored RNA as internal control. The 2 detection probes were labelled with the same fluorophore, namely, 6-carboxyfluorescein (FAM, at the 5' end; these probes could mutually combine, improving the power of the test. Results The limit of detection of the duplex primer/probe assay was 38.99 IU/ml. The sensitivity of the assay improved significantly, while the specificity was not affected. All HCV genotypes in the HCV RNA Genotype Panel for Nucleic Acid Amplification Techniques could be detected. In the testing of 109 serum samples, the performance of the duplex real-time RT-PCR assay was identical to that of the COBAS AmpliPrep (CAP/COBAS TaqMan (CTM assay and superior to 2 commercial HCV assay kits. Conclusions The duplex real-time RT-PCR assay is an efficient and effective viral assay. It is comparable with the CAP/CTM assay with regard to the power of the test and is appropriate for blood-donor screening and laboratory diagnosis of HCV infection.

  1. Hepatitis viral B y Delta en el Perú: epidemiología y bases para su control

    Directory of Open Access Journals (Sweden)

    César Cabezas

    2007-10-01

    Full Text Available El Perú está catalogado como un país de mediana endemicidad para la infección por la hepatitis B (HBV, sin embargo, esta enfermedad se está dispersando en el país por la intensa migración de áreas de alta endemicidad a zonas de baja que endemicidad. Además de los mecanismos clásicos de transmisión de la infección como la vía parenteral y la vía sexual, debe destacarse la transmisión horizontal sobre todo en población infantil de áreas hiperendémicas y la limitada ocurrencia de transmisión vertical a diferencia de Asia. Desde que se cuenta con una vacuna segura y eficaz contra la HBV, se ha desarrollado programas de vacunación piloto en el país, luego de lo cual se ha generalizado la inmunización de la población infantil primero de áreas endémicas y luego a todo el país, según la prioridad y disponibilidad de vacunas. Dada la dispersión de la infección, y para lograr un efectivo control del problema en personas susceptibles, en un menor tiempo, es necesaria la inmunización contra HBV de adolescentes, jóvenes y grupos de riesgo, intervención que es una de las más costo-efectivas en salud pública, mereciendo en el mediano y largo plazo la evaluación de su real impacto. Estos temas son los que se desarrollan en la presente revisión.

  2. Hepatitis C viral evolution in genotype 1 treatment-naïve and treatment-experienced patients receiving telaprevir-based therapy in clinical trials.

    Directory of Open Access Journals (Sweden)

    Tara L Kieffer

    Full Text Available In patients with genotype 1 chronic hepatitis C infection, telaprevir (TVR in combination with peginterferon and ribavirin (PR significantly increased sustained virologic response (SVR rates compared with PR alone. However, genotypic changes could be observed in TVR-treated patients who did not achieve an SVR.Population sequence analysis of the NS3•4A region was performed in patients who did not achieve SVR with TVR-based treatment.Resistant variants were observed after treatment with a telaprevir-based regimen in 12% of treatment-naïve patients (ADVANCE; T12PR arm, 6% of prior relapsers, 24% of prior partial responders, and 51% of prior null responder patients (REALIZE, T12PR48 arms. NS3 protease variants V36M, R155K, and V36M+R155K emerged frequently in patients with genotype 1a and V36A, T54A, and A156S/T in patients with genotype 1b. Lower-level resistance to telaprevir was conferred by V36A/M, T54A/S, R155K/T, and A156S variants; and higher-level resistance to telaprevir was conferred by A156T and V36M+R155K variants. Virologic failure during telaprevir treatment was more common in patients with genotype 1a and in prior PR nonresponder patients and was associated with higher-level telaprevir-resistant variants. Relapse was usually associated with wild-type or lower-level resistant variants. After treatment, viral populations were wild-type with a median time of 10 months for genotype 1a and 3 weeks for genotype 1b patients.A consistent, subtype-dependent resistance profile was observed in patients who did not achieve an SVR with telaprevir-based treatment. The primary role of TVR is to inhibit wild-type virus and variants with lower-levels of resistance to telaprevir. The complementary role of PR is to clear any remaining telaprevir-resistant variants, especially higher-level telaprevir-resistant variants. Resistant variants are detectable in most patients who fail to achieve SVR, but their levels decline over time after treatment.

  3. Exercise therapy, manual therapy, or both, for osteoarthritis of the hip or knee: a factorial randomised controlled trial protocol

    Directory of Open Access Journals (Sweden)

    Baxter G David

    2009-02-01

    Full Text Available Abstract Background Non-pharmacological, non-surgical interventions are recommended as the first line of treatment for osteoarthritis (OA of the hip and knee. There is evidence that exercise therapy is effective for reducing pain and improving function in patients with knee OA, some evidence that exercise therapy is effective for hip OA, and early indications that manual therapy may be efficacious for hip and knee OA. There is little evidence as to which approach is more effective, if benefits endure, or if providing these therapies is cost-effective for the management of this disorder. The MOA Trial (Management of OsteoArthritis aims to test the effectiveness of two physiotherapy interventions for improving disability and pain in adults with hip or knee OA in New Zealand. Specifically, our primary objectives are to investigate whether: 1. Exercise therapy versus no exercise therapy improves disability at 12 months; 2. Manual physiotherapy versus no manual therapy improves disability at 12 months; 3. Providing physiotherapy programmes in addition to usual care is more cost-effective than usual care alone in the management of osteoarthritis at 24 months. Methods This is a 2 × 2 factorial randomised controlled trial. We plan to recruit 224 participants with hip or knee OA. Eligible participants will be randomly allocated to receive either: (a a supervised multi-modal exercise therapy programme; (b an individualised manual therapy programme; (c both exercise therapy and manual therapy; or, (d no trial physiotherapy. All participants will continue to receive usual medical care. The outcome assessors, orthopaedic surgeons, general medical practitioners, and statistician will be blind to group allocation until the statistical analysis is completed. The trial is funded by Health Research Council of New Zealand Project Grants (Project numbers 07/199, 07/200. Discussion The MOA Trial will be the first to investigate the effectiveness and cost

  4. Radiotherapy of breast cancer and dispensary control after the therapy

    International Nuclear Information System (INIS)

    Odontuya, G.

    1995-01-01

    During the last several years breast cancer is increasing in Mongolia. During 5 years(1990-1994) 142 patients with breast cancer were treated in department of radiology. The 96(77,6%) of those patients were treated by combined radiation therapy and surgery. The 46(32,4%) of those patients were treated palliative therapy. A conclusion:1.Organizing the preventive different examinations among the population in the servicing sphere, involving the family doctors to them. 2.Detection and screening breast cancer in the first period, very important for treatment every patients

  5. Mindfulness-Based Cognitive Therapy as a Treatment for Chronic Tinnitus: A Randomized Controlled Trial

    OpenAIRE

    McKenna, L.; Marks, E. M.; Hallsworth, C. A.; Schaette, R.

    2017-01-01

    BACKGROUND: Tinnitus is experienced by up to 15% of the population and can lead to significant disability and distress. There is rarely a medical or surgical target and psychological therapies are recommended. We investigated whether mindfulness-based cognitive therapy (MBCT) could offer an effective new therapy for tinnitus. METHODS: This single-site randomized controlled trial compared MBCT to intensive relaxation training (RT) for chronic, distressing tinnitus in adults. Both treatments in...

  6. Multiparametric analysis of host response to murine cytomegalovirus in MHC class I-disparate mice reveals primacy of Dk-licensed Ly49G2+ NK cells in viral control.

    Science.gov (United States)

    Prince, Jessica; Lundgren, Alyssa; Stadnisky, Michael D; Nash, William T; Beeber, Amira; Turner, Stephen D; Brown, Michael G

    2013-11-01

    MHC class I D(k) and Ly49G2 (G2) inhibitory receptor-expressing NK cells are essential to murine CMV (MCMV) resistance in MA/My mice. Without D(k), G2(+) NK cells in C57L mice fail to protect against MCMV infection. As a cognate ligand of G2, D(k) licenses G2(+) NK cells for effector activity. These data suggested that D(k)-licensed G2(+) NK cells might recognize and control MCMV infection. However, a role for licensed NK cells in viral immunity is uncertain. We combined classical genetics with flow cytometry to visualize the host response to MCMV. Immune cells collected from individuals of a diverse cohort of MA/My × C57L offspring segregating D(k) were examined before infection and postinfection, including Ly49(+) NK subsets, receptor expression features, and other phenotypic traits. To identify critical NK cell features, automated analysis of 110 traits was performed in R using the Pearson correlation, followed with a Bonferroni correction for multiple tests. Hierarchical clustering of trait associations and principal component analyses were used to discern shared immune response and genetic relationships. The results demonstrate that G2 expression on naive blood NK cells was predictive of MCMV resistance. However, rapid G2(+) NK cell expansion following viral exposure occurred selectively in D(k) offspring; this response was more highly correlated with MCMV control than all other immune cell features. We infer that D(k)-licensed G2(+) NK cells efficiently detected missing-self MHC cues on viral targets, which elicited cellular expansion and target cell killing. Therefore, MHC polymorphism regulates licensing and detection of viral targets by distinct subsets of NK cells required in innate viral control.

  7. Effects of an aquatic therapy approach (Halliwick-Therapy) on functional mobility in subacute stroke patients: a randomized controlled trial.

    Science.gov (United States)

    Tripp, Florian; Krakow, Karsten

    2014-05-01

    To evaluate the effects of an aquatic physiotherapy method (Halliwick-Therapy) upon mobility in the post-acute phase of stroke rehabilitation. Randomized controlled trial. Hospital for neurological rehabilitation. Adult patients after first-ever stroke in post-acute inpatient rehabilitation at least two weeks after the onset of stroke (n = 30). In the Halliwick-Therapy group (n = 14) the treatment over a period of two weeks included 45 minutes of aquatic therapy three times per week and a conventional physiotherapeutic treatment twice a week. Subjects in the control group (n = 16) received conventional physiotherapeutic treatment over a period of two weeks five times per week. The primary outcome variable was postural stability (Berg Balance Scale). Secondary outcome variables were functional reach, functional gait ability and basic functional mobility. Compared to the control group, significantly more subjects in the Halliwick-Therapy group (83.3% versus 46.7%) attained significant improvement of the Berg Balance Scale (P stroke patients in post-acute rehabilitation and has positive effects upon some aspects of mobility.

  8. STAT2 Knockout Syrian Hamsters Support Enhanced Replication and Pathogenicity of Human Adenovirus, Revealing an Important Role of Type I Interferon Response in Viral Control.

    Directory of Open Access Journals (Sweden)

    Karoly Toth

    2015-08-01

    Full Text Available Human adenoviruses have been studied extensively in cell culture and have been a model for studies in molecular, cellular, and medical biology. However, much less is known about adenovirus replication and pathogenesis in vivo in a permissive host because of the lack of an adequate animal model. Presently, the most frequently used permissive immunocompetent animal model for human adenovirus infection is the Syrian hamster. Species C human adenoviruses replicate in these animals and cause pathology that is similar to that seen with humans. Here, we report findings with a new Syrian hamster strain in which the STAT2 gene was functionally knocked out by site-specific gene targeting. Adenovirus-infected STAT2 knockout hamsters demonstrated an accentuated pathology compared to the wild-type control animals, and the virus load in the organs of STAT2 knockout animals was 100- to 1000-fold higher than that in wild-type hamsters. Notably, the adaptive immune response to adenovirus is not adversely affected in STAT2 knockout hamsters, and surviving hamsters cleared the infection by 7 to 10 days post challenge. We show that the Type I interferon pathway is disrupted in these hamsters, revealing the critical role of interferon-stimulated genes in controlling adenovirus infection. This is the first study to report findings with a genetically modified Syrian hamster infected with a virus. Further, this is the first study to show that the Type I interferon pathway plays a role in inhibiting human adenovirus replication in a permissive animal model. Besides providing an insight into adenovirus infection in humans, our results are also interesting from the perspective of the animal model: STAT2 knockout Syrian hamster may also be an important animal model for studying other viral infections, including Ebola-, hanta-, and dengue viruses, where Type I interferon-mediated innate immunity prevents wild type hamsters from being effectively infected to be used as

  9. Clinical infection control in gene therapy : A multidisciplinary conference

    NARCIS (Netherlands)

    Evans, ME; Jordan, CT; Chang, SMW; Conrad, C; Gerberding, JL; Kaufman, HL; Mayhall, CG; Nolta, JA; Pilaro, AM; Sullivan, S; Weber, DJ; Wivel, NA

    2000-01-01

    Gene therapy is being studied for the treatment of a variety of acquired and inherited disorders. Retroviruses, adenoviruses, poxviruses, adeno-associated viruses, herpesviruses, and others are being engineered to transfer genes into humans. Treatment protocols using recombinant viruses are being

  10. Oxygen tension level and human viral infections

    Energy Technology Data Exchange (ETDEWEB)

    Morinet, Frédéric, E-mail: frederic.morinet@sls.aphp.fr [Centre des Innovations Thérapeutiques en Oncologie et Hématologie (CITOH), CHU Saint-Louis, Paris (France); Université Denis Diderot, Sorbonne Paris Cité Paris, Paris (France); Casetti, Luana [Institut Cochin INSERM U1016, Paris (France); François, Jean-Hugues; Capron, Claude [Institut Cochin INSERM U1016, Paris (France); Laboratoire d' Hématologie, Hôpital Ambroise Paré, Boulogne (France); Université de Versailles Saint-Quentin en Yvelynes, Versailles (France); Pillet, Sylvie [Laboratoire de Bactériologie-Virologie-Hygiène, CHU de Saint-Etienne, Saint-Etienne (France); Université de Lyon et Université de Saint-Etienne, Jean Monnet, GIMAP EA3064, F-42023 Saint-Etienne, Lyon (France)

    2013-09-15

    The role of oxygen tension level is a well-known phenomenon that has been studied in oncology and radiotherapy since about 60 years. Oxygen tension may inhibit or stimulate propagation of viruses in vitro as well as in vivo. In turn modulating oxygen metabolism may constitute a novel approach to treat viral infections as an adjuvant therapy. The major transcription factor which regulates oxygen tension level is hypoxia-inducible factor-1 alpha (HIF-1α). Down-regulating the expression of HIF-1α is a possible method in the treatment of chronic viral infection such as human immunodeficiency virus infection, chronic hepatitis B and C viral infections and Kaposi sarcoma in addition to classic chemotherapy. The aim of this review is to supply an updating concerning the influence of oxygen tension level in human viral infections and to evoke possible new therapeutic strategies regarding this environmental condition. - Highlights: • Oxygen tension level regulates viral replication in vitro and possibly in vivo. • Hypoxia-inducible factor 1 (HIF-1α) is the principal factor involved in Oxygen tension level. • HIF-1α upregulates gene expression for example of HIV, JC and Kaposi sarcoma viruses. • In addition to classical chemotherapy inhibition of HIF-1α may constitute a new track to treat human viral infections.

  11. Occupational therapy for elderly : evidence mapping of randomised controlled trials from 2004-2012

    NARCIS (Netherlands)

    Voigt-Radloff, S; Ruf, G.; Vogel, A.; van Nes, F.; Hüll, M.

    OBJECTIVE: Previous systematic reviews on occupational therapy for elderly included studies until 2003. The present evidence mapping summarizes recent evidence for the efficacy of occupational therapy with older persons based on randomised controlled trials from 2004-2012. METHOD: An electronic

  12. Understanding Image Virality

    Science.gov (United States)

    2015-06-07

    Example non-viral images. Figure 1: Top: Images with high viral scores in our dataset depict internet “celebrity” memes ex. “Grumpy Cat”; Bottom: Images...of images that is most similar to ours is the concurrently introduced viral meme generator of Wang et al., that combines NLP and Computer Vision (low...doing any of our tasks. The test included questions about widely spread Reddit memes and jargon so that anyone familiar with Reddit can easily get a high

  13. Rumination-focused cognitive behaviour therapy vs. cognitive behaviour therapy for depression: study protocol for a randomised controlled superiority trial.

    Science.gov (United States)

    Hvenegaard, Morten; Watkins, Ed R; Poulsen, Stig; Rosenberg, Nicole K; Gondan, Matthias; Grafton, Ben; Austin, Stephen F; Howard, Henriette; Moeller, Stine B

    2015-08-11

    Cognitive behavioural therapy is an effective treatment for depression. However, one third of the patients do not respond satisfactorily, and relapse rates of around 30 % within the first post-treatment year were reported in a recent meta-analysis. In total, 30-50 % of remitted patients present with residual symptoms by the end of treatment. A common residual symptom is rumination, a process of recurrent negative thinking and dwelling on negative affect. Rumination has been demonstrated as a major factor in vulnerability to depression, predicting the onset, severity, and duration of future depression. Rumination-focused cognitive behavioural therapy is a psychotherapeutic treatment targeting rumination. Because rumination plays a major role in the initiation and maintenance of depression, targeting rumination with rumination-focused cognitive behavioural therapy may be more effective in treating depression and reducing relapse than standard cognitive behavioural therapy. This study is a two-arm pragmatic randomised controlled superiority trial comparing the effectiveness of group-based rumination-focused cognitive behaviour therapy with the effectiveness of group-based cognitive behavioural therapy for treatment of depression. One hundred twenty-eight patients with depression will be recruited from and given treatment in an outpatient service at a psychiatric hospital in Denmark. Our primary outcome will be severity of depressive symptoms (Hamilton Rating Scale for Depression) at completion of treatment. Secondary outcomes will be level of rumination, worry, anxiety, quality of life, behavioural activation, experimental measures of cognitive flexibility, and emotional attentional bias. A 6-month follow-up is planned and will include the primary outcome measure and assessment of relapse. The clinical outcome of this trial may guide clinicians to decide on the merits of including rumination-focused cognitive behavioural therapy in the treatment of depression in

  14. A Pilot Prospective Randomized Control Trial Comparing Exercises Using Videogame Therapy to Standard Physical Therapy: 6 Months Follow-Up.

    Science.gov (United States)

    Parry, Ingrid; Painting, Lynda; Bagley, Anita; Kawada, Jason; Molitor, Fred; Sen, Soman; Greenhalgh, David G; Palmieri, Tina L

    2015-01-01

    Commercially available, interactive videogames that use body movements for interaction are used clinically in burn rehabilitation and have been shown to facilitate functional range of motion (ROM) but their efficacy with burn patients has not yet been proven. The purpose of this pilot randomized control study was to prospectively compare planar and functional ROM, compliance, pain, enjoyment, and exertion in pediatric burn patients receiving two types of rehabilitation therapy. Seventeen school-aged children with 31 affected limbs who demonstrated limited shoulder ROM from burn injury were randomized to receive exercises using either standard therapy ROM activities (ST) or interactive videogame therapy (VGT). Patients received 3 weeks of the designated therapy intervention twice daily. They were then given a corresponding home program of the same type of therapy to perform regularly for 6 months. Standard goniometry and three-dimensional motion analysis during functional tasks were used to assess ROM. Measures were taken at baseline, 3 weeks, 3 months, and 6 months. Pain was measured before and after each treatment session during the 3-week intervention. There was no difference in compliance, enjoyment, or exertion between the groups. Patients in both the ST and VGT groups showed significant improvement in shoulder flexion (P videogames were equally effective as traditional therapy for overall ROM gains and resulted in quicker recovery of motion with less pain experienced. Such videogames are a useful adjunct to therapy and should be considered as part of a holistic approach to rehabilitation within the hospital and at home after discharge in pediatric patients recovering from burn injury.

  15. Cytomegalovirus viral load kinetics in patients with HIV/AIDS admitted to a medical intensive care unit: a case for pre-emptive therapy.

    Directory of Open Access Journals (Sweden)

    Simnikiwe H Mayaphi

    Full Text Available BACKGROUND: Cytomegalovirus (CMV infection is associated with severe diseases in immunosuppressed patients; however, there is a lack of data for pre-emptive therapy in patients with HIV/AIDS. METHOD: This was a retrospective study, which enrolled patients diagnosed with HIV/AIDS (CD41,000 copies/ml at baseline testing had significantly higher mortality compared to those who had 5,100 copies/ml and did not receive ganciclovir had 100% mortality compared to 58% mortality in those who received ganciclovir at VLs of >5,100 copies/ml, 50% mortality in those who were not treated and had low VLs of <5,100 copies/ml, and 44% mortality in those who had ganciclovir treatment at VLs of <5,100 copies/ml (p = 0.084, 0.046, 0.037, respectively. CONCLUSION: This study showed a significantly increased mortality in patients with HIV/AIDS who had high CMV VLs, and suggests that a threshold value of 1,000 copies/ml may be appropriate for pre-emptive treatment in this group.

  16. Aggression control therapy for violent forensic psychiatric patients: method and clinical practice.

    NARCIS (Netherlands)

    Hornsveld, R.H.J.; Nijman, H.L.I.; Hollin, C.R.; Kraaimaat, F.W.

    2008-01-01

    Aggression control therapy is based on Goldstein, Gibbs, and Glick's aggression replacement training and was developed for violent forensic psychiatric in- and outpatients (adolescents and adults) with a (oppositional-defiant) conduct disorder or an antisocial personality disorder. First, the

  17. Glucose Control: non-insulin therapies* 9.1: Drug Summary ...

    African Journals Online (AJOL)

    Glucose Control: non-insulin therapies in 2017 SEMDSA Guideline for the Management of Type 2 Diabetes. Guideline ... Weight neutral or causes modest weight loss (-1.2kg). No weight ..... Older patients with multiple comorbidities. • Patients ...

  18. Creative art therapy to enhance rehabilitation for stroke patients: a randomized controlled trial.

    Science.gov (United States)

    Kongkasuwan, Ratcharin; Voraakhom, Kotchakorn; Pisolayabutra, Prim; Maneechai, Pichai; Boonin, Jiraporn; Kuptniratsaikul, Vilai

    2016-10-01

    To examine the efficacy of creative art therapy plus conventional physical therapy, compared with physical therapy only, in increasing cognitive ability, physical functions, psychological status and quality of life of stroke patients. Randomized controlled trial with blinded assessor. An in-patient setting PARTICIPANTS: One hundred and eighteen stroke patients aged ⩾50 years who could communicate verbally. All participants received conventional physical therapy five days per week. An intervention group received additional creative art therapy, twice a week for four weeks, in a rehabilitation ward. Cognitive function, anxiety and depression, physical performance and quality of life were measured with the Abbreviated Mental Test, the Hospital Anxiety and Depression Scale, the modified Barthel Index scale and the pictorial Thai Quality of Life questionnaire, respectively. Mean differences for the intervention group were significantly greater than the control group for depression (-4.5, 95% CI -6.5, -2.5, part therapy and most reported improved concentration (68.5%), emotion (79.6%), self-confidence (72.2%) and motivation (74.1%). Creative art therapy combined with conventional physical therapy can significantly decrease depression, improve physical functions and increase quality of life compared with physical therapy alone. © The Author(s) 2015.

  19. Viral hemorrhagic septicemia

    Science.gov (United States)

    Batts, William N.; Winton, James R.

    2012-01-01

    Viral hemorrhagic septicemia (VHS) is one of the most important viral diseases of finfish worldwide. In the past, VHS was thought to affect mainly rainbow trout Oncorhynchus mykiss reared at freshwater facilities in Western Europe where it was known by various names including Egtved disease and infectious kidney swelling and liver degeneration (Wolf 1988). Today, VHS is known as an important source of mortality for cultured and wild fish in freshwater and marine environments in several regions of the northern hemisphere (Dixon 1999; Gagné et al. 2007; Kim and Faisal 2011; Lumsden et al. 2007; Marty et al. 1998, 2003; Meyers and Winton 1995; Skall et al. 2005b; Smail 1999; Takano et al. 2001). Viral hemorrhagic septicemia is caused by the fish rhabdovirus, viral hemorrhagic septicemia virus (VHSV), a member of the genus Novirhabdovirus of the family Rhabdoviridae

  20. Hepatitis viral aguda

    Directory of Open Access Journals (Sweden)

    Héctor Rubén Hernández Garcés

    1998-10-01

    Full Text Available Se realizó una revisión bibliográfica de las hepatitis virales agudas sobre aspectos vinculados a su etiología. Se tuvieron en cuenta además algunos datos epidemiológicos, las formas clínicas más importantes, los exámenes complementarios con especial énfasis en los marcadores virales y el diagnóstico positivoA bibliographical review of acute viral hepatitis was made taking into account those aspects connected with its etiology. Some epidemiological markers, the most important clinical forms, and the complementary examinations with special emphasis on the viral markers and the positive diagnosis were also considered

  1. Wastewater viral community

    Data.gov (United States)

    U.S. Environmental Protection Agency — The dataset contains the information used to generate the figures in the manuscript. The data describes the viral loss measured at all steps of sample processing,...

  2. Viral pathogenesis in diagrams

    National Research Council Canada - National Science Library

    Tremblay, Michel; Berthiaume, Laurent; Ackermann, Hans-Wolfgang

    2001-01-01

    .... The 268 diagrams in Viral Pathogenesis in Diagrams were selected from over 800 diagrams of English and French virological literature, including one derived from a famous drawing by Leonardo da Vinci...

  3. 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.

  4. Institute of Medicine's Report on Viral Hepatitis

    Centers for Disease Control (CDC) Podcasts

    2010-05-18

    In this podcast, Dr. John Ward, Director of CDC’s Division of Viral Hepatitis, discusses the 2010 report, Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C, from the Institute of Medicine.  Created: 5/18/2010 by National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP).   Date Released: 5/18/2010.

  5. Effects of Hydroxychloroquine on Immune Activation and Disease Progression Among HIV-Infected Patients Not Receiving Antiretroviral Therapy A Randomized Controlled Trial

    Science.gov (United States)

    Paton, Nicholas I.; Goodall, Ruth L.; Dunn, David T.; Franzen, Samuel; Collaco-Moraes, Yolanda; Gazzard, Brian G.; Williams, Ian G.; Fisher, Martin J.; Winston, Alan; Fox, Julie; Orkin, Chloe; Herieka, Elbushra A.; Ainsworth, Jonathan G.; Post, Frank A.; Wansbrough-Jones, Mark; Kelleher, Peter

    2013-01-01

    Context Therapies to decrease immune activation might be of benefit in slowing HIV disease progression. Objective To determine whether hydroxychloroquine decreases immune activation and slows CD4 cell decline. Design, Setting, and Patients Randomized, double-blind, placebo-controlled trial performed at 10 HIV outpatient clinics in the United Kingdom between June 2008 and February 2011. The 83 patients enrolled had asymptomatic HIV infection, were not taking antiretroviral therapy, and had CD4 cell counts greater than 400 cells/μL. Intervention Hydroxychloroquine, 400 mg, or matching placebo once daily for 48 weeks. Main Outcome Measures The primary outcome measure was change in the proportion of activated CD8 cells (measured by the expression of CD38 and HLA-DR surface markers), with CD4 cell count and HIV viral load as secondary outcomes. Analysis was by intention to treat using mixed linear models. Results There was no significant difference in CD8 cell activation between the 2 groups (−4.8% and −4.2% in the hydroxychloroquine and placebo groups, respectively, at week 48; difference, −0.6%; 95% CI, −4.8% to 3.6%; P=.80). Decline in CD4 cell count was greater in the hydroxychloroquine than placebo group (−85 cells/μL vs −23 cells/μL at week 48; difference, −62 cells/μL; 95% CI, −115 to −8; P=.03). Viral load increased in the hydroxychloroquine group compared with placebo (0.61 log10 copies/mL vs 0.23 log10 copies/mL at week 48; difference, 0.38 log10 copies/mL; 95% CI, 0.13 to 0.63; P=.003). Antiretroviral therapy was started in 9 patients in the hydroxychloroquine group and 1 in the placebo group. Trial medication was well tolerated, but more patients reported influenza-like illness in the hydroxychloroquine group compared with the placebo group (29% vs 10%; P=.03). Conclusion Among HIV-infected patients not taking antiretroviral therapy, the use of hydroxychloroquine compared with placebo did not reduce CD8 cell activation but did result in

  6. Metabolism goes viral.

    Science.gov (United States)

    Miyake-Stoner, Shigeki J; O'Shea, Clodagh C

    2014-04-01

    Viral and cellular oncogenes converge in targeting critical protein interaction networks to reprogram the cellular DNA and protein replication machinery for pathological replication. In this issue, Thai et al. (2014) show that adenovirus E4ORF1 activates MYC glycolytic targets to induce a Warburg-like effect that converts glucose into nucleotides for viral replication. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Neuroprotective effect of non-viral gene therapy treatment based on tetanus toxin C-fragment in a severe mouse model of Spinal Muscular Atrophy.

    Directory of Open Access Journals (Sweden)

    Sara Olivan Garcia

    2016-08-01

    Full Text Available Spinal muscular atrophy (SMA is a hereditary childhood disease that causes paralysis and progressive degeneration of skeletal muscles and spinal motor neurons. SMA is associated with reduced levels of full-length Survival of Motor Neuron (SMN protein, due to mutations in the Survival of Motor Neuron 1 gene. Nowadays there are no effective therapies available to treat patients with SMA, so our aim was to test whether the non-toxic carboxy-terminal fragment of tetanus toxin heavy chain (TTC, which exhibits neurotrophic properties, might have a therapeutic role or benefit in SMA. In this manuscript, we have demonstrated that TTC enhance the SMN expression in motor neurons in vitro and evaluated the effect of intramuscular injection of TTC-encoding plasmid in the spinal cord and the skeletal muscle of SMNdelta7 mice. For this purpose, we studied the weight and the survival time, as well as, the survival and cell death pathways and muscular atrophy. Our results showed that TTC treatment reduced the expression of autophagy markers (Becn1, Atg5, Lc3 and p62 and pro-apoptotic genes such as Bax and Casp3 in spinal cord. In skeletal muscle, TTC was able to downregulate the expression of the main marker of autophagy, Lc3, to wild type levels and the expression of the apoptosis effector protein, Casp3. Regarding the genes related to muscular atrophy (Ankrd1, Calm1, Col19a1, Fbox32, Mt2, Myod1, NogoA, Pax7, Rrad, and Sln, TTC suggest a compensatory effect for muscle damage response, diminished oxidative stress and modulated calcium homeostasis. These preliminary findings suggest the need for further experiments to depth study the effect of TTC in SMA disease.

  8. Procalcitonin guided antibiotic therapy and hospitalization in patients with lower respiratory tract infections: a prospective, multicenter, randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Henzen Christoph

    2007-07-01

    Full Text Available Abstract Background: Lower respiratory tract infections like acute bronchitis, exacerbated chronic obstructive pulmonary disease and community-acquired pneumonia are often unnecessarily treated with antibiotics, mainly because of physicians' difficulties to distinguish viral from bacterial cause and to estimate disease-severity. The goal of this trial is to compare medical outcomes, use of antibiotics and hospital resources in a strategy based on enforced evidence-based guidelines versus procalcitonin guided antibiotic therapy in patients with lower respiratory tract infections. Methods and design: We describe a prospective randomized controlled non-inferiority trial with an open intervention. We aim to randomize over a fixed recruitment period of 18 months a minimal number of 1002 patients from 6 hospitals in Switzerland. Patients must be >18 years of age with a lower respiratory tract infections Discussion: Use of and prolonged exposure to antibiotics in lower respiratory tract infections is high. The proposed trial investigates whether procalcitonin-guidance may safely reduce antibiotic consumption along with reductions in hospitalization costs and antibiotic resistance. It will additionally generate insights for improved prognostic assessment of patients with lower respiratory tract infections. Trial registration: ISRCTN95122877

  9. Intensive Versus Distributed Aphasia Therapy: A Nonrandomized, Parallel-Group, Dosage-Controlled Study.

    Science.gov (United States)

    Dignam, Jade; Copland, David; McKinnon, Eril; Burfein, Penni; O'Brien, Kate; Farrell, Anna; Rodriguez, Amy D

    2015-08-01

    Most studies comparing different levels of aphasia treatment intensity have not controlled the dosage of therapy provided. Consequently, the true effect of treatment intensity in aphasia rehabilitation remains unknown. Aphasia Language Impairment and Functioning Therapy is an intensive, comprehensive aphasia program. We investigated the efficacy of a dosage-controlled trial of Aphasia Language Impairment and Functioning Therapy, when delivered in an intensive versus distributed therapy schedule, on communication outcomes in participants with chronic aphasia. Thirty-four adults with chronic, poststroke aphasia were recruited to participate in an intensive (n=16; 16 hours per week; 3 weeks) versus distributed (n=18; 6 hours per week; 8 weeks) therapy program. Treatment included 48 hours of impairment, functional, computer, and group-based aphasia therapy. Distributed therapy resulted in significantly greater improvements on the Boston Naming Test when compared with intensive therapy immediately post therapy (P=0.04) and at 1-month follow-up (P=0.002). We found comparable gains on measures of participants' communicative effectiveness, communication confidence, and communication-related quality of life for the intensive and distributed treatment conditions at post-therapy and 1-month follow-up. Aphasia Language Impairment and Functioning Therapy resulted in superior clinical outcomes on measures of language impairment when delivered in a distributed versus intensive schedule. The therapy progam had a positive effect on participants' functional communication and communication-related quality of life, regardless of treatment intensity. These findings contribute to our understanding of the effect of treatment intensity in aphasia rehabilitation and have important clinical implications for service delivery models. © 2015 American Heart Association, Inc.

  10. Role of complement and antibodies in controlling infection with pathogenic simian immunodeficiency virus (SIV in macaques vaccinated with replication-deficient viral vectors

    Directory of Open Access Journals (Sweden)

    Strasak Alexander

    2009-06-01

    Full Text Available Abstract Background We investigated the interplay between complement and antibodies upon priming with single-cycle replicating viral vectors (SCIV encoding SIV antigens combined with Adeno5-SIV or SCIV pseudotyped with murine leukemia virus envelope boosting strategies. The vaccine was applied via spray-immunization to the tonsils of rhesus macaques and compared with systemic regimens. Results Independent of the application regimen or route, viral loads were significantly reduced after challenge with SIVmac239 (p Conclusion The heterologous prime-boost strategy with replication-deficient viral vectors administered exclusively via the tonsils did not induce any neutralizing antibodies before challenge. However, after challenge, comparable SIV-specific humoral immune responses were observed in all vaccinated animals. Immunization with single cycle immunodeficiency viruses mounts humoral immune responses comparable to live-attenuated immunodeficiency virus vaccines.

  11. The effects of ear acupressure, massage therapy and no therapy on symptoms of dementia: a randomized controlled trial.

    Science.gov (United States)

    Rodríguez-Mansilla, Juan; González López-Arza, María Victoria; Varela-Donoso, Enrique; Montanero-Fernández, Jesús; González Sánchez, Blanca; Garrido-Ardila, Elisa María

    2015-07-01

    To assess the effectiveness of ear acupressure and massage vs. control in the improvement of pain, anxiety and depression in persons diagnosed with dementia. A pilot randomized controlled trial. Residential homes in Extremadura (Spain). A total of 120 elders with dementia institutionalized in residential homes. The participants were randomly allocated, in three groups. Control group - they continued with their routine activities; ear acupressure intervention group - they received ear acupressure treatment (pressure was applied to acupressure points on the ear); and massage therapy intervention group - they received relaxing massage therapy. The variables pain, anxiety and depression were assessed with the Doloplus2, Cornell and Campbell scales. The study was carried out during five months; three months of experimental treatment and two months with no treatment. The assessments were done at baseline, each month during the treatment and at one and two months of follow-up. In the statistical analysis the three groups were compared with each other. A total of 111 participants completed the study. Their aged ranged from 67 to 91 years old and 86 of them (77.4%) were women. The ear acupressure intervention group showed better improvements than the massage therapy intervention group in relation to pain and depression during the treatment period and at one month of follow-up. The best improvement in pain was achieved in the last (3rd) month of ear acupressure treatment (p  massage therapy showed better results than the control group in relation to pain, anxiety and depression. However, ear acupressure achieved more improvements. © The Author(s) 2014.

  12. Bio-Inspired Interaction Control of Robotic Machines for Motor Therapy

    OpenAIRE

    Zollo, Loredana; Formica, Domenico; Guglielmelli, Eugenio

    2007-01-01

    In this chapter basic criteria for the design and implementation of interaction control of robotic machines for motor therapy have been briefly introduced and two bio-inspired compliance control laws developed by the authors to address requirements coming from this specific application field have been presented. The two control laws are named the coactivation-based compliance control in the joint space and the torque-dependent compliance control in the joint space, respectively. They try to o...

  13. Manual therapy compared with physical therapy in patients with non-specific neck pain: a randomized controlled trial.

    Science.gov (United States)

    Groeneweg, Ruud; van Assen, Luite; Kropman, Hans; Leopold, Huco; Mulder, Jan; Smits-Engelsman, Bouwien C M; Ostelo, Raymond W J G; Oostendorp, Rob A B; van Tulder, Maurits W

    2017-01-01

    Manual therapy according to the School of Manual Therapy Utrecht (MTU) is a specific type of passive manual joint mobilization. MTU has not yet been systematically compared to other manual therapies and physical therapy. In this study the effectiveness of MTU is compared to physical therapy, particularly active exercise therapy (PT) in patients with non-specific neck pain. Patients neck pain, aged between 18-70 years, were included in a pragmatic randomized controlled trial with a one-year follow-up. Primary outcome measures were global perceived effect and functioning (Neck Disability Index), the secondary outcome was pain intensity (Numeric Rating Scale for Pain). Outcomes were measured at 3, 7, 13, 26 and 52 weeks. Multilevel analyses (intention-to-treat) were the primary analyses for overall between-group differences. Additional to the primary and secondary outcomes the number of treatment sessions of the MTU group and PT group was analyzed. Data were collected from September 2008 to February 2011. A total of 181 patients were included. Multilevel analyses showed no statistically significant overall differences at one year between the MTU and PT groups on any of the primary and secondary outcomes. The MTU group showed significantly lower treatment sessions compared to the PT group (respectively 3.1 vs. 5.9 after 7 weeks; 6.1 vs. 10.0 after 52 weeks). Patients with neck pain improved in both groups without statistical significantly or clinically relevant differences between the MTU and PT groups during one-year follow-up. ClinicalTrials.gov Identifier: NCT00713843.

  14. Inpatient Massage Therapy Versus Music Therapy Versus Usual Care: A Mixed-methods Feasibility Randomized Controlled Trial.

    Science.gov (United States)

    Roseen, Eric J; Cornelio-Flores, Oscar; Lemaster, Chelsey; Hernandez, Maria; Fong, Calvin; Resnick, Kirsten; Wardle, Jon; Hanser, Suzanne; Saper, Robert

    2017-01-01

    Little is known about the feasibility of providing massage or music therapy to medical inpatients at urban safety-net hospitals or the impact these treatments may have on patient experience. To determine the feasibility of providing massage and music therapy to medical inpatients and to assess the impact of these interventions on patient experience. Single-center 3-arm feasibility randomized controlled trial. Urban academic safety-net hospital. Adult inpatients on the Family Medicine ward. Massage therapy consisted of a standardized protocol adapted from a previous perioperative study. Music therapy involved a preference assessment, personalized compact disc, music-facilitated coping, singing/playing music, and/or songwriting. Credentialed therapists provided the interventions. Patient experience was measured with the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) within 7 days of discharge. We compared the proportion of patients in each study arm reporting "top box" scores for the following a priori HCAHPS domains: pain management, recommendation of hospital, and overall hospital rating. Responses to additional open-ended postdischarge questions were transcribed, coded independently, and analyzed for common themes. From July to December 2014, 90 medical inpatients were enrolled; postdischarge data were collected on 68 (76%) medical inpatients. Participants were 70% females, 43% non-Hispanic black, and 23% Hispanic. No differences between groups were observed on HCAHPS. The qualitative analysis found that massage and music therapy were associated with improved overall hospital experience, pain management, and connectedness to the massage or music therapist. Providing music and massage therapy in an urban safety-net inpatient setting was feasible. There was no quantitative impact on HCAHPS. Qualitative findings suggest benefits related to an improved hospital experience, pain management, and connectedness to the massage or music therapist.

  15. Inpatient Massage Therapy Versus Music Therapy Versus Usual Care: A Mixed-methods Feasibility Randomized Controlled Trial

    Science.gov (United States)

    Cornelio-Flores, Oscar; Lemaster, Chelsey; Hernandez, Maria; Fong, Calvin; Resnick, Kirsten; Wardle, Jon; Hanser, Suzanne; Saper, Robert

    2017-01-01

    Background Little is known about the feasibility of providing massage or music therapy to medical inpatients at urban safety-net hospitals or the impact these treatments may have on patient experience. Objective To determine the feasibility of providing massage and music therapy to medical inpatients and to assess the impact of these interventions on patient experience. Design Single-center 3-arm feasibility randomized controlled trial. Setting Urban academic safety-net hospital. Patients Adult inpatients on the Family Medicine ward. Interventions Massage therapy consisted of a standardized protocol adapted from a previous perioperative study. Music therapy involved a preference assessment, personalized compact disc, music-facilitated coping, singing/playing music, and/or songwriting. Credentialed therapists provided the interventions. Measurements Patient experience was measured with the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) within 7 days of discharge. We compared the proportion of patients in each study arm reporting “top box” scores for the following a priori HCAHPS domains: pain management, recommendation of hospital, and overall hospital rating. Responses to additional open-ended postdischarge questions were transcribed, coded independently, and analyzed for common themes. Results From July to December 2014, 90 medical inpatients were enrolled; postdischarge data were collected on 68 (76%) medical inpatients. Participants were 70% females, 43% non-Hispanic black, and 23% Hispanic. No differences between groups were observed on HCAHPS. The qualitative analysis found that massage and music therapy were associated with improved overall hospital experience, pain management, and connectedness to the massage or music therapist. Conclusions Providing music and massage therapy in an urban safety-net inpatient setting was feasible. There was no quantitative impact on HCAHPS. Qualitative findings suggest benefits related to an

  16. [Control of blood pressure in hypertensive patients on combination therapy].

    Science.gov (United States)

    de la Sierra, Alejandro; Oliveras, Anna; Armario, Pedro; Lucas, Silvia

    2015-02-20

    The impact of antihypertensive treatment on blood pressure (BP) control is fairly unknown. The aim of the study was to evaluate the degree of BP control and its relationship with treatment-related factors in hypertensive patients treated with 2 or 3 agents and attended in referral units. We studied 1,337 hypertensive subjects (41% women) with a mean age (SD) of 63 (12) years, who were receiving 2 or 3 antihypertensive drugs. The degree of BP control was estimated in a single visit by the proportion of patients with BP below 140/90mmHg. BP was controlled in 767 patients (57%). Lack of BP control was related to older age (12% risk for each 10-year increase) and the presence of microalbuminuria (64% risk increase). In those treated with 2 agents, BP control was 61%, without differences between those treated with fixed-drug or free combinations. BP control in those treated with 3 agents was 55%, higher in those receiving 3 agents in a fixed-drug combination (68%) compared with those on 3 agents administered separately (52%; P=.025). Drug classes used in combinations did not influence the degree of BP control. The degree of BP control in patients treated with 2 or 3 agents is 57%. Microalbuminuria is related to a lack of BP control. In those receiving 3 agents, the use of fixed-drug combinations is associated with better BP control. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  17. Junk DNA enhances pEI-based non-viral gene delivery

    NARCIS (Netherlands)

    Gaal, E.V.B. van; Oosting, R.S.; Hennink, W.E.; Crommelin, D.J.A.; Mastrobattista, E.

    Gene therapy aims at delivering exogenous DNA into the nuclei of target cells to establish expression of a therapeutic protein. Non-viral gene delivery is examined as a safer alternative to viral approaches, but is presently characterized by a low efficiency. In the past years several non-viral

  18. 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

  19. 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....

  20. Randomized Controlled Trials in Music Therapy: Guidelines for Design and Implementation.

    Science.gov (United States)

    Bradt, Joke

    2012-01-01

    Evidence from randomized controlled trials (RCTs) plays a powerful role in today's healthcare industry. At the same time, it is important that multiple types of evidence contribute to music therapy's knowledge base and that the dialogue of clinical effectiveness in music therapy is not dominated by the biomedical hierarchical model of evidence-based practice. Whether or not one agrees with the hierarchical model of evidence in the current healthcare climate, RCTs can contribute important knowledge to our field. Therefore, it is important that music therapists are prepared to design trials that meet current methodological standards and, equally important, are able to respond appropriately to those design aspects that may not be feasible in music therapy research. To provide practical guidelines to music therapy researchers for the design and implementation of RCTs as well as to enable music therapists to be well-informed consumers of RCT evidence. This article reviews key design aspects of RCTs and discusses how to best implement these standards in music therapy trials. A systematic presentation of basic randomization methods, allocation concealment strategies, issues related to blinding in music therapy trials and strategies for implementation, the use of treatment manuals, types of control groups, outcome selection, and sample size computation is provided. Despite the challenges of meeting all key design demands typical of an RCT, it is possible to design rigorous music therapy RCTs that accurately estimate music therapy treatment benefits.

  1. Initiating Antiretroviral Therapy for HIV at a Patient's First Clinic Visit: The RapIT Randomized Controlled Trial.

    Directory of Open Access Journals (Sweden)

    Sydney Rosen

    2016-05-01

    Full Text Available High rates of patient attrition from care between HIV testing and antiretroviral therapy (ART initiation have been documented in sub-Saharan Africa, contributing to persistently low CD4 cell counts at treatment initiation. One reason for this is that starting ART in many countries is a lengthy and burdensome process, imposing long waits and multiple clinic visits on patients. We estimated the effect on uptake of ART and viral suppression of an accelerated initiation algorithm that allowed treatment-eligible patients to be dispensed their first supply of antiretroviral medications on the day of their first HIV-related clinic visit.RapIT (Rapid Initiation of Treatment was an unblinded randomized controlled trial of single-visit ART initiation in two public sector clinics in South Africa, a primary health clinic (PHC and a hospital-based HIV clinic. Adult (≥18 y old, non-pregnant patients receiving a positive HIV test or first treatment-eligible CD4 count were randomized to standard or rapid initiation. Patients in the rapid-initiation arm of the study ("rapid arm" received a point-of-care (POC CD4 count if needed; those who were ART-eligible received a POC tuberculosis (TB test if symptomatic, POC blood tests, physical exam, education, counseling, and antiretroviral (ARV dispensing. Patients in the standard-initiation arm of the study ("standard arm" followed standard clinic procedures (three to five additional clinic visits over 2-4 wk prior to ARV dispensing. Follow up was by record review only. The primary outcome was viral suppression, defined as initiated, retained in care, and suppressed (≤400 copies/ml within 10 mo of study enrollment. Secondary outcomes included initiation of ART ≤90 d of study enrollment, retention in care, time to ART initiation, patient-level predictors of primary outcomes, prevalence of TB symptoms, and the feasibility and acceptability of the intervention. A survival analysis was conducted comparing attrition

  2. Gaze-Contingent Music Reward Therapy for Social Anxiety Disorder: A Randomized Controlled Trial.

    Science.gov (United States)

    Lazarov, Amit; Pine, Daniel S; Bar-Haim, Yair

    2017-07-01

    Patients with social anxiety disorder exhibit increased attentional dwelling on social threats, providing a viable target for therapeutics. This randomized controlled trial examined the efficacy of a novel gaze-contingent music reward therapy for social anxiety disorder designed to reduce attention dwelling on threats. Forty patients with social anxiety disorder were randomly assigned to eight sessions of either gaze-contingent music reward therapy, designed to divert patients' gaze toward neutral stimuli rather than threat stimuli, or to a control condition. Clinician and self-report measures of social anxiety were acquired pretreatment, posttreatment, and at 3-month follow-up. Dwell time on socially threatening faces was assessed during the training sessions and at pre- and posttreatment. Gaze-contingent music reward therapy yielded greater reductions of symptoms of social anxiety disorder than the control condition on both clinician-rated and self-reported measures. Therapeutic effects were maintained at follow-up. Gaze-contingent music reward therapy, but not the control condition, also reduced dwell time on threat, which partially mediated clinical effects. Finally, gaze-contingent music reward therapy, but not the control condition, also altered dwell time on socially threatening faces not used in training, reflecting near-transfer training generalization. This is the first randomized controlled trial to examine a gaze-contingent intervention in social anxiety disorder. The results demonstrate target engagement and clinical effects. This study sets the stage for larger randomized controlled trials and testing in other emotional disorders.

  3. Evaluation of Viral Meningoencephalitis Cases

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    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

  4. Peg-interferon plus nucleotide analogue treatment versus no treatment in patients with chronic hepatitis B with a low viral load: a randomised controlled, open-label trial

    NARCIS (Netherlands)

    de Niet, Annikki; Jansen, Louis; Stelma, Femke; Willemse, Sophie B.; Kuiken, Sjoerd D.; Weijer, Sebastiaan; van Nieuwkerk, Carin M. J.; Zaaijer, Hans L.; Molenkamp, Richard; Takkenberg, R. Bart; Koot, Maarten; Verheij, Joanne; Beuers, Ulrich; Reesink, Hendrik W.

    2017-01-01

    Antiviral treatment is currently not recommended for patients with chronic hepatitis B with a low viral load. However, they might benefit from acquiring a functional cure (hepatitis B surface antigen [HBsAg] loss with or without formation of antibodies against hepatitis B surface antigen

  5. Quantitative evaluation of infection control models in the prevention of nosocomial transmission of SARS virus to healthcare workers: implication to nosocomial viral infection control for healthcare workers.

    Science.gov (United States)

    Yen, Muh-Yong; Lu, Yun-Ching; Huang, Pi-Hsiang; Chen, Chen-Ming; Chen, Yee-Chun; Lin, Yusen E

    2010-07-01

    Healthcare workers (HCWs) are at high risk of acquiring emerging infections while caring for patients, as has been shown in the recent SARS and swine flu epidemics. Using SARS as an example, we determined the effectiveness of infection control measures (ICMs) by logistic regression and structural equation modelling (SEM), a quantitative methodology that can test a hypothetical model and validates causal relationships among ICMs. Logistic regression showed that installing hand wash stations in the emergency room (p = 0.012, odds ratio = 1.07) was the only ICM significantly associated with the protection of HCWs from acquiring the SARS virus. The structural equation modelling results showed that the most important contributing factor (highest proportion of effectiveness) was installation of a fever screening station outside the emergency department (51%). Other measures included traffic control in the emergency department (19%), availability of an outbreak standard operation protocol (12%), mandatory temperature screening (9%), establishing a hand washing setup at each hospital checkpoint (3%), adding simplified isolation rooms (3%), and a standardized patient transfer protocol (3%). Installation of fever screening stations outside of the hospital and implementing traffic control in the emergency department contributed to 70% of the effectiveness in the prevention of SARS transmission. Our approach can be applied to the evaluation of control measures for other epidemic infectious diseases, including swine flu and avian flu.

  6. Efficacy of Cognitive Behavioral Therapy for Insomnia in Adolescents: A Randomized Controlled Trial with Internet Therapy, Group Therapy and A Waiting List Condition.

    Science.gov (United States)

    de Bruin, Eduard J; Bögels, Susan M; Oort, Frans J; Meijer, Anne Marie

    2015-12-01

    To investigate the efficacy of cognitive behavioral therapy for insomnia (CBTI) in adolescents. A randomized controlled trial of CBTI in group therapy (GT), guided internet therapy (IT), and a waiting list (WL), with assessments at baseline, directly after treatment (post-test), and at 2 months follow-up. Diagnostic interviews were held at the laboratory of the Research Institute of Child Development and Education at the University of Amsterdam. Treatment for GT occurred at the mental health care center UvAMinds in Amsterdam, the Netherlands. One hundred sixteen adolescents (mean age = 15.6 y, SD = 1.6 y, 25% males) meeting DSM-IV criteria for insomnia, were randomized to IT, GT, or WL. CBTI of 6 weekly sessions, consisted of psychoeducation, sleep hygiene, restriction of time in bed, stimulus control, cognitive therapy, and relaxation techniques. GT was conducted in groups of 6 to 8 adolescents, guided by 2 trained sleep therapists. IT was applied through an online guided self-help website with programmed instructions and written feedback from a trained sleep therapist. Sleep was measured with actigraphy and sleep logs for 7 consecutive days. Symptoms of insomnia and chronic sleep reduction were measured with questionnaires. Results showed that adolescents in both IT and GT, compared to WL, improved significantly on sleep efficiency, sleep onset latency, wake after sleep onset, and total sleep time at post-test, and improvements were maintained at follow-up. Most of these improvements were found in both objective and subjective measures. Furthermore, insomnia complaints and symptoms of chronic sleep reduction also decreased significantly in both treatment conditions compared to WL. Effect sizes for improvements ranged from medium to large. A greater proportion of participants from the treatment conditions showed high end-state functioning and clinically significant improvement after treatment and at follow-up compared to WL. This study is the first randomized

  7. Human T-cell leukemia virus type 2 post-transcriptional control protein p28 is required for viral infectivity and persistence in vivo.

    Science.gov (United States)

    Yamamoto, Brenda; Li, Min; Kesic, Matthew; Younis, Ihab; Lairmore, Michael D; Green, Patrick L

    2008-05-12

    Human T-cell leukemia virus (HTLV) type 1 and type 2 are related but distinct pathogenic complex retroviruses. HTLV-1 is associated with adult T-cell leukemia and a variety of immune-mediated disorders including the chronic neurological disease termed HTLV-1-associated myelopathy/tropical spastic paraparesis. In contrast, HTLV-2 displays distinct biological differences and is much less pathogenic, with only a few reported cases of leukemia and neurological disease associated with infection. In addition to the structural and enzymatic proteins, HTLV encodes regulatory (Tax and Rex) and accessory proteins. Tax and Rex positively regulate virus production and are critical for efficient viral replication and pathogenesis. Using an over-expression system approach, we recently reported that the accessory gene product of the HTLV-1 and HTLV-2 open reading frame (ORF) II (p30 and p28, respectively) acts as a negative regulator of both Tax and Rex by binding to and retaining their mRNA in the nucleus, leading to reduced protein expression and virion production. Further characterization revealed that p28 was distinct from p30 in that it was devoid of major transcriptional modulating activity, suggesting potentially divergent functions that may be responsible for the distinct pathobiologies of HTLV-1 and HTLV-2. In this study, we investigated the functional significance of p28 in HTLV-2 infection, proliferation, and immortaliztion of primary T-cells in culture, and viral survival in an infectious rabbit animal model. An HTLV-2 p28 knockout virus (HTLV-2Deltap28) was generated and evaluated. Infectivity and immortalization capacity of HTLV-2Deltap28 in vitro was indistinguishable from wild type HTLV-2. In contrast, we showed that viral replication was severely attenuated in rabbits inoculated with HTLV-2Deltap28 and the mutant virus failed to establish persistent infection. We provide direct evidence that p28 is dispensable for viral replication and cellular immortalization of

  8. Human T-cell leukemia virus type 2 post-transcriptional control protein p28 is required for viral infectivity and persistence in vivo

    Directory of Open Access Journals (Sweden)

    Kesic Matthew

    2008-05-01

    Full Text Available Abstract Background Human T-cell leukemia virus (HTLV type 1 and type 2 are related but distinct pathogenic complex retroviruses. HTLV-1 is associated with adult T-cell leukemia and a variety of immune-mediated disorders including the chronic neurological disease termed HTLV-1-associated myelopathy/tropical spastic paraparesis. In contrast, HTLV-2 displays distinct biological differences and is much less pathogenic, with only a few reported cases of leukemia and neurological disease associated with infection. In addition to the structural and enzymatic proteins, HTLV encodes regulatory (Tax and Rex and accessory proteins. Tax and Rex positively regulate virus production and are critical for efficient viral replication and pathogenesis. Using an over-expression system approach, we recently reported that the accessory gene product of the HTLV-1 and HTLV-2 open reading frame (ORF II (p30 and p28, respectively acts as a negative regulator of both Tax and Rex by binding to and retaining their mRNA in the nucleus, leading to reduced protein expression and virion production. Further characterization revealed that p28 was distinct from p30 in that it was devoid of major transcriptional modulating activity, suggesting potentially divergent functions that may be responsible for the distinct pathobiologies of HTLV-1 and HTLV-2. Results In this study, we investigated the functional significance of p28 in HTLV-2 infection, proliferation, and immortaliztion of primary T-cells in culture, and viral survival in an infectious rabbit animal model. An HTLV-2 p28 knockout virus (HTLV-2Δp28 was generated and evaluated. Infectivity and immortalization capacity of HTLV-2Δp28 in vitro was indistinguishable from wild type HTLV-2. In contrast, we showed that viral replication was severely attenuated in rabbits inoculated with HTLV-2Δp28 and the mutant virus failed to establish persistent infection. Conclusion We provide direct evidence that p28 is dispensable for

  9. Trauma management therapy with virtual-reality augmented exposure therapy for combat-related PTSD: A randomized controlled trial.

    Science.gov (United States)

    Beidel, Deborah C; Frueh, B Christopher; Neer, Sandra M; Bowers, Clint A; Trachik, Benjamin; Uhde, Thomas W; Grubaugh, Anouk

    2017-08-23

    Virtual reality exposure therapy (VRET) realistically incorporates traumatic cues into exposure therapy and holds promise in the treatment of combat-related posttraumatic stress disorder (PTSD). In a randomized controlled trial of 92 Iraq and Afghanistan veterans and active duty military personnel with combat-related PTSD, we compared the efficacy of Trauma Management Therapy (TMT; VRET plus a group treatment for anger, depression, and social isolation) to VRET plus a psychoeducation control condition. Efficacy was evaluated at mid- and post-treatment, and at 3- and 6-month follow-up. Consistent with our hypothesis, VRET resulted in significant decreases on the Clinician Administered PTSD Scale and the PTSD Checklist-Military version for both groups. Also consistent with our hypothesis, significant decreases in social isolation occurred only for those participants who received the TMT group component. There were significant decreases for depression and anger for both groups, although these occurred after VRET and before group treatment. All treatment gains were maintained six-months later. Although not part of the original hypotheses, sleep was not improved by either intervention and remained problematic. The results support the use of VRET as an efficacious treatment for combat-related PTSD, but suggest that VRET alone does not result in optimal treatment outcomes across domains associated with PTSD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Design and construction of stepper motor controller for brachy-therapy equipment

    International Nuclear Information System (INIS)

    Ahmad Rifai; Usep Setia Gunawan; Indarzah Masbatin Putra

    2011-01-01

    Based on a microcontroller, a stepper motor controller for brachy-therapy equipment has been designed and prototyped. The embedded control program routine and its other associated routines enable the microcontroller to generate required pulses via external commands for stepper motor based position control. The controller receives ASCII text command via a serial port. The constructed algorithm implements the widely used method that allows motor to rotate in three phases, i.e: acceleration, constant speed, and deceleration. (author)

  11. View and review on viral oncology research

    Directory of Open Access Journals (Sweden)

    Parolin Cristina

    2010-05-01

    Full Text Available Abstract To date, almost one and a half million cases of cancer are diagnosed every year in the US and nearly 560,000 Americans are expected to die of cancer in the current year, more than 1,500 people a day (data from the American Cancer Society at http://www.cancer.org/. According to the World Health Organization (WHO, roughly 20% of all cancers worldwide results from chronic infections; in particular, up to 15% of human cancers is characterized by a viral aetiology with higher incidence in Developing Countries. The link between viruses and cancer was one of the pivotal discoveries in cancer research during the past Century. Indeed, the infectious nature of specific tumors has important implications in terms of their prevention, diagnosis, and therapy. In the 21st Century, the research on viral oncology field continues to be vigorous, with new significant and original studies on viral oncogenesis and translational research from basic virology to treatment of cancer. This review will cover different viral oncology aspects, starting from the history of viral oncology and moving to the peculiar features of oncogenic RNA and DNA viruses, with a special focus on human pathogens.

  12. Monitoring of HIV viral load, CD4 cell count, and clinical assessment versus clinical monitoring alone for antiretroviral therapy in low-resource settings (Stratall ANRS 12110/ESTHER) : a cost-effectiveness analysis

    OpenAIRE

    Boyer, S.; March, L.; Kouanfack, C.; Laborde-Balen, G.; Marino, P.; Aghokeng Fobang, Avelin; Mpoudi-Ngole, E.; Koulla-Shiro, S.; Delaporte, Eric; Carrieri, M. P.; Spire, B.; Laurent, Christian; Moatti, Jean-Paul

    2013-01-01

    Background In low-income countries, the use of laboratory monitoring of patients taking antiretroviral therapy (ART) remains controversial in view of persistent resource constraints. The Stratall trial did not show that clinical monitoring alone was non-inferior to laboratory and clinical monitoring in terms of immunological recovery. We aimed to evaluate the costs and cost-effectiveness of the ART monitoring approaches assessed in the Stratall trial. Methods The randomised, controlled, non-i...

  13. Comparing systemic therapy and cognitive behavioral therapy for social anxiety disorders: study protocol for a randomized controlled pilot trial.

    Science.gov (United States)

    Hunger, Christina; Hilzinger, Rebecca; Koch, Theresa; Mander, Johannes; Sander, Anja; Bents, Hinrich; Schweitzer, Jochen

    2016-03-31

    Social anxiety disorders are among the most prevalent anxiety disorders in the general population. The efficacy of cognitive behavioral therapy (CBT) for social anxiety disorders is well demonstrated. However, only three studies point to the efficacy of systemic therapy (ST) in anxiety disorders, and only two of them especially focus on social anxiety disorders. These ST studies either do not use a good comparator but minimal supportive therapy, they do not use a multi-person ST but a combined therapy, or they do not especially focus on social anxiety disorders but mood and anxiety disorders in general. Though ST was approved as evidence based in Germany for a variety of disorders in 2008, evidence did not include anxiety disorders. This is the first pilot study that will investigate multi-person ST, integrating a broad range of systemic methods, specifically for social anxiety disorders and that will compare ST to the "gold standard" CBT. This article describes the rationale and protocol of a prospective, open, interventive, balanced, bi-centric, pilot randomized controlled trial (RCT). A total of 32 patients with a primary SCID diagnosis of social anxiety disorder will be randomized to either CBT or ST. Both treatments will be manualized. The primary outcome will include social anxiety symptoms at the end of therapy. Therapy will be restricted to no more than 26 hours (primary endpoint). Secondary outcomes will include psychological, social systems and interpersonal functioning, symptom adjustment, and caregiver burden, in addition to change measures, therapist variables and treatment adherence. At the secondary endpoints, 9 and 12 months after the beginning of therapy, we will again assess all outcomes. The study is expected to pilot test a RCT which will be the first to directly compare CBT and multi-person ST, integrating a broad range of systemic methods, for social anxiety disorders, and it will provide empirical evidence for the calculation of the number of

  14. Increased protein-energy intake promotes anabolism in critically ill infants with viral bronchiolitis: a double‑blind randomised controlled trial

    Science.gov (United States)

    de Betue, Carlijn T; van Waardenburg, Dick A; Deutz, Nicolaas E; van Eijk, Hans M; van Goudoever, Johannes B; Luiking, Yvette C; Zimmermann, Luc J; Joosten, Koen F

    2011-01-01

    Objective The preservation of nutritional status and growth is an important aim in critically ill infants, but difficult to achieve due to the metabolic stress response and inadequate nutritional intake, leading to negative protein balance. This study investigated whether increasing protein and energy intakes can promote anabolism. The primary outcome was whole body protein balance, and the secondary outcome was first pass splanchnic phenylalanine extraction (SPEPhe). Design This was a double-blind randomised controlled trial. Infants (n=18) admitted to the paediatric intensive care unit with respiratory failure due to viral bronchiolitis were randomised to continuous enteral feeding with protein and energy enriched formula (PE-formula) (n=8; 3.1±0.3 g protein/kg/24 h, 119±25 kcal/kg/24 h) or standard formula (S-formula) (n=10; 1.7±0.2 g protein/kg/24 h, 84±15 kcal/kg/24 h; equivalent to recommended intakes for healthy infants <6 months). A combined intravenous-enteral phenylalanine stable isotope protocol was used on day 5 after admission to determine whole body protein metabolism and SPEPhe. Results Protein balance was significantly higher with PE-formula than with S-formula (PE-formula: 0.73±0.5 vs S-formula: 0.02±0.6 g/kg/24 h) resulting from significantly increased protein synthesis (PE-formula: 9.6±4.4, S-formula: 5.2±2.3 g/kg/24 h), despite significantly increased protein breakdown (PE-formula: 8.9±4.3, S-formula: 5.2±2.6 g/kg/24 h). SPEPhe was not statistically different between the two groups (PE-formula: 39.8±18.3%, S-formula: 52.4±13.6%). Conclusions Increasing protein and energy intakes promotes protein anabolism in critically ill infants in the first days after admission. Since this is an important target of nutritional support, increased protein and energy intakes should be preferred above standard intakes in these infants. Dutch Trial Register number: NTR 515. PMID:21673183

  15. Continuous Drug Infusion for Diabetes Therapy: A Closed-Loop Control System Design

    Directory of Open Access Journals (Sweden)

    Jiming Chen

    2008-03-01

    Full Text Available While a typical way for diabetes therapy is discrete insulin infusion based on long-time interval measurement, in this paper, we design a closed-loop control system for continuous drug infusion to improve the traditional discrete methods and make diabetes therapy automatic in practice. By exploring the accumulative function of drug to insulin, a continuous injection model is proposed. Based on this model, proportional-integral-derivative (PID and fuzzy logic controllers are designed to tackle a control problem of the resulting highly nonlinear plant. Even with serious disturbance of glucose, such as nutrition absorption at meal time, the proposed scheme can perform well in simulation experiments.

  16. A controlled study of virtual reality exposure therapy for the fear of flying.

    Science.gov (United States)

    Rothbaum, B O; Hodges, L; Smith, S; Lee, J H; Price, L

    2000-12-01

    Fear of flying (FOF) affects an estimated 10-25% of the population. Patients with FOF (N = 49) were randomly assigned to virtual reality exposure (VRE) therapy, standard exposure (SE) therapy, or a wait-list (WL) control. Treatment consisted of 8 sessions over 6 weeks, with 4 sessions of anxiety management training followed by either exposure to a virtual airplane (VRE) or exposure to an actual airplane at the airport (SE). A posttreatment flight on a commercial airline measured participants' willingness to fly and anxiety during flight immediately after treatment. The results indicated that VRE and SE were both superior to WL, with no differences between VRE and SE. The gains observed in treatment were maintained at a 6-month follow up. By 6 months posttreatment, 93% of VRE participants and 93% of SE participants had flown. VRE therapy and SE therapy for treatment of FOF were unequivocally supported in this controlled study.

  17. The Efficacy of Parent-Child Interaction Therapy with Chinese Families: Randomized Controlled Trial

    Science.gov (United States)

    Leung, Cynthia; Tsang, Sandra; Sin, Tammy C. S.; Choi, Siu-yan

    2015-01-01

    Objective: This study aimed to examine the efficacy of the Parent-Child Interaction Therapy (PCIT) in Hong Kong Chinese families, using randomized controlled trial design. Methods: The participants included 111 Hong Kong Chinese parents with children aged 2--7 years old, who were randomized into the intervention group (n = 54) and control group (n…

  18. The Effect of Music Therapy in Patients with Huntington's Disease: A Randomized Controlled Trial.

    Science.gov (United States)

    van Bruggen-Rufi, Monique C H; Vink, Annemieke C; Wolterbeek, Ron; Achterberg, Wilco P; Roos, Raymund A C

    2017-01-01

    Music therapy may have beneficial effects on improving communication and expressive skills in patients with Huntington's disease (HD). Most studies are, however, small observational studies and methodologically limited. Therefore we conducted a multi-center randomized controlled trial. To determine the efficacy of music therapy in comparison with recreational therapy in improving quality of life of patients with advanced Huntington's disease by means of improving communication. Sixty-three HD-patients with a Total Functional Capacity (TFC) score of ≤7, admitted to four long-term care facilities in The Netherlands, were randomized to receive either group music therapy or group recreational therapy in 16 weekly sessions. They were assessed at baseline, after 8, 16 and 28 weeks using the Behaviour Observation Scale for Huntington (BOSH) and the Problem Behaviour Assessment-short version (PBA-s). A linear mixed model with repeated measures was used to compare the scores between the two groups. Group music therapy offered once weekly for 16 weeks to patients with Huntington's disease had no additional beneficial effect on communication or behavior compared to group recreational therapy. This was the first study to assess the effect of group music therapy on HD patients in the advanced stages of the disease. The beneficial effects of music therapy, recorded in many, mainly qualitative case reports and studies, could not be confirmed with the design (i.e. group therapy vs individual therapy) and outcome measures that have been used in the present study. A comprehensive process-evaluation alongside the present effect evaluation is therefore performed.

  19. 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

    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. 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. 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. 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.

  20. Wake and light therapy for moderate-to-severe depression - a randomized controlled trial

    DEFF Research Database (Denmark)

    Kragh, M; Martiny, K; Videbech, P

    2017-01-01

    Objective: To examine the efficacy of using wake and light therapy as a supplement to standard treatment of hospitalized patients with depression. Method: In this randomized, controlled study, 64 patients with moderate-to-severe depression were allocated to standard treatment or to the intervention......, which additionally consisted of three wake therapy sessions in one week, 30-min daily light treatment and sleep time stabilization over the entire nine-week study period. Results: Patients in the wake therapy group had a significant decrease in depressive symptoms in week one as measured by HAM-D17, 17...

  1. Virtual reality exposure therapy for social anxiety disorder: a randomized controlled trial.

    Science.gov (United States)

    Anderson, Page L; Price, Matthew; Edwards, Shannan M; Obasaju, Mayowa A; Schmertz, Stefan K; Zimand, Elana; Calamaras, Martha R

    2013-10-01

    This is the first randomized trial comparing virtual reality exposure therapy to in vivo exposure for social anxiety disorder. Participants with a principal diagnosis of social anxiety disorder who identified public speaking as their primary fear (N = 97) were recruited from the community, resulting in an ethnically diverse sample (M age = 39 years) of mostly women (62%). Participants were randomly assigned to and completed 8 sessions of manualized virtual reality exposure therapy, exposure group therapy, or wait list. Standardized self-report measures were collected at pretreatment, posttreatment, and 12-month follow-up, and process measures were collected during treatment. A standardized speech task was delivered at pre- and posttreatment, and diagnostic status was reassessed at 3-month follow-up. Analysis of covariance showed that, relative to wait list, people completing either active treatment significantly improved on all but one measure (length of speech for exposure group therapy and self-reported fear of negative evaluation for virtual reality exposure therapy). At 12-month follow-up, people showed significant improvement from pretreatment on all measures. There were no differences between the active treatments on any process or outcome measure at any time, nor differences on achieving partial or full remission. Virtual reality exposure therapy is effective for treating social fears, and improvement is maintained for 1 year. Virtual reality exposure therapy is equally effective as exposure group therapy; further research with a larger sample is needed, however, to better control and statistically test differences between the treatments.

  2. A Randomized Controlled Trial of Cognitive-Behavior Therapy Plus Bright Light Therapy for Adolescent Delayed Sleep Phase Disorder

    Science.gov (United States)

    Gradisar, Michael; Dohnt, Hayley; Gardner, Greg; Paine, Sarah; Starkey, Karina; Menne, Annemarie; Slater, Amy; Wright, Helen; Hudson, Jennifer L.; Weaver, Edward; Trenowden, Sophie

    2011-01-01

    Objective: To evaluate cognitive-behavior therapy plus bright light therapy (CBT plus BLT) for adolescents diagnosed with delayed sleep phase disorder (DSPD). Design: Randomized controlled trial of CBT plus BLT vs. waitlist (WL) control with comparisons at pre- and post-treatment. There was 6-month follow-up for the CBT plus BLT group only. Setting: Flinders University Child & Adolescent Sleep Clinic, Adelaide, South Australia. Patients: 49 adolescents (mean age 14.6 ± 1.0 y, 53% males) diagnosed with DSPD; mean chronicity 4 y 8 months; 16% not attending school. Eighteen percent of adolescents dropped out of the study (CBT plus BLT: N = 23 vs WL: N = 17). Interventions: CBT plus BLT consisted of 6 individual sessions, including morning bright light therapy to advance adolescents' circadian rhythms, and cognitive restructuring and sleep education to target associated insomnia and sleep hygiene. Measurements and Results: DSPD diagnosis was performed via a clinical interview and 7-day sleep diary. Measurements at each time-point included online sleep diaries and scales measuring sleepiness, fatigue, and depression symptoms. Compared to WL, moderate-to-large improvements (d = 0.65-1.24) were found at post-treatment for CBT plus BLT adolescents, including reduced sleep latency, earlier sleep onset and rise times, total sleep time (school nights), wake after sleep onset, sleepiness, and fatigue. At 6-month follow-up (N = 15), small-to-large improvements (d = 0.24-1.53) continued for CBT plus BLT adolescents, with effects found for all measures. Significantly fewer adolescents receiving CBT plus BLT met DPSD criteria at post-treatment (WL = 82% vs. CBT plus BLT = 13%, P sleep and daytime impairments in the immediate and long-term. Studies evaluating the treatment effectiveness of each treatment component are needed. Clinical Trial Information: Australia – New Zealand Trials Registry Number: ACTRN12610001041044. Citation: Gradisar M; Dohnt H; Gardner G; Paine S; Starkey

  3. A systematic review of randomized controlled trials using music therapy for children.

    Science.gov (United States)

    Mrázová, Marcela; Celec, Peter

    2010-10-01

    Music therapy is a promising approach widening the potential applications of psychotherapy. Music influences both, psychologic and physiologic parameters, and children are especially responsive to this form of therapy. Many aspects of its action mechanisms remain to be elucidated, underscoring the need for evidence-based medicine (EBM) for clinical use of music therapy. This review seeks to highlight some of the issues of music therapy research and to initiate a discussion about the need for international multicenter cooperation to bring scientifically sound evidence of the benefits of music therapy in pediatric patients. Scientific bibliographic databases were searched for randomized controlled trials on use of music therapy for children. Identified articles were evaluated according to criteria for scientific quality. Twenty-eight studies were identified. Most of the trials were biased by the number of participants, and some trials showed the need to improve design of control groups. Indeed, the novelty of this area of study has produced a large number of different studies (with variability in diagnoses, interventions, control groups, duration, and/or outcome parameters), and there is a need for a more homogeneous and systematic approach. Available studies highlight the need to address reproducibility issues. This analysis identifies the need for a subsequent series of clinical studies on the efficacy of music in the pediatric population, with more focus on eligibility criteria with respect to EBM and reproducibility.

  4. Robotic Control of a Traditional Flexible Endoscope for Therapy

    NARCIS (Netherlands)

    Ruiter, Jeroen; Bonnema, Gerrit Maarten; van der Voort, Mascha C.; Broeders, Ivo Adriaan Maria Johannes

    2013-01-01

    In therapeutic flexible endoscopy a team of physician and assistant(s) is required to control all independent translations and rotations of the flexible endoscope and its instruments. As a consequence the physician lacks valuable force feedback information on tissue interaction, communication errors

  5. Impact of HIV on novel therapies for tuberculosis control

    NARCIS (Netherlands)

    Sánchez, María S.; Lloyd-Smith, James O.; Porco, Travis C.; Williams, Brian G.; Borgdorff, Martien W.; Mansoer, John; Salomon, Joshua A.; Getz, Wayne M.

    2008-01-01

    OBJECTIVE AND DESIGN: The increased risk for tuberculosis in HIV-infected people has fueled a worldwide resurgence of tuberculosis. A major hindrance to controlling tuberculosis is the long treatment duration, leading to default, jeopardizing cure, and generating drug resistance. We investigated how

  6. Pneumatocek therapy with Chiba needle desuflation by CT control

    International Nuclear Information System (INIS)

    Mach, P.; Zachar, M.

    1996-01-01

    The authors demonstrated 18 month old girl with pneumatocele. In girl on accout of the persistence of of pneumatocele for more than eight an half month, regard to the localisation desuflation with Chiba needle under CT control was performed. After this procedure pneumatocele deminished in size and complete recovery occurred after for and half month. (authors). 5 figs., 8 refs

  7. Installations for radiation therapy with remote controlled afterloading technique. Ferngesteuerte Applikationsanlagen zur Therapie mit umschlossenen radioaktiven Stoffen

    Energy Technology Data Exchange (ETDEWEB)

    1982-01-01

    Installations for radiation therapy with remote controlled afterloading technique; radiation protection rules for fabrication and construction; amendment 1 to draft standard (DIN) 6853. Compared to the draft standard of Semptember 1980, the following modifications are planned as amendment 1: a. Paragraph no. 1: In the title, the word ''scope'' is changed into ''field of application''. The words ''by moving the radiation source electromecanically'' are deleted. b. Paragraph no. 2'' Standards also applicable'' and the list of ''Additional standards'' are summarized under the heading ''Standards and supporting documents'' (without any paragraph number). c. Paragraph no. 3 ''Terms'' is completed by additional terms and their definitions.

  8. Controls and Beam Diagnostics for Therapy-Accelerators

    CERN Document Server

    Eickhoff, H

    2000-01-01

    During the last four years GSI has developed a new procedure for cancer treatment by means of the intensity controlled rasterscan-method. This method includes active variations of beam parameters during the treatment session and the integration of 'on-line' PET monitoring. Starting in 1997 several patients have been successfully treated within this GSI experimental cancer treatment program; within this program about 350 patients shall be treated in the next 5 years. The developments and experiences of this program accompanied by intensive discussions with the medical community led to a proposal for a hospital based light ion accelerator facility for the clinic in Heidelberg. An essential part for patients treatments is the measurement of the beam properties within acceptance and constancy tests and especially for the rasterscan method during the treatment sessions. The presented description of the accelerator controls and beam diagnostic devices mainly covers the requests for the active scanning method, which...

  9. Control system specification for a cyclotron and neutron therapy facility

    International Nuclear Information System (INIS)

    Jacky, J.; Risler, R.; Kalet, I.; Wootton, P.; Barke, A.; Brossard, S.; Jackson, R.

    1991-01-01

    It is usually considered an essential element of good practice in engineering to produce a specification for a system before building it. However, it has been found to be quite difficult to produce useful specifications of large software systems. The authors have nearly completed a comprehensive specification for the computer control system of a cyclotron and treatment facility that provides particle beams for cancer treatments with fast neutrons, production of medical isotopes, and physics experiments. They describe the control system as thoroughly as is practical using standard technical English, supplemented by tables, diagrams, and some algebraic equations. This specification comprises over 300 single-spaced pages. A more precise and compact specification might be achieved by making greater use of formal mathematical notations instead of English. They have begun work on a formal specification of the system, using the Z and Petri net notations

  10. Physical therapy applications of MR fluids and intelligent control

    Science.gov (United States)

    Dong, Shufang; Lu, Ke-Qian; Sun, J. Q.; Rudolph, Katherine

    2005-05-01

    Resistance exercise has been widely reported to have positive rehabilitation effects for patients with neuromuscular and orthopaedic conditions. This paper presents an optimal design of magneto-rheological fluid dampers for variable resistance exercise devices. Adaptive controls for regulating the resistive force or torque of the device as well as the joint motion are presented. The device provides both isometric and isokinetic strength training for various human joints.

  11. Treating viral hemorrhagic fever.

    NARCIS (Netherlands)

    Mairuhu, A.T.; Brandjes, D.P.; Gorp, E. van

    2003-01-01

    Viral hemorrhagic fevers are illnesses associated with a number of geographically restricted, mostly tropical areas. Over recent decades a number of new hemorrhagic fever viruses have emerged. Advances in our understanding of the pathophysiology of these diseases have improved our initial supportive

  12. HIV Viral Load

    Science.gov (United States)

    ... PF4 Antibody Hepatitis A Testing Hepatitis B Testing Hepatitis C Testing HER2/neu Herpes Testing High-sensitivity C-reactive Protein (hs-CRP) Histamine Histone Antibody HIV Antibody and HIV Antigen (p24) HIV Antiretroviral Drug Resistance Testing, Genotypic HIV Viral Load HLA Testing HLA- ...

  13. HIV and Viral Hepatitis

    Science.gov (United States)

    ... common causes of viral hepatitis are hepatitis A virus (HAV), hepatitis B virus (HBV), and hepatitis C virus (HCV). HBV and HCV are common ... gov/ mmwr/ preview/ mmwrhtml/ rr5516a1. htm? s_ cid= rr5516a1_ e. The Numbers • • Of people with HIV in the ...

  14. Immigration and viral hepatitis

    NARCIS (Netherlands)

    S. Sharma (Suraj); M. Carballo (Manuel); J.J. Feld (Jordan J.); H.L.A. Janssen (Harry)

    2015-01-01

    textabstractWHO 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

  15. Upper limb robot-assisted therapy in cerebral palsy: a single-blind randomized controlled trial.

    Science.gov (United States)

    Gilliaux, Maxime; Renders, Anne; Dispa, Delphine; Holvoet, Dominique; Sapin, Julien; Dehez, Bruno; Detrembleur, Christine; Lejeune, Thierry M; Stoquart, Gaëtan

    2015-02-01

    Several pilot studies have evoked interest in robot-assisted therapy (RAT) in children with cerebral palsy (CP). To assess the effectiveness of RAT in children with CP through a single-blind randomized controlled trial. Sixteen children with CP were randomized into 2 groups. Eight children performed 5 conventional therapy sessions per week over 8 weeks (control group). Eight children completed 3 conventional therapy sessions and 2 robot-assisted sessions per week over 8 weeks (robotic group). For both groups, each therapy session lasted 45 minutes. Throughout each RAT session, the patient attempted to reach several targets consecutively with the REAPlan. The REAPlan is a distal effector robot that allows for displacements of the upper limb in the horizontal plane. A blinded assessment was performed before and after the intervention with respect to the International Classification of Functioning framework: body structure and function (upper limb kinematics, Box and Block test, Quality of Upper Extremity Skills Test, strength, and spasticity), activities (Abilhand-Kids, Pediatric Evaluation of Disability Inventory), and participation (Life Habits). During each RAT session, patients performed 744 movements on average with the REAPlan. Among the variables assessed, the smoothness of movement (P robotic group than in the control group. This single-blind randomized controlled trial provides the first evidence that RAT is effective in children with CP. Future studies should investigate the long-term effects of this therapy. © The Author(s) 2014.

  16. Occupational therapy for stroke patients not admitted to hospital: a randomised controlled trial.

    Science.gov (United States)

    Walker, M F; Gladman, J R; Lincoln, N B; Siemonsma, P; Whiteley, T

    1999-07-24

    Patients who have a stroke are not always admitted to hospital, and 22-60% remain in the community, frequently without coordinated rehabilitation. We aimed to assess the efficacy of an occupational therapy intervention for patients with stroke who were not admitted to hospital. In this single-blind randomised controlled trial, consecutive stroke patients on a UK community register in Nottingham and Derbyshire were allocated randomly to up to 5 months of occupational therapy at home or to no intervention (control group) 1 month after their stroke. The aim of the occupational therapy was to encourage independence in personal and instrumental activities of daily living. Patients were assessed on outcome measures at baseline (before randomisation) and at 6 months. The primary outcome measure was the score on the extended activities of daily living (EADL) scale at 6 months. Other outcome measures included the Barthel index, the general health questionnaire 28, the carer strain index, and the London handicap scale. All assessments were done by an independent assessor who was unaware of treatment allocation. The analysis included only data from completed questionnaires. 185 patients were included: 94 in the occupational therapy group and 91 in the control group. 22 patients were not assessed at 6 months. At follow-up, patients who had occupational therapy had significantly higher median scores than the controls on: the EADL scale (16 vs 12, pstroke who were not admitted to hospital.

  17. A randomized controlled trial of metacognitive therapy vs. cognitive behavioral therapy vs. waiting list in the treatment of adults with generalized anxiety disorder: A preliminary analysis

    OpenAIRE

    Kvistedal, Draco Jon Torstein

    2011-01-01

    Forty two participants with generalized anxiety disorder were treated with either Metacognitive therapy or Cognitive Behavioral Therapy, in a randomized controlled study comparing the relative effect of the two treatments. A wait list condition comprised the control group. Statistical analysis proved MCT superior to CBT, and CBT proved superior to no treatment. Because this is a preliminary study it has some limitations, such as no follow-up data or treatment adherence control. Thus at the cu...

  18. Factors associated with mother-to-child transmission of HIV-1 despite a maternal viral load EPF-ANRS CO1).

    Science.gov (United States)

    Tubiana, Roland; Le Chenadec, Jerome; Rouzioux, Christine; Mandelbrot, Laurent; Hamrene, Karima; Dollfus, Catherine; Faye, Albert; Delaugerre, Constance; Blanche, Stephane; Warszawski, Josiane

    2010-02-15

    The rate of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) type 1 is as low as 0.5% in non-breast-feeding mothers who delivered at term while receiving antiretroviral therapy with a plasma viral load <500 copies/mL. This situation accounted for 20% of the infected children born during the period 1997-2006 in the French Perinatal Cohort. We aimed to identify factors associated with such residual transmission risk. We performed a case-control study nested in the aforementioned subpopulation of the French Perinatal Cohort. Nineteen case patients (transmitters) and 60 control subjects (nontransmitters) were included. Case patients and control subjects did not differ by geographical origin, gestational age at HIV diagnosis, type of antiretroviral therapy received, or elective Cesarean delivery. Case patients were less often receiving treatment at the time that they conceived pregnancy than control subjects (16% vs 45%; P=.017). A lower proportion of case patients had a viral load <500 copies/mL, compared with control subjects, at 14 weeks (0% vs 38.1%; P=.02), 28 weeks (7.7% vs 62.1%; P=.005), and 32 weeks: (21.4% vs 71.1%; P=.004). The difference remained significant when we restricted analysis to the 10 of 16 intrapartum transmission cases. In a multivariate analysis at 30+/-4 weeks adjusted for viral load, CD4(+) T cell count, and time at antiretroviral therapy initiation, viral load was the only factor independently associated with MTCT of HIV (adjusted odds ratio, 23.2; 95% confidence interval, 3.5-553; P<.001). Early and sustained control of viral load is associated with a decreasing residual risk of MTCT of HIV-1. Guidelines should take into account not only CD4(+) T cell count and risk of preterm delivery, but also baseline HIV-1 load for deciding when to start antiretroviral therapy during pregnancy.

  19. Control group design: enhancing rigor in research of mind-body therapies for depression.

    Science.gov (United States)

    Kinser, Patricia Anne; Robins, Jo Lynne

    2013-01-01

    Although a growing body of research suggests that mind-body therapies may be appropriate to integrate into the treatment of depression, studies consistently lack methodological sophistication particularly in the area of control groups. In order to better understand the relationship between control group selection and methodological rigor, we provide a brief review of the literature on control group design in yoga and tai chi studies for depression, and we discuss challenges we have faced in the design of control groups for our recent clinical trials of these mind-body complementary therapies for women with depression. To address the multiple challenges of research about mind-body therapies, we suggest that researchers should consider 4 key questions: whether the study design matches the research question; whether the control group addresses performance, expectation, and detection bias; whether the control group is ethical, feasible, and attractive; and whether the control group is designed to adequately control for nonspecific intervention effects. Based on these questions, we provide specific recommendations about control group design with the goal of minimizing bias and maximizing validity in future research.

  20. Rationale, study design and sample characteristics of a randomized controlled trial of directly administered antiretroviral therapy for HIV-infected prisoners transitioning to the community - a potential conduit to improved HIV treatment outcomes.

    Science.gov (United States)

    Saber-Tehrani, Ali Shabahang; Springer, Sandra A; Qiu, Jingjun; Herme, Maua; Wickersham, Jeffrey; Altice, Frederick L

    2012-03-01

    HIV-infected prisoners experience poor HIV treatment outcomes post-release. Directly administered antiretroviral therapy (DAART) is a CDC-designated, evidence-based adherence intervention for drug users, yet untested among released prisoners. Sentenced HIV-infected prisoners on antiretroviral therapy (ART) and returning to New Haven or Hartford, Connecticut were recruited and randomized 2:1 to a prospective controlled trial (RCT) of 6 months of DAART versus self-administered therapy (SAT); all subjects received case management services. Subjects meeting DSM-IV criteria for opioid dependence were offered immediate medication-assisted treatment. Trained outreach workers provided DAART once-daily, seven days per week, including behavioral skills training during the last intervention month. Both study groups were assessed for 6 months after the intervention period. Assessments occurred within 90 days pre-release (baseline), day of release, and then monthly for 12 months. Viral load (VL) and CD4 testing was conducted baseline and quarterly; genotypic resistance testing was conducted at baseline, 6 and 12 months. The primary outcome was pre-defined as viral suppression (VLHIV treatment outcomes after release from prison, a period associated with adverse HIV and other medical consequences. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. 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....

  2. Hepatitis A through E (Viral Hepatitis)

    Science.gov (United States)

    ... Treatment Eating, Diet, & Nutrition Clinical Trials Wilson Disease Hepatitis (Viral) View or Print All Sections What is Viral Hepatitis? Viral hepatitis is an infection that causes liver inflammation ...

  3. Interferon-associated therapies toward HIV control: The back and forth.

    Science.gov (United States)

    Noël, Nicolas; Jacquelin, Béatrice; Huot, Nicolas; Goujard, Cécile; Lambotte, Olivier; Müller-Trutwin, Michaela

    2018-03-09

    Human immunodeficiency virus (HIV) induces a persistent and incurable infection. However, the combined antiretroviral treatment (cART) has markedly changed the evolution of the infection and transformed a deadly disease into a manageable chronic infection. Withdrawal of cART generally leads though to resumption of the viral replication. The eradication of the virus from its cellular and anatomical reservoirs remains a goal-to-achieve for a cure. In this context, developing novel therapies contributing to this aim are an important field of research. Type I IFN has antiviral activity, which, before the presence of efficient anti-HIV drugs, has led to the testing of IFN-based therapeutic strategies during the early years of the pandemic. A historical overview of the results and its limitations that were put into light are reviewed here. In addition, several lessons could be drawn. For instance, the efficacy of the IFN-I depends on the timing of its administration and the context. Thus, the persistence of an endogenous IFN-signature, such as that generally observed in viremic patients, seems to be associated with a lower efficacy of IFN. Based on the lessons from previous trials, and in the context of cART and research for a cure, type I Interferon has regained interest and novel therapeutic approaches are currently tested in combination with cART, some with disappointing, other with encouraging results with regard to a reduction in the size of the HIV reservoir and/or delays in viral rebound after cessation of cART. Additional strategies are currently developed in addition to improve the antiviral function of the IFN-I, by using for instance other IFN subtypes than IFN-Iα2. In parallel, the development of innovative strategies aimed at counteracting the excessive activation of the IFN-pathways have been continued and their results are reviewed here as well. Altogether, the use of IFN-I in anti-HIV therapies has gone through distinct phases and many lessons could be

  4. A Randomized Controlled Trial of Internet-Delivered Cognitive Behavior Therapy and Acceptance and Commitment Therapy in the Treatment of Tinnitus

    Science.gov (United States)

    Hesser, Hugo; Gustafsson, Tore; Lunden, Charlotte; Henrikson, Oskar; Fattahi, Kidjan; Johnsson, Erik; Westin, Vendela Zetterqvist; Carlbring, Per; Maki-Torkko, Elina; Kaldo, Viktor; Andersson, Gerhard

    2012-01-01

    Objective: Our aim in this randomized controlled trial was to investigate the effects on global tinnitus severity of 2 Internet-delivered psychological treatments, acceptance and commitment therapy (ACT) and cognitive behavior therapy (CBT), in guided self-help format. Method: Ninety-nine participants (mean age = 48.5 years; 43% female) who were…

  5. 3-D conformal radiation therapy - Part II: Computer-controlled 3-D treatment delivery

    International Nuclear Information System (INIS)

    Benedick, A.

    1997-01-01

    Purpose/Objective: This course will describe the use of computer-controlled treatment delivery techniques for treatment of patients with sophisticated conformal therapy. In particular, research and implementation issues related to clinical use of computer-controlled conformal radiation therapy (CCRT) techniques will be discussed. The possible/potential advantages of CCRT techniques will be highlighted using results from clinical 3-D planning studies. Materials and Methods: In recent years, 3-D treatment planning has been used to develop and implement 3-D conformal therapy treatment techniques, and studies based on these conformal treatments have begun to show the promise of conformal therapy. This work has been followed by the development of commercially-available multileaf collimator and computer control systems for treatment machines. Using these (and other) CCRT devices, various centers are beginning to clinically use complex computer-controlled treatments. Both research and clinical CCRT treatment techniques will be discussed in this presentation. General concepts and requirements for CCRT will be mentioned. Developmental and clinical experience with CCRT techniques from a number of centers will be utilized. Results: Treatment planning, treatment preparation and treatment delivery must be approached in an integrated fashion in order to clinically implement CCRT treatment techniques, and the entire process will be discussed. Various CCRT treatment methodologies will be reviewed from operational, dosimetric, and technical points of view. The discussion will concentrate on CCRT techniques which are likely to see rather wide dissemination over the next several years, including particularly the use of multileaf collimators (MLC), dynamic and segmental conformal therapy, conformal field shaping, and other related techniques. More advanced CCRT techniques, such as the use of individualized intensity modulation of beams or segments, and the use of computer-controlled

  6. Value of Sharing: Viral Advertisement

    OpenAIRE

    Duygu Aydın; Aşina Gülerarslan; Süleyman Karaçor; Tarık Doğan

    2013-01-01

    Sharing motivations of viral advertisements by consumers and the impacts of these advertisements on the perceptions for brand will be questioned in this study. Three fundamental questions are answered in the study. These are advertisement watching and sharing motivations of individuals, criteria of liking viral advertisement and the impact of individual attitudes for viral advertisement on brand perception respectively. This study will be carried out via a viral advertise...

  7. 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...

  8. Manual therapy compared with physical therapy in patients with non-specific neck pain : A randomized controlled trial

    NARCIS (Netherlands)

    Groeneweg, Ruud; van Assen, Luite; Kropman, Hans; Leopold, Huco; Mulder, Jan; Smits-Engelsman, Bouwien C.M.; Ostelo, Raymond W.J.G.; Oostendorp, R.A.B.; van Tulder, Maurits W.

    2017-01-01

    Background: Manual therapy according to the School of Manual Therapy Utrecht (MTU) is a specific type of passive manual joint mobilization. MTU has not yet been systematically compared to other manual therapies and physical therapy. In this study the effectiveness of MTU is compared to physical

  9. The TOPSHOCK study: effectiveness of radial shockwave therapy compared to focused shockwave therapy for treating patellar tendinopath - design of a randomised controlled trial.

    Science.gov (United States)

    van der Worp, Henk; Zwerver, Johannes; van den Akker-Scheek, Inge; Diercks, Ron L

    2011-10-11

    Patellar tendinopathy is a chronic overuse injury of the patellar tendon that is especially prevalent in people who are involved in jumping activities. Extracorporeal Shockwave Therapy is a relatively new treatment modality for tendinopathies. It seems to be a safe and promising part of the rehabilitation program for patellar tendinopathy. Extracorporeal Shockwave Therapy originally used focused shockwaves. Several years ago a new kind of shockwave therapy was introduced: radial shockwave therapy. Studies that investigate the effectiveness of radial shockwave therapy as treatment for patellar tendinopathy are scarce. Therefore the aim of this study is to compare the effectiveness of focussed shockwave therapy and radial shockwave therapy as treatments for patellar tendinopathy. The TOPSHOCK study (Tendinopathy Of Patella SHOCKwave) is a two-armed randomised controlled trial in which the effectiveness of focussed shockwave therapy and radial shockwave therapy are directly compared. Outcome assessors and patients are blinded as to which treatment is given. Patients undergo three sessions of either focused shockwave therapy or radial shockwave therapy at 1-week intervals, both in combination with eccentric decline squat training. Follow-up measurements are scheduled just before treatments 2 and 3, and 1, 4, 7 and 12 weeks after the final treatment. The main outcome measure is the Dutch VISA-P questionnaire, which asks for pain, function and sports participation in subjects with patellar tendinopathy. Secondary outcome measures are pain determined with a VAS during ADL, sports and decline squats, rating of subjective improvement and overall satisfaction with the treatment. Patients will also record their sports activities, pain during and after these activities, and concurrent medical treatment on a weekly basis in a web-based diary. Results will be analysed according to the intention-to-treat principle. The TOPSHOCK study is the first randomised controlled trial that

  10. 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...

  11. 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.

    Directory of Open Access Journals (Sweden)

    Nay Thiha

    Full Text Available 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.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.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.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.

  12. Viral membrane fusion

    International Nuclear Information System (INIS)

    Harrison, Stephen C.

    2015-01-01

    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

  13. [History of viral hepatitis].

    Science.gov (United States)

    Fonseca, José Carlos Ferraz da

    2010-01-01

    The history of viral hepatitis goes back thousands of years and is a fascinating one. When humans were first infected by such agents, a natural repetitive cycle began, with the capacity to infect billions of humans, thus decimating the population and causing sequelae in thousands of lives. This article reviews the available scientific information on the history of viral hepatitis. All the information was obtained through extensive bibliographic review, including original and review articles and consultations on the internet. There are reports on outbreaks of jaundice epidemics in China 5,000 years ago and in Babylon more than 2,500 years ago. The catastrophic history of great jaundice epidemics and pandemics is well known and generally associated with major wars. In the American Civil War, 40,000 cases occurred among Union troops. In 1885, an outbreak of catarrhal jaundice affected 191 workers at the Bremen shipyard (Germany) after vaccination against smallpox. In 1942, 28,585 soldiers became infected with hepatitis after inoculation with the yellow fever vaccine. The number of cases of hepatitis during the Second World War was estimated to be 16 million. Only in the twentieth century were the main agents causing viral hepatitis identified. The hepatitis B virus was the first to be discovered. In this paper, through reviewing the history of major epidemics caused by hepatitis viruses and the history of discovery of these agents, singular peculiarities were revealed. Examples of this include the accidental or chance discovery of the hepatitis B and D viruses.

  14. 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.

  15. Development of quality control procedures at a new radiation therapy centre

    International Nuclear Information System (INIS)

    Cooper, A.

    1999-01-01

    Before patients can be treated with radiation therapy, the radiation therapist must be certain that the equipment is functioning within specified parameters. When commencing a new service, introducing appropriate Quality Control procedures on all equipment can be a major accomplishment. At the North Queensland Oncology Service, the Radiation Therapists are responsible for the daily Quality Control on all the radiation therapy equipment. The documentation and procedures were developed by radiation therapists to ensure that all machine parameter discrepancies would be detected before a patient was treated. Monthly Quality Control is the responsibility of the Physics Department. These are carried out on the bi-weekly service days rostered for each linear accelerator and monthly for the simulator. Ongoing Quality Control and Maintenance Meetings ensures reporting and feedback is ongoing between the Radiation Therapists and Physicists. All other liaising is done through the Deputy Chief Radiation Therapist and Senior Physicist. Copyright (1999) Australian Institute of Radiography

  16. Pancreatic Enzyme Replacement Therapy in Children with Severe Acute Malnutrition : A Randomized Controlled Trial

    NARCIS (Netherlands)

    Bartels, Rosalie H.; Bourdon, Celine; Potani, Isabel; Mhango, Brian; van den Brink, Deborah A.; Mponda, John S.; Kobold, Anneke C. Muller; Bandsma, Robert H.; van Hensbroek, Michael Boele; Voskuijl, Wieger P.

    Objective: To assess the benefits of pancreatic enzyme replacement therapy (PERT) in children with complicated severe acute malnutrition. Study design: We conducted a randomized, controlled trial in 90 children aged 6-60 months with complicated severe acute malnutrition at the Queen Elizabeth

  17. Pancreatic Enzyme Replacement Therapy in Children with Severe Acute Malnutrition: A Randomized Controlled Trial

    NARCIS (Netherlands)

    Bartels, Rosalie H.; Bourdon, Céline; Potani, Isabel; Mhango, Brian; van den Brink, Deborah A.; Mponda, John S.; Muller Kobold, Anneke C.; Bandsma, Robert H.; Boele van Hensbroek, Michael; Voskuijl, Wieger P.

    2017-01-01

    Objective To assess the benefits of pancreatic enzyme replacement therapy (PERT) in children with complicated severe acute malnutrition. Study design We conducted a randomized, controlled trial in 90 children aged 6-60 months with complicated severe acute malnutrition at the Queen Elizabeth Central

  18. Efficacy of Parent-Child Interaction Therapy with Chinese ADHD Children: Randomized Controlled Trial

    Science.gov (United States)

    Leung, Cynthia; Tsang, Sandra; Ng, Gene S. H.; Choi, S. Y.

    2017-01-01

    Purpose: This study aimed to evaluate the efficacy of Parent-Child Interaction Therapy (PCIT) in Chinese children with attention-deficit/hyperactivity disorder (ADHD) or ADHD features. Methods: This study adopted a randomized controlled trial design without blinding. Participants were randomized into either the intervention group (n = 32) and…

  19. Mobile Phone-Delivered Cognitive Behavioral Therapy for Insomnia : A Randomized Waitlist Controlled Trial

    NARCIS (Netherlands)

    Horsch, C.H.G.; Lancee, J.; Griffioen-Both, F.; Spruit, S.; Fitrianie, S.; Neerincx, M.A.; Beun, R.J.; Brinkman, W.-P.

    Background: This study is one of the first randomized controlled trials investigating cognitive behavioral therapy for insomnia (CBT-I) delivered by a fully automated mobile phone app. Such an app can potentially increase the accessibility of insomnia treatment for the 10% of people who have

  20. Mobile Phone-Delivered Cognitive Behavioral Therapy for Insomnia : A Randomized Waitlist Controlled Trial

    NARCIS (Netherlands)

    Horsch, C.H.G.; Lancee, J; Griffioen-Both, Fiemke; Spruit, Sandor; Fitrianie, S.; Neerincx, M.A.; Beun, RJ; Brinkman, W.P.

    2017-01-01

    Background: This study is one of the first randomized controlled trials investigating cognitive behavioral therapy for insomnia (CBT-I) delivered by a fully automated mobile phone app. Such an app can potentially increase the accessibility of insomnia treatment for the 10% of people who have

  1. A VIRTUAL REALITY EXPOSURE THERAPY FOR PTSD PATIENTS CONTROLLED BY A FUZZY LOGIC SYSTEM

    OpenAIRE

    Rosa Maria Esteves Moreira da Costa; Fernando Moraes de Oliveira; Regina Serrão Lanzillotti; Raquel Gonçalves; Luis Alfredo Vidal de Carvalho

    2014-01-01

    This paper describes the main characteristics of two integrated systems that explore Virtual Reality technology and Fuzzy Logic to support and to control the assessment of people with Post-Traumatic Stress Disorder during the Virtual Reality Exposure Therapy. The integration of different technologies, the development methodology and the test procedures are described throughout the paper.

  2. A VIRTUAL REALITY EXPOSURE THERAPY FOR PTSD PATIENTS CONTROLLED BY A FUZZY LOGIC SYSTEM

    Directory of Open Access Journals (Sweden)

    Rosa Maria Esteves Moreira da Costa

    2014-06-01

    Full Text Available This paper describes the main characteristics of two integrated systems that explore Virtual Reality technology and Fuzzy Logic to support and to control the assessment of people with Post-Traumatic Stress Disorder during the Virtual Reality Exposure Therapy. The integration of different technologies, the development methodology and the test procedures are described throughout the paper.

  3. A virtual reality exposure therapy for PTSD patients controlled by a fuzzy logic system

    OpenAIRE

    Oliveira, F. M.; Lanzillotti, R. S.; Da Costa, R. M. E. M.; Gonçalves, R.; Ventura, P.; Carvalho, L. A. V. de

    2014-01-01

    This paper describes the main characteristics of two integrated systems that explore Virtual Reality technology and Fuzzy Logic to support and to control the assessment of people with Post-Traumatic Stress Disorder during the Virtual Reality Exposure Therapy. The integration of different technologies, the development methodology and the test procedures are described throughout the paper. Peer Reviewed

  4. Cognitive behavior therapy for pediatric functional abdominal pain: a randomized controlled trial

    NARCIS (Netherlands)

    van der Veek, Shelley M. C.; Derkx, Bert H. F.; Benninga, Marc A.; Boer, Frits; de Haan, Else

    2013-01-01

    This randomized controlled trial investigated the effectiveness of a 6-session protocolized cognitive behavior therapy (CBT) compared with 6 visits to a pediatrician (intensive medical care; IMC) for the treatment of pediatric functional abdominal pain (FAP). One hundred four children aged 7 to 18

  5. Cognitive Behavioral Therapy Reduces Suicidal Ideation in Schizophrenia: Results from a Randomized Controlled Trial

    Science.gov (United States)

    Bateman, Katy; Hansen, Lars; Turkington, Douglas; Kingdon, David

    2007-01-01

    Patients with schizophrenia are at high risk of suicide. Cognitive behavior therapy (CBT) has been shown to reduce symptoms in schizophrenia. This study examines whether CBT also changes the level of suicidal ideation in patients with schizophrenia compared to a control group. Ninety ambulatory patients with symptoms of schizophrenia resistant to…

  6. Nucleocapsid-Independent Specific Viral RNA Packaging via Viral Envelope Protein and Viral RNA Signal

    OpenAIRE

    Narayanan, Krishna; Chen, Chun-Jen; Maeda, Junko; Makino, Shinji

    2003-01-01

    For any of the enveloped RNA viruses studied to date, recognition of a specific RNA packaging signal by the virus's nucleocapsid (N) protein is the first step described in the process of viral RNA packaging. In the murine coronavirus a selective interaction between the viral transmembrane envelope protein M and the viral ribonucleoprotein complex, composed of N protein and viral RNA containing a short cis-acting RNA element, the packaging signal, determines the selective RNA packaging into vi...

  7. Music therapy for mood disturbance during hospitalization for autologous stem cell transplantation: a randomized controlled trial.

    Science.gov (United States)

    Cassileth, Barrie R; Vickers, Andrew J; Magill, Lucanne A

    2003-12-15

    High-dose therapy with autologous stem cell transplantation (HDT/ASCT) is a commonly used treatment for hematologic malignancies. The procedure causes significant psychological distress and no interventions have been demonstrated to improve mood in these patients. Music therapy has been shown to improve anxiety in a variety of acute medical settings. In the current study, the authors determined the effects of music therapy compared with standard care on mood during inpatient stays for HDT/ASCT. Patients with hematologic malignancy admitted for HDT/ASCT at two sites (Memorial Sloan-Kettering Cancer Center and Ireland Cancer Center in Cleveland, Ohio) were randomized to receive music therapy given by trained music therapists or standard care. Outcome was assessed at baseline and every 3 days after randomization using the Profile of Mood States. Of 69 patients registered in the study, follow-up data were available for 62 (90%). During their inpatient stay, patients in the music therapy group scored 28% lower on the combined Anxiety/Depression scale (P = 0.065) and 37% lower (P = 0.01) on the total mood disturbance score compared with controls. Music therapy is a noninvasive and inexpensive intervention that appears to reduce mood disturbance in patients undergoing HDT/ASCT. Copyright 2003 American Cancer Society.

  8. Ear Acupuncture Therapy for Masticatory Myofascial and Temporomandibular Pain: A Controlled Clinical Trial

    Directory of Open Access Journals (Sweden)

    Luciano Ambrosio Ferreira

    2015-01-01

    Full Text Available Ear acupuncture works by reducing painful sensations with analgesic effect through microsystem therapy and has been demonstrated to be as effective as conventional therapies in the control of facial pain. This clinical trial aimed to evaluate the adjuvant action of auricular acupuncture through an observation of the evolution of temporomandibular and masticatory myofascial symptoms in two groups defined by the therapies elected: auricular acupuncture associated with occlusal splint (study and the use of the occlusal splint plate alone (control. We have selected 20 patients, who were randomly allocated into two groups of ten individuals. Symptoms were evaluated in five different moments, every seven days. We analyzed the orofacial muscle and joint palpation in order to measure the intensity of the experienced pain. Both groups showed a statistically significant decrease in muscle and joint symptoms (p<0.05. However, comparisons between the groups showed an expressive and significant reduction of symptomatology in the study group (p<0.05 already on the first week of therapy. According to the results, to the methodological criteria developed and statistical analysis applied, the conclusion is that auricular acupuncture therapy has synergistic action on conventional occlusal splint treatment. It was demonstrated to be effective in the reduction of symptoms in the short term.

  9. Music Therapy as Procedural Support for Young Children Undergoing Immunizations: A Randomized Controlled Study.

    Science.gov (United States)

    Yinger, Olivia Swedberg

    2016-01-01

    Children undergoing routine immunizations frequently experience severe distress, which may be improved through music therapy as procedural support. The purpose of this study was to examine effects of live, cognitive-behavioral music therapy during immunizations on (a) the behaviors of children, their parents, and their nurses; and (b) parental perceptions. Participants were children between the ages of 4 and 6 years (N = 58) who underwent immunizations, their parents (N = 62), and the nurses who administered the procedure (N = 19). Parent/child dyads were randomly assigned to receive music therapy (n = 29) or standard care (n = 29) during their immunization. Afterward, each parent rated their child's level of pain and the distress their child experienced compared to previous medical experiences. All procedures were videotaped and later viewed by trained observers, who classified child, parent, and nurse behaviors using the categories of the Child-Adult Medical Procedure Interaction Scale-Revised (CAMPIS-R). Significant differences between the music therapy and control groups were found in rates of child coping and distress behaviors and parent distress-promoting behaviors. Parents of children who received music therapy reported that their child's level of distress was less than during previous medical experiences, whereas parents of children in the control group reported that their child's level of distress was greater. No significant differences between groups were found in parents' ratings of children's pain or in rates of nurse behavior. Live, cognitive-behavioral music therapy has potential benefits for young children and their parents during immunizations. © the American Music Therapy Association 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. FEVER IN CHILDREN WITH RESPIRATORY VIRAL INFECTIONS: EFFECTIVE AND SAFE METHODS OF TREATMENT

    Directory of Open Access Journals (Sweden)

    T. E. Taranushenko

    2013-01-01

    Full Text Available One of the most important — the problem of treatment of fever in children with respiratory viral infections — is discussed in this article. It is fever as one of the first symptoms of disease which often frightens parents and leads to inappropriate and excess usage of antipyretic agents, which in its turn can cause unfavorable consequences. The authors represent their own data on frequency of antipyretic drugs usage in children with respiratory viral infections, as well as the answers of pediatricians to the questionnaires on methods of choice in temperature normalization. According to the modern Russian as well as European and American clinical guidelines on treatment of fever in children the management of selection of patients demanding antipyretic treatment is detailed, indications and contraindications to such therapy are described, the most effective methods of temperature normalization in children with acute respiratory infection are discussed. The authors suggested the data on recommended dosages of paracetamol, which were revised in 2011 by the UK Medicines Control Agency, to be very useful. The current information on advantages of ibuprofen in comparison to paracetamol in treatment of fever in children with respiratory viral infections is shown. The main target of this article is understanding and acceptance by pediatricians of the modern recommendation on differential and reasonable approach to administration of antipyretic drugs in children with respiratory viral infections.

  11. 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

  12. Viral skin diseases of the rabbit.

    Science.gov (United States)

    Meredith, Anna L

    2013-09-01

    This article describes the viral skin diseases affecting the domestic rabbit, the most important being myxomatosis. Transmission and pathogenesis, clinical signs, diagnosis, treatment, and control are described and the article will be of interest to veterinary practitioners who treat rabbits. Shope fibroma virus, Shope papilloma virus, and rabbitpox are also discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Meta-analyses on viral hepatitis

    DEFF Research Database (Denmark)

    Gluud, Lise L; Gluud, Christian

    2009-01-01

    This article summarizes the meta-analyses of interventions for viral hepatitis A, B, and C. Some of the interventions assessed are described in small trials with unclear bias control. Other interventions are supported by large, high-quality trials. Although attempts have been made to adjust...

  14. Institute of Medicine's Report on Viral Hepatitis

    Centers for Disease Control (CDC) Podcasts

    In this podcast, Dr. John Ward, Director of CDC’s Division of Viral Hepatitis, discusses the 2010 report, Hepatitis and Liver Cancer: A National Strategy for Prevention and Control of Hepatitis B and C, from the Institute of Medicine.

  15. Viral Organization of Human Proteins

    Science.gov (United States)

    Wuchty, Stefan; Siwo, Geoffrey; Ferdig, Michael T.

    2010-01-01

    Although maps of intracellular interactions are increasingly well characterized, little is known about large-scale maps of host-pathogen protein interactions. The investigation of host-pathogen interactions can reveal features of pathogenesis and provide a foundation for the development of drugs and disease prevention strategies. A compilation of experimentally verified interactions between HIV-1 and human proteins and a set of HIV-dependency factors (HDF) allowed insights into the topology and intricate interplay between viral and host proteins on a large scale. We found that targeted and HDF proteins appear predominantly in rich-clubs, groups of human proteins that are strongly intertwined among each other. These assemblies of proteins may serve as an infection gateway, allowing the virus to take control of the human host by reaching protein pathways and diversified cellular functions in a pronounced and focused way. Particular transcription factors and protein kinases facilitate indirect interactions between HDFs and viral proteins. Discerning the entanglement of directly targeted and indirectly interacting proteins may uncover molecular and functional sites that can provide novel perspectives on the progression of HIV infection and highlight new avenues to fight this virus. PMID:20827298

  16. Mortality in well controlled HIV in the continuous antiretroviral therapy arms of the SMART and ESPRIT trials compared with the general population.

    Science.gov (United States)

    Rodger, Alison J; Lodwick, Rebecca; Schechter, Mauro; Deeks, Steven; Amin, Janaki; Gilson, Richard; Paredes, Roger; Bakowska, Elzbieta; Engsig, Frederik N; Phillips, Andrew

    2013-03-27

    Due to the success of antiretroviral therapy (ART), it is relevant to ask whether death rates in optimally treated HIV are higher than the general population. The objective was to compare mortality rates in well controlled HIV-infected adults in the SMART and ESPRIT clinical trials with the general population. Non-IDUs aged 20-70 years from the continuous ART control arms of ESPRIT and SMART were included if the person had both low HIV plasma viral loads (≤400 copies/ml SMART, ≤500 copies/ml ESPRIT) and high CD4(+) T-cell counts (≥350 cells/μl) at any time in the past 6 months. Standardized mortality ratios (SMRs) were calculated by comparing death rates with the Human Mortality Database. Three thousand, two hundred and eighty individuals [665 (20%) women], median age 43 years, contributed 12,357 person-years of follow-up. Sixty-two deaths occurred during follow up. Commonest cause of death was cardiovascular disease (CVD) or sudden death (19, 31%), followed by non-AIDS malignancy (12, 19%). Only two deaths (3%) were AIDS-related. Mortality rate was increased compared with the general population with a CD4(+) cell count between 350 and 499 cells/μl [SMR 1.77, 95% confidence interval (CI) 1.17-2.55]. No evidence for increased mortality was seen with CD4(+) cell counts greater than 500 cells/μl (SMR 1.00, 95% CI 0.69-1.40). In HIV-infected individuals on ART, with a recent undetectable viral load, who maintained or had recovery of CD4(+) cell counts to at least 500 cells/μl, we identified no evidence for a raised risk of death compared with the general population.

  17. V-GAP: Viral genome assembly pipeline

    KAUST Repository

    Nakamura, Yoji

    2015-10-22

    Next-generation sequencing technologies have allowed the rapid determination of the complete genomes of many organisms. Although shotgun sequences from large genome organisms are still difficult to reconstruct perfect contigs each of which represents a full chromosome, those from small genomes have been assembled successfully into a very small number of contigs. In this study, we show that shotgun reads from phage genomes can be reconstructed into a single contig by controlling the number of read sequences used in de novo assembly. We have developed a pipeline to assemble small viral genomes with good reliability using a resampling method from shotgun data. This pipeline, named V-GAP (Viral Genome Assembly Pipeline), will contribute to the rapid genome typing of viruses, which are highly divergent, and thus will meet the increasing need for viral genome comparisons in metagenomic studies.

  18. V-GAP: Viral genome assembly pipeline

    KAUST Repository

    Nakamura, Yoji; Yasuike, Motoshige; Nishiki, Issei; Iwasaki, Yuki; Fujiwara, Atushi; Kawato, Yasuhiko; Nakai, Toshihiro; Nagai, Satoshi; Kobayashi, Takanori; Gojobori, Takashi; Ototake, Mitsuru

    2015-01-01

    Next-generation sequencing technologies have allowed the rapid determination of the complete genomes of many organisms. Although shotgun sequences from large genome organisms are still difficult to reconstruct perfect contigs each of which represents a full chromosome, those from small genomes have been assembled successfully into a very small number of contigs. In this study, we show that shotgun reads from phage genomes can be reconstructed into a single contig by controlling the number of read sequences used in de novo assembly. We have developed a pipeline to assemble small viral genomes with good reliability using a resampling method from shotgun data. This pipeline, named V-GAP (Viral Genome Assembly Pipeline), will contribute to the rapid genome typing of viruses, which are highly divergent, and thus will meet the increasing need for viral genome comparisons in metagenomic studies.

  19. Randomized controlled trial of cognitive behavioral therapy and acceptance and commitment therapy for social phobia: outcomes and moderators.

    Science.gov (United States)

    Craske, Michelle G; Niles, Andrea N; Burklund, Lisa J; Wolitzky-Taylor, Kate B; Vilardaga, Jennifer C Plumb; Arch, Joanna J; Saxbe, Darby E; Lieberman, Matthew D

    2014-12-01

    Cognitive behavioral therapy (CBT) is an empirically supported treatment for social phobia. However, not all individuals respond to treatment and many who show improvement do not maintain their gains over the long-term. Thus, alternative treatments are needed. The current study (N = 87) was a 3-arm randomized clinical trial comparing CBT, acceptance and commitment therapy (ACT), and a wait-list control group (WL) in participants with a diagnosis of social phobia based on criteria of the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; American Psychiatric Association, 1994). Participants completed 12 sessions of CBT or ACT or a 12-week waiting period. All participants completed assessments at baseline and posttreatment, and participants assigned to CBT and ACT also completed assessments 6 and 12 months following baseline. Assessments consisted of self-report measures, a public-speaking task, and clinician ratings. Multilevel modeling was used to examine between-group differences on outcomes measures. Both treatment groups outperformed WL, with no differences observed between CBT and ACT on self-report, independent clinician, or public-speaking outcomes. Lower self-reported psychological flexibility at baseline was associated with greater improvement by the 12-month follow-up in CBT compared with ACT. Self-reported fear of negative evaluation significantly moderated outcomes as well, with trends for both extremes to be associated with superior outcomes from CBT and inferior outcomes from ACT. Across treatment groups, higher perceived control and extraversion were associated with greater improvement, whereas comorbid depression was associated with poorer outcomes. Implications for clinical practice and future research are discussed.

  20. Randomized controlled trial of cognitive behavioral therapy and acceptance and commitment therapy for social phobia: outcomes and moderators

    Science.gov (United States)

    Craske, Michelle G; Niles, Andrea N.; Burklund, Lisa J.; Wolitzky-Taylor, Kate B.; Vilardaga, Jennifer C. Plumb; Arch, Joanna J.; Saxbe, Darby E.; Lieberman, Matthew D.

    2014-01-01

    Objective Cognitive behavioral therapy (CBT) is an empirically supported treatment for social phobia. However, not all individuals respond to treatment and many who show improvement do not maintain their gains over the long-term. Thus, alternative treatments are needed. Method The current study (N=87) was a 3-arm randomized clinical trial comparing CBT, Acceptance and Commitment therapy (ACT), and a waitlist control group (WL) in participants with a DSM-IV diagnosis of social phobia. Participants completed 12 sessions of CBT or ACT or a 12-week waiting period. All participants completed assessments at baseline and post-treatment, and participants assigned to CBT and ACT also completed assessments at 6 and 12 months following baseline. Assessments consisted of self-report measures, a public speaking task, and clinician ratings. Results Multilevel modeling was used to examine between-group differences on outcomes measures. Both treatment groups outperformed WL, with no differences observed between CBT and ACT on self-report, independent clinician, or public speaking outcomes. Lower self-reported psychological flexibility at baseline was associated with greater improvement by the 12-mo follow-up in CBT compared to ACT. Self-reported fear of negative evaluation significantly moderated outcomes as well, with trends for both extremes to be associated with superior outcomes from CBT and inferior outcomes from ACT. Across treatment groups, higher perceived control, and extraversion were associated with greater improvement, whereas comorbid depression was associated with poorer outcomes. Conclusions Implications for clinical practice and future research are discussed. PMID:24999670

  1. Effectiveness of individual music therapy with mentally ill children and adolescents: A controlled study

    DEFF Research Database (Denmark)

    Gold, Christian

    2003-01-01

    This research addressed the efficacy and effectiveness of music therapy for children and adolescents with mental disorders. Findings from previous experimental research, as summarised in a meta-analysis, suggest that music therapy is an efficacious treatment with a medium to large effect size....... However, little is known about its effectiveness in clinical settings and about factors that might influence its effectiveness. A controlled quasi-experimental pre-test post-test design was used to assess the development in children and adolescents who received on average 23 weekly sessions of music...

  2. The emergence of devastating impulse control disorders during dopamine agonist therapy of the restless legs syndrome.

    Science.gov (United States)

    Dang, Dien; Cunnington, David; Swieca, John

    2011-01-01

    The Restless Legs Syndrome is a common sensorimotor disorder, typically amenable to treatment with dopamine agonist therapy. Dopamine agonists have been associated with emergent impulse control disorders (ICDs) when used in patients with Parkinson disease, and ICDs have now been reported in individuals with RLS on dopamine agonist therapy. Our aim was to characterize cases of emergent ICDs in Australian patients with focus on the dopamine agonists implicated and the social significance of ICDs. A series of RLS patients on dopamine agonist therapy were identified with ICDs over a 2-year period. Additional cases of ICDs were found using a mailout questionnaire designed to capture those with high impulsivity. These patients were assessed using the Barratt Impulsiveness Scale, Version 11, and a modified Minnesota Impulse Disorders Interview. Case records and medication schedules were evaluated. Twelve cases of patients with de novo ICDs were found with a range of impulsive behaviors including pathological gambling, kleptomania, compulsive shopping, and hypersexuality. Criminality, suicidality, and marital discord also were featured. These occurred over a wide range of latencies and l-dopa exposures. This group of Australian RLS patients with ICDs display high levels of impulsivity and is the first to use the BIS-11 questionnaire in this setting. Impulse control disorders can occur over a wide range of dopamine agonist therapy types and dose exposures. Impulse control disorder tendencies may persist, despite withdrawal of dopamine agonists. The emergence of ICDs needs careful consideration in light of their potentially devastating financial, social, and marital consequences.

  3. Clinical importance of achieving biochemical control with medical therapy in adult patients with acromegaly

    Science.gov (United States)

    Christofides, Elena A

    2016-01-01

    In acromegaly, achieving biochemical control (growth hormone [GH] level acromegaly is challenging because it is rooted in observing subtle clinical manifestations, and it is typical for acromegaly to evolve for up to 10 years before it is recognized. This results in chronic exposure to elevated levels of GH and IGF-1 and delay in patients receiving appropriate treatment, which consequently increases mortality risk. In this review, the clinical impact of elevated GH and IGF-1 levels, the effectiveness of current therapies, and the potential role of novel treatments for acromegaly will be discussed. Clinical burden of acromegaly and benefits associated with management of GH and IGF-1 levels will be reviewed. Major treatment paradigms in acromegaly include surgery, medical therapy, and radiotherapy. With medical therapies, such as somatostatin analogs, dopamine agonists, and GH receptor antagonists, a substantial proportion of patients achieve reduced GH and normalized IGF-1 levels. In addition, signs and symptoms, quality of life, and comorbidities have also been reported to improve to varying degrees in patients who achieve biochemical control. Currently, there are several innovative therapies in development to improve patient outcomes, patient use, and access. Timely biochemical control of acromegaly ensures that the patient can ultimately improve morbidity and mortality from this disease and its extensive consequences. PMID:27471378

  4. Biosensor-controlled gene therapy/drug delivery with nanoparticles for nanomedicine

    Science.gov (United States)

    Prow, Tarl W.; Rose, William A.; Wang, Nan; Reece, Lisa M.; Lvov, Yuri; Leary, James F.

    2005-04-01

    Nanomedicine involves cell-by-cell regenerative medicine, either repairing cells one at a time or triggering apoptotic pathways in cells that are not repairable. Multilayered nanoparticle systems are being constructed for the targeted delivery of gene therapy to single cells. Cleavable shells containing targeting, biosensing, and gene therapeutic molecules are being constructed to direct nanoparticles to desired intracellular targets. Therapeutic gene sequences are controlled by biosensor-activated control switches to provide the proper amount of gene therapy on a single cell basis. The central idea is to set up gene therapy "nanofactories" inside single living cells. Molecular biosensors linked to these genes control their expression. Gene delivery is started in response to a biosensor detected problem; gene delivery is halted when the cell response indicates that more gene therapy is not needed. Cell targeting of nanoparticles, both nanocrystals and nanocapsules, has been tested by a combination of fluorescent tracking dyes, fluorescence microscopy and flow cytometry. Intracellular targeting has been tested by confocal microscopy. Successful gene delivery has been visualized by use of GFP reporter sequences. DNA tethering techniques were used to increase the level of expression of these genes. Integrated nanomedical systems are being designed, constructed, and tested in-vitro, ex-vivo, and in small animals. While still in its infancy, nanomedicine represents a paradigm shift in thinking-from destruction of injured cells by surgery, radiation, chemotherapy to cell-by-cell repair within an organ and destruction of non-repairable cells by natural apoptosis.

  5. A randomised controlled trial evaluating family mediated exercise (FAME therapy following stroke

    Directory of Open Access Journals (Sweden)

    Stokes Emma

    2008-06-01

    Full Text Available Abstract Background Stroke is a leading cause of disability among adults worldwide. Evidence suggests that increased duration of exercise therapy following stroke has a positive impact on functional outcome following stroke. The main objective of this randomised controlled trial is to evaluate the impact of additional family assisted exercise therapy in people with acute stroke. Methods/Design A prospective multi-centre single blind randomised controlled trial will be conducted. Forty patients with acute stroke will be randomised into either an experimental or control group. The experimental group will receive routine therapy and additional lower limb exercise therapy in the form of family assisted exercises. The control group will receive routine therapy with no additional formal input from their family members. Participants will be assessed at baseline, post intervention and followed up at three months using a series of standardised outcome measures. A secondary aim of the project is to evaluate the impact of the family mediated exercise programme on the person with stroke and the individual(s assisting in the delivery of exercises using a qualitative methodology. The study has gained ethical approval from the Research Ethics Committees of each of the clinical sites involved in the study. Discussion This study will evaluate a structured programme of exercises that can be delivered to people with stroke by their 'family members/friends'. Given that the progressive increase in the population of older people is likely to lead to an increased prevalence of stroke in the future, it is important to reduce the burden of this illness on the individual, the family and society. Family mediated exercises can maximise the carry over outside formal physiotherapy sessions, giving patients the opportunity for informal practice. Trial Registration The protocol for this study is registered with the US NIH Clinical trials registry (NCT00666744

  6. Can therapy dogs improve pain and satisfaction after total joint arthroplasty? A randomized controlled trial.

    Science.gov (United States)

    Harper, Carl M; Dong, Yan; Thornhill, Thomas S; Wright, John; Ready, John; Brick, Gregory W; Dyer, George

    2015-01-01

    The use of animals to augment traditional medical therapies was reported as early as the 9th century but to our knowledge has not been studied in an orthopaedic patient population. The purpose of this study was to evaluate the role of animal-assisted therapy using therapy dogs in the postoperative recovery of patients after THA and TKA. We asked: (1) Do therapy dogs have an effect on patients' perception of pain after total joint arthroplasty as measured by the VAS? (3) Do therapy dogs have an effect on patients' satisfaction with their hospital stay after total joint arthroplasty as measured by the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS)? A randomized controlled trial of 72 patients undergoing primary unilateral THA or TKA was conducted. Patients were randomized to a 15-minute visitation with a therapy dog before physical therapy or standard postoperative physical therapy regimens. Both groups had similar demographic characteristics. Reduction in pain was assessed using the VAS after each physical therapy session, beginning on postoperative Day 1 and continuing for three consecutive sessions. To ascertain patient satisfaction, the proportion of patients selecting top-category ratings in each subsection of the HCAHPS was compared. Patients in the treatment group had lower VAS scores after each physical therapy session with a final VAS score difference of 2.4 units (animal-assisted therapy VAS, 1.7; SD, 0.97 [95% CI, 1.4-2.0] versus control VAS, 4.1; SD, 0.97 [95% CI, 3.8-4.4], pphysical therapy session. Patients in the treatment group had a higher proportion of top-box HCAHPS scores in the following fields: nursing communication (33 of 36, 92% [95% CI, 78%-98%] versus 69%, 25 of 36 [95% CI, 52%-84%], p=0.035; risk ratio, 1.3 [95% CI of risk ratio, 1.0-1.7]; risk difference, 23% [95% CI of risk difference, 5%-40%]), pain management (34 of 36, 94% [95% CI, 81%-99%], versus 26 of 36, 72% [95% CI, 55%-86%], p=0.024; risk ratio, 1.3 [95

  7. One-year evaluation of the effect of physical therapy for masticatory muscle pain : A randomized controlled trial

    NARCIS (Netherlands)

    Craane, B.; Dijkstra, P. U.; Stappaerts, K.; De Laat, A.

    Physical therapy is widely used to decrease pain and restore function in patients suffering from masticatory muscle pain. Controlled studies on its efficacy are scarce. This study evaluated the 1-year effect of a 6-week physical therapy programme in a single blind, randomized, controlled trial.

  8. The effect of hormone replacement therapy on serum homocysteine levels in perimenopausal women : a randomized controlled trial

    NARCIS (Netherlands)

    Hak, AE; Bak, AAA; Lindemans, J; Planellas, J; Bennink, HJTC; Hofman, A; Grobbee, DE; Witteman, JCM

    2001-01-01

    Serum homocysteine levels may be lowered by hormone replacement therapy, but randomized controlled trial data are scarce. We performed a single center randomized placebo-controlled trial to assess the 6 months effect of hormone replacement therapy compared with placebo on fasting serum homocysteine

  9. The study of patient controlled analgesia undergoing interventional therapy for gynecology and obstetrics ailment

    International Nuclear Information System (INIS)

    She Shouzhang

    2006-01-01

    Uterine artery embolism is widely used for interventional therapy of gynecology and obstetrics ailment, but immediate incidence of pain occurs in 90% to 100% after uterine artery embolism and postoperative incidence of pain takes place from 80% to 90%. Patient controlled epidural analgesia (PCEA) could be adopted to treat pain with obviously outweighed effects over the traditional drug regimen or patient intravenous analgesia during the period of interventional therapy of uterine artery embolization. PCEA possesses good effect of analgesia and less adverse reaction and furthermore could eliminate or lessen the sufferings of patient and thus improve rehabilitation quality. Adding droperidol (0.005%) into the preparation of PCEA could decrease adverse effect incidence of nausea and vomiting; so it deserves recommendation for extending application in clinical interventional therapy. (authors)

  10. Mind-body therapies and control of inflammatory biology: A descriptive review.

    Science.gov (United States)

    Bower, Julienne E; Irwin, Michael R

    2016-01-01

    The use of mind-body therapies, including Tai Chi, Qigong, yoga, and meditation, has grown steadily in recent years. These approaches have been shown to be effective in reducing symptoms and improving quality of life, and research has begun to examine the impact of these therapies on biological processes, including inflammation. A review of 26 randomized controlled trials was conducted to describe the effects of mind-body therapies (MBTs) on circulating, cellular, and genomic markers of inflammation. This qualitative evaluation showed mixed effects of MBTs on circulating inflammatory markers, including CRP and IL-6, and on measures of stimulated cytokine production. More consistent findings were seen for genomic markers, with trials showing decreased expression of inflammation-related genes and reduced signaling through the proinflammatory transcription factor NF-κB. Potential mechanisms for these effects are discussed, including alterations in neuroendocrine, neural, and psychological and behavioral processes. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Budesonide and formoterol reduce early innate anti-viral immune responses in vitro.

    Directory of Open Access Journals (Sweden)

    Janet M Davies

    Full Text Available Asthma is a chronic inflammatory airways disease in which respiratory viral infections frequently trigger exacerbations. Current treatment of asthma with combinations of inhaled corticosteroids and long acting beta2 agonists improves asthma control and reduces exacerbations but what impact this might have on innate anti-viral immunity is unclear. We investigated the in vitro effects of asthma drugs on innate anti-viral immunity. Peripheral blood mononuclear cells (PBMC from healthy and asthmatic donors were cultured for 24 hours with the Toll-like receptor 7 agonist, imiquimod, or rhinovirus 16 (RV16 in the presence of budesonide and/or formoterol. Production of proinflammatory cytokines and expression of anti-viral intracellular signalling molecules were measured by ELISA and RT-PCR respectively. In PBMC from healthy donors, budesonide alone inhibited IP-10 and IL-6 production induced by imiquimod in a concentration-dependent manner and the degree of inhibition was amplified when budesonide and formoterol were used in combination. Formoterol alone had little effect on these parameters, except at high concentrations (10⁻⁶ M when IL-6 production increased. In RV16 stimulated PBMC, the combination of budesonide and formoterol inhibited IFNα and IP-10 production in asthmatic as well as healthy donors. Combination of budesonide and formoterol also inhibited RV16-stimulated expression of the type I IFN induced genes myxovirus protein A and 2', 5' oligoadenylate synthetise. Notably, RV16 stimulated lower levels of type Myxovirus A and oligoadenylate synthase in PBMC of asthmatics than control donors. These in vitro studies demonstrate that combinations of drugs commonly used in asthma therapy inhibit both early pro-inflammatory cytokines and key aspects of the type I IFN pathway. These findings suggest that budesonide and formoterol curtail excessive inflammation induced by rhinovirus infections in patients with asthma, but whether this inhibits

  12. HElmet therapy Assessment in infants with Deformed Skulls (HEADS: protocol for a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    van Wijk Renske M

    2012-07-01

    Full Text Available Abstract Background In The Netherlands, helmet therapy is a commonly used treatment in infants with skull deformation (deformational plagiocephaly or deformational brachycephaly. However, evidence of the effectiveness of this treatment remains lacking. The HEADS study (HElmet therapy Assessment in Deformed Skulls aims to determine the effects and costs of helmet therapy compared to no helmet therapy in infants with moderate to severe skull deformation. Methods/design Pragmatic randomised controlled trial (RCT nested in a cohort study. The cohort study included infants with a positional preference and/or skull deformation at two to four months (first assessment. At 5 months of age, all children were assessed again and infants meeting the criteria for helmet therapy were asked to participate in the RCT. Participants were randomly allocated to either helmet therapy or no helmet therapy. Parents of eligible infants that do not agree with enrolment in the RCT were invited to stay enrolled for follow up in a non-randomisedrandomised controlled trial (nRCT; they were then free to make the decision to start helmet therapy or not. Follow-up assessments took place at 8, 12 and 24 months of age. The main outcome will be head shape at 24 months that is measured using plagiocephalometry. Secondary outcomes will be satisfaction of parents and professionals with the appearance of the child, parental concerns about the future, anxiety level and satisfaction with the treatment, motor development and quality of life of the infant. Finally, compliance and costs will also be determined. Discussion HEADS will be the first study presenting data from an RCT on the effectiveness of helmet therapy. Outcomes will be important for affected children and their parents, health care professionals and future treatment policies. Our findings are likely to influence the reimbursement policies of health insurance companies. Besides these health outcomes, we will be able to

  13. A Randomized Controlled Trial of Acceptance-Based Behavior Therapy and Cognitive Therapy for Test Anxiety: A Pilot Study

    Science.gov (United States)

    Brown, Lily A.; Forman, Evan M.; Herbert, James D.; Hoffman, Kimberly L.; Yuen, Erica K.; Goetter, Elizabeth M.

    2011-01-01

    Many university students suffer from test anxiety that is severe enough to impair performance. Given mixed efficacy results of previous cognitive-behavior therapy (CBT) trials and a theoretically driven rationale, an acceptance-based behavior therapy (ABBT) approach was compared to traditional CBT (i.e., Beckian cognitive therapy; CT) for the…

  14. How to Control HTLV-1-Associated Diseases: Preventing de Novo Cellular Infection Using Antiviral Therapy

    Directory of Open Access Journals (Sweden)

    Amandine Pasquier

    2018-03-01

    Full Text Available Five to ten million individuals are infected by Human T-cell Leukemia Virus type 1 (HTLV-1. HTLV-1 is transmitted through prolonged breast-feeding, by sexual contacts and by transmission of infected T lymphocytes through blood transfusion. One to ten percent of infected carriers will develop a severe HTLV-1-associated disease: Adult-T-cell leukemia/lymphoma (ATLL, or a neurological disorder named Tropical Spastic Paraparesis/HTLV-1 Associated Myelopathy (TSP/HAM. In vivo, HTLV-1 is mostly detected in CD4+ T-cells, and to a lesser extent in CD8+ T cells and dendritic cells. There is a strong correlation between HTLV-1 proviral load (PVL and clinical status of infected individuals. Thus, reducing PVL could be part of a strategy to prevent or treat HTLV-1-associated diseases among carriers. Treatment of ATLL patients using conventional chemotherapy has very limited benefit. Some chronic and acute ATLL patients are, however, efficiently treated with a combination of interferon α and zidovudine (IFN-α/AZT, to which arsenic trioxide is added in some cases. On the other hand, no efficient treatment for TSP/HAM patients has been described yet. It is therefore crucial to develop therapies that could either prevent the occurrence of HTLV-1-associated diseases or at least block the evolution of the disease in the early stages. In vivo, reverse transcriptase (RT activity is low in infected cells, which is correlated with a clonal mode of viral replication. This renders infected cells resistant to nucleoside RT inhibitors such as AZT. However, histone deacetylase inhibitors (HDACi associated to AZT efficiently induces viral expression and prevent de novo cellular infection. In asymptomatic STLV-1 infected non-human primates, HDACi/AZT combination allows a strong decrease in the PVL. Unfortunately, rebound in the PVL occurs when the treatment is stopped, highlighting the need for better antiviral compounds. Here, we review previously used strategies

  15. A Randomized, Controlled Trial of Meditation Compared to Exposure Therapy and Education Control on PTSD in Veterans

    Science.gov (United States)

    2015-10-01

    score >45. Exclusion criteria: Service related trauma within last 3 months, history of schizophrenia, bipolar disorder , dementia, moderate or severe...7.7% 0.0% 8.3% 0.191 Bipolar disorder , % 7.7% 10.3% 13.9% 0.681 Substance use disorder , % 30.8% 43.6% 41.7% 0.458 Major depressive disorder ...Award Number: W81XWH-12-1-0576 TITLE: A Randomized, Controlled Trial of Meditation Compared to Exposure Therapy and Education Control on PTSD in

  16. Short-term additional enfuvirtide therapy is associated with a greater immunological recovery in HIV very late presenters: a controlled pilot study.

    Science.gov (United States)

    Bonora, S; Calcagno, A; Cometto, C; Fontana, S; Aguilar, D; D'Avolio, A; Gonzalez de Requena, D; Maiello, A; Dal Conte, I; Lucchini, A; Di Perri, G

    2012-02-01

    To evaluate whether the addition of enfuvirtide to standard highly active antiretroviral therapy (HAART) could confer immunovirological benefits in human immunodeficiency virus (HIV)-infected very late presenters. The current study is an open comparative therapeutic trial of standard protease inhibitor (PI)-based HAART ± additional enfuvirtide in treatment-naïve deeply immunologically impaired HIV-positive patients. Very late presenters (CD4 HIV RNA was intensively monitored in the first month, and, thereafter, monthly, as for CD4+ cell count and percentage, clinical data, and plasma drug concentrations. Of 22 enrolled patients (11 per arm), 19 completed the study (10 in the ENF arm). Baseline CD4+ cell counts and % were comparable, with 20 CD4+/mm(3) (12-37) and a percentage of 3.3 (1.7-7.1) in the ENF arm, and 16 CD4+/mm(3) (9-29) and a percentage of 3.1 (2.3-3.8) in the CO arm, respectively. The baseline viral load was also comparable between the two arms, with 5.77 log10 (5.42-6) and 5.39 log10 (5.06-6) in the ENF and CO arms, respectively. Enfuvirtide recipients had higher CD4+ percentage at week 8 (7.6 vs. 3.6%, p = 0.02) and at week 24 (10.7 vs. 5.9%, p = 0.02), and a greater CD4+ increase at week 24 (207 vs. 134 cells/mm(3), p = 0.04), with 70% of enfuvirtide intakers versus 12.5% of controls who achieved a CD4+ cell count >200/mm(3) (p = 0.01). At 48 weeks, patients in the ENF arm had CD4+ cell counts higher than controls (251 vs. 153cells/mm(3), p = 0.04) and were also found to be faster in reaching a CD4 cell count over 200/mm(3): 18 (8-24) versus 48 (36-108) weeks (p = 0.01). Viral load decay at week 4 was greater in the ENF arm (-3 vs. -2.2 log, p = 0.04), while the proportion of patients with viral load discovered HIV-positive patients with very low CD4+ cell counts. Induction strategies using an enfuvirtide-based approach in such subjects warrant further investigation.

  17. Music therapy for prisoners: pilot randomised controlled trial and implications for evaluating psychosocial interventions.

    Science.gov (United States)

    Gold, Christian; Assmus, Jörg; Hjørnevik, Kjetil; Qvale, Liv Gunnhild; Brown, Fiona Kirkwood; Hansen, Anita Lill; Waage, Leif; Stige, Brynjulf

    2014-12-01

    Mental health problems are common among prison inmates. Music therapy has been shown to reduce mental health problems. It may also be beneficial in the rehabilitation of prisoners, but rigorous outcome research is lacking. We compared group music therapy with standard care for prisoners in a pilot randomised controlled trial that started with the establishment of music therapy services in a prison near Bergen in 2008. In all, 113 prisoners agreed to participate. Anxiety (STAI-State [State-Trait Anxiety Inventory], STAI-Trait), depression (HADS-D [Hospital Anxiety and Depression Scale]), and social relationships (Quality of Life Enjoyment and Satisfaction Questionnaire [Q-LES-Q]) were assessed at baseline; every 2 weeks in the experimental group; after 1, 3, and 6 months in the control group; and at release. No restrictions were placed on the frequency, duration, or contents of music therapy. Duration of stay in the institution was short (62% stayed less than 1 month). Only a minority reached clinical cutoffs for anxiety and depression at baseline. Between-group analyses of effects were not possible. Music therapy was well accepted and attractive among the prisoners. Post hoc analysis of within-group changes suggested a reduction of state anxiety after 2 weeks of music therapy (d = 0.33, p = .025). Short sentences and low baseline levels of psychological disturbance impeded the examination of effects in this study. Recommendations for planning future studies are given, concerning the careful choice of participants, interventions and settings, comparison condition and design aspects, choice of outcomes, and integration of research approaches. Thus, the present study has important implications for future studies evaluating interventions for improving prisoners' mental health. ISRCTN22518605. © The Author(s) 2013.

  18. Massage therapy for fibromyalgia: a systematic review and meta-analysis of randomized controlled trials.

    Directory of Open Access Journals (Sweden)

    Yan-hui Li

    Full Text Available BACKGROUND: Although some studies evaluated the effectiveness of massage therapy for fibromyalgia (FM, the role of massage therapy in the management of FM remained controversial. OBJECTIVE: The purpose of this systematic review is to evaluate the evidence of massage therapy for patients with FM. METHODS: Electronic databases (up to June 2013 were searched to identify relevant studies. The main outcome measures were pain, anxiety, depression, and sleep disturbance. Two reviewers independently abstracted data and appraised risk of bias. The risk of bias of eligible studies was assessed based on Cochrane tools. Standardised mean difference (SMD and 95% confidence intervals (CI were calculated by more conservative random-effects model. And heterogeneity was assessed based on the I(2 statistic. RESULTS: Nine randomized controlled trials involving 404 patients met the inclusion criteria. The meta-analyses showed that massage therapy with duration ≥ 5 weeks significantly improved pain (SMD, 0.62; 95% CI 0.05 to 1.20; p = 0.03, anxiety (SMD, 0.44; 95% CI 0.09 to 0.78; p = 0.01, and depression (SMD, 0.49; 95% CI 0.15 to 0.84; p = 0.005 in patients with FM, but not on sleep disturbance (SMD, 0.19; 95% CI -0.38 to 0.75; p = 0.52. CONCLUSION: Massage therapy with duration ≥ 5 weeks had beneficial immediate effects on improving pain, anxiety, and depression in patients with FM. Massage therapy should be one of the viable complementary and alternative treatments for FM. However, given fewer eligible studies in subgroup meta-analyses and no evidence on follow-up effects, large-scale randomized controlled trials with long follow-up are warrant to confirm the current findings.

  19. Massage therapy for fibromyalgia: a systematic review and meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Li, Yan-hui; Wang, Feng-yun; Feng, Chun-qing; Yang, Xia-feng; Sun, Yi-hua

    2014-01-01

    Although some studies evaluated the effectiveness of massage therapy for fibromyalgia (FM), the role of massage therapy in the management of FM remained controversial. The purpose of this systematic review is to evaluate the evidence of massage therapy for patients with FM. Electronic databases (up to June 2013) were searched to identify relevant studies. The main outcome measures were pain, anxiety, depression, and sleep disturbance. Two reviewers independently abstracted data and appraised risk of bias. The risk of bias of eligible studies was assessed based on Cochrane tools. Standardised mean difference (SMD) and 95% confidence intervals (CI) were calculated by more conservative random-effects model. And heterogeneity was assessed based on the I(2) statistic. Nine randomized controlled trials involving 404 patients met the inclusion criteria. The meta-analyses showed that massage therapy with duration ≥ 5 weeks significantly improved pain (SMD, 0.62; 95% CI 0.05 to 1.20; p = 0.03), anxiety (SMD, 0.44; 95% CI 0.09 to 0.78; p = 0.01), and depression (SMD, 0.49; 95% CI 0.15 to 0.84; p = 0.005) in patients with FM, but not on sleep disturbance (SMD, 0.19; 95% CI -0.38 to 0.75; p = 0.52). Massage therapy with duration ≥ 5 weeks had beneficial immediate effects on improving pain, anxiety, and depression in patients with FM. Massage therapy should be one of the viable complementary and alternative treatments for FM. However, given fewer eligible studies in subgroup meta-analyses and no evidence on follow-up effects, large-scale randomized controlled trials with long follow-up are warrant to confirm the current findings.

  20. Dengue viral infections

    OpenAIRE

    Gurugama Padmalal; Garg Pankaj; Perera Jennifer; Wijewickrama Ananda; Seneviratne Suranjith

    2010-01-01

    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...

  1. Kinetics of viral shedding provide insights into the epidemiology of viral hemorrhagic septicemia in Pacific herring

    Science.gov (United States)

    Hershberger, Paul K.; Gregg, Jacob L.; Winton, James R.; Grady, Courtney; Collins, Rachael

    2010-01-01

    Losses from infectious diseases are an important component of natural mortality among marine fish species, but factors controlling the ecology of these diseases and their potential responses to anthropogenic changes are poorly understood. We used viral hemorrhagic septicemia virus (VHSV) and a laboratory stock of Pacific herring Clupea pallasii to investigate the kinetics of viral shedding and its effect on disease transmission and host mortality. Outbreaks of acute disease, accompanied by mortality and viral shedding, were initiated after waterborne exposure of herring to concentrations of VHSV as low as 101 plaque-forming units (pfu) ml–1. Shed virus in flow-through tanks was first detected 4 to 5 d post-exposure, peaked after 6 to 10 d, and was no longer detected after 16 d. Shedding rates, calculated from density, flow and waterborne virus titer reached 1.8 to 5.0 × 108 pfu fish–1 d–1. Onset of viral shedding was dose-dependent and preceded initial mortality by 2 d. At 21 d, cumulative mortality in treatment groups ranged from 81 to 100% and was dependent not on challenge dose, but on the kinetics and level of viral shedding by infected fish in the tank. Possible consequences of the viral shedding and disease kinetics are discussed in the context of epizootic initiation and perpetuation among populations of wild Pacific herring.

  2. A 2-arm, randomized, controlled trial of a motivational interviewing-based intervention to improve adherence to antiretroviral therapy (ART) among patients failing or initiating ART.

    Science.gov (United States)

    Golin, Carol E; Earp, Joanne; Tien, Hsiao-Chuan; Stewart, Paul; Porter, Carol; Howie, Lynn

    2006-05-01

    Motivational interviewing (MI) is a counseling technique that has been used effectively to change a number of health-related behaviors. We sought to assess the impact on patients' antiretroviral therapy (ART) adherence of a multicomponent, MI-based ART adherence intervention compared with that of an HIV informational control program. Two-arm, randomized, controlled trial. One hundred forty adult HIV-infected patients attending a large, academic center infectious diseases clinic who were either failing or newly initiating an ART regimen. STUDY ENDPOINTS: (1) Mean adherence level (% of prescribed doses take in the prior month) at the week 12 visit, (2) change in mean adherence, (3) percentage of patients achieving >95% adherence in the third 4-week block, and (4) change in viral load. The MI group's mean adherence improved by 4.5% compared with a decrease in the control group's adherence by 3.83% (P = 0.10). In the treatment group, 29% achieved >95% adherence compared with only 17% in the control group (P = 0.13). When we controlled for ethnicity, the intervention group had 2.75 times higher odds of achieving more than 95% adherence than did the controls (P = 0.045; 95% confidence interval: 1.023, 7.398). Although a number of mediating variables (beliefs about ART, coping style, social support, and goals set) had statistically significant changes in the expected direction in the MI group compared with controls, in the intent-to-treat analysis, the mean adherence at study exit for the intervention group was 76% (SD = 27%) and 71% (SD = 27%) for the control group (P = 0.62). Although not definitive, this study provides some evidence that MI offers an effective approach to improving adherence. Future studies able to build MI into the intervention for longer than 3 months may have a greater impact.

  3. Oral cryotherapy reduces mucositis and opioid use after myeloablative therapy--a randomized controlled trial.

    Science.gov (United States)

    Svanberg, Anncarin; Birgegård, Gunnar; Ohrn, Kerstin

    2007-10-01

    Mucositis is a major complication in myeloablative therapy, which often necessitates advanced pharmacological pain treatment, including i.v. opioids. Attempts to prevent oral mucositis have included oral cryotherapy, which has been shown to reduce mucositis, but there is a lack of knowledge concerning the effect of oral cryotherapy on opioid use by reducing the mucositis for patients treated with myeloablative therapy before bone marrow transplantation (BMT). The aim of the present study was to evaluate if oral cryotherapy could delay or alleviate the development of mucositis and thereby reduce the number of days with i.v. opioids among patients who receive myeloablative therapy before BMT. Eighty patients 18 years and older, scheduled for BMT, were included consecutively and randomised to oral cryotherapy or standard oral care. A stratified randomisation was used with regard to type of transplantation. Intensity of pain, severity of mucositis and use of opioids were recorded using pain visual analogue scale (VAS) scores, mucositis index scores and medical and nursing charts. This study showed that patients receiving oral cryotherapy had less pronounced mucositis and significantly fewer days with i.v. opioids than the control group. In the autologous setting, cryotherapy patients also needed significantly lower total dose of opioids. Oral cryotherapy is an effective and well-tolerated therapy to alleviate mucositis and consequently reduce the number of days with i.v. opioids among patients treated with myeloablative therapy before BMT.

  4. Efficacy of occupational therapy for patients with Parkinson's disease: a randomised controlled trial.

    Science.gov (United States)

    Sturkenboom, Ingrid H W M; Graff, Maud J L; Hendriks, Jan C M; Veenhuizen, Yvonne; Munneke, Marten; Bloem, Bastiaan R; Nijhuis-van der Sanden, Maria W

    2014-06-01

    There is insufficient evidence to support use of occupational therapy interventions for patients with Parkinson's disease. We aimed to assess the efficacy of occupational therapy in improving daily activities of patients with Parkinson's disease. We did a multicentre, assessor-masked, randomised controlled clinical trial in ten hospitals in nine Dutch regional networks of specialised health-care professionals (ParkinsonNet), with assessment at 3 months and 6 months. Patients with Parkinson's disease with self-reported difficulties in daily activities were included, along with their primary caregivers. Patients were randomly assigned (2:1) to the intervention or control group by a computer-generated minimisation algorithm. The intervention consisted of 10 weeks of home-based occupational therapy according to national practice guidelines; control individuals received usual care with no occupational therapy. The primary outcome was self-perceived performance in daily activities at 3 months, assessed with the Canadian Occupational Performance Measure (score 1-10). Data were analysed using linear mixed models for repeated measures (intention-to-treat principle). Assessors monitored safety by asking patients about any unusual health events during the preceding 3 months. This trial is registered with ClinicalTrials.gov, NCT01336127. Between April 14, 2011, and Nov 2, 2012, 191 patients were randomly assigned to the intervention group (n=124) or the control group (n=67). 117 (94%) of 124 patients in the intervention group and 63 (94%) of 67 in the control group had a participating caregiver. At baseline, the median score on the Canadian Occupational Performance Measure was 4·3 (IQR 3·5-5·0) in the intervention group and 4·4 (3·8-5·0) in the control group. At 3 months, these scores were 5·8 (5·0-6·4) and 4·6 (4·6-6·6), respectively. The adjusted mean difference in score between groups at 3 months was in favour of the intervention group (1·2; 95% CI 0·8-1·6

  5. The impact of occupational therapy in Parkinson's disease: a randomized controlled feasibility study.

    Science.gov (United States)

    Sturkenboom, Ingrid H; Graff, Maud J; Borm, George F; Veenhuizen, Yvonne; Bloem, Bastiaan R; Munneke, Marten; Nijhuis-van der Sanden, Maria W

    2013-02-01

    To evaluate the feasibility of a randomized controlled trial including process and potential impact of occupational therapy in Parkinson's disease. Process and outcome were quantitatively and qualitatively evaluated in an exploratory multicentre, two-armed randomized controlled trial at three months. Forty-three community-dwelling patients with Parkinson's disease and difficulties in daily activities, their primary caregivers and seven occupational therapists. Ten weeks of home-based occupational therapy according to the Dutch guidelines of occupational therapy in Parkinson's disease versus no occupational therapy in the control group. Process evaluation measured accrual, drop-out, intervention delivery and protocol adherence. Primary outcome measures of patients assessed daily functioning: Canadian Occupational Performance Measure (COPM) and Assessment of Motor and Process Skills. Primary outcome for caregivers was caregiver burden: Zarit Burden Inventory. Participants' perspectives of the intervention were explored using questionnaires and in-depth interviews. Inclusion was 23% (43/189), drop-out 7% (3/43) and unblinding of assessors 33% (13/40). Full intervention protocol adherence was 74% (20/27), but only 60% (71/119) of baseline Canadian Occupational Performance Measure priorities were addressed in the intervention. The outcome measures revealed negligible to small effects in favour of the intervention group. Almost all patients and caregivers of the intervention group were satisfied with the results. They perceived: 'more grip on the situation' and used 'practical advices that make life easier'. Therapists were satisfied, but wished for a longer intervention period. The positive perceived impact of occupational therapy warrants a large-scale trial. Adaptations in instructions and training are needed to use the Canadian Occupational Performance Measure as primary outcome measure.

  6. Effects of Voice Rehabilitation After Radiation Therapy for Laryngeal Cancer: A Randomized Controlled Study

    International Nuclear Information System (INIS)

    Tuomi, Lisa; Andréll, Paulin; Finizia, Caterina

    2014-01-01

    Background: Patients treated with radiation therapy for laryngeal cancer often experience voice problems. The aim of this randomized controlled trial was to assess the efficacy of voice rehabilitation for laryngeal cancer patients after having undergone radiation therapy and to investigate whether differences between different tumor localizations with regard to rehabilitation outcomes exist. Methods and Materials: Sixty-nine male patients irradiated for laryngeal cancer participated. Voice recordings and self-assessments of communicative dysfunction were performed 1 and 6 months after radiation therapy. Thirty-three patients were randomized to structured voice rehabilitation with a speech-language pathologist and 36 to a control group. Furthermore, comparisons with 23 healthy control individuals were made. Acoustic analyses were performed for all patients, including the healthy control individuals. The Swedish version of the Self Evaluation of Communication Experiences after Laryngeal Cancer and self-ratings of voice function were used to assess vocal and communicative function. Results: The patients who received vocal rehabilitation experienced improved self-rated vocal function after rehabilitation. Patients with supraglottic tumors who received voice rehabilitation had statistically significant improvements in voice quality and self-rated vocal function, whereas the control group did not. Conclusion: Voice rehabilitation for male patients with laryngeal cancer is efficacious regarding patient-reported outcome measurements. The patients experienced better voice function after rehabilitation. Patients with supraglottic tumors also showed an improvement in terms of acoustic voice outcomes. Rehabilitation with a speech-language pathologist is recommended for laryngeal cancer patients after radiation therapy, particularly for patients with supraglottic tumors

  7. Effects of Voice Rehabilitation After Radiation Therapy for Laryngeal Cancer: A Randomized Controlled Study

    Energy Technology Data Exchange (ETDEWEB)

    Tuomi, Lisa, E-mail: lisa.tuomi@vgregion.se [Department of Otorhinolaryngology, Head and Neck Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Gothenburg (Sweden); Andréll, Paulin [Department of Molecular and Clinical Medicine/Multidisciplinary Pain Center, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Gothenburg (Sweden); Finizia, Caterina [Department of Otorhinolaryngology, Head and Neck Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Gothenburg (Sweden)

    2014-08-01

    Background: Patients treated with radiation therapy for laryngeal cancer often experience voice problems. The aim of this randomized controlled trial was to assess the efficacy of voice rehabilitation for laryngeal cancer patients after having undergone radiation therapy and to investigate whether differences between different tumor localizations with regard to rehabilitation outcomes exist. Methods and Materials: Sixty-nine male patients irradiated for laryngeal cancer participated. Voice recordings and self-assessments of communicative dysfunction were performed 1 and 6 months after radiation therapy. Thirty-three patients were randomized to structured voice rehabilitation with a speech-language pathologist and 36 to a control group. Furthermore, comparisons with 23 healthy control individuals were made. Acoustic analyses were performed for all patients, including the healthy control individuals. The Swedish version of the Self Evaluation of Communication Experiences after Laryngeal Cancer and self-ratings of voice function were used to assess vocal and communicative function. Results: The patients who received vocal rehabilitation experienced improved self-rated vocal function after rehabilitation. Patients with supraglottic tumors who received voice rehabilitation had statistically significant improvements in voice quality and self-rated vocal function, whereas the control group did not. Conclusion: Voice rehabilitation for male patients with laryngeal cancer is efficacious regarding patient-reported outcome measurements. The patients experienced better voice function after rehabilitation. Patients with supraglottic tumors also showed an improvement in terms of acoustic voice outcomes. Rehabilitation with a speech-language pathologist is recommended for laryngeal cancer patients after radiation therapy, particularly for patients with supraglottic tumors.

  8. Massage therapy for patients with metastatic cancer: a pilot randomized controlled trial.

    Science.gov (United States)

    Toth, Maria; Marcantonio, Edward R; Davis, Roger B; Walton, Tracy; Kahn, Janet R; Phillips, Russell S

    2013-07-01

    The study objectives were to determine the feasibility and effects of providing therapeutic massage at home for patients with metastatic cancer. This was a randomized controlled trial. Patients were enrolled at Oncology Clinics at a large urban academic medical center; massage therapy was provided in patients' homes. Subjects were patients with metastatic cancer. There were three interventions: massage therapy, no-touch intervention, and usual care. Primary outcomes were pain, anxiety, and alertness; secondary outcomes were quality of life and sleep. In this study, it was possible to provide interventions for all patients at home by professional massage therapists. The mean number of massage therapy sessions per patient was 2.8. A significant improvement was found in the quality of life of the patients who received massage therapy after 1-week follow-up, which was not observed in either the No Touch control or the Usual Care control groups, but the difference was not sustained at 1 month. There were trends toward improvement in pain and sleep of the patients after therapeutic massage but not in patients in the control groups. There were no serious adverse events related to the interventions. The study results showed that it is feasible to provide therapeutic massage at home for patients with advanced cancer, and to randomize patients to a no-touch intervention. Providing therapeutic massage improves the quality of life at the end of life for patients and may be associated with further beneficial effects, such as improvement in pain and sleep quality. Larger randomized controlled trials are needed to substantiate these findings.

  9. Radioiodine therapy versus antithyroid drugs in Graves' disease: a meta-analysis of randomized controlled trials

    Science.gov (United States)

    Qin, Lan

    2016-01-01

    Objective: This meta-analysis was performed to compare radioiodine therapy with antithyroid drugs in terms of clinical outcomes, including development or worsening of ophthalmopathy, hyperthyroid cure rate, hypothyroidism, relapse rate and adverse events. Methods: Randomized controlled trials (RCTs) published in PubMed, Embase, Web of Science, SinoMed and National Knowledge Infrastructure, China, were systematically reviewed to compare the effects of radioiodine therapy with antithyroid drugs in patients with Graves' disease. Results were expressed as risk ratio with 95% confidence intervals (CIs) and weighted mean differences with 95% CIs. Pooled estimates were performed using a fixed-effects model or random-effects model, depending on the heterogeneity among studies. Results: 17 RCTs involving 4024 patients met the inclusion criteria and were included. Results showed that radioiodine treatment has increased risk in new ophthalmopathy, development or worsening of ophthalmopathy and hypothyroidism. Whereas, compared with antithyroid drugs, radioiodine treatment seems to have a higher hyperthyroid cure rate, lower recurrence rate and lower incidence of adverse events. Conclusion: Radioiodine therapy is associated with a higher hyperthyroid cure rate and lower relapse rate compared with antithyroid drugs. However, it also increases the risk of ophthalmopathy and hypothyroidism. Advances in knowledge: Considering that antithyroid drug treatment can be associated with unsatisfactory control of hyperthyroidism, we would recommend radioiodine therapy as the treatment of choice for patients with Graves' disease. PMID:27266544

  10. Luminescent nanoprobes for thermal bio-sensing: Towards controlled photo-thermal therapies

    Energy Technology Data Exchange (ETDEWEB)

    Jaque, Daniel, E-mail: daniel.jaque@uam.es [Fluorescence Imaging Group, Departamento de Fisica de Materiales, Universidad Autonoma de Madrid, Madrid 28049 (Spain); Grupo de Fotônica e Fluidos Complexos (GFFC), Instituto de Física, Universidade Federal de Alagoas, 57072-900 Maceió-AL (Brazil); Jacinto, Carlos [Grupo de Fotônica e Fluidos Complexos (GFFC), Instituto de Física, Universidade Federal de Alagoas, 57072-900 Maceió-AL (Brazil)

    2016-01-15

    Photo-thermal therapies, based on the light-induced local heating of cancer tumors and tissues, are nowadays attracting an increasing attention due to their effectiveness, universality, and low cost. In order to avoid undesirable collateral damage in the healthy tissues surrounding the tumors, photo-thermal therapies should be achieved while monitoring tumor’s temperature in such a way that thermal therapy could be stopped before reaching the damage limit. Measuring tumor temperature is not an easy task at all and novel strategies should be adopted. In this work it is demonstrated how luminescent nanoparticles, in particular Neodymium doped LaF{sub 3} nanoparticles, could be used as multi-functional agents capable of simultaneous heating and thermal sensing. Advantages and disadvantages of such nanoparticles are discussed and the future perspectives are briefly raised. - Highlights: • Thermal control is essential in novel photo-thermal therapies. • Thermal control and heating can be achieved by Neodymium doped nanoparticles. • Perspectives of Neodymium doped nanoparticles in potential in vivo applications are discussed.

  11. The Effect of Deep Oscillation Therapy in Fibrocystic Breast Disease. A Randomized Controlled Clinical Trial

    Directory of Open Access Journals (Sweden)

    Solangel Hernandez

    2018-02-01

    Full Text Available Introduction: Fibrocystic breast disease is the most widespread disorder in women during their phase of sexual maturity. Deep oscillation (DO therapy has been used on patients who have undergone an operation for breast cancer as a special form of manual lymphatic drainage. Method: Experimental, prospective case-control studies were conducted in 401 women diagnosed with fibrocystic breast disease. The sample was selected at random and was divided into three groups, a study group and two control groups. Results: Pain was reduced in the three therapies applied. This was statistically significant in the study group. The sonography study presented a predominance of its fibrous form. Upon completion of the treatment a resolution of the fibrosis was observed in the study group. The women were using their bra in an incorrect manner. Conclusions: Pain was reduced in the three therapies applied. In the study group this reduction was statistically significant. It is possible to verify the magnitude of the resonant vibration in the connective tissue from surface to deep layers by viewing the effect of the deep oscillations through the use of diagnostic ultrasound. The most frequent sonographic finding was fibrosis. Deep oscillation therapy produces a tissue-relaxing, moderate vasoconstriction effect, favours local oedema reabsorption and fibrosis reduction. A factor that may affect breast pain is incorrect bra use. The majority of women studied were using their bra incorrectly.

  12. A Randomized Controlled Comparison of Integrative Cognitive-Affective Therapy and Cognitive-Behavioral Therapy-Enhanced for Bulimia Nervosa

    Science.gov (United States)

    Wonderlich, Stephen A.; Peterson, Carol B.; Crosby, Ross D.; Smith, Tracey L.; Klein, Marjorie H.; Mitchell, James E.; Crow, Scott J.

    2016-01-01

    Background The purpose of this investigation was to compare a new psychotherapy for bulimia nervosa, Integrative Cognitive-Affective Therapy (ICAT), with an established treatment, Cognitive-Behavioral Therapy-Enhanced (CBT-E). Method Eighty adults with symptoms of bulimia nervosa were randomized to ICAT or CBT-E for 21 sessions over 19 weeks. Bulimic symptoms, measured by the Eating Disorder Examination, were assessed at baseline, end of treatment, and 4-month follow-up. Treatment outcome, as measured by binge eating frequency, purging frequency, global eating disorder severity, emotion regulation, self-oriented cognition, depression, anxiety, and self-esteem, was determined using generalized estimating equations, logistic regression, and a general linear model (intent-to-treat). Results Both treatments were associated with significant improvement in bulimic symptoms as well as all measures of outcome, and no statistically significant differences were observed between the two conditions at end of treatment or follow-up. Intent-to-treat abstinence rates for ICAT (37.5% at end of treatment, 32.5% at follow-up) and CBT-E (22.5% at both end of treatment and follow-up) were not significantly different. Conclusions ICAT was associated with significant improvements in bulimic and associated symptoms that did not differ from those obtained with CBT-E. This initial randomized controlled trial of a new individual psychotherapy for bulimia nervosa suggests that targeting emotion and self-oriented cognition in the context of nutritional rehabilitation may be efficacious and worthy of further study. PMID:23701891

  13. CHAMP: Cognitive behaviour therapy for health anxiety in medical patients, a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Murphy David

    2011-06-01

    Full Text Available Abstract Background Abnormal health anxiety, also called hypochondriasis, has been successfully treated by cognitive behaviour therapy (CBT in patients recruited from primary care, but only one pilot trial has been carried out among those attending secondary medical clinics where health anxiety is likely to be more common and have a greater impact on services. The CHAMP study extends this work to examine both the clinical and cost effectiveness of CBT in this population. Method/Design The study is a randomized controlled trial with two parallel arms and equal randomization of 466 eligible patients (assuming a 20% drop-out to an active treatment group of 5-10 sessions of cognitive behaviour therapy and to a control group. The aim at baseline, after completion of all assessments but before randomization, was to give a standard simple explanation of the nature of health anxiety for all participants. Subsequently the control group was to receive whatever care might usually be available in the clinics, which is normally a combination of clinical assessment, appropriate tests and reassurance. Those allocated to the active treatment group were planned to receive between 5 and 10 sessions of an adapted form of cognitive behaviour therapy based on the Salkovskis/Warwick model, in which a set of treatment strategies are chosen aimed at helping patients understand the factors that drive and maintain health anxiety. The therapy was planned to be given by graduate research workers, nurses or other health professionals trained for this intervention whom would also have their competence assessed independently during the course of treatment. The primary outcome is reduction in health anxiety symptoms after one year and the main secondary outcome is the cost of care after two years. Discussion This represents the first trial of adapted cognitive behaviour therapy in health anxiety that is large enough to test not only the clinical benefits of treatment but also

  14. Feasibility, Safety, and Compliance in a Randomized Controlled Trial of Physical Therapy for Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Jennifer L. McGinley

    2012-01-01

    Full Text Available Both efficacy and clinical feasibility deserve consideration in translation of research outcomes. This study evaluated the feasibility of rehabilitation programs within the context of a large randomized controlled trial of physical therapy. Ambulant participants with Parkinson's disease (PD (n=210 were randomized into three groups: (1 progressive strength training (PST; (2 movement strategy training (MST; or (3 control (“life skills”. PST and MST included fall prevention education. Feasibility was evaluated in terms of safety, retention, adherence, and compliance measures. Time to first fall during the intervention phase did not differ across groups, and adverse effects were minimal. Retention was high; only eight participants withdrew during or after the intervention phase. Strong adherence (attendance >80% did not differ between groups (P=.435. Compliance in the therapy groups was high. All three programs proved feasible, suggesting they may be safely implemented for people with PD in community-based clinical practice.

  15. Viral marketing as epidemiological model

    OpenAIRE

    Rodrigues, Helena Sofia; Fonseca, Manuel

    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...

  16. Avances recientes en HIV/SIDA: Patogénesis, historia natural y carga viral

    Directory of Open Access Journals (Sweden)

    Rafael E Campo

    1996-10-01

    Full Text Available Results of recent investigations have given us a new understanding of the pathogenesis of HIV infection. This findings provide us with a kinetic model of pathogenesis in which continuous, high-grade viral replication. This findings provide us with a kinetic model of pathogenesis in which continuous, high-grade viral replication is the principal force driving the destruction of CD4 lymphocytes. This knowledge will lead us to design better treatment strategies directed to curtail viral replication and prevent the emergence of viral resistance, and the use of combination antiretroviral therapy is a first example of these new strategies. The concept of viral load is introduced, and we discuss the usefulness of viral load in the clinical prognosis of this disease, and its use as an aid in the decision-making process when starling or mordifyng antiretroviral therapy in our patients. (Rev Med Hered 1996; 7: 182-188.

  17. Association of Insulin Pump Therapy vs Insulin Injection Therapy With Severe Hypoglycemia, Ketoacidosis, and Glycemic Control Among Children, Adolescents, and Young Adults With Type 1 Diabetes.

    Science.gov (United States)

    Karges, Beate; Schwandt, Anke; Heidtmann, Bettina; Kordonouri, Olga; Binder, Elisabeth; Schierloh, Ulrike; Boettcher, Claudia; Kapellen, Thomas; Rosenbauer, Joachim; Holl, Reinhard W

    2017-10-10

    Insulin pump therapy may improve metabolic control in young patients with type 1 diabetes, but the association with short-term diabetes complications is unclear. To determine whether rates of severe hypoglycemia and diabetic ketoacidosis are lower with insulin pump therapy compared with insulin injection therapy in children, adolescents, and young adults with type 1 diabetes. Population-based cohort study conducted between January 2011 and December 2015 in 446 diabetes centers participating in the Diabetes Prospective Follow-up Initiative in Germany, Austria, and Luxembourg. Patients with type 1 diabetes younger than 20 years and diabetes duration of more than 1 year were identified. Propensity score matching and inverse probability of treatment weighting analyses with age, sex, diabetes duration, migration background (defined as place of birth outside of Germany or Austria), body mass index, and glycated hemoglobin as covariates were used to account for relevant confounders. Type 1 diabetes treated with insulin pump therapy or with multiple (≥4) daily insulin injections. Primary outcomes were rates of severe hypoglycemia and diabetic ketoacidosis during the most recent treatment year. Secondary outcomes included glycated hemoglobin levels, insulin dose, and body mass index. Of 30 579 patients (mean age, 14.1 years [SD, 4.0]; 53% male), 14 119 used pump therapy (median duration, 3.7 years) and 16 460 used insulin injections (median duration, 3.6 years). Patients using pump therapy (n = 9814) were matched with 9814 patients using injection therapy. Pump therapy, compared with injection therapy, was associated with lower rates of severe hypoglycemia (9.55 vs 13.97 per 100 patient-years; difference, -4.42 [95% CI, -6.15 to -2.69]; P young patients with type 1 diabetes, insulin pump therapy, compared with insulin injection therapy, was associated with lower risks of severe hypoglycemia and diabetic ketoacidosis and with better glycemic control during the

  18. Recruitment to Online Therapies for Depression: Pilot Cluster Randomized Controlled Trial

    OpenAIRE

    Jones, Ray B; Goldsmith, Lesley; Hewson, Paul; Williams, Christopher J

    2013-01-01

    Background Raising awareness of online cognitive behavioral therapy (CBT) could benefit many people with depression, but we do not know how purchasing online advertising compares to placing free links from relevant local websites in increasing uptake. Objective To pilot a cluster randomized controlled trial (RCT) comparing purchase of Google AdWords with placing free website links in raising awareness of online CBT resources for depression in order to better understand research design issues....

  19. Behavior therapy for children with Tourette disorder: a randomized controlled trial.

    Science.gov (United States)

    Piacentini, John; Woods, Douglas W; Scahill, Lawrence; Wilhelm, Sabine; Peterson, Alan L; Chang, Susanna; Ginsburg, Golda S; Deckersbach, Thilo; Dziura, James; Levi-Pearl, Sue; Walkup, John T

    2010-05-19

    Tourette disorder is a chronic and typically impairing childhood-onset neurologic condition. Antipsychotic medications, the first-line treatments for moderate to severe tics, are often associated with adverse effects. Behavioral interventions, although promising, have not been evaluated in large-scale controlled trials. To determine the efficacy of a comprehensive behavioral intervention for reducing tic severity in children and adolescents. Randomized, observer-blind, controlled trial of 126 children recruited from December 2004 through May 2007 and aged 9 through 17 years, with impairing Tourette or chronic tic disorder as a primary diagnosis, randomly assigned to 8 sessions during 10 weeks of behavior therapy (n = 61) or a control treatment consisting of supportive therapy and education (n = 65). Responders received 3 monthly booster treatment sessions and were reassessed at 3 and 6 months following treatment. Comprehensive behavioral intervention. Yale Global Tic Severity Scale (range 0-50, score >15 indicating clinically significant tics) and Clinical Global Impressions-Improvement Scale (range 1 [very much improved] to 8 [very much worse]). Behavioral intervention led to a significantly greater decrease on the Yale Global Tic Severity Scale (24.7 [95% confidence interval {CI}, 23.1-26.3] to 17.1 [95% CI, 15.1-19.1]) from baseline to end point compared with the control treatment (24.6 [95% CI, 23.2-26.0] to 21.1 [95% CI, 19.2-23.0]) (P tic worsening was reported by 4% of children (5/126). Treatment gains were durable, with 87% of available responders to behavior therapy exhibiting continued benefit 6 months following treatment. A comprehensive behavioral intervention, compared with supportive therapy and education, resulted in greater improvement in symptom severity among children with Tourette and chronic tic disorder. clinicaltrials.gov Identifier: NCT00218777.

  20. Group art therapy as an adjunctive treatment for people with schizophrenia: a randomised controlled trial (MATISSE).

    OpenAIRE

    Crawford, MJ; Killaspy, H; Barnes, TR; Barrett, B; Byford, S; Clayton, K; Dinsmore, J; Floyd, S; Hoadley, A; Johnson, T; Kalaitzaki, E; King, M; Leurent, B; Maratos, A; O'Neill, FA

    2012-01-01

    OBJECTIVE To examine the clinical effectiveness and cost-effectiveness of referral to group art therapy plus standard care, compared with referral to an activity group plus standard care and standard care alone, among people with schizophrenia. DESIGN A three-arm, parallel group, single-blind, pragmatic, randomised controlled trial. Participants were randomised via an independent and remote telephone randomisation service using permuted blocks, stratified by study centre. SETTING Study partic...

  1. Group therapy task training versus individual task training during inpatient stroke rehabilitation: a randomised controlled trial.

    Science.gov (United States)

    Renner, Caroline Ie; Outermans, Jacqueline; Ludwig, Ricarda; Brendel, Christiane; Kwakkel, Gert; Hummelsheim, Horst

    2016-07-01

    To compare the efficacy of intensive daily applied progressive group therapy task training with equally dosed individual progressive task training on self-reported mobility for patients with moderate to severe stroke during inpatient rehabilitation. Randomized controlled clinical trial. In-patient rehabilitation center. A total of 73 subacute patients with stroke who were not able to walk without physical assistance at randomisation. Patients were allocated to group therapy task training (GT) or individual task training (IT). Both interventions were intended to improve walking competency and comprised 30 sessions of 90 minutes over six weeks. Primary outcome was the mobility domain of the Stroke Impact Scale (SIS-3.0). Secondary outcomes were the other domains of SIS-3.0, standing balance, gait speed, walking distance, stair climbing, fatigue, anxiety and depression. No adverse events were reported in either arm of the trial. There were no significant differences between groups for the SIS mobility domain at the end of the intervention (Z= -0.26, P = 0.79). No significant differences between groups were found in gait speed improvements (GT:0.38 ±0.23; IT:0.26±0.35), any other gait related parameters, or in non-physical outcomes such as depression and fatigue. Inpatient group therapy task training for patients with moderate to severe stroke is safe and equally effective as a dose-matched individual task training therapy. Group therapy task training may be delivered as an alternative to individual therapy or as valuable adjunct to increase time spent in gait-related activities. © The Author(s) 2015.

  2. Stability of rapid maxillary expansion and facemask therapy: a long-term controlled study.

    Science.gov (United States)

    Masucci, Caterina; Franchi, Lorenzo; Defraia, Efisio; Mucedero, Manuela; Cozza, Paola; Baccetti, Tiziano

    2011-10-01

    The aim of this prospective controlled study was to evaluate the long-term effects of rapid maxillary expansion and facemask therapy in Class III subjects. Twenty-two subjects (9 boys, 13 girls; mean age, 9.2 years ± 1.6) with Class III disharmony were treated consecutively with rapid maxillary expansion and facemask therapy followed by fixed appliances. The patients were reevaluated at the end of the 2-phase treatment (mean age, 14.5 years ± 1.9) and then recalled about 8.5 years after the end of rapid maxillary expansion and facemask treatment (mean age, 18.7 years ± 2.1). Two groups of controls with untreated Class III malocclusion were used for statistical comparisons of the short-term and long-term intervals. Statistical comparisons were performed with the Mann-Whitney U test. In the long term, no significant differences in maxillary changes were recorded, whereas the treatment group showed significantly smaller increases in mandibular protrusion. The sagittal maxillomandibular skeletal variables maintained significant improvements in the treatment group vs the control groups. In the long term, rapid maxillary expansion and facemask therapy led to successful outcomes in about 73% of the Class III patients. Favorable skeletal changes were mainly due to significant improvements in the sagittal position of the mandible. Copyright © 2011 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  3. Life-review therapy with computer supplements for depression in the elderly: a randomized controlled trial.

    Science.gov (United States)

    Preschl, Barbara; Maercker, Andreas; Wagner, Birgit; Forstmeier, Simon; Baños, Rosa M; Alcañiz, Mariano; Castilla, Diana; Botella, Cristina

    2012-01-01

    Life-review therapy has been recognized as an effective therapeutic approach for depression in older adults. Additionally, the use of new media is becoming increasingly common in psychological interventions. The aim of this study was to investigate a life-review therapy in a face-to-face setting with additional computer use. This study explored whether a six-week life-review therapy with computer supplements from the e-mental health Butler system constitutes an effective approach to treat depression in older adults aged 65 and over. A total of 36 participants with elevated levels of depressive symptoms were randomized to a treatment group or a waiting-list control group and completed the post-assessment. Fourteen individuals in the intervention group completed the follow-up assessment. Analyses revealed significant changes from pre- to post-treatment or follow-up for depression, well-being, self-esteem, and obsessive reminiscence, but not for integrative reminiscence and life satisfaction. Depressive symptoms decreased significantly over time until the three-month follow-up in the intervention group compared to the control group (pre to post: d = 1.13; pre to follow-up: d = 1.27; and group × time effect pre to post: d = 0.72). Furthermore, the therapy led to an increase in well-being and a decrease in obsessive reminiscence among the participants in the intervention group from pre-treatment to follow-up (well-being: d = 0.70; obsessive reminiscence: d = 0.93). Analyses further revealed a significant but small group × time effect regarding self-esteem (d = 0.19). By and large, the results indicate that the life-review therapy in this combined setting could be recommended for depressive older adults.

  4. Economic evaluation of occupational therapy in Parkinson's disease: A randomized controlled trial.

    Science.gov (United States)

    Sturkenboom, Ingrid H W M; Hendriks, Jan C M; Graff, Maud J L; Adang, Eddy M M; Munneke, Marten; Nijhuis-van der Sanden, Maria W G; Bloem, Bastiaan R

    2015-07-01

    A large randomized clinical trial (the Occupational Therapy in Parkinson's Disease [OTiP] study) recently demonstrated that home-based occupational therapy improves perceived performance in daily activities of people with Parkinson's disease (PD). The aim of the current study was to evaluate the cost-effectiveness of this intervention. We performed an economic evaluation over a 6-month period for both arms of the OTiP study. Participants were 191 community-dwelling PD patients and 180 primary caregivers. The intervention group (n = 124 patients) received 10 weeks of home-based occupational therapy; the control group (n = 67 patients) received usual care (no occupational therapy). Costs were assessed from a societal perspective including healthcare use, absence from work, informal care, and intervention costs. Health utilities were evaluated using EuroQol-5d. We estimated cost differences and cost utility using linear mixed models and presented the net monetary benefit at different values for willingness to pay per quality-adjusted life-year gained. In our primary analysis, we excluded informal care hours because of substantial missing data for this item. The estimated mean total costs for the intervention group compared with controls were €125 lower for patients, €29 lower for caregivers, and €122 higher for patient-caregiver pairs (differences not significant). At a value of €40,000 per quality-adjusted life-year gained (reported threshold for PD), the net monetary benefit of the intervention per patient was €305 (P = 0.74), per caregiver €866 (P = 0.01) and per patient-caregiver pair €845 (P = 0.24). In conclusion, occupational therapy did not significantly impact on total costs compared with usual care. Positive cost-effectiveness of the intervention was only significant for caregivers. © 2015 International Parkinson and Movement Disorder Society.

  5. A randomized controlled trial of stretch-and-flow voice therapy for muscle tension dysphonia.

    Science.gov (United States)

    Watts, Christopher R; Hamilton, Amy; Toles, Laura; Childs, Lesley; Mau, Ted

    2015-06-01

    To investigate the effect of stretch-and-flow voice therapy on vocal function and handicap. Randomized controlled trial. Participants with primary muscle tension dysphonia were randomly assigned to experimental or control groups. Experimental participants received vocal hygiene education followed by 6 weeks of stretch-and-flow voice therapy. Control participants received vocal hygiene education only. Outcome variables consisted of a measure of vocal handicap (Voice Handicap Index [VHI]), maximum phonation time, s/z ratio, and acoustic measures. All measures were obtained at baseline prior to treatment and within 2 weeks posttreatment or at the end of the control period. The pre- to posttreatment measurement change (delta Δ) was applied to statistical analyses. A multivariate analysis of variance revealed significant group differences in pre-to-post changes on measures of VHI, maximum phonation time, and cepstral peak prominence (CPP) in connected speech and vowels (P = 0.003, 0.013, 0.025, and 0.017 respectively), with a significant reduction of VHI (Cohen's d = 1.6), increase in maximum phonation time (Cohen's d = 1.2), increase of CPP in connected speech (Cohen's d = 1.2), and increase of CPP in vowels (Cohen's d = 1.1) in the experimental group compared to the control group. This preliminary small sample randomized controlled trial found significantly greater improvement in vocal handicap, maximum phonation time, and acoustic measures of vocal function after participants received stretch-and-flow voice therapy compared to participants receiving vocal hygiene education alone. Additional research incorporating larger samples will be needed to confirm and further investigate these findings. 1b. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

  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. Copyright © 2011 Elsevier España S.L. All rights reserved.

  7. Equine viral arteritis

    Directory of Open Access Journals (Sweden)

    Kosec Marjan

    2016-01-01

    Full Text Available Equine viral arteritis (EVA is a contagious disease of equids caused by equine artheritis virus (EAV, widespread in most countries in the world, where patients are diagnosed. The infection usually starts asymptomatic. Clinical signs indicate respiratory infection of different intensity and also abortions are present at different stages of gestation. Large prevalence of this disease in the world has become a growing economic problem. The disease is specific to a particular kind of animals, and it affects only equids (horses, donkeys, mules, mule and zebras. In countries where the infection has been confirmed, the percentage of positive animals differ. Likewise, there is difference in percentage among certain animal kinds. The highest percentage of positive animals has been found in totters and the lowest in cold-blooded.

  8. Viral pathogen discovery

    Science.gov (United States)

    Chiu, Charles Y

    2015-01-01

    Viral pathogen discovery is of critical importance to clinical microbiology, infectious diseases, and public health. Genomic approaches for pathogen discovery, including consensus polymerase chain reaction (PCR), microarrays, and unbiased next-generation sequencing (NGS), have the capacity to comprehensively identify novel microbes present in clinical samples. Although numerous challenges remain to be addressed, including the bioinformatics analysis and interpretation of large datasets, these technologies have been successful in rapidly identifying emerging outbreak threats, screening vaccines and other biological products for microbial contamination, and discovering novel viruses associated with both acute and chronic illnesses. Downstream studies such as genome assembly, epidemiologic screening, and a culture system or animal model of infection are necessary to establish an association of a candidate pathogen with disease. PMID:23725672

  9. Early Detection of Viral Hepatitis Can Save Lives - PSA (:30)

    Centers for Disease Control (CDC) Podcasts

    2010-05-12

    Early detection of viral hepatitis can help prevent liver damage, cirrhosis, and even liver cancer.  Created: 5/12/2010 by Centers for Disease Control and Prevention (CDC).   Date Released: 5/12/2010.

  10. Early Experience With CliniMACS Prodigy CCS (IFN-gamma) System in Selection of Virus-specific T Cells From Third-party Donors for Pediatric Patients With Severe Viral Infections After Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Kállay, Krisztián; Kassa, Csaba; Réti, Marienn; Karászi, Éva; Sinkó, János; Goda, Vera; Stréhn, Anita; Csordás, Katalin; Horváth, Orsolya; Szederjesi, Attila; Tasnády, Szabolcs; Hardi, Apor; Kriván, Gergely

    2018-04-01

    Viral reactivation is a frequent complication of allogeneic hematopoietic stem cell transplantation especially in children. For refractory cases, rapid virus-specific T-cell therapy would be ideally implemented within a few days. Over the course of a year in our pediatric cohort of 43 allogeneic transplantation, 9 patients fulfilled criteria for virus-specific T-cell therapy. Viral infections were due to cytomegalovirus (CMV) in 3, Epstein-Barr virus (EBV) in 2, and adenovirus (AdV) in 1 case, whereas >1 virus was detected in 3 cases. Viral diseases necessitating a T-cell therapy were CMV pneumonitis and colitis, AdV enteritis and cystitis, and EBV-induced posttransplantation lymphoproliferative disease. Cells were produced by the CliniMACS Prodigy CCS (IFN-gamma) System within 24 hours after mononuclear leukapheresis. Eight patients became completely asymptomatic, whereas 7 also cleared the virus. Six patients are alive without viral illness or sequelae demonstrating viral DNA clearance in peripheral blood with a median follow-up of 535 (350-786) days. One patient with CMV pneumonitis died of respiratory insufficiency. In 2 cases the viral illness improved or cleared, however, the patients died of invasive aspergillosis. No cases of graft-versus-host disease, rejection, organ toxicity, or recurrent infection were noticed. Virus-specific T-cell therapy implemented by the CliniMACS Prodigy CCS (IFN-gamma) System is an automated, fast, safe, and probably effective way to control resistant viral diseases after pediatric hematopoietic stem cell transplantation.

  11. The TOPSHOCK study: Effectiveness of radial shockwave therapy compared to focused shockwave therapy for treating patellar tendinopath - design of a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Diercks Ron L

    2011-10-01

    Full Text Available Abstract Background Patellar tendinopathy is a chronic overuse injury of the patellar tendon that is especially prevalent in people who are involved in jumping activities. Extracorporeal Shockwave Therapy is a relatively new treatment modality for tendinopathies. It seems to be a safe and promising part of the rehabilitation program for patellar tendinopathy. Extracorporeal Shockwave Therapy originally used focused shockwaves. Several years ago a new kind of shockwave therapy was introduced: radial shockwave therapy. Studies that investigate the effectiveness of radial shockwave therapy as treatment for patellar tendinopathy are scarce. Therefore the aim of this study is to compare the effectiveness of focussed shockwave therapy and radial shockwave therapy as treatments for patellar tendinopathy. Methods/design The TOPSHOCK study (Tendinopathy Of Patella SHOCKwave is a two-armed randomised controlled trial in which the effectiveness of focussed shockwave therapy and radial shockwave therapy are directly compared. Outcome assessors and patients are blinded as to which treatment is given. Patients undergo three sessions of either focused shockwave therapy or radial shockwave therapy at 1-week intervals, both in combination with eccentric decline squat training. Follow-up measurements are scheduled just before treatments 2 and 3, and 1, 4, 7 and 12 weeks after the final treatment. The main outcome measure is the Dutch VISA-P questionnaire, which asks for pain, function and sports participation in subjects with patellar tendinopathy. Secondary outcome measures are pain determined with a VAS during ADL, sports and decline squats, rating of subjective improvement and overall satisfaction with the treatment. Patients will also record their sports activities, pain during and after these activities, and concurrent medical treatment on a weekly basis in a web-based diary. Results will be analysed according to the intention-to-treat principle. Discussion

  12. Music-supported therapy in the rehabilitation of subacute stroke patients: a randomized controlled trial.

    Science.gov (United States)

    Grau-Sánchez, Jennifer; Duarte, Esther; Ramos-Escobar, Neus; Sierpowska, Joanna; Rueda, Nohora; Redón, Susana; Veciana de Las Heras, Misericordia; Pedro, Jordi; Särkämö, Teppo; Rodríguez-Fornells, Antoni

    2018-04-01

    The effect of music-supported therapy (MST) as a tool to restore hemiparesis of the upper extremity after a stroke has not been appropriately contrasted with conventional therapy. The aim of this trial was to test the effectiveness of adding MST to a standard rehabilitation program in subacute stroke patients. A randomized controlled trial was conducted in which patients were randomized to MST or conventional therapy in addition to the rehabilitation program. The intensity and duration of the interventions were equated in both groups. Before and after 4 weeks of treatment, motor and cognitive functions, mood, and quality of life (QoL) of participants were evaluated. A follow-up at 3 months was conducted to examine the retention of motor gains. Both groups significantly improved their motor function, and no differences between groups were found. The only difference between groups was observed in the language domain for QoL. Importantly, an association was encountered between the capacity to experience pleasure from music activities and the motor improvement in the MST group. MST as an add-on treatment showed no superiority to conventional therapies for motor recovery. Importantly, patient's intrinsic motivation to engage in musical activities was associated with better motor improvement. © 2018 New York Academy of Sciences.

  13. Effect of biomagnetic therapy versus physiotherapy for treatment of knee osteoarthritis: a randomized controlled trial.

    Science.gov (United States)

    Gremion, Gerald; Gaillard, David; Leyvraz, Pierre-Francois; Jolles, Brigitte M

    2009-11-01

    To assess the effectiveness of pulsed signal therapy in the treatment of knee osteoarthritis (Kellgren II or III). A randomized, double-blind controlled clinical trial. The first 95 patients sent to the clinic with knee osteo-arthritis were selected and randomized into treatment with pulsed signal therapy or conventional physiotherapy. Assessment included recording of usual demographic data, pertinent history, baseline medication and radiographs. Clinical evaluation was made at baseline, 6 weeks and 6 months after the end of treatment by the same blinded doctor. At each follow-up time, the patient was asked to complete a visual analogue pain scale and a Lequesne score. The doctor recorded the degree of pain on motion and the ability to move the affected knee. Both treatments resulted in significant improvements in pain and physical function. A statistical difference was observed only for activities of daily living, where the physiotherapy was more efficient (pphysiotherapy. Like physiotherapy, pulsed signal therapy has improved the clinical state of treated patients but with no significant statistical difference. Pulsed signal therapy is, however, more expensive.

  14. Radiation therapy for primary carcinoma of the eyelid. Tumor control and visual function

    Energy Technology Data Exchange (ETDEWEB)

    Hata, M.; Koike, I.; Odagiri, K.; Kasuya, T.; Minagawa, Y.; Kaizu, H.; Mukai, Y.; Inoue, T. [Yokohama City Univ. Graduate School of Medicine, Kanagawa (Japan). Dept. of Radiology; Maegawa, J. [Yokohama City Univ. Graduate School of Medicine, Kanagawa (Japan). Dept. of Plastic and Reconstructive Surgery; Kaneko, A. [Yokohama City Univ. Graduate School of Medicine, Kanagawa (Japan). Dept. of Ophthalmology

    2012-12-15

    Background and purpose: Surgical excision remains the standard and most reliable curative treatment for eyelid carcinoma, but frequently causes functional and cosmetic impairment of the eyelid. We therefore investigated the efficacy and safety of radiation therapy in eyelid carcinoma. Patients and methods: Twenty-three patients with primary carcinoma of the eyelid underwent radiation therapy. Sebaceous carcinoma was histologically confirmed in 16 patients, squamous cell carcinoma in 6, and basal cell carcinoma in 1. A total dose of 50-66.6 Gy (median, 60 Gy) was delivered to tumor sites in 18-37 fractions (median, 30 fractions). Results: All but 3 of the 23 patients had survived at a median follow-up period of 49 months. The overall survival and local progression-free rates were 87% and 93% at 2 years, and 80% and 93% at 5 years, respectively. Although radiation-induced cataracts developed in 3 patients, visual acuity in the other patients was relatively well preserved. There were no other therapy-related toxicities of grade 3 or greater. Conclusion: Radiation therapy is safe and effective for patients with primary carcinoma of the eyelid. It appears to contribute to prolonged survival as a result of good tumor control, and it also facilitates functional and cosmetic preservation of the eyelid. (orig.)

  15. The effect of burn rehabilitation massage therapy on hypertrophic scar after burn: a randomized controlled trial.

    Science.gov (United States)

    Cho, Yoon Soo; Jeon, Jong Hyun; Hong, Aram; Yang, Hyeong Tae; Yim, Haejun; Cho, Yong Suk; Kim, Do-Hern; Hur, Jun; Kim, Jong Hyun; Chun, Wook; Lee, Boung Chul; Seo, Cheong Hoon

    2014-12-01

    To evaluate the effect of burn rehabilitation massage therapy on hypertrophic scar after burn. One hundred and forty-six burn patients with hypertrophic scar(s) were randomly divided into an experimental group and a control group. All patients received standard rehabilitation therapy for hypertrophic scars and 76 patients (massage group) additionally received burn scar rehabilitation massage therapy. Both before and after the treatment, we determined the scores of visual analog scale (VAS) and itching scale and assessed the scar characteristics of thickness, melanin, erythema, transepidermal water loss (TEWL), sebum, and elasticity by using ultrasonography, Mexameter(®), Tewameter(®), Sebumeter(®), and Cutometer(®), respectively. The scores of both VAS and itching scale decreased significantly in both groups, indicating a significant intragroup difference. With regard to the scar characteristics, the massage group showed a significant decrease after treatment in scar thickness, melanin, erythema, TEWL and a significant intergroup difference. In terms of scar elasticity, a significant intergroup difference was noted in immediate distension and gross skin elasticity, while the massage group significant improvement in skin distensibility, immediate distension, immediate retraction, and delayed distension. Our results suggest that burn rehabilitation massage therapy is effective in improving pain, pruritus, and scar characteristics in hypertrophic scars after burn. Copyright © 2014 Elsevier Ltd and ISBI. All rights reserved.

  16. The effects of improvisational music therapy on joint attention behaviors in autistic children: A randomized controlled study

    DEFF Research Database (Denmark)

    Kim, Jinah; Wigram, Tony; Gold, Christian

    2008-01-01

    The purpose of this study was to investigate the effects of improvisational music therapy on joint attention behaviors in pre-school children with autism. It was a randomized controlled study employing a single subject comparison design in two different conditions, improvisational music therapy a...... skills in children than play. Session analysis showed significantly more and lengthier events of eye contact and turn-taking in improvisational music therapy than play sessions. The implications of these findings are discussed further....

  17. Phase II Pragmatic Randomized Controlled Trial of Patient-Led Therapies (Mirror Therapy and Lower-Limb Exercises) During Inpatient Stroke Rehabilitation.

    Science.gov (United States)

    Tyson, Sarah; Wilkinson, Jack; Thomas, Nessa; Selles, Ruud; McCabe, Candy; Tyrrell, Pippa; Vail, Andy

    2015-10-01

    Patient-led therapy has the potential to increase the amount of therapy patients undertake during stroke rehabilitation and to enhance recovery. Our objective was to assess the feasibility and acceptability of 2 patient-led therapies during the acute stages of stroke care: mirror therapy for the upper limb and lower-limb exercises for the lower limb. This was a blind assessed, multicenter, pragmatic randomized controlled trial of patient-led upper-limb mirror therapy and patient-led lower leg exercises. Stroke survivors with upper and lower limb limitations, undergoing inpatient rehabilitation and able to consent were recruited at least 1 week poststroke. Both interventions proved feasible, with >90% retention. No serious adverse events were reported. Both groups did less therapy than recommended; typically 5 to 15 minutes for 7 days or less. Participants receiving mirror therapy (n = 63) tended to do less practice than those doing lower-limb exercises (n = 31). Those with neglect did 69% less mirror therapy than those without (P = .02), which was not observed in the exercise group. Observed between-group differences were modest but neglect, upper-limb strength, and dexterity showed some improvement in the mirror therapy group. No changes were seen in the lower-limb group. Both patient-led mirror therapy and lower-limb exercises during inpatient stroke care are safe, feasible, and acceptable and warrant further investigation. Practice for 5 to 15 minutes for 7 days is a realistic prescription unless strategies to enhance adherence are included. © The Author(s) 2015.

  18. Metabolic control after years of completing a clinical trial on sensor-augmented pump therapy.

    Science.gov (United States)

    Quirós, Carmen; Giménez, Marga; Orois, Aida; Conget, Ignacio

    2015-11-01

    Sensor-augmented pump (SAP) therapy has been shown to be effective and safe for improving metabolic control in patients with type 1 diabetes mellitus (T1DM) in a number of trials. Our objective was to assess glycemic control in a group of T1DM patients on insulin pump or SAP therapy after years of participating in the SWITCH (Sensing With Insulin pump Therapy To Control HbA1c) trial and their return to routine medical monitoring. A retrospective, observational study of 20 patients who participated in the SWITCH trial at our hospital from 2008 to 2010. HbA1c values were compared at the start, during (at the end of the periods with/without SAP use - Sensor On/Sensor Off period respectively - of the cross-over design), and 3 years after study completion. HbA1c values of patients who continued SAP therapy (n=6) or only used insulin pump (n=14) were also compared. Twenty patients with T1DM (44.4±9.3 years, 60% women, baseline HbA1c level 8.43±0.55%) were enrolled into the SWITCH study). Three years after study completion, HbA1c level was 7.79±0.77 in patients on pump alone, with no significant change from the value at the end of the Off period of the study (7.85±0.57%; p=0.961). As compared to the end of the On period, HbA1c worsened less in patients who remained on SAP than in those on pump alone (0.18±0.42 vs. 0.55±0.71%; p=0.171), despite the fact that levels were similar at study start (8.41±0.60 vs. 8.47±0.45; p=0.831) and at the end of the On period (7.24±0.48 vs. 7.38±0.61; p=0.566). Frequency of CGM use in patients who continued SAP therapy was high (61.2% of the time in the last 3 months). Our study suggests that the additional benefit of SAP therapy achieved in a clinical trial may persist in the long term in routine clinical care of patients with T1DM. Copyright © 2015 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

  19. Effectiveness of occupational therapy in Parkinson's disease: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Sturkenboom, Ingrid H W M; Graff, Maud J; Borm, George F; Adang, Eddy M M; Nijhuis-van der Sanden, Maria W G; Bloem, Bastiaan R; Munneke, Marten

    2013-02-02

    Occupational therapists may have an added value in the care of patients with Parkinson's disease whose daily functioning is compromised, as well as for their immediate caregivers. Evidence for this added value is inconclusive due to a lack of rigorous studies. The aim of this trial is to evaluate the (cost) effectiveness of occupational therapy in improving daily functioning of patients with Parkinson's disease. A multicenter, assessor-blinded, two-armed randomized controlled clinical trial will be conducted, with evaluations at three and six months. One hundred ninety-two home-dwelling patients with Parkinson's disease and with an occupational therapy indication will be assigned to the experimental group or to the control group (2:1). Patients and their caregivers in the experimental group will receive ten weeks of home-based occupational therapy according to recent Dutch guidelines. The intervention will be delivered by occupational therapists who have been specifically trained to treat patients according to these guidelines. Participants in the control group will not receive occupational therapy during the study period. The primary outcome for the patient is self-perceived daily functioning at three months, assessed with the Canadian Occupational Performance Measure. Secondary patient-related outcomes include: objective performance of daily activities, self-perceived satisfaction with performance in daily activities, participation, impact of fatigue, proactive coping skills, health-related quality of life, overall quality of life, health-related costs, and effectiveness at six months. All outcomes at the caregiver level will be secondary and will include self-perceived burden of care, objective burden of care, proactive coping skills, overall quality of life, and care-related costs. Effectiveness will be evaluated using a covariance analysis of the difference in outcome at three months. An economic evaluation from a societal perspective will be conducted, as

  20. Use of Play Therapy in Nursing Process: A Prospective Randomized Controlled Study.

    Science.gov (United States)

    Sezici, Emel; Ocakci, Ayse Ferda; Kadioglu, Hasibe

    2017-03-01

    Play therapy is a nursing intervention employed in multidisciplinary approaches to develop the social, emotional, and behavioral skills of children. In this study, we aim to determine the effects of play therapy on the social, emotional, and behavioral skills of pre-school children through the nursing process. A single-blind, prospective, randomized controlled study was undertaken. The design, conduct, and reporting of this study adhere to the Consolidated Standards of Reporting Trials (CONSORT) guidelines. The participants included 4- to 5-year-old kindergarten children with no oral or aural disabilities and parents who agreed to participate in the study. The Pre-school Child and Family Identification Form and Social Competence and the Behavior Evaluation Scale were used to gather data. Games in the play therapy literature about nursing diagnoses (fear, social disturbance, impaired social interactions, ineffective coping, anxiety), which were determined after the preliminary test, constituted the application of the study. There was no difference in the average scores of the children in the experimental and control groups in their Anger-Aggression (AA), Social Competence (SC), and Anxiety-Withdrawal (AW) scores beforehand (t = 0.015, p = .988; t = 0.084, p = .933; t = 0.214, p = .831, respectively). The difference between the average AA and SC scores in the post-test (t = 2.041, p = .045; t = 2.692, p = .009, respectively), and the retests were statistically significant in AA and SC average scores in the experimental and control groups (t = 4.538, p = .000; t = 4.693; p = .000, respectively). In AW average scores, no statistical difference was found in the post-test (t = 0.700, p = .486), whereas in the retest, a significant difference was identified (t = 5.839, p = .000). Play therapy helped pre-school children to improve their social, emotional, and behavioral skills. It also provided benefits for the children to decrease their fear and anxiety levels, to improve

  1. Effective therapy to reduce edema after total knee arthroplasty Multi-layer compression therapy or standard therapy with cool pack - a randomized controlled pilot trial

    Science.gov (United States)

    Stocker, Brigitta; Babendererde, Christine; Rohner-Spengler, Manuela; Müller, Urs W; Meichtry, André; Luomajoki, Hannu

    2018-02-01

    Background: After total knee arthroplasty (TKA) efficient control and reduction of postoperative edema is of great importance. Aim: The aim of this pilot study (EKNZ 2014 – 225 DRKS00006271) was to investigate the effectiveness of multi-layer compression therapy (MLCT) to reduce edema in the early period after surgery compared to the standard treatment with Cool Pack. Methods: In this randomized controlled pilot trial, sixteen patients after TKA were randomized into an intervention group (IG) or a control group (CG). Circumferential measurements were used to assess edema. Secondary outcomes were range of motion (ROM), pain (numeric rating scale, NRS) and function as measured with the fast Self Paced Walking Test (fSPWT). Results: Clinically relevant differences in edema reduction between the two groups were found in the early postoperative period and at the six weeks follow up. Six days postoperatively the group time interaction (IE) in favor of the IG were −3.8 cm (95 % CI: −5.1; −2.4) when measured 10 cm proximal to the joint space and −2.7 cm (CI: −4.1; −1.3) when measured 5 cm proximally. We further observed differences in secondary outcomes in favor of the CG. Six days postoperatively the IE for knee flexion was –8.3 ° (CI: −22.0; 5.4) and for the fSPWT it was 12.8 seconds (CI: −16.4; 41.3). Six weeks postoperatively these differences diminished. Conclusions: The findings suggest that MLCT could be an alternative treatment to reduce postoperative edema in patients after total knee arthroplasty. Eventually possible negative effects on early knee flexion and function must be considered.

  2. KSHV Rta promoter specification and viral reactivation

    Directory of Open Access Journals (Sweden)

    Jonathan eGuito

    2012-02-01

    Full Text Available Viruses are obligate intracellular pathogens whose biological success depends upon replication and packaging of viral genomes, and transmission of progeny viruses to new hosts. The biological success of herpesviruses is enhanced by their ability to reproduce their genomes without producing progeny viruses or killing the host cells, a process called latency. Latency permits a herpesvirus to remain undetected in its animal host for decades while maintaining the potential to reactivate, or switch, to a productive life cycle when host conditions are conducive to generating viral progeny. Direct interactions between many host and viral molecules are implicated in controlling herpesviral reactivation, suggesting complex biological networks that control the decision. One viral protein that is necessary and sufficient to switch latent KSHV into the lytic infection cycle is called K-Rta. Rta is a transcriptional activator that specifies promoters by binding direct DNA directly and interacting with cellular proteins. Among these cellular proteins, binding of K-Rta to RBP-Jk is essential for viral reactivation.. In contrast to the canonical model for Notch signaling, RBP-Jk is not uniformly and constitutively bound to the latent KSHV genome, but rather is recruited to DNA by interactions with K-Rta. Stimulation of RBP-Jk DNA binding requires high affinity binding of Rta to repetitive and palindromic CANT DNA repeats in promoters, and formation of ternary complexes with RBP-Jk. However, while K-Rta expression is necessary for initiating KSHV reactivation, K-Rta’s role as the switch is inefficient. Many factors modulate K-Rta’s function, suggesting that KSHV reactivation can be significantly regulated post-Rta expression and challenging the notion that herpesviral reactivation is bistable. This review analyzes rapidly evolving research on KSHV K-Rta to consider the role of K-Rta promoter specification in regulating the progression of KSHV reactivation.

  3. MRI Customized Play Therapy in Children Reduces the Need for Sedation--A Randomized Controlled Trial.

    Science.gov (United States)

    Bharti, Bhavneet; Malhi, Prahbhjot; Khandelwal, N

    2016-03-01

    To evaluate the effectiveness of an MRI-specific play therapy intervention on the need for sedation in young children. All children in the age group of 4-10 y, who were advised an MRI scan over a period of one year were randomized. Exclusion criteria included children with neurodevelopmental disorders impairing cognition and children who had previously undergone diagnostic MRI. A total of 79 children were randomized to a control or an intervention condition. The intervention involved familiarizing the child with the MRI model machine, listing the steps involved in the scan to the child in vivid detail, training the child to stand still for 5 min, and conducting several dry runs with a doll or a favorite toy. The study was approved by the Institute ethical committee. The need for sedation was 41 % (n = 16) in the control group and this declined to 20 % (n = 8) in the intervention group (χ(2) = 4.13; P = 0.04). The relative risk of sedation decreased by 49 % in the intervention group as compared to the control group (RR 0.49; 95 % CI: 0.24-1.01) and this difference was statistically significant (P = 0.04). The absolute risk difference in sedation use between intervention and control group was 21 % (95 % CI 1.3 %-40.8 %). Even on adjusting for age, relative risk of sedation remained significantly lower in children undergoing play therapy as compared to the control (RR 0.57, 95 % CI: 0.32-0.98) with P value of 0.04. The use of an MRI customized play therapy with pediatric patients undergoing diagnostic MRI resulted in significant reduction of the use of sedation.

  4. Reinforcement Behavior Therapy by Kindergarten Teachers on Preschool Children’s Aggression: A Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Shahrzad Yektatalab

    2016-01-01

    Full Text Available Background: Aggression is a kind of behavior that causes damage or harm to others. The prevalence of aggression is 8–20% in 3–6 years old children. The present study aimed to assess the effect of training kindergarten teachers regarding reinforcement behavior therapy on preschoolers’ aggression. Methods: In this cluster randomized control trial, 14 out of 35 kindergarten and preschool centers of Mohr city, Iran, were chosen using random cluster sampling and then randomly assigned to an intervention and a control group. All 370 kindergarten and preschool children in 14 kindergarten were assessed by preschoolers’ aggression questionnaire and 60 children who obtained a minimum aggression score of 117.48 for girls and 125.77 for boys were randomly selected. The teachers in the intervention group participated in 4 educational sessions on behavior therapy and then practiced this technique under the supervision of the researcher for two months. Preschoolers’ aggression questionnaire was computed in both intervention and control groups before and after a two-month period. Results: The results demonstrated a significant statistical difference in the total aggression score (P=0.01, verbal (P=0.02 and physical (P=0.01 aggression subscales scores in the intervention group in comparison to the control group after the intervention. But the scores of relational aggression (P=0.09 and impulsive anger (P=0.08 subscales were not statistically different in the intervention group compared to the controls. Conclusion: This study highlighted the importance of teaching reinforcement behavior therapy by kindergarten teachers in decreasing verbal and physical aggression in preschoolers.

  5. Treating acute stress disorder and posttraumatic stress disorder with cognitive behavioral therapy or structured writing therapy: A randomized controlled trial

    NARCIS (Netherlands)

    van Emmerik, A.A.P.; Kamphuis, J.H.; Emmelkamp, P.M.G.

    2008-01-01

    Background: Writing assignments have shown promising results in treating traumatic symptomatology. Yet no studies have compared their efficacy to the current treatment of choice, cognitive behavior therapy (CBT). The present study evaluated the efficacy of structured writing therapy (SWT) and CBT as

  6. Nonablative 1550-nm fractional laser therapy versus triple topical therapy for the treatment of melasma: A randomized controlled pilot study

    NARCIS (Netherlands)

    Kroon, Marije W.; Wind, Bas S.; Beek, Johan F.; van der Veen, J. P. Wietze; Nieuweboer-Krobotová, Ludmila; Bos, Jan D.; Wolkerstorfer, Albert

    2011-01-01

    Various treatments are currently available for melasma. However, results are often disappointing. We sought to assess the efficacy and safety of nonablative 1550-nm fractional laser therapy and compare results with those obtained with triple topical therapy (the gold standard). Twenty female

  7. Analysis of host genetic diversity and viral entry as sources of between-host variation in viral load

    Science.gov (United States)

    Wargo, Andrew R.; Kell, Alison M.; Scott, Robert J.; Thorgaard, Gary H.; Kurath, Gael

    2012-01-01

    Little is known about the factors that drive the high levels of between-host variation in pathogen burden that are frequently observed in viral infections. Here, two factors thought to impact viral load variability, host genetic diversity and stochastic processes linked with viral entry into the host, were examined. This work was conducted with the aquatic vertebrate virus, Infectious hematopoietic necrosis virus (IHNV), in its natural host, rainbow trout. It was found that in controlled in vivo infections of IHNV, a suggestive trend of reduced between-fish viral load variation was observed in a clonal population of isogenic trout compared to a genetically diverse population of out-bred trout. However, this trend was not statistically significant for any of the four viral genotypes examined, and high levels of fish-to-fish variation persisted even in the isogenic trout population. A decrease in fish-to-fish viral load variation was also observed in virus injection challenges that bypassed the host entry step, compared to fish exposed to the virus through the natural water-borne immersion route of infection. This trend was significant for three of the four virus genotypes examined and suggests host entry may play a role in viral load variability. However, high levels of viral load variation also remained in the injection challenges. Together, these results indicate that although host genetic diversity and viral entry may play some role in between-fish viral load variation, they are not major factors. Other biological and non-biological parameters that may influence viral load variation are discussed.

  8. Role of olmesartan in combination therapy in blood pressure control and vascular function

    Directory of Open Access Journals (Sweden)

    Carlos M Ferrario

    2010-08-01

    Full Text Available Carlos M Ferrario, Ronald D SmithWake Forest University School of Medicine, Winston-Salem, North Carolina, USAAbstract: Angiotensin receptor blockers have emerged as a first-line therapy in the management of hypertension and hypertension-related comorbidities. Since national and international guidelines have stressed the need to control blood pressure to <140/90 mmHg in uncomplicated hypertension and <130/80 mmHg in those with associated comorbidities such as diabetes or chronic kidney disease, these goal blood pressures can only be achieved through combination therapy. Of several drugs that can be effectively combined to attain the recommended blood pressure goals, fixed-dose combinations of angiotensin receptor blockers and the calcium channel blocker amlodipine provide additive antihypertensive effects associated with a safe profile and increased adherence to therapy. In this article, we review the evidence regarding the beneficial effects of renin–angiotensin system blockade with olmesartan medoxomil and amlodipine in terms of blood pressure control and improvement of vascular function and target organ damage.Keywords: amlodipine, angiotensin receptor blockers, angiotensin-converting enzyme 2, hypertension, renin–angiotensin system

  9. De novo assembly of viral quasispecies using overlap graphs

    NARCIS (Netherlands)

    J.A. Baaijens (Jasmijn); A.Z. El Aabidine (Amal Zine); E. Rivals (Eric); A. Schönhuth (Alexander)

    2017-01-01

    textabstractAviral quasispecies, the ensemble of viral strains populating an infected person, can be highly diverse. For optimal assessment of virulence, pathogenesis, and therapy selection, determining the haplotypes of the individual strains can play a key role. As many viruses are subject to high

  10. Sensor-augmented pump therapy lowers HbA(1c) in suboptimally controlled Type 1 diabetes; a randomized controlled trial

    NARCIS (Netherlands)

    Hermanides, J.; Nørgaard, K.; Bruttomesso, D.; Mathieu, C.; Frid, A.; Dayan, C. M.; Diem, P.; Fermon, C.; Wentholt, I. M. E.; Hoekstra, J. B. L.; DeVries, J. H.

    2011-01-01

    To investigate the efficacy of sensor-augmented pump therapy vs. multiple daily injection therapy in patients with suboptimally controlled Type 1 diabetes. In this investigator-initiated multi-centre trial (the Eurythmics Trial) in eight outpatient centres in Europe, we randomized 83 patients with

  11. Profile of HIV-1 RNA viral load among HIV-TB co-infected patients in ...

    African Journals Online (AJOL)

    Profile of HIV-1 RNA viral load among HIV-TB co-infected patients in a tertiary health facility in Maiduguri, Northeastern Nigeria. ... This study aims to estimate the HIV-1 RNA viral load and impact of anti TB therapy (ATT) ... HOW TO USE AJOL.

  12. Mortality of treated HIV-1 positive individuals according to viral subtype in Europe and Canada

    DEFF Research Database (Denmark)

    Obel, Niels

    2016-01-01

    OBJECTIVES: To estimate prognosis by viral subtype in HIV-1-infected individuals from start of antiretroviral therapy (ART) and after viral failure. DESIGN: Collaborative analysis of data from eight European and three Canadian cohorts. METHODS: Adults (N>20 000) who started triple ART between 199...

  13. The Effects of Improvisational Music Therapy on Joint Attention Behaviors in Autistic Children: A Randomized Controlled Study

    Science.gov (United States)

    Kim, Jinah; Wigram, Tony; Gold, Christian

    2008-01-01

    The purpose of this study was to investigate the effects of improvisational music therapy on joint attention behaviors in pre-school children with autism. It was a randomized controlled study employing a single subject comparison design in two different conditions, improvisational music therapy and play sessions with toys, and using standardized…

  14. [YANG's pricking-cupping therapy for knee osteoarthritis: a multi-center randomized controlled trial].

    Science.gov (United States)

    Wang, Bo; Liu, Xiru; Hu, Zhihai; Sun, Aijun; Ma, Yanwen; Chen Yingying; Zhang, Xuzhi; Liu, Meiling; Wang, Yi; Wang, Shuoshuo; Zhang, Yunjia; Li, Yijing; Shen, Weidong

    2016-02-01

    To evaluate the clinical efficacy of YANG's pricking-cupping therapy for knee osteoar thritis (KOA). Methods This was a multi-center randomized parallel controlled trial. One hundred and seventy one patients with KOA were randomly allocated to a pricking-cupping group (89 cases) and a conventional acu puncture group (82 cases). Neixiyan (EX-LE 4), Dubi (ST 35) and ashi points were selected in the two groups. Patients in the pricking-cupping group were treated with YANG's pricking-cupping therapy; the seven-star needles were used to perform pricking at acupoints, then cupping was used until slight bleeding was observed. Patients in the conventional acupuncture group were treated with semi-standardized filiform needle therapy. The treatment was given for 4 weeks (from a minimum of 5 times to a maximum of 10 times). The follow-up visit was 4 weeks. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the visual analogue scale (VAS) were adopted for the efficacy assessments. The pain score, stiffness score, physical function score and total score of WOMAC were all reduced after 4-week treatment and during follow-up visit in the two groups (all P0. 05), each score and total score of WOMAC in the pricking-cupping group were lower than those in the conventional acupuncture group after 4-week treatment and during follow-up visit (Pcupping group were lower than those in the conventional acupuncture group after 4-week treatment and during follow-up visit (P cupping and conventional acupuncture therapy can both significantly improve knee joint pain and function in patients with KOA, which are relatively safe. The pricking cupping therapy is superior to conventional acupuncture with the identical selection of acupoints.

  15. Results of the quality control treatments plans in volume arc therapy modulated for thirty treated patients

    International Nuclear Information System (INIS)

    Fenoglietto, P.; Ailleres, N.; Simeon, S.; Santoro, L.; Dubois, J.B.; Azria, D.

    2009-01-01

    The intensity modulated radiotherapy (I.M.R.T.) provided by voluminal arc therapy was implemented at the Val d'Aurelle regional center against cancer in november 2008. In May 2009 more than 30 patients have benefited from this technique in our institution and for each of them, the dosimetry planing has been checked under the accelerator before the treatment. The analysis of these results of measures under accelerators equipped of 120 leave collimators and for optimizations realised with the Rapid-arc computer code from Varian. The issue of a treatment in intensity modulation by voluminal arc therapy gives satisfying results falling within the range of those previously found in conventional I.M.R.T.. Besides, the quality control is faster because of lesser number of beams to verify. (N.C.)

  16. Group Singing as a Therapy during Diabetes Training--A Randomized Controlled Pilot Study.

    Science.gov (United States)

    Groener, J B; Neus, I; Kopf, S; Hartmann, M; Schanz, J; Kliemank, E; Wetekam, B; Kihm, L; Fleming, T; Herzog, W; Nawroth, P P

    2015-11-01

    Comprehensive diabetes treatment has been shown to reduce quality of life in diabetic patients. However, there is evidence to suggest that group singing can have positive effects on quality of life in various clinical settings. In this randomized controlled pilot study, the effect of singing as a therapy to reduce stress and improve quality of life was investigated in insulin-dependent diabetic patients, undergoing a lifestyle intervention program. Patients from the singing group felt less discontented following treatment. This effect, however, was lost after 3 months. No effect on serum cortisol and plasma adrenocorticotropic hormone (ACTH) levels could be seen when comparing the singing group with the control group, although reduced levels of ACTH and cortisol 3 days after treatment could be found and were still present after 3 months within the group of patients who undertook singing as a therapy. Singing led to an increase in bodyweight, which interestingly had no effect on glucose control or methylglyoxal levels. Therefore, singing during a lifestyle intervention program for insulin-dependent diabetic patients had a short lasting and weak effect on patients' mood without affecting glucose control, but no significant effect on stress related hormones. © Georg Thieme Verlag KG Stuttgart · New York.

  17. Individual cognitive behavioral therapy for insomnia in breast cancer survivors: a randomized controlled crossover pilot study

    Science.gov (United States)

    Fiorentino, Lavinia; McQuaid, John R; Liu, Lianqi; Natarajan, Loki; He, Feng; Cornejo, Monique; Lawton, Susan; Parker, Barbara A; Sadler, Georgia R; Ancoli-Israel, Sonia

    2010-01-01

    Purpose Estimates of insomnia in breast cancer patients are high, with reports of poor sleep lasting years after completion of cancer treatment. This randomized controlled crossover pilot study looked at the effects of individual cognitive behavioral therapy for insomnia (IND-CBT-I) on sleep in breast cancer survivors. Patients and methods Twenty-one participants were randomly assigned to either a treatment group (six weekly IND-CBT-I sessions followed by six weeks of follow up) or a delayed treatment control group (no treatment for six weeks followed by six weekly IND-CBT-I sessions). Of these, 14 participants completed the pilot study (six in the treatment group and eight in the delayed treatment control group). Results Self-rated insomnia was significantly improved in the treatment group compared to the waiting period in the delayed treatment control group. The pooled pre-post-IND-CBT-I analyses revealed improvements in self-rated insomnia, sleep quality, and objective measures of sleep. Conclusions These preliminary results suggest that IND-CBT-I is appropriate for improving sleep in breast cancer survivors. Individual therapy in a clinic or private practice may be a more practical option for this population as it is more easily accessed and readily available in an outpatient setting. PMID:23616695

  18. Topical diclofenac therapy for osteoarthritis: a meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Deng, Zhen-Han; Zeng, Chao; Yang, Ye; Li, Yu-Sheng; Wei, Jie; Yang, Tuo; Li, Hui; Lei, Guang-Hua

    2016-05-01

    The objective of this study was to evaluate the efficacy and safety of topical diclofenac therapy for osteoarthritis (OA). A meta-analysis of randomized controlled trials was conducted. A comprehensive literature search, covering the databases of Medline, the Cochrane Central Register of Controlled Trials, and EMBASE, was conducted in September 2014 to identify the randomized controlled trials which adopted the topical diclofenac therapy for OA. A total of nine papers were included in this meta-analysis. Topical diclofenac appears to be effective in both pain relief (standard mean differences (SMD) = 0.40; 95 % confidence interval (CI) 0.19 to 0.62; P = 0.0003) and function improvement (SMD = 0.23; 95 % CI 0.03 to 0.43; P = 0.03) when compared with the control group. The sensitivity analysis and subgroup analysis showed that the result of pain intensity was stable and reliable, while the result of physical function improvement was vague. With respect to safety, topical diclofenac demonstrated a higher incidence of adverse events such as dry skin, rash, dermatitis, neck pain, and withdrawal. Topical diclofenac is effective in pain relief as a treatment of OA. It may also have a potential effect in function improvement, which needs further studies to be explored. Although, some adverse effects were observed in the application of topical diclofenac, none of them was serious.

  19. Walking adaptability therapy after stroke: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Timmermans, Celine; Roerdink, Melvyn; van Ooijen, Marielle W; Meskers, Carel G; Janssen, Thomas W; Beek, Peter J

    2016-08-26

    Walking in everyday life requires the ability to adapt walking to the environment. This adaptability is often impaired after stroke, and this might contribute to the increased fall risk after stroke. To improve safe community ambulation, walking adaptability training might be beneficial after stroke. This study is designed to compare the effects of two interventions for improving walking speed and walking adaptability: treadmill-based C-Mill therapy (therapy with augmented reality) and the overground FALLS program (a conventional therapy program). We hypothesize that C-Mill therapy will result in better outcomes than the FALLS program, owing to its expected greater amount of walking practice. This is a single-center parallel group randomized controlled trial with pre-intervention, post-intervention, retention, and follow-up tests. Forty persons after stroke (≥3 months) with deficits in walking or balance will be included. Participants will be randomly allocated to either C-Mill therapy or the overground FALLS program for 5 weeks. Both interventions will incorporate practice of walking adaptability and will be matched in terms of frequency, duration, and therapist attention. Walking speed, as determined by the 10 Meter Walking Test, will be the primary outcome measure. Secondary outcome measures will pertain to walking adaptability (10 Meter Walking Test with context or cognitive dual-task and Interactive Walkway assessments). Furthermore, commonly used clinical measures to determine walking ability (Timed Up-and-Go test), walking independence (Functional Ambulation Category), balance (Berg Balance Scale), and balance confidence (Activities-specific Balance Confidence scale) will be used, as well as a complementary set of walking-related assessments. The amount of walking practice (the number of steps taken per session) will be registered using the treadmill's inbuilt step counter (C-Mill therapy) and video recordings (FALLS program). This process measure will

  20. A systematic review of randomized controlled trials on curative and health enhancement effects of forest therapy

    Directory of Open Access Journals (Sweden)

    Kamioka H

    2012-07-01

    Full Text Available Hiroharu Kamioka,1 Kiichiro Tsutani,2 Yoshiteru Mutoh,3 Takuya Honda,4 Nobuyoshi Shiozawa,5 Shinpei Okada,6 Sang-Jun Park,6 Jun Kitayuguchi,7 Masamitsu Kamada,8 Hiroyasu Okuizumi,9 Shuichi Handa91Faculty of Regional Environment Science, Tokyo University of Agriculture, Tokyo, 2Department of Drug Policy and Management, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, 3Todai Policy Alternatives Research Institute, The University of Tokyo, Tokyo, 4Japanese Society for the Promotion of Science, Tokyo, 5Food Labeling Division, Consumer Affairs Agency, Cabinet Office, Government of Japan, Tokyo, 6Physical Education and Medicine Research Foundation, Nagano, 7Physical Education and Medicine Research Center Unnan, Shimane, 8Department of Environmental and Preventive Medicine, Shimane University School of Medicine, Shimane, 9Mimaki Onsen (Spa Clinic, Tomi City, Nagano, JapanObjective: To summarize the evidence for curative and health enhancement effects through forest therapy and to assess the quality of studies based on a review of randomized controlled trials (RCTs.Study design: A systematic review based on RCTs.Methods: Studies were eligible if they were RCTs. Studies included one treatment group in which forest therapy was applied. The following databases – from 1990 to November 9, 2010 – were searched: MEDLINE via PubMed, CINAHL, Web of Science, and Ichushi-Web. All Cochrane databases and Campbell Systematic Reviews were also searched up to November 9, 2010.Results: Two trials met all inclusion criteria. No specific diseases were evaluated, and both studies reported significant effectiveness in one or more outcomes for health enhancement. However, the results of evaluations with the CONSORT (Consolidated Standards of Reporting Trials 2010 and CLEAR NPT (A Checklist to Evaluate a Report of a Nonpharmacological Trial checklists generally showed a remarkable lack of description in the studies. Furthermore, there was a

  1. Negative pressure wound therapy after partial diabetic foot amputation: a multicentre, randomised controlled trial.

    Science.gov (United States)

    Armstrong, David G; Lavery, Lawrence A

    2005-11-12

    Diabetic foot wounds, particularly those secondary to amputation, are very complex and difficult to treat. We investigated whether negative pressure wound therapy (NPWT) improves the proportion and rate of wound healing after partial foot amputation in patients with diabetes. We enrolled 162 patients into a 16-week, 18-centre, randomised clinical trial in the USA. Inclusion criteria consisted of partial foot amputation wounds up to the transmetatarsal level and evidence of adequate perfusion. Patients who were randomly assigned to NPWT (n=77) received treatment with dressing changes every 48 h. Control patients (n=85) received standard moist wound care according to consensus guidelines. NPWT was delivered through the Vacuum Assisted Closure (VAC) Therapy System. Wounds were treated until healing or completion of the 112-day period of active treatment. Analysis was by intention to treat. This study has been registered with , number NCT00224796. More patients healed in the NPWT group than in the control group (43 [56%] vs 33 [39%], p=0.040). The rate of wound healing, based on the time to complete closure, was faster in the NPWT group than in controls (p=0.005). The rate of granulation tissue formation, based on the time to 76-100% formation in the wound bed, was faster in the NPWT group than in controls (p=0.002). The frequency and severity of adverse events (of which the most common was wound infection) were similar in both treatment groups. NPWT delivered by the VAC Therapy System seems to be a safe and effective treatment for complex diabetic foot wounds, and could lead to a higher proportion of healed wounds, faster healing rates, and potentially fewer re-amputations than standard care.

  2. Cognitive effects of calligraphy therapy for older people: a randomized controlled trial in Hong Kong

    Directory of Open Access Journals (Sweden)

    Kwok TCY

    2011-10-01

    Full Text Available Timothy CY Kwok1,2, Xue Bai1,3, Henry SR Kao4,5, Jessie CY Li1, Florence KY Ho11Jockey Club Centre for Positive Ageing; 2Department of Medicine and Therapeutics, The Chinese University of Hong Kong; 3Department of Social Work and Social Administration; 4Department of Psychology, The University of Hong Kong, Hong Kong; 5Department of Psychology, Fu Jen Catholic University, TaiwanBackground: This pilot study investigated the effects of calligraphy therapy on cognitive function in older Hong Kong Chinese people with mild cognitive impairment.Methods: A single-blind, randomized controlled trial was carried out in a sample of 31 adults aged 65 years or older with mild cognitive impairment. They were randomly assigned to receive either intensive calligraphy training led by a trained research assistant for eight weeks (calligraphy group, n = 14 or no calligraphy treatment (control group, n = 17. Participants' cognitive function was assessed by the Chinese version of the Mini-Mental State Examination (CMMSE before and after calligraphy treatment. Repeated measures analysis of variance and paired samples t-tests were used to analyze the data.Results: A significant interaction effect of time and intervention was detected [F (1, 29 = 9.11, P = 0.005, η2= 0.24]. The calligraphy group was found to have a prominent increase in CMMSE global score, and scores in the cognitive areas of orientation, attention, and calculation after two months (∆M = 2.36, P < 0.01, whereas their counterparts in the control group experienced a decline in CMMSE score (∆M = -0.41, P < 0.05.Conclusion: Calligraphy therapy was effective for enhancing cognitive function in older people with mild cognitive impairment and should be incorporated as part of routine programs in both community and residential care settings.Keywords: calligraphy therapy, Chinese elderly, mild cognitive impairment, cognitive function, randomized controlled trial

  3. Randomized Controlled Trial of Telephone-Delivered Cognitive Behavioral Therapy for Chronic Insomnia

    Science.gov (United States)

    Arnedt, J. Todd; Cuddihy, Leisha; Swanson, Leslie M.; Pickett, Scott; Aikens, James; Chervin, Ronald D.

    2013-01-01

    Study Objectives: To compare the efficacy of telephone-delivered cognitive-behavioral therapy for insomnia to an information pamphlet control on sleep and daytime functioning at pretreatment, posttreatment, and 12-wk follow-up. Design: Randomized controlled parallel trial. Setting: N/A. Participants: Thirty individuals with chronic insomnia (27 women, age 39.1 ± 14.4 years, insomnia duration 8.7 ± 10.7 years). Interventions: Cognitive behavioral therapy for insomnia (CBTI) delivered in up to eight weekly telephone sessions (CBTI-Phone, n = 15) versus an information pamphlet control (IPC, n = 15). Measurements and Results: Sleep/wake diary, sleep-related questionnaires (Insomnia Severity Index, Pittsburgh Sleep Quality Index, 16-item Dysfunctional Beliefs and Attitudes about Sleep), and daytime symptom assessments (fatigue, depression, anxiety, and quality of life) were completed at pretreatment, posttreatment, and 12-wk follow-up. Linear mixed models indicated that sleep/wake diary sleep efficiency and total sleep time improved significantly at posttreatment in both groups and remained stable at 12-wk follow-up. More CBTI-Phone than IPC patients showed posttreatment improvements in unhelpful sleep-related cognitions (P insomnia at follow-up (P insomnia. Future larger-scale studies with more diverse samples are warranted. Some individuals with insomnia may also benefit from pamphlet-delivered CBTI with brief telephone support. Citation: Arnedt JT; Cuddihy L; Swanson LM; Pickett S; Aikens J; Chervin RD. Randomized controlled trial of telephone-delivered cognitive behavioral therapy for chronic insomnia. SLEEP 2013;36(3):353-362. PMID:23450712

  4. Design and control of RUPERT: a device for robotic upper extremity repetitive therapy.

    Science.gov (United States)

    Sugar, Thomas G; He, Jiping; Koeneman, Edward J; Koeneman, James B; Herman, Richard; Huang, H; Schultz, Robert S; Herring, D E; Wanberg, J; Balasubramanian, Sivakumar; Swenson, Pete; Ward, Jeffrey A

    2007-09-01

    The structural design, control system, and integrated biofeedback for a wearable exoskeletal robot for upper extremity stroke rehabilitation are presented. Assisted with clinical evaluation, designers, engineers, and scientists have built a device for robotic assisted upper extremity repetitive therapy (RUPERT). Intense, repetitive physical rehabilitation has been shown to be beneficial overcoming upper extremity deficits, but the therapy is labor intensive and expensive and difficult to evaluate quantitatively and objectively. The RUPERT is developed to provide a low cost, safe and easy-to-use, robotic-device to assist the patient and therapist to achieve more systematic therapy at home or in the clinic. The RUPERT has four actuated degrees-of-freedom driven by compliant and safe pneumatic muscles (PMs) on the shoulder, elbow, and wrist. They are programmed to actuate the device to extend the arm and move the arm in 3-D space. It is very important to note that gravity is not compensated and the daily tasks are practiced in a natural setting. Because the device is wearable and lightweight to increase portability, it can be worn standing or sitting providing therapy tasks that better mimic activities of daily living. The sensors feed back position and force information for quantitative evaluation of task performance. The device can also provide real-time, objective assessment of functional improvement. We have tested the device on stroke survivors performing two critical activities of daily living (ADL): reaching out and self feeding. The future improvement of the device involves increased degrees-of-freedom and interactive control to adapt to a user's physical conditions.

  5. Effects of functional restoration versus 3 hours per week physical therapy: a randomized controlled study.

    Science.gov (United States)

    Jousset, Nathalie; Fanello, Serge; Bontoux, Luc; Dubus, Valérie; Billabert, Colette; Vielle, Bruno; Roquelaure, Yves; Penneau-Fontbonne, Dominique; Richard, Isabelle

    2004-03-01

    Randomized parallel-group comparative trial with a 6-month follow-up period. To compare, in chronic low back pain patients, the effectiveness of a functional restoration program, including intensive physical training, occupational therapy, and psychological support to an active individual therapy consisting of 3 hours physical therapy per week during 5 weeks. Controlled studies conducted in the United States showed a benefit of functional restoration in patients with low back pain, especially on return to work. Randomized Canadian and European trials had less favorable results. In France, there has been up to now no randomized study. Controlled studies suggested a positive effect of functional restoration programs. Eighty-six patients with low back pain were randomized to either the functional restoration (44 patients) or the active individual therapy (42 patients) program. One person in each group never started the program. Two patients did not complete the functional restoration program, and one was lost to follow-up at 6 months. The mean number of sick-leave days in the 2 previous years was 6 months. After adjustment on the variable "workplace enrolled in an ergonomic program", the mean number of sick-leave days was significantly lower in the functional restoration group. Physical criteria and treatment appreciation were also better. There was no significant difference in the intensity of pain, the quality of life and functional indexes, the psychological characteristics, the number of contacts with the medical system, and the drug intake. This study demonstrates the effectiveness of a functional restoration program on important outcome measures, such as sick leave, in a country that has a social system that protects people facing difficulties at work.

  6. [Efficacy on hemiplegic spasticity treated with plum blossom needle tapping therapy at the key points and Bobath therapy: a randomized controlled trial].

    Science.gov (United States)

    Wang, Fei; Zhang, Lijuan; Wang, Jianhua; Shi, Yan; Zheng, Liya

    2015-08-01

    To evaluate the efficacy on hemiplegic spasticity after cerebral infarction treated with plum blossom needle tapping therapy at the key points and Bobath therapy. Eighty patients were collected, in compliance with the inclusive criteria of hemiplegic spasticity after cerebral infarction, and randomized into an observation group and a control group, 40 cases in each one. In the control group, Bobath manipulation therapy was adopted to relieve spasticity and the treatment of 8 weeks was required. In the observation group, on the basis of the treatment as the control group, the tapping therapy with plum blossom needle was applied to the key points, named Jianyu (LI 15), Jianliao (LI 14), Jianzhen (SI 9), Hegu (LI 4), Chengfu (BL 36), Zusanli (ST 36), Xiyangguan (GB 33), etc. The treatment was given for 15 min each time, once a day. Before treatment, after 4 and 8 weeks of treatment, the Fugl-Meyer assessment (FMA) and Barthel index (BI) were adopted to evaluate the motor function of the extremity and the activity of daily life in the patients of the two groups separately. The modified Ashworth scale was used to evaluate the effect of anti-spasticity. In 4 and 8 weeks of treatment, FMA: scores and BI scores were all significantly increased as compared with those before treatment in the two groups: (both PBobath therapy effectively relieves hemiplegic spasticity in the patients of cerebral infarction and improves the motor function of extremity and the activity of daily life.

  7. Contagiousness under antiretroviral therapy and stigmatization toward people with HIV.

    Science.gov (United States)

    Drewes, Jochen; Kleiber, Dieter

    2014-01-01

    Perceived contagiousness is a major dimension underlying HIV-related stigmatization. Antiretroviral therapy (ART) can diminish contagiousness by reducing viral load levels in HIV-infected individuals. To test the assumption that reductions in contagiousness can lead to a decrease in stigmatizing reactions, we conducted an experimental online study. A sample of 752 participants (50.9% female) read a short vignette depicting an HIV-positive individual with either a high or a low viral load and were either given or not given information about the association between viral load and contagiousness. Subsequently, participants were asked to rate their willingness to stigmatize this individual by responding to two measures of social and physical distance. Differences between the low and the high viral load information groups and the combined no-information groups (forming a quasi-control group) were analyzed using analysis of covariance (ANCOVA), controlling for gender and baseline perceptions of contagiousness. The covariates, perceived contagiousness at baseline and gender, were associated with social and physical distancing, but the viral load/information factor was only significant in physical distancing. Planned contrast analyses confirmed that physical distancing in the informed group was lower in the low viral load condition compared to the high viral load condition and to the control group. We thus found evidence for the significant role of perceived contagiousness in the HIV-related stigma and were able to experimentally demonstrate the potential of ART to reduce HIV-related stigmatization by lowering viral load and contagiousness, when these changes are accompanied by a decreased perception of contagiousness.

  8. Constrained pattern of viral evolution in acute and early HCV infection limits viral plasticity.

    Directory of Open Access Journals (Sweden)

    Katja Pfafferott

    2011-02-01

    Full Text Available Cellular immune responses during acute Hepatitis C virus (HCV and HIV infection are a known correlate of infection outcome. Viral adaptation to these responses via mutation(s within CD8+ T-cell epitopes allows these viruses to subvert host immune control. This study examined HCV evolution in 21 HCV genotype 1-infected subjects to characterise the level of viral adaptation during acute and early HCV infection. Of the total mutations observed 25% were within described CD8+ T-cell epitopes or at viral adaptation sites. Most mutations were maintained into the chronic phase of HCV infection (75%. The lack of reversion of adaptations and high proportion of silent substitutions suggests that HCV has structural and functional limitations that constrain evolution. These results were compared to the pattern of viral evolution observed in 98 subjects during a similar phase in HIV infection from a previous study. In contrast to HCV, evolution during acute HIV infection is marked by high levels of amino acid change relative to silent substitutions, including a higher proportion of adaptations, likely reflecting strong and continued CD8+ T-cell pressure combined with greater plasticity of the virus. Understanding viral escape dynamics for these two viruses is important for effective T cell vaccine design.

  9. Statin therapy reduces the likelihood of suboptimal blood pressure control among Ugandan adult diabetic patients

    Directory of Open Access Journals (Sweden)

    Lumu W

    2017-02-01

    Full Text Available William Lumu,1 Leaticia Kampiire,2 George Patrick Akabwai,3 Daniel Ssekikubo Kiggundu,4 Davis Kibirige5 1Department of Medicine and Diabetes/Endocrine Unit, Mengo Hospital, 2Infectious Disease Research Collaboration, 3Baylor College of Medicine Children’s Foundation, 4Nephrology Unit, Mulago National Referral and Teaching Hospital, 5Department of Medicine, Uganda Martyrs Hospital Lubaga, Kampala, Uganda Background: Hypertension is one of the recognized risk factors of cardiovascular diseases in adult diabetic patients. High prevalence of suboptimal blood pressure (BP control has been well documented in the majority of studies assessing BP