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Sample records for systematic early antiviral

  1. Evasion of Early Antiviral Responses by Herpes Simplex Viruses

    Science.gov (United States)

    Suazo, Paula A.; Ibañez, Francisco J.; Retamal-Díaz, Angello R.; Paz-Fiblas, Marysol V.; Bueno, Susan M.; Kalergis, Alexis M.; González, Pablo A.

    2015-01-01

    Besides overcoming physical constraints, such as extreme temperatures, reduced humidity, elevated pressure, and natural predators, human pathogens further need to overcome an arsenal of antimicrobial components evolved by the host to limit infection, replication and optimally, reinfection. Herpes simplex virus-1 (HSV-1) and herpes simplex virus-2 (HSV-2) infect humans at a high frequency and persist within the host for life by establishing latency in neurons. To gain access to these cells, herpes simplex viruses (HSVs) must replicate and block immediate host antiviral responses elicited by epithelial cells and innate immune components early after infection. During these processes, infected and noninfected neighboring cells, as well as tissue-resident and patrolling immune cells, will sense viral components and cell-associated danger signals and secrete soluble mediators. While type-I interferons aim at limiting virus spread, cytokines and chemokines will modulate resident and incoming immune cells. In this paper, we discuss recent findings relative to the early steps taking place during HSV infection and replication. Further, we discuss how HSVs evade detection by host cells and the molecular mechanisms evolved by these viruses to circumvent early antiviral mechanisms, ultimately leading to neuron infection and the establishment of latency. PMID:25918478

  2. Corticosteroids vs corticosteroids plus antiviral agents in the treatment of Bell palsy: a systematic review and meta-analysis.

    Science.gov (United States)

    Goudakos, John K; Markou, Konstantinos D

    2009-06-01

    To review systematically and meta-analyze the results of all randomized controlled trials (RCTs) for the treatment of patients with Bell palsy with corticosteroids vs corticosteroids plus antiviral agents. A MEDLINE, EMBASE, Cochrane Library, and CENTRAL database search, followed by extensive hand-searching for the identification of relevant studies. No time and language limitations were applied. Prospective RCTs on the treatment of patients with Bell palsy. Odds ratios (ORs), 95% confidence intervals (CIs), and tests for heterogeneity were reported. Five studies were eventually identified and systematically reviewed. Meta-analysis was performed for 4 studies. Regarding the complete recovery rate of facial nerve paralysis 3 months after initiation of therapy, the current systematic review and meta-analysis suggests that the addition of an antiviral agent does not provide any benefit (OR, 1.03 [95% CI, 0.74-1.42]; P = .88). The same conclusion emerged at posterior (fourth, sixth, and ninth) months of assessment. Subgroup analysis, conducted on the basis of time point of therapy initiation, type of antiviral agent, and blindness of assessments did not change the results obtained. The occurrence rate of adverse effects attributable to therapy choice was not significantly different between patients receiving corticosteroids and those following combined treatment. The present systematic review and meta-analysis, based on the currently available evidence, suggests that the addition of an antiviral agent to corticosteroids for the treatment of Bell palsy is not associated with an increase in the complete recovery rate of the facial motor function.

  3. SPOC1-mediated antiviral host cell response is antagonized early in human adenovirus type 5 infection

    DEFF Research Database (Denmark)

    Schreiner, Sabrina; Kinkley, Sarah; Bürck, Carolin

    2013-01-01

    , and playing a role in DNA damage response. SPOC1 co-localized with viral replication centers in the host cell nucleus, interacted with Ad DNA, and repressed viral gene expression at the transcriptional level. We discovered that this SPOC1-mediated restriction imposed upon Ad growth is relieved by its...... viruses (HSV-1, HSV-2, HIV-1, and HCV) also depleted SPOC1 in infected cells. Our findings provide a general model for how pathogenic human viruses antagonize intrinsic SPOC1-mediated antiviral responses in their host cells. A better understanding of viral entry and early restrictive functions in host...

  4. 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

  5. Comparative cost-effectiveness of antiviral therapies in patients with chronic hepatitis B: a systematic review of economic evidence.

    Science.gov (United States)

    Sun, Xin; Qin, Wen-Xia; Li, You-Ping; Jiang, Xu-Hua

    2007-09-01

    Economic efficiency of the alternative antiviral therapies for chronic hepatitis B has not been systematically investigated and their quality remains unknown. The aim of the present study was to systematically overview economic evidence of antiviral therapies for chronic hepatitis B. We searched six databases and eight major journals supplemented with screening references of eligible studies. Full economic evaluations comparing alternative antiviral therapies in patients with chronic hepatitis B virus infection were included. Two investigators assessed the study quality and transferability, independently. Data were analyzed qualitatively with adjustment when appropriate. Fourteen studies (six modeling vs eight trials and database analyses) were included. Quality was high in five studies, moderate in one US and five Chinese studies, and low in three Chinese studies. The major problems of quality are costing methods and analysis and the presentation of results. In Australia and Poland, lamivudine-preferred strategies dominated interferon (IFN)-alpha and its related strategy from the health-care sector perspective. In the US, adefovir salvage produced US$8446 per additional quality-adjusted life years (QALY) compared with IFN-alpha. In Spain, the cost of adefovir was US$34,840 for additional virological response. In Taiwan, the use of pegylated IFN-alpha (pegIFN-alpha) produced US$11,711.4 per additional QALY, compared with lamivudine. In China, the incremental cost-effectiveness ratios of combination therapy lamivudine ranged from US$2860 to US$22,160 per additional loss of hepatitis B e antigen (HBeAg), and IFN-alpha versus lamivudine ranged from US$2490 to US$8890 per additional loss of HBeAg. The cost-effectiveness frontiers of treatment alternatives vary and are influenced by the comparators and socioeconomic conditions of countries. Lamivudine-containing therapy is cost-effective when newer antiviral agents (e.g. adefovir/pegIFN-alpha) were not available

  6. Antiviral potential of medicinal plants against HIV, HSV, influenza, hepatitis, and coxsackievirus: A systematic review.

    Science.gov (United States)

    Akram, Muhammad; Tahir, Imtiaz Mahmood; Shah, Syed Muhammad Ali; Mahmood, Zahed; Altaf, Awais; Ahmad, Khalil; Munir, Naveed; Daniyal, Muhammad; Nasir, Suhaila; Mehboob, Huma

    2018-05-01

    Viral infections are being managed therapeutically through available antiviral regimens with unsatisfactory clinical outcomes. The refractory viral infections resistant to available antiviral drugs are alarming threats and a serious health concern. For viral hepatitis, the interferon and vaccine therapies solely are not ultimate solutions due to recurrence of hepatitis C virus. Owing to the growing incidences of viral infections and especially of resistant viral strains, the available therapeutic modalities need to be improved, complemented with the discovery of novel antiviral agents to combat refractory viral infections. It is widely accepted that medicinal plant heritage is nature gifted, precious, and fueled with the valuable resources for treatment of metabolic and infectious disorders. The aims of this review are to assemble the facts and to conclude the therapeutic potential of medicinal plants in the eradication and management of various viral diseases such as influenza, human immunodeficiency virus (HIV), herpes simplex virus (HSV), hepatitis, and coxsackievirus infections, which have been proven in diverse clinical studies. The articles, published in the English language since 1982 to 2017, were included from Web of Science, Cochrane Library, AMED, CISCOM, EMBASE, MEDLINE, Scopus, and PubMed by using relevant keywords including plants possessing antiviral activity, the antiviral effects of plants, and plants used in viral disorders. The scientific literature mainly focusing on plant extracts and herbal products with therapeutic efficacies against experimental models of influenza, HIV, HSV, hepatitis, and coxsackievirus were included in the study. Pure compounds possessing antiviral activity were excluded, and plants possessing activity against viruses other than viruses in inclusion criteria were excluded. Hundreds of plant extracts with antiviral effect were recognized. However, the data from only 36 families investigated through in vitro and in vivo

  7. The Role of Antiviral Prophylaxis for the Prevention of Epstein-Barr Virus-Associated Posttransplant Lymphoproliferative Disease in Solid Organ Transplant Recipients: A Systematic Review.

    Science.gov (United States)

    AlDabbagh, M A; Gitman, M R; Kumar, D; Humar, A; Rotstein, C; Husain, S

    2017-03-01

    The role of antiviral prophylaxis for the prevention of posttransplant lymphoproliferative disease (PTLD) remains controversial for solid organ transplantation (SOT) recipients who are seronegative for Epstein-Barr virus (EBV) but who received organs from seropositive donors. We performed a systematic review and meta-analysis to address this issue. Two independent assessors extracted data from studies after determining patient eligibility and completing quality assessments. Overall, 31 studies were identified and included in the quantitative synthesis. Nine studies were included in the direct comparisons (total 2366 participants), and 22 were included in the indirect analysis. There was no significant difference in the rate of EBV-associated PTLD in SOT recipients among those who received prophylaxis (acyclovir, valacyclovir, ganciclovir, valganciclovir) compared with those who did not receive prophylaxis (nine studies; risk ratio 0.95, 95% confidence interval 0.58-1.54). No significant differences were noted across all types of organ transplants, age groups, or antiviral use as prophylaxis or preemptive therapy. There was no significant heterogeneity in the effect of antiviral prophylaxis on the incidence of PTLD. In conclusion, the use of antiviral prophylaxis in high-risk EBV-naive patients has no effect on the incidence of PTLD in SOT recipients. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  8. Antiviral Agents Added to Corticosteroids for Early Treatment of Adults With Acute Idiopathic Facial Nerve Paralysis (Bell Palsy).

    Science.gov (United States)

    Sullivan, Frank; Daly, Fergus; Gagyor, Ildiko

    Compared with oral corticosteroids alone, are oral antiviral drugs associated with improved outcomes when combined with oral corticosteroids in patients presenting within 72 hours of the onset of Bell palsy? Compared with oral corticosteroids alone, the addition of acyclovir, valacyclovir, or famcyclovir to oral corticosteroids for treatment of Bell palsy was associated with a higher proportion of people who recovered at 3- to 12-month follow-up. The quality of evidence is limited by heterogeneity, imprecision of the result estimates, and risk of bias.

  9. Systemic corticosteroids and early administration of antiviral agents for pneumonia with acute wheezing due to influenza A(H1N1pdm09 in Japan.

    Directory of Open Access Journals (Sweden)

    Koichiro Kudo

    Full Text Available BACKGROUND: Pneumonia patients with wheezing due to influenza A(H1N1pdm09 were frequently treated with systemic corticosteroids in Japan although systemic corticosteroid for critically ill patients with pneumonia caused by influenza A(H1N1pdm09 has been controversial. Applicability of systemic corticosteroid treatment needs to be evaluated. METHODS/PRINCIPAL FINDINGS: We retrospectively reviewed 89 subjects who were diagnosed with influenza A(H1N1pdm09 and admitted to a national hospital, Tokyo during the pandemic period. The median age of subjects (45 males was 8 years (range, 0-71. All subjects were treated with antiviral agents and the median time from symptom onset to initiation of antiviral agents was 2 days (range, 0-7. Subjects were classified into four groups: upper respiratory tract infection, wheezing illness, pneumonia with wheezing, and pneumonia without wheezing. The characteristics of each group was evaluated. A history of asthma was found more frequently in the wheezing illness (55.6% and pneumonia with wheezing (43.3% groups than in the other two groups (p = 0.017. Corticosteroid treatment was assessed among subjects with pneumonia. Oxygen saturation was lower in subjects receiving corticosteroids (steroid group than in subjects not receiving corticosteroids (no-steroid group (p<0.001. The steroid group required greater oxygen supply than the no-steroid group (p<0.001. No significant difference was found by the Kaplan-Meier method between the steroid and the no-steroid groups in hours to fever alleviation from the initiation of antiviral agents and hospitalization days. In logistic regression analysis, wheezing, pneumonia and oxygen saturation were independent factors associated with using systemic corticosteroids. CONCLUSION: Patients with wheezing and a history of asthma were frequently found in the study subjects. Systemic corticosteroids together with early administration of antiviral agents to pneumonia with wheezing and

  10. Growth monitoring as an early detection tool: a systematic review

    NARCIS (Netherlands)

    Scherdel, P.; Dunkel, L.; Dommelen, P. van; Goulet, O.; Salaün, J.F.; Brauner, R.; Heude, B.; Chalumeau, M.

    2016-01-01

    Growth monitoring of apparently healthy children aims at early detection of serious underlying disorders. However, existing growth-monitoring practices are mainly based on suboptimal methods, which can result in delayed diagnosis of severe diseases and inappropriate referrals. We did a systematic

  11. Results of a multinational study suggest the need for rapid diagnosis and early antiviral treatment at the onset of herpetic meningoencephalitis

    DEFF Research Database (Denmark)

    Erdem, Hakan; Cag, Yasemin; Ozturk-Engin, Derya

    2015-01-01

    survived, with sequelae. Age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02 to 1.05), Glasgow Coma Scale score (OR, 0.84; 95% CI, 0.77 to 0.93), and symptomatic periods of 2 to 7 days (OR, 1.80; 95% CI, 1.16 to 2.79) and >7 days (OR, 3.75; 95% CI, 1.72 to 8.15) until the commencement...... of treatment predicted unfavorable outcomes. The outcome in HME patients is related to a combination of therapeutic and host factors. This study suggests that rapid diagnosis and early administration of antiviral treatment in HME patients are keys to a favorable outcome....

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Early Disk dynamics Inferred from Isotope Systematics of Individual Chrondules

    DEFF Research Database (Denmark)

    Bollard, Jean Francois André

    imply that they must be the product of one of the most energetic processes that operated in the early Solar System. Chondrules are the only samples available to investigate the early Solar System and the chemical and thermal evolution of the Solar protoplanetary disk. Although relative 26Al-26Mg dating....../or reservoirs over time. Finally, the fifth chapter explores the Solar System 26Al homogeneity paradigm by comparing of Al-Mg systematics in chondrules with their respective Pb-Pb ages. We report a consistent age offset between the two chronometers that we infer reflects a reduced abundance of 26Al relative...... to different reservoirs. Lastly, a reduced abundance of 26Al relative to 27Al in inner Solar System objects implies that asteroid accretion must have occurred very early in the Solar System’s formation, to allow melting and differentiation driven by 26Al decay. With respect to our Pb-Pb chondrule chronology...

  14. Hepatitis C Virus and Antiviral Drug Resistance.

    Science.gov (United States)

    Kim, Seungtaek; Han, Kwang-Hyub; Ahn, Sang Hoon

    2016-11-15

    Since its discovery in 1989, hepatitis C virus (HCV) has been intensively investigated to understand its biology and develop effective antiviral therapies. The efforts of the previous 25 years have resulted in a better understanding of the virus, and this was facilitated by the development of in vitro cell culture systems for HCV replication. Antiviral treatments and sustained virological responses have also improved from the early interferon monotherapy to the current all-oral regimens using direct-acting antivirals. However, antiviral resistance has become a critical issue in the treatment of chronic hepatitis C, similar to other chronic viral infections, and retreatment options following treatment failure have become important questions. Despite the clinical challenges in the management of chronic hepatitis C, substantial progress has been made in understanding HCV, which may facilitate the investigation of other closely related flaviviruses and lead to the development of antiviral agents against these human pathogens.

  15. The Human Cytomegalovirus Major Immediate-Early Proteins as Antagonists of Intrinsic and Innate Antiviral Host Responses

    Directory of Open Access Journals (Sweden)

    Michael Nevels

    2009-11-01

    Full Text Available The major immediate-early (IE gene of human cytomegalovirus (CMV is believed to have a decisive role in acute infection and its activity is an important indicator of viral reactivation from latency. Although a variety of gene products are expressed from this region, the 72-kDa IE1 and the 86-kDa IE2 nuclear phosphoproteins are the most abundant and important. Both proteins have long been recognized as promiscuous transcriptional regulators. More recently, a critical role of the IE1 and IE2 proteins in counteracting nonadaptive host cell defense mechanisms has been revealed. In this review we will briefly summarize the available literature on IE1- and IE2-dependent mechanisms contributing to CMV evasion from intrinsic and innate immune responses.

  16. Social networks, support and early psychosis: a systematic review.

    Science.gov (United States)

    Gayer-Anderson, C; Morgan, C

    2013-06-01

    Background. There is strong evidence that those with a long-standing psychotic disorder have fewer social contacts and less social support than comparison groups. There is less research on the extent of social contacts and support prior to or at the onset of psychosis. In the light of recent evidence implicating a range of social experiences and contexts at the onset of psychosis, it is relevant to establish whether social networks and support diminished before or at the time of onset and whether the absence of such supports might contribute to risk, either directly or indirectly. We, therefore, conducted a systematic review of this literature to establish what is currently known about the relationship between social networks, support and early psychosis. Methods. We identified all studies investigating social networks and support in first episode psychosis samples and in general population samples with measures of psychotic experiences or schizotype by conducting systematic searches of electronic databases using pre-defined search terms and criteria. Findings were synthesized using non-quantitative approaches. Results. Thirty-eight papers were identified that met inclusion criteria. There was marked methodological heterogeneity, which limits the capacity to draw direct comparisons. Nonetheless, the existing literature suggests social networks (particularly close friends) and support diminished both among first episode samples and among non-clinical samples reporting psychotic experiences or with schizotype traits, compared with varying comparison groups. These differences may be more marked for men and for those from minority ethnic populations. Conclusions. Tentatively, reduced social networks and support appear to pre-date onset of psychotic disorder. However, the substantial methodological heterogeneity among the existing studies makes comparisons difficult and suggests a need for more robust and comparable studies on networks, support and early psychosis.

  17. Employment and educational outcomes in early intervention programmes for early psychosis: a systematic review.

    Science.gov (United States)

    Bond, G R; Drake, R E; Luciano, A

    2015-10-01

    Young adults with early psychosis want to pursue normal roles - education and employment. This paper summarises the empirical literature on the effectiveness of early intervention programmes for employment and education outcomes. We conducted a systematic review of employment/education outcomes for early intervention programmes, distinguishing three programme types: (1) those providing supported employment, (2) those providing unspecified vocational services and (3) those without vocational services. We summarised findings for 28 studies. Eleven studies evaluated early intervention programmes providing supported employment. In eight studies that reported employment outcomes separately from education outcomes, the employment rate during follow-up for supported employment patients was 49%, compared with 29% for patients receiving usual services. The two groups did not differ on enrolment in education. In four controlled studies, meta-analysis showed that the employment rate for supported employment participants was significantly higher than for control participants, odds ratio = 3.66 [1.93-6.93], p < 0.0001. Five studies (four descriptive and one quasi-experimental) of early intervention programmes evaluating unspecified vocational services were inconclusive. Twelve studies of early intervention programmes without vocational services were methodologically heterogeneous, using diverse methods for evaluating vocational/educational outcomes and precluding a satisfactory meta-analytic synthesis. Among studies with comparison groups, 7 of 11 (64%) reported significant vocational/education outcomes favouring early intervention over usual services. In early intervention programmes, supported employment moderately increases employment rates but not rates of enrolment in education. These improvements are in addition to the modest effects early programmes alone have on vocational/educational outcomes compared with usual services.

  18. Contemporary Management of Early-Stage Melanoma: A Systematic Review.

    Science.gov (United States)

    Rosko, Andrew J; Vankoevering, Kyle K; McLean, Scott A; Johnson, Timothy M; Moyer, Jeffrey S

    2017-05-01

    The incidence of melanoma is increasing, with 76 380 new cases of invasive melanoma and 68 480 new cases of melanoma in situ expected in 2016. To review the contemporary management of early-stage melanoma. We searched PubMed, MEDLINE, and the Cochrane Database of Systematic Reviews databases from January 1, 2011, to May 1, 2016, yielding 966 articles. We focused our search on early-stage (melanoma in situ, stage I, and stage II) cutaneous melanoma. After excluding articles, 41 articles were manually reviewed. A review of the bibliographies of selected articles generated additional references. While the majority of recent advances have been in the treatment of advanced melanoma, surgical excision with margins based on the presence and depth of invasion continues to be the cornerstone of management. Sentinel lymph node biopsy plays a central role in the staging and treatment of melanoma. Accurate diagnosis and adequate surgical excision are critical in reducing local recurrences and improving outcomes. Sentinel lymph node biopsy is useful in staging the regional nodal basin and guiding treatment in appropriately selected patients.

  19. Human Cytomegalovirus Encoded miR-US25-1-5p Attenuates CD147/EMMPRIN-Mediated Early Antiviral Response

    Directory of Open Access Journals (Sweden)

    Jun Chen

    2017-12-01

    Full Text Available Cellular receptor-mediated signaling pathways play critical roles during the initial immune response to Human Cytomegalovirus (HCMV infection. However, the involvement of type-I transmembrane glycoprotein CD147/EMMPRIN (extracellular matrix metalloproteinase inducer in the antiviral response to HCMV infection is still unknown. Here, we demonstrated the specific knockdown of CD147 significantly decreased HCMV-induced activation of NF-κB and Interferon-beta (IFN-β, which contribute to the cellular antiviral responses. Next, we confirmed that HCMV-encoded miR-US25-1-5p could target the 3′ UTR (Untranslated Region of CD147 mRNA, and thus facilitate HCMV lytic propagation at a low multiplicity of infection (MOI. The expression and secretion of Cyclophilin A (sCyPA, as a ligand for CD147 and a proinflammatory cytokine, were up-regulated in response to HCMV stimuli. Finally, we confirmed that CD147 mediated HCMV-triggered antiviral signaling via the sCyPA-CD147-ERK (extracellular regulated protein kinases/NF-κB axis signaling pathway. These findings reveal an important HCMV mechanism for evading antiviral innate immunity through its encoded microRNA by targeting transmembrane glycoprotein CD147, and a potential cause of HCMV inflammatory disorders due to the secretion of proinflammatory cytokine CyPA.

  20. Early childhood neurodevelopment after intrauterine growth restriction: a systematic review.

    Science.gov (United States)

    Levine, Terri A; Grunau, Ruth E; McAuliffe, Fionnuala M; Pinnamaneni, RagaMallika; Foran, Adrienne; Alderdice, Fiona A

    2015-01-01

    Children who experienced intrauterine growth restriction (IUGR) may be at increased risk for adverse developmental outcomes in early childhood. The objective of this study was to carry out a systematic review of neurodevelopmental outcomes from 6 months to 3 years after IUGR. PubMed, Embase, PsycINFO, Maternity and Infant Care, and CINAHL databases were searched by using the search terms intrauterine, fetal, growth restriction, child development, neurodevelopment, early childhood, cognitive, motor, speech, language. Studies were eligible for inclusion if participants met specified criteria for growth restriction, follow-up was conducted within 6 months to 3 years, methods were adequately described, non-IUGR comparison groups were included, and full English text of the article was available. A specifically designed data extraction form was used. The methodological quality of included studies was assessed using well-documented quality-appraisal guidelines. Of 731 studies reviewed, 16 were included. Poorer neurodevelopmental outcomes after IUGR were described in 11. Ten found motor, 8 cognitive, and 7 language delays. Other delays included social development, attention, and adaptive behavior. Only 8 included abnormal Doppler parameters in their definitions of IUGR. Evidence suggests that children are at risk for poorer neurodevelopmental outcomes following IUGR from 6 months to 3 years of age. The heterogeneity of primary outcomes, assessment measures, adjustment for confounding variables, and definitions of IUGR limits synthesis and interpretation. Sample sizes in most studies were small, and some examined preterm IUGR children without including term IUGR or AGA comparison groups, limiting the value of extant studies. Copyright © 2015 by the American Academy of Pediatrics.

  1. Smallpox Antiviral Drug

    Science.gov (United States)

    2007-01-01

    Candida albicans] A G1L (590 aa) Flag VV(WR) 30/ENDIDEILGIAHLLEHLLISF/50 107/HIKELENEYYFRNEVFH/123 H41A 30/ENDIDEILGIAALLEHLLISF/50 107...RSV) (Table 1). Additional antiviral drug examples include the use of interferon for human papilloma virus ( HPV ) [Cantell, 1995]. Antivirals are most...low oral bioavailability, and quick elimination from plasma [Ghosn et al., 2004; Hostetler et al., 1994; Kempf et al., 1991; Matsumoto et al., 2001

  2. Methodological Reflections on the Use of Systematic Reviews in Early Childhood Research

    Science.gov (United States)

    Ang, Lynn

    2018-01-01

    This article sets out to look critically at the use of systematic reviews in the cross-disciplinary field of early childhood and international development. Systematic reviews--a specialist methodology involving the secondary analysis of existing knowledge on a particular topic--is prevalently used to address complex questions in social and…

  3. Ophthalmic antiviral chemotherapy : An overview

    Directory of Open Access Journals (Sweden)

    Athmanathan Sreedharan

    1997-01-01

    Full Text Available Antiviral drug development has been slow due to many factors. One such factor is the difficulty to block the viral replication in the cell without adversely affecting the host cell metabolic activity. Most of the antiviral compounds are analogs of purines and pyramidines. Currently available antiviral drugs mainly inhibit viral nucleic acid synthesis, hence act only on actively replicating viruses. This article presents an overview of some of the commonly used antiviral agents in clinical ophthalmology.

  4. Lesbian and Gay Parents in Early Childhood Settings: A Systematic Review of the Research Literature

    Science.gov (United States)

    Averett, Paige; Hegde, Archana; Smith, Justin

    2017-01-01

    This article presents the first systematic review of all the existing peer-reviewed literature (n = 20) on gay and lesbian parents and their children in early childhood education settings. The review includes articles that were empirical or pedagogical practice oriented, focused exclusively on early childhood education (Birth to 5 years), and…

  5. Antiviral Drugs: Seasonal Flu

    Centers for Disease Control (CDC) Podcasts

    2010-09-29

    In this podcast, Dr. Joe Bresee explains the nature of antiviral drugs and how they are used for seasonal flu.  Created: 9/29/2010 by National Center for Immunization and Respiratory Diseases (NCIRD).   Date Released: 9/29/2010.

  6. Antiviral properties of photosensitizers

    International Nuclear Information System (INIS)

    Hudson, J.B.; Towers, G.H.N.

    1988-01-01

    We have studied the antiviral properties of three different groups of photo-sensitizers, viz. (i) various furyl compounds; (ii) β-carboline alkaloids; (iii) thiophenes and their acetylene derivatives. In general the antiviral potency of the furyl compounds correlated with their ability to produce DNA photoadducts. Among the naturally occurring β-carboline alkaloids, harmine was considerably more potent (in the presence of long wavelength UV radiation, UVA) than several other harmane-related compounds. Slight alterations in chemical structure had profound effects on their antiviral activities. Harmine was shown to inactivate the DNA-virus murine cytomegalovirus (MCMV) by inhibiting viral gene expression, although other targets may also exist. Several eudistomins, carboline derivatives isolated from a tunicate, were also photoactive against viruses. Various plant thiophenes and polyacetylenes were studied in detail. These compounds also required UVA for antiviral activity, and some of them were extremely potent against viruses with membranes, e.g. α-terthienyl, which showed significant activity at only 10 -5 μg/ml. When MCMV had been treated with α-terthienyl plus UVA, the virus retained its integrity and penetrated cells normally; but the virus did not replicate. (author)

  7. Early estimation of pandemic influenza Antiviral and Vaccine Effectiveness (EAVE): use of a unique community and laboratory national data-linked cohort study.

    Science.gov (United States)

    Simpson, Colin R; Lone, Nazir; McMenamin, Jim; Gunson, Rory; Robertson, Chris; Ritchie, Lewis D; Sheikh, Aziz

    2015-10-01

    After the introduction of any new pandemic influenza, population-level surveillance and rapid assessment of the effectiveness of a new vaccination will be required to ensure that it is targeted to those at increased risk of serious illness or death from influenza. We aimed to build a pandemic influenza reporting platform that will determine, once a new pandemic is under way: the uptake and effectiveness of any new pandemic vaccine or any protective effect conferred by antiviral drugs once available; the clinical attack rate of pandemic influenza; and the existence of protection provided by previous exposure to, and vaccination from, A/H1N1 pandemic or seasonal influenza/identification of susceptible groups. An observational cohort and test-negative study design will be used (post pandemic). A national linkage of patient-level general practice data from 41 Practice Team Information general practices, hospitalisation and death certification, virological swab and serology-linked data. We will study a nationally representative sample of the Scottish population comprising 300,000 patients. Confirmation of influenza using reverse transcription polymerase chain reaction and, in a subset of the population, serology. Future available pandemic influenza vaccination and antivirals will be evaluated. To build a reporting platform tailored towards the evaluation of pandemic influenza vaccination. This system will rapidly measure vaccine effectiveness (VE), adjusting for confounders, estimated by determining laboratory-confirmed influenza; influenza-related morbidity and mortality, including general practice influenza-like illnesses (ILIs); and hospitalisation and death from influenza and pneumonia. Once a validated haemagglutination inhibition assay has been developed (and prior to the introduction of any vaccination), cross-reactivity with previous exposure to A/H1N1 or A/H1N1 vaccination, other pandemic influenza or other seasonal influenza vaccination or exposure will be

  8. Efficacy and safety of an antiviral Iota-Carrageenan nasal spray: a randomized, double-blind, placebo-controlled exploratory study in volunteers with early symptoms of the common cold

    Directory of Open Access Journals (Sweden)

    Weinmüllner Regina

    2010-08-01

    Full Text Available Abstract Background The common cold, the most prevalent contagious viral disease in humans still lacks a safe and effective antiviral treatment. Iota-Carrageenan is broadly active against respiratory viruses in-vitro and has an excellent safety profile. This study investigated the efficacy and safety of an Iota-Carrageenan nasal spray in patients with common cold symptoms. Methods In a randomized, double-blind, placebo-controlled exploratory trial, 35 human subjects suffering from early symptoms of common cold received Iota-Carrageenan (0.12% in a saline solution three times daily for 4 days, compared to placebo. Results Administration of Iota-Carrageenan nasal spray reduced the symptoms of common cold (p = 0.046 and the viral load in nasal lavages (p = 0.009 in patients with early symptoms of common cold. Pro-inflammatory mediators FGF-2, Fractalkine, GRO, G-CSF, IL-8, IL-1α, IP-10, IL-10, and IFN-α2 were reduced in the Iota-Carrageenan group. Conclusions Iota-Carrageenan nasal spray appears to be a promising treatment for safe and effective treatment of early symptoms of common cold. Larger trials are indicated to confirm the results.

  9. Early mantle differentiation: constraint from 146Sm-142Nd systematics

    International Nuclear Information System (INIS)

    Caro, G.

    2005-07-01

    We present new ultra-high precision 142 Nd/ 144 Nd measurements of early Archaean rocks using the new generation thermal ionization mass spectrometer TRITON. Repeated measurements of the Ames Nd standard demonstrate that the 142 Nd/ 144 Nd ratio can be determined with external precision of 2 ppm (2s), allowing confident resolution of anomalies as small as 5 ppm. A major analytical improvement lies in the elimination of the double normalization procedure required to correct our former measurements from a secondary mass fractionation effect. Our new results indicate that metasediments, meta-basalts and orthogneisses from the 3.6 - 3.8 Ga West Greenland craton display positive 142 Nd anomalies ranging from 8 to 15 ppm. Using a simple two-stage model with initial e 143 Nd value of 1.9 ± 0.6 e-units, coupled 147 Sm- 143 Nd and 146 Sm- 142 Nd chronometry constrains mantle differentiation to 50 to 200 Ma after formation of the solar system. This chronological constraint is consistent with differentiation of the Earth's mantle during the late stage of crystallization of a magma ocean. We have developed a two-box model describing 142 Nd and 143 Nd isotopic evolution of depleted mantle during the subsequent evolution of the crust-mantle system. Our results indicate that early terrestrial proto-crust had a lifetime of ca. 500 Ma in order to produce the observed Nd isotope signature of Archaean rocks. In the context of this two box mantle-crust system, we model the evolution of isotopic and chemical heterogeneity of depleted mantle as a function of the mantle stirring time. Using the dispersion of 142 Nd/ 144 Nd and 143 Nd/ 144 Nd ratios observed in early Archaean rocks, we constrain the stirring time of early Earth's mantle to 100 - 150 Ma, a factor of 5 to 10 shorter than stirring time inferred from modern oceanic basalts. (author)

  10. Interventions to Promote Cancer Awareness and Early Presentation: Systematic Review

    OpenAIRE

    J Austoker; C Bankhead; Lindsay J. L. Forbes; L Atkins; F Martin; K Robb; J Wardle; A J. Ramirez

    2009-01-01

    Background: Low cancer awareness contributes to delay in presentation for cancer symptoms and may lead to delay in cancer diagnosis. The aim of this study was to review the evidence for the effectiveness of interventions to raise cancer awareness and promote early presentation in cancer to inform policy and future research. Methods: We searched bibliographic databases and reference lists for randomised controlled trials of interventions delivered to individuals, and controlled or uncontrolled...

  11. La respuesta inmune antiviral

    OpenAIRE

    Sánchez de la Rosa, Rainel; Sánchez de la Rosa, Ernesto; Rodríguez Hernández, Néstor

    1998-01-01

    Se expone que los virus son parásitos intracelulares obligados, puesto que no tienen metabolismo propio; esto obliga al sistema inmune a poner en marcha sus mecanismos más especializados para reconocer y eliminar, tanto a los virus libres, como a las células infectadas. Se señala que las células presentadoras de antígenos, los linfocitos B y los T unidos al complejo mayor de histocompatibilidad, forman parte de la organización de la respuesta inmune antiviral; la inducción de esta respuesta c...

  12. Integrating Early Child Development and Violence Prevention Programs: A Systematic Review

    Science.gov (United States)

    Efevbera, Yvette; McCoy, Dana C.; Wuermli, Alice J.; Betancourt, Theresa S.

    2018-01-01

    Limited evidence describes promoting development and reducing violence in low- and middle-income countries (LMICs), a missed opportunity to protect children and promote development and human capital. This study presents a systematic literature review of integrated early childhood development plus violence prevention (ECD+VP) interventions in…

  13. Techniques for early diagnosis of oral squamous cell carcinoma: Systematic review

    Science.gov (United States)

    Carreras-Torras, Clàudia

    2015-01-01

    Background and objectives The diagnosis of early oral potentially malignant disorders (OPMD) and oral squamous cell carcinoma (OSCC) is of paramount clinical importance given the mortality rate of late stage disease. The aim of this study is to review the literature to assess the current situation and progress in this area. Material and Methods A search in Cochrane and PubMed (January 2006 to December 2013) has been used with the key words “squamous cell carcinoma”, “early diagnosis” “oral cavity”, “Potentially Malignant Disorders” y “premalignant lesions”. The inclusion criteria were the use of techniques for early diagnosis of OSCC and OPMD, 7 years aged articles and publications written in English, French or Spanish. The exclusion criteria were case reports and studies in other languages. Results Out of the 89 studies obtained initially from the search 60 articles were selected to be included in the systematic review: 1 metaanalysis, 17 systematic reviews, 35 prospective studies, 5 retrospective studies, 1 consensus and 1 semi-structured interviews. Conclusions The best diagnostic technique is that which we have sufficient experience and training. Definitely tissue biopsy and histopathological examination should remain the gold standard for oral cancer diagnose. In this systematic review it has not been found sufficient scientific evidence on the majority of proposed techniques for early diagnosis of OSCC, therefore more extensive and exhaustive studies are needed. Key words: Squamous cell carcinoma, early diagnosis, oral cavity, potentially malignant disorders, premalignant lesions. PMID:25662554

  14. La respuesta inmune antiviral

    Directory of Open Access Journals (Sweden)

    Rainel Sánchez de la Rosa

    1998-02-01

    Full Text Available Se expone que los virus son parásitos intracelulares obligados, puesto que no tienen metabolismo propio; esto obliga al sistema inmune a poner en marcha sus mecanismos más especializados para reconocer y eliminar, tanto a los virus libres, como a las células infectadas. Se señala que las células presentadoras de antígenos, los linfocitos B y los T unidos al complejo mayor de histocompatibilidad, forman parte de la organización de la respuesta inmune antiviral; la inducción de esta respuesta con proteínas, péptidos y ADN desnudo, son alternativas actuales tanto en la prevención como en el tratamiento de las infecciones viralesIt is explained that viruses are compulsory intracellular parasites, since they don't have their own metabolism, which makes the immune system to start its mest specialized mechanisms to recognize and eliminate the free viruses and the infected cells. It is stated that the cells presenting antigens, and the B and T lymphocytes together with the major histocompatibility complex, are part of the organization of the immune antiviral response. The induction of this response with proteins, peptides and naked DNA are the present alternatives for the prevention and treatment of viral infections

  15. Aminoadamantanes versus other antiviral drugs for chronic hepatitis C

    DEFF Research Database (Denmark)

    Lamers, Mieke H; Broekman, Mark; Drenth, Joost Ph

    2014-01-01

    months after the end of treatment) in approximately 40% to 80% of treated patients, depending on viral genotype. Recently, a new class of drugs have emerged for hepatitis C infection, the direct acting antivirals, which in combination with standard therapy or alone can lead to sustained virological...... response in 80% or more of treated patients. Aminoadamantanes, mostly amantadine, are antiviral drugs used for the treatment of patients with chronic hepatitis C. We have previously systematically reviewed amantadine versus placebo or no intervention and found no significant effects of the amantadine...... on all-cause mortality or liver-related morbidity and on adverse events in patients with hepatitis C. Overall, we did not observe a significant effect of amantadine on sustained virological response. In this review, we systematically review aminoadamantanes versus other antiviral drugs. OBJECTIVES...

  16. Early Versus Delayed Motion After Rotator Cuff Repair: A Systematic Review of Overlapping Meta-analyses.

    Science.gov (United States)

    Houck, Darby A; Kraeutler, Matthew J; Schuette, Hayden B; McCarty, Eric C; Bravman, Jonathan T

    2017-10-01

    Previous meta-analyses have been conducted to compare outcomes of early versus delayed motion after rotator cuff repair. To conduct a systematic review of overlapping meta-analyses comparing early versus delayed motion rehabilitation protocols after rotator cuff repair to determine which meta-analyses provide the best available evidence. Systematic review. A systematic review was performed by searching PubMed and Cochrane Library databases. Search terms included "rotator cuff repair," "early passive motion," "immobilization," "rehabilitation protocol," and "meta-analysis." Results were reviewed to determine study eligibility. Patient outcomes and structural healing were extracted from these meta-analyses. Meta-analysis quality was assessed using the Oxman-Guyatt and Quality of Reporting of Meta-analyses (QUOROM) systems. The Jadad decision algorithm was then used to determine which meta-analyses provided the best level of evidence. Seven meta-analyses containing a total of 5896 patients met the eligibility criteria (1 Level I evidence, 4 Level II evidence, 2 Level III evidence). None of these meta-analyses found immobilization to be superior to early motion; however, most studies suggested that early motion would increase range of motion (ROM), thereby reducing time of recovery. Three of these studies suggested that tear size contributed to the choice of rehabilitation to ensure proper healing of the shoulder. A study by Chan et al in 2014 received the highest QUOROM and Oxman-Guyatt scores, and therefore this meta-analysis appeared to have the highest level of evidence. Additionally, a study by Riboh and Garrigues in 2014 was selected as the highest quality study in this systematic review according to the Jadad decision algorithm. The current, best available evidence suggests that early motion improves ROM after rotator cuff repair but increases the risk of rotator cuff retear. Lower quality meta-analyses indicate that tear size may provide a better strategy in

  17. The effect of early postnatal discharge from hospital for women and infants: a systematic review protocol.

    Science.gov (United States)

    Jones, Eleanor; Taylor, Beck; MacArthur, Christine; Pritchett, Ruth; Cummins, Carole

    2016-02-08

    The length of postnatal hospital stay has declined over the last 40 years. There is little evidence to support a policy of early discharge following birth, and there is some concern about whether early discharge of mothers and babies is safe. The Cochrane review on the effects of early discharge from hospital only included randomised controlled trials (RCTs) which are problematic in this area, and a systematic review including other study designs is required. The aim of this broader systematic review is to determine possible effects of a policy of early postnatal discharge on important maternal and infant health-related outcomes. A systematic search of published literature will be conducted for randomised controlled trials, non-randomised controlled trials (NRCTs), controlled before-after studies (CBA), and interrupted time series studies (ITS) that report on the effect of a policy of early postnatal discharge from hospital. Databases including Cochrane CENTRAL, MEDLINE, EMBASE, CINAHL and Science Citation Index will be searched for relevant material. Reference lists of articles will also be searched in addition to searches to identify grey literature. Screening of identified articles and data extraction will be conducted in duplicate and independently. Methodological quality of the included studies will be assessed using the Effective Practice and Organisation of Care (EPOC) criteria for risk of bias tool. Discrepancies will be resolved by consensus or by consulting a third author. Meta-analysis using a random effects model will be used to combine data. Where significant heterogeneity is present, data will be combined in a narrative synthesis. The findings will be reported according to the preferred reporting items for systematic reviews (PRISMA) statement. Information on the effects of early postnatal discharge from hospital will be important for policy makers and clinicians providing maternity care. This review will also identify any gaps in the current

  18. Aciclovir: nuevo antiviral

    Directory of Open Access Journals (Sweden)

    G. Repetto

    2017-05-01

    Full Text Available El aciclovir es un antiviral útil en infecciones graves causadas por el virus varicela-zoster. Es bien tolerado con escasas reacciones adversas. En pacientes deshidratados, en insuficiencia renal o si la infusión endovenosa es muy rápida, puede ocacionar una "nefropatía obstructiva" transitoria. Existen preparados de uso tópico, oftálmico, endovenoso y oral; esta última vía constituye una ventaja sobre la vidarabina con la que tiene en común el espectro de actividad. En razón de su selectividad, riesgo de resistencia y número reducido de antivirales, su prescripción debe restringirse a infecciones graves causadas por los agentes inmunodeprimidos; excluyendo por lo tanto las comunes y autolimitadas, frecuentes en el individuo normal.

  19. Systematic and Engaging Early Literacy: Examining the Effects of Paraeducator Implemented Early Literacy Instruction

    Science.gov (United States)

    Bingham, Gary E.; Hall-Kenyon, Kendra M.; Culatta, Barbara

    2010-01-01

    This study examined the effect of explicit and engaging supplemental early literacy instruction on at-risk kindergarten children's literacy development. Sixty-three kindergarten-aged children who had been ranked in the lowest 20th percentile on basic literacy skills participated in this study (38 treatment). Results reveal that children who…

  20. Non-pharmacological and pharmacological interventions in patients with early arthritis: a systematic literature review informing the 2016 update of EULAR recommendations for the management of early arthritis

    NARCIS (Netherlands)

    Daien, Claire Immediato; Hua, Charlotte; Combe, Bernard; Landewe, Robert

    2017-01-01

    To perform a systematic literature review (SLR) on pharmacological and non-pharmacological treatments, in order to inform the European League Against Rheumatism (EULAR) recommendations for the management of early arthritis (EA). The expert committee defined research questions concerning

  1. Early prediction of outcome of activities of daily living after stroke: a systematic review

    OpenAIRE

    Veerbeek, J.M.; Kwakkel, G.; Wegen, van, E.E.H.; Ket, J.C.F.; Heijmans, M.W.

    2011-01-01

    BACKGROUND AND PURPOSE-Knowledge about robust and unbiased factors that predict outcome of activities of daily living (ADL) is paramount in stroke management. This review investigates the methodological quality of prognostic studies in the early poststroke phase for final ADL to identify variables that are predictive or not predictive for outcome of ADL after stroke. METHODS-PubMed, Ebsco/Cinahl and Embase were systematically searched for prognostic studies in which stroke patients were inclu...

  2. Antiviral therapy: a perspective

    Directory of Open Access Journals (Sweden)

    Shahidi Bonjar AH

    2016-02-01

    s recovery to a large extent depends on their general health status. EVAC would be for single use and appropriately disposed of after each detoxification procedure. When sufficient research has yielded positive results in animal models, EVAC could be used as a supportive treatment in humans along with conventional antiviral therapies. EVAC would not be suitable for all viral infections, but could be expected to decrease the casualties resulting from blood-borne viral infections. The EVAC approach would be efficient in terms of time, effort, and expenditure in the research and treatment of blood-borne viral infections. Keywords: blood, virus, infection, antiviral, sepsis, HIV, Ebola

  3. Early Interventions Following the Death of a Parent: Protocol of a Mixed Methods Systematic Review.

    Science.gov (United States)

    Pereira, Mariana; Johnsen, Iren; Hauken, May Aa; Kristensen, Pål; Dyregrov, Atle

    2017-06-29

    Previous meta-analyses examined the effectiveness of interventions for bereaved children showing small to moderate effect sizes. However, no mixed methods systematic review was conducted on bereavement interventions following the loss of a parent focusing on the time since death in regard to the prevention of grief complications. The overall purpose of the review is to provide a rigorous synthesis of early intervention after parental death in childhood. Specifically, the aims are twofold: (1) to determine the rationales, contents, timeframes, and outcomes of early bereavement care interventions for children and/or their parents and (2) to assess the quality of current early intervention studies. Quantitative, qualitative, and mixed methods intervention studies that start intervention with parentally bereaved children (and/or their parents) up to 6 months postloss will be included in the review. The search strategy was based on the Population, Interventions, Comparator, Outcomes, and Study Designs (PICOS) approach, and it was devised together with a university librarian. The literature searches will be carried out in the Medical Literature Analysis and Retrieval System Online (MEDLINE), PsycINFO, Excerpta Medica Database (EMBASE), and Cumulative Index to Nursing and Allied Health Literature (CINAHL). The Mixed Methods Appraisal Tool will be used to appraise the quality of eligible studies. All data will be narratively synthetized following the Guidance on the Conduct of Narrative Synthesis in Systematic Reviews. The systematic review is ongoing and the data search has started. The review is expected to be completed by the end of 2017. Findings will be submitted to leading journals for publication. In accordance with the current diagnostic criteria for prolonged grief as well as the users' perspectives literature, this systematic review outlines a possible sensitive period for early intervention following the death of a parent. The hereby presented protocol ensures

  4. Antiviral Drug Research Proposal Activity

    Directory of Open Access Journals (Sweden)

    Lisa Injaian

    2011-03-01

    Full Text Available The development of antiviral drugs provides an excellent example of how basic and clinical research must be used together in order to achieve the final goal of treating disease. A Research Oriented Learning Activity was designed to help students to better understand how basic and clinical research can be combined toward a common goal. Through this project students gained a better understanding of the process of scientific research and increased their information literacy in the field of virology. The students worked as teams to research the many aspects involved in the antiviral drug design process, with each student becoming an "expert" in one aspect of the project. The Antiviral Drug Research Proposal (ADRP culminated with students presenting their proposals to their peers and local virologists in a poster session. Assessment data showed increased student awareness and knowledge of the research process and the steps involved in the development of antiviral drugs as a result of this activity.

  5. Promoting Early Child Development With Interventions in Health and Nutrition: A Systematic Review.

    Science.gov (United States)

    Vaivada, Tyler; Gaffey, Michelle F; Bhutta, Zulfiqar A

    2017-08-01

    Although effective health and nutrition interventions for reducing child mortality and morbidity exist, direct evidence of effects on cognitive, motor, and psychosocial development is lacking. To review existing evidence for health and nutrition interventions affecting direct measures of (and pathways to) early child development. Reviews and recent overviews of interventions across the continuum of care and component studies. We selected systematic reviews detailing the effectiveness of health or nutrition interventions that have plausible links to child development and/or contain direct measures of cognitive, motor, and psychosocial development. A team of reviewers independently extracted data and assessed their quality. Sixty systematic reviews contained the outcomes of interest. Various interventions reduced morbidity and improved child growth, but few had direct measures of child development. Of particular benefit were food and micronutrient supplementation for mothers to reduce the risk of small for gestational age and iodine deficiency, strategies to reduce iron deficiency anemia in infancy, and early neonatal care (appropriate resuscitation, delayed cord clamping, and Kangaroo Mother Care). Neuroprotective interventions for imminent preterm birth showed the largest effect sizes (antenatal corticosteroids for developmental delay: risk ratio 0.49, 95% confidence interval 0.24 to 1.00; magnesium sulfate for gross motor dysfunction: risk ratio 0.61, 95% confidence interval 0.44 to 0.85). Given the focus on high-quality studies captured in leading systematic reviews, only effects reported within studies included in systematic reviews were captured. These findings should guide the prioritization and scale-up of interventions within critical periods of early infancy and childhood, and encourage research into their implementation at scale. Copyright © 2017 by the American Academy of Pediatrics.

  6. Early versus delayed rehabilitation following arthroscopic rotator cuff repair: A systematic review.

    Science.gov (United States)

    Gallagher, Brian P; Bishop, Meghan E; Tjoumakaris, Fotios P; Freedman, Kevin B

    2015-05-01

    Early passive range of motion (ROM) following arthroscopic cuff repair is thought to decrease postoperative stiffness and improve functionality. However, early aggressive rehabilitation may compromise repair integrity. Our purpose was to perform a systematic review to determine if there are differences between early and delayed rehabilitation after arthroscopic rotator cuff repair in terms of clinical outcomes and healing. We performed a literature search with the terms 'arthroscopic rotator cuff', 'immobilization', 'early', 'delayed', 'late', and 'rehabilitation' using PubMed, Cochrane Central Register of Controlled Trials, and EMBASE. Selection criteria included: level I/II evidence ≤ 6 months in duration, comparing early versus delayed rehabilitation following arthroscopic repair. Data regarding demographics, sample sizes, duration, cuff pathology, surgery, rehabilitation, functional outcomes, pain, ROM and anatomic assessment of healing were analyzed. PRIMSA criteria were followed. We identified six articles matching our criteria. Three reported significantly increased functional scores within the first 3-6 months with early rehabilitation compared to the delayed group, only one of which continued to observe a difference at a final follow-up of 15 months. Four articles showed improved ROM in the first 3-6 months post-operatively with early rehabilitation. One noted transient differences in pain scores. Only one study noted significant differences in ROM at final follow-up. No study reported any significant difference in rates of rotator cuff re-tear. However, two studies noted a trend towards increased re-tear with early rehabilitation that did not reach significance. This was more pronounced in studies including medium-large tears. Early rehabilitation after arthroscopic cuff repair is associated with some initial improvements in ROM and function. Ultimately, similar clinical and anatomical outcomes between groups existed at 1 year. While there was no

  7. Early onset facioscapulohumeral dystrophy - a systematic review using individual patient data.

    Science.gov (United States)

    Goselink, Rianne J M; Voermans, Nicol C; Okkersen, Kees; Brouwer, Oebele F; Padberg, George W; Nikolic, Ana; Tupler, Rossella; Dorobek, Malgorzata; Mah, Jean K; van Engelen, Baziel G M; Schreuder, Tim H A; Erasmus, Corrie E

    2017-12-01

    Infantile or early onset is estimated to occur in around 10% of all facioscapulohumeral dystrophy (FSHD) patients. Although small series of early onset FSHD patients have been reported, comprehensive data on the clinical phenotype is missing. We performed a systematic literature search on the clinical features of early onset FSHD comprising a total of 43 articles with individual data on 227 patients. Additional data from four cohorts was provided by the authors. Mean age at reporting was 18.8 years, and 40% of patients were wheelchair-dependent at that age. Half of the patients had systemic features, including hearing loss (40%), retinal abnormalities (37%) and developmental delay (8%). We found an inverse correlation between repeat size and disease severity, similar to adult-onset FSHD. De novo FSHD1 mutations were more prevalent than in adult-onset FSHD. Compared to adult FSHD, our findings indicate that early onset FSHD is overall characterized by a more severe muscle phenotype and a higher prevalence of systemic features. However, similar as in adults, a significant clinical heterogeneity was observed. Based on this, we consider early onset FSHD to be on the severe end of the FSHD disease spectrum. We found natural history studies and treatment studies to be very scarce in early onset FSHD, therefore longitudinal studies are needed to improve prognostication, clinical management and trial-readiness. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Improving early detection of gastric cancer: a novel systematic alphanumeric-coded endoscopic approach.

    Science.gov (United States)

    Emura, Fabian; Gralnek, Ian; Baron, Todd H

    2013-01-01

    Despite extensive worldwide use of standard esophagogastroduodenoscopy (EGD) examinations, gastric cancer (GC) is one of the most common forms of cancer and ranks as the most common malignant tumor in East Asia, Eastern Europe and parts of Latin America. Current limitations of using non systematic examination during standard EGD could be at least partially responsible for the low incidence of early GC diagnosis in countries with a high prevalence of the disease. Originally proposed by Emura et al., systematic alphanumeric-coded endoscopy (SACE) is a novel method that facilitates complete examination of the upper GI tract based on sequential systematic overlapping photo-documentation using an endoluminal alphanumeric-coded nomenclature comprised of eight regions and 28 areas covering the entire surface upper GI surface. For precise localization or normal or abnormal areas, SACE incorporates a simple coordinate system based on the identification of certain natural axes, walls, curvatures and anatomical endoluminal landmarks. Efectiveness of SACE was recently demonstrated in a screening study that diagnosed early GC at a frequency of 0.30% (2/650) in healthy, average-risk volunteer subjects. Such a novel approach, if uniformly implemented worldwide, could significantly change the way we practice upper endoscopy in our lifetimes.

  9. Parental and Child Characteristics Related to Early-Onset Disordered Eating: A Systematic Review.

    Science.gov (United States)

    Larsen, Pernille Stemann; Strandberg-Larsen, Katrine; Micali, Nadia; Andersen, Anne-Marie Nybo

    2015-01-01

    After participating in this activity, learners should be better able to: Evaluate the evidence regarding parental and child characteristics related to early-onset disordered eating. Eating disorders are rare in children, but disordered eating is common. Understanding the phenomenology of disordered eating in childhood can aid prevention of full-blown eating disorders. The purpose of this review is to systematically extract and synthesize the evidence on parental and child characteristics related to early-onset disordered eating. Systematic searches were conducted in PubMED/MEDLINE, EMBASE, and PsycInfo using the following search terms: eating disorder, disordered eating, problem eating, anorexia nervosa, bulimia nervosa, binge eating, child, preadolescent, and early onset. Studies published from 1990 to 2013 addressing parental and child characteristics of disordered eating in children aged 6 to 12 years were eligible for inclusion. The search was restricted to studies with cross-sectional, case-control, or longitudinal designs, studies in English, and with abstracts available. Forty-four studies fit these criteria. Most studies were based on community samples with a cross-sectional design. The included studies varied considerably in size, instruments used to assess early-onset disordered eating, and parental and child characteristics investigated. Important determinants included the following: higher body weight, previously reported disordered eating, body dissatisfaction, depression, parental disordered eating, and parental comments/concerns about child's weight and eating. The findings were inconsistent for sex, age, socioeconomic status, ethnicity, self-esteem/worth, and parental body weight. In conclusion, characteristics related to early-onset disordered eating have mainly been explored with a cross-sectional design. Full understanding of causal pathways will require good-quality longitudinal studies designed to address the influence of parental eating

  10. ANTI-VIRAL ACTIVITY OF GLYCIRRHETINIC AND GLYCIRRHIZIC ACIDS

    Directory of Open Access Journals (Sweden)

    V. V. Zarubaev

    2016-01-01

    Full Text Available Influenza is a highly contagious human disease. In the course of use of antiviral drugs drug-resistant strains of the virus are formed, resulting in reduced efficiency of the chemotherapy. The review describes the biological activity of glycirrhetinic (GLA and glycirrhizic (GA acids in terms of their use as a therapeutic agent for viral infections. So, these compounds are against a broad spectrum of viruses, including herpes, corona-, alphaand flaviviruses, human immunodeficiency virus, vaccinia virus, poliovirus type I, vesicular stomatitis virus and influenza A virus. These data indicate that anti-viral effect of these compounds is due to several types of activity — direct antiviral effects, effects on cellular proand anti-viral and immunomodulating pathways, in particular by activation of innate immunity system. GA interferes with early steps of the viral reproductive cycle such as virus binding to its receptor, the absorption of the virus by endocytosis or virus decapsidation in the cytoplasm. This is due to the effect of GA-induced reduction of membrane fluidity. Thus, one mechanism for the antiviral activity of GA is that GA molecule increases the rigidity of cellular and viral membranes after incorporation in there. This results in increasing of energy threshold required for the formation of negative curvature at the fusion zones, as well as difficult lateral migration of the virus-receptor complexes. In addition, glycyrrhizin prevents interaction of viral nucleoprotein with cellular protein HMGB1, which is necessary for the viral life cycle. Glycyrrhizin also inhibits the induction of oxidative stress during influenza infection, exhibiting antioxidant properties, which leads to a reduction of virus-induced production of cytokines/chemokines, without affecting the replication of the virus. A wide spectrum of biological activity and effect on various aspects of the viral pathogenesis substantiate the effect of GA and GLA as a component

  11. Early economic evaluation of emerging health technologies: protocol of a systematic review

    Science.gov (United States)

    2014-01-01

    Background The concept of early health technology assessment, discussed well over a decade, has now been collaboratively implemented by industry, government, and academia to select and expedite the development of emerging technologies that may address the needs of patients and health systems. Early economic evaluation is essential to assess the value of emerging technologies, but empirical data to inform the current practice of early evaluation is limited. We propose a systematic review of early economic evaluation studies in order to better understand the current practice. Methods/design This protocol describes a systematic review of economic evaluation studies of regulated health technologies in which the evaluation is conducted prior to regulatory approval and when the technology effectiveness is not well established. Included studies must report an economic evaluation, defined as the comparative analysis of alternatives with respect to their associated costs and health consequences, and must evaluate some regulated health technology such as pharmaceuticals, biologics, high-risk medical devices, or biomarkers. We will conduct the literature search on multiple databases, including MEDLINE, EMBASE, the Centre for Reviews and Dissemination Databases, and EconLit. Additional citations will be identified via scanning reference lists and author searching. We suspect that many early economic evaluation studies are unpublished, especially those conducted for internal use only. Additionally, we use a chain-referral sampling approach to identify authors of unpublished studies who work in technology discovery and development, starting out with our contact lists and authors who published relevant studies. Citation screening and full-text review will be conducted by pairs of reviewers. Abstracted data will include those related to the decision context and decision problem of the early evaluation, evaluation methods (e.g., data sources, methods, and assumptions used to

  12. Antiviral therapy: a perspective.

    Science.gov (United States)

    Shahidi Bonjar, Amir Hashem

    2016-01-01

    research has yielded positive results in animal models, EVAC could be used as a supportive treatment in humans along with conventional antiviral therapies. EVAC would not be suitable for all viral infections, but could be expected to decrease the casualties resulting from blood-borne viral infections. The EVAC approach would be efficient in terms of time, effort, and expenditure in the research and treatment of blood-borne viral infections.

  13. Early parenteral nutrition and growth outcomes in preterm infants: a systematic review and meta-analysis.

    Science.gov (United States)

    Moyses, Helen E; Johnson, Mark J; Leaf, Alison A; Cornelius, Victoria R

    2013-04-01

    The achievement of adequate nutritional intakes in preterm infants is challenging and may explain the poor growth often seen in this group. The use of early parenteral nutrition (PN) is one potential strategy to address this problem, although the benefits and harms are unknown. We determined whether earlier administration of PN benefits growth outcomes in preterm infants. We conducted a systematic review of randomized controlled trials (RCTs) and observational studies. Eight RCTs and 13 observational studies met the inclusion criteria (n = 553 and 1796 infants). The meta-analysis was limited by disparate growth-outcome measures. An assessment of bias was difficult because of inadequate reporting. Results are given as mean differences (95% CIs). Early PN reduced the time to regain birth weight by 2.2 d (1.1, 3.2 d) for RCTs and 3.2 d (2.0, 4.4 d) in observational studies. The maximum percentage weight loss with early PN was lower by 3.1 percentage points (1.7, 4.5 percentage points) for RCTs and by 3.5 percentage points (2.6, 4.3 percentage points) for observational studies. Early PN improved weight at discharge or 36 wk postmenstrual age by 14.9 g (5.3, 24.5 g) (observational studies only), but no benefit was shown for length or head circumference. There was no evidence that early PN significantly affects risk of mortality, necrotizing enterocolitis, sepsis, chronic lung disease, intraventricular hemorrhage, or cholestasis. The results of this review, although subject to some limitations, show that early PN provides a benefit for some short-term growth outcomes. No evidence that early PN increases morbidity or mortality was found. Neonatal research would benefit from the development of a set of core growth outcome measures.

  14. The uses of outcome measures within multidisciplinary early childhood intervention services: a systematic review.

    Science.gov (United States)

    Calder, Samuel; Ward, Roslyn; Jones, Megan; Johnston, Jenelle; Claessen, Mary

    2017-07-18

    Purpose of the article: To review the use of outcome measures, across the domains of activity, participation, and environment, within multidisciplinary early childhood intervention services. A systematic literature search was undertaken that included four electronic databases: Medline, CINAHL, EMBASE, and the Cochrane Library and Cochrane Database of Systematic Review. Inclusion criteria were age 0-24 months, having or at risk of a developmental disability, in receipt of multidisciplinary early childhood intervention services, and included outcome measures across all domains of the International Classification of Functioning-Child & Youth (ICF-CY). Only peer-reviewed journal articles were considered. Eligible studies were coded using the Oxford Levels of Evidence. Methodological quality was assessed using the Physiotherapy Evidence Database (PEDro) Scale for randomised controlled trials and the QualSyst for non-randomised control trials. Of the total of 5764 records identified, 10 were considered to meet inclusion criteria. Fourteen outcome measures were identified, addressing the domains of activity, participation, and environment. Of these, eight have been recommended in the early intervention literature. While the methodological quality of the 10 studies varied, these papers make a contribution to the body of research that acknowledges the role of routine and enriched environments. Implications for Rehabilitation Core practice elements of multidisciplinary early childhood intervention services indicate it is necessary to select outcome measures framed within the International Classification of Functioning-Child & Youth to inform clinical decision-making for measuring intervention effectiveness across the domains of activity, participation and environment. Of the identified measures, three (Canadian Occupational Performance Measure, Pediatric Evaluation of Disability Inventory, and Goal Attainment Scaling) are well-established and identified in the literature as

  15. Viral ancestors of antiviral systems.

    Science.gov (United States)

    Villarreal, Luis P

    2011-10-01

    All life must survive their corresponding viruses. Thus antiviral systems are essential in all living organisms. Remnants of virus derived information are also found in all life forms but have historically been considered mostly as junk DNA. However, such virus derived information can strongly affect host susceptibility to viruses. In this review, I evaluate the role viruses have had in the origin and evolution of host antiviral systems. From Archaea through bacteria and from simple to complex eukaryotes I trace the viral components that became essential elements of antiviral immunity. I conclude with a reexamination of the 'Big Bang' theory for the emergence of the adaptive immune system in vertebrates by horizontal transfer and note how viruses could have and did provide crucial and coordinated features.

  16. Viral Ancestors of Antiviral Systems

    Directory of Open Access Journals (Sweden)

    Luis P. Villarreal

    2011-10-01

    Full Text Available All life must survive their corresponding viruses. Thus antiviral systems are essential in all living organisms. Remnants of virus derived information are also found in all life forms but have historically been considered mostly as junk DNA. However, such virus derived information can strongly affect host susceptibility to viruses. In this review, I evaluate the role viruses have had in the origin and evolution of host antiviral systems. From Archaea through bacteria and from simple to complex eukaryotes I trace the viral components that became essential elements of antiviral immunity. I conclude with a reexamination of the ‘Big Bang’ theory for the emergence of the adaptive immune system in vertebrates by horizontal transfer and note how viruses could have and did provide crucial and coordinated features.

  17. The Antiviral Effect of Baicalin on Enterovirus 71 In Vitro

    Directory of Open Access Journals (Sweden)

    Xiang Li

    2015-08-01

    Full Text Available Baicalin is a flavonoid compound extracted from Scutellaria roots that has been reported to possess antibacterial, anti-inflammatory, and antiviral activities. However, the antiviral effect of baicalin on enterovirus 71 (EV71 is still unknown. In this study, we found that baicalin showed inhibitory activity on EV71 infection and was independent of direct virucidal or prophylactic effect and inhibitory viral absorption. The expressions of EV71/3D mRNA and polymerase were significantly blocked by baicalin treatment at early stages of EV71 infection. In addition, baicalin could decrease the expressions of FasL and caspase-3, as well as inhibit the apoptosis of EV71-infected human embryonal rhabdomyosarcoma (RD cells. Altogether, these results indicate that baicalin exhibits potent antiviral effect on EV71 infection, probably through inhibiting EV71/3D polymerase expression and Fas/FasL signaling pathways.

  18. Antiviral agents: structural basis of action and rational design.

    Science.gov (United States)

    Menéndez-Arias, Luis; Gago, Federico

    2013-01-01

    During the last 30 years, significant progress has been made in the development of novel antiviral drugs, mainly crystallizing in the establishment of potent antiretroviral therapies and the approval of drugs inhibiting hepatitis C virus replication. Although major targets of antiviral intervention involve intracellular processes required for the synthesis of viral proteins and nucleic acids, a number of inhibitors blocking virus assembly, budding, maturation, entry or uncoating act on virions or viral capsids. In this review, we focus on the drug discovery process while presenting the currently used methodologies to identify novel antiviral drugs by using a computer-based approach. We provide examples illustrating structure-based antiviral drug development, specifically neuraminidase inhibitors against influenza virus (e.g. oseltamivir and zanamivir) and human immunodeficiency virus type 1 protease inhibitors (i.e. the development of darunavir from early peptidomimetic compounds such as saquinavir). A number of drugs in preclinical development acting against picornaviruses, hepatitis B virus and human immunodeficiency virus and their mechanism of action are presented to show how viral capsids can be exploited as targets of antiviral therapy.

  19. Mood and anxiety disorders as early manifestations of medical illness: a systematic review.

    Science.gov (United States)

    Cosci, Fiammetta; Fava, Giovanni A; Sonino, Nicoletta

    2015-01-01

    Affective disturbances involving alterations of mood, anxiety and irritability may be early symptoms of medical illnesses. The aim of this paper was to provide a systematic review of the literature with qualitative data synthesis. MEDLINE, PsycINFO, EMBASE, Cochrane, and ISI Web of Science were systematically searched from inception to February 2014. Search terms were 'prodrome/early symptom', combined using the Boolean 'AND' operator with 'anxiety/depression/mania/hypomania/irritability/irritable mood/hostility', combined with the Boolean 'AND' operator with 'medical illness/medical disorder'. PRISMA guidelines were followed. A total of 21 studies met the inclusion criteria and were analyzed. Depression was found to be the most common affective prodrome of medical disorders and was consistently reported in Cushing's syndrome, hypothyroidism, hyperparathyroidism, pancreatic and lung cancer, myocardial infarction, Wilson's disease, and AIDS. Mania, anxiety and irritability were less frequent. Physicians may not pursue medical workup of cases that appear to be psychiatric in nature. They should be alerted that disturbances in mood, anxiety and irritability may antedate the appearance of a medical disorder.

  20. Revisión sistemática de evaluaciones económicas de fármacos antivirales para el tratamiento de la hepatitis B crónica Economic evaluation of antiviral treatment for chronic hepatitis B: a systematic review

    Directory of Open Access Journals (Sweden)

    Lely Solari

    2010-03-01

    performed a systematic revision on MEDLINE, LILACS NICE and COCHRANE databases, searching for economic evaluations of antiviral regimens for treatment of chronic hepatitis B. We included original studies, systematic revisions and management guidelines including information on the cost-effectiveness of this treatment. We registered the characteristics and results of the retrieved documents. Results. We obtained 29 original papers, 4 revision articles and 4 management guidelines. Most of these publications have been done in the last 5 years. There was conflict of interest in 73% of original articles, due to authors working for the pharmaceutical industry. 93% of articles that evaluate the cost-effectiveness of giving treatment for chronic hepatitis B against management of its complications find that it is indeed cost-effective to give antiviral treatment. 3/6 studies that evaluate lamivudine against other drugs find it as a dominant strategy, 3/5 find entecavir as the dominant strategy, 1/1 find tenofovir dominant, ¼ find conventional interferon as dominant and none of them find adefovir or pegylated interferon as dominant strategies. Conclusions. We consider that the available evidence suggests that to give antiviral treatment for chronic hepatitis B is a cost-effective intervention for many health systems, including ours. It has varying indexes of cost-effectiveness according to the evaluated regimens. Ideally , we should perform local economic evaluations in this issue.

  1. Consequences of early extraction of compromised first permanent molar: a systematic review.

    Science.gov (United States)

    Saber, Afnan M; Altoukhi, Doua H; Horaib, Mariam F; El-Housseiny, Azza A; Alamoudi, Najlaa M; Sabbagh, Heba J

    2018-04-05

    The aim of this study was to systematically review the literature to determine the sequelae of early extraction of compromised first permanent molars (FPMs) with regard to the skeletal and dental development of 5- to 15-year-old children. Meta-analysis was conducted when applicable. Our research protocol included a search strategy, inclusion/exclusion criteria, and a data extraction plan. The search engines used were PubMed, Scopus, and Science Direct. Study selection was performed independently by three reviewers. Articles published from 1960 to 2017 were reviewed based on inclusion and exclusion criteria. Meta-analysis was performed to compare space closure between upper and lower arches. Eleven studies fulfilled the inclusion criteria. The consequences were decrease in post extraction space, accelerated development and eruption of second permanents molars (SPMs) and third molars, a decrease in caries and/or fillings on the proximal surfaces of adjacent teeth, lingual tipping and retrusion of incisors, and counter clockwise rotation of the occlusal plane. There were several consequences of early extraction of FPMs, which were related to skeletal and dental development. Our systematic review suggests that comprehensive evaluation of the compromised FPMs should be performed before planning an extraction. The ideal time for FPM extraction is when the SPM is at the early bifurcation stage in order to achieve complete closure of the extraction space by the SPM. Benefits should be weighed over the risks to decrease the risk of unfavorable outcomes as much as possible. However, due to the limited evidence on the outcomes and variables that influence them, high-quality prospective studies are needed.

  2. The future of antiviral immunotoxins

    DEFF Research Database (Denmark)

    Spiess, K.; Høy Jakobsen, Mette; Kledal, Thomas N

    2016-01-01

    There is a constant need for new therapeutic interventions in a wide range of infectious diseases. Over the past few years, the immunotoxins have entered the stage as promising antiviral treatments. Immunotoxins have been extensively explored in cancer treatment and have achieved FDA approval in ...

  3. A systematic review of early intensive intervention for autism spectrum disorders.

    Science.gov (United States)

    Warren, Zachary; McPheeters, Melissa L; Sathe, Nila; Foss-Feig, Jennifer H; Glasser, Allison; Veenstra-Vanderweele, Jeremy

    2011-05-01

    Early intensive behavioral and developmental interventions for young children with autism spectrum disorders (ASDs) may enhance developmental outcomes. To systematically review evidence regarding such interventions for children aged 12 and younger with ASDs. We searched Medline, PsycINFO, and ERIC (Education Resources Information Center) from 2000 to May 2010. Two reviewers independently assessed studies against predetermined inclusion/exclusion criteria. Two reviewers independently extracted data regarding participant and intervention characteristics, assessment techniques, and outcomes and assigned overall quality and strength-of-evidence ratings using predetermined criteria. Thirty-four unique studies met inclusion criteria. Seventeen studies were case series; 2 were randomized controlled trials. We rated 1 study as good quality, 10 as fair quality, and 23 as poor quality. The strength of the evidence overall ranged from insufficient to low. Studies of University of California Los Angeles/Lovaas-based interventions and variants reported clinically significant gains in language and cognitive skills in some children, as did 1 randomized controlled trial of an early intensive developmental intervention approach (the Early Start Denver Model). Specific parent-training approaches yielded gains in short-term language function and some challenging behaviors. Data suggest that subgroups of children displayed more prominent gains across studies, but participant characteristics associated with greater gains are not well understood. Studies of Lovaas-based approaches and early intensive behavioral intervention variants and the Early Start Denver Model resulted in some improvements in cognitive performance, language skills, and adaptive behavior skills in some young children with ASDs, although the literature is limited by methodologic concerns.

  4. Antiviral Polymer Therapeutics

    DEFF Research Database (Denmark)

    Smith, Anton Allen Abbotsford

    2014-01-01

    polymerized in a controlled manner with carrier monomers of historically proven biocompatible polymers. The carrier polymers, the loading of ribavirin as well as the size of the polymer were varied systematically with the aid of an automated synthesis platform. These polymers were tested in a cellular assay...... of reversible-addition-fragmentation chain transfer polymerization, which not only controls the size of polymer, but also allows the introduction of a terminal amine on the polymer which can be used for further conjugation. This has allowed for not only fluorescent labeling of the polymer, but also protein...... is mediated through specific transporters, it is thought that the accumulation can be alleviated through the attachment of ribavirin to a macromolecule. To this end, ribavirin was enzymatically modified into a monomer compatible with controlled polymerization techniques. The ribavirin monomers were...

  5. Effects of Early Neglect Experience on Recognition and Processing of Facial Expressions: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Victoria Doretto

    2018-01-01

    Full Text Available Background: Child neglect is highly prevalent and associated with a series of biological and social consequences. Early neglect may alter the recognition of emotional faces, but its precise impact remains unclear. We aim to review and analyze data from recent literature about recognition and processing of facial expressions in individuals with history of childhood neglect. Methods: We conducted a systematic review using PubMed, PsycINFO, ScIELO and EMBASE databases in the search of studies for the past 10 years. Results: In total, 14 studies were selected and critically reviewed. A heterogeneity was detected across methods and sample frames. Results were mixed across studies. Different forms of alterations to perception of facial expressions were found across 12 studies. There was alteration to the recognition and processing of both positive and negative emotions, but for emotional face processing there was predominance in alteration toward negative emotions. Conclusions: This is the first review to examine specifically the effects of early neglect experience as a prevalent condition of child maltreatment. The results of this review are inconclusive due to methodological diversity, implement of distinct instruments and differences in the composition of the samples. Despite these limitations, some studies support our hypothesis that individuals with history of early negligence may present alteration to the ability to perceive face expressions of emotions. The article brings relevant information that can help in the development of more effective therapeutic strategies to reduce the impact of neglect on the cognitive and emotional development of the child.

  6. Early infant male circumcision: Systematic review, risk-benefit analysis, and progress in policy.

    Science.gov (United States)

    Morris, Brian J; Kennedy, Sean E; Wodak, Alex D; Mindel, Adrian; Golovsky, David; Schrieber, Leslie; Lumbers, Eugenie R; Handelsman, David J; Ziegler, John B

    2017-02-08

    To determine whether recent evidence-based United States policies on male circumcision (MC) apply to comparable Anglophone countries, Australia and New Zealand. Articles in 2005 through 2015 were retrieved from PubMed using the keyword "circumcision" together with 36 relevant subtopics. A further PubMed search was performed for articles published in 2016. Searches of the EMBASE and Cochrane databases did not yield additional citable articles. Articles were assessed for quality and those rated 2+ and above according to the Scottish Intercollegiate Grading System were studied further. The most relevant and representative of the topic were included. Bibliographies were examined to retrieve further key references. Randomized controlled trials, recent high quality systematic reviews or meta-analyses (level 1++ or 1+ evidence) were prioritized for inclusion. A risk-benefit analysis of articles rated for quality was performed. For efficiency and reliability, recent randomized controlled trials, meta-analyses, high quality systematic reviews and large well-designed studies were used if available. Internet searches were conducted for other relevant information, including policies and Australian data on claims under Medicare for MC. Evidence-based policy statements by the American Academy of Pediatrics (AAP) and the Centers for Disease Control and Prevention (CDC) support infant and later age male circumcision (MC) as a desirable public health measure. Our systematic review of relevant literature over the past decade yielded 140 journal articles that met our inclusion criteria. Together, these showed that early infant MC confers immediate and lifelong benefits by protecting against urinary tract infections having potential adverse long-term renal effects, phimosis that causes difficult and painful erections and "ballooning" during urination, inflammatory skin conditions, inferior penile hygiene, candidiasis, various sexually transmissible infections in both sexes, genital

  7. Integrating Early Child Development and Violence Prevention Programs: A Systematic Review.

    Science.gov (United States)

    Efevbera, Yvette; McCoy, Dana C; Wuermli, Alice J; Betancourt, Theresa S

    2018-03-01

    Limited evidence describes promoting development and reducing violence in low- and middle-income countries (LMICs), a missed opportunity to protect children and promote development and human capital. This study presents a systematic literature review of integrated early childhood development plus violence prevention (ECD+VP) interventions in LMICs. The search yielded 5,244 unique records, of which N = 6 studies met inclusion criteria. Interventions were in Chile, Jamaica, Lebanon, Mexico, Mozambique, and Turkey. Five interventions were parent education programs, including center-based sessions (n = 3) and home visiting (n = 2), while one intervention was a teacher education program. All but one study reported improvements in both child development and maltreatment outcomes. The dearth of evidence on ECD+VP interventions suggests additional research is needed. Integrated ECD+VP interventions may improve multiple child outcome domains while leveraging limited resources in LMICs. © 2018 Wiley Periodicals, Inc.

  8. Insight on the anatomy, systematic relationships, and age of the Early Cretaceous ankylopollexian dinosaur Dakotadon lakotaensis

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    Clint A. Boyd

    2015-09-01

    Full Text Available Knowledge regarding the early evolution within the dinosaurian clade Ankylopollexia drastically increased over the past two decades, in part because of an increase in described taxa from the Early Cretaceous of North America. These advances motivated the recent completion of extensive preparation and conservation work on the holotype and only known specimen of Dakotadon lakotaensis, a basal ankylopollexian from the Lakota Formation of South Dakota. That specimen (SDSM 8656 preserves a partial skull, lower jaws, a single dorsal vertebra, and two caudal vertebrae. That new preparation work exposed several bones not included in the original description and revealed that other bones were previously misidentified. The presence of extensive deformation in areas of the skull is also noted that influenced inaccuracies in prior descriptions and reconstructions of this taxon. In addition to providing an extensive re-description of D. lakotaensis, this study reviews previously proposed diagnoses for this taxon, identifies two autapomorphies, and provides an extensive differential diagnosis. Dakotadon lakotaensis is distinct from the only other ankylopollexian taxon known from the Lakota Formation, Osmakasaurus depressus, in the presence of two prominent, anteroposteriorly oriented ridges on the ventral surfaces of the caudal vertebrae, the only overlapping material preserved between these taxa. The systematic relationships of D. lakotaensis are evaluated using both the parsimony and posterior probability optimality criteria, with both sets of analyses recovering D. lakotaensis as a non-hadrosauriform ankylopollexian that is more closely related to taxa from the Early Cretaceous (e.g., Iguanacolossus, Hippodraco, and Theiophytalia than to more basally situated taxa from the Jurassic (e.g., Camptosaurus, Uteodon. This taxonomic work is supplemented by field work that relocated the type locality, confirming its provenance from unit L2 (lower Fuson Member

  9. An early-stage epidemic: a systematic review of correlates of smoking among Chinese women.

    Science.gov (United States)

    Ding, Ding; Gebel, Klaus; Oldenburg, Brian F; Wan, Xia; Zhong, Xuefeng; Novotny, Thomas E

    2014-08-01

    Despite the historically low smoking prevalence among Chinese women, there is a trend of future increase. We systematically reviewed the correlates of smoking among Chinese girls and women. We conducted a systematic review of literature on correlates of smoking among Chinese women using Medline and China Academic Journals databases. Following the PRISMA statement, two investigators independently searched for literature, identified and reviewed papers, assessed the quality of the papers, and extracted information. The characteristics of studies and correlates of smoking were synthesized separately for youth and adults. A total of 15 articles (11 on adults, 4 on youth) met the inclusion criteria. Based on these studies, peer smoking was the most consistent correlate of smoking among Chinese girls. Among Chinese women, partner smoking, job-related stress, and exposure to cigarettes made for women were consistent correlates of smoking. Knowledge of harms and negative attitudes towards smoking were found to be negatively associated with smoking. Overall, the evidence base for smoking among Chinese women is limited. Although smoking among Chinese women is still at an early stage, it is becoming more prevalent among specific population subgroups, such as rural-to-urban migrant workers. Although further research is needed, findings from the current study provide a roadmap for research and policy on prevention of smoking among Chinese girls and women.

  10. Economics of Early Warning Scores for identifying clinical deterioration-a systematic review.

    Science.gov (United States)

    Murphy, A; Cronin, J; Whelan, R; Drummond, F J; Savage, E; Hegarty, J

    2018-02-01

    In 2013, a National Early Warning System (EWS) was implemented in Ireland. Whilst evidence exists to support the clinical effectiveness of EWS in the acute health care setting, there is a paucity of information on their cost and cost effectiveness. The objective of this systematic literature review was to critically evaluate the economic literature on the use of EWS in adult patients in acute health care settings for the timely detection of physiological deterioration. A systematic literature review was conducted to accumulate the economic evidence on the use of EWS in adult patients in acute health care settings. The search yielded one health technology assessment, two budget impact analyses and two cost descriptions. Three of the studies were Irish, and considered the national EWS system. A Dutch study reported financial consequences of a single parameter EWS, as part of a rapid response system, in a surgical ward. The fifth study examined an advanced triage system in a medical emergency admission unit in Wales. The economic evidence on the use of EWS amongst adult patients in acute health care settings for the timely detection of physiological deterioration is limited. Further research is required to investigate the cost effectiveness of EWS, and the appropriateness of using standard methods to do so. The recent implementation of a national EWS in Ireland offers a unique opportunity to bridge this gap in the literature to examine the costs and cost effectiveness of a nationally implemented EWS system.

  11. Arthroscopic coracoid transfer in the treatment of recurrent shoulder instability: a systematic review of early results.

    Science.gov (United States)

    Butt, Usman; Charalambous, Charalambos P

    2013-04-01

    Systematic review of the literature to characterize safety profile and complication rates associated with arthroscopic coracoid transfer procedures. We conducted a combined search of Medline, EMBASE, and the CINAHL databases from 1985 to November 2012. Articles were selected and data extracted according to standard criteria. Only 3 studies met the inclusion criteria, and these originated from the pioneers of this technique. These studies described the results of 172 arthroscopic coracoid transfer procedures with an overall complication rate of 19.8% ± 5.6%. Conversion to open surgery was necessary in 6/172 (3.5%) patients. Repeated surgery was described in 5/172 (2.9% ± 2.5%) cases, all for screw removal. The overall rate of recurrent instability was 3/172 cases (1.7% ± 2%). Hardware-related complications occurred in 4/172 patients (2.3% ± 2.3%). Coracoid grafts failed to unite in 14/172 patients (8.1% ± 4.1%); graft osteolysis was seen in 7/172 patients (4.1% ± 2.6%). The coracoid graft fractured in 2/172 cases (1.2% ± 1.6%); one of these occurred intraoperatively and one occurred early postoperatively. There was one transient nerve palsy (0.6% ± 1.1%). Results of arthroscopic coracoid transfer surgery for anterior shoulder instability are sparse, with the available studies originating from the pioneers of this technique. Early results suggest that arthroscopic coracoid transfer is a technically feasible procedure that is able to restore shoulder stability. However, this technique seems to be associated with a high complication rate and a steep learning curve. Results from the wider orthopaedic shoulder arthroscopic community are awaited. Extensive cadaveric training and experience with the open technique is recommended before performing the arthroscopic procedure. Systematic review of Level IV studies. Copyright © 2013 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

  12. Comprehensive geriatric assessment for older women with early breast cancer – a systematic review of literature

    Directory of Open Access Journals (Sweden)

    Parks Ruth M

    2012-05-01

    Full Text Available Abstract Background The Comprehensive Geriatric Assessment (CGA is an analytical tool increasingly implemented in clinical practice. Breast cancer is primarily a disease of older people; however, most evidence-based research is aimed at younger patients. Methods A systematic review of literature was carried out to assess the use of CGA in older breast cancer patients for clinical decision making. The PubMed, Embase and Cochrane databases were searched. Results A total of nine useful full text article results were found. Only five of these were exclusively concerned with early breast cancer; thus, studies involving a variety of cancer types, stages and treatments were accepted, as long as they included early breast cancer.The results comprised a series of low sources of evidence. However, all results shared a common theme: the CGA has a use in determining patient suitability for different types of cancer treatment and subsequently maximizing the patient’s quality of life. Conclusions There is not yet sufficient high level evidence to instate CGA guidelines as a mandatory practice in the management of breast cancer, due to the heterogeneity of available studies. More studies need to be conducted to cement current work on the benefits of the CGA. An area of particular interest is with regard to treatment options, especially surgery and chemotherapy, and identifying patients who may be suitable for these treatments.

  13. Diet and body fat in adolescence and early adulthood: a systematic review of longitudinal studies

    Directory of Open Access Journals (Sweden)

    Bruna Celestino Schneider

    Full Text Available Abstract Adipose tissue is a vital component of the human body, but in excess, it represents a risk to health. According to the World Health Organization, one of the main factors determining excessive body adiposity is the dietary habit. This systematic review investigated longitudinal studies that assessed the association between diet and body fat in adolescents and young adults. Twenty-one relevant papers published between 2001 and 2015 were selected. The most used method for estimating body fat was the body mass index (15 studies. Diet was most commonly assessed by estimating the consumption of food groups (cereals, milk and dairy products and specific foods (sugar-sweetened beverages, soft drinks, fast foods, milk, etc.. Ten studies found a direct association between diet and quantity of body fat. During adolescence, adhering to a dietary pattern characterized by high consumption of energy-dense food, fast foods, sugar-sweetened beverages and soft drinks, as well as low fiber intake, appears to contribute to an increase in body fat in early adulthood. The findings of the present study suggest that the frequent consumption of unhealthy foods and food groups (higher energy density and lower nutrient content in adolescence is associated with higher quantity of body fat in early adulthood.

  14. Early versus Late Decompression for Traumatic Spinal Cord Injuries; a Systematic Review and Meta-analysis

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    Mahmoud Yousefifard

    2017-01-01

    Full Text Available Introduction: Despite the vast number of surveys, no consensus has been reached on the optimum timing of spinal decompression surgery. This systematic review and meta-analysis aimed to compare the effects of early and late spinal decompression surgery on neurologic improvement and post-surgical complications in patients with traumatic spinal cord injuries.Methods: Two independent reviewers carried out an extended search in electronic databases. Data of neurological outcome and post-surgery complication were extracted. Finally, pooled relative risk (RR with a 95% confidence interval (CI was reported for comparing of efficacy of early and late surgical decompression.Results: Eventually 22 studies were included. The pooled RR was 0.77 (95% CI: 0.68-0.89 for at least one grade neurological improvement, and 0.84 (95% CI: 0.77-0.92 for at least two grade improvement. Pooled RR for surgical decompression performed within 12 hours after the injury was 0.26 (95% CI: 0.13-0.52; p<0.001, while it was 0.75 (95% CI: 0.63-0.90; p=0.002 when the procedure was performed within 24 hours, and 0.93 (95% CI: 0.76-1.14; p=0.48 when it was carried out in the first 72 hours after the injury. Surgical decompression performed within 24 hours after injury was found to be associated with significantly lower rates of post-surgical complications (RR=0.77; 95% CI: 0.68-0.86; p<0.001.Conclusion: The findings of this study indicate that early spinal decompression surgery can improve neurologic recovery and is associated with less post-surgical complications. The optimum efficacy is observed when the procedure is performed within 12 hours of the injury.

  15. Cellular Antiviral Factors that Target Particle Infectivity of HIV-1.

    Science.gov (United States)

    Goffinet, Christine

    2016-01-01

    In the past decade, the identification and characterization of antiviral genes with the ability to interfere with virus replication has established cell-intrinsic innate immunity as a third line of antiviral defense in addition to adaptive and classical innate immunity. Understanding how cellular factors have evolved to inhibit HIV-1 reveals particularly vulnerable points of the viral replication cycle. Many, but not all, antiviral proteins share type I interferon-upregulated expression and sensitivity to viral counteraction or evasion measures. Whereas well-established restriction factors interfere with early post-entry steps and release of HIV-1, recent research has revealed a diverse set of proteins that reduce the infectious quality of released particles using individual, to date poorly understood modes of action. These include induction of paucity of mature glycoproteins in nascent virions or self-incorporation into the virus particle, resulting in poor infectiousness of the virion and impaired spread of the infection. A better understanding of these newly discovered antiviral factors may open new avenues towards the design of drugs that repress the spread of viruses whose genomes have already integrated.

  16. Early orthodontic treatment for Class III malocclusion: A systematic review and meta-analysis.

    Science.gov (United States)

    Woon, See Choong; Thiruvenkatachari, Badri

    2017-01-01

    Class III malocclusion affects between 5% and 15% of our population. The 2 most common dilemmas surrounding Class III treatment are the timing of treatment and the type of appliance. A number of appliances have been used to correct a Class III skeletal discrepancy, but there is little evidence available on their effectiveness in the long term. Similarly, early treatment of Class III malocclusion has been practiced with increasing interest. However, there has been no solid evidence on the benefits in the long term. The aim of this systematic review was to evaluate the effectiveness of orthodontic/orthopedic methods used in the early treatment of Class III malocclusion in the short and long terms. Several sources were used to identify all relevant studies independently of language. The Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Embase (Ovid), and MEDLINE (Ovid) were searched to June 2016. The selection criteria included randomized controlled trials (RCTs) and prospective controlled clinical trials (CCTs) of children between the ages of 7 and 12 years on early treatment with any type of orthodontic/orthopedic appliance compared with another appliance to correct Class III malocclusion or with an untreated control group. The primary outcome measure was correction of reverse overjet, and the secondary outcomes included skeletal changes, soft tissue changes, quality of life, patient compliance, adverse effect, Peer Assessment Rating score, and treatment time. The search results were screened for inclusion, and the data extracted by 2 independent authors. The data were analyzed using software (version 5.1, Review Manager; The Nordic Cochrane Centre, The Cochrane Collaboration; Copenhagen, Denmark). The mean differences with 95% confidence intervals were expressed for the continuous data. Random effects were carried out with high levels of clinical or statistical heterogeneity and fixed affects when the heterogeneity was low

  17. Practice patterns and outcomes associated with early sedation depth in mechanically ventilated patients: a systematic review protocol.

    Science.gov (United States)

    Stephens, Robert J; Dettmer, Matthew R; Roberts, Brian W; Fowler, Susan A; Fuller, Brian M

    2017-06-09

    Mechanical ventilation is a commonly performed intervention in critically ill patients. Frequently, these patients experience deep sedation early in their clinical course. Emerging data suggest that the practice of early deep sedation may negatively impact patient outcomes. The purpose of this review is to assess the world's literature to describe and determine the impact of early deep sedation on the outcomes of mechanically ventilated patients. Randomised controlled trials and non-randomised studies will be eligible for inclusion in this systematic review. With the assistance of a medical librarian, we will comprehensively search MEDLINE, Embase, Scopus, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews and Effects, and Cochrane Database of Systematic Reviews for peer-reviewed literature. Grey literature from appropriate professional society conferences, held from 2010 to 2017, will be reviewed manually. Two authors will independently review all search results, and disagreements will be resolved through arbitration by a third author. If appropriate, meta-analysis will be used for quantitative analysis of the data. Heterogeneity between studies will be assessed using the I 2 statistic. The proposed systematic review will not collect data that are associated with individual patients and does not require ethical approval. Results of this study will contribute to the understanding of early sedation, identify future research targets and guide early care in mechanically ventilated patients. This systematic review has been registered in the international prospective register of systematic reviews (PROSPERO #CRD42017057264). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  18. Reconsideration of the systematics of the Early Pleistocene Cervavitus (Cervidae, Artiodactyla, Mammalia

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    Dong, W.

    2011-12-01

    Full Text Available Cervavitus were usually found from the Late Miocene and Pliocene deposits in East Europe, Middle Asia and North China, but they were found recently in many Early Pleistocene localities in southern China. The latter resulted in the discussion of their systematic status between Cervavitus and Cervus. Here we show the Early Pleistocene forms from southern China are morphometrically more similar to northern China Cervavitus species, and the cladistic analysis shows that the southern China forms are closer to classic Cervavitus species than Cervus and that also proves their systematic status in Cervavitus rather than in Cervus. Cervavitus originated in Moldovan forests of East Europe in the late Vallesian (MN10 from a brachyodont and holometacarpal ancestor with two/three-tined antlers and Palaeomeryx fold and evolved into C. novorossiae. It dispersed into West Europe forests in the earliest Turolian and further west to France in the Ruscinian. It dispersed into northern China forests in the early Turolian and represented by C. shanxius. The great quantity of C. shanxius specimens with brachyodont teeth and complete lateral metacarpals implies the arid Loess Plateau of today was a humid forested region in the Late Miocene. C. shanxius migrated southwards in the Plio-Pleistocene probably due to the drying environment in northern China with uplifting of Himalayas and evolved into C. ultimus and C. fenqii, which survived in southern China until the Early Pleistocene (MNQ18.La revisión sistemática de Cervivatus sugiere que deriva del principal clado de los cérvidos posteriores a los muntiacinos, e implica que Procervulinae, Dicrocerinae y la primeras formas de Munticiacinae serían holometacarpales, como también lo es Cervivatus, originario en los bosques de Moldavia (Europa del Este durante el Vallesiense final (MN 10, a partir de un antecesor braquiodonto y holometacarpal, con astas con dos o tres candiles y pliegue paleomerícido, y que da lugar a

  19. Early Pregnancy Biomarkers in Pre-Eclampsia: A Systematic Review and Meta-Analysis

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    Pensée Wu

    2015-09-01

    Full Text Available Pre-eclampsia (PE complicates 2%–8% of all pregnancies and is an important cause of perinatal morbidity and mortality worldwide. In order to reduce these complications and to develop possible treatment modalities, it is important to identify women at risk of developing PE. The use of biomarkers in early pregnancy would allow appropriate stratification into high and low risk pregnancies for the purpose of defining surveillance in pregnancy and to administer interventions. We used formal methods for a systematic review and meta-analyses to assess the accuracy of all biomarkers that have been evaluated so far during the first and early second trimester of pregnancy to predict PE. We found low predictive values using individual biomarkers which included a disintegrin and metalloprotease 12 (ADAM-12, inhibin-A, pregnancy associated plasma protein A (PAPP-A, placental growth factor (PlGF and placental protein 13 (PP-13. The pooled sensitivity of all single biomarkers was 0.40 (95% CI 0.39–0.41 at a false positive rate of 10%. The area under the Summary of Receiver Operating Characteristics Curve (SROC was 0.786 (SE 0.02. When a combination model was used, the predictive value improved to an area under the SROC of 0.893 (SE 0.03. In conclusion, although there are multiple potential biomarkers for PE their efficacy has been inconsistent and comparisons are difficult because of heterogeneity between different studies. Therefore, there is an urgent need for high quality, large-scale multicentre research in biomarkers for PE so that the best predictive marker(s can be identified in order to improve the management of women destined to develop PE.

  20. Understanding Factors that Shape Gender Attitudes in Early Adolescence Globally: A Mixed-Methods Systematic Review

    Science.gov (United States)

    Gibbs, Susannah; Blum, Robert Wm; Moreau, Caroline; Chandra-Mouli, Venkatraman; Herbert, Ann; Amin, Avni

    2016-01-01

    Background Early adolescence (ages 10–14) is a period of increased expectations for boys and girls to adhere to socially constructed and often stereotypical norms that perpetuate gender inequalities. The endorsement of such gender norms is closely linked to poor adolescent sexual and reproductive and other health-related outcomes yet little is known about the factors that influence young adolescents’ personal gender attitudes. Objectives To explore factors that shape gender attitudes in early adolescence across different cultural settings globally. Methods A mixed-methods systematic review was conducted of the peer-reviewed literature in 12 databases from 1984–2014. Four reviewers screened the titles and abstracts of articles and reviewed full text articles in duplicate. Data extraction and quality assessments were conducted using standardized templates by study design. Thematic analysis was used to synthesize quantitative and qualitative data organized by the social-ecological framework (individual, interpersonal and community/societal-level factors influencing gender attitudes). Results Eighty-two studies (46 quantitative, 31 qualitative, 5 mixed-methods) spanning 29 countries were included. Ninety percent of studies were from North America or Western Europe. The review findings indicate that young adolescents, across cultural settings, commonly express stereotypical or inequitable gender attitudes, and such attitudes appear to vary by individual sociodemographic characteristics (sex, race/ethnicity and immigration, social class, and age). Findings highlight that interpersonal influences (family and peers) are central influences on young adolescents’ construction of gender attitudes, and these gender socialization processes differ for boys and girls. The role of community factors (e.g. media) is less clear though there is some evidence that schools may reinforce stereotypical gender attitudes among young adolescents. Conclusions The findings from this

  1. Understanding Factors that Shape Gender Attitudes in Early Adolescence Globally: A Mixed-Methods Systematic Review.

    Science.gov (United States)

    Kågesten, Anna; Gibbs, Susannah; Blum, Robert Wm; Moreau, Caroline; Chandra-Mouli, Venkatraman; Herbert, Ann; Amin, Avni

    2016-01-01

    Early adolescence (ages 10-14) is a period of increased expectations for boys and girls to adhere to socially constructed and often stereotypical norms that perpetuate gender inequalities. The endorsement of such gender norms is closely linked to poor adolescent sexual and reproductive and other health-related outcomes yet little is known about the factors that influence young adolescents' personal gender attitudes. To explore factors that shape gender attitudes in early adolescence across different cultural settings globally. A mixed-methods systematic review was conducted of the peer-reviewed literature in 12 databases from 1984-2014. Four reviewers screened the titles and abstracts of articles and reviewed full text articles in duplicate. Data extraction and quality assessments were conducted using standardized templates by study design. Thematic analysis was used to synthesize quantitative and qualitative data organized by the social-ecological framework (individual, interpersonal and community/societal-level factors influencing gender attitudes). Eighty-two studies (46 quantitative, 31 qualitative, 5 mixed-methods) spanning 29 countries were included. Ninety percent of studies were from North America or Western Europe. The review findings indicate that young adolescents, across cultural settings, commonly express stereotypical or inequitable gender attitudes, and such attitudes appear to vary by individual sociodemographic characteristics (sex, race/ethnicity and immigration, social class, and age). Findings highlight that interpersonal influences (family and peers) are central influences on young adolescents' construction of gender attitudes, and these gender socialization processes differ for boys and girls. The role of community factors (e.g. media) is less clear though there is some evidence that schools may reinforce stereotypical gender attitudes among young adolescents. The findings from this review suggest that young adolescents in different cultural

  2. Understanding Factors that Shape Gender Attitudes in Early Adolescence Globally: A Mixed-Methods Systematic Review.

    Directory of Open Access Journals (Sweden)

    Anna Kågesten

    Full Text Available Early adolescence (ages 10-14 is a period of increased expectations for boys and girls to adhere to socially constructed and often stereotypical norms that perpetuate gender inequalities. The endorsement of such gender norms is closely linked to poor adolescent sexual and reproductive and other health-related outcomes yet little is known about the factors that influence young adolescents' personal gender attitudes.To explore factors that shape gender attitudes in early adolescence across different cultural settings globally.A mixed-methods systematic review was conducted of the peer-reviewed literature in 12 databases from 1984-2014. Four reviewers screened the titles and abstracts of articles and reviewed full text articles in duplicate. Data extraction and quality assessments were conducted using standardized templates by study design. Thematic analysis was used to synthesize quantitative and qualitative data organized by the social-ecological framework (individual, interpersonal and community/societal-level factors influencing gender attitudes.Eighty-two studies (46 quantitative, 31 qualitative, 5 mixed-methods spanning 29 countries were included. Ninety percent of studies were from North America or Western Europe. The review findings indicate that young adolescents, across cultural settings, commonly express stereotypical or inequitable gender attitudes, and such attitudes appear to vary by individual sociodemographic characteristics (sex, race/ethnicity and immigration, social class, and age. Findings highlight that interpersonal influences (family and peers are central influences on young adolescents' construction of gender attitudes, and these gender socialization processes differ for boys and girls. The role of community factors (e.g. media is less clear though there is some evidence that schools may reinforce stereotypical gender attitudes among young adolescents.The findings from this review suggest that young adolescents in different

  3. Diagnoses of Early and Late Readmissions after Hospitalization for Pneumonia. A Systematic Review

    Science.gov (United States)

    Sjoding, Michael W.; Iwashyna, Theodore J.

    2014-01-01

    Rationale: Pneumonia is a frequent cause of hospitalization, yet drivers of post-pneumonia morbidity remain poorly characterized. Causes of hospital readmissions may elucidate important sources of morbidity and are of particular interest given the U.S. Hospital Readmission Reductions Program. Objectives: To review the primary diagnoses of early (≤30 d) and late (≥31 d) readmissions after pneumonia hospitalization. Methods: Systematic review of MEDLINE, Embase, and CINAHL databases. We identified original research studies of adults aged 18 years or older, hospitalized for pneumonia, and for whom cause-specific readmission rates were reported. Two authors abstracted study results and assessed study quality. Measurements and Main Results: Of the 1,243 citations identified, 12 met eligibility criteria. Included studies were conducted in the United States, Spain, Canada, Croatia, and Sweden. All-cause 30-day readmission rates ranged from 16.8 to 20.1% across administrative studies; the weighted average for the studies using chart review was 11.6% (15.6% in United States–based studies). Pneumonia, heart failure/cardiovascular causes, and chronic obstructive pulmonary disease/pulmonary causes are the most common reasons for early readmission after pneumonia hospitalization. Although it was the single most common cause for readmission, pneumonia accounted for only 17.9 to 29.4% of all 30-day readmissions in administrative studies and a weighted average of 23.0% in chart review studies. After accounting for study population, there was no clear difference in findings between claims-based versus chart-review studies. Few studies assessed readmissions beyond 30 days, although the limited available data suggest similar primary diagnoses for early and late readmissions. No studies assessed whether reasons for readmission were similar to patients’ reasons for healthcare use before hospitalization. Conclusions: Pneumonia, heart failure/cardiovascular disease, and chronic

  4. How to get started with a systematic review in epidemiology: an introductory guide for early career researchers.

    Science.gov (United States)

    Denison, Hayley J; Dodds, Richard M; Ntani, Georgia; Cooper, Rachel; Cooper, Cyrus; Sayer, Avan Aihie; Baird, Janis

    2013-08-07

    Systematic review is a powerful research tool which aims to identify and synthesize all evidence relevant to a research question. The approach taken is much like that used in a scientific experiment, with high priority given to the transparency and reproducibility of the methods used and to handling all evidence in a consistent manner.Early career researchers may find themselves in a position where they decide to undertake a systematic review, for example it may form part or all of a PhD thesis. Those with no prior experience of systematic review may need considerable support and direction getting started with such a project. Here we set out in simple terms how to get started with a systematic review. Advice is given on matters such as developing a review protocol, searching using databases and other methods, data extraction, risk of bias assessment and data synthesis including meta-analysis. Signposts to further information and useful resources are also given. A well-conducted systematic review benefits the scientific field by providing a summary of existing evidence and highlighting unanswered questions. For the individual, undertaking a systematic review is also a great opportunity to improve skills in critical appraisal and in synthesising evidence.

  5. What You Should Know about Flu Antiviral Drugs

    Science.gov (United States)

    ... Other What You Should Know About Flu Antiviral Drugs Language: English (US) Español Recommend on Facebook Tweet ... used to treat flu illness. What are antiviral drugs? Antiviral drugs are prescription medicines (pills, liquid, an ...

  6. New pathogenic viruses and novel antiviral drugs

    NARCIS (Netherlands)

    Berkhout, Ben; Eggink, Dirk

    2011-01-01

    The journal Antiviral Research was conceived and born in 1980, and launched in 1981, a time when very few antiviral drugs were around. This 30-year celebration meeting was convened by the publisher Elsevier and chaired by Eric de Clercq (Leuven University), who has acted as editor-in-chief for the

  7. Early post-operative psychosocial and weight predictors of later outcome in bariatric surgery: a systematic literature review.

    Science.gov (United States)

    Hindle, A; de la Piedad Garcia, X; Brennan, L

    2017-03-01

    This is the first systematic review to synthesize the evidence concerning early post-operative variables predictive of later weight and psychosocial outcomes in bariatric surgery. Eight electronic databases for empirical studies were searched (1954 to 2016). Most of the 39 included studies reported solely on weight outcomes; eating and psychosocial outcomes were less common. A better early weight loss trajectory was the most consistent predictor of more successful medium-term weight outcome (≤24 months); however, its relationship to longer term weight loss maintenance is less certain. Early eating adaptation may be associated with later weight loss, but further research is needed. Evidence is lacking for associations between early adherence or early psychosocial variables and later outcome. In particular, the relationship between early post-operative depression and later weight remains unclear. Little research has considered early prediction of later eating or psychosocial outcomes. Consideration of mediating or moderating relationships is lacking. The body of evidence is limited, and synthesis is hampered by heterogeneity in the type and time at which predictors and outcomes are measured and quality of statistical reporting. Further research on prospective prediction of bariatric surgery outcome is needed to guide early post-operative intervention for those at greatest risk of poor outcomes. © 2017 World Obesity Federation.

  8. Utilisation of helicopter emergency medical services in the early medical response to major incidents: a systematic literature review.

    Science.gov (United States)

    Johnsen, Anne Siri; Fattah, Sabina; Sollid, Stephen J M; Rehn, Marius

    2016-02-09

    This systematic review identifies, describes and appraises the literature describing the utilisation of helicopter emergency medical services (HEMS) in the early medical response to major incidents. Early prehospital phase of a major incident. Systematic literature review performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Web of Science, PsycINFO, Scopus, Cinahl, Bibsys Ask, Norart, Svemed and UpToDate were searched using phrases that combined HEMS and 'major incidents' to identify when and how HEMS was utilised. The identified studies were subjected to data extraction and appraisal. The database search identified 4948 articles. Based on the title and abstract, the full text of 96 articles was obtained; of these, 37 articles were included in the review, and an additional five were identified by searching the reference lists of the 37 articles. HEMS was used to transport medical and rescue personnel to the incident and to transport patients to the hospital, especially when the infrastructure was damaged. Insufficient air traffic control, weather conditions, inadequate landing sites and failing communication were described as challenging in some incidents. HEMS was used mainly for patient treatment and to transport patients, personnel and equipment in the early medical management of major incidents, but the optimal utilisation of this specialised resource remains unclear. This review identified operational areas with improvement potential. A lack of systematic indexing, heterogeneous data reporting and weak methodological design, complicated the identification and comparison of incidents, and more systematic reporting is needed. CRD42013004473. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  9. Parental Factors Influencing the Development of Early Childhood Caries in Developing Nations: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Nayanjot Kaur Rai

    2018-03-01

    Full Text Available BackgroundEarly childhood caries (ECC is one of the most prevalent and chronic conditions of childhood. Various factors including biological and dietary factors along with an overlay of parental social factors have been found to be associated with the progression of ECC. The objective of this systematic review is to synthesize available literature and to identify parent-level proximal and distal risk factors associated with the development of ECC in developing nations.MethodsStudies conducted in developing nations, published between 2005 and 2017 in English, that included children younger than 6 years and examined ECC were included. The outcome of interest were parental risk factors, which included parental knowledge, behavior, attitudes, sense of coherence (SOC, stress, socioeconomic status (SES, education, and breastfeeding duration. The studies were retrieved from MEDLINE, Ovid Medline, and PubMed.ResultsThe search yielded 325 studies, of which 18 were considered eligible for inclusion in this review. Ten studies found maternal education, and seven studies found parental education to be significantly associated with ECC. SES was significantly associated with ECC in 13 studies in the form of annual household income and occupation level. Four studies observed the significant association between oral health knowledge and attitudes with ECC, whereas only two studies found maternal attitude to be associated with ECC. Breastfeeding duration was a significant risk factor in four studies. One study each found significant associations of SOC, parental distress, and secondary smoke with ECC.ConclusionTo date, most of the researches done in developing countries have reported distal parental factors such as income and education being significant risk factors in caries development compared to proximal risk factors in low-income groups. Only a few studies analyzed the psychosocial and behavioral factors. Interventions could be designed to improve

  10. Antibiotic exposure in neonates and early adverse outcomes: a systematic review and meta-analysis.

    Science.gov (United States)

    Esaiassen, Eirin; Fjalstad, Jon Widding; Juvet, Lene Kristine; van den Anker, John N; Klingenberg, Claus

    2017-07-01

    To systematically review and meta-analyse the relationship between antibiotic exposure in neonates and the following early adverse outcomes: necrotizing enterocolitis (NEC), invasive fungal infections (IFIs) and/or death. Data sources were PubMed, Embase, Medline and the Cochrane Database (to December 2016), supplemented by manual searches of reference lists. Randomized controlled trials (RCTs) and observational studies were included if they provided data on different categories of antibiotic exposures (yes versus no, long versus short duration, and/or broad- versus narrow-spectrum regimens) and the risk of developing NEC, IFI and/or death in the neonatal period. Two reviewers extracted data and evaluated the risk of bias using the Cochrane Handbook, adapted to include observational studies. When appropriate, meta-analyses were conducted using the random-effect model. We identified 9 RCTs and 38 observational studies. The quality of the majority of studies was poor to moderate. There was a significant association between prolonged antibiotic exposure and an increased risk of NEC in five observational studies (5003 participants) and/or risk of death in five observational studies (13 534 participants). Eleven of 15 studies with data on broad- versus narrow-spectrum regimens reported an increased risk of IFI after broad-spectrum antibiotic exposure, in particular with third-generation cephalosporins and carbapenems. Meta-analysis was limited by few and old RCTs, insufficient sample sizes and diversity of antibiotic exposure and outcomes reported. Prolonged antibiotic exposure in uninfected preterm infants is associated with an increased risk of NEC and/or death, and broad-spectrum antibiotic exposure is associated with an increased risk of IFI. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. Examining the Impacts of Systematic and Engaging Early Literacy (SEEL): Attention to Teacher Practices and Classroom Effects across the Kindergarten Year

    Science.gov (United States)

    Bingham, Gary E.; Culatta, Barbara; Hall-Kenyon, Kendra M.

    2016-01-01

    This study examined teachers' implementation of an early literacy intervention, Systematic and Engaging Early Literacy (SEEL), on kindergarten children's development of early literacy skills. One hundred forty-nine kindergarten children (102 treatment) across six classrooms participated in this study. Results reveal that children who received SEEL…

  12. Anti-viral effects of medicinal plants in the management of dengue: a ...

    African Journals Online (AJOL)

    Anti-viral effects of medicinal plants in the management of dengue: a systematic review. Éric Heleno Freira Ferreira Frederico, André Luiz Bandeira Dionísio Cardoso, Eloá Moreira-Marconi, Danúbia da Cunha de Sá-Caputo, Carlos Alberto Sampaio Guimarães, Carla da Fontoura Dionello, Danielle Soares Morel, Laisa ...

  13. Impact of body size, nutrition and socioeconomic position in early life on the epigenome: a systematic review protocol.

    Science.gov (United States)

    Maddock, Jane; Wulaningsih, Wahyu; Hardy, Rebecca

    2017-07-05

    Body size, nutrition and socioeconomic position (SEP) in early life have been associated with a range of later life health outcomes. Epigenetic regulation is one mechanism through which these early life factors may impact later life health. The aim of this review protocol is to outline procedures to document the influence of body size, nutrition and SEP in early life on the epigenome. MEDLINE, Embase and BIOSIS will be systematically searched using pre-defined keywords. Additional studies will be identified through manual searching of reference lists. Two independent researchers will assess the eligibility and quality of each study, with disagreements being resolved through discussion or a third reviewer. Studies will be included if they have epigenetic markers measured either at the same time as, or after, the early life exposure and, have a measure of body size, nutrition or SEP in early life (up to 12 years), are in the English language and are from a sample of community-dwelling participants. This protocol will be used to collate the evidence for the effect of early life factors on the epigenome. Findings will form a component of a wider research study examining epigenetic responses to exposures in early life and over the life course and its impact on healthy ageing using data from population-based cohort studies. PROSPERO CRD42016050193.

  14. Comparison the effects of poor health and low income on early retirement: a systematic review and meta-analysis.

    Science.gov (United States)

    Homaie Rad, Enayatollah; Rashidian, Arash; Arab, Mohamad; Souri, Ali

    2017-08-08

    The main aim of this study was to estimate the effects of poor health and low income on early retirement. For this purpose systematic review and meta-analysis were conducted. Web of Science, PUBMED and Scopus databases were searched systematically. Finally 17 surveys were added in meta-analysis. These studies were conducted in 13 countries. At the end a Meta regression was done to show the effects of welfare system type on effect sizes of poor health and low income. The results of this study showed that poor health had effect on the risk of early retirement. (Poor health pooled effect sizes: 1.279 CI: (1.15 1.41), low income pooled effect sizes: 1.042 CI: (0.92 1.17), (poor health pooled marginal effects: 0.046 CI: (-0.03 0.12), low income pooled marginal effects: -0.002 CI: (-0.003 0.000). The results of this study showed that association between poor health and early retirement was stronger in comparison with low income and early retirement.

  15. Comparative 187Re-187Os systematics of chondrites: Implications regarding early solar system processes

    Science.gov (United States)

    Walker, R.J.; Horan, M.F.; Morgan, J.W.; Becker, H.; Grossman, J.N.; Rubin, A.E.

    2002-01-01

    A suite of 47 carbonaceous, enstatite, and ordinary chondrites are examined for Re-Os isotopic systematics. There are significant differences in the 187Re/188Os and 187Os/188Os ratios of carbonaceous chondrites compared with ordinary and enstatite chondrites. The average 187Re/188Os for carbonaceous chondrites is 0.392 ?? 0.015 (excluding the CK chondrite, Karoonda), compared with 0.422 ?? 0.025 and 0.421 ?? 0.013 for ordinary and enstatite chondrites (1?? standard deviations). These ratios, recast into elemental Re/Os ratios, are as follows: 0.0814 ?? 0.0031, 0.0876 ?? 0.0052 and 0.0874 ?? 0.0027 respectively. Correspondingly, the 187Os/188Os ratios of carbonaceous chondrites average 0.1262 ?? 0.0006 (excluding Karoonda), and ordinary and enstatite chondrites average 0.1283 ?? 0.0017 and 0.1281 ?? 0.0004, respectively (1?? standard deviations). The new results indicate that the Re/Os ratios of meteorites within each group are, in general, quite uniform. The minimal overlap between the isotopic compositions of ordinary and enstatite chondrites vs. carbonaceous chondrites indicates long-term differences in Re/Os for these materials, most likely reflecting chemical fractionation early in solar system history. A majority of the chondrites do not plot within analytical uncertainties of a 4.56-Ga reference isochron. Most of the deviations from the isochron are consistent with minor, relatively recent redistribution of Re and/or Os on a scale of millimeters to centimeters. Some instances of the redistribution may be attributed to terrestrial weathering; others are most likely the result of aqueous alteration or shock events on the parent body within the past 2 Ga. The 187Os/188Os ratio of Earth's primitive upper mantle has been estimated to be 0.1296 ?? 8. If this composition was set via addition of a late veneer of planetesimals after core formation, the composition suggests the veneer was dominated by materials that had Re/Os ratios most similar to ordinary and

  16. Antibiotic Exposure in Early Life Increases Risk of Childhood Obesity: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Xiaoqing Shao

    2017-07-01

    Full Text Available A number of studies have previously assessed the impact of antibiotic exposure in early life on the risk of childhood obesity, but no systematic assessment is currently available. A systematic review and meta-analysis was performed to comprehensively and quantitatively elucidate the risk of childhood obesity caused by antibiotic exposure in early life. Literature search was performed in PubMed, Embase, and Web of Science. Random-effect meta-analysis was used to pool the statistical estimates. Fifteen cohort studies involving 445,880 participants were finally included, and all those studies were performed in developed countries. Antibiotic exposure in early life significantly increased risk of childhood overweight [relative risk (RR = 1.23, 95% confidence interval (CI 1.13–1.35, P < 0.001] and childhood obesity (RR = 1.21, 95% CI 1.13–1.30, P < 0.001. Antibiotic exposure in early life also significantly increased the z-score of childhood body mass index (mean difference: 0.07, 95% CI 0.05–0.09, P < 0.00001. Importantly, there was an obvious dose–response relationship between antibiotic exposure in early life and childhood adiposity, with a 7% increment in the risk of overweight (RR = 1.07, 95% CI 1.01–1.15, P = 0.03 and a 6% increment in the risk of obesity (RR = 1.06, 95% CI 1.02–1.09, P < 0.001 for each additional course of antibiotic exposure. In conclusion, antibiotic exposure in early life significantly increases risk of childhood obesity. Moreover, current analyses are mainly taken from developed countries, and therefore the impact of antibiotic exposure on risk of childhood obesity in vulnerable populations or developing countries still needs to be evaluated in future studies.

  17. A systematic review evaluating the role of nurses and processes for delivering early mobility interventions in the intensive care unit.

    Science.gov (United States)

    Krupp, Anna; Steege, Linsey; King, Barbara

    2018-04-19

    To investigate processes for delivering early mobility interventions in adult intensive care unit patients used in research and quality improvement studies and the role of nurses in early mobility interventions. A systematic review was conducted. Electronic databases PubMED, CINAHL, PEDro, and Cochrane were searched for studies published from 2000 to June 2017 that implemented an early mobility intervention in adult intensive care units. Included studies involved progression to ambulation as a component of the intervention, included the role of the nurse in preparing for or delivering the intervention, and reported at least one patient or organisational outcome measure. The System Engineering Initiative for Patient Safety (SEIPS) model, a framework for understanding structure, processes, and healthcare outcomes, was used to evaluate studies. 25 studies were included in the final review. Studies consisted of randomised control trials, prospective, retrospective, or mixed designs. A range of processes to support the delivery of early mobility were found. These processes include forming interdisciplinary teams, increasing mobility staff, mobility protocols, interdisciplinary education, champions, communication, and feedback. Variation exists in the process of delivering early mobility in the intensive care unit. In particular, further rigorous studies are needed to better understand the role of nurses in implementing early mobility to maintain a patient's functional status. Copyright © 2018 Elsevier Ltd. All rights reserved.

  18. Screening and Treatment for Early-Onset Gestational Diabetes Mellitus: a Systematic Review and Meta-analysis.

    Science.gov (United States)

    Immanuel, Jincy; Simmons, David

    2017-10-02

    We conducted a systematic review to evaluate the current evidence for screening and treatment for early-onset gestational diabetes mellitus (GDM) RECENT FINDINGS: Many of the women with early GDM in the first trimester do not have evidence of hyperglycemia at 24-28 weeks' gestation. A high proportion (15-70%) of women with GDM can be detected early in pregnancy depending on the setting, criteria used and screening strategy. However, there remains no good evidence for any of the diagnostic criteria for early-onset GDM. In a meta-analysis of 13 cohort studies, perinatal mortality (relative risk (RR) 3.58 [1.91, 6.71]), neonatal hypoglycemia (RR 1.61 [1.02, 2.55]), and insulin use (RR 1.71 [1.45, 2.03]) were greater among early-onset GDM women compared to late-onset GDM women, despite treatment. Considering the high likelihood of benefit from treatment, there is an urgent need for randomized controlled trials that investigate any benefits and possible harms of treatment of early-onset GDM.

  19. Radiofrequency ablation versus resection for Barcelona clinic liver cancer very early/early stage hepatocellular carcinoma: a systematic review.

    Science.gov (United States)

    He, Zhen-Xin; Xiang, Pu; Gong, Jian-Ping; Cheng, Nan-Sheng; Zhang, Wei

    2016-01-01

    To compare the long-term survival outcomes of radiofrequency ablation and liver resection for single very early/early stage hepatocellular carcinoma (HCC). The Cochrane Library (Issue 3, 2015), Embase (1974 to March 15, 2015), PubMed (1950 to March 15, 2015), Web of Science (1900 to March 15, 2015), and Chinese Biomedical Literature Database (1978 to March 15, 2015) were searched to identify relevant trials. Only trials that compared radiofrequency ablation and liver resection for single very early stage (≤2 cm) or early stage (≤3 cm) HCC according to the Barcelona clinic liver cancer (BCLC) staging system were considered for inclusion in this review. The primary outcomes that we analyzed were the 3-year and 5-year overall survival (OS) rates, and the secondary outcomes that we analyzed were the 3-year and 5-year disease-free survival (DFS) rates. Review Manager 5.3 was used to perform a cumulative meta-analysis. Possible publication bias was examined using a funnel plot. A random-effects model was applied to summarize the various outcomes. Six studies involving 947 patients were identified that compared radiofrequency ablation (n=528) to liver resection (n=419) for single BCLC very early HCC. In these six studies, the rates of 3-year OS, 5-year OS, 3-year DFS, and 5-year DFS were significantly lower in the radiofrequency ablation group than in the liver resection group (risk ratio [RR] =0.90, 95% confidence interval [CI]: 0.83-0.98, P=0.01; RR =0.84, 95% CI: 0.75-0.95, P=0.004; RR =0.77, 95% CI: 0.60-0.98, P=0.04; and RR =0.70, 95% CI: 0.52-0.94, P=0.02, respectively). Ten studies involving 2,501 patients were identified that compared radiofrequency ablation (n=1,476) to liver resection (n=1,025) for single BCLC early HCC. In these ten studies, the rates of 3-year OS, 5-year OS, 3-year DFS, and 5-year DFS were also significantly lower in the radiofrequency ablation group than in the liver resection group (RR =0.93, 95% CI: 0.88-0.98, P=0.003; RR =0.84, 95% CI

  20. Assessment of Inhibition of Ebola Virus Progeny Production by Antiviral Compounds.

    Science.gov (United States)

    Falzarano, Darryl

    2017-01-01

    Assessment of small molecule compounds against filoviruses, such as Ebola virus, has identified numerous compounds that appear to have antiviral activity and should presumably be further investigated in animal efficacy trials. However, despite the many compounds that are purported to have good antiviral activity in in vitro studies, there are few instances where any efficacy has been reported in nonhuman primate models. Many of the high-throughput screening assays use reporter systems that only recapitulate a portion of the virus life cycle, while other assays only assess antiviral activity at relatively early time points. Moreover, many assays do not assess virus progeny production. A more in-depth evaluation of small numbers of test compounds is useful to economize resources and to generate higher quality antiviral hits. Assessing virus progeny production as late as 5 days post-infection allows for the elimination of compounds that have initial antiviral effects that are not sustained or where the virus rapidly develops resistance. While this eliminates many potential lead compounds that may be worthy of further structure-activity relationship (SAR) development, it also quickly excludes compounds that in their current form are unlikely to be effective in animal models. In addition, the inclusion of multiple assays that assess both cell viability and cell cytotoxicity, via different mechanisms, provides a more thorough assessment to exclude compounds that are not direct-acting antivirals.

  1. Viruses and Antiviral Immunity in Drosophila

    Science.gov (United States)

    Xu, Jie; Cherry, Sara

    2013-01-01

    Viral pathogens present many challenges to organisms, driving the evolution of a myriad of antiviral strategies to combat infections. A wide variety of viruses infect invertebrates, including both natural pathogens that are insect-restricted, and viruses that are transmitted to vertebrates. Studies using the powerful tools available in the model organism Drosophila have expanded our understanding of antiviral defenses against diverse viruses. In this review, we will cover three major areas. First, we will describe the tools used to study viruses in Drosophila. Second, we will survey the major viruses that have been studied in Drosophila. And lastly, we will discuss the well-characterized mechanisms that are active against these diverse pathogens, focusing on non-RNAi mediated antiviral mechanisms. Antiviral RNAi is discussed in another paper in this issue. PMID:23680639

  2. Antiviral lead compounds from marine sponges

    KAUST Repository

    Sagar, Sunil; Kaur, Mandeep; Minneman, Kenneth P.

    2010-01-01

    ). The most important antiviral lead of marine origin reported thus far is nucleoside Ara-A (vidarabine) isolated from sponge Tethya crypta. It inhibits viral DNA polymerase and DNA synthesis of herpes, vaccinica and varicella zoster viruses. However due

  3. Nanoparticulate delivery systems for antiviral drugs.

    Science.gov (United States)

    Lembo, David; Cavalli, Roberta

    2010-01-01

    Nanomedicine opens new therapeutic avenues for attacking viral diseases and for improving treatment success rates. Nanoparticulate-based systems might change the release kinetics of antivirals, increase their bioavailability, improve their efficacy, restrict adverse drug side effects and reduce treatment costs. Moreover, they could permit the delivery of antiviral drugs to specific target sites and viral reservoirs in the body. These features are particularly relevant in viral diseases where high drug doses are needed, drugs are expensive and the success of a therapy is associated with a patient's adherence to the administration protocol. This review presents the current status in the emerging area of nanoparticulate delivery systems in antiviral therapy, providing their definition and description, and highlighting some peculiar features. The paper closes with a discussion on the future challenges that must be addressed before the potential of nanotechnology can be translated into safe and effective antiviral formulations for clinical use.

  4. Prenatal and Early Postnatal Diagnosis of Congenital Toxoplasmosis in a Setting With No Systematic Screening in Pregnancy

    Science.gov (United States)

    Stajner, Tijana; Bobic, Branko; Klun, Ivana; Nikolic, Aleksandra; Srbljanovic, Jelena; Uzelac, Aleksandra; Rajnpreht, Irena; Djurkovic-Djakovic, Olgica

    2016-01-01

    Abstract To determine the risk of congenital toxoplasmosis (CT) and provide early (pre- or postnatal) identification of cases of CT in the absence of systematic screening in pregnancy. In the presented cross-sectional study, serological criteria were used to date Toxoplasma gondii infection versus conception in 80 pregnant women with fetal abnormalities or referred to as suspected of acute infection, and in 16 women after delivery of symptomatic neonates. A combination of serological, molecular (qPCR), and biological (bioassay) methods was used for prenatal and/or postnatal diagnosis of CT. Most (77.5%) pregnant women were examined in advanced pregnancy. Of all the examined seropositive women (n = 90), infection could not be ruled out to have occurred during pregnancy in 93.3%, of which the majority (69%) was dated to the periconceptual period. CT was diagnosed in 25 cases, of which 17 prenatally and 8 postnatally. Molecular diagnosis proved superior, but the diagnosis of CT based on bioassay in 7 instances and by Western blot in 2 neonates shows that other methods remain indispensable. In the absence of systematic screening in pregnancy, maternal infection is often diagnosed late, or even only when fetal/neonatal infection is suspected. In such situations, use of a complex algorithm involving a combination of serological, biological, and molecular methods allows for prenatal and/or early postnatal diagnosis of CT, but lacks the preventive capacity provided by early maternal treatment. PMID:26945416

  5. Early Versus Delayed Passive Range of Motion After Rotator Cuff Repair: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Kluczynski, Melissa A; Nayyar, Samir; Marzo, John M; Bisson, Leslie J

    2015-08-01

    Postoperative rehabilitation has been shown to affect healing of the rotator cuff after surgical repair. However, it is unknown whether an early or delayed rehabilitation protocol is most beneficial for healing. To determine whether early versus delayed passive range of motion (PROM) affects rotator cuff (RC) retear rates after surgery. Systematic review and meta-analysis. A systematic review of the literature published between January 2003 and February 2014 was conducted. Retear rates were compared for early (within 1 week after surgery) versus delayed (3-6 weeks after surgery) PROM using χ(2) or Fisher exact tests as well as relative risks (RR) and 95% CIs. In the first analysis, data from evidence level 1 studies that directly compared early versus delayed PROM were pooled; and in the second analysis, data from level 1 to 4 studies that did not directly compare early versus delayed PROM were pooled. The second analysis was stratified by tear size and repair method. Twenty-eight studies (1729 repairs) were included. The first analysis of level 1 studies did not reveal a significant difference in retear rates for early (13.7%) versus delayed (10.5%) PROM (P = .36; RR = 1.30 [95% CI, 0.74-2.30]). The second analysis revealed that for ≤3 cm tears, the risk of retear was lower for early versus delayed PROM for transosseous (TO) plus single-row anchor (SA) repairs (18.7% vs 28.2%, P = .02; RR = 0.66 [95% CI, 0.47-0.95]). For >5 cm tears, the risk of retear was greater for early versus delayed PROM for double-row anchor (DA) repairs (56.4% vs 20%, P = .002; RR = 2.82 [95% CI, 1.31-6.07]) and for all repair methods combined (52.2% vs 22.6%, P = .01; RR = 2.31 [95% CI, 1.16-4.61]). There were no statistically significant associations for tears measuring 3 cm. Evidence is lacking with regard to the optimal timing of PROM after RC repair; however, this study suggests that tear size may be influential. © 2014 The Author(s).

  6. The impact of indicated prevention and early intervention on co-morbid eating disorder and depressive symptoms: a systematic review.

    Science.gov (United States)

    Rodgers, Rachel F; Paxton, Susan J

    2014-01-01

    Depressive and eating disorder symptoms are highly comorbid. To date, however, little is known regarding the efficacy of existing programs in decreasing concurrent eating disorder and depressive symptoms. We conducted a systematic review of selective and indicated controlled prevention and early intervention programs that assessed both eating disorder and depressive symptoms. We identified a total of 26 studies. The large majority of identified interventions (92%) were successful in decreasing eating disorder symptoms. However fewer than half (42%) were successful in decreasing both eating disorder and depressive symptoms. Intervention and participant characteristics did not predict success in decreasing depressive symptoms. Indicated prevention and early intervention programs targeting eating disorder symptoms are limited in their success in decreasing concurrent depressive symptoms. Further efforts to develop more efficient interventions that are successful in decreasing both eating disorder and depressive symptoms are warranted.

  7. Combined modality treatment improves tumor control and overall survival in patients with early stage Hodgkin's lymphoma: a systematic review

    DEFF Research Database (Denmark)

    Herbst, Christine; Rehan, Fareed A; Brillant, Corinne

    2010-01-01

    as well as conference proceedings from January 1980 to February 2009 for randomized controlled trials comparing chemotherapy alone versus the same chemotherapy regimen plus radiotherapy. Progression free survival and similar outcomes were analyzed together as tumor control. Effect measures used were......Combined modality treatment (CMT) of chemotherapy followed by localized radiotherapy is standard treatment for patients with early stage Hodgkin's lymphoma. However, the role of radiotherapy has been questioned recently and some clinical study groups advocate chemotherapy only for this indication....... We thus performed a systematic review with meta-analysis of randomized controlled trials comparing chemotherapy alone with CMT in patients with early stage Hodgkin's lymphoma with respect to response rate, tumor control and overall survival (OS). We searched Medline, EMBASE and the Cochrane Library...

  8. Development of alcohol expectancies and early alcohol use in children and adolescents: A systematic review

    NARCIS (Netherlands)

    Smit, K.; Voogt, C.V.; Hiemstra, J.M.; Kleinjan, M.; Otten, R.; Kuntsche, E.N.

    2018-01-01

    Purpose: Developmental changes in alcohol expectancies (AE) have been proposed to lead to alcohol use initiation and later alcohol use in adolescence. This systematic review aims to provide longitudinal evidence of the development of AE and the relation of AE to alcohol outcomes from childhood to

  9. Early versus late surgical intervention or medical management for infective endocarditis: a systematic review and meta-analysis.

    Science.gov (United States)

    Anantha Narayanan, Mahesh; Mahfood Haddad, Toufik; Kalil, Andre C; Kanmanthareddy, Arun; Suri, Rakesh M; Mansour, George; Destache, Christopher J; Baskaran, Janani; Mooss, Aryan N; Wichman, Tammy; Morrow, Lee; Vivekanandan, Renuga

    2016-06-15

    Infective endocarditis is associated with high morbidity and mortality and optimal timing for surgical intervention is unclear. We performed a systematic review and meta-analysis to compare early surgical intervention with conservative therapy in patients with infective endocarditis. PubMed, Cochrane, EMBASE, CINAHL and Google-scholar databases were searched from January 1960 to April 2015. Randomised controlled trials, retrospective cohorts and prospective observational studies comparing outcomes between early surgery at 20 days or less and conservative management for infective endocarditis were analysed. A total of 21 studies were included. OR of all-cause mortality for early surgery was 0.61 (95% CI 0.50 to 0.74, pendocarditis between the overall unmatched cohorts. The results of our meta-analysis suggest that early surgical intervention is associated with significantly lower risk of mortality in patients with infective endocarditis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  10. Social marketing approaches to nutrition and physical activity interventions in early care and education centres: a systematic review.

    Science.gov (United States)

    Luecking, C T; Hennink-Kaminski, H; Ihekweazu, C; Vaughn, A; Mazzucca, S; Ward, D S

    2017-12-01

    Social marketing is a promising planning approach for influencing voluntary lifestyle behaviours, but its application to nutrition and physical activity interventions in the early care and education setting remains unknown. PubMed, ISI Web of Science, PsycInfo and the Cumulative Index of Nursing and Allied Health were systematically searched to identify interventions targeting nutrition and/or physical activity behaviours of children enrolled in early care centres between 1994 and 2016. Content analysis methods were used to capture information reflecting eight social marketing benchmark criteria. The review included 135 articles representing 77 interventions. Two interventions incorporated all eight benchmark criteria, but the majority included fewer than four. Each intervention included behaviour and methods mix criteria, and more than half identified audience segments. Only one-third of interventions incorporated customer orientation, theory, exchange and insight. Only six interventions addressed competing behaviours. We did not find statistical significance for the effectiveness of interventions on child-level diet, physical activity or anthropometric outcomes based on the number of benchmark criteria used. This review highlights opportunities to apply social marketing to obesity prevention interventions in early care centres. Social marketing could be an important strategy for early childhood obesity prevention efforts, and future research investigations into its effects are warranted. © 2017 World Obesity Federation.

  11. Nonoperative management in children with early acute appendicitis: A systematic review.

    Science.gov (United States)

    Xu, Jane; Adams, Susan; Liu, Yingrui Cyril; Karpelowsky, Jonathan

    2017-09-01

    Appendectomy has remained the gold standard treatment of acute appendicitis for more than 100years. Nonoperative management (NOM) has been shown to be a valid treatment alternative for acute uncomplicated appendicitis in adults. A systematic review of available evidence comparing operative management (OM) and NOM in children with acute uncomplicated appendicitis was performed. Systematic searches of MedLine, Embase, and a clinical trial register (https://clinicaltrials.gov/) were performed in March 2016. Only articles that studied NOM for uncomplicated appendicitis in children were included. Data generation was performed independently by two authors, and quality was assessed using the rating schema by the Oxford Centre for Evidence-Based Medicine. 15 articles were selected: four retrospective analyses, four prospective cohort studies, four prospective nonrandomized comparative trials and one randomized controlled trial (RCT). Initial success of the NOM groups (a cure within two weeks of intervention) ranged from 58 to 100%, with 0.1-31.8% recurrence at one year. Although present literature is scarce, publications support the feasibility of further studies investigating NOM of acute uncomplicated appendicitis in children. Higher quality prospective RCTs with larger sample sizes and robust randomization methods, studying the noninferiority of NOM with antibiotics compared with OM are required to establish its utility. This manuscript is a systematic review and thus assigned the lowest evidence used from the manuscripts analyzed which is a Level IV. Copyright © 2017. Published by Elsevier Inc.

  12. The Clinical Utility and Diagnostic Performance of MRI for Identification of Early and Advanced Knee Osteoarthritis: A Systematic Review

    Science.gov (United States)

    Quatman, Carmen E.; Hettrich, Carolyn M.; Schmitt, Laura C.; Spindler, Kurt P.

    2013-01-01

    Background Current diagnostic strategies for detection of structural articular cartilage abnormalities, the earliest structural signs of osteoarthritis, often do not capture the condition until it is too far advanced for the most potential benefit of non-invasive interventions. Purpose Systematically review the literature relative to the following questions: (1) Is MRI a valid, sensitive, specific, accurate and reliable instrument to identify knee articular cartilage abnormalities compared to arthroscopy? (2) Is MRI a sensitive tool that can be utilized to identify early cartilage degeneration? Study Design Systematic Review Methods A systematic search was performed in November 2010 using PubMed MEDLINE (from 1966), CINAHL (from 1982), SPORTDiscus (from 1985), and SCOPUS (from 1996) databases. Results Fourteen level I and 13 level II studies were identified that met inclusion criteria and provided information related to diagnostic performance of MRI compared to arthroscopic evaluation. The diagnostic performance of MRI demonstrated a large range of sensitivities, specificities, and accuracies. The sensitivity for identifying articular cartilage abnormalities in the knee joint was reported between 26–96%. Specificity and accuracy was reported between 50–100% and 49–94%, respectively. The sensitivity, specificity, and accuracy for identifying early osteoarthritis were reported between 0–86%, 48–95%, and 5–94%, respectively. As a result of inconsistencies between imaging techniques and methodological shortcomings of many of the studies, a meta-analysis was not performed and it was difficult to fully synthesize the information to state firm conclusions about the diagnostic performance of MRI. Conclusions There is evidence in some MRI protocols that MRI is a relatively valid, sensitive, specific, accurate, and reliable clinical tool for identifying articular cartilage degeneration. Due to heterogeneity of MRI sequences it is not possible to make definitive

  13. Pacemaker implantation rate after transcatheter aortic valve implantation with early and new-generation devices: a systematic review.

    Science.gov (United States)

    van Rosendael, Philippe J; Delgado, Victoria; Bax, Jeroen J

    2018-02-06

    The incidence of new-onset conduction abnormalities requiring permanent pacemaker implantation (PPI) after transcatheter aortic valve implantation (TAVI) with new-generation prostheses remains debated. This systematic review analyses the incidence of PPI after TAVI with new-generation devices and evaluates the electrical, anatomical, and procedural factors associated with PPI. In addition, the incidence of PPI after TAVI with early generation prostheses was reviewed for comparison. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist, this systematic review screened original articles published between October 2010 and October 2017, reporting on the incidence of PPI after implantation of early and new-generation TAVI prostheses. Of the 1406 original articles identified in the first search for new-generation TAVI devices, 348 articles were examined for full text, and finally, 40 studies (n = 17 139) were included. The incidence of a PPI after the use of a new-generation TAVI prosthesis ranged between 2.3% and 36.1%. For balloon-expandable prostheses, the PPI rate remained low when using an early generation SAPIEN device (ranging between 2.3% and 28.2%), and with the new-generation SAPIEN 3 device, the PPI rate was between 4.0% and 24.0%. For self-expandable prostheses, the PPI rates were higher with the early generation CoreValve device (16.3-37.7%), and despite a reduction in PPI rates with the new Evolut R, the rates remained relatively higher (14.7-26.7%). When dividing the studies according to the highest (>26.0%) and the lowest (left ventricular outflow tract (anatomical factor), and balloon valvuloplasty and depth of implantation (procedural factors) were associated with increased risk of PPI. The rate of PPI after TAVI with new-generation devices is highly variable. Specific recommendations for implantation of each prosthesis, taking into consideration the presence of pre-existent conduction abnormalities and

  14. Antiviral Defense Mechanisms in Honey Bees

    Science.gov (United States)

    Brutscher, Laura M.; Daughenbaugh, Katie F.; Flenniken, Michelle L.

    2015-01-01

    Honey bees are significant pollinators of agricultural crops and other important plant species. High annual losses of honey bee colonies in North America and in some parts of Europe have profound ecological and economic implications. Colony losses have been attributed to multiple factors including RNA viruses, thus understanding bee antiviral defense mechanisms may result in the development of strategies that mitigate colony losses. Honey bee antiviral defense mechanisms include RNA-interference, pathogen-associated molecular pattern (PAMP) triggered signal transduction cascades, and reactive oxygen species generation. However, the relative importance of these and other pathways is largely uncharacterized. Herein we review the current understanding of honey bee antiviral defense mechanisms and suggest important avenues for future investigation. PMID:26273564

  15. Antiviral Activity of Polyacrylic and Polymethacrylic Acids

    Science.gov (United States)

    De Somer, P.; De Clercq, E.; Billiau, A.; Schonne, E.; Claesen, M.

    1968-01-01

    Polyacrylic acid (PAA) and polymethacrylic acid (PMAA) were investigated for their antiviral properties in tissue culture. Compared to other related polyanions, as dextran sulfate, polystyrene sulfonate, polyvinyl sulfate, and polyphloroglucinol phosphate, PAA and PMAA were found to be significantly more antivirally active and less cytotoxic. PMAA added 24 hr prior to virus inoculation inhibited viral growth most efficiently but it was still effective when added 3 hr after infection. Neither a direct irreversible action on the virus nor inhibition of virus penetration into the cell could explain the antiviral activity of PMAA. PMAA inhibited the adsorption of the virus to the host cell and suppressed the one-cycle viral synthesis in tissue cultures inoculated with infectious RNA. PMID:4302187

  16. Antiviral Activity of Novel Quinoline Derivatives against Dengue Virus Serotype 2

    Directory of Open Access Journals (Sweden)

    Carolina de la Guardia

    2018-03-01

    Full Text Available Dengue virus causes dengue fever, a debilitating disease with an increasing incidence in many tropical and subtropical territories. So far, there are no effective antivirals licensed to treat this virus. Here we describe the synthesis and antiviral activity evaluation of two compounds based on the quinoline scaffold, which has shown potential for the development of molecules with various biological activities. Two of the tested compounds showed dose-dependent inhibition of dengue virus serotype 2 in the low and sub micromolar range. The compounds 1 and 2 were also able to impair the accumulation of the viral envelope glycoprotein in infected cells, while showing no sign of direct virucidal activity and acting possibly through a mechanism involving the early stages of the infection. The results are congruent with previously reported data showing the potential of quinoline derivatives as a promising scaffold for the development of new antivirals against this important virus.

  17. Antiviral activity and specific modes of action of bacterial prodigiosin against Bombyx mori nucleopolyhedrovirus in vitro.

    Science.gov (United States)

    Zhou, Wei; Zeng, Cheng; Liu, RenHua; Chen, Jie; Li, Ru; Wang, XinYan; Bai, WenWen; Liu, XiaoYuan; Xiang, TingTing; Zhang, Lin; Wan, YongJi

    2016-05-01

    Prodigiosin, the tripyrrole red pigment, is a bacterial secondary metabolite with multiple bioactivities; however, the antiviral activity has not been reported yet. In the present study, we found the antiviral activity of bacterial prodigiosin on Bombyx mori nucleopolyhedrovirus (BmNPV)-infected cells in vitro, with specific modes of action. Prodigiosin at nontoxic concentrations selectively killed virus-infected cells, inhibited viral gene transcription, especially viral early gene ie-1, and prevented virus-mediated membrane fusion. Under prodigiosin treatment, both progeny virus production and viral DNA replication were significantly inhibited. Fluorescent assays showed that prodigiosin predominantly located in cytoplasm which suggested it might interact with cytoplasm factors to inhibit virus replication. In conclusion, the present study clearly indicates that prodigiosin possesses significant antiviral activity against BmNPV.

  18. Current Landscape of Antiviral Drug Discovery [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Wade Blair

    2016-02-01

    Full Text Available Continued discovery and development of new antiviral medications are paramount for global human health, particularly as new pathogens emerge and old ones evolve to evade current therapeutic agents. Great success has been achieved in developing effective therapies to suppress human immunodeficiency virus (HIV and hepatitis B virus (HBV; however, the therapies are not curative and therefore current efforts in HIV and HBV drug discovery are directed toward longer-acting therapies and/or developing new mechanisms of action that could potentially lead to cure, or eradication, of the virus. Recently, exciting early clinical data have been reported for novel antivirals targeting respiratory syncytial virus (RSV and influenza (flu. Preclinical data suggest that these new approaches may be effective in treating high-risk patients afflicted with serious RSV or flu infections. In this review, we highlight new directions in antiviral approaches for HIV, HBV, and acute respiratory virus infections.

  19. A Systematic Literature Review and Meta-Regression Analysis on Early-Life Energy Restriction and Cancer Risk in Humans.

    Science.gov (United States)

    Elands, Rachel J J; Simons, Colinda C J M; Dongen, Martien van; Schouten, Leo J; Verhage, Bas A J; van den Brandt, Piet A; Weijenberg, Matty P

    2016-01-01

    In animal models, long-term moderate energy restriction (ER) is reported to decelerate carcinogenesis, whereas the effect of severe ER is inconsistent. The impact of early-life ER on cancer risk has never been reviewed systematically and quantitatively based on observational studies in humans. We conducted a systematic review of observational studies and a meta-(regression) analysis on cohort studies to clarify the association between early-life ER and organ site-specific cancer risk. PubMed and EMBASE (1982 -August 2015) were searched for observational studies. Summary relative risks (RRs) were estimated using a random effects model when available ≥3 studies. Twenty-four studies were included. Eleven publications, emanating from seven prospective cohort studies and some reporting on multiple cancer endpoints, met the inclusion criteria for quantitative analysis. Women exposed to early-life ER (ranging from 220-1660 kcal/day) had a higher breast cancer risk than those not exposed (RRRE all ages = 1.28, 95% CI: 1.05-1.56; RRRE for 10-20 years of age = 1.21, 95% CI: 1.09-1.34). Men exposed to early-life ER (ranging from 220-800kcal/day) had a higher prostate cancer risk than those not exposed (RRRE = 1.16, 95% CI: 1.03-1.30). Summary relative risks were not computed for colorectal cancer, because of heterogeneity, and for stomach-, pancreas-, ovarian-, and respiratory cancer because there were <3 available studies. Longer duration of exposure to ER, after adjustment for severity, was positively associated with overall cancer risk in women (p = 0.02). Ecological studies suggest that less severe ER is generally associated with a reduced risk of cancer. Early-life transient severe ER seems to be associated with increased cancer risk in the breast (particularly ER exposure at adolescent age) and prostate. The duration, rather than severity of exposure to ER, seems to positively influence relative risk estimates. This result should be interpreted with caution due to the

  20. Early Childhood Education and Care Educators Supporting Parent-Child Relationships: A Systematic Literature Review

    Science.gov (United States)

    O'Connor, Amanda; Nolan, Andrea; Bergmeier, Heidi; Hooley, Merrilyn; Olsson, Craig; Cann, Warren; Williams-Smith, Janet; Skouteris, Helen

    2017-01-01

    Building strong relationships between children and parents is vital for children's social and emotional development. A majority of children attend early childhood education and care (ECEC) settings where they experience a range of relationships (educator-child, educator-parent, parent-child). Educators build relationships with children and…

  1. Early intraprosthetic dislocation in dual-mobility implants: a systematic review

    Directory of Open Access Journals (Sweden)

    Ivan De Martino, MD

    2017-09-01

    Conclusions: Based on the current data, most cases have been preceded by an attempted closed reduction in the setting of outer, large articulation dislocation, perhaps indicating an iatrogenic etiology for early IPD. Recognition of this possible failure mode is essential to its prevention and treatment.

  2. Obesity Prevention Interventions in Early Childhood Education and Care Settings with Parental Involvement: A Systematic Review

    Science.gov (United States)

    Morris, Heather; Skouteris, Helen; Edwards, Susan; Rutherford, Leonie

    2015-01-01

    Partnering early childhood education and care (ECEC) and the home together may be more effective in combating obesogenic risk factors in preschool children. Thus, an evaluation of ECEC obesity prevention interventions with a parental component was conducted, exploring parental engagement and its effect on obesity and healthy lifestyle outcomes. A…

  3. Dealing with subjectivity in early product design phase: a systematic approch to exploit QFD potentials

    NARCIS (Netherlands)

    Raharjo, H.; Brombacher, A.C.; Xie, M.

    2008-01-01

    Quality Function Deployment (QFD), as a customer-driven tool, is generally used in the early phase of new or improved products/services design process, and therefore most of the input parameters are highly subjective in nature. The five major input components of the QFD, which are laid in the House

  4. A Systematic Review of Fidelity of Implementation in Parent-Mediated Early Communication Intervention

    Science.gov (United States)

    Lieberman-Betz, Rebecca G.

    2015-01-01

    This article examined the reporting of four elements of fidelity of implementation (FOI) in parent-mediated early communication treatment studies. Thirty-five studies were reviewed to extract information regarding reporting of dosage, adherence, quality, and participant responsiveness for both practitioners and parents involved in parent-delivered…

  5. Effect of women's nutrition before and during early pregnancy on maternal and infant outcomes: a systematic review.

    Science.gov (United States)

    Ramakrishnan, Usha; Grant, Frederick; Goldenberg, Tamar; Zongrone, Amanda; Martorell, Reynaldo

    2012-07-01

    Current understanding of biologic processes indicates that women's nutritional status before and during early pregnancy may play an important role in determining early developmental processes and ensuring successful pregnancy outcomes. We conducted a systematic review of the evidence for the impact of maternal nutrition before and during early pregnancy (health outcomes and included 45 articles (nine intervention trials and 32 observational studies) that were identified through PubMed and EMBASE database searches and examining review articles. Intervention trials and observational studies show that periconceptional (importance of women's nutrition prior to and during the first trimester of pregnancy, but there is a need for well-designed prospective studies and controlled trials in developing country settings that examine relationships with low birthweight, SGA, PTD, stillbirth and maternal and neonatal mortality. The knowledge gaps that need to be addressed include the evaluation of periconceptional interventions such as food supplements, multivitamin-mineral supplements and/or specific micronutrients (iron, zinc, iodine, vitamin B-6 and B-12) as well as the relationship between measures of prepregnancy body size and composition and maternal, neonatal and child health outcomes. © 2012 Blackwell Publishing Ltd.

  6. Effects of healthcare professional delivered early feeding interventions on feeding practices and dietary intake: A systematic review.

    Science.gov (United States)

    Matvienko-Sikar, Karen; Toomey, Elaine; Delaney, Lisa; Harrington, Janas; Byrne, Molly; Kearney, Patricia M

    2018-04-01

    Childhood obesity is a global public health challenge. Parental feeding practices, such as responsive feeding, are implicated in the etiology of childhood obesity. This systematic review aimed to examine of effects of healthcare professional-delivered early feeding interventions, on parental feeding practices, dietary intake, and weight outcomes for children up to 2 years. The role of responsive feeding interventions was also specifically examined. Databases searched included: CINAHL, the Cochrane Library, EMBASE, Medline, PubMed, PsycINFO, and Maternity and Infant Care. participants are parents of children ≤2 years; intervention includes focus on early child feeding to prevent overweight and obesity; intervention delivered by healthcare professionals. Sixteen papers, representing 10 trials, met inclusion criteria for review. Six interventions included responsive feeding components. Interventions demonstrated inconsistent effects on feeding practices, dietary intake, and weight outcomes. Findings suggest some reductions in pressure to eat and infant consumption of non-core beverages. Responsive feeding based interventions demonstrate greater improvements in feeding approaches, and weight outcomes. The findings of this review highlight the importance of incorporating responsive feeding in healthcare professional delivered early feeding interventions to prevent childhood obesity. Observed inconsistencies across trials may be explained by methodological limitations. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Influence of shift work on early reproductive outcomes: a systematic review and meta-analysis.

    Science.gov (United States)

    Stocker, Linden J; Macklon, Nicholas S; Cheong, Ying C; Bewley, Susan J

    2014-07-01

    To determine whether an association exists between shift work and early reproductive outcomes. MEDLINE, Embase, and Web of Science were searched. Additional sources included Google Scholar, the Cochrane Library, online publications of national colleges, the ClinicalTrials.gov, and references of retrieved papers. Included studies compared female shift workers (work outside 8:00 AM to 6:00 PM) with nonshift workers with menstrual disruption (cycles less than 25 days or greater than 31 days), infertility (time-to-pregnancy exceeding 12 months), or early spontaneous pregnancy loss (less than 25 weeks). Two reviewers extracted adjusted and raw data. Random effect models were used to pool data weighting for the inverse of variance. Assessments of heterogeneity, bias, and subgroup analyses were performed. Sixteen independent cohorts from 15 studies (123,403 women) were subject to analysis. Shift workers had increased rates of menstrual disruption (16.05% [2,207/13,749] compared with 13.05% [7,561/57,932] [n=71.681, odds ratio {OR} 1.22, 95% confidence interval {CI} 1.15-1.29, I 0%]) and infertility (11.3% [529/4,668] compared with 9.9% [2,354/23,811] [OR 1.80, 95% CI 1.01-3.20, I 94%]) but not early spontaneous pregnancy loss (11.84% [939/7,931] compared with 12.11% [1,898/15,673] [n=23,604, OR 0.96, 95% CI 0.88-1.05, I 0%]). Night shifts were associated with increased early spontaneous pregnancy loss (n=13,018, OR 1.29, 95% CI 1.11-1.50, I 0%). Confounder adjustment led to persistent relationships between shift work and menstrual disruption (adjusted OR 1.15, 95% CI 1.01-1.31, I 70%) but not infertility (adjusted OR 1.11 95% CI 0.86-1.44, I 61%). The association between night shifts and early spontaneous pregnancy loss remained (adjusted OR 1.41 95% CI 1.22-1.63, I 0%). This review provides evidence for an association between performing shift work and early reproductive outcomes, consistent with later pregnancy findings. However, there is currently insufficient evidence

  8. Experiences of early labour management from perspectives of women, labour companions and health professionals: A systematic review of qualitative evidence.

    Science.gov (United States)

    Beake Rm Ma Research Associate, Sarah; Chang Ba MPhil PhD Lecturer, Yan-Shing; Cheyne Rm Rgn MSc PhD Professor Of Midwifery, Helen; Spiby MPhil Rn Rm Professor Of Midwifery, Helen; Sandall Rm MSc PhD Professor Of Social Science And Women's Health, Jane; Bick, Debra

    2018-02-01

    to examine evidence of women's, labour companions' and health professionals' experiences of management of early labour to consider how this could be enhanced to better reflect women's needs. a systematic review of qualitative evidence. women in early labour with term, low risk singleton pregnancies, not booked for a planned caesarean birth or post-dates induction of labour, their labour companions, and health professionals responsible for early labour care (e.g. midwives, nurse-midwives, obstetricians, family doctors). Studies from high and middle income country settings were considered. 21 publications were included from the UK, Ireland, Scandinavia, USA, Italy and New Zealand. Key findings included the impact of communication with health professionals (most usually midwives) on women's decision making; women wanting to be listened to by sympathetic midwives who could reassure that symptoms and signs of early labour were 'normal' and offer clear advice on what to do. Antenatal preparation which included realistic information on what to expect when labour commenced was important and appreciated by women and labour companions. Views of the optimal place for women to remain and allow early labour to progress differed and the perceived benefit of support and help offered by labour companions varied. Some were supportive and helped women to relax, while others were anxious and encouraged women to seek early admission to the planned place of birth. Web-based sources of information are increasingly used by women, with mixed views of the value of information accessed. women, labour companions and health professionals find early labour difficult to manage well, with women unsure of how decisions about admission to their planned place of birth are taken. It is unclear why women are effectively left to manage this aspect of their labour with minimal guidance or support. Tailoring management to meet individual needs, with provision of effective communication could reassure

  9. Global early warning systems for natural hazards: systematic and people-centred.

    Science.gov (United States)

    Basher, Reid

    2006-08-15

    To be effective, early warning systems for natural hazards need to have not only a sound scientific and technical basis, but also a strong focus on the people exposed to risk, and with a systems approach that incorporates all of the relevant factors in that risk, whether arising from the natural hazards or social vulnerabilities, and from short-term or long-term processes. Disasters are increasing in number and severity and international institutional frameworks to reduce disasters are being strengthened under United Nations oversight. Since the Indian Ocean tsunami of 26 December 2004, there has been a surge of interest in developing early warning systems to cater to the needs of all countries and all hazards.

  10. Efficacy of adjuvant chemotherapy in early stage uterine leiomyosarcoma: A systematic review and meta-analysis.

    Science.gov (United States)

    Bogani, Giorgio; Fucà, Giovanni; Maltese, Giuseppa; Ditto, Antonino; Martinelli, Fabio; Signorelli, Mauro; Chiappa, Valentina; Scaffa, Cono; Sabatucci, Ilaria; Lecce, Francesca; Raspagliesi, Francesco; Lorusso, Domenica

    2016-11-01

    We sought to review the current evidence in order to test the efficacy of adjuvant chemotherapy in improving disease-free survival in patients affected by early stage uterine leiomyosarcoma. On July 2016, literature was searched in order to identify trials comparing different postoperative adjuvant strategies for patients diagnosed with early stage uterine leiomyosarcoma. Our analysis included 360 patients: 145 (40%), 53 (15%), and 155 (43%) had chemotherapy (with or without radiotherapy), radiotherapy, and observation, respectively. Seven (2%) patients who had radiotherapy with or without chemotherapy were excluded from further analysis in order to reduce risk of biases. Administration of chemotherapy (with or without radiotherapy) did not improve outcomes in comparison to observation (OR: 0.79 (95%CI: 0.48, 1.29)), or radiotherapy (OR: 0.90 (95%CI: 0.42, 1.94)). Loco-regional recurrence rate was similar comparing patients undergoing chemotherapy (with or without radiotherapy) with having observation alone (OR: 0.84 (95%CI: 0.44, 1.60)). Similarly, pooled results suggested that chemotherapy administration did not affect distant recurrence rate in comparison to no chemotherapy (OR: 0.80 (95%CI: 0.50, 1.28)), and observation alone (OR: 0.99 (95%CI: 0.60, 1.64)). However, patients undergoing chemotherapy (with or without radiotherapy) experienced a trend towards lower risk of developing distant recurrences (OR: 0.49 (95%CI: 0.24, 1.03)) and a higher risk of developing loco-regional recurrences (OR: 3.45 (95%CI: 1.02, 11.73)) than patients undergoing radiotherapy. In early stage uterine leiomyosarcoma, the role of adjuvant chemotherapy remains unclear. Owing to the high recurrence rate, even in the early stage of disease, further innovative therapeutic strategies have to be tested. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Bioprospecting of Red Sea Sponges for Novel Antiviral Pharmacophores

    KAUST Repository

    O'Rourke, Aubrie

    2015-01-01

    the coast of Saudi Arabia serves as a newly accessible location, which provides the opportunity to bioprospect marine sponges with the purpose of identifying novel antiviral scaffolds. Antivirals are underrepresented in present day clinical trials, as well

  12. A systematic review and mixed treatment comparison of monotherapy in early Parkinson's disease: implications for Latin America.

    Science.gov (United States)

    Márquez-Cruz, Maribel; Díaz-Martínez, Juan Pablo; Soto-Molina, Herman; De Saráchaga, Adib Jorge; Cervantes-Arriaga, Amin; Llorens-Arenas, Rodrigo; Rodríguez-Violante, Mayela

    2016-01-01

    Parkinson's disease (PD) is the second most common neurodegenerative disease. There are no clinical trials comparing all available pharmacological therapies for the treatment of early PD. The objective of this review is to indirectly analyze the efficacy of antiparkinson drugs currently available in Latin America. A systematic review was performed exploring only placebo-controlled randomized trials comparing antiparkinson monotherapy (levodopa, pramipexole, rasagiline, or selegiline) in patients with PD on Hoehn and Yahr stages I through III published from January 1994 to May 2014. The primary outcome was the mean change in the Unified PD Rating Scale (UPDRS) I, II and III. A mixed treatment comparison analysis (indirect comparisons) through a random-effects model was performed. Levodopa demonstrated the highest effects in terms of UPDRS score improvement both from baseline and when compared to other treatments. Levodopa showed a 60.1% probability of granting the greatest reduction in UPDRS I, II and III.

  13. Towards a better understanding of caregiver distress in early psychosis: a systematic review of the psychological factors involved.

    Science.gov (United States)

    Jansen, Jens Einar; Gleeson, John; Cotton, Sue

    2015-02-01

    We sought to review empirical studies of psychological factors accounting for distress in caregivers of young people with early psychosis. Following the PRISMA guidelines, we included studies that empirically tested psychological models of caregiver distress in early psychosis by searching the following databases up until March 2014: PsycINFO, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL). This was followed by additional manual searches of reference lists and relevant journals. The search identified 15 papers describing 13 studies together comprising 1056 caregivers of persons with early psychosis. The mean age of caregivers was 47.2years (SD=9.8), of whom 71.5% were female and 74.4% were parents. Nine different psychological variables were examined in the included studies, which were categorised in the following non-mutually exclusive groups: coping, appraisal/attribution and interpersonal response. There was considerable data to support the link between distress and psychological factors such as avoidant coping, appraisal and emotional over-involvement. However, the possibilities of drawing conclusions were limited by a number of methodological issues, including cross-sectional data, small sample sizes, confounding variables not being accounted for, and a wide variation in outcome measures. The strengths of the review were the systematic approach, the exclusion of non-empirical papers and the rating of methodological quality by two independent raters. Limitations were that we excluded studies published in languages other than English, that data extraction forms were developed for this study and hence not tested for validity, and that there was a potential publication bias in favour of significant findings. A better grasp of the psychological factors accounting for caregiver distress early in the course of illness may help us understand the trajectory of distress. This is an important step in preventing long-term distress in caregivers and

  14. Treatment of thyroid disorders before conception and in early pregnancy: a systematic review.

    Science.gov (United States)

    Vissenberg, R; van den Boogaard, E; van Wely, M; van der Post, J A; Fliers, E; Bisschop, P H; Goddijn, M

    2012-07-01

    Thyroid disorders are associated with pregnancy complications. Universal screening is currently not recommended because of a lack of evidence on the effectiveness of treatment. Women with hyperthyroidism and hypothyroidism evidently require treatment but this is less clear for women with subclinical hypothyroidism and thyroid autoimmunity. Therefore, we conducted a systematic review to provide a comprehensive overview on the available treatment interventions. Relevant studies were identified by searching Medline, EMBASE and Cochrane Controlled Trials Register, published until December 2011. From a total of 7334 primary selected titles, 22 articles were included for the systematic review and 11 were appropriate for meta-analyses. Eight studies reported on hyperthyroidism. Propylthiouracil (PTU) and methimazole reduce the risk for preterm delivery [risk ratio (RR): 0.23, confidence interval (CI): 0.1-0.52], pre-eclampsia (RR: 0.23, CI: 0.06-0.89) and low birthweight (RR: 0.38, CI: 0.22-0.66). The nine studies that reported on clinical hypothyroidism showed that levothyroxine is effective in reducing the risk for miscarriage (RR: 0.19, CI: 0.08-0.39) and preterm delivery (RR: 0.41, CI: 0.24-0.68). For treatment of subclinical hypothyroidism, current evidence is insufficient. The five studies available on thyroid autoimmunity showed a not significant reduction in miscarriage (RR: 0.58, CI: 0.32-1.06), but significant reduction in preterm birth by treatment with levothyoxine (RR: 0.31, CI: 0.11-0.90). For hyperthyroidism, methimazole and PTU are effective in preventing pregnancy complications. For clinical hypothyroidism, treatment with levothyroxine is recommended. For subclinical hypothyroidism and thyroid autoimmunity, evidence is insufficient to recommend treatment with levothyroxine. The overall lack of evidence precludes a recommendation for universal screening and is only justified in a research setting.

  15. Antiviral Prophylaxis and H1N1

    Centers for Disease Control (CDC) Podcasts

    2011-07-14

    Dr. Richard Pebody, a consultant epidemiologist at the Health Protection Agency in London, UK, discusses the use of antiviral post-exposure prophylaxis and pandemic H1N1.  Created: 7/14/2011 by National Center for Emerging Zoonotic and Infectious Diseases (NCEZID).   Date Released: 7/18/2011.

  16. Generation of antiviral transgenic chicken using spermatogonial ...

    African Journals Online (AJOL)

    This study was conducted in order to generate anti-viral transgenic chickens through transfected spermatogonial stem cell with fusion gene EGFP-MMx. After injecting fusion gene EGFP-MMx into testes, tissues frozen section, polymerase chain reaction (PCR) and dot blot of testes was performed at 30, 40, 50, 60, 70 and 80 ...

  17. Quantitative Analysis of a Parasitic Antiviral Strategy

    OpenAIRE

    Kim, Hwijin; Yin, John

    2004-01-01

    We extended a computer simulation of viral intracellular growth to study a parasitic antiviral strategy that diverts the viral replicase toward parasite growth. This strategy inhibited virus growth over a wide range of conditions, while minimizing host cell perturbations. Such parasitic strategies may inhibit the development of drug-resistant virus strains.

  18. Early Cretaceous ribbed aptychi - a proposal for a new systematic classification

    Czech Academy of Sciences Publication Activity Database

    Měchová, L.; Vašíček, Zdeněk; Houša, Václav

    2010-01-01

    Roč. 85, č. 2 (2010), s. 219-274 ISSN 1214-1119 Institutional research plan: CEZ:AV0Z30860518; CEZ:AV0Z30130516 Keywords : Late Jurassic * J/K boundary * Early Cretaceous * aptychi Subject RIV: DB - Geology ; Mineralogy Impact factor: 1.202, year: 2010 http://apps.isiknowledge.com/full_record.do?product=WOS&search_mode=GeneralSearch&qid=6&SID=Z1P9aiFnKb7Ka2PiKmk&page=1&doc=2

  19. The interferon response circuit in antiviral host defense.

    Science.gov (United States)

    Haller, O; Weber, F

    2009-01-01

    Viruses have learned to multiply in the face of a powerful innate and adaptive immune response of the host. They have evolved multiple strategies to evade the interferon (IFN) system which would otherwise limit virus growth at an early stage of infection. IFNs induce the synthesis of a range of antiviral proteins which serve as cell-autonomous intrinsic restriction factors. For example, the dynamin-like MxA GTPase inhibits the multiplication of influenza and bunyaviruses (such as La Crosse virus, Hantaan virus, Rift Valley Fever virus, and Crimean-Congo hemorrhagic fever virus) by binding and sequestering the nucleocapsid protein into large perinuclear complexes. To overcome such intracellular restrictions, virulent viruses either inhibit IFN synthesis, bind and inactivate secreted IFN molecules, block IFN-activated signaling, or disturb the action of IFN-induced antiviral proteins. Many viruses produce specialized proteins to disarm the danger signal or express virulence genes that target members of the IFN regulatory factor family (IRFs) or components of the JAK-STAT signaling pathway. An alternative evasion strategy is based on extreme viral replication speed which out-competes the IFN response. The identification of viral proteins with IFN antagonistic functions has great implications for disease prevention and therapy. Virus mutants lacking IFN antagonistic properties represent safe yet highly immunogenic candidate vaccines. Furthermore, novel drugs intercepting viral IFN-antagonists could be used to disarm the viral intruders.

  20. A continuum of executive function deficits in early subcortical vascular cognitive impairment: A systematic review and meta-analysis.

    Science.gov (United States)

    Sudo, Felipe Kenji; Amado, Patricia; Alves, Gilberto Sousa; Laks, Jerson; Engelhardt, Eliasz

    2017-01-01

    Subcortical Vascular Cognitive Impairment (SVCI) is a clinical continuum of vascular-related cognitive impairment, including Vascular Mild Cognitive Impairment (VaMCI) and Vascular Dementia. Deficits in Executive Function (EF) are hallmarks of the disorder, but the best methods to assess this function have yet to be determined. The insidious and almost predictable course of SVCI and the multidimensional concept of EF suggest that a temporal dissociation of impairments in EF domains exists early in the disorder. This study aims to review and analyze data from the literature about performance of VaMCI patients on the most used EF tests through a meta-analytic approach. Medline, Web of Knowledge and PsycINFO were searched, using the terms: "vascular mild cognitive impairment" OR "vascular cognitive impairment no dementia" OR "vascular mild neurocognitive disorder" AND "dysexecutive" OR "executive function". Meta-analyses were conducted for each of the selected tests, using random-effect models. Systematic review showed major discrepancies among the results of the studies included. Meta-analyses evidenced poorer performance on the Trail-Making Test part B and the Stroop color test by VaMCI patients compared to controls. A continuum of EF impairments has been proposed in SVCI. Early deficits appear to occur in cognitive flexibility and inhibitory control.

  1. Economic evaluation of medical tests at the early phases of development: a systematic review of empirical studies.

    Science.gov (United States)

    Frempong, Samuel N; Sutton, Andrew J; Davenport, Clare; Barton, Pelham

    2018-02-01

    There is little specific guidance on the implementation of cost-effectiveness modelling at the early stage of test development. The aim of this study was to review the literature in this field to examine the methodologies and tools that have been employed to date. Areas Covered: A systematic review to identify relevant studies in established literature databases. Five studies were identified and included for narrative synthesis. These studies revealed that there is no consistent approach in this growing field. The perspective of patients and the potential for value of information (VOI) to provide information on the value of future research is often overlooked. Test accuracy is an essential consideration, with most studies having described and included all possible test results in their analysis, and conducted extensive sensitivity analyses on important parameters. Headroom analysis was considered in some instances but at the early development stage (not the concept stage). Expert commentary: The techniques available to modellers that can demonstrate the value of conducting further research and product development (i.e. VOI analysis, headroom analysis) should be better utilized. There is the need for concerted efforts to develop rigorous methodology in this growing field to maximize the value and quality of such analysis.

  2. Stem cell therapy for the treatment of early stage avascular necrosis of the femoral head: a systematic review

    Science.gov (United States)

    2014-01-01

    Background Avascular necrosis (AVN) of the femoral head (FH) is believed to be caused by a multitude of etiologic factors and is associated with significant morbidity in younger populations. Eventually, the disease progresses and results in FH collapse. Thus, a focus on early disease management aimed at joint preservation by preventing or delaying progression is key. The use of stem cells (SC) for the treatment of AVN of the FH has been proposed. We undertook a systematic review of the medical literature examining the use of SC for the treatment of early stage (precollapse) AVN of the FH, in both pre-clinical and clinical studies. Methods Data collected included: Pre-clinical studies – model of AVN, variety and dosage of SC, histologic and imaging analyses. Clinical studies – study design, classification and etiology of AVN, SC dosage and treatment protocol, incidence of disease progression, patient reported outcomes, volume of necrotic lesion and hip survivorship. Results In pre-clinical studies, the use of SC uniformly demonstrated improvements in osteogenesis and angiogenesis, yet source of implanted SC was variable. In clinical studies, groups treated with SC showed significant improvements in patient reported outcomes; however hip survivorship was not affected. Discrepancies regarding dose of SC, AVN etiology and disease severity were present. Conclusions Routine use of this treatment method will first require further research into dose and quality optimization as well as confirmed improvements in hip survivorship. PMID:24886648

  3. Greek states of the early historic period: systematizing the evidence contained in the Homeric poems

    Directory of Open Access Journals (Sweden)

    Olga A. Zolotnikova

    2013-06-01

    Based on the descriptions of the states occurring in the Homeric poems, it is supposed to demonstrate that, in terms of organization, a state of the early historic period presented a clear tripartite structure – a body of basileis (“kings”, a body of the elders and an assembly (“agora” of the people; an addition to those, there were also minor public offices, which could be held by representatives of the people. It is the intention of this paper to analyze these institutions with regard to their exact functions, roles, and importance in the states as described in the epic diction. In conclusion, it will be argued that a state as presented in the Homeric poems appeared as a self-governed autonomous community, which in its general features might approximate a city-state (polis; however, it was still too underdeveloped to be compared with states of that type.

  4. A Systematic Review of Early Prognostic Factors for Persistent Pain Following Acute Orthopedic Trauma

    Directory of Open Access Journals (Sweden)

    Fiona J Clay

    2012-01-01

    Full Text Available Persistent or chronic pain is prevalent in many developed countries, with estimates ranging from 10% to higher than 50%, and is a major economic burden to individuals and societies. However, the variation in pain outcomes after acute orthopedic trauma and treatment confronts treating physicians with uncertainty in providing prognostic advice regarding long-term recovery. Although several previous reviews have addressed the determinants of chronic pain outcomes secondary to acute trauma, they have primarily focused on specific injury samples and, furthermore, lack consistency with respect to the important prognostic factors, which limits the generalizability of findings. This review, however, aimed specifically to identify the early prognostic factors associated with variation in persistent pain outcomes following acute orthopedic trauma presenting with a spectrum of pathologies.

  5. Epidermal growth factor receptor overexpression and outcomes in early breast cancer: A systematic review and a meta-analysis.

    Science.gov (United States)

    Gonzalez-Conchas, Galileo A; Rodriguez-Romo, Laura; Hernandez-Barajas, David; Gonzalez-Guerrero, Juan F; Rodriguez-Fernandez, Ivan A; Verdines-Perez, Adrian; Templeton, Arnoud J; Ocana, Alberto; Seruga, Bostjan; Tannock, Ian F; Amir, Eitan; Vera-Badillo, Francisco E

    2018-01-01

    The epidermal growth factor receptor (EGFR) is a member of the ErbB family of membrane tyrosine-kinase receptors. Studies exploring the prognostic role of EGFR-overexpression in early breast cancer have shown variable results, and the true prognostic value of EGFR is unknown. A systematic review of identified publications exploring the association between EGFR-overexpression (as defined from different techniques and cut-offs) and outcomes [disease-free (DFS) and, overall survival (OS)] in women with early breast cancer. The hazard ratios (HR) for DFS and OS were weighted and pooled in a meta-analysis using generic inverse variance and random effects modeling. Fifty-three studies comprising 21,418 women were included. EGFR-overexpression was found in 27% of the patients. Primary analysis included studies reporting HRs from multivariable analyses (10 studies including 4857 patients with HRs for OS and 17 studies comprising 8747 patients with HRs for DFS), EGFR-overexpression was associated with worse OS (HR 1.98, 95% CI: 1.59-2.47, p overexpression on DFS was greater in women with triple negative tumors compared to women with non-triple negative tumors (HR 2.35 versus HR 1.45, respectively; p = .01). Analysis looking at odd ratios for both 5-year and 10-year for DFS and OS showed similar results. EGFR-overexpression appears to be associated with reduced OS and DFS in women with early breast cancer. Patients with triple negative and EGFR-overexpression have poorer OS and DFS than those with triple negative tumors and normal EGFR expression. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Does antibiotic prophylaxis at implant placement decrease early implant failures? A Cochrane systematic review.

    Science.gov (United States)

    Esposito, Marco; Grusovin, Maria Gabriella; Loli, Vasiliki; Coulthard, Paul; Worthington, Helen V

    2010-01-01

    Marco Esposito is the first author of two of the included studies; however, he was not involved in the quality assessment of these trials. This review is based on a Cochrane systematic review entitled 'Interventions for replacing missing teeth: antibiotics at dental implant placement to prevent complications' published in The Cochrane Library (see http://www.cochrane.org for more information). Cochrane systematic reviews are regularly updated to include new research, and in response to comments and criticisms from readers. If you wish to comment on this review, please send your comments to the Cochrane website or to Marco Esposito. The Cochrane Library should be consulted for the most recent version of the review. The results of a Cochrane Review can be interpreted differently, depending on people's perspectives and circumstances. Please consider the conclusions presented carefully. They are the opinions of the review authors, and are not necessarily shared by the Cochrane Collaboration. To assess the beneficial or harmful effects of systemic prophylactic antibiotics at dental implant placement versus no antibiotic/placebo administration and, if antibiotics are of benefit, to find which type, dosage and duration is the most effective. The Cochrane Oral Health Group's Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE were searched up to 2 June 2010 for randomised controlled clinical trials (RCTs) with a follow-up of at least 3 months comparing the administration of various prophylactic antibiotic regimens versus no antibiotics to patients undergoing dental implant placement. Outcome measures were prosthesis failures, implant failures, postoperative infections and adverse events (gastrointestinal, hypersensitivity, etc.). Screening of eligible studies, assessment of the methodological quality of the trials and data extraction were conducted in duplicate and independently by two review authors. Meta-analyses were

  7. Reducing discretionary food and beverage intake in early childhood: a systematic review within an ecological framework.

    Science.gov (United States)

    Johnson, Brittany J; Hendrie, Gilly A; Golley, Rebecca K

    2016-06-01

    To systematically review the literature and map published studies on 4-8-year-olds' intake of discretionary choices against an ecological framework (ANalysis Grid for Environments Linked to Obesity; ANGELO). Articles were identified through database searches (PubMed, PyscINFO®, Web of Science) in February and March 2014 and hand-searching reference lists. Studies were assessed for methodological quality and mapped against the ANGELO framework by environment size (macro and micro setting) and type (physical, economic, policy and socio-cultural influences). Studies were conducted in the USA (n 18), Australia (n 6), the UK (n 3), the Netherlands (n 3), Belgium (n 1), Germany (n 1) and Turkey (n 1). Children aged 4-8 years, or parents/other caregivers. Thirty-three studies met the review criteria (observational n 23, interventions n 10). Home was the most frequently studied setting (67 % of exposures/strategies), with the majority of these studies targeting family policy-type influences (e.g. child feeding practices, television regulation). Few studies were undertaken in government (5·5 %) or community (11 %) settings, or examined economic-type influences (0 %). Of the intervention studies only four were categorised as effective. The present review is novel in its focus on mapping observational and intervention studies across a range of settings. It highlights the urgent need for high-quality research to inform interventions that directly tackle the factors influencing children's excess intake of discretionary choices. Interventions that assist in optimising a range of environmental influences will enhance the impact of future public health interventions to improve child diet quality.

  8. Causes of mortality in early infantile epileptic encephalopathy: A systematic review.

    Science.gov (United States)

    Radaelli, Graciane; de Souza Santos, Francisco; Borelli, Wyllians Vendramini; Pisani, Leonardo; Nunes, Magda Lahorgue; Scorza, Fulvio Alexandre; da Costa, Jaderson Costa

    2018-06-12

    Early infantile epileptic encephalopathy syndrome (EIEE), also known as Ohtahara syndrome, is an age-dependent epileptic encephalopathy syndrome defined by clinical features and electroencephalographic findings. Epileptic disorders with refractory seizures beginning in the neonatal period and/or early infancy have a potential risk of premature mortality, including sudden death. We aimed to identify the causes of death in EIEE and conducted a literature survey of fatal outcomes. We performed a literature search in MEDLINE, EMBASE, and Web of Science for data from inception until September 2017. The terms "death sudden," "unexplained death," "SUDEP," "lethal," and "fatal" and the medical subject heading terms "epileptic encephalopathy," "mortality," "death," "sudden infant death syndrome," and "human" were used in the search strategy. The EIEE case report studies reporting mortality were included. The search yielded 1360 articles. After screening for titles and abstracts and removing duplicate entries, full texts of 15 articles were reviewed. After reading full texts, 11 articles met the inclusion criteria (9 articles in English and 2 in Japanese, dated from 1976 to 2015). The review comprised 38 unique cases of EIEE, 17 of which had death as an outcome. In all cases, the suppression-burst pattern on electroencephalographies (EEGs) was common. Most cases (55%) involved male infants. The mean (standard deviation [SD]) age at onset of seizure was 19.6 ± 33 days. The mean (SD) age at death was 12.9 ± 14.1 months. Most infants (58.8%) survived less than one year. The cause of death was described only in eight (47%) patients; the cause was pneumonia/respiratory illness or sudden unexpected death in epilepsy (SUDEP). The results show EIEE as a severe disease associated with a premature mortality, evidenced by a very young age at death. Increasing interest in the detection of new molecular bases of EIEE is leading us to a better understanding of this severe

  9. Systematics and paleobiogeography of .i.Sardolagus obscurus./i. n. gen. n. sp. (Leporidae, Lagomorpha) from the early Pleistocene of Sardinia

    Czech Academy of Sciences Publication Activity Database

    Angelone, Ch.; Čermák, Stanislav; Moncunill-Solé, B.; Quintana, J.; Tuveri, C.; Arca, M.; Kotsakis, T.

    2018-01-01

    Roč. 92, č. 3 (2018) ISSN 0022-3360 Institutional support: RVO:67985831 Keywords : Sardolagus obscurus n. gen. n. sp. * Leporidae * early Pleistocene * Sardinia * systematics Subject RIV: DB - Geology ; Mineralogy OBOR OECD: Paleontology Impact factor: 1.591, year: 2016

  10. Systematic review and meta-analysis of early life exposure to di(2-ethylhexyl) phthalate and obesity related outcomes in rodents

    NARCIS (Netherlands)

    Wassenaar, Pim Nicolaas Hubertus; Legler, Juliette

    Background It has been suggested that the plasticizer di(2-ethylhexyl) phthalate (DEHP) exerts obesogenic effects after pre- or perinatal exposure. Objective A systematic review with meta-analyses was conducted of early life exposure to DEHP, or its biologically active metabolite mono(2-ethylhexyl)

  11. [Evaluation of quality of service in Early Intervention: A systematic review].

    Science.gov (United States)

    Jemes Campaña, Inmaculada Concepción; Romero-Galisteo, Rita Pilar; Labajos Manzanares, María Teresa; Moreno Morales, Noelia

    2018-06-07

    Early Intervention (EI), as a paediatric service, has the duty of quantifying the results and the quality of its services provided. The accessibility of valid and reliable tools allows professionals to evaluate the quality of these services. The aim of this study is to review the scientific literature on tools used to measure the methodological and service quality in EI. A search was made in different databases: Medline (from PubMed), Web of Science, PsycINFO, Cochrane, Scopus, ERIC and Scielo. The methodological quality of the studies was tested using the COSMIN scale. A total of 13 manuscripts met the criteria to be included in this review. Ten of them received a "good" or "reasonable" score based on the COSMIN scale. Despite its importance, there is no consensus among authors on the measurement of service quality in EI. It is often the family of the children attended in EI that are considered the target to study, although the opinion of professionals carries more weight and completes the information. Copyright © 2018. Publicado por Elsevier España, S.L.U.

  12. Late Jurassic–Early Cretaceous oysters from Siberia: A systematic review

    Directory of Open Access Journals (Sweden)

    Igor N. Kosenko

    2017-11-01

    Full Text Available The present study reviews the taxonomy of Late Jurassic–Early Cretaceous oysters from the Northern and the Subpolar Urals (Western Siberia and northern East Siberia. Previous studies have documented 10 species from the genus Liostrea (L. delta, L. cucurbita, L. praeanabarensis, L. anabarensis, L. plastica, L. gibberosa, L. planoconvexa, L. siberica, L. uralensis, L. lyapinensis, and 3 species from the genus Gryphaea (G. borealis and 2 species in open nomenclature. Liostrea gibberosa, L. planoconvexa, L. uralensis, and L. cucurbita are transferred in this study to the genus Pernostrea. Furthermore, two new species of Pernostrea are described: P. mesezhnikovi sp. nov. and P.? robusta sp. nov. Liostrea siberica is transferred to the genus Praeexogyra. Liostrea praeanabarensis and L. anabarensis are attributed to the subgenus Boreiodeltoideum (genus Deltoideum as well as L. delta sensu Zakharov (1966 which is described here as new species Deltoideum (Boreiodeltoideum borealis sp. nov. The similar shell morphology of the genera Deltoideum and Pernostrea provides a basis to establish the new tribe Pernostreini trib. nov. in the subfamily Gryphaeinae. Three species are recorded for the first time from Siberia: Nanogyra? cf. thurmanni, “Ostrea” cf. moreana and Gryphaea (Gryphaea curva.

  13. Effects of Physical Activity on Motor Skills and Cognitive Development in Early Childhood: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Nan Zeng

    2017-01-01

    Full Text Available Objective. This study synthesized literature concerning casual evidence of effects of various physical activity programs on motor skills and cognitive development in typically developed preschool children. Methods. Electronic databases were searched through July 2017. Peer-reviewed randomized controlled trials (RCTs examining the effectiveness of physical activity on motor skills and cognitive development in healthy young children (4–6 years were screened. Results. A total of 15 RCTs were included. Of the 10 studies assessing the effects of physical activity on motor skills, eight (80% reported significant improvements in motor performance and one observed mixed findings, but one failed to promote any beneficial outcomes. Of the five studies investigating the influence of physical activity on cognitive development, four (80% showed significant and positive changes in language learning, academic achievement, attention, and working memory. Notably, one indicated no significant improvements were observed after the intervention. Conclusions. Findings support causal evidence of effects of physical activity on both motor skills and cognitive development in preschool children. Given the shortage of available studies, future research with large representative samples is warranted to explore the relationships between physical activity and cognitive domains as well as strengthen and confirm the dose-response evidence in early childhood.

  14. Effects of Physical Activity on Motor Skills and Cognitive Development in Early Childhood: A Systematic Review.

    Science.gov (United States)

    Zeng, Nan; Ayyub, Mohammad; Sun, Haichun; Wen, Xu; Xiang, Ping; Gao, Zan

    2017-01-01

    This study synthesized literature concerning casual evidence of effects of various physical activity programs on motor skills and cognitive development in typically developed preschool children. Electronic databases were searched through July 2017. Peer-reviewed randomized controlled trials (RCTs) examining the effectiveness of physical activity on motor skills and cognitive development in healthy young children (4-6 years) were screened. A total of 15 RCTs were included. Of the 10 studies assessing the effects of physical activity on motor skills, eight (80%) reported significant improvements in motor performance and one observed mixed findings, but one failed to promote any beneficial outcomes. Of the five studies investigating the influence of physical activity on cognitive development, four (80%) showed significant and positive changes in language learning, academic achievement, attention, and working memory. Notably, one indicated no significant improvements were observed after the intervention. Findings support causal evidence of effects of physical activity on both motor skills and cognitive development in preschool children. Given the shortage of available studies, future research with large representative samples is warranted to explore the relationships between physical activity and cognitive domains as well as strengthen and confirm the dose-response evidence in early childhood.

  15. Attitude and Practice Regarding Breast Cancer Early Detection among Iranian Women: A Systematic Review

    Science.gov (United States)

    Badakhsh, Mahin; Balouchi, Abbas; Taheri, Safiyeh; Bouya, Salehoddin; Ahmadidarehsima, Sudabeh; Aminifard, Mohammadnaem

    2018-01-01

    Objectives: To determining attitudes and practice regarding breast cancer early detection techniques (breast self-examination (BSE), clinical breast examination (CBE) and mammography) among Iranian woman. Methods: International (PubMed, ISI, and Google Scholar) and national (SID and Magiran) databases were reviewed up to September 2017 to identify articles related to the attitudes and practices of Iranian women concerning breast cancer screening behavior with reference to BSE , CBE and mammography. The screening steps, analysis of quality of the studies and extraction of the papers were performed by two reviewers. Results: Of the 532 studies included initially, 21 performed on 10,521 people were considered eligible. Subjects with a positive attitude toward BSE in various studies were 13.5% to 94.0% with an average of 47.6%. Positive attitudes to CBE and mammography were found in 21.0% and 26.4%, respectively. Participant performance of BSE ranged from 2.6% to 84.7%, with an average of 21.9%. The respective figures for CBE and mammography were 15.8% and 16.7%. Conclusion: Considering the poor performance and low rates for positive attitudes, it is suggested that educational programs should be conducted across the country. PMID:29373873

  16. Minimally Invasive Surgical Staging in Early-stage Ovarian Carcinoma: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Bogani, Giorgio; Borghi, Chiara; Leone Roberti Maggiore, Umberto; Ditto, Antonino; Signorelli, Mauro; Martinelli, Fabio; Chiappa, Valentina; Lopez, Carlos; Sabatucci, Ilaria; Scaffa, Cono; Indini, Alice; Ferrero, Simone; Lorusso, Domenica; Raspagliesi, Francesco

    Few studies investigated the efficacy and safety of minimally invasive surgery for the treatment of early-stage epithelial ovarian cancer (eEOC). In this context, we aimed to review the current evidence comparing laparoscopy and the laparotomic approach for staging procedures in eEOC. This systematic review was registered in the International Prospective Register of Systematic Reviews. Overall, 3065 patients were included: 1450 undergoing laparoscopy and 1615 undergoing laparotomic staging. Patients undergoing laparoscopy experienced a longer (but not statistically significant) operative time (weighted mean difference [WMD] = 28.3 minutes; 95% confidence interval [CI], -2.59 to 59.2), a lower estimated blood loss (WMD = -156.5 mL; 95% CI, -216.4 to -96.5), a shorter length of hospital stay (WMD = -3.7 days; 95% CI, -5.2 to -2.1), and a lower postoperative complication rate (odds ratio [OR] = 0.48; 95% CI, 0.29-0.81) than patients undergoing laparotomy. The upstaging (OR = 0.81; 95% CI, 0.55-1.20) and cyst rupture (OR = 1.32; 95% CI, 0.52-3.38) rates were similar between groups. Laparoscopic staging is associated with a shorter time to chemotherapy than laparotomic procedures (WMD = -5.16 days; 95% CI, -8.68 to -1.64). Survival outcomes were not influenced by the route of surgery. Pooled data suggested that the minimally invasive surgical approach is equivalent to laparotomy for the treatment of eEOC and may be superior in terms of perioperative outcomes. However, because of the low level of evidence of the included studies, further randomized trials are warranted. Copyright © 2017 AAGL. Published by Elsevier Inc. All rights reserved.

  17. Early Botulinum Toxin Injections in Infants With Musculoskeletal Disorders: A Systematic Review of Safety and Effectiveness.

    Science.gov (United States)

    Bourseul, Jean-Sébastien; Molina, Anais; Lintanf, Mael; Houx, Laetitia; Chaléat-Valayer, Emmanuelle; Pons, Christelle; Brochard, Sylvain

    2018-06-01

    To report current evidence regarding the safety of intramuscular botulinum toxin injection (BTI) in children with orthopedic- and neurologic-related musculoskeletal disorders >2 years of age. PubMed, Cochrane Library, and ScienceDirect, Google Scholar, and Web of Science. Two reviewers independently selected studies based on predetermined inclusion criteria. Data relating to the aim were extracted. Methodologic quality was graded independently by 2 reviewers using the Physiotherapy Evidence Database scale for randomized controlled trials (RCTs) and the Downs and Black evaluation tool for non-RCTs. Level of evidence was determined using the modified Sackett scale. Data of 473 infants were analyzed. Fifty-five infants had cerebral palsy, 112 had obstetric brachial plexus palsy, 257 had clubfoot, and 44 had congenital torticollis. No studies reported any severe adverse event that could be attributed to the BTI. The rate of mild to moderate adverse events reported varied from 5% to 25%. Results regarding efficacy were preliminary, dependent on the pathology, and limited by the small number of studies and their low levels of evidence. BTI is already widely used as an early treatment for this age group. The safety profile of BTI in infants appears similar to that of older children and risks appear more related to the severity of the pathology and the location of the injections than to the toxin itself. Regarding effectiveness, other studies with higher levels of evidence should be carried out for each specific pathology. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  18. Broad-spectrum antiviral properties of andrographolide.

    Science.gov (United States)

    Gupta, Swati; Mishra, K P; Ganju, Lilly

    2017-03-01

    Andrographolide, a diterpenoid, is known for its anti-inflammatory effects. It can be isolated from various plants of the genus Andrographis, commonly known as 'creat'. This purified compound has been tested for its anti-inflammatory effects in various stressful conditions, such as ischemia, pyrogenesis, arthritis, hepatic or neural toxicity, carcinoma, and oxidative stress, Apart from its anti-inflammatory effects, andrographolide also exhibits immunomodulatory effects by effectively enhancing cytotoxic T cells, natural killer (NK) cells, phagocytosis, and antibody-dependent cell-mediated cytotoxicity (ADCC). All these properties of andrographolide form the foundation for the use of this miraculous compound to restrain virus replication and virus-induced pathogenesis. The present article covers antiviral properties of andrographolide in variety of viral infections, with the hope of developing of a new highly potent antiviral drug with multiple effects.

  19. In vitro characterization of the antiviral activity of fucoidan from Cladosiphon okamuranus against Newcastle Disease Virus

    Directory of Open Access Journals (Sweden)

    Elizondo-Gonzalez Regina

    2012-12-01

    Full Text Available Abstract Background Newcastle Disease Virus (NDV causes a serious infectious disease in birds that results in severe losses in the worldwide poultry industry. Despite vaccination, NDV outbreaks have increased the necessity of alternative prevention and control measures. Several recent studies focused on antiviral compounds obtained from natural resources. Many extracts from marine organisms have been isolated and tested for pharmacological purposes, and their antiviral activity has been demonstrated in vitro and in vivo. Fucoidan is a sulfated polysaccharide present in the cell wall matrix of brown algae that has been demonstrated to inhibit certain enveloped viruses with low toxicity. This study evaluated the potential antiviral activity and the mechanism of action of fucoidan from Cladosiphon okamuranus against NDV in the Vero cell line. Methods The cytotoxicity of fucoidan was determined by the MTT assay. To study its antiviral activity, fusion and plaque-forming unit (PFU inhibition assays were conducted. The mechanism of action was determined by time of addition, fusion inhibition, and penetration assays. The NDV vaccine strain (La Sota was used in the fusion inhibition assays. PFU and Western blot experiments were performed using a wild-type lentogenic NDV strain. Results Fucoidan exhibited antiviral activity against NDV La Sota, with an obtained IS50 >2000. In time of addition studies, we observed viral inhibition in the early stages of infection (0–60 min post-infection. The inhibition of viral penetration experiments with a wild-type NDV strain supported this result, as these experiments demonstrated a 48% decrease in viral infection as well as reduced HN protein expression. Ribavirin, which was used as an antiviral control, exhibited lower antiviral activity than fucoidan and high toxicity at active doses. In the fusion assays, the number of syncytia was significantly reduced (70% inhibition when fucoidan was added before cleavage of

  20. Antiviral lead compounds from marine sponges

    KAUST Repository

    Sagar, Sunil

    2010-10-11

    Marine sponges are currently one of the richest sources of pharmacologically active compounds found in the marine environment. These bioactive molecules are often secondary metabolites, whose main function is to enable and/or modulate cellular communication and defense. They are usually produced by functional enzyme clusters in sponges and/or their associated symbiotic microorganisms. Natural product lead compounds from sponges have often been found to be promising pharmaceutical agents. Several of them have successfully been approved as antiviral agents for clinical use or have been advanced to the late stages of clinical trials. Most of these drugs are used for the treatment of human immunodeficiency virus (HIV) and herpes simplex virus (HSV). The most important antiviral lead of marine origin reported thus far is nucleoside Ara-A (vidarabine) isolated from sponge Tethya crypta. It inhibits viral DNA polymerase and DNA synthesis of herpes, vaccinica and varicella zoster viruses. However due to the discovery of new types of viruses and emergence of drug resistant strains, it is necessary to develop new antiviral lead compounds continuously. Several sponge derived antiviral lead compounds which are hopedto be developed as future drugs are discussed in this review. Supply problems are usually the major bottleneck to the development of these compounds as drugs during clinical trials. However advances in the field of metagenomics and high throughput microbial cultivation has raised the possibility that these techniques could lead to the cost-effective large scale production of such compounds. Perspectives on biotechnological methods with respect to marine drug development are also discussed. 2010 by the authors; licensee MDPI.

  1. Efficacy of light based detection systems for early detection of oral cancer and oral potentially malignant disorders: Systematic review.

    Science.gov (United States)

    Nagi, R; Reddy-Kantharaj, Y-B; Rakesh, N; Janardhan-Reddy, S; Sahu, S

    2016-07-01

    Earlier detection of oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMD) is essential for dental professionals to improve patient survival rates. The aim of this systematic review is to to evaluate the effectiveness of devices that utilise the principles of chemiluminescence and tissue autofluorescence as adjuncts in the detection of OSCC and OPMD. The electronic retrieval systems and databases searched for relevant articles were PubMed [MEDLINE] and Science direct. The search was for limited articles published in English or with an English abstract and articles published during the period from January 2005 to April 2014. Clinical trials utilized ViziLite, Microlux TM/DL and Visual Enhanced Light scope (VELscope) for early detection of OPMD and OSCC. Twenty primary studies published satisfied our criteria for selection - 10 utilised chemiluminescence and 10 tissue autofluorescence. Senstivity of Vizilite for detecting OSCC nad OPMD ranged from 77.1 % to 100% and specificity was low that ranged from 0% to 27.8%.Most have shown that chemiluminescence increases the brightness and margins of oral mucosal white lesions and thus assist in identification of mucosal lesions not considered under Conventional visual examination. However, it preferentially detects leukoplakia and may fail to spot red patches. Clinical trials demonstrated that sensitivity of VELscope in detecting malignancy and OPMD ranged from 22 % to 100 % and specificity ranged from 16 % to 100%. Most studies concluded that VELscope can help the experienced clinician to find oral precursor malignant lesions. But it couldnot differentiate between dysplasia and benign inflammatory conditions. Both devices are simple, non-invasive test of the oral mucosa but are suited for clinicians with sufficient experience and training. More clinical trials in future should be conducted to establish optical imaging as an efficacious adjunct tool in early diagnosis of OSCC and OPMD.

  2. Effect of health belief model and health promotion model on breast cancer early diagnosis behavior: a systematic review.

    Science.gov (United States)

    Ersin, Fatma; Bahar, Zuhal

    2011-01-01

    Breast cancer is an important public health problem on the grounds that it is frequently seen and it is a fatal disease. The objective of this systematic analysis is to indicate the effects of interventions performed by nurses by using the Health Belief Model (HBM) and Health Promotion Model (HPM) on the breast cancer early diagnosis behaviors and on the components of the Health Belief Model and Health Promotion Model. The reveiw was created in line with the Centre for Reviews and Dissemination guide dated 2009 (CRD) and developed by York University National Institute of Health Researches. Review was conducted by using PUBMED, OVID, EBSCO and COCHRANE databases. Six hundred seventy eight studies (PUBMED: 236, OVID: 162, EBSCO: 175, COCHRANE:105) were found in total at the end of the review. Abstracts and full texts of these six hundred seventy eight studies were evaluated in terms of inclusion and exclusion criteria and 9 studies were determined to meet the criteria. Samplings of the studies varied between ninety four and one thousand six hundred fifty five. It was detected in the studies that educations provided by taking the theories as basis became effective on the breast cancer early diagnosis behaviors. When the literature is examined, it is observed that the experimental researches which compare the concepts of Health Belief Model (HBM) and Health Promotion Model (HPM) preoperatively and postoperatively and show the effect of these concepts on education and are conducted by nurses are limited in number. Randomized controlled studies which compare HBM and HPM concepts preoperatively and postoperatively and show the efficiency of the interventions can be useful in evaluating the efficiency of the interventions.

  3. Nurses' worry or concern and early recognition of deteriorating patients on general wards in acute care hospitals: a systematic review.

    Science.gov (United States)

    Douw, Gooske; Schoonhoven, Lisette; Holwerda, Tineke; Huisman-de Waal, Getty; van Zanten, Arthur R H; van Achterberg, Theo; van der Hoeven, Johannes G

    2015-05-20

    Nurses often recognize deterioration in patients through intuition rather than through routine measurement of vital signs. Adding the 'worry or concern' sign to the Rapid Response System provides opportunities for nurses to act upon their intuitive feelings. Identifying what triggers nurses to be worried or concerned might help to put intuition into words, and potentially empower nurses to act upon their intuitive feelings and obtain medical assistance in an early stage of deterioration. The aim of this systematic review is to identify the signs and symptoms that trigger nurses' worry or concern about a patient's condition. We searched the databases PubMed, CINAHL, Psychinfo and Cochrane Library (Clinical Trials) using synonyms related to the three concepts: 'nurses', 'worry/concern' and 'deterioration'. We included studies concerning adult patients on general wards in acute care hospitals. The search was performed from the start of the databases until 14 February 2014. The search resulted in 4,006 records, and 18 studies (five quantitative, nine qualitative and four mixed-methods designs) were included in the review. A total of 37 signs and symptoms reflecting the nature of the criterion worry or concern emerged from the data and were summarized in 10 general indicators. The results showed that worry or concern can be present with or without change in vital signs. The signs and symptoms we found in the literature reflect the nature of nurses' worry or concern, and nurses may incorporate these signs in their assessment of the patient and their decision to call for assistance. The fact that it is present before changes in vital signs suggests potential for improving care in an early stage of deterioration.

  4. A systematic analysis of the early transcribed membrane protein family throughout the life cycle of Plasmodium yoelii.

    Science.gov (United States)

    MacKellar, Drew C; Vaughan, Ashley M; Aly, Ahmed S I; DeLeon, Sasha; Kappe, Stefan H I

    2011-11-01

    The early transcribed membrane proteins (ETRAMPs) are a family of small, highly charged transmembrane proteins unique to malaria parasites. Some members of the ETRAMP family have been localized to the parasitophorous vacuole membrane that separates the intracellular parasite from the host cell and thus presumably have a role in host-parasite interactions. Although it was previously shown that two ETRAMPs are critical for rodent malaria parasite liver-stage development, the importance of most ETRAMPs during the parasite life cycle remains unknown. Here, we comprehensively identify nine new etramps in the genome of the rodent malaria parasite Plasmodium yoelii, and elucidate their conservation in other malaria parasites. etramp expression profiles are diverse throughout the parasite life cycle as measured by RT-PCR. Epitope tagging of two ETRAMPs demonstrates protein expression in blood and liver stages, and reveals differences in both their timing of expression and their subcellular localization. Gene targeting studies of each of the nine uncharacterized etramps show that two are refractory to deletion and thus likely essential for blood-stage replication. Seven etramps are not essential for any life cycle stage. Systematic characterization of the members of the ETRAMP family reveals the diversity in importance of each family member at the interface between host and parasite throughout the developmental cycle of the malaria parasite. © 2011 Blackwell Publishing Ltd.

  5. Antiviral immunity following smallpox virus infection: a case-control study.

    Science.gov (United States)

    Hammarlund, Erika; Lewis, Matthew W; Hanifin, Jon M; Mori, Motomi; Koudelka, Caroline W; Slifka, Mark K

    2010-12-01

    Outbreaks of smallpox (i.e., caused by variola virus) resulted in up to 30% mortality, but those who survived smallpox infection were regarded as immune for life. Early studies described the levels of neutralizing antibodies induced after infection, but smallpox was eradicated before contemporary methods for quantifying T-cell memory were developed. To better understand the levels and duration of immunity after smallpox infection, we performed a case-control study comparing antiviral CD4(+) and CD8(+) T-cell responses and neutralizing antibody levels of 24 smallpox survivors with the antiviral immunity observed in 60 smallpox-vaccinated (i.e., vaccinia virus-immune) control subjects. We found that the duration of immunity following smallpox infection was remarkably similar to that observed after smallpox vaccination, with antiviral T-cell responses that declined slowly over time and antiviral antibody responses that remained stable for decades after recovery from infection. These results indicate that severe, potentially life-threatening disease is not required for the development of sustainable long-term immunity. This study shows that the levels of immunity induced following smallpox vaccination are comparable in magnitude to that achieved through natural variola virus infection, and this may explain the notable success of vaccination in eradicating smallpox, one of the world's most lethal diseases.

  6. Antiviral Immunity following Smallpox Virus Infection: a Case-Control Study▿

    Science.gov (United States)

    Hammarlund, Erika; Lewis, Matthew W.; Hanifin, Jon M.; Mori, Motomi; Koudelka, Caroline W.; Slifka, Mark K.

    2010-01-01

    Outbreaks of smallpox (i.e., caused by variola virus) resulted in up to 30% mortality, but those who survived smallpox infection were regarded as immune for life. Early studies described the levels of neutralizing antibodies induced after infection, but smallpox was eradicated before contemporary methods for quantifying T-cell memory were developed. To better understand the levels and duration of immunity after smallpox infection, we performed a case-control study comparing antiviral CD4+ and CD8+ T-cell responses and neutralizing antibody levels of 24 smallpox survivors with the antiviral immunity observed in 60 smallpox-vaccinated (i.e., vaccinia virus-immune) control subjects. We found that the duration of immunity following smallpox infection was remarkably similar to that observed after smallpox vaccination, with antiviral T-cell responses that declined slowly over time and antiviral antibody responses that remained stable for decades after recovery from infection. These results indicate that severe, potentially life-threatening disease is not required for the development of sustainable long-term immunity. This study shows that the levels of immunity induced following smallpox vaccination are comparable in magnitude to that achieved through natural variola virus infection, and this may explain the notable success of vaccination in eradicating smallpox, one of the world's most lethal diseases. PMID:20926574

  7. Antiviral Activity of Peanut (Arachis hypogaea L.) Skin Extract Against Human Influenza Viruses.

    Science.gov (United States)

    Makau, Juliann Nzembi; Watanabe, Ken; Mohammed, Magdy M D; Nishida, Noriyuki

    2018-05-30

    The high propensity of influenza viruses to develop resistance to antiviral drugs necessitates the continuing search for new therapeutics. Peanut skins, which are low-value byproducts of the peanut industry, are known to contain high levels of polyphenols. In this study, we investigated the antiviral activity of ethanol extracts of peanut skins against various influenza viruses using cell-based assays. Extracts with a higher polyphenol content exhibited higher antiviral activities, suggesting that the active components are the polyphenols. An extract prepared from roasted peanut skins effectively inhibited the replication of influenza virus A/WSN/33 with a half maximal inhibitory concentration of 1.3 μg/mL. Plaque assay results suggested that the extract inhibits the early replication stages of the influenza virus. It demonstrated activity against both influenza type A and type B viruses. Notably, the extract exhibited a potent activity against a clinical isolate of the 2009 H1N1 pandemic, which had reduced sensitivity to oseltamivir. Moreover, a combination of peanut skin extract with the anti-influenza drugs, oseltamivir and amantadine, synergistically increased their antiviral activity. These data demonstrate the potential application of peanut skin extract in the development of new therapeutic options for influenza management.

  8. Antiviral agents for infectious mononucleosis (glandular fever).

    Science.gov (United States)

    De Paor, Muireann; O'Brien, Kirsty; Fahey, Tom; Smith, Susan M

    2016-12-08

    Infectious mononucleosis (IM) is a clinical syndrome, usually caused by the Epstein Barr virus (EPV), characterised by lymphadenopathy, fever and sore throat. Most cases of symptomatic IM occur in older teenagers or young adults. Usually IM is a benign self-limiting illness and requires only symptomatic treatment. However, occasionally the disease course can be complicated or prolonged and lead to decreased productivity in terms of school or work. Antiviral medications have been used to treat IM, but the use of antivirals for IM is controversial. They may be effective by preventing viral replication which helps to keep the virus inactive. However, there are no guidelines for antivirals in IM. To assess the effects of antiviral therapy for infectious mononucleosis (IM). We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3, March 2016), which contains the Cochrane Acute Respiratory Infections (ARI) Group's Specialised Register, MEDLINE (1946 to 15 April 2016), Embase (1974 to 15 April 2016), CINAHL (1981 to 15 April 2016), LILACS (1982 to 15 April 2016) and Web of Science (1955 to 15 April 2016). We searched the World Health Organization (WHO) International Clinical Trials Registry Platform and ClinicalTrials.gov for completed and ongoing trials. We included randomised controlled trials (RCTs) comparing antivirals versus placebo or no treatment in IM. We included trials of immunocompetent participants of any age or sex with clinical and laboratory-confirmed diagnosis of IM, who had symptoms for up to 14 days. Our primary outcomes were time to clinical recovery and adverse events and side effects of medication. Secondary outcomes included duration of abnormal clinical examination, complications, viral shedding, health-related quality of life, days missing from school or work and economic outcomes. Two review authors independently assessed studies for inclusion, assessed the included studies' risk of bias and extracted data using a

  9. HIV-1 accessory proteins VPR and Vif modulate antiviral response by targeting IRF-3 for degradation

    International Nuclear Information System (INIS)

    Okumura, Atsushi; Alce, Tim; Lubyova, Barbora; Ezelle, Heather; Strebel, Klaus; Pitha, Paula M.

    2008-01-01

    The activation of IRF-3 during the early stages of viral infection is critical for the initiation of the antiviral response; however the activation of IRF-3 in HIV-1 infected cells has not yet been characterized. We demonstrate that the early steps of HIV-1 infection do not lead to the activation and nuclear translocation of IRF-3; instead, the relative levels of IRF-3 protein are decreased due to the ubiquitin-associated proteosome degradation. Addressing the molecular mechanism of this effect we show that the degradation is independent of HIV-1 replication and that virion-associated accessory proteins Vif and Vpr can independently degrade IRF-3. The null mutation of these two genes reduced the capacity of the HIV-1 virus to down modulate IRF-3 levels. The degradation was associated with Vif- and Vpr-mediated ubiquitination of IRF-3 and was independent of the activation of IRF-3. N-terminal lysine residues were shown to play a critical role in the Vif- and Vpr-mediated degradation of IRF-3. These data implicate Vif and Vpr in the disruption of the initial antiviral response and point to the need of HIV-1 to circumvent the antiviral response during the very early phase of replication

  10. Potential of small-molecule fungal metabolites in antiviral chemotherapy.

    Science.gov (United States)

    Roy, Biswajit G

    2017-08-01

    Various viral diseases, such as acquired immunodeficiency syndrome, influenza, and hepatitis, have emerged as leading causes of human death worldwide. Scientific endeavor since invention of DNA-dependent RNA polymerase of pox virus in 1967 resulted in better understanding of virus replication and development of various novel therapeutic strategies. Despite considerable advancement in every facet of drug discovery process, development of commercially viable, safe, and effective drugs for these viruses still remains a big challenge. Decades of intense research yielded a handful of natural and synthetic therapeutic options. But emergence of new viruses and drug-resistant viral strains had made new drug development process a never-ending battle. Small-molecule fungal metabolites due to their vast diversity, stereochemical complexity, and preapproved biocompatibility always remain an attractive source for new drug discovery. Though, exploration of therapeutic importance of fungal metabolites has started early with discovery of penicillin, recent prediction asserted that only a small percentage (5-10%) of fungal species have been identified and much less have been scientifically investigated. Therefore, exploration of new fungal metabolites, their bioassay, and subsequent mechanistic study bears huge importance in new drug discovery endeavors. Though no fungal metabolites so far approved for antiviral treatment, many of these exhibited high potential against various viral diseases. This review comprehensively discussed about antiviral activities of fungal metabolites of diverse origin against some important viral diseases. This also highlighted the mechanistic details of inhibition of viral replication along with structure-activity relationship of some common and important classes of fungal metabolites.

  11. Antiviral potential of a diterpenoid compound sugiol from Metasequoia glyptostroboides.

    Science.gov (United States)

    Bajpai, Vivek K; Kim, Na-Hyung; Kim, Kangmin; Kang, Sun Chul

    2016-05-01

    This research reports first time antiviral activity of sugiol, a diterpenoid isolated from Metasequoia glyptostroboides in terms of its ability to inhibit in vitro growth of H1N1 influenza virus. Antiviral potential of sugiol was evaluated through hcytopathogenic reduction assay using Madin-Darby canine kidney (MDCK) cell line. Sugiol (500 μg/ml) was found to exhibit considerable anti-cytopathic effect on MDCK cell line confirming its antiviral efficacy against H1N1 influenza virus. These findings strongly reinforce the suggestion that sugiol could be a candidate of choice in combinational regimen with potential antiviral efficacy.

  12. Early direct and indirect impact of quadrivalent HPV (4HPV) vaccine on genital warts: a systematic review.

    Science.gov (United States)

    Mariani, Luciano; Vici, Patrizia; Suligoi, Barbara; Checcucci-Lisi, Giovanni; Drury, Rosybel

    2015-01-01

    Since 2007, many countries have implemented national human papillomavirus (HPV) vaccination programs with the quadrivalent HPV (4HPV) vaccine that has been shown to be efficacious in clinical trials involving 25,000 subjects. Two vaccine serotypes, HPV16 and 18, are responsible for cervical cancer and other HPV-related cancers, but the impact of the 4HPV vaccine on these cancers cannot be seen immediately as there is a considerable lag between infection with HPV and cancer development. The other two serotypes, HPV6 and 11, are responsible for genital warts (GWs), which develop within a few months after infection, making GWs an early clinical endpoint for the assessment of the impact of 4HPV vaccination. We performed a systematic literature search in PubMed to identify all published studies on 4HPV vaccination, including those that assessed the impact of 4HPV vaccination programs on the incidence of GWs at a population level around the world. A total of 354 records were identified in the PubMed search. After screening and obtaining full papers for 56 publications, 16 publications presenting data on the impact or effectiveness of 4HPV vaccination on GWs were identified. These reported data on the impact or effectiveness of 4HPV in six countries [Australia (n = 6), New Zealand (n = 2), United States (n = 3), Denmark (n = 2), Germany (n = 1), and Sweden (n = 2)]. In Australia, no GWs were diagnosed in women aged <21 years who reported being vaccinated. A 92.6% reduction in GWs incidence was reported for all women in this age group, where the vaccine uptake rate (VUR) was 70% for 3 doses. The highest reductions were reported in countries with high VURs, mostly through school-based vaccination programs, although high VURs were obtained with some non-school-based programs. The results are coherent with the GWs incidence reduction reported in clinical trials and are an early indicator of what can be expected for the long-term clinical impact on vaccine-type HPV

  13. The antiviral effect of jiadifenoic acids C against coxsackievirus B3

    Directory of Open Access Journals (Sweden)

    Miao Ge

    2014-08-01

    Full Text Available Coxsackievirus B type 3 (CVB3 is one of the major causative pathogens associated with viral meningitis and myocarditis, which are widespread in the human population and especially prevalent in neonates and children. These infections can result in dilated cardiomyopathy (DCM and other severe clinical complications. There are no vaccines or drugs approved for the prevention or therapy of CVB3-induced diseases. During screening for anti-CVB3 candidates in our previous studies, we found that jiadifenoic acids C exhibited strong antiviral activities against CVB3 as well as other strains of Coxsackie B viruses (CVBs. The present studies were carried out to evaluate the antiviral activities of jiadifenoic acids C. Results showed that jiadifenoic acids C could reduce CVB3 RNA and proteins synthesis in a dose-dependent manner. Jiadifenoic acids C also had a similar antiviral effect on the pleconaril-resistant variant of CVB3. We further examined the impact of jiadifenoic acids C on the synthesis of viral structural and non-structural proteins, finding that jiadifenoic acids C could reduce VP1 and 3D protein production. A time-course study with Vero cells showed that jiadifenoic acids C displayed significant antiviral activities at 0–6 h after CVB3 inoculation, indicating that jiadifenoic acids C functioned at an early step of CVB3 replication. However, jiadifenoic acids C had no prophylactic effect against CVB3. Taken together, we show that jiadifenoic acids C exhibit strong antiviral activities against all strains of CVB, including the pleconaril-resistant variant. Our study could provide a significant lead for anti-CVB3 drug development.

  14. Does Early Versus Delayed Active Range of Motion Affect Rotator Cuff Healing After Surgical Repair? A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Kluczynski, Melissa A; Isenburg, Maureen M; Marzo, John M; Bisson, Leslie J

    2016-03-01

    The timing of passive range of motion (ROM) after surgical repair of the rotator cuff (RC) has been shown to affect healing. However, it is unknown if early or delayed active ROM affects healing. To determine whether early versus delayed active ROM affects structural results of RC repair surgery. Systematic review and meta-analysis. A systematic review of articles published between January 2004 and April 2014 was conducted. Structural results were compared for early (repair method. A total of 37 studies (2251 repairs) were included in the analysis, with 10 (649 repairs) in the early group and 27 (1602 repairs) in the delayed group. For tears ≤3 cm, the risk of a structural tendon defect was higher in the early versus delayed group for transosseous plus single-row suture anchor repairs (39.7% vs 24.3%; RR, 1.63 [95% CI, 1.28-2.08]). For tears >3 cm, the risk of a structural tendon defect was higher in the early versus delayed group for suture bridge repairs (48% vs 17.5%; RR, 2.74 [95% CI, 1.59-4.73]) and all repair methods combined (40.5% vs 26.7%; RR, 1.52 [95% CI, 1.17-1.97]). For tears >5 cm, the risk of structural tendon defect was higher in the early versus delayed group for suture bridge repairs (100% vs 16.7%; RR, 6.00 [95% CI, 1.69-21.26]). There were no statistically significant associations for tears measuring ≤1, 1-3, or 3-5 cm. Early active ROM was associated with increased risk of a structural defect for small and large RC tears, and thus might not be advisable after RC repair. © 2015 The Author(s).

  15. Atividade antiviral de Musa acuminata Colla, Musaceae

    Directory of Open Access Journals (Sweden)

    Fernanda Otaviano Martins

    Full Text Available O presente trabalho avalia a atividade antiviral de extratos e frações de Musa acuminata Colla, Musaceae, coletada em duas regiões do Estado do Rio de Janeiro (Petrópolis e Santo Antônio de Pádua. As inflorescências de M. acuminata apresentaram excelente atividade para os dois vírus avaliados: herpesvírus simples humano tipo 1 e herpesvírus simples humano tipo 2, ambos resistentes ao Aciclovir. Os resultados indicam que os extratos de M. acuminata testados podem constituir alvo potencial para uso em terapias antivirais.

  16. Tannins from Hamamelis virginiana bark extract: characterization and improvement of the antiviral efficacy against influenza A virus and human papillomavirus.

    Directory of Open Access Journals (Sweden)

    Linda L Theisen

    Full Text Available Antiviral activity has been demonstrated for different tannin-rich plant extracts. Since tannins of different classes and molecular weights are often found together in plant extracts and may differ in their antiviral activity, we have compared the effect against influenza A virus (IAV of Hamamelis virginiana L. bark extract, fractions enriched in tannins of different molecular weights and individual tannins of defined structures, including pseudotannins. We demonstrate antiviral activity of the bark extract against different IAV strains, including the recently emerged H7N9, and show for the first time that a tannin-rich extract inhibits human papillomavirus (HPV type 16 infection. As the best performing antiviral candidate, we identified a highly potent fraction against both IAV and HPV, enriched in high molecular weight condensed tannins by ultrafiltration, a simple, reproducible and easily upscalable method. This ultrafiltration concentrate and the bark extract inhibited early and, to a minor extent, later steps in the IAV life cycle and tannin-dependently inhibited HPV attachment. We observed interesting mechanistic differences between tannin structures: High molecular weight tannin containing extracts and tannic acid (1702 g/mol inhibited both IAV receptor binding and neuraminidase activity. In contrast, low molecular weight compounds (<500 g/mol such as gallic acid, epigallocatechin gallate or hamamelitannin inhibited neuraminidase but not hemagglutination. Average molecular weight of the compounds seemed to positively correlate with receptor binding (but not neuraminidase inhibition. In general, neuraminidase inhibition seemed to contribute little to the antiviral activity. Importantly, antiviral use of the ultrafiltration fraction enriched in high molecular weight condensed tannins and, to a lesser extent, the unfractionated bark extract was preferable over individual isolated compounds. These results are of interest for developing and

  17. [The advantages of early midtrimester targeted fetal systematic organ screening for the detection of fetal anomalies--will a global change start in Israel?].

    Science.gov (United States)

    Bronshtein, Moshe; Solt, Ido; Blumenfeld, Zeev

    2014-06-01

    Despite more than three decades of universal popularity of fetal sonography as an integral part of pregnancy evaluation, there is still no unequivocal agreement regarding the optimal dating of fetal sonographic screening and the type of ultrasound (transvaginal vs abdominal). TransvaginaL systematic sonography at 14-17 weeks for fetal organ screening. The evaluation of over 72.000 early (14-17 weeks) and late (18-24 weeks) fetal ultrasonographic systematic organ screenings revealed that 96% of the malformations are detectable in the early screening with an incidence of 1:50 gestations. Only 4% of the fetal anomalies are diagnosed later in pregnancy. Over 99% of the fetal cardiac anomalies are detectable in the early screening and most of them appear in low risk gestations. Therefore, we suggest a new platform of fetal sonographic evaluation and follow-up: The extensive systematic fetal organ screening should be performed by an expert sonographer who has been trained in the detection of fetal malformations, at 14-17 weeks gestation. This examination should also include fetal cardiac echography Three additional ultrasound examinations are suggested during pregnancy: the first, performed by the patient's obstetrician at 6-7 weeks for the exclusion of ectopic pregnancy, confirmation of fetal viability, dating, assessment of chorionicity in multiple gestations, and visualization of maternal adnexae. The other two, at 22-26 and 32-34 weeks, require less training and should be performed by an obstetrician who has been qualified in the sonographic detection of fetal anomalies. The advantages of early midtrimester targeted fetal systematic organ screening for the detection of fetal anomalies may dictate a global change.

  18. Exploiting Genetic Interference for Antiviral Therapy.

    Directory of Open Access Journals (Sweden)

    Elizabeth J Tanner

    2016-05-01

    Full Text Available Rapidly evolving viruses are a major threat to human health. Such viruses are often highly pathogenic (e.g., influenza virus, HIV, Ebola virus and routinely circumvent therapeutic intervention through mutational escape. Error-prone genome replication generates heterogeneous viral populations that rapidly adapt to new selection pressures, leading to resistance that emerges with treatment. However, population heterogeneity bears a cost: when multiple viral variants replicate within a cell, they can potentially interfere with each other, lowering viral fitness. This genetic interference can be exploited for antiviral strategies, either by taking advantage of a virus's inherent genetic diversity or through generating de novo interference by engineering a competing genome. Here, we discuss two such antiviral strategies, dominant drug targeting and therapeutic interfering particles. Both strategies harness the power of genetic interference to surmount two particularly vexing obstacles-the evolution of drug resistance and targeting therapy to high-risk populations-both of which impede treatment in resource-poor settings.

  19. Neurological outcomes in symptomatic congenital cytomegalovirus-infected infants after introduction of newborn urine screening and antiviral treatment.

    Science.gov (United States)

    Nishida, Kosuke; Morioka, Ichiro; Nakamachi, Yuji; Kobayashi, Yoko; Imanishi, Takamitsu; Kawano, Seiji; Iwatani, Sota; Koda, Tsubasa; Deguchi, Masashi; Tanimura, Kenji; Yamashita, Daisuke; Nibu, Ken-Ichi; Funakoshi, Toru; Ohashi, Masanobu; Inoue, Naoki; Iijima, Kazumoto; Yamada, Hideto

    2016-02-01

    Newborn screening for urinary cytomegalovirus (CMV) and early introduction of antiviral treatment are expected to improve neurological outcomes in symptomatic congenital CMV-infected infants. This cohort study prospectively evaluated neurological outcomes in symptomatic congenital CMV-infected infants following the introduction of hospital-based newborn urinary CMV screening and antiviral treatment. Following institutional review board approval and written informed consent from their parents, newborns were prospectively screened from 2009 to 2014 for urinary CMV-DNA by PCR within 1 week after birth at Kobe University Hospital and affiliated hospitals. CMV-positive newborns were further examined at Kobe University Hospital, and those diagnosed as symptomatic were treated with valganciclovir for 6 weeks plus immunoglobulin. Clinical neurological outcomes were evaluated at age ⩾12 months and categorized by the presence and severity of neurologic sequelae. Urine samples of 6348 newborns were screened, with 32 (0.50%) positive for CMV. Of these, 16 were diagnosed with symptomatic infection and 12 received antiviral treatment. Four infants developed severe impairment (33%), three developed mild impairment (25%), and five developed normally (42%). This is the first Japanese report of neurological assessments in infants with symptomatic congenital CMV infection who received early diagnosis and antiviral treatment. Urinary screening, resulting in early diagnosis and treatment, may yield better neurological outcomes in symptomatic congenital CMV-infected infants. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  20. CEACAM1 induces B-cell survival and is essential for protective antiviral antibody production

    Science.gov (United States)

    Khairnar, Vishal; Duhan, Vikas; Maney, Sathish Kumar; Honke, Nadine; Shaabani, Namir; Pandyra, Aleksandra A.; Seifert, Marc; Pozdeev, Vitaly; Xu, Haifeng C.; Sharma, Piyush; Baldin, Fabian; Marquardsen, Florian; Merches, Katja; Lang, Elisabeth; Kirschning, Carsten; Westendorf, Astrid M.; Häussinger, Dieter; Lang, Florian; Dittmer, Ulf; Küppers, Ralf; Recher, Mike; Hardt, Cornelia; Scheffrahn, Inka; Beauchemin, Nicole; Göthert, Joachim R.; Singer, Bernhard B.; Lang, Philipp A.; Lang, Karl S.

    2015-01-01

    B cells are essential for antiviral immune defence because they produce neutralizing antibodies, present antigen and maintain the lymphoid architecture. Here we show that intrinsic signalling of CEACAM1 is essential for generating efficient B-cell responses. Although CEACAM1 exerts limited influence on the proliferation of B cells, expression of CEACAM1 induces survival of proliferating B cells via the BTK/Syk/NF-κB-axis. The absence of this signalling cascade in naive Ceacam1−/− mice limits the survival of B cells. During systemic infection with cytopathic vesicular stomatitis virus, Ceacam1−/− mice can barely induce neutralizing antibody responses and die early after infection. We find, therefore, that CEACAM1 is a crucial regulator of B-cell survival, influencing B-cell numbers and protective antiviral antibody responses. PMID:25692415

  1. Effectiveness of systematic chromoendoscopy for diagnosis of early cancer and gastric premalignant lesions. Results of two consecutive screening campaigns in Colombia

    International Nuclear Information System (INIS)

    Emura, Fabian; Mejia, Juan; Mejia, Marcela; Osorio, Camilo

    2010-01-01

    Gastric cancer is the most common malignancy in South America and East Asia. In addition to the high mortality, in Colombia a great disvantage is the lack of data regarding premalignant lesions and early cancer. Aim: To evaluate the usefulness of systematic chromoendoscopy in the prevalence of early cancer and gastric premalignant lesions. A total of 950 were invited to participate, 800 fulfilled the inclusion criteria and finally 650 were analyzed. Results: None of participants had normal gastric mucosa. Mild antrum gastritis was found in 21.8% (142/650), meanwhile moderate or severe antrum gastritis in 77.4% (508/650). Atrophy and metaplasia was found in 14.5% (94/650) and 15.5% (101/650) respectively. H Pilory infection was found in 7.3%, 79.3% 75.5% 57.4% y 0% of subjects with mild, moderate and severe, atrophy, metaplasia and dysplasia respectively. Gastric premalignant lesion was found in 30% (195/650). Two subjects were diagnosed as early gastric cancer and treated by endoscopic submucosal dissection (ESD) with curability as final result. Conclusions: By systematic chromoendoscopy this series has demonstrated that 1/325 healthy volunteers had early gastric cancer and that 1/33 had a premalignant lesion explaining in part the high prevalence of gastric cancer in the region. Bases on this series, gastric cancer is diagnosable and curable among healthy volunteers in Colombia.

  2. Plants as sources of antiviral agents | Abonyi | African Journal of ...

    African Journals Online (AJOL)

    Antivirals are substances other than a virus or virus containing vaccine or specific antibody which can produce either a protective or therapeutic effect to the clear detectable advantage of the virus infected host. The search for antiviral agents began in earnest in the 1950s but this was directed mainly by chance, with little or ...

  3. Self-interest versus group-interest in antiviral control

    NARCIS (Netherlands)

    Boven, M. van; Klinkenberg, D.; Pen, I.; Weissing, F.J.; Heesterbeek, J.A.P.

    2008-01-01

    Antiviral agents have been hailed to hold considerable promise for the treatment and prevention of emerging viral diseases like H5N1 avian influenza and SARS. However, antiviral drugs are not completely harmless, and the conditions under which individuals are willing to participate in a

  4. 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 ...

  5. Antiviral activity and mechanism of action of arbidol against Hantaan ...

    African Journals Online (AJOL)

    Keywords: Hantavirus, Arbidol, Toll-like receptors, inducible nitric oxide synthase, Antiviral activity, ... hantavirus infection. Arbidol is a broad-spectrum antiviral compound that has been shown to have inhibitory effect on influenza virus [4,5], respiratory syncytial virus [6], ..... species in hantavirus cardiopulmonary syndrome.

  6. Is early detection of abused children possible?: a systematic review of the diagnostic accuracy of the identification of abused children

    Science.gov (United States)

    2013-01-01

    Background Early detection of abused children could help decrease mortality and morbidity related to this major public health problem. Several authors have proposed tools to screen for child maltreatment. The aim of this systematic review was to examine the evidence on accuracy of tools proposed to identify abused children before their death and assess if any were adapted to screening. Methods We searched in PUBMED, PsycINFO, SCOPUS, FRANCIS and PASCAL for studies estimating diagnostic accuracy of tools identifying neglect, or physical, psychological or sexual abuse of children, published in English or French from 1961 to April 2012. We extracted selected information about study design, patient populations, assessment methods, and the accuracy parameters. Study quality was assessed using QUADAS criteria. Results A total of 2 280 articles were identified. Thirteen studies were selected, of which seven dealt with physical abuse, four with sexual abuse, one with emotional abuse, and one with any abuse and physical neglect. Study quality was low, even when not considering the lack of gold standard for detection of abused children. In 11 studies, instruments identified abused children only when they had clinical symptoms. Sensitivity of tests varied between 0.26 (95% confidence interval [0.17-0.36]) and 0.97 [0.84-1], and specificity between 0.51 [0.39-0.63] and 1 [0.95-1]. The sensitivity was greater than 90% only for three tests: the absence of scalp swelling to identify children victims of inflicted head injury; a decision tool to identify physically-abused children among those hospitalized in a Pediatric Intensive Care Unit; and a parental interview integrating twelve child symptoms to identify sexually-abused children. When the sensitivity was high, the specificity was always smaller than 90%. Conclusions In 2012, there is low-quality evidence on the accuracy of instruments for identifying abused children. Identified tools were not adapted to screening because of

  7. Effect and safety of early weight-bearing on the outcome after open-wedge high tibial osteotomy: a systematic review and meta-analysis.

    Science.gov (United States)

    Lee, O-Sung; Ahn, Soyeon; Lee, Yong Seuk

    2017-07-01

    The purpose of this systematic review and meta-analysis was to evaluate the effectiveness and safety of early weight-bearing by comparing clinical and radiological outcomes between early and traditional delayed weight-bearing after OWHTO. A rigorous and systematic approach was used. The methodological quality was also assessed. Results that are possible to be compared in two or more than two articles were presented as forest plots. A 95% confidence interval was calculated for each effect size, and we calculated the I 2 statistic, which presents the percentage of total variation attributable to the heterogeneity among studies. The random-effects model was used to calculate the effect size. Six articles were included in the final analysis. All case groups were composed of early full weight-bearing within 2 weeks. All control groups were composed of late full weight-bearing between 6 weeks and 2 months. Pooled analysis was possible for the improvement in Lysholm score, but there was no statistically significant difference shown between groups. Other clinical results were also similar between groups. Four studies reported mechanical femorotibial angle (mFTA) and this result showed no statistically significant difference between groups in the pooled analysis. Furthermore, early weight-bearing showed more favorable results in some radiologic results (osseointegration and patellar height) and complications (thrombophlebitis and recurrence). Our analysis supports that early full weight-bearing after OWHTO using a locking plate leads to improvement in outcomes and was comparable to the delayed weight-bearing in terms of clinical and radiological outcomes. On the contrary, early weight-bearing was more favorable with respect to some radiologic parameters and complications compared with delayed weight-bearing.

  8. Grass Carp Laboratory of Genetics and Physiology 2 Serves As a Negative Regulator in Retinoic Acid-Inducible Gene I- and Melanoma Differentiation-Associated Gene 5-Mediated Antiviral Signaling in Resting State and Early Stage of Grass Carp Reovirus Infection

    OpenAIRE

    Rao, Youliang; Wan, Quanyuan; Yang, Chunrong; Su, Jianguo

    2017-01-01

    Laboratory of genetics and physiology 2 (LGP2) is a key component of RIG-I-like receptors (RLRs). However, the lack of the caspase recruitment domains (CARDs) results in its controversial functional performance as a negative or positive regulator in antiviral responses. Especially, no sufficient evidence uncovers the functional mechanisms of LGP2 in RLR signaling pathways in teleost. Here, negative regulation mechanism of LGP2 in certain situations in retinoic acid-inducible gene I (RIG-I) an...

  9. RNAi: antiviral therapy against dengue virus.

    Science.gov (United States)

    Idrees, Sobia; Ashfaq, Usman A

    2013-03-01

    Dengue virus infection has become a global threat affecting around 100 countries in the world. Currently, there is no licensed antiviral agent available against dengue. Thus, there is a strong need to develop therapeutic strategies that can tackle this life threatening disease. RNA interference is an important and effective gene silencing process which degrades targeted RNA by a sequence specific process. Several studies have been conducted during the last decade to evaluate the efficiency of siRNA in inhibiting dengue virus replication. This review summarizes siRNAs as a therapeutic approach against dengue virus serotypes and concludes that siRNAs against virus and host genes can be next generation treatment of dengue virus infection.

  10. Innate and intrinsic antiviral immunity in skin.

    Science.gov (United States)

    Kawamura, Tatsuyoshi; Ogawa, Youichi; Aoki, Rui; Shimada, Shinji

    2014-09-01

    As the body's most exposed interface with the environment, the skin is constantly challenged by potentially pathogenic microbes, including viruses. To sense the invading viruses, various types of cells resident in the skin express many different pattern-recognition receptors (PRRs) such as C-type lectin receptors (CLRs), Toll-like receptors (TLRs), nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) and cytosolic DNA sensors, that can detect the pathogen-associated molecular patterns (PAMPs) of the viruses. The detection of viral PAMPs initiates two major innate immune signaling cascades: the first involves the activation of the downstream transcription factors, such as interferon regulatory factors (IRFs), nuclear factor kappa B (NF-κB) and activator protein 1 (AP-1), which cooperate to induce the transcription of type I interferons and pro-inflammatory cytokines. The second signaling pathway involves the caspase-1-mediated processing of IL-1β and IL-18 through the formation of an inflammasome complex. Cutaneous innate immunity including the production of the innate cytokines constitutes the first line of host defence that limits the virus dissemination from the skin, and also plays an important role in the activation of adaptive immune response, which represents the second line of defence. More recently, the third immunity "intrinsic immunity" has emerged, that provides an immediate and direct antiviral defense mediated by host intrinsic restriction factors. This review focuses on the recent advances regarding the antiviral immune systems, highlighting the innate and intrinsic immunity against the viral infections in the skin, and describes how viral components are recognized by cutaneous immune systems. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  11. Amphipathic DNA polymers exhibit antiviral activity against systemic Murine Cytomegalovirus infection

    Directory of Open Access Journals (Sweden)

    Juteau Jean-Marc

    2009-12-01

    Full Text Available Abstract Background Phosphorothioated oligonucleotides (PS-ONs have a sequence-independent, broad spectrum antiviral activity as amphipathic polymers (APs and exhibit potent in vitro antiviral activity against a broad spectrum of herpesviruses: HSV-1, HSV-2, HCMV, VZV, EBV, and HHV-6A/B, and in vivo activity in a murine microbiocide model of genital HSV-2 infection. The activity of these agents against animal cytomegalovirus (CMV infections in vitro and in vivo was therefore investigated. Results In vitro, a 40 mer degenerate AP (REP 9 inhibited both murine CMV (MCMV and guinea pig CMV (GPCMV with an IC50 of 0.045 μM and 0.16 μM, respectively, and a 40 mer poly C AP (REP 9C inhibited MCMV with an IC50 of 0.05 μM. Addition of REP 9 to plaque assays during the first two hours of infection inhibited 78% of plaque formation whereas addition of REP 9 after 10 hours of infection did not significantly reduce the number of plaques, indicating that REP 9 antiviral activity against MCMV occurs at early times after infection. In a murine model of CMV infection, systemic treatment for 5 days significantly reduced virus replication in the spleens and livers of infected mice compared to saline-treated control mice. REP 9 and REP 9C were administered intraperitoneally for 5 consecutive days at 10 mg/kg, starting 2 days prior to MCMV infection. Splenomegaly was observed in infected mice treated with REP 9 but not in control mice or in REP 9 treated, uninfected mice, consistent with mild CpG-like activity. When REP 9C (which lacks CpG motifs was compared to REP 9, it exhibited comparable antiviral activity as REP 9 but was not associated with splenomegaly. This suggests that the direct antiviral activity of APs is the predominant therapeutic mechanism in vivo. Moreover, REP 9C, which is acid stable, was effective when administered orally in combination with known permeation enhancers. Conclusion These studies indicate that APs exhibit potent, well tolerated

  12. Impact of Early Enteral Nutrition on Nutritional and Immunological Outcomes of Gastric Cancer Patients Undergoing Gastrostomy: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Nikniaz, Zeinab; Somi, Mohammad Hossein; Nagashi, Shahnaz; Nikniaz, Leila

    2017-07-01

    The present systematic review and meta-analysis study evaluated the impact of early enteral nutrition (EN) on postoperative nutritional and immunological outcomes of gastric cancer (GC) patients. The databases of PubMed, Embase, Springer, and Cochrane library were searched till September 2016 to identify studies which evaluated the effects of EN compared with parenteral nutrition (PN) on postoperative immunological and nutritional status and hospitalization time in GC patients. Mean difference (MD) or standard mean difference (SMD) was calculated and I-square statistic test was used for heterogeneity analysis. The present systematic review and meta-analysis have consisted of seven trials, containing 835 GC patients. According to the result of meta-analysis, compared with PN, EN significantly resulted in more increase in the level of albumin [MD = 2.07 (0.49, 3.64)], prealbumin [MD = 9.41 (049, 33.55)], weight [MD = 1.52 (0.32, 2.72)], CD3+ [SMD = 1.96 (1.50, 2.43)], CD4+ [SMD = 2.45 (1.97, 2.93)], natural killers [MD = 5.80 (3.75, 7.85)], and also a decrease in the hospitalization time [MD=-2.39 (-2.74, -2.03)]. The results demonstrated that early administration of EN is more effective in improving postsurgical nutrition status and immune index in GC patients. So, based on these results, postoperative early administration of EN is recommended for GC patients where possible.

  13. WITHDRAWN. Antiviral treatment for Bell's palsy (idiopathic facial paralysis).

    Science.gov (United States)

    Gagyor, Ildiko; Madhok, Vishnu B; Daly, Fergus; Somasundara, Dhruvashree; Sullivan, Michael; Gammie, Fiona; Sullivan, Frank

    2015-05-04

    Corticosteroids are widely used in the treatment of idiopathic facial paralysis (Bell's palsy), but the effectiveness of additional treatment with an antiviral agent is uncertain. Significant morbidity can be associated with severe cases of Bell's palsy. To assess the effects of antiviral treatments alone or in combination with any other therapy for Bell's palsy. On 7 October 2014 we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE, EMBASE, LILACS, DARE, NHS EED, and HTA. We also reviewed the bibliographies of the identified trials and contacted trial authors and known experts in the field and relevant drug companies to identify additional published or unpublished data. We searched clinical trials registries for ongoing studies. We considered randomised controlled trials or quasi-randomised controlled trials of antivirals with and without corticosteroids versus control therapies for the treatment of Bell's palsy. We excluded trials that had a high risk of bias in several domains. Pairs of authors independently assessed trials for relevance, eligibility, and risk of bias, using standard Cochrane procedures. Eleven trials, including 2883 participants, met the inclusion criteria and are included in the final analysis. We added four studies to the previous review for this update. Some of the trials were small, and a number were at high or unclear risk of bias. Other trials did not meet current best standards in allocation concealment and blinding. Incomplete recoveryWe found no significant benefit from adding antivirals to corticosteroids in comparison with corticosteroids alone for people with Bell's palsy (risk ratio (RR) 0.69, 95% confidence interval (CI) 0.47 to 1.02, n = 1715). For people with severe Bell's palsy (House-Brackmann scores of 5 and 6 or the equivalent in other scales), we found a reduction in the rate of incomplete recovery at month six when antivirals plus corticosteroids were used (RR 0.64, 95% CI 0.41 to 0

  14. In vitro antiviral activities of Caesalpinia pulcherrima and its related flavonoids.

    Science.gov (United States)

    Chiang, L C; Chiang, W; Liu, M C; Lin, C C

    2003-08-01

    The aim of this study was to search for new antiviral agents from Chinese herbal medicine. Pure flavonoids and aqueous extracts of Caesalpinia pulcherrima Swartz were used in experiments to test their influence on a series of viruses, namely herpesviruses (HSV-1, HSV-2) and adenoviruses (ADV-3, ADV-8, ADV-11). The EC50 was defined as the concentration required to achieve 50% protection against virus-induced cytopathic effects, and the selectivity index (SI) was determined as the ratio of CC50 (concentration of 50% cellular cytotoxicity) to EC50. Results showed that aqueous extracts of C. pulcherrima and its related quercetin possessed a broad-spectrum antiviral activity. Among them, the strongest activities against ADV-8 were fruit and seed (EC50 = 41.2 mg/l, SI = 83.2), stem and leaf (EC50 = 61.8 mg/l, SI = 52.1) and flower (EC50 = 177.9 mg/l, SI = 15.5), whereas quercetin possessed the strongest anti-ADV-3 activity (EC50 = 24.3 mg/l, SI = 20.4). In conclusion, some compounds of C. pulcherrima which possess antiviral activities may be derived from the flavonoid of quercetin. The mode of action of quercetin against HSV-1 and ADV-3 was found to be at the early stage of multiplication and with SI values greater than 20, suggesting the potential use of this compound for treatment of the infection caused by these two viruses.

  15. Antiprotozoan and Antiviral Activities of Non-Cytotoxic Truncated and Variant Analogues of Mussel Defensin

    Directory of Open Access Journals (Sweden)

    Philippe Roch

    2004-01-01

    Full Text Available We previously reported the crucial role displayed by loop 3 of defensin isolated from the Mediterranean mussel, Mytilus galloprovincialis, in antibacterial and antifungal activities. We now investigated antiprotozoan and antiviral activities of some previously reported fragments B, D, E, P and Q. Two fragments (D and P efficiently killed Trypanosoma brucei (ID50 4–12 μM and Leishmania major (ID50 12–45 μM in a time/dose-dependent manner. Killing of T. brucei started as early as 1 h after initiation of contact with fragment D and reached 55% mortality after 6 h. Killing was temperature dependent and a temperature of 4°C efficiently impaired the ability to kill T. brucei. Fragments bound to the entire external epithelium of T. brucei. Prevention of HIV-1 infestation was obtained only with fragments P and Q at 20 μM. Even if fragment P was active on both targets, the specificity of fragments D and Q suggest that antiprotozoan and antiviral activities are mediated by different mechanisms. Truncated sequences of mussel defensin, including amino acid replacement to maintain 3D structure and increased positive net charge, also possess antiprotozoan and antiviral capabilities. New alternative and/or complementary antibiotics can be derived from the vast reservoir of natural antimicrobial peptides (AMPs contained in marine invertebrates.

  16. Alisporivir Has Limited Antiviral Effects Against Ebola Virus Strains Makona and Mayinga.

    Science.gov (United States)

    Chiramel, Abhilash I; Banadyga, Logan; Dougherty, Jonathan D; Falzarano, Darryl; Martellaro, Cynthia; Brees, Dominique; Taylor, R Travis; Ebihara, Hideki; Best, Sonja M

    2016-10-15

    Antiviral therapeutics with existing clinical safety profiles would be highly desirable in an outbreak situation, such as the 2013-2016 emergence of Ebola virus (EBOV) in West Africa. Although, the World Health Organization declared the end of the outbreak early 2016, sporadic cases of EBOV infection have since been reported. Alisporivir is the most clinically advanced broad-spectrum antiviral that functions by targeting a host protein, cyclophilin A (CypA). A modest antiviral effect of alisporivir against contemporary (Makona) but not historical (Mayinga) EBOV strains was observed in tissue culture. However, this effect was not comparable to observations for an alisporivir-susceptible virus, the flavivirus tick-borne encephalitis virus. Thus, EBOV does not depend on (CypA) for replication, in contrast to many other viruses pathogenic to humans. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  17. AGO/RISC-mediated antiviral RNA silencing in a plant in vitro system.

    Science.gov (United States)

    Schuck, Jana; Gursinsky, Torsten; Pantaleo, Vitantonio; Burgyán, Jozsef; Behrens, Sven-Erik

    2013-05-01

    AGO/RISC-mediated antiviral RNA silencing, an important component of the plant's immune response against RNA virus infections, was recapitulated in vitro. Cytoplasmic extracts of tobacco protoplasts were applied that supported Tombusvirus RNA replication, as well as the formation of RNA-induced silencing complexes (RISC) that could be functionally reconstituted with various plant ARGONAUTE (AGO) proteins. For example, when RISC containing AGO1, 2, 3 or 5 were programmed with exogenous siRNAs that specifically targeted the viral RNA, endonucleolytic cleavages occurred and viral replication was inhibited. Antiviral RNA silencing was disabled by the viral silencing suppressor p19 when this was present early during RISC formation. Notably, with replicating viral RNA, only (+)RNA molecules were accessible to RISC, whereas (-)RNA replication intermediates were not. The vulnerability of viral RNAs to RISC activity also depended on the RNA structure of the target sequence. This was most evident when we characterized viral siRNAs (vsiRNAs) that were particularly effective in silencing with AGO1- or AGO2/RISC. These vsiRNAs targeted similar sites, suggesting that accessible parts of the viral (+)RNA may be collectively attacked by different AGO/RISC. The in vitro system was, hence, established as a valuable tool to define and characterize individual molecular determinants of antiviral RNA silencing.

  18. Hedging against antiviral resistance during the next influenza pandemic using small stockpiles of an alternative chemotherapy.

    Directory of Open Access Journals (Sweden)

    Joseph T Wu

    2009-05-01

    Full Text Available The effectiveness of single-drug antiviral interventions to reduce morbidity and mortality during the next influenza pandemic will be substantially weakened if transmissible strains emerge which are resistant to the stockpiled antiviral drugs. We developed a mathematical model to test the hypothesis that a small stockpile of a secondary antiviral drug could be used to mitigate the adverse consequences of the emergence of resistant strains.We used a multistrain stochastic transmission model of influenza to show that the spread of antiviral resistance can be significantly reduced by deploying a small stockpile (1% population coverage of a secondary drug during the early phase of local epidemics. We considered two strategies for the use of the secondary stockpile: early combination chemotherapy (ECC; individuals are treated with both drugs in combination while both are available; and sequential multidrug chemotherapy (SMC; individuals are treated only with the secondary drug until it is exhausted, then treated with the primary drug. We investigated all potentially important regions of unknown parameter space and found that both ECC and SMC reduced the cumulative attack rate (AR and the resistant attack rate (RAR unless the probability of emergence of resistance to the primary drug p(A was so low (less than 1 in 10,000 that resistance was unlikely to be a problem or so high (more than 1 in 20 that resistance emerged as soon as primary drug monotherapy began. For example, when the basic reproductive number was 1.8 and 40% of symptomatic individuals were treated with antivirals, AR and RAR were 67% and 38% under monotherapy if p(A = 0.01. If the probability of resistance emergence for the secondary drug was also 0.01, then SMC reduced AR and RAR to 57% and 2%. The effectiveness of ECC was similar if combination chemotherapy reduced the probabilities of resistance emergence by at least ten times. We extended our model using travel data between 105

  19. An antiviral protein from Bougainvillea spectabilis roots; purification and characterisation.

    Science.gov (United States)

    Balasaraswathi, R; Sadasivam, S; Ward, M; Walker, J M

    1998-04-01

    An antiviral protein active against mechanical transmission of tomato spotted wilt virus was identified in the root tissues of Bougainvillea spectabilis Willd. Bougainvillea Antiviral Protein I (BAP I) was purified to apparent homogeneity from the roots of Bougainvillea by ammonium sulphate precipitation, CM- and DEAE-Sepharose chromatography and reverse phase HPLC. BAP I is a highly basic protein (pI value > 8.6) with an Mr of 28,000. The N-terminal sequence of BAP I showed homology with other plant antiviral proteins. Preliminary tests suggest that purified BAP I is capable of interfering with in vitro protein synthesis.

  20. The (146,147)Sm-(142,143)Nd systematics of early terrestrial differentiation and the lost continents of the early Earth

    Science.gov (United States)

    Harper, Charles L., Jr.; Jacobsen, Stein B.

    1992-01-01

    The very early history of the Earth has been one of the great enduring puzzles in the history of geology. We report evidence which clearly can be described as a vestige of a beginning, because the evidence that we report cannot be interpreted in any other way except as a geochemical signal of processes active in the very early history of the Earth. The evidence itself is a very small anomaly in the abundance of SM-146. The primary aims of this study were to: (1) verify the existence of the 'lost continents' of the Hadean era; and (2) determine their mean age.

  1. How Well Prepared Are Pre-Service Teachers to Teach Early Reading? A Systematic Review of the Literature

    Science.gov (United States)

    Meeks, Linda; Stephenson, Jennifer; Kemp, Coral; Madelaine, Alison

    2016-01-01

    This review examined studies that had addressed opinions of pre-service teachers (PSTs) concerning their preparedness for teaching early reading skills to all students, the extent of their content knowledge, and their attitudes towards code-based and/or meaning-based approaches to early reading. From the limited amount of research available, it…

  2. Discovery of dapivirine, a nonnucleoside HIV-1 reverse transcriptase inhibitor, as a broad-spectrum antiviral against both influenza A and B viruses.

    Science.gov (United States)

    Hu, Yanmei; Zhang, Jiantao; Musharrafieh, Rami Ghassan; Ma, Chunlong; Hau, Raymond; Wang, Jun

    2017-09-01

    The emergence of multidrug-resistant influenza viruses poses a persistent threat to public health. The current prophylaxis and therapeutic interventions for influenza virus infection have limited efficacy due to the continuous antigenic drift and antigenic shift of influenza viruses. As part of our ongoing effort to develop the next generation of influenza antivirals with broad-spectrum antiviral activity and a high genetic barrier to drug resistance, in this study we report the discovery of dapivirine, an FDA-approved HIV nonnucleoside reverse transcriptase inhibitor, as a broad-spectrum antiviral against multiple strains of influenza A and B viruses with low micromolar efficacy. Mechanistic studies revealed that dapivirine inhibits the nuclear entry of viral ribonucleoproteins at the early stage of viral replication. As a result, viral RNA and protein synthesis were inhibited. Furthermore, dapivirine has a high in vitro genetic barrier to drug resistance, and its antiviral activity is synergistic with oseltamivir carboxylate. In summary, the in vitro antiviral results of dapivirine suggest it is a promising candidate for the development of the next generation of dual influenza and HIV antivirals. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Current antiviral drugs and their analysis in biological materials - Part II: Antivirals against hepatitis and HIV viruses.

    Science.gov (United States)

    Nováková, Lucie; Pavlík, Jakub; Chrenková, Lucia; Martinec, Ondřej; Červený, Lukáš

    2018-01-05

    This review is a Part II of the series aiming to provide comprehensive overview of currently used antiviral drugs and to show modern approaches to their analysis. While in the Part I antivirals against herpes viruses and antivirals against respiratory viruses were addressed, this part concerns antivirals against hepatitis viruses (B and C) and human immunodeficiency virus (HIV). Many novel antivirals against hepatitis C virus (HCV) and HIV have been introduced into the clinical practice over the last decade. The recent broadening portfolio of these groups of antivirals is reflected in increasing number of developed analytical methods required to meet the needs of clinical terrain. Part II summarizes the mechanisms of action of antivirals against hepatitis B virus (HBV), HCV, and HIV, their use in clinical practice, and analytical methods for individual classes. It also provides expert opinion on state of art in the field of bioanalysis of these drugs. Analytical methods reflect novelty of these chemical structures and use by far the most current approaches, such as simple and high-throughput sample preparation and fast separation, often by means of UHPLC-MS/MS. Proper method validation based on requirements of bioanalytical guidelines is an inherent part of the developed methods. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. SUMO-interacting motifs of human TRIM5α are important for antiviral activity.

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    Gloria Arriagada

    2011-04-01

    Full Text Available Human TRIM5α potently restricts particular strains of murine leukemia viruses (the so-called N-tropic strains but not others (the B- or NB-tropic strains during early stages of infection. We show that overexpression of SUMO-1 in human 293T cells, but not in mouse MDTF cells, profoundly blocks N-MLV infection. This block is dependent on the tropism of the incoming virus, as neither B-, NB-, nor the mutant R110E of N-MLV CA (a B-tropic switch are affected by SUMO-1 overexpression. The block occurred prior to reverse transcription and could be abrogated by large amounts of restricted virus. Knockdown of TRIM5α in 293T SUMO-1-overexpressing cells resulted in ablation of the SUMO-1 antiviral effects, and this loss of restriction could be restored by expression of a human TRIM5α shRNA-resistant plasmid. Amino acid sequence analysis of human TRIM5α revealed a consensus SUMO conjugation site at the N-terminus and three putative SUMO interacting motifs (SIMs in the B30.2 domain. Mutations of the TRIM5α consensus SUMO conjugation site did not affect the antiviral activity of TRIM5α in any of the cell types tested. Mutation of the SIM consensus sequences, however, abolished TRIM5α antiviral activity against N-MLV. Mutation of lysines at a potential site of SUMOylation in the CA region of the Gag gene reduced the SUMO-1 block and the TRIM5α restriction of N-MLV. Our data suggest a novel aspect of TRIM5α-mediated restriction, in which the presence of intact SIMs in TRIM5α, and also the SUMO conjugation of CA, are required for restriction. We propose that at least a portion of the antiviral activity of TRIM5α is mediated through the binding of its SIMs to SUMO-conjugated CA.

  5. Potential Antiviral Agents from Marine Fungi: An Overview

    Directory of Open Access Journals (Sweden)

    Soheil Zorofchian Moghadamtousi

    2015-07-01

    Full Text Available Biodiversity of the marine world is only partially subjected to detailed scientific scrutiny in comparison to terrestrial life. Life in the marine world depends heavily on marine fungi scavenging the oceans of lifeless plants and animals and entering them into the nutrient cycle by. Approximately 150 to 200 new compounds, including alkaloids, sesquiterpenes, polyketides, and aromatic compounds, are identified from marine fungi annually. In recent years, numerous investigations demonstrated the tremendous potential of marine fungi as a promising source to develop new antivirals against different important viruses, including herpes simplex viruses, the human immunodeficiency virus, and the influenza virus. Various genera of marine fungi such as Aspergillus, Penicillium, Cladosporium, and Fusarium were subjected to compound isolation and antiviral studies, which led to an illustration of the strong antiviral activity of a variety of marine fungi-derived compounds. The present review strives to summarize all available knowledge on active compounds isolated from marine fungi with antiviral activity.

  6. Antiviral evaluation of an Hsp90 inhibitor, gedunin, against dengue ...

    African Journals Online (AJOL)

    Further, in silico molecular docking data revealed strong interaction of gedunin with the ATP/ADP ... Keywords: Dengue virus replication, Hsp90, Gedunin, Antiviral, Molecular docking ..... Conformational dynamics of the molecular chaperone.

  7. Bell's Palsy: Treatment with Steroids and Antiviral Drugs

    Science.gov (United States)

    ... Drooping of a corner of the mouth • Difficulty smiling, frowning, or making other facial expressions • Twitching or ... no definite added improvement. If there is any benefit to adding an antiviral to steroid treatment, it ...

  8. Antiviral Resistance to Influenza Viruses: Clinical and Epidemiological Aspects

    NARCIS (Netherlands)

    van der Vries, E.

    2017-01-01

    There are three classes of antiviral drugs approved for the treatment of influenza: the M2 ion channel inhibitors (amantadine, rimantadine), neuraminidase (NA) inhibitors (laninamivir, oseltamivir, peramivir, zanamivir), and the protease inhibitor (favipiravir); some of the agents are only available

  9. Antiviral activities of streptomycetes against tobacco mosaic virus ...

    African Journals Online (AJOL)

    Mahera Shinwari

    2012-01-26

    Jan 26, 2012 ... Key words: Antiviral activity, tobacco mosaic virus, actinomycetes, Streptomyces, Datura metel ... have received less attention than those caused by fungal .... leaves were divided in to three partitions each containing triplicates.

  10. Development of Small-Molecule Antivirals for Ebola

    Czech Academy of Sciences Publication Activity Database

    Janeba, Zlatko

    2015-01-01

    Roč. 35, č. 6 (2015), s. 1175-1194 ISSN 0198-6325 Institutional support: RVO:61388963 Keywords : antiviral * filovirus * Ebola virus * Marburg virus * hemorrhagic fever Subject RIV: CC - Organic Chemistry Impact factor: 9.135, year: 2015

  11. Research progress in antiviral therapy for chronic hepatitis C

    Directory of Open Access Journals (Sweden)

    YU Guoying

    2015-04-01

    Full Text Available Antiviral therapy is the most important treatment for chronic hepatitis C. This paper reviews the progress in antiviral treatment over recent years, including the combination therapy with polyethylene glycol-Interferon (PEG-IFN and ribavirin (RBV, specific target therapy, and gene therapy. The paper believes that the anti-hepatitis C virus treatment needs more effective drug combination therapies, shorter courses, less side effect, higher drug resistance threshold, etc.

  12. Antiviral resistance and the control of pandemic influenza.

    Directory of Open Access Journals (Sweden)

    Marc Lipsitch

    2007-01-01

    Full Text Available The response to the next influenza pandemic will likely include extensive use of antiviral drugs (mainly oseltamivir, combined with other transmission-reducing measures. Animal and in vitro studies suggest that some strains of influenza may become resistant to oseltamivir while maintaining infectiousness (fitness. Use of antiviral agents on the scale anticipated for the control of pandemic influenza will create an unprecedented selective pressure for the emergence and spread of these strains. Nonetheless, antiviral resistance has received little attention when evaluating these plans.We designed and analyzed a deterministic compartmental model of the transmission of oseltamivir-sensitive and -resistant influenza infections during a pandemic. The model predicts that even if antiviral treatment or prophylaxis leads to the emergence of a transmissible resistant strain in as few as 1 in 50,000 treated persons and 1 in 500,000 prophylaxed persons, widespread use of antivirals may strongly promote the spread of resistant strains at the population level, leading to a prevalence of tens of percent by the end of a pandemic. On the other hand, even in circumstances in which a resistant strain spreads widely, the use of antivirals may significantly delay and/or reduce the total size of the pandemic. If resistant strains carry some fitness cost, then, despite widespread emergence of resistance, antivirals could slow pandemic spread by months or more, and buy time for vaccine development; this delay would be prolonged by nondrug control measures (e.g., social distancing that reduce transmission, or use of a stockpiled suboptimal vaccine. Surprisingly, the model suggests that such nondrug control measures would increase the proportion of the epidemic caused by resistant strains.The benefits of antiviral drug use to control an influenza pandemic may be reduced, although not completely offset, by drug resistance in the virus. Therefore, the risk of resistance

  13. Mushrooms as a source of substances with antiviral activity

    Directory of Open Access Journals (Sweden)

    Martyna Kandefer-Szerszeń

    2014-08-01

    Full Text Available Water extracts the fructifications of 56 species of fungi were examined as a source of antiviral substances with activity against VS and vaccinia viruses. Extracts from 16 fungal species exhibited the antiviral activity. Water extracts from Boletus edulis active against vaccinia virus and extract from Armillariella mellea active against VS virus are particularly worth nothing. Both of them in applied concentrations were not toxic in chick embryo fibroblasts tissue culture.

  14. Translational control in plant antiviral immunity

    Directory of Open Access Journals (Sweden)

    João Paulo B. Machado

    Full Text Available Abstract Due to the limited coding capacity of viral genomes, plant viruses depend extensively on the host cell machinery to support the viral life cycle and, thereby, interact with a large number of host proteins during infection. Within this context, as plant viruses do not harbor translation-required components, they have developed several strategies to subvert the host protein synthesis machinery to produce rapidly and efficiently the viral proteins. As a countermeasure against infection, plants have evolved defense mechanisms that impair viral infections. Among them, the host-mediated translational suppression has been characterized as an efficient mean to restrict infection. To specifically suppress translation of viral mRNAs, plants can deploy susceptible recessive resistance genes, which encode translation initiation factors from the eIF4E and eIF4G family and are required for viral mRNA translation and multiplication. Additionally, recent evidence has demonstrated that, alternatively to the cleavage of viral RNA targets, host cells can suppress viral protein translation to silence viral RNA. Finally, a novel strategy of plant antiviral defense based on suppression of host global translation, which is mediated by the transmembrane immune receptor NIK1 (nuclear shuttle protein (NSP-Interacting Kinase1, is discussed in this review.

  15. Antiviral Roles of Abscisic Acid in Plants

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    Mazen Alazem

    2017-10-01

    Full Text Available Abscisic acid (ABA is a key hormone involved in tuning responses to several abiotic stresses and also has remarkable impacts on plant defense against various pathogens. The roles of ABA in plant defense against bacteria and fungi are multifaceted, inducing or reducing defense responses depending on its time of action. However, ABA induces different resistance mechanisms to viruses regardless of the induction time. Recent studies have linked ABA to the antiviral silencing pathway, which interferes with virus accumulation, and the micro RNA (miRNA pathway through which ABA affects the maturation and stability of miRNAs. ABA also induces callose deposition at plasmodesmata, a mechanism that limits viral cell-to-cell movement. Bamboo mosaic virus (BaMV is a member of the potexvirus group and is one of the most studied viruses in terms of the effects of ABA on its accumulation and resistance. In this review, we summarize how ABA interferes with the accumulation and movement of BaMV and other viruses. We also highlight aspects of ABA that may have an effect on other types of resistance and that require further investigation.

  16. Probiotics as Antiviral Agents in Shrimp Aquaculture

    Directory of Open Access Journals (Sweden)

    Bestha Lakshmi

    2013-01-01

    Full Text Available Shrimp farming is an aquaculture business for the cultivation of marine shrimps or prawns for human consumption and is now considered as a major economic and food production sector as it is an increasingly important source of protein available for human consumption. Intensification of shrimp farming had led to the development of a number of diseases, which resulted in the excessive use of antimicrobial agents, which is finally responsible for many adverse effects. Currently, probiotics are chosen as the best alternatives to these antimicrobial agents and they act as natural immune enhancers, which provoke the disease resistance in shrimp farm. Viral diseases stand as the major constraint causing an enormous loss in the production in shrimp farms. Probiotics besides being beneficial bacteria also possess antiviral activity. Exploitation of these probiotics in treatment and prevention of viral diseases in shrimp aquaculture is a novel and efficient method. This review discusses the benefits of probiotics and their criteria for selection in shrimp aquaculture and their role in immune power enhancement towards viral diseases.

  17. Viral respiratory diseases: vaccines and antivirals.

    Science.gov (United States)

    Lennette, E H

    1981-01-01

    Acute respiratory diseases, most of which are generally attributed to viruses, account for about 6% of all deaths and for about 60% of the deaths associated with all respiratory disease. The huge cost attributable to viral respiratory infections as a result of absenteeism and the disruption of business and the burden of medical care makes control of these diseases an important objective. The viruses that infect the respiratory tract fall taxonomically into five viral families. Although immunoprophylaxis would appear to be the logical approach, the development of suitable vaccines has been confronted with numerous obstacles, including antigenic drift and shift in the influenzaviruses, the large number of antigenically distinct immunotypes among rhinoviruses, the occurrence after immunization of rare cases of a severe form of the disease following subsequent natural infection with respiratory syncytial virus, and the risk of oncogenicity of adenoviruses for man. Considerable expenditure on the development of new antiviral drugs has so far resulted in only three compounds that are at present officially approved and licensed for use in the USA. Efforts to improve the tools available for control should continue and imaginative and inventive approaches are called for. However, creativity and ingenuity must operate within the constraints imposed by economic, political, ethical, and legal considerations.

  18. Perspective of Use of Antiviral Peptides against Influenza Virus

    Directory of Open Access Journals (Sweden)

    Sylvie Skalickova

    2015-10-01

    Full Text Available The threat of a worldwide influenza pandemic has greatly increased over the past decade with the emergence of highly virulent avian influenza strains. The increased frequency of drug-resistant influenza strains against currently available antiviral drugs requires urgent development of new strategies for antiviral therapy, too. The research in the field of therapeutic peptides began to develop extensively in the second half of the 20th century. Since then, the mechanisms of action for several peptides and their antiviral prospect received large attention due to the global threat posed by viruses. Here, we discussed the therapeutic properties of peptides used in influenza treatment. Peptides with antiviral activity against influenza can be divided into three main groups. First, entry blocker peptides such as a Flupep that interact with influenza hemagglutinin, block its binding to host cells and prevent viral fusion. Second, several peptides display virucidal activity, disrupting viral envelopes, e.g., Melittin. Finally, a third set of peptides interacts with the viral polymerase complex and act as viral replication inhibitors such as PB1 derived peptides. Here, we present a review of the current literature describing the antiviral activity, mechanism and future therapeutic potential of these influenza antiviral peptides.

  19. The relationship between the Early Childhood Environment Rating Scale and its revised form and child outcomes: A systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Ashley Brunsek

    Full Text Available The Early Childhood Environment Rating Scale (ECERS and its revised version (ECERS-R were designed as global measures of quality that assess structural and process aspects of Early Childhood Education and Care (ECEC programs. Despite frequent use of the ECERS/ECERS-R in research and applied settings, associations between it and child outcomes have not been systematically reviewed. The objective of this research was to evaluate the association between the ECERS/ECERS-R and children's wellbeing. Searches of Medline, PsycINFO, ERIC, websites of large datasets and reference sections of all retrieved articles were completed up to July 3, 2015. Eligible studies provided a statistical link between the ECERS/ECERS-R and child outcomes for preschool-aged children in ECEC programs. Of the 823 studies selected for full review, 73 were included in the systematic review and 16 were meta-analyzed. The combined sample across all eligible studies consisted of 33, 318 preschool-aged children. Qualitative systematic review results revealed that ECERS/ECERS-R total scores were more generally associated with positive outcomes than subscales or factors. Seventeen separate meta-analyses were conducted to assess the strength of association between the ECERS/ECERS-R and measures that assessed children's language, math and social-emotional outcomes. Meta-analyses revealed a small number of weak effects (in the expected direction between the ECERS/ECERS-R total score and children's language and positive behavior outcomes. The Language-Reasoning subscale was weakly related to a language outcome. The enormous heterogeneity in how studies operationalized the ECERS/ECERS-R, the outcomes measured and statistics reported limited our ability to meta-analyze many studies. Greater consistency in study methodology is needed in this area of research. Despite these methodological challenges, the ECERS/ECERS-R does appear to capture aspects of quality that are important for children

  20. The relationship between the Early Childhood Environment Rating Scale and its revised form and child outcomes: A systematic review and meta-analysis.

    Science.gov (United States)

    Brunsek, Ashley; Perlman, Michal; Falenchuk, Olesya; McMullen, Evelyn; Fletcher, Brooke; Shah, Prakesh S

    2017-01-01

    The Early Childhood Environment Rating Scale (ECERS) and its revised version (ECERS-R) were designed as global measures of quality that assess structural and process aspects of Early Childhood Education and Care (ECEC) programs. Despite frequent use of the ECERS/ECERS-R in research and applied settings, associations between it and child outcomes have not been systematically reviewed. The objective of this research was to evaluate the association between the ECERS/ECERS-R and children's wellbeing. Searches of Medline, PsycINFO, ERIC, websites of large datasets and reference sections of all retrieved articles were completed up to July 3, 2015. Eligible studies provided a statistical link between the ECERS/ECERS-R and child outcomes for preschool-aged children in ECEC programs. Of the 823 studies selected for full review, 73 were included in the systematic review and 16 were meta-analyzed. The combined sample across all eligible studies consisted of 33, 318 preschool-aged children. Qualitative systematic review results revealed that ECERS/ECERS-R total scores were more generally associated with positive outcomes than subscales or factors. Seventeen separate meta-analyses were conducted to assess the strength of association between the ECERS/ECERS-R and measures that assessed children's language, math and social-emotional outcomes. Meta-analyses revealed a small number of weak effects (in the expected direction) between the ECERS/ECERS-R total score and children's language and positive behavior outcomes. The Language-Reasoning subscale was weakly related to a language outcome. The enormous heterogeneity in how studies operationalized the ECERS/ECERS-R, the outcomes measured and statistics reported limited our ability to meta-analyze many studies. Greater consistency in study methodology is needed in this area of research. Despite these methodological challenges, the ECERS/ECERS-R does appear to capture aspects of quality that are important for children's wellbeing

  1. An Interferon Regulated MicroRNA Provides Broad Cell-Intrinsic Antiviral Immunity through Multihit Host-Directed Targeting of the Sterol Pathway

    Science.gov (United States)

    Robertson, Kevin A.; Hsieh, Wei Yuan; Forster, Thorsten; Blanc, Mathieu; Lu, Hongjin; Crick, Peter J.; Yutuc, Eylan; Watterson, Steven; Martin, Kimberly; Griffiths, Samantha J.; Enright, Anton J.; Yamamoto, Mami; Pradeepa, Madapura M.; Lennox, Kimberly A.; Behlke, Mark A.; Talbot, Simon; Haas, Jürgen; Dölken, Lars; Griffiths, William J.; Wang, Yuqin; Angulo, Ana; Ghazal, Peter

    2016-01-01

    In invertebrates, small interfering RNAs are at the vanguard of cell-autonomous antiviral immunity. In contrast, antiviral mechanisms initiated by interferon (IFN) signaling predominate in mammals. Whilst mammalian IFN-induced miRNA are known to inhibit specific viruses, it is not known whether host-directed microRNAs, downstream of IFN-signaling, have a role in mediating broad antiviral resistance. By performing an integrative, systematic, global analysis of RNA turnover utilizing 4-thiouridine labeling of newly transcribed RNA and pri/pre-miRNA in IFN-activated macrophages, we identify a new post-transcriptional viral defense mechanism mediated by miR-342-5p. On the basis of ChIP and site-directed promoter mutagenesis experiments, we find the synthesis of miR-342-5p is coupled to the antiviral IFN response via the IFN-induced transcription factor, IRF1. Strikingly, we find miR-342-5p targets mevalonate-sterol biosynthesis using a multihit mechanism suppressing the pathway at different functional levels: transcriptionally via SREBF2, post-transcriptionally via miR-33, and enzymatically via IDI1 and SC4MOL. Mass spectrometry-based lipidomics and enzymatic assays demonstrate the targeting mechanisms reduce intermediate sterol pathway metabolites and total cholesterol in macrophages. These results reveal a previously unrecognized mechanism by which IFN regulates the sterol pathway. The sterol pathway is known to be an integral part of the macrophage IFN antiviral response, and we show that miR-342-5p exerts broad antiviral effects against multiple, unrelated pathogenic viruses such Cytomegalovirus and Influenza A (H1N1). Metabolic rescue experiments confirm the specificity of these effects and demonstrate that unrelated viruses have differential mevalonate and sterol pathway requirements for their replication. This study, therefore, advances the general concept of broad antiviral defense through multihit targeting of a single host pathway. PMID:26938778

  2. An Interferon Regulated MicroRNA Provides Broad Cell-Intrinsic Antiviral Immunity through Multihit Host-Directed Targeting of the Sterol Pathway.

    Directory of Open Access Journals (Sweden)

    Kevin A Robertson

    2016-03-01

    Full Text Available In invertebrates, small interfering RNAs are at the vanguard of cell-autonomous antiviral immunity. In contrast, antiviral mechanisms initiated by interferon (IFN signaling predominate in mammals. Whilst mammalian IFN-induced miRNA are known to inhibit specific viruses, it is not known whether host-directed microRNAs, downstream of IFN-signaling, have a role in mediating broad antiviral resistance. By performing an integrative, systematic, global analysis of RNA turnover utilizing 4-thiouridine labeling of newly transcribed RNA and pri/pre-miRNA in IFN-activated macrophages, we identify a new post-transcriptional viral defense mechanism mediated by miR-342-5p. On the basis of ChIP and site-directed promoter mutagenesis experiments, we find the synthesis of miR-342-5p is coupled to the antiviral IFN response via the IFN-induced transcription factor, IRF1. Strikingly, we find miR-342-5p targets mevalonate-sterol biosynthesis using a multihit mechanism suppressing the pathway at different functional levels: transcriptionally via SREBF2, post-transcriptionally via miR-33, and enzymatically via IDI1 and SC4MOL. Mass spectrometry-based lipidomics and enzymatic assays demonstrate the targeting mechanisms reduce intermediate sterol pathway metabolites and total cholesterol in macrophages. These results reveal a previously unrecognized mechanism by which IFN regulates the sterol pathway. The sterol pathway is known to be an integral part of the macrophage IFN antiviral response, and we show that miR-342-5p exerts broad antiviral effects against multiple, unrelated pathogenic viruses such Cytomegalovirus and Influenza A (H1N1. Metabolic rescue experiments confirm the specificity of these effects and demonstrate that unrelated viruses have differential mevalonate and sterol pathway requirements for their replication. This study, therefore, advances the general concept of broad antiviral defense through multihit targeting of a single host pathway.

  3. Antiviral Activity of Lambda Interferon in Chickens

    Science.gov (United States)

    Reuter, Antje; Soubies, Sebastien; Härtle, Sonja; Schusser, Benjamin; Kaspers, Bernd

    2014-01-01

    Interferons (IFNs) are essential components of the antiviral defense system of vertebrates. In mammals, functional receptors for type III IFN (lambda interferon [IFN-λ]) are found mainly on epithelial cells, and IFN-λ was demonstrated to play a crucial role in limiting viral infections of mucosal surfaces. To determine whether IFN-λ plays a similar role in birds, we produced recombinant chicken IFN-λ (chIFN-λ) and we used the replication-competent retroviral RCAS vector system to generate mosaic-transgenic chicken embryos that constitutively express chIFN-λ. We could demonstrate that chIFN-λ markedly inhibited replication of various virus strains, including highly pathogenic influenza A viruses, in ovo and in vivo, as well as in epithelium-rich tissue and cell culture systems. In contrast, chicken fibroblasts responded poorly to chIFN-λ. When applied in vivo to 3-week-old chickens, recombinant chIFN-λ strongly induced the IFN-responsive Mx gene in epithelium-rich organs, such as lungs, tracheas, and intestinal tracts. Correspondingly, these organs were found to express high transcript levels of the putative chIFN-λ receptor alpha chain (chIL28RA) gene. Transfection of chicken fibroblasts with a chIL28RA expression construct rendered these cells responsive to chIFN-λ treatment, indicating that receptor expression determines cell type specificity of IFN-λ action in chickens. Surprisingly, mosaic-transgenic chickens perished soon after hatching, demonstrating a detrimental effect of constitutive chIFN-λ expression. Our data highlight fundamental similarities between the IFN-λ systems of mammals and birds and suggest that type III IFN might play a role in defending mucosal surfaces against viral intruders in most if not all vertebrates. PMID:24371053

  4. The Role of Omega-3 Fatty Acids in Developmental Psychopathology: A Systematic Review on Early Psychosis, Autism, and ADHD

    Directory of Open Access Journals (Sweden)

    Carlo Agostoni

    2017-12-01

    Full Text Available In this systematic review, we will consider and debate studies that have explored the effects of ω-3 polyunsaturated fatty acids (PUFAs in three major, and somehow related, developmental psychiatric disorders: Autism, Attention Deficit and Hyperactivity disorder and Psychosis. The impact of ω-3 PUFAs on clinical symptoms and, if possible, brain trajectory in children and adolescents suffering from these illnesses will be reviewed and discussed, considering the biological plausibility of the effects of omega-3 fatty acids, together with their potential perspectives in the field. Heterogeneity in study designs will be discussed in the light of differences in results and interpretation of studies carried out so far.

  5. Antiviral treatment for Bell's palsy (idiopathic facial paralysis).

    Science.gov (United States)

    Gagyor, Ildiko; Madhok, Vishnu B; Daly, Fergus; Somasundara, Dhruvashree; Sullivan, Michael; Gammie, Fiona; Sullivan, Frank

    2015-11-09

    Corticosteroids are widely used in the treatment of idiopathic facial paralysis (Bell's palsy), but the effectiveness of additional treatment with an antiviral agent is uncertain. Significant morbidity can be associated with severe cases of Bell's palsy. This review was first published in 2001 and revised several times, most recently in 2009. This version replaces an update of the review in Issue 7 of the Cochrane Library subsequently withdrawn because of an ongoing investigation into the reliability of data from an included study. To assess the effects of antiviral treatments alone or in combination with any other therapy for Bell's palsy. On 7 October 2014 we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE, EMBASE, LILACS, DARE, NHS EED, and HTA. We also reviewed the bibliographies of the identified trials and contacted trial authors and known experts in the field and relevant drug companies to identify additional published or unpublished data. We searched clinical trials registries for ongoing studies. We considered randomised controlled trials or quasi-randomised controlled trials of antivirals with and without corticosteroids versus control therapies for the treatment of Bell's palsy. We excluded trials that had a high risk of bias in several domains. Pairs of authors independently assessed trials for relevance, eligibility, and risk of bias, using standard Cochrane procedures. Ten trials, including 2280 participants, met the inclusion criteria and are included in the final analysis. Some of the trials were small, and a number were at high or unclear risk of bias. Other trials did not meet current best standards in allocation concealment and blinding. Incomplete recoveryWe found a significant benefit from adding antivirals to corticosteroids in comparison with corticosteroids alone for people with Bell's palsy (risk ratio (RR) 0.61, 95% confidence interval (CI) 0.39 to 0.97, n = 1315). For people with severe Bell

  6. Barriers and facilitators to implementing family support and education in Early Psychosis Intervention programmes: A systematic review.

    Science.gov (United States)

    Selick, Avra; Durbin, Janet; Vu, Nhi; O'Connor, Karen; Volpe, Tiziana; Lin, Elizabeth

    2017-10-01

    Family support is a core component of the Early Psychosis Intervention (EPI) model, yet it continues to have relatively low rates of implementation in practice. This paper reports results of a literature review on facilitators and barriers to delivering family interventions in EPI programmes. A search was conducted of 4 electronic databases, Medline, EMBASE, PsycINFO and Joanna Briggs, from 2000 to 2015 using terms related to early onset psychosis, family work and implementation. Four thousand four hundred and two unique studies were identified, 7 of which met inclusion criteria. Barriers and facilitators were coded and aggregated to higher-level themes using a consensus approach. Five of 7 studies examined structured multifamily psychoeducation. Uptake by families was affected by: family/client interest and readiness to participate; ability to access supports; and support needs/preferences. Implementation by programmes was affected by staff access to training and resources to provide family support. A key finding across the identified studies was that families have different needs and preferences regarding the timing, length, intensity and content of the intervention. One size does not fit all and many families do not require the intensive psychoeducational programmes typically provided. The reviewed literature suggests that flexible, tiered approaches to care may better meet family needs and increase rates of uptake of family support. However, more research is needed on the effectiveness of different models of family support in early psychosis and how they can be successfully implemented. © 2017 John Wiley & Sons Australia, Ltd.

  7. Bioprospecting of Red Sea Sponges for Novel Antiviral Pharmacophores

    KAUST Repository

    O'Rourke, Aubrie

    2015-05-01

    Natural products offer many possibilities for the treatment of disease. More than 70% of the Earth’s surface is ocean, and recent exploration and access has allowed for new additions to this catalog of natural treasures. The Central Red Sea off the coast of Saudi Arabia serves as a newly accessible location, which provides the opportunity to bioprospect marine sponges with the purpose of identifying novel antiviral scaffolds. Antivirals are underrepresented in present day clinical trials, as well as in the academic screens of marine natural product libraries. Here a high-throughput pipeline was initiated by prefacing the antiviral screen with an Image-based High-Content Screening (HCS) technique in order to identify candidates with antiviral potential. Prospective candidates were tested in a biochemical or cell-based assay for the ability to inhibit the NS3 protease of the West Nile Virus (WNV NS protease) as well as replication and reverse transcription of the Human Immunodeficiency Virus 1 (HIV-1). The analytical chemistry techniques of High-Performance Liquid Chromatograpy (HPLC), Liquid Chromatography-Mass Spectrometry (LC-MS), and Nuclear Magnetic Resonance (NMR) where used in order to identify the compounds responsible for the characteristic antiviral activity of the selected sponge fractions. We have identified a 3-alkyl pyridinium from Amphimedon chloros as the causative agent of the observed WNV NS3 protease inhibition in vitro. Additionally, we identified debromohymenialdisine, hymenialdisine, and oroidin from Stylissa carteri as prospective scaffolds capable of HIV-1 inhibition.

  8. Antiviral Screening of Multiple Compounds against Ebola Virus.

    Science.gov (United States)

    Dowall, Stuart D; Bewley, Kevin; Watson, Robert J; Vasan, Seshadri S; Ghosh, Chandradhish; Konai, Mohini M; Gausdal, Gro; Lorens, James B; Long, Jason; Barclay, Wendy; Garcia-Dorival, Isabel; Hiscox, Julian; Bosworth, Andrew; Taylor, Irene; Easterbrook, Linda; Pitman, James; Summers, Sian; Chan-Pensley, Jenny; Funnell, Simon; Vipond, Julia; Charlton, Sue; Haldar, Jayanta; Hewson, Roger; Carroll, Miles W

    2016-10-27

    In light of the recent outbreak of Ebola virus (EBOV) disease in West Africa, there have been renewed efforts to search for effective antiviral countermeasures. A range of compounds currently available with broad antimicrobial activity have been tested for activity against EBOV. Using live EBOV, eighteen candidate compounds were screened for antiviral activity in vitro. The compounds were selected on a rational basis because their mechanisms of action suggested that they had the potential to disrupt EBOV entry, replication or exit from cells or because they had displayed some antiviral activity against EBOV in previous tests. Nine compounds caused no reduction in viral replication despite cells remaining healthy, so they were excluded from further analysis (zidovudine; didanosine; stavudine; abacavir sulphate; entecavir; JB1a; Aimspro; celgosivir; and castanospermine). A second screen of the remaining compounds and the feasibility of appropriateness for in vivo testing removed six further compounds (ouabain; omeprazole; esomeprazole; Gleevec; D-LANA-14; and Tasigna). The three most promising compounds (17-DMAG; BGB324; and NCK-8) were further screened for in vivo activity in the guinea pig model of EBOV disease. Two of the compounds, BGB324 and NCK-8, showed some effect against lethal infection in vivo at the concentrations tested, which warrants further investigation. Further, these data add to the body of knowledge on the antiviral activities of multiple compounds against EBOV and indicate that the scientific community should invest more effort into the development of novel and specific antiviral compounds to treat Ebola virus disease.

  9. Antiviral Screening of Multiple Compounds against Ebola Virus

    Directory of Open Access Journals (Sweden)

    Stuart D. Dowall

    2016-10-01

    Full Text Available In light of the recent outbreak of Ebola virus (EBOV disease in West Africa, there have been renewed efforts to search for effective antiviral countermeasures. A range of compounds currently available with broad antimicrobial activity have been tested for activity against EBOV. Using live EBOV, eighteen candidate compounds were screened for antiviral activity in vitro. The compounds were selected on a rational basis because their mechanisms of action suggested that they had the potential to disrupt EBOV entry, replication or exit from cells or because they had displayed some antiviral activity against EBOV in previous tests. Nine compounds caused no reduction in viral replication despite cells remaining healthy, so they were excluded from further analysis (zidovudine; didanosine; stavudine; abacavir sulphate; entecavir; JB1a; Aimspro; celgosivir; and castanospermine. A second screen of the remaining compounds and the feasibility of appropriateness for in vivo testing removed six further compounds (ouabain; omeprazole; esomeprazole; Gleevec; D-LANA-14; and Tasigna. The three most promising compounds (17-DMAG; BGB324; and NCK-8 were further screened for in vivo activity in the guinea pig model of EBOV disease. Two of the compounds, BGB324 and NCK-8, showed some effect against lethal infection in vivo at the concentrations tested, which warrants further investigation. Further, these data add to the body of knowledge on the antiviral activities of multiple compounds against EBOV and indicate that the scientific community should invest more effort into the development of novel and specific antiviral compounds to treat Ebola virus disease.

  10. Screening for Antiviral Activities of Isolated Compounds from Essential Oils

    Directory of Open Access Journals (Sweden)

    Akram Astani

    2011-01-01

    Full Text Available Essential oil of star anise as well as phenylpropanoids and sesquiterpenes, for example, trans-anethole, eugenol, β-eudesmol, farnesol, β-caryophyllene and β-caryophyllene oxide, which are present in many essential oils, were examined for their antiviral activity against herpes simplex virus type 1 (HSV-1 in vitro. Antiviral activity was analyzed by plaque reduction assays and mode of antiviral action was determined by addition of the drugs to uninfected cells, to the virus prior to infection or to herpesvirus-infected cells. Star anise oil reduced viral infectivity by >99%, phenylpropanoids inhibited HSV infectivity by about 60–80% and sesquiterpenes suppressed herpes virus infection by 40–98%. Both, star anise essential oil and all isolated compounds exhibited anti-HSV-1 activity by direct inactivation of free virus particles in viral suspension assays. All tested drugs interacted in a dose-dependent manner with herpesvirus particles, thereby inactivating viral infectivity. Star anise oil, rich in trans-anethole, revealed a high selectivity index of 160 against HSV, whereas among the isolated compounds only β-caryophyllene displayed a high selectivity index of 140. The presence of β-caryophyllene in many essential oils might contribute strongly to their antiviral ability. These results indicate that phenylpropanoids and sesquiterpenes present in essential oils contribute to their antiviral activity against HSV.

  11. Recent developments in antiviral agents against enterovirus 71 infection.

    Science.gov (United States)

    Tan, Chee Wah; Lai, Jeffrey Kam Fatt; Sam, I-Ching; Chan, Yoke Fun

    2014-02-12

    Enterovirus 71 (EV-71) is the main etiological agent of hand, foot and mouth disease (HFMD). Recent EV-71 outbreaks in Asia-Pacific were not limited to mild HFMD, but were associated with severe neurological complications such as aseptic meningitis and brainstem encephalitis, which may lead to cardiopulmonary failure and death. The absence of licensed therapeutics for clinical use has intensified research into anti-EV-71 development. This review highlights the potential antiviral agents targeting EV-71 attachment, entry, uncoating, translation, polyprotein processing, virus-induced formation of membranous RNA replication complexes, and RNA-dependent RNA polymerase. The strategies for antiviral development include target-based synthetic compounds, anti-rhinovirus and poliovirus libraries screening, and natural compound libraries screening. Growing knowledge of the EV-71 life cycle will lead to successful development of antivirals. The continued effort to develop antiviral agents for treatment is crucial in the absence of a vaccine. The coupling of antivirals with an effective vaccine will accelerate eradication of the disease.

  12. Rigid amphipathic fusion inhibitors demonstrate antiviral activity against African swine fever virus.

    Science.gov (United States)

    Hakobyan, Astghik; Galindo, Inmaculada; Nañez, Almudena; Arabyan, Erik; Karalyan, Zaven; Chistov, Alexey A; Streshnev, Philipp P; Korshun, Vladimir A; Alonso, Covadonga; Zakaryan, Hovakim

    2018-01-01

    Rigid amphipathic fusion inhibitors (RAFIs) are a family of nucleoside derivatives that inhibit the infectivity of several enveloped viruses by interacting with virion envelope lipids and inhibiting fusion between viral and cellular membranes. Here we tested the antiviral activity of two RAFIs, 5-(Perylen-3-ylethynyl)-arabino-uridine (aUY11) and 5-(Perylen-3-ylethynyl)uracil-1-acetic acid (cm1UY11) against African swine fever virus (ASFV), for which no effective vaccine is available. Both compounds displayed a potent, dose-dependent inhibitory effect on ASFV infection in Vero cells. The major antiviral effect was observed when aUY11 and cm1UY11 were added at early stages of infection and maintained during the complete viral cycle. Furthermore, virucidal assay revealed a significant extracellular anti-ASFV activity for both compounds. We also found decrease in the synthesis of early and late viral proteins in Vero cells treated with cm1UY11. Finally, the inhibitory effect of aUY11 and cm1UY11 on ASFV infection in porcine alveolar macrophages was confirmed. Overall, our study has identified novel anti-ASFV compounds with potential for future therapeutic developments.

  13. Predictors of poor retention on antiretroviral therapy as a major HIV drug resistance early warning indicator in Cameroon: results from a nationwide systematic random sampling.

    Science.gov (United States)

    Billong, Serge Clotaire; Fokam, Joseph; Penda, Calixte Ida; Amadou, Salmon; Kob, David Same; Billong, Edson-Joan; Colizzi, Vittorio; Ndjolo, Alexis; Bisseck, Anne-Cecile Zoung-Kani; Elat, Jean-Bosco Nfetam

    2016-11-15

    Retention on lifelong antiretroviral therapy (ART) is essential in sustaining treatment success while preventing HIV drug resistance (HIVDR), especially in resource-limited settings (RLS). In an era of rising numbers of patients on ART, mastering patients in care is becoming more strategic for programmatic interventions. Due to lapses and uncertainty with the current WHO sampling approach in Cameroon, we thus aimed to ascertain the national performance of, and determinants in, retention on ART at 12 months. Using a systematic random sampling, a survey was conducted in the ten regions (56 sites) of Cameroon, within the "reporting period" of October 2013-November 2014, enrolling 5005 eligible adults and children. Performance in retention on ART at 12 months was interpreted following the definition of HIVDR early warning indicator: excellent (>85%), fair (85-75%), poor (sampling strategy could be further strengthened for informed ART monitoring and HIVDR prevention perspectives.

  14. Interaction between early-life stress and FKBP5 gene variants in major depressive disorder and post-traumatic stress disorder: A systematic review and meta-analysis.

    Science.gov (United States)

    Wang, Qingzhong; Shelton, Richard C; Dwivedi, Yogesh

    2018-01-01

    Gene-environment interaction contributes to the risks of psychiatric disorders. Interactions between FKBP5 gene variants and early-life stress may enhance the risk not only for mood disorder, but also for a number of other behavioral phenotypes. The aim of the present study was to review and conduct a meta-analysis on the results from published studies examining interaction between FKBP5 gene variants and early-life stress and their associations with stress-related disorders such as major depression and PTSD. A literature search was conducted using PsychINFO and PubMed databases until May 2017. A total of 14 studies with a pooled total of 15109 participants met the inclusion criteria, the results of which were combined and a meta-analysis was performed using the differences in correlations as the effect measure. Based on literature, rs1360780, rs3800373, and rs9470080 SNPs were selected within the FKBP5 gene and systematic review was conducted. Based on the Comprehensive Meta-Analysis software, no publication bias was detected. Sensitivity analysis and credibility of meta-analysis results also indicated that the analyses were stable. The meta-analysis showed that individuals who carry T allele of rs1360780, C-allele of rs3800373 or T-allele of rs9470080 exposed to early-life trauma had higher risks for depression or PTSD. The effects of ethnicity, age, sex, and different stress measures were not examined due to limited sample size. These results provide strong evidence of interactions between FKBP5 genotypes and early-life stress, which could pose a significant risk factor for stress-associated disorders such as major depression and PTSD. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Terapia antiviral para VIH-SIDA

    Directory of Open Access Journals (Sweden)

    Alicia Tarinas Reyes

    2000-12-01

    Full Text Available En los últimos años, muchos agentes antivirales nuevos han sido incorporados a la quimioterapéutica. En esta revisión se resumen tanto los fármacos establecidos de años atrás como los nuevos medicamentos desarrollados para el tratamiento de individuos infectados por VIH. El AZT fue el primero aprobado en marzo de 1987, le siguió el ddl (1991, ddC (1992, d4T (1994, 3TC (1995. Luego fue aprobado el primer inhibidor de proteasa, saquinavir en diciembre de 1995, seguido de ritonavir (1996, indinavir (1996, nelfinavir (1997; además de otros inhibidores de la reverso transcriptasa como nevirapine (1996, delavirdine (1997, efavirenz (1998, entre otros. En estos momentos se siguen buscando y desarrollando nuevas terapias alternativas para esta afección. En este trabajo se exponen algunas de las características de dichos medicamentos, como son: mecanismos de acción (sobre qué enzima actúa cada uno y cómo lo hacen, el ciclo viral, dosificación, incompatibilidades y reacciones adversas.During the last years many new antiviral agents have been incorporated to the chemotherapeutics. The pharmaceuticals established years ago as well as the new ones developed to treat HIV infected individuals are included in this review. The AZT was the first approved in March, 1987, followed by ddl (1991, ddc (1992, d4t (1994, and 3TC (1995. Later, the first protease inhibitor, saquinovir, was approved in December, 1995, followed by ritonavir (1996, indinavir (1996, and nelfinavir (1997; in addition to other inhibitors of the reverse transcriptase as neviparine (1996, delavirdine (1997, and efavirenz (1998, among others. At present new alternative therapies for this affection are being searched and developed. Some of the characteristics of these dugs, such as: action mechanisms (on which enzime each of them act and how they do it, viral cycle, dosage, incompatibilites and adverse reactions are dealt with in this paper.

  16. Broad and potent antiviral activity of the NAE inhibitor MLN4924.

    Science.gov (United States)

    Le-Trilling, Vu Thuy Khanh; Megger, Dominik A; Katschinski, Benjamin; Landsberg, Christine D; Rückborn, Meike U; Tao, Sha; Krawczyk, Adalbert; Bayer, Wibke; Drexler, Ingo; Tenbusch, Matthias; Sitek, Barbara; Trilling, Mirko

    2016-02-01

    In terms of infected human individuals, herpesviruses range among the most successful virus families. Subclinical herpesviral infections in healthy individuals contrast with life-threatening syndromes under immunocompromising and immunoimmature conditions. Based on our finding that cytomegaloviruses interact with Cullin Roc ubiquitin ligases (CRLs) in the context of interferon antagonism, we systematically assessed viral dependency on CRLs by utilizing the drug MLN4924. CRL activity is regulated through the conjugation of Cullins with the ubiquitin-like molecule Nedd8. By inhibiting the Nedd8-activating Enzyme (NAE), MLN4924 interferes with Nedd8 conjugation and CRL activity. MLN4924 exhibited pronounced antiviral activity against mouse and human cytomegalovirus, herpes simplex virus (HSV)- 1 (including multi-drug resistant clinical isolates), HSV-2, adeno and influenza viruses. Human cytomegalovirus genome amplification was blocked at nanomolar MLN4924 concentrations. Global proteome analyses revealed that MLN4924 blocks cytomegaloviral replication despite increased IE1 amounts. Expression of dominant negative Cullins assigned this IE regulation to defined Cullin molecules and phenocopied the antiviral effect of MLN4924.

  17. Favipiravir elicits antiviral mutagenesis during virus replication in vivo.

    Science.gov (United States)

    Arias, Armando; Thorne, Lucy; Goodfellow, Ian

    2014-10-21

    Lethal mutagenesis has emerged as a novel potential therapeutic approach to treat viral infections. Several studies have demonstrated that increases in the high mutation rates inherent to RNA viruses lead to viral extinction in cell culture, but evidence during infections in vivo is limited. In this study, we show that the broad-range antiviral nucleoside favipiravir reduces viral load in vivo by exerting antiviral mutagenesis in a mouse model for norovirus infection. Increased mutation frequencies were observed in samples from treated mice and were accompanied with lower or in some cases undetectable levels of infectious virus in faeces and tissues. Viral RNA isolated from treated animals showed reduced infectivity, a feature of populations approaching extinction during antiviral mutagenesis. These results suggest that favipiravir can induce norovirus mutagenesis in vivo, which in some cases leads to virus extinction, providing a proof-of-principle for the use of favipiravir derivatives or mutagenic nucleosides in the clinical treatment of noroviruses.

  18. Phytochemistry, cytotoxicity and antiviral activity of Eleusine indica (sambau)

    Science.gov (United States)

    Iberahim, Rashidah; Yaacob, Wan Ahmad; Ibrahim, Nazlina

    2015-09-01

    Goose grass also known as Eleusine indica (EI) is a local medicinal plant that displays antioxidant, antimicrobial and anticancer activities. The present study is to determine the phytochemical constituents, cytotoxicity and antiviral activities for both crude extract and fraction obtained from the plant. The crude extract contained more secondary metabolites compared to the hexane fraction as gauged using standard phytochemical tests. Cytotoxicity screening against Vero cells using MTT assay showed that the CC50 values for crude extract and hexane fraction were 2.07 and 5.62 mg/ml respectively. The antiviral activity towards Herpes Simplex Virus type 1 (HSV-1) was determined using plaque reduction assay. The selective indices (SI = CC50 / EC50) for both methanol extract and hexane fraction were 12.2 and 6.2 respectively. These results demonstrate that the extract prepared from E. indica possesses phytochemical compound that was non cytotoxic to the cell with potential antiviral activity.

  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. A Systematic Review of Early Warning Systems' Effects on Nurses' Clinical Performance and Adverse Events Among Deteriorating Ward Patients.

    Science.gov (United States)

    Lee, Ju-Ry; Kim, Eun-Mi; Kim, Sun-Aee; Oh, Eui Geum

    2018-04-25

    Early warning systems (EWSs) are an integral part of processes that aim to improve the early identification and management of deteriorating patients in general wards. However, the widespread implementation of these systems has not generated robust data regarding nurses' clinical performance and patients' adverse events. This review aimed to determine the ability of EWSs to improve nurses' clinical performance and prevent adverse events among deteriorating ward patients. The PubMed, CINAHL, EMBASE, and Cochrane Library databases were searched for relevant publications (January 1, 1997, to April 12, 2017). In addition, a grey literature search evaluated several guideline Web sites. The main outcome measures were nurses' clinical performance (vital sign monitoring and rapid response team notification) and patients' adverse events (in-hospital mortality, cardiac arrest, and unplanned intensive care unit [ICU] admission). The search identified 888 reports, although only five studies fulfilled the inclusion criteria. The findings of these studies revealed that EWSs implementation had a positive effect on nurses' clinical performance, based on their frequency of documenting vital signs that were related to the patient's clinical deterioration. In addition, postimplementation reductions were identified for cardiac arrest, unplanned ICU admission, and unexpected death. It seems that EWSs can improve nurses' clinical performance and prevent adverse events (e.g., in-hospital mortality, unplanned ICU admission, and cardiac arrest) among deteriorating ward patients. However, additional high-quality evidence is needed to more comprehensively evaluate the effects of EWSs on these outcomes.

  1. Effectiveness of Acupuncture for Early Recovery of Bowel Function in Cancer: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Liu, Yi-Hua; Dong, Guang-Tong; Ye, Yang; Zheng, Jia-Bin; Zhang, Ying; Lin, Hong-Sheng; Wang, Xue-Qian

    2017-01-01

    The aim of this study was to evaluate the effects of acupuncture therapy to reduce the duration of postoperative ileus (POI) and to enhance bowel function in cancer patients. A systematic search of electronic databases for studies published from inception until January 2017 was carried out from six databases. Randomized controlled trials (RCTs) involving the use of acupuncture and acupressure for POI and bowel function in cancer patients were identified. Outcomes were extracted from each study and pooled to determine the risk ratio and standardized mean difference. 10 RCTs involving 776 cancer patients were included. Compared with control groups (no acupuncture, sham acupuncture, and other active therapies), acupuncture was associated with shorter time to first flatus and time to first defecation. A subgroup analysis revealed that manual acupuncture was more effective on the time to first flatus and the time to first defecation; electroacupuncture was better in reducing the length of hospital stay. Compared with control groups (sham or no acupressure), acupressure was associated with shorter time to first flatus. However, GRADE approach indicated a low quality of evidence. Acupuncture and acupressure showed large effect size with significantly poor or inferior quality of included trials for enhancing bowel function in cancer patients after surgery. Further well-powered evidence is needed.

  2. Environmental characteristics of early childhood education and care centres and young children's weight status: A systematic review.

    Science.gov (United States)

    Zhang, Zhiguang; Pereira, João R; Sousa-Sá, Eduarda; Okely, Anthony D; Feng, Xiaoqi; Santos, Rute

    2018-01-01

    The aim of this systematic review was to summarize ECEC environmental correlates of weight status in children under the age of 6years. Six databases (PubMed, PsycINFO, CINAHL, SPORTDiscus, Scopus, and Web of Science) were searched until March 2017. Observational studies examining the relationship between ECEC environmental characteristics and weight status in children aged 0-6years were included. Data was extracted using a predesigned form. Eight studies, representing 4862 children, met the inclusion criteria. Twenty-two environmental characteristics were identified and classified into four domains (physical, political, economic, and sociocultural); of these, six correlates were found. 'Active environment' 'sedentary opportunities', 'active play time', 'high sugar and high fat served', 'educators' weight' and 'educators' habitual physical activity level' were associated with weight status in young children. However, for most environmental characteristics examined, strong evidence is not available yet, due to variations across studies on the measures of environmental characteristics and analytical methodologies. Stronger empirical evidence in greater quantity is needed. Future studies in this area are recommended to investigate the environmental influence using an ecological approach and to examine the potential mediators, with a focus on the settings of family-based centres and samples representing toddlers and/or infants. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Effectiveness of Acupuncture for Early Recovery of Bowel Function in Cancer: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Yi-Hua Liu

    2017-01-01

    Full Text Available Objectives. The aim of this study was to evaluate the effects of acupuncture therapy to reduce the duration of postoperative ileus (POI and to enhance bowel function in cancer patients. Methods. A systematic search of electronic databases for studies published from inception until January 2017 was carried out from six databases. Randomized controlled trials (RCTs involving the use of acupuncture and acupressure for POI and bowel function in cancer patients were identified. Outcomes were extracted from each study and pooled to determine the risk ratio and standardized mean difference. Results. 10 RCTs involving 776 cancer patients were included. Compared with control groups (no acupuncture, sham acupuncture, and other active therapies, acupuncture was associated with shorter time to first flatus and time to first defecation. A subgroup analysis revealed that manual acupuncture was more effective on the time to first flatus and the time to first defecation; electroacupuncture was better in reducing the length of hospital stay. Compared with control groups (sham or no acupressure, acupressure was associated with shorter time to first flatus. However, GRADE approach indicated a low quality of evidence. Conclusions. Acupuncture and acupressure showed large effect size with significantly poor or inferior quality of included trials for enhancing bowel function in cancer patients after surgery. Further well-powered evidence is needed.

  4. Systematic review of surveillance systems and methods for early detection of exotic, new and re-emerging diseases in animal populations.

    Science.gov (United States)

    Rodríguez-Prieto, V; Vicente-Rubiano, M; Sánchez-Matamoros, A; Rubio-Guerri, C; Melero, M; Martínez-López, B; Martínez-Avilés, M; Hoinville, L; Vergne, T; Comin, A; Schauer, B; Dórea, F; Pfeiffer, D U; Sánchez-Vizcaíno, J M

    2015-07-01

    In this globalized world, the spread of new, exotic and re-emerging diseases has become one of the most important threats to animal production and public health. This systematic review analyses conventional and novel early detection methods applied to surveillance. In all, 125 scientific documents were considered for this study. Exotic (n = 49) and re-emerging (n = 27) diseases constituted the most frequently represented health threats. In addition, the majority of studies were related to zoonoses (n = 66). The approaches found in the review could be divided in surveillance modalities, both active (n = 23) and passive (n = 5); and tools and methodologies that support surveillance activities (n = 57). Combinations of surveillance modalities and tools (n = 40) were also found. Risk-based approaches were very common (n = 60), especially in the papers describing tools and methodologies (n = 50). The main applications, benefits and limitations of each approach were extracted from the papers. This information will be very useful for informing the development of tools to facilitate the design of cost-effective surveillance strategies. Thus, the current literature review provides key information about the advantages, disadvantages, limitations and potential application of methodologies for the early detection of new, exotic and re-emerging diseases.

  5. Efficacy of Aloe Vera Supplementation on Prediabetes and Early Non-Treated Diabetic Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

    Science.gov (United States)

    Zhang, Yiyi; Liu, Wen; Liu, Dan; Zhao, Tieyun; Tian, Haoming

    2016-06-23

    The aim of this study was to evaluate evidence for the efficacy of aloe vera on managing prediabetes and early non-treated diabetes mellitus. We performed a systematic search of PubMed, Embase, and Cochrane Central Register of Controlled Trials until 28 January 2016. A total of five randomized controlled trials (RCTs) involving 415 participants were included. Compared with the controls, aloe vera supplementation significantly reduced the concentrations of fasting blood glucose (FBG) (p = 0.02; weighed mean difference [WMD]: -30.05 mg/dL; 95% confidence interval [CI]: -54.87 to -5.23 mg/dL), glycosylated hemoglobin A1c (HbA1c) (p Aloe vera was superior to placebo in increasing serum high density lipoprotein-cholesterol (HDL-C) levels (p = 0.04). Only one adverse event was reported. The evidence from RCTs showed that aloe vera might effectively reduce the levels of FBG, HbA1c, triglyceride, TC and LDL-C, and increase the levels of HDL-C on prediabetes and early non-treated diabetic patients. Limited evidence exists about the safety of aloe vera. Given the small number and poor quality of RCTs included in the meta-analysis, these results are inconclusive. A large-scale, well-designed RCT is needed to further address this issue.

  6. Antiviral and cytotoxic activities of some Indonesian plants.

    Science.gov (United States)

    Lohézic-Le Dévéhat, F; Bakhtiar, A; Bézivin, C; Amoros, M; Boustie, J

    2002-08-01

    Ten methanolic extracts from eight Indonesian medicinal plants were phytochemically screened and evaluated for antiviral (HSV-1 and Poliovirus) and cytotoxic activities on murine and human cancer lines (3LL, L1210, K562, U251, DU145, MCF-7). Besides Melastoma malabathricum (Melastomataceae), the Indonesian Loranthaceae species among which Elytranthe tubaeflora, E. maingayi, E. globosa and Scurrula ferruginea exhibited attractive antiviral and cytotoxic activities. Piper aduncum (Piperaceae) was found active on Poliovirus. S. ferruginea was selected for further studies because of its activity on the U251 glioblastoma cells.

  7. Antiviral activity of maca (Lepidium meyenii) against human influenza virus

    OpenAIRE

    Del Valle Mendoza, Juana; Pumarola, Tomas; Alzamora Gonzales, Libertad; Valle Mendoza, Luis Javier del

    2014-01-01

    Objective To investigate antiviral activity of maca to reduce viral load in Madin-Darby canine kidney (MDCK) cells infected with influenza type A and B viruses (Flu-A and Flu-B, respectively). Methods Maca were extracted with methanol (1:2, v/v). The cell viability and toxicity of the extracts were evaluated on MDCK cells using method MTT assay. Antiviral activity of compounds against Flu-A and Flu-B viruses was assayed using a test for determining the inhibition of the cytopathic ...

  8. RNA interference-mediated intrinsic antiviral immunity in invertebrates.

    Science.gov (United States)

    Nayak, Arabinda; Tassetto, Michel; Kunitomi, Mark; Andino, Raul

    2013-01-01

    In invertebrates such as insects and nematodes, RNA interference (RNAi) provides RNA-based protection against viruses. This form of immunity restricts viral replication and dissemination from infected cells and viruses, in turn, have evolved evasion mechanisms or RNAi suppressors to counteract host defenses. Recent advances indicate that, in addition to RNAi, other related small RNA pathways contribute to antiviral functions in invertebrates. This has led to a deeper understanding of fundamental aspects of small RNA-based antiviral immunity in invertebrates and its contribution to viral spread and pathogenesis.

  9. From genome to antivirals: SARS as a test tube.

    Science.gov (United States)

    Kliger, Yossef; Levanon, Erez Y; Gerber, Doron

    2005-03-01

    The severe acute respiratory syndrome (SARS) epidemic brought into the spotlight the need for rapid development of effective anti-viral drugs against newly emerging viruses. Researchers have leveraged the 20-year battle against AIDS into a variety of possible treatments for SARS. Most prominently, based solely on viral genome information, silencers of viral genes, viral-enzyme blockers and viral-entry inhibitors were suggested as potential therapeutic agents for SARS. In particular, inhibitors of viral entry, comprising therapeutic peptides, were based on the recently launched anti-HIV drug enfuvirtide. This could represent one of the most direct routes from genome sequencing to the discovery of antiviral drugs.

  10. Changes in soluble factor-mediated CD8+ cell-derived antiviral activity in cynomolgus macaques infected with simian immunodeficiency virus SIVmac251: relationship to biological markers of progression.

    Science.gov (United States)

    Dioszeghy, Vincent; Benlhassan-Chahour, Kadija; Delache, Benoit; Dereuddre-Bosquet, Nathalie; Aubenque, Celine; Gras, Gabriel; Le Grand, Roger; Vaslin, Bruno

    2006-01-01

    Cross-sectional studies have shown that the capacity of CD8+ cells from human immunodeficiency virus (HIV)-infected patients and simian immunodeficiency virus (SIV) SIVmac-infected macaques to suppress the replication of human and simian immunodeficiency viruses in vitro depends on the clinical stage of disease, but little is known about changes in this antiviral activity over time in individual HIV-infected patients or SIV-infected macaques. We assessed changes in the soluble factor-mediated noncytolytic antiviral activity of CD8+ cells over time in eight cynomolgus macaques infected with SIVmac251 to determine the pathophysiological role of this activity. CD8+ cell-associated antiviral activity increased rapidly in the first week after viral inoculation and remained detectable during the early phase of infection. The net increase in antiviral activity of CD8+ cells was correlated with plasma viral load throughout the 15 months of follow-up. CD8+ cells gradually lost their antiviral activity over time and acquired virus replication-enhancing capacity. Levels of antiviral activity correlated with CD4+ T-cell counts after viral set point. Concentrations of beta-chemokines and interleukin-16 in CD8+ cell supernatants were not correlated with this antiviral activity, and alpha-defensins were not detected. The soluble factor-mediated antiviral activity of CD8+ cells was neither cytolytic nor restricted to major histocompatibility complex. This longitudinal study strongly suggests that the increase in noncytolytic antiviral activity from baseline and the maintenance of this increase over time in cynomolgus macaques depend on both viral replication and CD4+ T cells.

  11. Changes in Soluble Factor-Mediated CD8+ Cell-Derived Antiviral Activity in Cynomolgus Macaques Infected with Simian Immunodeficiency Virus SIVmac251: Relationship to Biological Markers of Progression†

    Science.gov (United States)

    Dioszeghy, Vincent; Benlhassan-Chahour, Kadija; Delache, Benoit; Dereuddre-Bosquet, Nathalie; Aubenque, Celine; Gras, Gabriel; Le Grand, Roger; Vaslin, Bruno

    2006-01-01

    Cross-sectional studies have shown that the capacity of CD8+ cells from human immunodeficiency virus (HIV)-infected patients and simian immunodeficiency virus (SIV) SIVmac-infected macaques to suppress the replication of human and simian immunodeficiency viruses in vitro depends on the clinical stage of disease, but little is known about changes in this antiviral activity over time in individual HIV-infected patients or SIV-infected macaques. We assessed changes in the soluble factor-mediated noncytolytic antiviral activity of CD8+ cells over time in eight cynomolgus macaques infected with SIVmac251 to determine the pathophysiological role of this activity. CD8+ cell-associated antiviral activity increased rapidly in the first week after viral inoculation and remained detectable during the early phase of infection. The net increase in antiviral activity of CD8+ cells was correlated with plasma viral load throughout the 15 months of follow-up. CD8+ cells gradually lost their antiviral activity over time and acquired virus replication-enhancing capacity. Levels of antiviral activity correlated with CD4+ T-cell counts after viral set point. Concentrations of β-chemokines and interleukin-16 in CD8+ cell supernatants were not correlated with this antiviral activity, and α-defensins were not detected. The soluble factor-mediated antiviral activity of CD8+ cells was neither cytolytic nor restricted to major histocompatibility complex. This longitudinal study strongly suggests that the increase in noncytolytic antiviral activity from baseline and the maintenance of this increase over time in cynomolgus macaques depend on both viral replication and CD4+ T cells. PMID:16352548

  12. The Relations Between Maternal Prenatal Anxiety or Stress and Child's Early Negative Reactivity or Self-Regulation: A Systematic Review.

    Science.gov (United States)

    Korja, Riikka; Nolvi, Saara; Grant, Kerry Ann; McMahon, Cathy

    2017-12-01

    In the present review, we examine the association between maternal prenatal stress or anxiety and children's early negative reactivity or self-regulation. The review includes 32 studies that focus on pregnancy-related anxiety, state or trait anxiety, perceived stress, and stressful life events in relation to child's crying, temperament, or behavior during the first 2 years of life. We searched four electronic databases and 32 studies were selected based on the inclusion criteria. Twenty-three studies found an association between maternal prenatal anxiety or stress and a child's negative reactivity or self-regulation, and typically the effect sizes varied from low to moderate. The association was found regardless of the form of prenatal stress or anxiety and the trimester in which the prenatal stress or anxiety was measured. In conclusion, several forms of prenatal anxiety and stress may increase the risk of emotional and self-regulatory difficulties during the first 2 years of life.

  13. Novel α,β-unsaturated amide derivatives bearing α-amino phosphonate moiety as potential antiviral agents.

    Science.gov (United States)

    Lan, Xianmin; Xie, Dandan; Yin, Limin; Wang, Zhenzhen; Chen, Jin; Zhang, Awei; Song, Baoan; Hu, Deyu

    2017-09-15

    Based on flexible construction and broad bioactivity of ferulic acid, a series of novel α,β-unsaturated amide derivatives bearing α-aminophosphonate moiety were designed, synthesized and systematically evaluated for their antiviral activity. Bioassay results indicated that some compounds exhibited good antiviral activities against cucumber mosaic virus (CMV) and tobacco mosaic virus (TMV) in vivo. Especially, compound g18 showed excellent curative and protective activities against CMV, with half-maximal effective concentration (EC 50 ) values of 284.67μg/mL and 216.30μg/mL, which were obviously superior to that of Ningnanmycin (352.08μg/mL and 262.53μg/mL). Preliminary structure-activity relationships (SARs) analysis revealed that the introduction of electron-withdrawing group at the 2-position or 4-position of the aromatic ring is favorable for antiviral activity. Present work provides a promising template for development of potential inhibitor of plant virus. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Review of Factors Influencing Women's Choice of Mastectomy Versus Breast Conserving Therapy in Early Stage Breast Cancer: A Systematic Review.

    Science.gov (United States)

    Gu, Jeffrey; Groot, Gary; Boden, Catherine; Busch, Angela; Holtslander, Lorraine; Lim, Hyun

    2018-01-03

    We have performed a narrative synthesis. A literature search was conducted between January 2000 and June 2014 in 7 databases. The initial search identified 2717 articles; 319 underwent abstract screening, 67 underwent full-text screening, and 25 final articles were included. This review looked at early stage breast cancer in women only, excluding ductal carcinoma in situ and advanced breast cancer. A conceptual framework was created to organize the central constructs underlying women's choices: clinicopathologic factors, physician factors, and individual factors with subgroups of sociodemographic, geographic, and personal beliefs and preferences. This framework guided our review's synthesis and analysis. We found that larger tumor size and increasing stage was associated with increased rates of mastectomy. The results for age varied, but suggested that old and young extremes of diagnostic age were associated with an increased likelihood of mastectomy. Higher socioeconomic status was associated with higher breast conservation therapy (BCT) rates. Resident rural location and increasing distance from radiation treatment facilities were associated with lower rates of BCT. Individual belief factors influencing women's choice of mastectomy (mastectomy being reassuring, avoiding radiation, an expedient treatment) differed from factors influencing choice of BCT (body image and femininity, physician recommendation, survival equivalence, less surgery). Surgeon factors, including female gender, higher case numbers, and individual surgeon practice, were associated with increased BCT rates. The decision-making process for women with early stage breast cancer is complicated and affected by multiple factors. Organizing these factors into central constructs of clinicopathologic, individual, and physician factors may aid health-care professionals to better understand this process. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  15. A Systematic Review to Define the Speech and Language Benefit of Early (<12 Months) Pediatric Cochlear Implantation.

    Science.gov (United States)

    Bruijnzeel, Hanneke; Ziylan, Fuat; Stegeman, Inge; Topsakal, Vedat; Grolman, Wilko

    2016-01-01

    This review aimed to evaluate the additional benefit of pediatric cochlear implantation before 12 months of age considering improved speech and language development and auditory performance. We conducted a search in PubMed, EMBASE and CINAHL databases and included studies comparing groups with different ages at implantation and assessing speech perception and speech production, receptive language and/or auditory performance. We included studies with a high directness of evidence (DoE). We retrieved 3,360 articles. Ten studies with a high DoE were included. Four articles with medium DoE were discussed in addition. Six studies compared infants implanted before 12 months with children implanted between 12 and 24 months. Follow-up ranged from 6 months to 9 years. Cochlear implantation before the age of 2 years is beneficial according to one speech perception score (phonetically balanced kindergarten combined with consonant-nucleus-consonant) but not on Glendonald auditory screening procedure scores. Implantation before 12 months resulted in better speech production (diagnostic evaluation of articulation and phonology and infant-toddler meaningful auditory integration scale), auditory performance (Categories of Auditory Performance-II score) and receptive language scores (2 out of 5; Preschool Language Scale combined with oral and written language skills and Peabody Picture Vocabulary Test). The current best evidence lacks level 1 evidence studies and consists mainly of cohort studies with a moderate to high risk of bias. Included studies showed consistent evidence that cochlear implantation should be performed early in life, but evidence is inconsistent on all speech and language outcome measures regarding the additional benefit of implantation before the age of 12 months. Long-term follow-up studies are necessary to provide insight on additional benefits of early pediatric cochlear implantation. © 2016 S. Karger AG, Basel.

  16. Effect of Early Versus Late Tracheostomy or Prolonged Intubation in Critically Ill Patients with Acute Brain Injury: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    McCredie, Victoria A; Alali, Aziz S; Scales, Damon C; Adhikari, Neill K J; Rubenfeld, Gordon D; Cuthbertson, Brian H; Nathens, Avery B

    2017-02-01

    The optimal timing of tracheostomy placement in acutely brain-injured patients, who generally require endotracheal intubation for airway protection rather than respiratory failure, remains uncertain. We systematically reviewed trials comparing early tracheostomy to late tracheostomy or prolonged intubation in these patients. We searched 5 databases (from inception to April 2015) to identify randomized controlled trials comparing early tracheostomy (≤10 days of intubation) with late tracheostomy (>10 days) or prolonged intubation in acutely brain-injured patients. We contacted the principal authors of included trials to obtain subgroup data. Two reviewers extracted data and assessed risk of bias. Outcomes included long-term mortality (primary), short-term mortality, duration of mechanical ventilation, complications, and liberation from ventilation without a tracheostomy. Meta-analyses used random-effects models. Ten trials (503 patients) met selection criteria; overall study quality was moderate to good. Early tracheostomy reduced long-term mortality (risk ratio [RR] 0.57. 95 % confidence interval (CI), 0.36-0.90; p = 0.02; n = 135), although in a sensitivity analysis excluding one trial, with an unclear risk of bias, the significant finding was attenuated (RR 0.61, 95 % CI, 0.32-1.16; p = 0.13; n = 95). Early tracheostomy reduced duration of mechanical ventilation (mean difference [MD] -2.72 days, 95 % CI, -1.29 to -4.15; p = 0.0002; n = 412) and ICU length of stay (MD -2.55 days, 95 % CI, -0.50 to -4.59; p = 0.01; n = 326). However, early tracheostomy did not reduce short-term mortality (RR 1.25; 95 % CI, 0.68-2.30; p = 0.47 n = 301) and increased the probability of ever receiving a tracheostomy (RR 1.58, 95 % CI, 1.24-2.02; 0 tracheostomy in acutely brain-injured patients may reduce long-term mortality, duration of mechanical ventilation, and ICU length of stay. However, waiting longer leads to fewer tracheostomy procedures and

  17. Association of CDX2 Expression With Survival in Early Colorectal Cancer: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Tomasello, Gianluca; Barni, Sandro; Turati, Luca; Ghidini, Michele; Pezzica, Ezio; Passalacqua, Rodolfo; Petrelli, Fausto

    2018-02-15

    CDX2 is a homeobox gene encoding transcriptional factors for intestinal organogenesis and represents a specific marker of colorectal adenocarcinoma (CRC) differentiation. We have evaluated if CDX2 expression is associated with better overall and disease-free survival (OS and DFS) in patients with CRC. PubMed, SCOPUS, EMBASE, The Cochrane Library, and Web of Science (from inception to July 2017) were systematically reviewed for relevant studies on adult patients with CRC where OS and DFS were calculated according to CDX2 expression in uni- or multivariate analysis were included. Hazard ratio (HR) for mortality and/or disease progression was calculated. The search produced 16 studies suitable for inclusion (6291 individual patients). The meta-analysis showed a reduced risk of death for patients with CDX2-positive CRC in 14 studies (HR, 0.5; 95% confidence interval [CI], 0.38-0.66; P < .001 according to random effect model). In 6 studies where only DFS data was available, CDX2 expression led to a 52% lower risk of relapse or death (HR, 0.48; 95% CI, 0.39-0.59; P < .001 according to random effect model). The results did not change as a function of ethnicity, type of study, CDX2 detection modality, or stage. Interestingly, in stages II to III, CDX2 expression was associated with a 70% lower risk of death (HR, 0.3; 95% CI, 0.12-0.77; P = .01). CDX2 expression confirms to be a strong prognostic factor in stage II and III CRC. In this setting, along with other clinical and pathologic factors, the lack of expression of CDX2 may be considered an important variable when deciding for adjuvant chemotherapy. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Antiviral therapy for prevention of hepatocellular carcinoma in chronic hepatitis C

    DEFF Research Database (Denmark)

    Kimer, Nina; Dahl, Emilie Kristine; Gluud, Lise Lotte

    2012-01-01

    To determine whether antiviral therapy reduces the risk of developing hepatocellular carcinoma (HCC) in chronic hepatitis C.......To determine whether antiviral therapy reduces the risk of developing hepatocellular carcinoma (HCC) in chronic hepatitis C....

  19. Risk of early-onset neonatal infection with maternal infection or colonization: a global systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Grace J Chan

    2013-08-01

    Full Text Available Neonatal infections cause a significant proportion of deaths in the first week of life, yet little is known about risk factors and pathways of transmission for early-onset neonatal sepsis globally. We aimed to estimate the risk of neonatal infection (excluding sexually transmitted diseases [STDs] or congenital infections in the first seven days of life among newborns of mothers with bacterial infection or colonization during the intrapartum period.We searched PubMed, Embase, Scopus, Web of Science, Cochrane Library, and the World Health Organization Regional Databases for studies of maternal infection, vertical transmission, and neonatal infection published from January 1, 1960 to March 30, 2013. Studies were included that reported effect measures on the risk of neonatal infection among newborns exposed to maternal infection. Random effects meta-analyses were used to pool data and calculate the odds ratio estimates of risk of infection. Eighty-three studies met the inclusion criteria. Seven studies (8.4% were from high neonatal mortality settings. Considerable heterogeneity existed between studies given the various definitions of laboratory-confirmed and clinical signs of infection, as well as for colonization and risk factors. The odds ratio for neonatal lab-confirmed infection among newborns of mothers with lab-confirmed infection was 6.6 (95% CI 3.9-11.2. Newborns of mothers with colonization had a 9.4 (95% CI 3.1-28.5 times higher odds of lab-confirmed infection than newborns of non-colonized mothers. Newborns of mothers with risk factors for infection (defined as prelabour rupture of membranes [PROM], preterm <37 weeks PROM, and prolonged ROM had a 2.3 (95% CI 1.0-5.4 times higher odds of infection than newborns of mothers without risk factors.Neonatal infection in the first week of life is associated with maternal infection and colonization. High-quality studies, particularly from settings with high neonatal mortality, are needed to

  20. Treatment outcome of immediate, early and conventional single-tooth implants in the aesthetic zone : a systematic review to survival, bone level, soft-tissue, aesthetics and patient satisfaction

    NARCIS (Netherlands)

    den Hartog, Laurens; Huddleston Slater, James J. R.; Vissink, Arjan; Meijer, Henny J. A.; Raghoebar, Gerry M.

    2008-01-01

    den Hartog L, Huddleston Slater JJR, Vissink A, Meijer HJA, Raghoebar GM. Treatment outcome of immediate, early and conventional single-tooth implants in the aesthetic zone: a systematic review to survival, bone level, soft-tissue, aesthetics and patient satisfaction. J Clin Periodontol 2008; 35:

  1. Antiviral activity of maca (Lepidium meyenii) against human influenza virus.

    Science.gov (United States)

    Del Valle Mendoza, Juana; Pumarola, Tomàs; Gonzales, Libertad Alzamora; Del Valle, Luis J

    2014-09-01

    To investigate antiviral activity of maca to reduce viral load in Madin-Darby canine kidney (MDCK) cells infected with influenza type A and B viruses (Flu-A and Flu-B, respectively). Maca were extracted with methanol (1:2, v/v). The cell viability and toxicity of the extracts were evaluated on MDCK cells using method MTT assay. Antiviral activity of compounds against Flu-A and Flu-B viruses was assayed using a test for determining the inhibition of the cytopathic effect on cell culture and multiplex RT-PCR. The methanol extract of maca showed low cytotoxicity and inhibited influenza-induced cytopathic effect significantly, while viral load was reduced via inhibition of viral growth in MDCK infected cells. Maca contains potent inhibitors of Flu-A and Flu-B with a selectivity index [cytotoxic concentration 50%/IC50] of 157.4 and 110.5, respectively. In vitro assays demonstrated that maca has antiviral activity not only against Flu-A (like most antiviral agents) but also Flu-B viruses, providing remarkable therapeutic benefits. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  2. 78 FR 57166 - Antiviral Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-09-17

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001] Antiviral Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice. This notice announces a forthcoming meeting of a public advisory committee of the Food and Drug...

  3. Developing antiviral surgical gown using nonwoven fabrics for ...

    African Journals Online (AJOL)

    Objectives: To develop antiviral surgical gown comprising of Polypropylene nonwoven as outer layer, Polytetrafluroethylene (PTFE) film as middle layer and polyester nonwoven as inner layer and the surgical gown with a basic weight of 70 g/m2. Methods: The titanium dioxide (TiO2) nano dispersion was prepared with ...

  4. Antiviral acyclic nucleoside phosphonates: New structures and prodrugs

    Czech Academy of Sciences Publication Activity Database

    Krečmerová, Marcela; Tichý, Tomáš; Pomeisl, Karel; Andrei, G.; Balzarini, J.; Snoeck, R.

    2016-01-01

    Roč. 1, č. 2 (2016), s. 37 [PharmaMed-2016. International Conference on Medicinal and Pharmaceutical Chemistry . 05.12.2016-07.12.2016, Dubai] R&D Projects: GA ČR(CZ) GA14-00522S Institutional support: RVO:61388963 Keywords : acyclic nucleoside phosphonates * prodrugs * antivirals * 5-azacytosine Subject RIV: CC - Organic Chemistry

  5. The role of CC chemokine receptor 5 in antiviral immunity

    DEFF Research Database (Denmark)

    Nansen, Anneline; Christensen, Jan Pravsgaard; Andreasen, Susanne Ørding

    2002-01-01

    The CC chemokine receptor CCR5 is an important coreceptor for human immunodeficiency virus (HIV), and there is a major thrust to develop anti-CCR5-based therapies for HIV-1. However, it is not known whether CCR5 is critical for a normal antiviral T-cell response. This study investigated the immune...

  6. Interferon induced IFIT family genes in host antiviral defense.

    Science.gov (United States)

    Zhou, Xiang; Michal, Jennifer J; Zhang, Lifan; Ding, Bo; Lunney, Joan K; Liu, Bang; Jiang, Zhihua

    2013-01-01

    Secretion of interferons (IFNs) from virus-infected cells is a hallmark of host antiviral immunity and in fact, IFNs exert their antiviral activities through the induction of antiviral proteins. The IFN-induced protein with tetratricopeptide repeats (IFITs) family is among hundreds of IFN-stimulated genes. This family contains a cluster of duplicated loci. Most mammals have IFIT1, IFIT2, IFIT3 and IFIT5; however, bird, marsupial, frog and fish have only IFIT5. Regardless of species, IFIT5 is always adjacent to SLC16A12. IFIT family genes are predominantly induced by type I and type III interferons and are regulated by the pattern recognition and the JAK-STAT signaling pathway. IFIT family proteins are involved in many processes in response to viral infection. However, some viruses can escape the antiviral functions of the IFIT family by suppressing IFIT family genes expression or methylation of 5' cap of viral molecules. In addition, the variants of IFIT family genes could significantly influence the outcome of hepatitis C virus (HCV) therapy. We believe that our current review provides a comprehensive picture for the community to understand the structure and function of IFIT family genes in response to pathogens in human, as well as in animals.

  7. Antiviral evaluation of an Hsp90 inhibitor, gedunin, against dengue ...

    African Journals Online (AJOL)

    Purpose: To evaluate the antiviral potential of a tetranortriterpenoid, gedunin, against dengue virus (DENV) replication by targeting the host chaperone, Hsp90. Methods: The compound, gedunin, was tested against the replication of DENV in vitro using BHK-15 cells transfected with DENV-2 subgenomic replicon. Molecular ...

  8. Antiviral activity of exopolysaccharides from Arthrospira platensis against koi herpesvirus.

    Science.gov (United States)

    Reichert, M; Bergmann, S M; Hwang, J; Buchholz, R; Lindenberger, C

    2017-10-01

    Although koi herpesvirus (KHV) has a history of causing severe economic losses in common carp and koi farms, there are still no treatments available on the market. Thus, the aim of this study was to test exopolysaccharides (EPS) for its antiviral activity against KHV, by monitoring inhibition and cytotoxic effects in common carp brain cells. These substances can be easily extracted from extracellular algae supernatant and were identified as groups of sulphated polysaccharides. In order to reach this aim, Arthrospira platensis, which is well known for its antiviral activity of intra- and extracellular compounds towards mammalian herpesviruses, was investigated as standard organism and compared to commercial antiviral drug, ganciclovir, which inhibits the viral DNA polymerization. The antiviral activity of polysaccharides of A. platensis against KHV was confirmed in vitro using qualitative assessment of KHV life cycle genes, and it was found by RT-PCR that EPS, applied at a concentration of >18 μg mL -1 and a multiplicity of infection (MOI) of 0.45 of KHV, suppressed the viral replication in common carp brain (CCB) cells even after 22 days post-infection, entirely. Further, this study presents first data indicating an enormous potential using polysaccharides as an additive for aquacultures to lower or hinder the spread of the KHV and koi herpesvirus disease (KHVD) in future. © 2017 John Wiley & Sons Ltd.

  9. 75 FR 16151 - Antiviral Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2010-03-31

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001] Antiviral Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice. This notice announces a forthcoming meeting of a public advisory committee of the Food and Drug...

  10. 76 FR 62418 - Antiviral Drugs Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2011-10-07

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] Antiviral Drugs Advisory Committee; Notice of Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice. This notice announces a forthcoming meeting of a public advisory committee of the Food and Drug...

  11. Antiviral activity of the extracts of Rhodophyceae from Morocco

    African Journals Online (AJOL)

    Administrator

    2010-11-15

    Nov 15, 2010 ... replication of HSV-1 in vitro at an EC50 (Effective Concentration 50%) ranging from <2.5 to 75.9 µg mL-1. No cytotoxic effect ... Keywords: Antiviral, Aqueous extracts, Organic extracts, Rhodophyceae, Herpes simplex virus. INTRODUCTION ... from a species of Bryopsis as a possible treatment of lung cancer ...

  12. Bilirubin: an endogenous molecule with antiviral activity in vitro.

    Directory of Open Access Journals (Sweden)

    Rosaria eSantangelo

    2012-03-01

    Full Text Available Bilirubin-IX-alpha (BR is the final product of heme metabolism through the heme oxygenase/biliverdin reductase (HO/BVR system. Previous papers reported on the microbicidal effects of the HO by-products biliverdin-IX-alpha, carbon monoxide and iron, through either direct or indirect mechanisms. In this paper the evidence of a virucidal effect of BR against human herpes simplex virus type 1 (HSV-1 and the enterovirus EV71 was provided. Bilirubin-IX-alpha, at concentrations 1-10 µM, close to those found in blood and tissues, significantly reduced HSV-1 and EV71 replication in Hep-2 and Vero cell lines, respectively. Bilirubin-IX-alpha inhibited viral infection of Hep-2 and Vero cells when given 2 hours before, concomitantly and 2 hours after viral infection. Furthermore, BR retained its antiviral activity even complexed with a saturating concentration of human serum-albumin. Moreover, 10 µM BR increased the formation of nitric oxide and the phosphorylation of JNK in Vero and Hep-2 cell lines, respectively, thus implying a role of these two pathways in the mechanism of antiviral activity of the bile pigment. In conclusion, these results support the antiviral effect of BR against HSV-1 and enterovirus in vitro, and put the basis for further basic and clinical studies to understand the real role of BR as an endogenous antiviral molecule.

  13. INVESTMENT IN ANTIVIRAL DRUGS : A REAL OPTIONS APPROACH

    NARCIS (Netherlands)

    Attema, Arthur E.; Lugner, Anna K.; Feenstra, Talitha L.

    2010-01-01

    Real options analysis is a promising approach to model investment under uncertainty. We employ this approach to value stockpiling of antiviral drugs as a precautionary measure against a possible influenza pandemic. Modifications of the real options approach to include risk attitude and deviations

  14. Developing antiviral surgical gown using nonwoven fabrics for ...

    African Journals Online (AJOL)

    EB

    Developing antiviral surgical gown using nonwoven fabrics for health care sector. *Parthasarathi V, Thilagavathi G. Department of Fashion Technology, PSG college of Technology, Peelamedu, Coimbatore – 641 004,. India. Abstract. Background: Healthcare workers' uniforms including surgical gowns are used as barriers ...

  15. Testing of disease-resistance of pokeweed antiviral protein gene ...

    African Journals Online (AJOL)

    Transformation of pokeweed antiviral protein gene (PAP) into plants was shown to improve plant resistance to several viruses or fungi pathogens with no much negative effect on plant growth. The non-virulent defective PAP inhibits only the virus but does not interfere with the host. A non-virulent defective PAP gene ...

  16. DMPD: Regulation of mitochondrial antiviral signaling pathways. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18549796 Regulation of mitochondrial antiviral signaling pathways. Moore CB, Ting J...P. Immunity. 2008 Jun;28(6):735-9. (.png) (.svg) (.html) (.csml) Show Regulation of mitochondrial antiviral ...signaling pathways. PubmedID 18549796 Title Regulation of mitochondrial antiviral signaling pathways. Author

  17. DMPD: What is disrupting IFN-alpha's antiviral activity? [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 15283983 What is disrupting IFN-alpha's antiviral activity? Mbow ML, Sarisky RT. Tr...ends Biotechnol. 2004 Aug;22(8):395-9. (.png) (.svg) (.html) (.csml) Show What is disrupting IFN-alpha's ant...iviral activity? PubmedID 15283983 Title What is disrupting IFN-alpha's antiviral activity? Authors Mbow ML,

  18. DMPD: Negative regulation of cytoplasmic RNA-mediated antiviral signaling. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18703349 Negative regulation of cytoplasmic RNA-mediated antiviral signaling. Komur...Show Negative regulation of cytoplasmic RNA-mediated antiviral signaling. PubmedID 18703349 Title Negative r...egulation of cytoplasmic RNA-mediated antiviral signaling. Authors Komuro A, Bamm

  19. Sentinel lymph node dissection only versus complete axillary lymph node dissection in early invasive breast cancer: a systematic review and meta-analysis.

    Science.gov (United States)

    Glechner, Anna; Wöckel, Achim; Gartlehner, Gerald; Thaler, Kylie; Strobelberger, Michaela; Griebler, Ursula; Kreienberg, Rolf

    2013-03-01

    The Z0011-study, a landmark randomised controlled trial (RCT) challenged the benefits of complete axillary lymph node dissection (ALND) compared with sentinel lymph node dissection only (SLND) in breast cancer patients with positive sentinel nodes. The study, however, has been criticised for lack of power and low applicability. The aim of this review was to systematically assess the evidence on the comparative benefits and harms of ALND versus SLND for sentinel node positive breast cancer patients. We systematically searched PubMed, Embase, the Cochrane Library, and reference lists of pertinent review articles from January 2006 to August 2011. We dually reviewed the literature and rated the risk of bias of each study. For effectiveness, we included RCTs and observational studies of at least 1 year follow-up. In addition, we considered studies conducted in sentinel node-negative women to assess the risk of harms. If data were sufficient, we conducted random effects meta-analysis of outcomes of interest. Meta-analysis of three studies with 50,120 patients indicated similar 5-year survival and regional recurrence rates between patients treated with ALND or SLND, although prognostic tumour characteristics varied among the 3 study-populations. Results from 6 studies on more than 11,500 patients reported a higher risk for harms for ALND than SLND. Long-term evidence on pertinent health outcomes is missing. The available evidence indicates that for some women with early invasive breast cancer SLND appears to be a justifiable alternative to ALND. Surgeons need to discuss advantages and disadvantages of both approaches with their patients. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. A systematic review and methodological evaluation of published cost-effectiveness analyses of aromatase inhibitors versus tamoxifen in early stage breast cancer.

    Directory of Open Access Journals (Sweden)

    Ava A John-Baptiste

    Full Text Available BACKGROUND: A key priority in developing policies for providing affordable cancer care is measuring the value for money of new therapies using cost-effectiveness analyses (CEAs. For CEA to be useful it should focus on relevant outcomes and include thorough investigation of uncertainty. Randomized controlled trials (RCTs of five years of aromatase inhibitors (AI versus five years of tamoxifen in the treatment of post-menopausal women with early stage breast cancer, show benefit of AI in terms of disease free survival (DFS but not overall survival (OS and indicate higher risk of fracture with AI. Policy-relevant CEA of AI versus tamoxifen should focus on OS and include analysis of uncertainty over key assumptions. METHODS: We conducted a systematic review of published CEAs comparing an AI to tamoxifen. We searched Ovid MEDLINE, EMBASE, PsychINFO, and the Cochrane Database of Systematic Reviews without language restrictions. We selected CEAs with outcomes expressed as cost per life year or cost per quality adjusted life year (QALY. We assessed quality using the Neumann checklist. Using structured forms two abstractors collected descriptive information, sources of data, baseline assumptions on effectiveness and adverse events, and recorded approaches to assessing parameter uncertainty, methodological uncertainty, and structural uncertainty. RESULTS: We identified 1,622 citations and 18 studies met inclusion criteria. All CE estimates assumed a survival benefit for aromatase inhibitors. Twelve studies performed sensitivity analysis on the risk of adverse events and 7 assumed no additional mortality risk with any adverse event. Sub-group analysis was limited; 6 studies examined older women, 2 examined women with low recurrence risk, and 1 examined women with multiple comorbidities. CONCLUSION: Published CEAs comparing AIs to tamoxifen assumed an OS benefit though none has been shown in RCTs, leading to an overestimate of the cost-effectiveness of AIs

  1. Evaluation of systematic assessment of asthma-like symptoms and tobacco smoke exposure in early childhood by well-child professionals: a randomised trial.

    Directory of Open Access Journals (Sweden)

    Esther Hafkamp-de Groen

    Full Text Available This study aimed to evaluate the effectiveness of systematic assessment of asthma-like symptoms and environmental tobacco smoke (ETS exposure during regular preventive well-child visits between age 1 and 4 years by well-child professionals.Sixteen well-child centres in Rotterdam, the Netherlands, were randomised into 8 centres where the brief assessment form regarding asthma-like symptoms and ETS exposure was used and 8 centres that applied usual care. 3596 and 4179 children (born between April 2002 and January 2006 and their parents visited the intervention and control centres, respectively. At child's age 6 years, physician-diagnosed asthma ever, wheezing, fractional exhaled nitric oxide (FeNO, airway resistance (Rint, health-related quality of life (HRQOL and ETS exposure at home ever were measured. Linear mixed models were applied.No differences in asthma, wheezing, FeNO, Rint or HRQOL measurements between intervention and control group were found using multilevel regression in an intention-to-treat analysis (p>0.05. Children of whom the parents were interviewed by using the brief assessment form at the intervention well-child centres had a decreased risk on ETS exposure at home ever, compared to children who visited the control well-child centres, in an explorative per-protocol analysis (aOR = 0.71, 95% CI:0.59-0.87.Systematic assessment and counselling of asthma-like symptoms and ETS exposure in early childhood by well-child care professionals using a brief assessment form was not effective in reducing the prevalence of physician-diagnosed asthma ever and wheezing, and did not improve FeNO, Rint or HRQOL at age 6 years. Our results hold some promise for interviewing parents and using information leaflets at well-child centres to reduce ETS exposure at home in preschool children.Controlled-Trials.com ISRCTN15790308.

  2. Evaluation of systematic assessment of asthma-like symptoms and tobacco smoke exposure in early childhood by well-child professionals: a randomised trial.

    Science.gov (United States)

    Hafkamp-de Groen, Esther; van der Valk, Ralf J P; Mohangoo, Ashna D; van der Wouden, Johannes C; Duijts, Liesbeth; Jaddoe, Vincent W; Hofman, Albert; de Koning, Harry J; de Jongste, Johan C; Raat, Hein

    2014-01-01

    This study aimed to evaluate the effectiveness of systematic assessment of asthma-like symptoms and environmental tobacco smoke (ETS) exposure during regular preventive well-child visits between age 1 and 4 years by well-child professionals. Sixteen well-child centres in Rotterdam, the Netherlands, were randomised into 8 centres where the brief assessment form regarding asthma-like symptoms and ETS exposure was used and 8 centres that applied usual care. 3596 and 4179 children (born between April 2002 and January 2006) and their parents visited the intervention and control centres, respectively. At child's age 6 years, physician-diagnosed asthma ever, wheezing, fractional exhaled nitric oxide (FeNO), airway resistance (Rint), health-related quality of life (HRQOL) and ETS exposure at home ever were measured. Linear mixed models were applied. No differences in asthma, wheezing, FeNO, Rint or HRQOL measurements between intervention and control group were found using multilevel regression in an intention-to-treat analysis (p>0.05). Children of whom the parents were interviewed by using the brief assessment form at the intervention well-child centres had a decreased risk on ETS exposure at home ever, compared to children who visited the control well-child centres, in an explorative per-protocol analysis (aOR = 0.71, 95% CI:0.59-0.87). Systematic assessment and counselling of asthma-like symptoms and ETS exposure in early childhood by well-child care professionals using a brief assessment form was not effective in reducing the prevalence of physician-diagnosed asthma ever and wheezing, and did not improve FeNO, Rint or HRQOL at age 6 years. Our results hold some promise for interviewing parents and using information leaflets at well-child centres to reduce ETS exposure at home in preschool children. Controlled-Trials.com ISRCTN15790308.

  3. The HEART score for early rule out of acute coronary syndromes in the emergency department: a systematic review and meta-analysis.

    Science.gov (United States)

    Van Den Berg, Patricia; Body, Richard

    2018-03-01

    The objective of this systematic review was to summarise the current evidence on the diagnostic accuracy of the HEART score for predicting major adverse cardiac events in patients presenting with undifferentiated chest pain to the emergency department. Two investigators independently searched Medline, Embase and Cochrane databases between 2008 and May 2016 identifying eligible studies providing diagnostic accuracy data on the HEART score for predicting major adverse cardiac events as the primary outcome. For the 12 studies meeting inclusion criteria, study characteristics and diagnostic accuracy measures were systematically extracted and study quality assessed using the QUADAS-2 tool. After quality assessment, nine studies including data from 11,217 patients were combined in the meta-analysis applying a generalised linear mixed model approach with random effects assumption (Stata 13.1). In total, 15.4% of patients (range 7.3-29.1%) developed major adverse cardiac events after a mean of 6 weeks' follow-up. Among patients categorised as 'low risk' and suitable for early discharge (HEART score 0-3), the pooled incidence of 'missed' major adverse cardiac events was 1.6%. The pooled sensitivity and specificity of the HEART score for predicting major adverse cardiac events were 96.7% (95% confidence interval (CI) 94.0-98.2%) and 47.0% (95% CI 41.0-53.5%), respectively. Patients with a HEART score of 0-3 are at low risk of incident major adverse cardiac events. As 3.3% of patients with major adverse cardiac events are 'missed' by the HEART score, clinicians must ask whether this risk is acceptably low for clinical implementation.

  4. Activation of cGAS-dependent antiviral responses by DNA intercalating agents.

    Science.gov (United States)

    Pépin, Geneviève; Nejad, Charlotte; Thomas, Belinda J; Ferrand, Jonathan; McArthur, Kate; Bardin, Philip G; Williams, Bryan R G; Gantier, Michael P

    2017-01-09

    Acridine dyes, including proflavine and acriflavine, were commonly used as antiseptics before the advent of penicillins in the mid-1940s. While their mode of action on pathogens was originally attributed to their DNA intercalating activity, work in the early 1970s suggested involvement of the host immune responses, characterized by induction of interferon (IFN)-like activities through an unknown mechanism. We demonstrate here that sub-toxic concentrations of a mixture of acriflavine and proflavine instigate a cyclic-GMP-AMP (cGAMP) synthase (cGAS)-dependent type-I IFN antiviral response. This pertains to the capacity of these compounds to induce low level DNA damage and cytoplasmic DNA leakage, resulting in cGAS-dependent cGAMP-like activity. Critically, acriflavine:proflavine pre-treatment of human primary bronchial epithelial cells significantly reduced rhinovirus infection. Collectively, our findings constitute the first evidence that non-toxic DNA binding agents have the capacity to act as indirect agonists of cGAS, to exert potent antiviral effects in mammalian cells. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  5. RETRACTED: Effect of early versus late or no tracheostomy on mortality of critically ill patients receiving mechanical ventilation: a systematic review and meta-analysis.

    Science.gov (United States)

    Siempos, Ilias I; Ntaidou, Theodora K; Filippidis, Filippos T; Choi, Augustine M K

    2014-06-26

    Delay of tracheostomy for roughly 2 weeks after translaryngeal intubation of critically ill patients is the presently recommended practice and is supported by findings from large trials. However, these trials were suboptimally powered to detect small but clinically important effects on mortality. We aimed to assess the mortality benefit of early versus late or no tracheostomy in critically ill patients who need mechanical ventilation. We systematically searched PubMed, CINAHL, Embase, Web of Science, DOAJ, the Cochrane Library, references of relevant articles, scientific conference proceedings, and grey literature up to Aug 31, 2013, to identify randomised controlled trials comparing early tracheostomy (done within 1 week after translaryngeal intubation) with late (done any time after the first week of mechanical ventilation) or no tracheostomy and reporting on mortality or incidence of pneumonia in critically ill patients under mechanical ventilation. Our primary outcomes were all-cause mortality during the stay in the intensive-care unit and incidence of ventilator-associated pneumonia. We calculated pooled odds ratios (OR), pooled risk ratios (RR), and 95% CIs with a random-effects model. All but complications analyses were done on an intention-to-treat basis. Analyses of 13 trials (2434 patients, 800 deaths) showed that all-cause mortality in the intensive-care unit was significantly lower in patients assigned to the early versus the late or no tracheostomy group (OR 0·72, 95% CI 0·53-0·98; p=0·04). This finding represents an 18% reduction in the relative risk of death, translating to a 5% absolute improvement in survival (from 65% to 70%). This result persisted when we considered only trials with a low risk of bias (663 deaths; OR 0·68, 95% CI 0·49-0·95; p=0·02; eight trials with 1934 patients). There was no evidence of a difference between the compared groups for 1-year mortality (788 deaths; RR 0·93, 95% CI 0·85-1·02; p=0·14; three trials with

  6. Mediastinal lymph node dissection versus mediastinal lymph node sampling for early stage non-small cell lung cancer: a systematic review and meta-analysis.

    Science.gov (United States)

    Huang, Xiongfeng; Wang, Jianmin; Chen, Qiao; Jiang, Jielin

    2014-01-01

    This systematic review and meta-analysis aimed to evaluate the overall survival, local recurrence, distant metastasis, and complications of mediastinal lymph node dissection (MLND) versus mediastinal lymph node sampling (MLNS) in stage I-IIIA non-small cell lung cancer (NSCLC) patients. A systematic search of published literature was conducted using the main databases (MEDLINE, PubMed, EMBASE, and Cochrane databases) to identify relevant randomized controlled trials that compared MLND vs. MLNS in NSCLC patients. Methodological quality of included randomized controlled trials was assessed according to the criteria from the Cochrane Handbook for Systematic Review of Interventions (Version 5.1.0). Meta-analysis was performed using The Cochrane Collaboration's Review Manager 5.3. The results of the meta-analysis were expressed as hazard ratio (HR) or risk ratio (RR), with their corresponding 95% confidence interval (CI). We included results reported from six randomized controlled trials, with a total of 1,791 patients included in the primary meta-analysis. Compared to MLNS in NSCLC patients, there was no statistically significant difference in MLND on overall survival (HR = 0.77, 95% CI 0.55 to 1.08; P = 0.13). In addition, the results indicated that local recurrence rate (RR = 0.93, 95% CI 0.68 to 1.28; P = 0.67), distant metastasis rate (RR = 0.88, 95% CI 0.74 to 1.04; P = 0.15), and total complications rate (RR = 1.10, 95% CI 0.67 to 1.79; P = 0.72) were similar, no significant difference found between the two groups. Results for overall survival, local recurrence rate, and distant metastasis rate were similar between MLND and MLNS in early stage NSCLC patients. There was no evidence that MLND increased complications compared with MLNS. Whether or not MLND is superior to MLNS for stage II-IIIA remains to be determined.

  7. Discovery of potent broad spectrum antivirals derived from marine actinobacteria.

    Directory of Open Access Journals (Sweden)

    Avi Raveh

    Full Text Available Natural products provide a vast array of chemical structures to explore in the discovery of new medicines. Although secondary metabolites produced by microbes have been developed to treat a variety of diseases, including bacterial and fungal infections, to date there has been limited investigation of natural products with antiviral activity. In this report, we used a phenotypic cell-based replicon assay coupled with an iterative biochemical fractionation process to identify, purify, and characterize antiviral compounds produced by marine microbes. We isolated a compound from Streptomyces kaviengensis, a novel actinomycetes isolated from marine sediments obtained off the coast of New Ireland, Papua New Guinea, which we identified as antimycin A1a. This compound displays potent activity against western equine encephalitis virus in cultured cells with half-maximal inhibitory concentrations of less than 4 nM and a selectivity index of greater than 550. Our efforts also revealed that several antimycin A analogues display antiviral activity, and mechanism of action studies confirmed that these Streptomyces-derived secondary metabolites function by inhibiting the cellular mitochondrial electron transport chain, thereby suppressing de novo pyrimidine synthesis. Furthermore, we found that antimycin A functions as a broad spectrum agent with activity against a wide range of RNA viruses in cultured cells, including members of the Togaviridae, Flaviviridae, Bunyaviridae, Picornaviridae, and Paramyxoviridae families. Finally, we demonstrate that antimycin A reduces central nervous system viral titers, improves clinical disease severity, and enhances survival in mice given a lethal challenge with western equine encephalitis virus. Our results provide conclusive validation for using natural product resources derived from marine microbes as source material for antiviral drug discovery, and they indicate that host mitochondrial electron transport is a viable

  8. 186Os- 187Os systematics of Gorgona Island komatiites: implications for early growth of the inner core

    Science.gov (United States)

    Brandon, Alan D.; Walker, Richard J.; Puchtel, Igor S.; Becker, Harry; Humayun, Munir; Revillon, Sidonie

    2003-02-01

    The presence of coupled enrichments in 186Os/ 188Os and 187Os/ 188Os in some mantle-derived materials reflects long-term elevation of Pt/Os and Re/Os relative to the primitive upper mantle. New Os data for the 89 Ma Gorgona Island, Colombia komatiites indicate that these lavas are also variably enriched in 186Os and 187Os, with 186Os/ 188Os ranging between 0.1198397±22 and 0.1198470±38, and with γOs correspondingly ranging from +0.15 to +4.4. These data define a linear trend that converges with the previously reported linear trend generated from data for modern Hawaiian picritic lavas and a sample from the ca. 251 Ma Siberian plume, to a common component with a 186Os/ 188Os of approximately 0.119870 and γOs of +17.5. The convergence of these data to this Os isotopic composition may imply a single ubiquitous source in the Earth's interior that mixes with a variety of different mantle compositions distinguished by variations in γOs. The 187Os- and 186Os-enriched component may have been generated via early crystallization of the solid inner core and consequent increases in Pt/Os and Re/Os in the liquid outer core, with time leading to suprachondritic 186Os/ 188Os and γOs in the outer core. The presence of Os from the outer core in certain portions of the mantle would require a mechanism that could transfer Os from the outer core to the lower mantle, and thence to the surface. If this is the process that generated the isotopic enrichments in the mantle sources of these plume-derived systems, then the current understanding of solid metal-liquid metal partitioning of Pt, Re and Os requires that crystallization of the inner core began prior to 3.5 Ga. Thus, the Os isotopic data reported here provide a new source of data to better constrain the timing of inner core formation, complementing magnetic field paleo-intensity measurements as data sources that constrain models based on secular cooling of the Earth.

  9. Epimedium koreanum Nakai Displays Broad Spectrum of Antiviral Activity in Vitro and in Vivo by Inducing Cellular Antiviral State

    Directory of Open Access Journals (Sweden)

    Won-Kyung Cho

    2015-01-01

    Full Text Available Epimedium koreanum Nakai has been extensively used in traditional Korean and Chinese medicine to treat a variety of diseases. Despite the plant’s known immune modulatory potential and chemical make-up, scientific information on its antiviral properties and mode of action have not been completely investigated. In this study, the broad antiviral spectrum and mode of action of an aqueous extract from Epimedium koreanum Nakai was evaluated in vitro, and moreover, the protective effect against divergent influenza A subtypes was determined in BALB/c mice. An effective dose of Epimedium koreanum Nakai markedly reduced the replication of Influenza A Virus (PR8, Vesicular Stomatitis Virus (VSV, Herpes Simplex Virus (HSV and Newcastle Disease Virus (NDV in RAW264.7 and HEK293T cells. Mechanically, we found that an aqueous extract from Epimedium koreanum Nakai induced the secretion of type I IFN and pro-inflammatory cytokines and the subsequent stimulation of the antiviral state in cells. Among various components present in the extract, quercetin was confirmed to have striking antiviral properties. The oral administration of Epimedium koreanum Nakai exhibited preventive effects on BALB/c mice against lethal doses of highly pathogenic influenza A subtypes (H1N1, H5N2, H7N3 and H9N2. Therefore, an extract of Epimedium koreanum Nakai and its components play roles as immunomodulators in the innate immune response, and may be potential candidates for prophylactic or therapeutic treatments against diverse viruses in animal and humans.

  10. Effect of early versus late or no tracheostomy on mortality and pneumonia of critically ill patients receiving mechanical ventilation: a systematic review and meta-analysis.

    Science.gov (United States)

    Siempos, Ilias I; Ntaidou, Theodora K; Filippidis, Filippos T; Choi, Augustine M K

    2015-02-01

    Delay of tracheostomy for roughly 2 weeks after translaryngeal intubation of critically ill patients is the presently recommended practice and is supported by findings from large trials. However, these trials were suboptimally powered to detect small but clinically important effects on mortality. We aimed to assess the benefit of early versus late or no tracheostomy on mortality and pneumonia in critically ill patients who need mechanical ventilation. We systematically searched PubMed, CINAHL, Embase, Web of Science, DOAJ, the Cochrane Library, references of relevant articles, scientific conference proceedings, and grey literature up to Aug 31, 2013, to identify randomised controlled trials comparing early tracheostomy (done within 1 week after translaryngeal intubation) with late (done any time after the first week of mechanical ventilation) or no tracheostomy and reporting on mortality or incidence of pneumonia in critically ill patients under mechanical ventilation. Our primary outcomes were all-cause mortality during the stay in the intensive-care unit and incidence of ventilator-associated pneumonia. Mortality during the stay in the intensive-care unit was a composite endpoint of definite intensive-care-unit mortality, presumed intensive-care-unit mortality, and 28-day mortality. We calculated pooled odds ratios (OR), pooled risk ratios (RR), and 95% CIs with a random-effects model. All but complications analyses were done on an intention-to-treat basis. Analyses of 13 trials (2434 patients, 648 deaths) showed that all-cause mortality in the intensive-care unit was not significantly lower in patients assigned to the early versus the late or no tracheostomy group (OR 0·80, 95% CI 0·59-1·09; p=0·16). This result persisted when we considered only trials with a low risk of bias (511 deaths; OR 0·80, 95% CI 0·59-1·09; p=0·16; eight trials with 1934 patients). Incidence of ventilator-associated pneumonia was lower in mechanically ventilated patients assigned

  11. Systematic review and meta-analysis of published trials comparing the effectiveness of transanal endoscopic microsurgery and radical resection in the management of early rectal cancer.

    Science.gov (United States)

    Sajid, M S; Farag, S; Leung, P; Sains, P; Miles, W F A; Baig, M K

    2014-01-01

    A systematic analysis was conducted of trials comparing the effectiveness of transanal endoscopic microsurgery (TEMS) with radical resection (RR) for T1 and T2 rectal cancer. An electronic search was carried out of trials reporting the effectiveness of TEMS and RR in the treatment of T1 and T2 rectal cancers. Ten trials including 942 patients were retrieved. There was a trend toward a higher risk of local recurrence (odds ratio 2.78; 95% confidence interval 1.42, 5.44; z = 2.97; P TEMS compared with RR. The risk of distant recurrence, overall survival (odds ratio 0.90; 95% confidence interval 0.49, 1.66; z = 0.33; P = 0.74) and mortality was similar. TEMS was associated with a shorter operation time and hospital stay and a reduced risk of postoperative complications (P TEMS is superior to RR in the management of early rectal cancer. Larger, better designed and executed prospective studies are needed to answer this question. Colorectal Disease © 2013 The Association of Coloproctology of Great Britain and Ireland.

  12. Identification of a novel multiple kinase inhibitor with potent antiviral activity against influenza virus by reducing viral polymerase activity

    International Nuclear Information System (INIS)

    Sasaki, Yutaka; Kakisaka, Michinori; Chutiwitoonchai, Nopporn; Tajima, Shigeru; Hikono, Hirokazu; Saito, Takehiko; Aida, Yoko

    2014-01-01

    Highlights: • Screening of 50,000 compounds and subsequent lead optimization identified WV970. • WV970 has antiviral effects against influenza A, B and highly pathogenic viral strains. • WV970 inhibits viral genome replication and transcription. • A target database search suggests that WV970 may bind to a number of kinases. • KINOMEscan screening revealed that WV970 has inhibitory effects on 15 kinases. - Abstract: Neuraminidase inhibitors are the only currently available influenza treatment, although resistant viruses to these drugs have already been reported. Thus, new antiviral drugs with novel mechanisms of action are urgently required. In this study, we identified a novel antiviral compound, WV970, through cell-based screening of a 50,000 compound library and subsequent lead optimization. This compound exhibited potent antiviral activity with nanomolar IC 50 values against both influenza A and B viruses but not non-influenza RNA viruses. Time-of-addition and indirect immunofluorescence assays indicated that WV970 acted at an early stage of the influenza life cycle, but likely after nuclear entry of viral ribonucleoprotein (vRNP). Further analyses of viral RNA expression and viral polymerase activity indicated that WV970 inhibited vRNP-mediated viral genome replication and transcription. Finally, structure-based virtual screening and comprehensive human kinome screening were used to demonstrate that WV970 acts as a multiple kinase inhibitor, many of which are associated with influenza virus replication. Collectively, these results strongly suggest that WV970 is a promising anti-influenza drug candidate and that several kinases associated with viral replication are promising drug targets

  13. Identification of a novel multiple kinase inhibitor with potent antiviral activity against influenza virus by reducing viral polymerase activity

    Energy Technology Data Exchange (ETDEWEB)

    Sasaki, Yutaka; Kakisaka, Michinori; Chutiwitoonchai, Nopporn [Viral Infectious Diseases Unit, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Tajima, Shigeru [Department of Virology I, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku, Tokyo 162-8640 (Japan); Hikono, Hirokazu; Saito, Takehiko [Influenza and Prion Disease Research Center, National Institute of Animal Health, National Agriculture and Food Research Organization (NARO), 3-1-5 Kannondai, Tsukuba, Ibaraki 305-0856 (Japan); Aida, Yoko, E-mail: aida@riken.jp [Viral Infectious Diseases Unit, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan)

    2014-07-18

    Highlights: • Screening of 50,000 compounds and subsequent lead optimization identified WV970. • WV970 has antiviral effects against influenza A, B and highly pathogenic viral strains. • WV970 inhibits viral genome replication and transcription. • A target database search suggests that WV970 may bind to a number of kinases. • KINOMEscan screening revealed that WV970 has inhibitory effects on 15 kinases. - Abstract: Neuraminidase inhibitors are the only currently available influenza treatment, although resistant viruses to these drugs have already been reported. Thus, new antiviral drugs with novel mechanisms of action are urgently required. In this study, we identified a novel antiviral compound, WV970, through cell-based screening of a 50,000 compound library and subsequent lead optimization. This compound exhibited potent antiviral activity with nanomolar IC{sub 50} values against both influenza A and B viruses but not non-influenza RNA viruses. Time-of-addition and indirect immunofluorescence assays indicated that WV970 acted at an early stage of the influenza life cycle, but likely after nuclear entry of viral ribonucleoprotein (vRNP). Further analyses of viral RNA expression and viral polymerase activity indicated that WV970 inhibited vRNP-mediated viral genome replication and transcription. Finally, structure-based virtual screening and comprehensive human kinome screening were used to demonstrate that WV970 acts as a multiple kinase inhibitor, many of which are associated with influenza virus replication. Collectively, these results strongly suggest that WV970 is a promising anti-influenza drug candidate and that several kinases associated with viral replication are promising drug targets.

  14. In-Vitro Antiviral Activities of Extracts of Plants of The Brazilian Cerrado against the Avian Metapneumovirus (aMPV

    Directory of Open Access Journals (Sweden)

    LK Kohn

    2015-09-01

    Full Text Available ABSTRACTAvian metapneumovirus (aMPV is a negative-sense single-stranded RNA enveloped virus of the Metapneumovirus genus belonging to theParamyxoviridae family. This virus may cause significant economic losses to the poultry industry, despite vaccination, which is the main tool for controlling and preventing aMPV. The aim of this study was to evaluate the antiviral activity of extracts of four different native plants of the Brazilian Cerrado against aMPV. The antiviral activity against aMPV was determined by titration. This technique measures the ability of plant extract dilutions (25 to 2.5 µg mL-1 to inhibit the cytopathic effect (CPE of the virus, expressed as inhibition percentage (IP. The maximum nontoxic concentration (MNTC of the extracts used in antiviral assay was 25 µg mL-1for Aspidosperma tomentosumand Gaylussacia brasiliensis, and 2.5 µg mL-1for Arrabidaea chicaand Virola sebifera. Twelve different extracts derived from four plant species collected from the Brazilian Cerrado were screened for antiviral activity against aMPV. G. brasiliensis, A. chica,and V. sebifera extracts presented inhibition rates of 99% in the early viral replication stages, suggesting that these extracts act during the adsorption phase. On the other hand, A. tomentosum inhibited 99% virus replication after the virus entered the cell. The biomonitored fractioning of extracts active against aMPV may be a tool to identify the active compounds of plant extracts and to determine their precise mode of action.

  15. Interactions of macrophages with probiotic bacteria lead to increased antiviral response against vesicular stomatitis virus

    DEFF Research Database (Denmark)

    Ivec, Martin; Botic, Tanja; Koren, Srecko

    2007-01-01

    and by producing chemokines and immunoregulatory cytokines that enable the adaptive immune response to recognize infected cells and perform antiviral effector functions. Probiotics, as a part of the normal gut intestinal flora, are important in supporting a functional yet balanced immune system. Improving our...... understanding of their role in the activation of macrophages and their stimulation of proinflammatory cytokine production in early viral infection was the main goal of this study. Our in vitro model study showed that probiotic bacteria, either from the species Lactobacillus or Bifidobacteria have the ability...... dehydrogenases activity could be implied as the first indicator of potential inhibitory effects of the probiotics on virus replication. The interactions between probiotic bacteria, macrophages and vesicular stomatitis virus (VSV), markedly depended on the bacterial strain studied....

  16. Patient-centered early pregnancy care: a systematic review of quantitative and qualitative studies on the perspectives of women and their partners.

    Science.gov (United States)

    van den Berg, M M J; Dancet, E A F; Erlikh, T; van der Veen, F; Goddijn, M; Hajenius, P J

    2018-01-01

    Early pregnancy complications, defined as miscarriage, recurrent miscarriage or ectopic pregnancy, affect the physical and psychological well-being of intended parents. Research in this field so far has focused mainly on improving accuracy of diagnostic tests and safety and effectiveness of therapeutic management. An overview of aspects of care valued by women and/or their partners is missing. This systematic review aims to provide an overview of aspects of care valued by women and/or their partners faced with early pregnancy complications and to identify potential targets for improvement in early pregnancy healthcare. We searched five electronic databases for empirical quantitative or qualitative studies on patients' perspectives of early pregnancy care in July 2017. We first identified aspects of early pregnancy care valued by women and/or their partners based on qualitative and quantitative data and organized these aspects of care according to the eight dimensions of patient-centered care. Second, we extracted the assessment of service quality from women and/or their partners on each of these aspects of care based on quantitative data. Third, we combined the findings on patients' values with the findings of service quality assessment to identify potential targets for improvement in five groups according to how likely these targets are to require improvement. The search yielded 6240 publications, of which 27 studies were eligible for inclusion in this review. All included studies focused on miscarriage or recurrent miscarriage care. We identified 24 valued aspects of care, which all covered the eight dimensions of patient-centered care. The most frequently reported valued aspect was 'being treated as an individual person experiencing a significant life event rather than a common condition'. Assessment of service quality from women and/or their partners was available for 13 of the 24 identified aspects of care. Quantitative studies all documented service quality

  17. Novel drugs targeting Toll-like receptors for antiviral therapy.

    Science.gov (United States)

    Patel, Mira C; Shirey, Kari Ann; Pletneva, Lioubov M; Boukhvalova, Marina S; Garzino-Demo, Alfredo; Vogel, Stefanie N; Blanco, Jorge Cg

    2014-09-01

    Toll-like receptors (TLRs) are sentinel receptors of the host innate immune system that recognize conserved 'pathogen-associated molecular patterns' of invading microbes, including viruses. The activation of TLRs establishes antiviral innate immune responses and coordinates the development of long-lasting adaptive immunity in order to control viral pathogenesis. However, microbe-induced damage to host tissues may release 'danger-associated molecular patterns' that also activate TLRs, leading to an overexuberant inflammatory response and, ultimately, to tissue damage. Thus, TLRs have proven to be promising targets as therapeutics for the treatment of viral infections that result in inflammatory damage or as adjuvants in order to enhance the efficacy of vaccines. Here, we explore recent advances in TLR biology with a focus on novel drugs that target TLRs (agonists and antagonists) for antiviral therapy.

  18. Indian marine bivalves: Potential source of antiviral drugs

    Digital Repository Service at National Institute of Oceanography (India)

    Chatterji, A.; Ansari, Z.A.; Ingole, B.S.; Bichurina, M.A.; Sovetova, M.; Boikov, Y.A.

    in large quantities by traditional methods and sold live in the market for human consumption. The economically important sp e cies of marine bivalves are green mussel ( Perna viridis ), e s tuarine oyster ( Crassostrea madrasensis ), giant oyster... in developing an effecti ve drug has been the unique characteristics of antigenic variation of virus resulting in the emergence of new variant virus strains 14 . There are a number of antiviral drugs introduced in the market such as tricyclic sy m- metric...

  19. Human and Mouse Eosinophils Have Antiviral Activity against Parainfluenza Virus.

    Science.gov (United States)

    Drake, Matthew G; Bivins-Smith, Elizabeth R; Proskocil, Becky J; Nie, Zhenying; Scott, Gregory D; Lee, James J; Lee, Nancy A; Fryer, Allison D; Jacoby, David B

    2016-09-01

    Respiratory viruses cause asthma exacerbations. Because eosinophils are the prominent leukocytes in the airways of 60-70% of patients with asthma, we evaluated the effects of eosinophils on a common respiratory virus, parainfluenza 1, in the lung. Eosinophils recruited to the airways of wild-type mice after ovalbumin sensitization and challenge significantly decreased parainfluenza virus RNA in the lungs 4 days after infection compared with nonsensitized animals. This antiviral effect was also seen in IL-5 transgenic mice with an abundance of airway eosinophils (NJ.1726) but was lost in transgenic eosinophil-deficient mice (PHIL) and in IL-5 transgenic mice crossed with eosinophil-deficient mice (NJ.1726-PHIL). Loss of the eosinophil granule protein eosinophil peroxidase, using eosinophil peroxidase-deficient transgenic mice, did not reduce eosinophils' antiviral effect. Eosinophil antiviral mechanisms were also explored in vitro. Isolated human eosinophils significantly reduced parainfluenza virus titers. This effect did not involve degradation of viral RNA by eosinophil granule RNases. However, eosinophils treated with a nitric oxide synthase inhibitor lost their antiviral activity, suggesting eosinophils attenuate viral infectivity through production of nitric oxide. Consequently, eosinophil nitric oxide production was measured with an intracellular fluorescent probe. Eosinophils produced nitric oxide in response to virus and to a synthetic agonist of the virus-sensing innate immune receptor, Toll-like receptor (TLR) 7. IFNγ increased expression of eosinophil TLR7 and potentiated TLR7-induced nitric oxide production. These results suggest that eosinophils promote viral clearance in the lung and contribute to innate immune responses against respiratory virus infections in humans.

  20. In Vitro Bioavailability Study of an Antiviral Compound Enisamium Iodide

    OpenAIRE

    Eleonore Haltner-Ukomadu; Svitlana Gureyeva; Oleksii Burmaka; Andriy Goy; Lutz Mueller; Grygorii Kostyuk; Victor Margitich

    2018-01-01

    An investigation into the biopharmaceutics classification and a study of the in vitro bioavailability (permeability and solubility) of the antiviral compound enisamium iodide (4-(benzylcarbamoyl)-1-methylpyridinium iodide) were carried out. The solubility of enisamium iodide was determined in four different buffers. Apparent intestinal permeability (Papp) of enisamium iodide was assessed using human colon carcinoma (Caco-2) cells at three concentrations. The solubility of enisamium iodide in ...

  1. Anti-viral RNA silencing: do we look like plants ?

    Directory of Open Access Journals (Sweden)

    Lecellier Charles-Henri

    2006-01-01

    Full Text Available Abstract The anti-viral function of RNA silencing was first discovered in plants as a natural manifestation of the artificial 'co-suppression', which refers to the extinction of endogenous gene induced by homologous transgene. Because silencing components are conserved among most, if not all, eukaryotes, the question rapidly arose as to determine whether this process fulfils anti-viral functions in animals, such as insects and mammals. It appears that, whereas the anti-viral process seems to be similarly conserved from plants to insects, even in worms, RNA silencing does influence the replication of mammalian viruses but in a particular mode: micro(miRNAs, endogenous small RNAs naturally implicated in translational control, rather than virus-derived small interfering (siRNAs like in other organisms, are involved. In fact, these recent studies even suggest that RNA silencing may be beneficial for viral replication. Accordingly, several large DNA mammalian viruses have been shown to encode their own miRNAs. Here, we summarize the seminal studies that have implicated RNA silencing in viral infection and compare the different eukaryotic responses.

  2. Efficacy of Antiviral Drugs against Feline Immunodeficiency Virus

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    Katrin Hartmann

    2015-12-01

    Full Text Available Feline immunodeficiency virus (FIV is one of the most common infectious agents affecting cats worldwide .FIV and human immunodeficiency virus (HIV share many properties: both are lifelong persistent lentiviruses that are similar genetically and morphologically and both viruses propagate in T-lymphocytes, macrophages, and neural cells. Experimentally infected cats have measurable immune suppression, which sometimes progresses to an acquired immunodeficiency syndrome. A transient initial state of infection is followed by a long latent stage with low virus replication and absence of clinical signs. In the terminal stage, both viruses can cause severe immunosuppression. Thus, FIV infection in cats has become an important natural model for studying HIV infection in humans, especially for evaluation of antiviral compounds. Of particular importance for chemotherapeutic studies is the close similarity between the reverse transcriptase (RT of FIV and HIV, which results in high in vitro susceptibility of FIV to many RT-targeted antiviral compounds used in the treatment of HIV-infected patients. Thus, the aim of this article is to provide an up-to-date review of studies on antiviral treatment of FIV, focusing on commercially available compounds for human or animal use.

  3. Antiviral and Inflammatory Cellular Signaling Associated with Enterovirus 71 Infection

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    Yuefei Jin

    2018-03-01

    Full Text Available Enterovirus 71 (EV71 infection has become a major threat to global public health, especially in infants and young children. Epidemiological studies have indicated that EV71 infection is responsible for severe and even fatal cases of hand, foot, and mouth disease (HFMD. Accumulated evidence indicates that EV71 infection triggers a plethora of interactive signaling pathways, resulting in host immune evasion and inflammatory response. This review mainly covers the effects of EV71 infection on major antiviral and inflammatory cellular signal pathways. EV71 can activate cellular signaling networks including multiple cell surface and intracellular receptors, intracellular kinases, calcium flux, and transcription factors that regulate antiviral innate immunity and inflammatory response. Cellular signaling plays a critical role in the regulation of host innate immune and inflammatory pathogenesis. Elucidation of antiviral and inflammatory cellular signaling pathways initiated by EV71 will not only help uncover the potential mechanisms of EV71 infection-induced pathogenesis, but will also provide clues for the design of therapeutic strategies against EV71 infection.

  4. Antiviral activity of some South American medicinal plants.

    Science.gov (United States)

    Abad, M J; Bermejo, P; Sanchez Palomino, S; Chiriboga, X; Carrasco, L

    1999-03-01

    Folk medicinal plants are potential sources of useful therapeutic compounds including some with antiviral activities. Extracts prepared from 10 South American medicinal plants (Baccharis trinervis, Baccharis teindalensis, Eupatorium articulatum, Eupatorium glutinosum, Tagetes pusilla, Neurolaena lobata, Conyza floribunda, Phytolacca bogotensis, Phytolacca rivinoides and Heisteria acuminata) were screened for in vitro antiviral activity against herpes simplex type I (HSV-1), vesicular stomatitis virus (VSV) and poliovirus type 1. The most potent inhibition was observed with an aqueous extract of B. trinervis, which inhibited HSV-1 replication by 100% at 50-200 micrograms/mL, without showing cytotoxic effects. Good activities were also found with the ethanol extract of H. acuminata and the aqueous extract of E. articulatum, which exhibited antiviral effects against both DNA and RNA viruses (HSV-1 and VSV, respectively) at 125-250 micrograms/mL. The aqueous extracts of T. pusilla (100-250 micrograms/mL), B. teindalensis (50-125 micrograms/mL) and E. glutinosum (50-125 micrograms/mL) also inhibited the replication of VSV, but none of the extracts tested had any effect on poliovirus replication.

  5. Early trauma-focused cognitive-behavioural therapy to prevent chronic post-traumatic stress disorder and related symptoms: A systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Kirkehei Ingvild

    2008-09-01

    Full Text Available Abstract Background Early trauma-focused cognitive-behavioural therapy (TFCBT holds promise as a preventive intervention for people at risk of developing chronic post-traumatic stress disorder (PTSD. The aim of this review was to provide an updated evaluation of the effectiveness of early TFCBT on the prevention of PTSD in high risk populations. Methods We performed a systematic literature search in international electronic databases (MEDLINE, EMBASE, PsycINFO, CENTRAL, CINAHL, ISI and PILOTS and included randomised controlled trials comparing TFCBT delivered within 3 months of trauma, to alternative interventions. All included studies were critically appraised using a standardised checklist. Two independent reviewers selected studies for inclusion and assessed study quality. Data extraction was performed by one reviewer and controlled by another. Where appropriate, we entered study results into meta-analyses. Results Seven articles reporting the results of five RCTs were included. All compared TFCBT to supportive counselling (SC. The study population was patients with acute stress disorder (ASD in four trials, and with a PTSD diagnosis disregarding the duration criterion in the fifth trial. The overall relative risk (RR for a PTSD diagnosis was 0.56 (95% CI 0.42 to 0.76, 1.09 (95% CI 0.46 to 2.61 and 0.73 (95% CI 0.51 to 1.04 at 3–6 months, 9 months and 3–4 years post treatment, respectively. A subgroup analysis of the four ASD studies only resulted in RR = 0.36 (95% CI 0.17 to 0.78 for PTSD at 3–6 months. Anxiety and depression scores were generally lower in the TFCBT groups than in the SC groups. Conclusion There is evidence for the effectiveness of TFCBT compared to SC in preventing chronic PTSD in patients with an initial ASD diagnosis. As this evidence originates from one research team replications are necessary to assess generalisability. The evidence about the effectiveness of TFCBT in traumatised populations without an ASD

  6. Systematic review of the relationships between physical activity and health indicators in the early years (0-4 years

    Directory of Open Access Journals (Sweden)

    Valerie Carson

    2017-11-01

    Full Text Available Abstract Background Given the rapid development during the early years (0-4 years, an understanding of the health implications of physical activity is needed. The purpose of this systematic review was to examine the relationships between objectively and subjectively measured physical activity and health indicators in the early years. Methods Electronic databases were originally searched in April, 2016. Included studies needed to be peer-reviewed, written in English or French, and meet a priori study criteria. The population was apparently healthy children aged 1 month to 59.99 months/4.99 years. The intervention/exposure was objectively and subjectively measured physical activity. The comparator was various volumes, durations, frequencies, patterns, types, and intensities of physical activity. The outcomes were health indicators ranked as critical (adiposity, motor development, psychosocial health, cognitive development, fitness and important (bone and skeletal health, cardiometabolic health, and risks/harm. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE framework was used to assess the quality of evidence for each health indicator by each study design. Results Ninety-six studies representing 71,291 unique participants from 36 countries were included. Physical activity interventions were consistently (>60% of studies associated with improved motor and cognitive development, and psychosocial and cardiometabolic health. Across observational studies, physical activity was consistently associated with favourable motor development, fitness, and bone and skeletal health. For intensity, light- and moderate-intensity physical activity were not consistently associated with any health indicators, whereas moderate- to vigorous-intensity, vigorous-intensity, and total physical activity were consistently favourably associated with multiple health indicators. Across study designs, consistent favourable associations with

  7. Identifying Barriers to Delivering the Awakening and Breathing Coordination, Delirium, and Early Exercise/Mobility Bundle to Minimize Adverse Outcomes for Mechanically Ventilated Patients: A Systematic Review.

    Science.gov (United States)

    Costa, Deena Kelly; White, Matthew R; Ginier, Emily; Manojlovich, Milisa; Govindan, Sushant; Iwashyna, Theodore J; Sales, Anne E

    2017-08-01

    Improved outcomes are associated with the Awakening and Breathing Coordination, Delirium, and Early exercise/mobility bundle (ABCDE); however, implementation issues are common. As yet, no study has integrated the barriers to ABCDE to provide an overview of reasons for less successful efforts. The purpose of this review was to identify and catalog the barriers to ABCDE delivery based on a widely used implementation framework, and to provide a resource to guide clinicians in overcoming barriers to implementation. We searched MEDLINE via PubMed, CINAHL, and Scopus for original research articles from January 1, 2007, to August 31, 2016, that identified barriers to ABCDE implementation for adult patients in the ICU. Two reviewers independently reviewed studies, extracted barriers, and conducted thematic content analysis of the barriers, guided by the Consolidated Framework for Implementation Research. Discrepancies were discussed, and consensus was achieved. Our electronic search yielded 1,908 articles. After applying our inclusion/exclusion criteria, we included 49 studies. We conducted thematic content analysis of the 107 barriers and identified four classes of ABCDE barriers: (1) patient-related (ie, patient instability and safety concerns); (2) clinician-related (ie, lack of knowledge, staff safety concerns); (3) protocol-related (ie, unclear protocol criteria, cumbersome protocols to use); and, not previously identified in past reviews, (4) ICU contextual barriers (ie, interprofessional team care coordination). We provide the first, to our knowledge, systematic differential diagnosis of barriers to ABCDE delivery, moving beyond the conventional focus on patient-level factors. Our analysis offers a differential diagnosis checklist for clinicians planning ABCDE implementation to improve patient care and outcomes. Copyright © 2017 American College of Chest Physicians. All rights reserved.

  8. The added value of mifepristone to non-surgical treatment regimens for uterine evacuation in case of early pregnancy failure: a systematic review of the literature.

    Science.gov (United States)

    van den Berg, Joyce; Gordon, Bernardus B M; Snijders, Marcus P M L; Vandenbussche, Frank P H A; Coppus, Sjors F P J

    2015-12-01

    Early pregnancy failure (EPF) is a common complication of pregnancy. Surgical intervention carries a risk of complications and, therefore, medical treatment appears to be a safe alternative. Unfortunately, the current medical treatment with misoprostol alone has complete evacuation rates between 53% and 87%. Some reports suggest that sequential treatment with mifepristone and misoprostol leads to higher success rates than misoprostol alone. To evaluate the added value of mifepristone to current non-surgical treatment regimens in women with EPF we performed a systematic literature search. Electronic databases were searched: PubMed, Cochrane Library, Current Controlled Trials, and ClinicalTrials.gov. Clinical studies, both randomised and non-randomised trials, reporting on the added value of mifepristone to current non-surgical treatment regimens in women with EPF were included. Data of sixteen studies were extracted using a data extraction sheet (based on the Cochrane Consumers and Communication Review Group's data extraction template). The methodological quality was assessed using the Cochrane Collaboration Risk of Bias tool. In five randomised and eleven non-randomised trials, success rates of sequential treatment with mifepristone and misoprostol in case of EPF varied between 52% and 95%. Large heterogeneity existed in treatment regimens and comparators between studies. The existing evidence is insufficient to draw firm conclusions about the added value of mifepristone to misoprostol alone. A sufficiently powered randomised, double blinded placebo-controlled trial is urgently required to test whether, in EPF, the sequential combination of mifepristone with misoprostol is superior to misoprostol only. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  9. Biochemical and biophysical characterization of cell-free synthesized Rift Valley fever virus nucleoprotein capsids enables in vitro screening to identify novel antivirals.

    Science.gov (United States)

    Broce, Sean; Hensley, Lisa; Sato, Tomoharu; Lehrer-Graiwer, Joshua; Essrich, Christian; Edwards, Katie J; Pajda, Jacqueline; Davis, Christopher J; Bhadresh, Rami; Hurt, Clarence R; Freeman, Beverly; Lingappa, Vishwanath R; Kelleher, Colm A; Karpuj, Marcela V

    2016-05-14

    Viral capsid assembly involves the oligomerization of the capsid nucleoprotein (NP), which is an essential step in viral replication and may represent a potential antiviral target. An in vitro transcription-translation reaction using a wheat germ (WG) extract in combination with a sandwich ELISA assay has recently been used to identify small molecules with antiviral activity against the rabies virus. Here, we examined the application of this system to viruses with capsids with a different structure, such as the Rift Valley fever virus (RVFV), the etiological agent of a severe emerging infectious disease. The biochemical and immunological characterization of the in vitro-generated RVFV NP assembly products enabled the distinction between intermediately and highly ordered capsid structures. This distinction was used to establish a screening method for the identification of potential antiviral drugs for RVFV countermeasures. These results indicated that this unique analytical system, which combines nucleoprotein oligomerization with the specific immune recognition of a highly ordered capsid structure, can be extended to various viral families and used both to study the early stages of NP assembly and to assist in the identification of potential antiviral drugs in a cost-efficient manner. Reviewed by Jeffry Skolnick and Noah Isakov. For the full reviews please go to the Reviewers' comments section.

  10. Human Antiviral Protein IFIX Suppresses Viral Gene Expression during Herpes Simplex Virus 1 (HSV-1) Infection and Is Counteracted by Virus-induced Proteasomal Degradation.

    Science.gov (United States)

    Crow, Marni S; Cristea, Ileana M

    2017-04-01

    The interferon-inducible protein X (IFIX), a member of the PYHIN family, was recently recognized as an antiviral factor against infection with herpes simplex virus 1 (HSV-1). IFIX binds viral DNA upon infection and promotes expression of antiviral cytokines. How IFIX exerts its host defense functions and whether it is inhibited by the virus remain unknown. Here, we integrated live cell microscopy, proteomics, IFIX domain characterization, and molecular virology to investigate IFIX regulation and antiviral functions during HSV-1 infection. We find that IFIX has a dynamic localization during infection that changes from diffuse nuclear and nucleoli distribution in uninfected cells to discrete nuclear puncta early in infection. This is rapidly followed by a reduction in IFIX protein levels. Indeed, using immunoaffinity purification and mass spectrometry, we define IFIX interactions during HSV-1 infection, finding an association with a proteasome subunit and proteins involved in ubiquitin-proteasome processes. Using synchronized HSV-1 infection, microscopy, and proteasome-inhibition experiments, we demonstrate that IFIX co-localizes with nuclear proteasome puncta shortly after 3 h of infection and that its pyrin domain is rapidly degraded in a proteasome-dependent manner. We further demonstrate that, in contrast to several other host defense factors, IFIX degradation is not dependent on the E3 ubiquitin ligase activity of the viral protein ICP0. However, we show IFIX degradation requires immediate-early viral gene expression, suggesting a viral host suppression mechanism. The IFIX interactome also demonstrated its association with transcriptional regulatory proteins, including the 5FMC complex. We validate this interaction using microscopy and reciprocal isolations and determine it is mediated by the IFIX HIN domain. Finally, we show IFIX suppresses immediate-early and early viral gene expression during infection. Altogether, our study demonstrates that IFIX antiviral

  11. Decision Making with Regard to Antiviral Intervention during an Influenza Pandemic

    Science.gov (United States)

    Shim, Eunha; Chapman, Gretchen B.; Galvani, Alison P.

    2012-01-01

    Background Antiviral coverage is defined by the proportion of the population that takes antiviral prophylaxis or treatment. High coverage of an antiviral drug has epidemiological and evolutionary repercussions. Antivirals select for drug resistance within the population, and individuals may experience adverse effects. To determine optimal antiviral coverage in the context of an influenza outbreak, we compared 2 perspectives: 1) the individual level (the Nash perspective), and 2) the population level (utilitarian perspective). Methods We developed an epidemiological game-theoretic model of an influenza pandemic. The data sources were published literature and a national survey. The target population was the US population. The time horizon was 6 months. The perspective was individuals and the population overall. The interventions were antiviral prophylaxis and treatment. The outcome measures were the optimal coverage of antivirals in an influenza pandemic. Results At current antiviral pricing, the optimal Nash strategy is 0% coverage for prophylaxis and 30% coverage for treatment, whereas the optimal utilitarian strategy is 19% coverage for prophylaxis and 100% coverage for treatment. Subsidizing prophylaxis by $440 and treatment by $85 would bring the Nash and utilitarian strategies into alignment. For both prophylaxis and treatment, the optimal antiviral coverage decreases as pricing of antivirals increases. Our study does not incorporate the possibility of an effective vaccine and lacks probabilistic sensitivity analysis. Our survey also does not completely represent the US population. Because our model assumes a homogeneous population and homogeneous antiviral pricing, it does not incorporate heterogeneity of preference. Conclusions The optimal antiviral coverage from the population perspective and individual perspectives differs widely for both prophylaxis and treatment strategies. Optimal population and individual strategies for prophylaxis and treatment might

  12. A Systematic Review of the Effectiveness of Early Intervention and the Role of Parents in Language Development of Hearing Loss Children

    Directory of Open Access Journals (Sweden)

    Ehsan Shekari

    2017-03-01

    Discussion: Research showed the effectiveness of early intervention in the early development of language and vocabulary. In addition, early detection of hearing loss in the first 6 months of age has a positive impact on children and families interactions and consequently, on language and vocabulary development. The primary focus in the implementation of early intervention services is to reduce the negative effects of risk factors and facilitate optimum development over time. Finally, the combination of early diagnosis and early intervention for children with hearing impairment is necessary.

  13. Computational aspects of systematic biology.

    Science.gov (United States)

    Lilburn, Timothy G; Harrison, Scott H; Cole, James R; Garrity, George M

    2006-06-01

    We review the resources available to systematic biologists who wish to use computers to build classifications. Algorithm development is in an early stage, and only a few examples of integrated applications for systematic biology are available. The availability of data is crucial if systematic biology is to enter the computer age.

  14. Alpinone exhibited immunomodulatory and antiviral activities in Atlantic salmon.

    Science.gov (United States)

    Valenzuela, Beatriz; Rodríguez, Felipe E; Modak, Brenda; Imarai, Mónica

    2018-03-01

    In this study, we seek to identify flavonoids able to regulate the gene expression of a group of cytokines important for the control of infections in Atlantic salmon (Salmo salar). Particularly, we studied the potential immunomodulatory effects of two flavonoids, Alpinone and Pinocembrine, which were isolated and purified from resinous exudates of Heliotropium huascoense and Heliotropium sinuatum, respectively. The transcript levels of TNF-α and IL-1 (inflammatory cytokines), IFN-γ and IL-12 (T helper 1 type cytokines), IL4/13A (Th2-type cytokine), IL-17 (Th17 type cytokine) TGF-β1 (regulatory cytokine) and IFN-α (antiviral cytokine) were quantified by qRT-PCR in kidneys of flavonoid-treated and control fish. We demonstrated that the administration of a single intramuscular dose of purified Alpinone increased the transcriptional expression of five cytokines, named TNF-α, IL-1, IFN-α, IFN-γ and TGF-β1 in treated fish compared to untreated fish. Conversely, administration of purified Pinocembrine reduced the transcriptional expression of TNF-α, IL-1 and IL-12 in the kidney of treated fish. No other changes were observed. Interestingly, Alpinone also induced in vitro antiviral effects against Infectious Salmon Anaemia virus. Results showed that Alpinone but not Pinocembrine induces the expression of cytokines, which in vertebrates are essential to control viral infections while Pinocembrine reduces pro-inflammatory cytokines. Altogether results suggest that Alpinone is a good candidate to be further tested as immunostimulant and antiviral drug. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Predictors of poor retention on antiretroviral therapy as a major HIV drug resistance early warning indicator in Cameroon: results from a nationwide systematic random sampling

    Directory of Open Access Journals (Sweden)

    Serge Clotaire Billong

    2016-11-01

    Full Text Available Abstract Background Retention on lifelong antiretroviral therapy (ART is essential in sustaining treatment success while preventing HIV drug resistance (HIVDR, especially in resource-limited settings (RLS. In an era of rising numbers of patients on ART, mastering patients in care is becoming more strategic for programmatic interventions. Due to lapses and uncertainty with the current WHO sampling approach in Cameroon, we thus aimed to ascertain the national performance of, and determinants in, retention on ART at 12 months. Methods Using a systematic random sampling, a survey was conducted in the ten regions (56 sites of Cameroon, within the “reporting period” of October 2013–November 2014, enrolling 5005 eligible adults and children. Performance in retention on ART at 12 months was interpreted following the definition of HIVDR early warning indicator: excellent (>85%, fair (85–75%, poor (<75; and factors with p-value < 0.01 were considered statistically significant. Results Majority (74.4% of patients were in urban settings, and 50.9% were managed in reference treatment centres. Nationwide, retention on ART at 12 months was 60.4% (2023/3349; only six sites and one region achieved acceptable performances. Retention performance varied in reference treatment centres (54.2% vs. management units (66.8%, p < 0.0001; male (57.1% vs. women (62.0%, p = 0.007; and with WHO clinical stage I (63.3% vs. other stages (55.6%, p = 0.007; but neither for age (adults [60.3%] vs. children [58.8%], p = 0.730 nor for immune status (CD4351–500 [65.9%] vs. other CD4-staging [59.86%], p = 0.077. Conclusions Poor retention in care, within 12 months of ART initiation, urges active search for lost-to-follow-up targeting preferentially male and symptomatic patients, especially within reference ART clinics. Such sampling strategy could be further strengthened for informed ART monitoring and HIVDR prevention perspectives.

  16. Sexual risk factors for HIV infection in early and advanced HIV epidemics in sub-Saharan Africa: systematic overview of 68 epidemiological studies.

    Directory of Open Access Journals (Sweden)

    Li Chen

    2007-10-01

    Full Text Available It is commonly assumed that sexual risk factors for heterosexual HIV transmission in sub-Saharan Africa, such as multi-partner sex, paid sex and co-infections, become less important as HIV epidemics mature and prevalence increases.We conducted a systematic review of 68 African epidemiological studies from 1986 to 2006 involving 17,000 HIV positive adults and 73,000 controls. We used random-effects methods and stratified results by gender, time, background HIV prevalence rates and other variables. The number of sex partners, history of paid sex, and infection with herpes simplex virus (HSV-2 or other sexually-transmitted infections (STIs each showed significant associations with HIV infection. Among the general population, the odds ratio (OR of HIV infection for women reporting 3+ sex partners versus 0-2 was 3.64 (95%CI [2.87-4.62], with similar risks for men. About 9% of infected women reported ever having been paid for sex, versus 4% of control women (OR = 2.29, [1.45-3.62]. About 31% of infected men reported ever paying for sex versus 18% of uninfected men (OR = 1.75, [1.30-2.36]. HSV-2 infection carried the largest risk of HIV infection: OR = 4.62, [2.85-7.47] in women, and OR = 6.97, [4.68-10.38] in men. These risks changed little over time and stratification by lower and higher HIV background prevalence showed that risk ratios for most variables were larger in high prevalence settings. Among uninfected controls, the male-female differences in the number of sex partners and in paid sex were more extreme in the higher HIV prevalence settings than in the lower prevalence settings.Multi-partner sex, paid sex, STIs and HSV-2 infection are as important to HIV transmission in advanced as in early HIV epidemics. Even in high prevalence settings, prevention among people with high rates of partner change, such as female sex workers and their male clients, is likely to reduce transmission overall.

  17. Addressing the selectivity and toxicity of antiviral nucleosides.

    Science.gov (United States)

    Feng, Joy Y

    2018-01-01

    Nucleoside and nucleotide analogs have played significant roles in antiviral therapies and are valued for their impressive potency and high barrier to resistance. They have been approved for treatment of herpes simplex virus-1, HIV, HBV, HCV, and influenza, and new drugs are being developed for the treatment of RSV, Ebola, coronavirus MERS, and other emerging viruses. However, this class of compounds has also experienced a high attrition rate in clinical trials due to toxicity. In this review, we discuss the utility of different biochemical and cell-based assays and provide recommendations for assessing toxicity liability before entering animal toxicity studies.

  18. Antiviral therapy and prophylaxis of acute respiratory infections

    Directory of Open Access Journals (Sweden)

    L. V. Osidak

    2012-01-01

    Full Text Available Thearticle presents the results of years of studies (including biochemical and immunological of the effectiveness of application and prophylaxis (in relation to nosocomial infections and the safety of antiviral chemical preparation Arbidol in 694 children with influenza and influenza-like illness, including the coronavirus infection (43 children and combined lesions of respiratory tract (150, indicating the possible inclusion of the drug in the complex therapy for children with the listed diseases, regardless of the severity and nature of their course. The studies were conducted according to the regulated standard of test conditions and randomized clinical trials.

  19. Direct-acting antivirals for chronic hepatitis C

    DEFF Research Database (Denmark)

    Jakobsen, Janus C; Nielsen, Emil Eik; Feinberg, Joshua

    2017-01-01

    and Drug Administration (FDA) (www.fda.gov), and pharmaceutical company sources for ongoing or unpublished trials. Searches were last run in October 2016. SELECTION CRITERIA: Randomised clinical trials comparing DAAs versus no intervention or placebo, alone or with co-interventions, in adults with chronic......BACKGROUND: Millions of people worldwide suffer from hepatitis C, which can lead to severe liver disease, liver cancer, and death. Direct-acting antivirals (DAAs) are relatively new and expensive interventions for chronic hepatitis C, and preliminary results suggest that DAAs may eradicate...

  20. Efficacy and safety of direct-acting antivirals-based antiviral therapies for hepatitis C virus patients with stage 4-5 chronic kidney disease: a meta-analysis.

    Science.gov (United States)

    Li, Tao; Qu, Yundong; Guo, Ying; Wang, Yan; Wang, Lei

    2017-07-01

    The aim of this study was to assess the efficacy and safety of direct-acting antivirals (DAA)-based antiviral therapies for HCV patients with stage 4-5 chronic kidney disease. We conducted a systematic literature search in PubMed, EMBASE, Web of Science, and CENTRAL on the Cochrane Library without time and language limitations. The search strategy used was "(End stage renal disease OR chronic kidney failure OR severe renal impairment OR chronic kidney disease OR dialysis) AND (sofosbuvir OR simeprevir OR grazoprevir OR elbasvir OR ombitasvir OR paritaprevir OR ritonavir OR dasabuvir OR daclatasvir OR asuparevir OR direct-acting antiviral OR DAA)". Sustained virologic response at 12 weeks after the end of treatment (SVR12), adverse events (AEs) and/or serious adverse events (SAEs) with 95% confidence intervals (CI) were pooled. Eleven studies, comprising a total of 264 patients were included for our meta-analysis. The pooled SVR12 rate were 93.2% (95% CI 89.9%-95.9%, I 2 =0.0%), 89.4% (95% CI 82.0%-95.0%, I 2 =0.0%) and 94.7% (95% CI 91.0%-97.5%, I 2 =0.0%) in total population, patients with sofosbuvir-based therapies and patients with non-sofosbuvir-based therapies respectively. For HCV genotype 1 patients, the pooled SVR12 rate was 93.1% (95% CI 88.3%-96.7%, I 2 =20.0%). The pooled incidence of SAEs was 12.1% (95% CI 6.2%-19.7%, I 2 =55.0%). The pooled discontinuation rate because of AEs or SAEs in our meta-analysis was 2.2% (95% CI 0.8%-4.4%, I 2 =0.0%). DAA-based antiviral therapies are effective and well-tolerated for HCV patients with stage 4-5 chronic kidney disease. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Antiviral therapy and outcomes of patients with pneumonia caused by influenza A pandemic (H1N1 virus.

    Directory of Open Access Journals (Sweden)

    Shi-gui Yang

    Full Text Available BACKGROUND: There is limited data on the clinical outcome of patients with pandemic H1N1 (pH1N1 pneumonia who received oseltamivir treatment, especially when the treatment was administered more than 48 hours after symptom onset. METHODS: During the pandemic in 2009, a cohort of pH1N1 influenza pneumonia was built in China, and their clinical information was collected systematically, and analyzed with Cox models. RESULTS: 920 adults and 541 children with pneumonia who didn't receive corticosteroids were analyzed. In-hospital mortality was higher in adults who did not receive antiviral therapy (18.2% than those with who received oseltamivir ≤ 2 days (2.9%, between 2-5 days (4.6% and >5 days after illness onset (4.9%, p5 days, respectively. For males patients, aged ≥ 14 years and baseline PaO(2/FiO(23.8 mg/kg/d did not improve clinical outcome (mortality, higher dose 2.5% vs standard dose 2.8%, p>0.05. CONCLUSIONS: Antiviral therapy might reduce mortality of patients with pH1N1 pneumonia, even when initiated more than 48 hours after onset of illness. Greater protective effects might be in males, patients aged 14-60 years, and patients with PaO(2/FiO(2<200.

  2. Potencial antiviral da quercetina sobre o parvovírus canino Antiviral potencial of quercetin in canine parvovirus

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    O.V. Carvalho

    2013-04-01

    Full Text Available Avaliou-se o efeito do flavonoide quercetina na replicação do parvovírus canino in vitro por meio do ensaio de determinação da atividade virucida (ensaio 1, ensaio de determinação da atividade sobre a célula (ensaio 2 e ensaio de tempo de adição das drogas em diferentes etapas do ciclo replicativo viral (ensaio 3. A quercetina apresentou significante atividade antiviral, com valores máximos de redução do título viral de 96,3% no ensaio 1, 90% no ensaio 2 e 90% no ensaio 3. Os efeitos mais expressivos ocorreram nas etapas de adsorção e penetração viral. Os resultados deste trabalho sugerem a importância da quercetina para a medicina veterinária.The in vitro effect of the flavonoid quercetin against canine parvovirus was evaluated. The antiviral activity of quercetin was evaluated by determining the virucidal activity (assay 1, determining the activity on the cell (assay 2 and using the time of addition assay to test the inhibition of the viral replication cycle (assay 3. Quercetin showed a significant antiviral activity, with maximum viral titer reduction of 96.3% in assay 1, 90% in assay 2 and 90% in assay 3. The most expressive effects occurred in the stages of viral adsorption and penetration. The results show the importance of quercetin for veterinary medicine.

  3. Systematic review of influenza resistance to the neuraminidase inhibitors

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    Boivin Guy

    2011-05-01

    Full Text Available Abstract Background Antivirals play a critical role in the prevention and the management of influenza. One class of antivirals, neuraminidase inhibitors (NAIs, is effective against all human influenza viruses. Currently there are two NAI drugs which are licensed worldwide: oseltamivir (Tamiflu® and zanamivir (Relenza®; and two drugs which have received recent approval in Japan: peramivir and laninamivir. Until recently, the prevalence of antiviral resistance has been relatively low. However, almost all seasonal H1N1 strains that circulated in 2008-09 were resistant to oseltamivir whereas about 1% of tested 2009 pandemic H1N1 viruses were found to be resistant to oseltamivir. To date, no studies have demonstrated widespread resistance to zanamivir. It seems likely that the literature on antiviral resistance associated with oseltamivir as well as zanamivir is now sufficiently comprehensive to warrant a systematic review. The primary objectives were to systematically review the literature to determine the incidence of resistance to oseltamivir, zanamivir, and peramivir in different population groups as well as assess the clinical consequences of antiviral resistance. Methods We searched MEDLINE and EMBASE without language restrictions in September 2010 to identify studies reporting incidence of resistance to oseltamivir, zanamivir, and peramivir. We used forest plots and meta-analysis of incidence of antiviral resistance associated with the three NAIs. Subgroup analyses were done across a number of population groups. Meta-analysis was also performed to evaluate associations between antiviral resistance and clinical complications and symptoms. Results We identified 19 studies reporting incidence of antiviral resistance. Meta-analysis of 15 studies yielded a pooled incidence rate for oseltamivir resistance of 2.6% (95%CI 0.7% to 5.5%. The incidence rate for all zanamivir resistance studies was 0%. Only one study measured incidence of antiviral

  4. Cost-effectiveness of antiviral therapy during late pregnancy to prevent perinatal transmission of hepatitis B virus

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    Wenjun Wang

    2016-03-01

    Full Text Available Background. Hepatitis B virus (HBV infections are perinatally transmitted from chronically infected mothers. Supplemental antiviral therapy during late pregnancy with lamivudine (LAM, telbivudine (LdT, or tenofovir (TDF can substantially reduce perinatal HBV transmission compared to postnatal immunoprophylaxis (IP alone. However, the cost-effectiveness of these measures is not clear. Aim. This study evaluated the cost-effectiveness from a societal perspective of supplemental antiviral agents for preventing perinatal HBV transmission in mothers with high viral load (>6 log10 copies/mL. Methods. A systematic review and network meta-analysis were performed for the risk of perinatal HBV transmission with antiviral therapies. A decision analysis was conducted to evaluate the clinical and economic outcomes in China of four competing strategies: postnatal IP alone (strategy IP, or in combination with perinatal LAM (strategy LAM + IP, LdT (strategy LdT + IP, or TDF (strategy TDF + IP. Antiviral treatments were administered from week 28 of gestation to 4 weeks after birth. Outcomes included treatment-related costs, number of infections, and quality-adjusted life years (QALYs. One- and two-way sensitivity analyses were performed to identify influential clinical and cost-related variables. Probabilistic sensitivity analyses were used to estimate the probabilities of being cost-effective for each strategy. Results. LdT + IP and TDF + IP averted the most infections and HBV-related deaths, and gained the most QALYs. IP and TDF + IP were dominated as they resulted in less or equal QALYs with higher associated costs. LdT + IP had an incremental $2,891 per QALY gained (95% CI [$932–$20,372] compared to LAM + IP (GDP per capita for China in 2013 was $6,800. One-way sensitivity analyses showed that the cost-effectiveness of LdT + IP was only sensitive to the relative risk of HBV transmission comparing LdT + IP with LAM + IP. Probabilistic sensitivity analyses

  5. Antiviral Effects of Saffron and its Major Ingredients.

    Science.gov (United States)

    Soleymani, Sepehr; Zabihollahi, Rezvan; Shahbazi, Sepideh; Bolhassani, Azam

    2018-01-01

    The lack of an effective vaccine against viral infections, toxicity of the synthetic anti-viral drugs and the generation of resistant viral strains led to discover novel inhibitors. Recently, saffron and its compounds were used to treat different pathological conditions. In this study, we tested the anti-HSV-1 and anti-HIV-1 activities of Iranian saffron extract and its major ingredients including crocin and picrocrocin as well as cytotoxicity in vitro. The data showed that the aqueous saffron extract was not active against HIV-1 and HSV-1 virions at certain doses (i.e., a mild activity), but crocin and picrocrocin indicated significant anti-HSV-1 and also anti-HIV-1 activities. Crocin inhibited the HSV replication at before and after entry of virions into Vero cells. Indeed, crocin carotenoid suppressed HSV penetration in the target cells as well as disturbed virus replication after entry into the cells. Picrocrocin was also effective for inhibiting virus entry and also its replication. This monoterpen aldehyde showed higher anti-HSV effects after virus penetrating in the cells. Generally, these sugar-containing compounds extracted from saffron showed to be effective antiherpetic drug candidates. The recent study is the first report suggesting antiviral activities for saffron extract and its major ingredients. Crocin and picrocrocin could be a promising anti-HSV and anti-HIV agent for herbal therapy against viral infections. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. Mechanisms of Hepatitis C Viral Resistance to Direct Acting Antivirals.

    Science.gov (United States)

    Ahmed, Asma; Felmlee, Daniel J

    2015-12-18

    There has been a remarkable transformation in the treatment of chronic hepatitis C in recent years with the development of direct acting antiviral agents targeting virus encoded proteins important for viral replication including NS3/4A, NS5A and NS5B. These agents have shown high sustained viral response (SVR) rates of more than 90% in phase 2 and phase 3 clinical trials; however, this is slightly lower in real-life cohorts. Hepatitis C virus resistant variants are seen in most patients who do not achieve SVR due to selection and outgrowth of resistant hepatitis C virus variants within a given host. These resistance associated mutations depend on the class of direct-acting antiviral drugs used and also vary between hepatitis C virus genotypes and subtypes. The understanding of these mutations has a clear clinical implication in terms of choice and combination of drugs used. In this review, we describe mechanism of action of currently available drugs and summarize clinically relevant resistance data.

  7. Mechanisms of Hepatitis C Viral Resistance to Direct Acting Antivirals

    Directory of Open Access Journals (Sweden)

    Asma Ahmed

    2015-12-01

    Full Text Available There has been a remarkable transformation in the treatment of chronic hepatitis C in recent years with the development of direct acting antiviral agents targeting virus encoded proteins important for viral replication including NS3/4A, NS5A and NS5B. These agents have shown high sustained viral response (SVR rates of more than 90% in phase 2 and phase 3 clinical trials; however, this is slightly lower in real-life cohorts. Hepatitis C virus resistant variants are seen in most patients who do not achieve SVR due to selection and outgrowth of resistant hepatitis C virus variants within a given host. These resistance associated mutations depend on the class of direct-acting antiviral drugs used and also vary between hepatitis C virus genotypes and subtypes. The understanding of these mutations has a clear clinical implication in terms of choice and combination of drugs used. In this review, we describe mechanism of action of currently available drugs and summarize clinically relevant resistance data.

  8. RNAi and Antiviral Defense in the Honey Bee

    Science.gov (United States)

    Brutscher, Laura M.; Flenniken, Michelle L.

    2015-01-01

    Honey bees play an important agricultural and ecological role as pollinators of numerous agricultural crops and other plant species. Therefore, investigating the factors associated with high annual losses of honey bee colonies in the US is an important and active area of research. Pathogen incidence and abundance correlate with Colony Collapse Disorder- (CCD-) affected colonies in the US and colony losses in the US and in some European countries. Honey bees are readily infected by single-stranded positive sense RNA viruses. Largely dependent on the host immune response, virus infections can either remain asymptomatic or result in deformities, paralysis, or death of adults or larvae. RNA interference (RNAi) is an important antiviral defense mechanism in insects, including honey bees. Herein, we review the role of RNAi in honey bee antiviral defense and highlight some parallels between insect and mammalian immune systems. A more thorough understanding of the role of pathogens on honey bee health and the immune mechanisms bees utilize to combat infectious agents may lead to the development of strategies that enhance honey bee health and result in the discovery of additional mechanisms of immunity in metazoans. PMID:26798663

  9. RNAi and Antiviral Defense in the Honey Bee

    Directory of Open Access Journals (Sweden)

    Laura M. Brutscher

    2015-01-01

    Full Text Available Honey bees play an important agricultural and ecological role as pollinators of numerous agricultural crops and other plant species. Therefore, investigating the factors associated with high annual losses of honey bee colonies in the US is an important and active area of research. Pathogen incidence and abundance correlate with Colony Collapse Disorder- (CCD- affected colonies in the US and colony losses in the US and in some European countries. Honey bees are readily infected by single-stranded positive sense RNA viruses. Largely dependent on the host immune response, virus infections can either remain asymptomatic or result in deformities, paralysis, or death of adults or larvae. RNA interference (RNAi is an important antiviral defense mechanism in insects, including honey bees. Herein, we review the role of RNAi in honey bee antiviral defense and highlight some parallels between insect and mammalian immune systems. A more thorough understanding of the role of pathogens on honey bee health and the immune mechanisms bees utilize to combat infectious agents may lead to the development of strategies that enhance honey bee health and result in the discovery of additional mechanisms of immunity in metazoans.

  10. Antiviral Activity of Natural Products Extracted from Marine Organisms

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    Sobia Tabassum

    2011-11-01

    Full Text Available Many epidemics have broken out over the centuries. Hundreds and thousands of humans have died over a disease. Available treatments for infectious diseases have always been limited. Some infections are more deadly than the others, especially viral pathogens. These pathogens have continuously resisted all kinds of medical treatment, due to a need for new treatments to be developed. Drugs are present in nature and are also synthesized in vitro and they help in combating diseases and restoring health. Synthesizing drugs is a hard and time consuming task, which requires a lot of man power and financial aid. However, the natural compounds are just lying around on the earth, may it be land or water. Over a thousand novel compounds isolated from marine organisms are used as antiviral agents. Others are being pharmacologically tested. Today, over forty antiviral compounds are present in the pharmacological market. Some of these compounds are undergoing clinical and pre-clinical stages. Marine compounds are paving the way for a new trend in modern medicine.

  11. New antivirals for the treatment of chronic hepatitis B.

    Science.gov (United States)

    Soriano, Vincent; Barreiro, Pablo; Benitez, Laura; Peña, Jose M; de Mendoza, Carmen

    2017-07-01

    Current treatment with oral nucleos(t)ides entecavir or tenofovir provide sustained suppression of HBV replication and clinical benefit in most chronic hepatitis B virus (HBV) infected persons. However, HBV rebound generally occurs upon drug discontinuation due to persistence of genomic HBV reservoirs as episomic cccDNA and chromosomic integrated HBV-DNA. There is renewed enthusiasm on HBV drug discovery following recent successes with antivirals for hepatitis C and immunotherapies for some cancers. Areas covered: New drugs that target distinct steps of the HBV life cycle are been developed, including inhibitors of viral entry, new polymerase inhibitors, capsid and assembly inhibitors, virus release blockers, and disruptors of cccDNA formation and transcription. Alongside these antivirals, agents that enhance anti-HBV specific immune responses are being tested, including TLR agonists, checkpoint inhibitors and therapeutic vaccines. Expert opinion: The achievement of a 'functional cure' for chronic HBV infection, with sustained HBsAg clearance and undetectable viremia once medications are stopped, represents the next step in the pace towards HBV elimination. Hopefully, the combination of new drugs that eliminate or functionally inactivate the genomic HBV reservoirs (cccDNA and integrated HBV-DNA) along with agents that enhance or activate immune responses against HBV will lead to a 'definitive cure' for chronic HBV infection.

  12. Down-Regulation of p53 by Double-Stranded RNA Modulates the Antiviral Response

    Science.gov (United States)

    Marques, Joao T.; Rebouillat, Dominique; Ramana, Chilakamarti V.; Murakami, Junko; Hill, Jason E.; Gudkov, Andrei; Silverman, Robert H.; Stark, George R.; Williams, Bryan R. G.

    2005-01-01

    p53 has been well characterized as a tumor suppressor gene, but its role in antiviral defense remains unclear. A recent report has demonstrated that p53 can be induced by interferons and is activated after vesicular stomatitis virus (VSV) infection. We observed that different nononcogenic viruses, including encephalomyocarditis virus (EMCV) and human parainfluenza virus type 3 (HPIV3), induced down-regulation of p53 in infected cells. Double-stranded RNA (dsRNA) and a mutant vaccinia virus lacking the dsRNA binding protein E3L can also induce this effect, indicating that dsRNA formed during viral infection is likely the trigger for down-regulation of p53. The mechanism of down-regulation of p53 by dsRNA relies on translation inhibition mediated by the PKR and RNase L pathways. In the absence of p53, the replication of both EMCV and HPIV3 was retarded, whereas, conversely, VSV replication was enhanced. Cell cycle analysis indicated that wild-type (WT) but not p53 knockout (KO) fibroblasts undergo an early-G1 arrest following dsRNA treatment. Moreover, in WT cells the onset of dsRNA-induced apoptosis begins after p53 levels are down-regulated, whereas p53 KO cells, which lack the early-G1 arrest, rapidly undergo apoptosis. Hence, our data suggest that the down-regulation of p53 facilitates apoptosis, thereby limiting viral replication. PMID:16103161

  13. Synthesis, Antiviral Bioactivity of Novel 4-Thioquinazoline Derivatives Containing Chalcone Moiety

    Directory of Open Access Journals (Sweden)

    Zhihua Wan

    2015-06-01

    Full Text Available A series of novel 4-thioquinazoline derivatives containing chalcone moiety were designed, synthesized and systematically evaluated for their antiviral activity against TMV. The bioassay results showed that most of these compounds exhibited moderate to good anti-TMV activity. In particular, compounds M2 and M6 possessed appreciable protection activities against TMV in vivo, with 50% effective concentration (EC50 values of 138.1 and 154.8 μg/mL, respectively, which were superior to that of Ribavirin (436.0 μg/mL. The results indicated that chalcone derivatives containing 4-thioquinazoline moiety could effectively control TMV. Meanwhile, the structure-activity relationship (SAR of the target compounds, studied using the three-dimensional quantitative structure-activity relationship (3D-QSAR method of comparative molecular field analysis (CoMFA based on the protection activities against TMV, demonstrated that the CoMFA model exhibited good predictive ability with the cross-validated q2 and non-cross-validated r2 values of 0.674 and 0.993, respectively. Meanwhile, the microscale thermophoresis (MST experimental showed that the compound M6 may interaction with the tobacco mosaic virus coat protein (TMV CP.

  14. Antiviral effect of diammonium glycyrrhizinate on cell infection by porcine parvovirus

    Science.gov (United States)

    Porcine parvovirus (PPV) can cause reproductive failure in swine resulting in economic losses to the industry. Antiviral effects of diammonium glycyrrhizinate (DG) have been reported on several animal viruses; however, to date it has yet to be tested on PPV. In this study, the antiviral activity of ...

  15. Evaluation of in vitro antiviral activity of a brown alga ( Cystoseira ...

    African Journals Online (AJOL)

    The hot water extract of a brown marine alga, Cystoseira myrica, from the Persian Gulf was evaluated as an antiviral compound against KOS strain of HSV-1 in cell culture. The extract exhibited antiviral activity against herpes simplex virus type 1 (HSV-1) not only during absorption of virus to the cells, but also on post ...

  16. Antiviral activity of Aloe vera against herpes simplex virus type 2: An ...

    African Journals Online (AJOL)

    SERVER

    2007-08-06

    Aug 6, 2007 ... In this study we tested the antiviral activity of a crude hot glycerine extract of Aloe vera gel which was grown in Bushehr (Southwest of Iran) against HSV-2 replication in Vero cell line. The extract showed antiviral activity against HSV-2 not only before attachment and entry of virus to the Vero cells but also.

  17. Coxsackievirus cloverleaf RNA containing a 5' triphosphate triggers an antiviral response via RIG-I activation

    NARCIS (Netherlands)

    Feng, Qian; Langereis, Martijn A; Olagnier, David; Chiang, Cindy; van de Winkel, Roel; van Essen, Peter; Zoll, Jan; Hiscott, John; van Kuppeveld, Frank J M

    2014-01-01

    Upon viral infections, pattern recognition receptors (PRRs) recognize pathogen-associated molecular patterns (PAMPs) and stimulate an antiviral state associated with the production of type I interferons (IFNs) and inflammatory markers. Type I IFNs play crucial roles in innate antiviral responses by

  18. Antiviral treatment for chronic hepatitis C in patients with human immunodeficiency virus

    DEFF Research Database (Denmark)

    Iorio, Alfonso; Marchesini, Emanuela; Awad, Tahany

    2010-01-01

    Antiviral treatment for chronic hepatitis C may be less effective if patients are co-infected with human immunodeficiency virus (HIV).......Antiviral treatment for chronic hepatitis C may be less effective if patients are co-infected with human immunodeficiency virus (HIV)....

  19. Design, Synthesis and Antiviral Activity Studies of Schizonepetin Derivatives

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    Anwei Ding

    2013-08-01

    Full Text Available A series of schizonepetin derivatives have been designed and synthesized in order to obtain potent antivirus agents. The antiviral activity against HSV-1 and influenza virus H3N2 as well as the cytotoxicity of these derivatives was evaluated by using cytopathic effect (CPE inhibition assay in vitro. Compounds M2, M4, M5 and M34 showed higher inhibitory activity against HSV-1 virus with the TC50 values being in micromole. Compounds M28, M33, and M35 showed higher inhibitory activity against influenza virus H3N2 with their TC50 values being 96.4, 71.0 and 75.4 μM, respectively. Preliminary biological activity evaluation indicated that the anti-H3N2 and anti-HSV-1 activities improved obviously through the introduction of halogen into the structure of schizonepetin.

  20. Identification and Analysis of Antiviral Compounds Against Poliovirus.

    Science.gov (United States)

    Leyssen, Pieter; Franco, David; Tijsma, Aloys; Lacroix, Céline; De Palma, Armando; Neyts, Johan

    2016-01-01

    The Global Polio Eradication Initiative, launched in 1988, had as its goal the eradication of polio worldwide by the year 2000 through large-scale vaccinations campaigns with the live attenuated oral PV vaccine (OPV) (Griffiths et al., Biologicals 34:73-74, 2006). Despite substantial progress, polio remains endemic in several countries and new imported cases are reported on a regular basis ( http://www.polioeradication.org/casecount.asp ).It was recognized by the poliovirus research community that developing antivirals against poliovirus would be invaluable in the post-OPV era. Here, we describe three methods essential for the identification of selective inhibitors of poliovirus replication and for determining their mode of action by time-of-drug-addition studies as well as by the isolation of compound-resistant poliovirus variants.

  1. Resistance to Rhabdoviridae Infection and Subversion of Antiviral Responses

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    Danielle Blondel

    2015-07-01

    Full Text Available Interferon (IFN treatment induces the expression of hundreds of IFN-stimulated genes (ISGs. However, only a selection of their products have been demonstrated to be responsible for the inhibition of rhabdovirus replication in cultured cells; and only a few have been shown to play a role in mediating the antiviral response in vivo using gene knockout mouse models. IFNs inhibit rhabdovirus replication at different stages via the induction of a variety of ISGs. This review will discuss how individual ISG products confer resistance to rhabdoviruses by blocking viral entry, degrading single stranded viral RNA, inhibiting viral translation or preventing release of virions from the cell. Furthermore, this review will highlight how these viruses counteract the host IFN system.

  2. Resistance to Rhabdoviridae Infection and Subversion of Antiviral Responses.

    Science.gov (United States)

    Blondel, Danielle; Maarifi, Ghizlane; Nisole, Sébastien; Chelbi-Alix, Mounira K

    2015-07-07

    Interferon (IFN) treatment induces the expression of hundreds of IFN-stimulated genes (ISGs). However, only a selection of their products have been demonstrated to be responsible for the inhibition of rhabdovirus replication in cultured cells; and only a few have been shown to play a role in mediating the antiviral response in vivo using gene knockout mouse models. IFNs inhibit rhabdovirus replication at different stages via the induction of a variety of ISGs. This review will discuss how individual ISG products confer resistance to rhabdoviruses by blocking viral entry, degrading single stranded viral RNA, inhibiting viral translation or preventing release of virions from the cell. Furthermore, this review will highlight how these viruses counteract the host IFN system.

  3. Resistance to Rhabdoviridae Infection and Subversion of Antiviral Responses

    Science.gov (United States)

    Blondel, Danielle; Maarifi, Ghizlane; Nisole, Sébastien; Chelbi-Alix, Mounira K.

    2015-01-01

    Interferon (IFN) treatment induces the expression of hundreds of IFN-stimulated genes (ISGs). However, only a selection of their products have been demonstrated to be responsible for the inhibition of rhabdovirus replication in cultured cells; and only a few have been shown to play a role in mediating the antiviral response in vivo using gene knockout mouse models. IFNs inhibit rhabdovirus  replication at different stages via the induction of a variety of ISGs. This review will discuss how individual ISG products confer resistance to rhabdoviruses by blocking viral entry, degrading single stranded viral RNA, inhibiting viral translation or preventing release of virions from the cell. Furthermore, this review will highlight how these viruses counteract the host IFN system. PMID:26198243

  4. Towards antiviral therapies for treating dengue virus infections.

    Science.gov (United States)

    Kaptein, Suzanne Jf; Neyts, Johan

    2016-10-01

    Dengue virus is an emerging human pathogen that poses a huge public health burden by infecting annually about 390 million individuals of which a quarter report with clinical manifestations. Although progress has been made in understanding dengue pathogenesis, a licensed vaccine or antiviral therapy against this virus is still lacking. Treatment of patients is confined to symptomatic alleviation and supportive care. The development of dengue therapeutics thus remains of utmost importance. This review focuses on the few molecules that were evaluated in dengue virus-infected patients: balapiravir, chloroquine, lovastatin, prednisolone and celgosivir. The lessons learned from these clinical trials can be very helpful for the design of future trials for the next generation of dengue virus inhibitors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Optimal antiviral switching to minimize resistance risk in HIV therapy.

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    Rutao Luo

    Full Text Available The development of resistant strains of HIV is the most significant barrier to effective long-term treatment of HIV infection. The most common causes of resistance development are patient noncompliance and pre-existence of resistant strains. In this paper, methods of antiviral regimen switching are developed that minimize the risk of pre-existing resistant virus emerging during therapy switches necessitated by virological failure. Two distinct cases are considered; a single previous virological failure and multiple virological failures. These methods use optimal control approaches on experimentally verified mathematical models of HIV strain competition and statistical models of resistance risk. It is shown that, theoretically, order-of-magnitude reduction in risk can be achieved, and multiple previous virological failures enable greater success of these methods in reducing the risk of subsequent treatment failures.

  6. Griffithsin: An Antiviral Lectin with Outstanding Therapeutic Potential

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    Sabrina Lusvarghi

    2016-10-01

    Full Text Available Griffithsin (GRFT, an algae-derived lectin, is one of the most potent viral entry inhibitors discovered to date. It is currently being developed as a microbicide with broad-spectrum activity against several enveloped viruses. GRFT can inhibit human immunodeficiency virus (HIV infection at picomolar concentrations, surpassing the ability of most anti-HIV agents. The potential to inhibit other viruses as well as parasites has also been demonstrated. Griffithsin’s antiviral activity stems from its ability to bind terminal mannoses present in high-mannose oligosaccharides and crosslink these glycans on the surface of the viral envelope glycoproteins. Here, we review structural and biochemical studies that established mode of action and facilitated construction of GRFT analogs, mechanisms that may lead to resistance, and in vitro and pre-clinical results that support the therapeutic potential of this lectin.

  7. Antiviral Activity of Some Plants Used in Nepalese Traditional Medicine

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    M. Rajbhandari

    2009-01-01

    Full Text Available Methanolic extracts of 41 plant species belonging to 27 families used in the traditional medicine in Nepal have been investigated for in vitro antiviral activity against Herpes simplex virus type 1 (HSV-1 and influenza virus A by dye uptake assay in the systems HSV-1/Vero cells and influenza virus A/MDCK cells. The extracts of Astilbe rivularis, Bergenia ciliata, Cassiope fastigiata and Thymus linearis showed potent anti-herpes viral activity. The extracts of Allium oreoprasum, Androsace strigilosa, Asparagus filicinus, Astilbe rivularis, Bergenia ciliata and Verbascum thapsus exhibited strong anti-influenza viral activity. Only the extracts of A. rivularis and B. ciliata demonstrated remarkable activity against both viruses.

  8. Direct-acting antivirals for chronic hepatitis C

    DEFF Research Database (Denmark)

    Jakobsen, Janus C; Nielsen, Emil Eik; Feinberg, Joshua

    2017-01-01

    BACKGROUND: Millions of people worldwide suffer from hepatitis C, which can lead to severe liver disease, liver cancer, and death. Direct-acting antivirals (DAAs), e.g. sofosbuvir, are relatively new and expensive interventions for chronic hepatitis C, and preliminary results suggest that DAAs may...... eradicate hepatitis C virus (HCV) from the blood (sustained virological response). Sustained virological response (SVR) is used by investigators and regulatory agencies as a surrogate outcome for morbidity and mortality, based solely on observational evidence. However, there have been no randomised trials...... hepatitis C-related morbidity, serious adverse events, and health-related quality of life. Our secondary outcomes were all-cause mortality, ascites, variceal bleeding, hepato-renal syndrome, hepatic encephalopathy, hepatocellular carcinoma, non-serious adverse events (each reported separately), and SVR. We...

  9. Evaluation of Systematic Assessment of Asthma-Like Symptoms and Tobacco Smoke Exposure in Early Childhood by Well-Child Professionals: A Randomised Trial

    NARCIS (Netherlands)

    Groen, E.; van der Valk, R.J.P.; Mohangoo, A.D.; van der Wouden, J.C.; Duijts, L.; Jaddoe, V.W.; Hofman, A.; Koning, H.J.; de Jongste, J.C.; Raat, H.

    2014-01-01

    Objectives: This study aimed to evaluate the effectiveness of systematic assessment of asthma-like symptoms and environmental tobacco smoke (ETS) exposure during regular preventive well-child visits between age 1 and 4 years by wellchild professionals. Methods: Sixteen well-child centres in

  10. Evaluation of systematic assessment of asthma-like symptoms and tobacco smoke exposure in early childhood by well-child professionals: A randomised trial

    NARCIS (Netherlands)

    Hafkamp-de Groen, E.; Valk, R.J.P. van der; Mohangoo, A.D.; Wouden, J.C. van der; Duijts, L.; Jaddoe, V.W.; Hofman, A.; Koning, H.J. de; Jongste, J.C. de; Raat, H.

    2014-01-01

    Objectives: This study aimed to evaluate the effectiveness of systematic assessment of asthma-like symptoms and environmental tobacco smoke (ETS) exposure during regular preventive well-child visits between age 1 and 4 years by wellchild professionals. Methods: Sixteen well-child centres in

  11. Evidence of the innate antiviral and neuroprotective properties of progranulin.

    Directory of Open Access Journals (Sweden)

    Hyeon-Sook Suh

    Full Text Available Compelling data exist that show that normal levels of progranulin (PGRN are required for successful CNS aging. PGRN production is also modulated by inflammation and infection, but no data are available on the production and role of PGRN during CNS HIV infection.To determine the relationships between PGRN and HIV disease, neurocognition, and inflammation, we analyzed 107 matched CSF and plasma samples from CHARTER, a well-characterized HIV cohort. Levels of PGRN were determined by ELISA and compared to levels of several inflammatory mediators (IFNγ, IL-6, IL-10, IP-10, MCP-1, TNFα, IL-1β, IL-4 and IL-13, as well as clinical, virologic and demographic parameters. The relationship between HIV infection and PGRN was also examined in HIV-infected primary human microglial cultures.In plasma, PGRN levels correlated with the viral load (VL, p<0.001. In the CSF of subjects with undetectable VL, lower PGRN was associated with neurocognitive impairment (p = 0.046. CSF PGRN correlated with CSF IP-10, TNFα and IL-10, and plasma PGRN correlated with plasma IP-10. In vitro, microglial HIV infection increased PGRN production and PGRN knockdown increased HIV replication, demonstrating that PGRN is an innate antiviral protein.We propose that PGRN plays dual roles in people living with HIV disease. With active HIV replication, PGRN is induced in infected macrophages and microglia and functions as an antiviral protein. In individuals without active viral replication, decreased PGRN production contributes to neurocognitive dysfunction, probably through a diminution of its neurotrophic functions. Our results have implications for the pathogenesis, biomarker studies and therapy for HIV diseases including HIV-associated neurocognitive dysfunction (HAND.

  12. Evasion of the Interferon-Mediated Antiviral Response by Filoviruses

    Directory of Open Access Journals (Sweden)

    Washington B. Cárdenas

    2010-01-01

    Full Text Available The members of the filoviruses are recognized as some of the most lethal viruses affecting human and non-human primates. The only two genera of the Filoviridae family, Marburg virus (MARV and Ebola virus (EBOV, comprise the main etiologic agents of severe hemorrhagic fever outbreaks in central Africa, with case fatality rates ranging from 25 to 90%. Fatal outcomes have been associated with a late and dysregulated immune response to infection, very likely due to the virus targeting key host immune cells, such as macrophages and dendritic cells (DCs that are necessary to mediate effective innate and adaptive immune responses. Despite major progress in the development of vaccine candidates for filovirus infections, a licensed vaccine or therapy for human use is still not available. During the last ten years, important progress has been made in understanding the molecular mechanisms of filovirus pathogenesis. Several lines of evidence implicate the impairment of the host interferon (IFN antiviral innate immune response by MARV or EBOV as an important determinant of virulence. In vitro and in vivo experimental infections with recombinant Zaire Ebola virus (ZEBOV, the best characterized filovirus, demonstrated that the viral protein VP35 plays a key role in inhibiting the production of IFN-α/β. Further, the action of VP35 is synergized by the inhibition of cellular responses to IFN-α/β by the minor matrix viral protein VP24. The dual action of these viral proteins may contribute to an efficient initial virus replication and dissemination in the host. Noticeably, the analogous function of these viral proteins in MARV has not been reported. Because the IFN response is a major component of the innate immune response to virus infection, this chapter reviews recent findings on the molecular mechanisms of IFN-mediated antiviral evasion by filovirus infection.

  13. Molecular evolution of the primate antiviral restriction factor tetherin.

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    Jun Liu

    Full Text Available BACKGROUND: Tetherin is a recently identified antiviral restriction factor that restricts HIV-1 particle release in the absence of the HIV-1 viral protein U (Vpu. It is reminiscent of APOBEC3G and TRIM5a that also antagonize HIV. APOBEC3G and TRIM5a have been demonstrated to evolve under pervasive positive selection throughout primate evolution, supporting the red-queen hypothesis. Therefore, one naturally presumes that Tetherin also evolves under pervasive positive selection throughout primate evolution and supports the red-queen hypothesis. Here, we performed a detailed evolutionary analysis to address this presumption. METHODOLOGY/PRINCIPAL FINDINGS: Results of non-synonymous and synonymous substitution rates reveal that Tetherin as a whole experiences neutral evolution rather than pervasive positive selection throughout primate evolution, as well as in non-primate mammal evolution. Sliding-window analyses show that the regions of the primate Tetherin that interact with viral proteins are under positive selection or relaxed purifying selection. In particular, the sites identified under positive selection generally focus on these regions, indicating that the main selective pressure acting on the primate Tetherin comes from virus infection. The branch-site model detected positive selection acting on the ancestral branch of the New World Monkey lineage, suggesting an episodic adaptive evolution. The positive selection was also found in duplicated Tetherins in ruminants. Moreover, there is no bias in the alterations of amino acids in the evolution of the primate Tetherin, implying that the primate Tetherin may retain broad spectrum of antiviral activity by maintaining structure stability. CONCLUSIONS/SIGNIFICANCE: These results conclude that the molecular evolution of Tetherin may be attributed to the host-virus arms race, supporting the Red Queen hypothesis, and Tetherin may be in an intermediate stage in transition from neutral to pervasive

  14. An antiviral defense role of AGO2 in plants.

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    Jagger J W Harvey

    2011-01-01

    Full Text Available Argonaute (AGO proteins bind to small-interfering (siRNAs and micro (miRNAs to target RNA silencing against viruses, transgenes and in regulation of mRNAs. Plants encode multiple AGO proteins but, in Arabidopsis, only AGO1 is known to have an antiviral role.To uncover the roles of specific AGOs in limiting virus accumulation we inoculated turnip crinkle virus (TCV to Arabidopsis plants that were mutant for each of the ten AGO genes. The viral symptoms on most of the plants were the same as on wild type plants although the ago2 mutants were markedly hyper-susceptible to this virus. ago2 plants were also hyper-susceptible to cucumber mosaic virus (CMV, confirming that the antiviral role of AGO2 is not specific to a single virus. For both viruses, this phenotype was associated with transient increase in virus accumulation. In wild type plants the AGO2 protein was induced by TCV and CMV infection.Based on these results we propose that there are multiple layers to RNA-mediated defense and counter-defense in the interactions between plants and their viruses. AGO1 represents a first layer. With some viruses, including TCV and CMV, this layer is overcome by viral suppressors of silencing that can target AGO1 and a second layer involving AGO2 limits virus accumulation. The second layer is activated when the first layer is suppressed because AGO2 is repressed by AGO1 via miR403. The activation of the second layer is therefore a direct consequence of the loss of the first layer of defense.

  15. Comparison of Outcomes between Early Fascial Closure and Delayed Abdominal Closure in Patients with Open Abdomen: A Systematic Review and Meta-Analysis

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    Yu Chen

    2014-01-01

    Full Text Available Up to the present, the optimal time to close an open abdomen remains controversial. This study was designed to evaluate whether early fascial abdominal closure had advantages over delayed approach for open abdomen populations. Medline, Embase, and Cochrane Library were searched until April 2013. Search terms included “open abdomen,” “abdominal compartment syndrome,” “laparostomy,” “celiotomy,” “abdominal closure,” “primary,” “delayed,” “permanent,” “fascial closure,” and “definitive closure.” Open abdomen was defined as “fail to close abdominal fascia after a laparotomy.” Mortality, complications, and length of stay were compared between early and delayed fascial closure. In total, 3125 patients were included for final analysis, and 1942 (62% patients successfully achieved early fascial closure. Vacuum assisted fascial closure had no impact on pooled fascial closure rate. Compared with delayed abdominal closure, early fascial closure significantly reduced mortality (12.3% versus 24.8%, RR, 0.53, P<0.0001 and complication incidence (RR, 0.68, P<0.0001. The mean interval from open abdomen to definitive closure ranged from 2.2 to 14.6 days in early fascial closure groups, but from 32.5 to 300 days in delayed closure groups. This study confirmed clinical advantages of early fascial closure over delayed approach in treatment of patients with open abdomen.

  16. Early Rehabilitation in Elderly after Arthroplasty versus Internal Fixation for Unstable Intertrochanteric Fractures of Femur: Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Yoo, Jun Il; Ha, Yong Chan; Lim, Jae Young; Kang, Hyun; Yoon, Byung Ho; Kim, Hyunho

    2017-05-01

    The purpose of this study was to compare the outcomes focusing on the functional outcome and clinical results of replacement arthroplasty (AP) vs. internal fixation (IF) for the treatment of unstable intertrochanteric femoral fracture in elderly. Systematic review and meta-analysis were performed on 10 available clinical studies (2 randomized controlled trials and 8 comparative studies). Subgroup analysis was performed by type of methodological quality. Partial weight bearing time in AP group was earlier than that in IF group (SMD = -0.86; 95% CI = -0.42, 1.29; P = 0.050). The overall outcomes such as mortality, reoperation rate, and complication showed no significant diffrence between the 2 groups (AP vs. IF). Therefore, this systematic review demonstrates that AP provides superior functional outcomes especially earlier mobilization, as compared to IF in elderly patients with an unstable intertrochanteric femoral fracture. © 2017 The Korean Academy of Medical Sciences.

  17. Antiviral type I and type III interferon responses in the central nervous system.

    Science.gov (United States)

    Sorgeloos, Frédéric; Kreit, Marguerite; Hermant, Pascale; Lardinois, Cécile; Michiels, Thomas

    2013-03-15

    The central nervous system (CNS) harbors highly differentiated cells, such as neurons that are essential to coordinate the functions of complex organisms. This organ is partly protected by the blood-brain barrier (BBB) from toxic substances and pathogens carried in the bloodstream. Yet, neurotropic viruses can reach the CNS either by crossing the BBB after viremia, or by exploiting motile infected cells as Trojan horses, or by using axonal transport. Type I and type III interferons (IFNs) are cytokines that are critical to control early steps of viral infections. Deficiencies in the IFN pathway have been associated with fatal viral encephalitis both in humans and mice. Therefore, the IFN system provides an essential protection of the CNS against viral infections. Yet, basal activity of the IFN system appears to be low within the CNS, likely owing to the toxicity of IFN to this organ. Moreover, after viral infection, neurons and oligodendrocytes were reported to be relatively poor IFN producers and appear to keep some susceptibility to neurotropic viruses, even in the presence of IFN. This review addresses some trends and recent developments concerning the role of type I and type III IFNs in: i) preventing neuroinvasion and infection of CNS cells; ii) the identity of IFN-producing cells in the CNS; iii) the antiviral activity of ISGs; and iv) the activity of viral proteins of neurotropic viruses that target the IFN pathway.

  18. Antiviral Type I and Type III Interferon Responses in the Central Nervous System

    Directory of Open Access Journals (Sweden)

    Thomas Michiels

    2013-03-01

    Full Text Available The central nervous system (CNS harbors highly differentiated cells, such as neurons that are essential to coordinate the functions of complex organisms. This organ is partly protected by the blood-brain barrier (BBB from toxic substances and pathogens carried in the bloodstream. Yet, neurotropic viruses can reach the CNS either by crossing the BBB after viremia, or by exploiting motile infected cells as Trojan horses, or by using axonal transport. Type I and type III interferons (IFNs are cytokines that are critical to control early steps of viral infections. Deficiencies in the IFN pathway have been associated with fatal viral encephalitis both in humans and mice. Therefore, the IFN system provides an essential protection of the CNS against viral infections. Yet, basal activity of the IFN system appears to be low within the CNS, likely owing to the toxicity of IFN to this organ. Moreover, after viral infection, neurons and oligodendrocytes were reported to be relatively poor IFN producers and appear to keep some susceptibility to neurotropic viruses, even in the presence of IFN. This review addresses some trends and recent developments concerning the role of type I and type III IFNs in: i preventing neuroinvasion and infection of CNS cells; ii the identity of IFN-producing cells in the CNS; iii the antiviral activity of ISGs; and iv the activity of viral proteins of neurotropic viruses that target the IFN pathway.

  19. Global variations and time trends in the prevalence of childhood myopia, a systematic review and quantitative meta-analysis:implications for aetiology and early prevention

    OpenAIRE

    Rudnicka, Alicja R.; Kapetanakis, Venediktos V.; Wathern, Andrea K.; Logan, Nicola S.; Gilmartin, Bernard; Whincup, Peter H.; Cook, Derek G.; Owen, Christopher G.

    2016-01-01

    The aim of this review was to quantify the global variation in childhood myopia prevalence over time taking account of demographic and study design factors. A systematic review identified population-based surveys with estimates of childhood myopia prevalence published by February 2015. Multilevel binomial logistic regression of log odds of myopia was used to examine the association with age, gender, urban versus rural setting and survey year, among populations of different ethnic origins, adj...

  20. Positron emission tomography (PET) and magnetic resonance imaging (MRI) for the assessment of axillary lymph node metastases in early breast cancer: systematic review and economic evaluation.

    Science.gov (United States)

    Cooper, K L; Meng, Y; Harnan, S; Ward, S E; Fitzgerald, P; Papaioannou, D; Wyld, L; Ingram, C; Wilkinson, I D; Lorenz, E

    2011-01-01

    Breast cancer is the most common type of cancer in women. Evaluation of axillary lymph node metastases is important for breast cancer staging and treatment planning. To evaluate the diagnostic accuracy, cost-effectiveness and effect on patient outcomes of positron emission tomography (PET), with or without computed tomography (CT), and magnetic resonance imaging (MRI) in the evaluation of axillary lymph node metastases in patients with newly diagnosed early-stage breast cancer. A systematic review of literature and an economic evaluation were carried out. Key databases (including MEDLINE, EMBASE and nine others) plus research registers and conference proceedings were searched for relevant studies up to April 2009. A decision-analytical model was developed to determine cost-effectiveness in the UK. One reviewer assessed titles and abstracts of studies identified by the search strategy, obtained the full text of relevant papers and screened them against inclusion criteria. Data from included studies were extracted by one reviewer using a standardised data extraction form and checked by a second reviewer. Discrepancies were resolved by discussion. Quality of included studies was assessed using the quality assessment of diagnostic accuracy studies (QUADAS) checklist, applied by one reviewer and checked by a second. Forty-five citations relating to 35 studies were included in the clinical effectiveness review: 26 studies of PET and nine studies of MRI. Two studies were included in the cost-effectiveness review: one of PET and one of MRI. Of the seven studies evaluating PET/CT (n = 862), the mean sensitivity was 56% [95% confidence interval (CI) 44% to 67%] and mean specificity 96% (95% CI 90% to 99%). Of the 19 studies evaluating PET only (n = 1729), the mean sensitivity was 66% (95% CI 50% to 79%) and mean specificity 93% (95% CI 89% to 96%). PET performed less well for small metastases; the mean sensitivity was 11% (95% CI 5% to 22%) for micrometastases (≤ 2 mm

  1. Evaluation of the combination effect of different antiviral compounds against HIV in vitro

    DEFF Research Database (Denmark)

    Sørensen, A M; Nielsen, C; Mathiesen, Lars Reinhardt

    1993-01-01

    3'-azido-3'deoxythymidine (AZT), a clinically used anti-HIV compound, was evaluated for antiviral effect on HIV infection in combination with other antiviral compounds in vitro. Interactions were evaluated by the median-effect principle and the isobologram technique. Synergistic effect was obtained...... by combining many evaluated antiviral agents with AZT. We observed a difference in the degree of synergism depending on the evaluated compound; the results indicate that compounds with the same target in the viral replicative cycle (ddI: 2',3'-dideoxyinosine, didanosine; d4T: 2',3'-dideoxy-2...

  2. DMPD: TLR3 in antiviral immunity: key player or bystander? [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16027039 TLR3 in antiviral immunity: key player or bystander? Schroder M, Bowie AG.... Trends Immunol. 2005 Sep;26(9):462-8. (.png) (.svg) (.html) (.csml) Show TLR3 in antiviral immunity: key player... or bystander? PubmedID 16027039 Title TLR3 in antiviral immunity: key player or bystander? Authors Schr... File (.png) SVG File (.svg) HTML File (.html) CSML File (.csml) Open .csml file with CIOPlayer Open .csml file with CIOPlayer... - ※CIO Playerのご利用上の注意 Open .csml file with CIO Open .csml file with CIO - ※CIOのご利用上の注意 ...

  3. 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

  4. Risk Factors in Preschool Children for Predicting Asthma During the Preschool Age and the Early School Age: a Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Bao, Yixia; Chen, Zhimin; Liu, Enmei; Xiang, Li; Zhao, Deyu; Hong, Jianguo

    2017-11-18

    The aim of this study was to identify risk factors of asthma among children asthma during the preschool age and early school age (≤ 10 years of age). MEDLINE, Cochrane, EMBASE, and Google Scholar databases were searched until June 30, 2017. Prospective or retrospective cohort and case-control studies were included. Studies had to have evaluated risk factors or a predictive model for developing asthma in children ≤ 6 years of age or persistent asthma in early school age. A total of 17 studies were included in the analysis. Factors associated with developing asthma in children ≤ 10 years of age (both pre-school and early school age) included male gender (pooled OR = 1.70, P asthma (pooled OR = 2.20, P asthma in early school age (pooled OR = 1.51, P = 0.030 and pooled OR = 2.59, P asthma predictive models (e.g., API, PIAMA, PAPS) had relatively low sensitivity (range, 21% to 71.4%) but high specificity (range, 69% to 98%). The study found that male gender, exposure to smoke, atopic dermatitis, family history of asthma, history of wheezing, and serum IgE level ≥ 60 kU/l or having specific IgE were significantly associated with developing asthma by either preschool or early school age. Asthma predictive models can be developed by those risk factors.

  5. Interferon-Mediated Regression of Fibrosis During Antiviral Therapy for Chronic Hepatitis C in Different Variants of IL28B Gene Polymorphism

    Directory of Open Access Journals (Sweden)

    D.Ye. Telegin

    2014-02-01

    Full Text Available The article considers the relationship between the degree of reduction of HCV-induced liver fibrosis by the end of antiviral therapy (AVT for chronic hepatitis C (CHC and the main variants of IL28b gene polymorphism. Materials and Methods. Retrospectively we analyzed the outcomes of treatment of 324 patients who received standard antiviral therapy (a combination of pegylated interferons PegIFN-alpha2b or PegIFN-alpha2a and ribavirin for CHC genotype 1b. The total duration of treatment was 12 months. We evaluated three types of virologic response: rapid (RVR, 4th week of AVT, early (EVR, 12th week of AVT and sustained (SVR, 24th week after the AVT. Results and Discussion. All types of detected changes of fibrosis stages by the end of antiviral treatment in comparison with baseline values were distributed into the following groups : 1 — a significant reduction of fibrosis (25 % of treated patients, 2 — moderate decrease in fibrosis (64 % patients, 3 — unchanged degree of fibrosis (7.6 %, increased fibrosis (3.4 %. A comparison of fibrosis dynamics during antiviral therapy was carried out in the two groups of patients: without (N = 110 and with (N = 214 T-allele of the gene IL28b. The most significant decrease in the degree of fibrosis detected among patients with favorable CC gene IL28b variant, because exactly in this group of patients the frequency of SVR was highest. Among those who have reached sustained aviremia, the lowest degree of reduction of fibrosis was found in T-allele carriers of the gene IL28b. Conclusions. The findings suggest that not all patients with CHC who achieved sustained virologic response escape the risks associated with the effects of viral persistence of HCV.

  6. Separation methods for acyclovir and related antiviral compounds.

    Science.gov (United States)

    Loregian, A; Gatti, R; Palù, G; De Palo, E F

    2001-11-25

    Acyclovir (ACV) is an antiviral drug, which selectively inhibits replication of members of the herpes group of DNA viruses with low cell toxicity. Valaciclovir (VACV), a prodrug of ACV is usually preferred in the oral treatment of viral infections, mainly herpes simplex virus (HSV). Also other analogues such as ganciclovir and penciclovir are discussed here. The former acts against cytomegalovirus (CMV) in general and the latter against CMV retinitis. The action mechanism of these antiviral drugs is presented briefly here, mainly via phosphorylation and inhibition of the viral DNA polymerase. The therapeutic use and the pharmacokinetics are also outlined. The measurement of the concentration of acyclovir and related compounds in biological samples poses a particularly significant challenge because these drugs tend to be structurally similar to endogenous substances. The analysis requires the use of highly selective analytical techniques and chromatography methods are a first choice to determine drug content in pharmaceuticals and to measure them in body fluids. Chromatography can be considered the procedure of choice for the bio-analysis of this class of antiviral compounds, as this methodology is characterised by good specificity and accuracy and it is particularly useful when metabolites need to be monitored. Among chromatographic techniques, the reversed-phase (RP) HPLC is widely used for the analysis. C18 Silica columns from 7.5 to 30 cm in length are used, the separation is carried out mainly at room temperature and less than 10 min is sufficient for the analysis at 1.0-1.5 ml/min of flow-rate. The separation methods require an isocratic system, and various authors have proposed a variety of mobile phases. The detection requires absorbance or fluorescence measurements carried out at 250-254 nm and at lambdaex=260-285 nm, lambdaem=375-380 nm, respectively. The detection limit is about 0.3-10 ng/ml but the most important aspect is related to the sample treatment

  7. Poor neurological sequelae of herpes simplex virus encephalitis in an infant despite adequate antiviral and adjunct corticosteroid therapy

    Directory of Open Access Journals (Sweden)

    Ratna B Basak

    2011-01-01

    Full Text Available A 2-month-old infant presented to our emergency department with fever, altered consciousness, and focal seizures of acute onset. He had vesicular skin lesions over the right preauricular region. CT brain showed a large hypodense lesion involving the left temporo-parietal region, left basal ganglia and left thalamus. MRI brain revealed bilateral multifocal corticomedullary lesions suggestive of encephalitis. CSF-PCR was positive for herpes simplex virus (HSV type I. He was treated with standard dose intravenous acyclovir for 15 days along with a trial of pulse methylprednisolone, but was readmitted within a week with features of an early relapse. The infant survived but developed significant neurological sequelae. Although treatment of HSV is available, the neurological outcome is guarded even with adequate antiviral therapy. Adjunct corticosteroid therapy did not appear to attenuate the neurological sequelae.

  8. Zinc-finger antiviral protein inhibits XMRV infection.

    Directory of Open Access Journals (Sweden)

    Xinlu Wang

    Full Text Available BACKGROUND: The zinc-finger antiviral protein (ZAP is a host factor that specifically inhibits the replication of certain viruses, including Moloney murine leukemia virus (MoMLV, HIV-1, and certain alphaviruses and filoviruses. ZAP binds to specific viral mRNAs and recruits cellular mRNA degradation machinery to degrade the target RNA. The common features of ZAP-responsive RNA sequences remain elusive and thus whether a virus is susceptible to ZAP can only be determined experimentally. Xenotropic murine leukemia virus-related virus (XMRV is a recently identified γ-retrovirus that was originally thought to be involved in prostate cancer and chronic fatigue syndrome but recently proved to be a laboratory artefact. Nonetheless, XMRV as a new retrovirus has been extensively studied. Since XMRV and MoMLV share only 67.9% sequence identity in the 3'UTRs, which is the target sequence of ZAP in MoMLV, whether XMRV is susceptible to ZAP remains to be determined. FINDINGS: We constructed an XMRV-luc vector, in which the coding sequences of Gag-Pol and part of Env were replaced with luciferase-coding sequence. Overexpression of ZAP potently inhibited the expression of XMRV-luc in a ZAP expression-level-dependent manner, while downregulation of endogenous ZAP rendered cells more sensitive to infection. Furthermore, ZAP inhibited the spreading of replication-competent XMRV. Consistent with the previously reported mechanisms by which ZAP inhibits viral infection, ZAP significantly inhibited the accumulation of XMRV-luc mRNA in the cytoplasm. The ZAP-responsive element in XMRV mRNA was mapped to the 3'UTR. CONCLUSIONS: ZAP inhibits XMRV replication by preventing the accumulation of viral mRNA in the cytoplasm. Documentation of ZAP inhibiting XMRV helps to broaden the spectrum of ZAP's antiviral activity. Comparison of the target sequences of ZAP in XMRV and MoMLV helps to better understand the features of ZAP-responsive elements.

  9. Inhibition of Vaccinia virus entry by a broad spectrum antiviral peptide

    International Nuclear Information System (INIS)

    Altmann, S.E.; Jones, J.C.; Schultz-Cherry, S.; Brandt, C.R.

    2009-01-01

    Concerns about the possible use of Variola virus, the causative agent of smallpox, as a weapon for bioterrorism have led to renewed efforts to identify new antivirals against orthopoxviruses. We identified a peptide, EB, which inhibited infection by Vaccinia virus with an EC 50 of 15 μM. A control peptide, EBX, identical in composition to EB but differing in sequence, was inactive (EC 50 > 200 μM), indicating sequence specificity. The inhibition was reversed upon removal of the peptide, and EB treatment had no effect on the physical integrity of virus particles as determined by electron microscopy. Viral adsorption was unaffected by the presence of EB, and the addition of EB post-entry had no effect on viral titers or on early gene expression. The addition of EB post-adsorption resulted in the inhibition of β-galactosidase expression from an early viral promoter with an EC 50 of 45 μM. A significant reduction in virus entry was detected in the presence of the peptide when the number of viral cores released into the cytoplasm was quantified. Electron microscopy indicated that 88% of the virions remained on the surface of cells in the presence of EB, compared to 37% in the control (p < 0.001). EB also blocked fusion-from-within, suggesting that virus infection is inhibited at the fusion step. Analysis of EB derivatives suggested that peptide length may be important for the activity of EB. The EB peptide is, to our knowledge, the first known small molecule inhibitor of Vaccinia virus entry.

  10. Elevation of intact and proteolytic fragments of acute phase proteins constitutes the earliest systemic antiviral response in HIV-1 infection.

    Directory of Open Access Journals (Sweden)

    Holger B Kramer

    2010-05-01

    Full Text Available The earliest immune responses activated in acute human immunodeficiency virus type 1 infection (AHI exert a critical influence on subsequent virus spread or containment. During this time frame, components of the innate immune system such as macrophages and DCs, NK cells, beta-defensins, complement and other anti-microbial factors, which have all been implicated in modulating HIV infection, may play particularly important roles. A proteomics-based screen was performed on a cohort from whom samples were available at time points prior to the earliest positive HIV detection. The ability of selected factors found to be elevated in the plasma during AHI to inhibit HIV-1 replication was analyzed using in vitro PBMC and DC infection models. Analysis of unique plasma donor panels spanning the eclipse and viral expansion phases revealed very early alterations in plasma proteins in AHI. Induction of acute phase protein serum amyloid A (A-SAA occurred as early as 5-7 days prior to the first detection of plasma viral RNA, considerably prior to any elevation in systemic cytokine levels. Furthermore, a proteolytic fragment of alpha-1-antitrypsin (AAT, termed virus inhibitory peptide (VIRIP, was observed in plasma coincident with viremia. Both A-SAA and VIRIP have anti-viral activity in vitro and quantitation of their plasma levels indicated that circulating concentrations are likely to be within the range of their inhibitory activity. Our results provide evidence for a first wave of host anti-viral defense occurring in the eclipse phase of AHI prior to systemic activation of other immune responses. Insights gained into the mechanism of action of acute-phase reactants and other innate molecules against HIV and how they are induced could be exploited for the future development of more efficient prophylactic vaccine strategies.

  11. Systematic notes on Asian birds. 51. Dates of avian names introduced in early volumes of the Journal of the Asiatic Society of Bengal

    NARCIS (Netherlands)

    Dickinson, E.C.; Pittie, A.

    2006-01-01

    The Journal of the Asiatic Society of Bengal contains many new names of birds and other animals but accurate dating of the new names is difficult. The Society wanted it to contain a monthly meteorological report and in many, if not most, years deliberately issued the journal early in the month after

  12. Training for Quality: Improving Early Childhood Programs through Systematic Inservice Training. Monographs of the High/Scope Educational Research Foundation, Number Nine.

    Science.gov (United States)

    Epstein, Ann S.

    The Training of Trainers (ToT) Evaluation investigated the efficacy of the High/Scope model for improving the quality of early childhood programs on a national scale. To address this question, the High/Scope Foundation undertook a multimethod evaluation that collected anecdotal records from the consultants and 793 participants in 40 ToT projects,…

  13. The added value of mifepristone to non-surgical treatment regimens for uterine evacuation in case of early pregnancy failure: a systematic review of the literature

    NARCIS (Netherlands)

    Berg, J. van den; Gordon, B.B.; Snijders, M.P.M.L.; Vandenbussche, F.P.H.A.; Coppus, S.F.P.J.

    2015-01-01

    OBJECTIVE(S): Early pregnancy failure (EPF) is a common complication of pregnancy. Surgical intervention carries a risk of complications and, therefore, medical treatment appears to be a safe alternative. Unfortunately, the current medical treatment with misoprostol alone has complete evacuation

  14. The metallographic examination of sword no. 438 as part of a systematic survey of swords from the early medieval stronghold of Mikulčice, Czech Republic

    Czech Academy of Sciences Publication Activity Database

    Hošek, Jiří; Košta, J.; Bárta, P.

    2012-01-01

    Roč. 32, prosinec (2012), s. 87-102 ISSN 0436-029X R&D Projects: GA ČR GAP405/12/2289 Institutional support: RVO:67985912 Keywords : Mikulčice * Great Moravia * early medieval sword * archaeometallurgy Subject RIV: AC - Archeology, Anthropology, Ethnology

  15. Antiviral and immunoregulatory role against PCV2 in vivo of Chinese herbal medicinal ingredients

    Directory of Open Access Journals (Sweden)

    Yang Haifeng

    2017-12-01

    Full Text Available Introduction: The aim of the research was to investigate the antiviral and immunoregulatory effects of saikosaponin A, saikosaponin D, Panax notoginseng saponins, notoginsenoside R1, and anemoside B4 saponins commonly found in Chinese herbal medicines.

  16. Antiviral effect of lithium chloride on infection of cells by canine parvovirus.

    Science.gov (United States)

    Zhou, Pei; Fu, Xinliang; Yan, Zhongshan; Fang, Bo; Huang, San; Fu, Cheng; Hong, Malin; Li, Shoujun

    2015-11-01

    Canine parvovirus type 2 causes significant viral disease in dogs, with high morbidity, high infectivity, and high mortality. Lithium chloride is a potential antiviral drug for viruses. We determined the antiviral effect of Lithium Chloride on canine parvovirus type 2 in feline kidney cells. The viral DNA and proteins of canine parvovirus were suppressed in a dose-dependent manner by lithium chloride. Further investigation verified that viral entry into cells was inhibited in a dose-dependent manner by lithium chloride. These results indicated that lithium chloride could be a potential antiviral drug for curing dogs with canine parvovirus infection. The specific steps of canine parvovirus entry into cells that are affected by lithium chloride and its antiviral effect in vivo should be explored in future studies.

  17. Antiviral Efficacy of Verdinexor In Vivo in Two Animal Models of Influenza A Virus Infection

    Science.gov (United States)

    Perwitasari, Olivia; Johnson, Scott; Yan, Xiuzhen; Register, Emery; Crabtree, Jackelyn; Gabbard, Jon; Howerth, Elizabeth; Shacham, Sharon; Carlson, Robert; Tamir, Sharon; Tripp, Ralph A.

    2016-01-01

    Influenza A virus (IAV) causes seasonal epidemics of respiratory illness that can cause mild to severe illness and potentially death. Antiviral drugs are an important countermeasure against IAV; however, drug resistance has developed, thus new therapeutic approaches are being sought. Previously, we demonstrated the antiviral activity of a novel nuclear export inhibitor drug, verdinexor, to reduce influenza replication in vitro and pulmonary virus burden in mice. In this study, in vivo efficacy of verdinexor was further evaluated in two animal models or influenza virus infection, mice and ferrets. In mice, verdinexor was efficacious to limit virus shedding, reduce pulmonary pro-inflammatory cytokine expression, and moderate leukocyte infiltration into the bronchoalveolar space. Similarly, verdinexor-treated ferrets had reduced lung pathology, virus burden, and inflammatory cytokine expression in the nasal wash exudate. These findings support the anti-viral efficacy of verdinexor, and warrant its development as a novel antiviral therapeutic for influenza infection. PMID:27893810

  18. Antiviral Efficacy of Verdinexor In Vivo in Two Animal Models of Influenza A Virus Infection.

    Directory of Open Access Journals (Sweden)

    Olivia Perwitasari

    Full Text Available Influenza A virus (IAV causes seasonal epidemics of respiratory illness that can cause mild to severe illness and potentially death. Antiviral drugs are an important countermeasure against IAV; however, drug resistance has developed, thus new therapeutic approaches are being sought. Previously, we demonstrated the antiviral activity of a novel nuclear export inhibitor drug, verdinexor, to reduce influenza replication in vitro and pulmonary virus burden in mice. In this study, in vivo efficacy of verdinexor was further evaluated in two animal models or influenza virus infection, mice and ferrets. In mice, verdinexor was efficacious to limit virus shedding, reduce pulmonary pro-inflammatory cytokine expression, and moderate leukocyte infiltration into the bronchoalveolar space. Similarly, verdinexor-treated ferrets had reduced lung pathology, virus burden, and inflammatory cytokine expression in the nasal wash exudate. These findings support the anti-viral efficacy of verdinexor, and warrant its development as a novel antiviral therapeutic for influenza infection.

  19. Antiviral Potential of Algae Polysaccharides Isolated from Marine Sources: A Review

    Directory of Open Access Journals (Sweden)

    Azin Ahmadi

    2015-01-01

    Full Text Available From food to fertilizer, algal derived products are largely employed in assorted industries, including agricultural, biomedical, food, and pharmaceutical industries. Among different chemical compositions isolated from algae, polysaccharides are the most well-established compounds, which were subjected to a variety of studies due to extensive bioactivities. Over the past few decades, the promising results for antiviral potential of algae-derived polysaccharides have advocated them as inordinate candidates for pharmaceutical research. Numerous studies have isolated various algal polysaccharides possessing antiviral activities, including carrageenan, alginate, fucan, laminaran, and naviculan. In addition, different mechanisms of action have been reported for these polysaccharides, such as inhibiting the binding or internalization of virus into the host cells or suppressing DNA replication and protein synthesis. This review strives for compiling previous antiviral studies of algae-derived polysaccharides and their mechanism of action towards their development as natural antiviral agents for future investigations.

  20. Herpesvirus infections in immunocompromised patients : treatment, treatment failure and antiviral resistance

    NARCIS (Netherlands)

    Beek, Martha Trijntje van der

    2012-01-01

    The research described in this thesis aims to study determinants of the course and outcome of treatment of herpesvirus infections in immunocompromised patients. Both viral factors, such as antiviral resistance, and patient factors, including immunological parameters, were investigated. Techniques to

  1. A human genome-wide loss-of-function screen identifies effective chikungunya antiviral drugs.

    Science.gov (United States)

    Karlas, Alexander; Berre, Stefano; Couderc, Thérèse; Varjak, Margus; Braun, Peter; Meyer, Michael; Gangneux, Nicolas; Karo-Astover, Liis; Weege, Friderike; Raftery, Martin; Schönrich, Günther; Klemm, Uwe; Wurzlbauer, Anne; Bracher, Franz; Merits, Andres; Meyer, Thomas F; Lecuit, Marc

    2016-05-12

    Chikungunya virus (CHIKV) is a globally spreading alphavirus against which there is no commercially available vaccine or therapy. Here we use a genome-wide siRNA screen to identify 156 proviral and 41 antiviral host factors affecting CHIKV replication. We analyse the cellular pathways in which human proviral genes are involved and identify druggable targets. Twenty-one small-molecule inhibitors, some of which are FDA approved, targeting six proviral factors or pathways, have high antiviral activity in vitro, with low toxicity. Three identified inhibitors have prophylactic antiviral effects in mouse models of chikungunya infection. Two of them, the calmodulin inhibitor pimozide and the fatty acid synthesis inhibitor TOFA, have a therapeutic effect in vivo when combined. These results demonstrate the value of loss-of-function screening and pathway analysis for the rational identification of small molecules with therapeutic potential and pave the way for the development of new, host-directed, antiviral agents.

  2. Evaluation of the combination effect of different antiviral compounds against HIV in vitro

    DEFF Research Database (Denmark)

    Sørensen, A M; Nielsen, C; Mathiesen, Lars Reinhardt

    1993-01-01

    by combining many evaluated antiviral agents with AZT. We observed a difference in the degree of synergism depending on the evaluated compound; the results indicate that compounds with the same target in the viral replicative cycle (ddI: 2',3'-dideoxyinosine, didanosine; d4T: 2',3'-dideoxy-2......3'-azido-3'deoxythymidine (AZT), a clinically used anti-HIV compound, was evaluated for antiviral effect on HIV infection in combination with other antiviral compounds in vitro. Interactions were evaluated by the median-effect principle and the isobologram technique. Synergistic effect was obtained...... with the adhesion/penetration process of virus (ConA: Concanavalin A; DS: dextran sulfate) were most potent with AZT when used in rather high concentrations. At this moment in the HIV epidemic, these observations suggest that combinations of antiviral compounds should be evaluated in clinical trials, with the major...

  3. The role of fluoxetine in antiviral therapy for chronic hepatitis C

    OpenAIRE

    QIN Yuan; ZHANG Ying; ZHAO Jieru

    2016-01-01

    More than 20% of chronic hepatitis C (CHC) patients receiving the antiviral therapy with interferonα(IFNα) experience depression, and fluoxetine is often used to alleviate this symptom. Fluoxetine has anti-inflammatory properties and can change the synthesis of liver lipids, but its influence on antiviral therapy for CHC and related mechanism remain unknown. Recent studies show that fluoxetine can inhibit hepatitis C virus (HCV) infection and reduce the production of reactive oxygen species (...

  4. Arbidol (Umifenovir): A broad-spectrum antiviral drug that inhibits medically important arthropod-borne flaviviruses

    Czech Academy of Sciences Publication Activity Database

    Haviernik, J.; Štefánik, M.; Fojtíková, M.; Kali, S.; Tordo, N.; Rudolf, Ivo; Hubálek, Zdeněk; Eyer, Luděk; Růžek, Daniel

    2018-01-01

    Roč. 10, č. 4 (2018), č. článku 184. ISSN 1999-4915 R&D Projects: GA ČR(CZ) GA16-20054S Institutional support: RVO:68081766 ; RVO:60077344 Keywords : Antiviral activity * Arbidol * Cell-type dependent antiviral effect * Cytotoxicity * Flavivirus * Umifenovir Subject RIV: EE - Microbiology, Virology OBOR OECD: Virology Impact factor: 3.465, year: 2016

  5. Topoisomerase 1 Inhibition Promotes Cyclic GMP-AMP Synthase-Dependent Antiviral Responses

    OpenAIRE

    Pépin, Geneviève; Nejad, Charlotte; Ferrand, Jonathan; Thomas, Belinda J.; Stunden, H. James; Sanij, Elaine; Foo, Chwan-Hong; Stewart, Cameron R.; Cain, Jason E.; Bardin, Philip G.; Williams, Bryan R. G.; Gantier, Michael P.

    2017-01-01

    ABSTRACT Inflammatory responses, while essential for pathogen clearance, can also be deleterious to the host. Chemical inhibition of topoisomerase 1 (Top1) by low-dose camptothecin (CPT) can suppress transcriptional induction of antiviral and inflammatory genes and protect animals from excessive and damaging inflammatory responses. We describe the unexpected finding that minor DNA damage from topoisomerase 1 inhibition with low-dose CPT can trigger a strong antiviral immune response through c...

  6. Antiviral activity of an N-allyl acridone against dengue virus

    OpenAIRE

    Mazzucco, María Belén; Talarico, Laura Beatriz; Vatansever, Sezen; Carro, Ana Clara; Fascio, Mirta Liliana; D'Accorso, Norma Beatriz; Garcia, Cybele; Damonte, Elsa Beatriz

    2016-01-01

    Dengue virus (DENV), a member of the family Flaviviridae, is at present the most widespread causative agent of a human viral disease transmitted by mosquitoes. Despite the increasing incidence of this pathogen, there are no antiviral drugs or vaccines currently available for treatment or prevention. In a previous screening assay, we identified a group of N-allyl acridones as effective virus inhibitors. Here, the antiviral activity and mode of action targeted to viral RNA replication of one of...

  7. Antiviral treatment among older adults hospitalized with influenza, 2006-2012.

    Directory of Open Access Journals (Sweden)

    Mary Louise Lindegren

    Full Text Available To describe antiviral use among older, hospitalized adults during six influenza seasons (2006-2012 in Davidson County, Tennessee, USA.Among adults ≥50 years old hospitalized with symptoms of respiratory illness or non-localizing fever, we collected information on provider-initiated influenza testing and nasal/throat swabs for influenza by RT-PCR in a research laboratory, and calculated the proportion treated with antivirals.We enrolled 1753 adults hospitalized with acute respiratory illness. Only 26% (457/1753 of enrolled patients had provider-initiated influenza testing. Thirty-eight patients had a positive clinical laboratory test, representing 2.2% of total patients and 8.3% of tested patients. Among the 38 subjects with clinical laboratory-confirmed influenza, 26.3% received antivirals compared to only 4.5% of those with negative clinical influenza tests and 0.7% of those not tested (p<0.001. There were 125 (7.1% patients who tested positive for influenza in the research laboratory. Of those with research laboratory-confirmed influenza, 0.9%, 2.7%, and 2.8% received antivirals (p=.046 during pre-pandemic, pandemic, and post-pandemic influenza seasons, respectively. Both research laboratory-confirmed influenza (adjusted odds ratio [AOR] 3.04 95%CI 1.26-7.35 and clinical laboratory-confirmed influenza (AOR 3.05, 95%CI 1.07-8.71 were independently associated with antiviral treatment. Severity of disease, presence of a high-risk condition, and symptom duration were not associated with antiviral use.In urban Tennessee, antiviral use was low in patients recognized to have influenza by the provider as well as those unrecognized to have influenza. The use of antivirals remained low despite recommendations to treat all hospitalized patients with confirmed or suspected influenza.

  8. Stockpiling anti-viral drugs for a pandemic: the role of Manufacturer Reserve Programs.

    Science.gov (United States)

    Harrington, Joseph E; Hsu, Edbert B

    2010-05-01

    To promote stockpiling of anti-viral drugs by non-government organizations such as hospitals, drug manufacturers have introduced Manufacturer Reserve Programs which, for an annual fee, provide the right to buy in the event of a severe outbreak of influenza. We show that these programs enhance drug manufacturer profits but could either increase or decrease the amount of pre-pandemic stockpiling of anti-viral drugs.

  9. Synthesis and Antiviral Activity of 3-Aminoindole Nucleosides of 2-Acetamido-2-deoxy-D-glucose

    Energy Technology Data Exchange (ETDEWEB)

    Abdelrahman, Adel A. H.; Elessawy, Farag A.; Barakat, Yousif A. [Menoufia Univ., Shebin El-Koam (Egypt); Ellatif, Mona M. Abd [The British Univ. in Egypt, Cairo (Egypt)

    2012-10-15

    A new method for the construction of 3-aminoindole nucleosides of 2-acetamido-2-deoxy-D-glucose based is presented. Nitration and acetylation of the indole nucleosides by acetic anhydride-nitric acid mixture followed by reduction using silver catalyst (SNSM) impregnated on silica gel, afforded the corresponding amino indole nucleosides. The nucleosides were tested for antiviral activity against hepatitis B virus (HBV) to show different degrees of antiviral activities or inhibitory actions.

  10. Human influenza is more effective than avian influenza at antiviral suppression in airway cells.

    Science.gov (United States)

    Hsu, Alan Chen-Yu; Barr, Ian; Hansbro, Philip M; Wark, Peter A

    2011-06-01

    Airway epithelial cells are the initial site of infection with influenza viruses. The innate immune responses of airway epithelial cells to infection are important in limiting virus replication and spread. However, relatively little is known about the importance of this innate antiviral response to infection. Avian influenza viruses are a potential source of future pandemics; therefore, it is critical to examine the effectiveness of the host antiviral system to different influenza viruses. We used a human influenza (H3N2) and a low-pathogenic avian influenza (H11N9) to assess and compare the antiviral responses of Calu-3 cells. After infection, H3N2 replicated more effectively than the H11N9 in Calu-3 cells. This was not due to differential expression of sialic acid residues on Calu-3 cells, but was attributed to the interference of host antiviral responses by H3N2. H3N2 induced a delayed antiviral signaling and impaired type I and type III IFN induction compared with the H11N9. The gene encoding for nonstructural (NS) 1 protein was transfected into the bronchial epithelial cells (BECs), and the H3N2 NS1 induced a greater inhibition of antiviral responses compared with the H11N9 NS1. Although the low-pathogenic avian influenza virus was capable of infecting BECs, the human influenza virus replicated more effectively than avian influenza virus in BECs, and this was due to a differential ability of the two NS1 proteins to inhibit antiviral responses. This suggests that the subversion of human antiviral responses may be an important requirement for influenza viruses to adapt to the human host and cause disease.

  11. Antisense Phosphorodiamidate Morpholino Oligomers as Novel Antiviral Compounds

    Directory of Open Access Journals (Sweden)

    Yuchen Nan

    2018-04-01

    Full Text Available Phosphorodiamidate morpholino oligomers (PMO are short single-stranded DNA analogs that are built upon a backbone of morpholine rings connected by phosphorodiamidate linkages. As uncharged nucleic acid analogs, PMO bind to complementary sequences of target mRNA by Watson–Crick base pairing to block protein translation through steric blockade. PMO interference of viral protein translation operates independently of RNase H. Meanwhile, PMO are resistant to a variety of enzymes present in biologic fluids, a characteristic that makes them highly suitable for in vivo applications. Notably, PMO-based therapy for Duchenne muscular dystrophy (DMD has been approved by the United States Food and Drug Administration which is now a hallmark for PMO-based antisense therapy. In this review, the development history of PMO, delivery methods for improving cellular uptake of neutrally charged PMO molecules, past studies of PMO antagonism against RNA and DNA viruses, PMO target selection, and remaining questions of PMO antiviral strategies are discussed in detail and new insights are provided.

  12. Detection of the antiviral drug oseltamivir in aquatic environments.

    Directory of Open Access Journals (Sweden)

    Hanna Söderström

    Full Text Available Oseltamivir (Tamiflu is the most important antiviral drug available and a cornerstone in the defence against a future influenza pandemic. Recent publications have shown that the active metabolite, oseltamivir carboxylate (OC, is not degraded in sewage treatment plants and is also persistent in aquatic environments. This implies that OC will be present in aquatic environments in areas where oseltamivir is prescribed to patients for therapeutic use. The country where oseltamivir is used most is Japan, where it is used to treat seasonal flu. We measured the levels of OC in water samples from the Yodo River system in the Kyoto and Osaka prefectures, Japan, taken before and during the flu-season 2007/8. No OC was detected before the flu-season but 2-58 ng L(-1 was detected in the samples taken during the flu season. This study shows, for the first time, that low levels of oseltamivir can be found in the aquatic environment. Therefore the natural reservoir of influenza virus, dabbling ducks, is exposed to oseltamivir, which could promote the evolution of viral resistance.

  13. IFITM3 requires an amphipathic helix for antiviral activity.

    Science.gov (United States)

    Chesarino, Nicholas M; Compton, Alex A; McMichael, Temet M; Kenney, Adam D; Zhang, Lizhi; Soewarna, Victoria; Davis, Matthew; Schwartz, Olivier; Yount, Jacob S

    2017-10-01

    Interferon-induced transmembrane protein 3 (IFITM3) is a cellular factor that blocks virus fusion with cell membranes. IFITM3 has been suggested to alter membrane curvature and fluidity, though its exact mechanism of action is unclear. Using a bioinformatic approach, we predict IFITM3 secondary structures and identify a highly conserved, short amphipathic helix within a hydrophobic region of IFITM3 previously thought to be a transmembrane domain. Consistent with the known ability of amphipathic helices to alter membrane properties, we show that this helix and its amphipathicity are required for the IFITM3-dependent inhibition of influenza virus, Zika virus, vesicular stomatitis virus, Ebola virus, and human immunodeficiency virus infections. The homologous amphipathic helix within IFITM1 is also required for the inhibition of infection, indicating that IFITM proteins possess a conserved mechanism of antiviral action. We further demonstrate that the amphipathic helix of IFITM3 is required to block influenza virus hemagglutinin-mediated membrane fusion. Overall, our results provide evidence that IFITM proteins utilize an amphipathic helix for inhibiting virus fusion. © 2017 The Authors.

  14. Resistance to antivirals in human cytomegalovirus: mechanisms and clinical significance.

    Science.gov (United States)

    Pérez, J L

    1997-09-01

    Long term therapies needed for managing human cytomegalovirus (HCMV) infections in immunosupressed patients provided the background for the emergence of the resistance to antivirals active against HCMV. In addition, laboratory selected mutants have also been readily achieved. Both clinical and laboratory resistant strains share the same determinants of resistance. Ganciclovir resistance may be due to a few mutations in the HCMV UL97 gene and/or viral DNA pol gene, the former being responsible for about 70% of clinical resistant isolates. Among them, V464, V594, S595 and F595 are the most frequent mutations. Because of their less extensive clinical use, much less is known about resistance to foscarnet and cidofovir (formerly, HPMPC) but in both cases, it has been associated to mutations in the DNA pol. Ganciclovir resistant strains showing DNA pol mutations are cross-resistant to cidofovir and their corresponding IC50 are normally higher than those from strains harboring only mutations at the UL97 gene. To date, foscarnet resistance seems to be independent of both ganciclovir and cidofovir resistance.

  15. Chemical diversity and antiviral potential in the pantropical Diospyros genus.

    Science.gov (United States)

    Peyrat, Laure-Anne; Eparvier, Véronique; Eydoux, Cécilia; Guillemot, Jean-Claude; Stien, Didier; Litaudon, Marc

    2016-07-01

    A screening using a dengue replicon virus-cell-based assay was performed on 3563 ethyl acetate (EtOAc) extracts from different parts of 1500 plants. The screening led to the selection of species from the genus Diospyros (Ebenaceae), among which 25 species distributed in tropical areas showed significant inhibitory activity on dengue virus replication. A metabolic analysis was conducted from the UPLC-HRMS profiles of 33 biologically active and inactive plant extracts, and their metabolic proximity is presented in the form of a dendrogram. The results of the study showed that chemical similarity is not related to plant species or organ. Overall, metabolomic profiling allowed us to define large groups of extracts, comprising both active and inactive ones. Closely related profiles from active extracts might indicate that the common major components of these extracts were responsible for the antiviral activity, while the comparison of chemically similar active and inactive extracts, will permit to find compounds of interest. Eventually, the phytochemical investigation of Diospyros glans bark EtOAc extract afforded usnic acid and 7 known ursane- and lupane-type triterpenoids, among which 5 were found significantly active against dengue virus replication. The inhibitory potency of these compounds was also evaluated on a DENV-NS5 RNA-dependant RNA polymerase assay. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Ribavirin: recent insights into antiviral mechanisms of action.

    Science.gov (United States)

    Reyes, G R

    2001-09-01

    Ribavirin, a nucleoside analog, used in combination with interferon-alpha (IFN alpha) results in a substantial improvement in the sustained virologic response in chronic hepatitis C. Identified antiviral mechanisms of action for ribavirin include: (i) inhibition of viral encoded polymerases; (ii) inhibition of genomic RNA capping; and (iii) inhibition of cellular encoded enzymes that control de novo synthesis of purine nucleosides. More recently, ribavirin has been shown to engender a bias toward helper T-cell (CD4+) type 1 (Th1) cytokine responses in models of immunity. Recent detailed analysis has also shown that ribavirin can be utilized and incorporated by the polio viral polymerase into genomic and antigenomic transcripts, and is capable of base pairing with either UMP (uridine monophosphate) or CMP (cytidine monophosphate). This results in ribavirin-mediated mutagenesis of the viral genome and has the potential to push the virus beyond tolerable set points in its mutation rate, leading to an overall reduced fitness of the viral population. Of the many mechanisms of action demonstrated for ribavirin, the current clinical trials of selective inosine 5'-monophosphate dehydrogenase (IMPDH) inhibitors and immunomodulating agents in hepatitis may facilitate our understanding of what activity (if any) predominates when ribavirin is used in combination with IFN alpha.

  17. Prophylactic Antiviral Treatment in Recurrent Herpes Zoster: A Case Report

    Directory of Open Access Journals (Sweden)

    Hatice Gamze Bayram

    2011-06-01

    Full Text Available Herpes zoster (HZ occurs in older ages with activation of varicella-zoster virus (VZV which persists in a dormant phase within the dorsal root ganglia. The incidence of HZ in immunosuppressed patients is 20-100 times higher and the clinical progress is more severe than in immunocompetent individuals. A 48-year-old man who had been diagnosed with acute myelocytic leukemia type M3 and had been treated with immunosuppressive agents was admitted to our clinic. The patient was clinically diagnosed as having HZ. He was treated with acyclovir 800 mg five times daily for 7 days. In the consecutive three months, he attended our clinic again with similar complaints. The left cervical (C5, C6 dermatomes were involved at the fourth attack of HZ. Multinucleated giant cells were determined on the Tzanck smear. VZV DNA was detected by polymerase chain reaction (PCR. Treatment with valacyclovir 1 g three times daily for 14 days was prescribed and then, prophylactic treatment with valacyclovir 500 mg two times a day was administered. Although immunosuppressive treatment was continued, no new attacks of herpes zoster occurred. We think that prophylactic antiviral therapy should be initiated in immunosuppressive individuals who have recurrent herpes zoster attacks.

  18. Regulation of the Host Antiviral State by Intercellular Communications

    Directory of Open Access Journals (Sweden)

    Sonia Assil

    2015-08-01

    Full Text Available Viruses usually induce a profound remodeling of host cells, including the usurpation of host machinery to support their replication and production of virions to invade new cells. Nonetheless, recognition of viruses by the host often triggers innate immune signaling, preventing viral spread and modulating the function of immune cells. It conventionally occurs through production of antiviral factors and cytokines by infected cells. Virtually all viruses have evolved mechanisms to blunt such responses. Importantly, it is becoming increasingly recognized that infected cells also transmit signals to regulate innate immunity in uninfected neighboring cells. These alternative pathways are notably mediated by vesicular secretion of various virus- and host-derived products (miRNAs, RNAs, and proteins and non-infectious viral particles. In this review, we focus on these newly-described modes of cell-to-cell communications and their impact on neighboring cell functions. The reception of these signals can have anti- and pro-viral impacts, as well as more complex effects in the host such as oncogenesis and inflammation. Therefore, these “broadcasting” functions, which might be tuned by an arms race involving selective evolution driven by either the host or the virus, constitute novel and original regulations of viral infection, either highly localized or systemic.

  19. Targeted antiviral prophylaxis with oseltamivir in a summer camp setting.

    Science.gov (United States)

    Kimberlin, David W; Escude, Janell; Gantner, Janel; Ott, Jeanne; Dronet, Melissa; Stewart, Timothy A; Jester, Penelope; Redden, David T; Chapman, Whitney; Hammond, Rob

    2010-04-01

    To describe the effectiveness of containment of novel influenza A(H1N1) infection at a summer camp. Targeted use of oseltamivir phosphate by individuals in close contact with influenza-confirmed cases. Boys' camp in Alabama in July 2009. A total of 171 campers, 48 camp counselors, and 27 camp staff. Campers with confirmed influenza received oseltamivir and were immediately isolated and sent home. All boys and counselors in the infected child's adjoining cabins received prophylactic oseltamivir for 10 days, including 8 campers at higher risk for influenza infection (eg, those with asthma, seizure disorder, or diabetes). Alcohol-based hand sanitizer was provided at each of the daily activities, in the boys' cabins, and in the dining hall, and counselors were educated by the medical staff on the spread of influenza and its prevention through good hand hygiene. All cabins, bathrooms, and community sports equipment were sprayed or wiped down with disinfectant each day. Main Outcome Measure Virologic confirmation of influenza. Three of the 171 campers tested positive for influenza A during the course of the 2-week fourth session, for an attack rate of 1.8%. The probability of observing 3 or fewer infected campers if the attack rate was 12% is less than 1 in 10,000,000 (P hand sanitization and surface decontamination, a targeted approach to antiviral prophylaxis contained the spread of influenza in a summer camp setting.

  20. Antibacterial, antifungal, and antiviral activities of some flavonoids.

    Science.gov (United States)

    Orhan, Didem Deliorman; Ozçelik, Berrin; Ozgen, Selda; Ergun, Fatma

    2010-08-20

    Antibacterial and antifungal activities of six plant-derived flavonoids representing two different structural groups were evaluated against standard strains of Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, Klebsiella pneumoniae, Acinetobacter baumannii, Staphylococcus aureus, Enterococcus faecalis, Bacillus subtilis and their drug-resistant isolates, as well as fungi (Candida albicans, C. krusei) using the microdilution broth method. Herpes simplex virus Type-1 and Parainfluenza-3 virus were employed for antiviral assessment of the flavonoids using Madin-Darby bovine kidney and Vero cell lines. Ampicillin, gentamycin, ofloxacin, levofloxacin, fluconazole, ketoconazole, acyclovir, and oseltamivir were used as the control agents. All tested compounds (32-128 microg/ml) showed strong antimicrobial and antifungal activities against isolated strains of P. aeruginosa, A. baumanni, S. aureus, and C. krusei. Rutin, 5,7-dimethoxyflavanone-4'-O-beta-D-glucopyranoside and 5,7,3'-trihydroxy-flavanone-4'-O-beta-D-glucopyranoside (0.2-0.05 microg/ml) were active against PI-3, while 5,7-dimethoxyflavanone-4'-O-[2''-O-(5'''-O-trans-cinnamoyl)-beta-D-apiofuranosyl]-beta-D-glucopyranoside (0.16-0.2 microg/ml) inhibited potently HSV-1. Copyright 2009 Elsevier GmbH. All rights reserved.

  1. [Antiviral activity of representatives of the family Crassulaceae].

    Science.gov (United States)

    Shirobokov, V P; Evtushenko, A I; Lapchik, V F; Shirobokova, D N; Suptel', E A

    1981-12-01

    The antiviral properties of the juice of 11 species of the orpine family were studied. 8 of them belonged to the genera Kalanchoe, i. e. Kalanchoe diagremontiona R. Hamet, K. pinnata (Zam.) Persoon, K. Peteri Werd., K. prolifera (Bovie) R. Hamet, K. marnierriana (Mann. et Boit) Jacobs; K. blossfeldiana v. Poelln, K. beharensis Drake del Gastillo, K. waldheimii R. Hamet et Perr and 3 belonged to the Sedum genera, i. e. Sedum telephium L., S. spectabile Boreau, S. acre L. A high virus neutralizing activity of the juice from 4 species of Kalanchoe, i. e. K. blossfeldiana, K. waldheimii, K. pinnata and K. beharensis was shown. Inhibition of the virus infecting activity was observed at the juice dilutions from 1-2 to 1-8000 and higher. The viricidal factor of Kalanchoe is stable. It is not destroyed by ether, alcohol and potassium periodate. It is not absorbed by bentonite at the acid pH values. Addition of cattle serum or purified proteins to the juice resulted in their precipitation which suppressed the viricidal activity of the juice.

  2. In Vitro Bioavailability Study of an Antiviral Compound Enisamium Iodide

    Directory of Open Access Journals (Sweden)

    Eleonore Haltner-Ukomadu

    2018-01-01

    Full Text Available An investigation into the biopharmaceutics classification and a study of the in vitro bioavailability (permeability and solubility of the antiviral compound enisamium iodide (4-(benzylcarbamoyl-1-methylpyridinium iodide were carried out. The solubility of enisamium iodide was determined in four different buffers. Apparent intestinal permeability (Papp of enisamium iodide was assessed using human colon carcinoma (Caco-2 cells at three concentrations. The solubility of enisamium iodide in four buffer solutions from pH 1.2 to 7.5 is about 60 mg/mL at 25 °C, and ranges from 130 to 150 mg/mL at 37 °C, depending on the pH. Based on these results, enisamium iodide can be classified as highly soluble. Enisamium iodide demonstrated low permeability in Caco-2 experiments in all tested concentrations of 10–100 μM with permeability coefficients between 0.2 × 10−6 cm s−1 and 0.3 × 10−6 cm s−1. These results indicate that enisamium iodide belongs to class III of the Biopharmaceutics Classification System (BCS due to its high solubility and low permeability. The bioavailability of enisamium iodide needs to be confirmed in animal and human studies.

  3. Routine culture-based screening versus risk-based management for the prevention of early-onset group B streptococcus disease in the neonate: a systematic review.

    Science.gov (United States)

    Kurz, Ella; Davis, Deborah

    2015-04-17

    Early-onset group B streptococcus disease, recognized as the most common cause of early onset neonatal sepsis in developed countries, is transmitted vertically from the group B streptococcus carrier mother to the neonate in the peripartum. Accordingly, early-onset group B streptococcus disease is prevented by halting the transmission of the microorganism from the mother to the infant. Two main methods, routine culture-based screening and risk-based management, may be used in the identification of mothers requiring intrapartum antibiotic prophylaxis in labor. While there are advantages and disadvantages to each, there is limited high level evidence available as to which method is superior. To identify the effectiveness of risk-based management versus routine culture-based screening in the prevention of early-onset group B streptococcus disease in the neonate. This review considered studies which treated pregnant women with intrapartum antibiotic prophylaxis following risk- and culture-based protocols for the prevention of early-onset group B streptococcus disease in the neonate. Types of intervention: This review considered studies that evaluated risk-based management against routine culture-based screening for the prevention of early-onset group B streptococcus disease in the neonate. Types of studies: This review looked for highest evidence available which in this case consisted of one quasi experimental study and eight comparative cohort studies with historical or concurrent control groups. Types of outcomes: Incidence of early-onset group B streptococcus disease in neonates as measured by positive group B streptococcus culture from an otherwise sterile site. Secondary outcomes include neonatal death due to group B streptococcus sepsis and percentage of women who received intrapartum antibiotic prophylaxis. A multi-step search strategy was used to find studies which were limited to the English language and published between January 2000 and June 2013. The quality

  4. Using the ferret as an animal model for investigating influenza antiviral effectiveness

    Directory of Open Access Journals (Sweden)

    Ding Yuan Oh

    2016-02-01

    Full Text Available The concern of the emergence of a pandemic influenza virus has sparked an increased effort towards the development and testing of novel influenza antivirals. Central to this is the animal model of influenza infection, which has played an important role in understanding treatment effectiveness and the effect of antivirals on host immune responses. Among the different animal models of influenza, ferrets can be considered the most suitable for antiviral studies as they display most of the human-like symptoms following influenza infections, they can be infected with human influenza virus without prior viral adaptation and have the ability to transmit influenza virus efficiently between one another. However, an accurate assessment of the effectiveness of an antiviral treatment in ferrets is dependent on three major experimental considerations encompassing firstly, the volume and titre of virus, and the route of viral inoculation. Secondly, the route and dose of drug administration, and lastly, the different methods used to assess clinical symptoms, viral shedding kinetics and host immune responses in the ferrets. A good understanding of these areas is necessary to achieve data that can accurately inform the human use of influenza antivirals. In this review, we discuss the current progress and the challenges faced in these three major areas when using the ferret model to measure influenza antiviral effectiveness.

  5. Niclosamide is a proton carrier and targets acidic endosomes with broad antiviral effects.

    Science.gov (United States)

    Jurgeit, Andreas; McDowell, Robert; Moese, Stefan; Meldrum, Eric; Schwendener, Reto; Greber, Urs F

    2012-01-01

    Viruses use a limited set of host pathways for infection. These pathways represent bona fide antiviral targets with low likelihood of viral resistance. We identified the salicylanilide niclosamide as a broad range antiviral agent targeting acidified endosomes. Niclosamide is approved for human use against helminthic infections, and has anti-neoplastic and antiviral effects. Its mode of action is unknown. Here, we show that niclosamide, which is a weak lipophilic acid inhibited infection with pH-dependent human rhinoviruses (HRV) and influenza virus. Structure-activity studies showed that antiviral efficacy and endolysosomal pH neutralization co-tracked, and acidification of the extracellular medium bypassed the virus entry block. Niclosamide did not affect the vacuolar H(+)-ATPase, but neutralized coated vesicles or synthetic liposomes, indicating a proton carrier mode-of-action independent of any protein target. This report demonstrates that physico-chemical interference with host pathways has broad range antiviral effects, and provides a proof of concept for the development of host-directed antivirals.

  6. Niclosamide is a proton carrier and targets acidic endosomes with broad antiviral effects.

    Directory of Open Access Journals (Sweden)

    Andreas Jurgeit

    Full Text Available Viruses use a limited set of host pathways for infection. These pathways represent bona fide antiviral targets with low likelihood of viral resistance. We identified the salicylanilide niclosamide as a broad range antiviral agent targeting acidified endosomes. Niclosamide is approved for human use against helminthic infections, and has anti-neoplastic and antiviral effects. Its mode of action is unknown. Here, we show that niclosamide, which is a weak lipophilic acid inhibited infection with pH-dependent human rhinoviruses (HRV and influenza virus. Structure-activity studies showed that antiviral efficacy and endolysosomal pH neutralization co-tracked, and acidification of the extracellular medium bypassed the virus entry block. Niclosamide did not affect the vacuolar H(+-ATPase, but neutralized coated vesicles or synthetic liposomes, indicating a proton carrier mode-of-action independent of any protein target. This report demonstrates that physico-chemical interference with host pathways has broad range antiviral effects, and provides a proof of concept for the development of host-directed antivirals.

  7. Studies on Antiviral and Immuno-Regulation Activity of Low Molecular Weight Fucoidan from Laminaria japonica

    Science.gov (United States)

    Sun, Taohua; Zhang, Xinhui; Miao, Ying; Zhou, Yang; Shi, Jie; Yan, Meixing; Chen, Anjin

    2018-06-01

    The antiviral activity in vitro and in vivo and the effect of the immune system of two fucoidan fractions with low molecular weight and different sulfate content from Laminaria japonica (LMW fucoidans) were investigated in order to examine the possible mechanism. In vitro, I-type influenza virus, adenovirus and Parainfluenza virus I were used to infect Hep-2, Hela and MDCK cells, respectively. And 50% tissue culture infective dose was calculated to detect the antiviral activity of two LMW fucoidans. The results indicated that compared with the control group, 2 kinds of LMW fucoidans had remarkable antiviral activity in vitro in middle and high doses, while at low doses, the antiviral activity of 2 kinds of LMW fucoidans was not statistically different from that in the blank control group. And there was no statistically difference between two LMW fucoidans in antiviral activity. In vivo, LMW fucoidans could prolong the survival time of virus-infected mice, and could improve the lung index of virus-infected mice significantly, which have statistical differences with the control group significantly ( p 0.05). In this study, it was shown that both of two LMW fucoidans (LF1, LF2) could increase the thymus index, spleen index, phagocytic index, phagocytosis coefficient and half hemolysin value in middle and high doses, which suggested that LMW fucoidans could play an antiviral role by improving the quality of immune organs, improving immune cell phagocytosis and humoral immunity.

  8. Strategies for antiviral stockpiling for future influenza pandemics: a global epidemic-economic perspective.

    Science.gov (United States)

    Carrasco, Luis R; Lee, Vernon J; Chen, Mark I; Matchar, David B; Thompson, James P; Cook, Alex R

    2011-09-07

    Influenza pandemics present a global threat owing to their potential mortality and substantial economic impacts. Stockpiling antiviral drugs to manage a pandemic is an effective strategy to offset their negative impacts; however, little is known about the long-term optimal size of the stockpile under uncertainty and the characteristics of different countries. Using an epidemic-economic model we studied the effect on total mortality and costs of antiviral stockpile sizes for Brazil, China, Guatemala, India, Indonesia, New Zealand, Singapore, the UK, the USA and Zimbabwe. In the model, antivirals stockpiling considerably reduced mortality. There was greater potential avoidance of expected costs in the higher resourced countries (e.g. from $55 billion to $27 billion over a 30 year time horizon for the USA) and large avoidance of fatalities in those less resourced (e.g. from 11.4 to 2.3 million in Indonesia). Under perfect allocation, higher resourced countries should aim to store antiviral stockpiles able to cover at least 15 per cent of their population, rising to 25 per cent with 30 per cent misallocation, to minimize fatalities and economic costs. Stockpiling is estimated not to be cost-effective for two-thirds of the world's population under current antivirals pricing. Lower prices and international cooperation are necessary to make the life-saving potential of antivirals cost-effective in resource-limited countries.

  9. Early detection of breast cancer: benefits and risks of supplemental breast ultrasound in asymptomatic women with mammographically dense breast tissue. A systematic review

    International Nuclear Information System (INIS)

    Nothacker, Monika; Duda, Volker; Hahn, Markus; Warm, Mathias; Degenhardt, Friedrich; Madjar, Helmut; Weinbrenner, Susanne; Albert, Ute-Susann

    2009-01-01

    Mammographic screening alone will miss a certain fraction of malignancies, as evidenced by retrospective reviews of mammograms following a subsequent screening. Mammographic breast density is a marker for increased breast cancer risk and is associated with a higher risk of interval breast cancer, i.e. cancer detected between screening tests. The purpose of this review is to estimate risks and benefits of supplemental breast ultrasound in women with negative mammographic screening with dense breast tissue. A systematic search and review of studies involving mammography and breast ultrasound for screening of breast cancer was conducted. The search was performed for the period 1/2000-8/2008 within the data source of PubMed, DARE, and Cochrane databases. Inclusion and exclusion criteria were determined prospectively, and the Oxford evidence classification system for diagnostic studies was used for evidence level. The parameters biopsy rate, positive predictive value (PPV) for biopsy, cancer yield for breast ultrasound alone, and carcinoma detection rate by breast density were extracted or constructed. The systematic search identified no randomized controlled trials or systematic reviews, six cohort studies of intermediate level of evidence (3b) were found. Only two of the studies included adequate follow-up of subjects with negative or benign findings. Supplemental breast ultrasound after negative mammographic screening permitted diagnosis of primarily invasive carcinomas in 0.32% of women in breast density type categories 2-4 of the American College of Radiology (ACR); mean tumor size for those identified was 9.9 mm, 90% with negative lymph node status. Most detected cancers occurred in mammographically dense breast ACR types 3 and 4. Biopsy rates were in the range 2.3%-4.7%, with PPV of 8.4-13.7% for those biopsied due to positive ultrasound, or about one third of the PPV of biopsies due to mammography. Limitations: The study populations included wide age ranges, and

  10. The Effectiveness of Early Educational Interventions in the Emergency Department to Reduce Incidence or Severity of Postconcussion Syndrome Following a Concussion: A Systematic Review.

    Science.gov (United States)

    Eliyahu, Leeor; Kirkland, Scott; Campbell, Sandy; Rowe, Brian H

    2016-05-01

    Concussions or mild traumatic brain injury are a major public health concern accounting for 85% of all brain injuries. Postconcussion syndrome (PCS) has been found to affect between 15 and 25% of patients with concussion 1 year after the initial injury. The goal of this review is to assess the effectiveness of early educational information or interventions provided in the emergency department on the onset and/or severity of PCS. A comprehensive literature search strategy involving seven electronic databases was developed. A grey literature search of Google Scholar, recent conference proceedings in emergency medicine, bibliographies of included studies, and clinical trial registries was also performed. The citation list was reviewed independently by two reviewers; no restrictions on publication status or language of publication were applied. The Cochrane risk-of-bias tool and the Newcastle-Ottawa scale were used to assess quality. From 1,325 citations retrieved, four RCTs and one controlled clinical trial met inclusion criteria. Interventions identified in these studies included: educational information sheets, with or without telephone or in-person follow-up, and one study on bed rest. While rarely requested, one study offered referrals and additional treatment, if needed. None of the studies were deemed to be high quality. Heterogeneity among outcome reporting, follow-up dates and interventions used precluded a pooled analysis. Overall, only two of the five included studies involving adult patients receiving early educational interventions reported a significant improvement in PCS symptoms. No reduction in PCS symptoms was found in the study on bed rest interventions. Limited evidence exists regarding the effectiveness of early educational interventions following concussion. Standardization of the interventions, outcome measures, and follow-up periods would make quantitative comparisons more valid. Moreover, higher-quality research in the field of early

  11. Noninvasive Ventilation With vs Without Early Surfactant to Prevent Chronic Lung Disease in Preterm Infants: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Isayama, Tetsuya; Chai-Adisaksopha, Chatree; McDonald, Sarah D

    2015-08-01

    Controversy exists regarding which of the 2 major strategies currently used to prevent chronic lung disease (CLD) in preterm infants is optimal: noninvasive continuous positive airway pressure (NCPAP) or intubate-surfactant-extubate (INSURE). Preterm infants often require surfactant administration because of respiratory distress syndrome. To evaluate whether early INSURE or NCPAP alone is more effective in preventing CLD, death, or both. We searched the MEDLINE, EMBASE, Cochrane Controlled Trials Register, and Cumulative Index to Nursing and Allied Health Literature databases from their inception to January 2, 2015, along with conference proceedings and trial registrations. Randomized clinical trials that compared early INSURE with NCPAP alone in preterm infants who had never been intubated before the study entry were selected. Among 1761 initially identified articles, 9 trials (1551 infants) were included. Duplicate study selection and data extraction were performed. Meta-analysis was conducted using random-effects models with quality-of-evidence assessment according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Seven main outcomes were selected a priori to be assessed according to GRADE, including a composite outcome of CLD and/or death, CLD alone, death alone, air leakage, severe intraventricular hemorrhage, neurodevelopmental impairment, and a composite outcome of death and/or neurodevelopmental impairment. There were no statistically significant differences between early INSURE and NCPAP alone for all outcomes assessed. However, the relative risk (RR) estimates appeared to favor early INSURE over NCPAP alone, with a 12% RR reduction in CLD and/or death (RR, 0.88; 95% CI, 0.76-1.02; risk difference [RD], -0.04; 95% CI, -0.08 to 0.01; moderate quality of evidence), a 14% decrease in CLD (RR, 0.86; 95% CI, 0.71-1.03; RD, -0.03; 95% CI, -0.06 to 0.01; moderate quality of evidence), and a 50% decrease in air leakage (RR

  12. Colloids versus crystalloids in objective-guided fluid therapy, systematic review and meta-analysis. Too early or too late to draw conclusions

    Directory of Open Access Journals (Sweden)

    Javier Ripollés

    2015-08-01

    Full Text Available INTRODUCTION: Several clinical trials on Goal directed fluid therapy (GDFT were carried out, many of those using colloids in order to optimize the preload. After the decision of European Medicines Agency, there is such controversy regarding its use, benefits, and possible contribution to renal failure. The objective of this systematic review and meta-analysis is to compare the use of last-generation colloids, derived from corn, with crystalloids in GDFT to determine associated complications and mortality.METHODS: A bibliographic research was carried out in MEDLINE PubMed, EMBASE and Cochrane Library, corroborating randomized clinical trials where crystalloids are compared to colloids in GDFT for major non-cardiac surgery in adults.RESULTS: One hundred thirty references were found and among those 38 were selected and 29 analyzed; of these, six were included for systematic review and meta-analysis, including 390 patients. It was observed that the use of colloids is not associated with the increase of complications, but rather with a tendency to a higher mortality (RR [95% CI] 3.87 [1.121-13.38]; I2 = 0.0%; p = 0.635.CONCLUSIONS: Because of the limitations of this meta-analysis due to the small number of randomized clinical trials and patients included, the results should be taken cautiously, and the performance of new randomized clinical trials is proposed, with enough statistical power, comparing balanced and unbalanced colloids to balanced and unbalanced crystalloids, following the protocols of GDFT, considering current guidelines and suggestions made by groups of experts.

  13. Recommendation for axillary lymph node dissection in women with early breast cancer and sentinel node metastasis: A systematic review and meta-analysis of randomized controlled trials using the GRADE system.

    Science.gov (United States)

    Huang, Tsai-Wei; Kuo, Ken N; Chen, Kee-Hsin; Chen, Chiehfeng; Hou, Wen-Hsuan; Lee, Wei-Hwa; Chao, Tsu-Yi; Tsai, Jo-Ting; Su, Chih-Ming; Huang, Ming-Te; Tam, Ka-Wai

    2016-10-01

    In 2014, the American Society of Clinical Oncology published an updated clinical practice guideline on axillary lymph node dissection (ALND) for early-stage breast cancer patients. However, these recommendations have been challenged because they were based on data from only one randomized controlled trial (RCT). We evaluated the rationale of these recommendations by systematically reviewing RCTs using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) system. We searched articles in the PubMed, EMBASE, CINAHL, Scopus, and Cochrane databases. The primary endpoints were overall survival (OS) and disease-free survival (DFS). The secondary endpoints were recurrence rate and surgical complications of axillary dissection. The quality of evidence was assessed using the GRADE profiler. Five eligible studies were retrieved and analyzed. We divided sentinel lymph node (SLN) metastasis into two categories: SLN micrometastasis and SLN macrometastasis. In patients with 1 or 2 SLN micrometastasis, no significant difference was observed in OS, DFS, or recurrence rate between the ALND and non-ALND groups. For patients with 1 or 2 SLN marcometastasis, only one trial with a moderate risk of bias was included, and non-ALND was the preferred management overall. However, ALND might be appropriate for patients who placed a greater emphasis on longer-term survival at any cost. We recommend non-ALND management for early breast cancer patients with 1 or 2 SLN micrometastasis or macrometastasis on the basis of a systematic review of the current evidence conducted using the GRADE system. However, the optimal practice of evidence-based medicine should incorporate patient preferences, particularly when evidence is limited. Copyright © 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

  14. Antiviral Combination Approach as a Perspective to Combat Enterovirus Infections.

    Science.gov (United States)

    Galabov, Angel S; Nikolova, Ivanka; Vassileva-Pencheva, Ralitsa; Stoyanova, Adelina

    2015-01-01

    Human enteroviruses distributed worldwide are causative agents of a broad spectrum of diseases with extremely high morbidity, including a series of severe illnesses of the central nervous system, heart, endocrine pancreas, skeleton muscles, etc., as well as the common cold contributing to the development of chronic respiratory diseases, including the chronic obstructive pulmonary disease. The above mentioned diseases along with the significantly high morbidity and mortality in children, as well as in the high-risk populations (immunodeficiencies, neonates) definitely formulate the chemotherapy as the main tool for the control of enterovirus infections. At present, clinically effective antivirals for use in the treatment of enteroviral infection do not exist, in spite of the large amount of work carried out in this field. The main reason for this is the development of drug resistance. We studied the process of development of resistance to the strongest inhibitors of enteroviruses, WIN compounds (VP1 protein hydrophobic pocket blockers), especially in the models in vivo, Coxsackievirus B (CV-B) infections in mice. We introduced the tracing of a panel of phenotypic markers (MIC50 value, plaque shape and size, stability at 50℃, pathogenicity in mice) for characterization of the drug-mutants (resistant and dependent) as a very important stage in the study of enterovirus inhibitors. Moreover, as a result of VP1 RNA sequence analysis performed on the model of disoxaril mutants of CVB1, we determined the molecular basis of the drug-resistance. The monotherapy courses were the only approach used till now. For the first time in the research for anti-enterovirus antivirals our team introduced the testing of combination effect of the selective inhibitors of enterovirus replication with different mode of action. This study resulted in the selection of a number of very effective in vitro double combinations with synergistic effect and a broad spectrum of sensitive

  15. Early mantle differentiation: constraint from {sup 146}Sm-{sup 142}Nd systematics; Radioactivite eteinte du {sup 146}Sm et differenciation precoce du manteau terrestre

    Energy Technology Data Exchange (ETDEWEB)

    Caro, G

    2005-07-15

    We present new ultra-high precision {sup 142}Nd/{sup 144}Nd measurements of early Archaean rocks using the new generation thermal ionization mass spectrometer TRITON. Repeated measurements of the Ames Nd standard demonstrate that the {sup 142}Nd/{sup 144}Nd ratio can be determined with external precision of 2 ppm (2s), allowing confident resolution of anomalies as small as 5 ppm. A major analytical improvement lies in the elimination of the double normalization procedure required to correct our former measurements from a secondary mass fractionation effect. Our new results indicate that metasediments, meta-basalts and orthogneisses from the 3.6 - 3.8 Ga West Greenland craton display positive {sup 142}Nd anomalies ranging from 8 to 15 ppm. Using a simple two-stage model with initial e{sup 143}Nd value of 1.9 {+-} 0.6 e-units, coupled {sup 147}Sm-{sup 143}Nd and {sup 146}Sm-{sup 142}Nd chronometry constrains mantle differentiation to 50 to 200 Ma after formation of the solar system. This chronological constraint is consistent with differentiation of the Earth's mantle during the late stage of crystallization of a magma ocean. We have developed a two-box model describing {sup 142}Nd and {sup 143}Nd isotopic evolution of depleted mantle during the subsequent evolution of the crust-mantle system. Our results indicate that early terrestrial proto-crust had a lifetime of ca. 500 Ma in order to produce the observed Nd isotope signature of Archaean rocks. In the context of this two box mantle-crust system, we model the evolution of isotopic and chemical heterogeneity of depleted mantle as a function of the mantle stirring time. Using the dispersion of {sup 142}Nd/{sup 144}Nd and {sup 143}Nd/{sup 144}Nd ratios observed in early Archaean rocks, we constrain the stirring time of early Earth's mantle to 100 - 150 Ma, a factor of 5 to 10 shorter than stirring time inferred from modern oceanic basalts. (author)

  16. Antiviral activity of glycyrrhizin against hepatitis C virus in vitro.

    Directory of Open Access Journals (Sweden)

    Yoshihiro Matsumoto

    Full Text Available Glycyrrhizin (GL has been used in Japan to treat patients with chronic viral hepatitis, as an anti-inflammatory drug to reduce serum alanine aminotransferase levels. GL is also known to exhibit various biological activities, including anti-viral effects, but the anti-hepatitis C virus (HCV effect of GL remains to be clarified. In this study, we demonstrated that GL treatment of HCV-infected Huh7 cells caused a reduction of infectious HCV production using cell culture-produced HCV (HCVcc. To determine the target step in the HCV lifecycle of GL, we used HCV pseudoparticles (HCVpp, replicon, and HCVcc systems. Significant suppressions of viral entry and replication steps were not observed. Interestingly, extracellular infectivity was decreased, and intracellular infectivity was increased. By immunofluorescence and electron microscopic analysis of GL treated cells, HCV core antigens and electron-dense particles had accumulated on endoplasmic reticulum attached to lipid droplet (LD, respectively, which is thought to act as platforms for HCV assembly. Furthermore, the amount of HCV core antigen in LD fraction increased. Taken together, these results suggest that GL inhibits release of infectious HCV particles. GL is known to have an inhibitory effect on phospholipase A2 (PLA2. We found that group 1B PLA2 (PLA2G1B inhibitor also decreased HCV release, suggesting that suppression of virus release by GL treatment may be due to its inhibitory effect on PLA2G1B. Finally, we demonstrated that combination treatment with GL augmented IFN-induced reduction of virus in the HCVcc system. GL is identified as a novel anti-HCV agent that targets infectious virus particle release.

  17. Puromycin-sensitive aminopeptidase: an antiviral prodrug activating enzyme.

    Science.gov (United States)

    Tehler, Ulrika; Nelson, Cara H; Peterson, Larryn W; Provoda, Chester J; Hilfinger, John M; Lee, Kyung-Dall; McKenna, Charles E; Amidon, Gordon L

    2010-03-01

    Cidofovir (HPMPC) is a broad-spectrum antiviral agent, currently used to treat AIDS-related human cytomegalovirus retinitis. Cidofovir has recognized therapeutic potential for orthopox virus infections, although its use is hampered by its inherent low oral bioavailability. Val-Ser-cyclic HPMPC (Val-Ser-cHPMPC) is a promising peptide prodrug which has previously been shown by us to improve the permeability and bioavailability of the parent compound in rodent models (Eriksson et al., 2008. Molecular Pharmaceutics 5, 598-609). Puromycin-sensitive aminopeptidase was partially purified from Caco-2 cell homogenates and identified as a prodrug activating enzyme for Val-Ser-cHPMPC. The prodrug activation process initially involves an enzymatic step where the l-Valine residue is removed by puromycin-sensitive aminopeptidase, a step that is bestatin-sensitive. Subsequent chemical hydrolysis results in the generation of cHPMPC. A recombinant puromycin-sensitive aminopeptidase was generated and its substrate specificity investigated. The k(cat) for Val-pNA was significantly lower than that for Ala-pNA, suggesting that some amino acids are preferred over others. Furthermore, the three-fold higher k(cat) for Val-Ser-cHPMPC as compared to Val-pNA suggests that the leaving group may play an important role in determining hydrolytic activity. In addition to its ability to hydrolyze a variety of substrates, these observations strongly suggest that puromycin-sensitive aminopeptidase is an important enzyme for activating Val-Ser-cHPMPC in vivo. Taken together, our data suggest that puromycin-sensitive aminopeptidase makes an attractive target for future prodrug design.

  18. Mechanism of action of a pestivirus antiviral compound

    Science.gov (United States)

    Baginski, Scott G.; Pevear, Daniel C.; Seipel, Marty; Sun, Siu Chi Chang; Benetatos, Christopher A.; Chunduru, Srinivas K.; Rice, Charles M.; Collett, Marc S.

    2000-01-01

    We report here the discovery of a small molecule inhibitor of pestivirus replication. The compound, designated VP32947, inhibits the replication of bovine viral diarrhea virus (BVDV) in cell culture at a 50% inhibitory concentration of approximately 20 nM. VP32947 inhibits both cytopathic and noncytopathic pestiviruses, including isolates of BVDV-1, BVDV-2, border disease virus, and classical swine fever virus. However, the compound shows no activity against viruses from unrelated virus groups. Time of drug addition studies indicated that VP32947 acts after virus adsorption and penetration and before virus assembly and release. Analysis of viral macromolecular synthesis showed VP32947 had no effect on viral protein synthesis or polyprotein processing but did inhibit viral RNA synthesis. To identify the molecular target of VP32947, we isolated drug-resistant (DR) variants of BVDV-1 in cell culture. Sequence analysis of the complete genomic RNA of two DR variants revealed a single common amino acid change located within the coding region of the NS5B protein, the viral RNA-dependent RNA polymerase. When this single amino acid change was introduced into an infectious clone of drug-sensitive wild-type (WT) BVDV-1, replication of the resulting virus was resistant to VP32947. The RNA-dependent RNA polymerase activity of the NS5B proteins derived from WT and DR viruses expressed and purified from recombinant baculovirus-infected insect cells confirmed the drug sensitivity of the WT enzyme and the drug resistance of the DR enzyme. This work formally validates NS5B as a target for antiviral drug discovery and development. The utility of VP32947 and similar compounds for the control of pestivirus diseases, and for hepatitis C virus drug discovery efforts, is discussed. PMID:10869440

  19. Does the association between early life growth and later obesity differ by race/ethnicity or socioeconomic status? A systematic review.

    Science.gov (United States)

    Andrea, Sarah B; Hooker, Elizabeth R; Messer, Lynne C; Tandy, Thomas; Boone-Heinonen, Janne

    2017-09-01

    Rapid growth during infancy predicts higher risk of obesity later in childhood. The association between patterns of early life growth and later obesity may differ by race/ethnicity or socioeconomic status (SES), but prior evidence syntheses do not consider vulnerable subpopulations. We systemically reviewed published studies that explored patterns of early life growth (0-24 months of age) as predictors of later obesity (>24 months) that were either conducted in racial/ethnic minority or low-SES study populations or assessed effect modification of this association by race/ethnicity or SES. Literature searches were conducted in PubMed and SocINDEX. Ten studies met the inclusion criteria. Faster growth during the first 2 years of life was consistently associated with later obesity irrespective of definition and timing of exposure and outcome measures. Associations were strongest in populations composed of greater proportions of racial/ethnic minority and/or low-SES children. For example, ORs ranged from 1.17 (95% CI: 1.11, 1.24) in a heterogeneous population to 9.24 (95% CI: 3.73, 22.9) in an entirely low-SES nonwhite population. The impact of rapid growth in infancy on later obesity may differ by social stratification factors such as race/ethnicity and family income. More robust and inclusive studies examining these associations are needed. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. SOME ASPECTS OF THE MARKETING STUDIES FOR THE PHARMACEUTICAL MARKET OF ANTIVIRAL DRUGS

    Directory of Open Access Journals (Sweden)

    A. G. Salnikova

    2015-01-01

    Full Text Available Antiviral drugs are widely used in medicinal practice. They suppress the originator and stimulate the protection of an organism. The drugs are used for the treatment of flu and ARVI, herpetic infections, virus hepatitis, HIV-infection. Contemporary pharmaceutical market is represented by a wide range of antiviral drugs. Marketing studies are conducted to develop strategies, used for the enhancement of pharmacy organization activity efficiency. Conduction of the marketing researches of pharmaceutical market is the purpose of this study. We have used State Registry of Drugs, State Record of Drugs, List of vital drugs, questionnaires of pharmaceutical workers during our work. Historical, sociological, mathematical methods, and a method of expert evaluation were used in the paper. As the result of the study we have made the following conclusions. We have studied and generalized the literature data about classification and application of antiviral drugs, marketing, competition. The assortment of antiviral drugs on the pharmaceutical market of the Russian Federation was also studied. We have conducted an analysis for the obtainment of the information about antiviral drugs by pharmaceutical workers. We have determined the competitiveness of antiviral drugs, and on the basis of the research conducted we have submitted an offer for pharmaceutical organizations to form the range of antiviral drugs.

  1. Identification of Novel 5,6-Dimethoxyindan-1-one Derivatives as Antiviral Agents.

    Science.gov (United States)

    Patil, Siddappa A; Patil, Vikrant; Patil, Renukadevi; Beaman, Kenneth; Patil, Shivaputra A

    2017-01-01

    Discovery of novel antiviral agents is essential because viral infection continues to threaten human life globally. Various heterocyclic small molecules have been developed as antiviral agents. The 5,6-dimethoxyindan-1-on nucleus is of considerable interest as this ring is the key constituent in a range of bioactive compounds, both naturally occurring and synthetic, and often of considerable complexity. The main purpose of this research was to discover and develop small molecule heterocycles as broad-spectrum of antiviral agents. A focused small set of 5,6-dimethoxyindan-1-one analogs (6-8) along with a thiopene derivative (9) was screened for selected viruses (Vaccinia virus - VACA, Human papillomavirus - HPV, Zika virus - ZIKV, Dengue virus - DENV, Measles virus - MV, Poliovirus 3 - PV, Rift Valley fever virus - RVFV, Tacaribe virus - TCRV, Venezuelan equine encephalitis virus - VEEV, Herpes simplex virus 1 -HSV-1 and Human cytomegalovirus - HCMV) using the National Institute of Allergy and Infectious Diseases (NIAID)'s Division of Microbiology and Infectious Diseases (DMID) antiviral screening program. These molecules demonstrated moderate to excellent antiviral activity towards variety of viruses. The 5,6-dimethoxyindan-1-one analog (7) demonstrated high efficacy towards vaccinia virus (EC50: 30.00 µM) in secondary plaque reduction assay. The thiophene analog (9) has shown very good viral inhibition towards several viruses such as Human papillomavirus, Measles virus, Rift Valley fever virus, Tacaribe virus and Herpes simplex virus 1. Our research identified a novel 5,6-dimethoxyindan-1-one analog (compound 7), as a potent antiviral agent for vaccinia virus, and heterocyclic chalcone analog (compound 9) as a broad spectrum antiviral agent. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. Antiviral stockpiles for influenza pandemics from the household perspective: treatment alone versus treatment with prophylaxis.

    Science.gov (United States)

    Kwok, Kin On; Leung, Gabriel M; Mak, Peter; Riley, Steven

    2013-06-01

    Model-based studies of antiviral use to mitigate the impact of moderate and severe influenza pandemics implicitly take the viewpoint of a central public health authority. However, it seems likely that the key decision of when to use antivirals will be made at the household level. We used a stochastic compartmental model of the transmission of influenza within and between households to evaluate the expected mortality under two strategies: households saving available antivirals for treatment only and households implementing prophylaxis as well as treatment. Given that every individual in the population was allocated a single course of antivirals, we investigated the impact of these two strategies for a wide range of AVED, the efficacy of antivirals in preventing death in severe cases (AVED=1 for complete protection). We found a cross-over point for our baseline parameter values in a regime where antivirals were still highly effective in reducing the chance of death: below AVED=0.9 the optimal strategy was for households to use both treatment and prophylaxis. We also considered the possibility that a small number of households might "cheat" by choosing to follow the treatment-only strategy when other households were following treatment with prophylaxis. The cross-over point for cheating households was considerably lower, at AVED=0.6, but substantially above 0. These results suggest that unless antivirals are almost completely effective in reducing the chance of death in serious cases, households will likely be better served implementing prophylaxis as well as treatment. More generally, our study illustrates the potential value of considering viewpoints other than a central authority when conducting model-based analysis of interventions against infectious disease. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Effect of Dysphagia Screening Strategies on Clinical Outcomes After Stroke: A Systematic Review for the 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke.

    Science.gov (United States)

    Smith, Eric E; Kent, David M; Bulsara, Ketan R; Leung, Lester Y; Lichtman, Judith H; Reeves, Mathew J; Towfighi, Amytis; Whiteley, William N; Zahuranec, Darin B

    2018-03-01

    Dysphagia screening protocols have been recommended to identify patients at risk for aspiration. The American Heart Association convened an evidence review committee to systematically review evidence for the effectiveness of dysphagia screening protocols to reduce the risk of pneumonia, death, or dependency after stroke. The Medline, Embase, and Cochrane databases were searched on November 1, 2016, to identify randomized controlled trials (RCTs) comparing dysphagia screening protocols or quality interventions with increased dysphagia screening rates and reporting outcomes of pneumonia, death, or dependency. Three RCTs were identified. One RCT found that a combined nursing quality improvement intervention targeting fever and glucose management and dysphagia screening reduced death and dependency but without reducing the pneumonia rate. Another RCT failed to find evidence that pneumonia rates were reduced by adding the cough reflex to routine dysphagia screening. A smaller RCT randomly assigned 2 hospital wards to a stroke care pathway including dysphagia screening or regular care and found that patients on the stroke care pathway were less likely to require intubation and mechanical ventilation; however, the study was small and at risk for bias. There were insufficient RCT data to determine the effect of dysphagia screening protocols on reducing the rates of pneumonia, death, or dependency after stroke. Additional trials are needed to compare the validity, feasibility, and clinical effectiveness of different screening methods for dysphagia. © 2018 American Heart Association, Inc.

  4. Diagnostic performance of EUS in predicting advanced cancer among patients with Barrett's esophagus and high-grade dysplasia/early adenocarcinoma: systematic review and meta-analysis.

    Science.gov (United States)

    Qumseya, Bashar J; Brown, Jessica; Abraham, Merna; White, Donna; Wolfsen, Herbert; Gupta, Neil; Vennalaganti, Prashanth; Sharma, Prateek; Wallace, Michael B

    2015-04-01

    The role of EUS among patients with Barrett's esophagus (BE) with high-grade dysplasia (HGD) or suspected mucosal carcinoma is controversial. To define the role of EUS in detecting advanced disease among patients with BE. Systematic review and meta-analysis. MEDLINE, Embase, Web of Science, and Cochrane Central databases. Patients with BE and HGD or esophageal adenocarcinoma (EAC) who were referred for endoscopic evaluation and underwent EUS. EUS. Pooled proportion of patients with advanced EAC identified by EUS among patients with BE who are referred for HGD or EAC (with or without visible lesions). Forest plots were used to contrast effect sizes in each of the studies and random effect models when tests of heterogeneity were significant (I(2) > 50% or P statistic). Of 1278 articles, 47 were reviewed in full text, and 11 articles met the inclusion criteria, including a total of 656 patients. Based on a random-effects model, the proportion of patients with advanced disease detected on EUS was 14% (95% confidence interval, 8%-22%; P advanced disease on EUS in the absence of nodules was 4% (95% confidence interval, 2%-6%, P < .0001). Significant heterogeneity among studies. EUS will result in a change in the therapeutic approach among in a significant minority of patients with BE who are referred for HGD or EAC. Copyright © 2015. Published by Elsevier Inc.

  5. Matched-pair comparisons of stereotactic body radiotherapy (SBRT) versus surgery for the treatment of early stage non-small cell lung cancer: A systematic review and meta-analysis

    International Nuclear Information System (INIS)

    Zhang, Binglan; Zhu, Fuping; Ma, Xuelei; Tian, Ye; Cao, Dan; Luo, Songe; Xuan, Yu; Liu, Lei; Wei, Yuquan

    2014-01-01

    Purpose: A population-based matched-pair comparison was performed to compare the efficacy of stereotactic body radiotherapy (SBRT) versus surgery for early-stage non-small cell lung cancer (NSCLC). Methods: All the eligible studies were searched by PubMed, Medline, Embase, and the Cochrane Library. The meta-analysis was performed to compare odds ratios (OR) for overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), local control (LC), and distant control (DC). Results: Six studies containing 864 matched patients were included in the meta-analysis. The surgery was associated with a better long-term OS in patients with early-stage NSCLC. The pooled OR and 95% confidence interval (CI) for 1-year, 3-year OS were 1.31 [0.90, 1.91] and 1.82 [1.38, 2.40], respectively. However, the difference in 1-year and 3-year CSS, DFS, LC and DC was not significant. Conclusions: This systematic review found a superior 3-year OS after surgery compared with SBRT, which supports the need to compare both treatments in large prospective, randomized, controlled clinical trials

  6. La protéine CG4572 de Drosophile et la propagation du signal ARNi immun antiviral

    OpenAIRE

    Karlikow , Margot

    2015-01-01

    During viral infection, cell survival will depend on adequately giving, receiving and processing information to establish an efficient antiviral immune response. Cellular communication is therefore essential to allow the propagation of immune signals that will confer protection to the entire organism.The major antiviral defense in insects is the RNA interference (RNAi) mechanism that is activated by detection of viral double-stranded RNA (dsRNA). The antiviral RNAi mechanism can be divided in...

  7. Treatment of Decompensated Cirrhosis Secondary to Hepatitis C with Antiviral Therapy

    International Nuclear Information System (INIS)

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

    2013-01-01

    Objective: To treat decompensated hepatitis C patient with interferon, ribavirin and amantidine to ascertain the sustained viral response. Study Design: Descriptive study. Place and Duration of Study: Shifa International Hospital, Islamabad, from January 2007 to January 2012. Methodology: HCV PCR patients with decompensated hepatitis C, who had developed a complication like ascites, encephalopathy or variceal bleeding were included in the study. Those with uncontrolled ascites or other complications were excluded. Treatment with standard interferon 3 miU subcutaneously three times a week along with ribavirin 800 mg to 1200 mg and amantidine 100 mg b.i.d. was administered for 12 months. Patients were followed every month with CBC and ALT and HCV PCR was performed after 3 months to document early viral response. They had HCV PCR at the end of the treatment to document end of treatment response. All were further followed for another 6 months at monthly intervals and HCV PCR was performed at the end of this period to document sustained viral response. Results: In all, 165 patients were treated. Treatment had to be discontinued in 42 (26%) patients. Out of these, 16 patients died. Thus, 123 completed treatment. Sustained viral response was documented in 58 out of the 123 (47%) patients. Hepatic encephalopathy, gastrointestinal bleeding, sepsis and development of ascites were the major complications during treatment. Conclusion: Forty seven percent of patients with decompensated hepatitis C cirrhosis were able to achieve sustained viral response after one year treatment with anti-viral therapy. However, complications developed during treatment and, therefore, frequent and close monitoring is necessary in these patients. (author)

  8. Safety and effectiveness of stem cell therapies in early-phase clinical trials in stroke: a systematic review and meta-analysis.

    Science.gov (United States)

    Nagpal, Anjali; Choy, Fong Chan; Howell, Stuart; Hillier, Susan; Chan, Fiona; Hamilton-Bruce, Monica A; Koblar, Simon A

    2017-08-30

    Stem cells have demonstrated encouraging potential as reparative therapy for patients suffering from post-stroke disability. Reperfusion interventions in the acute phase of stroke have shown significant benefit but are limited by a narrow window of opportunity in which they are beneficial. Thereafter, rehabilitation is the only intervention available. The current review summarises the current evidence for use of stem cell therapies in stroke from early-phase clinical trials. The safety and feasibility of administering different types of stem cell therapies in stroke seem to be reasonably proven. However, the effectiveness needs still to be established through bigger clinical trials with more pragmatic clinical trial designs that address the challenges raised by the heterogeneous nature of stroke per se, as well those due to unique characteristics of stem cells as therapeutic agents.

  9. Do online prognostication tools represent a valid alternative to genomic profiling in the context of adjuvant treatment of early breast cancer? A systematic review of the literature.

    Science.gov (United States)

    El Hage Chehade, Hiba; Wazir, Umar; Mokbel, Kinan; Kasem, Abdul; Mokbel, Kefah

    2018-01-01

    Decision-making regarding adjuvant chemotherapy has been based on clinical and pathological features. However, such decisions are seldom consistent. Web-based predictive models have been developed using data from cancer registries to help determine the need for adjuvant therapy. More recently, with the recognition of the heterogenous nature of breast cancer, genomic assays have been developed to aid in the therapeutic decision-making. We have carried out a comprehensive literature review regarding online prognostication tools and genomic assays to assess whether online tools could be used as valid alternatives to genomic profiling in decision-making regarding adjuvant therapy in early breast cancer. Breast cancer has been recently recognized as a heterogenous disease based on variations in molecular characteristics. Online tools are valuable in guiding adjuvant treatment, especially in resource constrained countries. However, in the era of personalized therapy, molecular profiling appears to be superior in predicting clinical outcome and guiding therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Craniodental morphology and systematics of a new family of hystricognathous rodents (Gaudeamuridae from the late eocene and early oligocene of Egypt.

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    Hesham M Sallam

    Full Text Available BACKGROUND: Gaudeamus is an enigmatic hystricognathous rodent that was, until recently, known solely from fragmentary material from early Oligocene sites in Egypt, Oman, and Libya. Gaudeamus' molars are similar to those of the extant cane rat Thryonomys, and multiple authorities have aligned Gaudeamus with Thryonomys to the exclusion of other living and extinct African hystricognaths; recent phylogenetic analyses have, however, also suggested affinities with South American caviomorphs or Old World porcupines (Hystricidae. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe the oldest known remains of Gaudeamus, including largely complete but crushed crania and complete upper and lower dentitions. Unlike younger Gaudeamus species, the primitive species described here have relatively complex occlusal patterns, and retain a number of plesiomorphic features. Unconstrained parsimony analysis nests Gaudeamus and Hystrix within the South American caviomorph radiation, implying what we consider to be an implausible back-dispersal across the Atlantic Ocean to account for Gaudeamus' presence in the late Eocene of Africa. An analysis that was constrained to recover the biogeographically more plausible hypothesis of caviomorph monophyly does not place Gaudeamus as a stem caviomorph, but rather as a sister taxon of hystricids. CONCLUSIONS/SIGNIFICANCE: We place Gaudeamus species in a new family, Gaudeamuridae, and consider it likely that the group originated, diversified, and then went extinct over a geologically brief period of time during the latest Eocene and early Oligocene in Afro-Arabia. Gaudeamurids are the only known crown hystricognaths from Afro-Arabia that are likely to be aligned with non-phiomorph members of that clade, and as such provide additional support for an Afro-Arabian origin of advanced stem and basal crown members of Hystricognathi.

  11. Early subsidence of shape-closed hip arthroplasty stems is associated with late revision. A systematic review and meta-analysis of 24 RSA studies and 56 survival studies.

    Science.gov (United States)

    van der Voort, Paul; Pijls, Bart G; Nieuwenhuijse, Marc J; Jasper, Jorrit; Fiocco, Marta; Plevier, Josepha W M; Middeldorp, Saskia; Valstar, Edward R; Nelissen, Rob G H H

    2015-01-01

    Few studies have addressed the association between early migration of femoral stems and late aseptic revision in total hip arthroplasty. We performed a meta-regression analysis on 2 parallel systematic reviews and meta-analyses to determine the association between early migration and late aseptic revision of femoral stems. Of the 2 reviews, one covered early migration data obtained from radiostereometric analysis (RSA) studies and the other covered long-term aseptic revision rates obtained from survival studies with endpoint revision for aseptic loosening. Stems were stratified according to the design concept: cemented shape-closed, cemented force-closed, and uncemented. A weighted regression model was used to assess the association between early migration and late aseptic revision, and to correct for confounders. Thresholds for acceptable and unacceptable migration were determined in accordance with the national joint registries (≤ 5% revision at 10 years) and the NICE criteria (≤ 10% revision at 10 years). 24 studies (731 stems) were included in the RSA review and 56 studies (20,599 stems) were included in the survival analysis review. Combining both reviews for the 3 design concepts showed that for every 0.1-mm increase in 2-year subsidence, as measured with RSA, there was a 4% increase in revision rate for the shape-closed stem designs. This association remained after correction for age, sex, diagnosis, hospital type, continent, and study quality. The threshold for acceptable migration of shape-closed designs was defined at 0.15 mm; stems subsiding less than 0.15 mm in 2 years had revision rates of less than 5% at 10 years, while stems exceeding 0.15 mm subsidence had revision rates of more than 5%. There was a clinically relevant association between early subsidence of shape-closed femoral stems and late revision for aseptic loosening. This association can be used to assess the safety of shape-closed stem designs. The published research is not sufficient

  12. In vitro antiviral activity of plant extracts from Asteraceae medicinal plants.

    Science.gov (United States)

    Visintini Jaime, María F; Redko, Flavia; Muschietti, Liliana V; Campos, Rodolfo H; Martino, Virginia S; Cavallaro, Lucia V

    2013-07-27

    Due to the high prevalence of viral infections having no specific treatment and the constant appearance of resistant viral strains, the development of novel antiviral agents is essential. The aim of this study was to evaluate the antiviral activity against bovine viral diarrhea virus, herpes simplex virus type 1 (HSV-1), poliovirus type 2 (PV-2) and vesicular stomatitis virus of organic (OE) and aqueous extracts (AE) from: Baccharis gaudichaudiana, B. spicata, Bidens subalternans, Pluchea sagittalis, Tagetes minuta and Tessaria absinthioides. A characterization of the antiviral activity of B. gaudichaudiana OE and AE and the bioassay-guided fractionation of the former and isolation of one active compound is also reported. The antiviral activity of the OE and AE of the selected plants was evaluated by reduction of the viral cytopathic effect. Active extracts were then assessed by plaque reduction assays. The antiviral activity of the most active extracts was characterized by evaluating their effect on the pretreatment, the virucidal activity and the effect on the adsorption or post-adsorption period of the viral cycle. The bioassay-guided fractionation of B. gaudichaudiana OE was carried out by column chromatography followed by semipreparative high performance liquid chromatography fractionation of the most active fraction and isolation of an active compound. The antiviral activity of this compound was also evaluated by plaque assay. B. gaudichaudiana and B. spicata OE were active against PV-2 and VSV. T. absinthioides OE was only active against PV-2. The corresponding three AE were active against HSV-1. B. gaudichaudiana extracts (OE and AE) were the most selective ones with selectivity index (SI) values of 10.9 (PV-2) and > 117 (HSV-1). For this reason, both extracts of B. gaudichaudiana were selected to characterize their antiviral effects. Further bioassay-guided fractionation of B. gaudichaudiana OE led to an active fraction, FC (EC50 = 3.1 μg/ml; SI = 37

  13. Global variations and time trends in the prevalence of childhood myopia, a systematic review and quantitative meta-analysis: implications for aetiology and early prevention.

    Science.gov (United States)

    Rudnicka, Alicja R; Kapetanakis, Venediktos V; Wathern, Andrea K; Logan, Nicola S; Gilmartin, Bernard; Whincup, Peter H; Cook, Derek G; Owen, Christopher G

    2016-07-01

    The aim of this review was to quantify the global variation in childhood myopia prevalence over time taking account of demographic and study design factors. A systematic review identified population-based surveys with estimates of childhood myopia prevalence published by February 2015. Multilevel binomial logistic regression of log odds of myopia was used to examine the association with age, gender, urban versus rural setting and survey year, among populations of different ethnic origins, adjusting for study design factors. 143 published articles (42 countries, 374 349 subjects aged 1-18 years, 74 847 myopia cases) were included. Increase in myopia prevalence with age varied by ethnicity. East Asians showed the highest prevalence, reaching 69% (95% credible intervals (CrI) 61% to 77%) at 15 years of age (86% among Singaporean-Chinese). Blacks in Africa had the lowest prevalence; 5.5% at 15 years (95% CrI 3% to 9%). Time trends in myopia prevalence over the last decade were small in whites, increased by 23% in East Asians, with a weaker increase among South Asians. Children from urban environments have 2.6 times the odds of myopia compared with those from rural environments. In whites and East Asians sex differences emerge at about 9 years of age; by late adolescence girls are twice as likely as boys to be myopic. Marked ethnic differences in age-specific prevalence of myopia exist. Rapid increases in myopia prevalence over time, particularly in East Asians, combined with a universally higher risk of myopia in urban settings, suggest that environmental factors play an important role in myopia development, which may offer scope for prevention. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  14. Nucleic acid-induced antiviral immunity in invertebrates: an evolutionary perspective.

    Science.gov (United States)

    Wang, Pei-Hui; Weng, Shao-Ping; He, Jian-Guo

    2015-02-01

    Nucleic acids derived from viral pathogens are typical pathogen associated molecular patterns (PAMPs). In mammals, the recognition of viral nucleic acids by pattern recognition receptors (PRRs), which include Toll-like receptors (TLRs) and retinoic acid-inducible gene (RIG)-I-like receptors (RLRs), induces the release of inflammatory cytokines and type I interferons (IFNs) through the activation of nuclear factor κB (NF-κB) and interferon regulatory factor (IRF) 3/7 pathways, triggering the host antiviral state. However, whether nucleic acids can induce similar antiviral immunity in invertebrates remains ambiguous. Several studies have reported that nucleic acid mimics, especially dsRNA mimic poly(I:C), can strongly induce non-specific antiviral immune responses in insects, shrimp, and oyster. This behavior shows multiple similarities to the hallmarks of mammalian IFN responses. In this review, we highlight the current understanding of nucleic acid-induced antiviral immunity in invertebrates. We also discuss the potential recognition and regulatory mechanisms that confer non-specific antiviral immunity on invertebrate hosts. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Removal of the antiviral agent oseltamivir and its biological activity by oxidative processes

    International Nuclear Information System (INIS)

    Mestankova, Hana; Schirmer, Kristin; Escher, Beate I.; Gunten, Urs von

    2012-01-01

    The antiviral agent oseltamivir acid (OA, the active metabolite of Tamiflu ® ) may occur at high concentrations in wastewater during pandemic influenza events. To eliminate OA and its antiviral activity from wastewater, ozonation and advanced oxidation processes were investigated. For circumneutral pH, kinetic measurements yielded second-order rate constants of 1.7 ± 0.1 × 10 5 and 4.7 ± 0.2 × 10 9 M −1 s −1 for the reaction of OA with ozone and hydroxyl radical, respectively. During the degradation of OA by both oxidants, the antiviral activity of the treated aqueous solutions was measured by inhibition of neuraminidase activity of two different viral strains. A transient, moderate (two-fold) increase in antiviral activity was observed in solutions treated up to a level of 50% OA transformation, while for higher degrees of transformation the activity corresponded to that caused exclusively by OA. OA was efficiently removed by ozonation in a wastewater treatment plant effluent, suggesting that ozonation can be applied to remove OA from wastewater. - Highlights: ► Oseltamivir acid (OA) is oxidized by ozone and hydroxyl radical. ► Kinetics: We determined rate constants for the reaction with these oxidants. ► The specific activity of OA as neuraminidase inhibitor disappeared during oxidation. ► Ozonation and advanced oxidation can effectively remove OA from wastewaters. - Ozone and hydroxyl radical treatment processes can degrade aqueous oseltamivir acid and remove its antiviral activity.

  16. Antiviral Activities of Several Oral Traditional Chinese Medicines against Influenza Viruses.

    Science.gov (United States)

    Ma, Lin-Lin; Ge, Miao; Wang, Hui-Qiang; Yin, Jin-Qiu; Jiang, Jian-Dong; Li, Yu-Huan

    2015-01-01

    Influenza is still a serious threat to human health with significant morbidity and mortality. The emergence of drug-resistant influenza viruses poses a great challenge to existing antiviral drugs. Traditional Chinese medicines (TCMs) may be an alternative to overcome the challenge. Here, 10 oral proprietary Chinese medicines were selected to evaluate their anti-influenza activities. These drugs exhibit potent inhibitory effects against influenza A H1N1, influenza A H3N2, and influenza B virus. Importantly, they demonstrate potent antiviral activities against drug-resistant strains. In the study of mechanisms, we found that Xiaoqinglong mixture could increase antiviral interferon production by activating p38 MAPK, JNK/SAPK pathway, and relative nuclear transcription factors. Lastly, our studies also indicate that some of these medicines show inhibitory activities against EV71 and CVB strains. In conclusion, the 10 traditional Chinese medicines, as kind of compound combination medicines, show broad-spectrum antiviral activities, possibly also including inhibitory activities against strains resistant to available antiviral drugs.

  17. Cytotoxic, Virucidal, and Antiviral Activity of South American Plant and Algae Extracts

    Directory of Open Access Journals (Sweden)

    Paula Faral-Tello

    2012-01-01

    Full Text Available Herpes simplex virus type 1 (HSV-1 infection has a prevalence of 70% in the human population. Treatment is based on acyclovir, valacyclovir, and foscarnet, three drugs that share the same mechanism of action and of which resistant strains have been isolated from patients. In this aspect, innovative drug therapies are required. Natural products offer unlimited opportunities for the discovery of antiviral compounds. In this study, 28 extracts corresponding to 24 plant species and 4 alga species were assayed in vitro to detect antiviral activity against HSV-1. Six of the methanolic extracts inactivated viral particles by direct interaction and 14 presented antiviral activity when incubated with cells already infected. Most interesting antiviral activity values obtained are those of Limonium brasiliense, Psidium guajava, and Phyllanthus niruri, which inhibit HSV-1 replication in vitro with 50% effective concentration (EC50 values of 185, 118, and 60 μg/mL, respectively. For these extracts toxicity values were calculated and therefore selectivity indexes (SI obtained. Further characterization of the bioactive components of antiviral plants will pave the way for the discovery of new compounds against HSV-1.

  18. In vitro antiviral activity of chestnut and quebracho woods extracts against avian reovirus and metapneumovirus.

    Science.gov (United States)

    Lupini, C; Cecchinato, M; Scagliarini, A; Graziani, R; Catelli, E

    2009-12-01

    Field evidences have suggested that a natural extract, containing tannins, could be effective against poultry enteric viral infections. Moreover previous studies have shown that vegetable tannins can have antiviral activity against human viruses. Based on this knowledge three different Chestnut (Castanea spp.) wood extracts and one Quebracho (Schinopsis spp.) wood extract, all containing tannins and currently used in the animal feed industry, were tested for in vitro antiviral activity against avian reovirus (ARV) and avian metapneumovirus (AMPV). The MTT assay was used to evaluate the 50% cytotoxic compounds concentration (CC(50)) on Vero cells. The antiviral properties were tested before and after the adsorption of the viruses to Vero cells. Antiviral activities were expressed as IC(50) (concentration required to inhibit 50% of viral cytopathic effect). CC(50)s of tested compounds were > 200 microg/ml. All compounds had an extracellular antiviral effect against both ARV and AMPV with IC(50) values ranging from 25 to 66 microg/ml. Quebracho extract had also evident intracellular anti-ARV activity (IC(50) 24 microg/ml). These preliminary results suggest that the examined vegetable extracts might be good candidates in the control of some avian virus infections. Nevertheless further in vivo experiments are required to confirm these findings.

  19. The Efficacy of Bisphosphonates in Preventing Aromatase Inhibitor Induced Bone Loss for Postmenopausal Women with Early Breast Cancer: A Systematic Review and Meta-Analysis

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    Pooleriveetil Padikkal Anagha

    2014-01-01

    Full Text Available Objectives. We aim to determine the efficacy of bisphosphonates in preventing aromatase inhibitor induced bone loss (AIBL in postmenopausal women with early breast cancer. The secondary objective was to determine the safety of bisphosphonates. Materials and Methods. We searched electronic databases in a time period of 1995 January to 2013 June. Random effects meta-analytical models were used; between study heterogeneity and publication bias was assessed. Results. A total of six eligible studies reported the BMD T score of LS at 12 months and from that 3 trials of Zoledronic acid compared the change in BMD in immediate ZOL versus delayed ZOL done with subgroups like patients with normal BMD at baseline (OR = 5.402, 95% CI = 1.329–21.959, P value = 0.018 and osteopenic BMD at baseline (OR = 4.008, 95% CI = 2.249–7.143, P value = 0.0002. Both had a significant decrease in BMD that favoured the delayed ZOL; 3 trials of risedronate and ibandronate also had a significant decrease in BMD in AIs alone group. Immediate ZOL versus delayed ZOL also showed increased risk of getting an ADR in immediate group. Conclusion. Third generation bisphosphonates has an effect on BMD of patients who are on treatment of AIs in breast cancer. Furthermore, the patients treated with immediate ZOL had a significantly high risk of musculoskeletal ADR’s than patients with delayed ZOL.

  20. Differentiation of early from advanced coronary atherosclerotic lesions: systematic comparison of CT, intravascular US, and optical frequency domain imaging with histopathologic examination in ex vivo human hearts.

    Science.gov (United States)

    Maurovich-Horvat, Pál; Schlett, Christopher L; Alkadhi, Hatem; Nakano, Masataka; Stolzmann, Paul; Vorpahl, Marc; Scheffel, Hans; Tanaka, Atsushi; Warger, William C; Maehara, Akiko; Ma, Shixin; Kriegel, Matthias F; Kaple, Ryan K; Seifarth, Harald; Bamberg, Fabian; Mintz, Gary S; Tearney, Guillermo J; Virmani, Renu; Hoffmann, Udo

    2012-11-01

    To establish an ex vivo experimental setup for imaging coronary atherosclerosis with coronary computed tomographic (CT) angiography, intravascular ultrasonography (US), and optical frequency domain imaging (OFDI) and to investigate their ability to help differentiate early from advanced coronary plaques. All procedures were performed in accordance with local and federal regulations and the Declaration of Helsinki. Approval of the local Ethics Committee was obtained. Overall, 379 histologic cuts from nine coronary arteries from three donor hearts were acquired, coregistered among modalities, and assessed for the presence and composition of atherosclerotic plaque. To assess the discriminatory capacity of the different modalities in the detection of advanced lesions, c statistic analysis was used. Interobserver agreement was assessed with the Cohen κ statistic. Cross sections without plaque at coronary CT angiography and with fibrous plaque at OFDI almost never showed advanced lesions at histopathologic examination (odds ratio [OR]: 0.02 and 0.06, respectively; both Padvanced lesions (OR: 2.49, P=.0003; OR: 2.60, P=.002; and OR: 31.2, Padvanced lesions than intravascular US and coronary CT angiography (area under the receiver operating characteristic curve: 0.858 [95% confidence interval {CI}: 0.802, 0.913], 0.631 [95% CI: 0.554, 0.709], and 0.679 [95% CI: 0.618, 0.740]; respectively, Padvanced coronary plaques. © RSNA, 2012

  1. Design, synthesis, antiviral activity and mode of action of phenanthrene-containing N-heterocyclic compounds inspired by the phenanthroindolizidine alkaloid antofine.

    Science.gov (United States)

    Yu, Xiuling; Wei, Peng; Wang, Ziwen; Liu, Yuxiu; Wang, Lizhong; Wang, Qingmin

    2016-02-01

    The phenanthroindolizidine alkaloid antofine and its analogues have excellent antiviral activity against tobacco mosaic virus (TMV). To simplify the structure and the synthesis of the phenanthroindolizidine alkaloid, a series of phenanthrene-containing N-heterocyclic compounds (compounds 1 to 33) were designed and synthesised, based on the intermolecular interaction of antofine and TMV RNA, and systematically evaluated for their anti-TMV activity. Most of these compounds exhibited good to reasonable anti-TMV activity. The optimum compounds 5, 12 and 21 displayed higher activity than the lead compound antofine and commercial ribavirin. Compound 12 was chosen for field trials of antiviral efficacy against TMV, and was found to exhibit better activity than control plant virus inhibitors. Compounds 5 and 12 were chosen for mode of action studies. The changes in fluorescence intensity of compounds 5 and 12 on separated TMV RNA showed that these small molecules can also bind to TMV RNA, but the mode is very different from that of antofine. The compounds combining phenanthrene and an N-heterocyclic ring could maintain the anti-TMV activity of phenanthroindolizidines, but their modes of action are different from that of antofine. The present study lays a good foundation for us to find more efficient anti-plant virus reagents. © 2015 Society of Chemical Industry.

  2. An integrated approach of network-based systems biology, molecular docking, and molecular dynamics approach to unravel the role of existing antiviral molecules against AIDS-associated cancer.

    Science.gov (United States)

    Omer, Ankur; Singh, Poonam

    2017-05-01

    A serious challenge in cancer treatment is to reposition the activity of various already known drug candidates against cancer. There is a need to rewrite and systematically analyze the detailed mechanistic aspect of cellular networks to gain insight into the novel role played by various molecules. Most Human Immunodeficiency Virus infection-associated cancers are caused by oncogenic viruses like Human Papilloma Viruses and Epstein-Bar Virus. As the onset of AIDS-associated cancers marks the severity of AIDS, there might be possible interconnections between the targets and mechanism of both the diseases. We have explored the possibility of certain antiviral compounds to act against major AIDS-associated cancers: Kaposi's Sarcoma, Non-Hodgkin Lymphoma, and Cervical Cancer with the help of systems pharmacology approach that includes screening for targets and molecules through the construction of a series of drug-target and drug-target-diseases network. Two molecules (Calanolide A and Chaetochromin B) and the target "HRAS" were finally screened with the help of molecular docking and molecular dynamics simulation. The results provide novel antiviral molecules against HRAS target to treat AIDS defining cancers and an insight for understanding the pharmacological, therapeutic aspects of similar unexplored molecules against various cancers.

  3. Antiviral Properties of Caffeic Acid Phenethyl Ester and Its Potential Application

    Directory of Open Access Journals (Sweden)

    Haci Kemal Erdemli

    2015-12-01

    Full Text Available Caffeic acid phenethyl ester (CAPE is found in variety of plants and well known active ingredient of the honeybee propolis. CAPE showed anti-inflammatory, anticarcinogenic, antimitogenic, antiviral and immunomodulatory properties in several studies. The beneficial effects of CAPE on different health issues attracted scientists to make more studies on CAPE. Specifically, the anti-viral effects of CAPE and its molecular mechanisms may reveal the important properties of virus-induced diseases. CAPE and its targets may have important roles to design new therapeutics and understand the molecular mechanisms of virus related diseases. In this mini-review, we summarize the antiviral effects of CAPE under the light of medical and chemical literature. [J Intercult Ethnopharmacol 2015; 4(4.000: 344-347

  4. Phytochemical screening, cytotoxicity and antiviral activity of hexane fraction of Phaleria macrocarpa fruits

    Science.gov (United States)

    Ismaeel, Mahmud Yusef Yusef; Yaacob, Wan Ahmad; Tahir, Mariya Mohd.; Ibrahim, Nazlina

    2015-09-01

    Phaleria macrocarpa fruits have been widely used in the traditional medicine for the treatment of several infections. The current study was done to determine the phytochemical content, cytotoxicity and antiviral activity of the hexane fraction (HF) of P. macrocarpa fruits. In the hexane fraction of P. macarocarpa fruits, phytochemical screening showed the presence of terpenoids whereas saponins, alkaloids, tannins and anthraquinones were not present. Evaluation on Vero cell lines by using MTT assay showed that the 50% cytotoxic concentration (CC50) value was 0.48 mg/mL indicating that the fraction is not cytotoxic. Antiviral properties of the plant extracts were determined by plaque reduction assay. The effective concentration (EC50) was 0.18 mg/mL. Whereas the selective index (SI = CC50/EC50) of hexane fraction is 2.6 indicating low to moderate potential as antiviral agent.

  5. Antiviral Activities and Putative Identification of Compounds in Microbial Extracts from the Hawaiian Coastal Waters

    Directory of Open Access Journals (Sweden)

    Yuanan Lu

    2012-02-01

    Full Text Available Marine environments are a rich source of significant bioactive compounds. The Hawaiian archipelago, located in the middle of the Pacific Ocean, hosts diverse microorganisms, including many endemic species. Thirty-eight microbial extracts from Hawaiian coastal waters were evaluated for their antiviral activity against four mammalian viruses including herpes simplex virus type one (HSV-1, vesicular stomatitis virus (VSV, vaccinia virus and poliovirus type one (poliovirus-1 using in vitro cell culture assay. Nine of the 38 microbial crude extracts showed antiviral potencies and three of these nine microbial extracts exhibited significant activity against the enveloped viruses. A secosteroid, 5α(H,17α(H,(20R-beta-acetoxyergost-8(14-ene was putatively identified and confirmed to be the active compound in these marine microbial extracts. These results warrant future in-depth tests on the isolation of these active elements in order to explore and validate their antiviral potential as important therapeutic remedies.

  6. Viruses transfer the antiviral second messenger cGAMP between cells.

    Science.gov (United States)

    Bridgeman, A; Maelfait, J; Davenne, T; Partridge, T; Peng, Y; Mayer, A; Dong, T; Kaever, V; Borrow, P; Rehwinkel, J

    2015-09-11

    Cyclic GMP-AMP synthase (cGAS) detects cytosolic DNA during virus infection and induces an antiviral state. cGAS signals by synthesis of a second messenger, cyclic GMP-AMP (cGAMP), which activates stimulator of interferon genes (STING). We show that cGAMP is incorporated into viral particles, including lentivirus and herpesvirus virions, when these are produced in cGAS-expressing cells. Virions transferred cGAMP to newly infected cells and triggered a STING-dependent antiviral program. These effects were independent of exosomes and viral nucleic acids. Our results reveal a way by which a signal for innate immunity is transferred between cells, potentially accelerating and broadening antiviral responses. Moreover, infection of dendritic cells with cGAMP-loaded lentiviruses enhanced their activation. Loading viral vectors with cGAMP therefore holds promise for vaccine development. Copyright © 2015, American Association for the Advancement of Science.

  7. ANTIMICROBIAL, ENTOMOPATHOGENIC AND ANTIVIRAL ACTIVITY OF GAUPSIN BIOPREPARATION CREATED ON THE BASIS OF Pseudomonas chlororaphis STRAINS

    Directory of Open Access Journals (Sweden)

    E. A. Kiprianova

    2017-02-01

    Full Text Available The aim of this review was to present the results of more than ten-year study of gaupsin biopreparation created on the basis of two strains Pseudomonas chlororaphis subsp. aureofaciens UCM В-111 and UCM В-306 with antifungal, entomopathogenic and antiviral activities. Data about antibiotic substances produced by these strains — phenazine and phenylpyrrole derivatives — are presented. Entomocidal properties against the wide spectrum of insect pests have been found out in the strains-producers. Antiviral activity of gaupsin due to the production of thermostable exopolymers containing neutral monosaccharides has been shown using the tobacco mosaic virus as a model. Lipopolysaccharides of the strains В-111 and В-306 also appeared to be highly active antiviral agents. Structure of their O-specific polysaccharides has been established. The last one are structurally heterogenic, presented by linear tri-and tetrasaccharide repeated links and have specific structure that has not been described previously.

  8. Divergent antiviral effects of bioflavonoids on the hepatitis C virus life cycle

    Energy Technology Data Exchange (ETDEWEB)

    Khachatoorian, Ronik, E-mail: RnKhch@ucla.edu [Molecular Biology Interdepartmental Ph.D. Program (MBIDP), Molecular Biology Institute, David Geffen School of Medicine at University of California, Los Angeles, California, CA (United States); Molecular Biology Institute, David Geffen School of Medicine at University of California, Los Angeles, California, CA (United States); Arumugaswami, Vaithilingaraja, E-mail: VArumugaswami@mednet.ucla.edu [Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at University of California, Los Angeles, California, CA (United States); Department of Surgery, Regenerative Medicine Institute at Cedars-Sinai Medical Center, Los Angeles, California, CA (United States); Raychaudhuri, Santanu, E-mail: SRaychau@ucla.edu [Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles, California, CA (United States); Yeh, George K., E-mail: GgYeh@ucla.edu [Molecular Biology Interdepartmental Ph.D. Program (MBIDP), Molecular Biology Institute, David Geffen School of Medicine at University of California, Los Angeles, California, CA (United States); Molecular Biology Institute, David Geffen School of Medicine at University of California, Los Angeles, California, CA (United States); Maloney, Eden M., E-mail: EMaloney@ucla.edu [Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, California, CA (United States); Wang, Julie, E-mail: JulieW1521@ucla.edu [Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles, California, CA (United States); and others

    2012-11-25

    We have previously demonstrated that quercetin, a bioflavonoid, blocks hepatitis C virus (HCV) proliferation by inhibiting NS5A-driven internal ribosomal entry site (IRES)-mediated translation of the viral genome. Here, we investigate the mechanisms of antiviral activity of quercetin and six additional bioflavonoids. We demonstrate that catechin, naringenin, and quercetin possess significant antiviral activity, with no associated cytotoxicity. Infectious virion secretion was not significantly altered by these bioflavonoids. Catechin and naringenin demonstrated stronger inhibition of infectious virion assembly compared to quercetin. Quercetin markedly blocked viral translation whereas catechin and naringenin demonstrated mild activity. Similarly quercetin completely blocked NS5A-augmented IRES-mediated translation in an IRES reporter assay, whereas catechin and naringenin had only a mild effect. Moreover, quercetin differentially inhibited HSP70 induction compared to catechin and naringenin. Thus, the antiviral activity of these bioflavonoids is mediated through different mechanisms. Therefore combination of these bioflavonoids may act synergistically against HCV.

  9. 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.

  10. Cytotoxicity and antiviral activities of Asplenium nidus, Phaleria macrocarpa and Eleusine indica

    Science.gov (United States)

    Tahir, Mariya Mohd; Ibrahim, Nazlina; Yaacob, Wan Ahmad

    2014-09-01

    Three local medicinal plants namely Asplenium nidus (langsuyar), Eleusine indica (sambau) and Phaleria macrocarpa (mahkota dewa) were screened for the cytotoxicity and antiviral activities. Six plant extracts were prepared including the aqueous and methanol extracts from A. nidus leaf and root, aqueous extract from dried whole plant of E. indica and methanol extract from P. macrocarpa fruits. Cytotoxicity screening in Vero cell line by MTT assay showed that the CC50 values ranged from 15 to 60 mg/mL thus indicating the safety of the extracts even at high concentrations. Antiviral properties of the plant extracts were determined by plaque reduction assay. The EC50 concentrations were between 3.2 to 47 mg/mL. The selectivity indices (SI = CC50/EC50) of each tested extracts ranged from 4.3 to 63.25 indicating the usefulness of the extracts as potential antiviral agents.

  11. Antiviral Goes Viral: Harnessing CRISPR/Cas9 to Combat Viruses in Humans.

    Science.gov (United States)

    Soppe, Jasper Adriaan; Lebbink, Robert Jan

    2017-10-01

    The clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) systems are RNA-guided sequence-specific prokaryotic antiviral immune systems. In prokaryotes, small RNA molecules guide Cas effector endonucleases to invading foreign genetic elements in a sequence-dependent manner, resulting in DNA cleavage by the endonuclease upon target binding. A rewired CRISPR/Cas9 system can be used for targeted and precise genome editing in eukaryotic cells. CRISPR/Cas has also been harnessed to target human pathogenic viruses as a potential new antiviral strategy. Here, we review recent CRISPR/Cas9-based approaches to combat specific human viruses in humans and discuss challenges that need to be overcome before CRISPR/Cas9 may be used in the clinic as an antiviral strategy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Synthesis, biological evaluation and molecular modeling investigation of some new Benzimidazole analogs as antiviral agents

    International Nuclear Information System (INIS)

    Goda, Fatma E.; Tantawy, Atif S.; Abou-Zeid, Laila A.; Badr, Sahar M.; Selim, Khalid B.

    2008-01-01

    A set heterocyclic benzimidazole derivatives bearing 1, 3, 5-triazine group with different substituents at C-2 and C-5 of the benzimidazole ring have been synthesized and evaluated for their antiviral activities against HASV-1. The structures of these compounds have been established by analytical data, IR spectra, H NMR and mass spectra. Compounds 8a and 8b proved to be the most active antiherpetic agents in this study, at EC 50% concentrations of 2.9. 3.4 mg/ml, respectively. Computational evaluation of the quantum chemical descriptors such as hydrphobicity (log P), HOMO-LUMO and the gap energy were calculated and correlated with the antiviral activity. The tested compounds showed proper degree of hydrophobicity ( 5). The HOMO-LUMO gap energy values of the tested compounds are comparable with the observed values for the antiviral drug Acyclovir. (author)

  13. A Systematic Review and Meta-Analysis of a Measure of Staff/Child Interaction Quality (the Classroom Assessment Scoring System) in Early Childhood Education and Care Settings and Child Outcomes.

    Science.gov (United States)

    Perlman, Michal; Falenchuk, Olesya; Fletcher, Brooke; McMullen, Evelyn; Beyene, Joseph; Shah, Prakesh S

    2016-01-01

    The quality of staff/child interactions as measured by the Classroom Assessment Scoring System (CLASS) in Early Childhood Education and Care (ECEC) programs is thought to be important for children's outcomes. The CLASS is made of three domains that assess Emotional Support, Classroom Organization and Instructional Support. It is a relatively new measure that is being used increasingly for research, quality monitoring/accountability and other applied purposes. Our objective was to evaluate the association between the CLASS and child outcomes. Searches of Medline, PsycINFO, ERIC, websites of large datasets and reference sections of all retrieved articles were conducted up to July 3, 2015. Studies that measured association between the CLASS and child outcomes for preschool-aged children who attended ECEC programs were included after screening by two independent reviewers. Searches and data extraction were conducted by two independent reviewers. Thirty-five studies were systematically reviewed of which 19 provided data for meta-analyses. Most studies had moderate to high risk of bias. Of the 14 meta-analyses we conducted, associations between Classroom Organization and Pencil Tapping and between Instructional Support and SSRS Social Skills were significant with pooled correlations of .06 and .09 respectively. All associations were in the expected direction. In the systematic review, significant correlations were reported mainly from one large dataset. Substantial heterogeneity in use of the CLASS, its dimensions, child outcomes and statistical measures was identified. Greater consistency in study methodology is urgently needed. Given the multitude of factors that impact child development it is encouraging that our analyses revealed some, although small, associations between the CLASS and children's outcomes.

  14. Impact of hepatitis C virus genotype-4 eradication following direct acting antivirals on liver stiffness measurement

    Directory of Open Access Journals (Sweden)

    Tag-Adeen M

    2017-10-01

    (APRI and fibrosis-4 index (Fib-4 after achieving SVR; 91% showed AST improvement (p=0.01 and APRI improvement (p=0.01 and 81% showed Fib-4 improvement (p=0.04. Females, diabetics, patients with S3 steatosis and patients older than 50 years showed less LSM improvements than their counterparts. Baseline LSM ≥9 kPa, bilirubin ≥1 mg/dl, ALT ≥36 U/L and AST ≥31 U/L were significant predictors for LSM improvement.Conclusion: Successful HCV genotype-4 eradication results in significant LSM improvement; the best improvement occurs in F4 patients. But as the majority of cirrhotics are still at risk for liver decompensation and hepatocellular carcinoma development despite achieving SVR-24, early detection and treatment are highly recommended. Keywords: hepatitis C virus, direct acting antivirals, liver stiffness measurements, FibroScan, transient elastography

  15. Topoisomerase 1 Inhibition Promotes Cyclic GMP-AMP Synthase-Dependent Antiviral Responses.

    Science.gov (United States)

    Pépin, Geneviève; Nejad, Charlotte; Ferrand, Jonathan; Thomas, Belinda J; Stunden, H James; Sanij, Elaine; Foo, Chwan-Hong; Stewart, Cameron R; Cain, Jason E; Bardin, Philip G; Williams, Bryan R G; Gantier, Michael P

    2017-10-03

    Inflammatory responses, while essential for pathogen clearance, can also be deleterious to the host. Chemical inhibition of topoisomerase 1 (Top1) by low-dose camptothecin (CPT) can suppress transcriptional induction of antiviral and inflammatory genes and protect animals from excessive and damaging inflammatory responses. We describe the unexpected finding that minor DNA damage from topoisomerase 1 inhibition with low-dose CPT can trigger a strong antiviral immune response through cyclic GMP-AMP synthase (cGAS) detection of cytoplasmic DNA. This argues against CPT having only anti-inflammatory activity. Furthermore, expression of the simian virus 40 (SV40) large T antigen was paramount to the proinflammatory antiviral activity of CPT, as it potentiated cytoplasmic DNA leakage and subsequent cGAS recruitment in human and mouse cell lines. This work suggests that the capacity of Top1 inhibitors to blunt inflammatory responses can be counteracted by viral oncogenes and that this should be taken into account for their therapeutic development. IMPORTANCE Recent studies suggest that low-dose DNA-damaging compounds traditionally used in cancer therapy can have opposite effects on antiviral responses, either suppressing (with the example of CPT) or potentiating (with the example of doxorubicin) them. Our work demonstrates that the minor DNA damage promoted by low-dose CPT can also trigger strong antiviral responses, dependent on the presence of viral oncogenes. Taken together, these results call for caution in the therapeutic use of low-dose chemotherapy agents to modulate antiviral responses in humans. Copyright © 2017 Pépin et al.

  16. Coxsackievirus cloverleaf RNA containing a 5' triphosphate triggers an antiviral response via RIG-I activation.

    Directory of Open Access Journals (Sweden)

    Qian Feng

    Full Text Available Upon viral infections, pattern recognition receptors (PRRs recognize pathogen-associated molecular patterns (PAMPs and stimulate an antiviral state associated with the production of type I interferons (IFNs and inflammatory markers. Type I IFNs play crucial roles in innate antiviral responses by inducing expression of interferon-stimulated genes and by activating components of the adaptive immune system. Although pegylated IFNs have been used to treat hepatitis B and C virus infections for decades, they exert substantial side effects that limit their use. Current efforts are directed toward the use of PRR agonists as an alternative approach to elicit host antiviral responses in a manner similar to that achieved in a natural infection. RIG-I is a cytosolic PRR that recognizes 5' triphosphate (5'ppp-containing RNA ligands. Due to its ubiquitous expression profile, induction of the RIG-I pathway provides a promising platform for the development of novel antiviral agents and vaccine adjuvants. In this study, we investigated whether structured RNA elements in the genome of coxsackievirus B3 (CVB3, a picornavirus that is recognized by MDA5 during infection, could activate RIG-I when supplied with 5'ppp. We show here that a 5'ppp-containing cloverleaf (CL RNA structure is a potent RIG-I inducer that elicits an extensive antiviral response that includes induction of classical interferon-stimulated genes, as well as type III IFNs and proinflammatory cytokines and chemokines. In addition, we show that prophylactic treatment with CVB3 CL provides protection against various viral infections including dengue virus, vesicular stomatitis virus and enterovirus 71, demonstrating the antiviral efficacy of this RNA ligand.

  17. Functional genomics highlights differential induction of antiviral pathways in the lungs of SARS-CoV-infected macaques.

    Directory of Open Access Journals (Sweden)

    Anna de Lang

    2007-08-01

    Full Text Available The pathogenesis of severe acute respiratory syndrome coronavirus (SARS-CoV is likely mediated by disproportional immune responses and the ability of the virus to circumvent innate immunity. Using functional genomics, we analyzed early host responses to SARS-CoV infection in the lungs of adolescent cynomolgus macaques (Macaca fascicularis that show lung pathology similar to that observed in human adults with SARS. Analysis of gene signatures revealed induction of a strong innate immune response characterized by the stimulation of various cytokine and chemokine genes, including interleukin (IL-6, IL-8, and IP-10, which corresponds to the host response seen in acute respiratory distress syndrome. As opposed to many in vitro experiments, SARS-CoV induced a wide range of type I interferons (IFNs and nuclear translocation of phosphorylated signal transducer and activator of transcription 1 in the lungs of macaques. Using immunohistochemistry, we revealed that these antiviral signaling pathways were differentially regulated in distinctive subsets of cells. Our studies emphasize that the induction of early IFN signaling may be critical to confer protection against SARS-CoV infection and highlight the strength of combining functional genomics with immunohistochemistry to further unravel the pathogenesis of SARS.

  18. Antiviral activity of the dichloromethane extracts from Artocarpus heterophyllus leaves against hepatitis C virus

    OpenAIRE

    Achmad Fuad Hafid; Chie Aoki-Utsubo; Adita Ayu Permanasari; Myrna Adianti; Lydia Tumewu; Aty Widyawaruyanti; Sri Puji Astuti Wahyuningsih; Tutik Sri Wahyuni; Maria Inge Lusida; Soetjipto; Hak Hotta

    2017-01-01

    Objective: To determine anti-viral activities of three Artocarpus species: Artocarpus altilis, Artocarpus camansi, and Artocarpus heterophyllus (A. heterophyllus) against Hepatitis C Virus (HCV). Methods: Antiviral activities of the crude extracts were examined by cell culture method using Huh7it-1 cells and HCV genotype 2a strain JFH1. The mode of action for anti-HCV activities was determined by time-of-addition experiments. The effect on HCV RNA replication and HCV accumulation in cells ...

  19. The Antiviral Mechanism of an Influenza A Virus Nucleoprotein-Specific Single-Domain Antibody Fragment

    Energy Technology Data Exchange (ETDEWEB)

    Hanke, Leo; Knockenhauer, Kevin E.; Brewer, R. Camille; van Diest, Eline; Schmidt, Florian I.; Schwartz, Thomas U.; Ploegh, Hidde L. (Whitehead); (MIT)

    2016-12-13

    Alpaca-derived single-domain antibody fragments (VHHs) that target the influenza A virus nucleoprotein (NP) can protect cells from infection when expressed in the cytosol. We found that one such VHH, αNP-VHH1, exhibits antiviral activity similar to that of Mx proteins by blocking nuclear import of incoming viral ribonucleoproteins (vRNPs) and viral transcription and replication in the nucleus. We determined a 3.2-Å crystal structure of αNP-VHH1 in complex with influenza A virus NP. The VHH binds to a nonconserved region on the body domain of NP, which has been associated with binding to host factors and serves as a determinant of host range. Several of the NP/VHH interface residues determine sensitivity of NP to antiviral Mx GTPases. The structure of the NP/αNP-VHH1 complex affords a plausible explanation for the inhibitory properties of the VHH and suggests a rationale for the antiviral properties of Mx proteins. Such knowledge can be leveraged for much-needed novel antiviral strategies.

    IMPORTANCEInfluenza virus strains can rapidly escape from protection afforded by seasonal vaccines or acquire resistance to available drugs. Additional ways to interfere with the virus life cycle are therefore urgently needed. The influenza virus nucleoprotein is one promising target for antiviral interventions. We have previously isolated alpaca-derived single-domain antibody fragments (VHHs) that protect cells from influenza virus infection if expressed intracellularly. We show here that one such VHH exhibits antiviral activities similar to those of proteins of the cellular antiviral defense (Mx proteins). We determined the three-dimensional structure of this VHH in complex with the influenza virus nucleoprotein and identified the interaction site, which overlaps regions that determine sensitivity of the virus to Mx proteins. Our data define a new vulnerability of influenza virus, help us to better understand the cellular antiviral mechanisms, and

  20. Antiviral Inhibition of Enveloped Virus Release by Tetherin/BST-2: Action and Counteraction

    Directory of Open Access Journals (Sweden)

    Stuart J. D. Neil

    2011-05-01

    Full Text Available Tetherin (BST2/CD317 has been recently recognized as a potent interferon-induced antiviral molecule that inhibits the release of diverse mammalian enveloped virus particles from infected cells. By targeting an immutable structure common to all these viruses, the virion membrane, evasion of this antiviral mechanism has necessitated the development of specific countermeasures that directly inhibit tetherin activity. Here we review our current understanding of the molecular basis of tetherin’s mode of action, the viral countermeasures that antagonize it, and how virus/tetherin interactions may affect viral transmission and pathogenicity.

  1. A systematic review and meta-analysis of early goal-directed therapy for septic shock: the ARISE, ProCESS and ProMISe Investigators.

    Science.gov (United States)

    Angus, D C; Barnato, A E; Bell, D; Bellomo, R; Chong, C-R; Coats, T J; Davies, A; Delaney, A; Harrison, D A; Holdgate, A; Howe, B; Huang, D T; Iwashyna, T; Kellum, J A; Peake, S L; Pike, F; Reade, M C; Rowan, K M; Singer, M; Webb, S A R; Weissfeld, L A; Yealy, D M; Young, J D

    2015-09-01

    To determine whether early goal-directed therapy (EGDT) reduces mortality compared with other resuscitation strategies for patients presenting to the emergency department (ED) with septic shock. Using a search strategy of PubMed, EmBase and CENTRAL, we selected all relevant randomised clinical trials published from January 2000 to January 2015. We translated non-English papers and contacted authors as necessary. Our primary analysis generated a pooled odds ratio (OR) from a fixed-effect model. Sensitivity analyses explored the effect of including non-ED studies, adjusting for study quality, and conducting a random-effects model. Secondary outcomes included organ support and hospital and ICU length of stay. From 2395 initially eligible abstracts, five randomised clinical trials (n = 4735 patients) met all criteria and generally scored high for quality except for lack of blinding. There was no effect on the primary mortality outcome (EGDT: 23.2% [495/2134] versus control: 22.4% [582/2601]; pooled OR 1.01 [95% CI 0.88-1.16], P = 0.9, with heterogeneity [I(2) = 57%; P = 0.055]). The pooled estimate of 90-day mortality from the three recent multicentre studies (n = 4063) also showed no difference [pooled OR 0.99 (95% CI 0.86-1.15), P = 0.93] with no heterogeneity (I(2) = 0.0%; P = 0.97). EGDT increased vasopressor use (OR 1.25 [95% CI 1.10-1.41]; P < 0.001) and ICU admission [OR 2.19 (95% CI 1.82-2.65); P < 0.001]. Including six non-ED randomised trials increased heterogeneity (I(2) = 71%; P < 0.001) but did not change overall results [pooled OR 0.94 (95% CI 0.82 to 1.07); P = 0.33]. EGDT is not superior to usual care for ED patients with septic shock but is associated with increased utilisation of ICU resources.

  2. The metallographic examination of sword no. 438 as part of a systematic survey of swords from the early medieval stronghold of Mikulčice, Czech Republic

    Directory of Open Access Journals (Sweden)

    Hošek, Jiří

    2012-12-01

    Full Text Available The paper deals with a metallographic examination of a sword from grave No. 438, which was uncovered at the site of Mikulčice (Hodonín county, a former early medieval stronghold in Moravia (Czech Republic. Mikulčice was one of the main power centres of the Great Moravia – the first state formed by Slavs north of the Danube River – which was created in the first third of the 9th century and ended at the beginning of the 10th century. The sword, provided with a single flattened hemispherical pommel (Petersen X type, has a blade bearing an inscription that is no longer legible. According to the results of metallographic examination, the blade was hardened and consists of steel cutting edges welded on a core, which was composed of steel side-plates and a middle strip of iron or low-carbon steel. It was an excellent sword, undoubtedly one of the best swords excavated in Mikulčice.

    El artículo trata de un examen metalográfico de una espada de la tumba número 438, que fue descubierta en el yacimiento de Mikulčice (Hodonín Condado, antiguo bastión bajomedieval en Moravia (República Checa. Mikulčice fue uno de los centros de poder principales del Gran Moravia - la primera agrupación estatal de los eslavos del norte del río Danubio - que se creó en el primer tercio del siglo IX y fue abolido al comienzo del siglo X. La espada, que cuenta con un pomo aplanado hemiesféri-co (Petersen tipo X, tiene una hoja con una inscripción que ya no es legible. De acuerdo con los resulta-dos del examen metalográfico, la hoja fue endurecida y se compone de filos de corte de acero, soldados a un núcleo. Éste está compuesto de placas laterales de acero y una franja central de hierro o de acero dulce. Era una espada excelente, sin duda, una de las mejores espadas jamás excavadas en Mikulčice.

  3. Type I interferon production during herpes simplex virus infection is controlled by cell-type-specific viral recognition through Toll-like receptor 9, the mitochondrial antiviral signaling protein pathway, and novel recognition systems

    DEFF Research Database (Denmark)

    Rasmussen, Simon Brandtoft; Sørensen, Louise Nørgaard; Malmgaard, Lene

    2007-01-01

    Recognition of viruses by germ line-encoded pattern recognition receptors of the innate immune system is essential for rapid production of type I interferon (IFN) and early antiviral defense. We investigated the mechanisms of viral recognition governing production of type I IFN during herpes...... simplex virus (HSV) infection. We show that early production of IFN in vivo is mediated through Toll-like receptor 9 (TLR9) and plasmacytoid dendritic cells, whereas the subsequent alpha/beta IFN (IFN-alpha/beta) response is derived from several cell types and induced independently of TLR9...

  4. 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

  5. Unidentified angular recurrent ulceration responsive to antiviral therapy

    Directory of Open Access Journals (Sweden)

    Rahmi Amtha

    2013-03-01

    Full Text Available Background: Recurrent ulcer on angular area is usually called stomatitis angularis. It is caused by many factors such as vertical dimension reduce, vitamin B12, and immune system deficiency, C. albicans and staphylococcus involvement. Clinically is characterized by painful fissure with erythematous base without fever. Purpose: to describe an unidentified angular ulcer proceeded by recurrent ulcers with no response of topical therapy. Case: An 18-years old male came to Oral Medicine clinic in RSCM who complained of angular recurrent ulcers since 3 years ago which developed on skin and bleed easily on mouth opening. Patient had fever before the onset of ulcers. Large, painful, irregular ulcers covered by red crustae on angular area bilaterally. Patient has been treated with various drugs without improvement and lead to mouth opening limitation. Intra oral shows herpetiformtype of ulcer and swollen of gingival. Case management: Provisional diagnosis was established as viral infection thus acyclovir 200 mg five times daily for two weeks and topical anti inflammation gel were administered. Blood test for IgG/IgM of HSV1 and HSV2 were non reactive, however ulceration showed a remarkable improvement. The ulcers healed completely after next 2 weeks with acyclovir. Conclusion: The angular ulceration on above patient failed to fulfill the criteria of stomatitis angularis or herpes labialis lesion. However it showed a good response to antiviral. Therefore, unidentified angular ulceration was appointed, as the lesion might be triggered by other type of human herpes virus or types of virus that response to acyclovir.Latar belakang: ulser rekuren pada sudut mulut biasanya disebut stomatitis angularis. Kelainan ini disebabkan oleh banyak faktor seperti berkurangnya dimensi vertikal, defisiensi vitamin B12 dan sistem kekebalan tubuh, infeksi C. albicans serta staphylococcus. Secara klinis kelainan ini ditandai dengan fisur sakit pada sudut mulut dengan dasar

  6. Clinical effectiveness of decongestive treatments on excess arm volume and patient-centered outcomes in women with early breast cancer-related arm lymphedema: a systematic review

    Science.gov (United States)

    Jeffs, Eunice; Ream, Emma; Taylor, Cath; Bick, Debra

    2018-01-01

    outcome measures were not pooled in statistical meta-analysis. A narrative and tabular format was used to synthesize results from identified and included studies. Results: Seven studies reporting results for outcomes of interest were critically appraised and included in the review: five randomized controlled trials and two descriptive (uncontrolled) studies. Reported outcomes included excess arm volume (five studies), health-related quality of life (three studies), arm heaviness (one study), arm function (two studies) and patient-perceived benefit (two studies). There was some evidence that decongestive treatments were effective for women presenting within either 12 months or a mean of nine months of developing breast cancer-related arm lymphedema, but the wide range of data prevented comparison of treatment findings which limited our ability to answer the review questions. Conclusions: Weak evidence (grade B) for the impact of decongestive lymphedema treatment on women with early lymphedema (i.e. less than 12 months duration of BCRL symptoms) did not allow any conclusions to be drawn about the most effective treatment to be offered when these women first present for treatment. Findings provided no justification to support change to current practice. Future primary research needs to focus on the most effective treatment for women when they first present with lymphedema symptoms, e.g. treatment provided within 12 months of developing symptoms. Studies should be adequately powered and recruit women exclusively with less than 12 months duration of breast cancer-related lymphedema symptoms, provide longer follow-up to monitor treatment effect over time, with comparable treatment protocols, outcome measures and reporting methods. PMID:29419623

  7. Estudio de sensibilidad antiviral de Virus Herpes simplex en pacientes trasplantados Antiviral sensitivity of Herpes simplex virus in immunocompromised patients

    Directory of Open Access Journals (Sweden)

    H. Illán

    2004-06-01

    alteration in genes coding for the TK or the DNA-polymerase. A previous large-scale clinical study on ACVr HSV strains isolated from patients infected with human immunodeficiency virus indicated that 96 % of ACVr HSV mutants were low producers of, or deficient in, TK activity (TK-, with 4 % being TK mutants with an altered substrate specificity. No DNA Pol mutants were isolated. The pirophosphate analogs generate resistance in the gene of DNA-polymerase by mutation. In this paper we show the methodology used for the determination of sensibilite profiles to ACV and Phoscarnet (PFA in a population of inmunocompromised patients. We analized 46 HSV strain from vesicular injuries of transplanted patients. All samples, were inoculated in human fibroblasts and the HSV isolates were identified by inmunofluorescence whith monoclonal antibodies. These strains were amplified and the profile of susceptibility determinated in Vero cells, using 100 tissue culture inhibition dosis 50(TCID50of each Viral stock and the specific antiviral drugs in different concentrations. The cytopathic effect (CPE was evaluated after 72hs. post infection. The 50% inhibitory concentration (CI50 was calculated from the percentage of inhibition of the ECP based on the concentration of the drug. From 46 isolations, 26 were HSV-1 and 20 were HSV-2. Two of them, one HSV-1 andone HSV-2, were resistant to ACV and none of the isolates were resistant to PFA.

  8. Triazole nucleoside derivatives bearing aryl functionalities on the nucleobases show antiviral and anticancer activity.

    Science.gov (United States)

    Xia, Yi; Qu, Fanqi; Peng, Ling

    2010-08-01

    Synthetic nucleoside mimics are important candidates in the searing for antiviral and anticancer drugs. Ribavirin, the first antiviral nucleoside drug, is unique in its antiviral activity with mutilple modes of action, which are mainly due to its special triazole heterocycle as nucleobase. Additionally, introducing aromatic functionalities to the nucleobase is able to confer novel mechanisms of action for nucleoside mimics. With the aim to combine the special characteristics of unnatural triazole heterocycles with those of the appended aromatic groups on the nucleobases, novel 1,2,4-triazole nucleoside analogs bearing aromatic moieties were designed and developed. The present short review summarizes the molecular design, chemical synthesis and biological activity of these triazole nucleoside analogs. Indeed, the discovery of antiviral and anticancer activities shown by these triazole nucleosides as well as the new mechanism underlying the biological activity by one of the anticancer leads has validated the rationale for molecular design and impacted us to further explore the concept with the aim of developing structurally novel nucleoside drug candidates with new modes of action.

  9. Antiviral activity of Justicia gendarussa Burm.f. leaves against HIV ...

    African Journals Online (AJOL)

    Backgrounds: Justicia gendarussa Burm.f. has been known to have anti-HIV activity. This study was conducted to evaluate the effect of incubation time on the antiviral activity of the J. gendarussa leaves extract on HIV-infected MT-4 cells in vitro. Molecular docking test was also conducted to determine the interaction of ...

  10. Defense and counterdefense in the RNAi-based antiviral immune system in insects

    NARCIS (Netherlands)

    van Mierlo, J.T.; van Cleef, K.W.; Rij, R.P. van

    2011-01-01

    RNA interference (RNAi) is an important pathway to combat virus infections in insects and plants. Hallmarks of antiviral RNAi in these organisms are: (1) an increase in virus replication after inactivation of major actors in the RNAi pathway, (2) production of virus-derived small interfering RNAs

  11. In-vitro antiviral efficacy of ribavirin and interferon-alpha against canine distemper virus.

    Science.gov (United States)

    Carvalho, Otávio V; Saraiva, Giuliana L; Ferreira, Caroline G T; Felix, Daniele M; Fietto, Juliana L R; Bressan, Gustavo C; Almeida, Márcia R; Silva Júnior, Abelardo

    2014-10-01

    Canine distemper is a highly contagious disease with high incidence and lethality in the canine population. The objective of this study was to evaluate the efficacy of antiviral action with ribavirin (RBV), interferon-alpha (IFNα), and combinations of RBV and IFNα against canine distemper virus (CDV). Vero cells inoculated with CDV were treated with RBV, IFNα, and combinations of these drugs. The efficacy to inhibit viral replication was evaluated by adding the compounds at different times to determine which step of the viral replicative process was affected. Both drugs were effective against CDV in vitro. The IFNα was the most active compound, with an average IC50 (50% inhibitory concentration) value lower than the IC50 of the RBV. Ribavirin (RBV) was more selective than IFNα, however, and neither drug showed extracellular antiviral activity. The combination of RBV and IFNα exhibited antiviral activity for the intra- and extracellular stages of the replicative cycle of CDV, although the intracellular viral inhibition was higher. Both RBV and IFNα showed high antiviral efficacy against CDV, and furthermore, RBV + IFNα combinations have shown greater interference range in viral infectivity. These compounds could potentially be used to treat clinical disease associated with CDV infection.

  12. Use of competitive polymerase chain reaction to determine HIV-1 levels in response to antiviral treatments

    NARCIS (Netherlands)

    Bruisten, S. M.; Koppelman, M. H.; Roos, M. T.; Loeliger, A. E.; Reiss, P.; Boucher, C. A.; Huisman, H. G.

    1993-01-01

    OBJECTIVE: To develop a competitive polymerase chain reaction technique with which to evaluate the usefulness of HIV-1 level as a marker of response to antiviral treatment. DESIGN: HIV-1 sequences were assessed by competitive polymerase chain reaction in four subjects participating in a double-blind

  13. Middle East Respiratory Coronavirus Accessory Protein 4a Inhibits PKR-Mediated Antiviral Stress Responses

    NARCIS (Netherlands)

    Rabouw, Huib H; Langereis, Martijn A; Knaap, Robert C M; Dalebout, Tim J; Canton, Javier; Sola, Isabel; Enjuanes, Luis; Bredenbeek, Peter J; Kikkert, Marjolein; de Groot, Raoul J; van Kuppeveld, Frank J M

    2016-01-01

    Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe respiratory infections that can be life-threatening. To establish an infection and spread, MERS-CoV, like most other viruses, must navigate through an intricate network of antiviral host responses. Besides the well-known type I

  14. A small effect of adding antiviral agents in treating patients with severe Bell palsy.

    Science.gov (United States)

    van der Veen, Erwin L; Rovers, Maroeska M; de Ru, J Alexander; van der Heijden, Geert J

    2012-03-01

    In this evidence-based case report, the authors studied the following clinical question: What is the effect of adding antiviral agents to corticosteroids in the treatment of patients with severe or complete Bell palsy? The search yielded 250 original research articles. The 6 randomized trials of these that could be used all reported low-quality data for answering the clinical question; apart from apparent flaws, they did not primarily include patients with severe or complete Bell palsy. Complete functional facial nerve recovery was seen in 75% of the patients receiving prednisolone only and in 83% with additional antiviral treatment. The pooled risk difference of 7% (95% confidence interval, -1% to 15%) results in a number needed to treat of 14 (ie, slightly favors adding an antiviral agent). The authors conclude that although a strong recommendation for adding antiviral agents to corticosteroids to further improve the recovery of patients with severe Bell palsy is precluded by the lack of robust evidence, it should be discussed with the patient.

  15. A small effect of adding antiviral agents in treating patients with severe Bell palsy.

    NARCIS (Netherlands)

    Veen, E.L. van der; Rovers, M.M.; Ru, J.A. de; Heijden, G.J. van der

    2012-01-01

    In this evidence-based case report, the authors studied the following clinical question: What is the effect of adding antiviral agents to corticosteroids in the treatment of patients with severe or complete Bell palsy? The search yielded 250 original research articles. The 6 randomized trials of

  16. Antiviral activity of Dianthus superbusn L. against hepatitis B virus in ...

    African Journals Online (AJOL)

    Background: Hepatitis is a viral infection of hepatitis B virus (HBV). Limitations of drug used in the management of it opens the interest related to alternative medicine. The given study deals with the antiviral activity of Dianthus superbusn L. (DSL) against HBV in vitro & in vivo. Material and Methods: In vitro study liver cell line ...

  17. Ganciclovir Antiviral Therapy in Advanced Idiopathic Pulmonary Fibrosis: An Open Pilot Study

    Directory of Open Access Journals (Sweden)

    J. J. Egan

    2011-01-01

    Conclusion. This audit outcome suggests that 2-week course of ganciclovir (iv may attenuate disease progression in a subgroup of advanced IPF patients. These observations do not suggest that anti-viral treatment is a substitute for the standard care, however, suggests the need to explore the efficacy of ganciclovir as adjunctive therapy in IPF.

  18. Negative regulation of RIG-I-mediated antiviral signaling by TRK-fused gene (TFG) protein

    International Nuclear Information System (INIS)

    Lee, Na-Rae; Shin, Han-Bo; Kim, Hye-In; Choi, Myung-Soo; Inn, Kyung-Soo

    2013-01-01

    Highlights: •TRK-fused gene product (TFG) interacts with TRIM25 upon viral infection. •TFG negatively regulates RIG-I mediated antiviral signaling. •TFG depletion leads to enhanced viral replication. •TFG act downstream of MAVS. -- Abstract: RIG-I (retinoic acid inducible gene I)-mediated antiviral signaling serves as the first line of defense against viral infection. Upon detection of viral RNA, RIG-I undergoes TRIM25 (tripartite motif protein 25)-mediated K63-linked ubiquitination, leading to type I interferon (IFN) production. In this study, we demonstrate that TRK-fused gene (TFG) protein, previously identified as a TRIM25-interacting protein, binds TRIM25 upon virus infection and negatively regulates RIG-I-mediated type-I IFN signaling. RIG-I-mediated IFN production and nuclear factor (NF)-κB signaling pathways were upregulated by the suppression of TFG expression. Furthermore, vesicular stomatitis virus (VSV) replication was significantly inhibited by small inhibitory hairpin RNA (shRNA)-mediated knockdown of TFG, supporting the suppressive role of TFG in RIG-I-mediated antiviral signaling. Interestingly, suppression of TFG expression increased not only RIG-I-mediated signaling but also MAVS (mitochondrial antiviral signaling protein)-induced signaling, suggesting that TFG plays a pivotal role in negative regulation of RNA-sensing, RIG-I-like receptor (RLR) family signaling pathways

  19. Conformationally locked nucleoside analogues based on the bridgehead substituted 7-oxonorbornane and their antiviral properties

    Czech Academy of Sciences Publication Activity Database

    Dejmek, Milan; Hřebabecký, Hubert; Dračínský, Martin; Neyts, J.; Leyssen, P.; Mertlíková-Kaiserová, Helena; Nencka, Radim

    2011-01-01

    Roč. 76, č. 12 (2011), s. 1549-1566 ISSN 0010-0765 R&D Projects: GA MŠk 1M0508 Institutional research plan: CEZ:AV0Z40550506 Keywords : 1'-homonucleosides * Diels - Alder reaction * antiviral agents Subject RIV: CC - Organic Chemistry Impact factor: 1.283, year: 2011

  20. Arthropod-borne flaviviruses and RNA interference : seeking new approaches for antiviral therapy

    NARCIS (Netherlands)

    Diosa-Toro, Mayra; Urcuqui-Inchima, Silvio; Smit, Jolanda M

    2013-01-01

    Flaviviruses are the most prevalent arthropod-borne viruses worldwide, and nearly half of the 70 Flavivirus members identified are human pathogens. Despite the huge clinical impact of flaviviruses, there is no specific human antiviral therapy available to treat infection with any of the

  1. Prolonged influenza virus shedding and emergence of antiviral resistance in immunocompromised patients and ferrets.

    Directory of Open Access Journals (Sweden)

    Erhard van der Vries

    Full Text Available Immunocompromised individuals tend to suffer from influenza longer with more serious complications than otherwise healthy patients. Little is known about the impact of prolonged infection and the efficacy of antiviral therapy in these patients. Among all 189 influenza A virus infected immunocompromised patients admitted to ErasmusMC, 71 were hospitalized, since the start of the 2009 H1N1 pandemic. We identified 11 (15% cases with prolonged 2009 pandemic virus replication (longer than 14 days, despite antiviral therapy. In 5 out of these 11 (45% cases oseltamivir resistant H275Y viruses emerged. Given the inherent difficulties in studying antiviral efficacy in immunocompromised patients, we have infected immunocompromised ferrets with either wild-type, or oseltamivir-resistant (H275Y 2009 pandemic virus. All ferrets showed prolonged virus shedding. In wild-type virus infected animals treated with oseltamivir, H275Y resistant variants emerged within a week after infection. Unexpectedly, oseltamivir therapy still proved to be partially protective in animals infected with resistant virus. Immunocompromised ferrets offer an attractive alternative to study efficacy of novel antiviral therapies.

  2. Nose-to-Brain Delivery of Antiviral Drugs: A Way to Overcome Their Active Efflux?

    Directory of Open Access Journals (Sweden)

    Alessandro Dalpiaz

    2018-03-01

    Full Text Available Although several viruses can easily infect the central nervous system (CNS, antiviral drugs often show dramatic difficulties in penetrating the brain from the bloodstream since they are substrates of active efflux transporters (AETs. These transporters, located in the physiological barriers between blood and the CNS and in macrophage membranes, are able to recognize their substrates and actively efflux them into the bloodstream. The active transporters currently known to efflux antiviral drugs are P-glycoprotein (ABCB1 or P-gp or MDR1, multidrug resistance-associated proteins (ABCC1 or MRP1, ABCC4 or MRP4, ABCC5 or MRP5, and breast cancer resistance protein (ABCG2 or BCRP. Inhibitors of AETs may be considered, but their co-administration causes serious unwanted effects. Nasal administration of antiviral drugs is therefore proposed in order to overcome the aforementioned problems, but innovative devices, formulations (thermoreversible gels, polymeric micro- and nano-particles, solid lipid microparticles, nanoemulsions, absorption enhancers (chitosan, papaverine, and mucoadhesive agents (chitosan, polyvinilpyrrolidone are required in order to selectively target the antiviral drugs and, possibly, the AET inhibitors in the CNS. Moreover, several prodrugs of antiretroviral agents can inhibit or elude the AET systems, appearing as interesting substrates for innovative nasal formulations able to target anti-Human Immunodeficiency Virus (HIV agents into macrophages of the CNS, which are one of the most important HIV Sanctuaries of the body.

  3. Antiviral therapy for prevention of hepatocellular carcinoma and mortality in chronic hepatitis B

    DEFF Research Database (Denmark)

    Thiele, Maja; Gluud, Lise Lotte; Dahl, Emilie K

    2013-01-01

    The effect of antiviral therapy on clinical outcomes in chronic hepatitis B virus (HBV) is not established. We aimed to assess the effects of interferon and/or nucleos(t)ide analogues versus placebo or no intervention on prevention of hepatocellular carcinoma (HCC) and mortality in chronic HBV....

  4. Tannic acid modified silver nanoparticles show antiviral activity in herpes simplex virus type 2 infection.

    Directory of Open Access Journals (Sweden)

    Piotr Orlowski

    Full Text Available The interaction between silver nanoparticles and herpesviruses is attracting great interest due to their antiviral activity and possibility to use as microbicides for oral and anogenital herpes. In this work, we demonstrate that tannic acid modified silver nanoparticles sized 13 nm, 33 nm and 46 nm are capable of reducing HSV-2 infectivity both in vitro and in vivo. The antiviral activity of tannic acid modified silver nanoparticles was size-related, required direct interaction and blocked virus attachment, penetration and further spread. All tested tannic acid modified silver nanoparticles reduced both infection and inflammatory reaction in the mouse model of HSV-2 infection when used at infection or for a post-infection treatment. Smaller-sized nanoparticles induced production of cytokines and chemokines important for anti-viral response. The corresponding control buffers with tannic acid showed inferior antiviral effects in vitro and were ineffective in blocking in vivo infection. Our results show that tannic acid modified silver nanoparticles are good candidates for microbicides used in treatment of herpesvirus infections.

  5. Antiviral activity of human lactoferrin: inhibition of alphavirus interaction with heparan sulfate

    International Nuclear Information System (INIS)

    Waarts, Barry-Lee; Aneke, Onwuchekwa J.C.; Smit, Jolanda M.; Kimata, Koji; Bittman, Robert; Meijer, Dirk K.F.; Wilschut, Jan

    2005-01-01

    Human lactoferrin is a component of the non-specific immune system with distinct antiviral properties. We used alphaviruses, adapted to interaction with heparan sulfate (HS), as a tool to investigate the mechanism of lactoferrin's antiviral activity. Lactoferrin inhibited infection of BHK-21 cells by HS-adapted, but not by non-adapted, Sindbis virus (SIN) or Semliki Forest virus (SFV). Lactoferrin also inhibited binding of radiolabeled HS-adapted viruses to BHK-21 cells or liposomes containing lipid-conjugated heparin as a receptor analog. On the other hand, low-pH-induced fusion of the viruses with liposomes, which occurs independently of virus-receptor interaction, was unaffected. Studies involving preincubation of virus or cells with lactoferrin suggested that the protein does not bind to the virus, but rather blocks HS-moieties on the cell surface. Charge-modified human serum albumin, with a net positive charge, had a similar antiviral effect against HS-adapted SIN and SFV, suggesting that the antiviral activity of lactoferrin is related to its positive charge. It is concluded that human lactoferrin inhibits viral infection by interfering with virus-receptor interaction rather than by affecting subsequent steps in the viral cell entry or replication processes

  6. Antivirals Use During the Pandemic H1N1 2009 Outbreak

    Centers for Disease Control (CDC) Podcasts

    2012-01-23

    Charisma Atkins, CDC public health analyst, discusses antiviral use during the 2009 H1N1 pandemic flu outbreak.  Created: 1/23/2012 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 1/23/2012.

  7. NEOGLYCOPROTEINS AS CARRIERS FOR ANTIVIRAL DRUGS - SYNTHESIS AND ANALYSIS OF PROTEIN DRUG CONJUGATES

    NARCIS (Netherlands)

    Molema, Grietje; Jansen, Robert W.; Visser, Jan; Herdewijn, Piet; Moolenaar, Frits; Meijer, Dirk K.F.

    In order to investigate whether neoglycoproteins can potentially act as carriers for targeting of antiviral drugs to certain cell types in the body, various neoglycoproteins were synthesized using thiophosgene-activated p-aminophenyl sugar derivatives. These neoglycoproteins were conjugated with the

  8. Antiviral Goes Viral : Harnessing CRISPR/Cas9 to Combat Viruses in Humans

    NARCIS (Netherlands)

    Soppe, Jasper Adriaan; Lebbink, Robert Jan

    2017-01-01

    The clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) systems are RNA-guided sequence-specific prokaryotic antiviral immune systems. In prokaryotes, small RNA molecules guide Cas effector endonucleases to invading foreign genetic elements in a

  9. 75 FR 16810 - Determination and Declarations Regarding Emergency Use of Certain In vitro Diagnostic, Antiviral...

    Science.gov (United States)

    2010-04-02

    ... specified that these declarations are declarations of emergency as defined by former Secretary Michael O... essence in detecting, preventing, and treating illness and death by getting in vitro diagnostic, antiviral... that the declaration is a declaration of emergency, as defined in the December 17, 2008 Declaration...

  10. Transdermal Delivery and Cutaneous Targeting of Antivirals using a Penetration Enhancer and Lysolipid Prodrugs

    Czech Academy of Sciences Publication Activity Database

    Diblíková, D.; Kopečná, M.; Školová, B.; Krečmerová, Marcela; Roh, J.; Hrabálek, A.; Vávrová, K.

    2014-01-01

    Roč. 31, č. 4 (2014), s. 1071-1081 ISSN 0724-8741 Grant - others:GA ČR(CZ) GAP207/11/0365 Institutional support: RVO:61388963 Keywords : acyclic nucleoside phosphonate antivirals * lysolipid prodrug * penetration enhancer * skin absorption * transdermal drug delivery Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 3.420, year: 2014

  11. A molecular arms race between host innate antiviral response and emerging human coronaviruses.

    Science.gov (United States)

    Wong, Lok-Yin Roy; Lui, Pak-Yin; Jin, Dong-Yan

    2016-02-01

    Coronaviruses have been closely related with mankind for thousands of years. Community-acquired human coronaviruses have long been recognized to cause common cold. However, zoonotic coronaviruses are now becoming more a global concern with the discovery of highly pathogenic severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses causing severe respiratory diseases. Infections by these emerging human coronaviruses are characterized by less robust interferon production. Treatment of patients with recombinant interferon regimen promises beneficial outcomes, suggesting that compromised interferon expression might contribute at least partially to the severity of disease. The mechanisms by which coronaviruses evade host innate antiviral response are under intense investigations. This review focuses on the fierce arms race between host innate antiviral immunity and emerging human coronaviruses. Particularly, the host pathogen recognition receptors and the signal transduction pathways to mount an effective antiviral response against SARS and MERS coronavirus infection are discussed. On the other hand, the counter-measures evolved by SARS and MERS coronaviruses to circumvent host defense are also dissected. With a better understanding of the dynamic interaction between host and coronaviruses, it is hoped that insights on the pathogenesis of newly-identified highly pathogenic human coronaviruses and new strategies in antiviral development can be derived.

  12. Chronic Hepatitis C and Antiviral Treatment Regimens: Where Can Psychology Contribute?

    Science.gov (United States)

    Evon, Donna M.; Golin, Carol E.; Fried, Michael W.; Keefe, Francis J.

    2013-01-01

    Objective: Our goal was to evaluate the existing literature on psychological, social, and behavioral aspects of chronic hepatitis C viral (HCV) infection and antiviral treatment; provide the state of the behavioral science in areas that presently hinder HCV-related health outcomes; and make recommendations for areas in which clinical psychology…

  13. Application of Orem self-care theory on injection of interferon antiviral therapy in patients with

    Directory of Open Access Journals (Sweden)

    Xiujuan Tao

    2015-01-01

    Full Text Available Guided by Orem self-care theory, the nursing staff evaluate the injection of interferon antiviral therapy in patients, finding that patients with the presence of self-care was insufficient, so effective nursing care in different periods of application of different nursing system was necessary.

  14. Antiviral activity of ovine interferon tau 4 against foot-and-mouth disease virus.

    Science.gov (United States)

    Usharani, Jayaramaiah; Park, Sun Young; Cho, Eun-Ju; Kim, Chungsu; Ko, Young-Joon; Tark, Dongseob; Kim, Su-Mi; Park, Jong-Hyeon; Lee, Kwang-Nyeong; Lee, Myoung-Heon; Lee, Hyang-Sim

    2017-07-01

    Foot-and-mouth disease (FMD) is an economically important disease in most parts of the world and new therapeutic agents are needed to protect the animals before vaccination can trigger the host immune response. Although several interferons have been used for their antiviral activities against Foot-and-mouth disease virus (FMDV), ovine interferon tau 4 (OvIFN-τ4), with a broad-spectrum of action, cross-species antiviral activity, and lower incidence of toxicity in comparison to other type І interferons, has not yet been evaluated for this indication. This is the first study to evaluate the antiviral activity of OvIFN-τ4 against various strains of FMDV. The effective anti-cytopathic concentration of OvIFN-τ4 and its effectiveness pre- and post-infection with FMDV were tested in vitro in LFBK cells. In vivo activity of OvIFN-τ4 was then confirmed in a mouse model of infection. OvIFN-τ4 at a concentration of 500 ng, protected mice until 5days post-FMDV challenge and provided 90% protection for 10 days following FMDV challenge. These results suggest that OvIFN-τ4 could be used as an alternative to other interferons or antiviral agents at the time of FMD outbreak. Copyright © 2017. Published by Elsevier B.V.

  15. Molecular Mechanisms of Foot-and-Mouth Disease Virus Targeting the Host Antiviral Response.

    Science.gov (United States)

    Rodríguez Pulido, Miguel; Sáiz, Margarita

    2017-01-01

    Foot-and-mouth disease virus (FMDV) is the causative agent of an acute vesicular disease affecting pigs, cattle and other domestic, and wild animals worldwide. The aim of the host interferon (IFN) response is to limit viral replication and spread. Detection of the viral genome and products by specialized cellular sensors initiates a signaling cascade that leads to a rapid antiviral response involving the secretion of type I- and type III-IFNs and other antiviral cytokines with antiproliferative and immunomodulatory functions. During co-evolution with their hosts, viruses have acquired strategies to actively counteract host antiviral responses and the balance between innate response and viral antagonism may determine the outcome of disease and pathogenesis. FMDV proteases Lpro and 3C have been found to antagonize the host IFN response by a repertoire of mechanisms. Moreover, the putative role of other viral proteins in IFN antagonism is being recently unveiled, uncovering sophisticated immune evasion strategies different to those reported to date for other members of the Picornaviridae family. Here, we review the interplay between antiviral responses induced by FMDV infection and viral countermeasures to block them. Research on strategies used by viruses to modulate immunity will provide insights into the function of host pathways involved in defense against pathogens and will also lead to development of new therapeutic strategies to fight virus infections.

  16. Influence of antiviral therapy on survival of patients with hepatitis B ...

    African Journals Online (AJOL)

    The mortality rates in two groups were evaluated with Kaplan-Meier estimate. ... 274 (76.9 %) died, with 89 patients belonging to the antiviral group while the ... TACE is different from systemic ... and identification of study participants was not ..... Table 3: Cox regression analysis to deteermine variables associated with overall ...

  17. Quantitative autoradiographic mapping of focal herpes simplex virus encephalitis using a radiolabeled antiviral drug

    International Nuclear Information System (INIS)

    Price, R.

    1984-01-01

    A method of mapping herpes simplex viral infection comprising administering a radiolabeled antiviral active 5-substituted 1-(2'-deoxy-2'-substituted-D-arabinofuranosyl) pyrimidine nucleoside to the infected subject, and scanning the area in which the infection is to be mapped for the radiolabel

  18. Antiviral activity of Petiveria alliacea against the bovine viral diarrhea virus.

    Science.gov (United States)

    Ruffa, M J; Perusina, M; Alfonso, V; Wagner, M L; Suriano, M; Vicente, C; Campos, R; Cavallaro, L

    2002-07-01

    Natural products are a relevant source of antiviral drugs. Five medicinal plants used in Argentina have been assayed to detect inhibition of viral growth. Antiviral activity of the infusions and methanolic extracts of Aristolochia macroura, Celtis spinosa, Plantago major, Schinus areira, Petiveria alliacea and four extracts obtained from the leaves and stems of the last plant were evaluated by the plaque assay. P. alliacea, unlike A. macroura, C. spinosa, P. major and S. areira, inhibited bovine viral diarrhea virus (BVDV) replication. Neither P. alliacea nor the assays of the other plants were active against herpes simplex virus type 1, poliovirus type 1, adenovirus serotype 7 and vesicular stomatitis virus type 1. Four extracts of P. alliacea were assayed to detect anti-BVDV activity. Ethyl acetate (EC(50) of 25 microg/ml) and dichloromethane (EC(50) of 43 microg/ml) extracts were active; moreover, promising SI (IC(50)/EC(50)) values were obtained. BVDV is highly prevalent in the cattle population, there are no antiviral compounds available; additionally, it is a viral model of the hepatitis C virus. For these reasons and in view of the results obtained, the isolation and characterization of the antiviral components present in the P. alliacea extracts is worth carrying out in the future. Copyright 2002 S. Karger AG, Basel

  19. Phosphatidyl Inositol 3 Kinase-Gamma Balances Antiviral and Inflammatory Responses During Influenza A H1N1 Infection: From Murine Model to Genetic Association in Patients

    Directory of Open Access Journals (Sweden)

    Cristiana C. Garcia

    2018-05-01

    Full Text Available Influenza A virus (IAV infection causes severe pulmonary disease characterized by intense leukocyte infiltration. Phosphoinositide-3 kinases (PI3Ks are central signaling enzymes, involved in cell growth, survival, and migration. Class IB PI3K or phosphatidyl inositol 3 kinase-gamma (PI3Kγ, mainly expressed by leukocytes, is involved in cell migration during inflammation. Here, we investigated the contribution of PI3Kγ for the inflammatory and antiviral responses to IAV. PI3Kγ knockout (KO mice were highly susceptible to lethality following infection with influenza A/WSN/33 H1N1. In the early time points of infection, infiltration of neutrophils was higher than WT mice whereas type-I and type-III IFN expression and p38 activation were reduced in PI3Kγ KO mice resulting in higher viral loads when compared with WT mice. Blockade of p38 in WT macrophages infected with IAV reduced levels of interferon-stimulated gene 15 protein to those induced in PI3Kγ KO macrophages, suggesting that p38 is downstream of antiviral responses mediated by PI3Kγ. PI3Kγ KO-derived fibroblasts or macrophages showed reduced type-I IFN transcription and altered pro-inflammatory cytokines suggesting a ce